Bari, Italy
Bari, Italy

The University of Bari Aldo Moro is a higher education institution in Bari, Apulia, in southern Italy.The University of Bari was founded in 1925. It is a state-supported university which is divided into 12 faculties. Each faculty has its own set of departments that focus on the arts science, mathematics, social science, literature, medicine, law, and education.The university offers various courses for undergraduate, graduate and post-graduate students. Aside from teaching, the university is also focused on scientific research at the doctorate level. The University of Bari research centres are highly-interactive, having connections among different departments, universities, and other research centres.The University of Bari is one of the most prestigious universities in Southern Italy and it is one of the largest universities in Italy, with a student population of around 60,000.The University has been recently entitled to one of its most famous student, the statesman Aldo Moro. Moro taught for several years Criminal Law at the University of Bari.The University has been awarded the following ranking positions:ranked 305 by Performance Ranking of Scientific Papers for World Universities ranked 401-500 by Academic Ranking of World Universities - Shanghai Jiao Tong University ranked 350-400 by Times Higher Education Supplement Ranking of World Universities ranked 508 by QS World University Rankings ranked 186 by the Leiden Ranking The University is one of the 20 Italian higher education institutions in the ARWU list of the top 500 universities in the world for 2012. Moreover, it has been ranked between 151st and 200th in the world for Physics by Academic Ranking of World Universities - Shanghai Jiao Tong University . Wikipedia.

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University of Bari and Marche Polytechnic University | Date: 2016-04-14

Object of the present invention is the use of Irisin for the treatment and/or prevention of osteoporosis. In particular, the present invention refers to the use of recombinant irisin for the treatment and/or prevention of osteoporosis.

Lonigro A.,University of Bari | Montemurro N.,University of Bari | Laera G.,CNR Water Research Institute
Science of the Total Environment | Year: 2017

The accidental or continuous release of residual chlorine in water reclaimed for irrigational purposes could compromise the crop yield and increase the load of toxic organo-halogenated compounds, posing additional risks for environment and human health. This study was aimed at assessing the consequences of using chlorinated water for irrigating lettuce crops grown in pots with two different types of soil. The results show that the accumulation of extractable organo-halogenated compounds (EOX) in soil, roots and leaves is directly related to the chlorine concentration in the irrigation water. The accumulation of EOX in sandy soils is not significant, while it reached up to 300% of the control in the silty-clay soil, demonstrating that the phenomenon is linked to the organic matter content in the soil. The accumulation of EOX in the soil appears to play a significant role in subsequent bioaccumulation in cultures irrigated with tap water (long term memory effect). Chloramines also demonstrated to have similar impacts as the free chlorine from hypochlorite. The consistent bioaccumulation of 400–700 μgCl kg− 1 of EOX in the leaves of crops irrigated with just 0.2 mgCl L− 1 of residual chlorine, as compared to levels below the detection limit of 75 μgCl kg− 1 in the control crops, evidences the potential impact on food chain and human health. © 2017 Elsevier B.V.

Di Tria F.,University of Bari | Lefons E.,University of Bari | Tangorra F.,University of Bari
Information Systems | Year: 2017

Methodologies for data warehouse design are increasing more and more in last years, and each of them proposes a different point of view. Among all the methodologies present in literature, the promising ones are the hybrid methodologies—because they represent the only way to ensure a multidimensional schema to be both consistent with data sources and adherent to user business goals—and those able to support the designer by providing some kind of automation. However, the results obtainable by the methodologies can differ substantially in terms of schema quality and required efforts. In this paper, we provide metrics for evaluating the quality of multidimensional schemata in reference to the effort spent in the design process and the automation degree of the methodology. As a case study, we apply our evaluation to the major emerging hybrid methodologies for data warehouse schema design. © 2016

Coclite G.M.,Polytechnic of Bari | di Ruvo L.,University of Bari
ZAMM Zeitschrift fur Angewandte Mathematik und Mechanik | Year: 2017

We consider the Kudryashov-Sinelshchikov equation, which contains nonlinear dispersive effects. We prove that as the diffusion parameter tends to zero, the solutions of the dispersive equation converge to the entropy ones of the Burgers equation. The proof relies on deriving suitable a priori estimates together with an application of the compensated compactness method in the Lp setting. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Matera E.,University of Bari
Journal of Clinical Psychopharmacology | Year: 2017

PURPOSE/BACKGROUND: Although second-generation antipsychotics are used to treat and manage symptoms for several psychiatric disorders, data about their adverse effects in developmental age are limited. The aim of this prospective observational study was to verify the cardiovascular and metabolic risk in a sample of antipsychotic-naive children/adolescent patients starting risperidone therapy. METHODS: Twenty-two patients, younger than 18 years, were recruited. The assessment included anthropometric data, cardiovascular parameters, blood tests, and ultrasonographic abdominal study. RESULTS: After an average follow-up period of 7.6 months, statistically significant increases in mean values of waist circumference, body mass index (BMI), BMI percentile, BMI z score, total cholesterol, and prolactin were found. Other cardiometabolic parameters showed an upward trend in time. Subjects in pubertal/postpubertal stage and female patients were more susceptible to developing cardiometabolic changes. Moreover, significant correlations between changes in anthropometric and several metabolic parameters were found. A tendency to change in constitution of the liver parenchyma and distribution of the abdominal fat mass with ultrasonographic abdominal study was also evident. CONCLUSIONS: In our sample, several metabolic parameters showed a sensitivity to risperidone treatment. Because most of these parameters are age dependent, metabolic syndrome criteria used for adults were inappropriate in children and adolescents. Periodic clinical and instrumental evaluations and guidelines for monitoring of any metabolic, laboratory, and instrumental complications are necessary in the perspective of even long-time second-generation antipsychotics treatment in children and adolescents. Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.

Garrappa R.,University of Bari | Maione G.,Polytechnic of Bari
Lecture Notes in Electrical Engineering | Year: 2017

Fractional integrals and derivatives based on the Prabhakar function are useful to describe anomalous dielectric properties of materials whose behaviour obeys to the Havriliak–Negami model. In this work some formulas for defining these operators are described and investigated. A numerical method of product-integration type for solving differential equations with the Prabhakar derivative is derived and its convergence properties are studied. Some numerical experiments are presented to validate the theoretical results. © Springer International Publishing AG 2017.

D'Abbicco M.,University of Bari
Computers and Mathematics with Applications | Year: 2017

In this paper, we find the critical exponent of global small data solutions for a damped plate equation with power nonlinearity utt-δutt+δ2u+ut=|u|p,t≥0,x∈R2,and for a system of two weakly coupled damped plate equations. We show how assuming small data in the energy space H2×H1 and in L1 is sufficient to compensate the regularity-loss type decay effect created by the rotational inertia term -δutt. © 2017 Elsevier Ltd.

Leuzzi F.,University of Bari | Ferilli S.,University of Bari
Journal of Intelligent Information Systems | Year: 2017

Analogy is the cognitive process of matching the characterizing features of two different items. This may enable reuse of knowledge across domains, which can help to solve problems. Indeed, abstracting the ‘role’ of the features away from their specific embodiment in the single items is fundamental to recognize the possibility of an analogical mapping between them. The analogical reasoning process consists of five steps: retrieval, mapping, evaluation, abstraction and re-representation. This paper proposes two forms of an operator that includes all these elements, providing more power and flexibility than existing systems. In particular, the Roles Mapper leverages the presence of identical descriptors in the two domains, while the Roles Argumentation-based Mapper removes also this limitation. For generality and compliance with other reasoning operators in a multi-strategy inference setting, they exploit a simple formalism based on First-Order Logic and do not require any background knowledge or meta-knowledge. Applied to the most critical classical examples in the literature, they proved to be able to find insightful analogies. © 2017 Springer Science+Business Media New York

Ribatti D.,University of Bari | Ribatti D.,Italian National Cancer Institute
Experimental Cell Research | Year: 2017

All organs consist of an epithelium and an associated mesenchyme, so these epithelial-mesenchymal intercations are among the most important phenomena in nature. The aim of this article is the summarize the common mechanisms involved in the establishment of epithelial mesenchymal transition in three biological processes, namely organogenesis, tumor progression and metastasis, and angiogenesis, apparently independent each from other. A common feature of these processes is the fact that specialized epithelial cells lose their features, including cell adhesion and polarity, reorganize their cytoskeleton, and acquire a mesenchymal morphology and the ability to migrate. © 2017 Elsevier Inc.

Notarnicola B.,University of Bari | Tassielli G.,University of Bari | Renzulli P.A.,University of Bari | Castellani V.,European Commission - Joint Research Center Ispra | Sala S.,European Commission - Joint Research Center Ispra
Journal of Cleaner Production | Year: 2017

Food consumption is amongst the main drivers of environmental impacts. On one hand, there is the need to fulfil a fundamental human need for nutrition, and on the other hand this poses critical threats to the environment. In order to assess the environmental impact of food consumption, a lifecycle assessment (LCA)-based approach has been applied to a basket of products, selected as being representative of EU consumption. A basket of food products was identified as representative of the average food and beverage consumption in Europe, reflecting the relative importance of the products in terms of mass and economic value. The products in the basket are: pork, beef, poultry, milk, cheese, butter, bread, sugar, sunflower oil, olive oil, potatoes, oranges, apples, mineral water, roasted coffee, beer and pre-prepared meals. For each product in the basket, a highly disaggregated inventory model was developed based on a modular approach, and built using statistical data. The environmental impact of the average food consumption of European citizens was assessed using the International Reference Life Cycle Data System (ILCD) methodology. The overall results indicate that, for most of the impact categories, the consumed foods with the highest environmental burden are meat products (beef, pork and poultry) and dairy products (cheese, milk and butter). The agricultural phase is the lifecycle stage that has the highest impact of all the foods in the basket, due to the contribution of agronomic and zootechnical activities. Food processing and logistics are the next most important phases in terms of environmental impacts, due to their energy intensity and the related emissions to the atmosphere that occur through the production of heat, steam and electricity and during transport. Regarding the end-of-life phase, human excretion and wastewater treatments pose environmental burdens related to eutrophying substances whose environmental impacts are greater than those of the agriculture, transports and processing phases. Moreover, food losses which occur throughout the whole lifecycle, in terms of agricultural/industrial and domestic food waste, have also to be taken into consideration, since they can amount to up to 60% of the initial weight of the food products. The results of the study go beyond the mere assessment of the potential impacts associated with food consumption, as the overall approach may serve as a baseline for testing eco-innovation scenarios for impact reduction as well as for setting targets. © 2016 The Authors

Miniello G.,National Institute of Nuclear Physics, Italy | Miniello G.,University of Bari
Nuovo Cimento della Societa Italiana di Fisica C | Year: 2017

This contribution will present updates on Mono-Higgs analyses (with H → bb and H → YY) using data collected by ATLAS and CMS experiments in proton-proton collisions at 8TeV. The benchmark models used are simplified models (mainly the Z -two-Higgs-doublet model) and models from the Effective Field Theory. © CERN on behalf of the ATLAS and CMS Collaborations.

Bellantuono L.,University of Bari
Nuovo Cimento della Societa Italiana di Fisica C | Year: 2017

The thermalization of a strongly coupled plasma is examined in the holographic framework through non-local observables: the equal-time two-point correlation function of a large dimension boundary operator, and Wilson loops of different shapes. The evolution of the probes from an initial far-from-equilibrium state to a hydrodynamic regime is found to depend on their size. A hierarchy among the thermalization times of the energy density, the pressures and the large size probes, is identified: the relaxation process is faster at short distances. © CERN on behalf of the ATLAS and CMS Collaborations.

Buono P.,University of Bari
Proceedings - DMS 2016: 22nd International Conference on Distributed Multimedia Systems | Year: 2016

Logistics activities refer to transporting materials and/or storing them in specific warehouse (platforms) for a given period of time. Typical problems are related to route and vehicle load optimization and monitoring of transportation conditions. GPS availability in the vehicles allows transportation companies to remotely check if vehicles are on schedule. Such information is often related to a single shipment. This paper presents a web tool which aims to support analysts through an interactive visualization technique that shows all routes performed by the vehicles in a given period of time on a geographic map. The tool allows analysts to perform explorative analysis in order to obtain information that otherwise is difficult to get. Various filters help them to reduce the visualized data to a manageable quantity. The interface is simple, complex queries can be executed by specifying a few parameters and performing zoom & pan gestures on the map.

Doglioni A.,University of Bari | Simeone V.,University of Bari
Journal of Hydrologic Engineering | Year: 2017

The analysis of the dynamic response of aquifers to rainfall is a key issue for groundwater resource management. A data-driven evolutionary modeling approach, evolutionary polynomial regression, based on multiobjective optimization is used here in order to identify explicit equations that forecast groundwater piezometric levels as a function of past rainfall values and past measured values of groundwater table levels. This methodology is applied here to two aquifers located in the same climatic area of southeast Italy, representative of two completely different hydrogeological scenarios: a deep coastal karst aquifer and a shallow porous aquifer. An evolutionary polynomial regression approach using commercially available software returns highly reliable model that allow for describing the different hydrogeological behaviors of the two aquifers. These models can be used both for planning the management of groundwater resources and for obtaining new scientific insight about the aquifers, looking at the equations and at the variables identified by the software model. © 2016 American Society of Civil Engineers.

Mastroserio A.,University of Bari
Journal of Instrumentation | Year: 2017

The Silicon Pixel Detector (SPD) constitutes the two innermost layers of the Inner Tracking System of the ALICE experiment and it is the closest detector to the interaction point. As a vertex detector, it has the unique feature of generating a trigger signal that contributes to the L0 trigger of the ALICE experiment. The SPD started collecting data since the very first pp collisions at LHC in 2009 and since then it has taken part in all pp, Pb-Pb and p-Pb data taking campaigns. This contribution will present the main features of the SPD, the detector performance and the operational experience, including calibration and optimization activities from Run 1 to Run 2. © 2017 IOP Publishing Ltd and Sissa Medialab srl.

Ribatti D.,University of Bari | Ribatti D.,Italian National Cancer Institute
Oncotarget | Year: 2017

The immune system plays a major role in the surveillance against tumors. To avoid attack from the immune system, tumor cells develop different strategies to escape immune surveillance. Evidence of immune surveillance comes from both animal models and clinical observations. Mice with a wide variety of immunodeficiencies have a high rate of tumor incidence and are more susceptible to transplanted or chemical carcinogen-induced tumors. Immunosuppressed patients have a high incidence of tumors. However, many patients develop cancer even in the presence of an apparently normal immune system. This indicates that tumor cells are able to escape immune surveillance. The aim of this review article is to summarize the literature concerning the development of the theory of immune surveillance against tumors; to discuss the evidence for and against this theory, and to discuss the concept of immunoediting. Finally, the current approaches in anti-tumor immunotherapy will be analyzed.

Lollino P.,CNR Institute of Neuroscience | Andriani G.F.,University of Bari
Rock Mechanics and Rock Engineering | Year: 2017

The strength decay that occurs in the post-peak stage, under low confinement stress, represents a key factor of the stress–strain behaviour of rocks. However, for soft rocks this issue is generally underestimated or even neglected in the solution of boundary value problems, as for example those concerning the stability of underground cavities or rocky cliffs. In these cases, the constitutive models frequently used in limit equilibrium analyses or more sophisticated numerical calculations are, respectively, rigid-plastic or elastic–perfectly plastic. In particular, most of commercial continuum-based numerical codes propose a variety of constitutive models, including elasticity, elasto-plasticity, strain-softening and elasto-viscoplasticity, which are not exhaustive in simulating the progressive failure mechanisms affecting brittle rock materials, these being characterized by material detachment and crack opening and propagation. As a consequence, a numerical coupling with mechanical joint propagation is needed to cope with fracture mechanics. Therefore, continuum-based applications that treat the simulation of the failure processes of intact rock masses at low stress levels may need the adoption of numerical techniques capable of implementing fracture mechanics and rock brittleness concepts, as it is shown in this paper. This work is aimed at highlighting, for some applications of rock mechanics, the essential role of post-peak brittleness of soft rocks by means of the application of a hybrid finite–discrete element method. This method allows for a proper simulation of the brittle rock behaviour and the related mechanism of fracture propagation. In particular, the paper presents two ideal problems, represented by a shallow underground cave and a vertical cliff, for which the evolution of the stability conditions is investigated by comparing the solutions obtained implementing different brittle material responses with those resulting from the assumption of perfectly plastic behaviour. To this purpose, a series of petrophysical and mechanical tests were conducted on samples of soft calcarenite belonging to the Calcarenite di Gravina Fm. (Apulia, Southern Italy), focusing specific attention on the post-peak behaviour of the material under three types of loading (compression, indirect tension and shear). Typical geometrical features representative of real rock engineering problems observed in Southern Italy were assumed in the problems examined. The numerical results indicate the impact of soft rock brittleness in the assessment of stability and highlight the need for the adoption of innovative numerical techniques to analyse these types of problems properly. © 2017 Springer-Verlag Wien

Di Cagno R.,Sudan University of Science and Technology | Filannino P.,University of Bari | Gobbetti M.,Sudan University of Science and Technology
International Journal of Food Microbiology | Year: 2017

Pomegranate juice (PJ) fermented with Lactobacillus plantarum C2, POM1, and LP09, unstarted-PJ, and raw-PJ were characterized for the profile of the volatile components (VOC) by PT–GC–MS. Lactic acid fermentation through selected strains enhanced the flavor profile of PJ. Concentrations of desired compounds (e.g., alcohols, ketones, and terpenes) were positively affected, whereas those of non-desired aldehydes decreased. Unstarted-PJ mainly differentiated from fermented PJs for the highest levels of aldehydes and sulfur compounds, and in lesser extent of furans, whereas alcohols, ketones, and alkenes followed by terpenes and benzene derivatives mainly differentiated fermented PJs. As expected, the lowest level of VOC was found in raw-PJ. VOC profile reflected on the sensory features of fermented PJs, unstarted-PJ, and raw-PJ, which were evaluated using a consensus modified flavor profile based on 13 attributes. Fermented PJs were mainly discriminated by the higher intensity of floral, fruity and anise notes than the controls. © 2017 Elsevier B.V.

Cristella L.,University of Bari | Cristella L.,National Institute of Nuclear Physics, Italy
EPJ Web of Conferences | Year: 2017

The studies of the production of the X(3872), either prompt or from B hadron decays, and of the J/ψφ mass spectrum in B hadron decays have been carried out by using pp collisions at√ s = 7 TeV collected with the CMS detector at the LHC. The cross-section ratio of the X(3872) with respect to the ψ(2S) in the J/ψπ+π- decay channel and the fraction of X(3872) coming from B-hadron decays are measured as a function of transverse momentum (pT), covering unprecedentedly high values of pT. For the first time, the prompt production cross section for the X(3872) times the unknown branching fraction for the decay of X(3872) →J/ψπ+π- is extracted differentially in pT and compared to theoretical predictions based on the Non-Relativistic QCD (NRQCD) factorization approach. The dipion invariant-mass spectrum of the J/ψπ+π- system in the X(3872) decay is also investigated. A peaking structure in the J/ψφ mass spectrum near threshold is observed in B± → J/ψφ K± decays. The data sample, selected on the basis of the dimuon decay mode of the J/ψ, corresponds to an integrated luminosity of 5.2 fb-1. Fitting the structure to an S-wave relativistic Breit-Wigner lineshape above a three-body phase-space nonresonant component gives a signal statistical significance exceeding five standard deviations. The fitted mass and width values are m = 4148.0 ± 2.4(stat.) ± 6.3(syst.) MeV and Γ = 28-11 +15 (stat.) ± 19(syst.) MeV, respectively. Evidence for an additional peaking structure at higher J/ψφ mass is also reported. The search for resonance-like structures in the Bs 0π± invariant mass spectrum do not show any unexpected result. An upper limit on the relative production of the claimed X(5568) and Bs multiplied by the unknown branching fraction of the decay X(5568) → Bsπ± is estimated to be 3.9% at 95% CL in the most conservative case. © The Authors, published by EDP Sciences, 2017.

Cantacessi C.,University of Cambridge | Dantas-Torres F.,University of Bari | Nolan M.J.,Royal Veterinary College University of London | Otranto D.,University of Bari
Trends in Parasitology | Year: 2015

It has been nearly 10 years since the completion of the first entire genome sequence of a Leishmania parasite. Genomic and transcriptomic analyses have advanced our understanding of the biology of Leishmania, and shed new light on the complex interactions occurring within the parasite-host-vector triangle. Here, we review these advances and examine potential avenues for translation of these discoveries into treatment and control programs. In addition, we argue for a strong need to explore how disease in dogs relates to that in humans, and how an improved understanding in line with the 'One Health' concept may open new avenues for the control of these devastating diseases. © 2015 The Authors.

Dantas-Torres F.,University of Bari | Otranto D.,University of Bari
Ticks and Tick-borne Diseases | Year: 2013

A 2-year study was conducted from March 2010 to March 2012 in a forested area in southern Italy to evaluate the species diversity and abundance of free-living ticks in 3 different habitats: (i) a meadow habitat within an enclosure inhabited by roe deer (Capreolus capreolus); (ii) a man-made trail located in a high-altitude, forested area; and (iii) a grassland near a house inhabited by 3 people. In total, 10,795 ticks were collected. Ixodes ricinus was the most abundant species (69.0%), followed by Haemaphysalis inermis (19.1%), Rhipicephalus turanicus (6.7%), Dermacentor marginatus (3.2%), and Hyalomma marginatum (1.0%). The least frequently collected species were Rhipicephalus bursa, Haemaphysalis parva, Haemaphysalis sulcata, and Haemaphysalis concinna, representing together less than 1% of the collections. Immature ticks predominated over adult ticks. In particular, immature stages of Ix. ricinus (i.e., 3246 larvae and 3554 nymphs) represented 63% of the total number of ticks collected. High levels of species diversity and abundance of ticks were recorded in all habitats and the daily number of ticks collected was negatively correlated with daily mean temperature, evapotranspiration, and saturation deficit. This study indicates that the southern Italian climate is suitable for different tick species, which may find a preferred 'climate niche' during a specific season, when a combination of factors (e.g., suitable meteorological and environmental conditions) associated with the presence of suitable hosts will facilitate their development and reproduction. © 2012 Elsevier GmbH.

Starting with 1985, we discovered the possible existence of electrons with net helicity in biomolecules as amino acids and their possibility to discern between the two quantum spin states. It is well known that the question of a possible fundamental role of quantum mechanics in biological matter constitutes still a long debate. In the last ten years we have given a rather complete quantum mechanical elaboration entirely based on Clifford algebra whose basic entities are isomorphic to the well-known spin Pauli matrices. A number of our recent results indicate the possible logical origin of quantum mechanics and the direct admission of quantum mechanics in the field of cognitive sciences. In February 2011, Gohler et al. published their important discovery on Science about Spin Selectivity in Electron Transmission Through Self-Assembled Monolayers of Double-Stranded DNA confirming in such manner that the principles of quantum mechanics apply to biological systems.

Chiara M.,University of Milan | Pesole G.,National Research Council Italy | Pesole G.,University of Bari | Horner D.S.,University of Milan
Nucleic Acids Research | Year: 2012

Several bioinformatics methods have been proposed for the detection and characterization of genomic structural variation (SV) from ultra highthroughput genome resequencing data. Recent surveys show that comprehensive detection of SV events of different types between an individual resequenced genome and a reference sequence is best achieved through the combination of methods based on different principles (split mapping, reassembly, read depth, insert size, etc.). The improvement of individual predictors is thus an important objective. In this study, we propose a new method that combines deviations from expected library insert sizes and additional information from local patterns of read mapping and uses supervised learning to predict the position and nature of structural variants. We show that our approach provides greatly increased sensitivity with respect to other tools based on paired end read mapping at no cost in specificity, and it makes reliable predictions of very short insertions and deletions in repetitive and low-complexity genomic contexts that can confound tools based on split mapping of reads. © 2012 The Author(s).

Moretti M.,University of Bari | Owen G.,University of Swansea | Tropeano M.,University of Bari
Sedimentary Geology | Year: 2011

Soft-sediment deformation structures are exposed in sea cliffs in the lower part of the Calcarenite di Gravina Formation (late Pliocene-early Pleistocene) in the Cala Corvino area N of Monopoli (Adriatic sector of the Apulian Foreland, southern Italy). Deformation affects a thickness of about 5. m involving a lower calcareous-terrigenous sand and gravel unit and an upper heavily bioturbated grainstone and packstone unit. Deformation is absent from the overlying part of the succession. Large-scale soft-sediment deformation structures are collapse features comprising irregularly elongated conical zones of sinking. In vertical section, narrow "drop" zones occur in the lower sandy-gravelly facies and large gentle folds in the upper grainstone-packstone beds. The degree of deformation decreases upwards. Small-scale soft-sediment deformation structures adjacent to the large-scale conical collapse structures are narrow, vertically elongated load structures about 2. m high and 30-50. cm wide that involve only the basal terrigenous facies. The distribution of small- and large-scale soft-sediment deformation structures corresponds closely to zones of fracturing in the underlying Cretaceous limestones, and the elongation directions of soft-sediment deformation structures correspond to the orientation of major fractures in the limestones. The soft-sediment deformation occurred due to collapse associated with karstic sinkhole formation along fractures in the bedrock. Geometrical relationships between deformed and undeformed sedimentary units show that deformation occurred in a shallow marine environment. The structures at Cala Corvino provide a rare outcrop-scale record of sinkhole-induced soft-sediment deformation occurring in a shallow marine environment. © 2010 Elsevier B.V.

Owen G.,University of Swansea | Moretti M.,University of Bari
Sedimentary Geology | Year: 2011

Triggers for liquefaction-induced soft-sediment deformation structures in sands include seismic shaking, effects of water waves, rapid sediment accumulation and groundwater movements. Many soft-sediment deformation structures are attributed to a seismic trigger, but the evidence is often variable and inconclusive. Liquefaction and its effects are reviewed in the context of earthquakes, other triggers and experiments. The interpretation of liquefaction-induced soft-sediment deformation structures comprises two key stages: recognising liquefaction as the deformation mechanism, and determining the trigger for liquefaction. The characteristics of sediment that has undergone liquefaction include the pervasive, ductile character of deformation, preservation of stratification, a gradual upward increase in the extent or complexity of deformation, possible water-escape structures in the upper parts of a liquefied horizon, a horizontal upper surface, and a distinctive grain fabric. Approaches to determining the trigger for liquefaction include those based on criteria and those based on the sedimentological and palaeoenvironmental context. Few of the criteria applied to seismic triggers are diagnostic and several are not applicable on the scale of single outcrops. Criteria are poorly developed for non-seismic triggers. A methodology is proposed for analysing soft-sediment deformation structures within their overall sedimentological and palaeoenvironmental context in order to refine and improve criteria for distinguishing the action of 'external' (allogenic) triggers, including earthquakes, from 'internal' (autogenic) triggers. © 2010 Elsevier B.V.

Dantas-Torres F.,University of Bari | Otranto D.,University of Bari
Veterinary Parasitology | Year: 2013

Ixodes ricinus is a major vector of pathogens affecting animals and humans in Europe. Despite its wide distribution, data on the ecology of I. ricinus in some areas is meager, which might impair the elaboration of reliable models to predict the risk of pathogen transmission in areas where this tick is currently present. Herein, we analyze some aspects of the ecology of I. ricinus in a wooded area of southern Italy. From March 2010 to March 2012, ticks were collected on a monthly basis by dragging and flagging in three different sites in a wooded area located in southern Italy, within the boundaries of the Gallipoli Cognato Forest, in the Basilicata region, southern Italy. Immature ticks were more abundant than adults (immature:adult ratio, 10.5:1). The abundance of larvae on the ground-level vegetation was generally higher than on higher vegetation (19.1 vs. 8.3 ticks per hour), whereas nymphs, males and females were more abundant on the higher vegetation (22.3 vs. 14.2, 2.9 vs. 0.8, 2.7 vs. 1.0 ticks per hour, respectively). Larvae were most abundant in summer (27.4 ticks per hour), whereas nymphs, females, and males peaked in seasons other than summer. This study underlines that I. ricinus is well adapted to southern Italian conditions, where it remains active during the whole year, displaying spatiotemporal distribution patterns that are different from central and north European populations. Remarkably, it points out that the life cycle of I. ricinus in southern Italy may be completed in approximately 1 year. Data generated will be valuable to elaborate better models to predict the distribution of this tick in Europe and to assess the risk of transmitted diseases, particularly Lyme borreliosis and tick-borne encephalitis. © 2012 Elsevier B.V.

Palmieri F.,University of Bari | Pierri C.L.,University of Bari | De Grassi A.,Italian National Cancer Institute | Nunes-Nesi A.,Federal University of Viçosa | Fernie A.R.,Max Planck Institute of Molecular Plant Physiology
Plant Journal | Year: 2011

The mitochondrial carriers (MC) constitute a large family (MCF) of inner membrane transporters displaying different substrate specificities, patterns of gene expression and even non-mitochondrial organelle localization. In Arabidopsis thaliana 58 genes encode these six trans-membrane domain proteins. The number in other sequenced plant genomes varies from 37 to 125, thus being larger than that of Saccharomyces cerevisiae and comparable with that of Homo sapiens. In addition to displaying highly similar secondary structures, the proteins of the MCF can be subdivided into subfamilies on the basis of substrate specificity and the presence of specific symmetry-related amino acid triplets. We assessed the predictive power of these triplets by comparing predictions with experimentally determined data for Arabidopsis MCs, and applied these predictions to the not yet functionally characterized mitochondrial carriers of the grass, Brachypodium distachyon, and the alga, Ostreococcus lucimarinus. We additionally studied evolutionary aspects of the plant MCF by comparing sequence data of the Arabidopsis MCF with those of Saccharomyces cerevisiae and Homo sapiens, then with those of Brachypodium distachyon and Ostreococcus lucimarinus, employing intra- and inter-genome comparisons. Finally, we discussed the importance of the approaches of global gene expression analysis and in vivo characterizations in order to address the relevance of these vital carrier proteins. © 2011 The Authors.

Novielli N.,University of Bari | Marczak S.,Grande Rio University
Proceedings - 2013 IEEE 8th International Conference on Global Software Engineering Workshops, ICGSEW 2013 | Year: 2013

Software development is a collaborative activity in which social relationships among those involved throughout the life cycle are paramount for achieving the project goals. For instance, communication with, awareness of, and trust in others are relevant and necessary to facilitate collaboration. The identification of social relationships and their patterns can help us to better understand the dynamics of a project team. This understanding is crucial when working in a global setting where members have to virtually establish relationships and collaborate with remote colleagues. Social network analysis allows us to reveal relationship patterns in a fine-grained level. This tutorial provides basic concepts and measures on social network analysis and discusses their application in global software engineering. Practicing on a dataset from a real distributed software project is also part of this tutorial. The tutorial is suitable for anyone interested in global software development and the social relationships established among software developers in distributed teams. 978-0-7695-5055-8/13 $26.00 © 2013 IEEE.

Imbimbo B.P.,Chiesi Farmaceutici | Solfrizzi V.,University of Bari | Panza F.,Geriatric Unit and Gerontology Geriatrics Research Laboratory
Frontiers in Aging Neuroscience | Year: 2010

Several epidemiological studies suggest that long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) may protect subjects carrying one or more ε4 allele of the apolipoprotein E (APOE ε4) against the onset of Alzheimer's disease (AD). The biological mechanism of this protection is not completely understood and may involve the anti-inflammatory properties of NSAIDs or their ability of interfering with the β-amyloid (Aβ) cascade. Unfortunately, long-term, placebo-controlled clinical trials with both non-selective and cyclooxygenase-2 (COX-2) selective inhibitors in mild-to-moderate AD patients produced negative results. A secondary prevention study with rofecoxib, a COX-2 selective inhibitor, in patients with mild cognitive impairment was also negative. A primary prevention study (ADAPT trial) of naproxen (a non-selective COX inhibitor) and celecoxib (a COX-2 selective inhibitor) in cognitively normal elderly subjects with a family history of AD was prematurely interrupted for safety reasons after a median period of treatment of 2 years. Although both drugs did not reduce the incidence of dementia after 2 years of treatment, a 4-year follow-up assessment surprisingly revealed that subjects previously exposed to naproxen were protected from the onset of AD by 67% compared to placebo. Thus, it could be hypothesized that the chronic use of NSAIDs may be beneficial only in the very early stages of the AD process in coincidence of initial Aβ deposition, microglia activation and consequent release of pro-inflammatory mediators. When the Aβ deposition process is already started, NSAIDs are no longer effective and may even be detrimental because of their inhibitory activity on chronically activated microglia that on long-term may mediate Aβ clearance. The research community should conduct long-term trials with NSAIDs in cognitively normal APOE ε4 carriers. © 2010 Imbimbo, Solfrizzi and Panza.

Delvecchio M.,Unita Operativa Complessa di Pediatria | Cavallo L.,University of Bari
Journal of Endocrinological Investigation | Year: 2010

Background: Thalassemia major is an inherited hemoglobin disorder characterized by chronic anemia and iron overload due to transfusion therapy and gastrointestinal absorption. Iron overload causes most of the associated mortality and morbidity and frequently involves the endocrine glands. Aim: To review the most pertinent literature on the topic. Methods: One hundred and twenty-three papers were evaluated. Results: Disproportionate short stature is frequent and becomes more evident at puberty because of the lack of growth spurt. Later on, partial height recovery may occur. Long-term treatment with recombinant human GH seems ineffective to improve final height. Pubertal development is characterized by a clinical spectrum ranging from hypogonadism to a simple delay in starting and developing of puberty. Hormonal replacement is mandatory in cases of absent or arrested puberty. Pancreatic β-cells function may be impaired during adolescence or later on. Its impairment ranges from hyperinsulinemia, secondary to insulin resistance, with normal glucose tolerance to β-cells failure with insulin-dependent diabetes mellitus. Primary hypothyroidism may affect thalassemic patients from the second decade of life. The thyroid dysfunction may be reversible (if an intensive chelation therapy regimen is started in the precocious phase), stationary, or slowly progressive. Central hypothyroidism is less common and autoimmune thyroiditis absent. Conclusion: Despite the improvement of the treatment, the involvement of the endocrine system still burdens the life of these patients. Further therapeutic improvement would reasonably reduce morbidity and, hopefully, mortality of thalassemic patients and make the endocrine disorders easier to treat. ©2010, Editrice Kurtis.

Aresta M.,National University of Singapore | Aresta M.,University of Bari
Coordination Chemistry Reviews | Year: 2016

This paper tells part of the contemporary CO2 story through the chemistry developed in my laboratory at the University of Bari or wherever I have been in the world, since the discovery of the first Ni-CO2 complex up to the various catalytic conversion reactions of CO2 into several added-value products. Most of the reactions are described with relevant reaction mechanisms. Here and there, some failures are discussed just to show that the way to success is paved with hidden traps or holes of knowledge that must be filled before one can progress. © 2016 Elsevier B.V.

Dantas-Torres F.,University of Bari | Otranto D.,University of Bari
Trends in Parasitology | Year: 2016

Vector-borne diseases constitute a diversified group of illnesses, which are caused by a multitude of pathogens transmitted by arthropod vectors, such as mosquitoes, fleas, ticks, and sand flies. Proper management of these diseases is important from both human and veterinary medicine standpoints, given that many of these pathogens are transmissible to humans and dogs, which often live in close contact. In this review, we summarize the most important vector-borne diseases of dogs and humans and the best practices for their prevention. The control of these diseases would ultimately improve animal and human health and wellbeing, particularly in developing countries in the tropics, where the risk of these diseases is high and access to health care is poor. © 2015 Elsevier Ltd.

Gikas P.,Technical University of Crete | Ranieri E.,University of Bari | Tchobanoglous G.,University of California at Davis
Journal of Chemical Technology and Biotechnology | Year: 2013

Background: Two pilot scale horizontal subsurface flow constructed wetlands (HSFCWs), with a planted area of 15 m2 each, were constructed in Puglia, Italy, and planted with hydrophytes (Phragmites australis and Typha latifolia), while a similar field of equal size was used as a control. The primary aim of the present work was to assess the removal of three heavy metals from waste water, in relation to the evapotranspiration, using HSFCWs. Results: Residence time distributions in both planted HSFCWs indicated that the Typha field had porosity of 0.16 and exhibited more ideal plug flow behavior (Pe=29.7), compared with the Phragmites field (Pe=26.7), which had similar porosity. The measured hydraulic residence times in the planted fields were 35.8 and 36.7 h, for Typha and Phragmites, respectively, at waste water flow rates of 1 m3 d-1 (corresponding to hydraulic loading rate of 66.7 mm d-1). Heavy metals concentrations at the inlet were 2 mg/L, for each heavy metal, while at the outlet of the fields were Cr=0.23 mg L-1, Pb=0.21 mg L-1 and Fe=0.18 mg L-1 in the Phragmites field, and the removal rates were 87, 88 and 92% of Cr, Pb and Fe, respectively. The Typha field showed a similar behavior with concentrations equal to Cr=0.19 mg L-1, Pb=0.23 mg L-1 and Fe=0.16 mg L-1 and removal percentages of 90, 87, and 95% of Cr, Pb and Fe, respectively. The control field showed metal removals slightly lower (86, 78 and 88% for Cr, Pb and Fe, respectively). Conclusions: HSFCWs are appropriate for removing heavy metals from waste water. Evapotranspiration may significantly reduce the amount of discharged flow and may influence the removal rate of heavy metals. © 2013 Society of Chemical Industry.

Ranieri E.,University of Bari | Gikas P.,Technical University of Crete | Tchobanoglous G.,University of California at Davis
Desalination and Water Treatment | Year: 2013

Benzene, toluene, ethylbenzene, and xylenes (BTEX) are commonly encountered pollutants. The focus of the present work is on the removal of BTEX using pilot-scale constructed wetlands (CWs). Experiment carried out in three similar pilot-scale horizontal sub-surface flow constructed wetlands with an area of 35m2 (each), two of which were planted with different macrophytes (Phragmites australis and Typha latifolia), while an unplanted one was used as control. A number of hydraulic tests were carried out using lithium bromide as tracer, to assess the hydraulic residence time. Residence time distributions for the two CWs indicated that the Typha field was characterized by a void volume fraction (porosity) of 0.16 and exhibited more ideal plug flow behavior (Pe = 29.7) compared with the Phragmites field (Pe = 26.7), which had similar porosity. The measured hydraulic residence times in the planted fields were 35.8, 36.7, and 34.1 h for Typha, Phragmites, and unplanted respectively, at wastewater flow rates equal to 1m3/d. The observed percentage removal for BTEX ranged between 46 and 55%. The average removal in the Phragmites field was 5% higher than the Typha field and 23% higher than the unplanted field. BTEX removal was primarily attributed to volatilization; however, biodegradation also played a significant role. © 2013 Balaban Desalination Publications.

Donnez J.,Catholic University of Leuven | Tomaszewski J.,Prywatna Klinika Polozniczo Ginekologiczna | Bouchard P.,University Paris - Sud | Lemieszczuk B.,Gabinet Lekarski Specjalistyczny Sonus | And 8 more authors.
New England Journal of Medicine | Year: 2012

BACKGROUND: The efficacy and side-effect profile of ulipristal acetate as compared with those of leuprolide acetate for the treatment of symptomatic uterine fibroids before surgery are unclear. METHODS: In this double-blind noninferiority trial, we randomly assigned 307 patients with symptomatic fibroids and excessive uterine bleeding to receive 3 months of daily therapy with oral ulipristal acetate (at a dose of either 5 mg or 10 mg) or once-monthly intramuscular injections of leuprolide acetate (at a dose of 3.75 mg). The primary outcome was the proportion of patients with controlled bleeding at week 13, with a prespecified noninferiority margin of -20%. RESULTS: Uterine bleeding was controlled in 90% of patients receiving 5 mg of ulipristal acetate, in 98% of those receiving 10 mg of ulipristal acetate, and in 89% of those receiving leuprolide acetate, for differences (as compared with leuprolide acetate) of 1.2 percentage points (95% confidence interval [CI], -9.3 to 11.8) for 5 mg of ulipristal acetate and 8.8 percentage points (95% CI, 0.4 to 18.3) for 10 mg of ulipristal acetate. Median times to amenorrhea were 7 days for patients receiving 5 mg of ulipristal acetate, 5 days for those receiving 10 mg of ulipristal acetate, and 21 days for those receiving leuprolide acetate. Moderate-to-severe hot flashes were reported for 11% of patients receiving 5 mg of ulipristal acetate, for 10% of those receiving 10 mg of ulipristal acetate, and for 40% of those receiving leuprolide acetate (P<0.001 for each dose of ulipristal acetate vs. leuprolide acetate). CONCLUSIONS: Both the 5-mg and 10-mg daily doses of ulipristal acetate were noninferior to oncemonthly leuprolide acetate in controlling uterine bleeding and were significantly less likely to cause hot flashes. (Funded by PregLem; number, NCT00740831.) Copyright © 2012 Massachusetts Medical Society.

Calefato F.,University of Bari | Damian D.,University of Victoria | Lanubile F.,University of Bari
Empirical Software Engineering | Year: 2012

Requirements engineering is one of the most communication-intensive activities in software development, greatly affected by project stakeholder geographical distribution. Despite advances in collaboration technologies, global software teams continue to experience significant challenges in the elicitation and negotiation of requirements. Deciding which communication technologies to deploy to achieve effective communication in distributed requirements engineering activities is not a trivial task. Is face-to-face or text-based communication more appropriate for requirements elicitations and negotiations? In teams that do not have access to face-to-face communication, is text-based communication more useful in requirements elicitations than in requirements negotiations? Here, we report an empirical study that analyzes the effectiveness of synchronous computer-mediated communication in requirements elicitations and negotiations. Our investigation is guided by a theoretical framework that we developed from theories of computer-mediated communication, common ground, and media selection for group tasks; a framework that considers the effectiveness of a communication medium in relation to the information richness needs of requirements elicitation and negotiation tasks. Our findings bring forward empirical evidence about the perceived as well as objective fit between synchronous communication technology and requirements tasks. First, face-to-face is not always the most preferred medium for requirements tasks, and we reveal a number of conditions in which, in contrast to common belief, text-based communication is preferred for requirements communication. Second, we find that in evaluating outcomes of requirements elicitations and negotiations objectively, group performance is not affected by the communication medium. Third, when groups interact only via text-based communication, common ground in requirements negotiations takes longer to achieve than in requirements elicitations, indicating that distributed requirements elicitation is the task where computer-mediated communication tools have most opportunity for successful application. © Springer Science+Business Media, LLC 2011.

Giorgino F.,University of Bari | Benroubi M.,Athens General Hospital | Sun J.-H.,Chang Gung Memorial Hospital | Zimmermann A.G.,Eli Lilly and Company | Pechtner V.,Eli Lilly and Company
Diabetes Care | Year: 2015

OBJECTIVE This study compared the efficacy and safety of once-weekly dulaglutide, a glucagonlike peptide-1 receptor agonist, with daily insulin glargine, both combined with maximally tolerated doses of metformin and glimepiride in patients with type 2 diabetes. The primary objective was noninferiority of dulaglutide 1.5 mg to glargine in the HbA1c change from baseline at 52 weeks. RESEARCH DESIGN AND METHODS In this 78-week, open-label study, 810 patients were randomized to dulaglutide 1.5 mg, dulaglutide 0.75 mg, or glargine. RESULTS The baselinemean ± SD HbA1c was 8.1 ± 1.0% (65.5 ± 10.8mmol/mol). The least squares mean ± SE HbA1c change from baseline to the primary end point was 21.08 ± 0.06% (211.8 ± 0.7 mmol/mol) for dulaglutide 1.5 mg, 20.76 ± 0.06% (28.3 ± 0.7 mmol/mol) for dulaglutide 0.75 mg, and 20.63 ± 0.06% (26.9 ± 0.7 mmol/mol) for glargine, with an end point mean ± SD dose of 29 ± 26 units (0.3360.24 units/kg), and a fasting plasma glucose (mean6SD) of 118623 mg/dL from self-monitored plasma glucose. Statistical criteria for superiority were met with dulaglutide 1.5 mg and for noninferiority with dulaglutide 0.75 mg. More patients on dulaglutide 1.5 mg achieved HbA1c targets <7.0% (53 mmol/mol) versus glargine (P < 0.001). Body weight decreased with dulaglutide and increased with glargine. Total hypoglycemia rates were lower with dulaglutide; severe hypoglycemia was minimal. Increases in pancreatic enzymes were observed for dulaglutide. Incidence of nausea (15.4, 7.7, and 1.5%) and diarrhea (10.6, 9.2, and 5.7%) were more common with dulaglutide 1.5 mg and 0.75 mg than with glargine. CONCLUSIONS Once-weekly dulaglutide 1.5 mg, compared with daily insulin glargine without forced titration, demonstrated greater HbA1c reduction and weight loss, with a higher incidence of gastrointestinal adverse events and a lower risk of hypoglycemia. © 2015 by the American Diabetes Association.

Giagulli V.A.,University of Bari | Carbone M.D.,Institute of Clinical and Hormonal Research | Carbone M.D.,Biomedical Research Association Guglielmo Telesforo
International Journal of Andrology | Year: 2011

Given the lack of clarity regarding the value of varicocele correction in improving male fertility, we examined whether divergent results in this regard could be attributed to selection of patients, especially with regard to the duration of their infertility or to the length of patients' androgen receptor CAG repeats. In a prospective study, involving all varicocele patients consulted consecutively for infertility, we compared the pregnancy rate (PR) over 1year produced by patients who opted not to have varicocele correction after extensive information concerning fertility prospects (N=185), with that by patients who had varicocele correction (N=137). In the second study involving another smaller group of varicocele subjects (N=72), we investigated whether CAG repeat length in the androgen receptor gene had any influence on fertility of varicocele-corrected patients. Overall, the PR in corrected and uncorrected varicocele groups did not differ significantly, but when subjects with infertility beyond 2years were considered, varicocele-corrected subjects had a significantly greater PR than uncorrected varicocele patients (p=0.025). Together with infertility duration, spermatozoa progressive motility appears the most important predictor of fertility, whereas neither grade of varicocele nor age of the couple (within the age limits of this study) influenced the outcome. Similarly, CAG repeat length did not affect the outcome of varicocele correction. These data suggest that varicocele correction at 1year of infertility does not result in a significantly higher PR than that achieved by men with uncorrected varicocele. In view of the high spontaneous PR in subjects with an infertility of less than 2years, varicocele correction aimed at restoring fertility appears to be most appropriate for men whose infertility extends beyond 2 years. © 2010 The Authors. International Journal of Andrology © 2011 European Academy of Andrology.

Panza F.,University of Bari | Solfrizzi V.,University of Bari | Imbimbo B.P.,Chiesi Farmaceutici | Tortelli R.,University of Bari | And 2 more authors.
Expert Review of Clinical Immunology | Year: 2014

Both active and passive anti-β-amyloid (Aβ) immunotherapies for the treatment of Alzheimer's disease (AD) have demonstrated clearance of brain Aβ deposits. Among passive immunotherapeutics, two Phase III clinical trials in mild-to-moderate AD patients with bapineuzumab, a humanized monoclonal antibody directed at the N-terminal sequence of Aβ, were disappointing. Also solanezumab, directed at the mid-region of Aβ, failed in two Phase III trials in mild-to-moderate AD. Another Phase III trial with solanezumab is ongoing in mildly affected AD patients based on encouraging results in this subgroup. Second-generation active Aβ vaccines (CAD106, ACC-001, and Affitope AD02) and new passive anti-Aβ immunotherapies (gantenerumab and crenezumab) have been developed and are under clinical testing. These new anti-Aβ immunotherapies are being tested in prodromal AD, in presymptomatic subjects with AD-related mutations, or in asymptomatic subjects at risk of developing AD. These primary and secondary prevention trials will definitely test the Aβ cascade hypothesis of AD. © 2014 Informa UK Ltd.

Panza F.,University of Bari | Solfrizzi V.,University of Bari | Imbimbo B.P.,Chiesi Farmaceutici | Logroscino G.,University of Bari
Expert Opinion on Biological Therapy | Year: 2014

Introduction: Two humanized monoclonal antibodies, bapineuzumab and solanezumab, directed against the N terminus and mid-region of β-amyloid (Aβ), respectively, were recently tested in large, long-term Phase III trials in patients with mild-to-moderate Alzheimer's disease (AD). Areas covered: This review discusses current clinical data on solanezumab, bapineuzumab and their failure in Phase III trials to show significant clinical benefits, as well as other monoclonal antibodies under investigation for AD. Expert opinion: Solanezumab showed some beneficial cognitive effects in mildly affected AD patients and this subgroup of AD patients is currently being tested in another Phase III trial to this subgroup of AD patients to confirm previous encouraging observations. Two other monoclonal antibodies, gantenerumab, which preferentially binds to fibrillar Aβ, and crenezumab, which preferentially binds to soluble, oligomeric and fibrillar Aβ deposits, are being tested in secondary prevention trials in presymptomatic subjects with autosomal dominant AD mutations. Solanezumab is also being tested in a prevention study in asymptomatic older subjects, who have positive positron emission tomography scans for brain amyloid deposits. These ongoing secondary prevention trials will tell us if Aβ really plays a crucial role in the pathophysiology of AD. © Informa UK, Ltd.

Arnesano F.,University of Bari | Natile G.,University of Bari
European Journal of Inorganic Chemistry | Year: 2013

Cisplatin, or cis-diamminedichloridoplatinum(II) cis-[PtCl 2(NH3)2], is a platinum-based anticancer drug largely used for the treatment of various types of cancers, including ovarian and colorectal carcinomas, sarcomas, and lymphomas. Together with other platinum-based drugs, it triggers malignant cell death by binding to nuclear DNA, which appears to be the ultimate target. In addition to passive diffusion across the cell membrane, other transport mechanisms, including endocytosis and some active or facilitated transport, are currently proposed to play a pivotal role in the uptake of platinum-based drugs. In this microreview, we will give an updated view of the current literature regarding cisplatin transport and processing inside the cell, with special emphasis on the membrane copper transporter Ctr1 and the soluble copper chaperone Atox1. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Conteduca V.,Irccs Instituto Scientifico Romagnolo Per Lo Studio E La Cura Dei Tumori Irst | Sansonno D.,University of Bari | Russi S.,University of Bari | Dammacco F.,University of Bari
International Journal of Oncology | Year: 2013

Colorectal cancer (CRC) is a common and often lethal tumor. Over the last 25 years, remarkable progress has been made in understanding its biological and molecular features and in elucidating the steps involved in colon carcinogenesis. This, in turn, has led to a more rational and effective clinical approach to the treatment of CRC. While colorectal adenoma is the most frequent precancerous lesion, other potentially premalignant conditions, including chronic inflammatory bowel diseases and hereditary syndromes, such as familial adenomatous polyposis, Peutz-Jeghers syndrome and juvenile polyposis, involve different sites of the gastrointestinal tract with an overall incidence of less than 5%. In all such cases, disease recognition at an early stage is essential to devise suitable preventive cancer strategies. These topics are addressed in this review, along with the most important epidemiological, pathogenetic and clinical features that lead to malignant transformation. Novel biomarkers for early cancer prediction, detection, prognostic evolution, and the response to treatment are critically assessed as well. Continued improvements in our knowledge of the molecular basis of CRC and the transfer of this information into daily clinical practice will reduce the burden of this disease.

Dantas-Torres F.,Oswaldo Cruz Foundation | Dantas-Torres F.,University of Bari | Chomel B.B.,University of California at Davis | Otranto D.,University of Bari
Trends in Parasitology | Year: 2012

Tick-borne diseases are common occurrences in both the medical and veterinary clinical settings. In addition to the constraints related to their diagnosis and clinical management, the control and prevention of these diseases is often difficult, because it requires the disruption of a complex transmission chain, involving vertebrate hosts and ticks, which interact in a constantly changing environment. We provide a contemporary review of representative tick-borne diseases of humans and discuss aspects linked to their medical relevance worldwide. Finally, we emphasize the importance of a One Health approach to tick-borne diseases, calling physicians and veterinarians to unify their efforts in the management of these diseases, several of which are zoonoses. © 2012 Elsevier Ltd.

Bruno G.,University of Bari | Vessia G.,National Research Council Italy | Bobbo L.,Freelance Civil Engineer
Rock Mechanics and Rock Engineering | Year: 2013

A study was conducted to propose a new empirical relationship between the uniaxial compressive strength of rock and the Schmidt hammer rebound index (R) measurements, based on the statistical percentile method applied to sedimentary carbonate rocks whose uniaxial resistance was within the range of feasibility of the Schmidt hammer test. The R measurements were performed using two types of Schmidt's hammer, such as the L and N types. The indirect estimation of the uniaxial compressive strength of rock from measurements was a common practice performed by means of several empirical relationships. A four-step statistical procedure was proposed to derive the regression equation and to verify the presence of outliers in the two datasets by means of the EDA technique. The statistical procedure also aimed to generate a new sample dataset of percentile values from each sample's cumulative function.

Owen G.,University of Swansea | Moretti M.,University of Bari | Alfaro P.,University of Alicante
Sedimentary Geology | Year: 2011

Most of the 16 papers in this special issue were presented at a session entitled "The recognition of trigger mechanisms for soft-sediment deformation" at the 27th IAS Meeting of Sedimentology in Alghero, Sardinia, Italy, which took place from 20th-23rd September 2009. They describe soft-sediment deformation structures that range widely in morphology, age, depositional environment and tectonic setting. In their interpretations, the authors have been asked to focus on identifying the agent that triggered deformation. Our aims in this introductory overview are to: (1) review the definition and scope of soft-sediment deformation; (2) clarify the significance and role of the trigger; (3) set the contributions in context and summarise their findings; and (4) discuss strategies for reliably identifying triggers and make recommendations for future study of this widespread and significant category of sedimentary structures. We recommend a three-stage approach to trigger recognition, combining the assessment of facies, potential triggers, and available criteria. This focus on the trigger for deformation distinguishes this collection of papers on soft-sediment deformation from other important collections, notably those edited by Jones and Preston (1987), Maltman (1994), Maltman et al. (2000), Shiki et al. (2000), Ettensohn et al. (2002b), Van Rensbergen et al. (2003) and Storti and Vannucchi (2007). © 2011 Elsevier B.V.

Degirolamo C.,IRCCS Instituto Oncologico Giovanni Paolo II | Rainaldi S.,Fondazione Mario Negri Sud | Bovenga F.,IRCCS Instituto Oncologico Giovanni Paolo II | Murzilli S.,Fondazione Mario Negri Sud | And 2 more authors.
Cell Reports | Year: 2014

Gut microbiota influences host health status by providing trophic, protective, and metabolic functions, including bile acid (BA) biotransformation. Microbial imprinting on BA signature modifies pool size and hydrophobicity, thus contributing to BA enterohepatic circulation. Microbiota-targeted therapies are now emerging as effective strategies for preventing and/or treating gut-related diseases. Here, we show that gut microbiota modulation induced by VSL#3 probiotics enhances BA deconjugation and fecal excretion in mice. These events are associated with changes in ileal BA absorption, repression of the enterohepatic farnesoid X receptor-fibroblast growth factor 15 (FXR-FGF15) axis, and increased hepatic BA neosynthesis. Treatment with a FXR agonist normalized fecal BA levels in probiotic-administered mice, whereas probiotic-induced alterations in BA metabolism are abolished upon FXR and FGF15 deficiency. Our data provide clear invivo evidence that VSL#3 probiotics promote ileal BA deconjugation with subsequent fecal BA excretion and induce hepatic BA neosynthesis via downregulation of the gut-liver FXR-FGF15 axis. © 2014 The Authors.

Frisardi V.,University of Bari
Journal of Alzheimer's Disease | Year: 2011

In an aging world, maintaining good health and independence for as long as possible is essential. Instead of hospitalization or institutionalization, the elderly with chronic conditions, especially those with cognitive impairment, can be assisted in their own environment with numerous 'smart' devices that support them in their activity of daily living. A "smart home" is a residence equipped with technology that facilitates monitoring of residents to improve quality of life and promote physical independence, as well as to reduce caregiver burden. Several projects worldwide have been conducted, but some ethical and legal issues are still unresolved and, at present, there is no evidence of the effects of smart homes on health outcomes. Randomized controlled trials are needed to understand the plus and minuses of these projects, but this will only be possible with a widespread proliferation and penetration of smart homes in the social network. © 2011 - IOS Press and the authors. All rights reserved.

Pagliarulo V.,University of Bari | Eisenberger M.A.,Johns Hopkins University | Schroder F.H.,Erasmus Medical Center | Sternberg C.N.,San Camillo Forlanini Hospital | Studer U.E.,University of Bern
European Urology | Year: 2012

Context: Androgen deprivation therapy (ADT) for prostate cancer (PCa) represents one of the most effective systemic palliative treatments known for solid tumors. Although clinical trials have assessed the role of ADT in patients with metastatic and advanced locoregional disease, the risk-benefit ratio, especially in earlier stages, remains poorly defined. Given the mounting evidence for potentially life-threatening adverse effects with short- and long-term ADT, it is important to redefine the role of ADT for this disease. Objective: Review the published experience with currently available ADT approaches in various contemporary clinical settings of PCa and reported serious treatment-related adverse events. This review addresses the level of evidence associated with the use of ADT in PCa, focusing upon survival outcome measures. Furthermore, this paper discusses evolving approaches targeting androgen receptor signaling pathways and emerging evidence from clinical trials with newer compounds. Evidence acquisition: A comprehensive review of the literature was performed, focusing on data from the last 10 yr (January 2000 to July 2011) and using the terms androgen deprivation, hormone treatment, prostate cancer and adverse effects. Abstracts from trials reported at international conferences held in 2010 and 2011 were also evaluated. Evidence synthesis: Data from randomized controlled trials and population-based studies were analyzed in different clinical paradigms. Specifically, the role of ADT was evaluated in patients with nonmetastatic disease as the primary and sole treatment, in combination with radiation therapy (RT) or after surgery, and in patients with metastatic disease. The data suggest that in men with nonmetastatic disease, the use of primary ADT as monotherapy has not shown a benefit and is not recommended, while ADT combined with conventional-dose RT (<72 Gy) for patients with high-risk disease may delay progression and prolong survival. The postoperative use of ADT remains poorly evaluated in prospective studies. Likewise, there are no trials evaluating the role of ADT in patients with biochemical relapses after surgery or RT. In patients with metastatic disease, there is a clear benefit in terms of quality of life, reduction of disease-associated morbidity, and possibly survival. Treatment with bilateral orchiectomy, luteinizing hormone-releasing hormone agonist therapy, with and without antiandrogens has been associated with various serious adverse events, including cardiovascular disease, diabetes, and skeletal complications that may also affect mortality. Conclusions: Although ADT is an effective treatment of PCa, consistent long-term benefits in terms of quality and quantity of life are predominantly evident in patients with advanced/metastatic disease or when ADT is used in combination with RT (<72 Gy) in patients with high-risk tumors. Implementation of ADT should be evidence based, with special consideration to adverse events and the risk-benefit ratio. © 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Panza F.,University of Bari | Logroscino G.,University of Bari | Imbimbo B.P.,Chiesi Farmaceutici | Solfrizzi V.,University of Bari
Current Opinion in Psychiatry | Year: 2014

PURPOSE OF REVIEW: We reviewed clinical trials on active and passive anti-β-amyloid (Aβ) immunotherapy for the treatment of Alzheimer's disease with a particular focus on monoclonal antibodies against Aβ. RECENT FINDINGS: Studies on anti-Alzheimer's disease immunotherapy published in the period from January 2012 to October 2013 were reviewed. SUMMARY: Both active and passive anti-Aβ immunotherapies were shown to clear brain Aβ deposits. However, an active anti-Aβ vaccine (AN1792) has been discontinued because it caused meningoencephalitis in 6% of Alzheimer's disease patients treated. Among passive immunotherapeutics, two Phase III clinical trials in mild-to-moderate Alzheimer's disease patients with bapineuzumab, a humanized monoclonal antibody directed at the N-terminal sequence of Aβ, were disappointing. Another antibody, solanezumab, directed at the mid-region of Aβ, failed in two Phase III clinical trials in mild-to-moderate Alzheimer's disease patients. A third Phase III study with solanezumab is ongoing in mildly affected Alzheimer's disease patients based on encouraging results in this subgroup of patients. Second-generation active Aβ vaccines (ACC-001, CAD106, and Affitope AD02) and new passive anti-Aβ immunotherapies (gantenerumab and crenezumab) are being tested in prodromal Alzheimer's disease patients, in presymptomatic individuals with Alzheimer's disease-related mutations, or in asymptomatic individuals at risk of developing Alzheimer's disease to definitely test the Aβ cascade hypothesis of Alzheimer's disease. © 2014 Wolters Kluwer Health | Lippincott Williams &Wilkins.

Gadaleta R.M.,Imperial College London | Cariello M.,IRCCS Instituto Oncologico Giovanni Paolo II | Sabba C.,University of Bari | Moschetta A.,IRCCS Instituto Oncologico Giovanni Paolo II | Moschetta A.,University of Bari
Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids | Year: 2015

The nuclear Farnesoid X Receptor (FXR) is a transcription factor critically involved in metabolic homeostasis in the gut-liver axis. FXR activity is mediated by hormonal and dietary signals and driven by bile acids (BAs), which are the natural FXR ligands. Given the great physiological importance in BA homeostasis, as well as in the regulation of glucose and lipid metabolism, FXR plays a pivotal role in the pathogenesis of a wide range of disease of the liver, biliary tract and intestine, including hepatic and colorectal cancer. In the last years several studies have shown the relative FXR tissue-specific importance, highlighting synergism and additive effects in the liver and intestine. Gain- and loss-of-FXR-function mouse models have been generated in order to identify the biological processes and the molecular FXR targets. Taking advantage of the knowledge on the structure-activity relationship of BAs for FXR, semi-synthetic and synthetic molecules have been generated to obtain more selective and powerful FXR activators than BAs. This article is part of a Special Issue entitled: Linking transcription to physiology in lipodomics. © 2014 Elsevier Ltd. All rights reserved.

Caricasole P.,Old Dominion University | Provenzano M.R.,University of Bari | Hatcher P.G.,Old Dominion University | Senesi N.,University of Bari
Bioresource Technology | Year: 2010

This research aimed at assessing the chemical changes occurring in DOM extracted from different composting substrates by means of 13C CPMAS NMR spectroscopy. During composting a reduction of carbohydrates and an increase of aromatic, phenolic, carboxylic and carbonylic C were observed. The highest increase in alkyl C and the lowest increase in aromatic C were explained by the presence of hardly degradable pine needles in the substrate, whereas the highest reduction in carbohydrates and the highest increase of the alkyl C/O-alkyl C ratio were attributed to the presence of highly degradable materials such as spent yeast from beer production. © 2010 Elsevier Ltd.

Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2013.2.2.1-2 | Award Amount: 8.13M | Year: 2013

Mental disorders are leading causes of disability, absence from work and premature retirement in Europe. While magnetic resonance imaging (MRI) facilities are broadly available and a vast research literature exists, few neuroimaging applications have reached clinical practice in psychiatry. A major problem is that mental illnesses are currently diagnosed as discrete entities defined clinically. Instead, recent results show that mental disorders are best understood as quantitative alterations in neural systems relevant across traditional diagnostic boundaries that reflect individual, genetic and environmental risk factors. In the IMAGEMEND consortium, we aim to discover these systems to identify the patient characteristics most relevant for treatment, derive biomarkers and decision rules from this systems-level dimensional account, and systematically validate biomarker panels in patient, high-risk and epidemiological samples to produce automated imaging-based diagnostic and predictive tests tailored for wide distribution throughout Europe in standard clinical settings. Focusing on schizophrenia, bipolar disorder and attention deficit-hyperactivity disorder, we have assembled Europes largest dataset combining neuroimaging, genetic, environmental, cognitive and clinical information on approximately 13000 participants, and have recruited international replication datasets of more than 30000 people. This unique resource will be processed using a new generation of multivariate statistical analysis to optimize existing imaging technology for the benefit of patients. We will also develop new imaging technology to enable the direct imaging-based therapeutic modification of neural circuits through rapid real-time MRI. Our deliverables will promote personalized treatment through more accurate patient stratification, allow diagnoses at the pre-symptomatic stage for early intervention and prevention, and improve prediction of treatment response and disease progression.

Agency: European Commission | Branch: FP7 | Program: CP | Phase: ENV.2013.6.2-5 | Award Amount: 7.21M | Year: 2013

GREEN SURGE will identify, develop and test ways of connecting green spaces, biodiversity, people and the green economy, in order to meet the major urban challenges related to land use conflicts, climate change adaptation, demographic changes, and human health and wellbeing. It will provide a sound evidence base for green infrastructure planning and implementation, exploring the innovation potential, and linking environmental, social and economic services with local communities. Working from the local to the city-regional level, the project aims to: 1) Develop urban green infrastructure as a planning concept for both integration and promotion of biodiversity and ecosystem services, and adapt it to local contexts; 2) apply an innovative biocultural diversity perspective to develop successful governance arrangements facilitating socio-ecological integration and local engagement in planning of urban green spaces; and 3) explore how valuation and real market integration of biodiversity and ecosystem services can facilitate choices in favour of the development of multifunctional green spaces in urban areas. Approaches and tools under these three interlinked objectives will be developed and implemented through an integrative, iterative and transdisciplinary process. GREEN SURGE will embrace a three-tiered approach of comparative European cases, synthesis of good practices, and establishment of five Urban Learning Labs strategically selected to represent different urban situations in Europe. GREEN SURGE will work within cooperative Learning Alliances, a specific type of multi-stakeholder involvement designed to enhance a process of shared learning and understanding in situations with a high degree of complexity and un-predictability. Two-loop learning applied combines a project-wide science-driven approach based on a common framework methodology with a bottom-up knowledge or experience-based approach at the local level.

Agency: European Commission | Branch: FP7 | Program: CP | Phase: ICT-2013.9.5 | Award Amount: 2.29M | Year: 2014

The need for machine learning (ML) and data mining (DM) is ever growing due to the increased pervasiveness of data analysis tasks in almost every area of life, including business, science and technology. Not only is the pervasiveness of data analysis tasks increasing, but so is their complexity. We are increasingly often facing predictive modelling tasks involving one or several of the following complexity aspects: (a)structured data as input or output of the prediction process, (b)very large/massive datasets, with many examples and/or many input/output dimensions, where data may be streaming at high rates, (c)incompletely/partially labelled data, and (d)data placed in a spatio-temporal or network context. Each of these is a major challenge to current ML/DM approaches and is the central topic of active research in areas such as structured-output prediction, mining data streams, semi-supervised learning, and mining network data. The simultaneous presence of several of them is a much harder, currently insurmountable, challenge and severely limits the applicability of ML/DM approaches.The proposed project will develop predictive modelling methods capable of simultaneously addressing several (ultimately all) of the above complexity aspects. In the most complex case, the methods would be able to address massive sets of network data incompletely labelled with structured outputs. We will develop the foundations (basic concepts and notions) for and the methodology (design and implementation of algorithms) of such approaches. We will demonstrate the potential and utility of the methods on showcase problems from a diverse set of application areas (molecular biology, sensor networks, mutimedia, and social networks). Some of these applications, such as relating the composition of microbiota to human health and the design of social media aggregators, have the potential of transformational impact on important aspects of society, such as personalized medicine and social media.

Agency: European Commission | Branch: H2020 | Program: MSCA-ITN-ETN | Phase: MSCA-ITN-2016 | Award Amount: 3.20M | Year: 2017

FOIE GRAS provides innovative training for 13 early stage researchers (ESRs) to answer two critical and unanswered questions: a) Is hepatic bioenergetic remodelling involved in NAFLD pathogenesis, and target for stratification or therapeutic/lifestyle interventions? and b) Is the disruption of the gut-liver axis involved in NAFLD progression? In Western Societies, there has been a recent surge of non-alcoholic fatty liver disease (NAFLD). Its progression to nonalcoholic steatohepatitis (NASH) is a leading risk factor for development of Type 2 diabetes, cirrhosis, and hepatocellular carcinoma. FOIE GRAS is first in supporting a cohesive and synergistic intersection of complementary and interdisciplinary training skills from academic and non-academic partners. FOIE GRAS combines strong scientific expertise with integrated and complementary training in translational research, clinical practice, technology commercialization, and public outreach, the combination of which in targeting NAFLD is lacking in the EU. Industrial partners CETICS, Mediagnost and Seahorse Biosciences provide experience on technology commercialization alongside scientific contributions while the affiliated patient organization will contribute with important training in societal awareness topics. ESRs training will utilize network-wide workshops and secondments to foster translation of basic research to clinical applications and SME creation. This diverse yet integrated skill set enhances the employment prospects of the trained researchers in both academic and non-academic sectors. Researchers will be endowed with excellent basic scientific knowledge and timely technology transfer know-how for developing novel therapeutic approaches for reversing the burden of NAFLD, thereby advancing both health and economic well-being of European citizens and approaching NAFLD research in the EU from its counterparts in the US and Asia.

Agency: European Commission | Branch: H2020 | Program: RIA | Phase: SFS-03a-2014 | Award Amount: 6.92M | Year: 2015

This proposal SFS-03a-2014-aligned focuses to minimize the risk of introduction/impact of emerging pests threatening EU agriculture and forestry. The targets are: 1) Xylella fastidiosa and its vectors in olive, grapevine, citrus, stone fruit, ornamentals and landscape trees of high socio-economic importance; 2) Ca. Liberibacter solanacearum and its vectors affecting a number of strategic crops such as potato, tomato and carrot; and 3) Hymenoscyphus pseudoalbidus (anomorph. Chalara fraxinea) and Phytophtora spp. seriously affecting broadleaf and conifer species in forest ecosystems. Targeted pests, their vectors and the host response will be explored using innovative approaches (NGS, transcriptomic). Diseases surveillance and epidemiology given by current methods will integrate improved survey protocols and remote sensing. Innovative IPM will include studies of microbiome to develop sustainable solutions in line with the EU plant health legislation. New knowledge gained with POnTE will result in an outcome-based pest prevention and management work plan to: a) implement area-wide pest risk assessments; b) prevent the entry and develop surveillance and early detection tools (diagnostic kits, lab-on-chip, new biomarkers); c) mitigate the spread and reduce the socio-economic impact; d) IPM based on disease resistance, disease-free seeds, cultural practices and physical environmentally-friendly treatments; e) support knowledge-based decision-making policies at EU level. The proposal fosters and promotes a multi-actor approach and transnational research collaborations among 25 Partners at the forefront of research in plant protection, agro-engineering and economics. It involves key industries/SMEs that develop diagnostic kits and services, agrochemical and seed companies, stakeholder groups. End-users will participate in the development of the project and immediately implement the practical solutions derived from the outcomes to solve these serious emerging diseases.

Agency: European Commission | Branch: H2020 | Program: MSCA-RISE | Phase: MSCA-RISE-2016 | Award Amount: 454.50K | Year: 2017

Non-Alcoholic Fatty Liver Disease (NAFLD), including its more pathologic consequence, non-alcoholic steatohepatitis (NASH), is believed to be the most common chronic liver disease worldwide, affecting between 6 to 37% of the population. NAFLD is a so called silent killer, as clinical symptoms only surface at late stages of the disease, when it is no longer treatable: untreated, NAFLD/NASH can lead to cirrhosis and hepatocellular carcinoma, culminating in liver failure. Currently the best method of diagnosing and staging the disease is liver biopsy, a costly, invasive and somewhat risky procedure, not to mention unfit for routine assessment. Besides, no therapeutic consensus exists for NAFLD/NASH treatment. mtFOIE GRAS (Foie Gras being French for fat liver) proposes to address the pressing need for non-invasive, accurate, rapid assessment of NAFLD/NASH stages, before and after intervention, through the development of biomarkers and innovative tools to follow mitochondrial (mt) dysfunction, a central mediator of fatty liver disease pathogenesis. This promising R&D strategy will also bring new knowledge about the disease mechanisms and improved understanding of the pathogenic process and disease drivers. To that end, mtFOIE GRAS envisages a training-through-work plan that brings together an intersectoral, multidisciplinary team of researchers and technicians experts in their fields, from basic to translational research, clinical practice, technology commercialization and public advocacy. Together with several PhD students, the team will share expertises and work synergistically along the value creation chain to address the unmet medical need of more informative NAFLD assessment. In the process, mtFOIE GRAS will endow the involved staff with excellent scientific knowledge and transferable skills while building and strengthening intersectoral cooperation among partners, thus contributing to EU RD&I excellence.

Agency: European Commission | Branch: FP7 | Program: CP-TP | Phase: KBBE.2013.1.2-09 | Award Amount: 11.84M | Year: 2013

The European aquaculture is a modern industry employing 190,000 people, with a 7 billion ex-farm value. This sector is well situated to be among world leaders in the efficient and sustainable production of safe seafood of the highest quality and nutritional value, taking into account consumer preferences and the large diversity of aquatic products from the wild. DIVERSIFY identified a number of new/emerging finfish species, with a great potential for the expansion of the EU aquaculture industry. The emphasis is on Mediterranean or warm-water cage culture, but also addressed are cold-water, pond/extensive and fresh water aquaculture. These new/emerging species are fast growing and/or large finfishes, marketed at a large size and can be processed into a range of products to provide the consumer with both a greater diversity of fish species and new value-added products. DIVERSIFY focuses on meagre (Argyrosomus regius) and greater amberjack (Seriola dumerili) for warm-water marine cage culture, wreckfish (Polyprion americanus) for warm- and cool-water marine cage culture, Atlantic halibut (Hippoglossus hippoglossus) for marine cold-water culture, grey mullet (Mugil cephalus) a euryhaline herbivore for pond/extensive culture, and pikeperch (Sanders lucioperca) for freshwater intensive culture using RAS. These species were selected based both on their biological and economical potential, and to cover the entire European geographic area and stimulate different aquaculture types. In collaboration with a number of SMEs, DIVERSIFY will build on recent/current national initiatives for species diversification in aquaculture, in order to overcome the documented bottlenecks in the production of these species. The combination of biological, technological and socioeconomic research planned in DIVERSIFY are expected to support the diversification of the aquaculture industry and help in expanding production, increasing aquaculture products and development of new markets.

Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH-2011.2.2.1-3 | Award Amount: 8.07M | Year: 2011

This project will undertake pre-clinical and cohort studies that address susceptibility factors for paediatric and adolescent tic disorders, with a particular focus on comorbid obsessive-compulsive symptomatology, from clinical, epidemiological, genetic, microbiological and immunological angles. EMTICS aims to elucidate the complex aetiology of the onset and clinical course of chronic tic disorders and associated obsessive-compulsive symptoms, through disentangling the interplay between environmental factors and genetic background; translate research findings into clinical applications by developing disease prediction models and investigation of a treatment strategy; and will establish a Pan-European infrastructure for the study of tic disorders. We hypothesise that the onset and/or exacerbation of tic and comorbid obsessive-compulsive disorders is associated with increased preceding occurrence of Group A beta-haemolytic Streptococcus (GAS) infections of specific molecular subtypes, and that this association is based on genetic susceptibility factors and mediated through immunological mechanisms related to psychosocial stress and immunological factors in host and GAS strains. Large-scale cohort studies will involve affected patients and at-risk first-degree relatives within an integrated, multidisciplinary research strategy. Treatment effects of active surveillance and standardized antibiotic treatment of GAS colonisation, thus addressing one of the main environmental factors involved (GAS infections) will be evaluated. Our approach will result in the identification of genetic and environmental susceptibility factors and will greatly contribute to a better understanding of the underlying mechanisms of tic disorders, with a focus on elucidating the role of autoimmunity. Our consortium brings together the highest expertise in the field of tic disorders across Europe in academia and industry, including a number of SMEs and a professional management company.

Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: KBBE-2007-1-2-09 | Award Amount: 4.41M | Year: 2008

SELFDOTT proposes to implement knowledge already obtained on the artificial control of reproduction of the Atlantic bluefin tuna (BFT), Thunnus thynnus, to obtain viable eggs, and study embryonic and larval development for the production of fry (juveniles). At the same time, suitable and environmentally performing feeds for the growout of BFT will be developed, thus reducing or eliminating the practice of raw fish importation and feeding by the fattening industry. Wild juvenile and mature BFT will be reared in captivity at two sites in the Mediterranean, and will be used to study puberty, gametogenesis, and the influence of diet on reproductive maturation and gamete quality. Mature fish will be induced to spawn using hormone implants and the eggs will be collected using devices designed specifically for cages. To establish the knowledge-base for controlled development of BFT larvae, the mesocosm and artificial larval rearing methods will be employed. The ontogenesis of essential biological functions will be studied, including environmental perception, digestion, immunity and behaviour. A protocol for the commercial-scale larval rearing of BFT will be recommended at the end of the project. Whole body and stomach composition of wild fish will be analyzed and serve as a guide to formulate nutritionally complete artificial feeds for BFT. Juveniles will be captured from the wild, adapted to captive conditions and used to carry out weaning and feeding experiments, using moist and dry pelleted diets. The environmental impact of the formulated feeds will be examined and compared to existing raw-fish practises. SELFDOTT will produce the basic knowledge necessary for the development of a self-sustained aquaculture industry for the BFT in the Mediterranean, thus enhancing the competitiveness of the EU aquaculture industry, while at the same time reducing the pressure on the wild BFT stocks and ensuring the conservation and recovery of this magnificent fish.

Agency: European Commission | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-2012-ITN | Award Amount: 3.31M | Year: 2012

Chronic liver diseases (CLD) and their end-stages, cirrhosis and hepatocellular carcinoma (HCC), are leading causes of morbidity and mortality worldwide with enormous socio-economic costs. Patients with liver cirrhosis are at high risk of deadly hepatic failure and over 80% of HCC develop on a cirrhotic background. HCC ranks as the 5th most common cancer and with >600,000 deaths per annum it constitutes a major global health problem. The main etiologies of CLD are chronic HCV and HBV infections, alcohol abuse and nonalcoholic steatohepatitis (NASH) as a result of the metabolic syndrome taking epidemic proportions. Liver transplantation is currently the only available therapy for terminal liver failure. It is well recognized that the cytokine TGF-Beta plays a pivotal role in the sequence of events leading to end-stage CLD, but the complexity of the underlying aberrant responses in the cells and the organ that lead to the drastic changes seen in CLD and HCC is poorly understood. A broad spectrum of scientific and technological capacities is needed to accomplish the goal of discovering drugs and treatment modalities for CLD and HCC.As a result, there is a lack in academia and industry alike - of internationally oriented researchers and research leaders, capable of seamless and bi-directional transfer of goal-oriented scientific knowledge and technologies between the basic, translational and clinical research and industrial capacities; a conditio sine qua non for effectively and efficiently combating CLD and HCC and alleviate its medical and socio-economic burdens. Consequently, the ITN formulated the mission to provide a multidisciplinary and intersectorial Research Training Programme for talented young researchers, so as to prepare them for leading roles in CLD research and drug discovery in European industry and academia.

Agency: European Commission | Branch: FP7 | Program: CP | Phase: ENERGY.2013.2.4.1 | Award Amount: 13.30M | Year: 2013

The IMAGE project will develop a reliable science based exploration and assessment method to IMAGE geothermal reservoirs using an interdisciplinary approach based on three general pillars: 1 Understanding the processes and properties that control the spatial distribution of critical exploration parameters at European to local scales. The focus will be on prediction of temperatures, in-situ stresses, fracture permeability and hazards which can be deduced from field analogues, public datasets, predictive models and remote constraints. It provides rock property catalogues for 2 and 3. 2 Improving well-established exploration techniques for imaging and detection beyond the current state of the art and testing of novel geological, geophysical and geochemical methods to provide reliable information on critical subsurface exploration parameters. Methods include a) geophysical techniques such as ambient seismic noise correlation and magnetotellurics with improved noise filtering, b) fibre-optic down-hole logging tools to assess subsurface structure, temperature and physical rock properties, and c) the development of new tracers and geothermometers. 3 Demonstration of the added value of an integrated and multidisciplinary approach for site characterization and well-siting, based on conceptual advances, improved models/parameters and exploration techniques developed in 1 and 2. Further, it provides recommendations for a standardized European protocol for resource assessment and supporting models. The IMAGE consortium comprises the leading European geothermal research institutes and industry partners who will perform testing and validation of the new methods at existing geothermal sites owned by the industry partners, both in high temperature magmatic, including supercritical, and in basement/deep sedimentary systems. Application of the methods as part of exploration in newly developed fields will provide direct transfer from the research to the demonstration stage.

Agency: European Commission | Branch: FP7 | Program: CSA | Phase: ICT-2007.8.0 | Award Amount: 797.38K | Year: 2008

One of the most important challenges of the emerging Information Age is to effectively utilise the immense wealth of information and data acquired, computed and stored by modern information systems. On the one hand, the appropriate use of available information volumes offers large potential to realize technological progress and business success. On the other hand, there exists the severe danger that users and analysts easily get lost in irrelevant, or inappropriately processed or presented information, a problem which is generally called the information overload problem. Visual Analytics is an emerging research discipline developing technology to make the best possible use of huge information loads in a wide variety of applications. The basic idea is to appropriately combine the strengths of intelligent automatic data analysis with the visual perception and analysis capabilities of the human user. We propose a Coordination Action to join European academic and industrial RandD excellence from several individual disciplines, forming a strong Visual Analytics research community. An array of thematic working groups set up by this consortium will focus on advancing the state of the art in Visual Analytics. Specifically, the working groups will join excellence in the fields of data management, data analysis, spatial-temporal data, and human visual perception research with the wider visualisation research community. This Coordination Action will (1.) form and shape a strong European Visual Analytics community, (2.) define the European Visual Analytics Research Roadmap, (3.) expose public and private stakeholders to Visual Analytics technology and (4.) set the stage for larger follow-up Visual Analytics research initiatives in Europe.

Agency: European Commission | Branch: H2020 | Program: RIA | Phase: SFS-09-2016 | Award Amount: 7.06M | Year: 2016

XF-ACTORS aims to establish a multidisciplinary research program to answer the urgent need to improve prevention, early detection and control of Xylella fastidiosa (Xf). Recently, Xf was introduced into Italy, where it is causing severe damage to olive crops, and in France, where so far it is limited to ornamental plants and some landscape trees. The overall goal of the research program is to assess Xf potential to spread throughout EU territory, while maximizing its impact through a multifactor approach, based on a seamless integration amongst the 29 partners involved. Proposed actions will be complementary to those carried out under the Project POnTE - 635646, thus ensuring an unbroken continuity with currently ongoing efforts. Specific objectives have been outlined following a step-by-step route, from preventing its introduction into pest-free areas to the establishment of successful eradication strategies in infected zones. Preventive measures against Xf will be strengthened by implementing EU certification programs and developing a plan for establishing a EU Clean Plant Network. EU policy makers will be supported through the development of pest risk assessment tools, focused on current outbreaks and forecasting potentially threatened regions. Surveillance will be properly implemented, supporting the development of early detection tools for field use, remote sensing technology and predictive modelling. Critical information on the pathogen biology, epidemiological traits and hosts under threat, will be gathered with the guidance of the American research groups with long-established research. At the same time, the insect-bacteria interactions will be determined, for developing strategic control measures. The final overall objective is a comprehensive integrated management strategy for diseases associated with Xf, applicable both IPM and organic farming systems, to prevent Xf spread, control its economic, environmental/social impact, when an outbreak would occur.

News Article | October 28, 2015

On 29 September, the XPRIZE Foundation based in Culver City, California, announced a 4½-year competition that will award US$20 million to the research team that can come up with the best way to turn carbon dioxide from a liability into an asset. With gigatonnes of the gas pouring into the atmosphere each year, and with the consequences for global climate becoming increasingly obvious, the Carbon XPRIZE would reward technologies that can convert CO emissions from coal and natural-gas power plants into useful products such as alternative building materials, fuels and raw material for the manufacture of plastics and other chemicals. The invitation should have plenty of takers: a growing number of companies and research chemists are already pursuing that goal. In Reykjavik, what looks like an overgrown playground climbing frame is actually a small chemical plant that turns CO into methanol: a fuel that can also be used to manufacture products ranging from paints to wrinkle-resistant textiles. In Houston, Texas, another small plant is turning CO into materials that go on to become coatings and adhesives. And in Tokyo, Japan, Asahi Kasei Chemicals is widely licensing its technique for turning CO into the polycarbonate plastics used in bulletproof glass, spectacle lenses and electronic parts. Using this greenhouse gas as a raw material is an idea that many scientists once dismissed as hopeless, says Chunshan Song, a chemical engineer at Pennsylvania State University, University Park. As a practical matter, he says, “lots of people believed that nothing could be done with CO utilization” after the stuff went up the smokestack. As a source of carbon, sceptics argued, the gas was far more difficult and expensive to obtain than the petroleum, coal and natural gas that now provide the raw material for most chemical manufacturing. And even if CO could be captured cheaply enough, converting such a stable molecule into more-useful chemicals would generally require lots of energy, which might well come from fossil-fuel plants. The conversion could cost a fortune and make more CO than it consumed. But the balance is starting to shift. New conversion technologies are allowing the energy-hungry chemical reactions to proceed more efficiently. Renewable sources such as solar and wind can increasingly supply that energy at a competitive cost without the carbon penalty. And solutions to the capture problem may be forthcoming if governments follow the recommendations of the Intergovernmental Panel on Climate Change (IPCC) and mandate carbon capture and storage — grabbing the CO coming out of power plants and other industries, and locking it away underground. But rather than simply burying it, companies could defray the cost of capture by putting the gas to productive use (see Nature 526, 306–307; 2015). Michele Aresta, a chemist at the University of Bari in Italy, estimates that if currently known processes were deployed most efficiently and at the greatest possible scale, they could directly use some 300 million tonnes of CO per year, while indirectly reducing emissions by around a gigatonne per year — roughly 5% of the total net emissions1. This is hardly a total solution to the CO problem, he says, but it is substantial nonetheless. And that is not counting the additional benefits, which include a shift away from relying on fossil fuels as a source of carbon for materials and chemicals, as well as the use of CO -derived fuels to store and transport energy from wind, solar and other intermittent sources. The Carbon XPRIZE may well accelerate these developments. But research into CO conversion has already been receiving support from funding agencies worldwide. Since 2009, for example, the German Ministry of Education and Research has pumped in around €100 million (US$110 million) to support research on the use of CO in chemical and synthetic-fuel production. In 2011, the US Department of Energy invested $106 million in various CO -utilization projects. The European Union has lined up a 2020 Horizon Prize worth €1.5 million for a technology that demonstrates viable CO reuse. And over the next five years, China is expected to invest some 30 billion yuan ($4.7 billion) in CO recycling in the coal, steel, cement and paper industries. Industrial uses of CO have been around for generations. Every year, about 20 million tonnes of the gas are used 'as is': for example, it's the 'fizz' in fizzy drinks, and it can also be used as a high-pressure solvent to clean electronics. But gas used in this way quickly returns to the atmosphere, where it contributes to global warming. Another 114 million tonnes of CO go into the production of urea fertilizer every year, accounting for more than 60% of the total worldwide consumption of the gas. But urea is usually made by reacting CO with ammonia — most of which is made with hydrogen derived from fossil fuels. Researchers such as Peter Styring, a chemical engineer at the University of Sheffield, UK, are working with industrial partners to develop catalysts and reaction conditions that will allow the production of urea directly from nitrogen, water and CO . But currently, the urea industry is still a net source of CO . In the quest to make more materials from CO without adding to the greenhouse problem, chemists' first challenge is to overcome the molecule's stability. Unlike a carbon atom in isolation, which has four electrons that are available to form bonds, the carbon in CO has given up all four to the tight grip of the oxygen atoms. That grip has to be loosened before the carbon can form new bonds — and that takes energy (see 'The Carbon Challenge'). “If it [energy] comes from fossil fuels, it's pointless,” says Styring. “Everything has to be from renewable energy.” This energy cost of separating the carbon and oxygen atoms is so exorbitant that some researchers in the field simply sidestep the problem. They focus on products such as calcium carbonate (CaCO ), which can be made by combining CO with calcium compounds in low-energy reactions that leave the carbon–oxygen bonds relatively undisturbed. Calcium carbonate also happens to have a large potential market: it is used as a construction material and for whitening factory-produced paper. And because it is more inert than CO , it could be used to store the gas over long time scales — something that already happens naturally in limestone deposits and coral reefs. “Nature has used mineralization to store millions of billions of tonnes of CO ,” says Martin Devenney, chief operating officer at Calera, a green-energy company in Los Gatos, California. Most of the calcium carbonate now used in industry, an estimated 15 billion tonnes per year, comes from mining such deposits. But since 2013, Calera has been operating a demonstration facility that produces the material from CO and carbide residue: an industrial waste that comes from the production of polyvinyl chloride (PVC). Calera first adds water to the residue to extract calcium hydroxide, then bubbles CO -rich flue gas from a nearby industrial plant through the solution to obtain pure calcium carbonate, which is turned into fibre cement boards that can be used in construction. After factoring in energy costs, says Devenney, the company's process captures about 170 kilograms of CO for every tonne of calcium carbonate manufactured — versus zero kilograms for every tonne that is mined. In Asia, meanwhile, manufacturers licensing technology developed by Asahi Kasei Chemicals are using CO to produce about 660,000 tonnes of polycarbonates annually, roughly 14% of the global total. Polycarbonates are plastics used in products ranging from water bottles to spectacle lenses. They are usually made in a reaction involving phosgene (COCl ): a toxic compound that is infamous for its use as a poison gas in the First World War. It is typically produced by combining chlorine with carbon monoxide made by burning coal. The Asahi Kasei process replaces phosgene with CO — overcoming the molecule's stability by putting it through three intermediate transformations. Asahi Kasei's process is still unable to make polycarbonate chains that are long enough for applications such as water bottles. But it is cost-competitive with the standard method, and according to Aresta's estimates, reduces indirect CO emissions from 6 tonnes for every tonne of polycarbonate produced to 1 tonne. Yet another promising area for low-energy CO utilization is in the production of polyols: a group of sugar-like molecules that are often used as the raw material for polymers such as polyurethanes, which are then used in mattresses, adhesives, coatings, refrigerator insulation and Spandex. Polyols are mostly made from precursor molecules known as epoxides. But Novomer, a green-chemistry company in Waltham, Massachusetts, has developed a cobalt-based catalyst that allows half of the epoxides to be replaced with CO . “Our catalyst will not work without the carbon dioxide,” says Peter Shepard, executive vice-president of Novomer. The Novomer process is currently being tested at a plant in Houston, he says, where it is producing 3,000–4,000 tonnes of polyols per year while generating about one-third of the CO that would be produced through conventional methods. And the company has begun designing a facility with a capacity of 100,000 tonnes per year, scheduled for completion in 2017. Despite these successes, the demand for low-energy products such as polycarbonates and inorganic carbonates is relatively limited. The big money is in hydrocarbons, which consist of one or more carbon atoms, often arranged in long chains or complex rings, surrounded by hydrogen atoms. As well as their many other uses, hydrocarbons are ubiquitous in petrol, diesel, jet fuel and just about every other liquid energy source on Earth — a market roughly 14 times larger than that for non-fuel chemicals. Making hydrocarbons out of CO is a “completely different story” from making low-energy products, says Aresta. In addition to the energy required to break the carbon atom free from oxygen so that it can link up with other carbons, the process needs a source of cheap hydrogen — which currently comes from fossil fuels. And it is not easy to control the reactions to get a target hydrocarbon molecule instead of a related molecule that is one carbon shorter or longer. “This is tricky,” says Song. Still, researchers are making progress. Since 2010, for example, Song has developed a series of catalysts based on iron and cobalt that can bring CO molecules close together with hydrogen molecules at 300 °C and about 10 atmospheres, forming ethylene, propylene and butane2. Because his experiments are still being done in the laboratory, Song cannot yet say how much his process could reduce greenhouse-gas emissions when carried out on an industrial scale. But any headway could have a large effect: these three chemicals are among the most heavily used in the chemical industry, says Song, with demand measured in the hundreds of millions of tonnes per year. Song is also developing palladium–copper catalysts that can efficiently turn CO and hydrogen into methanol. “Mother Nature makes biomass and it takes months and years,” he says. “We can do it in seconds.” As with other efforts to make fuels from CO , however, the challenge is to do it efficiently: even in the laboratory, the known methods consume far more energy than the resulting fuels can provide. Among the most vexing problems is how to obtain the hydrogen. Right now, the choices are to extract the gas from fossil fuels, a source that is cheap but hardly green, or to make it by splitting water, a process that is both energy intensive and costly. “We need at least 15 years of good research” to do better, estimates Aresta. And even then, he says, the conversion will probably not have a net benefit for climate unless the manufacturing plants can make extensive use of cheap energy from solar, wind and other renewables. “If we don't use these kinds of energy, we will never be able to go to large-scale deployment,” he says. Some companies are already trying to do just that. In Reykjavik, for example, Carbon Recycling International (CRI) makes methanol from CO and hydrogen using the emissions and electricity from a neighbouring geothermal power plant. The CO in this case comes not from fossil fuel but from carbonate rocks baking in Earth's heat deep underground. The hydrogen comes from the electrolysis of water — a source that would be prohibitively expensive if the power plant's electricity were not so abundant. CRI currently produces about 5 million litres of methanol per year, or about 0.005% of the global production of methanol, which has 95% less CO emissions than petrol. The advantage for Iceland is that methanol, being a liquid fuel, is a much easier way to export the country's wealth of geothermal energy than, say, laying an underground electricity cable to Europe. But for CRI, the plant is a test bed for wider deployment of its CO -to-fuels technology, which it plans to market in other countries such as Germany as a way to capture and store large amounts of renewable energy at times of low demand. “It's a matter of accessing energy at the right time,” says K.-C. Tran, cofounder and chief executive of CRI. In most places, because renewable energy isn't widely and cheaply available, the fuels from CO are still not competitive with those currently being made from crude oil, says Jim Yang Lee, a chemical engineer at the National University of Singapore. “It solves certain, localized problems, assuming you have certain resources,” he says, “but it's not solving the global CO problem.” The response from proponents is that it does not have to solve the problem all on its own: if some researchers manage to make progress with CO -to-fuels conversion, they argue, while CO -based chemical manufacturing continues to expand, CO utilization could make a noticeable dent in greenhouse-gas emissions in the near future. This year, Styring evaluated various scenarios of CO utilization3. If 100% of urea, 30% of minerals, 20% of specific chemicals and polymers, 10% of methane and 5% of diesel and aviation fuels were supplied by currently known CO -utilization methods, he estimates that around 1.34 gigatonnes of CO would be consumed per year. This equals around 83% of the IPPC's 2030 global target for emissions reductions through CO capture and storage. “These are very conservative estimates,” says Styring. “It is likely that the impact will be much greater.” For this to happen, researchers acknowledge that it will take far more than clever chemistry. Governments and industries worldwide might have to consider CO utilization along with storage, or even implement a carbon tax to help synthetic fuels stay competitive. “If you have to pay for CO to go into the atmosphere, then the story will change,” says Song. Aresta is optimistic. “If we are able, in 20 years from now, to use solar and wind energy in a concrete way,” he says, “and use it to bring back CO into fuels, we can very, very easily reduce the emissions of CO by greater than 10%.”

Corona G.,Maggiore Bellaria Hospital | Giorda C.B.,Metabolism and Diabetes Unit | Cucinotta D.,Policlinico di Messina | Guida P.,University of Bari | Nada E.,Chaira Medical Association
Journal of Sexual Medicine | Year: 2014

Introduction: Several data have emphasized the importance of early diagnosis of erectile dysfunction (ED) and meticulous cardiovascular investigation in the type 2 diabetic mellitus (T2DM) patients. Aim: To estimate the prevalence of ED and its associated determinants in a sample of male patients with new or recently diagnosed T2DM. Methods: The SUBITO-DE study is an observational, multicenter, prospective study involving 27 Italian diabetes centers. Male patients recently diagnosed with T2DM were consecutively interviewed by their attending physician at the diabetes care centers and asked whether they had experienced a change in their sexual function or found it unsatisfactory. Those responding positively were then invited to participate in the study. Main Outcome Measure: Several hormonal and biochemical parameters were studied. Results: A nonselected series of 1,503 patients was interviewed, 499 of which (mean age, 58.8±8.8 years) entered the study, yielding a final enrolment rate of 33.3%. ED was classified as mild in 19.4%, mild-to-moderate in 15.4%, moderate in 10.4%, and severe in 21.6% of patients, respectively. In addition, premature ejaculation, delayed ejaculation, and hypoactive sexual desire (HSD) were comorbid in 28.3%, 32.9%, and 58.4%, respectively. Finally, hypogonadism, showed an estimated prevalence of almost 20%. Both organic (at least one chronic DM-associated complication) and psychological factors (severe depressive symptoms) increased the risk of ED. Severe depressive symptoms were also associated with ejaculatory problems, HSD, and hypogonadism. Conclusions: A high prevalence of sexual dysfunction in men with recently diagnosed T2DM was detected. Early diagnosis of ED could help prevent emotional and physical discomfort in men and aid in identifying reversible cardiovascular risk factors. Screening of sexual dysfunction should become a part of routine care in the management of T2DM patients. Corona G, Giorda CB, Cucinotta D, Guida P, Nada E, and Gruppo di studio SUBITO-DE. Sexual dysfunction at the onset of type 2 diabetes: The interplay of depression, hormonal and cardiovascular factors. J Sex Med 2014;11:2065-2073. © 2014 International Society for Sexual Medicine.

Ribatti D.,University of Bari | Ribatti D.,Italian National Cancer Institute
Experimental Cell Research | Year: 2015

Mast cells are critical regulators of the pathogenesis of the central nervous system diseases, including stroke, multiple sclerosis, and traumatic brain injury, and brain tumors. Here, we have summarized the literature data concerning the involvement of mast cells in blood-brain barrier alterations, and we have suggested a possible role of angiogenic mediators stored in mast cell granules in the vasoproliferative reactions occurring in these pathological conditions. It is conceivable to hypothesize that mast cells might be regarded in a future perspective as a new target for the adjuvant treatment of neurodegenerative diseases and brain tumors through the selective inhibition of angiogenesis, tissue remodeling and tumor-promoting molecules, favoring the secretion of cytotoxic cytokines and preventing mast cell-mediated immune suppression. © 2015 Elsevier Inc.

Picardi E.,University of Bari | Horner D.S.,University of Milan | Chiara M.,University of Milan | Schiavon R.,University of Padua | And 3 more authors.
Nucleic Acids Research | Year: 2010

RNA editing is a widespread post-transcriptional molecular phenomenon that can increase proteomic diversity, by modifying the sequence of completely or partially non-functional primary transcripts, through a variety of mechanistically and evolutionarily unrelated pathways. Editing by base substitution has been investigated in both animals and plants. However, conventional strategies based on directed Sanger sequencing are time-consuming and effectively preclude genome wide identification of RNA editing and assessment of partial and tissue-specific editing sites. In contrast, the high-throughput RNA-Seq approach allows the generation of a comprehensive landscape of RNA editing at the genome level. Short reads from Solexa/Illumina GA and ABI SOLiD platforms have been used to investigate the editing pattern in mitochondria of Vitis vinifera providing significant support for 401 C-to-U conversions in coding regions and an additional 44 modifications in non-coding RNAs. Moreover, 76% of all C-to-U conversions in coding genes represent partial RNA editing events and 28% of them were shown to be significantly tissue specific. Solexa/Illumina and SOLiD platforms showed different characteristics with respect to the specific issue of large-scale editing analysis, and the combined approach presented here reduces the false positive rate of discovery of editing events. © The Author(s) 2010. Published by Oxford University Press.

de Lillo E.,University of Bari | Craemer C.,ARC Plant Protection Research Institute | Amrine Jr. J.W.,West Virginia University | Nuzzaci G.,University of Bari
Experimental and Applied Acarology | Year: 2010

Methods used for sample storage, specimen clearing, slide mounting, species illustration and morphometric description in alpha-taxonomic studies are essential for the Eriophyoidea. Eriophyoid mites are very tiny and delicate, for which truly permanent specimen slides currently cannot be prepared, resulting in eventual loss of material, including type specimens. Often, published descriptions and drawings have not achieved the required level of quality, and thus many relevant taxonomic details have been permanently lost or neglected. These shortcomings can make certain identifications impossible and cause significant confusion. Consequently, there is a considerable need for accurate and uniform descriptive and illustrative data for the Eriophyoidea. Based on their expertise on this topic, the authors provide guidelines and advices, assisted also by illustrations, of the main critical aspects in managing eriophyoid mites in order to supplement and improve techniques for handling and preparation of specimens, and for improving their taxonomic study. The effects of the short- and long-term preservation methods (i.e., fresh, dried and liquid preservative choices) on digesting the internal tissues of the mites are discussed. Clearing and mounting procedures are analyzed, and special tips are suggested for handling mites and designing tools needed during these steps. Methods for recovering specimens from unsuitable slides (i.e., undercleared and overcleared specimens) are proposed and described. Techniques and tricks to produce descriptive line drawings of good quality are highlighted, and the content to include in plates is stressed. Finally, detailed instructions for standardization of measurements are given. © 2009 Springer Science+Business Media B.V.

Ribatti D.,University of Bari | Ranieri G.,Italian National Cancer Institute | Nico B.,University of Bari | Benagiano V.,University of Bari | Crivellato E.,University of Udine
International Journal of Developmental Biology | Year: 2011

Human mast cells (MCs) are divided in two types depending on the expression of tryptase and chymase in their granules. Literature data indicate that both tryptase and chymase are angiogenic, but there is currently no evidence of their direct angiogenic activity in vivo. In this study, we have investigated the capacity of tryptase and chymase to promote vasoproliferation in chick embryo chorioallantoic membrane (CAM), a well established in vivo assay to study angiogenesis and anti-angiogenesis. The results showed that both tryptase and chymase stimulate angiogenesis and that the response is similar to that obtained with vascular endothelial growth factor (VEGF), a well-known angiogenic cytokine, and confirm the angiogenic activity of these two proteases stored in MC granules. © 2011 UBC Press.

Ribatti D.,University of Bari | Ribatti D.,Italian National Cancer Institute
Experimental Cell Research | Year: 2016

The understanding of mast cell (MC) differentiation is derived mainly from in vitro studies of different stages of stem and progenitor cells. The hematopoietic lineage development of human MCs is unique compared to other myeloid-derived cells. Human MCs originate from CD34+/CD117+/CD13+multipotent hematopoietic progenitors, which undergo transendothelial recruitment into peripheral tissues, where they complete differentiation. Stem cell factor (SCF) is a major chemotactic factor for MCs and their progenitors. SCF also elicits cell-cell and cell-substratum adhesion, facilitates the proliferation, and sustains the survival, differentiation, and maturation, of MCs. Because MC maturation is influenced by local microenvironmental factors, different MC phenotypes can develop in different tissues and organs. © 2016 Elsevier Inc.

Erez O.,Ben - Gurion University of the Negev | Mastrolia S.A.,Ben - Gurion University of the Negev | Mastrolia S.A.,University of Bari | Thachil J.,Royal Infirmary
American Journal of Obstetrics and Gynecology | Year: 2015

Disseminated intravascular coagulation (DIC) is a life-threatening situation that can arise from a variety of obstetrical and nonobstetrical causes. Obstetrical DIC has been associated with a series of pregnancy complications including the following: (1) acute peripartum hemorrhage (uterine atony, cervical and vaginal lacerations, and uterine rupture); (2) placental abruption; (3) preeclampsia/eclampsia/hemolysis, elevated liver enzymes, and low platelet count syndrome; (4) retained stillbirth; (5) septic abortion and intrauterine infection; (6) amniotic fluid embolism; and (7) acute fatty liver of pregnancy. Prompt diagnosis and understanding of the underlying mechanisms of disease leading to this complication in essential for a favorable outcome. In recent years, novel diagnostic scores and treatment modalities along with bedside point-of-care tests were developed and may assist the clinician in the diagnosis and management of DIC. Team work and prompt treatment are essential for the successful management of patients with DIC. © 2015 Elsevier Inc.

Bovenga F.,University of Bari | Bovenga F.,Italian National Cancer Institute | Sabba C.,University of Bari | Moschetta A.,University of Bari | Moschetta A.,Italian National Cancer Institute
Cell Metabolism | Year: 2015

Liver X receptors (LXRs) are members of the nuclear receptor superfamily of DNA-binding transcription factors and act as sensors of cholesterol homeostasis. Under normal conditions, when intracellular cholesterol concentration increases, cells synthesize oxysterols and activate the LXR transcriptional network to drive cholesterol efflux and reduce cholesterol influx and synthesis. During normal and cancer cell proliferation, there is a net uncoupling between intracellular cholesterol increase and LXR activation resulting from the reduced intracellular oxysterol concentration. This review dissects the novel mechanisms of a previously unrecognized metabolic uncoupling, supporting the activation of the LXR axis as a bona fide therapeutic approach in cancer. © 2015 Elsevier Inc.

Sanzani S.M.,University of Bari | Schena L.,University of Reggio Calabria | De Cicco V.,University of Molise | Ippolito A.,University of Bari
Postharvest Biology and Technology | Year: 2012

Detection of Botrytis cinerea latent infections on grapes before storage is essential for effective control strategies. In the present study, a molecular detection method was developed to detect and quantify B. cinerea in grape tissues. Preliminary investigations, conducted on local varieties by fruit freezing, identified the 'Red Globe' variety as the less contaminated one and confirmed the preferential localization of latent infections in the berry-pedicel attachment zone (berry calottes) and pathogen presence on stamens. A quantitative real-time PCR (qPCR) detection method, based on a probe designed on B. cinerea intergenic spacer (IGS) regions and a reported probe for Vitis vinifera as internal control, was utilized to reveal the presence of symptomless infections on bunches. The system proved to be highly specific and sensitive, enabling quantification of as little as 10fg of B. cinerea DNA and detection of single conidia in artificially inoculated grape berries; moreover, it allowed reliable detection of the pathogen in naturally infected asymptomatic tissues. In particular, the qPCR assay revealed the presence of B. cinerea in 80 and 65% of apparently healthy calottes and stamens, respectively, with an efficiency higher than that obtained from freezing and plating techniques. Furthermore, significant correlations (R 2=0.89 and 0.94) were found between qPCR results and the actual disease incidence on bunches from which calottes and stamens were sampled. © 2012 Elsevier B.V..

Ribatti D.,University of Bari | Mangialardi G.,Royal Infirmary | Vacca A.,University of Bari
Current Cancer Drug Targets | Year: 2012

Angiogenesis is a constant hallmark of multiple myeloma (MM) progression and has prognostic potential. The pathophysiology of MM-induced angiogenesis involves both direct production of angiogenic cytokines by plasma cells and their induction within the bone marrow microenvironment. An improved understanding of the importance of angiogenesis-related signaling in MM has allowed for the rational use of antiangiogenic therapies in this tumor. This review article summarizes the literature data concerning the employment of the most important antiangiogenic therapeutic agents actually used in preclinical models and clinical settings for the treatment of MM. © 2012 Bentham Science Publishers.

Ribatti D.,University of Bari | Ribatti D.,Italian National Cancer Institute
Immunology Letters | Year: 2016

The discovery of immunoglobulin E (IgE) was a breakthrough in the field of allergy and immunology. Our understanding of mechanisms of allergic reactions and the role of IgE in these disorders has paralleled to the discovery of treatment modalities for patients with allergy. The first clue to the existence of a substance responsible for hypersensitivity reactions was demonstrated in 1921 by Prausnitz and Kustner, and after four decades it was identified as an immunoglobulin subclass by Ishizakas and co-workers. In 1968, the WHO International Reference Centre for Immunoglobulins announced the presence of a fifth immunoglobulin isotype, IgE. © 2016 Elsevier B.V.

Sanzani S.M.,University of Bari | Schena L.,University of Reggio Calabria | Ippolito A.,University of Bari
Molecules | Year: 2014

Stored citrus fruit suffer huge losses because of the development of green mould caused by Penicillium digitatum. Usually synthetic fungicides are employed to control this disease, but their use is facing some obstacles, such public concern about possible adverse effects on human and environmental health and the development of resistant pathogen populations. In the present study quercetin, scopoletin and scoparone - phenolic compounds present in several agricultural commodities and associated with response to stresses - were firstly tested in vitro against P. digitatum and then applied in vivo on oranges cv. Navelina. Fruits were wound-treated (100 μg), pathogen-inoculated, stored and surveyed for disease incidence and severity. Although only a minor (≤13%) control effect on P. digitatum growth was recorded in vitro, the in vivo trial results were encouraging. In fact, on phenolic-treated oranges, symptoms appeared at 6 days post-inoculation (DPI), i.e., with a 2 day-delay as compared to the untreated control. Moreover, at 8 DPI, quercetin, scopoletin, and scoparone significantly reduced disease incidence and severity by 69%-40% and 85%-70%, respectively, as compared to the control. At 14 DPI, scoparone was the most active molecule. Based on the results, these compounds might represent an interesting alternative to synthetic fungicides. © 2014 by the authors.

Ribatti D.,University of Bari | Ribatti D.,Italian National Cancer Institute | Ranieri G.,Italian National Cancer Institute | Annese T.,University of Bari | Nico B.,University of Bari
Biochimica et Biophysica Acta - General Subjects | Year: 2014

Background The aquaporins (AQPs) are a family of 13 small hydrophobic integral transmembrane water channel proteins involved in transcellular and transepithelial water movement, transport of fluid and cell migration. Scope of the review This review article summarizes our knowledge concerning the involvement of AQPs in tumor growth, angiogenesis and metastatic process. Major conclusions Tumor cells types express AQPs and a positive correlation exists between histological tumor grade and the AQP expression. Moreover, AQPs are involved also in tumor edema formation and angiogenesis in several solid and hematological tumors. General significance AQPs inhibition in endothelial and tumor cells might limit tumor growth and spread, suggesting a potential therapeutic use in the treatment of tumors. This article is part of a Special Issue entitled Aquaporins. © 2013 Elsevier B.V.

Cunden F.D.,University of Bari | Cunden F.D.,National Institute of Nuclear Physics, Italy | Vivo P.,University Paris - Sud
Physical Review Letters | Year: 2014

We derive an analytical formula for the covariance cov(A,B) of two smooth linear statistics A=ia(λi) and B=ib(λi) to leading order for N→, where {λi} are the N real eigenvalues of a general one-cut random-matrix model with Dyson index β. The formula, carrying the universal 1/β prefactor, depends on the random-matrix ensemble only through the edge points [λ-,λ+] of the limiting spectral density. For A=B, we recover in some special cases the classical variance formulas by Beenakker and by Dyson and Mehta, clarifying the respective ranges of applicability. Some choices of a(x) and b(x) lead to a striking decorrelation of the corresponding linear statistics. We provide two applications - the joint statistics of conductance and shot noise in ideal chaotic cavities, and some new fluctuation relations for traces of powers of random matrices. © 2014 American Physical Society.

Lenzen M.,University of Sydney | Moran D.,University of Sydney | Kanemoto K.,University of Sydney | Kanemoto K.,Tohoku University | And 5 more authors.
Nature | Year: 2012

Human activities are causing Earth's sixth major extinction event 1-an accelerating decline of the world's stocks of biological diversity at rates 100 to 1,000 times pre-human levels2. Historically, low-impact intrusion into species habitats arose from local demands for food, fuel and living space3. However, in today's increasingly globalized economy, international trade chains accelerate habitat degradation far removed from the place of consumption. Although adverse effects of economic prosperity and economic inequality have been confirmed 4,5, the importance of international trade as a driver of threats to species is poorly understood. Here we show that a significant number of species are threatened as a result of international trade along complex routes, and that, in particular, consumers in developed countries cause threats to species through their demand of commodities that are ultimately produced in developing countries. We linked 25,000 Animalia species threat records from the International Union for Conservation of Nature Red List to more than 15,000 commodities produced in 187 countries and evaluated more than 5 billion supply chains in terms of their biodiversity impacts. Excluding invasive species, we found that 30% of global species threats are due to international trade. In many developed countries, the consumption of imported coffee, tea, sugar, textiles, fish and other manufactured items causes a biodiversity footprint that is larger abroad than at home. Our results emphasize the importance of examining biodiversity loss as a global systemic phenomenon, instead of looking at the degrading or polluting producers in isolation. We anticipate that our findings will facilitate better regulation, sustainable supply-chain certification and consumer product labelling. © 2012 Macmillan Publishers Limited.

Ribatti D.,University of Bari | Ribatti D.,Italian National Cancer Institute
Immunology Letters | Year: 2015

Gerald M. Edelman began working to the structure of antibodies when joined as graduate student the laboratory of Henry Kunkel in 1958 at the "Rockefeller University" in New York, obtaining his doctorate in 1960. Edelman's focus on the structure of antibodies led to the 1972 Nobel Prize in Physiology or Medicine along with Rodney R. Porter. Edelman and Porter decided to approach the problem of antibodies structure by splitting. In 1959, Porter published a report in which he used the enzyme papain to cleave the antibody molecule into three pieces of about 50,000. Da, corresponding to the two Fab (antigen-binding) and constant Fc (crystallizable) fragments. In the same year, Edelman showed that reduction of the disulfide bonds of antibodies in the presence of denaturizing agents led to dissociation of the molecule into smaller pieces, now known to be the light (L) and heavy (H) chains. © 2015 European Federation of Immunological Societies.

Notarnicola B.,University of Bari | Hayashi K.,Japan National Agriculture and Food Research Organization | Curran M.A.,U.S. Environmental Protection Agency | Huisingh D.,University of Tennessee at Knoxville
Journal of Cleaner Production | Year: 2012

The human health and environmental issues related to food, feed, and bio-based systems, range widely from greenhouse gas emissions and energy use to land use, water availability, soil quality, water quality and quantity, biodiversity losses, and chemical exposure. Threats that stem from other issues, including food quality and food security, the development of genetically modified organisms, desertification, pesticide exposure, antibiotic-resistant strains of microorganisms, growth hormone residues in food, etc.; are of concern. Life Cycle Assessment (LCA) methodology provides the organizing framework to holistically evaluate the environmental impacts of products and production systems, whether it's to make a durable, disposable or edible good. The use of LCA in environmental management and sustainability has grown rapidly in recent years as demonstrated by the increasing number of published papers on LCA methodology and case studies, which totaled over 4,500 by 2010. Recognizing the need to focus on the impacts of the agri-food industry, this special issue was developed by selecting sixteen papers from the 85 presented at the Bari LCA Food 2010 conference, and publishing them with eight papers submitted as part of the normal flow to the Journal of Cleaner Production on food-related subjects. The papers in this special issue include case studies from LCAs on relevant dimensions of production of a wide array of types of food, discussions on methodological issues, especially water and land use, the application of product certification schemes, and food preservation. The editors of this special issue acknowledge that progress has been made in strengthening the LCA tools but challenge all LCA practitioners and researchers to push the envelope on LCA methodology and encourage them to develop tools that dynamically address the diverse, rapidly evolving issues related to agricultural products that are not currently addressed. It is hoped the challenges that are outlined in this Special Issue will stimulate many to make progress on improving the food LCA tools prior to the next food LCA conference in this series, which will be held in Saint-Malo, France, on 2-4 October 2012. For more information, visit: © 2011 Elsevier Ltd. All rights reserved.

Mazzocca A.,Section of Internal Medicine | Dituri F.,Section of Internal Medicine | Lupo L.,University of Bari | Quaranta M.,Italian National Cancer Institute | And 2 more authors.
Hepatology | Year: 2011

Hepatocellular carcinoma (HCC) occurs in fibrotic liver as a consequence of underlying cirrhosis. The goal of this study was to investigate how the interaction between HCC cells and stromal fibroblasts affects tumor progression. We isolated and characterized carcinoma-associated fibroblasts (CAFs) and paired peritumoral tissue fibroblasts (PTFs) from 10 different patients with HCC and performed coculture experiments. We demonstrated a paracrine mechanism whereby HCC cells secrete lysophostatidic acid (LPA), which promotes transdifferentiation of PTFs to a CAF-like myofibroblastic phenotype. This effect is mediated by up-regulation of specific genes related to a myo/contractile phenotype. After transdifferentiation, PTFs expressed α-smooth muscle actin (α-SMA) and enhanced proliferation, migration, and invasion of HCC cells occur. A pan-LPA inhibitor (α-bromomethylene phosphonate [BrP]-LPA), or autotaxin gene silencing, inhibited this PTF transdifferentiation and the consequent enhanced proliferation, migration, and invasion of HCC cells. In vivo, PTFs coinjected with HCC cells underwent transdifferentiation and promoted tumor progression. Treatment with BrP-LPA blocked transdifferentiation of PTFs, down-regulated myofibroblast-related genes, and slowed HCC growth and progression. Patients with larger and metastatic HCC and shorter survival displayed higher serum levels of LPA. Analysis of microdissected tissues indicated that stroma is the main target of the LPA paracrine loop in HCC. As a consequence, α-SMA-positive cells were more widespread in tumoral compared with paired peritumoral stroma. Conclusion: Our data indicate that LPA accelerates HCC progression by recruiting PTFs and promoting their transdifferentiation into myofibroblasts. Inhibition of LPA could prove effective in blocking transdifferentiation of myofibroblasts and tumor progression. © 2011 American Association for the Study of Liver Diseases.

Cassibba R.,University of Bari | van Ijzendoorn M.H.,Leiden University | Coppola G.,University of Chieti Pescara
Child: Care, Health and Development | Year: 2012

Background The presence of limits or distortions in the children's communicative behaviours (due to a chronic illness) may interfere with the possibility to build secure attachment relationships. Moreover, the distress that the atypical chronic illness condition brings to family life may interfere the intergenerational transmission of attachment. Methods This study evaluated the associations between maternal attachment representations, emotional availability and mother-child attachment in a clinical and in a comparison group. Forty infants (23 female) in their 14th month of life and their mothers participated in this study, 20 dyads with clinical infants (10 premature infants and 10 infants affected by atopic dermatitis) and 20 full-term and healthy comparison infants. The Adult Attachment Interview, the Emotional Availability Scales (EAS) and the Strange Situation Procedure were used to assess, respectively, the security of mothers' attachment representations, the emotional availability and the quality of mother-child attachment. Results We found that the two groups (clinical vs. comparison) did not differ with respect to the Adult Attachment Interview and the Emotional Availability Scales measures. A significant difference was found in the distribution of the infant-mother attachment patterns, with a higher incidence of insecure infants in the clinical group. In the typically developing group, more secure maternal attachment representations predicted more emotional availability in mother-infant interactions, which predicted more secure infant-mother attachments. However, we did not find similar support for intergenerational transmission of attachment in the clinical group. Conclusions We speculate that constant concerns about the child's health condition and communicative difficulties of clinical infants may hamper or even mitigate the intergenerational transmission of attachment. © 2011 Blackwell Publishing Ltd.

Mavelli F.,University of Bari | Ruiz-Mirazo K.,University of the Basque Country
Physical Biology | Year: 2010

'ENVIRONMENT' is a computational platform that has been developed in the last few years with the aim to simulate stochastically the dynamics and stability of chemically reacting protocellular systems. Here we present and describe some of its main features, showing how the stochastic kinetics approach can be applied to study the time evolution of reaction networks in heterogeneous conditions, particularly when supramolecular lipid structures (micelles, vesicles, etc) coexist with aqueous domains. These conditions are of special relevance to understand the origins of cellular, self-reproducing compartments, in the context of prebiotic chemistry and evolution. We contrast our simulation results with real lab experiments, with the aim to bring together theoretical and experimental research on protocell and minimal artificial cell systems. © 2010 IOP Publishing Ltd.

Cea P.,University of Bari | Cosmai L.,National Institute of Nuclear Physics, Italy | D'Elia M.,University of Pisa | Papa A.,University of Calabria | And 2 more authors.
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2012

We determine the (pseudo)critical lines of QCD with two degenerate staggered fermions at nonzero temperature and quark or isospin density, in the region of imaginary chemical potentials; analytic continuation is then used to prolongate to the region of real chemical potentials. We obtain an accurate determination of the curvatures at zero chemical potential, quantifying the deviation between the case of finite quark and of finite isospin chemical potential. Deviations from a quadratic dependence of the pseudocritical lines on the chemical potential are clearly seen in both cases: we try different extrapolations and, for the case of nonzero isospin chemical potential, confront them with the results of direct Monte Carlo simulations. Finally we find that, as for the finite quark density case, an imaginary isospin chemical potential can strengthen the transition until turning it into strong first order. © 2012 American Physical Society.

Portincasa P.,University of Bari | Scaccianoce G.,Umberto I Hospital | Palasciano G.,University of Bari
European Journal of Clinical Investigation | Year: 2013

Background: Familial Mediterranean fever (FMF) is a rare inherited autosomal recessive autoinflammatory disorder characterized by recurrent and self-limited episodes of fever and painful serositis, lasting 1-3 days. FMF occurs almost exclusively among ethnic groups of the Mediterranean basin, although cases have also been found in Japan and Korean populations. Diagnosis is based on clinical features, response to colchicine and genetic analysis. Novel drugs are emerging, allowing better management of colchicine-resistant/colchicine-intolerant patients. This review aims to attract the attention of the readers on differential diagnosis and management of patients with FMF. Methods: The current state-of-the-art on FMF is outlined, with respect to epidemiological, genetic, pathophysiological and therapeutic characteristics, based on critical analysis of solid scientific literature. Results: FMF is more frequent than it was thought before. The phenotypic expression of M694V is more severe than that of V726A. Patients with M694V/M694V homozygosity are exposed to a higher risk of developing renal amyloidosis, arthritis, dermatologic and oral lesions, higher fever and more frequent painful attacks. Life-long therapy with colchicine (1·0-2·4 mg/day) is effective and safe to prevent recurrent attacks and renal amyloidosis and to reverse proteinuria. In nonresponder patients, alternative novel approaches include interleukin-1 receptor antagonist anakinra and the interleukin-1 decoy receptor rilonacept. Conclusions: The prognosis of FMF is normal if AA amyloidosis is prevented. Colchicine remains the first-line therapy to treat pain and prevent amyloidosis. A follow-up should include clinical evaluation, therapeutic adjustments, measurement of serum amyloid A and proteinuria. © 2013 Stichting European Society for Clinical Investigation Journal Foundation.

Bonamassa B.,Laboratory of Lipid Metabolism and Cancer | Moschetta A.,Laboratory of Lipid Metabolism and Cancer | Moschetta A.,University of Bari | Moschetta A.,Italian National Cancer Institute | Moschetta A.,National Institute for Digestive Diseases
Trends in Endocrinology and Metabolism | Year: 2013

Modulation of the cholesterol-sensing liver X receptors (LXRs) and their downstream targets has emerged as promising therapeutic avenues in atherosclerosis. The intestine is important for its unique capabilities to act as a gatekeeper for cholesterol absorption and to participate in the process of cholesterol elimination in the feces and reverse cholesterol transport (RCT). Pharmacological and genetic intestine-specific LXR activation have been shown to protect against atherosclerosis. In this review we discuss the LXR-targeted molecular players in the enterocytes as well as the intestine-driven pathways contributing to cholesterol homeostasis with therapeutic potential as targets in the prevention and treatment of atherosclerosis. © 2012 Elsevier Ltd.

Ribatti D.,University of Bari | Ribatti D.,Italian National Cancer Institute
Immunology Letters | Year: 2014

Vertebrate make billions of different antibodies, each with a binding site that recognizes a specific region of a macromolecule. The hybridoma technique allows monoclonal antibodies, highly specific antibodies produced in the laboratory by a variety of methods. In the last 35 years since the first process for creating monoclonal antibodies was introduced, their application have improved the growing biotechnology industry, but the most important application concerns the therapy of human malignancies. © 2014 Elsevier B.V.

Ribatti D.,University of Bari | Ribatti D.,Italian National Cancer Institute | Crivellato E.,Section of Anatomy
Immunology Letters | Year: 2014

Mast cells were first identified by Paul Ehrlich in 1878, when he was still a medical student. Many fundamental aspects of mast cell ontogeny have been elucidated since Ehrlich's first identification. Demonstration of mast cell derivation from bone marrow precursors could be established in 1977 when Kitamura's group first showed reconstitution of mast cells in mast cell-deficient mice by the adaptive transfer of wild type bone marrow and indicated that these cells were of hematopoietic origin. It is now definitively established that development of mast cells in bone marrow occurs along the myeloid pathway. However, several aspects need further clarification. In particular, identification and chemical characterization of growth factors expressing mast cell differentiating properties and the relationship between mast cell and basophils developmental pathways. © 2014 Elsevier B.V.

Ribatti D.,University of Bari | Ribatti D.,Italian National Cancer Institute | Moschetta M.,University of Bari | Vacca A.,University of Bari
Immunology Letters | Year: 2014

Tumor associated macrophages (TAMs) are a rich source of pro-angiogenic cytokines and growth factors, and a relationship between the TAMs content, the rate of tumor growth and the extent of vascularization has been shown in several tumors. In this article, we have summarized the literature and our data concerning the involvement of TAMs in angiogenesis occurring in multiple myeloma. Finally, therapeutic aspects concerning the potential role of molecules which inhibit macrophage recruitment in the tumor side are also discussed. © 2013 Elsevier B.V.

Castellana S.,University of Bari | Vicario S.,CNR Institute of Biomedical Technologies | Saccone C.,CNR Institute of Biomedical Technologies | Saccone C.,University of Bari
Genome Biology and Evolution | Year: 2011

The mitochondrial genome is a fundamental component of the eukaryotic domain of life, encoding for several important subunits of the respiratory chain, the main energy production system in cells. The processes by means of which mitochondrial DNA (mtDNA) replicates, expresses itself and evolves have been explored over the years, although various aspects are still debated. In this review, we present several key points in modern research on the role of evolutionary forces in affecting mitochondrial genomes in Metazoa. In particular, we assemble the main data on their evolution, describing the contributions of mutational pressure, purifying, and adaptive selection, and how they are related. We also provide data on the evolutionary fate of the mitochondrial synonymous variation, related to the nonsynonymous variation, in comparison with the pattern detected in the nucleus. Elevated mutational pressure characterizes the evolution of the mitochondrial synonymous variation, whereas purging selection, physiologically due to phenomena such as cell atresia and intracellular mtDNA selection, guarantees coding sequence functionality. This enables mitochondrial adaptive mutations to emerge and fix in the population, promoting mitonuclear coevolution. © The Author(s) 2010.

Ribatti D.,University of Bari | Ribatti D.,Italian National Cancer Institute
Immunology Letters | Year: 2014

This article outlines the fundamental contribution of Max D. Cooper to the analysis of the role of the thymus and of the bursa of Fabricius in the development of immunologic competence both before and after birth, placing a new scientific paradigm in the definition of the ontogeny of the lymphoid tissues. © 2014 Elsevier B.V.

Cicione C.,Laboratory of Lipid Metabolism and Cancer | Degirolamo C.,Laboratory of Lipid Metabolism and Cancer | Moschetta A.,Laboratory of Lipid Metabolism and Cancer | Moschetta A.,University of Bari | Moschetta A.,Italian National Cancer Institute
Hepatology | Year: 2012

Fibroblast growth factors (FGFs) 15/19 and 21 belong to the FGF endocrine subfamily. They present the intriguing characteristic to be transcribed and secreted in certain tissues and to act as hormones. The insulin-mimetic properties of FGF21 and the regulatory role of FGF15/19 in bile acid and glucose homeostasis endorse these hormones as druggable targets in metabolic disorders. Here, we present details on discoveries, identification, transcriptional regulation, and mechanism of actions of FGF15/19 and FGF21 with a critical perspective view on their putative role as metabolic integrators in the liver. © 2012 American Association for the Study of Liver Diseases.

Morga M.,AIT Austrian Institute of Technology | Marano G.C.,University of Bari
International Journal of Concrete Structures and Materials | Year: 2015

Most of the diffusion models of chloride ions in reinforced concrete (RC) elements proposed in literature are related to an isotropic homogeneous semi-infinite medium. This assumption reduces the mathematical complexity, but it is correct only for plane RC elements. This work proposes a comparison between the diffusion model of chloride ions in RC circular columns and in RC slab elements. The durability of RC cylindric elements estimated with the circular model instead of the plane model is shown to be shorter. Finally, a guideline is formulated to properly use the standard and more simple plane model instead of the circular one to estimate the time to corrosion initiation of cylindrical RC elements. © 2015, The Author(s).

Mavelli F.,University of Bari | Ruiz-Mirazo K.,University of the Basque Country
Integrative Biology (United Kingdom) | Year: 2013

In previous works we have explored the dynamics of chemically reacting proto-cellular systems, under different experimental conditions and kinetic parameters, by means of our stochastic simulation platform 'ENVIRONMENT'. In this paper we, somehow, turn the question around: accepting some broad modeling assumptions, we investigate the conditions under which simple protocells will spontaneously settle into a stationary reproducing regime, characterized by a regular growth/division cycle and the maintenance of a certain standard size and chemical composition across generations. In the first part, starting from purely geometric considerations, the condition for stationary reproduction of a protocell will be expressed in terms of a growth control coefficient (γ). Then, an explicit relationship, the osmotic synchronization condition, will be analytically derived under a set of kinetic simplifications and taking into account the osmotic pressure balance operating across the protocell membrane. In the second part of the paper, this general condition that constrains different molecular/kinetic parameters and features of the system (reaction rates, permeability coefficients, metabolite concentrations, system volume) will be applied to different cases of self-producing vesicles, predicting the stationary protocell size or lifetime. Finally, in order to test the validity of our analytic results and predictions, the case study is contrasted with data obtained through both stochastic and deterministic computational algorithms. © 2013 The Royal Society of Chemistry.

Foti D.,University of Bari | Ivorra Chorro S.,University of Alicante | Sabba M.F.,Civil Engineer
Open Construction and Building Technology Journal | Year: 2012

This paper shows the results of an experimental analysis on the bell tower of "Chiesa della Maddalena" (Mola di Bari, Italy), to better understand the structural behavior of slender masonry structures. The research aims to calibrate a numerical model by means of the Operational Modal Analysis (OMA) method. In this way realistic conclusions about the dynamic behavior of the structure are obtained. The choice of using an OMA derives from the necessity to know the modal parameters of a structure with a non-destructive testing, especially in case of cultural-historical value structures. Therefore by means of an easy and accurate process, it is possible to acquire in-situ environmental vibrations. The data collected are very important to estimate the mode shapes, the natural frequencies and the damping ratios of the structure. To analyze the data obtained from the monitoring, the Peak Picking method has been applied to the Fast Fourier Transforms (FFT) of the signals in order to identify the values of the effective natural frequencies and damping factors of the structure. The main frequencies and the damping ratios have been determined from measurements at some relevant locations. The responses have been then extrapolated and extended to the entire tower through a 3-D Finite Element Model. In this way, knowing the modes of vibration, it has been possible to understand the overall dynamic behavior of the structure. © Foti et al.; Licensee Bentham Open.

Otranto D.,University of Bari | Eberhard M.L.,Centers for Disease Control and Prevention
Parasites and Vectors | Year: 2011

Nowaday, zoonoses are an important cause of human parasitic diseases worldwide and a major threat to the socio-economic development, mainly in developing countries. Importantly, zoonotic helminths that affect human eyes (HIE) may cause blindness with severe socio-economic consequences to human communities. These infections include nematodes, cestodes and trematodes, which may be transmitted by vectors (dirofilariasis, onchocerciasis, thelaziasis), food consumption (sparganosis, trichinellosis) and those acquired indirectly from the environment (ascariasis, echinococcosis, fascioliasis). Adult and/or larval stages of HIE may localize into human ocular tissues externally (i.e., lachrymal glands, eyelids, conjunctival sacs) or into the ocular globe (i.e., intravitreous retina, anterior and or posterior chamber) causing symptoms due to the parasitic localization in the eyes or to the immune reaction they elicit in the host. Unfortunately, data on HIE are scant and mostly limited to case reports from different countries. The biology and epidemiology of the most frequently reported HIE are discussed as well as clinical description of the diseases, diagnostic considerations and video clips on their presentation and surgical treatment. Homines amplius oculis, quam auribus credunt. Seneca Ep 6,5. Men believe their eyes more than their ears. © 2011 Otranto and Eberhard.

Palumbo F.,CNR Institute of Inorganic Methodologies and Plasmas | Di Mundo R.,University of Bari | Cappelluti D.,University of Bari | Dagostino R.,CNR Institute of Inorganic Methodologies and Plasmas | Dagostino R.,Plasma Solution Srl
Plasma Processes and Polymers | Year: 2011

Versatility of plasma processing is demonstrated for the preparation of nanotextured polycarbonate surfaces with superior wettability properties. Tens of nanometers wide pillar structures are produced on the polymer by means of oxygen plasma etching, inducing on the surface a pronounced hydrophilic behavior. As well known from literature, however, treated surfaces undergo a fast hydrophobic recovery, but a post-deposition process can ensure the formation of transparent and stable superhydrophylic or superhydrophobic surfaces. Stable super hydrophobic and super hydrophilic polycarbonate has been prepared by simple plasma etching and PECVD of coatings of suitable chemistry. The etching process allows for formation of nanopillars tens of nanometers wide and up to a micrometer high, responsible for the unique behavior. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Ribatti D.,University of Bari | Ribatti D.,Italian National Cancer Institute | Ranieri G.,Italian National Cancer Institute
Experimental Cell Research | Year: 2015

Human mast cells (MCs) are a rich reservoir of neutral proteases, packed in large amounts in their granules and comprising a high fraction of all cellular proteins. Among these proteases, tryptase is involved in angiogenesis after its release from activated MC granules, as it has been demonstrated in different in vitro and in vivo assays. Moreover, tryptase-positive MCs increase in number and vascularization increases in a linear fashion in different solid and hematological tumors. This complex interplay between MCs and tumor angiogenesis have led to consider the therapeutic use of angiogenesis inhibitors, which specifically target the angiogenic activity of tryptase, such as gabexate mesilate and nafamostat mesilate, two inhibitors of trypsin-like serine proteases. © 2014 Elsevier Inc.

Pio G.,University of Bari | Ceci M.,University of Bari | D'Elia D.,CNR Institute of Biomedical Technologies | Loglisci C.,University of Bari | Malerba D.,University of Bari
BMC Bioinformatics | Year: 2013

Background: microRNAs (miRNAs) are a class of small non-coding RNAs which have been recognized as ubiquitous post-transcriptional regulators. The analysis of interactions between different miRNAs and their target genes is necessary for the understanding of miRNAs' role in the control of cell life and death. In this paper we propose a novel data mining algorithm, called HOCCLUS2, specifically designed to bicluster miRNAs and target messenger RNAs (mRNAs) on the basis of their experimentally-verified and/or predicted interactions. Indeed, existing biclustering approaches, typically used to analyze gene expression data, fail when applied to miRNA:mRNA interactions since they usually do not extract possibly overlapping biclusters (miRNAs and their target genes may have multiple roles), extract a huge amount of biclusters (difficult to browse and rank on the basis of their importance) and work on similarities of feature values (do not limit the analysis to reliable interactions).Results: To overcome these limitations, HOCCLUS2 i) extracts possibly overlapping biclusters, to catch multiple roles of both miRNAs and their target genes; ii) extracts hierarchically organized biclusters, to facilitate bicluster browsing and to distinguish between universe and pathway-specific miRNAs; iii) extracts highly cohesive biclusters, to consider only reliable interactions; iv) ranks biclusters according to the functional similarities, computed on the basis of Gene Ontology, to facilitate bicluster analysis.Conclusions: Our results show that HOCCLUS2 is a valid tool to support biologists in the identification of context-specific miRNAs regulatory modules and in the detection of possibly unknown miRNAs target genes. Indeed, results prove that HOCCLUS2 is able to extract cohesiveness-preserving biclusters, when compared with competitive approaches, and statistically confirm (at a confidence level of 99%) that mRNAs which belong to the same biclusters are, on average, more functionally similar than mRNAs which belong to different biclusters. Finally, the hierarchy of biclusters provides useful insights to understand the intrinsic hierarchical organization of miRNAs and their potential multiple interactions on target genes. © 2013 Pio et al.; licensee BioMed Central Ltd.

Bukvic N.,University of Bari | Elling J.W.,Genomics Usa, Inc.
Gene | Year: 2015

"Healing is best accomplished when art and science are conjoined, when body and spirit are probed together", says Bernard Lown, in his book "The Lost Art of Healing". Art has long been a witness to disease either through diseases which affected artists or diseases afflicting objects of their art. In particular, artists have often portrayed genetic disorders and malformations in their work. Sometimes genetic disorders have mystical significance; other times simply have intrinsic interest. Recognizing genetic disorders is also an art form. From the very beginning of my work as a Medical Geneticist I have composed personal "algorithms" to piece together evidence of genetics syndromes and diseases from the observable signs and symptoms.In this paper we apply some 'gestalt' Genetic Syndrome Diagnostic algorithms to virtual patients found in some art masterpieces. In some the diagnosis is clear and in others the artists' depiction only supports a speculative differential diagnosis. © 2014 Elsevier B.V.

Agency: European Commission | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-2013-ITN | Award Amount: 3.78M | Year: 2013

Organic Bioelectonics is a new discipline which holds promise to shape, direct, and change future medical treatments in a revolutionary manner over the next decades. At the moment Europe has a unique leading position in this area, being almost all the world-leading groups in this field located in Europe and constituting the core of this international training network. However, realizing the promise of Organic bioelectronics requires research and training not only crossing disciplines, such as electrical engineering, biology, chemistry, physics, and materials science, but also crossing our European countries. The EU will add value on the global scene only if it acts jointly. OrgBIO is at the core of European technological innovation and will become an indispensable part of the educational canon. It will establish a world-class training platform spreading around the highly interdisciplinary / intersectorial European-led area of organic bioelectronics. Education along with science and entrepreneurial mindsets and attitudes is the core of the OrgBIO training programme, which aims at excellence and innovation, at all level. Excellence in science is guaranteed by the world-leading groups which founded this research area. Innovation in education is guaranteed by the involvement of researchers on education, business experts. Using different sensors, actuators, electronic and interconnect technologies the network will develop multifunctional systems based on organic devices and materials with high sensitivity that are also flexible, conformable and present over large areas for various biomedical / biological applications in the life science. Multi-analyte and disposable analytical systems manufactured by large-area printing methods will provide services to the individuals and healthcare community. Targeted implemented interactions with a wide network of venture capitals and business actors will immediately transfer the research outcome to the European Industry.

Agency: European Commission | Branch: H2020 | Program: RIA | Phase: LCE-23-2016 | Award Amount: 10.00M | Year: 2016

The GEMex project is a complementary effort of a European consortium with a corresponding consortium from Mexico, who submitted an equivalent proposal for cooperation. The joint effort is based on three pillars: 1 Resource assessment at two unconventional geothermal sites, for EGS development at Acoculco and for a super-hot resource near Los Humeros. This part will focus on understanding the tectonic evolution, the fracture distribution and hydrogeology of the respective region, and on predicting in-situ stresses and temperatures at depth. 2 Reservoir characterization using techniques and approaches developed at conventional geothermal sites, including novel geophysical and geological methods to be tested and refined for their application at the two project sites: passive seismic data will be used to apply ambient noise correlation methods, and to study anisotropy by coupling surface and volume waves; newly collected electromagnetic data will be used for joint inversion with the seismic data. For the interpretation of these data, high-pressure/ high-temperature laboratory experiments will be performed to derive the parameters determined on rock samples from Mexico or equivalent materials. 3 Concepts for Site Development: all existing and newly collected information will be applied to define drill paths, to recommend a design for well completion including suitable material selection, and to investigate optimum stimulation and operation procedures for safe and economic exploitation with control of undesired side effects. These steps will include appropriate measures and recommendations for public acceptance and outreach as well as for the monitoring and control of environmental impact. The consortium was formed from the EERA joint programme of geothermal energy in regular and long-time communication with the partners from Mexico. That way a close interaction of the two consortia is guaranteed and will continue beyond the duration of the project.

Agency: European Commission | Branch: FP7 | Program: CP | Phase: SPA.2010.1.1-04 | Award Amount: 3.16M | Year: 2010

BIO_SOS (BIOdiversity multi-SOurce monitoring System: from Space TO Species is a response to the Call for proposals FP7- SPACE-2010-1, addressing topic SPACE.2010.1.1-04 Stimulating the development of GMES services in specific areas with application to (B) BIODIVERSITY. BIO_SOS is a pilot project for effective and timely multi-annual monitoring of NATURA 2000 sites and their surrounding in support to management decisions in sample areas, mainly in Mediterranean regions and for the reporting on status and trends according to National and EU obligations. The aim of BIO_SOS is two-fold: 1) the development and validation of a prototype multi-modular system to provide a reliable long term biodiversity monitoring service at high to very high-spatial resolution; 2) to embed monitoring information (changes) in innovative ecological (environmental) modelling for Natura 2000 site management. The system will be developed and validated within ecologically sensitive sampling sites and their borders exposed to combined human-induced pressures. Different environmental characteristics of the selected sites have been considered in order to ensure system robustness. Sites characteristics ranges from mountain rough to flat coastal morphologies, from rangeland to human dominated landscapes and land uses. BIO_SOS intends to deeply investigate issues related to very high spatial (VHR) (and spectral) resolution Earth Observation data (EO) image processing for automatic land cover maps updating and change detection. Such maps are at the base of biodiversity indicators provision. On the other hand, it intends to develop a modelling framework to combine multi-scale (high to very high resolution) EO data and in-situ/ancillary data to provide indicators and their trends. This means the development of more appropriate and accurate models in support to a deeper understanding, assessment and prediction of the impacts that human induced pressures may have on biodiversity loss.

Falgari P.,University Utrecht | Falgari P.,University of Bari | Giannuzzi F.,National Institute of Nuclear Physics, Italy | Mellor P.,Durham University | Signer A.,Durham University
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2011

In this work we present a calculation of both t-channel and s-channel single-top production at next-to-leading order in QCD for the Tevatron and for the LHC at a center-of-mass energy of 7TeV. All the cross sections and kinematical distributions presented include leading nonfactorizable corrections arising from interferences of the production and decay subprocesses, extending previous results beyond the narrow-width approximation. The new off shell effects are found to be generally small, but can be sizeable close to kinematical endpoints and for specific distributions. © 2011 American Physical Society.

Ribatti D.,University of Bari | Ribatti D.,Italian National Cancer Institute
Oncotarget | Year: 2016

Vascular endothelial growth factor (VEGF) has been identified as the most potent cytokine involved in tumor angiogenesis and metastasis formation. Clinical results of anti-angiogenic therapies targeting VEGF and its receptors are very modest, resulting in a moderate improvement of overall survival. The clinical outcome is associated with the development of resistance and the increased risk of invasion and metastasis. In this article, I have analyzed the principal mechanisms of resistance to VEGF pathway inhibitors, including normalization of tumor blood vessels, hypoxia, recruitment of inflammatory cells and immature myeloid cells, alternative mechanisms of tumor vessel formation, genomic instability of tumor endothelial cells. In this context, the concept and strategies of anti-angiogenic therapies should be extensively reconsidered and re-evaluated. In particular, rational combinations of anti-angiogenic agents based on pharmacokinetic and pharmacodynamics data are needed to overcome resistance and it is extremely important to determine the optimal duration and scheduling of anti-VEGF agents.

University of Bari and University of Chieti Pescara | Date: 2010-11-03

The present invention refers to the use of a compound selected from 3,4-diphenyl-5-ethylisoxazole and 3,4-diphenyl-5-methylisoxazole as inhibitors of cyclooxygenase, in particular of cyclooxygenase 1 and 2 (COX-1) (COX-2).

Rocchi M.,University of Bari | Archidiacono N.,University of Bari | Schempp W.,Albert Ludwigs University of Freiburg | Capozzi O.,University of Bari | Stanyon R.,University of Florence
Heredity | Year: 2012

The evolutionary history of chromosomes can be tracked by the comparative hybridization of large panels of bacterial artificial chromosome clones. This approach has disclosed an unprecedented phenomenon: centromere repositioning, that is, the movement of the centromere along the chromosome without marker order variation. The occurrence of evolutionary new centromeres (ENCs) is relatively frequent. In macaque, for instance, 9 out of 20 autosomal centromeres are evolutionarily new; in donkey at least 5 such neocentromeres originated after divergence from the zebra, in less than 1 million years. Recently, orangutan chromosome 9, considered to be heterozygous for a complex rearrangement, was discovered to be an ENC. In humans, in addition to neocentromeres that arise in acentric fragments and result in clinical phenotypes, 8 centromere-repositioning events have been reported. These real-time repositioned centromere-seeding events provide clues to ENC birth and progression. In the present paper, we provide a review of the centromere repositioning. We add new data on the population genetics of the ENC of the orangutan, and describe for the first time an ENC on the X chromosome of squirrel monkeys. Next-generation sequencing technologies have started an unprecedented, flourishing period of rapid whole-genome sequencing. In this context, it is worth noting that these technologies, uncoupled from cytogenetics, would miss all the biological data on evolutionary centromere repositioning. Therefore, we can anticipate that classical and molecular cytogenetics will continue to have a crucial role in the identification of centromere movements. Indeed, all ENCs and human neocentromeres were found following classical and molecular cytogenetic investigations. © 2012 Macmillan Publishers Limited All rights reserved.

Serino G.,University of Bari | Serino G.,R.Ø.S.A. | Sallustio F.,University of Bari | Sallustio F.,R.Ø.S.A. | And 4 more authors.
Journal of the American Society of Nephrology | Year: 2012

Aberrant O-glycosylation in the hinge region of IgA1 characterizes IgA nephropathy. The mechanisms underlying this abnormal glycosylation are not well understood, but reduced expression of the enzyme core 1, β1,3- galactosyltransferase 1 (C1GALT1) may contribute. In this study, high-throughput microRNA (miRNA) profiling identified 37 miRNAs differentially expressed in PBMCs of patients with IgA nephropathy compared with healthy persons. Among them, we observed upregulation of miR-148b, which potentially targets C1GALT1. Patients with IgA nephropathy exhibited lower C1GALT1 expression, which negatively correlated with miR-148b expression. Transfection of PBMCs from healthy persons with a miR-148b mimic reduced endogenous C1GALT1 mRNA levels threefold. Conversely, loss of miR-148b function in PBMCs of patientswith IgA nephropathy increased C1GALT1 mRNA and protein levels to those observed in healthy persons. Moreover, we found that upregulation of miR-148b directly correlated with levels of galactose-deficient IgA1. In vitro, we used an IgA1-producing cell line to confirm that miR-148b modulates IgA1 O-glycosylation and the levels of secreted galactose-deficient IgA1. Taken together, these data suggest a role for miRNAs in the pathogenesis of IgA nephropathy. Abnormal expression of miR-148b may explain the aberrant glycosylation of IgA1, providing a potential pharmacologic target for IgA nephropathy. Copyright © 2012 by the American Society of Nephrology.

Ben-Dayan I.,Canadian Institute for Theoretical Astrophysics | Ben-Dayan I.,Perimeter Institute for Theoretical Physics | Gasperini M.,University of Bari | Gasperini M.,National Institute of Nuclear Physics, Italy | And 4 more authors.
Physical Review Letters | Year: 2013

The effect of a stochastic background of cosmological perturbations on the luminosity-redshift relation is computed to second order through a recently proposed covariant and gauge-invariant light-cone averaging procedure. The resulting expressions are free from both ultraviolet and infrared divergences, implying that such perturbations cannot mimic a sizable fraction of dark energy. Different averages are estimated and depend on the particular function of the luminosity distance being averaged. The energy flux being minimally affected by perturbations at large z is proposed as the best choice for precision estimates of dark-energy parameters. Nonetheless, its irreducible (stochastic) variance induces statistical errors on ΩΛ(z) typically lying in the few-percent range. © 2013 American Physical Society.

Sieber F.,University of Strasbourg | Placido A.,University of Strasbourg | Placido A.,University of Bari | El Farouk-Ameqrane S.,University of Strasbourg | And 2 more authors.
Nucleic Acids Research | Year: 2011

Mitochondria play a key role in essential cellular functions. A deeper understanding of mitochondrial molecular processes is hampered by the difficulty of incorporating foreign nucleic acids into organelles. Mitochondria of most eukaryotic species import cytosolic tRNAs. Based on this natural process, we describe here a powerful shuttle system to internalize several types of RNAs into isolated mitochondria. We demonstrate that this tool is useful to investigate tRNA processing or mRNA editing in plant mitochondria. Furthermore, we show that the same strategy can be used to address both tRNA and mRNA to isolated mammalian mitochondria. We anticipate our novel approach to be the starting point for various studies on mitochondrial processes. Finally, our study provides new insights into the mechanism of RNA import into mitochondria. © 2011 The Author(s).

De Gara L.,Biomedical University of Rome | Locato V.,Biomedical University of Rome | Dipierro S.,University of Bari | de Pinto M.C.,University of Bari
Respiratory Physiology and Neurobiology | Year: 2010

Plants are not only obligate aerobic organisms requiring oxygen for mitochondrial energy production, but also produce oxygen during photosynthesis. Therefore, plant cells have to cope with a hyperoxic cellular environment that determines a production of reactive oxygen species (ROS) higher than the one occurring in animal cells. In order to maintain redox homeostasis under control, plants evolved a particularly complex and redundant ROS-scavenging system, in which enzymes and metabolites are linked in a network of reactions. This review gives an overview of the mechanisms active in plant cells for controlling redox homeostasis during optimal growth conditions, when ROS are produced in a steady-state low amount, and during stress conditions, when ROS production is increased. Particular attention is paid to the aspects of oxygen/ROS management for which plant and animal cells differ. © 2010 Elsevier B.V.

Palmieri L.,University of Bari | Palmieri L.,National Research Council Italy | Persico A.M.,Biomedical University of Rome
Biochimica et Biophysica Acta - Bioenergetics | Year: 2010

Autism Spectrum Disorders encompass severe developmental disorders characterized by variable degrees of impairment in language, communication and social skills, as well as by repetitive and stereotypic patterns of behaviour. Substantial percentages of autistic patients display peripheral markers of mitochondrial energy metabolism dysfunction, such as (a) elevated lactate, pyruvate, and alanine levels in blood, urine and/or cerebrospinal fluid, (b) serum carnitine deficiency, and/or (c) enhanced oxidative stress. These biochemical abnormalities are accompanied by highly heterogeneous clinical presentations, which generally (but by no means always) encompass neurological and systemic symptoms relatively unusual in idiopathic autistic disorder. In some patients, these abnormalities have been successfully explained by the presence of specific mutations or rearrangements in their mitochondrial or nuclear DNA. However, in the majority of cases, abnormal energy metabolism cannot be immediately linked to specific genetic or genomic defects. Recent evidence from post-mortem studies of autistic brains points toward abnormalities in mitochondrial function as possible downstream consequences of dysreactive immunity and altered calcium (Ca2+) signalling. © 2010 Elsevier B.V.

de Pinto M.C.,University of Bari | Locato V.,Biomedical University of Rome | Sgobba A.,University of Bari | Romero-Puertas M.C.,CSIC - Experimental Station of El Zaidín | And 3 more authors.
Plant Physiology | Year: 2013

Nitric oxide (NO) is a small redox molecule that acts as a signal in different physiological and stress-related processes in plants. Recent evidence suggests that the biological activity of NO is also mediated by S-nitrosylation, a well-known redox-based posttranslational protein modification. Here, we show that during programmed cell death (PCD), induced by both heat shock (HS) or hydrogen peroxide (H2O2) in tobacco (Nicotiana tabacum) Bright Yellow-2 cells, an increase in S-nitrosylating agents occurred. NO increased in both experimentally induced PCDs, although with different intensities. In H2O2-treated cells, the increase in NO was lower than in cells exposed to HS. However, a simultaneous increase in S-nitrosoglutathione (GSNO), another NO source for S-nitrosylation, occurred in H2O2-treated cells, while a decrease in this metabolite was evident after HS. Consistently, different levels of activity and expression of GSNO reductase, the enzyme responsible for GSNO removal, were found in cells subjected to the two different PCD-inducing stimuli: low in H2O2-treated cells and high in the heat-shocked ones. Irrespective of the type of S-nitrosylating agent, S-nitrosylated proteins formed upon exposure to both of the PCD-inducing stimuli. Interestingly, cytosolic ascorbate peroxidase (cAPX), a key enzyme controlling H2O2 levels in plants, was found to be S-nitrosylated at the onset of both PCDs. In vivo and in vitro experiments showed that S-nitrosylation of cAPX was responsible for the rapid decrease in its activity. The possibility that S-nitrosylation induces cAPX ubiquitination and degradation and acts as part of the signaling pathway leading to PCD is discussed. © 2013 American Society of Plant Biologists. All Rights Reserved.

Degirolamo C.,University of Bari | Degirolamo C.,Instituto Of Ricovero E Cura A Carattere Scientifico Irccs | Degirolamo C.,Letscom Srl | Sabba C.,University of Bari | And 2 more authors.
Nature Reviews Drug Discovery | Year: 2016

The endocrine fibroblast growth factors (FGFs), FGF19, FGF21 and FGF23, are critical for maintaining whole-body homeostasis, with roles in bile acid, glucose and lipid metabolism, modulation of vitamin D and phosphate homeostasis and metabolic adaptation during fasting. Given these functions, the endocrine FGFs have therapeutic potential in a wide array of chronic human diseases, including obesity, type 2 diabetes, cancer, and kidney and cardiovascular disease. However, the safety and feasibility of chronic endocrine FGF administration has been challenged, and FGF analogues and mimetics are now being investigated. Here, we discuss current knowledge of the complex biology of the endocrine FGFs and assess how this may be harnessed therapeutically. © 2016 Macmillan Publishers Limited. All rights reserved.

Savonarola A.,University of Bari | Savonarola A.,San Raffaele Scientific Institute | Palmirotta R.,San Raffaele Scientific Institute | Guadagni F.,San Raffaele Scientific Institute | Silvestris F.,University of Bari
Pharmacogenomics Journal | Year: 2012

The goal of cancer pharmacogenomics is to obtain benefit from personalized approaches of cancer treatment and prevention. Recent advances in genomic research have shed light on the crucial role of genetic variants, mainly involving genes encoding drug-metabolizing enzymes, drug transporters and targets, in driving different treatment responses among individuals, in terms of therapeutic efficacy and safety. Although a considerable amount of new targeted agents have been designed based on a finely understanding of molecular alterations in cancer, a wide gap between pharmacogenomic knowledge and clinical application still persists. This review focuses on the relevance of mutational analyses in predicting individual response to antitumor therapy, in order to improve the translational impact of genetic information on clinical practice. © 2012 Macmillan Publishers Limited. All rights reserved.

Giustolisi O.,University of Bari | Walski T.M.,Bentley Systems Incorporated
Journal of Water Resources Planning and Management | Year: 2012

Solving water distribution network hydraulics depends to a greatextent on demand representation in the related simulation models. The classical approach of simulation models for water distribution networks (WDNs) is described as demand-driven. The demands are fixed a priori in the model as an assumption or from field observations. Recentlya more realist approach to predict the hydraulic system behavior, described as head/pressure-driven, better accounts for the fact that thedemands depend in some ways on head status of the network. Thus, thispaper presents a comprehensive view of demands in the enhanced WDN simulation models, including considerations of humanbased, volume-based,uncontrolled orifice-based, and leakage-based demands as distinct types of network outflows. The paper proposes and discusses the representation of each type of demand in a comprehensive framework that is consistent with the hydraulic principles and the specific working condition. © 2012 American Society of Civil Engineers.

Candela A.M.,University of Bari | Romero A.,University of Granada | Sanchez M.,University of Granada
Archive for Rational Mechanics and Analysis | Year: 2013

We analyze the extendability of the solutions to a certain second order differential equation on a Riemannian manifold (M, g), which is defined by a general class of forces (both prescribed on M or depending on the velocity). The results include the general time-dependent anholonomic case, and further refinements for autonomous systems or forces derived from a potential are obtained. These extend classical results for Lagrangian and Hamiltonian systems. Several examples show the optimality of the assumptions as well as the utility of the results, including an application to relativistic pp-waves. © 2012 Springer-Verlag Berlin Heidelberg.

Petrera M.,Sinai University | Patella V.,University of Bari | Patella S.,Rizzoli Orthopaedic Institute | Theodoropoulos J.,Sinai University
Knee Surgery, Sports Traumatology, Arthroscopy | Year: 2010

Purpose of this study is to conduct a meta-analysis comparing the results of open and arthroscopic Bankart repair using suture anchors in recurrent traumatic anterior shoulder instability. Using Medline Pubmed, Cochrane and Embase databases we performed a search of all published articles. We included only studies that compared open and arthroscopic repair using suture anchors. Statistical analysis was performed using chi-square test. Six studies met the inclusion criteria. The total number of patients was 501, 234 suture anchors and 267 open. The rate of recurrent instability in the arthroscopic group was 6% versus 6.7% in the open group; rate of reoperation was 4.7% in the arthroscopic group vs. 6.6% in open (difference not statistically significant). The difference was statistically significant only in the studies after 2002 (2.9% of recurrence in the arthroscopic group vs. 9.2% in open; 2.2% of reoperation in the arthroscopic group vs. 9.2% in open). Results regarding function couldn't be combined because of non-homogeneous scores reported in the original articles, but the arthroscopic treatment led to better functional results. Arthroscopic repair using suture anchors results in similar redislocation and reoperation rate compared to open Bankart repair; however, we need larger and more homogeneous prospective studies to confirm these findings. © 2010 Springer-Verlag.

Rettinger A.,Karlsruhe Institute of Technology | Losch U.,Karlsruhe Institute of Technology | Tresp V.,Siemens AG | D'Amato C.,University of Bari | Fanizzi N.,University of Bari
Data Mining and Knowledge Discovery | Year: 2012

In the SemanticWeb vision of theWorldWideWeb, content will not only be accessible to humans but will also be available in machine interpretable form as ontological knowledge bases. Ontological knowledge bases enable formal querying and reasoning and, consequently, a main research focus has been the investigation of how deductive reasoning can be utilized in ontological representations to enable more advanced applications. However, purely logic methods have not yet proven to be very effective for several reasons: First, there still is the unsolved problem of scalability of reasoning to Web scale. Second, logical reasoning has problems with uncertain information, which is abundant on SemanticWeb data due to its distributed and heterogeneous nature. Third, the construction of ontological knowledge bases suitable for advanced reasoning techniques is complex, which ultimately results in a lack of such expressive real-world data sets with large amounts of instance data. From another perspective, the more expressive structured representations open up new opportunities for data mining, knowledge extraction and machine learning techniques. If moving towards the idea that part of the knowledge already lies in the data, inductive methods appear promising, in particular since inductive methods can inherently handle noisy, inconsistent, uncertain and missing data. While there has been broad coverage of inducing concept structures from less structured sources (text, Web pages), like in ontology learning, given the problems mentioned above, we focus on new methods for dealing with Semantic Web knowledge bases, relying on statistical inference on their standard representations. We argue that machine learning research has to offer a wide variety of methods applicable to different expressivity levels of SemanticWeb knowledge bases: ranging from weakly expressive but widely available knowledge bases in RDF to highly expressive first-order knowledge bases, this paper surveys statistical approaches to mining the Semantic Web. We specifically cover similarity and distance-based methods, kernel machines, multivariate prediction models, relational graphical models and first-order probabilistic learning approaches and discuss their applicability to Semantic Web representations. Finally, we present selected experimentswhich were conducted on SemanticWebmining tasks for some of the algorithms presented before. This is intended to show the breadth and general potential of this exiting new research and application area for data mining. © The Author(s) 2012.

Leone P.,University of Bari | Shin E.-C.,KAIST | Perosa F.,University of Bari | Vacca A.,University of Bari | And 2 more authors.
Journal of the National Cancer Institute | Year: 2013

The surface presentation of peptides by major histocompatibility complex (MHC) class I molecules is critical to all CD8+ T-cell adaptive immune responses, including those against tumors. The generation of peptides and their loading on MHC class I molecules is a multistep process involving multiple molecular species that constitute the so-called antigen processing and presenting machinery (APM). The majority of class I peptides begin as proteasome degradation products of cytosolic proteins. Once transported into the endoplasmic reticulum by TAP (transporter associated with antigen processing), peptides are not bound randomly by class I molecules but are chosen by length and sequence, with peptidases editing the raw peptide pool. Aberrations in APM genes and proteins have frequently been observed in human tumors and found to correlate with relevant clinical variables, including tumor grade, tumor stage, disease recurrence, and survival. These findings support the idea that APM defects are immune escape mechanisms that disrupt the tumor cells' ability to be recognized and killed by tumor antigen-specific cytotoxic CD8+ T cells. Detailed knowledge of APM is crucial for the optimization of T cell-based immunotherapy protocols. © The Author 2013.

Sallustio F.,R.Ø.S.A. | Costantino V.,R.Ø.S.A. | Cox S.N.,R.Ø.S.A. | Loverre A.,R.Ø.S.A. | And 4 more authors.
Kidney International | Year: 2013

Acute kidney injury (AKI) is emerging as a worldwide public health problem. Recent studies have focused on the possibility of using human adult renal stem/progenitor cells (ARPCs) to improve the repair of AKI. Here we studied the influence of ARPCs on the healing of cisplatin-injured renal proximal tubular epithelial cells. Tubular, but not glomerular, ARPCs provided a protective effect promoting proliferation of surviving tubular cells and inhibiting cisplatin-induced apoptosis. The recovery effect was specific to tubular ARPCs, occurred only after damage sensing, and was completely cancelled by TLR2 blockade on tubular ARPCs. Moreover, tubular, but not glomerular, ARPCs were resistant to the apoptotic effect of cisplatin. Tubular ARPCs operate mainly through the engagement of TLR2, the secretion of inhibin-A protein, and microvesicle-shuttled decorin, inhibin-A, and cyclin D1 mRNAs. These factors worked synergistically and were essential to the repair process. The involvement of tubular ARPC-secreted inhibin-A and decorin mRNA in the pathophysiology of AKI was also confirmed in transplant patients affected by delayed graft function. Hence, identification of this TLR2-driven recovery mechanism may shed light on new therapeutic strategies to promote the recovery capacity of the kidney in acute tubular damage. Use of these components, derived from ARPCs, avoids injecting stem cells. © 2012 International Society of Nephrology.

Capozzi O.,University of Bari | Carbone L.,Childrens Hospital Oakland Research Institute | Carbone L.,Oregon Health And Science University | Stanyon R.R.,University of Florence | And 6 more authors.
Genome Research | Year: 2012

Chromosome rearrangements in small apes are up to 20 times more frequent than in most mammals. Because of their complexity, the full extent of chromosome evolution in these hominoids is not yet fully documented. However, previous work with array painting, BAC-FISH, and selective sequencing in two of the four karyomorphs has shown that highresolution methods can precisely define chromosome breakpoints and map the complex flow of evolutionary chromosome rearrangements. Here we use these tools to precisely define the rearrangements that have occurred in the remaining two karyomorphs, genera Symphalangus (2n = 50) and Hoolock (2n = 38). This research provides the most comprehensive insight into the evolutionary origins of chromosome rearrangements involved in transforming small apes genome. Bioinformatics analyses of the human-gibbon synteny breakpoints revealed association with transposable elements and segmental duplications, providing some insight into the mechanisms that might have promoted rearrangements in small apes. In the near future, the comparison of gibbon genome sequences will provide novel insights to test hypotheses concerning the mechanisms of chromosome evolution. The precise definition of synteny block boundaries and orientation, chromosomal fusions, and centromere repositioning events presented here will facilitate genome sequence assembly for these close relatives of humans.

Spalluto L.,University of Bari | Caffau M.,National Institute of Oceanography and Applied Geophysics - OGS
Italian Journal of Geosciences | Year: 2010

The geological mapping of the 438 Sheet «Bari» (scale 1:50.000), located in the northern part of the Murge area (Apulia, southern Italy), offered the opportunity to revise the local stratigraphy of the mid-Cretaceous carbonate succession belonging to the Calcare di Bari Fm. Despite the flat topography, the strong urbanization and a widespread cover of «terra rossa» soils prevented the study of a continuous and undisturbed succession, several fragmentary lithostrati-graphic and biostratigraphic data have been collected and correlated along many stratigraphic sections. This correlation allowed us to reconstruct a 470 m-thick composite section mostly made up of mud-supported shallow-water limestones and dolomites. This thickness is considerably lower than about 1000 m estimated before in the same area for the same time interval. In agreement with the previous edition of the Geologic Map of Italy few stratigraphic intervals showing a rich content in rudist assemblages and an interval of dolomitic breccias have been used as reference layers and successfully used for lithostratigraphic correlations. New biostratigraphic data show the first record of «primitive» orbitolinid assemblages and other important index taxa which refer the lower and the middle part of the studied succession to the Albian in disagreement with the previous attribution to the Cenomanian.

Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2011.2.4.1-2 | Award Amount: 3.92M | Year: 2012

Multiple Myeloma (MM) is a currently incurable rare malignant plasma cell disease, which invariably relapses despite therapy. The objective of OVER-MYR is to understand the causes of drug resistance and relapse, develop novel strategies to overcome these, provide proof of principal for phase I/II trial, and thus impact on MM-patients survival.Currently-used drugs target both MM cells (MMC) and cells of the bone marrow (BM) microenvironment or niche that are critical for supporting MMC survival, proliferation and growth. Since patients repeatedly relapse after such treatments, the following mechanisms of relapse are considered and need to be investigated: i) drugs have spared specific subclones or subpopulations of MMC ii) drugs induce alterations in cells of the niche that promote drug-resistance. OVER-MYR integrates a network of outstanding researchers from 6 EU countries with internationally recognized experience in clinics and human and animal models of MM, who will jointly: WP1: Study the molecular alterations in primary MM and environment cells in samples obtained from a large number of patients at treatment inclusion and relapse, using high throughput techniques. WP2: Implement in vitro and in vivo models of drug resistance to evaluate molecular and cellular mechanisms and compare their characteristics with drug resistant cells isolated from patients. Combined results of WP1 and WP2 will permit the identification of 10 prominent (altered) candidate genes involved in MM relapse. Changes in drug resistance, cell survival and proliferation will be assessed in WP2 by modulating the expression of the selected genes. WP3: Determine how cells from the niche alter their functions in the presence of drugs, and how drug-altered cells impact on MM cells during therapy. WP4: Screen chemical libraries for drugs active on generated sensitive cell lines, develop innovative inhibitors and provide proof of principle for a phase I/II trial

de Pinto M.C.,University of Bari | Locato V.,Biomedical University of Rome | de Gara L.,Biomedical University of Rome
Plant, Cell and Environment | Year: 2012

Programmed cell death (PCD) is a genetically controlled process described both in eukaryotic and prokaryotic organisms. Even if it is clear that PCD occurs in plants, in response to various developmental and environmental stimuli, the signalling pathways involved in the triggering of this cell suicide remain to be characterized. In this review, the main similarities and differences in the players involved in plant and animal PCD are outlined. Particular attention is paid to the role of reactive oxygen species (ROS) as key inducers of PCD in plants. The involvement of different kinds of ROS, different sites of ROS production, as well as their interaction with other molecules, is crucial in activating PCD in response to specific stimuli. Moreover, the importance is stressed on the balance between ROS production and scavenging, in various cell compartments, for the activation of specific steps in the signalling pathways triggering this cell suicide process. The review focuses on the complexity of the interplay between ROS and antioxidant molecules and enzymes in determining the most suitable redox environment required for the occurrence of different forms of PCD. © 2011 Blackwell Publishing Ltd.

Agency: European Commission | Branch: FP7 | Program: CP | Phase: ICT-2009.3.3 | Award Amount: 2.37M | Year: 2010

Electronic transduction can open new perspectives for point-of-care diagnosis and treatment monitoring. In this respect, label free, organic field-effect transistor (OFET) sensors have recently raised the interest of the organic-electronic community. The EGOFET biosensor aims at an electronic transduction of a bio-recognition event, eventually leading to an amplified response. The sensor combines the specificity of a defined bio-probe with the label-free and high sensitivity of the field-effect transduction principle. The recognition will be achieved through antigens, antibodies or membrane proteins placed on top of the organic semiconductor, right where the electrical transport occurs in this dielectrics/oxide-free structure. Supramolecular architectures will be used to immobilize the bio-probes into polymeric or phospholipid layers to maximise recognition capabilities and minimize non-specific binding and fouling. High sensitivity will be achieved by exploiting conformational changes and/or charge generation effects occurring upon the recognition process. To attain low-operating voltage and low-power consumption, the OFET will take advantage of the high capacitance offered by the electrolytic or protonic medium used to carry the analyte up to the semi-conductor surface. Implementation of the devices on paper and plastic substrates will be realized by low-cost printing-compatible technologies. The sensors figures of merit will be assessed by exploiting the highly specific biotin/avidin affinity reaction. A proof-of-principle for a point-of-care relevant application, using the immunoassay approach, will be pursued afterwards.

Sansalone J.,University of Florida | Kuang X.,Louisiana State University | Ying G.,University of Florida | Ranieri V.,University of Bari
Water Research | Year: 2012

Permeable pavement, as a sustainable infrastructure material can promote hydrologic restoration, particulate matter (PM) and solute control. However, filtration and commensurate clogging are two aspects of continued interest and discussion. This study quantifies filtration and clogging of cementitious permeable pavement (CPP) for loadings from 50 to 200 mg/L of hetero-disperse sandy-silt PM. The CPP mix design provides a hetero-disperse pore size distribution (PSD)pore, effective porosity (e) of 24% and median pore size of 658 μm with a standard deviation of 457 μm. The PM mass separation across the entire particle size distribution (PSD)PM exceeds 80%; with complete separation for PM greater than 300 μm and 50% separation for suspended PM. Turbidity is reduced (42-95%), and effluent is below 10 NTU in the first quartile of a loading period. Permeable pavement illustrates reductions in initial (clean-bed) hydraulic conductivity (k0) with loading time. For all PM loadings, k0 (3.1 × 10-1 mm/s) was reduced to 10-4 mm/s for runoff loading durations from 100 to 250 h, respectively. Temporal hydraulic conductivity (k) follows exponential profiles. Maintenance by vacuuming and sonication illustrate that 96-99% of k0 is recovered. Permeable pavement constitutive properties integrated with measured PM loads and a year of continuous rainfall-runoff simulation illustrate k reduction with historical loadings. Study results measure and model filtration and hydraulic conductivity phenomena as well as maintenance requirements of permeable pavement directly loaded by urban drainage. © 2011.

Chio A.,University of Turin | Logroscino G.,University of Bari | Traynor B.J.,U.S. National Institute on Aging | Collins J.,United Biosource Corporation | And 3 more authors.
Neuroepidemiology | Year: 2013

Background: Amyotrophic lateral sclerosis (ALS) is relatively rare, yet the economic and social burden is substantial. Having accurate incidence and prevalence estimates would facilitate efficient allocation of healthcare resources. Objective: To provide a comprehensive and critical review of the epidemiological literature on ALS. Methods: MEDLINE and EMBASE (1995-2011) databases of population-based studies on ALS incidence and prevalence reporting quantitative data were analyzed. Data extracted included study location and time, design and data sources, case ascertainment methods and incidence and/or prevalence rates. Medians and interquartile ranges (IQRs) were calculated, and ALS case estimates were derived using 2010 population estimates. Results: In all, 37 articles met the inclusion criteria. In Europe, the median incidence rate (/100,000 population) was 2.08 (IQR 1.47-2.43), corresponding to an estimated 15,355 (10,852-17,938) cases. Median prevalence (/100,000 population) was 5.40 (IQR 4.06-7.89), or 39,863 (29,971-58,244) prevalent cases. Conclusions: Disparity in rates among ALS incidence and prevalence studies may be due to differences in study design or true variations in population demographics such as age and geography, including environmental factors and genetic predisposition. Additional large-scale studies that use standardized case ascertainment methods are needed to more accurately assess the true global burden of ALS. Copyright © 2013 S. Karger AG, Basel.

Marrie R.A.,University of Manitoba | Reingold S.,University of Manitoba | Cohen J.,Scientific and Clinical Review Assoc. LLC | Stuve O.,Cleveland Clinic | And 4 more authors.
Multiple Sclerosis Journal | Year: 2015

Background: Psychiatric comorbidity is associated with lower quality of life, more fatigue, and reduced adherence to disease-modifying therapy in multiple sclerosis (MS). Objectives: The objectives of this review are to estimate the incidence and prevalence of selected comorbid psychiatric disorders in MS and evaluate the quality of included studies. Methods: We searched the PubMed, PsychInfo, SCOPUS, and Web of Knowledge databases and reference lists of retrieved articles. Abstracts were screened for relevance by two independent reviewers, followed by full-text review. Data were abstracted by one reviewer, and verified by a second reviewer. Study quality was evaluated using a standardized tool. For population-based studies we assessed heterogeneity quantitatively using the I2 statistic, and conducted meta-analyses. Results: We included 118 studies in this review. Among population-based studies, the prevalence of anxiety was 21.9% (95% CI: 8.76%35.0%), while it was 14.8% for alcohol abuse, 5.83% for bipolar disorder, 23.7% (95% CI: 17.4%30.0%) for depression, 2.5% for substance abuse, and 4.3% (95% CI: 0%10.3%) for psychosis. Conclusion: This review confirms that psychiatric comorbidity, particularly depression and anxiety, is common in MS. However, the incidence of psychiatric comorbidity remains understudied. Future comparisons across studies would be enhanced by developing a consistent approach to measuring psychiatric comorbidity, and reporting of age-, sex-, and ethnicity-specific estimates.

Marrie R.A.,University of Manitoba | Cohen J.,Cleveland Clinic | Stuve O.,Southwestern University | Trojano M.,University of Bari | And 4 more authors.
Multiple Sclerosis Journal | Year: 2015

Background: Comorbidity is an area of increasing interest in multiple sclerosis (MS). Objective: The objective of this review is to estimate the incidence and prevalence of comorbidity in people with MS and assess the quality of included studies. Methods: We searched the PubMed, SCOPUS, EMBASE and Web of Knowledge databases, conference proceedings, and reference lists of retrieved articles. Two reviewers independently screened abstracts. One reviewer abstracted data using a standardized form and the abstraction was verified by a second reviewer. We assessed study quality using a standardized approach. We quantitatively assessed population-based studies using the I2 statistic, and conducted random-effects meta-analyses. Results: We included 249 articles. Study designs were variable with respect to source populations, case definitions, methods of ascertainment and approaches to reporting findings. Prevalence was reported more frequently than incidence; estimates for prevalence and incidence varied substantially for all conditions. Heterogeneity was high. Conclusion: This review highlights substantial gaps in the epidemiological knowledge of comorbidity in MS worldwide. Little is known about comorbidity in Central or South America, Asia or Africa. Findings in North America and Europe are inconsistent. Future studies should report age-, sex- and ethnicityspecific estimates of incidence and prevalence, and standardize findings to a common population.

Carlo Marano G.,University of Bari | Greco R.,University of Bari | Chiaia B.,University of Turin
Journal of Sound and Vibration | Year: 2010

Tuned mass sampers (TMDs) are widely used strategies for vibration control in many engineering applications, so that many TMD optimization criteria have been proposed till now. However, they normally consider only TMD stiffness and damping as design variables and assume that the tuned mass is a pre-selected value. In this work a more complete approach is proposed and then also TMD mass ratio is optimized. A standard single degree of freedom system is investigated to evaluate TMD protection efficiency in case of excitation at the support. More precisely, this model is used to develop two different optimizations criteria which minimize the main system displacement or the inertial acceleration. Different environmental conditions described by various characterizations of the input, here modelled by a stationary filtered stochastic process, are considered. Results show that all solutions obtained considering also the mass of the TMD as design variable are more efficient if compared with those obtained without it. However, in many cases these solutions are inappropriate because the optimal TMD mass is greater than real admissible values in practical technical applications for civil and mechanical engineering. Anyway, one can deduce that there are some interesting indications for applications in some actual contexts. In fact, the results show that there are some ranges of environmental parameters ranges where results attained by the displacement criterion are compatible with real applications requiring some percent of main system mass. Finally, the present research gives promising indications for complete TMD optimization application in emerging technical contexts, as micromechanical devices and nano resonant beams. © 2010 Elsevier Ltd. All rights reserved.

Huddleston J.,University of Washington | Huddleston J.,Howard Hughes Medical Institute | Ranade S.,Pacific Biosciences | Malig M.,University of Washington | And 12 more authors.
Genome Research | Year: 2014

Obtaining high-quality sequence continuity of complex regions of recent segmental duplication remains one of the major challenges of finishing genome assemblies. In the human and mouse genomes, this was achieved by targeting large-insert clones using costly and laborious capillary-based sequencing approaches. Sanger shotgun sequencing of clone inserts, however, has now been largely abandoned, leaving most of these regions unresolved in newer genome assemblies generated primarily by next-generation sequencing hybrid approaches. Here we show that it is possible to resolve regions that are complex in a genome-wide context but simple in isolation for a fraction of the time and cost of traditional methods using long-read single molecule, real-time (SMRT) sequencing and assembly technology from Pacific Biosciences (PacBio). We sequenced and assembled BAC clones corresponding to a 1.3-Mbp complex region of chromosome 17q21.31, demonstrating 99.994% identity to Sanger assemblies of the same clones. We targeted 44 differences using Illumina sequencing and find that PacBio and Sanger assemblies share a comparable number of validated variants, albeit with different sequence context biases. Finally, we targeted a poorly assembled 766-kbp duplicated region of the chimpanzee genome and resolved the structure and organization for a fraction of the cost and time of traditional finishing approaches. Our data suggest a straightforward path for upgrading genomes to a higher quality finished state. © 2014 Huddleston et al.

Lorenzo J.M.,Centro Tecnologico Of La Carne Of Galicia | Sarries M.V.,Public University of Navarra | Tateo A.,University of Bari | Polidori P.,University of Camerino | And 2 more authors.
Meat Science | Year: 2014

Meat has exerted a crucial role in human evolution and is an important component of a healthy and well balanced diet due to its nutritional richness. The aim of the present review was to shed light on the nutritional composition of horsemeat and their benefits for human health. One of the reasons for such interest was the occurrence, in Europe several years ago, of dioxin, Bovine Encephalopathy and foot-and-mouth disease problems in farm animals. Therefore, consumers began to look for alternative red meats from other non-traditional species. There is no carcass classification system on horses designated to meat consumption. It would be advisable to standardize the equine meat market to reduce variations that may reflect differences in meat quality. The nutritional composition of horsemeat by comparison with pork, beef or poultry is characterized by low levels of fat and cholesterol (about 20% less), relatively high concentrations of n-3 fatty acids and heme iron indicating that its consumption may be beneficial for health. Therefore, horsemeat may supplement the meat market with good quality products, although as in other dietary components moderation is advisable. © 2013 Elsevier Ltd.

Solfrizzi V.,University of Bari | Solfrizzi V.,Laboratory of Gerontology and Geriatrics | Panza F.,University of Bari | Panza F.,Laboratory of Gerontology and Geriatrics
Journal of Alzheimer's Disease | Year: 2015

Among nutraceuticals and nutritional bioactive compounds, the standardized Ginkgo biloba extract EGb 761 is the most extensively clinically tested herbal-based substance for cognitive impairment, dementia, and Alzheimer's disease (AD). In the last three years, notwithstanding negative meta-analytic findings and the discouraging results of preventive trials against AD, some randomized controlled trials focusing particularly on dementia, AD, and mild cognitive impairment (MCI) subgroups with neuropsychiatric symptoms (NPS) and some recent meta-analyses have suggested a renowned role for EGb 761 for cognitive impairment and dementia. Meta-analytic findings suggested overall benefits of EGb 761 for stabilizing or slowing decline in cognition of subjects with cognitive impairment and dementia. The safety and tolerability of EGb 761 appeared to be excellent at different doses. Subgroup analyses showed that these clinical benefits of EGb 761 were mainly associated with the 240 mg/day dose, and also confirmed in the AD subgroup. More importantly, one of these meta-analyses showed clinical benefits in cognition, behavior, functional status, and global clinical change of EGb 761 at a dose of 240 mg/day in the treatment of patients with dementia, AD, and MCI with NPS. The inclusion of the recent randomized controlled trials focusing on dementia, AD, and MCI subgroups with NPS may partly explain the conflicting results of these recent meta-analyses and previous pooled findings. © 2015 IOS Press and the authors. All rights reserved.

Monaci L.,CNR Institute of Sciences of Food Production | Losito I.,University of Bari | Palmisano F.,University of Bari | Visconti A.,CNR Institute of Sciences of Food Production
Journal of Chromatography A | Year: 2010

A method based on capillary liquid chromatography combined with electrospray ionization-tandem mass spectrometry (CapLC-ESI-MS-MS) for the detection and identification of casein deriving peptides in fined white wine is described. This is the first step towards the development of a liquid chromatography mass spectrometric method for the detection/identification of markers of potentially allergenic milk proteins used as wine fining agents. The method demonstrated to be capable of detecting some peptides arising from α and β casein (with the relative aminoacidic sequences elucidated) in extracts of white wine fined with casein at 100 and 1000 μg/mL. This MS based approach appears to be a useful tool for screening purposes as well as a confirmatory tool for the unequivocal identification of caseins in ELISA positive samples. © 2010 Elsevier B.V.

Chio A.,University of Turin | Defazio G.,University of Bari
Neurology | Year: 2016

Prognosis has always represented one the main goals of medicine. For example, stroke prognosis was discussed by Ibn Sina (Avicenna) in his Canon of Medicine published in 1025. 1 Not too far off from our current concepts, Ibn Sina stated that stroke prognostic factors were respiratory status and impairment of the swallowing reflex. In modern medicine, oncology is the area in which the determination of prognostic factors has reached the highest reliability, with development of the first version of TNM staging by Pierre Denoix during the 1940s. 2 The awareness of the necessity to develop prognostic rating scales in the area of neurodegenerative disorders is more recent, probably driven by the increasing range of available therapies and therapeutic trials. However, it is largely recognized that attaining a reliable outcome prediction in neurodegenerative disorders is complex, due to their clinical and pathogenic heterogeneity. © 2016 American Academy of Neurology.

Maliogka V.I.,Aristotle University of Thessaloniki | Martelli G.P.,University of Bari | Fuchs M.,Cornell University | Katis N.I.,Aristotle University of Thessaloniki
Advances in Virus Research | Year: 2015

Grapevine is a high value vegetatively propagated fruit crop that suffers from numerous viruses, including some that seriously affect the profitability of vineyards. Nowadays, 64 viruses belonging to different genera and families have been reported in grapevines and new virus species will likely be described in the future. Three viral diseases namely leafroll, rugose wood, and infectious degeneration are of major economic importance worldwide. The viruses associated with these diseases are transmitted by mealybugs, scale and soft scale insects, or dagger nematodes. Here, we review control measures of the major grapevine viral diseases. More specifically, emphasis is laid on (i) approaches for the production of clean stocks and propagative material through effective sanitation, robust diagnosis, as well as local and regional certification efforts, (ii) the management of vectors of viruses using cultural, biological, and chemical methods, and (iii) the production of resistant grapevines mainly through the application of genetic engineering. The benefits and limitations of the different control measures are discussed with regard to accomplishments and future research directions. © 2015 Elsevier Inc.

Mori G.,University of Foggia | D'Amelio P.,University of Turin | Faccio R.,University of Washington | Brunetti G.,University of Bari
Clinical and Developmental Immunology | Year: 2013

In the last two decades, numerous scientists have highlighted the interactions between bone and immune cells as well as their overlapping regulatory mechanisms. For example, osteoclasts, the bone-resorbing cells, are derived from the same myeloid precursor cells that give rise to macrophages and myeloid dendritic cells. On the other hand, osteoblasts, the bone-forming cells, regulate hematopoietic stem cell niches from which all blood and immune cells are derived. Furthermore, many of the soluble mediators of immune cells, including cytokines and growth factors, regulate the activities of osteoblasts and osteoclasts. This increased recognition of the complex interactions between the immune system and bone led to the development of the interdisciplinary osteoimmunology field. Research in this field has great potential to provide a better understanding of the pathogenesis of several diseases affecting both the bone and immune systems, thus providing the molecular basis for novel therapeutic strategies. In these review, we reported the latest findings about the reciprocal regulation of bone and immune cells. © 2013 Giorgio Mori et al.

Poltronieri P.,CNR Institute of Sciences of Food Production | D'Urso P.I.,University of Bari | D'Urso P.I.,King's College | Mezzolla V.,University of Salento | D'Urso O.F.,University of Salento
Chemical Biology and Drug Design | Year: 2013

MicroRNAs are aberrantly expressed in many cancers and can exert tumour-suppressive or oncogenic functions. As oncomirs promote growth of cancer cells and support survival during chemotherapy, thus microRNA-silencing therapies could be a valuable approach to be associated with anticancer drugs and chemotherapy treatments. miR-155 microRNA was found overexpressed in different types of cancer, such as leukaemias (PML, B-cell lymphomas), lung cancer and glioblastoma. GABA-A receptor downregulation was found correlated with glioma grading, with decreasing levels associated with higher grade of malignancies. A relationship between knock-down of miR-155 and re-expression of GABRA 1 protein in vivo was recently individuated. This finding has implication on the effectiveness of RNA-silencing approaches against miR-155 with the scope to control proliferation and signalling pathways regulated by GABA-A receptor. Applying microRNAs for treatment of brain tumours poses several problems, and fields to be solved are mainly the passage of the brain-blood barrier and the targeted delivery to specific cell types. Glioblastoma multiforme cells bud off microvesicles that deliver cytoplasmic contents to nearby cells. Thus, the exploitation of these mechanisms to deliver antagomir therapeutics targeting microvescicles in the brain could take the lead in the near future in the treatment for brain cancers in substitution of invasive surgical intervention. The decrease in viability of primary cultures of glioblastoma multiforme (GBM) in response to GABA stimulation, evaluated with MTT [3-(4.5-dimethylthiazol-2-yl)-2.5-diphenol tetrazolium bromide] assays. Glioblastoma multiforme cells transfected with a 2′-O-methyl-oligonucleotide complementary to miR-155 (2′OMe-miR-155) and an irrelevant 2′-O-methyloligonucleotide (2′OMe-EGFP) were grown for 48h. The induction of GABRA1 mRNA expression after transfection with the anti-miR-155 antisense was monitored by means of Northern blot assays, and confirmed that GABA receptors are re-expressed when miR-155 is depleted in GBM cells. © 2012 John Wiley & Sons A/S.

Fiorillo F.,University of Sannio | Doglioni A.,University of Bari
Hydrogeology Journal | Year: 2010

The relation between rainfall and the discharge from two springs, located at the base of different karst massifs in southern Italy, is investigated by cross-correlation analyses. Data are derived from a continuous time window of 13 years. The input signal involves multiple rainfall time series (cumulative rainfall over varying time windows), while the time series of daily spring discharges are used as the output signal. Analyses were first conducted on the unprocessed data and then on data for which linear trends and seasonal components had been removed, the latter by a spectral analysis. Analyses contributed to the investigation of the time required for water to flow through the karst aquifers at the two sites. Long time intervals of the cumulative rainfall (>60days) appear to be the main component affecting the spring discharge hydrographs; shorter time intervals seem to be related to quick-flow paths. Some statistics about the linear regression and the meaning of the cross-correlation analysis are discussed. Cross-correlation analysis can provide strong support for identification of the main rainfall contribution and the travel time through the main infiltration pathways in aquifers. © 2010 Springer-Verlag.

Agency: European Commission | Branch: H2020 | Program: MSCA-RISE | Phase: MSCA-RISE-2015 | Award Amount: 1.58M | Year: 2016

Technological advances in remote sensing have increased the availability of satellite images with different spatiotemporal and spectral characteristics.There is difficulty for retrieving the most appropriate data for each users needs.One key challenge is to connect the quantitative information of the EO images with the qualitative (high-level user queries) and be able to mine these connections in big archives.An inherent question arises; how to retrieve EO images based on user semantically aware questions.Content based EO image retrieval techniques have been introduced for bridging the gap between low-level image features and high-level queries.The main constraint of the existing approaches is the generalization of the problem.The formulated ontologies are not focused on the constraints of EO images.The main objective of SEO-DWARF is to realize the content-based search of EO images on an application specific basis.The marine application domain and data from Sentinels 1,2,3, ENVISAT will be used.Queries such as Calculate the rate of increasing chlorophyll in the NATURA area will be answered by the SEO-DWARF, helping users to retrieve the appropriate EO images for their specific needs or alert them when a specific phenomenon occurs.The research contains the:a) ontology formalization for the specific research topics,b) determination of the semantic queries for the application domains,c) algorithm development for extracting metadata from the EO images,d) design of an architecture of the platform to perform the semantic image retrieval and storage and management of the extracted metadata.All four aspects will be integrated in an innovative and user-friendly web based platform enabling the users to retrieve images for marine applications or register for a semantic alert.A strong and experienced research team, of 4 academic and 5 industrial partners, coming from Greece(3), Italy(2), Germany(1), France(1), Cyprus(1) and Switzerland(1) constitute the projects consortium.

Agency: European Commission | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-2013-ITN | Award Amount: 3.97M | Year: 2013

NR-NET is a multidisciplinary consortium, whose activities are directed towards the understanding of the role of Nuclear Receptors (NRs) and coregulators in metaflammatory disease. Metaflammation - metabolic disorders linked to chronic inflammation is an emerging concept explaining the pathogenesis of a wide-spectrum of diseases. Since several nuclear receptors can directly sense metabolic alterations, we propose that they could be considered as important endogenous modulators of metaflammatory pathways further expanding the repertoire of diseases that can be intervened by NR-modulating drugs. NR-NET is expected to deliver important new knowledge on the basic biological processes involved in the mechanism of epigenetic control of gene expression by nuclear receptors, on structural and functional aspects of nuclear receptor action with an ultimate goal of better understanding the pathogenesis of metabolic disorders and inflammation. The composition of the network was designed to contain a balanced mix of labs with experience and skills in academic and industry based research, so that it can provide young researchers the opportunity to acquire skills and expertise in: a. Structural and functional aspects of NR-regulated gene expression b. Genomics and proteomics approaches to analyze complex regulatory networks c. Systems biology approaches and bioinformatics tools to define composite regulatory modules d. Studying metabolic and inflammatory pathways in model organisms The research will be conducted under the framework of a structured training program, which includes a myriad of Individual and Network-wide training activities. Apart from training in academic and industry-based research projects, specific emphasis will be given to training in transferable skills and the stimulation of creativity and entrepreneurial mindset of researchers.

Agency: European Commission | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-ITN-2008 | Award Amount: 3.83M | Year: 2010

The FlexSMELL concept is to realize a hybrid (organic-inorganic) very low-cost, ultra low-power olfaction system based on bio-receptor and implemented on a flexible substrate. Such a system is to be compatible with wireless read-out, setting the ground for the future development of smart sensing RFID tags. The FlexSMELL technology platform will be in principle suitable for different applications with the main ones envisaged for the in the field of logistics for the monitoring of perishable goods along their transport and storing, though smart packaging solutions. Teaching and training strategies will be implemented to prepare the next generation of scientists in this fast developing strategic research area. Eventually this effort will leverage the strength of the EU in organic electronics and micro-technologies for sensing applications as well as their integration into systems providing services to the individuals and to the community in the areas of food control though smart packaging, but also health, environment, communication and security.

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.

Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2011.2.4.1-2 | Award Amount: 4.28M | Year: 2012

Multiple Myeloma (MM) is an incurable disease with rapidly growing prevalence and poor prognosis. Consequently, it is the goal of the OPTATIO consortium to seek out novel strategies for the development of novel diagnostic and therapeutic options. The MM pathogenesis involves not only genetic changes within the tumour cells but also the emergence of supportive conditions by the bone marrow microenvironment (BMM). To target the essential components of this support system, it is the goal of the project to establish preclinical in vitro and in vivo models of MM that include functionally relevant elements of the BMM. The OPTATIO consortium will therefore analyse clinical data to correlate the presence of particular MM-BMM interactions with the pathogenesis of MM, with its intrinsic therapy resistance as well as with disease relapse due to the development of acquired drug resistance. These correlative data will be validated using autologous MM-BMM co-culture assays and reverse translated into in vitro screening and in vivo models, which will be subsequently used to develop lead compounds that target myeloma cells within their microenvironment. The clinical expertise of several oncological divisions, the research experience of academic laboratories and the pharmaceutical know-how of small and medium sized enterprises as well as biotech industry joined their efforts within the OPTATIO consortium to drive this important development and to ensure translation towards clinical trials. Expected impacts of the project include establishment of better diagnostics, new drug screening approaches for MM and novel personalised therapies based on individual ex vivo phenotyping leading to reduced patient mortality. Since envisaged drug screening methods are applicable to other areas of research and development, the project results will open new markets for industry partners in the fields of drug discovery and pharmaceutical development of products and services for personalized medicine.

News Article | February 15, 2017

PARSIPPANY, N.J.--(BUSINESS WIRE)--Zoetis Inc. (NYSE:ZTS) today announced that the European Commission has granted the company a license for Stronghold® Plus (selamectin/sarolaner), a topical combination of parasiticides that treats ticks, fleas, ear mites, lice and gastrointestinal nematodes and prevents heartworm disease in cats. Veterinarians across the European Union now have a treatment choice that leverages the benefits of sarolaner, a new innovation in the class of isoxazolines, without sacrificing the broad spectrum protection, safety or ease of use they expect. ”The approval of Stronghold Plus enables Zoetis to offer veterinarians a new topical choice that treats the parasites commonly presenting a threat to cats with one convenient monthly dose,” said Dr. Catherine Knupp, Executive Vice President and President, Research and Development at Zoetis. “For the first time, we have combined our new, versatile parasiticide sarolaner with the active ingredient in Stronghold, selamectin, resulting in the first approval of sarolaner for use in cats. We see sarolaner as a promising platform for future product lines and lifecycle innovations and are pleased with the positive data that sarolaner and its combination continue to generate in studies.” The market for companion animal parasitic medicines was valued at more than $4.2 billion in 2015, with a compound annual growth rate of about 5% over the previous five years, according to Vetnosis1. Domenico Otranto, Professor of Parasitology at The University of Bari in Italy, who recently reviewed the product data of Stronghold Plus, said: “A number of laboratory and field studies show the efficacy of the single spot-on application of Stronghold Plus for at least one month. Veterinarians in the European Union will now have a very effective option for the treatment and control of four prominent species of ticks commonly found on cats while maintaining proven efficacy against fleas, GI worms, heartworms, ear mites and lice. Ultimately, pet owners and practitioners have a new tool for improving the health and welfare of cats.” Dr. Michael Stegemann, Senior Director of Veterinary Research and Development at Zoetis, said: “Stronghold Plus was entirely discovered and developed by Zoetis scientists. It provides fast, sustained coverage from the fleas and ticks most often found on cats. The combined action of sarolaner and selamectin allows Stronghold Plus to kill four species of ticks, and it lengthens the duration of protection against fleas to five full weeks with no drop in efficacy at the end of the dosing period -- all without sacrificing protection from other important internal and external feline parasites. We’re excited to be able to bring this innovation to veterinarians across the European Union.” About Stronghold Plus product efficacy and safety: The active substances in Stronghold Plus are selamectin and sarolaner, a new combination of parasiticides. Selamectin has adulticidal, ovicidal and larvicidal activity against fleas (Ctenocephalides spp). Selamectin is also active against ear mites, lice, gastrointestinal nematodes and prevents heartworm disease through its efficacy against Dirofilaria immitis larvae. Sarolaner is a new acaricide and insecticide belonging to the isoxazoline class: it is efficacious against ticks, fleas and mites. The most common side effects of Stronghold Plus are mild and transient pruritus at the application site. Mild to moderate alopecia at the application site, erythema and drooling have been uncommonly observed. For more information about Stronghold Plus, click here. Zoetis is the leading animal health company, dedicated to supporting its customers and their businesses. Building on more than 60 years of experience in animal health, Zoetis discovers, develops, manufactures and markets veterinary vaccines and medicines, complemented by diagnostic products and genetic tests and supported by a range of services. Zoetis serves veterinarians, livestock producers and people who raise and care for farm and companion animals with sales of its products in more than 100 countries. In 2015, the company generated annual revenue of $4.8 billion with approximately 9,000 employees. For more information, visit Forward-Looking Statements: This press release contains forward-looking statements, which reflect the current views of Zoetis with respect to business plans or prospects, expectations regarding products and other future events. These statements are not guarantees of future performance or actions. Forward-looking statements are subject to risks and uncertainties. If one or more of these risks or uncertainties materialize, or if management's underlying assumptions prove to be incorrect, actual results may differ materially from those contemplated by a forward-looking statement. Forward-looking statements speak only as of the date on which they are made. Zoetis expressly disclaims any obligation to update or revise any forward-looking statement, whether as a result of new information, future events or otherwise. A further list and description of risks, uncertainties and other matters can be found in our Annual Report on Form 10-K for the fiscal year ended December 31, 2015, including in the sections thereof captioned “Forward-Looking Statements and Factors That May Affect Future Results” and “Item 1A. Risk Factors,” in our Quarterly Reports on Form 10-Q and in our Current Reports on Form 8-K. These filings and subsequent filings are available online at,, or on request from Zoetis.

Escobedo M.A.,TU Munich | Giannuzzi F.,University of Bari | Mannarelli M.,National Institute of Nuclear Physics, Italy | Soto J.,University of Barcelona
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2013

By means of effective field theory techniques, we study the modifications of some properties of weakly coupled heavy quarkonium states propagating through a quark-gluon plasma at temperatures much smaller than the heavy quark mass, mQ. Two different cases are considered, corresponding to two different hierarchies between the typical size of the bound state, r, the binding energy, E, the temperature, T, and the screening mass, mD. The first case corresponds to the hierarchy mQ1/rTEmD, relevant for moderate temperatures, and the second one to the hierarchy m QT1/r, mDE, relevant for studying the dissociation mechanism. In the first case we determine the perturbative correction to the binding energy and to the decay width of states with arbitrary angular momentum, finding that the width is a decreasing function of the velocity. A different behavior characterizes the second kinematical case, where the width of s-wave states becomes a nonmonotonic function of the velocity, increasing at moderate velocities and decreasing in the ultrarelativistic limit. We obtain a simple analytical expression of the decay width for T1/rmDE at moderate velocities, and we derive the s-wave spectral function for the more general case T1/r, mDE. A brief discussion of the possible experimental signatures as well as a comparison with the relevant lattice data are also presented. © 2013 American Physical Society.

Cea P.,University of Bari | Cea P.,National Institute of Nuclear Physics, Italy
Monthly Notices of the Royal Astronomical Society | Year: 2014

Recent Planck data confirm that the cosmic microwave background displays the quadrupole power suppression together with large-scale anomalies. Progressing from previous results, that focused on the quadrupole anomaly, we strengthen the proposal that the slightly anisotropic ellipsoidal universe may account for these anomalies.We solved at large scales the Boltzmann equation for the photon distribution functions by taking into account both the effects of the inflation produced primordial scalar perturbations and the anisotropy of the geometry in the ellipsoidal universe. We showed that the low quadrupole temperature correlations allowed us to fix the eccentricity at decoupling, edec=(0.86±0.14) 10-2, and to constraint the direction of the symmetry axis.We found that the anisotropy of the geometry of the universe contributes only to the large-scale temperature anisotropies without affecting the higher multipoles of the angular power spectrum. Moreover, we showed that the ellipsoidal geometry of the universe induces sizeable polarization signal at large scales without invoking the reionization scenario. We explicitly evaluated the quadrupole TE and EE correlations. We found an average largescale polarization ΔTpol= (1.20 ± 0.38) μK. We point out that great care is needed in the experimental determination of the large-scale polarization correlations since the average temperature polarization could be misinterpreted as foreground emission leading, thereby, to a considerable underestimate of the cosmic microwave background polarization signal. © 2014 The Author Published by Oxford University Press on behalf of the Royal Astronomical Society.

Cassidy A.,University of East Anglia | Rimm E.B.,Harvard University | Rimm E.B.,Channing Laboratory | O'Reilly E.J.,Harvard University | And 4 more authors.
Stroke | Year: 2012

Background and Purpose-To date, few studies have examined associations between the wide range of flavonoid subclasses and risk of ischemic, hemorrhagic, and total stroke. Methods-We conducted a prospective study among 69 622 women from the Nurses' Health Study. Total flavonoid and subclass intakes were calculated from semiquantitative food frequency questionnaires collected every 4 years using an updated and extended US Department of Agriculture flavonoid database. Results-During 14 years of follow-up, 1803 incident strokes were confirmed. After adjusting for potential confounders, women in the highest compared with the lowest quintile of flavanone intake had a relative risk of ischemic stroke of 0.81 (95% CI, 0.66-0.99; P=0.04). Citrus fruits/juices, the main dietary source of flavanones, tended to be associated with a reduced risk for ischemic stroke (relative risk, 0.90; 95% CI, 0.77-1.05) comparing extreme quintiles. Conclusions-Total flavonoid intake was not inversely associated with risk of stroke; however, increased intake of the flavanone subclass was associated with a reduction in the risk of ischemic stroke. Citrus fruit consumption may be associated with a reduction in stroke risk, and experimental data support these epidemiological associations that the flavanone content of citrus fruits may potentially be cardioprotective. Further prospective studies are needed to confirm these associations. © 2012 2012 American Heart Association, Inc.

Biancofiore P.,University of Bari | Biancofiore P.,National Institute of Nuclear Physics, Italy | Colangelo P.,National Institute of Nuclear Physics, Italy | De Fazio F.,National Institute of Nuclear Physics, Italy
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2013

The BABAR measurements of the ratios R(D(*))=B(B→D(*) τν̄τ)B(B→D(*) μν ̄μ) deviate from the standard model expectation, while new results on the purely leptonic B→τν̄τ mode show a better consistency with the standard model, within the uncertainties. In a new physics scenario, one possibility to accommodate these two experimental facts consists in considering an additional tensor operator in the effective weak Hamiltonian. We study the effects of such an operator in a set of observables, in semileptonic B→D(*) modes as well as in semileptonic B and B s decays to excited positive-parity charmed mesons. © 2013 American Physical Society.

Cea P.,University of Bari | Cea P.,National Institute of Nuclear Physics, Italy
Monthly Notices of the Royal Astronomical Society | Year: 2010

We discuss the large-scale polarization of the cosmic microwave background induced by the anisotropy of the spatial geometry of our Universe. Assuming an eccentricity at decoupling of about 0.64 × 10-2, we find an average large-scale polarization Δ Tpol/T0 = (0.5-1.0) × 10-6. We suggest that the forthcoming polarization data at large scales from Planck will be able to discriminate between our proposal and the generally accepted re-ionization scenario. © 2010 The Author. Journal compilation © 2010 RAS.

Altomare D.F.,University of Bari | Giuratrabocchetta S.,University of Bari | Knowles C.H.,Queen Mary, University of London | Duyos A.M.,Hospital Universitari Mutua Terrassa | And 2 more authors.
British Journal of Surgery | Year: 2015

Background: Sacral nerve stimulation (SNS) has proven short- to medium-term effectiveness for the treatment of faecal incontinence (FI); fewer long-term outcomes have been presented and usually in small series. Here, the long-term effectiveness of SNS was evaluated in a large European cohort of patients with a minimum of 5 years' follow-up. Methods: Prospectively registered data from patients with FI who had received SNS for at least 5 years from ten European centres were collated by survey. Daily stool diaries, and Cleveland Clinic and St Mark's incontinence scores were evaluated at baseline, after implantation and at the last follow-up. SNS was considered successful when at least 50 per cent symptom improvement was maintained at last follow-up. Results: A total of 407 patients underwent temporary stimulation, of whom 272 (66·8 per cent) had an impulse generator implanted; 228 (56·0 per cent) were available for long-term follow-up at a median of 84 (i.q.r. 70-113) months. Significant reductions in the number of FI episodes per week (from median 7 to 0·25) and summative symptom scores (median Cleveland Clinic score from 16 to 7, St Mark's score from 19 to 6) were recorded after implantation (all P <0·001) and maintained in long-term follow-up. In per-protocol analysis, long-term success was maintained in 71·3 per cent of patients and full continence was achieved in 50·0 per cent; respective values based on intention-to-treat analysis were 47·7 and 33·4 per cent. Predictive analyses determined no significant association between pretreatment variables and successful outcomes. Risk of long-term failure correlated withminor symptom score improvement during the temporary test phase. Conclusion: SNS remains an effective treatment for FI in the long term for approximately half of the patients starting therapy. © 2015 BJS Society Ltd Published by John Wiley & Sons Ltd.

Stramaglia S.,University of Bari | Stramaglia S.,Cruces University Hospital | Stramaglia S.,Ikerbasque | M Cortes J.,Cruces University Hospital | And 2 more authors.
New Journal of Physics | Year: 2014

We analyze, by means of Granger causality (GC), the effect of synergy and redundancy in the inference (from time series data) of the information flow between subsystems of a complex network. While we show that fully conditioned GC (CGC) is not affected by synergy, the pairwise analysis fails to prove synergetic effects. In cases when the number of samples is low, thus making the fully conditioned approach unfeasible, we show that partially conditioned GC (PCGC) is an effective approach if the set of conditioning variables is properly chosen. Here we consider two different strategies (based either on informational content for the candidate driver or on selecting the variables with highest pairwise influences) for PCGC and show that, depending on the data structure, either one or the other might be equally valid. On the other hand, we observe that fully conditioned approaches do not work well in the presence of redundancy, thus suggesting the strategy of separating the pairwise links in two subsets: those corresponding to indirect connections of the CGC (which should thus be excluded) and links that can be ascribed to redundancy effects and, together with the results from the fully connected approach, provide a better description of the causality pattern in the presence of redundancy. Finally we apply these methods to two different real datasets. First, analyzing electrophysiological data from an epileptic brain, we show that synergetic effects are dominant just before seizure occurrences. Second, our analysis applied to gene expression time series from HeLa culture shows that the underlying regulatory networks are characterized by both redundancy and synergy. © 2014 IOP Publishing Ltd and Deutsche Physikalische Gesellschaft.

Colangelo P.,National Institute of Nuclear Physics, Italy | De Fazio F.,National Institute of Nuclear Physics, Italy | Giannuzzi F.,National Institute of Nuclear Physics, Italy | Giannuzzi F.,University of Bari | And 2 more authors.
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2012

All the available experimental information on open charm and beauty mesons is used to classify the observed states in heavy quark doublets. The masses of some of the still unobserved states are predicted, in particular in the beauty sector. Adopting an effective Lagrangian approach based on the heavy quark and chiral symmetry, individual decay rates and ratios of branching fractions are computed, with results useful to assign the quantum numbers to recently observed charmed states which still need to be properly classified. Implications and predictions for the corresponding beauty mesons are provided. The experimental results are already copious, and are expected to grow up thanks to the experiments at the LHC and to the future high-luminosity flavor and p-p̄ facilities. © 2012 American Physical Society.

Biancofiore P.,University of Bari | Biancofiore P.,National Institute of Nuclear Physics, Italy | Colangelo P.,National Institute of Nuclear Physics, Italy | De Fazio F.,National Institute of Nuclear Physics, Italy
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2012

We study the radiative B→Kη(′)γ decays, which are important to investigate CP violation, and are also relevant to assess the role of the exclusive modes induced by the b→sγ transition to saturate the inclusive B→X sγ decay rate. Moreover, these channels do not display the same hierarchy as B→Kη(′) modes, for which the decay into η′ is enhanced with respect to one into η. The three-body radiative decays reverse the role: we find that this experimentally observed behavior (although affected by a large uncertainty in the case of the η′) is reproduced in the theoretical analysis. We compute a B *→K form factor, needed for this study, using light cone QCD sum rules, and discuss a relation expected to hold in the large energy limit for the light meson. Finally, we examine B→Kηγ in two extensions of the standard model with universal extra dimensions, to investigate the sensitivity of this rare mode to such a kind of new physics effects. © 2012 American Physical Society.

Cea P.,University of Bari | Cea P.,National Institute of Nuclear Physics, Italy
Modern Physics Letters B | Year: 2012

We investigate the quantum Hall effect in graphene. We argue that in graphene in presence of an external magnetic field there is dynamical generation of mass by a rearrangement of the Dirac sea. We show that the mechanism breaks the lattice valley degeneracy only for the n = 0 Landau levels and leads to the new observed ν = ±1 quantum Hall plateaus. We suggest that our result can be tested by means of numerical simulations of planar Quantum Electro Dynamics with dynamical fermions in an external magnetic fields on the lattice. © 2012 World Scientific Publishing Company.

Fanizza G.,University of Bari | Tedesco L.,National Institute of Nuclear Physics, Italy
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2015

In this paper, we introduce a Lemaître-Tolman-Bondi (LTB) Bianchi type I (plane symmetric) model of the Universe. We study and solve Einstein field equations. We investigate the effects of such a model of the Universe; in particular, these results are important in understanding the effect of the combined presence of an inhomogeneous and anisotropic universe. The observational magnitude-redshift data deviated from the UNION 2 catalog have been analyzed in the framework of this LTB anisotropic universe, and the fit has been achieved without the inclusion of any dark energy. © 2015 American Physical Society.

Pascazio S.,University of Bari | Pascazio S.,National Institute of Nuclear Physics, Italy
Open Systems and Information Dynamics | Year: 2014

This is a primer on the quantum Zeno effect, addressed to students and researchers with no previous knowledge on the subject. The prerequisites are the Schrödinger equation and the von Neumann notion of projective measurement. © 2014 World Scientific Publishing Company.

Colangelo P.,National Institute of Nuclear Physics, Italy | De Fazio F.,National Institute of Nuclear Physics, Italy | Sanz-Cillero J.J.,National Institute of Nuclear Physics, Italy | Giannuzzi F.,University of Bari | Nicotri S.,University of Bari
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2012

We consider the vertex function of two vector and one axial-vector currents using the soft-wall holographic model of QCD with the Chern-Simons term. Two structure functions w L and w T describe such a vertex in the special case in which one of the two vector currents corresponds to an on-shell soft photon. We briefly review the QCD results for these functions, obtained from triangular loop diagrams with quarks having mass m q=0 or m q 0, we compute w L and w T in the soft-wall model and compare the outcome to the QCD findings. We also calculate and discuss the two-point Π VV-Π AA correlation function, together with a few low-energy constants, which turn out to be close to the QCD results. Finally, we comment on a relation proposed by Son and Yamamoto between w T and Π VV-Π AA. © 2012 American Physical Society.

Palmer S.C.,University of Otago | Mavridis D.,University of Ioannina | Navarese E.,Nicolaus Copernicus University | Craig J.C.,University of Sydney | And 9 more authors.
The Lancet | Year: 2015

Background The comparative efficacy and safety of pharmacological agents to lower blood pressure in adults with diabetes and kidney disease remains controversial. We aimed to investigate the benefits and harms of blood pressure-lowering drugs in this population of patients. Methods We did a network meta-analysis of randomised trials from around the world comparing blood pressure-lowering agents in adults with diabetic kidney disease. Electronic databases (the Cochrane Collaboration, Medline, and Embase) were searched systematically up to January, 2014, for trials in adults with diabetes and kidney disease comparing orally administered blood pressure-lowering drugs. Primary outcomes were all-cause mortality and end-stage kidney disease. We also assessed secondary safety and cardiovascular outcomes. We did random-effects network meta-analysis to obtain estimates for primary and secondary outcomes and we presented these estimates as odds ratios or standardised mean differences with 95% CIs. We ranked the comparative effects of all drugs against placebo with surface under the cumulative ranking (SUCRA) probabilities. Findings 157 studies comprising 43 256 participants, mostly with type 2 diabetes and chronic kidney disease, were included in the network meta-analysis. No drug regimen was more effective than placebo for reducing all-cause mortality. However, compared with placebo, end-stage renal disease was significantly less likely after dual treatment with an angiotensin-receptor blocker (ARB) and an angiotensin-converting-enzyme (ACE) inhibitor (odds ratio 0·62, 95% CI 0·43-0·90) and after ARB monotherapy (0·77, 0·65-0·92). No regimen significantly increased hyperkalaemia or acute kidney injury, although combined ACE inhibitor and ARB treatment had the lowest rank among all interventions because of borderline increases in estimated risks of these harms (odds ratio 2·69, 95% CI 0·97-7·47 for hyperkalaemia; 2·69, 0·98-7·38 for acute kidney injury). Interpretation No blood pressure-lowering strategy prolonged survival in adults with diabetes and kidney disease. ACE inhibitors and ARBs, alone or in combination, were the most effective strategies against end-stage kidney disease. Any benefits of combined ACE inhibitor and ARB treatment need to be balanced against potential harms of hyperkalaemia and acute kidney injury. Funding Canterbury Medical Research Foundation, Italian Medicines Agency. © 2015 Elsevier Ltd.

Elia G.,Northumbria University | Amorosi A.,University of Bari | Chan A.H.C.,University of Birmingham | Kavvadas M.J.,National Technical University of Athens
Geotechnique | Year: 2011

The paper studies the seismic behaviour of an existing homogeneous earth dam using a fully coupled finite element effective stress approach in conjunction with a recently developed multi-surface, elasto-plastic constitutive model for structured soils. The model is calibrated using laboratory test results for the embankment material and the foundation soils. The initial state variables (stress, hardening parameters) are determined by simulating a simplified geological history of the foundation soil, dam construction stages and reservoir impounding, prior to the application of the earthquake shaking at the bedrock level. The paper critically reviews the role of the constitutive model parameters, the hysteretic damping introduced by the model and the additional viscous damping parameters in the accumulation of permanent displacements and in the development and subsequent dissipation of excess pore water pressures due to the seismic loading. The analyses, carried out with reference to a set of earthquake records related to different return periods, show that the overall behaviour of the system in terms of displacements is characterised by a more enhanced deformation pattern of the downstream slope as compared with the upstream one. The large plastic strains accumulation induced throughout the shaking is followed by the development of excess pore water pressures inside the dam and the foundation deposit. Nonetheless, the results are indicative of a satisfactory dynamic performance of the dam, even when subjected to severe seismic loading conditions.

Barile F.,University of Bari | Barile F.,National Institute of Nuclear Physics, Italy
EPJ Web of Conferences | Year: 2013

Nuclear matter under extreme conditions of temperature and density can be investigated in ultrarelativistic heavy-ion collisions. The measurement of transverse momentum (pT) distributions and yields of identified particles is a fundamental step in understanding collective and thermal properties of the matter produced in such collisions. At intermediate transverse momentum, it allows for testing the "recombination models" where hadrons could be formed by the coalescence of quarks from a deconfined quark-gluon plasma (QGP). At higher transverse momenta, particle spectra allow one to investigate the mechanism of parton energy loss in the hot and dense hadronic medium. The measurement of spectra in pp collisions not only provides the baseline for the heavy-ion data but also allows for the tuning and optimization of QCD-inspired models. The latest ALICE results on identified and inclusive light-flavour charged particles in pp collisions at √s = 0.9, 2.76 and 7 TeV and Pb-Pb collisions at √sNN = 2.76 TeV is reviewed. pT spectra, yields and ratios in pp as a function of the collision energy is shown and compared to previous experiments and Monte Carlo predictions. Recent Pb-Pb results in different centrality intervals is presented and compared to √sNN = 200 GeV Au-Au collisions at RHIC. Comparison with predictions from thermal and hydrodynamic models is also discussed. © 2013 Owned by the authors, published by EDP Sciences.

Biancofiore P.,National Institute of Nuclear Physics, Italy | Biancofiore P.,University of Bari | Colangelo P.,National Institute of Nuclear Physics, Italy | De Fazio F.,National Institute of Nuclear Physics, Italy
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2014

Recent LHCb measurements show small discrepancies with respect to the Standard Model (SM) predictions in selected angular distributions of the mode B0→K*0μ+μ-. The possibility of explaining such tensions within theories beyond the SM crucially depends on the size of the deviations of the Wilson coefficients of the effective Hamiltonian for this mode, in comparison to their SM values. We analyze this issue in the framework of the Randall-Sundrum model with custodial protection (RSc); in our study we also consider the mode with τ leptons in the final state. We discuss the small deviations of RSc results from SM ones, found scanning the parameter space of the model. © 2014 American Physical Society.

Cunden F.D.,University of Bristol | Cunden F.D.,University of Bari | Cunden F.D.,National Institute of Nuclear Physics, Italy
Physical Review E - Statistical, Nonlinear, and Soft Matter Physics | Year: 2015

We derive the joint distribution of the moments TrQκ(κ≥1) of the Wigner-Smith matrix for a chaotic cavity supporting a large number of scattering channels n. This distribution turns out to be asymptotically Gaussian, and we compute explicitly averages and covariances. The results are in a compact form and have been verified numerically. The general methodology of proof and computations has a wide range of applications. © 2015 American Physical Society.

Indrio F.,University of Bari | Neu J.,University of Florida
Current Opinion in Pediatrics | Year: 2011

PURPOSE OF REVIEW: The increasing use of probiotics in neonates deserves scrutiny of the therapeutic as well as potentially harmful effects of these bacteria. In this review we describe the possible application of probiotics in the more common diseases in the neonatal period. RECENT FINDINGS: Recent advances in our capability to identify microbes and their function in the gastrointestinal tract offer exciting opportunities to discover the pathophysiology of enigmatic diseases such as necrotizing enterocolitis (NEC) and late-onset sepsis (LOS) in the neonate. The relationship of the resident intestinal microbes to neural and muscular processes such as intestinal motility and neurodevelopment are also being evaluated. SUMMARY: We focus on the possibility of the application of probiotics for disorders of motility in the infant, NEC and LOS. Here we will summarize some of the recent advances in these areas as they relate to clinical practice and discuss areas where additional research is needed. © 2011 Lippincott Williams & Wilkins, Inc.

Chruscinski D.,Nicolaus Copernicus University | Kossakowski A.,Nicolaus Copernicus University | Kossakowski A.,University of Naples Federico II | Pascazio S.,University of Bari | Pascazio S.,National Institute of Nuclear Physics, Italy
Physical Review A - Atomic, Molecular, and Optical Physics | Year: 2010

If the dynamics of an open quantum system is non-Markovian, its asymptotic state strongly depends on the initial conditions, even if the dynamics possesses an invariant state. This is the very essence of memory effects. In particular, the asymptotic state can remember and partially preserve its initial entanglement. Interestingly, even if the non-Markovian evolution relaxes to an equilibrium state, this state needs not be invariant. Therefore, the noninvariance of equilibrium becomes a clear sign of non-Markovianity. © 2010 The American Physical Society.

News Article | December 21, 2016

Sounds, such as music and noise, are capable of reliably affecting individuals' moods and emotions, possibly by regulating brain dopamine, a neurotransmitter strongly involved in emotional behavior and mood regulation Sounds, such as music and noise, are capable of reliably affecting individuals' moods and emotions, possibly by regulating brain dopamine, a neurotransmitter strongly involved in emotional behavior and mood regulation. However, the relationship of sound environments with mood and emotions is highly variable across individuals. A putative source of variability is genetic background. In this regard, a new imaging genetics study directed by Professor Elvira Brattico from Aarhus University and conducted in two Italian hospitals in collaboration with the University of Helsinki (Finland) has provided the first evidence that the effects of music and noise on affective behavior and brain physiology are associated with genetically determined dopamine functionality. In particular, this study, published in the journal Neuroscience, revealed that a functional variation in dopamine D2 receptor gene (DRD2 rs1076560) modulates the impact of music as opposed to noise on mood states and emotion-related prefrontal and striatal brain activity, evidencing a differential susceptibility for the affect-modulatory effects of music and noise on the GG and GT genotypes. In more details, results showed mood improvement after music exposure in GG subjects and mood deterioration after noise exposure in GT subjects. Moreover, the music as opposed to noise environment decreased the striatal activity of GT subjects as well as the prefrontal activity of GG subjects while processing emotional faces. These results are novel in identifying a biological source of variability in the impact of sound environments on emotional responses. The first author of the study, Tiziana Quarto, Ph.D. student at University of Helsinki under supervision of Prof. Brattico, further comments: "Our approach allowed the observation of the link between genes and phenotypes via a true biological path that goes from functional genetic variations (for which the effects on molecular function is known) to brain physiology subtending behavior. The use of this approach is especially important when the investigated behavior is complex and very variable across subjects, because this means that many biological factors are involved". "This study represents the first use of the imaging genetics approach in the field of music and sounds in general. We are really excited about our results because they suggest that even a non-pharmacological intervention such as music, might regulate mood and emotional responses at both the behavioral and neuronal level," says Professor Elvira Brattico. "More importantly, these findings encourage the search for personalized music-based interventions for the treatment of brain disorders associated with aberrant dopaminergic neurotransmission as well as abnormal mood and emotion-related brain activity". Principal Investigator on the study was: Professor Elvira Brattico, Center for Music in the Brain, Department of Clinical Medicine, Aarhus University. The study was performed in collaboration with: Cognitive Brain Research Unit, Institute of Behavioral Science, University of Helsinki, Helsinki, Finland; Department of Basic Medical Sciences, Neuroscience, and Sense Organs, University of Bari 'Aldo Moro', Bari, Italy.

Arnesano F.,University of Bari | Banci L.,University of Florence | Bertini I.,University of Florence | Felli I.C.,University of Florence | And 2 more authors.
Journal of the American Chemical Society | Year: 2011

Among anticancer therapeutics, platinum-based drugs have a prominent role. They carry out their antitumor activity by forming stable adducts with DNA, thus interfering with replication and transcription processes. Cellular uptake of these drugs is tightly connected to copper transport. The major Cu(I) influx transporter Ctr1 has been found to mediate transport of cisplatin and its analogues. Evidence also suggests that ATP7A and ATP7B mediate cisplatin sequestration and efflux from cells, thus influencing drug resistance. The copper-chaperone Atox1, which normally binds Cu(I) via two cysteines and delivers the metal to ATP7A/B, has also been reported to interact with cisplatin in in vitro experiments. In the present investigation we apply a combined approach, using solution and in-cell NMR spectroscopy methods, to probe intracellular drug delivery and interaction of cisplatin with Atox1. The intracellular environment provides itself the suitable conditions for the preservation of the protein in its active form. Initially a {Pt(NH 3) 2}-Atox1 adduct is formed. At longer reaction time we observed protein dimerization and loss of the ammines. Such a process is reminiscent of the copper-promoted formation of Atox1 dimers which have been proposed to be able to cross the nuclear membrane and act as a transcription factor. We also show that overexpression of Atox1 in E. coli reduces the amount of DNA platination and, consequently, the degree of cell filamentation. © 2011 American Chemical Society.

Bertini A.,University of Florence | Toti F.,University of Florence | Marino M.,University of Bari | Ciaranfi N.,University of Bari
Quaternary International | Year: 2015

Pollen analysis of the Montalbano Jonico marine succession (MJS), southern Italy, provides a continuous vegetational record between 858 ka and 745.13 ka which includes Marine Isotope Stage (MIS) 19, now considered the closest orbital analogue to the Holocene. A comparison between paleoclimate proxies and global signals of past climate change allows the pollen record to be interpreted in terms of major environmental and climate modifications through MIS 21-18 at the orbital- and sub-orbital-scale. This is also central to understanding migration patterns of the genus Homo. Interglacials are expressed by the dominance of a mesophilic vegetation typical of a (warm) temperate and relatively humid climate. Deciduous Quercus dominated fully temperate arboreal forest already devoid of subtropical taxa. Wooded steppes to steppes expanded during glacials when cold and dry conditions prevailed. At MJS the main expansion of temperate forest, dominated by broad-leaved trees, correlates to MIS 19.3, whereas the expansion of steppe vegetation, during drier conditions, marks MIS 19.2 directly above the volcaniclastic layer V4, dated at 773.9 ± 1.3 ka. More intensively arid conditions developed during MIS 20 and MIS 18; the Pollen Temperature Index reaches its minimum in uppermost MIS 20 in agreement with a significant cold and arid climate phase of wide significance in the North Hemisphere, as documented by prominent peaks in North Atlantic ice rafted debris (IRD) and Mediterranean aeolian dust records. On the other hand, Artemisia, a significant component of steppes, shows its maximum expansion during earlier phases of MIS 18. Millennial to sub-millenial-scale climate variability is evidenced by two abrupt short-term pollen events within MIS 19.3, which show a dominant increase of the cosmopolitan herbaceous component at around 783.54 ka and 774.84 ka, respectively. The vegetational and inferred climate changes for MIS 19 offer two possibilities: (1) to investigate the interglacial climate variability and discuss the linkage between climate and changes in geomagnetic field intensity close to the Matuyama-Brunhes paleomagnetic boundary (MBB), and (2) to help evaluate the role of the MBB in defining the Middle Pleistocene global boundary stratotype section and point (GSSP). With respect to point 2, a comparison of data at MJS with the pollen record at the nearby and coeval Valle di Manche section is relevant and evidences the complex response of vegetation to climate events possibly under the effects of both astronomical and local factors. © 2015 Elsevier Ltd and INQUA.

Mulla M.Y.,University of Bari | Tuccori E.,University of Manchester | Magliulo M.,University of Bari | Lattanzi G.,University of Bari | And 3 more authors.
Nature Communications | Year: 2015

Peripheral events in olfaction involve odorant binding proteins (OBPs) whose role in the recognition of different volatile chemicals is yet unclear. Here we report on the sensitive and quantitative measurement of the weak interactions associated with neutral enantiomers differentially binding to OBPs immobilized through a self-assembled monolayer to the gate of an organic bio-electronic transistor. The transduction is remarkably sensitive as the transistor output current is governed by the small capacitance of the protein layer undergoing minute changes as the ligand-protein complex is formed. Accurate determination of the free-energy balances and of the capacitance changes associated with the binding process allows derivation of the free-energy components as well as of the occurrence of conformational events associated with OBP ligand binding. Capacitance-modulated transistors open a new pathway for the study of ultra-weak molecular interactions in surface-bound protein-ligand complexes through an approach that combines bio-chemical and electronic thermodynamic parameters. © 2015 Macmillan Publishers Limited. All rights reserved.

Salvatore N.,University of Bari | Caponio A.,University of Bari | Neri F.,University of Jyväskylä | Stasi S.,University of Bari | Cascella G.L.,University of Bari
IEEE Transactions on Industrial Electronics | Year: 2010

This paper proposes the employment of the differential evolution (DE) to offline optimize the covariance matrices of a new reduced delayed-state Kalman-filter (DSKF)-based algorithm which estimates the stator-flux linkage components, in the stationary reference frame, to realize sensorless control of induction motors (IMs). The DSKF-based algorithm uses the derivatives of the stator-flux components as mathematical model and the stator-voltage equations as observation model so that only a vector of four variables has to be offline optimized. Numerical results, carried out using a low-speed training test, show that the proposed DE-based approach is very promising and clearly outperforms a classical local search and three popular metaheuristics in terms of quality of the final solution for the problem considered in this paper. A novel simple stator-flux-oriented sliding-mode (SFO-SM) control scheme is online used in conjunction with the optimized DSKF-based algorithm to improve the robustness of the sensorless IM drive at low speed. The SFO-SM control scheme has closed loops of torque and stator-flux linkage without proportionalplus- integral controllers so that a minimum number of gains has to be tuned. Copyright © 2010 IEEE.

Walde P.,ETH Zurich | Umakoshi H.,Osaka University | Stano P.,Third University of Rome | Mavelli F.,University of Bari
Chemical Communications | Year: 2014

This article deals with artificial vesicles and their membranes as reaction promoters and regulators. Among the various molecular assemblies which can form in an aqueous medium from amphiphilic molecules, vesicle systems are unique. Vesicles compartmentalize the aqueous solution in which they exist, independent on whether the vesicles are biological vesicles (existing in living systems) or whether they are artificial vesicles (formed in vitro from natural or synthetic amphiphiles). After the formation of artificial vesicles, their aqueous interior (the endovesicular volume) may become-or may be made-chemically different from the external medium (the exovesicular solution), depending on how the vesicles are prepared. The existence of differences between endo- and exovesicular composition is one of the features on the basis of which biological vesicles contribute to the complex functioning of living organisms. Furthermore, artificial vesicles can be formed from mixtures of amphiphiles in such a way that the vesicle membranes become molecularly, compositionally and organizationally highly complex, similarly to the lipidic matrix of biological membranes. All the various properties of artificial vesicles as membranous compartment systems emerge from molecular assembly as these properties are not present in the individual molecules the system is composed of. One particular emergent property of vesicle membranes is their possible functioning as promoters and regulators of chemical reactions caused by the localization of reaction components, and possibly catalysts, within or on the surface of the membranes. This specific feature is reviewed and highlighted with a few selected examples which range from the promotion of decarboxylation reactions, the selective binding of DNA or RNA to suitable vesicle membranes, and the reactivation of fragmented enzymes to the regulation of the enzymatic synthesis of polymers. Such type of emergent properties of vesicle membranes may have been important for the prebiological evolution of protocells, the hypothetical compartment systems preceding the first cells in those chemical and physico-chemical processes that led to the origin of life. This journal is © the Partner Organisations 2014.

Mininno E.,University of Jyväskylä | Mininno E.,Academy of Finland | Neri F.,Academy of Finland | Cupertino F.,University of Bari | Naso D.,Polytechnic of Bari
IEEE Transactions on Evolutionary Computation | Year: 2011

This paper proposes the compact differential evolution (cDE) algorithm. cDE, like other compact evolutionary algorithms, does not process a population of solutions but its statistic description which evolves similarly to all the evolutionary algorithms. In addition, cDE employs the mutation and crossover typical of differential evolution (DE) thus reproducing its search logic. Unlike other compact evolutionary algorithms, in cDE, the survivor selection scheme of DE can be straightforwardly encoded. One important feature of the proposed cDE algorithm is the capability of efficiently performing an optimization process despite a limited memory requirement. This fact makes the cDE algorithm suitable for hardware contexts characterized by small computational power such as micro-controllers and commercial robots. In addition, due to its nature cDE uses an implicit randomization of the offspring generation which corrects and improves the DE search logic. An extensive numerical setup has been implemented in order to prove the viability of cDE and test its performance with respect to other modern compact evolutionary algorithms and state-of-the-art population-based DE algorithms. Test results show that cDE outperforms on a regular basis its corresponding population-based DE variant. Experiments have been repeated for four different mutation schemes. In addition cDE outperforms other modern compact algorithms and displays a competitive performance with respect to state-of-the-art population-based algorithms employing a DE logic. Finally, the cDE is applied to a challenging experimental case study regarding the on-line training of a nonlinear neural-network-based controller for a precise positioning system subject to changes of payload. The main peculiarity of this control application is that the control software is not implemented into a computer connected to the control system but directly on the micro-controller. Both numerical results on the test functions and experimental results on the real-world problem are very promising and allow us to think that cDE and future developments can be an efficient option for optimization in hardware environments characterized by limited memory. © 2010 IEEE.

Caggiani M.C.,University Pierre and Marie Curie | Caggiani M.C.,University of Bari | Colomban P.,University Pierre and Marie Curie
Journal of Raman Spectroscopy | Year: 2011

Five French pastels and a sanguine drawing dating from the 17th to the 20th century were studied by Raman spectroscopy. Different operative conditions were used: the pastels were investigated through their protective glass, and the results obtained were compared with those obtained after removing the glass and after sampling a micrometric particle of pigment. Different parameters (wavelengths, powers of excitation and objectives) were tested in order to assess the optimal procedure of analysis for this fragile work of art. The results obtained for black (carbons), yellow (chrome/cobalt yellow), red (lead oxide, vermillion, orpiment), brown (red lead and chrome yellow), blue (Prussian blue, lapis lazuli/ultramarine), green (mixture of above blue and yellow pigments) and white (calcite, lead white, anatase) pigments are presented and the consistency of the pigments' period of use with the dating proposed for each pastel is evaluated. In one of the pastels, the blackening of the carnation colour made of an unstable mixture of lead white, red lead and vermilion was studied. Raman spectroscopy is used to investigate six French pastels dating from the 17th to the 20th century experimenting different operative conditions and parameters, in order to assess the optimal procedure of analysis for this fragile kind of work of art through their protective glass. The results obtained for the different pigments, the relative criteria of dating and the blackening process in one of the pastels are presented. Copyright © 2010 John Wiley & Sons, Ltd.

Caggiani M.C.,University Pierre and Marie Curie | Caggiani M.C.,University of Bari | Colomban P.,University Pierre and Marie Curie
Journal of Raman Spectroscopy | Year: 2011

To get black decorations requires high ceramic technology and there are different ways of achieving this. Their identification can be very useful to discriminate between different manufactures or periods of production but this information is often very hard to achieve because of their strong absorption of the illuminating laser beam, whatever the wavelength used, causing a very low scattering intensity and, in case of power increase, a transformation of phase which may lead to the misinterpretation of the spectra obtained. We test the use of five instruments with different characteristics (wavelength and power of excitation, spectral resolution, filters and microscope) applied to a group of heterogeneous samples which have in common the presence of a black glaze. The results obtained (manganese oxides, cobalt oxides or a mixture of the two even with the addition of haematite) are compared considering the different methodologies used and leading to a preference towards high-sensitivity rather than high-resolution spectrometers, notch-filtered rather than edge-filtered instruments and microscopic configuration used on freshly created cross-sections. The importance of the objective choice is demonstrated. Small grains may be preferred. The problems encountered in the analysis of dark to black ceramic pigments are discussed. Advantages of high-sensitivity low-cost instruments versus more expensive ones are pointed out. The importance of excitation power control is emphasised. Copyright © 2010 John Wiley & Sons, Ltd.

Neri F.,University of Jyväskylä | Caponio A.,University of Bari
International Journal of Bio-Inspired Computation | Year: 2010

This paper proposes a novel variant of differential evolution (DE) tailored to the optimisation of noisy fitness functions. The proposed algorithm, namely noise analysis differential evolution (NADE), combines the stochastic properties of a randomised scale factor and a statistically rigorous test which supports one-to-one spawning survivor selection that automatically selects a proper sample size and then selects, among parent and offspring, the most promising solution. The actions of these components are separately analysed and their combined effect on the algorithmic performance is studied by means of a set of numerous and various test functions perturbed by Gaussian noise. Various noise amplitudes are considered in the result section. The performance of the NADE has been extensively compared with a classical algorithm and two modern metaheuristics designed for optimisation in the presence of noise. Numerical results show that the proposed NADE has very good performance with most of the problems considered in the benchmark set. The NADE seems to be able to detect high quality solutions despite the noise and display high performance in terms of robustness. Copyright © 2010 Inderscience Enterprises Ltd.

Ribatti D.,University of Bari | Baiguera S.,University of Florence
Expert Opinion on Investigational Drugs | Year: 2013

Introduction: Therapeutic angiogenesis is a strategy of inducing new collateral vessels and stimulating new capillaries that enhance tissue oxygen exchange in ischemic cardiovascular disorders, including acute myocardial infarction, chronic cardiac ischemia, peripheral artery disease and stroke. Areas covered: Over the last 10 years, promising results of early clinical trials have generated great expectation on the potential of therapeutic angiogenesis. However, even if large randomized placebo-controlled and double-blinded Phase II clinical trials have confirmed the feasibility, safety and potential effectiveness of therapeutic angiogenesis, they provided very limited evidence of its efficacy in terms of clinical benefit. Expert opinion: Results of the latest trials on therapeutic angiogenesis have not provided satisfactory results. Much is still unknown about the optimal delivery of angiogenic factors. Trials using alternative growth factors, dose regimens and methods of delivery are needed to enhance the treatment benefit of therapeutic angiogenesis. © 2013 Informa UK, Ltd.

Baiguera S.,University of Florence | Ribatti D.,University of Bari
Angiogenesis | Year: 2013

One of the main limitation in obtaining thick, 3-dimensional viable engineered constructs is the inability to provide a sufficient and functional blood vessel system essential for the in vitro survival and the in vivo integration of the construct. Different strategies have been proposed to simulate the ingrowth of new blood vessels into engineered tissue, such as the use of growth factors, fabrication scaffold technologies, in vivo prevascularization and cell-based strategies, and it has been demonstrated that endothelial cells play a central role in the neovascularization process and in the control of blood vessel function. In particular, different "environmental" settings (origin, presence of supporting cells, biomaterial surface, presence of hemodynamic forces) strongly influence endothelial cell function, angiogenic potential and the in vivo formation of durable vessels. This review provides an overview of the different techniques developed so far for the vascularization of tissue-engineered constructs (with their advantages and pitfalls), focusing the attention on the recent development in the cell-based vascularization strategy and the in vivo applications. © 2012 Springer Science+Business Media Dordrecht.

Baiguera S.,University of Florence | Macchiarini P.,University of Florence | Ribatti D.,University of Bari
Journal of Biomedical Materials Research - Part B Applied Biomaterials | Year: 2012

In tissue engineering approach, the scaffold plays a key role for a suitable outcome of cell-scaffold interactions and for the success of tissue healing and regeneration. As a consequence, the characterization of scaffold properties and the in vivo evaluation of tissue responses and effects result to be essential in the development of suitable implantable device. Among the in vivo methods, the chick embryo chorioallantoic membrane (CAM) assay represents a rather simple and cost-effective procedure to study the biocompatibility responses of graft materials. CAM is indeed characterized by low experiment costs, simplicity, relative speed in obtaining the expected results, limited ethical concern, no need of high-level technical skill, and the absence of a mature immune system, resulting in an inexpensive, simple, and practical method to evaluate and characterize tissue-engineered constructs. The results till now obtained suggest that CAM assay can be used as a pre-screening assay, before in vivo animal studies, to determine whether the scaffold is liable to cause an adverse reaction and to evaluate its future enhancement of existing materials for tissue engineering. A review of the more recent results related to the use of CAM for in vivo biomaterial property evaluation is herein reported. © 2012 Wiley Periodicals, Inc.

Brugnano L.,University of Florence | Iavernaro F.,University of Bari
Computer Physics Communications | Year: 2012

We introduce a family of fourth-order two-step methods that preserve the energy function of canonical polynomial Hamiltonian systems. As is the case with linear mutistep and one-leg methods, a prerogative of the new formulae is that the associated nonlinear systems to be solved at each step of the integration procedure have the very same dimension of the underlying continuous problem. The key tools in the new methods are the line integral associated with a conservative vector field (such as the one defined by a Hamiltonian dynamical system) and its discretization obtained by the aid of a quadrature formula. Energy conservation is equivalent to the requirement that the quadrature is exact, which turns out to be always the case in the event that the Hamiltonian function is a polynomial and the degree of precision of the quadrature formula is high enough. The non-polynomial case is also discussed and a number of test problems are finally presented in order to compare the behavior of the new methods to the theoretical results. © 2012 Elsevier B.V. All rights reserved.

Dal Monte M.,University of Pisa | Casini G.,University of Pisa | Filippi L.,University of Florence | Nicchia G.P.,University of Bari | And 2 more authors.
Journal of Molecular Medicine | Year: 2013

β-adrenergic signaling is thought to facilitate cancer progression and blockade of β-adrenergic receptors (β-ARs) may slow down tumor growth. A possible role of β3-ARs in tumor growth has not been investigated so far and the lack of highly specific antagonists makes difficult the evaluation of this role. In the present study, β3-AR expression in mouse B16F10 melanoma cells was demonstrated and the effects of two widely used β3-AR blockers, SR59230A and L-748,337, were evaluated in comparison with propranolol, a β1-/β2-AR blocker with poor affinity for β3-ARs, and with siRNAs targeting specific β-ARs. Both SR59230A and L-748,337 reduced cell proliferation and induced apoptosis, likely through the involvement of the inducible isoform of nitric oxide synthase. In addition, hypoxia upregulated β3-ARs and vascular endothelial growth factor (VEGF) in B16F10 cells, whereas SR59230A or L-748,337 prevented the hypoxia-induced VEGF upregulation. Melanoma was induced in mice by inoculation of B16F10 cells. Intra-tumor injections of SR59230A or L-748,337 significantly reduced melanoma growth by reducing cell proliferation and stimulating apoptosis. SR59230A or L-748,337 treatment also resulted in significant decrease of the tumor vasculature. The decrease in tumor vasculature was due to apoptosis of endothelial cells and not to downregulation of angiogenic factors. These results demonstrate that SR59230A and L-748,337 significantly inhibit melanoma growth by reducing tumor cell proliferation and activating tumor cell death. In addition, both drugs reduce tumor vascularization by inducing apoptosis of endothelial cells. Together, these findings indicate β3-ARs as promising, novel targets for anti-cancer therapy. Key message: β3-ARs are expressed in B16F10 melanoma cells β3-ARs are involved in B16F10 cell proliferation and apoptosis Reduced β3-AR function decreases the growth of melanoma induced by B16F10 cell inoculation Drugs targeting β3-ARs reduce tumor vasculature β3-ARs can be regarded as promising, novel targets for anti-cancer therapy © 2013 Springer-Verlag Berlin Heidelberg.

Carloni V.,University of Florence | Mazzocca A.,University of Bari | Mello T.,University of Florence | Galli A.,University of Florence | Capaccioli S.,University of Florence
Oncogene | Year: 2013

Chemoresistance is an important concern in the treatment of metastatic colon cancer. It may emerge through selection of clones that are inherently resistant from the outset or through mechanisms acquired during treatment. Cell fusion represents an efficient means of rapid phenotypic evolution that make cells with new properties at a rate exceeding that achievable by random mutagenesis. Here, we first identified a number of proteins involved in cell fusion using a shotgun proteomics approach, then we investigated the role of these proteins namely tetraspanin CD81/CD9, ADAM10, GTP-binding protein α13, radixin, myosin regulatory light chain and RhoA in the regulation of colon cancer cell fusion. We also found a previously unrecognized role of ADAM10, Gα13 and RhoA in promoting cell fusion. Finally, we show that the occurrence of cell fusion in a metastatic model of colon carcinoma causes the appearance of cells resistant to both 5-fluorouracil and oxaliplatin. These findings highlight the importance of cell fusion in cancer progression and raise significant implications for overcoming chemoresistance in metastatic colon cancer. © 2013 Macmillan Publishers Limited. All rights reserved 0950-9232/13.

Brugnano L.,University of Florence | Iavernaro F.,University of Bari
AIP Conference Proceedings | Year: 2012

The numerical solution of conservative problems, i.e., problems characterized by the presence of constants of motion, is of great interest in the computational practice. Such problems, indeed, occur in many real-life applications, ranging from the nano-scale of molecular dynamics to the macro-scale of celestial mechanics. Often, they are formulated as Hamiltonian problems. Concerning such problems, recently the energy conserving methods named Hamiltonian Boundary Value Methods (HBVMs) have been introduced. In this paper we review the main facts about HBVMs, as well as the existing connections with other approaches to the problem. A few new directions of investigation will be also outlined. In particular, we will place emphasis on the last contributions to the field of Prof. Donato Trigiante, passed away last year. © 2012 American Institute of Physics.

Brugnano L.,University of Florence | Iavernaro F.,University of Bari
AIP Conference Proceedings | Year: 2012

We show that many Runge-Kutta methods derived in the framework of Geometric Integration can be elegantly formalized by using special matrices defined by a suitable polynomial basis. © 2012 American Institute of Physics.

Cruz-Monteagudo M.,University of Porto | Cruz-Monteagudo M.,Santa Clara University | Medina-Franco J.L.,Mayo Medical School | Perez-Castillo Y.,Santa Clara University | And 3 more authors.
Drug Discovery Today | Year: 2014

The impact activity cliffs have on drug discovery is double-edged. For instance, whereas medicinal chemists can take advantage of regions in chemical space rich in activity cliffs, QSAR practitioners need to escape from such regions. The influence of activity cliffs in medicinal chemistry applications is extensively documented. However, the 'dark side' of activity cliffs (i.e. their detrimental effect on the development of predictive machine learning algorithms) has been understudied. Similarly, limited amounts of work have been devoted to propose potential solutions to the drawbacks of activity cliffs in similarity-based approaches. In this review, the duality of activity cliffs in medicinal chemistry and computational approaches is addressed, with emphasis on the rationale and potential solutions for handling the 'ugly face' of activity cliffs. © 2014 Elsevier Ltd.

Kuchler A.,ETH Zurich | Yoshimoto M.,Yamaguchi University | Luginbuhl S.,ETH Zurich | Mavelli F.,University of Bari | Walde P.,ETH Zurich
Nature Nanotechnology | Year: 2016

Within each biological cell, surface- and volume-confined enzymes control a highly complex network of chemical reactions. These reactions are efficient, timely, and spatially defined. Efforts to transfer such appealing features to in vitro systems have led to several successful examples of chemical reactions catalysed by isolated and immobilized enzymes. In most cases, these enzymes are either bound or adsorbed to an insoluble support, physically trapped in a macromolecular network, or encapsulated within compartments. Advanced applications of enzymatic cascade reactions with immobilized enzymes include enzymatic fuel cells and enzymatic nanoreactors, both for in vitro and possible in vivo applications. In this Review, we discuss some of the general principles of enzymatic reactions confined on surfaces, at interfaces, and inside small volumes. We also highlight the similarities and differences between the in vivo and in vitro cases and attempt to critically evaluate some of the necessary future steps to improve our fundamental understanding of these systems. © 2016 Macmillan Publishers Limited.

Agency: European Commission | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-2011-ITN | Award Amount: 3.93M | Year: 2011

With over 3 million new cases and 1.5 million arising deaths each year in Europe, cancer is a major public health problem with an urgent need for new therapies. This proposal builds upon mounting evidence that ion channels and transporters underlie many of the hallmarks of cancer. Thus, proteins involved in membrane transport, long known as important drug targets in other pathologies (channelopathies), are a new class of therapeutic and/or diagnostic targets in oncology. IonTraC is first to propose a systematic analysis of the expression, function, as well as therapeutic and diagnostic potential of proteins involved in ion transport (the transportome) in cancer. This paradigm will be implemented in pancreatic ductal adenocarcinoma (PDAC) which has one of the worst prognoses of all cancers, with an overall 5-year survival rate of less than 5%. IonTraC thereby provides the framework for an inter- and supra-disciplinary training for early stage researchers in a highly innovative, exponentially growing field in oncology which will have a major impact on other disciplines such as immunology and angiology as well. The main objectives of IonTraC are: to provide a scientific and methodological platform for supra-disciplinary training of early stage researchers in and beyond the fields of ion transport and oncology to provide an inter-sectoral training programme with special focus on career development of young researchers to determine the concerted expression and function of ion channels and transporters required for the progression of PDAC, and to provide validated therapeutic and diagnostic concepts and tools that are based on transport proteins serving as novel drug targets and/or biomarkers.

Cuff A.L.,University College London | Sillitoe I.,University College London | Lewis T.,University College London | Clegg A.B.,University College London | And 6 more authors.
Nucleic Acids Research | Year: 2011

CATH version 3.3 (class, architecture, topology, homology) contains 128 688 domains, 2386 homologous superfamilies and 1233 fold groups, and reflects a major focus on classifying structural genomics (SG) structures and transmembrane proteins, both of which are likely to add structural novelty to the database and therefore increase the coverage of protein fold space within CATH. For CATH version 3.4 we have significantly improved the presentation of sequence information and associated functional information for CATH superfamilies. The CATH superfamily pages now reflect both the functional and structural diversity within the superfamily and include structural alignments of close and distant relatives within the superfamily, annotated with functional information and details of conserved residues. A significantly more efficient search function for CATH has been established by implementing the search server Solr ( The CATH v3.4 webpages have been built using the Catalyst web framework. © The Author(s) 2010.

Tiribocchi A.,University of Bari | Gonnella G.,University of Bari | Marenduzzo D.,University of Edinburgh | Orlandini E.,University of Padua
Applied Physics Letters | Year: 2010

We investigate the switching dynamics of multistable nematic liquid crystal devices. In particular, we identify a remarkably simple two-dimensional device which exploits hybrid alignment at the surfaces to yield a bistable response. We also consider a three-dimensional tristable nematic device with patterned anchoring, recently implemented in practice, and discuss how the director and disclination patterns change during switching. © 2010 American Institute of Physics.

Leonardini A.,University of Bari | Avogaro A.,University of Padua
Archives of Physiology and Biochemistry | Year: 2013

Diabetic cardiomyopathy consists of a series of structural and functional changes. Accumulating evidence supports the concept that a "cardiac stem cell compartment disease" plays an important role in the pathophysiology of diabetic cardiomyopathy. In diabetic hearts, human cardiac stem/progenitor cells (CSPC) are reduced and manifest defective proliferative capacity. Hyperglycaemia, hyperlipidemia, inflammation, and the consequent oxidative stress are enhanced in diabetes: these conditions can induce defects in both growth and survival of these cells with an imbalance between cell death and cell replacement, thus favouring the onset of diabetic cardiomyopathy and its progression towards heart failure. The preservation of CSPC compartment can contribute to counteract the negative impact of diabetes on the myocardium. The recent studies summarized in this review have improved our understanding of the development and stem cell biology within the cardiovascular system. However, several issues remain unsolved before cell therapy can become a clinical therapeutically relevant strategy. © 2013 Informa UK Ltd.

Valentine G.A.,State University of New York at Buffalo | Doronzo D.M.,University of Bari | Dellino P.,University of Bari | de Tullio M.D.,Polytechnic of Bari
Geology | Year: 2011

Explosive activity and lava dome collapse at stratovolcanoes can lead to pyroclastic density currents (PDCs; mixtures of volcanic gas, air, and volcanic particles) that produce complex deposits and pose a hazard to surrounding populations. Two-dimensional computer simulations of dilute PDCs (characterized by a turbulent suspended load and deposition through a bed load) show that PDC transport, deposition, and hazard potential are sensitive to the shape of the volcano slope (profile) down which they flow. We focus on three generic volcano profiles: straight, concave-upward, and convex-upward. Dilute PDCs that flow down a constant slope gradually decelerate over the simulated run-out distance (5 km in the horizontal direction) due to a combination of sedimentation, which reduces the density of the PDC, and mixing with the atmosphere. However, dilute PDCs down a concave-upward slope accelerate high on the volcano flanks and have less sedimentation until they begin to decelerate over the shallow lower slopes. A convex-upward slope causes dilute PDCs to lose relatively more of their pyroclast load on the upper slopes of a volcano, and although they accelerate as they reach the lower, steeper slopes, the acceleration is reduced because of the upstream loss of pyroclasts (lower density contrast with the atmosphere). Dynamic pressure, a measure of the damage that can be caused by PDCs, reflects these complex relations. © 2011 Geological Society of America.

Doronzo D.M.,University of Bari | Valentine G.A.,State University of New York at Buffalo | Dellino P.,University of Bari | de Tullio M.D.,Polytechnic of Bari
Earth and Planetary Science Letters | Year: 2010

Pyroclastic density currents (PDCs) vary between two end members, concentrated and dilute. When a PDC interacts with an uneven topography, the flow field variables (velocity, pressure, bulk density, particle concentration) may drastically change near the flow-substrate boundary. These changes may significantly affect the sediment flux and the resulting deposits can record the effects in their facies architecture. Here we show, by means of numerical simulations, how a dilute pyroclastic density current interacts with four different types of simple topography, namely: flat, one hill, one valley and two hills. Our numerical scheme treats the very fine particles as being in full thermo-mechanical equilibrium with the volcanic gas, i.e. a dusty gas. A dusty gas-air mixture is defined as a mixture of dusty gas and atmospheric air. The trajectories of the coarser particles or discrete phase (three grain-size classes of 1mm, 5mm and 10mm and density of 1500kg/m3) are tracked as Lagrangian particles that interact with the dusty gas-air mixture through two-way momentum and energy coupling. Numerical results are used to analyze the local effects of topography on the deposition of the Lagrangian particles, by monitoring with time and space the local changes at the boundary between the current and the substrate. The results show that the sediment flux in the flow boundary zone increases near the stoss sides of hills and in the valleys, relative to the flat reference case, whereas it decreases along the lee flanks and on top of the hills. We use the sediment flux in the flow boundary zone and the grain-size distribution of the Lagrangian particles as proxies of the deposit features, and by these parameters we qualitatively compare simulations with deposits of known eruptions. © 2010 Elsevier B.V.

Guidolin D.,University of Padua | Albertin G.,University of Padua | Ribatti D.,University of Bari
Peptides | Year: 2010

Angiogenesis, the process through which new blood vessels arise from pre-existing ones, is regulated by numerous "classic" factors and other "nonclassic" regulators of angiogenesis. Among these latter urotensin-II is a cyclic 11-amino acid (human) or 15-amino acid (rodent) peptide, originally isolated from the fish urophysis, which exerts a potent systemic vasoconstrictor and hypertensive effect. This review article summarizes the literature data concerning the involvement of urotensin-II in angiogenesis. © 2010 Elsevier Inc. All rights reserved.

Benci V.,University of Pisa | Fortunato D.,University of Bari
Communications in Mathematical Physics | Year: 2010

The nonlinear Klein-Gordon-Maxwell equations provide models for the interaction between the electromagnetic field and matter. We assume that the nonlinear term W is positive and W(0) = 0. This fact makes the theory more suitable for physical models (for example models in supersymmetry theory and in cosmology; see e.g. [16, 22, 28] and their references). A three dimensional vortex is a finite energy, stationary solution of the Klein-Gordon-Maxwell equations such that the matter field has nontrivial angular momentum and the magnetic field looks like the field created by a finite solenoid. Under suitable assumptions, we prove the existence of three dimensional vortex-solutions. © Springer-Verlag 2010.

Andriani G.F.,University of Bari | Germinario L.,University of Padua
Environmental Earth Sciences | Year: 2014

This paper deals with the effects of thermal stresses on selected carbonate rocks used as dimension stones. They are Mesozoic calcareous and dolomitic rocks cropping out in Apulia (southern Italy) that, for their physico-mechanical and aesthetic properties, have always been finding a large application both as ornamental stones and as simple construction materials; their use is attested not only in Italy, in works of archaeological, historical and artistic interest too. The cause–effect relationships of thermal degradation were studied by means of an artificial accelerated ageing test, in order to provide a perspective about the decay of carbonate stones due to diurnal and seasonal temperature fluctuations, as well as thermal shocks during events of fire development. The stone samples were subjected to thermal cycles in a muffle furnace, ranging from 100 to 700 °C; after each cycle, several non-destructive and semi-destructive tests were carried out: mass and volume measurements, mercury intrusion porosimetry, sclerometer tests, ultrasonic tests, thin-section observations and determination of chromatic alterations through image analysis and Munsell charts method. In this way, the qualitative and quantitative modifications induced in fabric, physical and mechanical properties were discussed. The results highlight the fundamental role of depositional and diagenetic fabric that, together with mineralogical composition, represents the most significant discriminating factor in the response of the stone to thermal stresses. © 2014, Springer-Verlag Berlin Heidelberg.

Loiacono F.V.,University of Natural Resources and Life Sciences, Vienna | De Tullio M.C.,University of Bari
OMICS A Journal of Integrative Biology | Year: 2012

A large number of studies have investigated the relationship between different forms of abiotic stress and antioxidants. However, misconceptions and technical flaws often affect studies on this important topic. Reactive oxygen species (ROS) generated under stress conditions should not be considered just as potential threats, because they are essential components of the signaling mechanism inducing plant defenses. Similarly, the complexity of the antioxidant system should be considered, to avoid misleading oversimplifications. Recent literature is discussed, highlighting the importance of accurate experimental setups for obtaining reliable results in this delicate field of research. A tentative "troubleshooting guide" is provided to help researchers interested in improving the quality of their work on the role of antioxidants in plant stress resistance. Significant advancements in the field could be reached with the development of antioxidomics, defined here as a new branch of research at the crossroads of other disciplines including metabolomics and proteomics, studying the complex relationship among antioxidants and their functions. © Copyright 2012, Mary Ann Liebert, Inc.

Moschetta M.,Dana-Farber Cancer Institute | Moschetta M.,University of Bari | Mishima Y.,Dana-Farber Cancer Institute | Sahin I.,Dana-Farber Cancer Institute | And 5 more authors.
Biochimica et Biophysica Acta - Reviews on Cancer | Year: 2014

Tumor-associated neovasculature is a critical therapeutic target; however, despite significant progress made in the clinical efficacy of anti-vessel drugs, the effect of these agents remains transient: over time, most patients develop resistance, which inevitably leads to tumor progression. To develop more effective treatments, it is imperative that we better understand the mechanisms involved in tumor vessel formation, how they participate to the tumor progression and metastasis, and the best way to target them.Several mechanisms contribute to the formation of tumor-associated vasculature: i) neoangiogenesis; ii) vascular co-option; iii) mosaicism; iv) vasculogenic mimicry, and v) postnatal vasculogenesis. These mechanisms can also play a role in the development of resistance to anti-angiogenic drugs, and could serve as targets for designing new anti-vascular molecules to treat solid as well as hematological malignancies. Bone marrow-derived endothelial progenitor cell (EPC)-mediated vasculogenesis represents an important new target, especially at the early stage of tumor growth (when EPCs are critical for promoting the "angiogenic switch"), and during metastasis, when EPCs promote the transition from micro- to macro-metastases. In hematologic malignancies, the EPC population could be related to the neoplastic clone, and both may share a common ontogeny. Thus, characterization of tumor-associated EPCs in blood cancers may provide clues for more specific anti-vascular therapy that has both direct and indirect anti-tumor effects. Here, we review the role of vasculogenesis, mediated by bone marrow-derived EPCs, in the progression of cancer, with a particular focus on the role of these cells in promoting progression of hematological malignancies. © 2014 Elsevier B.V.

Smith L.,U.S. Department of Agriculture | de Lillo E.,University of Bari | Amrine Jr. J.W.,West Virginia University
Experimental and Applied Acarology | Year: 2010

Eriophyid mites have been considered to have a high potential for use as classical biological control agents of weeds. We reviewed known examples of the use of eriophyid mites to control weedy plants to learn how effective they have been. In the past 13 years, since Rosenthal's 1996 review, 13 species have undergone some degree of pre-release evaluation (Aceria genistae, A. lantanae, Aceria sp. [boneseed leaf buckle mite (BLBM)], A. salsolae, A. sobhiani, A. solstitialis, A. tamaricis, A. thalgi, A. thessalonicae, Cecidophyes rouhollahi, Floracarus perrepae, Leipothrix dipsacivagus and L. knautiae), but only four (A. genistae, Aceria sp. [BLBM], C. rouhollahi and F. perrepae) have been authorized for introduction. Prior to this, three species (Aceria chondrillae, A. malherbae and Aculus hyperici) were introduced and have become established. Although these three species impact the fitness of their host plant, it is not clear how much they have contributed to reduction of the population of the target weed. In some cases, natural enemies, resistant plant genotypes, and adverse abiotic conditions have reduced the ability of eriophyid mites to control target weed populations. Some eriophyid mites that are highly coevolved with their host plant may be poor prospects for biological control because of host plant resistance or tolerance of the plant to the mite. Susceptibility of eriophyids to predators and pathogens may also prevent them from achieving population densities necessary to reduce host plant populations. Short generation time, high intrinsic rate of increase and high mobility by aerial dispersal imply that eriophyids should have rapid rates of evolution. This raises concerns that eriophyids may be more likely to lose efficacy over time due to coevolution with the target weed or that they may be more likely to adapt to nontarget host plants compared to insects, which have a longer generation time and slower population growth rate. Critical areas for future research include life history, foraging and dispersal behavior, mechanisms controlling host plant specificity, and evolutionary stability of eriophyid mites. This knowledge is critical for designing and interpreting laboratory and field experiments to measure host plant specificity and potential impact on target and nontarget plants, which must be known before they can be approved for release. One of the more successful examples of an eriophyid mite controlling an invasive alien weed is Phyllocoptes fructiphilus, whose impact is primarily due to transmission of a virus pathogenic to the target, Rosa multiflora. Neither the mite nor the virus originated from the target weed, which suggests that using "novel enemies" may sometimes be an effective strategy for using eriophyid mites. © 2009 Springer Science+Business Media B.V.

Doronzo D.M.,Georgia Institute of Technology | Doronzo D.M.,University of Bari | Doronzo D.M.,State University of New York at Buffalo
Bulletin of Volcanology | Year: 2013

An aeromechanic analysis of pyroclastic density currents (PDCs) past a building is carried out on the results of a computer simulation. The analysis shows that PDCs strongly interact with buildings, resulting in turbulent boundary layer separation and recirculation. These results could be used to better assess the hazard of PDCs impacting urban areas and be of service to civil protection authorities and urban planners who work in active volcanic areas. © 2013 Springer-Verlag Berlin Heidelberg.

Tiribocchi A.,University of Bari | Gonnella G.,University of Bari | Marenduzzo D.,University of Edinburgh | Orlandini E.,University of Padua | Salvadore F.,Caspur
Physical Review Letters | Year: 2011

Blue phases are liquid crystals made up by networks of defects, or disclination lines. While existing phase diagrams show a striking variety of competing metastable topologies for these networks, very little is known as to how to kinetically reach a target structure, or how to switch from one to the other, which is of paramount importance for devices. We theoretically identify two confined blue phase I systems in which by applying an appropriate series of electric field it is possible to select one of two bistable defect patterns. Our results may be used to realize new generation and fast switching energy-saving bistable devices in ultrathin surface treated blue phase I wafers. © 2011 American Physical Society.

D'Ovidio R.,Trichology Associazione Italiana Dermatologi Ambulatoriali AI DA | Vessio M.,Ospedale Generale Regionale F. Miulli | D'Ovidio F.D.,University of Bari
Dermato-Endocrinology | Year: 2013

Current observations link vitamin D deficiency to many autoimmune diseases. There are limited data on vitamin D inAlopecia Areata, an autoimmune disease which in our experience shows seasonality in most of its remitting- relapsingforms. Our results demonstrate the presence of insufficiency of 25-hydroxyvitamin D (25OH -D) in many patients withvarious clinical forms, correlated with the expected increase of the values of Parathyroid Hormone (PTH ). This couldsuggest the possible clinical use of vitamin D in the management of this frustrating disease.© 2013 Landes Bioscience.

Tiribocchi A.,University of Bari | Gonnella G.,University of Bari | Marenduzzo D.,University of Edinburgh | Orlandini E.,University of Padua
Soft Matter | Year: 2011

Blue phases are networks of disclination lines, which occur in cholesteric liquid crystals near the transition to the isotropic phase. They have recently been used for the new generation of fast switching liquid crystal displays. Here we study numerically the steady states and switching hydrodynamics of blue phase I (BPI) and blue phase II (BPII) cells subjected to an electric field. When the field is on, there are three regimes: for very weak fields (and strong anchoring at the boundaries) the blue phases are almost unaffected, for intermediate fields the disclinations twist (for BPI) and unzip (for BPII), whereas for very large voltages the network dissolves in the bulk of the cell. Interestingly, we find that a BPII cell can recover its original structure when the field is switched off, whereas a BPI cell is found to be trapped more easily into metastable configurations. The kinetic pathways followed during switching on and off entails dramatic reorganisation of the discli nation networks. We also discuss the effect of changing the director field anchoring at the boundary planes and of varying the direction of the applied field. © The Royal Society of Chemistry 2011.

Alonso A.,University of Minnesota | Alonso A.,Public University of Navarra | Logroscino G.,University of Bari | Hernan M.A.,Harvard University | Hernan M.A.,Harvard-MIT Division of Health Sciences and Technology
Journal of Neurology, Neurosurgery and Psychiatry | Year: 2010

Background: Epidemiologic studies have provided inconsistent results on the association of cigarette smoking with the incidence of amyotrophic lateral sclerosis (ALS). To summarise published evidence and explore sources of heterogeneity, we conducted a systematic review and meta-analysis of studies that evaluated this association. Methods: Published studies evaluating the association of smoking with incidence of ALS were searched in bibliographic databases, with relevant information collected from each article. A random effects approach was used to pool the relative rate (RR) estimates from different studies. Between study heterogeneity was explored with a meta-regression approach. Results: 18 publications reported associations between smoking and ALS risk in 15 case control studies and five cohort studies. The pooled RR (95% CI) of ALS was 1.28 (0.97 to 1.68) for current versus never smokers and 1.12 (0.98 to 1.27) for ever versus never smokers. The study specifics RRs were heterogeneous (p<0.01). The proportion of women in the study population explained 46% of between study variability. The estimated RR (95% CI) of ALS for ever versus never smokers was 0.86 (0.71 to 1.03) in men and 1.66 (1.31 to 2.10) in women. Interpretation: This meta-analysis does not support an overall strong association of smoking with ALS risk but suggests that smoking might be associated with a higher risk of ALS in women.

Moschetta M.,Dana-Farber Cancer Institute | Moschetta M.,University of Bari | Reale A.,University of Bari | Marasco C.,University of Bari | And 2 more authors.
British Journal of Pharmacology | Year: 2014

The mammalian target of rapamycin (mTOR) plays an important role in the regulation of protein translation, cell growth and metabolism. The mTOR protein forms two distinct multi-subunit complexes: mTORC1 and mTORC2. The mTORC1 complex is activated by diverse stimuli, such as growth factors, nutrients, energy and stress signals; and essential signalling pathways, such as PI3K and MAPK, in order to control cell growth, proliferation and survival. mTORC1 also activates S6K1 and 4EBP1, which are involved in mRNA translation. The mTORC2 complex is resistant to rapamycin inhibitory activity and is generally insensitive to nutrient- and energy-dependent signals. It activates PKC-α and Akt and regulates the actin cytoskeleton. Deregulation of the mTOR-signalling pathway (PI3K amplification/mutation, PTEN loss of function, Akt overexpression, and S6K1, 4EBP1 and eIF4E overexpression) is common in cancer, and alterations in components of the mTOR pathway have a major role in tumour progression. Therefore, mTOR is an appealing therapeutic target in many tumours. Here we summarize the upstream regulators and downstream effectors of the mTORC1 and mTORC2 pathways, the role of mTOR in cancer, and the potential therapeutic values and issues related to the novel agents targeting the mTOR-signalling pathway. © 2014 The British Pharmacological Society.

Antonietti R.,University of Padua | Cainelli G.,University of Bari | Cainelli G.,CNR Institute for Economic Research on Firms and Growth
Annals of Regional Science | Year: 2011

In this article, using a large sample of Italian manufacturing firms, we estimate a structural model of research, innovation, productivity and export performance augmented to take account for the role played by spatial agglomeration externalities. This model, which is an 'augmented' version of Crépon et al. (Econ Innov New Technol 7(2):115-158, 1998) model, comprises five main equations. The first two identify the factors underlying the decision and intensity of Research and Development (R&D) investments; the third links R&D capital to innovation output; the fourth focuses on Total Factor Productivity (TFP) as determined by innovation; the fifth relates TFP to export performance. Our estimates show the significant role played by local externalities in these processes. In particular, related variety and urbanization positively affect the creation of new ideas through R&D, while specialization impacts on TFP to complement innovation output. Finally, urbanization economies support TFP in driving firms' export performance. © Springer-Verlag 2009.

Cafarchia C.,University of Bari | Iatta R.,University of Bari | Latrofa M.S.,University of Bari | Graser Y.,Charité - Medical University of Berlin | Otranto D.,University of Bari
Infection, Genetics and Evolution | Year: 2013

Dermatophytes are fungi that invade and propagate in the keratinized skin of mammals, including humans, often causing contagious infections. The species of medical concern belong to the genera Microsporum, Trichophyton, Epidermophyton (in their anamorphic state) and Arthroderma (in their telomorphic state), which were traditionally identified based on their morphology and biochemical characters. Nonetheless, limitations linked to the differentiation of closely related agents at species and strains level have been recently overcome by molecular studies. Indeed, an accurate identification of dermatophytes is pivotal for the establishment of effective control and prevention programs as well as for determining the most appropriate and effective antifungal therapies to be applied. This article reviews the DNA techniques and the molecular markers used to identify and to characterize dermatophyte species, as well as aspects of their phylogeny and evolution. The applications of typing molecular strain to both basic and applied research (e.g., taxonomy, ecology, typing of infection, antifungal susceptibility) have also been discussed. © 2013 Elsevier B.V.

Dantas-Torres F.,Oswaldo Cruz Foundation | Dantas-Torres F.,University of Bari | Solano-Gallego L.,Autonomous University of Barcelona | Baneth G.,Hebrew University of Jerusalem | And 3 more authors.
Trends in Parasitology | Year: 2012

Canine leishmaniosis is a potentially life-threatening disease which is spreading geographically in the Old and New Worlds, where different diagnostic procedures, treatments, and control strategies are currently in place. This Opinion article outlines the similarities and differences between canine leishmaniosis in the Old and New Worlds, with emphasis on South America and Europe. Finally, it calls the attention of veterinary and public health authorities to standardize and improve practices for diagnosing, treating, and preventing the disease. © 2012 Elsevier Ltd.

Lorusso V.,Instituto Oncologico Giovanni Paolo II | Marech I.,University of Bari
Expert Opinion on Therapeutic Targets | Year: 2013

Isoliquiritigenin (ISL) is a chalcone compound with valuable pharmacological properties such as antioxidant, anti-inflammatory, anticancer and anti-allergic activities. With regard to anticancer property, ISL was able to suppress HIF-1α level, VEGF expression and secretion, cell migration and to decrease the expression and secretion of MMP-9/-2. These effects may be mediated through inhibition of p38, PI3K/Akt and NF-κB signaling pathways. Thus, low concentration of ISL may have therapeutic potential in the treatment of aggressive breast carcinoma and other neoplasms. © 2013 Informa UK, Ltd.

Palazzo G.,University of Bari | De Tullio D.,University of Bari | Magliulo M.,University of Bari | Mallardi A.,CNR Institute for Chemical and Physical Processes | And 6 more authors.
Advanced Materials | Year: 2015

A systematic study of the sensor response as a function of the Debye's length, the receptor charge, and the distance at which the binding event occurred addressed the basic functional mechanisms of a bio-electrolyte-gated organic field-effect transistors (EGOFET). A bio-EGOFET sensing platform comprising a biological layer at the interface between the OSC and the electrolyte was used to conduct the investigations. The biological layer was composed of a phospholipid (PL) bilayer covalently anchored to the OSC surface through a plasma-deposited (?COOH)-functionalized thin coating. It was observed that some of the anchored PLs were endowed with a biotin moiety, having an incomparably high binding affinity for streptavidin (SA) or avidin (AV) proteins.

Lisi F.A.,University of Bari | Straccia U.,CNR Institute of Information Science and Technologies Alessandro Faedo
Fundamenta Informaticae | Year: 2013

Fuzzy Description Logics (DLs) are logics that allow to deal with structured vague knowledge. Although a relatively important amount of work has been carried out in the last years concerning the use of fuzzy DLs as ontology languages, the problem of automatically managing the evolution of fuzzy ontologies has received very little attention so far. We describe here a logic-based computational method for the automated induction of fuzzy ontology axioms which follows the machine learning approach of Inductive Logic Programming. The potential usefulness of the method is illustrated by means of an example taken from the tourism application domain.

Vogel H.,University of Cologne | Zanchetta G.,University of Pisa | Sulpizio R.,University of Bari | Wagner B.,University of Cologne | Nowaczyk N.,Helmholtz Center Potsdam
Journal of Quaternary Science | Year: 2010

Here we present a tephrostratigraphic record (core Co1202) recovered from the northeastern part of Lake Ohrid (Republics of Macedonia and Albania) reaching back to Marine Isotope Stage (MIS) 6. Overall ten horizons (OT0702-1 to OT0702-10) containing volcanic tephra have been recognised throughout the 14.94m long sediment succession. Four tephra layers were visible at macroscopic inspection (OT0702-4, OT0702-6, OT0702-8 and OT0702-9), while the remaining six are cryptotephras (OT0702-1, OT0702-2, OT0702-3, OT0702-5, OT0702-7 and OT0702-10) identified from peaks in K, Zr and Sr intensities, magnetic susceptibility measurements, and washing and sieving of the sediments. Glass shards of tephra layers and cryptotephras were analysed with respect to their major element composition, and correlated to explosive eruptions of Italian volcanoes. The stratigraphy and the major element composition of tephra layers and cryptotephras allowed the correlation of OT0702-1 to AD 472 or AD 512 eruptions of Somma-Vesuvius, OT0702-2 to the FL eruption of Mount Etna, OT0702-3 to the Mercato from Somma-Vesuvius, OT0702-4 to SMP1-e/Y-3 eruption from the Campi Flegrei caldera, OT0702-5 to the Codola eruption (Somma-Vesuvius or Campi Flegrei), OT0702-6 to the Campanian Ignimbrite/Y-5 from the Campi Flegrei caldera, OT0702-7 to the Green Tuff/Y-6 eruption from Pantelleria Island, OT0702-8 to the X-5 eruption probably originating from the Campi Flegrei caldera, OT0702-9 to the X-6 eruption of generic Campanian origin, and OT0702-10 to the P-11 eruption from Pantelleria Island. The fairly well-known ages of these tephra layers and parent eruptions provide new data on the dispersal and deposition of these tephras and, furthermore, allow the establishment of a chronological framework for core Co1202 for a first interpretation of major sedimentological changes. © 2009 John Wiley & Sons, Ltd.

Carr B.I.,National Institute for Digestive Diseases | Cavallini A.,National Institute for Digestive Diseases | D'Alessandro R.,National Institute for Digestive Diseases | Refolo M.G.,National Institute for Digestive Diseases | And 3 more authors.
BMC Cancer | Year: 2014

Background: Thrombocytopenia has been reported to be associated with small size HCCs, and thrombocytosis to be associated with large size HCCs. The aim was to examine the effects of platelets in relation to HCC cell growth.Methods: The effects of time-expired pooled normal human platelets were examined on human HCC cell line growth and invasion.Results: Blood platelet numbers increased with increasing HCC tumor size and portal vein invasion. Platelet extracts enhanced cell growth in 4 human HCC cell lines, as well as cell migration, medium AFP levels and decreased apoptosis. Cell invasion was significantly enhanced, using a Matrigel-coated trans-well membrane and3D (Real-Time Imaging) invasion assay. Western blots showed that platelets caused enhanced phospho-ERK and phospho-JNK signaling and anti-apoptotic effect with increase of Bcl-xL (anti-apoptotic marker) and decrease of Bid (pro-apoptotic marker) levels. Their growth effects were blocked by a JNK inhibitor.Conclusions: Platelets stimulated growth and invasion of several HCC cell lines in vitro, suggesting that platelets or platelet growth factors could be a potential pharmacological target. © 2014 Carr et al.; licensee BioMed Central Ltd.

Tampoia M.,University of Bari | Giavarina D.,San Bortolo Hospital | Di Giorgio C.,University of Bari | Bizzaro N.,San Antonio Hospital
Autoimmunity Reviews | Year: 2012

Background: Systematic reviews and meta-analysis are essential tools to accurately and reliably summarize evidence, and can be used as a starting point for developing practice guidelines for the diagnosis and treatment of patients. Aim: To estimate the diagnostic accuracy of enzyme-linked immunosorbent assays (ELISA) to detect anti-BP180 and anti-desmoglein 3 (Dsg3) autoantibodies in the diagnosis of autoimmune blistering skin diseases. Methods: A Medline search of English written articles, published between 1994 and 2011, reporting data on the sensitivity and specificity of diagnostic tests was conducted using the following search terms: "BP180 autoantibodies", "Dsg3 autoantibodies", and "enzyme linked immunosorbent assay". The selected articles have been evaluated according to the quality of the statistical methods used to calculate diagnostic accuracy (definition of cutoff value, use of ROC curves, and selection of control cases). The meta-analysis was performed using a summary ROC (SROC) curve and a random-effect model to independently combine sensitivity and specificity across studies. Results: The search yielded 69 publications on BP180 autoantibodies and 178 on Dsg3 autoantibodies. A total of 30 studies met the inclusion criteria: 17 provided data on the assays to detect autoantibodies to BP180 in a sample of 583 patients with bullous pemphigoid (BP), while 13 studies provided data on the assays to search for anti-Dsg3 autoantibodies in a sample of 1058 patients with pemphigus vulgaris (PV). The 17 studies on BP180 autoantibodies yielded a pooled sensitivity of 0.87 (95% confidence interval (CI) 0.85 to 0.89) and a pooled specificity of 0.98 (CI, 0.98 to 0.99). The area under the curve (AUC) for the SROC curve was 0.988, and the summary diagnostic odds ratio was 374.91 (CI, 249.97 to 562.30). The 13 studies on Dsg3 autoantibodies which met the inclusion criteria, yielded a pooled sensitivity of 0.97 (CI, 0.95 to 0.98), and a pooled specificity of 0.98 (CI, 0.98 to 0.99). The AUC for the SROC curve was 0.995 and the summary diagnostic odds ratio was 1466.11 (95% CI, 750.36 to 2864.61). Conclusions: Results of the meta-analysis demonstrated that ELISA tests for anti-BP180 and anti-Dsg3 autoantibodies have high sensitivity and specificity for BP and PV, respectively, and can be used in daily laboratory practice for the initial diagnosis of autoimmune blistering skin diseases. © 2012 Elsevier B.V.

An integrated approach, based on the use of trace fossils combined with analysis of physical and biogenic structures, identification of key surfaces, and reconstruction of stratigraphic architecture, proved to be of critical value in defining the depositional environments, elucidating the dynamics of progradation, and characterizing the various systems tracts of Upper Pliocene progradational wedges (Capodarso area, Sicily) generated by cool-water carbonate ramps. The studied succession consists of a stack of six cycles, consisting of terrigenous mudstones passing upwards into biocalcarenite wedges with distinct clinoforms. The prograding biocalcarenite bodies show seaward-increasing height and steepness of the clinoformed front as a result of development into increasingly deeper water, and may be regarded as the record of distally steepened ramps, dominated by storm-induced downwelling flows. Evidence of forced-regressive progradation is provided by stratal geometries, physical structures, and trace fossil assemblages existing at the top of the bodies, which attest to a gradual increase in energy level at the top of the ramp, concurrently with the progression of seaward outbuilding of the bodies. Three trace-fossil suites (Thalassinoides/Piscichnus, Scolicia, Dactyloidites) are shown to be linked with the successive growth stages of individual prograding wedges, whereas abandonment stages, characterized by starvation of sediment input, are marked by the Ophiomorpha suite. The Capodarso ramps, like other Plio-Pleistocene equivalents of the Mediterranean area, are small, high-gradient ramps, with stratigraphical architecture controlled by high-amplitude, orbitally driven glacio-eustatic changes. An ecologically and bathymetrically based subdivision of the ramps into inner, mid and outer ramp environments is hardly applicable, as most of the wedge progradation occurs in highly dynamic conditions, dominated by physical processes of transport and resedimentation of skeletal material, which result in faunal composition dominated by allochthonous material. The use of trace fossils is of critical value in this context, due to the scarcity of ecological information provided by faunal elements. © 2009 Springer-Verlag.

Agency: European Commission | Branch: FP7 | Program: MC-IAPP | Phase: FP7-PEOPLE-2012-IAPP | Award Amount: 2.45M | Year: 2014

The LUSTRE-IAPP has emerged from a background of successful bilateral academic and industrial collaborations within the UK and Italian partners, in which the knowledge transfer and training of ERs and ESRs are centred on four key aspects of academic research leading to KT and commercialisation activities. These are in the areas of: a) in the engineering and fabrication of laser glass hosts for surgical dentistry, b) mode-locked laser cavity engineering for laboratory prototype, c) laser system development for dental surface tissue engineering and d) application of laser system in ex-vivo and in vitro scenarios for future in vivo clinical trials. The main goal for the project is to demonstrate applications of mode-locked laser systems in ex vivo and in vitro scenarios, which provides engineering acid erosion resistant enamel on extracted human and bovine tissues. Relevant training activity will provide the necessary safety regulations for implementation of laser systems for ultimate clinical use in the future. For enabling such KT activities, the UK partners have strong evidence for previous KT activities through collaborative training at PhD research, which led to the proofs-of-concept and formed the basis for LUSTRE-IAPP. The flow of knowledge transfer is also geared towards manufacturing within the SME sector via value addition for commercialisation, by accruing benefits for the knowledge generating partners, long term collaboration, impact on sustainable training, and commercial exploitation opportunities in future for public health impact in the area of oral and dental health. Immediate impact is expected in reducing the spread of acid erosion and tooth loss in the general population. Beyond 10 years the impact of such knowledge transfer should also be seen in other areas of hard and musculoskeletal tissues and regenerative therapies.

Fuentes I.,Institute Salud Carlos III | Montes I.,Ciudad de Coria | Saugar J.M.,Institute Salud Carlos III | Latrofa S.,University of Bari | And 2 more authors.
Emerging Infectious Diseases | Year: 2012

After Thelazia callipaeda infection in dogs and cats were reported in Spain, a human case of thelaziosis in this country was reported, suggesting zoonotic transmission. The active reproductive status of this nematode in situ indicates that humans are competent hosts for this parasite.

News Article | February 15, 2017

Braving the choppy waters of the South Atlantic four days a week, fisherman David Shoshola says a mobile phone app is helping him worry less about the risk of not being able to support his family. The 50-year-old and three colleagues fish from two small, open-deck boats based in the seaside town of Lambert's Bay, on South Africa's windswept west coast. Fishing using lines rather than nets, they typically catch just 20 fish a day per vessel, with the main species being snoek (a type of mackerel), and sea bream. It's a tough life, and like anyone in his trade, Mr Shoshola has two main concerns - finding the fish in the first place, and then being able to sell his catch. A new app called Abalobi is helping him to do both more easily. The app, which is being piloted by the University of Cape Town, utilises GPS so Mr Shoshola can record for future reference exactly where he had a good haul. And he can now sell the fish via Abalobi before he has returned to shore, easily finding out the best possible price. "It has removed a lot of the worry," he says. "I have a wife and three kids to support, and it gives me much more security." With the help of a growing number of apps and digital services such as Abalobi, it has never been easier to pinpoint the exact spot where the prized fish await, and then sell them after you have caught them. But with ever increasing concerns about depleting global fish stocks - the United Nations claims that 90% of the world's stocks are either full-fished or over-fished - is that a good thing? Many of the digital fish trackers, including Abalobi, claim to have conservation at their heart, but not everybody is convinced. "The problem is that in practice all that happens is unscrupulous people use apps to target the fish and wipe them out even quicker," says UK fishing expert Matt Hayes, who runs an Atlantic salmon fishery in Norway. He is also worried that small-scale fishermen could ultimately become unemployed. "You don't want to deprive someone of a living, but you don't want to bestow upon them the tech that means they will fish themselves out of existence. "I wrestle with it a lot. It concerns me." However, Dr Clive Trueman, associate professor of marine ecology at the UK's National Oceanography Centre, is more positive about apps like Abalobi. "It's nothing that commercial fishermen haven't been doing by word of mouth for centuries," he says. "Some of these apps may also end up being very effective for scientists and managers to work out where the fish are, and where they are going. "We can use them to catch more fish, but also to direct conservation." Serge Raemaekers, a fisheries researcher at Abalobi, says that conservation is at the very centre of their scheme. Using Google's cloud platform technology, data collected by the fishermen is to be shared with students at the University of Cape Town who are monitoring the sustainability of South Africa's fish stocks. The fishermen can also use the technology to monitor stocks, and stay away from any areas where they themselves think the fish population should be left to recover. Technology is also being used on a worldwide scale to protect fish stocks. In September last year, Google joined with ocean conservation group Oceana to launch Global Fishing Watch (GFW), a free platform that tracks the location of the world's commercial fishing boats. It does this by utilising the fact that more than 200,000 sea vessels constantly transmit their position, speed and direction via the global automatic identification system (AIS). GFW, which also uses Google's cloud computing services, already has more than 25,000 registered users, and more using the website without logging in. "Anyone who is interested in a vessel, and wants to know where it is today, can go to a variety of sources that provide real-time data, and see where it is at that moment," says Jackie Savitz, senior vice president at Oceana. "Authorities find out suspicious activity and then track vessels down." Suspicious activity includes ships that switch off AIS or don't use it at all. "It's possible the bad guys turn off AIS," says Ms Savitz. "But we can see when they turn it off, and we see it when it comes back on." GFW has already notched up some success stories - using its data, a vessel was caught fishing in the Phoenix Islands Protected Area in the Central Pacific and forced to pay a $2m (£1.6m) fine to the Republic of Kiribati, one of the poorest countries in the world. In Italy, the University of Bari has partnered with US technology group IBM since 2012 to pilot a similar cloud-based fishing app to Abalobi. The organisations say it has resulted in more targeted fishing, with the fishermen only catching as many fish as the market demands. Back at Abalobi - which means "traditional fisher" in the isiXhosa language - the project has secured grants from the South African government. It has also been helped by mobile phone network Vodacom allowing the app to be used data-free. More than 100 South African fishermen are now signed up, and Mr Raemaekers says Abalobi is receiving interest from groups in the Seychelles and the UK. Mr Shoshola adds that using the service is helping him and his three friends expand the business, because for the first time they have recorded data that they can take to the bank and use as evidence to help them hook some loans to grow their fishing operation. "I have got the numbers of every daily catch," says Mr Shoshola.

Caliandro R.,CNR Institute of Crystallography | Di Profio G.,CNR Institute on Membrane Technology | Nicolotti O.,University of Bari
Journal of Pharmaceutical and Biomedical Analysis | Year: 2013

Co-crystallization brings new opportunities for improving the solubility and dissolution rate of drugs with the chance of finely tuning some relevant chemical-physical properties of mixtures containing bioactive compounds. As co-crystallization process involves several molecular species, which are generally solid at room conditions, its control requires accurate knowledge and monitoring of the different phase that might appear during the formulation stage. In the present study the suitability of X-ray powder diffraction (XRPD) and Fourier-transformed infrared (FTIR) spectroscopy in quantifying mixtures of carbamazepine polymorphs (forms I and III), saccharin, and carbamazepine-saccharin cocrystals (form I) is assessed. Quaternary crystalline mixtures typically produced in the process of co-crystal production were analyzed by multivariate methods. Principal component analysis (PCA) was used for the identification of the crystal phases, while unsupervised simultaneous fitting of the spectra from pure phases, or supervised partial least squares (PLS) methods were used for their quantitative determination. The performance of data analysis was enhanced by applying peculiar pre-processing methods, such as SNIP filtering in case of FTIR and PCA filtering in case of XRPD. It was found that, for XRPD data, the automatic multi-fitting procedures and PLS models developed in this study are able to quantify single phases in mixtures to an accuracy level comparable to that obtained by the widely used Rietveld method, which, however, requires knowledge of the crystal structures. For FTIR data the results here obtained prove that this technique can be used as a fast method for polymorph characterization. © 2013 Elsevier B.V.

Airoldi I.,G Gaslini Institute | Ribatti D.,University of Bari
Journal of Leukocyte Biology | Year: 2011

Chemokines have pleiotropic effects in regulating immunity, angiogenesis, and tumor growth. CXC and CC chemokine families members and their receptors are able to exert a proangiogenic or an antiangiogenic effect in experimental models and in human tumors. In this review article, we have summarized literature data and our studies concerning the angiostatic activity of chemokines. Their angiostatic activity may be a result of a direct effect on the biological functions of endothelial cells and/or an effect on tumor cells inhibiting their capability to stimulate new blood vessel formation. Moreover, chemokines have a pro- and antitumor effect within the tumor microenvironment by regulating immune cell infiltration and its antitumor activities. We have focused our interest on the role of IL-12 and IL-27 in solid and hematological tumors, and we have suggested and discussed their potential use as antiangiogenic agents in the treatment of such tumors. © Society for Leukocyte Biology.

Dantas-Torres F.,Oswaldo Cruz Foundation | Dantas-Torres F.,University of Bari | Latrofa M.S.,University of Bari | Annoscia G.,University of Bari | And 3 more authors.
Parasites and Vectors | Year: 2013

Background: The taxonomic status of the brown dog tick (Rhipicephalus sanguineus sensu stricto), which has long been regarded as the most widespread tick worldwide and a vector of many pathogens to dogs and humans, is currently under dispute. Methods. We conducted a comprehensive morphological and genetic study of 278 representative specimens, which belonged to different species (i.e., Rhipicephalus bursa, R. guilhoni, R. microplus, R. muhsamae, R. pusillus, R. sanguineus sensu lato, and R. turanicus) collected from Europe, Asia, Americas, and Oceania. After detailed morphological examination, ticks were molecularly processed for the analysis of partial mitochondrial (16S rDNA, 12S rDNA, and cox1) gene sequences. Results: In addition to R. sanguineus s.l. and R. turanicus, three different operational taxonomic units (namely, R. sp. I, R. sp. II, and R. sp. III) were found on dogs. These operational taxonomical units were morphologically and genetically different from R. sanguineus s.l. and R. turanicus. Ticks identified as R. sanguineus s.l., which corresponds to the so-called "tropical species" (=northern lineage), were found in all continents and genetically it represents a sister group of R. guilhoni. R. turanicus was found on a wide range of hosts in Italy and also on dogs in Greece. Conclusions: The tropical species and the temperate species (=southern lineage) are paraphyletic groups. The occurrence of R. turanicus in the Mediterranean region is confirmed. A consensual re-description of R. sanguineus s.s. and R. turanicus will be necessary to solve the taxonomic problems within the so-called R. sanguineus group. © 2013 Dantas-Torres et al.; licensee BioMed Central Ltd.

Peschechera A.,University of Bari | Eckel J.,Paul Langerhans Group
Archives of Physiology and Biochemistry | Year: 2013

Obesity is considered a worldwide health concern. Most of obesity therapies are aimed at decreasing energy intake. However, recent data suggest that increasing cellular energy expenditure could be a useful approach to reduce adiposity. Adaptive thermogenesis, a biological process within the brown fat by which energy is dissipated in mitochondria, is a great tool to increase energy expenditure. Several studies have confirmed the presence of brown adipose tissue in adult humans, whose activity may make it a target for the treatment of obesity. Differentiation of brown adipocytes could be a potent tool to promote weight loss by increasing energy expenditure. Here we review the mechanisms potentially associated with expansion and activation of brown adipose tissue, and modulation of adaptive thermogenesis. Controlling one or more of these pathways could induce a positive regulation of brown adipogenesis. A better understanding of these molecular pathways could potentially result in novel anti-obesity therapies. © 2013 Informa UK Ltd.

Guida P.,University of Bari | Mastro F.,University of Bari | Scrascia G.,University of Bari | Whitlock R.,McMaster University | And 2 more authors.
Journal of Thoracic and Cardiovascular Surgery | Year: 2014

Objectives A systematic review of the European System for Cardiac Operative Risk Evaluation (euroSCORE) II performance for prediction of operative mortality after cardiac surgery has not been performed. We conducted a meta-analysis of studies based on the predictive accuracy of the euroSCORE II.© 2014 The American Association for Thoracic Surgery Methods We searched the Embase and PubMed databases for all English-only articles reporting performance characteristics of the euroSCORE II. The area under the receiver operating characteristic curve, the observed/expected mortality ratio, and observed-expected mortality difference with their 95% confidence intervals were analyzed.Results Twenty-two articles were selected, including 145,592 procedures. Operative mortality occurred in 4293 (2.95%), whereas the expected events according to euroSCORE II were 4802 (3.30%). Meta-analysis of these studies provided an area under the receiver operating characteristic curve of 0.792 (95% confidence interval, 0.773-0.811), an estimated observed/expected ratio of 1.019 (95% confidence interval, 0.899-1.139), and observed-expected difference of 0.125 (95% confidence interval, -0.269 to 0.519). Statistical heterogeneity was detected among retrospective studies including less recent procedures. Subgroups analysis confirmed the robustness of combined estimates for isolated valve procedures and those combined with revascularization surgery. A significant overestimation of the euroSCORE II with an observed/expected ratio of 0.829 (95% confidence interval, 0.677-0.982) was observed in isolated coronary artery bypass grafting and a slight underestimation of predictions in high-risk patients (observed/expected ratio 1.253 and observed-expected difference 1.859).Conclusions Despite the heterogeneity, the results from this meta-analysis show a good overall performance of the euroSCORE II in terms of discrimination and accuracy of model predictions for operative mortality. Validation of the euroSCORE II in prospective populations needs to be further studied for a continuous improvement of patients' risk stratification before cardiac surgery.

Naumenko V.S.,RAS Institute of Cytology and Genetics | Popova N.K.,RAS Institute of Cytology and Genetics | Lacivita E.,University of Bari | Leopoldo M.,University of Bari | Ponimaskin E.G.,Hannover Medical School
CNS Neuroscience and Therapeutics | Year: 2014

Serotonin (5-hydroxytryptamine or 5-HT) is an important neurotransmitter regulating a wide range of physiological and pathological functions via activation of heterogeneously expressed 5-HT receptors. Besides the important role of 5-HT receptors in the pathogenesis of depressive disorders and in their clinical medications, underlying mechanisms are far from being completely understood. This review focuses on possible cross talk between two serotonin receptors, 5-HT1A and the 5-HT7. Although these receptors are highly co-expressed in brain regions implicated in depression, and most agonists developed for the 5-HT1A or 5-HT7 receptors have cross-reactivity, their functional interaction has not been yet established. It has been recently shown that 5-HT1A and 5-HT7 receptors form homo- and heterodimers both in vitro and in vivo. From the functional point of view, heterodimerization has been shown to play an important role in regulation of receptor-mediated signaling and internalization, suggesting the implication of heterodimerization in the development and maintenance of depression. Interaction between these receptors is also of clinical interest, because both receptors represent an important pharmacological target for the treatment of depression and anxiety. © 2014 John Wiley & Sons Ltd.

Iacobazzi V.,University of Bari | Iacobazzi V.,CNR Institute of Neuroscience | Castegna A.,University of Bari | Infantino V.,University of Bari | And 2 more authors.
Molecular Genetics and Metabolism | Year: 2013

Recent expansion of our knowledge on epigenetic changes strongly suggests that not only nuclear DNA (nDNA), but also mitochondrial DNA (mtDNA) may be subjected to epigenetic modifications related to disease development, environmental exposure, drug treatment and aging. Thus, mtDNA methylation is attracting increasing attention as a potential biomarker for the detection and diagnosis of diseases and the understanding of cellular behavior in particular conditions.In this paper we review the current advances in mtDNA methylation studies with particular attention to the evidences of mtDNA methylation changes in diseases and physiological conditions so far investigated. Technological advances for the analysis of epigenetic variations are promising tools to provide insights into methylation of mtDNA with similar resolution levels as those reached for nDNA. However, many aspects related to mtDNA methylation are still unclear. More studies are needed to understand whether and how changes in mtDNA methylation patterns, global and gene specific, are associated to diseases or risk factors. © 2013 Elsevier Inc.

Procaccini C.,University of Naples Federico II | Jirillo E.,University of Bari | Matarese G.,University of Naples Federico II | Matarese G.,University of Bari
Molecular Aspects of Medicine | Year: 2012

Leptin is an adipocyte-derived hormone/cytokine that links nutritional status with neuroendocrine and immune functions. In humans, leptin influences energy homeostasis and regulates neuroendocrine function primarily in states of energy deficiency. Initially described as an antiobesity hormone, leptin has subsequently been shown also to influence basal metabolism, hematopoiesis, thermogenesis, reproduction, and angiogenesis. As a cytokine, leptin can affect thymic homeostasis and the secretion of acute-phase reactants such as interleukin-1 (IL-1) and tumor-necrosis factor-alpha (TNF-α). Leptin links nutritional status and proinflammatory T helper 1 (Th1) immune responses and the decrease in leptin plasma concentration during food deprivation leads to impaired immune function. Similar to other pro-inflammatory cytokines, leptin promotes Th1-cell differentiation and can modulate the onset and progression of autoimmune responses in several animal models of disease. Here, we review the advances and controversy for a role of leptin in the pathophysiology of immune responses and discuss novel possible therapeutic implications for leptin modulators. © 2012 Elsevier Inc. All rights reserved.

Daniel C.,University of Nottingham | Bell C.,University of Nottingham | Burton C.,University of Nottingham | Harguindey S.,Institute for Clinical Biology and Metabolism | And 2 more authors.
Biochimica et Biophysica Acta - Molecular Basis of Disease | Year: 2013

With a projected 382.4 per 100,000 people expected to suffer from some form of malignant neoplasm in 2015, improving treatment is an essential focus of cancer research today. Multi-drug resistance (MDR) is the leading cause of chemotherapeutic failure in the treatment of cancer, the term denoting a characteristic of the disease-causing agent to avoid damage by drugs designed to bring about their destruction. MDR is also characterised by a reversal of the pH gradient across cell membranes leading to an acidification of the outer milieu and an alkalinisation of the cytosol that is maintained by the proton pump vacuolar-type ATPase (V-ATPase) and the proton transporters: Na+/H+ exchanger (NHE1), Monocarboxylate Transporters (MCTs), Carbonic anhydrases (CAs) (mainly CA-IX), adenosinetriphosphate synthase, Na+/HCO3 - co-transporter and the Cl-/HCO3 -exchanger. This review aims to give an introduction to MDR. It will begin with an explanation for what MDR actually is and go on to look at the proposed mechanisms by which a state of drug resistance is achieved. The role of proton-pumps in creating an acidic extracellular pH and alkaline cytosol, as well as key biomechanical processes within the cell membrane itself, will be used to explain how drug resistance can be sustained. © 2013 Elsevier B.V.

Paparella D.,University of Bari | Whitlock R.,Hamilton Health Sciences
Seminars in Thrombosis and Hemostasis | Year: 2016

Cardiac surgery patients are prone to anemia from several mechanisms: intraoperative blood loss, preexisting anemia, and hemodilution. Patients are very frequently transfused with allogeneic red blood cells (RBC), which in itself is associated with harm. The use of RBC salvage technology has been advocated to salvage blood lost in the operative field and to reduce the need of homologous blood transfusion. Direct cardiotomy suction from the surgical field and unprocessed blood retransfusion is a common practice during cardiopulmonary bypass, but which is associated with a powerful activation of the coagulation and inflammatory systems: thrombin generation, excessive fibrinolysis, and release of proinflammatory cytokines. Compared with direct cardiotomy suction, the use of RBC salvage technology is able to reduce the amount of microparticles and activated proteins of autologous blood before retransfusion. However, when compared with no retransfusion of blood from the operative field, processed blood also triggers coagulopathy and inflammation. Clinical studies are discordant regarding the benefit of RBC salvage use during and after cardiac operations. Meta-analysis suggests reduced need of homologous blood transfusion, but no effects on mortality and morbidity. Copyright © 2016 by Thieme Medical Publishers, Inc.

Stojanova D.,Jožef Stefan International Postgraduate School | Ceci M.,University of Bari | Appice A.,University of Bari | Dzeroski S.,Jožef Stefan International Postgraduate School
Data Mining and Knowledge Discovery | Year: 2012

Network data describe entities represented by nodes, which may be connected with (related to) each other by edges.Many network datasets are characterized by a form of autocorrelation, where the value of a variable at a given node depends on the values of variables at the nodes it is connected with. This phenomenon is a direct violation of the assumption that data are independently and identically distributed. At the same time, it offers an unique opportunity to improve the performance of predictive models on network data, as inferences about one entity can be used to improve inferences about related entities. Regression inference in network data is a challenging task. While many approaches for network classification exist, there are very few approaches for network regression. In this paper, we propose a data mining algorithm, calledNCLUS, that explicitly considers autocorrelationwhen building regression models from network data. The algorithm is based on the concept of predictive clustering trees (PCTs) that can be used for clustering, prediction and multitarget prediction, including multi-target regression and multi-target classification.We evaluate our approach on several real world problems of network regression, coming from the areas of social and spatial networks. Empirical results showthat our algorithm performs better than PCTs learned by completely disregarding network information, as well as PCTs that are tailored for spatial data, but do not take autocorrelation into account, and a variety of other existing approaches. © The Author(s) 2012.

Franciosi M.,Consorzio Mario Negri Sud | Lucisano G.,Consorzio Mario Negri Sud | Lapice E.,University of Naples Federico II | Strippoli G.F.M.,Consorzio Mario Negri Sud | And 4 more authors.
PLoS ONE | Year: 2013

Aims/Hypothesis:Diabetes treatments were related with either an increased or reduced risk of cancer. There is ongoing debate about a potential protective action of metformin. To summarize evidence on the association between metformin and risk of cancer and cancer mortality in patients with diabetes.Methods:Data source: MEDLINE and EMBASE (January 1966-April 2012). We selected randomized studies comparing metformin and other hypoglycaemic agents and observational studies exploring the association between exposure to metformin and cancer. Outcomes were cancer mortality, all malignancies and site-specific cancers.Results:Of 25307 citations identified, 12 randomized controlled trials (21,595 patients) and 41 observational studies (1,029,389 patients) met the inclusion criteria. In observational studies there was a significant association of exposure to metformin with the risk of cancer death [6 studies, 24,410 patients, OR:0.65, 95%CI: 0.53-0.80], all malignancies [18 studies, 561,836 patients, OR:0.73, 95%CI: 0.61-0.88], liver [8 studies, 312,742 patients, OR:0.34; 95%CI: 0.19-0.60] colorectal [12 studies, 871,365 patients, OR:0.83, 95%CI: 0.74-0.92], pancreas [9 studies, 847,248 patients, OR:0.56, 95%CI: 0.36-0.86], stomach [2 studies, 100701 patients, OR:0.83, 95%CI: 0.76-0.91], and esophagus cancer [2 studies, 100694 patients, OR:0.90, 95%CI: 0.83-0.98]. No significant difference of risk was observed in randomized trials. Metformin was not associated with the risk of: breast cancer, lung cancer, ovarian cancer, uterus cancer, prostate cancer, bladder cancer, kidney cancer, and melanoma.Conclusions/Interpretation:Results suggest that Metformin might be associated with a significant reduction in the risk of cancer and cancer-related mortality. Randomized trials specifically designed to evaluate the efficacy of metformin as an anticancer agent are warranted. © 2013 Franciosi et al.

Reshkin S.J.,University of Bari | Cardone R.A.,University of Bari | Harguindey S.,Institute for Clinical Biology and Metabolism
Recent Patents on Anti-Cancer Drug Discovery | Year: 2013

Cancer cells and tissues, regardless of their origin and genetic background, have an aberrant regulation of hydrogen ion dynamics leading to a reversal of the intracellular to extracellular pH gradient (ApHi to ApHe) in cancer cells and tissue as compared to normal tissue. This perturbation in pH dynamics rises very early in carcinogenesis and is one of the most common patho-physiological hallmarks of tumors. Recently, there has been a very large increase in our knowledge of the importance and roles of pHi and pHe in developing and driving a series of tumor hallmarks. This reversed proton gradient is driven by a series of proton export mechanisms that underlie the initiation and progression of the neoplastic process. In this context, one of the primary and best studied regulators of both pHi and pHe in tumors is the Na+/H+ exchanger isoform 1 (NHE1). The NHE1 is an integral membrane transport protein involved in regulating pH and in tumor cells is a major contributor to the production and maintenance of their reversed proton gradient. It is activated during onco-gene-dependent transformation resulting in cytosolic alkalinization which then drives subsequent hallmark behaviors including growth factor- and substrate-independent growth, and glycolytic metabolism. It is further activated by various growth factors, hormone, the metabolic microenvironment (low serum, acidic pHe and hypoxia) or by ECM receptor activation. This review will present the recent progress in understanding the role the NHE1 in determining tumor progression and invadopo-dia-guided invasion/metastasis and recent patents for NHE1 inhibitors and novel therapeutic protocols for anti-NHE1 pharmacological approaches. These may represent a real possibility to open up new avenues for wide-spread and efficient treatments against cancer. © 2013 Bentham Science Publishers.

Pace V.,University of Vienna | Luisi R.,University of Bari
ChemCatChem | Year: 2014

Revitalising organolithiums: Important advancements in the field of palladium-catalyzed cross-coupling reactions have been gained recently through the direct use of notoriously difficult organolithium reagents as coupling partners. Such tactics can improve synthetic procedures for carbon-carbon bond formation under mild conditions. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Kagohara D.M.,Victoria University of Wellington | Sigafoos J.,Victoria University of Wellington | Achmadi D.,Victoria University of Wellington | O'Reilly M.,University of Texas at Austin | Lancioni G.,University of Bari
Research in Autism Spectrum Disorders | Year: 2012

This study aimed to teach two students with autism spectrum disorders (ASD) to check the spelling of words using the spell-check function on common word processor programs. A multiple-baseline across participants design with baseline, video modeling, and follow-up phases was implemented. During baseline, the participants performed less than 40% of the task-analyzed steps correctly. When the video modeling intervention was introduced via an iPad®, both participants reached the 76-100% correct level on the task analysis and became more successful in using the word processor programs to check the spelling of words. Follow-up data showed 100% correct performance by both participants. The results suggest that the video modeling intervention, delivered via an iPad®, was effective in teaching two adolescents with ASD to check the spelling of words using common word processing programs. © 2011 Elsevier Ltd.

Van Der Meer L.,Victoria University of Wellington | Sutherland D.,University of Canterbury | O'Reilly M.F.,University of Texas at Austin | Lancioni G.E.,University of Bari | Sigafoos J.,Victoria University of Wellington
Research in Autism Spectrum Disorders | Year: 2012

We compared acquisition of, and preference for, manual signing (MS), picture exchange (PE), and speech-generating devices (SGDs) in four children with autism spectrum disorders (ASD). Intervention was introduced across participants in a non-concurrent multiple-baseline design and acquisition of the three communication modes was compared in an alternating treatments design. Children's preference for using MS, PE or the SGD was also assessed. With intervention, all four participants learned to make specific requests using at least one of the three communication modes. The children also showed a preference for one mode. These results extend previous studies by demonstrating (in four new children with ASD) differential acquisition of, and idiosyncratic preferences for, three commonly used alternative communication modes. The present results further suggest faster acquisition and better maintenance with the preferred mode. We conclude that children's preferences for MS, PE, and SGDs should be considered when designing and implementing augmentative and alternative communication interventions. © 2012 Elsevier Ltd. All rights reserved.

De Lorenzo S.,University of Bari | Zollo A.,University of Naples Federico II | Zito G.,University of Bari
Journal of Geophysical Research: Solid Earth | Year: 2010

The attenuation of P waves, the site responses, and the source parameters (seismic moment, corner frequency, source dimension) of 490 seismic events that occurred during the 1997 Colfiorito, Umbria-Marche seismic sequence have been inferred from the inversion of P wave velocity spectra. The Boatwright source model has been assumed to model the source spectra. A global nonlinear inversion scheme was developed to avoid any a priori selection of the initial Q P and the corner frequency. To establish if a frequency-dependent QP model fits the data better than a constant QP model, two inversion results have been compared. Application of the Akaike information criterion indicates that the constant QP model represents the best compromise between model simplicity and data misfit. The station QP values are small: in the range of 50 to 200. A one-dimensional QP model is obtained by back projecting the inverted t*. Our results indicate both well-defined near-site attenuation effects at some sites and heterogeneity in the inelastic properties of the crust. With the exception of the amplification response at five seismic stations, most of the recording sites did not show amplification peaks at particular frequencies. The stress drop clearly increases as a function of the seismic moment, which indicates a deviation from self-similarity, whereas it does not show an increase with depth, probably owing to the effects of fluid pressurization in the crust. A stress drop of about 39 MPa is inferred. The relationship between the seismic moment and the local magnitude for P waves has been calibrated. © Copyright 2010 by the American Geophysical Union.

Miller D.H.,University College London | Fazekas F.,Medical University of Graz | Montalban X.,Vall dHebron University Hospital | Reingold S.C.,Scientific and Clinical Review Associates | Trojano M.,University of Bari
Multiple Sclerosis Journal | Year: 2014

Background: Multiple sclerosis (MS) is influenced by pregnancy, sex and hormonal factors.Objectives: A comprehensive understanding of the role of pregnancy, sex and hormonal factors can provide insights into disease mechanisms, and new therapeutic developments and can provide improved patient care and treatment. Methods: Based on an international conference of experts and a comprehensive PubMed search for publications on these areas in MS, we provide a review of what is known about the impact of these factors on disease demographics, etiology, pathophysiology and clinical course and outcomes. Results and conclusions: Recommendations are provided for counseling and management of people with MS before conception, during pregnancy and after delivery. The use of disease-modifying and symptomatic therapies in pregnancy is problematic and such treatments are normally discontinued. Available knowledge about the impact of treatment on the mother, fetus and newborn is discussed. Recommendations for future research to fill knowledge gaps and clarify inconsistencies in available data are made. © The Author(s) 2013.

Altomare D.F.,C o Azienda Ospedaliero | Di Lena M.,C o Azienda Ospedaliero | Porcelli F.,University of Bari | Trizio L.,University of Bari | And 5 more authors.
British Journal of Surgery | Year: 2013

Background: An effective screening tool for colorectal cancer is still lacking. Analysis of the volatile organic compounds (VOCs) linked to cancer is a new frontier in cancer screening, as tumour growth involves several metabolic changes leading to the production of specific compounds that can be detected in exhaled breath. This study investigated whether patients with colorectal cancer have a specific VOC pattern compared with the healthy population. Methods: Exhaled breath was collected in an inert bag (Tedlar®) from patients with colorectal cancer and healthy controls (negative at colonoscopy), and processed offline by thermal-desorber gas chromatography-mass spectrometry to evaluate the VOC profile. During the trial phase VOCs of interest were identified and selected, and VOC patterns able to discriminate patients from controls were set up; in the validation phase their discriminant performance was tested on blinded samples. A probabilistic neural network (PNN) validated by the leave-one-out method was used to identify the pattern of VOCs that better discriminated between the two groups. Results: Some 37 patients and 41 controls were included in the trial phase. Application of a PNN to a pattern of 15 compounds showed a discriminant performance with a sensitivity of 86 per cent, a specificity of 83 per cent and an accuracy of 85 per cent (area under the receiver operating characteristic (ROC) curve 0·852). The accuracy of PNN analysis was confirmed in the validation phase on a further 25 subjects; the model correctly assigned 19 patients, giving an overall accuracy of 76 per cent. Conclusion: The pattern of VOCs in patients with colorectal cancer was different from that in healthy controls. The PNN in this study was able to discriminate patients with colorectal cancer with an accuracy of over 75 per cent. Breath VOC analysis appears to have potential clinical application in colorectal cancer screening, although further studies are required to confirm its reliability in heterogeneous clinical settings. Copyright © 2012 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.

Fanti M.P.,Polytechnic of Bari | Mangini A.M.,Polytechnic of Bari | Mazzia F.,University of Bari | Ukovich W.,University of Trieste
Automatica | Year: 2015

The paper introduces a new class of consensus protocols to reach an agreement in networks of agents with discrete time dynamics. In order to guarantee the convergence of the proposed algorithms, some general results are proved in the framework of non-negative matrix theory. Moreover, we characterize the set of the consensus protocols and we specify the algorithm that each agent has to employ. Furthermore, we show that in the case of balanced graphs, the agents can apply the consensus protocols by a decentralized and scalable computation. The convergence properties are studied by a set of tests that show the good performance of the proposed algorithm for different network topologies, even in the cases in which the standard protocols do not exhibit satisfying performances. In particular, a rigorous theoretical analysis of the proposed protocol convergence for networks with ring topology is provided and compared with the standard algorithm. © 2015 Elsevier Ltd.

Infantino V.,University of Bari | Infantino V.,University of Basilicata | Iacobazzi V.,University of Bari | Menga A.,University of Bari | And 2 more authors.
Biochimica et Biophysica Acta - Gene Regulatory Mechanisms | Year: 2014

The chronic induction of inflammation underlies multiple pathological conditions, including metabolic, autoimmune disorders and cancer. The mitochondrial citrate carrier (CIC), encoded by the SLC25A1 gene, promotes the export of citrate from the mitochondria to the cytoplasm, a process that profoundly influences energy balance in the cells. We have previously shown that SLC25A1 is a target gene for lipopolysaccharide signaling and promotes the production of inflammatory mediators. We now demonstrate that SLC25A1 is induced at the transcriptional level by two key pro-inflammatory cytokines, tumor necrosis factor-α (TNFα) and interferon-γ (IFNγ), and such induction involves the activity of the nuclear factor kappa B and STAT1 transcription factors. By studying the down-stream events following SLC25A1 activation during signals that mimic inflammation, we demonstrate that CIC is required for regulating the levels of nitric oxide and of prostaglandins by TNFα or IFNγ Importantly, we show that the citrate exported from mitochondria via CIC and its downstream metabolic intermediate, acetyl-coenzyme A, are necessary for TNFα or IFNγ to induce nitric oxide and prostaglandin production. These findings provide the first line of evidence that the citrate export pathway, via CIC, is central for cytokine-induced inflammatory signals and shed new light on the relationship between energy metabolism and inflammation. © 2014 Elsevier B.V.

Guerrieri A.,University of Basilicata | Ciriello R.,University of Basilicata | Cataldi T.R.I.,University of Bari
Analytica Chimica Acta | Year: 2013

An amperometric biosensor for the determination of l-lysine based on l-lysine-α-oxidase immobilized by co-crosslinking on a platinum electrode previously modified by an overoxidized polypyrrole film is described. The optimization of experimental parameters, such as pH and flow rate, permitted to minimize significantly substrate interferences even using a low specific, commercial enzyme. The relevant biases introduced in the measurement of lysine were just about 1% for l-arginine, l-histidine and l-ornithine, roughly 4% for l-phenylalanine and l-tyrosine. The developed approach allowed linear lysine responses from 0.02mM up to 2mM with a sensitivity of 41nA/(mM×mm2) and a detection limit of 4μM (S/N=3). No appreciable loss in lysine sensitivity was observed up to about 40 days. Allowing polypyrrole layer to remove interference from electroactive compounds, the present method revealed suitable to detect l-lysine in a pharmaceutical and cheese sample, showing a good agreement with the expected values. © 2013 Elsevier B.V.

Garrappa R.,University of Bari | Moret I.,University of Trieste | Popolizio M.,University of Salento
Journal of Computational Physics | Year: 2014

The time-fractional Schrödinger equation is a fundamental topic in physics and its numerical solution is still an open problem. Here we start from the possibility to express its solution by means of the Mittag-Leffler function; then we analyze some approaches based on the Krylov projection methods to approximate this function; their convergence properties are discussed, together with related issues. Numerical tests are presented to confirm the strength of the approach under investigation. © 2014 Elsevier Inc.

Palazzo G.,University of Bari | Lopez F.,University of Molise | Mallardi A.,CNR Institute for Chemical and Physical Processes
Biochimica et Biophysica Acta - Proteins and Proteomics | Year: 2010

We report on the response of reaction center (RC) from Rhodobacter sphaeroides (an archetype of membrane proteins) to the exposure at high temperature. The RCs have been solubilized in aqueous solution of the detergent N,N-dimethyldodecylamine-N-oxide (LDAO). Changes in the protein conformation have been probed by monitoring the variation in the absorbance of the bacteriochlorine cofactors and modification in the efficiency of energy transfer from tryptophans to cofactors and among the cofactors (through fluorescence measurements). The RC aggregation taking place at high temperature has been investigated by means of dynamic light scattering. Two experimental protocols have been used: (i) isothermal kinetics, in which the time evolution of RC after a sudden increase of the temperature is probed, and (ii) T-scans, in which the RCs are heated at constant rate. The analysis of the results coming from both the experiments indicates that the minimal kinetic scheme requires an equilibrium step and an irreversible process. The irreversible step is characterized by a activation energy of 205 ± 14 kJ/mol and is independent from the detergent concentration. Since the temperature dependence of the aggregation rate was found to obey to the same law, the aggregation process is unfolding-limited. On the other hand, the equilibrium process between the native and a partially unfolded conformations was found to be strongly dependent on the detergent concentration. Increasing the LDAO content from 0.025 to 0.5 wt.% decreases the melting temperature from 49 to 42 °C. This corresponds to a sizeable (22 kJ/mol at 25 °C) destabilization of the native conformation induced by the detergent. The nature of the aggregates formed by the denatured RCs depends on the temperature. For temperature below 60 °C compact aggregates are formed while at 60 °C the clusters are less dense with a scaling relation between mass and size close to that expected for diffusion-limited aggregation. The aggregate final sizes formed at different temperatures indicate the presence of an even number of proteins suggesting that these clusters are formed by aggregation of dimers. © 2009 Elsevier B.V. All rights reserved.

Colonna G.,CNR Institute of Inorganic Methodologies and Plasmas | D'Angola A.,University of Basilicata | Capitelli M.,CNR Institute of Inorganic Methodologies and Plasmas | Capitelli M.,University of Bari
Physics of Plasmas | Year: 2012

In this paper, we have discussed the effects of electronically excited states of atomic species in affecting the isentropic coefficients of plasmas, focusing on mixtures representing the atmospheres of Jupiter, Mars, and Earth. General behaviors have been rationalized on the basis of simplified approaches. The contribution of the electronically excited states has been evidenced by comparing results obtained considering only the ground state and those obtained using either Fermi or Griem cutoff criteria. © 2012 American Institute of Physics.

Iacobazzi V.,University of Bari | Iacobazzi V.,CNR Institute of Neuroscience | Infantino V.,University of Bari | Infantino V.,University of Basilicata
Biological Chemistry | Year: 2014

Citrate is an important substrate in cellular energy metabolism. It is produced in the mitochondria and used in the Krebs cycle or released into cytoplasm through a specific mitochondrial carrier, CIC. In the cytosol, citrate and its derivatives, acetyl-CoA and oxaloacetate, are used in normal and pathological processes. Beyond the classical role as metabolic regulator, recent studies have highlighted that citrate is involved in inflammation, cancer, insulin secretion, histone acetylation, neurological disorders, and non-alcoholic fatty liver disease. Monitoring changes in the citrate levels could therefore potentially be used as diagnostic tool. This review highlights these new aspects of citrate functions.© 2014 by Walter de Gruyter Berlin/Boston.

Giacovazzo C.,CNR Institute of Crystallography | Giacovazzo C.,University of Bari | Mazzone A.,CNR Institute of Crystallography
Acta Crystallographica Section A: Foundations of Crystallography | Year: 2011

The expected mean-square error of electron-density maps (observed and difference) is traditionally estimated as a function of the variance of the observed amplitudes. The usual purpose is to evaluate the reliability of the structural parameters suggested by the final electron-density maps. Accordingly, such calculations are performed after the refinement stage, when the phases are considered perfectly determined. In this paper a mathematical expression for the variance (observed, difference and hybrid) is obtained for each point of an electron-density map for the space group P1 under a different hypothesis: the current phases are distributed on the trigonometric circle about the correct values, according to von Mises distributions. The variance calculation may then be performed at any stage of the phasing process, starting from a random up to a highly correlated model. It has been shown that the variance does not change dramatically from point to point of the map; therefore emphasis has been given to the concept of map variance, which allows an easier study of its properties. When the model is highly correlated with the target structure the conclusive formulas reduce to those previously described in the literature. The properties of the variance are discussed: it is shown that they are the basis for the most successful phasing procedures. © 2011 International Union of Crystallography.

Burla M.C.,University of Perugia | Giacovazzo C.,CNR Institute of Crystallography | Giacovazzo C.,University of Bari | Polidori G.,University of Perugia
Journal of Applied Crystallography | Year: 2010

A recent probabilistic reformulation of the difference electron-density Fourier synthesis [Burla, Caliandro, Giacovazzo & Polidori (2010). Acta Cryst. A66, 347-361] suggested that the most suitable Fourier coefficients are the sum of the classical difference term (mF-DF p) with a flipping term, depending on the model and on its quality. The flipping term is dominant when the model is poor and is negligible when the model is a good representation of the target structure. In the case of a random model the Fourier coefficient does not vanish and therefore could allow the recovery of the target structure from a random model. This paper describes a new phasing algorithm which does not require use of the concept of structure invariants or semi-invariants: it is based only on the properties of the new difference electron density and of the observed Fourier synthesis. The algorithm is cyclic and very easy to implement. It has been applied to a large set of small-molecule structures to verify the suitability of the approach. © 2010 International Union of Crystallography Printed in Singapore - all rights reserved.

Capozzi M.A.M.,University of Bari | Capitelli F.,CNR Institute of Crystallography | Cardellicchio C.,CNR Institute of Chemistry of organometallic Compounds
Crystal Growth and Design | Year: 2014

A series of enantiopure crystalline aryl benzyl sulfoxides, bearing different substituents on both the aryl groups, were synthesized by an enantioselective oxidation of the corresponding sulfides. Structural investigations, achieved by means of single-crystal X-ray diffraction, allowed us to recognize the main assembling interactions. The same procedure was repeated for some corresponding fluorinated aryl benzyl sulfoxides. The synthesis of the enantiomers of a new fluorinated compound, which shows unusual structural patterns, prompted us to compare the structural motifs of the two families of sulfoxides (fluorinated and unfluorinated) and to investigate the changes due to the fluorine substitution. Some short contacts involving the fluorine atom were discussed in more details, taking into account the recent interest in these sometimes controversial interactions. (Chemical Equation Presented). © 2014 American Chemical Society.

Riccardi D.,University of Cardiff | Valenti G.,University of Bari
Nature Reviews Nephrology | Year: 2016

The ability to monitor changes in the ionic composition of the extracellular environment is a crucial feature that has evolved in all living organisms. The cloning and characterization of the extracellular calcium-sensing receptor (CaSR) from the mammalian parathyroid gland in the early 1990s provided the first description of a cellular, ion-sensing mechanism. This finding demonstrated how cells can detect small, physiological variations in free ionized calcium (Ca 2+) in the extracellular fluid and subsequently evoke an appropriate biological response by altering the secretion of parathyroid hormone (PTH) that acts on PTH receptors expressed in target tissues, including the kidney, intestine, and bone. Aberrant Ca 2+ sensing by the parathyroid glands, as a result of altered CaSR expression or function, is associated with impaired divalent cation homeostasis. CaSR activators that mimic the effects of Ca 2+ (calcimimetics) have been designed to treat hyperparathyroidism, and CaSR antagonists (calcilytics) are in development for the treatment of hypercalciuric disorders. The kidney expresses a CaSR that might directly contribute to the regulation of many aspects of renal function in a PTH-independent manner. This Review discusses the roles of the renal CaSR and the potential impact of pharmacological modulation of the CaSR on renal function. © 2016 Macmillan Publishers Limited.

Aresta M.,University of Bari | Dibenedetto A.,University of Bari | Pastore C.,University of Bari | Angelini A.,University of Bari | And 2 more authors.
Journal of Catalysis | Year: 2010

In this paper we show that modification of ceria by loading alumina strongly reduces the oxidation of methanol and the consequent reduction of Ce(IV) to Ce(III) with increase of both the life of the catalysts and their selectivity. The combination of surface techniques (XPS and BET) with structural techniques (XRD) has allowed a good characterisation of the working catalysts. Spectroscopic analyses (DRIFT and multinuclear solid state and solution NMR) have permitted the monitoring of the species formed on the surface of the catalyst and released from it. The formation of DMC takes place in successive steps such as (i) interaction of methanol with the catalyst surface with the formation of the surface-bound {single bond}OCH3; (ii) building on the catalyst surface of the hemicarbonate moiety [-OCH3 → -OC(O)OCH3]; and (iii) reaction of the latter with the gas-phase methanol to afford the organic carbonate. © 2009 Elsevier Inc. All rights reserved.

Barile S.,University of Bari | Figueiredo G.M.,Federal University of Pará
Advanced Nonlinear Studies | Year: 2014

In this paper we prove an existence result for a least energy nodal (or sign-changing) solution for the class of p&q problems given by -div(a(|∇u|p)| ∇u|p-2∇u) = f (u) in Ω, u = 0 on ∂Ω, where Ω is a smooth bounded domain in ℝN, N ≥ 3 and 2 ≤ p < N. The function a : ℝ+ → ℝ+ grows like t q-p/p as t → +∞ for some p ≤ q < N, the case q = p meaning that a is bounded away from zero and infinity. The nonlinearity f : ℝ → ℝ grows like |t|m-1 at infinity with q < m < q* = Nq/N-q. Moreover, we find that u has exactly two nodal domains or changes sign exactly once in Ω. The functions f and a satisfy suitable additional growth and monotonicity conditions which allow this result to extend previous ones to a larger class of p&q type problems. The proof is based on a minimization argument and a variant of quantitative deformation lemma.

Papp H.,Hungarian Academy of Sciences | Matthijnssens J.,Rega Institute for Medical Research | Martella V.,University of Bari | Ciarlet M.,Novartis | Banyai K.,Hungarian Academy of Sciences
Vaccine | Year: 2013

Group A rotavirus (RVA) is a major cause of diarrhea and diarrhea-related mortality in foals in parts of the world. In addition to careful horse farm management, vaccination is the only known alternative to reduce the RVA associated disease burden on horse farms. The precise evaluation of vaccine effectiveness against circulating strains needs enhanced surveillance of equine RVAs in areas where vaccine is already available or vaccine introduction is anticipated. Therefore, we undertook the overview of relevant information on epidemiology of equine RVA strains through systematic search of public literature databases. Our findings indicated that over 99% of equine RVA strains characterized during the past three decades belonged to two common genotypes, G3P[12] and G14P[12], whereas most of the minority equine RVA strains were probably introduced from a heterologous host by interspecies transmission. These baseline data on RVA strains in horses shall contribute to a better understanding of the spatiotemporal dynamics of strain prevalence in vaccinated and non-vaccinated herds. © 2013 Elsevier Ltd.

Monne M.,University of Bari | Monne M.,University of Basilicata | Palmieri F.,University of Bari
Current Topics in Membranes | Year: 2014

The eukaryotic transport protein family SLC25 consists of mitochondrial carriers (MCs) that are recognized on the sequence level by a threefold repeated and conserved signature motif. The majority of MCs characterized so far catalyzes strict exchanges of substrates across the mitochondrial inner membrane. The substrates are nucleotides, metabolic intermediates, and cofactors that are required in cytoplasmic and matrix metabolism. This review summarizes and discusses the current knowledge of the antiport mechanism(s) of MCs that has been deduced from determining transport characteristics and by analyzing structural, sequence, and mutagenesis data. The mode of transport varies among different MCs with respect to how the substrate translocation depends on the electrical and pH gradients across the mitochondrial inner membrane, for example, the ADP/ATP carrier is electrogenic (electrophoretic), the GTP/GDP carrier is dependent on the pH gradient, the aspartate/glutamate carrier is dependent on both, and the oxoglutarate/malate carrier is independent of them. The structure of the bovine ADP/ATP carrier consists of a six-transmembrane α-helix bundle with a pseudo-threefold symmetry and a closed matrix gate. By using this structure as a template in homology modeling, residues engaged in substrate binding and the formation of a cytoplasmic gate in MCs have been proposed. The functional importance of the residues of the binding site, the matrix, and the cytoplasmic gates is supported by transport activities of different MCs with single point mutations. Cumulative evidence has been used to postulate a general transport mechanism for MCs. © 2014 Elsevier Inc.

Longhitano S.G.,University of Basilicata | Sabato L.,University of Bari | Tropeano M.,University of Bari | Gallicchio S.,University of Bari
Journal of Sedimentary Research | Year: 2010

Tide-dominated depositional systems are very common in macro tidal and meso tidal settings. They are less developed in micro tidal marine areas where sediments are dispersed mostly under the effects of waves and currents. In some specific coastal settings, the influence of the dominant hydrodynamics can be reduced or attenuated by the presence of promontories forming engulfed sectors or by the occurrence of submarine passageways or straits. In these conditions, as well as in micro tidal settings, the tidal influence can be amplified, producing a significant signature in the sedimentary record. A number of tide-influenced deposits can be recognized in the Neogene of the Southern Apennine, Italy, although the Mediterranean area is characterized by minor tidal ranges. Spectacular exposure of middle to upper Pliocene deposits cropping out around Tricarico allows the analysis of the architecture and internal complexities of a mixed bioclastic-siliciclastic succession deposited in a thrust-top basin. Undulations forming along the hinge of an anticline favored the onset of seaway conditions, which produced hydraulic amplification of marine currents flowing towards the chain and subjected to tidal influences. The mixed deposits of Tricarico exhibit prominent large-scale, unidirectional cross stratification and a suite of additional dune- and ripple-bedded structures of various dimensions. Cross stratification can be subdivided into four hierarchical levels based on their increasing degree of internal complexity of different ranks (from first-order to fourth-order sets). Processes invoked for the formation of such a complex suite of larger- and smaller-scale sedimentary structures are related to cyclical events, such as high-frequency sea-level oscillations and tidal cycles of various durations. First-order sets are interpreted as produced by migrating subaqueous dunes along a SSW-NNE-trending seaway at water depths below the wave base. These sets exhibit bed-thickness vertical patterns which have been related to the influence of highfrequency base-level oscillations that occurred during dune accumulation, producing alternating stages of accelerating and decelerating currents. Second-order cross stratification has been interpreted to have formed by dunes with varying sinuosity, superposition, and flow conditions, under the effect of varying current strengths but constant sediment production. Formset successions were produced by large compound dunes and are considered as the expression of low-energy and decaying dune fields that developed during times of decreasing sediment transport. Cross lamination of third-order and fourth-order sets shows series of bundles and couplets of coarser and finer laminae which, at a different scale, recorded repeated cycles of tidal ranges of different amplitudes. These considerations allow us to propose an original depositional model represented by a flood-tidal delta, which questions the absence of macro tidal sedimentation within the purportedly micro tidal oceanographic setting of the Mediterranean during the Pliocene. Copyright © 2010, SEPM (Society for Sedimentary Geology).

Crupi P.,University of Bari | Bizzarri A.,Italian National Institute of Geophysics and Volcanology
Annals of Geophysics | Year: 2013

We have investigated the role of the radiation damping term (RDT) on repeated earthquake ruptures by modeling the faulting process through a single one-dimensional analog fault system governed by different constitutive laws. The RDT expresses the energy lost by the seismic waves. The RDT is inherently accounted for in more elaborated, fully dynamic models of extended fault, whereas it is neglected in one-dimensional fault models. In this study, we adopt various formulations of the laboratoryderived rate-dependent and state-dependent friction constitutive laws: the Dieterich-Ruina law, the Ruina-Dieterich law and the Chester and Higgs law. Our numerical results clearly indicate that the RDT significantly affects the system dynamics. More specifically, the more the RDT is effective, the more frequent the slip failures are (with a cycle-time reduction of ca. 30%). We also show that inclusion of the RDT tends to promote smaller but more frequent earthquake instabilities, irrespective of the choice of the governing law. Our data shed light on the limitations implied by the conventional formulation of the equation of motion for the spring system, in which the energy radiation is ignored. © 2013 by the Istituto Nazionale di Geofisica e Vulcanologia. All rights reserved.

Lelario F.,University of Basilicata | Bianco G.,University of Basilicata | Bufo S.A.,University of Basilicata | Cataldi T.R.I.,University of Bari
Phytochemistry | Year: 2012

Glucosinolates (GLSs) are sulfur-rich plant secondary metabolites which occur in a variety of cruciferous vegetables and among various classes of them, genus Brassica exhibits a rich family of these phytochemicals at high, medium and low abundances. Liquid chromatography (LC) with electrospray ionization in negative ion mode (ESI-) coupled to a hybrid quadrupole linear ion trap (LTQ) and Fourier transform ion cyclotron resonance mass spectrometer (FTICRMS) was employed for the selective and sensitive determination of intact GLSs in crude sample extracts of broccoli (Brassica oleracea L. Var. italica), cauliflower (B. oleracea L. Var. Botrytis) and rocket salad (Eruca sativa L.) with a wide range of contents. When LTQ and FTICR mass analyzers are compared, the magnitude of the limit of detection was ca. 5/6-fold lower with the FTICR MS. In addition, the separation and detection by LC-ESI-FTICR MS provides a highly selective assay platform for unambiguous identification of GLSs, which can be extended to lower abundance (minor) GLSs without significant interferences of other compounds in the sample extracts. The analysis of Brassicaceae species emphasized the presence of eight minor GLSs, viz. 1-methylpropyl-GLS, 2-methylpropyl-GLS, 2-methylbutyl-GLS, 3-methylbutyl-GLS, n-pentyl-GLS, 3-methylpentyl-GLS, 4-methylpentyl-GLS and n-hexyl-GLS. The occurrence of these GLSs belonging to the saturated aliphatic side chain families C 4, C 5 and C 6, presumably formed by chain elongation of leucine, homoleucine and dihomoleucine as primary amino acid precursors, is described. Based on their retention behavior and tandem MS spectra, all these minor compounds occurring in plant extracts of B. oleracea L. Var. italica, B. oleracea L. Var. Botrytis and E. sativa L. were tentatively identified. © 2011 Elsevier Ltd. All rights reserved.

Salomone A.,University of Bari | Perna F.M.,University of Bari | Falcicchio A.,CNR Institute of Crystallography | Nilsson Lill S.O.,Gothenburg University | And 5 more authors.
Chemical Science | Year: 2014

α-Lithiated epoxides, long considered "fleeting" intermediates in the reactions of epoxides with strong bases, have nowadays proven to be key synthons for asymmetric synthesis. In this study, the solution and the solid state structure of an α-lithiated aryloxirane, namely α-lithiated ortho-trifluoromethyl styrene oxide (1-Li), were determined. Single crystal X-ray diffraction analysis of 1-Li performed at 100 K applying the X-TEMP-2 device revealed a self-assembled heterochiral dimeric structure with a rare central six-membered (O-Li-C)2 planar core, which is unprecedented in Li/oxygen carbenoids. Multinuclear magnetic resonance ( 1H, 13C, 19F, 7Li) studies suggested that 1-Li exists in THF solution as a mixture of two interconverting diastereomeric dimeric aggregates, each one featuring a single σ-contact between lithium and a carbon atom. Line shape analysis provided activation parameters for both the dynamic interconversion of the two dimers and the enantiomerisation of 1-Li, which proved to be mostly entropy controlled. The structural assignment in solution was supported by density functional theory computations through the investigation of conformers of monomeric and dimeric complexes of 1-Li featuring different degrees of specific solvation. A mechanism based on the equilibration of six-membered homo- and heterochiral dimers was proposed to explain the configurational instability exhibited by 1-Li in THF. © 2014 The Royal Society of Chemistry.

Bizzarri A.,Italian National Institute of Geophysics and Volcanology | Crupi P.,University of Bari
Bulletin of the Seismological Society of America | Year: 2013

The prediction of impending earthquakes undoubtedly remains one of the most pursued goals of modern seismology. Within the framework of a deterministic description of earthquake faulting, the initial state of the fault system and the choice of the governing model describing its rheological behavior play a fundamental role in the description of the earthquake recurrence. In classical models of faulting, this initial state is basically described by the initial shear-stress distribution (prior to the next earthquake event) and by the initial sliding velocity. In this paper, by assuming a rate-, state-, and temperature-dependent rheology, we investigate whether the initial thermal state of the fault can also have a significant role in earthquake dynamics. Our numerical results clearly demonstrate that the initial temperature greatly influences the cosesimic slip (and thus the earthquake magnitude), the released stress (and thus the radiated energy), and the interevent time (i.e., the earthquake recurrence). Despite the remaining issues on the concept of earthquake cyclicity, our results can contribute to the lively debate on the deterministic hazard assessment, illuminating that the temperature field also plays a fundamental role in earthquake dynamics, not only because it controls possible phase changes and the chemical environment of the fault zone, but also because it affects the response of a brittle fault and earthquake cycles.

Cataldi T.R.I.,University of Bari | Lelario F.,University of Basilicata | Orlando D.,University of Basilicata | Bufo S.A.,University of Basilicata
Analytical Chemistry | Year: 2010

An approach is presented that can be of general applicability for structural elucidation of naturally occurring glucosinolates (GLSs) in crude plant extracts based on the fragmentation of isotopic A and A + 2 peaks. The most important fragmentation pathways were studied by tandem mass spectrometry (MSn, n = 2, 3) using a linear quadrupole ion trap (LTQ) upon GLSs separation by optimized reversed-phase liquid chromatography (RPLC) and electrospray ionization (ESI) in negative ion mode. As the LTQ MS analyzer ensures high sensitivity and linearity, the fragmentation behavior under collision induced dissociation (CID) of the isotopic peaks A and A + 2 as precursor ions was carefully examined. All GLSs (R-C7H 11O9NS2 -) share a common structure with at least two sulfur atoms and significant isotopic abundance of 34S. Thus, dissociation of the +2 Da isotopomeric ions results in several fragment ion doublets containing a combination of 32S and 34S. Accordingly, their relative abundances allow one to speed up the structural recognition of GLSs with great confidence, as it produces more structurally informative ions than conventional tandem MS performed on A ions. This approach has been validated on known GLSs bearing two, three, four, and six sulfur atoms by comparing expected and measured isotopic peak abundance ratios (IA/IA+2). Both group- and compound-specific fragments were observed; the predominant pathway of fragmentation of GLSs gives rise to species having the following m/z values, [M - SO3 - H] -, [M - 196 - H]-, [M - 178 - H]-, and [M - 162 - H]- after H rearrangement from the R- side chain. The present strategy was successfully applied to extracts of rocket salad leaves (Eruca sativa L.), which was sufficient for the chemical identification of a not already known 6-methylsulfonyl-3-oxohexyl-GLS, a long-chain-length aliphatic glucosinolate, which contains three sulfurs and exhibits a deprotonated molecular ion at m/z 494.1. © 2010 American Chemical Society.