Perugia, Italy
Perugia, Italy

University of Perugia is a public-owned university based in Perugia, Italy. It was founded in 1308, as attested by the Bull issued by Pope Clement V certifying the birth of the Studium Generale.The official seal of the university portraits Saint Herculan, one of the saint patrons, and the rampant crowned griffin, which is the city symbol: they represent the ecclesiastical and civil powers, respectively, which gave rise to the university in the Middle Ages. Wikipedia.


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Gadducci F.,University of Pisa | Santini F.,University of Perugia
Information Processing Letters | Year: 2017

Soft constraint formalisms are an abstract representation of Constraint Satisfaction Problems (CSPs): the set of preferences is now parametric, often forming (a variety of) an absorptive semiring. However, the latter is suitable only for negative preferences, i.e., such that the combination of constraints worsens the quality of the solution. This work comments on related work and exploits residuated semirings in order to lift the Local Consistency heuristics that hold for classical CSPs. As a result, we merge and generalise existent formalisms for modelling soft CSPs with bipolar (positive and negative) preferences. © 2016 Elsevier B.V.


Menconi M.E.,University of Perugia | Grohmann D.,University of Perugia | Mancinelli C.,University of Perugia
Land Use Policy | Year: 2017

Farmers are those who daily supervise and manage rural areas, but still their collaborations with those institutions entitled to decide the transformation of these territories are not managed properly. The experiences of participatory processes with the involvement of farmers are analyzed in many agricultural studies. A systematic review has allowed us to analyse experiences related to 35 participation paths aimed at rural regions’ development. The analysis has been made on the basis of 14 variables describing the path followed and its purpose, the agricultural holding involved and the areas surveyed. The work has the objectives to identify some strengths and weaknesses in the involvement of farmers in decision-making and the strengths and weaknesses of the processes themselves. The review has shown that too often in participatory processes farmers are considered only as a source of information to be used by researchers rather than as active participants in the choices for the protection, management and transformation of the rural territory. An effective participatory rural appraisal requires greater empowerment of farmers. In general, compared to the methods and tools used, farmers are wary of paths that are too complex and prefer the use of low-tech tools. This result can be attributed to the farmers’ demand of direct contact with the researchers to build trust and also to the average age of European farmers, which is pretty high. In participation contexts, it is not possible to establish standardized methods and tools, because each process should be tailored for the community that expresses it. Nevertheless, the work has highlighted the need to establish some minimum principles to avoid considering unsuccessful some participation paths which, in reality, have been only scarcely participated. In the work, these principles have been presented through the development of key questions, to which those who design the path for an effective engagement of agricultural stakeholder must respond: representativeness, empowerment, empirical knowledge, relationships, group type, numerosity and involvement stage. © 2016 Elsevier Ltd


Tarpani L.,University of Perugia | Latterini L.,University of Perugia
Journal of Luminescence | Year: 2017

The interactions of dye molecules with gold nanoparticles are of great interest owing to the potential applications in the areas of bioimaging, sensing and photodynamic therapy applications. In many cases the distances between fluorophores and the metal particles can change during the experiment and the spectral features of the units are not taken into account. In this work, the fluorescence behaviour of two dyes with different spectral properties (Rhodamine B and 9-aminoacridine) are investigated in the presence of gold nanoparticles having diameters of 2 or 26 nm and hence different plasmonic properties. In order to fix the distance between the dye and the gold nanoparticles, the dyes are entrapped in 20 nm silica nanoparticles, and the metal colloids are adsorbed on the silica surface. The distance between the fluorescent units and the metal particles is tuned by growing additional silica layers on the pristine nanoparticles. Steady-state and time-resolved fluorescence measurements show that in the presence of gold nanoparticles, having 2 nm diameter, a drastic quenching of the dye emission is observed, for all the prepared samples, despite the average dye-metal distances. When gold nanoparticles with 26 nm diameters are used, their interactions with the dyes are strongly dependent on the averaged distances between the metal colloids and the dyes and on the overlap of their spectral properties. Indeed, an enhanced emission is observed for 9-aminoacridine while the fluorescence of longer wavelength emitting Rhodamine B is quenched. The steady state and time-resolved data are analysed to evaluate the plasmonic impact of the radiative and non-radiative rate constants of the dyes. © 2017


Petrini C.,Instituto Superiore Of Sanita | Morresi A.,University of Perugia
Annali dell'Istituto Superiore di Sanita | Year: 2017

Early experiments in womb transplants have increased interest in the possibility of performing this procedure in women who have no womb, usually for congenital reasons. The present article describes past experiments and summarises the most relevant reference documents before indicating the key ethical implications involved in womb transplants.


Cicerone S.,University of L'Aquila | Di Stefano G.,University of L'Aquila | Navarra A.,University of Perugia
Distributed Computing | Year: 2017

The paper considers variants of the gathering problem of oblivious and asynchronous robots moving in the plane. When (Formula presented.) robots are free to gather anywhere in the plane, the problem has been solved in Cieliebak et al. (SIAM J Comput 41(4):829–879, 2012). We propose a new natural and challenging model that requires robots to gather only at some predetermined points in the plane, referred to as meeting-points. Robots operate in standard Look-Compute-Move cycles. In one cycle, a robot perceives the current configuration in terms of robots’ positions and meeting-points (Look) according to its own coordinate system, decides whether to move toward some direction (Compute), and in the positive case it moves (Move). Cycles are performed asynchronously for each robot. Robots are anonymous and execute the same distributed and deterministic algorithm. In the new proposed model, we fully characterize when gathering can be accomplished. We design an algorithm that solves the problem for all configurations with (Formula presented.) robots but those identified as ungatherable. After that, we consider the classical notion of optimization algorithms and extend it to the context of robot-based computing systems. With this new notion, we re-consider the gathering on meeting-points problem but with respect to two objective functions. In particular, we first solve the gathering by minimizing the overall traveled distance performed by all robots and then we address the minimization of the maximum traveled distance performed by a single robot. For the former objective function, we fully characterize when optimal gathering can be achieved by providing a distributed algorithm along with the proof of correctness. For the latter objective function, we design another gathering algorithm that ensures optimal gathering almost for all the cases where it is possible, and discuss some insights on the remaining cases. © 2017 Springer-Verlag Berlin Heidelberg


Francesconi M.,University of Perugia | Mugnai D.,University of Perugia
Nonlinear Analysis: Real World Applications | Year: 2017

We consider a class of pseudo-relativistic Hartree equations in presence of general nonlinearities not satisfying the Ambrosetti–Rabinowitz condition. Using variational methods based on critical point theory, we show the existence of two non trivial signed solutions, one positive and one negative. © 2016 Elsevier Ltd


Di Schino A.,University of Perugia | Di Nunzio P.E.,Centro Sviluppo Materiali S.p.A
Acta Metallurgica Slovaca | Year: 2017

The need of even longer rolling sessions is driving the improvement of back up rolls in terms of wear resistance. This is also aimed to reduce costs. In this paper the effect of steel chemical composition on contact fatigue phenomena, bringing to the macroscopic damage named spalling is reported. Results show that the removal by grinding operations of damaged portion of rolls surface should be not sufficient to restore the initial performances of material. Experimental tests showed that a portion of material below the damaged one keeps memory of the last fatigue cycle, and has to be removed. © 2017, Technical University of Kosice. All Rights Reserved.


Di Schino A.,University of Perugia | Di Nunzio P.E.,Centro Sviluppo Materiali S.p.A
Acta Metallurgica Slovaca | Year: 2017

The development of steels for line pipes during the last decades has been driven by the need to obtain improved combinations of high strength, toughness, weldability on industrial scale at affordable prices. The effect of niobium content on the heat affected zone (HAZ) microstructure is reported in this paper. Niobium, for its specific thermodynamic and kinetic attitude to form carbide and nitride precipitates, played a key role in the development of modern HSLA steels Results show that niobium addition is able to refine both the bainitic packet and cells size in the heat affected zone during welding. This implies that niobium addition leads to an improvement of both toughness and hardness of welded joints manufactured by Nb micro-alloyed steels. © 2017, Technical University of Kosice. All Rights Reserved.


Cardelli E.,University of Perugia | Faba A.,University of Perugia | Laudani A.,Third University of Rome | Antonio S.Q.,University of Perugia | And 2 more authors.
IEEE Transactions on Industrial Electronics | Year: 2017

Rotational magnetizations of an Ni-Fe alloy are simulated using two different computer modeling approaches, physical and phenomenological. The first one is a model defined using a single hysteron operator based on the Stoner and Wohlfarth theory and the second one is a model based on a suitable system of neural networks. The models are identified and validated using experimental data, and, finally, an example of their application for a finite-element analysis is given. © 2016 IEEE.


Di Schino A.,University of Perugia | Di Nunzio P.E.,Centro Sviluppo Materiali S.p.A
Materials Letters | Year: 2017

The effect of Nb content in the range 0.07–0.10% on the HAZ microstructure of large diameter pipes is reported in this paper. Results show that Nb is able to influence the size of the bainitic packet and cells in the heat affected zone, i.e. the microstructural parameters affecting impact toughness and hardness behavior. Such an effect leads to an improvement of both toughness and hardness for the steel with higher Nb content. © 2016 Elsevier B.V.


Capotorti A.,University of Perugia | Talamanca G.F.,University of Perugia
Advances in Intelligent Systems and Computing | Year: 2017

In this paper we extend our previous contributions on the elicitation of the fuzzy volatility membership function in option pricing models. More specifically we generalize the SMART disjunction for a multi-model volatility behavior (Uniform, LogNormal, Gamma, …) and within a double-source (direct vs. indirect) information set. The whole procedure is then applied to the Cox-Ross-Rubinstein framework for option pricing on the S&P500 Index where the historical volatility, computed from the Index returns’ time series, and the VIX Index observed data are respectively considered as the direct and indirect sources of knowledge.Asuitable distance among the resulting fuzzy option prices and the market bid-ask spread make us appreciate the proposed procedure against the classical fuzzy mean. © Springer International Publishing Switzerland 2017.


Petturiti D.,University of Perugia | Vantaggi B.,University of Rome La Sapienza
Advances in Intelligent Systems and Computing | Year: 2017

The aim is to determine the envelopes of the class of joint probabilities (provided it is not empty) with assigned marginals, under the constraint of absolute continuity or equivalence with respect to a given reference measure. © Springer International Publishing Switzerland 2017.


Gentili P.L.,University of Perugia | Giubila M.S.,University of Perugia | Heron B.M.,University of Huddersfield
ChemPhysChem | Year: 2017

This work demonstrates the computational power of a hydrodynamic photochemical oscillator based on a photochromic naphthopyran generating aperiodic time series. The chaotic character of the time series is tested by calculating its largest Lyapunov exponent and the correlation dimension of its attractor after building its phase space through the Takens' theorem. Then, the chaotic dynamic is shown to be suitable to implement all the fundamental Boolean two-inputs-one-output logic gates. Finally, the strategy to implement fuzzy logic systems (FLSs) based on the time series is described. Such FLSs promise to be useful in the field of computational linguistics, which is concerned with the development of artificial intelligent systems able to transform collections of numerical data into natural language texts. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.


Tomassetti N.,University of Perugia | Feng J.,Sun Yat Sen University | Feng J.,Academia Sinica, Taiwan
Astrophysical Journal Letters | Year: 2017

A new analysis of cosmic ray (CR) data collected by the SOKOL experiment in space found that the deuteron-to-helium ratio at energies between 500 and 2000 GeV/nucleon takes the value d/He ∼ 1.5. As we will show, this result cannot be explained by standard models of secondary CR production in the interstellar medium and points to the existence of a high-energy source of CR deuterons. To account for the deuteron excess in CRs, we argue that the only viable solution is hadronic interaction processes of accelerated particles inside old supernova remnants (SNRs). From this mechanism, however, the B/C ratio is also expected to increase at energies above ∼50 of GeV/nucleon, in conflict with new precision data just released by the AMS-02 experiment. Hence, if this phenomenon is a real physical effect, hadronic production of CR deuterons must occur in SNRs characterized by low metal abundance. In such a scenario, the sources accelerating C - O nuclei are not the same as those accelerating helium or protons, so that the connection between d/He ratio and B/C ratio is broken, and the latter cannot be used to place constraints on the production of light isotopes or antiparticles. © 2017. The American Astronomical Society. All rights reserved.


Bigerna S.,University of Perugia | Bollino C.A.,University of Perugia | Ciferri D.,John Cabot University | Polinori P.,University of Perugia
Renewable and Sustainable Energy Reviews | Year: 2017

In the electricity market, sudden price jumps occur more frequently than in other markets due to the peculiarity of electricity. Furthermore, the structural spot characteristics of the electricity market determine high price variability. All these characteristics have been accentuated by the dramatic increase of renewable energy supply in Italy starting in 2010. These features suggest the possibility of contagion effects across Italian regional electricity markets, considering contagion such as a sudden and significant increase in cross-market links arising from a shock to a specific market. In this paper we investigate whether such a renewable energy increase has affected the contagion behavior in the Italian electricity spot market taking into account both the difference between interdependence and contagion and the direction of the shock. We find empirical evidence, with significant tests, that no changes have occurred in interdependence mechanism, nor in contagion effects due to renewable energy sources development in Italy. © 2016 Elsevier Ltd


Trippella O.,University of Perugia | Trippella O.,National Institute of Nuclear Physics, Italy | Cognata M.L.,National Institute of Nuclear Physics, Italy
Astrophysical Journal | Year: 2017

The 13C(a, n)16O reaction is considered to be the main neutron source responsible for the production of heavy nuclides (from Sr to Bi) through slow n-capture nucleosynthesis (s-process) at low temperatures during the asymptotic giant branch phase of low-mass stars (≲3-4 M, or LMSs). In recent years, several direct and indirect measurements have been carried out to determine the cross section at the energies of astrophysical interest (around 190 40 keV). However, they yield inconsistent results that cause a highly uncertain reaction rate and affect the neutron release in LMSs. In this work we have combined two indirect approaches, the asymptotic normalization coefficient and the Trojan horse method, to unambiguously determine the absolute value of the 13C(a, n)16O astrophysical factor. With these, we have determined a very accurate reaction rate to be introduced into astrophysical models of s-process nucleosynthesis in LMSs. Calculations using this recommended rate have shown limited variations in the production of those neutron-rich nuclei (with 86 A 209) that receive contribution only by slow neutron captures. © 2017. The American Astronomical Society. All rights reserved.


Lollini R.,National Institute of Nuclear Physics, Italy | Lollini R.,University of Perugia
Nuovo Cimento della Societa Italiana di Fisica C | Year: 2017

NA62 is a high-energy physics experiment located at the CERN SPS. NA62 aims at measuring the ultra-rare decay K+ → φ+vv with a 10% precision. The K+ → μ+v decay is the main background which needs to be suppressed by a factor 2 × 1012. This goal can be achieved by kinematical cuts, different stopping power of μ+/φ+ and a RICH detector able to measure particles velocity in a momentum range between 15 and 35GeV/c. Moreover, the RICH detector measures the pion crossing time with a resolution of 100 ps and produces the L0 trigger for a charged track. In this paper the NA62 RICH will be described, and the preliminar results regarding pion/muon separation in the 2015 data taking will be presented. © CERN on behalf of the ATLAS and CMS Collaborations.


Graziani M.,National Institute of Nuclear Physics, Italy | Graziani M.,University of Perugia
Nuovo Cimento della Societa Italiana di Fisica C | Year: 2017

The Alpha Magnetic Spectrometer (AMS-02) is a state-of-the-art particle physics detector which operates onboard the International Space Station since May 2011. The main goals of the AMS-02 project are the indirect search of dark matter, the search of primordial antimatter, and the determination of the cosmic ray energy spectra and composition at the TeV scale. In these proceedings, the main results achieved by AMS-02 in 5 years of operations will be presented and discussed. © CERN on behalf of the ATLAS and CMS Collaborations.


Salmasi L.,University of Perugia | Celidoni M.,University of Perugia | Celidoni M.,University of Padua
Economics and Human Biology | Year: 2017

This paper investigates the effect of income- and wealth-based poverty on the probability of being obese for the elderly in Europe by analysing data drawn from the Survey of Health, Ageing and Retirement (SHARE) and the English Longitudinal Study of Ageing (ELSA). We use early-life economic conditions and regional circumstances as instruments for poverty later in life to account for endogeneity issues. After controlling for a large set of covariates at the individual, household, regional and country level, the results show that poverty significantly increases the probability of being obese and the Body Mass Index (BMI), for men and women. The results show that, accounting for endogeneity with a bivariate probit model, poor individuals are from 10 to 20% points more likely to be obese than non-poor individuals. The effect on BMI ranges from 0.295 points (2.39 kg) to 0.395 points (2.75 kg). These results are robust to a series of checks and suggest that anti-poverty interventions might have positive side effects in terms of reducing food-related health inequalities. © 2017 Elsevier B.V.


Bonafoni S.,University of Perugia | Tosi G.,University of Perugia
IEEE Geoscience and Remote Sensing Letters | Year: 2017

A regression-based downscaling of land surface temperature was developed over the heterogeneous urban area of Aprilia, Central Italy, using high resolution (HR) airborne data. Airborne sensors provided thermal and visible- near infrared (VNIR) measurements at 2-m pixel size. Coarse resolution images at 40, 30, and 20 m, upscaled by aggregation from the native airborne data, were sharpened to the finer resolution of 2 m. The main core of the downscaling method is the use of the spectral mixture analysis (SMA) to derive fractional pixel composition as predictors of the regression scheme. The HR VNIR data allow choosing detailed land cover types in the application of SMA, such as bright/dark roofs, and the benefit of this detailed selection is proved. The estimation error of the custom technique improves of about 10%-15% with respect to a classical regression downscaling. © 2016 IEEE.


Ceccopieri F.A.,University of Perugia | Ceccopieri F.A.,University of Liège
European Physical Journal C | Year: 2017

We present predictions for single-diffractive low-mass Drell–Yan pair production in pp collisions at the LHC at s=13 TeV. Predictions are obtained adopting a factorised form for the relevant cross sections and are based on a new set of diffractive parton distributions resulting from the QCD analysis of combined HERA leading proton data. We discuss a number of observables useful to characterise the expected factorisation breaking effects. © 2017, The Author(s).


Chiaravalloti A.,University of Rome Tor Vergata | Danieli R.,San Raffaele Telematic University of Rome | Lacanfora A.,University of Rome Tor Vergata | Palumbo B.,University of Perugia | And 2 more authors.
Current Alzheimer Research | Year: 2017

In the last decade, several radiolabeled compounds have been developed for the imaging in vivo of amyloid pathology by means of Positron Emission Tomography (PET). Among these, 18F Florbetaben appear to be one of the most reliable for its high affinity for amyloid plaques in brain and its radio-chemical properties that make it usable in common clinical routine. The aim of this review is to provide a general overview of the application in vivo of 18F Florbetaben, describing for first the physiopathological basis of amyloid pathology. Afterwards, the chemical characteristics of this radiolabeled compound will be described, with a particular attention to the synthesis process and the kinetic in vivo. An overview on the imaging protocols and image interpretation will be provided as well and, as a last aspect, the results of the main studies performed in subjects with advanced and early AD will be summarized. © 2017 Bentham Science Publishers.


Traina G.,University of Perugia
Frontiers in Bioscience - Landmark | Year: 2016

A large body of evidence points to the positive effects of dietary supplementation of acetyl-Lcarnitine (ALC). Its use has shown health benefits in neuroinflammation, which is a common denominator in a host of neurodegenerative diseases. ALC is the principal acetyl ester of L-Carnitine (LC), and it plays an essential role in intermediary metabolism, acting as a donor of acetyl groups and facilitating the transfer of fatty acids from cytosol to mitochondria during betaoxidation. Dietary supplementation of ALC exerts neuroprotective, neurotrophic, antidepressive and analgesic effects in painful neuropathies. ALC also has antioxidant and anti-apoptotic activity. Moreover, ALC exhibits positive effects on mitochondrial metabolism, and shows promise in the treatment of aging and neurodegenerative pathologies by slowing the progression of mental deterioration. In addition, ALC plays neuromodulatory effects on both synaptic morphology and synaptic transmission. These effects are likely due to affects of ALC through modulation of gene expression on several targets in the central nervous system. Here, we review the current state of knowledge on effects of ALC in the nervous system.


Salciarini D.,University of Perugia | Fanelli G.,University of Perugia | Tamagnini C.,University of Perugia
Landslides | Year: 2017

This paper presents a new probabilistic physically-based computational model (called PG_TRIGRS) for the probabilistic analysis of rainfall-induced landslide hazard at a regional scale. The model is based on the deterministic approach implemented in the original TRIGRS code, developed by Baum et al. (USGS Open File Report 02–424, 2002) and Baum et al. (USGS Open File Report 08–1159, 2008). Its key innovative features are: (a) the application of Ordinary Kriging for the estimation of the spatial distributions of the first two statistical moments of the probability density functions of the relevant soil properties over the entire area, based on limited available information gathered from available information from limited site investigation campaigns, and (b) the use of Rosenblueth’s Point Estimate method as a more efficient alternative to the classical Monte Carlo method for the reliability analysis performed at the single-cell level to obtain the probability of failure associated to a given rainfall event. The application of the PG_TRIGRS code to a selected study area located in the Umbria Region for different idealized but realistic rainfall scenarios has demonstrated the computational efficiency and the accuracy of the proposed methodology, assessed by comparing predicted landslide densities with available field observations reported by the IFFI project. In particular, while the model might fail to identify all individual landslide events, its predictions are remarkably good in identifying the areas of higher landslide density. © 2017 Springer-Verlag Berlin Heidelberg


Pisello A.L.,University of Perugia
Solar Energy | Year: 2017

Urban systems, from their early origins, were acknowledged to be responsible for both benefits and penalties due to anthropogenic actions affecting human wellbeing. In this view, local overheating exacerbated by urban heat island phenomenon has been identified as a result of anthropogenic actions responsible for citizens’ health issues and other serious socio-economic consequences in urban areas, where almost the 70% of the world population is expected to live in thirty years. This fact imposes to respond to an urgent research question concerning the development and the real-world application of effective mitigation strategies against urban climate change phenomena, for a better population resilience. Among the variety of these strategies, the implementation of “cool” coatings over urban surfaces exposed to the solar radiation, i.e. cool roofs and cool pavements, represents a proved solution to counteract such overheating effect and its negative consequences on the population living in urban context. In this view, the present work reviews the state of the art about the development of new materials and their main applications as cool roofing and paving systems for passive cooling purpose of buildings and cities, which have been published in more than 260 papers in the last decades. Both indoor and outdoor passive cooling benefits were clearly demonstrated and quantified with varying climate conditions, material characteristics and the built environment context. Despite that, the investigation around this issue is still active worldwide, from chemistry, material science and engineering fields. Additionally, new triggers were highlighted as possible starting points for future scientific focus. In particular, still active discussions give rise to promising research findings expected to clarify (i) the effect of cool coatings on pedestrians’ glare, possibly mitigated by directionally-reflective materials, (ii) the role of cool coatings for HVAC optimization, (iii) the combined benefits of cool coatings and thermal-energy storage techniques for UHI mitigation. © 2017 Elsevier Ltd


Mezzasoma L.,University of Perugia | Antognelli C.,University of Perugia | Talesa V.N.,University of Perugia
Mediators of Inflammation | Year: 2017

Interleukin-1β (IL-1β) is a pleiotropic cytokine and a crucial mediator of inflammatory and immune responses. IL-1β processing and release are tightly controlled by complex pathways such as NF-kB/ERK1/2, to produce pro-IL-1β, and NALP3/ASC/Caspase-1 inflammasome, to produce the active secreted protein. Dysregulation of both IL-1β and its related pathways is involved in inflammatory/autoimmune disorders and in a wide range of other diseases. Identifying molecules modulating their expression is a crucial need to develop new therapeutic agents. IL-1β is a strong regulator of Brain Natriuretic Peptide (BNP), a hormone involved in cardiovascular homeostasis by guanylyl cyclase Natriuretic Peptide Receptor (NPR-1). An emerging role of BNP in inflammation and immunity, although proposed, remains largely unexplored. Here, we newly demonstrated that, in human THP-1 monocytes, LPS/ATP-induced IL-1β secretion is strongly inhibited by BNP/NPR-1/cGMP axis at all the molecular mechanisms that tightly control its production and release, NF-kB, ERK 1/2, and all the elements of NALP3/ASC/Caspase-1 inflammasome cascade, and that NALP3 inflammasome inhibition is directly related to BNP deregulatory effect on NF-kB/ERK 1/2 activation. Our findings reveal a novel potent anti-inflammatory and immunomodulatory role for BNP and open new alleys of investigation for a possible employment of this endogenous agent in the treatment of inflammatory/immune-related and IL-1β/NF-kB/ERK1/2/NALP3/ASC/Caspase-1-associated diseases. © 2017 Letizia Mezzasoma et al.


Biscarini A.,University of Perugia | Bonafoni S.,University of Perugia
Proceedings of the Institution of Mechanical Engineers, Part P: Journal of Sports Engineering and Technology | Year: 2017

We established a set of analytical equations that constitute the biomechanical framework for the optimal design of plate-loaded strength training machines. Specifically, we assessed the effect on the exercise kinetics of a change in the distance dP between the site P of the resistance lever where the weight plates are loaded and the axis of rotation of the lever. To this end, the distance dP was increased, while keeping the value of the resistance torque T,R unchanged by a simultaneous decrease in the mass mP of plates loaded on the lever (dPmP = const). A progressive increase in dP (under the condition dPmP = const) yielded a sharp decrease, followed by a steady increase, in the moment of inertia of the loaded resistance lever (relative to its axis of rotation). The impact of this change on the kinetic effects related to the inertia of the moving equipment masses (inertial effects) has been discussed for maximal and explosive exercises, and for sub-maximal exercises executed at controlled cadence. We also detected a specific value of dP for which the torque related to the inertial effects, expressed as a percentage of T,R, turns out to be independent of the selected level of external resistance. This condition precisely reflects the linear-dynamic condition that occurs when lifting free weights. © 2017 Institution of Mechanical Engineers.


Aquilanti V.,University of Perugia | Aquilanti V.,Federal University of Bahia | Aquilanti V.,CNR Institute of Structure of Matter | Coutinho N.D.,University of Brasilia | Carvalho-Silva V.H.,State University of Goiás
Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences | Year: 2017

This article surveys the empirical information which originated both by laboratory experiments and by computational simulations, and expands previous understanding of the rates of chemical processes in the low-temperature range, where deviations from linearity of Arrhenius plots were revealed. The phenomenological two-parameter Arrhenius equation requires improvement for applications where interpolation or extrapolations are demanded in various areas of modern science. Based on Tolman's theorem, the dependence of the reciprocal of the apparent activation energy as a function of reciprocal absolute temperature permits the introduction of a deviation parameter d covering uniformly a variety of rate processes, from those where quantum mechanical tunnelling is significant and d<0, to those where d>0, corresponding to the Pareto-Tsallis statistical weights: these generalize the Boltzmann-Gibbs weight, which is recovered for d=0. It is shown here how the weights arise, relaxing the thermodynamic equilibrium limit, either for a binomial distribution if d>0 or for a negative binomial distribution if d<0, formally corresponding to Fermionlike or Boson-like statistics, respectively. The current status of the phenomenology is illustrated emphasizing case studies; specifically (i) the super-Arrhenius kinetics, where transport phenomena accelerate processes as the temperature increases; (ii) the sub-Arrhenius kinetics, where quantum mechanical tunnelling propitiates low-temperature reactivity; (iii) the anti-Arrhenius kinetics, where processes with no energetic obstacles are rate-limited by molecular reorientation requirements. Particular attention is given for case (i) to the treatment of diffusion and viscosity, for case (ii) to formulation of a transition rate theory for chemical kinetics including quantum mechanical tunnelling, and for case (iii) to the stereodirectional specificity of the dynamics of reactions strongly hindered by the increase of temperature.


Fravolini M.L.,University of Perugia | Yucelen T.,Missouri University of Science and Technology | Napolitano M.,West Virginia University
Journal of Guidance, Control, and Dynamics | Year: 2017

A crucial aspect that could facilitate the applications of adaptive control systems in aerospace applications is the development of effective validation and verification procedures. Most of the existing analysis and design frameworks for adaptive controllers are based on the Lyapunov direct method. One well-known drawback of this approach is the conservatism in the estimation of the uniform ultimate boundedness region with little practical utility. To overcome this limitation, a probabilistic framework for the design of uniform ultimate boundedness regions is proposed where uncertain parameters and adaptive controls are considered as random variables. In this framework, the design is translated into a stochastic convex optimization. This brings the benefit that (probabilistic) linear matrix inequality constraints can be derived without the need of matrix majorizations resulting therefore in less conservative conditions. Although the results are probabilistic, the level of confidence in the violation of linear matrix inequality constraints can be effectively established at the design level, exploiting the recent results of the probabilistic scenario design method. The approach is here applied for the design of uniform ultimate boundedness regions with prespecified componentwise error requirements for a model reference adaptive control scheme in the presence of matched and input uncertainty. The approach is validated using the short-period longitudinal dynamics of an F-16 aircraft. © 2016 by Aaron Estes and Manoranjan Majji.


The paper deals with the potential of high energy-efficient windows with granular silica aerogel for energy saving in building refurbishment. Different glazing systems were investigated considering two kinds of granular silica aerogel and different glass layers. Thermal transmittance and optical properties of the samples were measured and used in building simulations. The aerogel impact on heat transfer is remarkable, allowing a thermal transmittance of 1.0-1.1 W/(m2.K) with granular aerogel in interspace only 15 mm in thickness. A 63% reduction in U-value was achieved when compared to the corresponding conventional windows, together with a significant reduction (30%) in light transmittance. When assembled with a low-e glass, the U-value reduction was lower (31%), but a moderate reduction in light transmittance (about 10%) was observed for larger granules. Energy simulations for a case study in different climate conditions (hot, moderate, and cold) showed a reduction in energy demand both for heating and cooling for silica aerogel glazing systems, when compared to the conventional ones. The new glazings are a suitable solution for building refurbishment, thanks to low U-values and total solar transmittance, also in warm climate conditions. © 2017 by the authors.


Vijayan P. P.,Qatar University | Puglia D.,University of Perugia | Al-Maadeed M.A.S.A.,Qatar University | Kenny J.M.,University of Perugia | Thomas S.,Mahatma Gandhi University
Materials Science and Engineering R: Reports | Year: 2017

The approach of simultaneously exploit the use of microscale elastomers/thermoplastics and nanoscale fillers for the modification of epoxy systems is presently an active research topic. Such hybrid modification of epoxy primarily helps to tailor multiple mechanical properties, without compromising other required properties. The current review reports about the development and properties of multicomponent epoxy systems modified with both elastomers/thermoplastics and nanofillers, on the basis of an updated literature survey. For a better understanding and comparison, the review initially provides a short discussion on key findings in binary blends of epoxy and elastomers/thermoplastic and binary epoxy nanocomposites. Successful studies dealing with multicomponent epoxy systems are also reported, where it is demonstrated that microscale modification individually, sometimes synergistically, enhances the fracture toughness of epoxy without affecting the properties optimized by nanoscale modification. The mutual role of microscale elastomer/thermoplastic and nanoscale filler on morphology, cure reaction, mechanical and thermal properties of epoxy multicomponent system is discussed. The complex interaction between the micro- and nano-phases determines phase separated morphologies in the multicomponent system, essentially related to the function of microscale modifiers in dispersion/intercalation/distribution of nanofillers and to the role of nanofillers in phase separation kinetics and mechanisms. The specific effect of nanofillers in phase separation mechanisms for epoxy blends, that place via nucleation and growth (NG) and spinodal decomposition, is analysed looking at the final morphology and hence performance of multicomponent system. Moreover, the fracture mechanism that operates in such multicomponent epoxy systems is discussed. © 2017 Elsevier B.V.


Cristina Diamantini M.,University of Perugia | Trugenberger C.A.,SwissScientific
EPJ Web of Conferences | Year: 2017

We present a new Higgsless model of superconductivity, inspired from anyon superconductivity but P- and T-invariant and generalizable to any dimension. While the original anyon superconductivity mechanism was based on incompressible quantum Hall fluids as average field states, our mechanism involves topological insulators as average field states. In D space dimensions it involves a (D-1)-form fictitious pseudovector gauge field which originates from the condensation of topological defects in compact lowenergy effective BF theories. There is no massive Higgs scalar as there is no local order parameter. When electromagnetism is switched on, the photon acquires mass by the topological BF mechanism. Although the charge of the gapless mode (2) and the topological order (4) are the same as those of the standard Higgs model, the two models of superconductivity are clearly different since the origins of the gap, reflected in the high-energy sectors are totally different. In 2D thi! s type of superconductivity is explicitly realized as global superconductivity in Josephson junction arrays. In 3D this model predicts a possible phase transition from topological insulators to Higgsless superconductors. © The Authors, published by EDP Sciences, 2017.


Costantini S.,University of L'Aquila | Formisano A.,University of Perugia
Proceedings of the International Joint Conference on Autonomous Agents and Multiagent Systems, AAMAS | Year: 2016

In this paper we consider the software-engineering problem of how to empower modular agent architectures with the capability to perform quantitative reasoning in a uniform and principled way. Copyright © 2016, International Foundation for Autonomous Agents and Multiagent Systems (www.ifaamas.org). All rights reserved.


Mancusi A.,University of Perugia | Ruggeri L.,University of Perugia | Velardi A.,University of Perugia
Blood | Year: 2016

The present review describes the biology of human leukocyte antigen haplotype mismatched ("haploidentical") transplantation, its translation to clinical practice to cure leukemia, and the results of current transplantation protocols. The 1990s saw what had been major drawbacks of haploidentical transplantation, ie, very strong host-versus-graft and graft-versus-host alloresponses, which led respectively to rejection and graft-versus-host disease (GVHD), being overcome through transplantation of a "mega-dose" of T cell-depleted peripheral blood hematopoietic progenitor cells and no posttransplant pharmacologic immunosuppression. The absence of posttransplant immunosuppression was an opportunity to discover natural killer cell alloreactions that eradicated acute myeloid leukemia and improved survival. Furthermore, it also unveiled the benefits of transplantation from mother donors, a likely consequence of the mother-to-child interaction during pregnancy. More recent transplantation protocols use unmanipulated (without ex vivo T-cell depletion) haploidentical grafts combined with enhanced posttransplant immunosuppression to help prevent GVHD. Unmanipulated grafts substantially extended the use of haploidentical transplantation with results than even rival those of matched hematopoietic transplantation. In T cell-depleted haploidentical transplantation, recent advances were made by the adoptive transfer of regulatory and conventional T cells. © 2016 by The American Society of Hematology.


Antognelli S.,University of Perugia | Vizzari M.,University of Perugia
Ecological Indicators | Year: 2017

In recent years, landscape liveability has become a leading objective in policy and strategic planning. In the anthropocentric view of landscape, ecosystems fulfil important societal needs similarly to urban systems. Urban systems can meet a variety of such needs through Urban Services, which are historically and typically provided within cities. In this view, Ecosystem Services (ES) and Urban Services (US) influence landscape liveability in a comparable manner, so that liveability assessments based on both ES and US can be effective for landscape planning and policy-making purposes. As liveability is strongly dependent not only on objective landscape features, but also on the subjective perception of stakeholders, their involvement becomes essential for a coherent liveability assessment. The present study aims to develop a LIveability Spatial Assessment Model (LISAM) capable of considering both the local accessibility of services and their perceived relevance as expressed by stakeholders. To this end, a conceptual framework to detangle the spatial relationships between service sources, sinks, and delivery points was developed. From this base, consistent and comparable ES and US indices were calculated using GIS spatialisation techniques and then aggregated hierarchically through a Spatial Multicriteria Decision Making Analysis approach. Results include relevant maps showing explicit spatial indices of liveability that integrate, at various hierarchical levels, the local accessibility of ES and US, along with their local perceived relevance. By calculating complex indices able to highlight both the agri-natural and urban system roles on landscape liveability and by taking subjective and objective aspects into account, the model proved to be effective for spatial decision-making. In future applications, indicator and weight uncertainties should be considered and adequately analysed to assess reliability of the final output. The integration of ecosystem and urban disservices would also be relevant for including those landscape factors that reduce the overall level of place liveability. © 2016 Elsevier Ltd


Ludovisi A.,University of Perugia | Scharler U.M.,University of KwaZulu - Natal
Ecological Indicators | Year: 2017

Various indicators rooted in the concepts of information and entropy have been proposed to be used for ecological network analysis. They are theoretically well grounded and widely used in the literature, but have always been difficult to interpret due to an apparent lack of strict relations with node and link weight. We generated several sets of 10,000 networks in order to explore such relations and work towards a sounder interpretation. The indices we explored are based on network composition (i.e., type and importance of network compartments), or network flows (i.e., type and importance of flows among compartments), including Structural Information (SI), Total System Throughput (TST), Average Mutual Information (AMI), Flow Diversity (H), and Ascendency (ASC). A correlation analysis revealed a lack of strict relationships among the responses of the investigated indicators within the simulated space of variability of the networks. However, fairly coherent patterns of response were revealed when networks were sorted by following a “bottom-up” criterion, i.e. by increasing the dominance of the large-sized top predator in the network. This ranking is reminiscent of ecosystem succession, along which the prominence of higher trophic level organisms progressively increases. In particular, the results show that a simple increase in organisms having large size and low consumption rates is potentially able to simultaneously lead to an increase of different types of information (as SI, H and AMI), thus also emphasizing the importance of bionomic traits related to body size in affecting information-related properties in a trophically connected community. The observed trends suffer from a certain dispersion of data, which was diminished by imposing specific and ecologically meaningful constraints, such as mass balancing and restriction to certain range of the ratio A/C, an index related to the viability of ecological networks. These results suggest that the identification of a set of effective constraints may help to identify improved conditions for applicability of the investigated flow-based indicators, and also provide indication on how to normalise them with respect to meaningful network properties or reference states. Thus, in order to increase confidence in the derived network metrics describing a particular ecosystem state, and thus increase their applicability, it is advisable to construct replicate networks by taking the variability of input data into account, and by applying uncertainty and sensitivity analyses. © 2016 Elsevier Ltd


Saha A.,University of Perugia
Journal of Instrumentation | Year: 2017

The pixel tracker of the Compact Muon Solenoid (CMS) experiment is the innermost sub-detector, located close to the collision point, and is used for reconstruction of the tracks and vertices of charged particles. The present pixel detector was designed to work efficiently with the maximum instantaneous luminosity of 1 × 1034 cm-2 s-1. In 2017 the Large Hadron Collider (LHC) is expected to deliver a peak luminosity reaching up to 2 × 1034 cm-2 s-1, increasing the mean number of primary vertices to 50. Due to the radiation damage and significant data losses due to high occupancy in the readout chip of the pixel detector, the present system must be replaced by a new one in an extended end-of-year shutdown during winter 2016/2017 in order to maintain the excellent tracking and other physics performances. The main new features of the upgraded pixel detector are a ultra-light mechanical design with four barrel layers and three end-cap disks, digital readout chip with higher rate capability and a new cooling system. In this document, we discuss the motivations for the upgrade, the design, and technological choices made, the status of the construction of the new detector and the future plans for the installation and commissioning. © 2017 IOP Publishing Ltd and Sissa Medialab srl.


Falcinelli S.,University of Perugia
Acta Physica Polonica A | Year: 2017

Main properties of multiply charged molecular ions (energetics, structure, stability, lifetime and fragmentation dynamics) are relevant to know and to model the behavior of gaseous plasmas, planetary ionospheres, and astrophysical environments. Experimental measurements of the kinetic energy released of fragment ions produced by the Coulomb explosion of molecular dications (doubly charged molecular species) originating by double photoionization of CO2 molecules, are reported and discussed. The kinetic energy released, as a function of the UV photon energy in the range of 34-50 eV, is extracted from the electron-ion-ion coincidence spectra recorded by using tunable synchrotron radiation coupled with ion imaging techniques at the GasPhase beam line of ELETTRA Synchrotron Light Laboratory Trieste, Italy. This kind of experiment allows assessing the probability of escape for simple ionic species in the ionosphere of Mars and Titan. The kinetic energy released, measured in the case of O+ and CO+ fragment ions, are ranging between 1.0-5.0 and 0.4-3.0 eV, respectively. These values are large enough to allow such ionic species in participating in the atmospheric escape from Mars (only O+ ions) and Titan (both O+ and CO+ ions) into space. In the case of Mars, we suggest a possible rationalization for the observed behavior of the O+ and CO2+ 2 ion density profiles by Viking 1 lander and Mariner 6 spacecraft.


Costarelli D.,University of Perugia | Minotti A.M.,University of Perugia | Vinti G.,University of Perugia
Journal of Mathematical Analysis and Applications | Year: 2017

In this paper, the behavior of the sampling Kantorovich operators has been studied, when discontinuous functions (signals) are considered in the above sampling series. Moreover, the rate of approximation for the family of the above operators is estimated, when uniformly continuous and bounded signals are considered. Finally, several examples of (duration-limited) kernels which satisfy the assumptions of the present theory have been provided, and also the problem of the linear prediction by sampling values from the past is analyzed. © 2017 Elsevier Inc.


de Giorgi V.,University of Perugia
Melanoma Research | Year: 2017

Currently, there are no specific clinical and dermoscopic features for diagnosing truly amelanotic plantar melanoma (TAPM). The present study aimed to investigate the dermoscopic features of all clinical variants of TAMPS and to evaluate their histopathological correlations. A retrospective analysis of prospectively collected data was carried out during a 10-year period (2003–2013). We analyzed the clinical data of 1321 patients, who had received a histological diagnosis of melanoma at the Melanoma Unit of the University of Florence. We selected the clinical and dermoscopic images of TAPMs and analyzed the presence of dermoscopic parameters. Incorrect preoperative diagnoses were analyzed to highlight peculiar dermoscopic features of pinkish plantar melanomas, the clinical diagnosis of which is extremely challenging for the dermatologist. Of all 1321 patients, 29 (24%) had TAPMs. Importantly, only 20.7% of patients with TAPMs had a correct preoperative diagnosis of suspicious melanocytic lesion. On the basis of the initial misdiagnosis, TAPMs were categorized as eczema-like, verruca-like, angioma-like lesions. Dermoscopically, all TAPMs showed the presence of a well-defined ‘erythematous homogeneous area’ with an atypical polymorphous vascular pattern with dotted, globular, and glomerular vessels. Our study highlights a crucial dermoscopic feature of TAPMs, the ‘erythematous homogeneous area’ that is characteristic of the plantar region, and, to our knowledge and experience, has not been described in nonacral amelanotic melanomas. Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.


Boccuto A.,University of Perugia | Gerace I.,University of Perugia
2016 International Workshop on Computational Intelligence for Multimedia Understanding, IWCIM 2016 | Year: 2016

We consider the problem of restoration of images corrupted by blur and noise. We find the minimum of the primal energy function, which has two terms. The former is related to faith fulness to the data and the latter is associated with smoothness constraints. In general, we have to estimate the discontinuities of the ideal image. We require that the obtained images are piecewise continuous and with thin edges. We associate with the primal energy function a dual energy function, which treats discontinuities implicitly. In order to have thin edges, we determine a dual energy function, which is convex and takes into account non-parallelism constraints. The proposed dual energy can be used as initial function in a GNC (Graduated Non-Convexity)-type algorithm, to obtain reconstructed images with Boolean discontinuities. In the experimental re-sults, we show that the parallel lines are inhibited. © 2016 IEEE.


NEW YORK--(BUSINESS WIRE)--Rasna Therapeutics, Inc. (OTCQX:RASP), a clinical stage biotechnology company focused on the development of disease-modifying drugs for hematological malignancies, today provided an update from further studies towards the development of formulated RASP-101, a novel modality for treatment of NPM1-mutated acute myeloid leukemia (AML). NPM1-mutated AML is a specific genetic variation of leukemia that accounts for approximately one third cases of AML in adults. A phase II clinical trial which was initiated in 2014 and completed in two and a half years, involved patients with refractory or relapsed NPM1-mutated AML treated with cycles of dactinomycin at a dose of 15µg per kilogram per day for 5 consecutive days (EudraCT number 2014-000693-18). As earlier published, intravenous treatment of refractory or relapsed AML patients with dactinomycin (12.5µg or 15µg per day) for 5 consecutive days had produced hematological complete response in specific patients (Falini et al., N Eng J Med. 373: 12, 2015). “We are pleased to report an update to these initial promising findings, which are now corroborated by the follow up of a phase II clinical study which achieved complete response in 40% of patients. Although further studies are warranted to understand the mechanism of action of dactinomycin in NPM1-mutated AML, we are delighted to move forward with development of a formulated RASP-101 for treatment of AML patients,” said Dr. Brunangelo Falini, a member of the scientific advisory board of Rasna Therapeutics, Inc. “We believe that our approach is a breakthrough and a first-in-class treatment for AML patients. We are determined to rapidly develop formulation of RASP-101 to enable multi-center clinical studies in NPM1-mutated AML. Patient stratification, based on specific AML gene mutations, is part of Rasna’s strategy to improve clinical outcome for this unmet clinical need,” commented Alessandro Padova, Chairman of Rasna. Brunangelo Falini is the head of the Institute of Hematology and Hemopoietic Stem Cell Transplantation at the University of Perugia, Perugia, Italy. His research activity has mainly focused on the genetic characterization of lymphomas and leukemias using monoclonal antibodies and, more recently, NGS technologies. He led the research group who discovered NPM1 mutations in AML in 2005 and the BRAF-V600E mutation in hairy cell leukemia in 2011. Both of these seminal discoveries have translated into a better diagnosis and therapy of patients affected by these hematological malignancies. Dr. Falini is the recipient of numerous prestigious prizes, including the “Josè Carreras Award” from EHA (Barcelona, 2010) and the “Leopold Griffuel Prize” from ARC (Paris, 2015). Rasna Therapeutics, Inc. is a clinical stage biotechnology company focused primarily on the development of drug candidates for leukemia and lymphoma. Abnormal epigenetic modification is recognized to play an important role in the pathogenesis of acute myeloid leukemia (AML), leading to silencing of genes involved in tumor suppression and cellular reproduction. Rasna has a balanced portfolio targeting NPM1-mutated AML through direct and indirect disease-modifying approaches. Rasna is also exploiting inhibition of lysine specific demethylase-1 (LSD1), an enzyme involved in epigenetic control, as a promising and novel approach against AML. Rasna is entering preclinical development with a novel class of potent and selective reversible LSD1 regulators that have shown efficacy and LSD1 target modulation in in-vitro and in IND-enabling pre-clinical studies. Certain statements in this press release are forward-looking within the meaning of the Private Securities Litigation Reform Act of 1995. These statements may be identified by the use of forward-looking words such as "anticipate," "believe," "forecast," "estimated," and "intend," among others. These forward-looking statements are based on Rasna's current expectations and actual results could differ materially. There are a number of factors that could cause actual events to differ materially from those indicated by such forward-looking statements. These factors include, but are not limited to, our ability to continue as a going concern; our need for additional financing; uncertainties of patent protection and litigation; uncertainties with respect to lengthy and expensive clinical trials, that results of earlier studies and trials may not be predictive of future trial results; uncertainties of government or third party payer reimbursement; limited sales and marketing efforts and dependence upon third parties; and risks related to failure to obtain FDA clearances or approvals and noncompliance with FDA regulations. As with any drug candidates under development, there are significant risks in the development, regulatory approval, and commercialization of new products. There are no guarantees that future clinical trials discussed in this press release will be completed or successful, or that any product will receive regulatory approval for any indication or prove to be commercially successful. Rasna does not undertake an obligation to update or revise any forward-looking statement. Investors should read the risk factors set forth in Rasna’s Form 10-K for the year ended September 30, 2016 and other periodic reports filed with the Securities and Exchange Commission.


Lagana A.,University of Perugia | Rampino S.,CNR Institute of Molecular Science and Technologies
Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics) | Year: 2014

The capability of the so called Grid Empowered Molecular Simulator GEMS of enabling fully ab initio virtual experiments (based on rigorous theoretical and computational procedures) has allowed us to parallel crossed beam experimental measurements with values obtained from first principles with no intermediation of empirical models. In this way a quantitative reproduction of the decrease with collision energy of the measured reactive integral cross section of the Li + HF fluorine exchange process for energy values lower than 0.1 eV was obtained. This quantitatively confirmed the outcomes of previous approximate quantum calculations performed on an ab initio potential energy surface fitted to a polynomial in bond order coordinates while disagreeing with the previous outcomes of quantum calculations performed on a different ab initio fitted potential energy surface. © 2014 Springer International Publishing.


Cappelletti D.,University of Perugia | Ronca E.,University of Perugia | Belpassi L.,CNR Institute of Molecular Science and Technologies | Tarantelli F.,University of Perugia | And 2 more authors.
Accounts of Chemical Research | Year: 2012

An understanding of the interactions involving water and other small hydrogenated molecules such as H2S and NH3 at the molecular level is an important and elusive scientific goal with potential implications for fields ranging from biochemistry to astrochemistry. One longstanding question about water's intermolecular interactions, and notably hydrogen bonding, is the extent and importance of charge transfer (CT), which can have important implications for the development of reliable model potentials for water chemistry, among other applications.The weakly bound adducts, commonly regarded as pure van der Waals systems, formed by H2O, H2S, and NH3 with noble gases or simple molecules such as H2, provide an interesting case study for these interactions. Their binding energies are approximately 1 or 2 kJ/mol at most, and CT effects in these systems are thought to be negligible. Our laboratory has performed high-resolution molecular-beam scattering experiments that probe the (absolute scale) intermolecular potential of various types of these gas-phase binary complexes with extreme sensitivity. These experiments have yielded surprising and intriguing quantitative results. The key experimental measurable is the "glory" quantum interference shift that shows a systematic, anomalous energy stabilization for the water complexes and clearly points to a significant role for CT effects.To investigate these findings, we have performed very accurate theoretical calculations and devised a simple approach to study the electron displacement that accompanies gas-phase binary intermolecular interactions in extreme detail. These calculations are based on a partial progressive integration of the electron density changes. The results unambiguously show that water's intermolecular interactions are not typical van der Waals complexes. Instead, these interactions possess a definite, strongly stereospecific CT component, even when very weak, where a water molecule may act as electron donor or acceptor depending on its orientation. CT is mediated by an asymmetric role played by the two hydrogen atoms, which causes strong orientation effects. The careful comparison of these calculations with the experimental results shows that the stabilization energy associated to CT is approximately 2-3 eV per electron transferred and may make up for a large portion of the total interaction energy. A simple electron delocalization model helps to validate and explain these findings. © 2012 American Chemical Society.


Donnadio A.,CNR Institute on Membrane Technology | Casciola M.,University of Perugia | Di Vona M.L.,University of Rome Tor Vergata | Tamilvanan M.,University of Rome Tor Vergata
Journal of Power Sources | Year: 2012

Proton conductivity and hydration of sulfonated polyethersulfone (SPES) membranes, with ion exchange capacity of 1.31 meq g -1, is determined under different conditions of temperature, in the range 70-120 °C, and relative humidity (RH) in the range 50-90%. Conductivity measurements are performed by the impedance technique, and the impedance data are analyzed on the basis of a simple equivalent circuit in order to compare the evolution of the membrane conductivity with that of the electrical capacitance of the electrode-electrolyte interface during heating and cooling runs. Temperature cycling at constant RH, as well as RH cycling at constant temperature, give rise to hydration hysteresis and to the concomitant conductivity hysteresis. The highest conductivity (4.5·10 -2 S cm -1) is measured at 100 °C-90% RH with 8.4 water molecules per sulfonic group. The hysteresis associated with temperature cycling is avoided by filling SPES with zirconium phosphate which makes hydration easier at low temperature. © 2012 Elsevier B.V. All rights reserved.


Ciancaleoni G.,CNR Institute of Molecular Science and Technologies | Belpassi L.,CNR Institute of Molecular Science and Technologies | Tarantelli F.,University of Perugia | Zuccaccia D.,University of Udine | MacChioni A.,University of Perugia
Dalton Transactions | Year: 2013

The interionic structure of four gold(i) π-alkyne ion pairs, with general formula [(PR1 2R2)Au(η2- 3-hexyne)]BF4 (R1 = R2 = tBu, 1a; R1 = tBu, R2 = o-diphenyl, 2a; R1 = R2 = 2,4,6-trimethoxyphenyl, 3a; R1 = R2 = 2,4-di-tert-butylphenoxy, 4a), was studied by 19F, 1H-HOESY NMR spectroscopy. In all the cases the anion locates mainly close to the alkyne, but the degree of specificity of location strongly depends on the P-ligand and it is high for ion pairs bearing poorly electron donating PR1 2R2 ligands (particularly, 4a) and low for ion pairs with strongly electron donating PR1 2R 2 ones (such as 3a). This result is rationalized through relativistic DFT calculations, showing that the electronic properties of the P-ligand finely tune the charge accumulation on the alkyne and, consequently, its ability of attracting the anion. This journal is © 2013 The Royal Society of Chemistry.


Agnelli G.,University of Perugia | Cohen A.,King's College | Curto M.,Pfizer | Gallus A.S.,Flinders University | And 4 more authors.
New England Journal of Medicine | Year: 2013

BACKGROUND: Apixaban, an oral factor Xa inhibitor that can be administered in a simple, fixed-dose regimen, may be an option for the extended treatment of venous thromboembolism. METHODS: In this randomized, double-blind study, we compared two doses of apixaban (2.5 mg and 5 mg, twice daily) with placebo in patients with venous thromboembolism who had completed 6 to 12 months of anticoagulation therapy and for whom there was clinical equipoise regarding the continuation or cessation of anticoagulation therapy. The study drugs were administered for 12 months. RESULTS: A total of 2486 patients underwent randomization, of whom 2482 were included in the intention-to-treat analyses. Symptomatic recurrent venous thromboembolism or death from venous thromboembolism occurred in 73 of the 829 patients (8.8%) who were receiving placebo, as compared with 14 of the 840 patients (1.7%) who were receiving 2.5 mg of apixaban (a difference of 7.2 percentage points; 95% confidence interval [CI], 5.0 to 9.3) and 14 of the 813 patients (1.7%) who were receiving 5 mg of apixaban (a difference of 7.0 percentage points; 95% CI, 4.9 to 9.1) (P<0.001 for both comparisons). The rates of major bleeding were 0.5% in the placebo group, 0.2% in the 2.5-mg apixaban group, and 0.1% in the 5-mg apixaban group. The rates of clinically relevant nonmajor bleeding were 2.3% in the placebo group, 3.0% in the 2.5-mg apixaban group, and 4.2% in the 5-mg apixaban group. The rate of death from any cause was 1.7% in the placebo group, as compared with 0.8% in the 2.5-mg apixaban group and 0.5% in the 5-mg apixaban group. CONCLUSIONS: Extended anticoagulation with apixaban at either a treatment dose (5 mg) or a thromboprophylactic dose (2.5 mg) reduced the risk of recurrent venous thromboembolism without increasing the rate of major bleeding. (Funded by Bristol-Myers Squibb and Pfizer; AMPLIFY-EXT ClinicalTrials.gov number, NCT00633893.) Copyright © 2012 Massachusetts Medical Society.


Bolli G.B.,University of Perugia | Owens D.R.,University of Swansea
Diabetes, Obesity and Metabolism | Year: 2014

Recent advances in therapies for the treatment of type 2 diabetes mellitus (T2DM) have led to the development of glucagon-like peptide-1 receptor agonists (GLP-1 RAs), which, unlike insulin and sulphonylurea, are effective, with a low risk of hypoglycaemia. Lixisenatide is recommended as a once-daily GLP-1 RA for the treatment of T2DM. In persons with T2DM, lixisenatide 20μg once-daily given by bolus subcutaneous injection improves insulin secretion and suppresses glucagon secretion in a glucose-dependent manner. Compared with the longer-acting GLP-1 RA liraglutide, lixisenatide achieved a significantly greater reduction in postprandial plasma glucose (PPG) during a standardized test breakfast in persons with T2DM otherwise insufficiently controlled on metformin alone. This is primarily due to the greater inhibition of gastric motility by lixisenatide compared with liraglutide. The efficacy and safety of lixisenatide was evaluated across a spectrum of T2DM in a series of phase III, randomized, placebo-controlled trials known as the GetGoal programme. Lixisenatide monotherapy or as add-on to oral antidiabetic agents or basal insulin achieved significant reductions in glycated haemoglobin, PPG and fasting plasma glucose, with either weight loss or no weight gain. The most frequent adverse events were gastrointestinal and transient in nature. Lixisenatide provides an easy, once-daily, single-dose, add-on treatment to oral antidiabetic agents or basal insulin for the management of T2DM, with little or no increased risk of hypoglycaemia and a potential beneficial effect on body weight. © 2013 John Wiley & Sons Ltd.


Ronca E.,CNR Institute of Molecular Science and Technologies | Ronca E.,University of Perugia | Pastore M.,CNR Institute of Molecular Science and Technologies | Belpassi L.,CNR Institute of Molecular Science and Technologies | And 3 more authors.
Energy and Environmental Science | Year: 2013

We report a thorough theoretical and computational investigation of the effect of dye adsorption on the TiO2 conduction band energy in dye-sensitized solar cells that is aimed at assessing the origin of the shifts induced by surface adsorbed species in the position of the TiO2 conduction band. We thus investigate a series of working dye sensitizers and prototypical surface adsorbers and apply an innovative approach to disentangle electrostatic and charge-transfer effects occurring at the crucial dye-TiO 2 interface. We clearly demonstrate that an extensive charge rearrangement accompanies the dye-TiO2 interaction, which amounts to transfer of up to 0.3-0.4 electrons from the dyes bound in a dissociative mode to the semiconductor. Molecular monodentate adsorption leads to a much smaller CT. We also find that the amount of CT is modulated by the dye donor groups, with the coumarin dyes showing a stronger CT. A subtle modulation of the semiconductor conduction band edge energy is found by varying the nature of the dye, in line with the experimental data from the literature obtained by capacitance and open circuit voltage measurements. We then decompose the total conduction band shift into contributions directly related to the sensitizer properties, considering the effect of the electric field generated by the dye on the semiconductor conduction band. This effect, which amounts to ca. 40% of the total shift, shows a linear correlation with the TiO2 conduction band shifts. A direct correlation between the dye dipole and the observed conduction band shift is retrieved only for dyes of similar structure and dimensions. We finally found a near-exact proportionality between the amount of charge transfer and the residual contribution to the conduction band shift, which may be as large as 60% of the total shift. The present findings constitute the basis for obtaining a deeper understanding of the crucial interactions taking place at the dye-semiconductor interface, and establish new design rules for dyes with improved DSC functionality. © The Royal Society of Chemistry 2013.


Nunzi F.,CNR Institute of Molecular Science and Technologies | Nunzi F.,University of Perugia | Mosconi E.,CNR Institute of Molecular Science and Technologies | Storchi L.,University of Chieti Pescara | And 5 more authors.
Energy and Environmental Science | Year: 2013

We report a quantum mechanical investigation on the nature of electronic trap states in realistic models of individual and sintered anatase TiO 2 nanocrystals (NCs) of ca. 3 nm diameter. We find unoccupied electronic states of lowest energy to be localized within the central part of the NCs, and to originate from under-coordinated surface Ti atoms lying mainly at the edges between the (100) and (101) facets. These localized states are found at about 0.3-0.4 eV below the fully delocalized conduction band states, in good agreement with both electrochemical and spectro-electrochemical results. The overall Density-Of-States (DOS) below the conduction band (CB) can be accurately fitted to an exponential distribution of states, in agreement with capacitance data. Water molecules adsorbed on the NC surface raise the energy and reduce the number of localized states, thus modifying the DOS. As a possible origin of additional trap states, we further investigated the oriented attachment of two TiO2 NCs at various possible interfaces. For the considered models, we found only minor differences between the DOS of two interacting NCs and those of the individual constituent NCs. Our results point at the presence of inherent trap states even in perfectly stoichiometric and crystalline TiO2 NCs due to the unavoidable presence of under-coordinated surface Ti(iv) ions at the (100) facets. This journal is © The Royal Society of Chemistry 2013.


Angelini T.,University of Perugia | Lanari D.,University of Perugia | Pizzo F.,University of Perugia | Vaccaro L.,University of Perugia
Advanced Synthesis and Catalysis | Year: 2012

Novel solid fluorides were prepared to optimize the β-azidation of α,β-unsaturated ketones. The higher loading of these catalysts compared to that of commercially available fluorides has allowed the use of a smaller mass of catalyst helping the mixing of the reaction mixture. Porous polymeric supports have proved to be more efficient in the presence of water as reaction medium. Water has played a crucial role showing a beneficial effect on the reactivity by improving dispersion of the reaction mixture and also by avoiding organic fouling caused by the retention of the reaction mixture within the polymeric matrix. This has facilitated the recovery of the products from the catalyst. The protocol reported has allowed a significant reduction in the organic solvent required for the complete recovery of the pure product whilst leaving the catalyst clean and reusable. E-factors are in the range of 5.9-10.5 and therefore ca. 3 times smaller than previous procedures operating under solvent-free conditions. To further improve the efficiency of our approach we have developed a protocol operating in a continuous-flow manner that has allowed us to achieve an E-factor of 1.7-1.9, with a reduction of ca. 80% of the corresponding batch conditions. The continuous-flow protocol has allowed us to minimize the use of trimethylsilyl azide making the recovery and reuse of water and catalyst 5f very efficient and simple. Finally, a novel reduction system using palladium on alumina (5 mol%) and equimolar amount of formic acid has been used in the presence of 1 equivalent of di-tert-butyl pyrocarbonate to set a multistep protocol operating in continuous-flow conditions for the preparation of two representative N-Boc-β-amino ketones starting from the corresponding enones with E-factors of 3.2 and 2.7, respectively. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Tombesi S.,University of Perugia | Johnson R.S.,University of California at Davis | Day K.R.,University of California at Davis | Dejong T.M.,University of California at Davis
Annals of Botany | Year: 2010

Background and Aims Previous studies indicate that the size-controlling capacity of peach rootstocks is associated with reductions of scion water potential during mid-day that are caused by the reduced hydraulic conductance of the rootstock. Thus, shoot growth appears to be reduced by decreases in stem water potential. The aim of this study was to investigate the mechanism of reduced hydraulic conductance in size-controlling peach rootstocks. Methods Anatomical measurements (diameter and frequency) of xylem vessels were determined in shoots, trunks and roots of three contrasting peach rootstocks grown as trees, each with different size-controlling characteristics: 'Nemaguard' (vigorous), 'P30-135' (intermediate vigour) and 'K146-43' (substantially dwarfing). Based on anatomical measurements, the theoretical axial xylem conductance of each tissue type and rootstock genotype was calculated via the Poiseuille-Hagen law. Key Results Larger vessel dimensions were found in the vigorous rootstock ('Nemaguard') than in the most dwarfing one ('K146-43') whereas vessels of 'P30-135' had intermediate dimensions. The density of vessels per xylem area in 'Nemaguard' was also less than in 'P30-135'and 'K146-43'. These characteristics resulted in different estimated hydraulic conductance among rootstocks: 'Nemaguard' had higher theoretical values followed by 'P30-135' and 'K146-43'.Conclusions These data indicate that phenotypic differences in xylem anatomical characteristics of rootstock genotypes appear to influence hydraulic conductance capacity directly, and therefore may be the main determinant of dwarfing in these peach rootstocks.


Rocchigiani L.,University of Perugia | Jia M.,University of Bologna | Bandini M.,University of Bologna | Macchioni A.,University of Perugia | Macchioni A.,CNR Institute of Molecular Science and Technologies
ACS Catalysis | Year: 2015

The counterion effect in the gold(I)-catalyzed dearomative condensation of indoles with allenamides is unveiled by means of 1D- and 2D-NMR investigation. The different coordination ability and hydrogen bonding tendency of TFA- and OTf- led to specific interactions with the reaction partners dictating the regiodivergent outcome. © 2015 American Chemical Society.


Masseria C.,LSE Health | Giannoni M.,University of Perugia
European Journal of Public Health | Year: 2010

Background: Equitable access to health care is a core objective of the Italian health care system. Despite having achieved universal coverage for a fairly comprehensive set of health services for decades, there is still evidence of inequities systematically associated with income. Method: Income-related inequity indices were estimated for the probability of general practitioner (GP), specialist, inpatient care and also emergency care using a variety of need indicators. The data used were the Multiscopo survey, 2000 matched with the European Community Household Panel survey for Italy. The contribution of regional inequality was also estimated. Horizontal inequity indices for health care utilization measures were computed separately for people reporting hypertension, arthritis, tumour and heart disease. Results: Significant pro-rich income related inequity was found for GP, specialist and emergency care, no inequity was found for inpatient care. The disease approach showed statistically significant inequity in the probability of specialist care in three of the four chronic conditions analysed, and pro-poor inequity in GP care for all conditions. Inequity was mainly caused by income and regional variations. Conclusions: By reducing regional variation it would be possible to significantly reduce the pro-rich inequity in GP, specialist and emergency care. For specialist care inequity was found for the overall adult population and also among people with serious chronic conditions, and was caused not only by income and regional variation, but also by educational attainment and insurance. © The Author 2009. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.


Amat A.,CNR Institute of Molecular Science and Technologies | Mosconi E.,CNR Institute of Molecular Science and Technologies | Ronca E.,CNR Institute of Molecular Science and Technologies | Ronca E.,University of Perugia | And 6 more authors.
Nano Letters | Year: 2014

Organohalide lead perovskites have revolutionized the scenario of emerging photovoltaic technologies. The prototype MAPbI3 perovskite (MA = CH3NH3+) has dominated the field, despite only harvesting photons above 750 nm (∼1.6 eV). Intensive research efforts are being devoted to find new perovskites with red-shifted absorption onset, along with good charge transport properties. Recently, a new perovskite based on the formamidinium cation ((NH2)2CH+ = FA) has shown potentially superior properties in terms of band gap and charge transport compared to MAPbI3. The results have been interpreted in terms of the cation size, with the larger FA cation expectedly delivering reduced band-gaps in Pb-based perovskites. To provide a full understanding of the interplay among size, structure, and organic/inorganic interactions in determining the properties of APbI3 perovskites, in view of designing new materials and fully exploiting them for solar cells applications, we report a fully first-principles investigation on APbI3 perovskites with A = Cs +, MA, and FA. Our results evidence that the tetragonal-to-quasi cubic structural evolution observed when moving from MA to FA is due to the interplay of size effects and enhanced hydrogen bonding between the FA cations and the inorganic matrix altering the covalent/ionic character of Pb-I bonds. Most notably, the observed cation-induced structural variability promotes markedly different electronic and optical properties in the MAPbI3 and FAPbI3 perovskites, mediated by the different spin-orbit coupling, leading to improved charge transport and red-shifted absorption in FAPbI3 and in general in pseudocubic structures. Our theoretical model constitutes the basis for the rationale design of new and more efficient organohalide perovskites for solar cells applications. © 2014 American Chemical Society.


Bistoni G.,CNR Institute of Molecular Science and Technologies | Bistoni G.,University of Perugia | Belpassi L.,CNR Institute of Molecular Science and Technologies | Tarantelli F.,CNR Institute of Molecular Science and Technologies | Tarantelli F.,University of Perugia
Angewandte Chemie - International Edition | Year: 2013

A charge-displacement analysis of gold-ethyne complexes shows the existence of a quantitative relationship between measurable properties and the chemical bond constituents in the Dewar-Chatt-Duncanson model. Through suitable experiments, these constituents may be disentangled and crucial insight into the nature of coordination bonds may thus be gained. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Rosi F.,CNR Institute of Molecular Science and Technologies | Miliani C.,CNR Institute of Molecular Science and Technologies | Braun R.,Bruker | Harig R.,Bruker | And 3 more authors.
Angewandte Chemie - International Edition | Year: 2013

Cultural detective work: Remote hyperspectral imaging in the mid-infrared region enables the identification and localization of the painting materials used by artists (see brightness temperature difference image overlayed with the corresponding portion of the painting Sestante 10 by Alberto Burri and IR reflection spectra for this area). The resulting molecular images are thus of great value for art conservation. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Balucani C.,University of Perugia | Balucani C.,SUNY Downstate Medical Center | Viticchi G.,Marche Polytechnic University | Falsetti L.,Internal and Subintensive Medicine | Silvestrini M.,Marche Polytechnic University
Neurology | Year: 2012

Objectives: To evaluate cognitive performance in subjects with bilateral asymptomatic carotid stenosis (B-ACS) compared to subjects with unilateral ACS and to subjects with no carotid stenosis (CS) and to explore the relationship between cognitive performance and cerebral hemodynamics status in B-ACS. Methods: The neuropsychological investigation included phonemic (ph) and categorical (ca) Verbal Fluency (VF) tests for exploring the left brain functions and Colored Progressive Matrices (CPM) and Complex Figure Copy Test (CFCT) for the right brain. Cerebral hemodynamics status was assessed using the transcranial Doppler-based breath-holding index test. Results: A total of 333 subjects were included: 127 B-ACS, 73/77 left/right unilateral ACS, 56 no CS, mean age 70 ± 3.78 years, 65% male. Subjects with B-ACS and subjects with unilateral ACS showed significantly lower scores in all cognitive tests compared to subjects with no CS (p < 0.05). Subjects with B-ACS with left impaired hemodynamics status showed a significantly reduced ph-VF score, from 13.4 (95% confidence interval [CI] 11.2-15.8) to 7.5 (95% CI 5.4-9.7), and a reduced ca-VF score, from 19.7 (95% CI 18.1-24.1) to 10.8 (95% CI 9.5-15.1), compared to subjects with no CS. Similarly, impaired cerebral hemodynamics in the right side was associated with a significantly reduced CPM score, from an estimated mean of 34.2 (95% CI 29.8-35.4) to 24.6 (95% CI 20.2-25.8), and CFCT score from 37.0 (95% CI 32.0-37.4) to 27.1 (95% CI 23.3-28.7). All comparisons were p < 0.05. Conclusion: Subjects with B-ACS and subjects with unilateral ACS are more likely to have cognitive dysfunction compared to subjects with no CS. There appears to be a link between cognitive dysfunction and hemodynamics impairment due to carotid stenosis. Copyright © 2012 by AAN Enterprises, Inc.


Blesa J.,University of San Pablo - CEU | Trigo-Damas I.,University of San Pablo - CEU | Quiroga-Varela A.,University of Perugia | Jackson-Lewis V.R.,Columbia University
Frontiers in Neuroanatomy | Year: 2015

Parkinson disease (PD) is a chronic, progressive neurological disease that is associated with a loss of dopaminergic neurons in the substantia nigra pars compacta of the brain. The molecular mechanisms underlying the loss of these neurons still remain elusive. Oxidative stress is thought to play an important role in dopaminergic neurotoxicity. Complex I deficiencies of the respiratory chain account for the majority of unfavorable neuronal degeneration in PD. Environmental factors, such as neurotoxins, pesticides, insecticides, dopamine (DA) itself, and genetic mutations in PD-associated proteins contribute to mitochondrial dysfunction which precedes reactive oxygen species formation. In this mini review, we give an update of the classical pathways involving these mechanisms of neurodegeneration, the biochemical and molecular events that mediate or regulate DA neuronal vulnerability, and the role of PD-related gene products in modulating cellular responses to oxidative stress in the course of the neurodegenerative process. © 2015 Blesa, Trigo-Damas, Quiroga-Varela and Jackson-Lewis.


Mosconi E.,CNR Institute of Molecular Science and Technologies | Yum J.-H.,Institution of Chemical science and Engineering | Kessler F.,Institution of Chemical science and Engineering | Gomez Garcia C.J.,University of Valencia | And 6 more authors.
Journal of the American Chemical Society | Year: 2012

We report a combined experimental and computational investigation to understand the nature of the interactions between cobalt redox mediators and TiO2 surfaces sensitized by ruthenium and organic dyes, and their impact on the performance of the corresponding dye-sensitized solar cells (DSSCs). We focus on different ruthenium dyes and fully organic dyes, to understand the dramatic loss of efficiency observed for the prototype Ru(II) N719 dye in conjunction with cobalt electrolytes. Both N719- and Z907-based DSSCs showed an increased lifetime in iodine-based electrolyte compared to the cobalt-based redox shuttle, while the organic D21L6 and D25L6 dyes, endowed with long alkoxy chains, show no significant change in the electron lifetime regardless of employed electrolyte and deliver a high photovoltaic efficiency of 6.5% with a cobalt electrolyte. Ab initio molecular dynamics simulations show the formation of a complex between the cobalt electrolyte and the surface-adsorbed ruthenium dye, which brings the [Co(bpy)3] 3+ species into contact with the TiO2 surface. This translates into a high probability of intercepting TiO2-injected electrons by the oxidized [Co(bpy)3]3+ species, lying close to the N719-sensitized TiO2 surface. Investigation of the dye regeneration mechanism by the cobalt electrolyte in the Marcus theory framework led to substantially different reorganization energies for the high-spin (HS) and low-spin (LS) reaction pathways. Our calculated reorganization energies for the LS pathways are in excellent agreement with recent data for a series of cobalt complexes, lending support to the proposed regeneration pathway. Finally, we systematically investigate a series of Co(II)/Co(III) complexes to gauge the impact of ligand substitution and of metal coordination (tris-bidentate vs bis-tridentate) on the HS/LS energy difference and reorganization energies. Our results allow us to trace structure/property relations required for further development of cobalt electrolytes for DSSCs. © 2012 American Chemical Society.


Zuccaccia D.,University of Udine | Belpassi L.,CNR Institute of Molecular Science and Technologies | Macchioni A.,University of Perugia | Tarantelli F.,University of Perugia
European Journal of Inorganic Chemistry | Year: 2013

We critically review recent experimental and theoretical investigations into some key aspects of the chemistry of gold(I) complexes of the type [L-Au-S]+X- (L = NHC carbenes and phosphanes, S = alkenes and alkynes, and X- = weakly coordinating counterion). These systems are important intermediates formed during gold-catalyzed nucleophilic additions to an unsaturated substrate, and their specific activity is largely governed by two fundamental factors: the nature of the gold-substrate bond and the role of the ion-pair structure in solution. Both are crucially influenced by the nature and properties of the auxiliary ligand L, and on this interplay we focus our discussion. The relative anion-cation orientation, investigated by NOE NMR spectroscopy and DFT calculations, shows that the exact position of the counterion is determined by the natures of the ancillary ligand and substrate: the counterion is located near the substrate in the phosphane complexes, while for the NHC complexes the preferred position of the counterion is near the ligand. This tunable interionic structure opens the way to greater control over the properties and activity of these catalysts. The bond between AuI and the unsaturated substrate is investigated using an original and powerful theoretical method of analysis. Our approach permits a rigorous definition and assessment of the charge-displacement (CD) components at the heart of the Dewar-Chatt-Duncanson model: substrate-to-metal (σ donation) and metal-to-substrate (π back-donation) and how these change with different ligands. The results consistently reveal that π back-donation is a large and crucially important component of the AuI-substrate bond in all systems: π back-donation penetrates the external side of coordinated alkynes, where nucleophile attack is directed, thus partially mitigating the electron depletion caused by σ donation. We review our results concerning the relative orientation of the anion and cation and the characterization of the carbon-gold bond in the first intermediates (L-Au-S)+X- (L = NHC carbenes and phosphanes, S = alkenes and alkynes, X- = weakly coordinating counterion) formed during nucleophilic attack on unsaturated systems. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Tombesi S.,University of Perugia | Almehdi A.,University of California at Davis | DeJong T.M.,University of California at Davis
Scientia Horticulturae | Year: 2011

In peach, xylem anatomical characteristics have been shown to be related to vigour of selected rootstocks. The goal of this research was to determine if xylem characteristics of a new set of rootstocks that exhibit a range of size-controlling potential and have a different genetic background from previously examined material would also exhibit similar differences in xylem characteristics. If so, then anatomical analysis of xylem may be a useful means of predicting the vigour control capacity of selected peach rootstock genotypes. Samples of xylem tissue were taken from roots, trunks and shoots of four new rootstocks that were derived from a genetic cross between 'Harrow Blood' and 'Okinawa' peaches and compared with tissue from 'Nemaguard', a vigorous control. Xylem samples were sectioned and analysed by optical microscope. The number and dimensions of vessels in recently developed xylem of each rootstock were measured and compared. The more dwarfing rootstocks had fewer large vessels and more small vessels than the more vigorous rootstocks. Weighted mean vessel diameter (Wm) and calculated hydraulic conductance (Kh) differed among rootstocks: more vigorous rootstocks had higher Kh and Wm than dwarfing rootstocks. Rootstock xylem vessel dimensions varied in relation to the vigour they imparted to a common scion cultivar ('O'Henry'). After the 'Nemaguard' control, 'HBOK 50' was the most vigorous rootstock followed by 'HBOK 10', 'HBOK 32' and 'HBOK 27', respectively. Thus, as was seen in previous research with a separate set of rootstocks, the vigour-control capacity of this new series of peach rootstocks was strongly related to their xylem hydraulic characteristics and it appears likely that it would be possible to use xylem anatomical characteristics of shoots or roots of young trees to pre-select for size-controlling potential in a rootstock development program. © 2010 Elsevier B.V.


Agnelli G.,University of Perugia | Cohen A.,King's College | Curto M.,Pfizer | Gallus A.S.,Flinders University | And 6 more authors.
New England Journal of Medicine | Year: 2013

BACKGROUND: Apixaban, an oral factor Xa inhibitor administered in fixed doses, may simplify the treatment of venous thromboembolism. METHODS: In this randomized, double-blind study, we compared apixaban (at a dose of 10 mg twice daily for 7 days, followed by 5 mg twice daily for 6 months) with conventional therapy (subcutaneous enoxaparin, followed by warfarin) in 5395 patients with acute venous thromboembolism. The primary efficacy outcome was recurrent symptomatic venous thromboembolism or death related to venous thromboembolism. The principal safety outcomes were major bleeding alone and major bleeding plus clinically relevant nonmajor bleeding. RESULTS: The primary efficacy outcome occurred in 59 of 2609 patients (2.3%) in the apixaban group, as compared with 71 of 2635 (2.7%) in the conventional-therapy group (relative risk, 0.84; 95% confidence interval [CI], 0.60 to 1.18; difference in risk [apixaban minus conventional therapy], -0.4 percentage points; 95% CI, -1.3 to 0.4). Apixaban was noninferior to conventional therapy (P<0.001) for predefined upper limits of the 95% confidence intervals for both relative risk (<1.80) and difference in risk (<3.5 percentage points). Major bleeding occurred in 0.6% of patients who received apixaban and in 1.8% of those who received conventional therapy (relative risk, 0.31; 95% CI, 0.17 to 0.55; P<0.001 for superiority). The composite outcome of major bleeding and clinically relevant nonmajor bleeding occurred in 4.3% of the patients in the apixaban group, as compared with 9.7% of those in the conventional-therapy group (relative risk, 0.44; 95% CI, 0.36 to 0.55; P<0.001). Rates of other adverse events were similar in the two groups. CONCLUSIONS: A fixed-dose regimen of apixaban alone was noninferior to conventional therapy for the treatment of acute venous thromboembolism and was associated with significantly less bleeding. Copyright © 2013 Massachusetts Medical Society.


Rosenstock J.,Dallas Diabetes and Endocrine Center | Balas B.,Hoffmann-La Roche | Charbonnel B.,University of Nantes | Bolli G.B.,University of Perugia | And 2 more authors.
Diabetes Care | Year: 2013

OBJECTIVEdTaspoglutide is a long-acting glucagon-like peptide 1 receptor agonist developed for treatment of type 2 diabetes. The efficacy and safety of once-weekly taspoglutide was compared with twice-daily exenatide. RESEARCH DESIGN AND METHODSdOverweight adults with inadequately controlled type 2 diabetes on metformin 6 a thiazolidinedione were randomized to subcutaneous taspoglutide 10 mg weekly (n = 399), taspoglutide 20 mg weekly (n = 398), or exenatide 10 mg twice daily (n = 392) in an open-label, multicenter trial. The primary end point was change in HbA1c after 24 weeks. RESULTSdMean baseline HbA1c was 8.1%. Both doses of taspoglutide reduced HbA1c significantly more than exenatide (taspoglutide 10 mg:-1.24%[SE 0.09], difference-0.26, 95%CI-0.37 to-0.15, P < 0.0001; taspoglutide 20 mg:-1.31% [0.08], difference-0.33,-0.44 to-0.22, P < 0.0001; exenatide:-0.98% [0.08]). Both taspoglutide doses reduced fasting plasma glucose significantly more than exenatide. Taspoglutide reduced body weight (taspoglutide 10 mg,-1.6 kg; taspoglutide 20 mg,-2.3 kg) as did exenatide (-2.3 kg), which was greater than with taspoglutide 10 mg (P < 0.05). HbA1c and weight effects were maintained after 52 weeks. More adverse eventswith taspoglutide 10 and 20mgthan exenatide developed over time (nausea in 53, 59, and 35% and vomiting in 33, 37, and 16%, respectively). Allergic and injection-site reactions were more common with taspoglutide. Discontinuations were greater with taspoglutide. Antitaspoglutide antibodies were detected in 49% of patients. CONCLUSIONSdOnce-weekly taspoglutide demonstrated greater glycemic control than twice-daily exenatide with comparable weight loss, but with unacceptable levels of nausea/vomiting, injection-site reactions, and systemic allergic reactions. Copyright © 2013 by the American Diabetes Association.


Mosconi E.,CNR Institute of Molecular Science and Technologies | Ronca E.,CNR Institute of Molecular Science and Technologies | Ronca E.,University of Perugia | De Angelis F.,CNR Institute of Molecular Science and Technologies
Journal of Physical Chemistry Letters | Year: 2014

We investigate the prototypical interface between organohalide perovskites and TiO2 by first-principles electronic structure calculations. The investigated heterointerface is representative of conventional dye-sensitized solar cells based on a mesoporous TiO2 scaffold and of flat devices in which a compact TiO2 film is used as electron selective layer. We find that the MAPbI3 and MAPbI3-xClx perovskites tend to grow in (110)-oriented films on TiO2, due to the better structural matching between rows of adjacent perovskite surface halides and TiO2 undercoordinated titanium atoms. Interfacial chlorine atoms further stabilize the (110) surface, due to an enhanced binding energy. We find that the stronger interaction of MAPbI3-xClx with TiO 2 modifies the interface electronic structure, leading to a stronger interfacial coupling and to a slight TiO2 conduction band energy upshift. Our modeling study may constitute the basis for a further exploitation of perovskite solar cells. © 2014 American Chemical Society.


Fantacci S.,CNR Institute of Molecular Science and Technologies | Ronca E.,CNR Institute of Molecular Science and Technologies | Ronca E.,University of Perugia | De Angelis F.,CNR Institute of Molecular Science and Technologies
Journal of Physical Chemistry Letters | Year: 2014

Relativistic TDDFT calculations have been performed employing a novel computational approach to evaluate the impact of spin-orbit coupling (SOC) in the optical and photovoltaic properties of panchromatic RuII dyes for dye-sensitized solar cells (DSCs). The employed computational setup accurately reproduces the optical properties of the investigated dyes, allowing an assessment of the factors responsible for the varying SOC with the dye metal-ligand environment. While for the prototypical panchromatic black dye sensitizer a negligible SOC effect is found, the SOC-induced spectral broadening calculated for the recently reported DX1 dye partly enhances the light-harvesting efficiency and consequently the photocurrent generation in DSCs based on this dye. © 2013 American Chemical Society.


Bolli G.B.,University of Perugia | Riddle M.C.,Oregon Health And Science University | Bergenstal R.M.,International Diabetes Center at Park Nicollet | Ziemen M.,Sanofi S.A. | And 3 more authors.
Diabetes, Obesity and Metabolism | Year: 2015

Aims: To compare the efficacy and safety of new insulin glargine 300U/ml (Gla-300) with that of glargine 100U/ml (Gla-100) in insulin-naïve people with type 2 diabetes using oral glucose-lowering drugs. Methods: The EDITION 3 study was a multicentre, open-label, parallel-group study. Participants were randomized to Gla-300 or Gla-100 once daily for 6months, discontinuing sulphonylureas and glinides, with a dose titration aimed at achieving pre-breakfast plasma glucose concentrations of 4.4-5.6mmol/l (80-100mg/dl). The primary endpoint was change in glycated haemoglobin (HbA1c) from baseline to month6. The main secondary endpoint was percentage of participants with ≥1 nocturnal confirmed [≤3.9mmol/l (≤70mg/dl)] or severe hypoglycaemia from week9 to month6. Other measures of glycaemia and hypoglycaemia, weight change and insulin dose were assessed. Results: Randomized participants (n=878) had a mean (standard deviation) age of 57.7 (10.1)years, diabetes duration 9.8 (6.4)years, body mass index 33.0 (6.7)kg/m2 and HbA1c 8.54 (1.06)% [69.8 (11.6)mmol/mol]. HbA1c levels decreased by equivalent amounts with the two treatments; the least squares mean difference in change from baseline was 0.04 [95% confidence interval (CI) -0.09 to 0.17]% or 0.4 (-1.0 to 1.9)mmol/mol. Numerically fewer participants reported ≥1 nocturnal confirmed (≤3.9mmol/l) or severe hypoglycaemia from week9 to month6 [relative risk (RR) 0.89 (95% CI 0.66 to 1.20)] with Gla-300 versus Gla-100; a significantly lower risk of hypoglycaemia with this definition was found over the 6-month treatment period [RR 0.76 (95% CI 0.59 to 0.99)]. No between-treatment differences in adverse events were identified. Conclusions: Gla-300 is as effective as Gla-100 in reducing HbA1c in insulin-naïve people with type 2 diabetes, with lower hypoglycaemia risk. © 2015 The Authors.


Ronca E.,CNR Institute of Molecular Science and Technologies | Ronca E.,University of Perugia | De Angelis F.,CNR Institute of Molecular Science and Technologies | Fantacci S.,CNR Institute of Molecular Science and Technologies
Journal of Physical Chemistry C | Year: 2014

We report on the relevance of spin-orbit coupling on the optical properties of Ru(II)- and Os(II)-polypyridyl dyes effectively employed in dye-sensitized solar cells (DSCs). We include relativistic effects on time-dependent density functional theory calculations of selected complexes by using different levels of calculations, i.e., the scalar zero-order regular approximation (ZORA) and the fully relativistic ZORA including spin-orbit coupling, in such a way so as to disentangle and evaluate the spin-orbit effect. The widely investigated [M(bpy)3]2+ (M = Ru(II) and Os(II)) have been selected as benchmark complexes in our calculations; this is followed by investigation of "realistic" dyes used in DSCs, such as the prototypical N3 dye, its Os-based analogue, and a panchromatic Os(II) dye. We find that in Ru(II) complexes, spin-orbit coupling leads to a slight correction of the spectral shape, whereas only when we include the spin-orbit coupling we are able to reproduce the low-energy absorption bands characteristic of the Os(II) complexes. This study allows us to find a quantitative correlation between the strength of spin-orbit coupling and the metal center, highlighting the secondary effect of the different ligands experienced by the metal center. © 2014 American Chemical Society.


Owens D.R.,University of Swansea | Monnier L.,Montpellier University | Bolli G.B.,University of Perugia
Diabetes and Metabolism | Year: 2013

Metabolic consequences of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are the result of enhanced glucose-stimulated insulin secretion, inhibition of glucagon release, delayed gastric emptying and increased satiety. These attributes make GLP-1 agonists a treatment option in type 2 diabetes mellitus (T2DM). To optimise treatment choice, a detailed understanding of the effects of GLP-1 RAs on glucose homeostasis in individuals with T2DM is necessary. Although the various GLP-1 RAs share the same basic mechanisms of action, differences in pharmacokinetic/pharmacodynamic characteristics translate into differential effects on parameters of glycaemia. Head-to-head comparisons between long-acting non-prandial (liraglutide once daily and exenatide once weekly) and shorter-acting prandial (exenatide twice daily and lixisenatide once daily prandial) GLP-1 RAs confirm their differential effects on fasting plasma glucose (FPG) and post-prandial glucose (PPG). Liraglutide once daily and exenatide once weekly demonstrate greater reductions in FPG but lesser impacts on PPG excursions plasma than exenatide twice daily. Prandial GLP-1 RAs have a profound effect on post-prandial glycaemia, mediated by delaying gastric emptying, which is not subject to the tachyphylaxis occurring due to the sustained elevated plasma GLP-1 concentrations after treatment with long-acting GLP-1 RAs. Lixisenatide once-daily prandial, in contrast to liraglutide, strongly suppresses post-prandial glucagon secretion, further contributing to the more pronounced PPG-lowering effect found with lixisenatide. Evidence suggests that the GLP-1 RAs that predominantly target the prandial glucose excursions, such as exenatide twice daily and lixisenatide once-daily prandial, are therefore best used as combination therapy with basal insulin and will form an important new treatment option for individuals with T2DM. © 2013.


Rampino S.,CNR Institute of Molecular Science and Technologies | Belpassi L.,CNR Institute of Molecular Science and Technologies | Tarantelli F.,University of Perugia | Storchi L.,University of Chieti Pescara
Journal of Chemical Theory and Computation | Year: 2014

A full distributed-memory implementation of the Dirac-Kohn-Sham (DKS) module of the program BERTHA (Belpassi et al., Phys. Chem. Chem. Phys. 2011, 13, 12368-12394) is presented, where the self-consistent field (SCF) procedure is replicated on all the parallel processes, each process working on subsets of the global matrices. The key feature of the implementation is an efficient procedure for switching between two matrix distribution schemes, one (integral-driven) optimal for the parallel computation of the matrix elements and another (block-cyclic) optimal for the parallel linear algebra operations. This approach, making both CPU-time and memory scalable with the number of processors used, virtually overcomes at once both time and memory barriers associated with DKS calculations. Performance, portability, and numerical stability of the code are illustrated on the basis of test calculations on three gold clusters of increasing size, an organometallic compound, and a perovskite model. The calculations are performed on a Beowulf and a BlueGene/Q system. © 2014 American Chemical Society.


Cartechini L.,CNR Institute of Molecular Science and Technologies | Vagnini M.,CNR Institute of Molecular Science and Technologies | Palmieri M.,CNR Institute of Molecular Science and Technologies | Pitzurra L.,University of Perugia | And 3 more authors.
Accounts of Chemical Research | Year: 2010

Diagnostic immunology is a powerful tool, widely used in clinical and biochemical laboratories for detecting molecules. In recent years, the technique has been adaptated to materials sciences as a result of the extensive advances achieved in immunology. Today, many companies supply custom antibodies as well as new high-performance bioprobes for virtually any use. The idea of using immunodetection in the field of conservation science is not new. This analytical methodology is, in fact, particularly attractive for investigating biopolymers in painting materials; it is highly sensitive and selective with respect to the biological source of the target molecules. Among biopolymers, proteins have been widely used in the past as painting binders, adhesives, and additives in coating layers. An accurate assessment of these materials is necessary to obtain deeper insights into an artists technique as well as to design proper restoration and conservation methods. In spite of the diagnostic potential offered by immunodetection-based techniques, some analytical drawbacks had, until recently, limited their use in routine applications in conservation science. In this Account, we highlight the most important results achieved in our research on the development of analytical methodologies based on the use of enzyme-linked immunosorbent assay (ELISA) and immuno-fluorescence microscopy (IFM) techniques for the highly sensitive and specific identification of proteins in artistic and archeological materials. ELISA and IFM offer two alternative analytical routes to this final goal: ELISA provides a fast, cost-effective, quantitative analysis of microsamples put in solution, whereas IFM combines the immunodetection of the targeted molecules with the characterization of their spatial distribution. The latter approach is of great value in the stratigraphic investigation of paintings. We discuss the limits and strengths of these methodologies in the context of the complex matrixes usually found in the investigated materials and the prolonged aging that they have undergone. Immunology is a relatively new technique in conservation science, providing a rich new field for innovation. We see two areas that are particularly ripe for future contributions. The commercial manufacture of antibodies specifically tailored for use in cultural heritage studies holds enormous potential. Moreover, the need for further refinement of detection systems in immuno-fluorescence techniques, especially the suppression of the autofluorescence background in painting materials, offers an abundance of opportunities for researchers. Immunology is a relatively new technique in conservation science, providing a rich new field for innovation. © 2010 American Chemical Society.


Ciancaleoni G.,CNR Institute of Molecular Science and Technologies | Rampino S.,CNR Institute of Molecular Science and Technologies | Zuccaccia D.,University of Udine | Tarantelli F.,University of Perugia | And 2 more authors.
Journal of Chemical Theory and Computation | Year: 2014

High level ab initio calculations have been carried out on an archetypal gold(I)-catalyzed reaction: hydroamination of ethyne. We studied up to 12 structures of possible gold(I)-coordinated species modeling different intermediates potentially present in a catalytic cycle for the addition of a protic nucleophile to an alkyne. The benchmark is used to evaluate the performances of some popular density functionals for describing geometries and relative energies of stationary points along the reaction profile. Most functionals (including hybrid or meta-hybrid) give accurate structures but large nonsystematic errors (4-12 kcal/mol) along the reaction energy profile. The double hybrid functional B2PLYP outperforms all considered functionals and compares very nicely with our reference ab initio benchmark energies. Moreover, we present an assessment of the accuracy of commonly used approaches to include relativistic effects, such as relativistic effective potentials and a scalar ZORA Hamiltonian, by a comparison with the results obtained using a relativistic all-electron four-component Dirac-Kohn-Sham method. The contribution of nonscalar relativistic effects in gold(I)-catalyzed reactions, as we investigated here, is expected to be on the order of 1 kcal/mol. © 2014 American Chemical Society.


Falorni A.,Section of Internal Medicine and Endocrine and Metabolic science | Minarelli V.,Section of Internal Medicine and Endocrine and Metabolic science | Bartoloni E.,University of Perugia | Alunno A.,University of Perugia | Gerli R.,University of Perugia
Autoimmunity Reviews | Year: 2014

Autoimmmune hypophysitis (AH) is the consequence of an immune-mediated inflammation of the pituitary gland. The initial pituitary enlargement, secondary to infiltration and oedema, can evolve to remission, for spontaneous or pharmacological resolution of the inflammation, or evolve to progressive diffuse destruction with gland atrophy for fibrotic replacement, thus leading to various degrees of pituitary dysfunction. The autoimmune process against the pituitary gland is made evident by the appearance of circulating autoantibodies (APA), mainly detected by indirect immunofluorescence on cryostatic sections of human or primate pituitary. Among the target autoantigens recognized by APA are alpha-enolase, gamma-enolase, the pituitary gland specific factors (PGSF) 1 and 2 and corticotroph-specific transcription factor (TPIT). However, the low diagnostic sensitivity and specificity of APA for AH strongly limit the clinical use of this marker. AH should be considered in the differential diagnosis of non-secreting space-occupying lesions of sella turcica, to avoid misdiagnosis that may lead to an aggressive surgery approach, since endocrine dysfunction and the compressive effect may be transient. © 2014 Elsevier B.V.


Guandalini R.,University of Hertfordshire | Guandalini R.,University of Perugia | Cristallo S.,National institute for astrophysics
Astronomy and Astrophysics | Year: 2013

Context. Stars evolving along the asymptotic giant branch can become carbon-rich in the final part of their evolution. They replenish the inter-stellar medium with nuclear processed material via strong radiative stellar winds. The determination of the luminosity function of these stars, even if far from being conclusive, is extremely important for testing the reliability of theoretical models. In particular, strong constraints on the mixing treatment and the mass-loss rate can be derived. Aims. We present an updated luminosity function of Galactic carbon stars (LFGCS) obtained from a re-analysis of available data already published in previous papers. Methods. Starting from available near-and mid-infrared photometric data, we re-determined the selection criteria. Moreover, we took advantage of updated distance estimates and period-luminosity relations and we adopted a new formulation for the computation of bolometric corrections (BCs). This led us to collect an improved sample of carbon-rich sources from which we constructed an updated luminosity function. Results. The LFGCS peaks at magnitudes around-4.9, confirming the results obtained in a previous work. Nevertheless, the luminosity function presents two symmetrical tails instead of the larger high-luminosity tail characterizing the former luminosity function. Conclusions. The derived LFCGS matches the indications from recent theoretical evolutionary asymptotic giant branch models, thus confirming the validity of the choices of mixing treatment and mass-loss history. Moreover, we compare our new luminosity function with its counterpart in the Large Magellanic Cloud finding that the two distributions are very similar for dust-enshrouded sources, as expected from stellar evolutionary models. Finally, we derive a new fitting formula aimed to better determine BCs for C-stars. © 2013 ESO.


Milano F.,University of Perugia
Methods in Molecular Biology | Year: 2014

Dendritic cells (DC) are unique antigen-presenting cells that initiate and orchestrate adaptive immunity. Theoretically, cancer cells that express tumor-specific antigens can be destroyed by cytotoxic T cells. However, inherent antitumor responses are often not efficient, since tumor cells can mask their antigens and do not activate DC, an event required for the development of tumor antigen-specific cytotoxic T cell responses. Over a decade ago, the ex vivo preparation of autologous tumor antigen-loaded monocyte-derived DC vaccines as a novel potent anticancer strategy was launched. Phase I and II trials have been performed employing this strategy to treat several malignancies, such as B cell lymphoma, myeloma, melanoma, prostate, colon, ovarian, pancreatic, breast cancer, and renal cell carcinoma. So far, DC immuno-therapy is well tolerated with little side or toxic effects. An issue of concern is the way DC are loaded with tumor antigens. An effective strategy is the loading of DC with tumor antigen through electroporation with tumor RNA. In this chapter, a comprehensive description of a protocol for loading of ex vivo-derived DC with total tumor RNA through electroporation is provided. © Springer Science+Business Media New York 2014.


Bilotta M.,University of Perugia | Venturi F.,University of Perugia
Lethaia | Year: 2010

The critical Jurassic event known as Early Toarcian Oceanic Anoxic Event (OAE) has been the subject of several studies, but its palaeontological characterization is still problematic, and its dating is therefore debated. The rich ammonite faunas of the Mediterranean Tethys (Italy, Greece, Albania, North Africa, southern Spain, etc.) demonstrate that the OAE separates two very different assemblages, resulting from a strong post-OAE biological renewal. Faunas before the anoxic event include many taxa already present in late Pliensbachian (evolute Phylloceratida; Reynesocoeloceratinae, Protogrammoceratinae and Arieticeratinae), whereas after the anoxic event new forms radiated (Nodicoeloceratinae, Harpoceratinae and Hildoceratinae; afterwards also groups as Mercaticeratinae, Phymatoceratidae and Hammatoceratidae). As these assemblages show remarkable differences from their Northwest European equivalents, in the Apennine it is necessary to use a Mediterranean zonation, here formally established. The examined data suggest accurate boundaries for the OAE, which separates our first two Toarcian Zones, corresponding to Tenuicostatum and Serpentinum standard chronozones. Within this context, the Apennine assemblage placed immediately below the anoxic event is an endemic fauna with more than 15 ammonite genera, two of which (Secchianoceras and Petranoceras) are exclusive of the interval in question. Most abundant are Phylloceratidae (Phylloceras, Lavizzaroceras, Calaiceras and Harpophylloceras), Juraphyllitidae (Meneghiniceras) and Lytoceratidae (Lytoceras); Dactylioceratidae (Dactylioceras, Eodactylites and Secchianoceras) and Hildoceratidae are comparatively less numerous, but these latter show the largest taxonomic diversity (Fontanelliceras, Trinacrioceras, Protogrammoceras, Petranoceras, etc.). The description of this fauna improves the knowledge of a poorly understood interval immediately preceding the OAE, thus allowing better correlations in the Mediterranean area. □Ammonites, chronostratigraphy, Early Jurassic, OAE, Tethys. © 2009 The Authors, Journal compilation © 2009 The Lethaia Foundation.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-IP | Phase: KBBE-2009-1-2-04 | Award Amount: 7.82M | Year: 2010

SOLIBAM will develop specific and novel breeding approaches integrated with management practices to improve the performance, quality, sustainability and stability of crops adapted to organic and low-input systems, in their diversity in Europe and taking into account small-scale farms in Africa. SOLIBAM will: 1. Identify traits specific for adaptation to low-input/organic conditions over a wide range of agro-climatic conditions in Europe 2. Develop efficient phenotyping, genotyping and molecular tools to monitor heritable variation during selection. Molecular analysis of functional polymorphisms will increase accuracy in breeding methodologies and improve monitoring of genetic diversity and adaptation along generations. It will also increase the understanding of adaptive phenomena 3. Develop the use of within-crop diversity to stabilise yield and quality in the face of current and increasing variation in organic and low-input agriculture 4. Design, develop and test innovative arable and vegetable cropping systems based on integration of a high level of diversification in crop management with the use of genetically diverse populations or varieties 5. Compare the effectiveness of different breeding strategies under conventional, low input and certified organic farming to set up optimal strategies for the production of varieties suitable for organic and low input farming taking into account the traits which are avoided in conventional breeding 6. Develop methodologies for farmers participatory research that exploit SOLIBAMs advances in low-input and organic farming 7. Quantify the effects and interactions of breeding and management innovations on crop nutritional, organoleptic and end-use quality 8. Evaluate socio-economic and environmental impacts of SOLIBAM breeding and management innovations in order to identify farm business, consumer preference, food supply and legislation related issues that are likely to influence their adoption


Grant
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: ICT-02-2014 | Award Amount: 3.99M | Year: 2015

Water management requires massive, low-cost monitoring means coping with differentiated and evolving requirements. However, the majority of multifunctional water sensors only supports predefined goals hindering interoperability, with a high cost, impeding large scale deployments. Addressing this, PROTEUS aims at offering x10 reduction in both size and unit function cost compared to state of the art. To this end, an increased number of functions will be integrated at a reduced cost and PROTEUS will deliver a reconfigurable microfluidic-and nano-enabled sensor platform for cognitive water quality monitoring. Innovative embedded software will provide reconfigurability of the sensing board to support several differentiated applicative goals while cognitive capabilities will manage evolving requirements during exploitation. Energy autonomy will be made by harvesting water flow energy. In addition, low cost of additional sensing components will enable redundancy increasing life span of the systems. The main challenge relates to the heterogeneous integration into a monolithic, microfluidic sensing chip of carbon-nanotubes-based resistive chemical sensors, of MEMS physical and rheological resistive sensors and of a multifunctional adaptive deep-submicron CMOS system on chip. Upstream, high level system design addressing industrial use cases, manufacturability and cost-effectiveness, packaging, energy budget and interfaces between building blocks, will enable consistency and efficiency of the whole approach. Downstream, system validation will be carried out at different levels: benchmarking, reliability assessment to guarantee service time, model deployments and field testing. The consortium brings together renowned actors along the whole value chain, including system integration and end users. This will contribute to post-project exploitation prepared by ensuring appropriate inclusion of business requirements within the system design.


Grant
Agency: European Commission | Branch: FP7 | Program: CSA | Phase: ICT-2013.9.8 | Award Amount: 1.21M | Year: 2013

The goal of this proposal is to create a coordination activity among consortia involved in the ICT-ENERGY subject with specific reference to bringing together the existing Toward Zero-Power ICT community organized within the ZEROPOWER C.A. and the novel MINECC (Minimising energy consumption of computing to the limit) community recently funded under the FET Proactive Call 8 (FP7-ICT-2011-8) Objective 9.8. The coordination activity is aimed at assessing the impact of the research efforts developed in the groups involved in the different consortia and proposing measures to increase the visibility of ICT-Energy related initiatives to the scientific community, targeted industries and to the public at large through exchange of information, dedicated networking events and media campaigns. The activities of our C.A. will inspire more research projects in this emerging area by generating broader acceptance for the developed technology and the benefits of its applications. ICT-Energy C.A. will facilitate broader interaction and feedback among the consortia members and stakeholders, thereby, consolidating progress in the field. Positive benefits to the European Community are foreseen in all great challenges of energy, security, environment and health by developing a strategic research agenda in low power, energy efficient ICT and making it happen.


Grant
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: DRS-11-2015 | Award Amount: 6.56M | Year: 2016

HERACLES main objective is to design, validate and promote responsive systems/solutions for effective resilience of CH against climate change effects, considering as a mandatory premise an holistic, multidisciplinary approach through the involvement of different expertise (end-users, industry/SMEs, scientists, conservators/restorators and social experts, decision, and policy makers). This will be operationally pursued with the development of a system exploiting an ICT platform able to collect and integrate multisource information in order to effectively provide complete and updated situational awareness and support decision for innovative measurements improving CH resilience, including new solutions for maintenance and conservation. The HERACLES effectiveness will be ensured by the design and validation of manageable methodologies also for the definition of operational procedures and guidelines for risk mitigation and management. It will be validated in two challenging test beds, key study cases for the climate change impact on European CH assets. The strength of HERACLES solutions is their flexibility in evaluating a big quantity of different information that can be changed and tailored to the specific CH assets needs, guaranteeing in that way a general applicability. In this context, a fundamental role will be played by end-users, which will be active part in the project activities. HERACLES system will be designed and developed by accounting for the economic sustainability and future acceptance by the market and for the social and economic impact for public and local communities while respecting the integrity of CH and the value it hold for communities. Effective technological transfer of HERACLES outcomes to large companies, SMEs and end users, suitable dissemination, communication, education and training activities are also organized to disseminate vision and progresses obtained to different communities, in a vision of wide audiences awareness.


Grant
Agency: European Commission | Branch: H2020 | Program: MSCA-ITN-EJD | Phase: MSCA-ITN-2014-EJD | Award Amount: 3.79M | Year: 2015

Theoretical Chemistry and Computational Modelling (TCCM) is emerging as a powerful tool to help in the rational design of new products and materials for pharmaceutical, chemical, energy, computer, and new-materials industries. To achieve this goal, it is necessary to go beyond the traditional electronic structure studies, and merge complementary techniques that are normally not available at a single research group. The research programme of the TCCM-EJD aims at applying computational modelling to problems demanded by the industry and with high societal relevance, namely Materials with special properties, Biomolecules for new therapies and Energy storage. The objective of the Joint Doctorate is to prepare future research leaders, able to develop and use multidisciplinary computational techniques (methods and software), with solid communication skills, with many contacts established through the intensive relationship with worldwide leading researchers of 12 European universities and 14 additional partners, including 7 industrial and spin-off companies. A Joint Doctorate in TCCM is already operative since 2011, based on a fully participative scientific discussion and assessment of all research projects with a clear interdisciplinary character and the direct participation of the non-academic sector. The training programme puts the emphasis in common training, including 3 annual International Workshops, 3 schools on High Performance Computing and 3 tutorials in new computer codes. Career development opportunities are enhanced with regular inter-sectoral activities, transferable skill education and career coaching.


Grant
Agency: European Commission | Branch: H2020 | Program: MSCA-RISE | Phase: MSCA-RISE-2015 | Award Amount: 252.00K | Year: 2016

Insects can be accidentally introduced into non-native ecosystems by humans, or expand their geographical range toward the poles as a consequence of global warming. As they invade new environments, exotic species interact with local species, modifying the structure of local food webs. New associations arising from with biological invasions can impact the strength of existing links with effects cascading through trophic levels. When invasive species are herbivores that can attack economically important crops, they can cause serious economic losses. For example, recent invasion of the brown marmorated stink bug (BMSB) (Halyomorpha halys) in Europe and North America has the potential to interfere with local trophic webs and poses a serious threat to several agro-ecosystems. In this project, we will adopt a multidisciplinary approach to study the ecological consequences of BMSB invasions. In particular, we will focus on the effect of alien herbivore invasion on local natural enemies using the following work packages: 1) the impact of exotic herbivores on infochemical communication between plants, herbivores and natural enemies; 2) Learned responses of parasitoids to infochemical evolutionary traps in a climate change context; 3) Contest behaviour of local egg parasitoids for possession of co-evolved and non-coevolved hosts; 4) Patch time allocation of local egg parasitoids after alien herbivore invasion: behavioural and modelling approaches; 5) Molecular aspects of indirect plant defences against invasive and local species 6) Genetic structure of invasive alien herbivores across Europe and North America The proposed research will be of great relevance for the RISE call as it will be an unparalleled opportunity for complementary European and Canadian research groups to join forces, resulting in the development of lasting research collaborations, the transfer of knowledge between research institutions and improving research potential at the European and global levels.


Grant
Agency: European Commission | Branch: FP7 | Program: CP | Phase: ENERGY-2007-8.5-01 | Award Amount: 24.01M | Year: 2008

RENAISSANCE aims to develop a valid, reliable and integrated package of access and mobility measures for historic cities. These will make possible the rediscovery, preservation and enhancement of historic cities in Europe, together with the sustainable development of the local economy, to the benefit of visitors, residents and local business alike. RENAISSANCE brings together a group of historic/tourism cities across Europe that are in the vanguard of sustainable development. The RENAISSANCE cities have a strong reliance on heritage and tourism, which must marry environmental concerns, and sustainable access and mobility, with economic development. The partners face common problems: they are all historic cities with common layouts, and very valuable heritage to be preserved and enhanced. The partners also face unique local and regional challenges, including those brought about by social and economic integration within the EU. There is great added value in RENAISSANCE because the best practices that will be demonstrated will have resonance and relevance throughout the range of European Historic Cities.


Grant
Agency: European Commission | Branch: FP7 | Program: CSA | Phase: ICT-2009.8.9 | Award Amount: 625.75K | Year: 2011

The goal of this project is to create a coordination activity among consortia involved in Toward Zero-Power ICT research projects (FET proactive call FP7-ICT-2009-5, Objective 8.6) and communities of scientists interested in energy harvesting and low power, energy efficient ICT. This activity is aimed at assessing the impact of our research efforts and proposing measures to increase the visibility of ICT-Energy related initiatives to the scientific community, targeted industries and to the public at large through exchange of information, dedicated networking events and media campaigns. The ZEROPOWER activities will inspire more research projects in this emerging area by generating broader acceptance for the developed technology and the benefits of its applications. ZEROPOWER will facilitate broader interaction and feedback among the Toward Zero-Power ICT consortia members and stakeholders, thereby, consolidating progress in the field. Positive benefits to the European Community are foreseen in all great challenges of energy, security, environment and health by developing a strategic research agenda in low power, energy efficient ICT and making it happen.


Grant
Agency: European Commission | Branch: H2020 | Program: MSCA-RISE | Phase: MSCA-RISE-2015 | Award Amount: 1.39M | Year: 2016

In EU and Australia, every year thousands of square miles of forests and other lands burn due to wildfires. These fires cause important economic and ecological losses, and often, human casualties. Both EU and Australian governments are aware of how crucial it is to improve wildfires management and containment . Scientists from different specialties, both in EU and Australia, have already developed methods and models in order to improve the management and decision process pertaining to preparedness and response phases in case of bushfire. The present project, named Geospatial based Environment for Optimisation Systems Addressing Fire Emergencies (GEO SAFE), aims at creating a network enabling the two regions to exchange knowledge, ideas and experience , thus boosting the progress of wildfires knowledge and the related development of innovative methods for dealing efficiently with such fires. More precisely, the GEO SAFE project will focus on developing the tools enabling to set up an integrated decision support system optimizing the resources during the response phase, through: Developing a dynamic risk cartography of a region with regard to the possibility of a wildfire. The task will involve data collection (satellite and remote sensors), risk analysis and development of a tool enabling to forecast fire extension i, and in particular to predict fire and risk evolution during the response phase Designing and testing a resource allocation tool for the response phase using the dynamic risk cartography. One of the problems to consider will be the resource allocation for securing key places (schools, hospitals, .) given time dependent constraints. Problems will be identified through connections with final users, and the proposed solutions will be tested on simulated data. Developing analyses of relevant management processes as well as training tools in order to facilitate the implementation of such solutionto be completed


HarmonicSS vision is to create an International Network and Alliance of partners and cohorts, entrusted with the mission of addressing the unmet needs in primary Sjogren Syndrome; working together to create and maintain a platform with open standards and tools, designed to enable secure storage, governance, analytics, access control and controlled sharing of information at multiple levels along with methods to make results of analyses and outcomes comparable across centers and sustainable through Rheumatology associations. The overall idea of the HarmonicSS project is to bring together the largest well characterized regional, national and international longitudinal cohorts of patients with Primary Sjgrens Syndrome (pSS) including those participating in clinical trials, and after taking into consideration the ethical, legal, privacy and IPR issues for sharing data from different countries, to semantically interlink and harmonize them into an integrative pSS cohort structure on the cloud. Upon this harmonized cohort, services for big data mining, governance and visual analytics will be integrated, to address the identified clinical and health policy pSS unmet needs. In addition, tools for specific diagnostic procedures (e.g. ultrasonography image segmentation), patient selection for clinical trials and training will be also provided. The users of the HarmonicSS platform are researchers (basic/translational), clinicians, health policy makers and pharma companies. pSS is relevant not only due to its clinical impact but also as one of the few model diseases to link autoimmunity, cancer development (lymphoproliferation) and the pathogenetic role of infection. Thus, the study of pSS can facilitate research in many areas of medicine; for this reason, the possibility for sustainability and expandability of the platform is enhanced. Moreover, pSS has a significant impact on the healthcare systems, similar to that of rheumatoid arthritis.


Rajagopal K.R.,Texas College | Saccomandi G.,University of Perugia
Zeitschrift fur Angewandte Mathematik und Physik | Year: 2014

In this paper, we show that circularly polarized transverse stress waves, standing shear stress waves, and oscillatory shear stress waves can propagate in a new class of viscoelastic solid bodies which are a subclass of bodies described by implicit constitutive theories. The class of models that is being considered includes as sub-classes, the classical Kelvin–Voigt model, the new models introduced by Rajagopal wherein the Cauchy–Green tensor is a non-linear function of the stress, and the Navier–Stokes fluid model. The solutions established in this paper are generalizations of solutions that have been established within the context of nonlinear elasticity by Carroll, and Destrade and Saccomandi, to the new class of elastic and viscoelastic bodies that are being considered. © 2013, Springer Basel.


Balucani C.,SUNY Downstate Medical Center | Balucani C.,University of Perugia | Grotta J.C.,UTHealth Medical School
Neurology | Year: 2012

There is a great need for new treatments for acute ischemic stroke that will achieve greater rates of arterial recanalization and increase the population of patients who may benefit. Of several approaches under investigation, intra-arterial therapy (IAT) is the farthest along in clinical development, but experience has shown that the increased rates of recanalization achieved are not always translated to improved patient outcomes. Proper patient selection, allied to efficient strategies aiming at faster recanalization and reperfusion, may result in better clinical outcomes and more rational use of therapeutic resources. While high-tech multimodal imaging has the great promise of identifying hypoperfused but still viable brain tissue, a number of clues suggest that relatively low-tech approaches similar to those that were used to demonstrate the efficacy of systemic thrombolysis, and which have emphasized the key role of time and clinical factors such as age, glucose, stroke severity, and infarct on noncontrast CT scan, deserve greater study as an efficient way to optimize IAT. Eventually it will be a combination of predictors that will enable us to most precisely identify the best patients for IAT and any other new revascularization therapies. Copyright © 2012 by AAN Enterprises, Inc.


Cherubini A.,Geriatric Hospital | Cherubini A.,University of Perugia | Corsonello A.,Italian National Research Center on Aging | Lattanzio F.,Italian National Research Centres on Aging INRCA
Drugs and Aging | Year: 2012

Underprescription of potentially useful drugs is widespread among older people and may herald several adverse outcomes. We aimed to review the evidence pertaining to the epidemiology, causes and consequences of underprescribing, as well as recent advances in the development of interventions able to reduce underprescribing and improve outcomes in older people.Underprescribing is highly prevalent across different settings, including in the community, hospitals and nursing homes. Multimorbidity, polypharmacy, ageism, lack of scientific evidence, fear of adverse events and economic problems may contribute to the underprescription of indicated drugs, although in some patients, a limited life expectancy, the lack of a favourable risk-to-benefit ratio or a patients refusal might represent appropriate reasons not to prescribe a drug.Selected interventions may help to improve the quality of prescriptions and reduce the burden of underprescribing. Among these, comprehensive geriatric assessment (CGA) has been demonstrated to effectively improve prescribing practice. Interventions based on service delivery changes, such as those that include a clinical pharmacist or a case manager in the process of care, were also found to improve the quality of pharmacological prescriptions. Educational interventions may also be effective in reducing underprescribing.More recently, the clinical application of the Screening Tool to Alert Doctors to Right Treatment (START) criteria has been able to significantly reduce underprescribing. Since START criteria are easier to apply in clinical practice than other instruments, it is conceivable that their systematic use may contribute to reducing underprescribing and to improving health outcomes in older patients. © 2012 Springer International Publishing AG. All rights reserved.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-TP | Phase: HEALTH-2007-2.3.3-4 | Award Amount: 3.64M | Year: 2008

Influenza is an extremely contagious infection that is caused by distinct virus types and subtypes. Early diagnosis is crucial for disease treatment and control as it reduces the inappropriate use of antibiotics and provides the indication for antiviral therapy. Rapid diagnosis is also a key component of surveillance activity. This requires the ability to detect and accurately diagnose infection at or close to the source/outbreak with minimum delay, a tactic consistent with the global experience during the SARS epidemic in 2003. This experience underlines the need for specific, sensitive point-of-care testing capable of discriminating between influenza subtypes. None of the available influenza diagnostic assays combines a point-of-care format with the multiplex capability to identify a large repertoire of human and animal viruses. This project exploits the knowledge and the expertise of the partners to convert microarray assays, that have a powerful multiplex capability but are laborious, complex and expensive to perform, into a simple, robust and affordable automated point-of-care system for the diagnosis of influenza. The system will utilize three components: 1) a microarray immunoassay that distinguishes influenza A and B virus as well as A subtypes; 2) an innovative self-contained disposable lateral-flow device that allows the addition of specimens and reagents in a temporally-controlled manner; 3) a robust automated processing reading instrument of novel conception that employs a low cost, high performance optical module. This project will provide small laboratories, health offices, veterinary clinics and outposts (airports) with the diagnostic capability of major research institutions and reference centres, thus providing better care for patients and most importantly, facilitating the implementation of surveillance activities and guiding response measures that are being built to face a possible influenza pandemic caused by a highly virulent virus.


Grant
Agency: European Commission | Branch: FP7 | Program: MC-IAPP | Phase: PEOPLE-2007-3-1-IAPP | Award Amount: 1.87M | Year: 2008

People living in malaria endemic areas develop, with time, a form of immunity to infection and clinical disease mediated by antibodies directed against P. falciparum antigens. Currently there are no assays or clinical parameters that predict whether an exposed person is protected against malaria. This represents a major obstacle for vaccine development. Here research institutions and industrial partners, combining cutting edge expertise in protein microarrays, immunoassay development, immunology, protein expression and epidemiology join their efforts with the objective of translating the genome sequence information of Plasmodium falciparum into a tool to unravel correlates of protection against human malaria. Recombinant P. falciparum proteins, encompassing the repertoire of secreted and surface antigens, will be printed onto microarrays to develop an immunoassay capable of unraveling antibodies directed against a vast number of parasite molecules. This assay will be utilized to compare the antigen-antibody recognition profiles of protected and non-protected persons in malaria-exposed communities, thus facilitating the identification of the antigens that either alone or in combination function as targets of protective immunity. The underlying project structure in terms of research activities, task distribution and management has been planned with the priority of facilitating the interactions of human resources, between academic institutions and industry. Exchange of staff and networking activities will bridge the scientific and cultural differences existing between the academic and industrial partners. Exchange of scientific knowledge and technical skill will unleash the full potential of the collective expertise of the participating laboratories towards the objectives of the proposal and will be instrumental in building collaborative links that will extend beyond the duration of the project.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH-2007-2.3.2-9 | Award Amount: 3.01M | Year: 2009

Malaria, one of the worlds most devastating diseases, is caused by protozoan parasites of the genus Plasmodium and is obligatory transmitted to humans by anopheline mosquitoes. The African mosquito species Anopheles gambiae s.s., is the major vector of this disease. Research groups from 3 European countries and 3 African teams will integrate their resources and scientific expertise in malaria research to expand knowledge of mosquito biology and of vector-parasite interactions, exploiting the opportunities provided by the recently available genome information and technological developments for mosquito vectors. The joint scientific program of the MALVECBLOK Consortium integrates for the first time three crucial aspects of biology of An. gambiae: reproduction, immunity and population biology, with the aim to ultimately provide novel concepts and targets for malaria control. The main objectives will address: (i) The molecular bases of reproductive biology of the mosquito vector, and its effects on immunity and Plasmodium transmission; (ii) The molecular mechanisms which determine the mosquito immune status and regulate Plasmodium sporogony and transmission, in both laboratory settings and natural populations; (iii) The role of genetic polymorphism in genes controlling reproduction and immunity on structure of mosquito populations and malaria transmission in Africa. In order to reach these objectives, MALVECBLOK will employ a number of concerted strategies in support of its 3-year agenda. Special attention will be given to cutting-edge training opportunities and sharing of resources, by implementing interactive programmes for the training and exchange of personnel at all levels, and by rationalising and coordinating investment. The innovative knowledge generated under this trans-disciplinary project will promote European scientific competitiveness and will impact global health issues.


Grant
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: NMBP-01-2016 | Award Amount: 7.59M | Year: 2017

Objectives The H-CCAT project designs, upscales and shapes hybrid catalysts for the C-H functionalization of aromatic compounds. These solid catalysts will possess better recoverability, higher turnover numbers and better selectivity than current homogeneous catalysts for these reactions. The solid catalysts are applied at demonstration scale in the step-economical production of arylated or alkenylated aromatics, yielding motifs of active pharmaceutical ingredients. Methodology We will design heterogeneous hybrid catalysts featuring deactivation-resistant active sites, based on N-heterocyclic carbenes (NHCs) or diimine ligands and active metal ions. Via efficient, one-step protocols based on self-assembly, these sites will be embedded in robust porous hybrid materials like hybrid silica or metal-organic frameworks. Deactivation or metal aggregation will be prevented by site isolation or by efficient metal reoxidation (for the oxidative alkenylations). Metal leaching is precluded by using strong bonds between metals and embedded ligands like NHCs. Flow protocols will be designed to maximize the turnover numbers. Catalyst synthesis will be scaled up to kg scale, using efficient one-step protocols, minimizing use of solvents or waste formation. Soft shaping methods, e.g. spray drying, will preserve porosity and activity of the hybrid solids. A demonstration is conducted at minipilot scale at the J&J site (Belgium), allowing LCA analysis, techno-economic assessment and elaboration of the business plan. Relevance to work program The catalysts feature new, deactivation resistant active sites; their TOF/TON is maximized by an appropriate porous structure which even can be swelling. Catalysts are produced using innovative one-step protocols to form porous hybrid catalysts as powders or even immediately as shaped objects. The molecules targeted have strong biological and pharmaceutical relevance; they target diseases like influenza, cancer or HIV (case study: Rilpivirine).


Grant
Agency: European Commission | Branch: FP7 | Program: JTI-CP-FCH | Phase: SP1-JTI-FCH.2009.3.2 | Award Amount: 2.26M | Year: 2011

Low equivalent weight ionomers are required to reach the membrane conductivity and MEA performance targets for stationary operation and enable stationary PEMFC systems to achieve superior overall system yield to competitive technologies. Perfluorosulfonic acid ionomers (PFSA) demonstrate excellent properties in terms of chemical resistance in a fuel cell environment. In stationary applications, where the situation of deep MEA dehydration and frequent open circuit voltage events can be reasonably avoided, (this is not true in automotive applications) the most relevant failure mode in extended life time operation is associated with membrane mechanical failure. The use of a pre-formed inert support for mechanical stabilisation within the membrane has the drawback of reducing membrane specific conductivity, and this frequently imposes a reduction in membrane thickness to very low values. The objective of this proposal is to improve the mechanical properties of low equivalent weight state of the art perfluorosulfonic acid membranes using chemical, thermal, and processing and filler reinforcement methodologies by maintaining high proton conductivity. The baseline product for further development is the short side chain perfluoroionomer that already shows the best combination between ionic conductivity and mechanical stability. Stabilised membranes will be comprehensively characterised for their ex situ properties and screened and selected membranes will be integrated into MEAs and validation by evaluating single cell performance and durability under conditions relevant for stationary operation and comparison with those of reference membrane materials and MEAs, including the development and application of accelerated stress testing. In the final phase of the project the most promising membranes will be tested in a 4000 h durability test, simulating 10% of the expected lifetime of a stationary system to have a realistic projection of the expected degradation at 40,000 h.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH-2007-2.3.2-1 | Award Amount: 3.90M | Year: 2008

Standard therapy of infection with the human immunodeficiency virus type 1 (HIV-1) is based on potent cocktails of drugs targeting viral proteins. This treatment is associated with severe side effects and is almost unaffordable for the patients living in sub-Saharan Africa. Incomplete suppression of HIV replication results in drug-resistance. Therefore, a continued research effort is required to develop more potent, cheaper and less toxic antivirals. The insight has grown that HIV requires cellular proteins to serve as co-factors for viral replication. Our over-all objective is to develop novel drugs by targeting co-factors required for HIV replication. The virus will find it difficult to develop antiviral resistance against drugs targeting interaction between invariable cellular proteins and conserved viral protein domains. We will focus on the cellular proteins that mediate HIV trafficking, nuclear import and integration, such as Lens Epithelium Derived Growth Factor (LEDGF/p75), a novel cofactor of HIV-1 integration. THINC is composed of 3 virologists, 2 medicinal chemists, 1 virologist from South Africa, 1 structural biologist, 1 pharmaceutical company. Our first objective is to identify and validate novel co-factors of HIV trafficking, nuclear import and integration as novel targets for anti-HIV therapy. The second objective is to develop new drugs against the validated cellular target LEDGF/p75. The third objective is to perform this work in the perspective of those who will benefit most: the HIV infected people all over the world. The initial steps of target validation and hit identification will mainly be taken by academic groups, while optimization and (pre)clinical development of drugs requires the participation of Tibotec, a European company devoted to the development of antiviral drugs. The project will also increase our generic understanding of protein-protein interactions (PPI).


Grant
Agency: European Commission | Branch: FP7 | Program: CP-CSA-Infra | Phase: INFRA-2008-1.1.1 | Award Amount: 9.65M | Year: 2009

CHARISMA is an Integrated Infrastructure Initiative that brings together 22 leading European institutions developing research on artwork materials and their deterioration finalised to the conservation of cultural heritage. The consortium has the objective to optimise the use of infrastructures through a coordinated program of transnational access, joint research and networking activities. Transnational access offers applicants opportunities to exploit the services of three different and complementary groups of facilities, embedded in a multidisciplinary environment involving material science and artwork conservation/restoration. They are: i) a group of six archives containing a huge amount of analytical data, hosted by the most prestigious European museums and institutions developing safeguard and conservation of cultural heritage; ii) a set of advanced portable instrumentation for in-situ non-invasive measurements in the same site where the artworks are located or exhibited; iii) two platforms, one in France and one in Hungary, where large scale facilities are coupled to a set of medium scale instrumentations, open to users for the most advanced studies on artwork materials and their alterations. Research is devoted: i) to improve access to databases exploiting digitalisation of data and their harmonisation; ii) to design and set-up innovative instrumentations, for in-situ 2D and 3D examinations of artworks, and new cleaning techniques; iii) to develop new methodologies for the study of organic materials and their distribution in micro-samples or directly at the surface of the object. Through networking, the way infrastructures are working is improved, harmonising methodologies and best practices in analysis and conservation, pursuing the establishment of a multidisciplinary synergic working method, based on shared use of knowledge and resources.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH-2007-2.4.4-1 | Award Amount: 3.97M | Year: 2008

Autoimmune Addisons disease (AAD) is an endocrine disease resulting from the immune systems destruction of hormone producing cells in the adrenal cortex. Diagnosis is frequently first established after a life-threatening adrenal crisis, often resulting in untimely fatalities. The disease is rare, more common in women than in men, and also affects children. AAD very frequently occurs with other autoimmune diseases, such as type 1 diabetes mellitus, autoimmune thyroid disease and/or premature ovarian failure. Based on a European network of patient registry and biobanks, a translational approach using genetics, immunology, clinical management, and epidemiology, the project aims to unravel the pathogenesis and natural course of AAD, ultimately to improve diagnosis and treatment as well as to offer strategies for disease prevention. The consortium capitalises on the joint cutting edge expertise of leading European investigators covering all these fields. Exploiting these resources, we will describe the natural course of the disease with focus on factors limiting quality of life, and identify and characterise the disease-causing genes, using the corresponding disease in a spontaneous dog model and a gene targeted mouse model. In parallel, the cellular and molecular mechanisms of autoimmunity directed at the adrenal cortex will be unravelled both in humans with ADD and in the genetic mouse model. Together, these efforts will increase our still incomplete understanding of pathogenic pathways operational in AAD and pave the way for new therapies of this debilitating disorder. Moreover, clinical studies will be performed to evaluate more physiological and personalised treatment with cortisol also aimed at prevention. As an autoimmune model disease the results of the project will not only lead to the development of novel diagnostic and therapeutic interventions for Addison patients, but also increase our understanding of the pathogenesis of autoimmune diseases in general.


Grant
Agency: European Commission | Branch: FP7 | Program: MC-IRSES | Phase: FP7-PEOPLE-2013-IRSES | Award Amount: 145.90K | Year: 2014

Modern viticulture and oenology were born in the last century responding to the need to innovate in traditional technologies. However, current economic, ecological and social changes require new strategies for wine production that take an integrated view of the entire wine production chain to ensure sustainability. Current management systems of vineyards and fermentations are indeed not economically or environmentally sustainable. The present proposal will approach this topic from both an environmental, focusing on the theme of biodiversity and its protection, and from an economic/social point of view. Optimization will promote the use of yeasts to reduce pests in pre/post-harvesting and to produce low-alcoholic and/or sulphite wines. In particular, the identification of fermentative yeasts isolated from ancient (Italy, Georgia, and Slovenia) and new (Sweden, Canada, and South Africa) vine-growing areas will allow the selection of species/strains that could be useful to evaluate both the possible interaction between genomes and phenotypes and the interplay of wine-related organisms in the oenological environment. Finally, the network aims to produce non-GMO yeasts for the participative selection of strains by the wineries. The consortium research units possess complementary competencies and are all working with success in wine research; partners have consolidated expertise in chemistry, biochemistry, microbiology, physiology, genetics, bioinformatics, and taxonomy. The level of quality of the involved institutions and the appropriate staff exchange scheme (early and experienced researches) will allow an efficient transfer of knowledge during three years and for long-term collaborations. The expected impact of the consortium will be to contribute to the wine research field and to transfer its know-how to wine-makers.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2010.2.4.5-2 | Award Amount: 7.31M | Year: 2010

The ALLFUN proposal aims at defining the cellular and molecular mechanisms by which ubiquitous airborne or commensal fungi contribute to immune homeostasis and its dysregulation leading to allergy and inflammatory diseases. Breakthroughs in understanding how mucosal homeostasis is established, maintained or disrupted in the presence of fungi should be sources of new therapeutic targets and drugs (i.e. anti-inflammatory, immunomodulatory and anti-infectious molecules). European scientists representing the leading edge of this field are brought together here in a unique synergistic and cross-cutting collaboration that addresses a major medical and economic problem of considerable importance to the health care sector. The study will be centered on yeasts and filamentous fungi known to be associated with a number of inflammatory, autoimmune and allergic diseases. Via a multidisciplinary systems biology study combining fungal genetics, clinical research and animal models in a systems biology approach, integrating traditional wet-lab methods with those of functional genomics, immunomics, allergomics and bioinformatics, the ALLFUN project meets the criteria of the call, the strategic objective of which is to elucidate mechanisms by which infections may lead to aberrant activation of inflammation, the lack of resolution of which is responsible for inflammatory diseases. The anticipated results are highly relevant to society in terms of reducing the burden of mortality and suffering in patients with fungus-related diseases, identifying more accurate biomarkers for immunological disorders, optimizing and possibly reducing the cost of antifungal therapy by association with anti-inflammatory strategies that targets pathogenicity rather than microbial growth, the host-pathogen interface rather than the pathogen. Understanding the spectrum of immunological responses to fungi is perhaps the single most important challenge in the field of medical mycology.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: KBBE.2010.1.1-03 | Award Amount: 3.65M | Year: 2011

The goal of agrobiodiversity conservation, unlike other forms of conservation, is not only the conservation of species and intra-specific genetic diversity related to agriculture, but also to promote its sustainable use in facilitating agricultural production. Although significant progress has been made in the conservation and management of plant genetic resources for food and agriculture (PGRFA) globally and in Europe, there remain two critical areas where progress has been limited: (a) the use of conserved agrobiodiversity by breeders and (b) the systematic conservation of crop wild relative (CWR) and landrace (LR) diversity. Specifically for breeders and CWR / LR diversity conservationists, the status quo is no longer an option as human-induced climate change is threatening the maintenance of the very diversity breeders require to mitigate the adverse impact of climate change. Conventionally, breeders have used their own lines and stocks to generate novel crop varieties, but these materials are relatively genetically uniform and it is now increased recognition that CWR and LR offer the breadth of genetic diversity required by breeders to meet the novel challenges of climate change and rapidly changing consumer demands. Therefore, the aim of PGR Secure is to research novel characterization techniques and conservation strategies for European crop wild relative and landrace diversity, and further, to enhance crop improvement by breeders, as a means of underpinning European food security in the face of climate change. To achieve these goals PGR Secure has four research themes: 1. Investigation of novel characterization techniques, including: (1a) Genomics, phenotyping and metabolomics, (1b) Transcriptomics, (1c) Focused Identification of Germplasm Strategy; 2. CWR and LR conservation, including: (2a) Europe-wide CWR inventory, (2b) Exemplar national CWR inventories, (2c) European CWR strategy, (2d) Europe-wide LR inventory, (2e) Exemplar national LR inventories, (2f) European LR strategy; 3. Facilitating breeders CWR and LR use, including: (3a) Identifying breeders needs, (3b) Meeting breeders needs, (3c) Integration of conservation and user communities, (3d) Pre-breeding - channelling potential interesting germplasm into commercial breeding programmes; and 4. Informatics development, including: (4a) CWR and LR inventory information web availability, (4b) Novel characterization information web availability, (4c) Inter-information system operability. The research requires the integration and collaboration of European policy, conservation and breeding sectors and the products will be disseminated Europe-wide to all appropriate stakeholders. The project, initiated by the European Cooperative Programme for Plant Genetic Resources In Situ and On-Farm Conservation Network will involve 42 European countries, as well as both large and smaller European plant breeding companies.


Grant
Agency: European Commission | Branch: FP7 | Program: MC-ITN | Phase: PEOPLE-2007-1-1-ITN | Award Amount: 3.64M | Year: 2008

The vision of the FINSysB Network is to generate bright, ambitious and well-trained young researchers capable of contributing significantly to the knowledge-base and economy of the European Union. We will achieve this goal by providing a strong, multidisciplinary training for early stage and experienced researchers in the pathobiology, genomics, molecular biology, bioinformatics and systems biology of the medically important fungus, Candida albicans. This microbe causes frequent infections in otherwise healthy individuals and is a common cause of potentially lethal hospital acquired infections in intensive care patients in the EU. Our well-integrated research programme will dissect and model the molecular interactions that take place between this fungal pathogen and its human host during disease progression. FINSysB partners are all internationally renowned, contributing complementary expertise in pathobiology, genomics, molecular biology, bioinformatics and systems biology. Our two SME partners provide a well-defined route for the translation of our research into the development of novel, clinically useful diagnostic tools and antifungal therapies. Our research activities will be supplemented by well-structured training programmes in research skills and complementary transferable skills. This training extends successful programmes that were established during FP6. They will impart state-of-the-art skills in modern predictive and experimental biology as well as useful generic skills. The personal development plans of our young researchers will be enhanced further by secondments to industrial and academic partners and by attendance at advanced summer schools (e.g. on Human Fungal Pathogens, and Yeast Systems Biology). Using this combination of approaches we will provide our early stage and experienced researchers with well-defined career opportunities and equip them with the tools to compete effectively on the international stage.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-IP | Phase: HEALTH.2010.2.4.2-4 | Award Amount: 15.96M | Year: 2011

More than 50% of heart failure (HF) patients present without a major deficit of left ventricular (LV) systolic function and are presumed to suffer from diastolic HF (DHF) because diastolic LV distensibility is usually impaired in these patients. The vast majority (~80%) of DHF patients is exposed to metabolic risk factors. The MEDIA consortium therefore investigates:1) how metabolic derangements contribute to DHF; 2) how diagnostic algorithms for DHF can be improved by assessing metabolic risk; 3) how correction of metabolic risk can open new therapeutic perspectives for DHF.Hereto MEDIA will: 1) Expose animal models of DHF to intense metabolic risk in order to accelerate DHF development. 2) Perform mechanistic studies in cardiomyocytes derived from DHF animal models or from DHF patients. Because of the acquired nature of metabolic risk, these studies will focus on posttranslational modifications of proteins and on epigenetic control of hypertrophy development. Their relevance for global LV function will also be appraised; 3) Perform mechanistic studies on myocardial collagen synthesis, which is enhanced by metabolic risk, and execute a phase II trial in DHF with cardiac specific antifibrotic therapy; 4) Explore the use of biomarkers as premorbid identifiers of DHF in existing cohorts of patients exposed to metabolic risk; 5) Prospectively test biomarkers and arterial stiffening, which is accelerated by metabolic risk, for their diagnostic potential in a large DHF cohort; 6) Assess myocardial metabolic substrate preference with modern imaging techniques and improve diastolic LV dysfunction through modified substrate utilization in a phase II trial. Expected results of MEDIA are: 1) Identification of metabolic risk-related mechanisms as therapeutic targets; 2) Improved diagnostic algorithms through inclusion of biomarkers and arterial stiffness tests. 3) Novel treatments consisting of modified myocardial substrate utilization and myocardial antifibrotic therapy.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-CSA-Infra | Phase: INFRA-2008-1.1.1 | Award Amount: 10.78M | Year: 2009

Mosquitoes transmit a variety of infectious diseases that cause a tremendous burden to public health. Due to climate changes and to the increase in international trade and tourism the threats posed by mosquitoes are increasingly affecting large parts of Europe, causing understandable concerns among the populations of many Member States. Control methods, mainly based on insecticide usage, are struggling to cope with the challenges posed by the biology and ecology of mosquito vectors. INFRAVEC aims at bridging the gap between the recent advances in transgenic technology and its implementation as a novel powerful approach for vector control. To this aim, a large European Infrastructure will be established, in which the coordination of efforts, expertise and facilities provided by the individual research groups and institutions will bolster and considerably expand the overall research capabilities of the research community. INFRAVEC will operate, through a number of Networking, Joint Research, Transnational and Service activities, towards the objective of considerably strengthening research capability in Europe by sharing knowledge, resources and technology. INFRAVEC will mainly focus on Anopheles gambiae, the major vector of malaria, and Aedes albopictus, a viral disease vector that is rapidly spreading through Europe. Four Infrastructure facilities will be integrated in the project: 1) the Genetically Modified mosquito laboratory of Imperial College London; 2) the Mosquito Mass-rearing facility at the Centro Agricoltura ed Ambiente (with the support of the International Atomic Energy Agency); 3) the Bioinformatics facility at EMBLEBI, UK; and 4) the Mosquito Confined Release facility at ISRIM. INFRAVEC will provide a formidable research capability to external users and facilitate the performance of five research projects aimed at utilizing basic knowledge of mosquito genetics and biology in an unprecedented effort to develop novel opportunities for mosquito control.


Grant
Agency: European Commission | Branch: FP7 | Program: CPCSA | Phase: INFRA-2007-1.2-03 | Award Amount: 49.02M | Year: 2008

A globally distributed computing Grid now plays an essential role for large-scale, data intensive science in many fields of research. The concept has been proven viable through the Enabling Grids for E-sciencE project (EGEE and EGEE-II, 2004-2008) and its related projects. EGEE-II is consolidating the operations and middleware of this Grid for use by a wide range of scientific communities, such as astrophysics, computational chemistry, earth and life sciences, fusion and particle physics. Strong quality assurance, training and outreach programmes contribute to the success of this production Grid infrastructure. \nBuilt on the pan-European network GANT2, EGEE has become a unique and powerful resource for European science, allowing researchers in all regions to collaborate on common challenges. Worldwide collaborations have extended its reach to the benefit of European science.\nThe proposed EGEE-III project has two clear objectives that are essential for European research infrastructures: to expand, optimize and simplify the use of Europes largest production Grid by continuous operation of the infrastructure, support for more user communities, and addition of further computational and data resources; to prepare the migration of the existing Grid from a project-based model to a sustainable federated infrastructure based on National Grid Initiatives. \nBy strengthening interoperable, open source middleware, EGEE-III will actively contribute to Grid standards, and work closely with businesses to ensure commercial uptake of the Grid, which is a key to sustainability. \nFederating its partners on a national or regional basis, EGEE-III will have a structuring effect on the European Research Area. In particular, EGEE-III will ensure that the European Grid does not fragment into incompatible infrastructures of varying maturity. EGEE-III will provide a world class, coherent and reliable European Grid, ensuring Europe remains at the forefront of scientific excellence.


Grant
Agency: European Commission | Branch: FP7 | Program: CPCSA | Phase: INFRA-2013-1.2.1 | Award Amount: 85.21M | Year: 2013

This proposal details activities that will ensure the continued enhancement and ongoing operation of the leading-edge GANT network, supporting a range of network and added-value services, targeted at users across the GANT service area.\nIn the area of multi-domain network service operation, GN3plus plans to deliver fast, efficient provisioning of advanced services, develop operational support across management domains, and improve security to ensure service integrity and protect network resources. These initiatives will be complemented by the development of application services in a federated environment such as mobile and wireless roaming supported by safe and secure Authentication and Authorisation Infrastructure.\nNetworking Activities will provide management and support for all GN3plus activities through communication, promotion, international liaison and business development. Emphasis will be placed on supporting and encouraging service take-up among users by working closely with NRENs. GANT will increase digital inclusion through closer collaboration between NRENs, exchange of staff and specialist expertise, as well as by seeking synergies between public administrations and the GN3plus partners using their vast, shared knowledge base.\nJoint Research Activities will be targeted at providing critical analyses of future network and application technologies, with a view to future deployment of emerging technologies within and outside the GANT community.\nThe governance model aims to increase effectiveness and user influence. The GN3plus Partners Assembly will deal with overall policy and an Executive Board will oversee its implementation. An International User Advisory Committee and External Advisory Committee will ensure users views and senior industry and service provider expertise are channelled directly to the Assembly. Specialised Advisory Boards will ensure highly efficient decision making, and that the voice of the stakeholder community is heard.


Grant
Agency: European Commission | Branch: FP7 | Program: CPCSA | Phase: INFRA-2010-1.2.1 | Award Amount: 70.14M | Year: 2010

Scientific research is no longer conducted within national boundaries and is becoming increasing dependent on the large-scale analysis of data, generated from instruments or computer simulations housed in trans-national facilities, by using e Infrastructure (distributed computing and storage resources linked by high-performance networks).\nThe 48 month EGI-InSPIRE project will continue the transition to a sustainable pan-European e-Infrastructure started in EGEE-III. It will sustain support for Grids of high-performance and high-throughput computing resources, while seeking to integrate new Distributed Computing Infrastructures (DCIs), i.e. Clouds, SuperComputing, Desktop Grids, etc., as they are required by the European user community. It will establish a central coordinating organisation, EGI.eu, and support the staff throughout Europe necessary to integrate and interoperate individual national grid infrastructures. EGI.eu will provide a coordinating hub for European DCIs, working to bring existing technologies into a single integrated persistent production infrastructure for researchers within the European Research Area.\nEGI-InSPIRE will collect requirements and provide user-support for the current and new (e.g. ESFRI) users. Support will also be given for the current heavy users as they move their critical services and tools from a central support model to ones driven by their own individual communities. The project will define, verify and integrate within the Unified Middleware Distribution, the middleware from external providers needed to access the e-Infrastructure. The operational tools will be extended by the project to support a national operational deployment model, include new DCI technologies in the production infrastructure and the associated accounting information to help define EGIs future revenue model.


News Article | March 30, 2016
Site: www.nature.com

By half past four in the morning, PhD student Warren Stevenson has been awake for 22 hours. “I'm tired — but we work now or we don't work at all,” he says, leaning back on his swivel chair and staring resolutely at two computer screens. “We plan to take a nap at 6 a.m. and wake up at 8. It'll be intense.” Stevenson's intensity is warranted: he has just a few precious hours to collect data crucial for his PhD about the structure of liquid crystals. And he is not the only scientist determined to defy sleep on this freezing November night. Nearby, in rooms positioned around a vast circular chamber, workers are simultaneously conducting 28 separate experiments. This is the European Synchrotron Radiation Facility (ESRF) in Grenoble, France — a giant science factory that, for 24 hours a day and as many days a year as its engineers can safely manage, pulses out the most intense high-energy X-ray beams in the world. The teams who come here work in different fields: some study fossils, others batteries, still others proteins, minerals, artwork or archaeological treasures. But each visits for the same reason: to examine the structure of material by exposing it to light with the short wavelength that's needed to reveal details at the scale of atoms. Work hours are long: most of the current visitors arrived yesterday and have been granted only a few 8-hour shifts to collect their data. And competition to use the machine is so fierce — around 45% of requests are granted — that the facility operates around the clock to fit in as many as possible. Altogether, some 8,000 scientists visit here each year, conducting upwards of 2,000 experiments and producing the raw material for around 1,800 papers. In the past seven years, two Nobel prizes have been awarded for discoveries made at the synchrotron. It is a non-stop, international, interdisciplinary laboratory — which is why Nature spent 24 hours walking its tunnels to observe a slice of contemporary science as it unfolds (see 'The synchrotron that never sleeps'). “Our time here is precious. It will be months before our next visit — or it could be a year if we aren't lucky,” says Xiangbing Zeng, Stevenson's PhD supervisor. Some visitors have teams large enough to rotate in shifts; many others will return home with dark circles under their eyes. But the scientists don't mind. They value the opportunity to bury themselves in data collection while escaping the rest of life. “For the week after, you feel jet-lagged,” says biochemist Andrea Schmidt. “It doesn't get any easier. But it's always exciting to come here.” Schmidt is already looking harried. She and two colleagues flew in yesterday from the Charité medical university in Berlin, bringing with them 120 precious protein crystals frozen in a flask of liquid nitrogen. The German biochemists have just 24 hours to deduce the structure of their crystal — a bacterial protein that has been engineered to fluoresce when hit by red light and that is used to tag and study structures in living tissue. What's not clear is how such proteins work at the level of atoms and molecules. It would be an “important publication” if the team can explain it, says Schmidt. Synchrotrons are the workhorses of structural biology. There are around 50 of them in the world, and the vast majority of the 6,000 or so atomic-resolution protein structures reported by scientists last year were solved at these facilities, by examining the diffraction patterns formed when high-power X-rays are fired at crystallized proteins. At the ESRF, working quarters consist of a small office opening onto a cramped experimental room called a hutch, which is where Schmidt and her colleagues will analyse their crystals — each less than a hair's width across, and trapped in frozen solvent in the centre of a half-millimetre loop of nylon. As soon as Schmidt's team arrived this morning, the researchers began sticking tape over every visible light they could find. Light could cause molecules in the protein crystal to wiggle, making it impossible to capture an atomic-resolution picture. Schmidt flicks the light switch on and off, checking to see whether the rigged-up room is now completely dark. “It's MacGyver-like stuff,” grins her PhD student Dennis Kwiatkowski. Inside the 844-metre central ring of the synchrotron, electrons are circling at nearly the speed of light and spitting out X-rays like water flicking from a spinning car wheel. The X-rays are channelled through thin pipes to as many as 43 stations, called beamlines, around the ESRF ring, with a hutch and office attached to each (see ‘Circle of science’). Earlier this morning, specialist engineers injected fresh bunches of accelerated particles into the ring because the machine had been off for maintenance the day before. Each beamline has its own dedicated ESRF scientist who calibrates the X-ray beam for that day's experiment, and often sits with the team all day. “There are a lot of critical components and a lot of possible modes of failure,” says David von Stetten, the support scientist for Schmidt's team. “It's important to check it every day.” Stevenson, Zeng and a third member of the team, PhD student Huanjun Lu, have started their day by preparing samples of the liquid crystals that they want to image. The group, from the University of Sheffield, UK, wants to work out how molecules are aligned inside the crystals, which are similar to those found inside LCD televisions. The work might one day lead to improved screens that can flicker on and off at higher rates. The team is one scientist down: a Chinese national couldn't get his visa in time, so it's impossible for the rest to pair up in shifts as they had planned. There won't be any chance to leave the building, says Stevenson, but he shrugs. “It's just the work ethic. We never see Grenoble when we come here.” In a hutch 200 metres away, PhD student Annalisa Chieli is using a microtome to painstakingly cut ultra-thin slivers of dry paint from a block. It is her first time at the synchrotron. Yesterday, at home with her parents in Perugia, Italy, she watched a YouTube video about it. Now she is here, she says, “you can feel the research in the air”. Chieli, from the University of Perugia, is preparing to shine X-rays at samples taken from one of the four versions of The Scream, a painting by the famously melancholic Norwegian artist Edvard Munch, as well as samples from Jackson Pollock's Alchemy. Yellowish hues in both artworks have faded over time, and museum curators are not sure why. The synchrotron work could help to explain it, and perhaps protect the art. Today is prep work, explains team leader Letizia Monico, from the Institute of Molecular Science and Technology of Perugia: they are scanning various samples of yellow paint to build up a reference library showing how pigments of different elemental composition absorb X-ray light and how that changes with age. Tomorrow, precious flakes from the real paintings will be scanned and compared with this gallery to decipher how the compounds in them have changed with time. Like most of the researchers here, Monico and Chieli need pay nothing to visit. Twenty-one countries have signed up as partners of the synchrotron, contributing a combined €110 million (US$124 million) to operate it each year. The cash covers all the food and accommodation expenses for three members of each team visiting from a partner nation. Because the clientele is international, the two canteens have to be, too. The larger one is buzzing as visitors and staff scientists tuck into a selection of meat, fish, pizza, pasta, desserts, cheese, yogurt — and a choice of wines (often French). Altogether, the canteen doles out some 1,000 meals a day. The working language of the ESRF is English, but here the multilingual chatter is like a session at the United Nations. Monico's team picks the quieter, upper canteen. “For me, salad, and lots of vegetables,” says Monico, a small, brown-haired Italian who gesticulates animatedly as she explains the chemistry of the cadmium sulfide yellow pigment that she expects to find in Munch's work. “Art is my passion,” she says. The third member of the group, Frederik Vanmeert, of the University of Antwerp in Belgium, says his passions lie elsewhere. “I'm interested in the techniques,” he says. Back at her hutch, Schmidt's expression grows — if possible — slightly more anxious. The team is behind schedule: half the day has been spent setting up everything for the experiment on the light-sensitive protein. “If you don't have a good method to overcome frustration, then you are in the wrong field,” she says, staring at a magnified computer-screen image of her frozen sample. Schmidt and her group leader, Patrick Scheerer, want to get a picture with better than 2.8-ångström resolution to distinguish the separate amino-acid side chains of the protein. But Schmidt is on the 9th sample out of 100, and hasn't seen a discernible image yet. “Ninety per cent of the experiments go wrong,” she says, as she moves her mouse to decide where to aim the X-ray beam next. She clicks the mouse button — and throws up her hands in frustration. “Aah, 4.85 ångströms. You can only see a sheet or a helix, nothing else. Patrick will kill me if I don't collect the data.” Schmidt knows she could be in for a slog. When US structural biologist Brian Kobilka used the ESRF's tightly focused beamline in 2007 to take the first picture of a G-protein-coupled receptor — a structure that would win him the 2012 Nobel Prize in Chemistry — his team worked through 1,043 crystals before it hit the jackpot. Next door, Matthew Bowler is looking relaxed. He has already scanned 80 crystal samples, couriered in from Helsinki the day before, and has successfully determined 3 protein structures without breaking a sweat. Bowler hasn't done this all by himself. Rather, he works on one of the world's only automated X-ray crystallography beamlines. The robot, which Bowler built with other ESRF staff scientists, loads up crystal samples, scans each frozen blob, decides where to fire the X-rays for best results, collects data sets and then moves on to the next one. “It does this 24 hours a day, and it doesn't get tired,” Bowler says with pride. The robot has processed 15,000 crystals over the past year. (Unfortunately for Schmidt, the specialized light conditions required by her protein make it impossible for the robot to handle.) Bowler supervises the machinery and loads crystals into a sample-changer at the beginning of the day, but doesn't need to intervene regularly: researchers who send in samples to be analysed are informed of results by automated e-mails. The best part? It keeps Bowler's hours regular: he works from 8 a.m. until 6 p.m. each day. “I'm going to pick up my daughter from a piano lesson, then I'm done for the day,” he says. Nearby, Alexey Nikulin and Natalia Lekontseva are filling up a vacuum flask at a liquid-nitrogen dispenser. They flew in from the Institute of Protein Research in Pushchino, near Moscow, on Monday, and depart at the end of the week. “Hamburg's synchrotron doesn't work at the moment, and Berlin's is full up,” says Nikulin, as the two trundle the full, heavy vessel back to their hutch. The liquid nitrogen will be used to keep their crystals, of an RNA-binding protein, frozen until they are ready for use. Out in the corridor, Magnus Larsson walks past, on his way home for the day. He's easily identifiable as a non-researcher from his suit. Larsson is an industrial liaison officer who is visiting from the MAX IV synchrotron in Lund, Sweden, the world's first 'fourth-generation' machine, which promises to produce tighter, brighter beams of X-rays when it opens in June. He has been visiting to get tips on how the ESRF works with industry researchers, who pay their own way but are allowed no more than 10% of the synchrotron's beamtime. After he's gone, the synchrotron's grey corridors are empty. The air conditioning clanks and hums. Although each group works just a minute or two's walk away from its neighbours, the teams rarely interact. As darkness falls outside, researchers begin drifting back towards the synchrotron's canteen for dinner. The superior intensity of the X-rays generated by modern machines — which collect data in minutes, where older ones took hours — means that scientists who come to synchrotrons now have less time away from their hutches, says Joanne McCarthy, who's in charge of the ESRF's user programme. “In the olden days, you prepared your samples for measurement and went off to have dinner in town,” she says. The synchrotron's electrons are tiring out. The lead-lined pipe is not a perfect vacuum, and occasional collisions with air molecules make the tightly focused bunches of electrons spread out slightly and lose energy, causing the flux of each X-ray beam to drop. Engineers pump replacements into the synchrotron's storage ring to maintain the beams through the night. In hutch ID22, the computer emits a gong sound — an alert signifying that the most recent measurement has ended. The team of five scientists, led by Boaz Pokroy from the Technion in Haifa, Israel, applied for time here eight months ago. It was worth the wait, Pokroy says: “The ESRF is, no question, the best synchrotron on this Earth.” The researchers are here in the name of materials science: they are examining the crystals that form when biological molecules, such as amino acids, are mixed with inorganic minerals such as copper oxide, so that the two crystallize together in a composite. The team is exploring whether this changes the electronic properties of the minerals in predictable ways, Pokroy says, perhaps leading to semiconductors with new properties. Carlotta Giacobbe, their Italian staff-support scientist, points to a closed-circuit-television picture on the computer monitor, which shows a tall yellow robotic arm dipping to remove some tubes of powdered crystalline samples from the X-ray beam. “There are a lot of sounds,” Giacobbe says: “there's a train whistle when the measurement starts, a gong when it stops and a scream if there's a problem with data backup.” (There's also a donkey bray and the sound of laughter, which play when the scientists make mistakes.) The researchers in Monico's team are finishing their paint analyses and are about to retire to the ESRF's guesthouse, which has 173 rooms and is full up tonight. Vanmeert is entering code on the computer, instructing a robot to move a sample of pigments slowly through the X-ray beam while they're gone. “If you make a single error, you lose the night,” warns ESRF beamline scientist Marine Cotte. Vanmeert is careful, but he is also looking forward to bed. “I will read a book and dream about beamlines,” he says. At Pokroy's beamline, things aren't going so well. The gong sounds, and Giacobbe looks at the camera, expecting the yellow arm to move towards a fresh array of samples. Nothing. “No … shit. Wait, it didn't work,” she sighs. “OK. This means that the night will be longer than expected.” Pokroy leans over. “The robot is shy? Why didn't it change?” She and Pokroy go inside the hutch and fish around at cables, while the rest of the team looks concerned. Pokroy finds a possible culprit — a red cable that appears to have been cut. But no-one is sure of the problem, and it is too late to call in a technician, so data collection will stop. “We will lose a night,” Giacobbe says, looking downcast. The six scientists put on their coats, pick up their bags, and leave for the guesthouse. Behind them, the robot is still. The guesthouse is so full that some scientists couldn't get rooms. Georgios Kalantzopoulos and Erik Glesne, two materials scientists from the University of Oslo, set out to walk the 40 minutes into Grenoble for a hotel they have booked there instead. It's raining, and by the time they arrive, they are drenched. At last, a breakthrough. By slogging through dozens of crystals, Schmidt's team has managed to get a 2.5-ångström-resolution picture of the light-sensitive protein — enough for the core of a research paper, although they won't know the protein's full shape until the researchers can analyse the data later on. “If we have exciting results like these, we don't need any coffee to stay up,” says Schmidt's colleague, Bilal Qureshi. Qureshi says he likes the single-minded focus the team can achieve on a synchrotron visit. “We generate a lot of ideas, and we don't think about much else.” The synchrotron is emptying — but where samples can't be changed by robot or need careful supervision, dozens of experimenters remain in their hutches. One of them is Stefan Mebs, a cheery German chemist from the Free University in Berlin; he and his colleague Peer Schrapers have elected to do night shifts for the next two weeks, because their samples must be changed every half-hour by hand. “On the day shift, you can sleep at normal times — but the experiments are more stressful,” says Mebs. “At night, it's more relaxed. It's quite calm.” This group is blasting X-ray pulses at haemoglobin — the oxygen-carrying protein in red blood cells — in the hope of working out exactly how oxygen molecules bind to its iron-atom core. The team wants to examine this at room temperature as well as the sub-zero conditions that are usual for working with crystals, to see whether the binding is different at each, says Mebs. On the far side of the synchrotron, three scientists are still up — although they have installed a sofa in their office in case they have time to catch a nap, says Julie Villanova, the ESRF staffer on the beamline. “When people come here, they are really motivated, and they push us all,” she says. Her two users for the day — Peter Joergenesen and Salvatore De Angelis of the Technical University of Denmark in Kongens Lyngby — are taking pictures of tiny pits in electrodes from different samples of solid oxide fuel cells to see how they have degraded over time. Villanova makes an espresso in a kitchen nearby, although she does not drink it herself — something that impresses the Danish visitors, who can't imagine how else one would stay up. “Sometimes people jog around the inside of the tunnel,” Villanova says. “Though there's a nice river not far away.” Despite their earlier success, Schmidt and her team have come unstuck because of a broken sample holder. After half an hour trying to fix it, they give up for the night. With 30 crystals not yet analysed, they creep wearily back to the guesthouse for 5 hours' sleep before they fly back to Germany. Schmidt will be back in two weeks to do it all again. Stevenson and Zeng have been up for well over 24 hours, but they have managed to obtain results on two liquid crystal samples. “I'm as pleased as I can be in the present circumstances,” Stevenson says. “I think I'll just pass out, eventually.” With the night shift ending, cleaners mop and vacuum the tunnels before a new tide of scientists pours into the synchrotron. Giacobbe returns early with two colleagues to try to sort out last night's problem. “We thought it was the wires, but it was actually a software fault,” she says. “I feel relieved. It's nice when you discover what the problem is and fix it.” The gong sounds, and then the train whistle, and in the hutch beyond, a robotic arm whisks around to pick up a sample. Giacobbe smiles. “It's OK to lose one shift. They can recover the time.” Two fresh-faced researchers walk into the office just vacated by Schmidt's group and put down their bags. Theodoras Goulas and Mariana Castrillo Bricenyo have just arrived from the Institute of Molecular Biology in Barcelona, Spain — and now, like their predecessors, they have 24 hours in the hutch. Goulas is looking forward to the long day ahead. “I'm pretty sure we'll get something,” he says.


Mirabella F.,University of Perugia | Brozzetti F.,University of Chieti Pescara | Lupattelli A.,University of Perugia | Barchi M.R.,University of Perugia
Tectonics | Year: 2011

Broad geological and geophysical documentation is available on regional extensional systems driven by low-angle normal faults. However, little information exists about the three-dimensional geometry and the offset distribution of such extensional structures. We present a new set of balanced geological sections across the extensional fault system driven by the Altotiberina low-angle normal fault in the Northern Apennines of Italy. We document this extensional system throughout a large set of surface (field surveys and geological maps) and subsurface data (seismic reflection profiles and boreholes). The subsurface data allowed us to define the fault deep geometry and to obtain its structural contours. The fault geometry is characterized by both along-dip and along-strike irregularities. In cross-section, the fault displays a staircase trajectory with the shallowest part being dome-shaped and flattened to horizontal. This bending could be due to the footwall uplift triggered by a footwall uploading greater than about 115 MPa. The sequential restoration of five geological cross-sections yields a maximum extension of about 10 km accumulated over approximately 3 Ma. The resulting long-term slip-rate is about 3 mm/yr, which is of the same order as the present-day extensional rate measured by GPS (2.5-3.0 mm/yr), suggesting an almost steady state extension over the last 3 Ma. The distribution of the extension values along the fault strike is bell-shaped, as expected for a continuous surface. Copyright © 2011 by the American Geophysical Union.


Smith S.A.F.,Durham University | Holdsworth R.,Durham University | Collettini C.,University of Perugia | Collettini C.,Italian National Institute of Geophysics and Volcanology
Bulletin of the Geological Society of America | Year: 2011

The late Miocene to early Pliocene Zuccale low-angle normal fault on the Island of Elba, Italy, was one of the principal structures active during extensional collapse of the Apennine fold-and-thrust belt. We investigate the relationships among the Zuccale fault, subsidiary footwall fault networks, and igneous bodies that were intruded into the immediate footwall of the Zuccale fault. Both brittle and ductile kinematic indicators found in association with fault zones and igneous bodies yield a consistent WNW-ESE extension direction, suggesting that faulting and intrusion overlapped in time. Structure contour analysis indicates that the Zuccale fault has a regional domal morphology. The dimensions and spatial location of the dome correlate with the likely subsurface position of the Porto Azzurro pluton, originally intruded at ~6 km depth. We propose that doming of the Zuccale fault may have been related in part to emplacement of the Porto Azzurro pluton as a tabular intrusion, involving some component of vertical inflation and roof uplift. The immediate footwall of the Zuccale fault is everywhere crosscut by a complex, linked network of high- and low-angle extensional faults with observed displacements of <10 m. Mutual crosscutting relationships suggest that low- and high-angle faults were active broadly contemporaneously. The final geometry of the footwall fault networks is adequately explained by their position with respect to the regional domal structure, and they suggest that certain sections of the Zuccale fault were back-rotated-during doming-out of an orientation capable of accommodating continued regional extension. © 2011 Geological Society of America. © 2011 Geological Society of America.


Pauselli C.,University of Perugia | Ranalli G.,Carleton University | Federico C.,University of Perugia
Tectonophysics | Year: 2010

A thermorheological WSW-ENE profile along the Northern Apennines is presented. The variations in rheology are estimated using two different models: the conventional model in which only frictional sliding and power-law creep are taken into account, and a new model in which in addition to the previous two mechanisms, a high-pressure brittle fracture mechanism is included. Upper and lower bounds for the rheology are considered: a hard case where the lower crust is mafic granulite and the lithospheric mantle is dry peridotite, and a soft case where the lower crust is felsic granulite and the lithospheric mantle is wet peridotite. Important differences in lithospheric rheological structure are inferred between the western and the eastern sectors of the chain. In the former a "crème brulée" structure generally applies; in the latter a "jelly-sandwich" structure applies. These rheological models, therefore, are not alternative but end members of a continuous spectrum of rheological behaviours. © 2009 Elsevier B.V. All rights reserved.


Massaro F.,Kavli Institute for Particle Astrophysics and Cosmology | Paggi A.,Smithsonian Astrophysical Observatory | D'Abrusco R.,Smithsonian Astrophysical Observatory | Tosti G.,University of Perugia | Tosti G.,National Institute of Nuclear Physics, Italy
Astrophysical Journal Letters | Year: 2012

The identification of low-energy counterparts for γ-ray sources is one of the biggest challenges in modern γ-ray astronomy. Recently, we developed and successfully applied a new association method to recognize γ-ray blazar candidates that could be possible counterparts for the unidentified γ-ray sources above 100 MeV in the second Fermi Large Area Telescope Catalog. This method is based on the infrared colors of the recent Wide-Field Infrared Survey Explorer (WISE) all-sky survey. In this Letter, we applied our new association method to the case of unidentified INTEGRAL sources (UISs) listed in the fourth soft gamma-ray source catalog. Only 86 UISs out of the 113 can be analyzed due to the sky coverage of the WISE Preliminary Data Release. Among these 86 UISs, we found that 18 appear to have a γ-ray blazar candidate within their positional error region. Finally, we analyzed Swift archival data available for 10 out of these 18 γ-ray blazar candidates, and we found that 7 out of 10 are clearly detected in soft X-rays and/or in the optical-ultraviolet band. We cannot confirm the associations between the UISs and the selected γ-ray blazar candidates due to the discrepancies between the INTEGRAL and the soft X-ray spectra. However, the discovery of the soft X-ray counterparts for the selected γ-ray blazar candidates adds an important clue to help us understand their origin and to confirm their blazar nature. © 2012. The American Astronomical Society. All rights reserved.


Oliva C.F.,L.E.S.S. | Damiens D.,International Atomic Energy Agency | Benedict M.Q.,University of Perugia
Acta Tropica | Year: 2014

Among Aedes mosquitoes are species responsible for transmission of serious pathogens to humans. To cope with the current threats to long-term effectiveness of the traditional vector control methods, non-conventional control strategies are being developed. These include autocidal control such as the release of sterile males (sterile insect technique) and the release of Wolbachia-infected males to induce sexual sterility (incompatible insect technique) and pathogen-refractory strain replacement variations using Wolbachia. Sterile male types of techniques particularly depend on released males' ability to successfully mate with wild females. For that reason, a good understanding of male mating biology, including a thorough understanding of the reproductive system and mating capacity, increases the likelihood of success of such genetic vector control programmes. Here we review the literature concerning the reproduction of Aedes mosquitoes with an emphasis on the male biology. We consider sexual maturation, mate finding, insemination, male reproductive capacity, and the occurrence of multiple matings. We also discuss which parameters are of greatest importance for the successful implementation of autocidal control methods and propose questions for future research. © 2013 International Atomic Energy Agency 2013.


Cardelli E.,University of Perugia | Cardelli E.,Center for Electrical and Magnetic Applied Research | Faba A.,University of Perugia | Faba A.,Center for Electrical and Magnetic Applied Research
Physica B: Condensed Matter | Year: 2014

In this work we present an identification procedure for a vector hysteresis model defined by a H-moving approach. The model parameters are identified by means of a suitable implementation of a genetic algorithm with a set of experimental data. The analytical formulation of the model and the characteristics of the genetic algorithm used are described. A comparison between computed data and experimental measurements for a not oriented grain Si-Fe magnetic steel with a weak lamination anisotropy are reported. © 2013 Elsevier B.V.


Cardelli E.,University of Perugia | Cardelli E.,Center for Electrical and Magnetic Applied Research | Faba A.,University of Perugia | Faba A.,Center for Electrical and Magnetic Applied Research
Physica B: Condensed Matter | Year: 2014

This work discusses the vector measurement of the effective magnetic field inside a not oriented grain SiFe steel sample, taking into account the effect of the demagnetizing field. We propose an array of biaxial Hall sensors, placed up to the sample surface. The calibration of the system and a suitable extrapolation data strongly reduce the uncertainties of the direct measurement and provide an accurate evaluation of the magnetic field inside the material sample. Although the approach proposed can be also used for industrial frequencies, 50-60 Hz or more, the analysis is limited here to the static case, because we are mainly interested in static magnetic measurements. These measurements are especially useful for the vector characterization of soft magnetic materials and, in particular, for the identification and the experimental validation of vector hysteresis models. The experimental analysis presented in the paper deals with commercial not oriented grain SiFe steels. Experimental data about hysteresis loops and static power losses are given. © 2013 Elsevier B.V.


Belcastro V.,SantAnna Hospital | D'Egidio C.,University of Chieti Pescara | Striano P.,University of Genoa | Verrotti A.,University of Perugia
Epilepsy Research | Year: 2013

Treatment of epileptic patients with valproic acid (VPA) may be associated with substantial weight changes that may increase morbidity and impair adherence to the treatment regimen. VPA-induced weight gain seems to be associated with many metabolic disturbances; the most frequent are hyperinsulinemia and insulin resistance, hyperleptinemia and leptin resistance. Patients who gain weight during VPA therapy can develop dyslipidemia and metabolic syndrome that are associated with long-term vascular complications such as hypertension and atherosclerosis. Moreover, an elevation in the levels of uric acid and homocysteine, together with oxidative stress, may contribute to atherosclerotic risk in patients under long-term therapy with VPA.The aim of this review is to discuss the metabolic and endocrine effects of VPA chronic treatment in patients with epilepsy. © 2013 Elsevier B.V.


Verrotti A.,University of Perugia | Filippini M.,CNR Institute of Neurological Sciences | Matricardi S.,University of Chieti Pescara | Agostinelli M.F.,University of Chieti Pescara | Gobbi G.,CNR Institute of Neurological Sciences
Brain and Cognition | Year: 2014

Benign Epilepsy with centrotemporal spikes (BECTS) is considered a benign type of epilepsy; nevertheless a significant number of children present clear and heterogeneous cognitive deficits such as memory disturbances. Thus far, evidence about memory impairment has been less than conclusive. To clarify the quality of memory functioning in BECTS children, an analysis of existing findings has been conducted trying to identify the type of memory deficits and their underlying factors. Short- and long-term declarative memory are impaired in BECTS children, with both verbal and non-verbal material; co-occurrence of attentional, linguistic and behavioral disturbances is reported. In children with continuous spikes and waves during the slow-wave sleep pattern the normal downscaling of slow-wave activity is absent, disrupting plastic brain processes of sleep-related memory consolidation. In BECTS children, NREM sleep interictal epileptiform discharges (IED) may interfere in the dialogue between temporal and frontal cortex, causing declarative memory deficits: the role of NREM sleep IED acquires a special importance, leading to methodological guidance and suggesting aims for future researches in the field of childhood neuroscience. © 2013 Elsevier Inc.


Pols T.W.H.,Ecole Polytechnique Federale de Lausanne | Nomura M.,Ecole Polytechnique Federale de Lausanne | Harach T.,Ecole Polytechnique Federale de Lausanne | Lo Sasso G.,Ecole Polytechnique Federale de Lausanne | And 8 more authors.
Cell Metabolism | Year: 2011

The G protein-coupled receptor TGR5 has been identified as an important component of the bile acid signaling network, and its activation has been linked to enhanced energy expenditure and improved glycemic control. Here, we demonstrate that activation of TGR5 in macrophages by 6α-ethyl-23(S)- methylcholic acid (6-EMCA, INT-777), a semisynthetic BA, inhibits proinflammatory cytokine production, an effect mediated by TGR5-induced cAMP signaling and subsequent NF-κB inhibition. TGR5 activation attenuated atherosclerosis in Ldlr -/-Tgr5 +/+ mice but not in Ldlr -/-Tgr5 -/- double-knockout mice. The inhibition of lesion formation was associated with decreased intraplaque inflammation and less plaque macrophage content. Furthermore, Ldlr -/- animals transplanted with Tgr5 -/- bone marrow did not show an inhibition of atherosclerosis by INT-777, further establishing an important role of leukocytes in INT-777-mediated inhibition of vascular lesion formation. Taken together, these data attribute a significant immune modulating function to TGR5 activation in the prevention of atherosclerosis, an important facet of the metabolic syndrome. © 2011 Elsevier Inc.


Guzzetti F.,CNR Research Institute for Geo-hydrological Protection | Mondini A.C.,CNR Research Institute for Geo-hydrological Protection | Mondini A.C.,University of Perugia | Cardinali M.,CNR Research Institute for Geo-hydrological Protection | And 5 more authors.
Earth-Science Reviews | Year: 2012

Landslides are present in all continents, and play an important role in the evolution of landscapes. They also represent a serious hazard in many areas of the world. Despite their importance, we estimate that landslide maps cover less than 1% of the slopes in the landmasses, and systematic information on the type, abundance, and distribution of landslides is lacking. Preparing landslide maps is important to document the extent of landslide phenomena in a region, to investigate the distribution, types, pattern, recurrence and statistics of slope failures, to determine landslide susceptibility, hazard, vulnerability and risk, and to study the evolution of landscapes dominated by mass-wasting processes. Conventional methods for the production of landslide maps rely chiefly on the visual interpretation of stereoscopic aerial photography, aided by field surveys. These methods are time consuming and resource intensive. New and emerging techniques based on satellite, airborne, and terrestrial remote sensing technologies, promise to facilitate the production of landslide maps, reducing the time and resources required for their compilation and systematic update. In this work, we first outline the principles for landslide mapping, and we review the conventional methods for the preparation of landslide maps, including geomorphological, event, seasonal, and multi-temporal inventories. Next, we examine recent and new technologies for landslide mapping, considering (i) the exploitation of very-high resolution digital elevation models to analyze surface morphology, (ii) the visual interpretation and semi-automatic analysis of different types of satellite images, including panchromatic, multispectral, and synthetic aperture radar images, and (iii) tools that facilitate landslide field mapping. Next, we discuss the advantages and the limitations of the new remote sensing data and technology for the production of geomorphological, event, seasonal, and multi-temporal inventory maps. We conclude by arguing that the new tools will help to improve the quality of landslide maps, with positive effects on all derivative products and analyses, including erosion studies and landscape modeling, susceptibility and hazard assessments, and risk evaluations. © 2012 Elsevier B.V..


Vizzari M.,University of Perugia | Modica G.,University of Reggio Calabria
Environmental Management | Year: 2013

Environmental issues related to swine production are still a major concern for the general public and represent a key challenge for the swine industry. The environmental impact of higher livestock concentration is particularly significant where it coincides with weaker policy standards and poor manure management. Effective tools for environmental monitoring of the swine sewage management process become essential for verifying the environmental compatibility of farming facilities and for defining suitable policies aimed at increasing swine production sustainability. This research aims at the development and application of a model for a quick assessment of the environmental effectiveness of the pig farming sewage management process. In order to define the model, multicriteria techniques, and in particular, Saaty's analytic hierarchy process, were used to develop an iterative process in which the various key factors influencing the process under investigation were analyzed. The model, named EASE (Environmental Assessment of Sewages management Effectiveness), was optimized and applied to the Lake Trasimeno basin (Umbria, Italy), an area of high natural, environmental and aesthetic value. In this context, inadequate disposal of pig sewage represents a potential source of very considerable pollution. The results have demonstrated how the multicriteria model can represent a very effective and adaptable tool also in those decision-making processes aimed at the sustainable management of livestock production. © 2013 Springer Science+Business Media New York.


Iannitti R.G.,University of Perugia | Carvalho A.,University of Perugia | Carvalho A.,University of Minho | Carvalho A.,ICVS 3Bs PT Government Associate Laboratory | Romani L.,University of Perugia
Trends in Immunology | Year: 2012

Fungal infections and related diseases have a high morbidity and mortality rate. Human antifungal vaccines are therefore of great interest, however, their development is challenging. Major hurdles include fungal species-specific differences in pathogenic mechanisms and strategies to escape immune surveillance, as well as the fact that individuals susceptible to infection do not necessarily share the same risk factors. Progress in antifungal vaccines demands the integration of immunology with systems biology, immunogenetics and bioinformatics in the arena of both fungal and host biology. Bridging the fields of basic immunology and vaccine research is needed to create individualized host immune profiles that will direct the rational development of customized adjuvants and vaccines with a predicted efficacy in each target population. © 2012 Elsevier Ltd.


Abate M.,University of Chieti Pescara | Salini V.,University of Chieti Pescara | Antinolfi P.,University of Perugia | Schiavone C.,University of Chieti Pescara
Foot and Ankle International | Year: 2014

Background: The prevalence of tendinopathies is increased in subjects with diabetes mellitus. However, there are few data on the structural abnormalities of Achilles tendons in asymptomatic diabetic patients. The aim of the study was to assess the morphologic characteristics of the Achilles tendon in subjects with diabetes in comparison with controls without diabetes. Methods: Participants were consecutively recruited from an outpatient population. Ultrasound longitudinal and transverse scans were performed bilaterally along the full length of Achilles tendon from the musculotendinous junction to the insertion. Degenerative features (abnormal fibrillar pattern, hypo-hyperechoic areas), signs of enthesopathy (bony erosion, enthesophytes, and bursitis), and intratendinous neovessel formation were recorded. Results: Asymptomatic sonographic abnormalities (ASA) were significantly increased in subjects with diabetes (35/136 [25.7%] vs 32/273 [11.7%], P = .0003). Sixty tendons with ASA were observed in the first group and 45 in the latter because ASA were bilateral in 25 and in 13 subjects, respectively. ASA were more frequently localized at the enthesis (32/60 [53.3%] vs 9/45 [20%], P = .0005) in the diabetes group, whereas, on the contrary, they were more prevalent at the midportion in controls (38/45 [84.4%] vs 36/60 [60%], P .006). Conclusion: Diabetes may predispose to Achilles tendinopathy and particularly to Achilles enthesopathy. Longitudinal studies, evaluating the progression of the lesions not only in the midportion of the tendon but also at the insertion are needed to support this conclusion. Level of Evidence: Level III, comparative series. © 2013 Reprints and permissions: sagepub.com/journalsPermissions.nav.


Paineau E.,University Paris - Sud | Albouy P.-A.,University Paris - Sud | Rouzieire S.,University Paris - Sud | Orecchini A.,Laue Langevin Institute | And 3 more authors.
Nano Letters | Year: 2013

We present in situ monitoring of water filling of single-walled carbon nanotubes at room temperature, using X-ray scattering. A systematic method is developed to determine the water radial density profile. Water filling is homogeneous below about 5% in mass, whereas it structures into three layers above. These results should motivate further theoretical and simulations studies and allow getting a better understanding of the very peculiar properties of water confined in hydrophobic environment. © 2013 American Chemical Society.


Asdrubali F.,University of Perugia | Baldassarri C.,University of Perugia | Fthenakis V.,Brookhaven National Laboratory
Energy and Buildings | Year: 2013

Life Cycle Assessment (LCA) is a widely known methodology for "cradle to grave" investigation of the environmental impacts of products and technological lifecycles; however, this methodology has not been yet broadly used as an eco-design tool among the practitioners of the building sector. We applied LCA on three conventional Italian buildings - a detached residential house, a multi-family and a multi-story office building. Our analysis includes all the life stages, from the production of the construction materials, to their transportation, assembling, lighting, appliances, cooling- and heating-usages during the operating phase, to the end of life of all the materials and components. We found that the operation phase has the greatest contribution to the total impact (from 77% of that of the detached house, up to 85% of the office building), whereas the impact of the construction phase ranges from about 14% (office building) to 21% (detached house). We carried further analyses to evaluate the influence of various optimizations of the buildings, e.g., more efficient envelopes and facilities, on the entire life cycle of the three buildings. In addition, we propose a methodological approach, which can contribute to the acceptance of LCA as a tool in the eco-friendly design of buildings, especially those buildings whose impact during the construction phase needs to be carefully checked, such as Nearly Zero Energy Buildings. © 2013 Elsevier B.V. All rights reserved.


Hutton J.L.,University of Warwick | Stanghellini E.,University of Perugia
Statistics in Medicine | Year: 2011

Health care interventions that use quality of life or health scores often provide data which are skewed and bounded. The scores are typically formed by adding up numerical responses to a number of questions. Different questions might have different weights, but the scores will be bounded, and are often scaled to the range 0-100. If improvement in health over time is measured, scores will tend to cluster near the 'healthy' or 'good' boundary as time progresses, leading to a skew distribution. Further, some patients will drop-out as time progresses, hence the scores reflect a selected population.We fit models based on the skew-normal distribution to data from a randomized controlled trial of treatments for sprained ankles, in which scores were recorded at baseline and at 1, 3 and 9 months after injury. We consider the extent to which skewness in the data can be explained by clustering at the boundary via a comparison between a censored normal and a censored skew-normal model.As this analysis is based on the complete data only, a formula for the bias of the treatment effects due to informative drop-out is given. This allows us to assess under what conditions the conclusions drawn from the complete data might be either reinforced or reversed, when the informative drop-out process is taken into account. Copyright © 2010 John Wiley & Sons, Ltd.


De Angelis A.,University of Perugia | Fischione C.,KTH Royal Institute of Technology
IEEE Journal on Selected Areas in Communications | Year: 2015

Accurate estimation of the position of network nodes is essential, e.g., in localization, geographic routing, and vehicular networks. Unfortunately, typical positioning techniques based on ranging or on velocity and angular measurements are inherently limited. To overcome the limitations of specific positioning techniques, the fusion of multiple and heterogeneous sensor information is an appealing strategy. In this paper, we investigate the fundamental performance of linear fusion of multiple measurements of the position of mobile nodes, and propose a new distributed recursive position estimator. The Cramér-Rao lower bounds for the parametric and a-posteriori cases are investigated. The proposed estimator combines information coming from ranging, speed, and angular measurements, which is jointly fused by a Pareto optimization problem where the mean and the variance of the localization error are simultaneously minimized. A distinguished feature of the method is that it assumes a very simple dynamical model of the mobility and therefore it is applicable to a large number of scenarios providing good performance. The main challenge is the characterization of the statistical information needed to model the Fisher information matrix and the Pareto optimization problem. The proposed analysis is validated by Monte Carlo simulations, and the performance is compared to several Kalman-based filters, commonly employed for localization and sensor fusion. Simulation results show that the proposed estimator outperforms the traditional approaches that are based on the extended Kalman filter when no assumption on the model of motion is used. In such a scenario, better performance is achieved by the proposed method, but at the price of an increased computational complexity. © 2015 IEEE.


Benet L.Z.,University of California at San Francisco | Broccatelli F.,University of California at San Francisco | Broccatelli F.,University of Perugia | Oprea T.I.,Sunset Molecular Discovery LLC | And 2 more authors.
AAPS Journal | Year: 2011

Here, we compile the Biopharmaceutics Drug Disposition Classification System (BDDCS) classification for 927 drugs, which include 30 active metabolites. Of the 897 parent drugs, 78.8% (707) are administered orally. Where the lowest measured solubility is found, this value is reported for 72.7% (513) of these orally administered drugs and a dose number is recorded. The measured values are reported for percent excreted unchanged in urine, LogP, and LogD 7.4 when available. For all 927 compounds, the in silico parameters for predicted Log solubility in water, calculated LogP, polar surface area, and the number of hydrogen bond acceptors and hydrogen bond donors for the active moiety are also provided, thereby allowing comparison analyses for both in silico and experimentally measured values. We discuss the potential use of BDDCS to estimate the disposition characteristics of novel chemicals (new molecular entities) in the early stages of drug discovery and development. Transporter effects in the intestine and the liver are not clinically relevant for BDDCS class 1 drugs, but potentially can have a high impact for class 2 (efflux in the gut, and efflux and uptake in the liver) and class 3 (uptake and efflux in both gut and liver) drugs. A combination of high dose and low solubility is likely to cause BDDCS class 4 to be underpopulated in terms of approved drugs (N∈=∈53 compared with over 200 each in classes 1-3). The influence of several measured and in silico parameters in the process of BDDCS category assignment is discussed in detail. © 2011 American Association of Pharmaceutical Scientists.


Amison R.T.,King's College London | Momi S.,University of Perugia | Morris A.,King's College London | Manni G.,University of Perugia | And 4 more authors.
Journal of Allergy and Clinical Immunology | Year: 2015

Background Clinical studies reveal platelet activation in patients with asthma, allergic rhinitis, and eczema. This is distinct from platelet aggregation, which is critical for the maintenance of hemostasis and in which a role for platelet purinergic receptors is well documented. However, purines are also essential for inflammatory cell trafficking in animal models of allergic lung inflammation, which are known to be platelet dependent, yet the role of purines in the platelet activation accompanying inflammation is unknown. Objectives We investigated whether the involvement of purine activation of platelets during allergic inflammation is distinct from purine involvement in platelet aggregation. Methods BALB/c mice were sensitized to ovalbumin and subsequent airway ovalbumin challenge. Bronchoalveolar lavage fluid was analyzed for inflammatory cells, and blood samples were assessed for platelet activation. The role of platelet purinergic receptors and associated signaling mechanisms (RhoA) were assessed. Results P2Y1, but not P2Y12 or P2X1, antagonism inhibited pulmonary leukocyte recruitment. The formation of platelet-leukocyte complexes in vivo and platelet/P-selectin-dependent polymorphonuclear cell migration in vitro were exclusively platelet P2Y1 receptor dependent. Furthermore, platelet P2Y1 activation resulted in RhoA activity in vivo after allergen challenge, and RhoA signaling in platelets through P2Y1 stimulation was required for platelet-dependent leukocyte chemotaxis in vitro. Leukocyte recruitment in thrombocytopenic mice remained suppressed after reinfusion of platelets pretreated with a P2Y1 antagonist or a Rho-associated kinase 1 inhibitor, confirming the crucial role of platelet P2Y1 receptor and subsequent activation of RhoA. Conclusion RhoA signaling downstream of platelet P2Y1, but not P2Y12, represents a clear dichotomy in platelet activation during allergic inflammation versus hemostasis. © 2014 American Academy of Allergy, Asthma & Immunology.


Mangera A.,Sheffield Teaching Hospitals NHS Trust | Apostolidis A.,Aristotle University of Thessaloniki | Andersson K.E.,Wake forest University | Dasgupta P.,King's College London | And 4 more authors.
European Urology | Year: 2014

Context Botulinum toxin A (BoNTA) has received regulatory approval for use in neurogenic detrusor overactivity (NDO) and overactive bladder (OAB), but it remains unlicensed in other lower urinary tract symptoms (LUTS) indications such as nonneurogenic LUTS in men with benign prostatic enlargement (LUTS/BPE), bladder pain syndrome (BPS), and detrusor sphincter dyssynergia (DSD). Objective To compare statistically the outcomes of high level of evidence (LE) studies with placebo using BoNTA for LUTS indications; NDO, OAB, LUTS/BPE, BPS and DSD. Evidence acquisition We conducted a systematic review of the published literature on PubMed, Scopus, and Embase reporting on BoNTA use in LUTS dysfunction. Statistical comparison was made between high LE studies with placebo and low LE studies. Evidence synthesis In adult NDO, there are significantly greater improvements with BoNTA in daily incontinence and catheterisation episodes (-63% and -18%, respectively; p < 0.01), and the urodynamic parameters of maximum cystometric capacity (MCC), reflex volume, and maximum detrusor pressure (MDP) (68%, 61%, and -42%, respectively; all p < 0.01). In OAB, BoNTA leads to significant improvements in bladder diary parameters such as daily frequency (-29%), daily urgency (-38%), and daily incontinence (-59%) (all p < 0.02). The urodynamic parameters of MCC and MDP improved by 58% (p = 0.04) and -29% (p = 0.002), respectively. The risk of urinary tract infection was significantly increased from placebo at 21% versus 7% (p < 0.001), respectively; the risk of intermittent self-catherisation increased from 0% to 12% (p < 0.001). Men with LUTS/BPE showed no significant improvements in International Prostate Symptom Score, maximum flow rate, or prostate volume. There were insufficient data for statistical analysis in DSD, BPS, and paediatric studies. Low LE studies were found to overestimate the effects of BoNTA in all indications, but differences from high LE studies were significant in only a few parameters. Conclusions BoNTA significantly improves all symptoms and urodynamic parameters in NDO and OAB. The effect of BoNTA in treating LUTS dysfunction appears to be overestimated in lower as opposed to higher LE studies. © 2013 European Association of Urology.


Folletti I.,University of Perugia | Zock J.-P.,CIBER ISCIII | Moscato G.,Institute of Care and Research | Siracusa A.,University of Perugia
Journal of Asthma | Year: 2014

Objective: This article presents a systematic review of epidemiological studies linking cleaning work and risk of asthma and rhinitis. Methods: Published reports were identified from PubMed covering the years from 1976 through June 30, 2012. In total, we identified 24 papers for inclusion in the review. The quality of studies was evaluated using the Strengthening of the Reporting of Observational Studies in Epidemiology (STROBE) statement checklist of 22 items for cross-sectional, cohort and case-control studies. Results: Increased risk of asthma or rhinitis has been shown in 79% of included epidemiological studies. In four studies the increased risk of asthma in cleaning workers was confirmed by objective tests, such as bronchial hyper-reactivity or airflow obstruction. Level of exposure to cleaning products, cleaning sprays, bleach, ammonia, mixing products and specific job tasks has been identified as specific causes of asthma and rhinitis. Conclusions: Possible preventive measures encompass the substitution of cleaning sprays, bleach and ammonia, avoidance of mixing products, the use of respiratory protective devices, worker education and medical surveillance. © 2014 Informa Healthcare USA, Inc.


Verrotti A.,University of Perugia | Loiacono G.,University of Chieti Pescara | Rossi A.,University of Chieti Pescara | Zaccara G.,U.O. Neurologia
Epilepsy Research | Year: 2014

Epilepsy is a common neurological disorder. Despite a broad range of commonly used antiepileptic drugs, approximately 30% of patients with epilepsy have drug resistance or encounter significant adverse effects. Eslicarbazepine acetate is a new central nervous system-active compound with anticonvulsant activity whose mechanism of action is by blocking the voltage-gated sodium channel. Eslicarbazepine acetate was approved by the European Medicines Agency and launched onto the European market in 2009 for adjunctive treatment in adult subjects of partial-onset seizures, with or without secondary generalization. This article provides an overview on the recent studies on eslicarbazepine acetate in the treatment of drug-resistant partial epilepsy. Efficacy and safety of this drug for partial-onset seizures were assessed in four randomized clinical trials with responder rates ranged between 17% and 43%. Adverse events were usually mild to moderate in intensity and the most common were dizziness, somnolence, nausea, diplopia, headache, vomiting, abnormal coordination, blurred vision, vertigo and fatigue. Eslicarbazepine acetate is not recommended below 18 years, but a published phase II trial had the main goal to evaluate the pharmacokinetics, efficacy and safety of this drug in pediatric population. Eslicarbazepine acetate appears to be a safe and effective drug with a linear pharmacokinetics, very low potential for drug-drug interactions and therefore it can offer a valid alternative to current antiepileptic drugs. Additionally, it is undergoing investigation for monotherapy in subjects with partial epilepsy, and other neurological and psychiatric disorders. © 2013 Elsevier B.V.


Federici L.,University of Chieti Pescara | Falini B.,University of Perugia
Protein Science | Year: 2013

Nucleophosmin (NPM1) is an abundant, ubiquitously expressed protein mainly localized at nucleoli but continuously shuttling between nucleus and cytoplasm. NPM1 plays a role in several cellular functions, including ribosome biogenesis and export, centrosome duplication, chromatin remodeling, DNA repair, and response to stress stimuli.Much of the interest in this protein arises fromits relevance in humanmalignancies. NPM1 is frequently overexpressed in solid tumors and is the target of several chromosomal translocations in hematologic neoplasms. Notably, NPM1 has been characterized as the most frequently mutated gene in acute myeloid leukemia (AML).Mutations alter the C-terminal DNAbinding domain of the protein and result in its aberrant nuclear export and stable cytosolic localization. In this review, we focus on the leukemia-associated NPM1 C-terminal domain and describe its structure, function, and the effect exerted by leukemicmutations. Finally,we discuss the possibility to target NPM1 for the treatment of cancer and, in particular, of AML patientswithmutated NPM1 gene. © 2013 The Protein Society.


Marcos V.,Autonomous University of Madrid | Aleman J.,Autonomous University of Madrid | Garcia Ruano J.L.,Autonomous University of Madrid | Marini F.,University of Perugia | Tiecco M.,University of Perugia
Organic Letters | Year: 2011

A new organocatalytic approach for the synthesis of a variety of α-alkyl, α-phenylselenyl ketones as well as their corresponding esters and amides, by the addition of α-selenocarbonyl derivatives to nitroalkenes catalyzed by thiourea or squaramide cinchona catalysts, is presented. This catalytic system allows the preparation in high yields of enantiomerically enriched selenocarbonyl derivatives bearing two chiral centers with excellent ee's and dr's by using catalytic loadings of 3 mol %. © 2011 American Chemical Society.


Brahmer J.,Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Reckamp K.L.,City of Hope Comprehensive Cancer Center | Baas P.,Netherlands Cancer Institute | Crino L.,University of Perugia | And 21 more authors.
New England Journal of Medicine | Year: 2015

BACKGROUND Patients with advanced squamous-cell non-small-cell lung cancer (NSCLC) who have disease progression during or after first-line chemotherapy have limited treatment options. This randomized, open-label, international, phase 3 study evaluated the efficacy and safety of nivolumab, a fully human IgG4 programmed death 1 (PD-1) immune-checkpoint-inhibitor antibody, as compared with docetaxel in this patient population. METHODS We randomly assigned 272 patients to receive nivolumab, at a dose of 3 mg per kilogram of body weight every 2 weeks, or docetaxel, at a dose of 75 mg per square meter of body-surface area every 3 weeks. The primary end point was overall survival. RESULTS The median overall survival was 9.2 months (95% confidence interval [CI], 7.3 to 13.3) with nivolumab versus 6.0 months (95% CI, 5.1 to 7.3) with docetaxel. The risk of death was 41% lower with nivolumab than with docetaxel (hazard ratio, 0.59; 95% CI, 0.44 to 0.79; P<0.001). At 1 year, the overall survival rate was 42% (95% CI, 34 to 50) with nivolumab versus 24% (95% CI, 17 to 31) with docetaxel. The response rate was 20% with nivolumab versus 9% with docetaxel (P = 0.008). The median progression-free survival was 3.5 months with nivolumab versus 2.8 months with docetaxel (hazard ratio for death or disease progression, 0.62; 95% CI, 0.47 to 0.81; P<0.001). The expression of the PD-1 ligand (PD-L1) was neither prognostic nor predictive of benefit. Treatment-related adverse events of grade 3 or 4 were reported in 7% of the patients in the nivolumab group as compared with 55% of those in the docetaxel group. CONCLUSIONS Among patients with advanced, previously treated squamous-cell NSCLC, overall survival, response rate, and progression-free survival were significantly better with nivolumab than with docetaxel, regardless of PD-L1 expression level. Copyright © 2015 Massachusetts Medical Society.


De Angelis F.,University of Perugia | Fantacci S.,University of Perugia | Fantacci S.,Italian Institute of Technology | Gebauer R.,Abdus Salam International Center For Theoretical Physics | Gebauer R.,CNR Institute of Materials
Journal of Physical Chemistry Letters | Year: 2011

Dye-sensitized solar cells (DSCs) represent a valuable, efficient, and low-cost alternative to conventional semiconductor photovoltaic devices. A deeper understanding of the dye/semiconductor heterointerface and of the dye-sensitized semiconductor/electrolyte interactions are fundamental for further progress in DSC technology. Here we report an ab initio molecular dynamics simulation of a dye-sensitized TiO2 heterointerface "immersed" in an explicit water environment for an efficient organic dye, followed by TDDFT excited state calculations of the coupled dye/semiconductor/solvent system. This new computational protocol and the extended model system allows us to gain unprecedented insight into the excited state changes occurring for the solvated dye-sensitized heterointerface at room temperature, and to provide an atomistic picture of water-mediated dye desorption. © 2011 American Chemical Society.


Cardelli E.,University of Perugia | Cardelli E.,Center for Electrical and Magnetic Applied Research
IEEE Transactions on Magnetics | Year: 2011

This paper deals with the modeling of vector fields that exhibit hysteresis. A general class of models of vector magnetizations with hysteresis that form a natural extension of the Classical Scalar Preisach Model is defined. Although the modeling was done for the 2-d case, the same theory can be extended to the 3-d case as well. After reviewing some general properties of conservative fields, the specific case of unit magnitude vector fields is discussed. The paper focuses on discussing the properties of a general vector hysteresis operator (hysteron). The mathematical approach followed here can be applied not only to the magnetic hysteresis, but also to any hysteresis process. Some examples of vector hysterons, deduced from the general definition, are presented and their properties analyzed. © 2011 IEEE.


Bernardini E.,University of Notre Dame | Spence S.M.J.,University of Notre Dame | Gioffre M.,University of Perugia
Engineering Structures | Year: 2012

The wind loads on tall buildings can be estimated from the measurement of the base moments on rigid scale models with a high frequency force balance. Two main methods exist to this end, the most common of which is based on the definition of correction coefficients exploiting the close relation between the first three generalized forces and the base moments. In alternative, an approach based on calibrating spatio-temporal/-frequency models of the wind load distribution over the building height can be adopted. The main limitation inherent to both approaches consists in the introduction of uncertainties due to the lack of information concerning the wind load distribution. This source of error has not been sufficiently investigated especially in consideration of modern tall buildings characterized by complex profiles and coupled dynamic modes. The aim of this work is to study the errors induced in the response parameters by the aforementioned uncertainties. Results from specific wind tunnel tests are used to compare structural systems with both uncoupled and coupled dynamic modes and with geometrically simple and complex profiles. A quantitative evaluation of the error spread is proposed highlighting the significant sensitivity of irregular coupled buildings. © 2012 Elsevier Ltd.


Perticaroli S.,University of Perugia | Comez L.,University of Perugia | Comez L.,CNR Institute of Materials | Paolantoni M.,University of Perugia | And 3 more authors.
Journal of the American Chemical Society | Year: 2011

We have studied the influence of the amphiphilic model peptide N-acetyl-leucine-methylamide (NALMA) on the dynamics of water using extended frequency range depolarized light scattering (EDLS), between 0.3 GHz and 36 THz. This technique allowed us to separate solute from solvent dynamics and bulk from hydration water, providing both characteristic times and relative fractions. In the temperature range 5-65 °C, a retardation factor from 9 to 7 is found for water hydrating NALMA. Moreover, in the same range, a hydration number from 62 to 50 is observed, corresponding to more than two hydration layers. This strong perturbation suggests the existence of a collective effect of amphiphilic molecules on surrounding water molecules. © 2011 American Chemical Society.


D'Abrusco R.,Smithsonian Astrophysical Observatory | Massaro F.,Kavli Institute for Particle Astrophysics and Cosmology | Paggi A.,Smithsonian Astrophysical Observatory | Masetti N.,Istituto di Astrofisica Spaziale e Fisica Cosmica | And 4 more authors.
Astrophysical Journal, Supplement Series | Year: 2013

We present a new method for identifying blazar candidates by examining the locus, i.e., the region occupied by the Fermi γ-ray blazars in the three-dimensional color space defined by the WISE infrared colors. This method is a refinement of our previous approach that made use of the two-dimensional projection of the distribution of WISE γ-ray-emitting blazars (the Strip) in the three WISE color-color planes. In this paper, we define the three-dimensional locus by means of a principal component analysis of the color distribution of a large sample of blazars composed of all the ROMA-BZCAT sources with counterparts in the WISE All-Sky Catalog associated with γ-ray sources in the second Fermi-LAT catalog (2FGL; the WISE Fermi blazars sample, WFB). Our new procedure yields a total completeness of c tot ∼ 81% and a total efficiency of e tot ∼ 97%. We also obtain local estimates of the efficiency and completeness as functions of the WISE colors and galactic coordinates of the candidate blazars. The catalog of all WISE candidate blazars associated with the WFB sample is also presented, complemented by archival multi-frequency information for the alternative associations. Finally, we apply the new association procedure to all γ-ray blazars in the 2FGL and provide a catalog containing all the γ-ray candidate blazars selected according to our procedure. © 2013. The American Astronomical Society. All rights reserved.


Azevedo R.T.,University of Rome La Sapienza | Macaluso E.,IRCCS Fondazione Santa Lucia | Avenanti A.,IRCCS Fondazione Santa Lucia | Avenanti A.,University of Bologna | And 5 more authors.
Human Brain Mapping | Year: 2013

Recent advances in social neuroscience research have unveiled the neurophysiological correlates of race and intergroup processing. However, little is known about the neural mechanisms underlying intergroup empathy. Combining event-related fMRI with measurements of pupil dilation as an index of autonomic reactivity, we explored how race and group membership affect empathy-related responses. White and Black subjects were presented with video clips depicting white, black, and unfamiliar violet-skinned hands being either painfully penetrated by a syringe or being touched by a Q-tip. Both hemodynamic activity within areas known to be involved in the processing of first and third-person emotional experiences of pain, i.e., bilateral anterior insula, and autonomic reactivity were greater for the pain experienced by own-race compared to that of other-race and violet models. Interestingly, greater implicit racial bias predicted increased activity within the left anterior insula during the observation of own-race pain relative to other-race pain. Our findings highlight the close link between group-based segregation and empathic processing. Moreover, they demonstrate the relative influence of culturally acquired implicit attitudes and perceived similarity/familiarity with the target in shaping emotional responses to others' physical pain. © 2012 Wiley Periodicals, Inc.


Massaro F.,Kavli Institute for Particle Astrophysics and Cosmology | Giroletti M.,National institute for astrophysics | Paggi A.,Smithsonian Astrophysical Observatory | D'Abrusco R.,Smithsonian Astrophysical Observatory | And 2 more authors.
Astrophysical Journal, Supplement Series | Year: 2013

Blazars are the most extreme class of active galactic nuclei. Despite a previous investigation at 102 MHz for a small sample of BL Lac objects and our recent analysis of blazars detected in the Westerbork Northern Sky Survey, a systematic study of the blazar spectral properties at frequencies below 100 MHz has been never carried out. In this paper, we present the first analysis of the radio spectral behavior of blazars based on the recent Very Large Array Low-frequency Sky Survey (VLSS) at 74 MHz. We search for blazar counterparts in the VLSS catalog, confirming that they are detected at 74 MHz. We then show that blazars present radio-flat spectra (i.e., radio spectral indices of 0.5) when evaluated, which also about an order of magnitude in frequency lower than previous analyses. Finally, we discuss the implications of our findings in the context of the blazars-radio galaxies connection since the low-frequency radio data provide a new diagnostic tool to verify the expectations of the unification scenario for radio-loud active galaxies. © 2013. The American Astronomical Society. All rights reserved..


Massaro F.,Kavli Institute for Particle Astrophysics and Cosmology | D'Abrusco R.,Smithsonian Astrophysical Observatory | Paggi A.,Smithsonian Astrophysical Observatory | Masetti N.,Istituto di Astrofisica Spaziale e Fisica Cosmica | And 5 more authors.
Astrophysical Journal, Supplement Series | Year: 2013

A significant fraction (∼30%) of the high-energy gamma-ray sources listed in the second Fermi Large Area Telescope catalog (2FGL) are still of unknown origin, being not yet associated with counterparts at low energies. We recently developed a new association method to identify if there is a γ-ray blazar candidate within the positional uncertainty region of a generic 2FGL source. This method is entirely based on the discovery that blazars have distinct infrared colors with respect to other extragalactic sources found, thanks to the Wide-field Infrared Survey Explorer (WISE) all-sky observations. Several improvements have also been performed to increase the efficiency of our method in recognizing γ-ray blazar candidates. In this paper we applied our method to two different samples, the first constituted by unidentified γ-ray sources (UGSs), and the second by active galaxies of uncertain type, both listed in the 2FGL. We present a catalog of IR counterparts for ∼20% of the UGSs investigated. Then, we also compare our results for the associated sources with those present in the literature. In addition, we illustrate the extensive archival research carried out to identify the radio, infrared, optical, and X-ray counterparts of the WISE-selected, γ-ray blazar candidates. Finally, we discuss the future developments of our method based on ground-based follow-up observations. © 2013. The American Astronomical Society. All rights reserved.


The effect of co-digesting sludge with bio-waste was investigated using an experimental apparatus set for reproducing the operating conditions of a full-scale digester in an existing wastewater treatment plant of 90,000 PE (population equivalent). An increase in the organic loading rate from 1.46 kgVS/m3 day to 2.1 kgVS/m3 day obtained by introducing 40 kg of biowaste per m3 of sludge in the digester caused an increase in the specific methane generation from 90 NL/kgVS to 435 NL/kgVS. These results were used to assess the energetic potential of digesters in eight existing wastewater treatment plants operating in an Italian province with 28,000 PE to 90,000 PE. Results showed that these facilities were able to co-digest globally about 2900 tonnes per year of bio-waste and to generate about 3400 MWh/year of electricity. © 2016 Elsevier Ltd.


Massaro F.,Kavli Institute for Particle Astrophysics and Cosmology | Paggi A.,Smithsonian Astrophysical Observatory | Errando M.,Barnard College | D'Abrusco R.,Smithsonian Astrophysical Observatory | And 3 more authors.
Astrophysical Journal, Supplement Series | Year: 2013

BL Lac objects are the most numerous class of extragalactic TeV-detected sources. One of the biggest difficulties in investigating their TeV emission is due to their limited number, since only 47 BL Lac objects are known to be TeV emitters. In this paper, we propose new criteria to select TeV BL Lac candidates based on infrared and X-ray observations. We apply our selection criteria to the BL Lac objects listed in the ROMA-BZCAT catalog, thereby identifying 41 potential TeV emitters. We then perform a search over a more extended sample combining the ROSAT bright source catalog and the WISE all-sky survey, revealing 54 additional candidates for TeV observations. Our investigation also led to a tentative classification of 16 unidentified X-ray sources as BL Lac candidates. This analysis provides new interesting BL Lac targets for future observations with ground-based Cherenkov telescopes. © 2013. The American Astronomical Society. All rights reserved.


Grant
Agency: European Commission | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-2013-ITN | Award Amount: 3.56M | Year: 2014

Explosive volcanic eruptions are an unavoidable natural hazard: Volcanic ash, the ejected lethal mixture of crystals, lava, glass and older rocks, is the most far-reaching threat. In April 2010, the ash cloud from Eyjafjall volcano in Iceland, a comparatively small event, paralysed large parts of Europe for up to one week in a manner unique in history. The impact was dramatic: several million passengers were grounded due to closed air pace and decelerated or halted industrial production caused several billion Euros of estimated economic loss. This scenario was largely amplified by the quasi-Babylonian lack of understanding and interaction amongst volcanologists, meteorologists, atmospheric researchers, engineers, private sector and politics. This eruption was not a singular accident: Europe has active volcanoes and is surrounded by others and must be prepared for similar future events. This requires a comprehensive and supra-disciplinary approach to allow for an encompassing mechanistic and quantitative understanding of the physico-chemical processes during the lifecycle of volcanic ash: from formation in a volcano, through changes during the dispersal in the atmosphere to the impacts on life and society. VERTIGO will address this challenging issue with a unique and innovative portfolio of partners from academia, research institutes and the private sector from eight European countries. We will offer an unmatched platform for research and training for highly-skilled students with a background in geology/volcanology, petrology/chemistry, informatics, biology, toxicology, fluid dynamics and/or engineering. The research-through-training projects for 13 students accomplish the EUROPE2020 strategy for a modern system of education. They will be educated in scientific and transferable skills, spiced with experience in private sector applications, to qualify for career opportunities in academia, research institutes, civil protection and private sector.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-IP | Phase: SSH.2011.5.1-1 | Award Amount: 10.40M | Year: 2012

The central objective of ANTICORRP is to investigate and explain the factors that promote or hinder the development of effective anticorruption policies and impartial government institutions. ANTICORRP directly addresses the objective in the Work Program by examining what the causes of corruption are, how corruption can be conceptualized, measured and analysed, what the impact of corruption on societies is and how policy responses can be tailored as to deal effectively with this phenomenon. The starting point for this project is the following: The knowledge about the very negative impact that corruption has on a great number of factors that are important for human well-being (economic prosperity, population health, life satisfaction, gender equality, social trust, political legitimacy, etc.) is now well established. At the same time, knowledge about how corruption can be successfully fought by political means is much less developed. While this project concentrates on corruption in Europe, ANTICORRP also has a global scope. The project will identify general global trends concerning corruption and select over-performing and under-performing countries in terms of their progress towards less corrupt governance regimes and conduct more detailed qualitative analyses of these cases. The project includes participants from anthropology, criminology, economics, gender studies, history, legal studies, political science, public policy and administration and sociology at twenty-one units in sixteen European countries. Research will be conduced using a various set of methods including historical case-studies, large-scale surveys and ethnographical approaches. The project will strive to ensure that the research findings are spread to policy makers and the general public by using high profile multimedia and data visualisation tools as well as research-to-policy workshops at different levels and for different target audiences.


Grant
Agency: European Commission | Branch: H2020 | Program: CSA | Phase: LCE-20-2014 | Award Amount: 4.30M | Year: 2015

Following the EC SET-Plan Education and Training Roadmap, the concept of this proposal is to develop a joint PhD programme between universities and research centres, on the topic of Thermal Energy Storage (TES). The goal of INPATH-TES is to create a network of universities and research institutes to implement a joint PhD programme on TES technologies. The final result of such a network is to educate professionals on these technologies for the European research and industry institutions. The consortium includes 14 universities that will implement the joint PhD programme, two research institutions (AIT and PROMES-CNRS), three companies and two SME (Arcelik, Abengoa Solar NT, KIC InnoEnergy, UFP and LAIF), that will cooperate in defining the programme and in its implementation and deployment. The specific objectives of the project will lead to the qualification of professionals for the European research and industry institutions, bringing Europe to continue being leaders in these technologies. The partners in the proposal will be the core of a future larger network of excellent R&D institutions, and industries for co-funding and industrial placement, sharing infrastructure capacities, and enhancing mobility of students. The overall approach of the project involves a work plan divided in six work packages, being either coordination or support activities. Coordination activities: WP1 Management and coordination; WP3 Developing, maintaining and updating a PhD programme in TES; and WP4 Implementation of the PhD programme in TES. Support activities: WP2 External communication and dissemination; WP5 Stakeholder involvement and extension of partnerships; and WP6 Framework for monitoring and evaluation of INPATH-TES as well as IPR and regulatory issues.


Grant
Agency: European Commission | Branch: FP7 | Program: CP | Phase: ICT-2007.3.6 | Award Amount: 3.92M | Year: 2008

ARASCOM OBJECTIVESOur project is focused on Research & Development for efficient use of micro-nano devices as basis of agile antennas with moderate cost, that are more and more required in advanced systems for Communication, Safety and Security. We will assess this until representative prototypes at a very large and innovative level:\tvery large because the developed agile reflectarray antennas for Communication (to be implemented in base-stations and satellites) will comprise thousands of RF-MEMS switches integrated in the radiating board for phase-controlling the reflected waves\tinnovative: first because such quantities will require both accurate & safe design, and setting-up industrial processes including on-wafer packaging and automatic assembling, to reach higher reproducibility in top-level performances (improving reliability) than previous European projects on RF-MEMS\tinnovative especially because to operate at the very high frequencies suited to security imaging, safe-landing & anti-collision radar (typically around 77 GHz), will be developed new phase-shifters combining MEMS with nematic Liquid Crystals ; the latter provide variable permittivity by adjusting molecules orientation, so may be called nano-scale control devices.So both Micro (MEMS) & Nano (nematic LC) technologies will be deeply investigated, for their best properties in agile antennas.PROJECT TEAMTo reach the presented objectives, we gathered 9 complementary partners from 4 large member-states:-\t3 among the best European academies for MEMS & LC design (U. Perugia, T.U.Darmstadt), as for reflectarray antennas (U.P.Madrid & Perugia)-\t2 public Research institutes, leaders for RF-MEMS development over a large range of frequencies (LETI, FBK)-\t4 industrial end-users among the main players in Communication, Security & Safety: SELEX-SI for concealed weapon detection, EADS-Innovation Works for helicopters landing radar, Thales Alenia Space for satellites and S.R.F.Moyano for base-stations.


Grant
Agency: European Commission | Branch: FP7 | Program: BSG-SME-AG | Phase: SME-2 | Award Amount: 2.04M | Year: 2009

The European olive oil sector is nowadays facing several stresses that push towards a new approach to production. Despite worldwide consumption rises; new producer countries enter the markets and increase competition, threatening European producers position. Besides, the high polluting character of its residues, poses serious problems to the olive mills, especially in the case of small and medium ones. All the groups involved agree on the need for a more sustainable approach to production, where environmental conditions are taken into consideration without damaging productivity. Even though efforts have been made so far for bringing the results obtained to practice, many local producers associations still lack a clear guidance adapted to their needs in specific fields, resulting in giving up the implementation of these activities after the institutional support is over. The proposing IAGs intend to take an integrated and more proactive approach to the problem: This polluting charge of olive mill waste (OMW) can be taken as an advantage to produce energy: OMW has many uses in renewable energy: it can, for instance, be gasified to obtain hydrogen, digested in an anaerobic process to obtain methane, or directly used in combustion. RESOLIVE will also explore other processes to obtain a valuable outcome from olive mill residues: solar distillation, composting, etc. The main objectives of the proposed project are: - To define the needs for the implementation of renewable energy solutions specific to the olive oil industry and proceed to test in practice their performance. - To create a comprehensive set of guidelines that will advice the associates of olive oil producers cooperatives deciding which of the available options for the implementation of renewable energy suits their conditions best. - To summarize the existing knowledge in olive waste valorisation and transfer this knowledge to its end users, supporting them in the further implementation.


Couret J.,Emory University | Dotson E.,Centers for Disease Control and Prevention | Benedict M.Q.,University of Perugia
PLoS ONE | Year: 2014

Many environmental factors, biotic and abiotic interact to influence organismal development. Given the importance of Aedes aegypti as a vector of human pathogens including dengue and yellow fever, understanding the impact of environmental factors such as temperature, resource availability, and intraspecific competition during development is critical for population control purposes. Despite known associations between developmental traits and factors of diet and density, temperature has been considered the primary driver of development rate and survival. To determine the relative importance of these critical factors, wide gradients of conditions must be considered. We hypothesize that 1) diet and density, as well as temperature influence the variation in development rate and survival, 2) that these factors interact, and this interaction is also necessary to understand variation in developmental traits. Temperature, diet, density, and their twoway interactions are significant factors in explaining development rate variation of the larval stages of Ae. aegypti mosquitoes. These factors as well as two and three-way interactions are significantly associated with the development rate from hatch to emergence. Temperature, but not diet or density, significantly impacted juvenile mortality. Development time was heteroskedastic with the highest variation occurring at the extremes of diet and density conditions. All three factors significantly impacted survival curves of experimental larvae that died during development. Complex interactions may contribute to variation in development rate. To better predict variation in development rate and survival in Ae. aegypti, factors of resource availability and intraspecific density must be considered in addition, but never to the exclusion of temperature.


Grant
Agency: European Commission | Branch: FP7 | Program: BSG-SME-AG | Phase: SME-2 | Award Amount: 2.90M | Year: 2009

The EU malting barley industry supplies almost 50% of global malting barley requirements. The sustainability of thousands of EU SME farmers depend on the competitiveness of this industry, as is the quality of our brewing and distilling industries. Malting barley demands a premium at the farm gate but, in return, must exceed a range of malting quality (MQ) parameters laid down by the processing industries. Determination of barley MQ is a critical issue, as the accuracy of its assessment determines if the barley is suitable to be taken into the plant, influencing its price and subsequent quality of the end product. MQ is a complex character. To date its grading is largely dependent on a combination of visual appraisals of the barley and other assessments, including wet chemistry techniques, to segregate malting barley into grades of different end use value. Current assessment practices are plagued with limitations: time and labour intensive, prone to operator interpretation, etc. This project will provide the Malting Barley chain with a novel MQ assessment tool to replace the expensive, laborious and non-objective standard analyses currently used by the sector. Novel inspection techniques will be researched (NIRS, NIT, Raman, Imaging fluorescence spectroscopy and FT-IR/PAS) to determine their potential for predicting MQ parameters. A prototype measuring instrument will be designed, developed and calibrated against existing reference methods. It will be validated for use along the malting barley chain and will provide analyses in individual and whole barley grains and in a large number of samples in order to assess the homogeneity of the incoming raw material, vital for good MQ determination, and will assist in analysing the malting process. The RTD results will raise the quality of the EU malting barley supply chain, safeguarding growth and employment in many rural economies across EU-27, and ensuring consistent quality in industries dependent on high quality malt


Grant
Agency: European Commission | Branch: FP7 | Program: CP | Phase: SEC-2010.4.3-1 | Award Amount: 3.53M | Year: 2011

The objective of this project proposal is to develop an alerting tool that (a) allows for a rapid simulation of the impact of different alerting strategies (depending on the selected media-mix and current availability of communication media), (b) supports the composition of the optimal mix of communication channels (individualized alerting channels and mass media), (c) improves alert compliance through socio-cultural adaptation and personalization of alert messages and communication channels, (d) supports the rapid and automated implementation of a selected alert strategy, (e) can simultaneously address a plethora of communication channels to facilitate efficient high-throughput alerting, and (f), can be integrated with existing tools and legacy systems via well-defined interfaces. These objectives will be supported by the following key research activities: (a) In-depth analysis of the impact which socio-cultural and regional factors have on risk perception and risk communication, (b) Analysis of the influence which the observed socio-cultural differences have on regional alerting strategies, (c) Analysis of the impact of individualized alerting (via SMS, E-Mail etc.) and alerting via the mass media, (d) Identification of best-practices in alerting via mass media, (e) Definition of appropriate algorithms for the simulation of alert propagation within the population, depending on the selected mix of communication channels. One innovative aspect of this project is to improve the impact of alerts by developing alert strategies which take socio-cultural characteristics of the recipients into account. This can refer both to differences in risk perceptions and different usage patterns with respect to media and communication channels. Based upon the situational and socio-cultural context of an alert situation, the authorities can swiftly simulate different alerting strategies and select the most appropriate one.


Grant
Agency: European Commission | Branch: H2020 | Program: IA | Phase: EE-02-2015 | Award Amount: 4.22M | Year: 2015

In ZERO-PLUS, a comprehensive, cost-effective system for Net Zero Energy (NZE) settlements will be developed and implemented. The system will be composed of innovative solutions for the building envelope, for building energy generation and management, and for energy management at the settlement level. A reduction of operational energy usage to an average of 0-20 kWh/m2 per year (compared with the current average of 70-230 kWh/m2) will be achieved through a transition from single NZE buildings to NZE settlements, in which the energy loads and resources are optimally managed. A primary objective of the project will be to develop a system whose investment costs will be at least 16% lower than current costs. In order to reduce balance of system costs, an approach of mass customization will be employed. Mass produced technologies will be integrated in a system that is optimally designed according to the local climate and site of each project in which it is implemented. To this end, a structured process will be developed and applied for the integration, optimization and verification of the design. The projects work programme will ensure a rapid market uptake, within its four-year scope, of the innovative solutions that will be developed. These solutions will be implemented in four different demonstration projects throughout the EU, with varying climates and building types. The results of their implementation will be monitored, analyzed and disseminated. A comprehensive market analysis and business plan will support the commercial exploitation of the projects results. The project will be carried out by a consortium that includes universities, project owners, technology providers and organizations, which will closely collaborate in all the projects phases.


Madami M.,University of Perugia | Bonetti S.,KTH Royal Institute of Technology | Consolo G.,Messina University | Tacchi S.,University of Perugia | And 8 more authors.
Nature Nanotechnology | Year: 2011

Spin torque oscillators with nanoscale electrical contacts are able to produce coherent spin waves in extended magnetic films, and offer an attractive combination of electrical and magnetic field control, broadband operation, fast spin-wave frequency modulation, and the possibility of synchronizing multiple spin-wave injection sites. However, many potential applications rely on propagating (as opposed to localized) spin waves, and direct evidence for propagation has been lacking. Here, we directly observe a propagating spin wave launched from a spin torque oscillator with a nanoscale electrical contact into an extended Permalloy (nickel iron) film through the spin transfer torque effect. The data, obtained by wave-vector-resolved micro-focused Brillouin light scattering, show that spin waves with tunable frequencies can propagate for several micrometres. Micromagnetic simulations provide the theoretical support to quantitatively reproduce the results. © 2011 Macmillan Publishers Limited. All rights reserved.


Grant
Agency: European Commission | Branch: H2020 | Program: MSCA-ITN-ETN | Phase: MSCA-ITN-2016 | Award Amount: 3.81M | Year: 2016

The NDTonAIR consortium involves Universities, Research Organisations and major European companies working on new Non-Destructive Testing (NDT) and Structural Health Monitoring (SHM) techniques for aerospace, of which both are key technologies. The goal is to train a new generation of scientists and engineers with a wide background of theoretical and experimental skills, capable of developing their research and entrepreneurial activities both in academy and industry and playing an active role in promoting the importance of quality inspection and structural monitoring in aerospace components. The objective of the training programme is to provide the recruited researchers with an extensive and varied training on: (1) Fundamentals skills for NDT and SHM through participation in short-courses and seminars organized by the Consortium; (2) NDT and SHM Techniques for Aerospace through research training at host institutions and participation in Workshops and Conferences organized by the Consortium and major international research associations; (3) Technology Transfer and Entrepreneurship through participation in short-courses and seminars organized by the Consortium. The objective of the research programme is to consolidate and innovate current NDT and SHM techniques for Aircraft inspection by (1) investigating new physical phenomena and sensors; (2) developing analytical and numerical models to correlate the results of inspection with material properties; (3) quantifying NDT techniques through their probability of detecting reference defects; (4) developing procedures for the automatic detection and classification of defects; (5) transferring these results to industry. The members of the Consortium will work together for realizing this training programme and scientific collaboration will be stimulated by secondment of the recruited researchers and it will be aimed at improving the integration and comparison of different NDT techniques.


Grant
Agency: European Commission | Branch: FP7 | Program: CSA-SA | Phase: HEALTH-2007-2.2.2-4 | Award Amount: 840.61K | Year: 2008

AIM. To investigate the reasons for the exclusion of the elderly in clinical trials and to provide solutions for this problem. INTRODUCTION. Although the elderly account for high drug consumption, they are underrepresented in clinical trials. With an increasingly ageing European population it is essential to demonstrate the efficacy and safety of drugs. Clinical trials need to take into account the relevant issues of this population, i.e. changed metabolism, multiple chronic conditions and poly-pharmacy. To examine this issue and effect a paradigm shift it is necessary to target gatekeepers and stakeholders of clinical trials. METHODS. The project will be coordinated by the Medical Economics and Research Centre, Sheffield, with guidance from the Centre for Interdisciplinary Research on Ageing at Keele University, UK. The 5 work packages (WP) will be carried out by a multi-disciplinary team of highly qualified experts in Geriatrics, Gerontology and social sciences. WP1 will involve a systematic review of the literature and review of ongoing clinical trials to assess the extent of exclusion of the elderly. Based on these findings WP2 and WP 3 will investigate why the elderly are underrepresented in clinical trials and what can be done to improve their participation. This will be carried out in 9 countries: UK, Spain, Holland, Italy, Poland, Lithuania, Romania, Israel and the Czech Republic. WP2 will research the views of health professionals and ethicists using structured questionnaires. WP3 will explore the perceptions of older patients and carers using a focus group methodology. For WP4, the recommendations from WP2 and WP3 will be used to develop a charter for the elderly in clinical trials. WP5 will disseminate and implement the findings. CONCLUSION. PREDICT will promote the inclusion of the elderly in clinical trials in Europe. This project will facilitate the improvement of the rights of older people and the quality of health care for the ageing population.


Grant
Agency: European Commission | Branch: H2020 | Program: CSA | Phase: FETOPEN-2-2014 | Award Amount: 532.34K | Year: 2015

In recent years, several research groups have been created in the emerging research area of molecular communications. This is seen as a fundamental enabler for nano-scale networked devices. The heterogeneity of the biological environments that can host nano-scale communications has produced different proposals (e.g. neuronal networks, molecular diffusion, flow-based carrier mobility) analyzed by means of different research approaches and tools (different analytical models, simulators, lab experiments). For this reason, the need of integrating research activities at an EU level has emerged. The main objective of the CIRCLE is to integrate islands of heterogeneous research activities in a common research framework. The nature of the proposal is therefore strategic for the EU research objectives, highly interdisciplinary, inclusive of any input coming from any research activities that can contribute to identifying a research roadmap for the future years and feasible future exploitation plans. In the short term, CIRCLE will facilitate the creation of an EU wide Molecular Communications (CIRCLE) forum and provide a support infrastructure for coordination of research across Europe. In the medium term, it will foster knowledge sharing via the CIRCLE forum and a dedicated web portal. This will focus on the sharing of both research methodologies and simulation code repositories. It will establish expert working groups in different research topics within the Molecular Communications domain and develop strategic Roadmaps for both academic research and industry involvement. In the long term, CIRCLE will push the Roadmaps at a Member State and EU level to ensure Molecular Communications research converges rapidly towards feasible products of interest in the marketplace.


ELASTISLET aims to create a breakthrough development in encapsulation technology and its use in cell and tissue therapies for the treatment of type 1 and 2 diabetes. ELASTISLET will combine leading technologies in biomaterial design, production and processing, cross-linking/grafting technology and cell therapy, to synergistically integrate them into a new immune-isolation and biomimetic scaffolding approach for islet and cell transplantation in diabetes treatment. ELASTISLETs starting point is a highly innovative and versatile family of superior biomaterials, the Elastin-like Recombinamers (ELRs). Those innovative materials will be combined with the most cutting-edge encapsulation technologies, such as reactive LbL. ELASTISLET relies on the most innovative ideas taken from synthetic biology, nanobiotechnology and molecular and cellular biology to build the ideal niche for islet/cell encapsulation and transplantation. ELASTISLET main objective is to achieve a functional coating that fulfils, first, the basic requirements of optimal biocompatibility and physical properties (permselectivity) but, second, generate a capsule that can promote an intense and directed cross talk through all cell-material interfaces involved: the implant-surrounding tissue (outer) interface and cargo cells-capsule (inner) interface. At the end, a capsule that is able not only to cloak its content and isolate it from the immune rejection but that it is able to biologically interact with the surrounding tissues and its cargo simultaneously in a way that the implanted capsule will immediately interact and fuse with the surrounding tissues creating a real continuity of the extracellular matrix from the core of the capsule to the surrounding hosts tissues and procuring adequate nutrient supply. That will provide a physiologically ideal biomimetic environment for the implanted islets/cells to survive and function in the long term without perceiving a foreign, unusual or hostile environment.


News Article | March 28, 2016
Site: phys.org

The findings, published in the Proceedings of the National Academy of Sciences today (Monday, March 28) will inform a variety of genetically based mosquito control strategies that focus on creating more males than females. Male mosquitoes do not bite and are harmless to humans, while female mosquitoes bite humans to get the blood they need for egg production. "Thirteen years after the publication of a draft genome of the Anopheles gambiae mosquito, we've finally characterized its Y chromosome," said co-author Zhijian Jake Tu, a professor of biochemistry in the College of Agriculture and Life Sciences and a Fralin Life Science Institute affiliate. "This is one of the last pieces of the puzzle. Having the Y will help us figure out the genetic basis of male biology in future studies." The new information about the Y chromosome will facilitate efforts to reduce female mosquitoes or create sterile males—strategies of interest to research teams across the world. "The Y chromosome had previously not been characterized because it mostly consists of repetitive DNA sequences that stump the algorithms used by computers to assemble the mosquito's entire genetic make-up", said co-author Brantley Hall of Christiansburg, Va., a doctoral student in the genetics, bioinformatics and computational biology program. "We were able to get around this obstacle (at least partially) by using a new long single-molecule sequencing technology, a new bioinformatics algorithm specifically designed to identify Y sequences, and physical mapping of DNA directly to the Y chromosome," said co-author Igor Sharakhov, an associate professor of entomology in the College of Agriculture and Life Sciences and a Fralin Life Science Institute affiliate. "Our study provides a long-awaited foundation for studying mosquito Y chromosome biology and evolution." "Our combined efforts have resulted in the most extensive characterization of Y chromosome to date in additional malaria vectors as well, which will help identify targeted vector control approaches for different species," said co-author Atashi Sharma, a doctoral student in the department of entomology in the College of Agriculture and Life Sciences. The research was in collaboration with Nora Besansky, the Rev. John Cardinal O'Hara C.S.C. professor of biological sciences at the University of Notre Dame. Three graduate students at Virginia Tech were involved in the study, with Brantley Hall and Atashi Sharma being co-first authors on the paper. Xiaofang Jiang, a graduate student in the genetics, bioinformatics, and computational biology and biochemistry, Vladimir Timoshevskiy, a research associate, and Maria Sharakhova, an assistant professor of entomology in the College of Agriculture and Life Sciences, from Virginia Tech also participated in the study. Philippos-Aris Papathanos of the University of Perugia and Changde Cheng of the University of Norte Dame are also co-first authors. Malaria causes as many as 907,000 deaths each year, mostly among children in sub-Saharan Africa. Anopheles mosquitoes, which bite mainly between dusk and dawn, transmit human malaria by spreading Plasmodium parasites that multiply in the human liver and infect red blood cells. Explore further: Mosquito genetics may offer clues to malaria control More information: Radical remodeling of the Y chromosome in a recent radiation of malaria mosquitoes, Proceedings of the National Academy of Sciences, www.pnas.org/cgi/doi/10.1073/pnas.1525164113


Grant
Agency: European Commission | Branch: FP7 | Program: CP-CSA-Infra | Phase: INFRA-2011-1.1.16. | Award Amount: 10.28M | Year: 2011

The European Strategy Forum on Research Infrastructures (ESFRI) recognizes in its roadmap for Research Infrastructures that in the near future, hydrogen, as an energy carrier derived from a number of other fuels, and fuel cells, as energy transformers, are expected to play a major role, for mobile and stationary applications. With the current fragmentation of the European R&D infrastructures and the uncoordinated approaches adopted, the demand for effective support of the Hydrogen and Fuel Cells (H2FC) technology developers cannot be satisfied. Therefore this proposal is built to integrate the European R&D community around rare and/or unique infrastructural elements that will facilitate and significantly enhance the R&D outcome. H2FCEuropean Infrastructure addresses the topic INFRA-2011-1.1.16 Research Infrastructures for H2FC Facilities and the related energy-chains, by bringing together, for the first time in Europe, the leading European R&D institutions of the H2 community together with those of the fuel cell community, covering the entire life-cycle of H2FC, i.e. hydrogen production, storage, distribution, and final use in fuel cells. The three pillars of the proposal are networking, transnational access and joint research activities. All are strongly interrelated and oriented towards the resolution of identified bottlenecks. The aim is to provide: A single integrated virtual infrastructure accommodating H2FC test and analysis facilities Transnational access for the H2FC R&D communities to advanced infrastructures Expert working groups to enhance work at the provided facilities and coordination in aspects of safety, performance and durability Central databases and libraries for safety, performance and durability data and modelling codes Coordination of relevant education and training actions Integration, enhancement and improvement of the existing infrastructures Coordination with national / international bodies and industrial activities (incl.


Grau A.,University of Granada | Pancheri G.,National Institute of Nuclear Physics, Italy | Shekhovtsova O.,National Institute of Nuclear Physics, Italy | Srivastava Y.N.,University of Perugia
Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics | Year: 2010

To settle the question whether the growth with energy is universal for different hadronic total cross-sections, we present results from theoretical models for Πp, and (pp, pp̄) total cross-sections. We show that present and planned experiments at LHC can differentiate between different models, all of which are consistent with presently available (lower energy) data. This study is also relevant for the analysis of those very high energy cosmic ray data which require reliable Πp total cross-sections as seeds. A preliminary study of the total ΠΠ cross-sections is also made. © 2010 .


Giannantoni A.,University of Perugia | Bini V.,University of Perugia | Dmochowski R.,Vanderbilt University | Hanno P.,University of Pennsylvania | And 3 more authors.
European Urology | Year: 2012

Context: Different types of behavioural, dietary, interventional, pharmacologic, and surgical therapies have been used to treat painful bladder syndrome/interstitial cystitis (PBS/IC). Because of the paucity of randomised placebo-controlled studies on different treatments, an evidence-based management approach has not yet been developed. Objective: To critically review and synthesize data from a wide range of current therapeutic approaches to PBS/IC, to quantify the effect size from randomised controlled trials (RCTs), and to reach clinical agreement on the efficacy of treatments for PBS/IC. Evidence acquisition: We performed a systematic review of the literature to identify articles published between 1990 and September 2010 on the management of PBS/IC. We included articles restricted to the English language published since 1990 to date that reported on oral and intravesical treatment, multimodal or combined treatment, and surgical treatment. For all RCTs, standardised mean differences (SMDs) were extracted and combined in a meta-analysis applying a random-effect model that incorporated the heterogeneity of effects. The four outcomes assessed in all studies were a change in the Interstitial Cystitis Symptom Index (ICSI), pain, urgency, and frequency. Non-RCTs (nRCTs) were analysed with a narrative synthesis of the evidence from all research designs. Evidence synthesis: We included 7709 adult patients from 29 RCTs and 57 nRCTs. Meta-analysis of RCTs showed that only cyclosporine A provided a simultaneous great effect size of SMD on ICSI, pain, and frequency. Amitriptyline at different dosages showed a great effect size of SMD on pain and urgency or on ICSI and frequency. The remaining RCTs showed sporadic significant changes in only one of the four considered parameters. The attributed levels of evidence for treatments reported in RCTs were 1b; grades of recommendations ranged from A to C. According to the Jadad score, 11 RCTs were high-quality studies. Meta-analysis of RCTs showed a great heterogeneity in the applied methodologies, clinical outcomes assessed, and the obtained results in different studies. The results from the nRCTs showed that the most frequently adopted treatment is oral pentosan polysulfate and that the use of botulinum A toxin intradetrusorial injections in PBS/IC is increasing. A high heterogeneity in drugs and treatment modalities, clinical outcomes, and obtained results was also found for nRCTs. Conclusions: Limited evidence exists for the few treatments for PBS/IC. The lack of definitive conclusions is due to the great heterogeneity in methodology, symptoms assessment, duration of treatment, and follow-up in both RCTs and nRCTs. © 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.


Van der Ploeg J.D.,Wageningen University | Van der Ploeg J.D.,China Agricultural University | Ventura F.,University of Perugia
Current Opinion in Environmental Sustainability | Year: 2014

Farming styles are distinctive patterns through which agricultural production is organized and developed. Different styles result in different levels of intensity and sustainability. This means that encouraging and stimulating specific farming styles might result in considerable agricultural development and growth of total food production. Currently, peasant-like styles of farming offer a great deal of promise for feeding the world in a sustainable way. © 2014 Elsevier B.V.


Palmerini S.,University of Perugia | La Cognata M.,University of Catania | La Cognata M.,National Institute of Nuclear Physics, Italy | Cristallo S.,University of Granada | Busso M.,University of Perugia
Astrophysical Journal | Year: 2011

We present computations of nucleosynthesis in low-mass (LM) red giant branch (RGB) and asymptotic giant branch (AGB) stars of Population I experiencing extended mixing. We adopt the updated version of the FRANEC evolutionary model, a new post-process code for non-convective mixing and the most recent revisions for solar abundances. In this framework, we discuss the effects of recent improvements in relevant reaction rates for proton captures on intermediate-mass (IM) nuclei (from carbon to aluminum). For each nucleus, we briefly discuss the new choices and their motivations. The calculations are then performed on the basis of a parameterized circulation, where the effects of the new nuclear inputs are best compared to previous works. We find that the new rates (and notably the one for the 14N(p, γ)15O reaction) imply considerable modifications in the composition of post-main-sequence stars. In particular, the slight temperature changes due to the reduced efficiency of proton captures on 14N induce abundance variations at the first dredge-up (especially for 17O, whose equilibrium ratio to 16O is very sensitive to the temperature). In this new scenario, presolar oxide grains of AGB origin turn out to be produced almost exclusively by very low mass stars (M ≤ 1.5-1.7 M), never becoming C-rich. The whole population of grains with 18O/16O below 0.0015 (the limit permitted by first dredge-up) is now explained. Also, there is now no forbidden area for very low values of 17O/16O (below 0.0005), contrary to previous findings. A rather shallow type of transport seems to be sufficient for the CNO changes in RGB stages. Both thermohaline diffusion and magnetic-buoyancy-induced mixing might provide a suitable physical mechanism for this. Thermohaline mixing is in any case certainly inadequate to account for the production of 26Al on the AGB. Other transport mechanisms must therefore be at play. In general, observational constraints from RGB and AGB stars, as well as from presolar grains, are well reproduced by our approach. The nitrogen isotopic ratio in mainstream SiC grains remains an exception. For the low values measured in them (i.e., for 14N/15N ≤2000), we have no explanation. Actually, for the several grains with subsolar nitrogen isotopic ratios, no known stellar process acting in LM stars can provide a clue. This might be an evidence that some form of contamination from cosmic ray spallation occurs in the interstellar medium, adding fresh 15N to the grains. © 2011. The American Astronomical Society. All rights reserved.


D'Alessandro B.,BIONET Biomass and New Technologies S.r.l. | D'Amico M.,University of Perugia | Desideri U.,University of Perugia | Fantozzi F.,University of Perugia
Applied Energy | Year: 2013

The concept of integrated pyrolysis regenerated plant (IPRP) is based on a Gas Turbine (GT) fuelled by pyrogas produced in a rotary kiln slow pyrolysis reactor, where waste heat from GT is used to sustain the pyrolysis process. The IPRP plant provides a unique solution for microscale (below 250. kW) power plants, opening a new and competitive possibility for distributed biomass or wastes to energy conversion systems. The paper summarizes the state of art of the IPRP technology, from preliminary numerical simulation to pilot plant facility, including some new available data on pyrolysis gas from laboratory and pilot plants. © 2012 Elsevier Ltd.


Fiorucci S.,University of Perugia | Mencarelli A.,University of Perugia | Distrutti E.,Azienda Ospedaliera di Perugia | Zampella A.,University of Naples Federico II
Future Medicinal Chemistry | Year: 2012

The farnesoid X receptor (FXR) is a bile sensor that acts in coordination with other nuclear receptors to regulate essential steps in bile acid uptake, metabolism and excretion. In addition, FXR is an ancillary receptor involved in lipid and glucose homeostasis. Steroidal and non-steroidal FXR ligands are currently available. Both groups have shown limitations in the preclinical studies regarding absorption, metabolism, specificity of target and intrinsic toxicity. FXR ligands endowed with agonistic activity are under development for the treatment of cholestatic liver diseases, including primary biliary cirrhosis and metabolic disorders linked to insulin resistance. Despite the fact that results from preclinical models are encouraging, targeting FXR holds potential for side effects (i.e., impaired cholesterol disposal and cholestasis). Thus, results from FXR gene-ablated mice and mice administered an FXR antagonist support a role for FXR antagonists or modulators (i.e., FXR agonists that selectively activate specific subsets of FXR target genes in a tissue) or co-regulator-specific manner. © 2012 Future Science Ltd.


Bolli G.B.,University of Perugia | Munteanu M.,Victor Babes University of Medicine and Pharmacy Timisoara | Dotsenko S.,Zaporozhye State Medical University | Niemoeller E.,Sanofi S.A. | And 3 more authors.
Diabetic Medicine | Year: 2014

Aims: To assess the efficacy and safety of one- and two-step dose-increase regimens of lixisenatide once daily in participants with Type 2 diabetes mellitus insufficiently controlled with metformin. Methods: This was a randomized, double-blind, placebo-controlled, parallel-group, multi-centre study enrolling participants with Type 2 diabetes (n = 484) treated with metformin. Participants were randomized to receive either lixisenatide in a one-step dose increase or a two-step dose increase vs. placebo for 24 weeks, followed by a ≥ 52-week variable double blind period. Primary outcome was HbA1c reduction at week 24. Results: Lixisenatide one-/two-step once daily significantly improved HbA1c at week 24 compared with placebo (P < 0.0001) and allowed more participants to achieve HbA1c < 53 mmol/mol (< 7.0%) (P ≤ 0.0005). Improvements were observed in fasting plasma glucose (-0.5/-0.6 vs. +0.1 mmol/l; P < 0.001) and body weight (-2.6/-2.7 vs. -1.6 kg; P < 0.005). At week 24, adverse events were reported by 67.7/70.8/65.6% of participants treated with lixisenatide one-/two-step/placebo, respectively-nausea and vomiting being reported most frequently. Symptomatic hypoglycaemia occurred in 1.9/2.5% of participants on one-/two-step lixisenatide and 0.6% with placebo, with no severe episodes. Lixisenatide continued to be efficacious and well tolerated during the variable double-blind extension period of at least 52 weeks. Conclusions: Lixisenatide one- or two-step dose-increase regimens significantly improved glycaemic control and decreased body weight over 24 weeks and during a long-term extension period without increasing hypoglycaemia. The study confirmed that tolerability in the one-step group was at least similar to the two-step dose increase, with nausea/vomiting and hypoglycaemia frequency being lower in the one-step regimen. © 2013 Diabetes UK.


Ubertini F.,University of Perugia | Gentile C.,Polytechnic of Milan | Materazzi A.L.,University of Perugia
Engineering Structures | Year: 2013

The increasing diffusion of long term dynamic monitoring systems for structural condition assessment is currently driving a strong interest towards automated procedures of output-only modal identification. Different approaches have been recently developed in the literature for this purpose, often based on Stochastic Subspace Identification (SSI) methods. Such procedures usually rely on heuristic decisional criteria, hence demanding for independent checks with validation purposes.The aim of this paper is to propose an automated modal identification procedure, belonging to the class of SSI techniques and based on the popular tool of clustering analysis, and to exemplify its application in the operational modal analysis of two bridges, with different levels of complexity from the system identification viewpoint: a historic iron arch bridge and a long-span footbridge. In order to address reliability and accuracy of the procedure, the modal estimates automatically extracted from the data recorded on the two bridges were compared to those independently obtained by using well-established manual techniques. The results demonstrated very good accuracy and robust performance of the developed procedure, also in the case of weakly excited and closely spaced modes, so that its application to process the data collected in continuous monitoring systems seems highly promising. © 2012 Elsevier Ltd.


Palombo F.,University of Exeter | Madami M.,University of Perugia | Stone N.,University of Exeter | Stone N.,Gloucestershire Hospital | Fioretto D.,University of Perugia
Analyst | Year: 2014

We describe the first application of confocal Brillouin and Raman microscopy to ex vivo human epithelial tissue-Barrett's oesophagus. This non-invasive label-free approach provides high-resolution mechanical mapping with chemical specificity, opening the route to a new integrated method for multiple biomedical and bioengineering applications, and potentially in vivo real-time diagnostics. © 2014 The Royal Society of Chemistry.


Grau A.,University of Granada | Pacetti S.,University of Perugia | Pancheri G.,National Institute of Nuclear Physics, Italy | Srivastava Y.N.,University of Perugia
Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics | Year: 2012

We parametrize TOTEM data for the elastic differential pp cross section at s=7TeV in terms of two exponentials with a relative phase. We employ two previously derived sum rules for pp elastic scattering amplitude in impact parameter space to check whether asymptotia has been reached at the LHC. A detailed study of the TOTEM data for the elastic differential cross section at s=7TeV is made and it is shown that, within errors, the asymptotic sum rules are satisfied at LHC. We propose to use this parametrization to study forthcoming higher energy data. © 2012 Elsevier B.V.


Sepe V.,University of Naples Federico II | Bifulco G.,University of Salerno | Renga B.,University of Perugia | D'Amore C.,University of Perugia | And 2 more authors.
Journal of Medicinal Chemistry | Year: 2011

We report the biochemical characterization of sulfated polyhydroxysterols isolated from marine invertebrates as potent antagonists of farnesoid-X-receptor (FXR), a ligand-regulated transcription factor involved in the regulation of lipid and glucose homeostasis in mammals. Molecular characterization of a library of sulfated polyhydroxysteroids resulted in the identification of a first FXR antagonist. In contrast to partial antagonists, this compound was endowed with an antagonistic activity on the expression of a subset of FXR-regulated genes in liver cells and abrogated the release of nuclear coreceptor from the promoter of these genes. The putative binding mode to FXR, obtained through docking calculations, suggested the crucial role played by the bent shape of the molecule as well as the presence of one hydroxyl group in its side chain. This compound is a major tool to explore the effect of FXR inhibition in pharmacological settings. © 2011 American Chemical Society.


Fiorucci S.,University of Perugia | Distrutti E.,Azienda Ospedaliera di Perugia
Trends in Molecular Medicine | Year: 2015

The composition of the bile acid pool is a function of the microbial metabolism of bile acids in the intestine. Perturbations of the microbiota shape the bile acid pool and modulate the activity of bile acid-activated receptors (BARs) even beyond the gastrointestinal tract, triggering various metabolic axes and altering host metabolism. Bile acids, in turn, can also regulate the composition of the gut microbiome at the highest taxonomic levels. Primary bile acids from the host are preferential ligands for the farnesoid X receptor (FXR), while secondary bile acids from the microbiota are ligands for G-protein-coupled bile acid receptor 1 (GPBAR1). In this review, we examine the role of bile acid signaling in the regulation of intestinal microbiota and how changes in bile acid composition affect human metabolism. Bile acids may offer novel therapeutic modalities in inflammation, obesity, and diabetes. © 2015 Elsevier Ltd.


D'Ambrisi A.,University of Florence | Mezzi M.,University of Perugia | Feo L.,University of Salerno | Berardi V.P.,University of Salerno
Composite Structures | Year: 2014

The seismic rehabilitation techniques of masonry structures based on the use of plasters reinforced with steel nets have been widely utilized in the last decades. More recently nets made of materials other than steel have been used as plaster reinforcement, among them there are the polymeric nets. These nets allow to overcome some of the limitations of the other strengthening materials and present a good cost-benefit ratio. Experimental campaigns performed on masonry panels reinforced with polymeric nets have allowed to define their mechanical properties for practical design applications and for assessing their seismic capacity. Considering the results of these experimental campaigns in the present study analysis methods of masonry structures made of masonry brick panels strengthened with plasters reinforced with polymeric nets are proposed. The strength and ductility increments of the strengthened panels are accounted for in the global analysis of the construction adopting suitable values of the behavior factor. In the ambit of the limit analysis of the in plane and out of plane collapse mechanisms criteria that allow to account for the contribution of the polymeric net in the containment of the evolution of these mechanisms are defined. © 2014 Elsevier Ltd.


Pedale T.,University of Rome La Sapienza | Pedale T.,Cognitive Neuroscience Group | Santangelo V.,Cognitive Neuroscience Group | Santangelo V.,University of Perugia
Frontiers in Human Neuroscience | Year: 2015

One of the most important issues in the study of cognition is to understand which are the factors determining internal representation of the external world. Previous literature has started to highlight the impact of low-level sensory features (indexed by saliency-maps) in driving attention selection, hence increasing the probability for objects presented in complex and natural scenes to be successfully encoded into working memory (WM) and then correctly remembered. Here we asked whether the probability of retrieving high-saliency objects modulates the overall contents of WM, by decreasing the probability of retrieving other, lower-saliency objects. We presented pictures of natural scenes for 4 s. After a retention period of 8 s, we asked participants to verbally report as many objects/details as possible of the previous scenes. We then computed how many times the objects located at either the peak of maximal or minimal saliency in the scene (as indexed by a saliency-map; Itti et al., 1998) were recollected by participants. Results showed that maximal-saliency objects were recollected more often and earlier in the stream of successfully reported items than minimal- saliency objects. This indicates that bottom-up sensory salience increases the recollection probability and facilitates the access to memory representation at retrieval, respectively. Moreover, recollection of the maximal- (but not the minimal-) saliency objects predicted the overall amount of successfully recollected objects: The higher the probability of having successfully reported the most-salient object in the scene, the lower the amount of recollected objects. These findings highlight that bottom-up sensory saliency modulates the current contents of WM during recollection of objects from natural scenes, most likely by reducing available resources to encode and then retrieve other (lower saliency) objects. © 2015 Her Majesty the Queen in Right of Canada.


Felicetti L.,University of Perugia | Femminella M.,University of Perugia | Reali G.,University of Perugia | Nakano T.,Osaka University | Vasilakos A.V.,University of Western Macedonia
IEEE Journal on Selected Areas in Communications | Year: 2014

In this paper, we present a communication protocol between a pair of biological nanomachines, i.e., a transmitter and a receiver, built upon molecular communications in an aqueous environment. In our proposal, the receiver, acting as a control node, sends a connection setup signal to the transmitter, which stokes molecules, to start molecule transmission. The molecules transmitted by the transmitter propagate in the environment and are absorbed by the receiver through its receptors. When the receiver absorbs the desired quantity of molecules, it releases a tear-down signal to notify the transmitter to stop the transmission. The proposed protocol implements a bidirectional communication by using a number of techniques originally designed for the TCP. In fact, the proposed protocol is connection-oriented and uses the TCP-like probing to find a suitable transmission rate between the transmitter and the receiver to avoid receiver congestion. Unlike the TCP, however, explicit acknowledgments are not used since they would degrade the communication throughput due to the large delay, which is a characteristic feature of molecular communications. Thus, the proposed protocol uses implicit acknowledgments, and feedback signals are sent by the receiver to throttle the transmission rate at the transmitter, i.e., explicit negative feedback. We also present the results of an extensive simulation campaign, used to validate the proposed protocol and to properly dimension the main protocol parameters. © 2014 IEEE.


Home P.D.,Northumbria University | Bergenstal R.M.,International Diabetes Center at Park Nicollet | Bolli G.B.,University of Perugia | Ziemen M.,Sanofi S.A. | And 3 more authors.
Diabetes Care | Year: 2015

OBJECTIVE Insulin therapy in type 1 diabetes still provides suboptimal outcomes. Insulin glargine 300 units/mL (Gla-300), with a flatter pharmacodynamic profile compared with insulin glargine 100 units/mL (Gla-100), is an approach to this problem. RESEARCH DESIGN AND METHODS People with type 1 diabetes, using a mealtime and basal insulin regimen, were randomized open-label to Gla-300 or Gla-100 and to morning or evening injection, continuing the mealtime analog, and followed for 6 months. RESULTS Participants (n = 549) were a mean age of 47 years and had a mean duration of diabetes of 21 years and BMI of 27.6 kg/m2. The change in HbA1c (primary end point; baseline 8.1%) was equivalent in the two treatment groups (difference, 0.04% [95% CI 20.10 to 0.19]) (0.4 mmol/mol [21.1 to 2.1]), and Gla-300 was thus noninferior. Similar results with wider 95% CIs were found for morning and evening injection times and for prebreakfast self-measured plasma glucose (SMPG) overall. Results were also similar for Gla-300 when morning and evening injection time was compared, including overlapping 8-point SMPG profiles. Hypoglycemia did not differ, except for the first 8 weeks of the study, when nocturnal confirmed or severe hypoglycemia was lower with Gla-300 (rate ratio 0.69 [95% CI 0.53-0.91]). Hypoglycemia with Gla-300 did not differ by time of injection. The basal insulin dose was somewhat higher at 6 months for Gla-300. The adverse event profile did not differ and was independent of the Gla-300 time of injection. Weight gain was lower with Gla-300. CONCLUSIONS In long-duration type 1 diabetes, Gla-300 provides similar glucose control to Gla-100, with a lower risk of hypoglycemia after transfer from other insulins, independent of time of injection, and less weight gain. © 2015 by the American Diabetes Association.


Verdecchia P.,Hospital of Assisi | Angeli F.,Hospital Sm Della Misericordia | Gentile G.,Royal Cornwall Hospitals | Reboldi G.,University of Perugia
Hypertension | Year: 2016

Several randomized trials compared a more versus less intensive blood pressure-lowering strategy on the risk of major cardiovascular events and death. Cumulative meta-analyses and trial sequential analyses can establish whether and when firm evidence favoring a specific intervention has been reached from accrued literature. Therefore, we conducted a cumulative trial sequential analysis of 18 trials that randomly allocated 53 405 patients to a more or less intensive blood pressure-lowering strategy. We sought to ascertain the extent to which trial evidence added to previously accrued data. Outcome measures were stroke, myocardial infarction, heart failure, cardiovascular death, and all-cause death. Achieved blood pressure was 7.6/4.5 mm Hg lower with the more intensive than the less intensive blood pressure-lowering strategy. For stroke and myocardial infarction, the cumulative Z curve crossed the efficacy monitoring boundary solely after the SPRINT (Systolic Blood Pressure Intervention Trial) study, thereby providing firm evidence of superiority of a more intensive over a less intensive blood pressure-lowering strategy. For cardiovascular death and heart failure, the cumulative Z curve crossed the conventional significance boundary, but not the sequential monitoring boundary, after SPRINT. For all-cause death, the SPRINT trial pushed the cumulative Z curve away from the futility area, without reaching the conventional significance boundary. We conclude that evidence accrued to date strongly supports the superiority of a more intensive versus a less intensive blood pressure-lowering strategy for prevention of stroke and myocardial infarction. Cardiovascular death and heart failure are likely to be reduced by a more intensive blood pressure-lowering strategy, but evidence is not yet conclusive. © 2016 American Heart Association, Inc.


Santangelo V.,University of Perugia | Santangelo V.,Cognitive Neuroscience Group
Behavioural Brain Research | Year: 2015

The last decades have seen a rapid growing in the attempt to understand the key factors involved in the internal memory representation of the external world. Visual salience have been found to provide a major contribution in predicting the probability for an item/object embedded in a complex setting (i.e., a natural scene) to be encoded and then remembered later on. Here I review the existing literature highlighting the impact of perceptual- (based on low-level sensory features) and semantics-related salience (based on high-level knowledge) on short-term memory representation, along with the neural mechanisms underpinning the interplay between these factors. The available evidence reveal that both perceptual- and semantics-related factors affect attention selection mechanisms during the encoding of natural scenes. Biasing internal memory representation, both perceptual and semantics factors increase the probability to remember high- to the detriment of low-saliency items. The available evidence also highlight an interplay between these factors, with a reduced impact of perceptual-related salience in biasing memory representation as a function of the increasing availability of semantics-related salient information. The neural mechanisms underpinning this interplay involve the activation of different portions of the frontoparietal attention control network. Ventral regions support the assignment of selection/encoding priorities based on high-level semantics, while the involvement of dorsal regions reflects priorities assignment based on low-level sensory features. © 2015 Elsevier B.V.


Monaco P.,University of Perugia | Rodriguez-Tovar F.J.,University of Granada | Uchman A.,Jagiellonian University
Palaios | Year: 2012

Dark, pelagic sediments of the uppermost Cenomanian Bonarelli Level (OAE2 event) interval, in two classical sections Contessa and Bottaccione in the Central Apennines, contain unbioturbated and bioturbated beds suggesting fluctuations in pore water oxygenation from anoxic to oxic or dysoxic conditions. The oxic and dysoxic improvement events prior to, during, and after the event are marked by biogenic structures showing an increase in the diversity of the trace fossils (Chondrites, Planolites, Thalassinoides, Trichichnus, and Zoophycos) from none to five ichnotaxa in individual beds. The number of anoxic events differs in the Contessa and Bottaccione sections, even though they are only 2.5 km apart. Comparison with sections from the Carpathians (Poland) and the Betic Cordillera (Spain), reveals that minor anoxic events below and above the Bonarelli Level are absent in the studied Apennine sections. Moreover, the diversity and density of trace fossils in the Apennine sections are lower than those from other studied sections in the Tethys, most likely indicating a comparatively lower availability of food in the Gubbio area as a result of its paleogeographic location. The preservation of trace fossils, controlled by the consistency of sediments and diagenetic processes, can mask diversity and density in some beds. © 2012 SEPM (Society for Sedimentary Geology).


Riddle M.C.,Oregon Health And Science University | Bolli G.B.,University of Perugia | Ziemen M.,Sanofi S.A. | Muehlen-Bartmer I.,Sanofi S.A. | And 2 more authors.
Diabetes Care | Year: 2014

OBJECTIVE To compare the efficacy and safety of new insulin glargine 300 units/mL (Gla-300) with glargine 100 units/mL (Gla-100) in people with type 2 diabetes on basal insulin (≥42 units/day) plus mealtime insulin.RESEARCH DESIGN AND METHODS EDITION 1 (NCT01499082) was a 6-month, multinational, open-label, parallelgroup study. Adults with glycated hemoglobin A1c (HbA1c) 7.0-10.0% (53-86 mmol/mol) were randomized to Gla-300 or Gla-100 once daily with dose titration seeking fasting plasma glucose 4.4-5.6 mmol/L. Primary end point was HbA1c change from baseline; main secondary end point was percentage of participants with one or more confirmed (≤3.9 mmol/L) or severe nocturnal hypoglycemia from week 9 to month 6.RESULTS Participants (n = 807) had mean age 60 years, diabetes duration 16 years, BMI 36.6 kg/m2, and HbA1c 8.15% (65.6 mmol/mol). HbA1c reduction was equivalent between regimens; least squares mean difference -0.00% (95% CI -0.11 to 0.11) (-0.00 mmol/mol [-1.2 to 1.2]). Fewer participants reported one or more confirmed (≤3.9 mmol/L) or severe nocturnal hypoglycemic events between week 9 and month 6 with Gla-300 (36 vs. 46% with Gla-100; relative risk 0.79 [95% CI 0.67-0.93]; P < 0.005); nocturnal hypoglycemia incidence and event rates were also lower with Gla-300 in the first 8 weeks of treatment. No between-treatment differences in tolerability or safety were identified.CONCLUSIONS Gla-300 controls HbA1c as well as Gla-100 for people with type 2 diabetes treated with basal and mealtime insulin but with consistently less risk of nocturnal hypoglycemia. © 2014 by the American Diabetes Association.


Balucani N.,University of Perugia | Balucani N.,University Grenoble Alpes | Balucani N.,French National Center for Scientific Research | Ceccarelli C.,University Grenoble Alpes | And 2 more authors.
Monthly Notices of the Royal Astronomical Society: Letters | Year: 2015

While astrochemical models are successful in reproducing many of the observed interstellar species, they have been struggling to explain the observed abundances of complex organic molecules. Current models tend to privilege grain surface over gas-phase chemistry in their formation. One key assumption of those models is that radicals trapped in the grain mantles gain mobility and react on lukewarm (≳30 K) dust grains. Thus, the recent detections of methyl formate (MF) and dimethyl ether (DME) in cold objects represent a challenge and may clarify the respective role of grain-surface and gas-phase chemistry. We propose here a new model to form DME and MF with gas-phase reactions in cold environments, where DME is the precursor of MF via an efficient reaction overlooked by previous models. Furthermore, methoxy, a precursor of DME, is also synthesized in the gas phase from methanol, which is desorbed by a non-thermal process from the ices. Our new model reproduces fairly well the observations towards L1544. It also explains, in a naturalway, the observed correlation between DME and MF. We conclude that gas-phase reactions are major actors in the formation of MF, DME and methoxy in cold gas. This challenges the exclusive role of grain-surface chemistry and favours a combined grain-gas chemistry. © 2015 The Authors.


Senin N.,University of Perugia | Colosimo B.M.,Polytechnic of Milan | Pacella M.,University of Salento
Robotics and Computer-Integrated Manufacturing | Year: 2013

In multisensor coordinate metrology scenarios involving the fusion of homogenous data, specifically 3D point clouds like those originated by CMMs and structured light scanners, the problem of registration, i.e. The proper localization of the clouds in the same coordinate system, is of central importance. For fine registration, known variants of the Iterative Closest Point (ICP) algorithm are commonly adopted; however, no attempt seems to be done to tweak such algorithms to better suit the distinctive multisensor nature of the data. This work investigates an original approach that targets issues which are specific to multisensor coordinate metrology scenarios, such as coexistence of point sets with different densities, different spatial arrangements (e.g. sparse CMM points vs. gridded sets from light scanners), and different noise levels associated to the point sets depending on the metrological performances of the sensors involved. The proposed approach is based on combining known ICP variants with novel point set augmentation techniques, where new points are added to existing sets with the purpose of improving registration performance and robustness to measurement error. In particular, augmentation techniques based on advanced fitting solutions promote a paradigm shift for registration, which is not seen as a geometric problem consisting in moving point sets as close as possible to each other, but as a problem where it is not the original points, but the underlying geometries that must be brought together. In this work, promising combinations of ICP and point augmentation techniques are investigated through the application to virtual scenarios involving synthetic geometries and simulated measurements. Guidelines for approaching registration problems in industrial scenarios involving multisensor data fusion are also provided. © 2012 Elsevier Ltd.


Grant
Agency: European Commission | Branch: FP7 | Program: CP | Phase: ENERGY.2010.2.5-1 | Award Amount: 5.91M | Year: 2010

This project will develop and verify a novel modular air cooled condenser (MACC) for concentrated solar power (CSP) plants. This technology will enable CSP plants to increase net power output, and reduce costs compared to existing dry cooled plants. Conventional dry cooling is unresponsive to changes in ambient conditions. However, the MACC will incorporate sensors which detect changes in temperature, ambient wind, and fan flow rate, and control algorithms, which will communicate with these sensors to continuously vary fan speed. The MACC will therefore maintain optimum condenser pressure and temperature irrespective of ambient conditions. As a result, turbine outlet conditions will always be optimised, thus maximising power output and reducing operating costs. Also, because the MACC is modular, installation and maintenance costs will be significantly reduced. The project will first optimise and characterise the performance at module level. Fan control algorithms will be developed and interfaced with temperature and flow sensors which will be developed. At system level, module layouts will be investigated to assess the possibility of harnessing the wind to assist fan operation. Both system and module level development will involve numerical simulation, analytical modelling, physical scale modelling, and measurements on full scale prototypes. The effects of all design options will be assessed using thermodynamic models. Techno-economic modelling will assess the life time cost implications of various design options. To prove the merits of the MACC, full scale testing in an operational CSP plant will be performed. The main outputs of the project will be patented MACC designs, an industrial scale prototype, and dissemination of project activities to ensure a lasting project legacy.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-IP | Phase: NMP-2008-4.0-1 | Award Amount: 7.39M | Year: 2009

We propose a multidisciplinary program, focusing on the development of novel approaches for directing the differentiation, proliferation and tissue-tropism of specific hematopoietic lineages, using micro- and nano-fabricated cell chips. We will use advanced nanofabricated surfaces functionalized with specific biomolecules, and microfluidics cell chips to specify and expend regulatory immune cells for treating diverse inflammatory and autoimmune disorders in an organ- and antigen-specific manner. The proposed cell-chip will create ex-vivo microenvironments mimicking in-vivo cell-cell interactions and molecular signals involved in differentiation and proliferation of hematopoietic cells. Cell chip development and optimization will be supported by high throughput microscopy to select for optimal conditions. Educated cells will be employed for in vivo experiments in mice and the methodology will be further adapted for human cell populations, and applied for clinical diagnosis and therapy as well as the developments of clinically-relevant devices. Regulatory T-cells are extremely promising cells for treatment of inflammatory and auto-immune disease, as well as for tolerance induction in organ transplantation. To be effective they must be produced conveniently, at large numbers with an optimally tuned phenotype. The methodology is suggested to overcome current obstacles in obtaining therapeutically significant numbers of T cells. We propose to apply the suggested methodology for treating different inflammatory or autoimmune diseases including type-1 diabetes using targeted immunotherapeutic approaches. Developing new methods for producing large numbers of finely-tuned and tissue-targeted regulatory cells will make this approach clinically viable. This novel methodology can be extended to directing differentiation of other specific T-cell and hematopoietic lineages, with possible applications for targeting other autoimmune diseases and treating tumors or graft rejection.


Grant
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: SFS-14a-2014 | Award Amount: 5.35M | Year: 2016

The OLEUM project will generate innovative, more effective and harmonized analytical solutions to detect and fight the most common and emerging frauds and to verify the overall quality of olive oils (OOs). By a core group of 20 partners from 15 countries OLEUM will undertake RESEARCH ACTIVITIES based on the development of IMPROVED and NEW ANALYTICAL METHODS by targeted and omics approaches with the aim: i) to detect new markers of the soft deodorization process; ii) to discover illegal blends between OOs and other vegetable oils; iii) to control OO quality (e.g. freshness); iv) to improve the organoleptic assessment with a Quantitative Panel Test, based on current official methods, and supported by tailored reference materials for better calibration of the sensory panels coupled with rapid screening tools to facilitate the work of the panelists. The most promising OLEUM solutions will be subjected to VALIDATION in conformity with internationally agreed standards by peer laboratories. OLEUM will recreate a realistic deodorization scenario by producing tailored, soft deodorized OOs by lab-scale and up-scaled pilot plants to apply analytical solutions to known samples. Substantial KNOWLEDGE and TECHNOLOGY TRANSFER activities will be envisaged to aid in implementation of: a) a web-based easily-accessible, scalable and constantly updated OLEUM DATABANK, containing all the information from OLEUM research and other reliable international sources, will be available for download data and spectra and to help achieve satisfactory harmonization of analytical approaches among control laboratories; b) the OLEUM NETWORK of relevant OOs stakeholders to maximize the impact of proposed analytical solutions. Finally, a robust dissemination strategy by the OLEUM project aimed at effectively sharing results with all stakeholders in the OO supply chain has the potential to improve consumer and market confidence, and preserve the image of OOs on a global scale.


Grant
Agency: European Commission | Branch: H2020 | Program: CSA | Phase: MSCA-NIGHT-2016 | Award Amount: 512.74K | Year: 2016

Researchers love to engage with nature, society, with future and ultimately with all the complex challenges that will allow them to contribute to a better world. Researchers also love to engage with other people to make the quest theyre involved in a collective endeavour. All this make researchers persons passionate for engagement who are developing a growing sense of responsibility related to their work and their role in society. In such a professional life researchers experience strong driving forces such as enthusiasm, emotions, combined with new knowledge and innovative discoveries. All these elements are summarized in the acronym SHARPER - Sharing Researchers Passion for Engagement and Responsibility the name of the European Researchers Night in the Centre and South of Italy that will take place on the 30th of September 2016 and on the 29th of September 2017 simultaneously in five cities: Perugia, LAquila, Ancona and Palermo the four capital cities of the regions Marche, Umbria, Abruzzo, Sicily and in Cascina the city hosting the European Gravitational Observatory one of the cutting edge European research facilities. This network of cities combined with their Research Institutions and with their social and cultural actors provides a team of excellence and reliability both in the fields of research and science communication at national and international level. The SHARPER project will create effective communication bridges between researchers and the cities and communities they live and act within, through: street labs, exhibitions, performances in city squares or activities that will take place in focal city venues, where citizens use to spend their everyday life. SHARPER 2016-2017 will geographically broaden the impact of the communication actions of European Researchers Night in Italy massively engaging kids, young students, schools, associations and citizens at large actively involved by researchers since the planning phase of the activities.


Grant
Agency: European Commission | Branch: FP7 | Program: BSG-SME | Phase: SME-1 | Award Amount: 1.48M | Year: 2008

The consortium has a lead series of p38 inhibitors with unusual anti-inflammatory properties. The drug leads were originally elaborated as a potential therapy for inflammatory bowel disease, however, the potency of the compounds and their general anti-inflammatory mode of action has raised the possibility of studying their utility in other diseases including rheumatoid arthritis. In addition, feedback from licensing partners has indicated that clear activity in a range of other disease models would dramatically increase interest. A key issue in bringing substances of this class to the clinic is variable patient response to p38 inhibitors in previous trials. Data to date have indicated that there is a potential groups of responders for whom therapy with this class is highly beneficial. The effect of non-responders has, however, made trial outcomes to variable to warrant further development. To solve this problem, we intend to further extend proof-of-concept in patient stratification to allow us to select responder populations for initial patient trials. The objectives of the project are, therefore: To prepare analogs of the existing compounds Conduct pre-clinical models for rheumatoid arthritis, IBD, sepsis, liver fibrosis and motilin dependent gut stimulation Examine the activity of the compounds in human tissue explant models Select a pre-clinical candidate class Develop a scaled-up process for GMP synthesis of the lead Conduct a survey of p38 expression in IBD and RA sub-types at various stages of disease and correlate this plasma markers. Based on results of tissue explant studies and p38 expression, select a patient stratification protocol for phase 2A studies in man.


Grant
Agency: European Commission | Branch: FP7 | Program: CP | Phase: ICT-2011.1.5 | Award Amount: 6.04M | Year: 2011

During the last century, significant scientific progress has more than doubled the average lifetime of developed countries inhabitants. This amazing result is the indirect consequence of X-rays discoveryin 1901, of antibiotics in the late 20s, of advances in surgery with the first heart transplant in the late 60s, to name just a few representative examples. In the new millennium, eHealth will likely constitute the next disruptive big jump: this goal will be fostered by the networking technology that CONCERTO envisions to develop, which addresses the delivery of interactive multimedia applications over wirelessnetworks. In this fast-paced world, early diagnosis (i.e., before even the patient reaches an hospital) and remote care (i.e., without physical presence of medical doctors) are important cornerstones to make this big jump become a reality.At a technical level, this interactive and real-time multimedia adaptation and delivery, is extremely challenging due to the necessity of flawless 3D/4D images and video quality, which is for doctors andparamedics a hard constraint to yield correct diagnosis.CONCERTO intends to design and validate radically new techniques for media content fusion, adaptation, delivery and interactive access. Advanced algorithms and codecs to improve the compression and the protection of medical images and videos will be developed. Near-instantaneous adaptation will be then used for coping with variable bandwidth availability, error-prone links, etc., that may affect the received quality. More particularly, the project will design adaptive solutions considering not only the network capabilities but also the specific context of the delivery, such as patient-specific data and status. Finally, media-caching aided content-aware wireless delivery (e.g., LTE / LTE Advanced) schemes will be designed for advanced content-aware networking. In this challenge, each partner will play the right instrument to ensure the validity of the CONCERTO solution: this will tackle from low-level technical aspects, to the realization of a proof-of-concept demonstrator and to the achievement of high level objectives, where physicians of the hospital of Perugia will assess the actual quality of experience, orchestrating and exploiting the consortium skills at best.


Grant
Agency: European Commission | Branch: FP7 | Program: CSA-SA | Phase: FP7-PEOPLE-2013-NIGHT | Award Amount: 108.26K | Year: 2013

SHARP stands for Sharing Researchers Passions and is the name of the first European Researchers Night in Umbria, a region in the centre of Italy, a long night with researchers that will take place on the 27th of September 2013. Locations for the event will be the three Umbria main cities: Perugia, Terni and Foligno, where departments of the 700 year old University and public and private research centres are located. Piazzas, streets, characteristic corners and unusual location will be the backdrop to meet researchers. With a curious public entering into the spirit of original and lively performances will be easy to bridge the gap that many times separates the researchers world and the general public. SHARP activities will engage the public to identify shared passions, attitudes, expectations and way of thinking they have in common with the researchers. 24 different activities arranged in 39 events proposed during the Night will be inspired by passions for music, sport, arts, cooking, tv, movies, games. Events will help to present the researchers work in various cutting edge research fields. SHARP night will present researchers as passionate people, with passions about the real world we all live in. Passion is also a key for motivation and commitment, a relevant message that will be covered to youngster. Passions are definitely a shared ground among humans. Sharing passion is a form of dialogue that helps to better recognize the researchers role.


Grant
Agency: European Commission | Branch: H2020 | Program: MSCA-RISE | Phase: MSCA-RISE-2014 | Award Amount: 1.30M | Year: 2015

The project aims at establishing a multi-lateral network of research and innovation staff active in olive germplasm access, conservation, evaluation and exploitation, strengthening research capacities through the exchange of knowledge and expertise on a shared research programme focused on developing integrated common protocols to phenotype and characterize plants at molecular, morphological and physiological level, and evaluating the olive oil quality related to varieties. The scientific results of the project will contribute at improving the potential of the olive germplasm collections, repositories and banks as main sources of variability and of the evaluation tools to be used to increase oliviculture sustainability. Particular attention will be paid to issues concerned to international intellectual property rights for conserving, exchanging and using the olive genetic resources. Another aim is to create a long lasting network among partners also promoting new common projects in the frame of Horizon2020 and other international funding sources. The joint exchange programme will involve 9 beneficiaries and 6 partners belonging to AC and NAC sectors and will be performed through a series of short and long term staff exchanges and workshops among European (Italy, Spain, Greece and France) and third countries (Morocco, Lebanon, Jordan, Argentina, Chile and Mexico). The International Olive Council (IOC), represented by IOC Executive Director, Jean-Louis Barjol, expressed its strong support to BeFOre planning to play an important role in dissemination activities. Experienced and early stage researchers, technicians and managers, are expected to be exchanged between EU and TC to ensure a good scientific transfer of knowledge and training. Enhancement of careers for the staff involved is expected. The project coordination and management will be ensured by the contribution of a well established coordination group and a Steering Committee.


Grant
Agency: European Commission | Branch: H2020 | Program: CSA | Phase: MSCA-NIGHT-2014 | Award Amount: 332.06K | Year: 2014

The SHARPER project (Sharing Researchers Passion for Excellence and Results - The European Researchers Night in the Centre of Italy, 2014 2015) wants to make the researchers quest for excellence accessible to everybody in cities and communities where researchers act and live. Excellence is one of the main goal that researchers aim at through high level research projects that can generate innovative results. Enthusiasm, emotions and knowledge are the driving force leading researchers constantly to face new challenges. Making this process accessible means to share with people this quest for innovative results. SHARPER will take place on 26th of September 2014 and the 25th of September 2015 simultaneously in Perugia, Ancona and LAquila, the capital cities of three regions in the centre of Italy: Umbria, Marche and Abruzzo. The network of cities together with their Research Institutions and science communication teams provides a group of excellence at national and international level. Perugia combines its tradition as University city with the presence in the city of a fifteen years experienced team (Psiquadro) of science communicators with a European profile. In LAquila, The Laboratori Nazionali del Gran Sasso (LNGS), of the Italian Institute for Nuclear Physics, the University and the GSSI (Gran Sasso Science Institute) provide examples of world leading researchers teams. The Universit Politecnica of Ancona is a growing Institution in the field of technological applications of research. SHARPER will include: street labs, exhibitions, performances or other communication actions in venues plenty of symbolic and practical value for the future development of the cities and their future based on excellence and innovation. The SHARPER communication actions will engage students, family groups and citizens actively involved since the planning phase of the project. At least 20.000 visitors are expected in the three cities each year during the Night.


Grant
Agency: European Commission | Branch: FP7 | Program: BSG-SME | Phase: SME-2013-1 | Award Amount: 1.48M | Year: 2013

Buildings are called upon to be integrated in the urban spaces, which needs aesthetic requirements of the external envelop. Moreover, the faades of buildings must be long-lasting and ensure well-being inside the building (thermal isolation, walls breathing). Nowadays major activity in the construction sector in Europe is retrofitting, representing the 42% of existing buildings and making up about 75% of the building stock in 2050. Most of these activities are linked to ageing of the faades and solving of insulation problems, where the Ventilated faades are considered as one of the most efficient systems. Current systems present disadvantages related to corrosion, environmental impact (aluminium), recyclability, size and weight (ceramic, stone). An environmental-friendly solution, overcoming all the mentioned drawbacks and with natural aesthetic appeal is wood, but the material lacks the necessary durability for outdoor exposition. This drawback can be addressed by new technological materials which incorporate wood in a high per cent, combining it with polymers (Wood Polymer Composites/WPCs). WPCs offer better thermal and acoustic isolation than aluminium, and better durability than wood. However it can be stated that although durability is highly increased, it continues being the main problem. When using WPCs as building components another problem arising is their poor fire performance. HIFIVENT aims the development of a WPC based ventilated faade addressing the following issues: -Improve weathering properties by fibre hydrophobation and highly protective co-extruded layer; -Use of nanotechnology to improve mechanical and fire properties. Goal of Euroclass B-s3,d0 fire performance (halogen-free system). -Improve mechanical performance by using long fibres for structural parts. -Fully recyclable system. Partners with complementary expertise; 5 SMEs: BAVE (DE), BEOLOGIC (BE), ESCANERO (SP), UXAMA (SP), PROLABIN (IT) and 3 RTDs:TECNALIA (SP), WKI (DE) and UNIPG (IT).


Hollywood, Feb. 09, 2017 (GLOBE NEWSWIRE) -- Earth Science Tech, Inc. (OTC PINK: ETST) ("ETST" or "the Company"),   an innovative biotech company, which focuses on cannabis-industrial hemp, cannabinoid research and development, nutraceuticals and pharmaceuticals is proud to announce that four new scientists and doctors have joined the company’s Advisory Board. ETST strategy of recruiting industry experts to help expand and increase the Development of Cannabinoids' Therapeutic Indications, R&D, Technology, IP and Treatments. These Four Distinguished Scientists and Doctors will serve on the board of advisory for Earth Science Tech and or its two (2) wholly owned subsidiaries, Cannabis Therapeutics Inc., and Earth Science Pharmaceutical Inc. Dr. Laurent Azoulay, PhD. Laurent Azoulay, Ph.D., has joined both the Cannabis Therapeutics Inc. and Earth Science Pharmaceutical Inc. Advisory Boards. He is an Associate Professor of Oncology at McGill University, where he actively researches cancer pharmacoepidemiology, which includes evaluating the safety of cancer drugs at a societal level. After receiving his PhD in 2007 from the Université de Montréal, he completed a postdoctoral fellowship in pharmacoepidemiology at the Department of Epidemiology, Biostatistics and Occupational Health, McGill University. He then joined the Gerald Department of Oncology as an Assistant Professor in 2009. In 2016, he was promoted to the rank of Associate Professor with a cross-appointment with the Department of Epidemiology, Biostatistics and Occupational Health. Dr. Chandra Panchal, PhD. Chandra Panchal, Ph.D., has joined the Cannabis Therapeutics Inc., Earth Science Pharmaceutical Inc., and Earth Science Tech Inc. Advisory Boards. He is a serial entrepreneur with a wealth of expertise acquired from 28 years of experience in the biotech/pharmaceutical sector. Dr. Panchal founded Axcelon in 2001 and was a co-founder of Procyon Biopharma Inc., a publicly traded biotechnology company involved in the development of wound healing, cancer therapeutic, and diagnostic products. Now known as Ambrilia BioPharma Inc., the company listed on the Alberta Stock Exchange in 1998 and the TSX in 2000. He served as Procyon Biopharma Inc.’s Chairman, President, and CEO; and Ambrilia Biopharma Inc.’s Senior Executive Vice-President, Business Development, Licensing, and Intellectual Property in charge of both out-licensing, in-licensing and M&A activities. He retired from Ambrilia Biopharma Inc. in February 2008. Since then, Dr. Panchal has been actively involved in Axcelon.  Prior to founding Procyon Biopharma Inc., Dr. Panchal was a senior scientist/group leader supervising activities related to yeast genetics, fermentations, and product development at John Labatt Ltd., a multinational food and beverage company. Dr. Panchal sits on the board of directors of several public and private companies.  He has authored/co-authored over 60 scientific papers and has edited a book entitled Yeast Strain Selection. Dr. Panchal has been an Adjunct Professor at the University of Western Ontario where he obtained his Ph.D. in biochemical engineering. Dr. Domenico Fuoco, PhD. Domenico Fuoco, Ph.D., has joined the Cannabis Therapeutics Inc. Advisory Board. Dr. Fuoco has over 16 years’ experience in the research and development of innovative solutions for the pharmaceutical industry. Dr. Fuoco trained at the prestigious Department of Oncology of McGill University Health Centre (MUHC) in Montreal, from 2012 to 2015. During this time, Dr. Fuoco worked on the next generation of medications for AVEO Oncology and Helsinn Therapeutics.  Prior to this, Dr. Fuoco obtained his PhD and Post-Doc training in medicinal chemistry and drug discovery at the University of Perugia in Italy with further studies at the University of Salamanca School of Pharmacy in Spain. Dr. Fuoco is recognized for the transdisciplinary approach of his work. In 2010, Dr. Fuoco was Principal Scientist of the Italian Mission in Amazonia, Bogotà, Colombia.  Dr. Fuoco’s publications cover a wide-range of chemical fields, from functional foods to autoimmune diseases. In 2015, Dr. Fuoco was honored with the prestigious Dr. Henry Shibata Fellowship from the Cedar Cancer Foundation for his work in the field of palliative care. Dr. Fuoco is an active member of the Italian Canadian Community Foundation and is very active within his community.  He is also the chairman from Smart Medicines Consortium for the advancement of health care. Dr. Fuoco’s expertise in human health and functional foods are highly valued as strategic assets by ETST. Calvin Higgins, M.D. Calvin Higgins, M.D., has joined the Earth Science Tech Inc. Advisory Board. Dr. Calvin Higgins is board-certified in internal medicine. Diplomate of the American Board of Internal Medicine. He was born in Kingston, Jamaica. He came to the United States in 1979. He attended Cornell Medical School and graduated in 1985. In 1998, he completed his residency at Lenox Hill Medical Center in Manhattan, New York in Internal Medicine. In 1998 he moved to Florida and completed 3 years in office-based medicine. He then moved onto hospital-based medicine in 2001 to present. Dr. Higgins is affiliated with Memorial Hospital Miramar, Memorial Hospital Pembroke, Memorial Hospital West and Memorial Regional Hospital. Dr. Higgins has a great core for alternative medicine. He always encourages his patients to seek lifestyle changes in diet, exercise, meditation and mental wellness, just to name a few. “We are very excited to have so much new talent joining our Advisory Boards,” said President, Director, and COO Nickolas Tabraue, “We are well on our way to developing top-notch treatments to some of the most common health problems people face, and bringing on such esteemed talent to advise us will only get us there quicker.” About Earth Science Tech: (www.earthsciencetech.com) is a publicly traded (ETST) unique Science based Biotechnology company focused on cutting edge Nutraceuticals, Bioceuticals, and Phytoceuticals for the Health, Wellness and Alternative Medicine Markets to help improve the quality of life for Consumers Worldwide. ETST is also dedicated to providing Natural Alternatives to prescription medications through the use of its cutting edge Nutritional and Dietary Supplements. This may include products such as its High-Grade Hemp CBD (Cannabidiol) Oil, Vitamins, Minerals, Herbs, Botanicals, Personal Care Products, Homeopathies, Functional Foods and other products. These products may be in various formulations and delivery systems including (but not limited to) capsules, tablets, soft gels, chewables, liquids, creams, sprays, powders, and whole herbs. ETST is focused on researching and developing innovative Hemp extracts and to make them accessible Worldwide. ETST plans to be the premier supplier of the highest quality and purity of High Grade Hemp CBD (Cannabidiol) Oil. ETST's primary goal is to advance different High Quality Hemp extracts with a broad profile of Cannabinoids and additional natural molecules found in Industrial Hemp and to identify their distinct properties. The company is dedicated in offering its consumers the finest and purest quality All Natural-Organic Hemp CBD Oil while never compromising on quality. ETST High Grade Hemp CBD (Cannabidiol) Oil is classified as "food based" and therefore perfectly permissible in all 50 states and more than 40 countries. Cannabinoids (Cannabidiol/CBD) are natural constituents of the Hemp plant and CBD is derived from Hemp stalk and seed. Hemp oil is a well-known dietary supplement and the naturally occurring CBD possesses no psychoactive qualities and presents a continuing stream of overwhelming evidence of significant Wellness benefits. With no psychoactive ingredient, Hemp CBD Oil is a ready-for-market Hemp-basedNutraceutical. The United States Food and Drug Administration (FDA) currently considers non-THC hemp based cannabinoids, including CBD, to be "food based" and therefore salable. These new non-psychoactive CBD-rich hemp oil products that ETST has geared up to market and distribute are beyond reproach. CBD (Cannabidiol), a naturally occurring constituent of the Industrial Hemp plant, promotes and supports the nutritional health of aging bodies in particular. Source: US Government Patent #6,630,507 "Cannabinoids as antioxidants and neuroprotectants." ETST does not grow, sell or distribute any substances that violate United States Law or the controlled substance act. ETST does sell and distribute cannabis industrial hemp based products. About Cannabis Therapeutics: Cannabis Therapeutics, Inc. is a wholly owned subsidiary of Earth Science Tech, Inc (ETST). Cannabis Therapeutics, Inc. was formed as an emerging biotechnology company poised to become a world leader in cannabinoid research and development for a broad line of cannabis cannabinoid-based pharmaceuticals, nutraceuticals as well as other products & solutions. Cannabis Therapeutics mission it to help change the healthcare landscape by introducing their proprietary cannabis-cannabinoid based products made for both the pharmaceutical and retail consumer markets worldwide. The company is currently working on finishing the launch of its new corporate website at www.Cannabisthera.com About Earth Science Pharmaceutical: Earth Science Pharmaceutical, Inc. is a wholly owned subsidiary of Earth Science Tech, Inc (ETST). Earth Science Pharmaceutical is focused on becoming a world leader in the development of low cost, non-invasive diagnostic tools, medical devices, testing processes and vaccines for STIs (Sexually Transmitted Infections and/or Diseases). Earth Science Pharmaceutical CEO, Dr. Michel Aubé, a renowned scientist, is committed to help grow ETST in the medical and pharmaceutical industry. The company is currently working on finishing the launch of its new corporate website at www.Earthsciencepharmaceutical.com FOOD AND DRUG ADMINISTRATION (FDA) DISCLOSURE: These statements and products have not been evaluated by the FDA and are not intended to diagnose, treat or cure any disease. Always check with your physician before starting a new dietary supplement program. The FDA has not evaluated the validity or truthfulness of these claims; therefore, we encourage you to review published researches relating to the benefits and properties of CBD hemp oils and other CBD products. SAFE HARBOR ACT: Forward-Looking Statements are included within the meaning of Section 27A of the Securities Act of 1933, and Section 21E of the Securities Exchange Act of 1934, as amended. All statements regarding our expected future financial position, results of operations, cash flows, financing plans, business strategy, products and services, competitive positions, growth opportunities, plans and objectives of management for future operations, including words such as "anticipate," "if," "believe," "plan," "estimate," "expect," "intend," "may," "could," "should," "will," and other similar expressions are forward-looking statements and involve risks, uncertainties and contingencies, many of which are beyond our control, which may cause actual results, performance, or achievements to differ materially from anticipated results, performance, or achievements. We are under no obligation to (and expressly disclaim any such obligation to) update or alter our forward-looking statements, whether as a result of new information, future events or otherwise.


Galluzzi G.,Bioversity International | Eyzaguirre P.,Third University of Rome | Negri V.,University of Perugia
Biodiversity and Conservation | Year: 2010

Over the last two decades, the importance of conserving genetic resources has received increasing attention. In this context the role of home gardens as repositories of biological diversity has been acknowledged but still a comprehensive, interdisciplinary investigation of their agro-biodiversity is lacking. Home gardens, whether found in rural or urban areas, are characterized by a structural complexity and multifunctionality which enables the provision of different benefits to ecosystems and people. Studies carried out in various countries demonstrate that high levels of inter- and intra-specific plant genetic diversity, especially in terms of traditional crop varieties and landraces, are preserved in home gardens. Families engage in food production for subsistence or small-scale marketing and the variety of crops and wild plants provides nutritional benefits. At the same time, home gardens are important social and cultural spaces where knowledge related to agricultural practices is transmitted and through which households may improve their income and livelihoods. The present article summarizes available literature on the biological and cultural significance of agro-biodiversity in home gardens. It discusses future constraints and opportunities in home garden research, in the prospect of defining and promoting their role in conservation of agricultural biodiversity and cultural heritage. © 2010 Springer Science+Business Media B.V.


Cravotto G.,University of Turin | Garella D.,University of Turin | Carnaroglio D.,University of Turin | Gaudino E.C.,University of Turin | Rosati O.,University of Perugia
Chemical Communications | Year: 2012

Organosulphur compounds can be easily and selectively oxidized to sulfones using a small excess of Oxone® (1.6 eq.) under solventless mechanical milling conditions. This green procedure has been efficiently applied to a series of model compounds and to the desulphurization of medium/high sulphur content paraffins (up to 3000 mg kg -1). © 2012 The Royal Society of Chemistry.


Broccatelli F.,University of Perugia | Mannhold R.,Heinrich Heine University Düsseldorf | Moriconi A.,Dompe S.p.a. | Giuli S.,Dompe S.p.a. | Carosati E.,University of Perugia
Molecular Pharmaceutics | Year: 2012

We collected 1173 hERG patch clamp (PC) data (IC50) from the literature to derive twelve classification models for hERG inhibition, covering a large variety of chemical descriptors and classification algorithms. Models were generated using 545 molecules and validated through 258 external molecules tested in PC experiments. We also evaluated the suitability of the best models to predict the activity of 26 proprietary compounds tested in radioligand binding displacement (RBD). Results proved the necessity to use multiple validation sets for a true estimation of model accuracy and demonstrated that using various descriptors and algorithms improves the performance of ligand-based models. Intriguingly, one of the most accurate models uncovered an unexpected link between extent of metabolism and hERG liability. This hypothesis was fairly reinforced by using the Biopharmaceutics Drug Disposition Classification System (BDDCS) that recognized 94% of the hERG inhibitors as extensively metabolized in vivo. Data mining suggested that high Torsades de Pointes (TdP) risk results from an interplay of hERG inhibition, extent of metabolism, active transport, and possibly solubility. Overall, these new findings might improve both the decision making skills of pharmaceutical scientists to mitigate hERG liability during the drug discovery process and the TdP risk assessment during drug development. © 2012 American Chemical Society.


Manos B.,Aristotle University of Thessaloniki | Partalidou M.,A.U.Th | Fantozzi F.,University of Perugia | Arampatzis S.,Tero Ltd. | Papadopoulou O.,Tero Ltd.
Renewable and Sustainable Energy Reviews | Year: 2014

The current economic downturn has put public budgets under pressure, reducing investments and revenues for local stakeholders to cope, among other things, with contemporary demands of environmental protection. Local-based partnerships may provide an efficient tool by adopting, integrating and implementing actions based on awareness and participation of a set of different players. This need is even more evident in rural areas in which a proposed decentralized bio-energy production model established in Agro-energy districtscan provide incentive and create a comfortable ground for the development of an energy production plant based on a mixed public-private partnership. Drawing on the implementation of a European co-funded research project the paper presents the efforts being made to build a partnership at a local level in order to cover the lack of an institutional plan and public investment for handling biomass production. Our aim is not primarily to present the best technical solution to bio-energy production but rather to illustrate the networking between different players, the public consultation, and the agreements being made under the form of Public Private Partnerships, as well as the levels of commitment and the risks taken. The gist of this study is that despite the civic engagements the inconsistent administrative environment, the dominance of the public sector and the State intervention through legislation and different political decisions, makes it still difficult for local partnerships to exercise their power and turn from government to governance in order to cope with the environmental challenges and tackle inequalities faced in rural areas. © 2013 Elsevier Ltd.


Agnelli G.,University of Perugia | George D.J.,Duke University | Kakkar A.K.,University College London | Fisher W.,McGill University | And 6 more authors.
New England Journal of Medicine | Year: 2012

BACKGROUND: Patients receiving chemotherapy for cancer are at increased risk for venous thromboembolism. Limited data support the clinical benefit of antithrombotic prophylaxis. METHODS: In this double-blind, multicenter trial, we evaluated the efficacy and safety of the ultralow- molecular-weight heparin semuloparin for prevention of venous thromboembolism in patients receiving chemotherapy for cancer. Patients with metastatic or locally advanced solid tumors who were beginning to receive a course of chemotherapy were randomly assigned to receive subcutaneous semuloparin, 20 mg once daily, or placebo until there was a change of chemotherapy regimen. The primary efficacy outcome was the composite of any symptomatic deep-vein thrombosis, any nonfatal pulmonary embolism, and death related to venous thromboembolism. Clinically relevant bleeding (major and nonmajor) was the main safety outcome. RESULTS: The median treatment duration was 3.5 months. Venous thromboembolism occurred in 20 of 1608 patients (1.2%) receiving semuloparin, as compared with 55 of 1604 (3.4%) receiving placebo (hazard ratio, 0.36; 95% confidence interval [CI], 0.21 to 0.60; P<0.001), with consistent efficacy among subgroups defined according to the origin and stage of cancer and the baseline risk of venous thromboembolism. The incidence of clinically relevant bleeding was 2.8% and 2.0% in the semuloparin and placebo groups, respectively (hazard ratio, 1.40; 95% CI, 0.89 to 2.21). Major bleeding occurred in 19 of 1589 patients (1.2%) receiving semuloparin and 18 of 1583 (1.1%) receiving placebo (hazard ratio, 1.05; 95% CI, 0.55 to 1.99). Incidences of all other adverse events were similar in the two study groups. CONCLUSIONS: Semuloparin reduces the incidence of thromboembolic events in patients receiving chemotherapy for cancer, with no apparent increase in major bleeding. (Funded by Sanofi; ClinicalTrials.gov number, NCT00694382.) Copyright © 2012 Massachusetts Medical Society.


Buller H.R.,University of Amsterdam | Prins M.H.,Maastricht University | Lensing A.W.A.,Bayer AG | Decousus H.,Jean Monnet University | And 15 more authors.
New England Journal of Medicine | Year: 2012

BACKGROUND: A fixed-dose regimen of rivaroxaban, an oral factor Xa inhibitor, has been shown to be as effective as standard anticoagulant therapy for the treatment of deep-vein thrombosis, without the need for laboratory monitoring. This approach may also simplify the treatment of pulmonary embolism. METHODS: In a randomized, open-label, event-driven, noninferiority trial involving 4832 patients who had acute symptomatic pulmonary embolism with or without deep-vein thrombosis, we compared rivaroxaban (15 mg twice daily for 3 weeks, followed by 20 mg once daily) with standard therapy with enoxaparin followed by an adjusted-dose vitamin K antagonist for 3, 6, or 12 months. The primary efficacy outcome was symptomatic recurrent venous thromboembolism. The principal safety outcome was major or clinically relevant nonmajor bleeding. RESULTS: Rivaroxaban was noninferior to standard therapy (noninferiority margin, 2.0; P = 0.003) for the primary efficacy outcome, with 50 events in the rivaroxaban group (2.1%) versus 44 events in the standard-therapy group (1.8%) (hazard ratio, 1.12; 95% confidence interval [CI], 0.75 to 1.68). The principal safety outcome occurred in 10.3% of patients in the rivaroxaban group and 11.4% of those in the standardtherapy group (hazard ratio, 0.90; 95% CI, 0.76 to 1.07; P = 0.23). Major bleeding was observed in 26 patients (1.1%) in the rivaroxaban group and 52 patients (2.2%) in the standard-therapy group (hazard ratio, 0.49; 95% CI, 0.31 to 0.79; P = 0.003). Rates of other adverse events were similar in the two groups. CONCLUSIONS: A fixed-dose regimen of rivaroxaban alone was noninferior to standard therapy for the initial and long-term treatment of pulmonary embolism and had a potentially improved benefit-risk profile. (Funded by Bayer HealthCare and Janssen Pharmaceuticals; EINSTEIN-PE ClinicalTrials.gov number, NCT00439777.). Copyright © 2012 Massachusetts Medical Society.


Fiorucci S.,University of Perugia | Distrutti E.,Science Gastroenterologia | Ricci P.,University of Perugia | Giuliano V.,Science Gastroenterologia | And 2 more authors.
Expert Opinion on Therapeutic Targets | Year: 2014

Introduction: Bile acids, the end product of cholesterol metabolism, are signaling molecules. The farnesoid X receptor (FXR) is a bile acid sensor and is part of a network of nuclear receptors that regulate bile acid homeostasis. In addition to FXR, bile acids activate other nuclear receptors (CAR, PXR and VDR), cell surface receptors including the G protein-coupled bile acid receptor 1 (GP-BAR1/TGR5), muscarinic receptor and calcium-gated potassium channels.Areas covered: The semisynthetic bile acid derivative 6-ethyl chenodeoxycholic acid (6-ECDCA, INT-747 later christened obeticholic acid) is a dual FXR/GP-BAR1 ligand that attenuates bile flow impairment in cholestasis induced by 17β-estradiol; a model of pregnancy-induced cholestasis. Phase II trials with this agent in early stage primary biliary cirrhosis have shown beneficial effects on surrogate markers of damage progression, specifically alkaline phosphatase, with a dose-dependent itching being the most severe and common side effect (up to 70% of patients) leading to therapy discontinuation in 38% of patients. GP-BAR1 activation in the skin triggers itching, thus providing a molecular explanation for this side effect.Expert opinion: While the role of FXR activation in treating severe cholestasis needs confirmation, the activation of GP-BAR1 is likely involved in pruritus development that associates with clinical use of dual FXR/GP-BAR1 ligands. FXR antagonist could be an interesting opportunity for treatment of severe/obstructive cholestasis. © 2014 Informa UK, Ltd.


Cottone F.,University Paris Est Creteil | Gammaitoni L.,University of Perugia | Vocca H.,University of Perugia | Ferrari M.,University of Brescia | Ferrari V.,University of Brescia
Smart Materials and Structures | Year: 2012

Among the main vibration-to-electricity conversion systems, resonant harvesters suffer from a series of strong limits like their narrow frequency response and poor output power at small scale. Most of all, realistic vibration sources are variable in time and abundant at relatively low frequencies. Nonlinear vibration harvesters, on the other hand, are more attractive, thanks to their large bandwidth response and flexibility to convert kinetic energy of the natural frequency of the sources. In particular, bistable oscillators have been proven to show higher global performances when excited by random vibrations. In this paper, such an approach is investigated for piezoelectric beams by exerting an increasing axial compression. An advantage of this technique is the absence of magnetic forces to create bistable dynamics. Athin piezoelectric axially loaded beam is theoretically modelled and experimentally investigated under wideband random vibrations. In the buckled configuration, the device exhibits superior power generation over a large interval of resistive load, with gains up to more than a factor of ten compared to the unbuckled state. The numerical model and experimental results are in good qualitative agreement. © 2012 IOP Publishing Ltd.


Mangera A.,Sheffield Teaching Hospitals NHS Trust | Andersson K.-E.,Wake forest University | Apostolidis A.,Aristotle University of Thessaloniki | Chapple C.,Sheffield Teaching Hospitals NHS Trust | And 4 more authors.
European Urology | Year: 2011

Context: The use of botulinum toxin A (BoNTA) in the treatment of lower urinary tract dysfunction has expanded in recent years and the off-licence usage list includes neurogenic detrusor overactivity (NDO), idiopathic detrusor overactivity (IDO), painful bladder syndrome (PBS), and lower urinary tract symptoms resulting from bladder outflow obstruction (BOO) or detrusor sphincter dyssynergia (DSD). There are two commonly used preparations of BoNTA: Botox (onabotulinumtoxinA) and Dysport (abobotulinumtoxinA). Objective: To compare the reported outcomes of onabotulinumtoxinA and abobotulinumtoxinA in the treatment of NDO, IDO, PBS, DSD, and BOO for adults and children. Evidence acquisition: We performed a systematic review of the published literature on PubMed, Scopus, and Embase in the English language reporting on outcomes of both BoNTA preparations. Review articles and series with <10 cases were excluded. The articles were graded for level of evidence and conclusions drawn separately for data with higher-level evidence. Evidence synthesis: There is high-level evidence for the use of onabotulinumtoxinA and abobotulinumtoxinA in adults with NDO but only for abobotulinumtoxinA in children with NDO. Only onabotulinumtoxinA has level 1 evidence supporting its use in IDO, BOO, DSD, and PBS/interstitial cystitis. Conclusions: We identified good-quality studies that evaluated onabotulinumtoxinA for all the indications described above in adults; such was not the case with abobotulinumtoxinA. Although this does not imply that onabotulinumtoxinA is more effective than abobotulinumtoxinA, it should be a consideration when counselling patients on the use of botulinum toxin in urologic applications. The two preparations should not be used interchangeably, either in terms of predicting outcome or in determining doses to be used. © 2011 European Association of Urology.


Mueck W.,Bayer AG | Lensing A.W.A.,Bayer AG | Agnelli G.,University of Perugia | Decousus H.,French Institute of Health and Medical Research | And 3 more authors.
Clinical Pharmacokinetics | Year: 2011

Background and Objective: Rivaroxaban is an oral, direct Factor Xa inhibitor, which is at an advanced stage of clinical development for prevention and treatment of thromboembolic disorders. Two phase II studies, ODIXa-DVT and EINSTEIN DVT, assessed the efficacy and safety of oral rivaroxaban (once daily or twice daily) for treatment of acute deep-vein thrombosis (DVT). Population pharmacokinetic and pharmacodynamic analyses of rivaroxaban in patients in these two phase II studies were conducted to characterize the pharmacokinetics/ pharmacodynamics of rivaroxaban and the relationship between important patient covariates and model parameters. Exposure simulations in patients with atrial fibrillation (AF) were also performed in order to predict the exposure of rivaroxaban, using modified demographic data reflecting the characteristics of a typical AF population. Methods: A population pharmacokinetic model was developed using plasma samples from these patients. Various simulations were conducted to explore the pharmacokinetics of rivaroxaban in patients with DVT and to predict exposure in those with AF. Correlations between plasma rivaroxaban concentrations and the prothrombin time, Factor Xa activity, HepTest and activated partial thromboplastin time were also described. Results: The pharmacokinetics of rivaroxaban in patients with DVT were found to be consistent and predictable across all doses studied. The area under the plasma concentration-time curve (AUC) increased dose dependently. The same total daily doses given once daily achieved higher maximum plasma concentration (Cmax) values (~20%) and lower trough (minimum) plasma concentration (Ctrough) values (~60%) than when given twice daily; however, the 5th-95th percentile ranges for these parameters overlapped. Rivaroxaban clearance was moderately influenced by age and renal function, and the volume of distribution was influenced by age, body weight and sex; the effects were within the observed interindividual variability. Simulations in virtual patient populations with AF showed that a rivaroxaban dose of 15mg once daily in patients with creatinine clearance of 30-49mL/min would achieve AUC and Cmax values similar to those observed with 20 mg once daily in patients with normal renal function. The prothrombin time correlated almost linearly with plasma rivaroxaban concentrations (£500 mg/L). Conclusion: Population analyses of phase II clinical data indicated that the pharmacokinetics and pharmacodynamics of all rivaroxaban doses were predictable and were affected by expected demographic factors in patients with acute DVT. © 2011 Adis Data Information BV. All rights reserved.


Grant
Agency: European Commission | Branch: H2020 | Program: MSCA-RISE | Phase: MSCA-RISE-2014 | Award Amount: 1.05M | Year: 2015

In the recent years an unprecedented effort has been made to increase the rates of childhood immunization in resource poor countries. This has translated into an increased number of children receiving vaccines and a parallel decrease in the rate of illnesses from vaccine preventable diseases. However, in some regions it has proven difficult to achieve optimal levels of immunization mainly because of issues concerning communication, management and poor utilization of resources. Recent studies have questioned the validity of available vaccine coverage data and the way they are collected. Currently, both the progress of the vaccination programs and indirectly the level of protection in a population are inferred on the basis of administrative records. This largely unverified information is also utilized as performance indicator to allocate funds from government and donor agencies. Such self-certification practice does not incentivize the optimization of resources while it has been increasingly questioned in terms of its validity and integrity. We propose to develop and validate an innovative technical solution based on an assay system that integrates multiplex capability and analytical performance, to simultaneously quantify antibody levels against the major vaccine components, with both automation and wireless connectivity to produce spatial-temporal co-ordinates of individual determinations. The multiplex capability will facilitate the analysis of cross coverage monitoring while generating reactivity profiles against the different vaccine components to discriminate vaccinated versus infected individuals. Spatial temporal co-ordinates of assay results will be used to generate interactive data sets for modeling changes in the age-specific risk of infection and the risk of outbreaks. The proposed system represents a formidable tool of unprecedented power to monitor the progress of different vaccination programs and experimentally validate record-based coverage data.


Grant
Agency: European Commission | Branch: H2020 | Program: MSCA-RISE | Phase: MSCA-RISE-2016 | Award Amount: 1.86M | Year: 2017

The project trans-making aims to establish a multilateral network of research and innovation staff active in the fields of placemaking/place-based art activities as a space to create alternative narratives for social, economic and democratic renewal. It will investigate and experiment with placemaking to contribute actively to the democratization/well-being of society, educating and empowering individuals and disadvantaged minorities through research and production in the connection between art and new technologies. The objective is to strengthen research capacities, through exchange of knowledge and expertise between academic and non-academic partners from Europe and Third Countries in a shared research programme focused on: collecting, documenting / Exploring, experimenting / Performing / Designing. Trough those work programme of Research and Innovation, the consortium, academic and non-academics partners, aims to foster links between art and culture, economy, democracy and innovation at EU level and beyond. To foster entrepreneurial skills, risk taking adaptability, innovation capacity (economic, social and democratic). And it will contribute actively to education and empowerment of individuals and disadvantaged minorities trough research and production between art and new technologies. The project through its consortium will be to foster a better understanding and knowledge sharing between scientific community, stakeholders and policy-makers. Which will be achieved with the respective networks of the involved partners. The final aim of trans-making will be to establish a long term collaboration among the partners in order to have a scientific and innovative worldwide community devoted to the research, (including art-based research), innovation, education activity in the matters concerned by the project. Moreover, the proposed measures of the project will be conceived in order to have the widest possible impact of the society.


Grant
Agency: European Commission | Branch: FP7 | Program: CP | Phase: SPA.2009.2.1.01 | Award Amount: 2.79M | Year: 2010

One of the major technological challenges associated with the access to planetary surfaces is the entry of the space vehicle in the planetary atmospheres at superorbital speeds. The problem is the very large heat released to the vehicle surface by the surrounding gas either as convective heating or as radiation. Optimization of the thermal shield design can have a profound impact on the overall mission mass, volume (and therefore energy and cost) budgets. However, a poor knowledge of the physics of hypersonic entry is the limiting factor. Uncertainties increase with the entry speed, in particular as radiation becomes a considerable contribution to the overall heat load. Significant advance can only be achieved when the uncertainties in the physical modelling have been considerably reduced. The main goal of this study is, therefore, a thorough analysis of the physics behind space vehicle entry into planetary atmospheres and an improvement of crucial elements of the modelling that allows reliable predictions of flight conditions. This study is therefore concerned with the development of advanced chemico-physical and plasma models of hypersonic entry flows. Advanced models mean the description of the nonequilibrium chemical kinetics of the high temperature medium on the basis of a state-to-state approach. This approach, in turn, calls for a microscopic description of the elementary processes that play a role in the high temperature reactive gas mixtures surrounding the space vehicles during the entry phase. The predictive capabilities of the theoretical models will be assessed against well defined experimental measurements and their impact on the overall heat flux to the surface will be estimated by Computational Fluid Dynamics simulations of realistic ground and flight tests.


News Article | December 14, 2016
Site: www.bbc.co.uk

Footprints made by early humans millions of years ago have been uncovered in Tanzania close to where similar tracks were found in the 1970s. The impressions were made when some of our distant relatives walked together across wet volcanic ash. Their makers, most likely Australopithecus afarensis, appear to have had a wide range of body sizes. Scientists say this gives clues to how this ancient species of human lived. Australopithecus afarensis is one of the longest-lived and best-known early human species. The fossil of "Lucy", a young adult female who lived in Ethiopia 3.2 million years ago, is perhaps the most famous individual. The newly discovered footprints may have been made by a male walking with smaller females. "This novel evidence, taken as a whole with the previous findings, portrays several early hominins moving as a group through the landscape following a volcanic eruption and subsequent rainfall. But there is more," said lead researcher Prof Giorgio Manzi, director of the archaeological project in Tanzania. "The footprints of one of the new individuals are astonishingly larger than anyone else's in the group, suggesting that he was a large male member of the species. "In fact, the 165cm stature indicated by his footprints makes him the largest Australopithecus specimen identified to date." In 1976, preserved footprints thought to be made by Australopithecus were discovered at a site in Laetoli, Tanzania. At 3.66 million years old, they are the oldest documented bipedal footprint trails. Now, the discovery of a second set of footprints has been revealed in the journal, eLife. "Now that we've found a new set of footprints it opens up a completely different window and there could be a number of new possibilities to study what is a photograph in time of the everyday life of this species," said Jacopo Moggi-Cecchi of the University of Florence. The tracks were found during excavations for a museum only 150m south of the original discovery. The researchers, based in Italy and Tanzania, think the two sets could belong together, giving clues to the lifestyle of Australopithecus. "A tentative conclusion is that the group consisted of one male, two or three females, and one or two juveniles, which leads us to believe that the male - and therefore other males in the species - had more than one female mate," said Dr Marco Cherin, director of the school of paleoanthropology at the University of Perugia. The finding of a male perhaps walking with several females could mean their social structure was "closer to a gorilla-like model than to chimpanzees or modern humans". In gorillas, one male and a number of females form a mating and child-rearing group. The study also raises questions about how human feet were made for walking. Australopithecus were capable of walking upright on two legs, but we don't know how much they resembled modern humans in the way they walked. Prof Robin Crompton of the University of Liverpool, who is not connected to the study, said the latest footprints will give more information, once statistical work is done. "Some people have argued that they have a slightly different gait, but I don't think there's any good evidence for that," he told BBC News. "If humans have been walking the same way as we do now for more or less 3.65 million years, and human ancestors - in another genus - Australopithecus - then that's really fairly exciting."


Evans R.J.,Statistical Laboratory | Forcina A.,University of Perugia
Computational Statistics and Data Analysis | Year: 2013

The two main algorithms that have been considered for fitting constrained marginal models to discrete data, one basedon Lagrange multipliers and the other on a regression model, are studied in detail. It is shown that the updates produced by the two methods are identical, but that the Lagrangian method is more efficient in the case of identically distributed observations. A generalization is given of the regression algorithm for modelling the effect of exogenous individual-level covariates, a context in which the use of the Lagrangian algorithm would be infeasible for even moderate sample sizes. An extension of the method to likelihood-based estimation under L 1-penalties is also considered. © 2013 Elsevier B.V. All rights reserved.


Nucci M.C.,University of Perugia | Nucci M.C.,National Institute of Nuclear Physics, Italy | Busso M.,National Institute of Nuclear Physics, Italy | Busso M.,University of Perugia
Astrophysical Journal | Year: 2014

The advection of thermonuclear ashes by magnetized domains emerging near the H shell was suggested to explain asymptotic giant branch (AGB) star abundances. Here we verify this idea quantitatively through exact MHD models. Starting with a simple two-dimensional (2D) geometry and in an inertia frame, we study plasma equilibria avoiding the complications of numerical simulations. We show that below the convective envelope of an AGB star, variable magnetic fields induce a natural expansion, permitted by the almost ideal MHD conditions, in which the radial velocity grows as the second power of the radius. We then study the convective envelope, where the complexity of macroturbulence allows only for a schematic analytical treatment. Here the radial velocity depends on the square root of the radius. We then verify the robustness of our results with 3D calculations for the velocity, showing that for both studied regions the solution previously found can be seen as a planar section of a more complex behavior, in which the average radial velocity retains the same dependency on the radius found in 2D. As a final check, we compare our results to approximate descriptions of buoyant magnetic structures. For realistic boundary conditions, the envelope crossing times are sufficient to disperse in the huge convective zone any material transported, suggesting magnetic advection as a promising mechanism for deep mixing. The mixing velocities are smaller than for convection but larger than for diffusion and adequate for extra mixing in red giants. © 2014. The American Astronomical Society. All rights reserved..


Menculini L.,University of Perugia | Panella O.,National Institute of Nuclear Physics, Italy | Roy P.,Indian Statistical Institute
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2013

We study the (2+1)-dimensional Dirac equation in a homogeneous magnetic field (relativistic Landau problem) within a minimal length or generalized uncertainty principle scenario. We derive exact solutions for a given explicit representation of the generalized uncertainty principle and provide expressions of the wave functions in the momentum representation. We find that in the minimal length case, the degeneracy of the states is modified, and that there are states that do not exist in the ordinary quantum mechanics limit (β→0). We also discuss the massless case, which may find application in describing the behavior of charged fermions in new materials like graphene. © 2013 American Physical Society.


Martino S.,University of Perugia | D'Angelo F.,University of Perugia | Armentano I.,University of Perugia | Kenny J.M.,University of Perugia | And 2 more authors.
Biotechnology Advances | Year: 2012

The synergism of stem cell biology and biomaterial technology promises to have a profound impact on stem-cell-based clinical applications for tissue regeneration. Biomaterials development is rapidly advancing to display properties that, in a precise and physiological fashion, could drive stem-cell fate both in vitro and in vivo. Thus, the design of novel materials is trying to recapitulate the molecular events involved in the production, clearance and interaction of molecules within tissue in pathologic conditions and regeneration of tissue/organs. In this review we will report on the challenges behind translating stem cell biology and biomaterial innovations into novel clinical therapeutic applications for tissue and organ replacements (graphical abstract). © 2011 Elsevier Inc.


Fantacci S.,University of Perugia | De Angelis F.,University of Perugia | Nazeeruddin M.K.,Institute of Chemical science and Engineering | Gratzel M.,Institute of Chemical science and Engineering
Journal of Physical Chemistry C | Year: 2011

The molecular structures and electronic and optical properties of 2,2′7,7′-tetrakis-(N,N-di-p-methoxyphenyl amine)-9,9′- spirobifluorene (spiro-MeOTAD) in different oxidation states have been investigated by means of DFT/TDDFT methods. Spiro-MeOTAD has been demonstrated to be an efficient hole-transport material (HTM) in organic light-emitting devices (OLEDs) and in solid-state dye-sensitized solar cells (ssDSCs), and to date spiro-MeOTAD, has yielded the highest ssDSC efficiency. The spiro-MeOTAD radical cation exhibits long-term stability, even though the 2+ and 4+ formal oxidation states are accessible. DFT and TDDFT allow the characterization of the excited states involved in the absorption processes of the spiro-MeOTAD-derived cations, an important aspect considering that the oxidized species absorb in the visible region. The excellent agreement between theory and experiment for both neutral spiro-MeOTAD and its oxidized forms opens the possibility for identifying the features that make it an efficient HTM, thus helping in the design of chemically modified or substituted spirobifluorenes. © 2011 American Chemical Society.


Reboldi G.,University of Perugia | Angeli F.,University of Perugia | De Simone G.,University of Naples Federico II | Staessen J.A.,Catholic University of Leuven | And 2 more authors.
Hypertension | Year: 2014

An excessive blood pressure (BP) reduction might be dangerous in high-risk patients with cardiovascular disease. In the Studio Italiano Sugli Effetti CARDIOvascolari del Controllo della Pressione Arteriosa SIStolica (Cardio-Sis), 1111 nondiabetic patients with systolic BP ≥150 mm Hg were randomly assigned to a systolic BP target <140 mm Hg (standard control) or <130 mm Hg (tight control). We stratified patients by absence (n=895) or presence (n=216) of established cardiovascular disease at entry. Antihypertensive treatment was open-label and tailored to each patient's needs. After 2-year follow-up, the primary end point of the study, electrocardiographic left ventricular hypertrophy, occurred less frequently in the tight than in the standard control group in the patients without (10.8% versus 15.2%) and with (14.1% versus 23.5%) established cardiovascular disease (P for interaction=0.82). The main secondary end point, a composite of cardiovascular events and all-cause death, occurred less frequently in the tight than in the standard control group both in patients without (1.47 versus 3.68 patient-years; P=0.016) and with (7.87 versus 11.22 patient-years; P=0.049) previous cardiovascular disease. In a multivariable Cox model, allocation to tight BP control reduced the risk of cardiovascular events to a similar extent in patients with or without overt cardiovascular disease at randomization (P for interaction=0.43). In conclusion, an intensive treatment aimed to lower systolic BP<130 mm Hg reduced left ventricular hypertrophy and improved clinical outcomes to a similar extent in patients with hypertension and without established cardiovascular disease. © 2013 American Heart Association, Inc.


Tomassoni C.,University of Perugia | Bastioli S.,RS Microwave Company Inc. | Sorrentino R.,MicroTech
IEEE Transactions on Microwave Theory and Techniques | Year: 2011

A new cavity arrangement, namely, the generalized TM dual-mode cavity, is presented in this paper. In contrast with the previous contributions on TM dual-mode filters, the generalized TM dual-mode cavity allows the realization of both symmetric and asymmetric filtering functions, simultaneously exploiting the maximum number of finite frequency transmission zeros. The high design flexibility in terms of number and position of transmission zeros is obtained by exciting and exploiting a set of nonresonating modes. Five structure parameters are used to fully control its equivalent transversal topology. The relationship between structure parameters and filtering function realized is extensively discussed. The design of multiple cavity filters is presented along with the experimental results of a sixth-order filter having six asymmetrically located transmission zeros. © 2006 IEEE.


Biondini S.,University of Perugia | Panella O.,National Institute of Nuclear Physics, Italy | Pancheri G.,National Institute of Nuclear Physics, Italy | Srivastava Y.N.,University of Perugia | Fano L.,University of Perugia
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2012

We consider the production at the LHC of exotic composite leptons of charge Q=+2e. Such states are allowed in composite models that contain extended isospin multiplets (I W=1 and I W=3/2). These doubly charged leptons couple with standard model (SM) fermions via gauge interactions, thereby delineating and restricting their possible decay channels. We discuss the production cross section at the LHC of L ++(pp→L ++,ℓ -) and concentrate on the leptonic signature deriving from the cascade decays L ++→W +ℓ +→ℓ +ℓ +ν ℓ i.e. pp→ℓ -(ℓ +ℓ +) ν ℓ showing that the invariant mass distribution of the like-sign dilepton has a sharp end point corresponding to excited lepton mass m *. We find that the √s=7TeV run is sensitive at the 3-sigma (5-sigma) level to a mass of the order of 600 GeV if L=10fb -1 (L=20fb -1). The √s=14TeV run can reach a sensitivity at 3-sigma (5-sigma) level up to m *=1TeV for L=20fb -1 (L=60fb -1). © 2012 American Physical Society.


Zucchi A.,University of Perugia | Silvani M.,Ospedale Degli Infermi | Pecoraro S.,Urologic
Asian Journal of Andrology | Year: 2013

The surgical techniques used by Austoni and Egydio in the treatment of Peyronie's disease are based on geometric principles. The aim of this paper is to report our multicentric experience and technical changes to Austoni's original technique, focusing on several tips and tricks to make this technique easy to perform, even by less experienced practitioners. We performed operations in three different Italian institutions. We implanted a small soft Virilis I® axial prostheses (Ø 7 Fr.), using a bovine pericardium collagen matrix patch (Hydrix®) to cover the defect in the tunica albuginea. Sixty patients with a mean age of 58 years (range 44-76 years) underwent surgery between September 2005 and January 2010. After surgery, mean lengthening of the shaft was 2 cm (range 1.2-2.3 cm) with complete correction of penile recurvatum. Thirty-nine patients resumed sexual activity 60 days later, 14 after 90 days and 7 after 120 days. The international index of erectile function (IIEF) score was 15.5 before surgery and it improved to 23 at 12 and 24 months after surgery. Furthermore, the visual analogue scale (VAS) showed good results in terms of the recovery of natural sexual intercourse (over 80% of couples) and of the original length and girth of the penis. The soft implant we used takes advantage of erection that occurs spontaneously, using the residual erection of the spared cavernous tissue. The method is easy to learn and reproducible, and the use of pericardium speeds up the operation, while also covering large defects of the tunica albuginea that result from complex recurvatum. © 2013 AJA, SIMM & SJTU. All rights reserved.


Menculini L.,University of Perugia | Panella O.,National Institute of Nuclear Physics, Italy | Roy P.,Indian Statistical Institute
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2015

We obtain exact solutions of the (2+1)-dimensional Dirac oscillator in a homogeneous magnetic field within a minimal-length (Δx0=β) or generalized uncertainty principle scenario. This system in ordinary quantum mechanics has a single left-right chiral quantum phase transition (QPT). We show that a nonzero minimal length turns on an infinite number of quantum phase transitions which accumulate towards the known QPT when β→0. It is also shown that the presence of the minimal length modifies the degeneracy of the states and that in this case there exists a new class of states which do not survive in the ordinary quantum mechanics limit β→0. © 2015 American Physical Society.


Seri M.,University of Perugia | Marrocchi A.,University of Perugia | Bagnis D.,Northwestern University | Bagnis D.,Konarka Technologies | And 4 more authors.
Advanced Materials | Year: 2011

The synthesis and characterization of a new series of anthracene-based derivatives and their use as donors in bulk-heterojunction solar cells is reported. It is found that when using well-defined building blocks in constructing the chromophore, the donor molecular shape dramatically affects organic photovoltaic (OPV) performance in a previously unrecognized way. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Lip G.Y.H.,University of Birmingham | Agnelli G.,University of Perugia
European Heart Journal | Year: 2014

Long-term anticoagulation treatment with warfarin has been associated with a number of limitations in clinical practice and there is a need for more convenient long-term anticoagulation treatment. One of the non-vitamin K oral anticoagulants in development is edoxaban, a factor Xa inhibitor that is administered once daily. The pharmacological properties of edoxaban have various advantages in anticoagulant therapy. Edoxaban quickly reaches peak plasma concentrations in 1.5 h, has a half-life of 10-14 h, has relatively high bioavailability of 62% and exhibits highly selective, competitive, concentration-dependent inhibition of human factor Xa. The plasma concentrations of edoxaban are also closely correlated with suppression of thrombin generation and a range of platelet activation parameters (fragment 1+2, thrombin-antithrombin complex, and β-thromboglobulin), which edoxaban has been shown to rapidly inhibit. The anticoagulant activity of edoxaban is not affected by food intake or ethnicity and a number of drug-drug interaction studies have been performed. Co-administration of edoxaban with strong P-glycoprotein inhibitors, such as dronedarone, quinidine, and verapamil requires edoxaban dose-reduction by 50% to avoid the risk of over-exposure. The exposure of edoxaban may also increase in patients with a body weight ≤60 kg and moderate renal impairment. This meant a dose-reduction strategy in patients at risk of over-exposure was utilized in Phase III clinical studies. In conclusion, the pharmacological properties of edoxaban provide rapid and specific inhibition of factor Xa, which is closely related to plasma concentrations. Given the limitations with long-term warfarin therapy, once-daily edoxaban may provide a convenient long-term alternative for patients. © 2014 European Society of Cardiology.


Brinchi L.,University of Perugia | Cotana F.,University of Perugia | Fortunati E.,University of Perugia | Kenny J.M.,University of Perugia | Kenny J.M.,CSIC - Institute of Polymer Science and Technology
Carbohydrate Polymers | Year: 2013

The use of renewables materials for industrial applications is becoming impellent due to the increasing demand of alternatives to scarce and unrenewable petroleum supplies. In this regard, nanocrystalline cellulose, NCC, derived from cellulose, the most abundant biopolymer, is one of the most promising materials. NCC has unique features, interesting for the development of new materials: the abundance of the source cellulose, its renewability and environmentally benign nature, its mechanical properties and its nano-scaled dimensions open a wide range of possible properties to be discovered. One of the most promising uses of NCC is in polymer matrix nanocomposites, because it can provide a significant reinforcement. This review provides an overview on this emerging nanomaterial, focusing on extraction procedures, especially from lignocellulosic biomass, and on technological developments and applications of NCC-based materials. Challenges and future opportunities of NCC-based materials will be are discussed as well as obstacles remaining for their large use. © 2013 Elsevier Ltd. All rights reserved.


Widom A.,Northeastern University | Swain J.,Northeastern University | Srivastava Y.N.,University of Perugia
Journal of Physics G: Nuclear and Particle Physics | Year: 2013

A theoretical explanation is provided for the experimental evidence that fracturing piezoelectric rocks produces neutrons. The elastic energy micro-crack production ultimately yields the macroscopic fracture. The mechanical energy is converted by the piezoelectric effect into electric field energy. The electric field energy decays via radio frequency (microwave) electric field oscillations. The radio frequency electric fields accelerate the condensed matter electrons which then collide with protons producing neutrons and neutrinos. © 2013 IOP Publishing Ltd.


Unfer V.,Agunco Obstetric And Gynecological Center | Porcaro G.,University of Perugia
Expert Review of Clinical Pharmacology | Year: 2014

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders affecting women of reproductive age. It is characterized by chronic anovulation, hyperandrogenism, and insulin resistance. It is the main cause of infertility due to the menstrual dysfunction and metabolic disorders. Women with PCOS also have an increased cardiovascular risk because of dyslipidemia and insulin resistance. So far, we have a lot of information about the etiology of PCOS, and many steps forward have been made about the diagnosis of this syndrome, but there is still no certainty about the therapy. Myo-inositol (MI) and D-chiro-inositol, two inositol stereoisomers, have been proven to be effective in PCOS treatment. However, only MI has been shown to have beneficial effects on reproductive function, whereas the administration of MI/D-chiro-inositol, in the physiological plasma ratio (i.e., 40:1) ensures better clinical results, such as the reduction of insulin resistance, androgens' blood levels, cardiovascular risk and regularization of menstrual cycle with spontaneous ovulation. © 2014 Informa UK Ltd.


Distrutti E.,Science di Gastroenterologia ed Epatologia | Cipriani S.,University of Perugia | Mencarelli A.,University of Perugia | Renga B.,University of Perugia | Fiorucci S.,University of Perugia
PLoS ONE | Year: 2013

Background and Aims:Irritable bowel syndrome (IBS) is linked to post-inflammatory and stress-correlated factors that cause changes in the perception of visceral events. Probiotic bacteria may be effective in treating IBS symptoms. Here, we have investigated whether early life administration of VSL#3, a mixture of 8 probiotic bacteria strains, protects against development of visceral hypersensitivity driven by neonatal maternal separation (NMS), a rat model of IBS.Methods:Male NMS pups were treated orally with placebo or VSL#3 from days 3 to 60, while normal, not separated rats were used as controls. After 60 days from birth, perception of painful sensation induced by colorectal distension (CRD) was measured by assessing the abdominal withdrawal reflex (score 0-4). The colonic gene expression was assessed by using the Agilent Whole Rat Genome Oligo Microarrays platform and confirmed by real time PCR.Results:NMS rats exhibited both hyperalgesia and allodynia when compared to control rats. VSL#3 had a potent analgesic effect on CRD-induced pain without changing the colorectal compliance. The microarray analysis demonstrated that NMS induces a robust change in the expression of subsets of genes (CCL2, NOS3, THP1, NTRK1, CCR2, BDRKRB1, IL-10, TNFRSF1B, TRPV4, CNR1 and OPRL1) involved in pain transmission and inflammation. TPH1, tryptophan hydroxylase 1, a validated target gene in IBS treatment, was markedly upregulated by NMS and this effect was reversed by VSL#3 intervention.Conclusions:Early life administration of VSL#3 reduces visceral pain perception in a model of IBS and resets colonic expression of subsets of genes mediating pain and inflammation.Transcript profiling: Accession number of repository for expression microarray data is GSE38942 (http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc = GSE38942). © 2013 Distrutti et al.


Bounameaux H.,University of Geneva | Agnelli G.,University of Perugia
Thrombosis and Haemostasis | Year: 2013

The outcomes of thromboprophylactic trials have been debated for decades. Recently, the 9th edition of the American College of Chest Physicians (ACCP) evidence-based clinical practice guidelines based their strong recommendations only on patient-important outcomes. Practically, symptoms were considered the crucial element. Consequently, studies that primarily aimed at reducing venographic thrombi were considered less pertinent than studies that focused on symptomatic thrombosis. In the present viewpoint, we challenge the argument that "symptomatic" and "clinically relevant" are interchangeable. In particular, the case is made that asymptomatic events may be clinically relevant and that asymptomatic venographically detected thrombosis is a clinically relevant surrogate outcome for fatal pulmonary embolism. © Schattauer 2013.


Cannoni M.,University of Perugia | Panella O.,National Institute of Nuclear Physics, Italy
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2010

We reexamine the prospects for the detection of Higgs-mediated lepton flavor violation at LHC, at a photon collider and in τ decays such as τ→μη, τ→μγ. We allow for the presence of a large, model independent, source of lepton flavor violation in the slepton mass matrix in the τ-μ sector by the mass insertion approximation and constrain the parameter space using the τ lepton flavor violating decays together with the B-mesons physics observables, the anomalous magnetic moment of the muon, and the dark matter relic density. We further impose the exclusion limit on spin-independent neutralino-nucleon scattering from CDMS and the CDF limits from direct search of the heavy neutral Higgs at the TEVATRON. We find rates probably too small to be observed at future experiments if models have to accommodate for the relic density measured by WMAP and explain the (g-2)μ anomaly: better prospects are found if these two constraints are applied only as upper bounds. The spin-independent neutralino-nucleon cross section in the studied constrained parameter space is just below the present CDMS limit and the running XENON100 experiment will cover the region of the parameter space where the lightest neutralino has large gaugino-Higgsino mixing. © 2010 The American Physical Society.


Bonilla J.,Polytechnic University of Valencia | Fortunati E.,University of Perugia | Atares L.,Polytechnic University of Valencia | Chiralt A.,Polytechnic University of Valencia | And 2 more authors.
Food Hydrocolloids | Year: 2014

Chitosan (CH) was blended with poly vinyl alcohol (PVA) in different compositions to obtain biodegradable films (PVA90:CH10, PVA80:CH20, PVA70:CH30). Blends and neat polymer films (PVA100, CH100) were characterized for their thermal behavior, structural, mechanical and barrier properties as well as antimicrobial activity. Both polymers showed good compatibility, as demonstrated by FESEM images and thermal behavior. A reduction in crystallinity of the blend was observed as the chitosan content was increased. Moreover, chitosan addition strongly reduced the film stretchability while increased the film rigidity and resistance to fracture, mainly at 70:30 PVA:CH ratio. Additional advantages of chitosan incorporation to PVA films are the reduction of the UV-transmittance while providing antimicrobial properties. © 2013 Elsevier Ltd.


Monti M.,University of Perugia | Natali M.,University of Perugia | Torre L.,University of Perugia | Kenny J.M.,University of Perugia | Kenny J.M.,CSIC - Institute of Polymer Science and Technology
Carbon | Year: 2012

The alignment of single walled carbon nanotubes (SWCNTs) in an epoxy monomer liquid medium by the application of a DC electric field has been investigated, taking into account the various transport phenomena involved: the tube rotation in the electric field, the translation of polarized SWCNTs toward each other to form a chain-like structure and the migration of the tubes toward the positive electrode. Moreover, the relaxation mechanism which takes place when the electric field is switched off has also been considered. Experimental tests, performed to verify the effectiveness of the model, are based on the application of an electric field to a liquid epoxy-SWCNT colloid (0.025 wt.%) while measuring the current and observing the system by optical microscopy. As a result of the modeling it is possible to identify the processing conditions that allow the alignment of SWCNTs in an epoxy resin through the short-time application of a DC electric field. Experimental measurements are in agreement with the model's predictions. © 2012 Elsevier Ltd. All rights reserved.


Pacetti S.,University of Perugia | Baldini Ferroli R.,National Institute of Nuclear Physics, Italy | Tomasi-Gustafsson E.,CEA Saclay Nuclear Research Center | Tomasi-Gustafsson E.,French National Center for Scientific Research
Physics Reports | Year: 2015

The aim of this report is to give basic notions on electromagnetic hadron form factors (FFs), as they are understood at the present time, to summarize and analyze the present experimental results and available theoretical models and to open a view on future perspectives.FFs are fundamental quantities, which describe the internal, dynamical structure of hadrons. Although the theoretical formalism was settled in the middle of last century, as well as the first experiments in electron-proton elastic scattering for which R. Hofstadter got the Nobel prize in 1961, a renewed activity is due to recent, surprising results and to the opening of new experimental possibilities. An elegant formalism was built on the assumption of a hadron electromagnetic interaction based on the exchange of a virtual photon of four-momentum q2. In this case FFs are analytic functions of only one variable, q2, and the electromagnetic vertex γ* hh(h is any hadron) is defined by two structure functions, which, in turn, are expressed in terms of 2S+1 FFs, S being the hadron spin, assuming parity and time-invariance.Our aim is to anticipate the potentiality contained in the future data, combined with the present knowledge, to point out the relevant observables and the most significative measurements, and to give predictions to be compared to the data when they will be available. © 2014 Elsevier B.V.


Aldred S.,University of Birmingham | Mecocci P.,University of Perugia
Archives of Gerontology and Geriatrics | Year: 2010

DHEA is secreted by the adrenal cortex and is also a neurosteroid. Its sulfate (DHEAS) is the most abundant steroid in circulation. The levels of both are seen to decline in concentration with age. Evidence is available for altered levels of DHEA and DHEAS in AD but is limited to relatively few studies assessing small cohorts. This study assessed plasma DHEA and DHEAS levels in AD sufferers (n=72) and compared them to age-matched controls (n=72). Plasma DHEA concentrations were significantly lower in AD patients compared to control (4.24 ± 0.4. ng/ml for AD; 3.38 ± 0.3. ng/ml for control, p=0.027, Mann-Whitney 1-tailed) and DHEA levels were significantly correlated to DHEAS levels in both control and AD conditions (Spearman's rho correlation coefficient=0.635 in controls and 0.467 in AD, p≤0.01). This study highlighted a measurable difference in DHEA and DHEAS concentrations in plasma from a large cohort of patients suffering from AD when compared to age-matched controls. © 2009 Elsevier Ireland Ltd.


Peponi L.,CSIC - Institute of Polymer Science and Technology | Puglia D.,University of Perugia | Torre L.,University of Perugia | Valentini L.,University of Perugia | And 3 more authors.
Materials Science and Engineering R: Reports | Year: 2014

The control of the nanostructure and the addition of nanoparticles to polymers have led to structural and functional property enhancements in a number of polymeric systems as a material answer to continuous requirements from advanced industrial sectors. The availability of new nanoparticles with extraordinary properties (i.e. carbon nanotubes, graphenes, but also nanoclays, nanocellulose, metals and ceramics) have determined new and exciting possibilities for a continuous enlargement of polymer markets. However, the potentialities of these new materials are still strongly dependent on the development and scaling-up of reliable processing routes. Therefore, the purpose of this report is to review the main processing approaches for nanostructured polymers and nanocomposites starting with a brief review of available nanoparticles and on their functionalization to promote a better polymer-particle interaction. Regarding processing, the review firstly addresses the bottom-up approaches typically adopted for nanostructured polymers, blends and copolymers. Then, the different technologies required by the top-down processing of thermoplastic and thermosetting polymer matrix systems are reviewed. Finally, the report addresses the recent applications of nanostructured polymers and nanocomposites as matrices of advanced composite materials. In all cases, the main processing approaches and the main structural and functional properties characterizing these materials and their potential and current industrial applications are specifically addressed. © 2014 Published by Elsevier B.V.


Verdecchia P.,Hospital of Assisi | Angeli F.,University of Perugia | Lip G.Y.H.,University of Birmingham | Reboldi G.,University of Perugia
PLoS ONE | Year: 2014

Background: Edoxaban recently proved non-inferior to warfarin for prevention of thromboembolism in patients with non-valvular atrial fibrillation (AF). We conducted an imputed-placebo analysis with estimates of the proportion of warfarin effect preserved by each non vitamin K antagonist oral anticoagulant (NOAC) and indirect comparisons between edoxaban and different NOACs. Methods and Findings: We performed a literature search (up to January 2014), clinical trials registers, conference proceedings, and websites of regulatory agencies. We selected non-inferiority randomised controlled phase III trials of dabigatran, rivaroxaban, apixaban and edoxaban compared with adjusted-dose warfarin in non-valvular AF. Compared to imputed placebo, all NOACs reduced the risk of stroke (ORs between 0.24 and 0.42, all p<0.001) and all-cause mortality (ORs between 0.55 and 0.59, all p<0.05). Edoxaban 30 mg and 60 mg preserved 87% and 112%, respectively, of the protective effect of warfarin on stroke, and 133% and 121%, respectively, of the protective effect of warfarin on all-cause mortality. The risk of primary outcome (stroke/systemic embolism), all strokes and ischemic strokes was significantly higher with edoxaban 30 mg than dabigatran 150 mg and apixaban. There were no significant differences between edoxaban 60 mg and other NOACs for all efficacy outcomes except stroke, which was higher with edoxaban 60 mg than dabigatran 150 mg. The risk of major bleedings was lower with edoxaban 30 mg than any other NOAC, odds ratios (ORs) ranging between 0.45 and 0.67 (all p<0.001). Conclusions: This study suggests that all NOACs preserve a substantial or even larger proportion of the protective warfarin effect on stroke and all-cause mortality. Edoxaban 30 mg is associated with a definitely lower risk of major bleedings than other NOACs. This is counterbalanced by a lower efficacy in the prevention of thromboembolism, although with a final benefit on all-cause mortality. © 2014 Verdecchia et al.


Grant
Agency: European Commission | Branch: FP7 | Program: CP | Phase: ICT-2009.8.6 | Award Amount: 3.46M | Year: 2010

Nanoscale energy management is a new, exciting field that is gaining increasing importance with the realization that a new generation of micro-to-nanoscale devices aimed at sensing, processing, actuating and communication will not be possible without solving the powering issue. The scientific objective of this project is thus to study energy efficiency with the specific aim of identifying new directions for energy-harvesting technologies at the nanometre and molecular scale. The technological objective of the project is to integrate such technologies into autonomous nanoscale systems to allow new, low-power ICT architectures to find their way into devices. In a joint effort, the nanopower consortium composed by world leading experts in the fabrication of Si and III-V semiconductor nanodevices, fundamental and applied modelling as well as design and integration of ICT architectures will fabricate, test and evaluate new conception devices: nanomechanical nonlinear oscillators, phonon rectifiers and quantum harvesters addressing applied prototypes and non-equilibrium processes down to the quantum level.


Grant
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: INFRAIA-1-2014-2015 | Award Amount: 5.09M | Year: 2015

We propose a set of integrated Activities in the High Energy Astrophysics Domain (AHEAD) in response to the INFRAIA-2014-2015 call Research Infrastructures for High EnergyAstrophysics. The overall objective of AHEAD is to integrate national efforts in high-energy Astrophysics and to promote the domain at the European level, to keep its community at the cutting edge of science and technology in this competitive research area and ensure that space observatories for high-energy astrophysics are at the state of the art. AHEAD will integrate key research infrastructures for on-ground test and calibration of space-based sensors and electronics and promote their coordinated use. In parallel, the best facilities for data analysis of high-energy astrophysical observatories will be made available to the European community. The technological development will focus on the improvement of selected critical technologies, background modeling, cross calibration, and feasibility studies of space-based instrumentation for the benefit of future X-ray and gamma-ray missions, and the best exploitation of existing observatories. AHEAD will support the community via grants for collaborative studies, dissemination of results, and promotion of workshops. A strong public outreach package will ensure that the domain is well publicized at national, European and International level. The virtual circle infrastructure - networking - joint research activities, as devised in AHEAD, serves to establish strong connections between institutes and industry to create the basis for a more rapid advancement of high-energy astrophysical science, space-oriented instrumentation and cutting-edge sensor technology in Europe. This enables the development of new technologies and the associated growth of the European technology market, - with a dedicated technology innovation package - as well as the creation of a new generation of researchers.


Grant
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: FETPROACT-01-2016 | Award Amount: 5.99M | Year: 2017

Guaranteed numerical precision of each elementary step in a complex computation has been the mainstay of traditional computing systems for many years. This era, fueled by Moores law and the constant exponential improvement in computing efficiency, is at its twilight: from tiny nodes of the Internet-of-Things, to large HPC computing centers, sub-picoJoule/operation energy efficiency is essential for practical realizations. To overcome the power wall, a shift from traditional computing paradigms is now mandatory. OPRECOMP aims at demolishing the ultra-conservative precise computing abstraction and replacing it with a more flexible and efficient one, namely transprecision computing. OPRECOMP will investigate the theoretical and practical understanding of the energy efficiency boost obtainable when accuracy requirements on data being processed, stored and communicated can be lifted for intermediate calculations. While approximate computing approaches have been used before, in OPRECOMP for the first time ever, a complete framework for transprecision computing, covering devices, circuits, software tools, and algorithms, along with the mathematical theory and physical foundations of the ideas will be developed that not only will provide error bounds with respect to full precision results, but also will enable major energy efficiency improvements even when there is no freedom to relax end-to-end application quality-of-results. The mission of OPRECOMP is to demonstrate using physical demonstrators that this idea holds in a huge range of application scenarios in the domains of IoT, Big Data Analytics, Deep Learning, and HPC simulations: from the sub-milliWatt to the MegaWatt range, spanning nine orders of magnitude. In view of industrial exploitation, we will prove the quality and reliability and demonstrate that transprecision computing is the way to think about future systems.


News Article | October 23, 2015
Site: news.mit.edu

Nature has had billions of years to perfect photosynthesis, which directly or indirectly supports virtually all life on Earth. In that time, the process has achieved almost 100 percent efficiency in transporting the energy of sunlight from receptors to reaction centers where it can be harnessed — a performance vastly better than even the best solar cells. One way plants achieve this efficiency is by making use of the exotic effects of quantum mechanics — effects sometimes known as “quantum weirdness.” These effects, which include the ability of a particle to exist in more than one place at a time, have now been used by engineers at MIT to achieve a significant efficiency boost in a light-harvesting system. Surprisingly, the researchers at MIT and Eni, the Italian energy company, achieved this new approach to solar energy not with high-tech materials or microchips — but by using genetically engineered viruses. This achievement in coupling quantum research and genetic manipulation, described this week in the journal Nature Materials, was the work of MIT professors Angela Belcher, an expert on engineering viruses to carry out energy-related tasks, and Seth Lloyd, an expert on quantum theory and its potential applications; research associate Heechul Park; and 14 collaborators at MIT, Eni, and Italian universities. Lloyd, the Nam Pyo Suh Professor in the Department of Mechanical Engineering, explains that in photosynthesis, a photon hits a receptor called a chromophore, which in turn produces an exciton — a quantum particle of energy. This exciton jumps from one chromophore to another until it reaches a reaction center, where that energy is harnessed to build the molecules that support life. But the hopping pathway is random and inefficient unless it takes advantage of quantum effects that allow it, in effect, to take multiple pathways at once and select the best ones, behaving more like a wave than a particle. This efficient movement of excitons has one key requirement: The chromophores have to be arranged just right, with exactly the right amount of space between them. This, Lloyd explains, is known as the “Quantum Goldilocks Effect.” That’s where the virus comes in. By engineering a virus that Belcher has worked with for years, the team was able to get it to bond with multiple synthetic chromophores — or, in this case, organic dyes. The researchers were then able to produce many varieties of the virus, with slightly different spacings between those synthetic chromophores, and select the ones that performed best. In the end, they were able to more than double excitons’ speed, increasing the distance they traveled before dissipating — a significant improvement in the efficiency of the process. The project started at a workshop held at Eni's laboratories in Novara, Italy. Lloyd and Belcher, the James Mason Crafts Professor in the Department of Biological Engineering, were reporting on different projects they had worked on, and began discussing, along with Eni researchers, the possibility of a project encompassing their very different expertise. Lloyd, whose work is mostly theoretical, pointed out that the viruses Belcher works with have the right length scales to potentially support quantum effects. In 2008, Lloyd had published a paper demonstrating that photosynthetic organisms transmit light energy efficiently because of these quantum effects. When he saw Belcher’s report on her work with engineered viruses, he wondered if that might provide a way to artificially induce a similar effect, in an effort to approach nature’s efficiency. “I had been talking about potential systems you could use to demonstrate this effect, and Angela said, ‘We’re already making those,’” Lloyd recalls. Eventually, after much analysis, “We came up with design principles to redesign how the virus is capturing light, and get it to this quantum regime.” Within two weeks, Belcher’s team had created their first test version of the engineered virus. Many months of work then went into perfecting the receptors and the spacings. Once the team engineered the viruses, they were able to use laser spectroscopy and dynamical modeling to watch the light-harvesting process in action, and to demonstrate that the new viruses were indeed making use of quantum coherence to enhance the transport of excitons. “It was really fun,” Belcher says. “A group of us who spoke different [scientific] languages worked closely together, to both make this class of organisms, and analyze the data. That’s why I’m so excited by this.” While this initial result is essentially a proof of concept rather than a practical system, it points the way toward an approach that could lead to inexpensive and efficient solar cells or light-driven catalysis, the team says. So far, the engineered viruses collect and transport energy from incoming light, but do not yet harness it to produce power (as in solar cells) or molecules (as in photosynthesis). But this could be done by adding a reaction center, where such processing takes place, to the end of the virus where the excitons end up. “This is exciting and high-quality research,” says Alán Aspuru-Guzik, a professor of chemistry and chemical biology at Harvard University who was not involved in this work. The research, he says, “combines the work of a leader in theory (Lloyd) and a leader in experiment (Belcher) in a truly multidisciplinary and exciting combination that spans biology to physics to potentially, future technology.” “​Access to controllable excitonic systems is a goal shared by many researchers in the field,” Aspuru-Guzik adds. “This work provides fundamental understanding that can allow for the development of devices with an increased control of exciton flow.” The research was supported by Eni through the MIT Energy Initiative. In addition to MIT postdocs Nimrod Heldman and Patrick Rebentrost, the team included researchers at the University of Florence, the University of Perugia, and Eni.


News Article | December 14, 2016
Site: news.yahoo.com

The ancient relative of humanity dubbed "Lucy" may have been one of a harem of gals who mated with a single male, according to research that suggests her species was polygynous. Among the earliest known relatives of humanity whose skeletons were made for walking upright was Australopithecus afarensis, the species that included the famed 3.2-million-year-old Lucy. Members of the Australopithecus lineage, known as australopithecines, are among the leading candidates for direct ancestors of the human lineage, living about 2.9 million to 3.8 million years ago in East Africa. [Photos: New Human Ancestor Species Discovered] To learn more about Lucy's species, researchers investigated the area of Laetoli in northern Tanzania, which previously yielded the earliest known footprints belonging to hominins— humans and related species dating back to the split from the chimpanzee lineage. Those footprints, which date to 3.66 million years ago, were excavated in 1978 at a place dubbed "site G." They are thought to belong to three members of A. afarensis walking in the same direction across wet volcanic ash. Now, a team of researchers from institutions in Italy and Tanzania has discovered new 3.66-million-year-old tracks at Laetoli that they suggest also belonged to A. afarensis. "It is amazing that, almost four decades after the original discovery, we have new footprints from the very same sediments," said William Jungers, a paleoanthropologist at Stony Brook University in New York who did not take part in this research. "They could have been made on the same day millions of years ago." These footprints — a kind of ichnofossil, or trace fossil — reveal that this extinct species may have had major differences in sizes between the sexes. This difference, in turn, suggests that the species might have been polygynous, where males have multiple female mates, the researchers said. Previous research suggested the fact that polygyny leads to a few males monopolizing all females leads to intense competition between males, which favors the evolution of larger males that can better deal with their rivals. [10 Greatest Mysteries of the First Humans] "For me, the most important implication is that the area might harbor more ichnofossils— knowledge that could be used to solve many problems regarding different aspects of hominins," said lead study author Fidelis Masao, a palaeolithic archaeologist at the University of Dar es Salaam in Tanzania. The new sets of footprints belong to two individuals, and were discovered at a place now dubbed "site S," located about 490 feet (150 meters) south of the prints discovered in 1978. Surrounded by dozens of other animal footprints — such as those belonging to a rhino, a giraffe, some horses and guinea fowl — along with raindrop impressions, the new tracks were apparently made on the same surface at the same time, and went in the same direction and at a similar speed as the A. afarensis prints found in 1978. Back when this ancient hominin was alive, the landscape was a bit like it is today — a mix of bushland, woodland and grassland with a nearby forest along the river. Masao said that, after they had discovered the new footprints, one of the local Maasai workers said to him,"in not too good Swahili, 'Masao umepata choo.'" The worker meant to say, "Masao, you have become famous," but the Swahili word for "famous"is "cheo," not "choo," Masao explained. "The latter means 'toilet' or 'poop,'" Masao said. Judging by the impressions each foot made in the earth and the distance between each track, the researchers could estimate the size and weight of the individuals who made each set of prints. One individual was likely male, about 5 feet 5 inches (1.65 m) tall and 98.5 lbs. (44.7 kilograms). The other was likely female, about 4 feet 10 inches (1.46 m) tall and 87 lbs. (39.5 kg), the researchers said. [In Photos: 'Little Foot' Human Ancestor Walked With Lucy]  The estimates from the new male exceed the estimated height and weight of the tallest previous specimen from Laetoli by more than 7.8 inches (20 cm) and 13.2 lbs. (6 kg). Indeed, the estimated size of the new male individual "makes him the largest Australopithecus afarensis specimen identified so far," said senior study author Giorgio Manzi, a paleoanthropologist at Sapienza University in Rome. Study co-author Marco Cherin, a vertebrate paleontologist at the University of Perugia in Italy, noted that he and some of the other researchers walked barefoot at the site to avoid damaging the tracks. "We realized that the feet of many of us fit well with the footprints," Cherin told Live Science. Similarly, the new female is an estimated 1.2 to 1.6 inches (3 to 4 cm) taller than previous female specimens from Laetoli, the researchers said. This new female is also more than 11.8 inches (30 cm) taller than Lucy. When these new prints are considered together with the prints discovered in 1978, it suggests "several early bipedal hominids moving as a group through the landscape, after a volcanic eruption and a subsequent rainfall," Manzi told Live Science. One tentative conclusion from these findings is that the group might have consisted of "one male, two or three females, and one or two juveniles," Manzi said. This idea, in turn, potentially suggests that this male — and, therefore, other males in the species — may have had more than one female mate, Cherin said. However, Cherin did caution that "the inferences on sexual dimorphism [differences between the sexes] and on social structure need to be evaluated carefully." These findings suggest that sexual dimorphism may have been much more pronounced and certain in A. afarensis than scientists had thought. Prior work found that high sexual dimorphism is linked with polygyny — for example, in gorillas. In contrast, humans and their closest living relatives, chimpanzees and bonobos, are only moderately sexually dimorphic. Scientists have hotly debated the level of sexual dimorphism in A. afarensis for nearly 40 years, "with some researchers supporting the notion of an only moderate degree of dimorphism, not too different from Homo sapiens, while the rest of the world supports the idea of marked sexual dimorphism," Cherin said. Their findings are "strong evidence that this fossil hominin was characterized by a strong variation in size." Future research will aim to excavate more tracks from Laetoli to learn more about how these ancient relatives of humanity walked, Cherin said. The authors of this new study "should be applauded for their efforts and the exciting but preliminary results," Jungers told Live Science. "There is much more analytical work to be done. I'm sure the authors would agree and look forward to the 'next steps' in their research program." Masao, Cherin, Manzi and their colleagues detailed their findings online Dec. 14 in the journal eLife. In Photos: New Human Ancestor Possibly Unearthed in Spanish Cave


News Article | December 14, 2016
Site: www.newscientist.com

Three has become five. Laetoli in northern Tanzania is the site of iconic ancient footprints, capturing the moment – 3.66 million years ago – when three members of Lucy’s species (Australopithecus afarensis) strode out across the landscape. Now something quite unexpected has come to light: the footprints of two other individuals. “Our discovery left us without words,” says Marco Cherin at the University of Perugia, Italy. The find looks set to transform our understanding of the Laetoli site and the social dynamics of australopiths, as well as their style of walking. The original Laetoli footprints were discovered in 1976. Nothing quite like them had ever been found before. They remain by far the oldest hominin footprints we know, fortuitously preserved because a group of australopiths walked across damp volcanic ash during the brief window of time before it turned from soft powder into hard rock. “Geologists say this hardening process must have occurred in just a few hours,” says Cherin. The new discovery came about by chance. Keen to build a museum at Laetoli to attract tourists, the authorities asked Fidelis Masao, a researcher at the University of Dar es Salaam, Tanzania, to investigate the impact that building work would have on the site’s valuable geology, says Cherin. Masao and his colleagues excavated about 65 pits to get a better sense of the extent of the ash layer in which the footprints were found. One of the pits contained the new footprints – and more archaeologists, including Cherin, began to study them. So far the researchers have uncovered 13 prints belonging to a large individual – dubbed S1 – and a single print belonging to a smaller S2 australopith. Once the whole area has been excavated, there could be as many as 50 prints belonging to S1, they say. S1 seems to have been walking in the same direction, at the same speed – and in all probability at the same time – as the australopiths whose footprints were uncovered in the 1970s. It has been all too tempting to interpret the original trackways – often reconstructed as belonging to two adults and one juvenile – as evidence of a prehistoric “nuclear family”. The new footprints show more adults were present, including one who was much larger, the S1 individual. That has spawned a new hypothesis about australopith social groups. “They were probably similar in certain respects to those of our cousins, the gorillas, with a single dominant big male accompanied by his females and their offspring,” says Giorgio Manzi at the Sapienza University of Rome, Italy, who was also involved in the excavations. However, in other respects australopiths might have been different from gorillas. A 2011 study of isotopes in australopith teeth – which can reveal where an individual grew up – suggests it was the smaller (probably female) australopiths that left their family groups to wander and join a new social group. This is unlike gorillas, where it’s larger males that leave their family to establish a new social group. The new footprints find could also help us determine if the australopiths walked like us, a controversial issue. Some researchers, like Robin Crompton at the University of Liverpool, UK, have studied the Laetoli prints found in the 1970s. They say the depth profiles of the prints show clearly that australopiths walked in a broadly modern way: the hominins seem to have had a well-developed arch in the foot, and they used their big toe to push off the ground. Other researchers, including Kevin Hatala at Chatham University in Pittsburgh, Pennsylvania, have interpreted the prints differently. Earlier this year, Hatala and his colleagues concluded that the australopith gait might have looked a little strange to modern eyes, with the knees slightly bent as each foot struck the ground. “A substantially long trackway could prove very informative,” says Hatala. For Cherin, one of the most exciting aspects of the new finds is the size of the S1 australopith. Its feet were 26 centimetres in length – 3.5 cm longer than the other Laetoli prints. The scientists estimate S1 might have stood 1.65 metres tall, comparable with modern humans. However, William Jungers at Stony Brook University School of Medicine, New York, says we should treat that figure with caution. Hominin foot bones are exceptionally rare in the fossil record, and it’s not at all clear that australopiths had feet in the same proportion to their bodies as we do. “Australopiths aren’t modern people in many respects,” he says. We can expect to hear more when the researchers return to Laetoli to continue excavations, potentially as early as mid-2017.


Rinaldi M.,University of Perugia | Scopetta S.,University of Perugia | Vento V.,University of Valencia
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2013

Double parton correlations, having effects on the double parton scattering processes occurring in high-energy hadron-hadron collisions, for example at the LHC, are studied in the valence quark region by means of constituent quark models. In this framework, two particle correlations are present without any additional prescription, at variance with what happens, for example, in independent particle models, such as the MIT bag model in its simplest version. From the present analysis, conclusions similar to the ones obtained recently in a modified version of the bag model can be drawn: correlations in the longitudinal momenta of the active quarks are found to be sizable, while those in transverse momentum are much smaller. However, the framework used allows us to understand clearly the dynamical origin of the correlations. In particular, it is shown that the small size of the correlations in transverse momentum is a model-dependent result, which would not occur if models with sizable quark orbital angular momentum were used to describe the proton. Our analysis permits us, therefore, to clarify the dynamical origin of the double parton correlations and to establish which, among the features of the results, are model independent. The possibility of testing the studied effects experimentally is discussed. © 2013 American Physical Society.


Azpiroz J.M.,Donostia International Physics Center | Azpiroz J.M.,University of Perugia | Mosconi E.,University of Perugia | Angelis F.D.,University of Perugia
Journal of Physical Chemistry C | Year: 2011

We report the computational modeling of ZnS and ZnO nanostructures by defining realistic nanoparticle models ∼1.5 nm sized for each material and investigating their structural, electronic, and optical properties by means of DFT/TDDFT calculations. To provide a direct comparison of calculated data to experimentally characterized nanoparticles, 3D (ZnX) 111 nanoclusters of prismatic shape have been set up starting from the bulk wurtzite (X = O, S), with two different saturation patterns of the polar surfaces. The investigated models have been optimized by means of Car-Parrinello molecular dynamics and local geometry optimization techniques. The investigated systems exhibit a well-opened HOMO-LUMO energy gap, without any artificial intraband-gap states. TDDFT calculation of the lowest excitation energies are in excellent agreement, within 0.1-0.2 eV, with the experimental absorption onsets reported for similarly sized ZnO and ZnS nanoparticles (3.70 and 4.40 eV, respectively). We have also investigated the electronic structure of the considered nanoparticles, with reference to the valence band structure, finding calculated binding energies for the Zn d-shell to be only slightly displaced toward lower values compared to experimental values, possibly due to quantum confinement effects. This work provides the required computational framework for modeling ZnX and in general II-VI semiconductor nanomaterials, opening the way to simulation of ligand/semiconductor interactions. © 2011 American Chemical Society.


Valentini L.,University of Perugia | Bon S.B.,University of Perugia | Monticelli O.,University of Genoa | Kenny J.M.,University of Perugia
Journal of Materials Chemistry | Year: 2012

The reaction between amino-functionalized polyhedral oligomeric silsesquioxanes (POSS-NH 2) and graphene oxide (GO) sheets was used to graft POSS-NH 2 onto a GO layer immobilized onto a layer of (3-aminopropyl)triethoxysilane, self-assembled onto Si substrate. The chemical composition and surface morphology as well as the surface properties of the prepared films were investigated by means of Fourier transform infrared spectroscopy, water contact angle measurements and field emission electron microscopy. Tribological measurements performed with a nanoindenter showed that such hydrophobic trilayer film exhibited a reduced friction coefficient suitable for applications in lubricant coatings. This journal is © The Royal Society of Chemistry 2012.


Silvestri F.,University of Milan Bicocca | Silvestri F.,ETH Zurich | Marrocchi A.,University of Perugia
International Journal of Molecular Sciences | Year: 2010

Fossil fuel alternatives, such as solar energy, are moving to the forefront in a variety of research fields. Organic photovoltaic systems hold the promise of a lightweight, flexible, cost-effective solar energy conversion platform, which could benefit from simple solution-processing of the active layer. The discovery of semiconductive polyacetylene by Heeger et al. in the late 1970s was a milestone towards the use of organic materials in electronics; the development of efficient protocols for the palladium catalyzed alkynylation reactions and the new conception of steric and conformational advantages of acetylenes have been recently focused the attention on conjugated triple-bond containing systems as a promising class of semiconductors for OPVs applications. We review here the most important and representative (poly)arylacetylenes that have been used in the field. A general introduction to (poly)arylacetylenes, and the most common synthetic approaches directed toward making these materials will be firstly given. After a brief discussion on working principles and critical parameters of OPVs, we will focus on molecular arylacetylenes, (co)polymers containing triple bonds, and metallopolyyne polymers as p-type semiconductor materials. The last section will deal with hybrids in which oligomeric/polymeric structures incorporating acetylenic linkages such as phenylene ethynylenes have been attached onto C60, and their use as the active materials in photovoltaic devices. © 2010 by the authors.


Cametti C.,University of Rome La Sapienza | Marchetti S.,University of Florence | Onori G.,University of Perugia
Journal of Physical Chemistry B | Year: 2013

Water close to proteins plays a key role in determining their structural and functional properties. Despite being a subject of considerable interest, the characterization of hydration water, as far as its total amount is concerned, is still controversial and its influence on protein structure and folding is not yet fully understood. In this work, we have investigated the dielectric properties of lysozyme aqueous solutions over the frequency range where the orientational polarization relaxation of the aqueous phase occurs (from 500 MHz to 50 GHz). Measurements extend over a wide concentration range, up to 300 mg/mL, corresponding to a volume fraction of the order of 0.4. The analysis of the dielectric spectra, based on the decrease of the dielectric increment of the γ-dispersion as a function of protein concentration, allows us to estimate the total amount of hydration water (both bound water and loosely bound water) present in the system investigated. We observe a decrease of the hydration number as a function of the protein concentration. This behavior is well accounted for by considering the formation of small equilibrium clusters with aggregation number of some units, as recently reported by Stradner et al.(1) on the basis of small-angle X-ray and neutron scattering measurements. © 2012 American Chemical Society.


D'Ambrisi A.,University of Florence | Mezzi M.,University of Perugia | Caporale A.,University of Cassino and Southern Lazio
Composite Structures | Year: 2013

Plasters reinforced with polymeric nets as strengthening technique for masonry structures subjected to seismic actions can be an effective and inexpensive alternative to the currently utilized techniques. In this study the results of experimental tests performed on masonry panels reinforced with polymeric nets embedded in the plaster layer are presented. The masonry panels have been subjected to cyclic load tests for analyzing their behavior and for defining their mechanical parameters to use in design and in particular in the evaluation of their seismic capacity. Diagonal compression tests, shear-compression tests and tests with the load applied orthogonally to the panels plane have been performed. The obtained results evidence the effectiveness of the polymeric net in containing the in plane and the out-of-plane collapse mechanisms and in increasing the ductility and the dissipative capacity of the masonry panels. © 2013 Elsevier Ltd.


Cametti C.,University of Rome La Sapienza | Marchetti S.,University of Florence | Gambi C.M.C.,University of Florence | Onori G.,University of Perugia
Journal of Physical Chemistry B | Year: 2011

The dielectric properties of lysozyme aqueous solutions have been investigated over a wide frequency range, from 1 MHz to 50 GHz, where different polarization mechanisms, at a molecular level, manifest. The dielectric relaxation spectra show a multimodal structure, reflecting the complexity of the protein-water interactions, made even more intricate with the increase of the protein concentration. The deconvolution of the spectra into their different components is not unambiguous and is generally a delicate process which requires caution. We have analyzed the whole relaxation region, on the basis of the sum of simple Debye-type relaxation functions, considering three main contributions. Particular attention has been payed to the δ-dispersion, intermediate between the β-dispersion (rotational dynamics of the protein) and the γ-dispersion (orientational polarization of the water molecules). This intermediate contribution to the dielectric spectrum is attributed to the orientational polarization of water molecules in the immediate vicinity of the protein surface (hydration water). Our measurements clearly demonstrate that, at least at high protein concentrations, the δ-dispersion has a bimodal structure associated with two kinds of hydration water, i.e., tightly bound and loosely bound hydration water. In the concentration range investigated, the existence of a three-modal δ-dispersion, as recently suggested, is not supported, on the basis of statistical tests, by the analysis of the dielectric relaxations we have performed and a bimodal dispersion is accurate enough to describe the experimental data. The amount of the hydration water has been evaluated both from the dielectric parameters associated with the δ-dispersion and from the decrement of the loss peak of the γ-dispersion. The relative weight of tightly bound and loosely bound hydration water is briefly discussed. © 2011 American Chemical Society.


Raman S.V.,Ohio State University | Simonetti O.P.,Ohio State University | Winner III M.W.,Ohio State University | Dickerson J.A.,Ohio State University | And 3 more authors.
Journal of the American College of Cardiology | Year: 2010

Objectives: The aim of this study was to define the prevalence and significance of myocardial edema in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS). Background: Most patients with NSTE-ACS undergo angiography, yet not all have obstructive coronary artery disease (CAD) requiring revascularization. Identifying patients with myocardium at risk could enhance the effectiveness of an early invasive strategy. Cardiac magnetic resonance (CMR) can demonstrate edematous myocardium subjected to ischemia but has not been used to evaluate NSTE-ACS patients. Methods: One hundred consecutive patients with NSTE-ACS were prospectively enrolled to undergo 30-min CMR, including T2-weighted edema imaging and late gadolinium enhancement before coronary angiography. Clinical management including revascularization decision-making was performed without CMR results. Results: Of 88 adequate CMR studies, 57 (64.8%) showed myocardial edema. Obstructive CAD requiring revascularization was present in 87.7% of edema-positive patients versus 25.8% of edema-negative patients (p < 0.001). By multiple logistic regression analysis after adjusting for late gadolinium enhancement, perfusion, and wall motion scores, TIMI risk score was not predictive of obstructive CAD. Conversely, an increase in T2 score by 1 U increased the odds of subsequent coronary revascularization by 5.70 times (95% confidence interval: 2.38 to 13.62, p < 0.001). Adjusting for peak troponin-I, patients with edema showed a higher hazard of a cardiovascular event or death within 6 months after NSTE-ACS compared with those without edema (hazard ratio: 4.47, 95% confidence interval: 1.00 to 20.03; p = 0.050). Conclusions: In NSTE-ACS patients, rapid CMR identifies reversibly injured myocardium due to obstructive CAD and predicts worse outcomes. Identifying myocardium at risk may help direct appropriate patients toward early invasive management. © 2010 American College of Cardiology Foundation.


Noguera S.,University of Valencia | Scopetta S.,University of Perugia
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2012

The eta-photon transition form factor is evaluated in a formalism based on a phenomenological description at low values of the photon virtuality, and a QCD-based description at high photon virtualities, matching at a scale Q02. The high photon virtuality description makes use of a distribution amplitude calculated in the Nambu-Jona-Lasinio model with Pauli-Villars regularization at the matching scale Q02, and QCD evolution from Q02 to higher values of Q2. A good description of the available data is obtained. The analysis indicates that the recent data from the