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Pisa, Italy

The University of Pisa , is an Italian public research university located in Pisa, Italy. It was founded in 1343 by an edict of Pope Clement VI. It is the 19th oldest extant university in the world and the 10th oldest in Italy. The prestigious university is ranked between first and third places nationally, in the top 30 in Europe and the top 300 in the world. It houses the Orto botanico di Pisa, Europe's oldest academic botanical garden, which was founded in 1544.The University of Pisa is part of the Pisa University System, which includes the Scuola Normale Superiore and the Sant'Anna School of Advanced Studies. The university has about 57,000 students .In the fields of philology and cultural studies, the University of Pisa is a leading member of ICoN, an inter-university consortium of 21 Italian universities supported by the Ministry of Education, Universities and Research, as well as a member of the European University Association, the Partnership of a European Group of Aeronautics and Space Universities network and the Cineca consortium. It's the only university in Italy which has become a member of the prestigious Universities Research Association.Among its notable graduates there are several national and foreign political leaders including two Italian presidents, five Popes, five Italian prime ministers and three Nobel Laureates as students, faculty or staff affiliates.Pisa has an intense athletic rivalry with the University of Pavia, which traditionally culminates in the Pisa-Pavia Regatta , the oldest competition of this kind in Italy, and second in Europe only to the Oxford Cambridge boat race.In 2013, the University of Pisa finished with La Sapienza University of Rome in first place among the Italian universities, according to the Academic Ranking of World Universities. Wikipedia.


Synthetic procedures for bis(η6-arene) metal derivatives and aspects of their reactivity are reviewed. Attention is focused on early transition metals (Groups 4-6) but, when necessary, reference will be made to arene derivatives of Groups 7-10, lanthanides and actinides. After a short historical presentation of bis(η6-arene) derivatives, aimed at illustrating the relevance of this class of compounds to the origin and the evolution of organometallic chemistry, the synthetic procedures to bis(η6-arenes) will be discussed in the light of the most recent results. As far as the reactivity of bis(η6-arene) compounds is concerned, particular attention is given to the electron transfer reactions occurring with or without arene displacement; data are reported for the use of low-valent bis(η6-arene) compounds as a useful entry into the inorganic and coordination chemistry of the corresponding metal in non aqueous systems. The use of bis(η6-arene) derivatives of transition metals in low oxidation states (0, +1) as precursors to catalytic systems for the oligomerisation and polymerization of unsaturated monomers and as starting compounds for the preparation of molecule-based magnets, ordered crystals and new materials and supports is described. © 2009 Elsevier B.V. All rights reserved.


Tian Z.,Michigan Technological University | Leus G.,Technical University of Delft | Lottici V.,University of Pisa
IEEE Journal on Selected Areas in Communications | Year: 2011

This paper investigates the issue of dynamic resource allocation (DRA) in the context of multi-user cognitive radio networks. We present a general framework adopting generalized signal expansion functions for representation of physical-layer radio resources as well as for synthesis of transmitter and receiver waveforms, which allow us to join DRA with waveform adaptation, two procedures that are currently carried out separately. Based on the signal expansion framework, we develop noncooperative games for distributed DRA, which seek to improve the spectrum utilization on a per-user basis under both transmit power and cognitive spectral mask constraints. The proposed DRA games can handle many radio platforms such as frequency, time or code division multiplexing (FDM, TDM, CDM), and even agile platforms with combinations of different types of expansion functions. To avoid the complications of having too many active expansion functions after optimization, we also propose to combine DRA with sparsity constraints. Generally, the sparsity-constrained DRA approach improves convergence of distributed games at little performance loss, since the effective resources required by a cognitive radio are in fact sparse. Finally, to acquire the channel and interference parameters needed for DRA, we develop compressed sensing techniques that capitalize on the sparse properties of the wideband signals to reduce the number of samples used for sensing and hence the sensing time. © 2006 IEEE.


Del Prato S.,University of Pisa | Camisasca R.,Takeda Development Center Europe Ltd. | Wilson C.,Takeda Development Center Americas Inc. | Fleck P.,Takeda Development Center Americas Inc.
Diabetes, Obesity and Metabolism | Year: 2014

Aims: To evaluate the long-term durability of the efficacy of alogliptin compared with glipizide in combination with metformin in people with type 2 diabetes inadequately controlled on stable-dose metformin. Methods: This multicentre, double-blind, active-controlled study randomized 2639 patients aged 18-80 years to 104 weeks of treatment with metformin in addition to alogliptin 12.5 mg once daily (n = 880), alogliptin 25 mg once daily (n = 885) or glipizide 5 mg once daily, titrated to a maximum of 20 mg (n = 874). The primary endpoint was least square mean change from baseline in HbA1c level at 104 weeks. Results: The mean patient age was 55.4 years, the mean diabetes duration was 5.5 years and the mean baseline HbA1c was 7.6%. HbA1c reductions at week 104 were -0.68%, -0.72% and -0.59% for alogliptin 12.5 and 25 mg and glipizide, respectively [both doses met the criteria for non-inferiority to glipizide (p<0.001); alogliptin 25 mg met superiority criteria (p=0.010)]. Fasting plasma glucose concentration decreased by 0.05 and 0.18 mmol/l for alogliptin 12.5 and 25 mg, respectively, and increased by 0.30 mmol/l for glipizide (p < 0.001 for both comparisons with glipizide). Mean weight changes were -0.68, -0.89 and 0.95 kg for alogliptin 12.5 and 25 mg and glipizide, respectively (p < 0.001 for both comparisons with glipizide). Hypoglycaemia occurred in 23.2% of patients in the glipizide group vs. 2.5 and 1.4% of patients in the alogliptin 12.5 and 25 mg groups, respectively. Pancreatitis occurred in one patient in the alogliptin 25 mg group and three in the glipizide group. Conclusions: Alogliptin efficacy was sustained over 2 years in patients with inadequate glycaemic control on metformin alone. © 2014 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.


Biver T.,University of Pisa
Applied Spectroscopy Reviews | Year: 2012

Abstract: Ultraviolet-visible (UV-Vis) spectrometries (absorbance, linear dichroism [LD], and circular dichroism [CD]) are relatively simple techniques that can provide important information on the mode of binding of small molecules (dyes, drugs) to DNA and RNA helices. In this article the spectral characteristics of three families of dyes upon interaction with polynucleotides are reviewed. Each of them is representative for one of the major binding modes: acridines for intercalation, Hoechst dyes for groove binding, and porphyrins for external dye stacking. The purpose is to help the reader who is not accustomed to using these systems to gain a simple picture of what the predominant UV-Vis features of each binding mode are. These data are discussed and tables are provided to collect and compare the absorbance, LD, and CD spectral features of several examples of the three dye families chosen. © 2012 Copyright Taylor and Francis Group, LLC.


Mennucci B.,University of Pisa
Wiley Interdisciplinary Reviews: Computational Molecular Science | Year: 2012

The polarizable continuum model (PCM) is a computational method originally formulated 30 years ago but still today it represents one of the most successful examples among continuum solvation models. Such a success is mainly because of the continuous improvements, both in terms of computational efficiency and generality, made by all the people involved in the PCM project. The result of these efforts is that nowadays, PCM, with all its different variants, is the default choice in many computational codes to couple a quantum-mechanical (QM) description of a molecular system with a continuum description of the environment. In this review, a brief presentation of the main methodological and computational aspects of the method will be given together with an analysis of strengths and critical issues of its coupling with different QM methods. Finally, some examples of applications will be presented and discussed to show the potentialities of PCM in describing the effects of environments of increasing complexity. © 2012 John Wiley & Sons, Ltd.


Domenici V.,University of Pisa
Progress in Nuclear Magnetic Resonance Spectroscopy | Year: 2012

Graphical abstract: Highlights: Order parameters by 2H NMR of 2H-labelled liquid crystal elastomers and 2H-labelled probes in LCEs. Crosslinking density vs. thermodynamic features of the paranematic-nematic transition. Heterogeneity of real samples, phase biaxiality and coupling between strain and order. Comparison between liquid crystal elastomers and non-mesogenic elastomers. Comparison between liquid crystal polymers and liquid crystal elastomers. © 2011 Elsevier B.V. All rights reserved.


Objective: The authors sought to determine study design factors that may influence clinical trial outcome in augmentation/combination trials for antidepressant partial responders/nonresponders with major depressive disorder (MDD) and to examine whether the use of a prospective treatment phase (lead-in) to assess antidepressant nonresponse may result in a better chance to detect a drug-placebo separation in such trials. Data Sources: MEDLINE/PubMed publication databases were searched for randomized, double-blind, placebo-controlled trials of adjunctive pharmacologic strategies for antidepressant partial responders/nonresponders with MDD. The search term depression was successively cross-referenced with the terms augmentation, adjunct, and adjunctive to identify pertinent trials. (The search was limited to articles published between January 1980 and October 2010.) Study Selection: Thirty-five articles involving 40 adjunctive drug versus placebo comparisons were pooled (n = 4,676). Final inclusion of articles was determined by consensus between the authors. Data Extraction: Data extracted included whether there was a lead-in phase and, if so, the drugs, the doses, and the total duration of the lead-in phase. Additional data extracted included the number of patients enrolled, patient characteristics, methods used to define treatment resistance, drug dosages, duration of the adjunctive trial, response and remission rates, and rates of discontinuation for any reason and for adverse events. Results: The risk ratio of responding to the adjunctive drug versus placebo was not influenced by any of the study design factors analyzed (probability of receiving placebo, year of publication, severity of depression at baseline). Meta-regression analysis yielded no significant difference in the risk ratio of responding and remitting to the adjunctive drug versus placebo between studies that did versus did not include an antidepressant lead-in phase. However, pooled response/remission rates for adjunctive drug and placebo were statistically significantly lower in trials that did versus did not include a lead-in phase (response rates: for adjunctive drug, 42.6% vs 47.4%, respectively, P = .014; for adjunctive placebo, 29.7% vs 36.2%, respectively, P = .002; remission rates: for adjunctive drug, 31.0% vs 37.3%, respectively, P = .003; and adjunctive placebo, 18.1% vs 24.7%, respectively, P = .001). Conclusions: These results suggest that the choice to use historical data only to define treatment resistance prior to patient enrollment and randomization rather than requiring patients to first undergo a prospective lead-in phase can be a reasonable and evidence-supported approach to design effective clinical trials on augmentation/combination strategies for partial responders/nonresponders with MDD. © Copyright 2012 Physicians Postgraduate Press, Inc.


Fanti L.,University of Pisa
Environmental and Resource Economics | Year: 2015

In this paper the dynamic effects of public environmental policies are investigated in a Cournot duopoly with both heterogeneous and homogeneous expectations in a context of limited rationality. It is shown that the increase in upper limits to emissions always tends to destabilise markets and generate a chaotic market dynamics in both cases. The policy implication of this result is that the use of environmental policies may favour market stability. It is also shown that higher costs of abatement technology entail a higher likelihood of stability loss (although in the heterogeneous expectations case also a decrease in costs may destabilise). © 2014, Springer Science+Business Media Dordrecht.


Fine-needle aspiration biopsy (FNA) is usually applied to distinguish benign from malignant thyroid nodules. However, cytological analysis cannot always allow a proper diagnosis. We believe that the improvement of the diagnostic capability of pre-surgical FNA could avoid unnecessary thyroidectomy. In a previous study, we performed a proteome analysis to examine FNA collected after thyroidectomy. With the present study, we examined the applicability of these results on pre-surgical FNA. We collected pre-surgical FNA from 411 consecutive patients, and to obtain a correct comparison with our previous results, we processed only benign (n=114), papillary classical variant (cPTC) (n=34) and papillary tall cell variant (TcPTC) (n=14) FNA. We evaluated levels of five proteins previously found up-regulated in thyroid cancer with respect to benign nodules. ELISA and western blot (WB) analysis were used to assay levels of L-lactate dehydrogenase B chain (LDHB), Ferritin heavy chain, Ferritin light chain, Annexin A1 (ANXA1), and Moesin in FNA. ELISA assays and WB analysis confirmed the increase of LDHB, Moesin, and ANXA1 in pre-surgical FNA of thyroid papillary cancer. Sensitivity and specificity of ANXA1 were respectively 87 and 94% for cPTC, 85 and 100% for TcPTC. In conclusion, a proteomic analysis of FNA from patients with thyroid nodules may help to distinguish benign versus malignant thyroid nodules. Moreover, ANXA1 appears to be an ideal candidate given the high sensitivity and specificity obtained from ROC curve analysis.


Panagopoulos H.,University of Cyprus | Vicari E.,University of Pisa
Journal of High Energy Physics | Year: 2011

We study the scaling behavior of the 4D SU(3) lattice gauge theory in the presence of a θ term, by Monte Carlo simulations computing the topological properties at imaginary θ. The numerical results provide a good evidence of scaling in the continuum limit. The imaginary θ dependence of the ground-state energy turns out to be well described by the first few terms of related expansions around θ = 0, providing accurate estimates of the first few coefficients, up to O(θ6). © SISSA 2011.


Anastasi G.,University of Pisa | Conti M.,CNR Institute for Informatics and Telematics | Di Francesco M.,University of Texas at Arlington
IEEE Transactions on Industrial Informatics | Year: 2011

Wireless Sensor Networks (WSNs) represent a very promising solution in the field of wireless technologies for industrial applications. However, for a credible deployment of WSNs in an industrial environment, four main properties need to be fulfilled, i.e., energy efficiency, scalability, reliability, and timeliness. In this paper, we focus on IEEE 802.15.4 WSNs and show that they can suffer from a serious unreliability problem. This problem arises whenever the power management mechanism is enabled for energy efficiency, and results in a very low packet delivery ratio, also when the number of sensor nodes in the network is very low (e.g., 5). We carried out an extensive analysis - based on both simulation and experiments on a real WSN - to investigate the fundamental reasons of this problem, and we found that it is caused by the contention-based Medium Access Control (MAC) protocol used for channel access and its default parameter values. We also found that, with a more appropriate MAC parameters setting, it is possible to mitigate the problem and achieve a delivery ratio up to 100%, at least in the scenarios considered in this paper. However, this improvement in communication reliability is achieved at the cost of an increased latency, which may not be acceptable for industrial applications with stringent timing requirements. In addition, in some cases this is possible only by choosing MAC parameter values formally not allowed by the standard. © 2006 IEEE.


Ferrannini E.,University of Pisa | Cushman W.C.,University of Tennessee Health Science Center
The Lancet | Year: 2012

High blood pressure is reported in over two-thirds of patients with type 2 diabetes, and its development coincides with the development of hyperglycaemia. Many pathophysiological mechanisms underlie this association. Of these mechanisms, insulin resistance in the nitric-oxide pathway; the stimulatory effect of hyperinsulinaemia on sympathetic drive, smooth muscle growth, and sodium-fluid retention; and the excitatory effect of hyperglycaemia on the renin-angiotensin-aldosterone system seem to be plausible. In patients with diabetes, hypertension confers an enhanced risk of cardiovascular disease. A blood pressure of lower than 140/85 mm Hg is a reasonable therapeutic goal in patients with type 2 diabetes according to clinical trial evidence. People with controlled diabetes have a similar cardiovascular risk to patients without diabetes but with hypertension. A renin-angiotensin system blocker combined with a thiazide-type diuretic might be the best initial antihypertensive regimen for most people with diabetes. In general, the positive effects of antihypertensive drugs on cardiovascular outcomes outweigh the negative effects of antihypertensive drugs on glucose metabolism.


Marazziti D.,University of Pisa
European review for medical and pharmacological sciences | Year: 2012

Binge-eating disorder (BED) is a relatively new disorder characterized by binge eating without purging. The purpose of this article is to review the potential use of the recently proposed compounds for the treatment of BED. A medline of published articles from 1980 to December 2012 was carried out using the following keywords: BED and treatment, topiramate, zonisamide, ghrelin. The pharmacological treatment of BED is still heterogenous and poorly established, mainly for the lack of controlled studies in large samples of patients. The data on serotonin and norepinephrine reuptake inhibitors and on novel anticonvulsants seem quite promising in terms of efficacy and tolerability. In addition, the preliminary findings on the possibility of modulating appetite through the interference with the ghrelin system suggest new and intriguing ways of intervention in BED.


We aimed to assess the prevalence of patients with either primary Sjögren's syndrome (pSS) and positive anticentromere antibodies (ACA) and secondary Sjögren's syndrome (sSS) and limited cutaneous ACA positive-systemic sclerosis (SSc) in two large cohorts of patients with pSS and SSç and also to compare the clinical features of these two subsets with those of patients affected by 'ACA-positive SSc without sicca symptoms' and 'pSS'. In this retrospective monocentric study, the case records of 'overlap' patients fulfilling both the classification criteria for SS and the LeRoy criteria for early SSc were identified from two datasets of patients with limited cutaneous ACA positive SSc (209 subjects) and with pSS (402 subjects) who attended our Rheumatology Unit in the years between 1989 and 2011. Control groups were represented by SSc subjects without sicca symptoms ('SSc group') and ACA negative Pss patients ('pSS group'). SSc patients with sicca symptoms ('Sicca-SSc group') who did not complete the diagnostic algorithm for SS were excluded from the analysis. Demographic, clinical and immunological data of the patients enrolled were collected cumulatively over the entire follow up period. Statistical analysis was performed using SPSS 13 (SPSS Inc., Chicago IL, USA). Out of the two datasets 41 'overlap' patients were selected. The control groups were represented by 102/209 SSc subjects without sicca symptoms ('SSc group') and 387/402 pSS patients ('pSS group'). Eighty-one 'sicca-SSc' with an incomplete work-up for SS were excluded from the analysis. The prevalence of ACA positive pSS patients among pSS was 3.7% (15/402), while the frequency of patients with definite sSS in the SSc cohort was 20% (26/128). No differences were detected between 'overlap' patients and control groups, relatively to demographic characteristics. 'Overlap patients' were characterised by a milder SSc disease (i.e. lower frequency of sclerodactily, negative evolution of the capillaroscopy pattern or absence of severe systemic involvement) whereas, as far as the SS-related manifestations were concerned, although often lacking in specific autoantibodies (i.e. rheumatoid factor, anti-Ro/SSA, anti-La/SSB), the 'overlap patients' displayed a full blown SS phenotype with recurrent salivary gland enlargement, purpura, fatigue, arthralgias, and leukocytopenia. It is noteworthy that the prevalence of non-Hodgkin's lymphoma in the 'overlap patients' was higher than in pSS. Taken together, the results of our work emphasise the existence of a novel distinct clinical entity which might tentatively be called 'ACA-positive limited scleroderma/SS overlap syndrome' characterised by a benign SSc clinical course but at a high risk of non-Hodgkin's lymphoma.


Morrone M.C.,University of Pisa | Morrone M.C.,Scientific Institute Stella Maris
Current Biology | Year: 2010

Recent work has shown that visual deprivation of humans during a critical period leads to motion area MT+ responding to auditory motion. This cross-sensory plasticity, an important form of brain reorganization, may be mediated by top-down brain circuits from pre-frontal cortex. © 2010 Elsevier Ltd. All rights reserved.


Lencioni R.,University of Pisa
Digestive and Liver Disease | Year: 2010

Patients at high risk for developing hepatocellular carcinoma (HCC) should be enrolled in surveillance programs based on ultrasound (US) examinations performed at 6-month intervals. Nodules found during US surveillance that are smaller than 1 cm should be followed-up with US at 3-month intervals. If the nodule found during US surveillance is larger than 1 cm, it should be investigated further with contrast-enhanced dynamic radiological studies, including US, multidetector computed tomography, or magnetic resonance imaging. If the appearance is typical for HCC (i.e., the lesion shows hypervascularization in the arterial phase with washout in the portal venous or the equilibrium phase), biopsy is considered unnecessary and the lesion can be treated as HCC. For nodules between 1 and 2 cm, it is currently recommended that such non-invasive diagnosis be based on the evidence of coincidental features typical for HCC from at least two dynamic imaging techniques. If the vascular profile on imaging is not characteristic or the nodule is detected in a non-cirrhotic liver, biopsy should be performed. If the biopsy is negative for HCC, patients should be followed-up by imaging studies performed at 3-month intervals until the nodule either disappears, enlarges, or displays diagnostic characteristics of HCC. © 2010 Editrice Gastroenterologica Italiana S.r.l.


This is a personal account on how our research group has exploited trivalent boron-containing organic compounds to create new synthetic methods using small-ring heterocycles. A variety of new regioselective ring-opening reactions (including phenolysis and arylation) that exhibit unusual syn-stereoselectivities can be achieved by making use of the Lewis acidity of boron in aryloxyboranes. On the other hand, the use of the nucleophilic character of diboron derivatives permits regio- and stereocontrolled formation of new C-B bonds. An up-to-date critical coverage of recent relevant literature in the field is also provided. 1 Introduction 2 Ring-Opening Reactions with Triaryloxyboranes 2.1 Carbon-Oxygen Bond Formation with Epoxides, Aziridines, Oxetanes, and Azetidines 2.2 Carbon-Carbon Bond Formation: Stereoselective Arylations of Epoxides and Aziridines 3 Ring Opening with Diboron Compounds 3.1 Metal-Catalyzed and Metal-Free Borylations of Allylic Epoxides and Aziridines 4 Conclusions. © Georg Thieme Verlag Stuttgart. New York.


Foglia P.,University of Pisa | Comparetti M.,R and D
Journal of Supercomputing | Year: 2014

Wire delays and leakage energy consumption are both growing problems in the design of large on chip caches built in deep submicron technologies. D-NUCA caches (Dynamic-Nonuniform Cache Architecture) exploit an aggressive subbanking of the cache and a migration mechanism to speed up frequently accessed data access latency, to limit wire delays effects on performances. Way Adaptable D-NUCA is a leakage power reduction technique specifically suited for D-NUCA caches. It dynamically varies the portion of the powered-on cache area based on the running workload caching needs, but it relies on application dependent parameters that must be evaluated off-line. This limits the effectiveness of Way Adaptable D-NUCA in the general purpose, multiprogrammed environment. In this paper, we propose a new power reduction technique for D-NUCA caches, which still adapts the powered-on cache area to the needs of the running workload, but it does not rely on application-dependent parameters. Results show that our proposal saves around 49 % of total cache energy consumption in a single core environment and 44 % in CMP environment. By adding a timer, it performs similarly to previously proposed techniques to reduce leakage power consumptions, and outperforms them when they are applied in a workload independent manner. © 2013 Springer Science+Business Media New York.


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.


Mastroeni G.,University of Pisa
Journal of Global Optimization | Year: 2010

By means of the Image Space Analysis, duality properties of a constrained extremum problem are investigated. The analysis of the lower semicontinuity of the perturbation function, related to a right-hand side perturbation of the given problem, leads to a characterization of zero duality gap in the image space. © 2009 Springer Science+Business Media, LLC.


Di Francesco M.,University of Texas at Arlington | Anastasi G.,University of Pisa | Conti M.,National Research Council Italy | Das S.K.,University of Texas at Arlington | Neri V.,Avionics Laboratory
IEEE Journal on Selected Areas in Communications | Year: 2011

A major concern in wireless sensor networks (WSNs) is energy conservation, since battery-powered sensor nodes are expected to operate autonomously for a long time, e.g., for months or even years. Another critical aspect of WSNs is reliability, which is highly application-dependent. In most cases it is possible to trade-off energy consumption and reliability in order to prolong the network lifetime, while satisfying the application requirements. In this paper we propose an adaptive and cross-layer framework for reliable and energy-efficient data collection in WSNs based on the IEEE 802.15.4/ZigBee standards. The framework involves an energy-aware adaptation module that captures the application's reliability requirements, and autonomously configures the MAC layer based on the network topology and the traffic conditions in order to minimize the power consumption. Specifically, we propose a low-complexity distributed algorithm, called ADaptive Access Parameters Tuning (ADAPT), that can effectively meet the application-specific reliability under a wide range of operating conditions, for both single-hop and multi-hop networking scenarios. Our solution can be integrated into WSNs based on IEEE 802.15.4/ZigBee without requiring any modification to the standards. Simulation results show that ADAPT is very energy-efficient, with near-optimal performance. © 2006 IEEE.


This paper deals with detection algorithms for impulse-radio ultrawideband transmitted-reference systems. For binary modulation schemes, we propose a novel detector that operates on the partial autocorrelations of the received signal as computed over time intervals (bins) of size less than the symbol period. Assuming that the receiver has knowledge of the partial autocorrelations of the channel response over those bins, we derive the minimum error probability detector (MEPD). In doing so, we exploit some invariance properties of the detection problem under consideration. It turns out that the receiver adopting such a strategy is superior to a conventional TR system, the more so the smaller the bin size is. Also, we address the problem of estimating the partial autocorrelations of the channel response and propose a simple solution by exploiting a training sequence. The impact of the estimation errors on the receiver performance is shown to be marginal. © 2010 IEEE.


Scharp D.W.,Prodo Laboratories and Scharp Lacy Research Institute | Marchetti P.,University of Pisa
Advanced Drug Delivery Reviews | Year: 2014

Insulin therapy became a reality in 1921 dramatically saving lives of people with diabetes, but not protecting them from long-term complications. Clinically successful free islet implants began in 1989 but require life long immunosuppression. Several encapsulated islet approaches have been ongoing for over 30. years without defining a clinically relevant product. Macro-devices encapsulating islet mass in a single device have shown long-term success in large animals but human trials have been limited by critical challenges. Micro-capsules using alginate or similar hydrogels encapsulate individual islets with many hundreds of promising rodent results published, but a low incidence of successful translation to large animal and human results. Reduction of encapsulated islet mass for clinical transplantation is in progress. This review covers the status of both early and current studies including the presentation of corporate efforts involved. It concludes by defining the critical items requiring solution to enable a successful clinical diabetes therapy. © 2013 Elsevier B.V.


de Bruyn M.,University of Pisa | de Bruyn M.,Durham University
Proceedings. Biological sciences / The Royal Society | Year: 2014

Genetic diversity provides the raw material for populations to respond to changing environmental conditions. The evolution of diversity within populations is based on the accumulation of mutations and their retention or loss through selection and genetic drift, while migration can also introduce new variation. However, the extent to which population growth and sustained large population size can lead to rapid and significant increases in diversity has not been widely investigated. Here, we assess this empirically by applying approximate Bayesian computation to a novel ancient DNA dataset that spans the life of a southern elephant seal (Mirounga leonina) population, from initial founding approximately 7000 years ago to eventual extinction within the past millennium. We find that rapid population growth and sustained large population size can explain substantial increases in population genetic diversity over a period of several hundred generations, subsequently lost when the population went to extinction. Results suggest that the impact of diversity introduced through migration was relatively minor. We thus demonstrate, by examining genetic diversity across the life of a population, that environmental change could generate the raw material for adaptive evolution over a very short evolutionary time scale through rapid establishment of a large, stable population.


Ngai K.L.,University of Pisa | Prevosto D.,CNR Institute of Neuroscience | Grassia L.,The Second University of Naples
Journal of Polymer Science, Part B: Polymer Physics | Year: 2013

The nanobubble inflation method is the only experimental technique that can measure the viscoelastic creep compliance of unsupported ultrathin films of polymers over the glass-rubber transition zone as well as the dependence of the glass transition temperature (Tg) on film thickness. Sizeable reduction of Tg was observed in polystyrene (PS) and bisphenol A polycarbonate by the shift of the creep compliance to shorter times. The dependence of Tg on film thickness is consistent with the published data of free-standing PS ultrathin films. However, accompanying the shift of the compliance to shorter times, a decrease in the rubbery plateau compliance is observed. The decrease becomes more dramatic in thinner films and at lower temperatures. This anomalous viscoelastic behavior was also observed in poly(vinyl acetate) and poly (n-butyl methacrylate), but with large variation in the change of either the Tg or the plateau compliance. By now, well established in bulk polymers is the presence of three different viscoelastic mechanisms in the glass-rubber transition zone, namely, the Rouse modes, the sub-Rouse modes, and the segmental α-relaxation. Based on the thermorheological complexity of the three mechanisms, the viscoelastic anomaly observed in ultrathin polymer films and its dependence on chemical structure are explained in the framework of the Coupling Model. © 2012 Wiley Periodicals, Inc.


Kraan A.C.,University of Pisa
Frontiers in Oncology | Year: 2015

Hadron therapy allows for highly conformal dose distributions and better sparing of organs-at-risk, thanks to the characteristic dose deposition as function of depth. However, the quality of hadron therapy treatments is closely connected with the ability to predict and achieve a given beam range in the patient. Currently, uncertainties in particle range lead to the employment of safety margins, at the expense of treatment quality. Much research in particle therapy is therefore aimed at developing methods to verify the particle range in patients. Non-invasive in-vivo monitoring of the particle range can be performed by detecting secondary radiation, emitted from the patient as a result of nuclear interactions of charged hadrons with tissue, including β+ emitters, prompt photons, and charged fragments. The correctness of the dose delivery can be verified by comparing measured and pre-calculated distributions of the secondary particles. The reliability of Monte Carlo (MC) predictions is a key issue. Correctly modelling the production of secondaries is a non-trivial task, because it involves nuclear physics interactions at energies, where no rigorous theories exist to describe them. The goal of this review is to provide a comprehensive overview of various aspects in modelling the physics processes for range verification with secondary particles produced in proton, carbon, and heavier ion irradiation. We discuss electromagnetic and nuclear interactions of charged hadrons in matter, which is followed by a summary of some widely used MC codes in hadron therapy. Then we describe selected examples of how these codes have been validated and used in three range verification techniques: PET, prompt gamma, and charged particle detection. We include research studies and clinically applied methods. For each of the techniques we point out advantages and disadvantages, as well as clinical challenges still to be addressed, focusing on MC simulation aspects. © 2015 Kraan.


Bonanni E.,University of Pisa
Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society | Year: 2012

To evaluate the modifications of EEG activity during slow-wave sleep in patients with dementia compared with healthy elderly subjects, using spectral analysis and period-amplitude analysis. Five patients with dementia and 5 elderly control subjects underwent night polysomnographic recordings. For each of the first three nonrapid eye movement-rapid eye movement sleep cycles, a well-defined slow-wave sleep portion was chosen. The delta frequency band (0.4-3.6 Hz) in these portions was analyzed with both spectral analysis and period-amplitude analysis. Spectral analysis showed an increase in the delta band power in the dementia group, with a decrease across the night observed only in the control group. For the dementia group, period-amplitude analysis showed a decrease in well-defined delta waves of frequency lower than 1.6 Hz and an increase in such waves of frequency higher than 2 Hz, in incidence and amplitude. Our study showed (1) a loss of the dynamics of delta band power across the night sleep, in dementia, and (2) a different distribution of delta waves during slow-wave sleep in dementia compared with control subjects. This kind of computer-based analysis can highlight the presence of a pathologic delta activity during slow-wave sleep in dementia and may support the hypothesis of a dynamic interaction between sleep alteration and cognitive decline.


Grossi R.,University of Pisa
Theoretical Computer Science | Year: 2011

Suffix arrays are a key data structure for solving a run of problems on texts and sequences, from data compression and information retrieval to biological sequence analysis and pattern discovery. In their simplest version, they can just be seen as a permutation of the elements in 1,2,...,n, encoding the sorted sequence of suffixes from a given text of length n, under the lexicographic order. Yet, they are on a par with ubiquitous and sophisticated suffix trees. Over the years, many interesting combinatorial properties have been devised for this special class of permutations: for instance, they can implicitly encode extra information, and they are a well characterized subset of the n! permutations. This paper gives a short tutorial on suffix arrays and their compressed version to explore and review some of their algorithmic features, discussing the space issues related to their usage in text indexing, combinatorial pattern matching, and data compression. © 2010 Elsevier B.V. All rights reserved.


Giuca M.R.,University of Pisa
Minerva stomatologica | Year: 2010

This study explores the possibility that the celiac disease (CD) may be correlated with the insurgence of some oral signs, as based on a systematic review of the literature. Should this correlation be proven, any dentistry's screening would then be important to diagnose early celiac sprue pathogenesis. A literature survey was accomplished by using the Medline database (Entrez PubMed). The survey, which covered the period from the year 1972 to 2009, provided 382 published articles. Of these, 29 articles were selected according to inclusionary/exclusionary criteria, and consequently qualified for the final review analysis. Manual searching through the reference lists of the selected articles allowed the obtainment of others 17 articles. Findings gathered through this literature's review corroborate the significance of a causal relationship between some oral signs and CD. There are enough evidence making the correlation between CD and oral defects scientifically sustainable. This recognition should lead dentists to play more significant roles in screening for CD, as otherwise, if not properly diagnosed and not treated with a gluten-free diet, may eventually cause some malignancies.


Marazziti D.,University of Pisa
CNS spectrums | Year: 2013

Data on the specific effects of sex on pharmacokinetics, as well as tolerability, safety, and efficacy of psychotropic medications are still meager, mainly because only recently sex-related issues have attracted a certain degree of interest within the pharmacological domain. Therefore, with the present study, we aimed to provide a comprehensive review of the literature on this topic, through careful MEDLINE and PubMed searches of the years 1990-2012. Generally, data on pharmacokinetics are more consistent and numerous than those on pharmacodynamics. Sex-related differences have been reported for several parameters that influence pharmacokinetics, such as gastric acidity, intestinal motility, body weight and composition, blood volume, liver enzymes (mainly the cytochrome P450), or renal excretion, which may alter plasma drug levels. Sex-related peculiarities may also account for a different sensitivity of men and women to side effects and toxicity of psychotropic drugs. Further, some differences in drug response, mainly to antipsychotics and antidepressants, have been described. Further studies are, however, necessary to explore more thoroughly the impact of sex on the pharmacokinetics and pharmacodynamics of psychotropic drugs, in order to reach the most appropriate and tailored prescription for each patient.


Sellari-Franceschini S.,University of Pisa
Operative Techniques in Otolaryngology - Head and Neck Surgery | Year: 2012

Graves' ophthalmopathy is an inflammatory disease of the orbital tissues that especially affects extraocular muscles and fat. Orbital decompression is performed to reverse compressive neuropathy and reduce proptosis. The most widely used technique is the inferomedial orbital decompression, which may provide an insufficient decompression in patients with serious proptosis. A balanced decompression of the medial and lateral orbital walls provides >5 mm of proptosis reduction with a low occurrence of postoperative diplopia.© 2012 Elsevier Inc.


Solini A.,University of Pisa | Ruilope L.M.,Autonomous University of Madrid
Nature Reviews Cardiology | Year: 2013

Resistant hypertension is highly prevalent, and is the form of arterial hypertension that is most difficult to treat. Many patients diagnosed with this disease do not have resistant hypertension, but rather have mismanaged primary hypertension. In many cases blood pressure can be controlled by directly addressing underlying causes such as primary aldosteronism, obstructive sleep apnoea, or excessive neurogenic stimulation. Clinicians should ensure that appropriate blood-pressure measurements are used to diagnose resistant hypertension, explore a variety of drug combinations, and battle clinical inertia. Patients should comply with medication schedules and dietary modifications. Correction of these factors will greatly diminish the prevalence of 'resistant' hypertension and avoid the consequences of a persistently elevated blood pressure in these patients. © 2013 Macmillan Publishers Limited.


Lamorgese A.G.,City College of New York | Mauri R.,University of Pisa
Physics of Fluids | Year: 2011

We simulate the phase separation of a low-viscosity binary mixture, assuming that the fluid system is confined between two walls that are cooled down to different temperatures below the critical point of the mixture, corresponding to quenches within the unstable range of its phase diagram. Spinodal decomposition patterns for off-critical mixtures are studied numerically in two dimensions in the creeping flow limit and for a large Lewis number, together with their dependence on the fluidity coefficient. Our numerical results reproduce the large-scale unidirectional migration of phase-separating droplets that was observed experimentally by Califano et al. ["Large-scale, unidirectional convection during phase separation of a density-matched liquid mixture," Phys. Fluids17, 094109 (2005)], who measured typical speeds that are quite larger than the Marangoni velocity. To understand this finding, we then studied the temperature-gradient-induced motion of an isolated droplet of the minority phase embedded in a continuous phase, showing that when the drop is near local equilibrium, its speed is of the same order as the Marangoni velocity, i.e., it is proportional to the unperturbed temperature gradient and the fluidity coefficient. However, far from local equilibrium, i.e., for very large unperturbed temperature gradients, the drop first accelerates to a speed that is larger than the Marangoni velocity, then, later, it decelerates, exhibiting an increase-decrease behavior, as described by Yin et al. ["Thermocapillary migration of nondeformable drops," Phys. Fluids20, 082101 (2008)]. Such behavior is due to the large nonequilibrium, Korteweg-driven convection, which at first accelerates the droplets to relatively large velocities, and then tends to induce an approximately uniform inside temperature distribution so that the drop experiences an effective temperature gradient that is much smaller than the unperturbed one and, consequently, decelerates. © 2011 American Institute of Physics.


Strumia A.,University of Pisa | Strumia A.,Estonian National Institute of Chemical Physics and Biophysics
Journal of High Energy Physics | Year: 2011

LHC already probed and excluded half of the parameter space of the Con-strained Minimal Supersymmetric Standard Model allowed by previous experiments. Only about 0:7% of the CMSSM parameter space survives. This fraction rises to about 2% if the bound on the Higgs mass can be circumvented. © SISSA 2011.


Paolicchi P.,University of Pisa | Kryszczynska A.,Adam Mickiewicz University
Planetary and Space Science | Year: 2012

Only in a limited number of cases the observations supply complete information on the spin vectors of asteroids. A complex analysis is required to compute the orientation (latitude and longitude) of poles, and often multiple solutions and strong discrepancies among the outcomes of different methods are present. The spin vector catalog, maintained at Poznan observatory, lists the available (presently less than 200, and not always unambiguous) pole data. The statistical analysis of the data, published in 2007, is now becoming obsolete, due to a significant growth of the database. In the present paper we update the analysis, confirming several features already highlighted by the previous paper, and finding some new results. In particular, the excess of prograde vs. retrograde Main Belt asteroids is now significant for all cataloged bodies smaller than 100 km. The rarity of poles close to the ecliptic plane, resulting from the previous analysis, but recently questioned, is confirmed, with a fundamental contribution of bodies smaller than 40 km. Only after a future - both qualitative and quantitative - improvement of the database, such as that expected to come out from forthcoming space missions, such as GAIA, we will be able to obtain a statistically robust scenario, hopefully free from possible relevant selection effects. © 2012 Elsevier Ltd. All rights reserved.


Villa-Moruzzi E.,University of Pisa
Analytical Cellular Pathology | Year: 2011

Background: HER2 activation in tumours supports multiple signalling pathways, including those regulating invasion and metastasis. Among the involved genes, Tyrosine and Dual Specificity Phosphatases (PTPs and DSPs) may play a relevant, though not completely clear role. Methods: HER2 was silenced in ovarian SKOV-3 cells, a genome-wide expression analysis of PTPs and DSPs was performed, the effects on cell motility were analysed and compared with those of PTPN12-silencing, focusing on FAK. Results: HER2-silencing altered the expression of 4 PTPs and 6 DSPs; PTPN12 displayed also 3-4-fold protein increase. Conversely, PTPN12-silencing enhanced migration, suggesting that PTPN12 down-modulation by HER2 favours motility. HER2-silencing inactivated FAK, in quiescent and migrating cells, involving FAK dephosphorylation at Y397 and S910. Conversely, in PTPN12-silenced cells FAK activity was close to control, altogether suggesting that PTPN12 targets Y397. As regards to S910, cell-treatment with the MEK inhibitor UO126 and ERK5-silencing indicated its targeting by ERK5. Loss of pS910 and decreased ERK5 kinase activity in HER2-silenced cells confirmed their control by HER2. Conclusions: The results indicate the contribution of PTPN12, targeting FAK Y397, and ERK5, targeting FAK S910, to the HER2-driven cell motility, thus depicting new aspects of the complex crosstalk between HER2 and the motility machinery. © 2011 - IOS Press and the authors. All rights reserved.


Lazzeroni M.,University of Pisa
European Urban and Regional Studies | Year: 2010

Within the field of the geography of knowledge and technological innovation, specific attention has been paid to the phenomenon of the spatial concentration of high-tech activities and to the factors that influence the growth of new industrial areas. Within this research stream, the present work is focused on areas characterized by high levels of specialization in high-tech, and more specifically on the concept of technological districts. Technological districts (TDs) are considered to be territorial systems specialized in high-tech activities and characterized by the presence of innovative resources, such as qualified human capital, advanced research activities, the capacity to generate innovation and new technologies, and an entrepreneurial culture. Beyond discussing theoretical concepts, a methodology is proposed for the analysis and identification of TDs through the definition of a taxonomy of local systems with different levels of concentration of high-tech activities and innovative resources. The methodology has been applied to Italy and allows the identification of the most advanced technological areas, which present the basic characteristics of TDs. This methodology is also important because it can be used to compare different geographical contexts and to discuss and evaluate different possibilities in the field of innovation development policies. © The Author(s), 2010.


The treatment of hepatocellular carcinoma (HCC) is rapidly evolving as developments in loco-regional therapies continue to improve. Image-guided radiofrequency (RF) ablation is established as the treatment of choice for patients with early-stage HCC when transplantation or resection are precluded. Recent refinements in technique have substantially increased the ability of RF ablation to achieve sustained complete response of target tumors in properly selected patients, and new alternate thermal and non-thermal methods for local tumor treatment are currently under investigation. Transarterial chemoembolization (TACE) is the standard of care for patients with multinodular disease at the intermediate stage. The introduction of drug-eluting beads - that enhance drug delivery to the tumor and reduce systemic exposure - appears to improve anticancer activity and the safety profile of TACE compared to conventional regimens. Despite these advances, the long-term outcomes of patients treated with loco-regional therapies remain unsatisfactory because of the high rate of tumor recurrence. The introduction of molecular targeted therapies that inhibit tumor proliferation and angiogenesis has opened new prospects in this regard. Clinical trials focused on combining interventional treatment with systemically active drugs are ongoing. The outcomes of such studies are eagerly awaited, as they have the potential to revolutionize treatment of HCC. Copyright © 2010 S. Karger AG.


Bacterial infections are common in the neonates and are a major cause of morbidity and mortality. Sixty percent of preterm infants admitted to neonatal intensive care units received at least one antibiotic during the first week of life. Penicillins, aminoglycosides and cephalosporins comprised 53, 43 and 16%, respectively. Kinetic parameters such as the half-life (t1/2), clearance (Cl), and volume of distribution (Vd) change with development, so the kinetics of penicillins, cephalosporins and aminoglycosides need to be studied in order to optimise therapy with these drugs. The aim of this study is to review the pharmacokinetics of penicillins, cephalosporins and aminoglycosides in the neonate in a single article in order to provide a critical analysis of the literature and thus provide a useful tool in the hands of physicians. The bibliographic search was performed electronically using PubMed, as the search engine, until February 2nd, 2010. Medline search terms were as follows: pharmacokinetics AND (penicillins OR cephalosporins OR aminoglycosides) AND infant, newborn, limiting to humans. Penicillins, cephalosporins and aminoglycosides are fairly water soluble and are mainly eliminated by the kidneys. The maturation of the kidneys governs the pharmacokinetics of penicillins, cephalosporins and aminoglycosides in the neonate. The renal excretory function is reduced in preterms compared to term infants and Cl of these drugs is reduced in premature infants. Gestational and postnatal ages are important factors in the maturation of the neonate and, as these ages proceed, Cl of penicillins, cephalosporins and aminoglycosides increases. Cl and t1/2 are influenced by development and this must be taken into consideration when planning a dosage regimen with these drugs. More pharmacokinetic studies are required to ensure that the dose recommended for the treatment of sepsis in the neonate is evidence based. © 2010 by the authors.


True fruit flies (Diptera: Tephritidae) include over 4000 species, many of which constitute enormous threats to fruit and vegetable production worldwide. A number of Tephritidae are lekking species, forming aggregations in which males fight to defend a small territory where they court females and mate. Male-male contests also occur in non-lekking species, characterized by resource defense polygyny. Tephritidae females display agonistic behavior to maintain single oviposition sites and reduce larval competition for food. Here, how, where, when and why aggressive interactions occur in Tephritidae flies is reviewed. A number of neglected issues deserving further research are highlighted, with a special focus on diel periodicity of aggression, cues evoking aggressive behavior, the role of previous experience on fighting success and the evolution of behavioral lateralization of aggressive displays. In the final section, future directions to exploit this knowledge in Integrated Pest Management, with particular emphasis on enhancement of Sterile Insect Technique and interspecific competitive displacement in the field are suggested. © 2014 by the authors; licensee MDPI, Basel, Switzerland.


Tomasi J.,University of Pisa
Wiley Interdisciplinary Reviews: Computational Molecular Science | Year: 2011

The characteristics of a computational method addressing the description of solvent effects are here presented in a concise way, by selecting for the presentation a topic of large interest, i.e., the electronic, electric, and magnetic properties of molecules. The selection of these properties imposes a choice on the computational methods. They must be of quantum ab initio nature, and possibly treated at a high level of the quantum theory. In such a framework, continuum models are more adequate than the alternative models based on a discrete description of the solvent, because of the high computational cost associated with discrete models coupled to high quantum mechanics levels. © 2011 John Wiley & Sons, Ltd.


Benelli G.,University of Pisa
Parasitology Research | Year: 2015

Mosquitoes (Diptera: Culicidae) are a key threat for millions of people worldwide, since they act as vectors for devastating pathogens and parasites. In this scenario, vector control is crucial. Mosquito larvae are usually targeted using organophosphates, insect growth regulators, and microbial agents. Indoor residual spraying and insecticide-treated bed nets are also employed. However, these chemicals have negative effects on human health and the environment and induce resistance in a number of vectors. Newer and safer tools have been recently implemented to enhance control of mosquitoes. Here, I focus on some crucial challenges about eco-friendly control of mosquito vectors, mainly the improvement of behavior-based control strategies (sterile insect technique (“SIT”) and “boosted SIT”) and plant-borne mosquitocidals, including green-synthesized nanoparticles. A number of hot areas that need further research and cooperation among parasitologists, entomologists, and behavioral ecologists are highlighted. © 2015, Springer-Verlag Berlin Heidelberg.


Introduction: Cardio-renal syndromes are characterized by the impairment of cardiac and renal functions. Plasma and urinary neutrophil gelatinase-associated lipocalin (NGAL), and plasma B-type natriuretic peptide (BNP) are markers of acute kidney injury (AKI) and heart failure (HF), respectively.The aim of this study was to assess the effect of the reduction of glomerular filtration rate (GFR) on plasma BNP and on plasma and urinary NGAL concentrations in stable chronic kidney disease (CKD) patients at different functional stages.Methods: GFR (99mTc-DTPA), plasma BNP, and plasma and urinary concentrations of NGAL were measured in 310 clinically stable CKD patients, at functional stages from 1 to 5. Serum and urinary low-molecular-weight proteins cystatin C and β2-microglobulin, and urinary tubular enzymes were measured for comparison. Plasma BNP, NGAL, cystatin C and β2-microglobulin were measured also in 31 maintenance hemodialysis patients.Results: Plasma NGAL increased with the reduction of GFR in CKD patients from stage 2. In the different CKD stages modest differences were found for BNP values. Urinary NGAL increased slightly but significantly in patients at CKD stages 4 and 5, similarly to urinary cystatin C and β2-microglobulin. In maintenance hemodialysis patients, plasma NGAL and BNP were markedly increased, and high-flux hemodialysis significantly decreased their plasma concentrations.Conclusions: Plasma NGAL increases markedly with the reduction in GFR, generating a very high number of false positive diagnoses of AKI in stable CKD patients. The grade of GFR impairment and the cause of kidney disease have a lower effect on urinary NGAL and on plasma BNP. In any case, specific reference values of NGAL and BNP should be used in chronic kidney disease patients, according to their functional stage, when assessing acute kidney injury, heart failure, and cardio-renal syndromes in patients with impaired GFR. © 2014 Donadio; licensee BioMed Central Ltd.


Giusi G.,Messina University | Iannaccone G.,University of Pisa
IEEE Electron Device Letters | Year: 2013

One-transistor dynamic random access memories (DRAMs) (1T-DRAMs) are considered a promising candidate to overcome the limits of scalability of conventional one-transistor/one-capacitor DRAMs. Robust and reproducible operation has been demonstrated by experiments in MOSFET devices with a gate length (L) down to ∼50 nm, which prevents their use in future technological nodes. The main factors limiting the retention time of 1T-DRAMs are the Shockley-Read-Hall recombination in the channel and the band-to-band tunneling between channel and source/drain junctions, both enhanced by the relatively high field at both junctions. In this letter, we show through statistical device simulations on a template double-gate MOSFET that, by introducing an underlap of ∼16 nm between the drain (source) junction and the gate, it is possible to reduce both the electric field at the junction and the impact of process variability, achieving 1T-DRAMs with L = 10 nm with a retention time in excess of 100 ms. We also show that field plates at the source and drain contacts do not provide additional advantages and that the junctionless transistor operation as 1T-DRAM is totally undermined by the impact of random dopants. © 1980-2012 IEEE.


Ampomah-Amoako E.,University of Ghana | Ambrosini W.,University of Pisa
Annals of Nuclear Energy | Year: 2013

The paper presents the first results of a systematic methodology aimed at assessing the feasibility of analyses by CFD codes of flow instabilities in heated channels containing supercritical fluids. The research makes use of features presently available in CFD models, in the aim to move step-by-step from simple channel cases towards the analysis of more realistic fuel bundle subchannels. In the present step, basing on previous experience, the STAR-CCM+ code is adopted to solve flow stability problems in circular channels and fuel bundle slices without heating structures, in the aim to characterise the response of CFD models in the analysis of purely thermal-hydraulic instability phenomena. Some of the effects related to numerical discretisation, flow direction with respect to gravity and fluid properties are studied, comparing the stability thresholds identified by transient calculations with maps set up by in-house 1D codes developed and adopted in previous work. Both static and dynamic instabilities are observed, clearly showing the contiguity of these two kinds of phenomena as a function of inlet fluid subcooling. Conclusions are finally drawn about the promising features of CFD codes for such applications, sketching the lines of the work already going on in order to address more realistic reactor scale conditions. © 2012 Elsevier B.V. All rights reserved.


Venturini R.,University of Pisa
Algorithmica | Year: 2016

In this paper we study the problem of estimating the number of occurrences of substrings in textual data: A text T on some alphabet Σ=[σ] of length n is preprocessed and an index I is built. The index is used in lieu of the text to answer queries of the form Count≈(P), returning an approximated number of the occurrences of an arbitrary pattern $$P$$P as a substring of T. The problem has its main application in selectivity estimation related to the LIKE predicate in textual databases. Our focus is on obtaining an algorithmic solution with guaranteed error rates and small footprint. To achieve that, we first enrich previous work in the area of compressed text-indexing providing an optimal data structure that, for a given additive error ℓ≥1, requires Θnℓlogσ bits. We also approach the issue of guaranteeing exact answers for sufficiently frequent patterns, providing a data structure whose size scales with the amount of such patterns. Our theoretical findings are supported by experiments showing the practical impact of our data structures. © 2014, Springer Science+Business Media New York.


Elze H.-T.,University of Pisa
EPJ Web of Conferences | Year: 2014

We summarize a recent study of discrete (integer-valued) Hamiltonian cellular automata (CA) showing that their dynamics can only be consistently defined, if it is linear in the same sense as unitary evolution described by the Schrödinger equation. This allows to construct an invertible map between such CA and continuous quantum mechanical models, which incorporate a fundamental scale. Presently, we emphasize general aspects of these findings, the construction of admissible CA observables, and the existence of solutions of the modified dispersion relation for stationary states. © Owned by the authors, published by EDP Sciences.


Moretti M.,University of Pisa | Perez-Neira A.I.,Polytechnic University of Catalonia
IEEE Transactions on Wireless Communications | Year: 2013

In this paper we address the problem of margin adaptive scheduling in the downlink of an orthogonal frequency division multiple access (OFDMA) multiple-input multiple-output (MIMO) system. Optimal resource allocation in MIMO systems requires the joint optimization of: a) linear transmit and receive spatial filters, b) channel assignment and c) power allocation. This problem is not convex and its complexity becomes thus intractable already for small sets of users and subcarriers. To reduce the complexity of the problem at hand, we propose a novel heuristic strategy that partitions the users in different groups according to their average channel quality and addresses the original problem by solving a succession of lower-complexity allocation problems. The spatial dimension is employed to prevent multiple access interference from hindering the performance of the sequential allocation. To further reduce the complexity burden we introduce a linear programming formulation in combination with a waterfilling-based strategy to allocate channels and power to the groups of users. Numerical results and evaluation of the computational complexity show that, though suboptimal, in most cases the proposed algorithm manages to exploit in an original way the inherent multi-user diversity of multi-carrier systems to ease the task of resource allocation with a very limited performance loss from the theoretic optimum. © 2013 IEEE.


Denny M.,Stanford University | Benedetti-Cecchi L.,University of Pisa
Annual Review of Ecology, Evolution, and Systematics | Year: 2012

Ecologists have long grappled with the problem of scaling up from tractable, small-scale observations and experiments to the prediction of large-scale patterns. Although there are multiple approaches to this formidable task, there is a common underpinning in the formulation, testing, and use of mechanistic response functions to describe how phenomena interact across scales. Here, we review the principles of response functions to illustrate how they provide a means to guide research, extrapolate beyond measured data, and simplify our conceptual grasp of reality. We illustrate these principles with examples of mechanistic approaches ranging from explorations of the ecological niche, random walks, and macrophysiology to theories dealing with scale transition, self-organization, and the prediction of extremes. © 2012 by Annual Reviews. All rights reserved.


Pannocchia G.,University of Pisa | Rawlings J.B.,University of Wisconsin - Madison | Wright S.J.,University of Wisconsin - Madison
Systems and Control Letters | Year: 2011

We address the inherent robustness properties of nonlinear systems controlled by suboptimal model predictive control (MPC), i.e., when a suboptimal solution of the (generally nonconvex) optimization problem, rather than an element of the optimal solution set, is used for the control. The suboptimal control law is then a set-valued map, and consequently, the closed-loop system is described by a difference inclusion. Under mild assumptions on the system and cost functions, we establish nominal exponential stability of the equilibrium, and with a continuity assumption on the feasible input set, we prove robust exponential stability with respect to small, but otherwise arbitrary, additive process disturbances and state measurement/estimation errors. These results are obtained by showing that the suboptimal cost is a continuous exponential Lyapunov function for an appropriately augmented closed-loop system, written as a difference inclusion, and that recursive feasibility is implied by such (nominal) exponential cost decay. These novel robustness properties for suboptimal MPC are inherited also by optimal nonlinear MPC. We conclude the paper by showing that, in the absence of state constraints, we can replace the terminal constraint with an appropriate terminal cost, and the robustness properties are established on a set that approaches the nominal feasibility set for small disturbances. The somewhat surprising and satisfying conclusion of this study is that suboptimal MPC has the same inherent robustness properties as optimal MPC. © 2011 Elsevier B.V. All rights reserved.


Ferruzzi J.,University of Pisa | Vorp D.A.,University of Pittsburgh | Humphrey J.D.,Texas A&M University
Journal of the Royal Society Interface | Year: 2011

The abdominal aorta (AA) in older individuals can develop an aneurysm, which is of increasing concern in our ageing population. The structural integrity of the ageing aortic wall, and hence aneurysm, depends primarily on effective elastin and multiple families of oriented collagen fibres. In this paper, we show that a structurally motivated phenomenological 'four-fibre family' constitutive relation captures the biaxial mechanical behaviour of both the human AA, from ages less than 30 to over 60, and abdominal aortic aneurysms. Moreover, combining the statistical technique known as non-parametric bootstrap with a modal clustering method provides improved confidence intervals for estimated best-fit values of the eight associated constitutive parameters. It is suggested that this constitutive relation captures the well-known loss of structural integrity of elastic fibres owing to ageing and the development of abdominal aneurysms, and that it provides important insight needed to construct growth and remodelling models for aneurysms, which in turn promise to improve our ability to predict disease progression. © 2010 The Royal Society.


Ciccarelli D.,University of Pisa
Environmental Management | Year: 2014

The aim of the present work was to assess the conservation status of coastal dune systems in Tuscany (Italy). Emphasis was given to the presence and abundance of plant communities identified as habitat in accordance with the Directive 92/43/EEC. Twenty transects perpendicular to the shoreline were randomly positioned on the whole coastal area (30 km in length) in order to sample the full spectrum of plant communities. Vegetation zonation and relationships with the most frequent disturbance factors in the study area-beach cleaning, coastline erosion, presence of paths and roads, bathing settlements and trampling-were investigated through principal coordinate analysis and canonical correspondence analysis. Natural factors, such as distance from the sea and total length, were also considered. Differences in the conservation status of the sites were found, ranging from the total disappearance of the foredune habitats to the presence of the complete psammophilous (sand-loving) plant communities. Erosion, trampling, and paths were found to be closely correlated with degradation and habitat loss. Furthermore, the overall plant species diversity of dunes was measured with NHDune, a modified version of the Shannon index; while the incidence of invasive taxa was calculated using N, a naturalness index. However, these diversity indices proved to be a weaker bioindicator of ecosystem integrity than habitat composition along transects. A possible strategy for the conservation and management of these coastal areas could be to protect the foredunes from erosion and limit trampling through the installation of footbridges or the use of appropriate fences. © 2014 Springer Science+Business Media.


Cangiano L.,University of Pisa | Dell'Orco D.,University of Verona
FEBS Letters | Year: 2013

Rod photoreceptors detect single photons through a tradeoff of light collecting ability, amplification and speed. Key roles are played by rhodopsin (Rh) and transducin (Gt), whose complex supramolecular organization in outer segment disks begs for a functional interpretation. Here we review past and recent evidence of a temperature-dependence of photon detection by mammalian rods, and link this phenomenon with the putative oligomeric organization of Rh and new ideas on the dynamics of Rh-Gt interaction. Identifying an electrophysiological correlate of the supramolecular organization of Rh and Gt may shed light on the evolutionary advantage it confers to night vision. © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.


Caruso G.,University of Pisa | Kampf J.H.,Ecole Polytechnique Federale de Lausanne
Solar Energy | Year: 2015

The purpose of this paper is to analyse the optimal three-dimensional form of buildings that minimise energy consumption due to solar irradiation. We use an evolutionary algorithm (hybrid CMA-ES/HDE algorithm) already applied to maximise solar energy utilisation (Kämpf and Robinson, 2010), which uses a cumulative sky model approach for the computation of incident irradiation on the building envelope. Various families of possible building forms are investigated with this methodology to find the optimal building form, in two locations with radically different climatic conditions, showing the features that a building should posses in order to optimise its energy performance with respect to the solar irradiation. © 2015 Elsevier Ltd.


Solini A.,University of Pisa
Acta Diabetologica | Year: 2016

In the last ten years, knowledge on pathophysiology of type 2 diabetes (T2DM) has significantly increased, with multiple failures (decreased incretin effect, increased lipolysis, increased glucagon secretion, neurotransmitters dysfunction) recognized as important contributors, together with decreased insulin secretion and reduced peripheral glucose uptake. As a consequence, the pharmacologic therapy of T2DM has been progressively enriched by several novel classes of drugs, trying to overcome these defects. The last, intriguing compounds come into the market are SGLT2 inhibitors, framing the kidney in a different scenario, not as site of a harmful disease complication, but rather as the means to correct hyperglycemia and fight the disease. This review aims to offer a short, updated overview of the role of these compounds in the treatment of T2DM, focusing on efficacy, ancillary albeit relevant clinical effects, safety, potential cardiovascular protection, positioning in common therapeutic algorithms. © 2016 Springer-Verlag Italia


Villaggio P.,University of Pisa
Meccanica | Year: 2011

Continued research efforts in the field of solid mechanics completed sixty years. The first place of development of solid mechanics was initiated by a number researchers at Rode Island close to New York in the US. Prager and Rivlin from Germany and England originated two disjoint schools destined to develop into two popular subjects of research, such as structural limit analysis and non-linear elasticity. A first advance in the field was caused by the translation of the treatise of the Russian mathematician, Muskhelishvili into English. Another development in the field was registered in contact mechanics, involving the analysis of stress transmission between two elastic bodies pressed together. A subchapter of contact mechanics was also constituted by the study of the stress transmission between a linear elastic stiffener and a bonded infinite or semi-infinite plate.


Taddei S.,University of Pisa
Current Medical Research and Opinion | Year: 2015

Objective: Treatment of hypertension remains challenging in clinical practice. One major problem is incorrect utilization of the principal drug classes. Drugs from each class are currently used in accordance with an assumption that the blood pressure (BP) lowering effect is dose dependent. While this is true for most drugs, it is not appropriate for all drugs that block the renin-angiotensin system (RAS). Methods: This review is based on a PubMed/Cochrane database search for articles on the dose-dependent effect of RAS blockers on BP and cardiovascular protection. Results: Of the RAS blockers, most angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) have a flat dose-response curve for BP decrease, meaning an increase in dose prolongs duration of action, but does not yield greater potency. Perindopril is the only ACE inhibitor to show a real dose-response curve for BP decrease. While the effectiveness of RAS blockers on target organ damage is dose dependent and at least partially unrelated to BP control, there is evidence that the only way to obtain a beneficial effect is to use them at full dose. Thus, RAS blockers need to be used at the correct dose, based on the results of controlled clinical trials and meta-analysis. Furthermore, for all-cause mortality, ACE inhibitors have been shown to be better than ARBs, a specific efficacy supported by perindopril-based studies including ASCOT-BPLA (the Anglo-Scandinavian Cardiac Outcomes Trial-BP Lowering Arm), ADVANCE (the Action in Diabetes and Vascular disease: PreterAx and DiamicroN-MR Controlled Evaluation trial) and HYVET (HYpertension in the Very Elderly Trial). Conclusion: In hypertensive patients, a strategy based on ACE inhibitors with dose-dependent efficacy such as perindopril as optimal treatment should lead both to improved BP control and to a better protection from target organ damage, thereby reducing the incidence of cardiovascular events. © 2015 All rights reserved: reproduction in whole or part not permitted.


Riemann D.,Albert Ludwigs University of Freiburg | Nissen C.,Albert Ludwigs University of Freiburg | Palagini L.,University of Pisa | Otte A.,Offenburg University of Applied Sciences | And 2 more authors.
The Lancet Neurology | Year: 2015

Chronic insomnia is defined by difficulties in falling asleep, maintaining sleep, and early morning awakening, and is coupled with daytime consequences such as fatigue, attention deficits, and mood instability. These symptoms persist over a period of at least 3 months (Diagnostic and Statistical Manual 5 criteria). Chronic insomnia can be a symptom of many medical, neurological, and mental disorders. As a disorder, it incurs substantial health-care and occupational costs, and poses substantial risks for the development of cardiovascular and mental disorders, including cognitive deficits. Family and twin studies confirm that chronic insomnia can have a genetic component (heritability coefficients between 42% and 57%), whereas the investigation of autonomous and central nervous system parameters has identified hyperarousal as a final common pathway of the pathophysiology, implicating an imbalance of sleep-wake regulation consisting of either overactivity of the arousal systems, hypoactivity of the sleep-inducing systems, or both. Insomnia treatments include benzodiazepines, benzodiazepine-receptor agonists, and cognitive behavioural therapy. Treatments currently under investigation include transcranial magnetic or electrical brain stimulation, and novel methods to deliver psychological interventions. © 2015 Elsevier Ltd.


Longoni B.,University of Pisa
Diabetes technology & therapeutics | Year: 2010

BACKGROUND: Pancreatic islet transplantation is a promising cell-based therapy for type 1 diabetes (insulin-dependent diabetes mellitus), a disease triggered by the immune response against autoantigens of beta-cells. However, the recurrence of immune response after transplantation and the diabetogenic and growth-stunting side effects of immunosuppressants are major challenges to the application of islet transplantation. Mesenchymal stem cells (MSCs) have recently been reported to modulate the immune response in allogeneic transplantation. METHODS: The ability of MSCs, either syngeneic or allogeneic to recipients, to prevent acute rejection and improve glycemic control was investigated in rats with diabetes given a marginal mass of pancreatic islets through the portal vein. RESULTS: Reduced glucose levels and low-grade rejections were observed up to 15 days after transplantation upon triple-dose administration of MSCs, indicating that MSCs prolong graft function by preventing acute rejection. The efficacy of MSCs was associated with a reduction of pro-inflammatory cytokines and was independent of the administration route. Efficacy was similar for MSCs whether syngeneic or allogeneic to recipients and comparable to that of immunosuppressive therapy. CONCLUSIONS: The results show that MSCs modulate the immune response through a down-regulation of pro-inflammatory cytokines, suggesting that MSCs may prevent acute rejection and improve graft function in portal vein pancreatic islet transplantation.


Chiappe C.,University of Pisa | Mele A.,Polytechnic of Milan
Topics in Current Chemistry | Year: 2010

Aiming to develop environmentally compatible chemical syntheses, the replacement of traditional organic solvents with ionic liquids (ILs) has attracted considerable attention. ILs are special molten salts with melting points below 100°C that are typically constituted of organic cations (imidazolium, pyridinium, sulfonium, phosphonium, etc.) and inorganic anions. Due to their ionic nature, they are endowed with high chemical and thermal stability, good solvent properties, and non-measurable vapor pressure. Although the recovery of unaltered ILs and recycling partly compensate their rather high cost, it is important to develop new synthetic approaches to less expensive and environmentally sustainable ILs based on renewable raw materials. In fact, most of these alternative solvents are still prepared starting from fossil feedstocks. Until now, only a limited number of ILs have been prepared from renewable sources. Surprisingly, the most available and inexpensive raw material, i.e., carbohydrates, has been hardly exploited in the synthesis of ILs. In 2003 imidazolium-based ILs were prepared from d-fructose and used as solvents in Mizoroki-Heck and Diels-Alder reactions. Later on, the first chiral ILs derived from sugars were prepared from methyl d-glucopyranoside. In the same year, a family of new chiral ILs, obtained from commercial isosorbide (dianhydro-d-glucitol), was described. A closely related approach was followed by other researchers to synthesize mono- and bis-ammonium ILs from isomannide (dianhydro-d-mannitol). Finally, a few ILs bearing a pentofuranose unit as the chiral moiety were prepared using sugar phosphates as glycosyl donors and 1-methylimidazole as the acceptor. © 2010 Springer-Verlag Berlin Heidelberg.


The worldwide explosion of the rates of diabetes and other metabolic diseases in the last few decades cannot be fully explained only by changes in the prevalence of classical lifestyle-related risk factors, such as physical inactivity and poor diet. For this reason, it has been recently proposed that other "nontraditional" risk factors could contribute to the diabetes epidemics. In particular, an increasing number of reports indicate that chronic exposure to and accumulation of a low concentration of environmental pollutants (especially the so-called persistent organic pollutants (POPs)) within the body might be associated with diabetogenesis. In this review, the epidemiological evidence suggesting a relationship between dioxin and other POPs exposure and diabetes incidence will be summarized, and some recent developments on the possible underlying mechanisms, with particular reference to dioxin, will be presented and discussed. © 2014 by the authors; licensee MDPI, Basel, Switzerland.


Franco A.,University of Pisa
Energy for Sustainable Development | Year: 2011

Much remains to be done in binary geothermal power plant technology, especially for exploiting low-enthalpy resources. Due to the great variability of available resources (temperature, pressure, chemical composition), it is really difficult to "standardize the technology".The problem involves many different variables: working fluid selection, heat recovery system definition, heat transfer surfaces sizing and auxiliary systems consumption. Electricity generation from geothermal resources is convenient if temperature of geothermal resources is higher than 130. °C. Extension of binary power technology to use low-temperature geothermal resources has received much attention in the last years. This paper analyzes and discusses the exploitation of low temperature, water-dominated geothermal fields with a specific attention to regenerative Organic Rankine Cycles (ORC). The geothermal fluid inlet temperatures considered are in the 100-130. °C range, while the return temperature of the brine is assumed to be between 70 and 100. °C. The performances of different configurations, two basic cycle configurations and two recuperated cycles are analyzed and compared using dry organic fluids as the working fluids. The dry organic fluids for this study are R134a, isobutane, n-pentane and R245fa. Effects of the operating parameters such as turbine inlet temperature and pressure on the thermal efficiency, exergy destruction rate and Second Law efficiency are evaluated. The possible advantages of recuperated configurations in comparison with basic configurations are analyzed, showing that in a lot of cases the advantage in terms of performance increase is minimal but significant reductions in cooling systems surface area can be obtained (up to 20%). © 2011 International Energy Initiative.


Oggioni G.,University of Brescia | Riccardi R.,University of Brescia | Toninelli R.,University of Pisa
Energy Policy | Year: 2011

Chemical reactions and the combustion of dirty fuels, such as coal and petroleum coke (petcoke), that are used in cement production processes generate a significant amount of CO2 emissions. In this paper, we provide an eco-efficiency measure for 21 prototypes of cement industries operating in many countries by applying both a data envelopment analysis (DEA) and a directional distance function approach, which are particularly suitable for models where several production inputs and desirable and undesirable outputs are taken into account. To understand whether this eco-efficiency is due to a rational utilization of inputs or to a real carbon dioxide reduction as a consequence of environmental regulation, we analyze the cases where CO2 emissions can either be considered as an input or as an undesirable output. Empirical results show that countries where cement industries invest in technologically advanced kilns and adopt alternative fuels and raw materials in their production processes are eco-efficient. This gives a comparative advantage to emerging countries, such as India and China, which are incentivized to modernize their production processes. © 2011 Elsevier Ltd.


Santini F.,University of Pisa
Clinica Terapeutica | Year: 2015

The importance of the Type-1 helper (Th1) chemokines in RSV (respiratory syncytial virus) infection has been shown by several studies, in animal models, and in humans. The production of Th1 chemokines within the lower respiratory tract has been shown in patients with RSV bronchiolitis, particularly chemokine (C-X-C motif) ligand (CXCL)10/interferon-γ-inducible protein 10 (IP-10), whose plasma levels were markedly elevated in acute infection. RSV fusion (F) or large (G) protein treatment of fully differentiated primary normal human bronchial epithelial cells induces apical secretion of IP-10 and other chemokines. Exposure to environmental tobacco smoke is associated with an increase in the frequency and severity of respiratory infections, including bronchiolitis, and inhibited RSV-induced Interferon (IFN)-α in plasmacytoid dendritic cells as well as the release of IP-10. Vitamin D in airway epithelium decreases RSV induction of NF-kappaB-driven genes such as IFN-β and IP-10. These findings highlight the role for the IP-10: chemokine (C-X-C motif) receptor (CXCR)3 signaling axis in RSV-infection by recruiting virus-specific T cells into the lung and promoting viral clearance.


Coppede F.,University of Pisa
TheScientificWorldJournal | Year: 2011

Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND), is an adult onset neurodegenerative disorder characterised by the degeneration of cortical and spinal cord motor neurons, resulting in progressive muscular weakness and death. Increasing evidence supports mitochondrial dysfunction and oxidative DNA damage in ALS motor neurons. Several DNA repair enzymes are activated following DNA damage to restore genome integrity, and impairments in DNA repair capabilities could contribute to motor neuron degeneration. After a brief description of the evidence of DNA damage in ALS, this paper focuses on the available data on DNA repair activity in ALS neuronal tissue and disease animal models. Moreover, biochemical and genetic data on DNA repair in ALS are discussed in light of similar findings in other neurodegenerative diseases. Copyright © 2011 Fabio Copped.


Turi M.,University of Pisa | Turi M.,University of Florence | Burr D.,University of Florence | Burr D.,University of Western Australia
Proceedings of the Royal Society B: Biological Sciences | Year: 2012

How our perceptual experience of the world remains stable and continuous despite the frequent repositioning eye movements remains very much a mystery. One possibility is that our brain actively constructs a spatiotopic representation of the world, which is anchored in external-or at least head-centred-coordinates. In this study, we show that the positional motion aftereffect (the change in apparent position after adaptation to motion) is spatially selective in external rather than retinal coordinates, whereas the classic motion aftereffect (the illusion of motion after prolonged inspection of a moving source) is selective in retinotopic coordinates. The results provide clear evidence for a spatiotopic map in humans: one which can be influenced by image motion. © 2012 The Royal Society.


Peruzzi L.,University of Pisa | Eroglu H.E.,Bozok University
Comparative Cytogenetics | Year: 2013

One of the most popular, cheap and widely used approaches in comparative cytogenetics-especially by botanists-is that concerning intrachromosomal and interchromosomal karyotype asymmetry. Currently, there is no clear indication of which method, among the many different ones reported in literature, is the most adequate to infer karyotype asymmetry (especially intrachromosomal), above all in view of the criticisms recently moved to the most recent proposal published. This work addresses a critical review of the methods so far proposed for estimation of karyotype asymmetry, using both artificial and real chromosome datasets. It is shown once again how the concept karyotype of asymmetry is composed by two kinds of estimation: interchromosomal and intrachromosomal asymmetries. For the first one, the use of Coefficient of Variation of Chromosome Length, a powerful statistical parameter, is here confirmed. For the second one, the most appropriate parameter is the new Mean Centromeric Asymmetry, where Centromeric Asymmetry for each chromosome in a complement is easily obtained by calculating the difference of relative lengths of long arm and short arm. The Coefficient of Variation of Centromeric Index, strongly criticized in recent literature, is an additional karyological parameter, not properly connected with karyotype asymmetry. This shows definitively what and how to measure to correctly infer karyotype asymmetry, by proposing to couple two already known parameters in a new way. Hopefully, it will be the basic future reference for all those scientists dealing with cytotaxonomy. © L. Peruzzi, H.E. Eroǧlu.


Frangioni A.,University of Pisa | Gentile C.,CNR Institute for System Analysis and Computer Science Antonio Ruberti | Lacalandra F.,United Investments
International Journal of Electrical Power and Energy Systems | Year: 2011

The short-term Unit Commitment (UC) problem in hydro-thermal power generation is a fundamental problem in short-term electrical generation scheduling. Historically, Lagrangian techniques have been used to tackle this large-scale, difficult Mixed-Integer NonLinear Program (MINLP); this requires being able to efficiently solve the Lagrangian subproblems, which has only recently become possible (efficiently enough) for units subject to significant ramp constraints. In the last years, alternative approaches have been devised where the nonlinearities in the problem are approximated by means of piecewise-linear functions, so that UC can be approximated by a Mixed-Integer Linear Program (MILP); in particular, using a recently developed class of valid inequalities for the problem, called "Perspective Cuts", significant improvements have been obtained in the efficiency and effectiveness of the solution algorithms. These two different approaches have complementary strengths; Lagrangian ones provide very good lower bounds quickly, but they require sophisticated heuristics - which may need to be changed every time that the mathematical model changes - for producing actual feasible solutions. MILP approaches have been shown to be able to provide very good feasible solutions quickly, but their lower bound is significantly worse. We present a sequential approach which combines the two methods, trying to exploit each one's strengths; we show, by means of extensive computational experiments on realistic instances, that the sequential approach may exhibit significantly better efficiency than either of the two basic ones, depending on the degree of accuracy requested to the feasible solutions. © 2010 Elsevier Ltd. All rights reserved.


Gadducci A.,University of Pisa
Best Practice and Research: Clinical Obstetrics and Gynaecology | Year: 2011

Uterine sarcomas usually have an aggressive clinical behaviour, with great tendency to local and distant spread, with unfavourable clinical outcome, excluding endometrial stromal sarcomas and adenosarcoma. Tumour stage is the strongest prognostic factor for all uterine sarcomas, with 5-year survival of about 50-55% for stage I and 8-12% for more advanced stages. Multivariate analysis of some studies have shown that women with leiomyosarcoma have a poorer survival than those with carcinosarcoma. The key issues that will be discussed include the prognostic relevance of pathological and biological variables other than tumour stage in the different histological subtypes of uterine sarcoma. Immunomarkers for cell proliferation and apoptosis have been tested for the identification of tumours with different clinical behaviour, but they are still subject to research and are not currently used in clinical practice. © 2011 Elsevier Ltd. All rights reserved.


OBJECTIVE - To determine the functional health status and treatment satisfaction in patients with type 2 diabetes from the Evaluation of Lantus Effect ON Optimization of use of single dose Rapid insulin (ELEONOR) study that investigated whether a telecare program helps optimization of basal insulin glargine with one bolus injection of insulin glulisine. RESEARCH DESIGN AND METHODS - Functional health status and treatment satisfaction were investigated using the 36-Item Short-Form (SF-36) Health Survey, the World Health OrganizationWell-Being Questionnaire (WBQ), and the Diabetes Treatment Satisfaction Questionnaire. RESULTS - Of 291 randomized patients, 238 completed the study (telecare: 114; self-monitoring blood glucose: 124). Significant improvements were detected in most SF-36 domains, in WBQ depression and anxiety scores, and in treatment satisfaction, without differences between study groups. CONCLUSIONS - An insulin regimen that substantially improves metabolic control, while minimizing the risk of hypoglycemia, can positively affect physical and psychologic well-being and treatment satisfaction irrespective of the educational support system used. © 2011 by the American Diabetes Association.


Siljak-Yakovlev S.,CNRS Ecology, Systematic and Evolution Laboratory | Peruzzi L.,University of Pisa
Plant Biosystems | Year: 2012

Following an overview of the classification scheme for endemic species, the authors propose to complement it based on modern molecular cytogenetic techniques. Molecular cytogenetics provides new possibilities in the study of chromosomal evolution and genome organization, and contributes to a better characterization of the karyotype of endemic species. Through several examples, the authors demonstrate the advantages of molecular cytogenetic techniques in resolving relationships between endemic and related species, leading to a more precise categorisation, especially in the absence of polyploidy. The authors recommend some caution in the interpretation of cytogenetic data alone, and stress the importance of comparing cytogenetic results with those obtained from independent sources (i.e., molecular phylogenetics, phytogeography, ecology). Finally, the current classification of endemic species is revised in the light of molecular cytogenetics and other newly available evidence. © 2012 Copyright Taylor and Francis Group, LLC.


Ambrosini W.,University of Pisa
Annals of Nuclear Energy | Year: 2011

This paper presents results on the stability of a simple heated channel containing fluids at supercritical pressure with an external imposed pressure drop. Basing on a recent work that discussed stability characteristics in a fluid-to-fluid comparison perspective, additional data are presented in order to discuss relevant parametric effects, also including a more accurate fluid-to-fluid comparison. Three different analysis tools, including a system code and in-house linear and transient analysis programs, were adopted to evaluate stability thresholds at different channel throttling conditions and orientations; four different supercritical fluids were considered. The diversity of the adopted tools and the good level of agreement observed in the comparison of their results provide adequate confidence on the general reliability of the obtained information. Among the addressed phenomena, both Ledinegg and density-wave oscillations are considered, pointing out a fundamental continuity between the two phenomena that occur in adjoining regions of the parameter space. Numerical effects are also highlighted, quantifying the impact of truncation error occurring in the use of system codes in the analysis of flow instabilities. The results obtained by different fluids provide further support to the conclusion that, when an appropriate dimensionless formalism is used, the differences obtained in the stability behaviour at imposed heat flux are relatively small for a number of fluids of interest for experimental analyses. © 2010 Elsevier Ltd. All rights reserved.


Molli G.,University of Pisa | Molli G.,CNR Institute of Geosciences and Earth Resources | Malavieille J.,French National Center for Scientific Research
International Journal of Earth Sciences | Year: 2011

The Alps/Apennines system, as well as many collisional orogens through the world, shows a finite deformation produced during a long geological history which involves numerous superimposed tectonic events. As a result, complex and often contrasted reconstructions for the setting and tectonics of the different stages of the growing and interfering Alps/Apennines system have been proposed. To enlight some of the geometric and kinematic signatures related to past geodynamics in the composite Alps(Corsica)/Apennines system, we analyse the major deformation processes, their superimposition, and resulting finite structural geometries in the currently growing Taiwan orogenic system. The Taiwan island and its offshore northward and southward prolongations represent the emerged and the sub-marine parts of an orogenic wedge related to the interactions between the Eurasian and the Philippine Sea and recording different subduction settings. Using the Taiwan actualistic geodynamic scenarios and the related first-order geometric-kinematic constraints, we will attempt a reconstruction of the tectonic evolution for the Corsica/Apennines orogenic system foregrounding the key role of continental subduction and subduction reversal during such evolution. © 2010 Springer-Verlag.


Viccica G.,University of Pisa
Journal of endocrinological investigation | Year: 2010

Peroxisome proliferator-activated receptor γ (PPARγ) is a ligand-activated transcription factor that belongs to the nuclear hormone receptor superfamily and functions as a heterodimer with a retinoid X receptor by binding to PPAR responsive elements. PPARγ plays an important role in adipocyte differentiation and is activated by long-chain fatty acid, peroxisome proliferators, and thiazolidinedione (TZD). TZD are agonists of PPARγ, act as insulin-sensitizing agents, and are widely prescribed in the management of different conditions characterized by insulin resistance. Osteoblasts and marrow adipocytes derive from common multipotential mesenchymal stem cell (MSC) progenitors. Lineage commitment of MSC is determined by expression and/or activation of specific transcription factors, such as Runx2 and Osterix in the case of osteoblasts, and PPARγ in the case of adipocytes. Many evidences indicate an important role of PPARγ in bone metabolism. Heterozygous PPARγ-deficient (PPARγ +/-) mice exhibit enhanced bone formation with increased osteoblastogenesis. Embryonic stem cells derived from PPARγ +/- mice spontaneously differentiate into osteoblasts. In mice and rats, the activation of PPARγ by TZD treatment, such as rosiglitazone (Rosi), causes bone loss, which results from an increase of marrow adipocytes and a decrease of osteoblasts, leading to a reduction of bone formation rate. Human studies have shown that pre- and post-menopausal women treated with Rosi have an increased risk of fracture compared to women treated with metformin and glyburide. Moreover, the modulation of the PPARγ expression is also implicated in the effects of mechanical loading on bone and in age-related bone loss.


This article explores the simultaneous use of pre-classification and postclassification change-detection techniques to map and monitor land-cover and land-use change using multi-temporal Landsat Multi-spectral Scanner and Enhanced Thematic Mapper plus data over one of the most important tourism centres of Italy (e.g. Pisa Province) for 1972, 2000 and 2006. Pre-classification approaches of principal-component analysis and band combination are potentially tailored to reduce data redundancy of the satellite imagery in order to highlight different objects of significance for change-detection analysis across time-series data. In this work, the application of pre-classification techniques could contribute to produce land-cover and land-use maps with higher quality of classification. At this point, the average value of overall classification accuracies for the three classification outputs was an estimated 90%. Then, 'from-to' change information, as well as the area and the type of landscape transformations, are provided through the post-classification technique. The findings of this study show that the province of Pisa has significantly experienced a high rate of deforestation and urban development over past decades. It is revealed that artificial structures (e.g. urban and industrial zones) in Pisa Province increased at a change rate of around 265% and forested land decreased from approximately 45% to 32% of the total area of the province between 1972 and 2006. Likewise, the perceptible growth of built-up structures from about 4% to 10.6% in Pisa City during this 34-year period has imposed a heavy pressure on the landscape of Pisa. © 2011 Taylor & Francis.


Pescitelli G.,University of Pisa | Woody R.W.,Colorado State University
Journal of Physical Chemistry B | Year: 2012

The visible CD spectrum of bacteriorhodpsin (bR) in purple membrane has a negative CD band at ∼600 nm and a positive band at ∼530 nm and has been variously interpreted as resulting from exciton coupling within the bR trimer, heterogeneity in protein conformation, or the presence of two distinct low-energy electronic transitions in bR. We have performed time-dependent density functional theory (TDDFT) calculations on the protonated Schiff base of retinal (retPSB) in bR to predict the intrinsic CD. The resulting spectroscopic parameters have been used to predict the long-wavelength CD spectrum of retPSB trimers. TDDFT, exciton theory, and classical polarizability (DeVoe) predict a strong negative couplet centered near 570 nm, with a magnitude in good agreement with experiment. Coupling of the retPSB chromophore with aromatic and peptide chromophores has been considered by means of perturbation theory and is responsible for the net positive CD of the 570 nm band. The visible CD spectrum of bR is dominated by exciton interactions. © 2012 American Chemical Society.


Valvo P.S.,University of Pisa
International Journal of Fracture | Year: 2015

The standard virtual crack closure technique may calculate negative values of the modal contributions to the energy release rate when analysing problems with highly asymmetric cracks. To avoid such physically meaningless results, a method is proposed, where the partitioning of fracture modes is based on the decomposition of the crack-tip nodal force into energetically orthogonal components. As an example, a delaminated cantilever beam subjected to bending moments is analysed. Both geometric and algebraic interpretations of the method are discussed. © 2015, Springer Science+Business Media Dordrecht.


Mancuso M.,University of Pisa
Advances in Experimental Medicine and Biology | Year: 2010

Abstract Alzheimer's disease (AD) is a neurodegenerative disorder which results in the irreversible loss of cortical neurons, particularly in the associative neocortex and hippocampus. AD is the most common form of dementia in the elderly people. Apart from the neuronal loss, the pathological hallmarks are extracellular senile plaques containing the peptide beta-amyloid (A) and neurofibrillary tangles. The A cascade hypothesis remains the main pathogenetic model, as suggested by familiar AD, mainly associated to mutation in amyloid precursor protein and presenilin genes. The remaining 95% of AD patients are mostly sporadic late-onset cases, with a complex aetiology due to interactions between environmental conditions and genetic features of the individual. Mitochondria play a central role in the bioenergetics of the cell and apoptotic cell death. Morphological, biochemical and genetic abnormalities of the mitochondria in several AD tissues have been reported. Impaired mitochondrial respiration, particularly COX deficiency, has been observed in brain, platelets and fibroblasts of AD patients. Somatic mutations in mitochondrial DNA (mtDNA) could cause energy failure and increased oxidative stress. No causative mutations in the mtDNA have been detected and studies on mtDNA polymorphisms are controversial, but the "mitochondrial cascade hypothesis", here revised, could explain many of the biochemical, genetic and pathological features of sporadic AD. © 2010 Landes Bioscience and Springer Science+Business Media.


Perrini P.,University of Pisa
Neurological Sciences | Year: 2012

Spontaneous resolution of syringomyelia in adult patients with Chiari malformation is exceptionally rare, with only 10 cases having been reported. A 21-year-old man working as a carpenter presented with a 1-year history of paresthesias in his right arm. A magnetic resonance imaging scan disclosed a cervicothoracic syrinx associated with tight tonsillar impaction of the cisterna magna without herniation. The patient left the carpentry job and underwent close monitoring with serial clinical and neuroradiological controls. The patient's symptoms gradually disappeared and magnetic resonance imaging studies revealed progressive shrinkage of the syrinx despite persistence of crowding of posterior fossa structures at the level of the foramen magnum. This case suggests that spontaneous resolution of syringomyelia can occasionally be triggered by the cessation of daily physical strain in patients with tight cisterna magna. Health care professionals should be aware that strenuous physical activities could affect the natural history of syringomyelia. © The Author(s) 2011.


Cazzoli G.,University of Bologna | Cludi L.,University of Bologna | Buffa G.,University of Pisa | Puzzarini C.,University of Bologna
Astrophysical Journal, Supplement Series | Year: 2012

Ground-state rotational spectra of HCO +, N2H +, and CF + (both 12C- and 13C-containing isotopologues) have been recorded in the 1.0-1.6 THz frequency range. Present measurements allowed us to improve the spectroscopic parameters, which in turn enabled the prediction of rotational transitions up to 2.0-2.5 THz with good accuracy. We therefore consider the present results to be of great value in view of the extended spectral coverage made available by the Herschel Space Observatory, Stratospheric Observatory for Infrared Astronomy, and the Atacama Large Millimeter Array. Furthermore, we re-investigated the ground-state rotational spectrum of N2H + in the 93-750GHz frequency range, thus addressing the open issue of the frequency of the J = 1← 0 transition as well as resolving the hyperfine structure of the J+ 1← J transitions with J = 1, 2, and 3 for the first time. © 2012. The American Astronomical Society. All rights reserved..


Tamargo J.,Complutense University of Madrid | Solini A.,University of Pisa | Ruilope L.M.,Autonomous University of Madrid
Seminars in Nephrology | Year: 2014

The first aldosterone blocker, spironolactone, initially was used as a diuretic but was accompanied by a significant amount of side effects that necessitated the withdrawal of the drug in a relevant number of patients. The discovery of the many receptor-mediated actions of aldosterone in several different organs greatly contributed to expand the indications of aldosterone blockers. Eplerenone was the second component of this class of drugs and differed from spironolactone because of its significantly better safety, albeit this was accompanied by a lower potency when used at equinumeric doses. Although these two drugs were being used in clinical practice, the epithelial sodium channel blockers, amiloride and triamterene, with a similar antialdosterone action, continued to be used in clinical practice in combination with thiazides and loop diuretics. New members of the third and fourth generation of mineralocorticoid receptor antagonists and aldosterone synthase inhibitors are in development. These new compounds, which include the new nonsteroidal mineralocorticoid-receptor antagonists and aldosterone synthase inhibitors, try to maintain adequate efficacy, avoiding the drawbacks of spironolactone and eplerenone. Ongoing studies will show the certainty of the capacities of these new compounds to override the virtues of the first mineralocorticoid-receptor spironolactone while avoiding the side effects leading so frequently to the withdrawal of the drug, including a significantly lower prevalence of hyperkalemia when chronic kidney disease is present. © 2014 Elsevier Inc.


Domning D.P.,Howard University | Sorbi S.,University of Pisa
Journal of Vertebrate Paleontology | Year: 2011

A species of the dugongine dugongid genus Rytiodus from the Miocene (Burdigalian-Langhian; 19-14 Ma) deposits of Jabal Zaltan (= Gebel Zelten), Libya, is re-described, considered a valid species differing from Rytiodus capgrandi from the lower Miocene (Aquitanian) of the Aquitaine Basin (SW France), and named Rytiodus heali. R. heali, together with R. capgrandi and Corystosiren varguezi appear to constitute a taxon of dugongines characterized by broad, mediolaterally compressed, blade-like tusks with enamel mainly on the medial side, and a modified nasal process of the premaxilla. They are regarded as specialized seagrass feeders, using their tusks in excavation of seagrass rhizomes. Rytiodus lived sympatrically with the generalist small-tusked halitheriine dugongid genus Metaxytherium. © 2011 by the Society of Vertebrate Paleontology.


Coppede F.,University of Pisa
Current Genomics | Year: 2010

Alzheimer's disease (AD) represents the most common form of dementia in the elderly, characterized by progressive loss of memory and cognitive capacity severe enough to interfere with daily functioning and the quality of life. Rare, fully penetrant mutations in three genes (APP, PSEN1 and PSEN2) are responsible for familial forms of the disease. However, more than 90% of AD is sporadic, likely resulting from complex interactions between genetic and environmental factors. Increasing evidence supports a role for epigenetic modifications in AD pathogenesis. Folate metabolism, also known as one-carbon metabolism, is required for the production of S-adenosylmethionine (SAM), which is the major DNA methylating agent. AD individuals are characterized by decreased plasma folate values, as well as increased plasma homocysteine (Hcy) levels, and there is indication of impaired SAM levels in AD brains. Polymorphisms of genes participating in one-carbon metabolism have been associated with AD risk and/or with increased Hcy levels in AD individuals. Studies in rodents suggest that early life exposure to neurotoxicants or dietary restriction of folate and other B vitamins result in epigenetic modifications of AD related genes in the animal brains. Similarly, studies performed on human neuronal cell cultures revealed that folate and other B vitamins deprivation from the media resulted in epigenetic modification of the PSEN1 gene. There is also evidence of epigenetic modifications in the DNA extracted from blood and brains of AD subjects. Here I review one-carbon metabolism in AD, with emphasis on possible epigenetic consequences. © 2010 Bentham Science Publishers Ltd.


Cevasco G.,University of Genoa | Cevasco G.,CNR Methodological Chemistry Institute | Chiappe C.,University of Pisa
Green Chemistry | Year: 2014

It is well known that ionic liquids (ILs) possess extraordinary characteristics, making them greener solvents with unique properties, which allow processes that would otherwise be difficult or impossible with common solvents to be carried out. In this review, we describe and discuss, in the light of possible future large scale applications, some fundamental studies showing the efficacy of ILs in several "hot" fields, from dissolution and transformation of biopolymers to extraction and capture of important inorganic components (metals) or pollutants (CO2). © the Partner Organisations 2014.


Macchi A.,National Research Council Italy | Macchi A.,University of Pisa | Borghesi M.,Queens University of Belfast | Borghesi M.,ASCR Institute of Physics Prague | Passoni M.,Polytechnic of Milan
Reviews of Modern Physics | Year: 2013

Ion acceleration driven by superintense laser pulses is attracting an impressive and steadily increasing effort. Motivations can be found in the applicative potential and in the perspective to investigate novel regimes as available laser intensities will be increasing. Experiments have demonstrated, over a wide range of laser and target parameters, the generation of multi-MeV proton and ion beams with unique properties such as ultrashort duration, high brilliance, and low emittance. An overview is given of the state of the art of ion acceleration by laser pulses as well as an outlook on its future development and perspectives. The main features observed in the experiments, the observed scaling with laser and plasma parameters, and the main models used both to interpret experimental data and to suggest new research directions are described. © 2013 American Physical Society.


Guido C.A.,Ecole Centrale Paris | Cortona P.,Ecole Centrale Paris | Mennucci B.,University of Pisa | Adamo C.,CNRS Chemistry Laboratory | Adamo C.,Institut Universitaire de France
Journal of Chemical Theory and Computation | Year: 2013

A new index is defined with the aim of further exploring the metric of excited electronic states in the framework of the time-dependent density functional theory. This descriptor, called Δr, is based on the charge centroids of the orbitals involved in the excitations and can be interpreted in term of the hole-electron distance. The tests carried out on a set of molecules characterized by a significant number of charge-transfer excitations well illustrate its ability in discriminating between short (Δr ≤ 1.5 Å) and long-range (Δr ≥ 2.0 Å) excitations. On the basis of the well-known pitfalls of TD-DFT, its values can be then associated to the functional performances in reproducing different type of transitions and allow for the definition of a "trust radius" for GGA and hybrid functionals. The study of other systems, including some well-known difficult cases for other metric descriptors, gives further evidence of the high discrimination power of the proposed index. The combined use with other density or orbital-based descriptors is finally suggested to have a reliable diagnostic test of TD-DFT transitions. © 2013 American Chemical Society.


Guido C.A.,Ecole Centrale Paris | Knecht S.,University of Southern Denmark | Kongsted J.,University of Southern Denmark | Mennucci B.,University of Pisa
Journal of Chemical Theory and Computation | Year: 2013

We analyze potentials and limits of the Time-Dependent Density Functional Theory (TD-DFT) approach for the determination of excited-state geometries of organic molecules in gas-phase and in solution. Three very popular DFT exchange-correlation functionals, two hybrids (B3LYP and PBE0) and one long-range corrected (CAM-B3LYP), are here investigated, and the results are compared to the correlated RI-CC2 wave function approach. Solvent effects are further analyzed by means of a polarizable continuum model. A total of 15 organic chromophores (including both small molecules and larger push-pull systems) are considered as prototypes of n → π* and π → π* singlet excitations. Our analysis allows to point out specific correlations between the accuracy of the various functionals and the type of excitation and/or the type of chemical bonds involved. We find that while the best ground-state geometries are obtained with PBE0 and B3LYP, CAM-B3LYP yields the most accurate description of electronic and geometrical characteristics of excited states, both in gas-phase and in solution. © 2013 American Chemical Society.


Cupisti A.,University of Pisa | Kalantar-Zadeh K.,University of California at Irvine
Seminars in Nephrology | Year: 2013

Phosphorus retention occurs from higher dietary phosphorus intake relative to its renal excretion or dialysis removal. In the gastrointestinal tract the naturally existing organic phosphorus is only partially (̃60%) absorbable; however, this absorption varies widely and is lower for plant-based phosphorus including phytate (<40%) and higher for foods enhanced with inorganic phosphorus-containing preservatives (>80%). The latter phosphorus often remains unrecognized by patients and health care professionals, even though it is widely used in contemporary diets, in particular, low-cost foods. In a nonenhanced mixed diet, digestible phosphorus correlates closely with total protein content, making protein-rich foods a main source of natural phosphorus. Phosphorus burden is limited more appropriately in predialysis patients who are on a low-protein diet (̃0.6 g/kg/d), whereas dialysis patients who require higher protein intake (̃1.2 g/kg/d) are subject to a higher dietary phosphorus load. An effective and patient-friendly approach to reduce phosphorus intake without depriving patients of adequate proteins is to educate patients to avoid foods with high phosphorus relative to protein such as egg yolk and those with high amounts of phosphorus-based preservatives such as certain soft drinks and enhanced cheese and meat. Phosphorus rich foods should be prepared by boiling, which reduces phosphorus as well as sodium and potassium content, or by other types of cooking-induced demineralization. The dose of phosphorus-binding therapy should be adjusted separately for the amount and absorbability of phosphorus in each meal. Dietician counseling to address the emerging aspects of dietary phosphorus management is instrumental for achieving a reduction of phosphorus load. © 2013 Elsevier Inc.


Brandi F.,Italian Institute of Technology | Giammanco F.,University of Pisa
Optics Express | Year: 2011

A compact modular high-speed high-sensitivity second-harmonic interferometer is used to characterize a pulsed gas jet. The temporal evolution of the line-integrated gas density is measured with a resolution of 1 μs revealing detailed information on its dynamics. The actual radial gas density distribution in the jet is obtained applying the Abel's inversion method. The sensitivity of the interferometer is 1 mrad, and its robustness, compactness and modularity make the instrument suitable for practical application. Possible use of the instrument in monitoring cluster formation, and phase-dispersion microscopy is discussed. © 2011 Optical Society of America.


In July 2010, at the Muscle Fatigue Meeting, I presented an overview of Chronic Fatigue Syndrome and Cancer Related Fatigue, emphasizing a critical interpretation of the potential association between Chronic Fatigue Syndrome and Cancer Related Fatigue and a newly discovered retrovirus: Xenotropic Murine Related Virus. Since this association was hotly debated at that time, I suggested at the Meeting that it was wrong and most likely due to the identification of the wrong virus culprit. Today, 20. months after the Meeting, the first part of our prediction has turned out to be correct, as Xenotropic Murine Related Virus was shown to be a laboratory-created artefact. Still, the potential association of fatigue-syndromes with an infection (most likely viral) is sustained by a plethora of evidence and this overview will initially summarize data suggesting prior viral infection(s). The principal hypothesized mechanisms for both peripheral and central Chronic Fatigue Syndrome/Cancer Related Fatigue will be then summarized, also indicating plausible associations and triggering factors. All evidence accrued so far suggests that further research work should be performed in this interesting area and in order to identify an infectious agent for Chronic Fatigue Syndrome/Cancer Related Fatigue. One candidate RNA virus, Micro-Foci inducing Virus, will be described in this overview. © 2012 Elsevier B.V.


Rajabpour M.A.,Federal University of Fluminense | Sotiriadis S.,University of Pisa
Physical Review B - Condensed Matter and Materials Physics | Year: 2015

We study the equilibration properties of observables in long-range field theories after the mass quench in d=1, 2, and 3 dimensions. We classify the regimes where we expect equilibration or its absence in different dimensions. In addition, we study the effect of the initial state in the equilibration properties of our system. In the case of free field theories, we show that whenever we have equilibration, the long-time limit of correlations can be described by the generalized Gibbs ensemble. We prove that all integrals of motion in our system are nonlocal. © 2015 American Physical Society.


Gagliardo A.,University of Pisa
Journal of Experimental Biology | Year: 2013

Forty years ago, Papi and colleagues discovered that anosmic pigeons cannot find their way home when released at unfamiliar locations. They explained this phenomenon by developing the olfactory navigation hypothesis: pigeons at the home loft learn the odours carried by the winds in association with wind direction; once at the release site, they determine the direction of displacement on the basis of the odours perceived locally and orient homeward. In addition to the old classical experiments, new GPS tracking data and observations on the activation of the olfactory system in displaced pigeons have provided further evidence for the specific role of olfactory cues in pigeon navigation. Although it is not known which odours the birds might rely on for navigation, it has been shown that volatile organic compounds in the atmosphere are distributed as fairly stable gradients to allow environmental odour-based navigation. The investigation of the potential role of olfactory cues for navigation in wild birds is still at an early stage; however, the evidence collected so far suggests that olfactory navigation might be a widespread mechanism in avian species. © 2013. Published by The Company of Biologists Ltd.


SOS Rosarno was launched in 2011 by a group of small farmers and activists based in the Gioia Tauro Plain, Calabria, Southern Italy. The idea was to sell organic citrus fruits through short self-organized supply chains, essentially based on Solidarity Purchase Groups, in order to allow producers to pay migrant workers according to the law, to receive a fair remuneration, to guarantee healthy and affordable food to consumers, to protect the integrity of the environment. This paper aims to reconstruct the ideological frame and the genealogy, the organization and the practices, the impact and the limits of SOS Rosarno, drawing mainly on the political documents produced by the association and in-depth interviews with its diverse members. It clarifies, on one side, the strategies of alternative economy and the new social alliances implemented in order to challenge those conditions which impoverish small producers and let migrant farmworkers be exploited and become the target of racism in many Italian countrysides. It explores, on the other side, the development of a new peasant civilization as alternative to the current economic and envi-ronmental crises, in terms of decommodification of nature and labour, construction of a convivial democratic society, transition from monoculture to food sovereignty. © 2015 - University of Salento.


Giuliani E.,University of Pisa | Giuliani E.,University of Sussex
Regional Studies | Year: 2011

Giuliani E. Role of technological gatekeepers in the growth of industrial clusters: evidence from Chile, Regional Studies. Industrial clusters are often associated with innovative success. However, there is very little research on what types of organizational models apply to clusters as they grow. This paper uses longitudinal micro-level data for a wine cluster in Chile. It shows that the most advanced firms in the cluster behave as technological gatekeepers - that is, they acquire knowledge outside cluster boundaries and contribute to diffusing knowledge to other local firms - and do so persistently over time. The results are explained by combining three theoretical perspectives: evolutionary economics theory; business studies on communities of practice and knowledge workers' know-how trade; and embeddedness theory. © 2011 Copyright Regional Studies Association.


Meola M.,University of Pisa
Giornale italiano di nefrologia : organo ufficiale della Società italiana di nefrologia | Year: 2012

When a renal mass is suspected, conventional ultrasound and color Doppler imaging are often used for initial assessment. Ultrasound screening has many advantages over contrast-enhanced CT and MRI, such as accessibility, low costs, and no need for intravenous iodine contrast administration or ionizing radiation. Sonography is very helpful to distinguish cystic from solid lesions and to monitor the growth and structural pattern of cysts. Detection of small renal carcinoma of less than 3 cm in diameter is limited, however, and small tumors are detected by conventional ultrasound only in 67-79% of cases. In fact, small renal malignancies may have an echogenicity similar to the normal renal parenchyma. In these cases it is very hard to distinguish the tumor, particularly when there is no evident disarrangement of the normal renal contours and no extension into the central renal complex. Renal cell carcinoma can also be hypo- or hyperechoic and indistinguishable from renal adenoma/oncocytoma or angiomyolipomas, which are commonly described as hyperechoic masses. In other words, the pattern and ultrasound characteristics of renal masses often overlap between benign and malignant tumors. A diagnosis of a malignant cystic lesion requires evidence of multiple, thickened internal septa, calcifications, vascularity, and parietal nodularity. When a solid lesion does not show the typical appearance of a simple cyst (a round anechoic lesion with a smooth well-defined wall, without internal debris, and showing increased through-transmission), further evaluation with contrast-enhanced CT or MRI is necessary. Contrast-enhanced ultrasound (CEUS) improves the sensitivity for detection of small renal masses. Compared to CT, CEUS is able to better visualize the number of septa, the septum and wall thickness, the presence of a solid component, and enhancement in some cases, resulting in upgrading of the Bosniak classification and affecting treatment planning.


Anselmi D.,University of Pisa
European Physical Journal C | Year: 2013

We investigate the renormalization of gauge theories without assuming cohomological properties. We define a renormalization algorithm that preserves the Batalin-Vilkovisky master equation at each step and automatically extends the classical action till it contains sufficiently many independent parameters to reabsorb all divergences into parameter-redefinitions and canonical transformations. The construction is then generalized to the master functional and the field-covariant proper formalism for gauge theories. Our results hold in all manifestly anomaly-free gauge theories, power-counting renormalizable or not. The extension algorithm allows us to solve a quadratic problem, such as finding a sufficiently general solution of the master equation, even when it is not possible to reduce it to a linear (cohomological) problem. © 2013 Springer-Verlag Berlin Heidelberg and Società Italiana di Fisica.


Papucci M.,Institute for Advanced Study | Strumia A.,University of Pisa | Strumia A.,CERN
Journal of Cosmology and Astroparticle Physics | Year: 2010

We derive robust model-independent bounds on Dark Matter (DM) annihilations and decays from the first year of FERMI γ-ray observations of the whole sky. These bounds only have a mild dependence on the DM density profile and allow the following DM interpretations of the PAMELA and Fermi excesses: primary channels μ+μ-, μ+μ -μ+μ- or e+e-e +e-. An isothermal-like density profile is needed for annihilating DM. In all such cases, FERMI γ spectra must contain a significant DM component, that may be probed in the future. © 2010 IOP Publishing Ltd and SISSA.


summary: Biomass, Biovalue and Sustainability: Some Thoughts on the Definition of the Bioeconomy The success of innovation policies addressing the bioeconomy - and particularly those related to agriculture and food - will depend on how the concept is translated into policies, and therefore on how the term is understood and defined. In this article, different 'clusters' of definitions are considered, alternatively biotechnologies, biomass, and biochemical and biophysical processes as key criteria for identification. It is argued that none of these definitions properly address the issue of sustainability. In fact, a 'broad' definition of bioeconomy, encompassing all biochemical and biophysical processes, would make it useless for policy purposes. The article proposes building a definition of the bioeconomy around the concept of biovalue. It identifies the goal of the bioeconomy as the capacity to mobilise science to obtain high biovalue returns from low-cost living matter, for example organic waste, and includes the value of non-market goods associated with agriculture and food. In this regard, a distinction is made between 'natural biovalue', produced by quality agriculture, and 'biotechnological biovalue'. It is argued that the bioeconomy and the production of natural biovalue deserve specific attention and that a sustainable bioeconomy should not undermine the potential of natural biovalue through competition for the same land and water resources. © 2013 The Agricultural Economics Society and the European Association of Agricultural Economists.


Bacci G.,University of Pisa
IEEE Communications Letters | Year: 2012

A distributed, energy-efficient power control algorithm for the uplink of a CDMA wireless data network over a frequency-selective and slow-fading channel is derived through the application of noncooperative game theory, focusing on the issue of initial code synchronization. To capture the tradeoff between obtaining good synchronization performance and saving as much energy as possible, we derive a distributed criterion to properly set the receiver decision threshold and the transmit power, using the generalized Nash solution, and we propose a practical algorithm, based on iterative best-response dynamics. © 2011 IEEE.


Danesi R.,University of Pisa | Boni J.P.,Pfizer | Ravaud A.,Bordeaux University Hospital Center
Cancer Treatment Reviews | Year: 2013

Identification of the role of biological pathways in metastatic renal cell carcinoma (mRCC) has led to the development of targeted agents for its treatment, in particular those that inhibit the vascular endothelial growth factor pathway, and inhibitors of mammalian target of rapamycin (mTOR). mTOR is central to signalling pathways that regulate cellular growth, proliferation and survival, and this paper focuses on the two currently licensed mTOR inhibitors, temsirolimus and everolimus. These agents are administered via different routes (intravenously and orally, respectively), and this has an impact on their pharmacokinetics; intravenous temsirolimus is not affected by variable absorption in the gastrointestinal tract or by food intake, unlike the orally administered mTOR inhibitor everolimus. Temsirolimus is administered weekly, whereas everolimus is currently approved for daily dosing. In general, intravenous administration is likely to ensure better control of plasma drug concentrations, greater treatment adherence, and more regular monitoring of toxicity and therapeutic response, although it can be uncomfortable and inconvenient for patients. Oral administration is preferred by patients for its convenience, but can be associated with suboptimal adherence to treatment, and poor and variable bioavailability. Temsirolimus and everolimus have both been associated with improved outcomes in patients with mRCC but, as reviewed in this paper, the pharmacokinetic characteristics of these agents differ in many respects. © 2013 Elsevier Ltd.


Molinaro E.,University of Pisa
Journal of endocrinological investigation | Year: 2012

Due to the growing incidence of differentiated thyroid carcinoma (DTC) and in particular of small papillary thyroid cancer observed in the last few decades, the indications, the activity of radioiodine (131I) to be administered, and the efficacy of post surgical thyroid 131I remnant ablation (RRA) have been widely discussed. In the last 10 years, the use of recombinant human TSH (rhTSH) or thyroid hormone withdrawal (THW) to stimulate the 131I remnant uptake has also interested many authors. The general agreement is that small (≤1 cm) intrathyroidal unifocal DTC with a favorable histology and no node metastases should not be submitted to RRA because of the low risk of relapse and cancer specific mortality. Conversely, RRA is indicated in patients with a higher risk level since it seems to reduce recurrence rates and mortality. The recent demonstration that the RRA preparation with rhTSH is as effective as THW using either high (100 mCi) or low (30 mCi) 131I activities suggests that rhTSH preparation and low activity of 131I should be considered as the standard of care for both low- and intermediate-risk DTC patients in the near future. Moreover, the use of low 131I activities and rhTSH reduces whole body radiation exposure and improves the quality of life which are very important advantages for DTC patients.


Pasqualetti F.,University of California at Santa Barbara | Bicchi A.,University of Pisa | Bullo F.,University of California at Santa Barbara
IEEE Transactions on Automatic Control | Year: 2012

This paper addresses the problem of ensuring trustworthy computation in a linear consensus network. A solution to this problem is relevant for several tasks in multi-agent systems including motion coordination, clock synchronization, and cooperative estimation. In a linear consensus network, we allow for the presence of misbehaving agents, whose behavior deviate from the nominal consensus evolution. We model misbehaviors as unknown and unmeasurable inputs affecting the network, and we cast the misbehavior detection and identification problem into an unknown-input system theoretic framework. We consider two extreme cases of misbehaving agents, namely faulty (non-colluding) and malicious (Byzantine) agents. First, we characterize the set of inputs that allow misbehaving agents to affect the consensus network while remaining undetected and/or unidentified from certain observing agents. Second, we provide worst-case bounds for the number of concurrent faulty or malicious agents that can be detected and identified. Precisely, the consensus network needs to be $2k+1$ (resp. $k+1$) connected for $k$ malicious (resp. faulty) agents to be generically detectable and identifiable by every well behaving agent. Third, we quantify the effect of undetectable inputs on the final consensus value. Fourth, we design three algorithms to detect and identify misbehaving agents. The first and the second algorithm apply fault detection techniques, and affords complete detection and identification if global knowledge of the network is available to each agent, at a high computational cost. The third algorithm is designed to exploit the presence in the network of weakly interconnected subparts, and provides local detection and identification of misbehaving agents whose behavior deviates more than a threshold, which is quantified in terms of the interconnection structure. © 2006 IEEE.


Lombardini F.,University of Pisa | Cai F.,SELEX Galileo
IEEE Transactions on Geoscience and Remote Sensing | Year: 2014

Much interest is continuing to grow in advanced interferometric synthetic aperture radar (SAR) methods for full 3-D imaging, particularly of volumetric forest scatterers. Multibaseline (MB) SAR tomographic elevation beam forming, i.e., spatial spectral estimation, is a promising technique in this framework. In this paper, the important effect of temporal decorrelation during the repeat-pass MB acquisition is tackled, analyzing the impact on superresolution (MUSIC) tomography with limited sparse data. Moreover, new tomographic methods robust to temporal decorrelation phenomena are proposed, exploiting the advanced differential tomography concept that produces 'space-time' signatures of scattering dynamics in the SAR cell. To this aim, a 2-D version of MUSIC and a generalized MUSIC method matched to nonline spectra are applied to decouple the nuisance temporal signal components in the spatial spectral estimation. Simulated analyses are reported for different geometrical and temporal parameters, showing that the new concept of restoring tomographic performance in temporal decorrelating forest scenarios through differential tomography is promising. © 2014 IEEE.


Giannetti F.,University of Salerno | Camarri S.,University of Pisa | Luchini P.,University of Salerno
Journal of Fluid Mechanics | Year: 2010

The sensitivity of the three-dimensional secondary instability of a circular-cylinder wake to a structural perturbation of the associated linear equations is investigated. In particular, for a given flow condition, the region of maximum coupling between the velocity components is localized by using the most unstable Floquet mode and its adjoint mode. The variation of this region in time is also found by considering a structural perturbation which is impulsively applied in time at a given phase of the vortex-shedding process. The analysis is carried out for both mode A and mode B types of transition in the wake of a circular cylinder using a finite-difference code. The resulting regions identified as the core of the instability are in full agreement with the results reported in the literature and with the a posteriori checks documented here. © 2010 Cambridge University Press.


The linear Amplitude-Versus-Angle (AVA) inversion has become a standard tool in deep-sediments hydrocarbon exploration since its introduction in the oil and gas industry. However, in the last decades, with the increase of offshore construction activity, applications of this method have been also extended to predict overpressured zones and/or to evaluate the geotechnical properties of shallow sea bottom layers. Among the input parameters requested by linear AVA inversion there is the background Vp/Vs ratio across the reflecting interface and a Vp/Vs ratio of two is frequently assumed. This value is usually very close to the true ratio in case of deep, compacted sediments but it can be a gross underestimation of the true value in case of shallow or overpressured sediments. Despite that, the importance of the background Vp/Vs ratio in AVA inversion is frequently underrated and thus I consider two frequently used approximations of the Zoeppritz equations to study their impact on the outcomes of linear AVA inversion: the three-term Aki and Richards equation and the two-term Ursenbach and Stewart formula. These equations are then analysed, varying the Vp/Vs value, using tools frequently applied in sensitivity analysis. It turns out that the background Vp/Vs ratio controls the error propagation from data to model space and determines the cross-talk between the inverted parameters. Moreover, an increasing Vp/Vs ratio causes a decrease of stability of the AVA inversion and worsens the estimate of the Vs contrast at the reflecting interface. © 2015 - OGS.


Zhang T.,University of Minnesota | Wiesel A.,Hebrew University of Jerusalem | Greco M.S.,University of Pisa
IEEE Transactions on Signal Processing | Year: 2013

We consider covariance estimation in the multivariate generalized Gaussian distribution (MGGD) and elliptically symmetric (ES) distribution. The maximum likelihood optimization associated with this problem is non-convex, yet it has been proved that its global solution can be often computed via simple fixed point iterations. Our first contribution is a new analysis of this likelihood based on geodesic convexity that requires weaker assumptions. Our second contribution is a generalized framework for structured covariance estimation under sparsity constraints. We show that the optimizations can be formulated as convex minimization as long the MGGD shape parameter is larger than half and the sparsity pattern is chordal. These include, for example, maximum likelihood estimation of banded inverse covariances in multivariate Laplace distributions, which are associated with time varying autoregressive processes. © 1991-2012 IEEE.


Meggiolaro E.,University of Pisa | Morda A.,Aix - Marseille University
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2013

We discuss the role of the U(1) axial symmetry for the scalar and pseudoscalar meson mass spectrum of QCD at finite temperature, above the chiral transition at Tc, using a chiral effective Lagrangian model, which, in addition to the usual chiral condensate q Y, also includes a (possible) genuine U(1)A-breaking condensate that (possibly) survives across the chiral transition. The motivations for considering this Lagrangian (and a critical comparison with other effective Lagrangian models existing in the literature) are presented. A detailed comparison between the case N f≥3 and the (remarkably different) case Nf=2 is performed. The results obtained in the case Nf=2 are also critically compared with the available lattice results. © 2013 American Physical Society.


Lencioni R.,University of Pisa
Hepatology | Year: 2010

Loco-regional treatments play a key role in the management of hepatocellular carcinoma (HCC). Image-guided tumor ablation is recommended in patients with early-stage HCC when surgical options are precluded. Radiofrequency ablation has shown superior anticancer effects and greater survival benefit with respect to the seminal percutaneous technique, ethanol injection, in meta-analyses of randomized controlled trials, and is currently established as the standard method for local tumor treatment. Novel thermal and nonthermal techniques for tumor ablation - including microwave ablation, irreversible electroporation, and light-activated drug therapy - seem to have potential to overcome the limitations of radiofrequency ablation and warrant further clinical investigation. Transcatheter arterial chemoembolization (TACE) is the standard of care for patients with asymptomatic, noninvasive multinodular tumors at the intermediate stage. The recent introduction of embolic microspheres that have the ability to release the drug in a controlled and sustained fashion has been shown to significantly increase safety and efficacy of TACE with respect to conventional, lipiodol-based regimens. The available data for radioembolization with yttrium-90 suggests that this is a potential new option for patients with HCC, which should be investigated in the setting of randomized controlled trials. Despite the advances and refinements in loco-regional approaches, the long-term survival outcomes of patients managed with interventional techniques are not fully satisfactory, mainly because of the high rates of tumor recurrence. The recent addition of molecular targeted drugs with antiangiogenic and antiproliferative properties to the therapeutic armamentarium for HCC has prompted the design of clinical trials aimed at investigating the synergies between loco-regional and systemic treatments. The outcomes of these trials are eagerly awaited, because they have the potential to revolutionize the treatment of HCC. Copyright © 2010 by the American Association for the Study of Liver Diseases.


Peruzzi L.,University of Pisa
Plant Biosystems | Year: 2011

A new heterostylous species, Linum katiae, is described from Calabria (southern Italy). This species differs from the closely related Linum alpinum 7 occurring in Alps and Apennines 7 by leaf width (3.1±0.5 mm vs. 1.6±0.4 mm), different flower color (bluish-white vs. blue), petals' size (25.8±1.3 mm vs. 16.0±4 mm), sepals' size (9.4±0.7 mm vs. 6.1±1.2 mm), and stigma shape (2.5 vs. 1.4-1.5 length/width ratio). The taxonomic relationships of the new species with Linum perenne group representatives (L. alpinum, Linum austriacum, Linum punctatum) and with other sect. Linum taxa (i.e. Linum narbonense) are discussed. © 2011 Società Botanica Italiana.


Camarri S.,University of Pisa | Giannetti F.,University of Salerno
Journal of Fluid Mechanics | Year: 2010

This paper investigates the three-dimensional stability of the wake behind a symmetrically confined circular cylinder by a linear stability analysis. Emphasis has been placed on discussing analogies and differences with the unconfined case to highlight the role of the inversion of the von Kármán street in the nature of the three-dimensional transition. Indeed, in this flow, the vortices of opposite sign that are alternately shed from the body into the wake cross the symmetry line further downstream and they assume a final configuration which is inverted with respect to the unconfined case. It is shown that the transition to a three-dimensional state has the same space-time symmetries of the unconfined case, although the shape of the linearly unstable modes is affected by the inversion of the wake vortices. A possible interpretation of this result is given here. © 2010 Cambridge University Press.


The impact of crystalline forces on the solid-state circular dichroism (CD) spectrum of hypothemycin (), a biologically active molecule extracted from natural sources, has been analyzed by means of time-dependent density functional theory CD calculations. Input structures were extracted from the X-ray geometry of and consisted in the isolated molecule, its cluster with five water molecules, and 20 different dimers (plus water molecules) representative of all the closest neighbors found in the crystal. The effects of solid-state intermolecular hydrogen bonds and through-space exciton couplings in determining the solid-state CD spectrum of hypothemycin were evaluated and compared. Chirality 24:718-724, 2012. © 2012 Wiley Periodicals, Inc.


Pelissetto A.,University of Rome La Sapienza | Vicari E.,University of Pisa
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2013

We investigate the nature of the finite-temperature chiral transition in QCD with two light flavors, in the case of an effective suppression of the U(1)A symmetry breaking induced by the axial anomaly, which implies the symmetry breaking U(2)L⊠- U(2)R→ U(2)V, instead of SU(2)L⊠- SU(2) R→SU(2)V. For this purpose, we perform a high-order field-theoretical perturbative study of the renormalization-group flow of the corresponding three-dimensional multiparameter Landau-Ginzburg-Wilson Φ4 theory with the same symmetry-breaking pattern. We confirm the existence of a stable fixed point and determine its attraction domain in the space of the bare quartic parameters. Therefore, the chiral QCD transition might be continuous also if the U(1)A symmetry is effectively restored at Tc. However, the corresponding universality class differs from the O(4) vector universality class which would describe a continuous transition in the presence of a substantial U(1)A symmetry breaking at Tc. We estimate the critical exponents of the U(2)L⊠- U(2)R→U(2)V universality class by computing and analyzing the corresponding perturbative expansions. These results are important to discriminate among the different scenarios for the scaling behavior of QCD with two light flavors close to the chiral transition. © 2013 American Physical Society.


I conducted new vorticity and deformation temperatures studies to test competing models of the exhumation of the mid-crustal rocks exposed in the Dolpo region (West Nepal). My results indicate that the Main Central Thrust is located ~5 km structurally below the previous mapped locations. Deformation temperature increasing up structural section from ~450 °C to ~650 °C and overlap with peak metamorphic temperature indicating that penetrative shearing was responsible for the exhumation of the GHS occurred at "close" to peak metamorphic conditions. I interpreted the telescoping and the inversion of the paleo-isotherms at the base of the GHS as produced mainly by a sub-simple shearing (Wm = 0.88-1) pervasively distributed through the lower portion of the GHS. My results are consistent with hybrid channel flow-type models where the boundary between lower and upper portions of the GHS, broadly corresponding to the tectonometamorphic discontinuity recently documented in west Nepal, represents the limit between buried material, affected by dominant simple shearing, and exhumed material affected by a general flow dominates by pure shearing. This interpretation is consistent with the recent models suggesting the simultaneous operation of channel flow- and critical wedge-type processes at different structural depth. © 2015 Elsevier Ltd.


Venutelli M.,University of Pisa
Journal of Hydraulic Engineering | Year: 2011

The models for flood propagation in an open channel are governed by Saint-Venant's equations or by their simplified forms. Assuming the full form of hyperbolic type nonlinear expressions, the complete or dynamic wave model is obtained. Hence, after first-order linearization procedure, the dispersion relation is obtained by using the classical Fourier analysis. From this expression, the phase and group speed and the variations of the amplitude of the waves are defined and investigated. Adopting Manning's resistance formula, the effects of the variations of the Froude number, Courant number, and friction parameter are examined in the wave number domain for progressive and regressive waves. For small and high wave numbers, the simplified kinematic and gravity wave models are recovered, respectively. Moreover, the analysis confirms, according to the Vedernikov criterion, the Froude number value corresponding to the stability condition to contrast the development of roll waves. In addition, for stable flow on the group speed versus wave number curves, the results show critical points, maximum and minimum for progressive and regressive waves, respectively. © 2011 American Society of Civil Engineers.


Romano G.,University of Pisa | Guerrini A.,University of Verona
Utilities Policy | Year: 2011

This study provides an analysis of Italian water utilities to determine the effects on their efficiency of certain relevant variables that have been broadly discussed in the existing literature. We reviewed the annual financial statements of 43 Italian water utility companies and obtained other technical data from Co.n.vi.r.i., the Italian national authority for water. Using data envelopment analysis we assessed their cost efficiencies and, using non-parametric statistic methods, we discuss the significant differences among clusters.We found that ownership structure, size and geographical location had an impact on the performance of water utilities, although with different degrees of significance. © 2011 Elsevier Ltd.


Alba V.,Normal School of Pisa | Tagliacozzo L.,University of Queensland | Calabrese P.,University of Pisa
Physical Review B - Condensed Matter and Materials Physics | Year: 2010

We study the scaling of the Rényi and entanglement entropy of two disjoint blocks of critical Ising models as function of their sizes and separations. We present analytic results based on conformal field theory that are quantitatively checked in numerical simulations of both the quantum spin chain and the classical two-dimensional Ising model. Theoretical results match the ones obtained from numerical simulations only after taking properly into account the corrections induced by the finite length of the blocks to their leading scaling behavior. © 2010 The American Physical Society.


Bianchi M.,University of Pisa
Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference | Year: 2011

During manual palpation, clinicians rely on distributed tactile information to identify and localize hard lumps embedded in soft tissue. The development of tactile feedback systems to enhance palpation using robot-assisted minimally invasive surgery (RMIS) systems is challenging due to size and weight constraints, motivating a pneumatic actuation strategy. Recently, an air jet approach has been proposed for generating a lump percept. We use this technique to direct a thin stream of air through an aperture directly on the finger pad, which indents the skin in a hemispherical manner, producing a compelling lump percept. We hypothesize that the perceived parameters of the lump (e.g. size and stiffness) can be controlled by jointly adjusting air pressure and the aperture size through which air escapes. In this work, we investigate how these control variables interact to affect perceived pressure on the finger pad. First, we used a capacitive tactile sensor array to measure the effect of aperture size on output pressure, and found that peak output pressure increases with aperture size. Second, we performed a psychophysical experiment for each aperture size to determine the just noticeable difference (JND) of air pressure on the finger pad. Subject-averaged pressure JND values ranged from 19.4-24.7 kPa, with no statistical differences observed between aperture sizes. The aperture-pressure relationship and the pressure JND values will be fundamental for future display control.


Pennelli G.,University of Pisa
Beilstein Journal of Nanotechnology | Year: 2014

A big research effort is currently dedicated to the development of thermoelectric devices capable of a direct thermal-to-electrical energy conversion, aiming at efficiencies as high as possible. These devices are very attractive for many applications in the fields of energy recovery and green energy harvesting. In this paper, after a quick summary of the fundamental principles of thermoelectricity, the main characteristics of materials needed for high efficiency thermoelectric conversion will be discussed, and a quick review of the most promising materials currently under development will be given. This review paper will put a particular emphasis on nanostructured silicon, which represents a valid compromise between good thermoelectric properties on one side and material availability, sustainability, technological feasibility on the other side. The most important bottom-up and top-down nanofabrication techniques for large area silicon nanowire arrays, to be used for high efficiency thermoelectric devices, will be presented and discussed. © 2014 Pennelli; licensee Beilstein-Institut.


Sacco R.,University of Pisa
European Review for Medical and Pharmacological Sciences | Year: 2014

INTRODUCTION: Although most HBV infections are effectively managed by the available therapies, the treatment of the most complex cases of hepatitis B still represents an unmet medical need. Entecavir is considered a first-line therapeutic option for hepatitis B, due to its demonstrated efficacy in rapidly suppressing the viral load. Its activity is also characterized by a high genetic barrier and an overall favorable safety profile. AIM: This review provides an overview of the most recent evidence related to the use of entecavir in the management of the most complex forms of hepatitis B. MATERIALS AND METHODS: Original articles for inclusion in this review were retrieved from online databases such as PubMed/Medline and EMBASE; their reference list was browsed to found other relevant papers. The identified papers were selected for inclusion in the present manuscript according to their relevance for the topic. The search was last updated on December 2013. RESULTS: Several studies have proven the efficacy and safety of entecavir in the treatment of patients affected by complex forms of hepatitis B, as those with decompensated cirrhosis, exacerbations of HBV infection and fulminant hepatic failure or in transplanted subjects. CONCLUSIONS: Overall, entecavir seems a powerful therapeutic strategy for the treatment of HBV infection, even in patients affected by the most complex forms of hepatitis. The high efficacy of entecavir, associated with its safety profile, its high genetic barrier to resistance and its cost-effectiveness, allowed this molecule to become one of the preferred first-line options of treatment to manage HBV infections. However, further researches and trials are still needed to definitively elucidate its effectiveness in the daily clinical practice.


Rossi M.,University of Pisa
Clinical hemorheology and microcirculation | Year: 2013

Abnormalities in labyrinth vasculature, resulting in labyrinth ischemia may be responsible for acute unilateral vestibular syndrome (AVS). However, since no tools for the study of the labyrinth microvasculature are available in clinical settings, labyrinth microvascular abnormalities in AVS patients (AVS-pts) can only be hypothesized on the basis of the their cardiovascular risk profile. Considering that skin microcirculation may mirror vascular function in other body districts, we examined skin endothelial function in 20AVS-pts and in 20 healthy control subjects (CS), with the aim of predicting labyrinth microvascular abnormalities in the same AVS-pts, potentially involved in the pathogenesis of their AVS. AVS-pts and CS underwent laser-Doppler flowmetry measurement of the skin forearm vasodilator response (SVR) to iontophoresis of the endothelial-dependent vasodilator acetylcholine (ACh) and to the endothelial-independent vasodilator sodium nitroprusside (SNP). SVR to ACh was significantly lower than to SNP in AVS patients (p < 0.005, ANOVA for repeated measures), consistent with skin endothelial dysfunction, while no significant differences in SVR between ACh and SNP were observed in CS. Accordingly with an arbitrary cut-off of 30% or greater reduction in SVR to ACh compared to SNP, endothelial dysfunction was found in 4 (20%) of CS, and in 14 (70%) of AVS-pts (6 with associated co-morbidities potentially responsible for endothelial dysfunction, and 8 without these co-morbodities). This study shows that the investigation of skin endothelial function in AVS-pts may be helpful in identifying AVS-pts in whom an ischemic origin of AVS might be more probable, in spite of their low cardiovascular risk profile.


Galli E.,University of Pisa | Pingitore A.,CNR Institute of Neuroscience | Iervasi G.,CNR Institute of Neuroscience
Heart Failure Reviews | Year: 2010

Thyroid hormone (TH) has a fundamental role in cardiovascular homeostasis in both physiological and pathological conditions, influencing cardiac contractility, heart rate (HR), diastolic function and systemic vascular resistance (SVR) through genomic and non-genomic mediated effects. In heart failure (HF) the main alteration of thyroid function is referred to as "low-triiodothyronine (T3) syndrome" (LT3S) characterized by decreased total serum T3 and free T3 (fT3) with normal levels of thyroxine (T4) and thyrotropin (TSH). Even if commonly interpreted as an adaptive factor, LT3S may have potential negative effects, contributing to the progressive deterioration of cardiac function and myocardial remodeling in HF and representing a powerful predictor of mortality in HF patients. All these observations, together with the early evidence of the benefits of T3 administration in HF patients indicate that placebo-controlled prospective studies are now needed to better define the safety and prognostic effects of chronic treatment with synthetic TH in HF. © Springer Science+Business Media, LLC 2008.


Giordano M.,Hungarian Academy of Sciences | Meggiolaro E.,University of Pisa
Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics | Year: 2015

We discuss how hadronic total cross sections at high energy depend on the details of QCD, namely on the number of colours Nc and the quark masses. We find that while a "Froissart"-type behaviour σtot~Blog2s is rather general, relying only on the presence of higher-spin stable particles in the spectrum, the value of B depends quite strongly on the quark masses. Moreover, we argue that B is of order O(Nc0) at large Nc, and we discuss a bound for B which does not become singular in the Nf=2 chiral limit, unlike the Froissart-Łukaszuk-Martin bound. © 2015.


Indomethacin is a non-steroidal anti-inflammatory drug that is a potent inhibitor of prostaglandin E2 synthesis. After birth, the ductus arteriosus closes spontaneously within 2-4 days in term infants. The major factor closing the ductus arteriosus is the tension of oxygen, which increases significantly after birth. Prostaglandin E2 has the opposite effect to that of oxygen; it relaxes smooth muscle and tends to inhibit the closure of the ductus arteriosus. In preterm infants with respiratory distress syndrome, the ductus arteriosus fails to close (patent ductus arteriosus [PDA]) because the concentration of prostaglandin E2 is relatively high. PDA occurs in more than 70 % of neonates weighing less than 1,500 g at birth. The aim of this article was to review the published data on the clinical pharmacology of indomethacin in preterm infants in order to provide a critical analysis of the literature and a useful tool for physicians. The bibliographic search was performed electronically using the PubMed and EMBASE databases as search engines and February 2012 was the cutoff point. A remarkable interindividual variability was observed for the half-life (tO), clearance (CL), and volume of distribution (Vd) of indomethacin. Prophylactic indomethacin consists of a continuous infusion of low levels of indomethacin and may be useful in preterm infants. Extremely preterm infants are less likely to respond to indomethacin. Infants with a postnatal age of 2 months do not respond to treatment with indomethacin. Indomethacin has several adverse effects, the most common of which is renal failure. An increase in serum creatinine of ≥0.5 % mg/dL after indomethacin was observed in about 10-15 % of the patients and creatinine returns to a normal level about 1 week after cessation of therapy. Indomethacin should be administered intravenously by syringe pump for at least 30 min to minimize adverse effects on cerebral, gastrointestinal, and renal blood flow velocities. A prolonged course of indomethacin appears to reduce the risk of severe intracranial hemorrhage and renal impairment in patients with PDA. In conclusion, indomethacin is a useful drug to treat PDA. © 2013 Springer International Publishing Switzerland.


Lencioni R.,University of Pisa
Critical Reviews in Oncology/Hematology | Year: 2012

The clinical management of hepatocellular carcinoma (HCC) is often complicated by poor liver function. Treatment options for intermediate- and advanced-stage disease are limited. Transcatheter arterial chemoembolization (TACE) is an effective first-line therapy for intermediate-stage HCC. By interrupting blood flow to the tumor and administering concentrated chemotherapy locoregionally, TACE induces necrosis at the tumor site, but may create conditions that permit or encourage angiogenesis and recurrence of the tumor. Combination of TACE with new targeted agents may be an effective way to treat intermediate-stage HCC, particularly in higher risk patients. Because of the efficacy and safety of sorafenib-the first systemic therapy to show significant clinical benefit in advanced HCC-there is great interest in its potential use in combination with existing treatment modalities. The synergistic combination of TACE plus sorafenib represents a promising opportunity for tumor control. © 2011 Elsevier Ireland Ltd.


Viviani M.,National Institute of Nuclear Physics, Italy | Girlanda L.,University of Salento | Kievsky A.,National Institute of Nuclear Physics, Italy | Marcucci L.E.,National Institute of Nuclear Physics, Italy | Marcucci L.E.,University of Pisa
Physical Review Letters | Year: 2013

We present a detailed study of the effect of different three-nucleon interactions in p-He3 elastic scattering at low energies. In particular, two interactions have been considered: one derived from effective field theory at next-to-next-to-leading order and one derived from a more phenomenological point of view - the so-called Illinois model. The four-nucleon scattering observables are calculated by using the Kohn variational principle and the hyperspherical harmonics technique, and the results are compared with available experimental data. We have found that the inclusion of both interactions improves the agreement with the experimental data, in particular, for the proton vector analyzing power. © 2013 American Physical Society.


Taccola L.,University of Pisa
International journal of nanomedicine | Year: 2011

It has recently been demonstrated that zinc oxide nanoparticles (ZnO NPs) induce death of cancerous cells whilst having no cytotoxic effect on normal cells. However, there are several issues which need to be resolved before translation of zinc oxide nanoparticles into medical use, including lack of suitable biocompatible dispersion protocols and a better understanding being needed of the mechanism of their selective cytotoxic action. Nanoparticle dose affecting cell viability was evaluated in a model of proliferating cells both experimentally and mathematically. The key issue of selective toxicity of ZnO NPs toward proliferating cells was addressed by experiments using a biological model of noncancerous cells, ie, mesenchymal stem cells before and after cell differentiation to the osteogenic lineage. In this paper, we report a biocompatible protocol for preparation of stable aqueous solutions of monodispersed zinc oxide nanoparticles. We found that the threshold of intracellular ZnO NP concentration required to induce cell death in proliferating cells is 0.4 ± 0.02 mM. Finally, flow cytometry analysis revealed that the threshold dose of zinc oxide nanoparticles was lethal to proliferating pluripotent mesenchymal stem cells but exhibited negligible cytotoxic effects to osteogenically differentiated mesenchymal stem cells. Results confirm the ZnO NP selective cytotoxic action on rapidly proliferating cells, whether benign or malignant.


Saponara S.,University of Pisa
Journal of Real-Time Image Processing | Year: 2012

The 3D discrete cosine transform and its inverse (3D DCT/IDCT) extend the spatial compression properties of conventional 2D DCT to the spatio-temporal coding of 2D videos. The 3D DCT/IDCT transform is particularly suited for embedded systems needing the low-complexity implementation of both video encoder and decoder, such as mobile terminals with video-communication capabilities. This paper addresses the problem of real-time and low-power 3D DCT/IDCT processing by presenting a context-aware fast transform algorithm and a family of VLSI architectures characterized by different levels of parallelism. Implemented in submicron CMOS technology, the proposed hardware macrocells support the real-time processing of main video formats (up to high definition ones with an input rate of tens of Mpixels/s) with different trade-offs between circuit complexity, power consumption and computational throughput. Voltage scaling and adaptive clock-gating strategies are applied to reduce the power consumption versus the state of the art. © 2010 Springer-Verlag.


Ciuffoletti A.,University of Pisa
Computer Communication Review | Year: 2010

Infrastructure as a Service (IaaS) providers keep extending with new features the computing infrastructures they offer on a pay per use basis. In this paper we explore reasons and opportunities to include networking within such features, meeting the demand of users that need composite computing architectures similar to Grids. The introduction of networking capabilities within IaaSs would further increase the potential of this technology, and also foster an evolution of Grids towards a confluence, thus incorporating the experiences matured in this environment. Network monitoring emerges as a relevant feature of such virtual architectures, which must exhibit the distinguishing properties of toe IaaS paradigm: scalability, dynamic configuration, accounting. Monitoring tools developed with the same purpose in Grids provide useful insights on problems and solutions.


Beyond serving in complex decision-making, both the Analytic Hierarchy Process (AHP) and the Analytic Network Process (ANP) for the measurement of both tangibles and intangibles can be used in prediction rather effectively. This paper examines the potential of these models to help one discern current states and situations as well as suggest future outcomes. The first example uses the AHP to predict the Democratic Nominee in the 2008 United States presidential election and then uses that information to predict the overall election winner. The second example uses the ANP to predict the market share for ski equipment. The general structure of these models can be applied in many and diverse situations. © 2010 Elsevier B.V. All rights reserved.


Bisson M.,Istituto Nazionale di Geofisica a Vulcanologia | Bini M.,University of Pisa
International Journal of Geographical Information Science | Year: 2012

This article presents a multidisciplinary study implemented in Geographic Information System (GIS) environment to investigate the palaeo-hydrography in a sector of the Magra River alluvial plain (north-western Italy) where the famous ruins of the Roman colony of Luna (now Luni) are located. The approach proposed here combines the results obtained by different remote sensing images (satellite and airborne photos) with the data derived from historical cartography and recent field surveys. The traces are mapped and organised in two vector databases organised in linear or polygonal features consistent with fluvial elements (e.g. palaeo-channels, abandoned streams, etc.) and marshy/swamp areas, respectively. This database represents a useful starting point that can be implemented by further more detailed studies aimed to better understand the evolution of the landscape and the possible relationship with the story of the archaeological site of Luna about which many questions are still unresolved. © 2012 Copyright Taylor and Francis Group, LLC.


This article aims to explore whether procedural rights and administrative law mechanisms - such as, for example, the right to a hearing, the duties to provide a reasoned decision and to disclose relevant information - can enhance the accountability and democratic legitimacy of earth system governance.The democracy-enhancing potential of such mechanisms and rights - which in the national context have proved to be beneficial in strengthening citizens' participation and the acceptance of decisions - can be limited in the global arena, by a number of factors. One of these factors is "legal imperialism", understood as the grafting onto the global level rules and institutions that impose the hegemony of western values.In fact, administrative law mechanisms, being a construct of a certain type of western, liberal model of the state (and its capitalist model of development), could be perceived, in developing countries as an instrument to reproduce the dominant position of advanced industrialized countries and their economic actors.The analysis suggests that in order to realize their democracy-enhancing potential, these mechanisms should draw, as far as possible, on cross-cultural principles, and be supported by financial and technical instruments enabling "developing countries" and marginalized groups to engage in dialog with the most powerful actors. © 2011 Elsevier B.V.


Marcelloni F.,University of Pisa | Vecchio M.,French Institute for Research in Computer Science and Automation
Information Sciences | Year: 2010

Nodes of wireless sensor networks (WSNs) are typically powered by batteries with a limited capacity. Thus, energy is a primary constraint in the design and deployment of WSNs. Since radio communication is in general the main cause of power consumption, the different techniques proposed in the literature to improve energy efficiency have mainly focused on limiting transmission/reception of data, for instance, by adopting data compression and/or aggregation. The limited resources available in a sensor node demand, however, the development of specifically designed algorithms. To this aim, we propose an approach to perform lossy compression on single node based on a differential pulse code modulation scheme with quantization of the differences between consecutive samples. Since different combinations of the quantization process parameters determine different trade-offs between compression performance and information loss, we exploit a multi-objective evolutionary algorithm to generate a set of combinations of these parameters corresponding to different optimal trade-offs. The user can therefore choose the combination with the most suitable trade-off for the specific application. We tested our lossy compression approach on three datasets collected by real WSNs. We show that our approach can achieve significant compression ratios despite negligible reconstruction errors. Further, we discuss how our approach outperforms LTC, a lossy compression algorithm purposely designed to be embedded in sensor nodes, in terms of compression rate and complexity. © 2010 Elsevier Inc. All rights reserved.


Baroni M.,University of Trento | Lenci A.,University of Pisa
Computational Linguistics | Year: 2010

Research into corpus-based semantics has focused on the development of ad hoc models that treat single tasks, or sets of closely related tasks, as unrelated challenges to be tackled by extracting different kinds of distributional information from the corpus. As an alternative to this "one task, one model" approach, the Distributional Memory framework extracts distributional information once and for all from the corpus, in the form of a set of weighted word-link-word tuples arranged into a third-order tensor. Different matrices are then generated from the tensor, and their rows and columns constitute natural spaces to deal with different semantic problems. In this way, the same distributional information can be shared across tasks such as modeling word similarity judgments, discovering synonyms, concept categorization, predicting selectional preferences of verbs, solving analogy problems, classifying relations between word pairs, harvesting qualia structures with patterns or example pairs, predicting the typical properties of concepts, and classifying verbs into alternation classes. Extensive empirical testing in all these domains shows that a Distributional Memory implementation performs competitively against task-specific algorithms recently reported in the literature for the same tasks, and against our implementations of several state-of-the-art methods. The Distributional Memory approach is thus shown to be tenable despite the constraints imposed by its multi-purpose nature. © 2010 Association for Computational Linguistics.


Vecchio M.,University of Vigo | Lopez-Valcarce R.,University of Vigo | Marcelloni F.,University of Pisa
Applied Soft Computing Journal | Year: 2012

To know the location of nodes plays an important role in many current and envisioned wireless sensor network applications. In this framework, we consider the problem of estimating the locations of all the nodes of a network, based on noisy distance measurements for those pairs of nodes in range of each other, and on a small fraction of anchor nodes whose actual positions are known a priori. The methods proposed so far in the literature for tackling this non-convex problem do not generally provide accurate estimates. The difficulty of the localization task is exacerbated by the fact that the network is not generally uniquely localizable when its connectivity is not sufficiently high. In order to alleviate this drawback, we propose a two-objective evolutionary algorithm which takes concurrently into account during the evolutionary process both the localization accuracy and certain topological constraints induced by connectivity considerations. The proposed method is tested with different network configurations and sensor setups, and compared in terms of normalized localization error with another metaheuristic approach, namely SAL, based on simulated annealing. The results show that, in all the experiments, our approach achieves considerable accuracies and significantly outperforms SAL, thus manifesting its effectiveness and stability. © 2011 Elsevier B.V. All rights reserved.


Lopriore L.,University of Pisa
Computer Journal | Year: 2012

A salient aspect of protection system design is the set of the mechanisms for the representation, distribution, verification and revocation of access privileges. With reference to a segmented virtual memory space, we present an approach that is based on the use of symmetric-key cryptography to represent segment pointers, including access right specifications. Our design effort has been guided by three main objectives: (i) to maintain the simplicity of access privilege representation that characterizes classical capability and password-capability systems; (ii) to keep the memory requirements low even in the case of complex access privileges expressed in terms of several access rights; and (iii) to allow an easy implementation of effective techniques for access privilege review and revocation. © 2011 The Author. Published by Oxford University Press on behalf of The British Computer Society. All rights reserved.


Cipriani M.,University of Pisa | Cipriani M.,National Institute of Nuclear Physics, Italy | Nitta M.,Keio University
Physical Review Letters | Year: 2013

We study the effects of the internal coherent (Rabi) coupling in vortex lattices in two-component BECs under rotation. We find how the vortex lattices without the Rabi coupling known before are connected to the Abrikosov lattice of integer vortices with increasing the Rabi coupling. We find that (1) for small Rabi couplings, fractional vortices in a triangular or square lattice for small or large intercomponent coupling constitute hexamers or tetramers, namely multidimer bound states made of six or four vortices, respectively, (2) these bound states are broken into a set of dimers at intermediate Rabi couplings, and (3) vortices change their partners in various ways depending on the intercomponent coupling, to organize themselves for constituting the Abrikosov lattice of integer vortices at strong Rabi couplings. © 2013 American Physical Society.


Ferrannini E.,University of Pisa
Endocrinology and Metabolism Clinics of North America | Year: 2012

An input-output schematization of plasma glucose homeostasis provides quantitative information on glucose fluxes and their control by insulin. Insulin action is dependent on the target tissue, the route of delivery, and the kinetics of insulin activation and deactivation, which are different for glucose production and disposal and are a function of insulin resistance. Under normal conditions, the closed-loop control of minute-by-minute insulin release by arterial glucose levels protects against both hyperglycemia and hypoglycemia. Open-loop insulin therapy faces the complexities of insulin pharmacokinetics and pharmacodynamics. Insulin therapy thus remains defiantly empiric. © 2012 Elsevier Inc.


Ferrannini E.,University of Pisa | Ramos S.J.,Hospital Jardines de Guadalupe | Salsali A.,Bristol Myers Squibb | Tang W.,Bristol Myers Squibb | List J.F.,Bristol Myers Squibb
Diabetes Care | Year: 2010

OBJECTIVE - Dapagliflozin, a highly selective inhibitor of the renal sodium-glucose cotransporter-2, increases urinary excretion of glucose and lowers plasma glucose levels in an insulin-independent manner. We evaluated the efficacy and safety of dapagliflozin in treatmentnaive patients with type 2 diabetes. RESEARCH DESIGN AND METHODS - This was a 24-week parallel-group, double-blind, placebo-controlled phase 3 trial. Patients with A1C 7.0-10% (n = 485) were randomly assigned to one of seven arms to receive once-daily placebo or 2.5, 5, or 10 mg dapagliflozin once daily in the morning (main cohort) or evening (exploratory cohort). Patients with A1C 10.1-12% (high-A1C exploratory cohort; n = 73) were randomly assigned 1:1 to receive blinded treatment with a morning dose of 5 or 10 mg/day dapagliflozin. The primary end point was change from baseline in A1C in the main cohort, statistically tested using an ANCOVA. RESULTS - In the main cohort, mean A1C changes from baseline at week 24 were -0.23% with placebo and -0.58, -0.77 (P = 0.0005 vs. placebo), and -0.89% (P < 0.0001 vs. placebo) with 2.5, 5, and 10 mg dapagliflozin, respectively. Signs, symptoms, and other reports suggestive of urinary tract infections and genital infection were more frequently noted in the dapagliflozin arms. There were no major episodes of hypoglycemia. Data from exploratory cohorts were consistent with these results. CONCLUSIONS - Dapagliflozin lowered hyperglycemia in treatment-naive patients with newly diagnosed type 2 diabetes. The near absence of hypoglycemia and an insulin-independent mechanism of action make dapagliflozin a unique addition to existing treatment options for type 2 diabetes. © 2010 by the American Diabetes Association.


Anselmi D.,University of Pisa
European Physical Journal C | Year: 2013

We develop a general field-covariant approach to quantum gauge theories. Extending the usual set of integrated fields and external sources to "proper" fields and sources, which include partners of the composite fields, we define the master functional Ω, which collects one-particle irreducible diagrams and upgrades the usual Γ-functional in several respects. The functional Ω is determined from its classical limit applying the usual diagrammatic rules to the proper fields. Moreover, it behaves as a scalar under the most general perturbative field redefinitions, which can be expressed as linear transformations of the proper fields. We extend the Batalin-Vilkovisky formalism and the master equation. The master functional satisfies the extended master equation and behaves as a scalar under canonical transformations. The most general perturbative field redefinitions and changes of gauge-fixing can be encoded in proper canonical transformations, which are linear and do not mix integrated fields and external sources. Therefore, they can be applied as true changes of variables in the functional integral, instead of mere replacements of integrands. This property overcomes a major difficulty of the functional Γ. Finally, the new approach allows us to prove the renormalizability of gauge theories in a general field-covariant setting. We generalize known cohomological theorems to the master functional and show that when there are no gauge anomalies all divergences can be subtracted by means of parameter redefinitions and proper canonical transformations. © 2013 Springer-Verlag Berlin Heidelberg and Società Italiana di Fisica.


Ristori L.,National Institute of Nuclear Physics, Italy | Punzi G.,University of Pisa
Annual Review of Nuclear and Particle Science | Year: 2010

For a number of interesting processes in the sector of heavy flavors, the quality of measurements made at hadron colliders is very similar to the quality achieved at e+e- colliders (known as B factories). The key to performing such measurements in a hadron environment is the ability to select rare processes from background in real time, that is, to trigger on them. Two distinctive features of heavy-flavor decays have been used for this purpose: the presence of leptons in the final state and secondary vertices produced by the relatively long lifetime. The selection of events based on long lifetime, although technically very challenging, is the most inclusive of all such techniques, allowing access to the widest range of channels. The focus of this review is on the innovative concepts that permitted the reconstruction of tracks produced in hadron collisions with sufficient speed and accuracy for use at trigger level to detect heavy-flavor decays. © 2010 by Annual Reviews. All rights reserved.


Costa F.,University of Pisa
IEEE Transactions on Instrumentation and Measurement | Year: 2013

A simple approach to estimate the surface impedance of a thin ink deposition on dielectric substrates is described. The measured sample is transversally accommodated in a waveguide, and the scattering parameters are measured. Then, the surface impedance value is recovered by recurring to an efficient transmission-line approach. Closed-form relations are proposed, which allow removing the dispersive effect of the substrate on the estimated surface impedance. The robustness of the retrieving procedure is analyzed, showing that the one based on the transmission coefficient provides more accurate results than the reflection-based one. The positioning of the sample is also investigated, highlighting that the placement inside the waveguide leads to incorrect estimations of the surface impedance with fictitious high imaginary parts because of the presence of air gaps between the sample and the waveguide walls, which transform the uniform layer to a capacitive resistive frequency selective surface. A modified setup with a uniform resistive ink deposition pressed between the waveguide flanges is therefore adopted. Additional experimental results on the effect of the dielectric substrate and on the homogeneity of the ink deposition are reported. © 1963-2012 IEEE.


Menotti P.,University of Pisa
Classical and Quantum Gravity | Year: 2010

In the context of the semiclassical treatment of the Hawking radiation, we prove the universality of the reduced canonical momentum for the system of a massive shell self-gravitating in a spherical gravitational field within the Painlevé family of gauges. We show that one can construct modes which are regular on the horizon both by considering as a Hamiltonian the exterior boundary term and by using as a Hamiltonian the interior boundary term. The late-time expansion is given in both approaches and their time Fourier expansion is computed to reproduce the self-reaction correction to the Hawking spectrum. © 2010 IOP Publishing Ltd.


Konishi K.,University of Pisa
International Journal of Modern Physics A | Year: 2010

We discuss some of the latest results concerning the non-Abelian vortices. The first concerns the construction of non-Abelian BPS vortices based on general gauge groups of the form G = G′×U(1). In particular detailed results about the vortex moduli space have been obtained for G′ = SO(N) or U Sp(2N). The second result is about the "fractional vortices", i.e., vortices of the minimum winding but having substructures in the tension (or flux) density in the transverse plane. Thirdly, we discuss briefly the monopole-vortex complex. © 2010 World Scientific Publishing Company.


Farina M.,Normal School of Pisa | Pappadopulo D.,Ecole Polytechnique Federale de Lausanne | Strumia A.,University of Pisa | Strumia A.,CERN
Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics | Year: 2010

Motivated by the two candidate Dark Matter events observed by the CDMS experiment, we consider a Constrained Dark Matter Singlet (CDMS) model that, with no free parameters, predicts the DM mass and the DM direct cross section to be in the range weakly favored by CDMS. © 2010 Elsevier B.V. All rights reserved.


Meade P.,Institute for Advanced Study | Papucci M.,Institute for Advanced Study | Strumia A.,University of Pisa | Volansky T.,Institute for Advanced Study
Nuclear Physics B | Year: 2010

The cosmic-ray excess observed by PAMELA in the positron fraction and by FERMI and HESS in e- + e+ can be interpreted in terms of DM annihilations or decays into leptonic final states. Final states into τ's or 4μ give the best-fit to the excess. However, in the annihilation scenario, they are incompatible with photon and neutrino constraints, unless DM has a quasi-constant density profile. Final states involving e's are less constrained but poorly fit the excess, unless hidden sector radiation makes their energy spectrum smoother, allowing a fit to all the data with a combination of leptonic modes. In general, DM lighter than about a TeV cannot fit the excesses, so PAMELA should find a greater positron fraction at higher energies. The DM interpretation can be tested by FERMI γ observations above 10 GeV: if the e± excess is everywhere in the DM halo, Inverse Compton scattering on ambient light produces a well-predicted γ excess that FERMI should soon detect. © 2010 Elsevier B.V. All rights reserved.


Bulleri F.,University of Pisa
Marine Biology | Year: 2013

The role played by the urchins, Paracentrotus lividus and Arbacia lixula, in the formation and persistence of barren areas dominated by encrusting coralline macroalgae is yet to be fully elucidated. This study, carried out in the NW Mediterranean (43° 30′N, 10° 20′E) between February 2005 and April 2006, investigated how the loss or density decrease in one or both urchin species influences the recovery of erect macroalgal stands (dominated by filamentous forms) at the margins of barren areas. At a depth of 4-6 m, three barren patches were assigned to each of the following treatments: (1) control (natural densities of A. lixula and P. lividus); (2) 50 % of the natural density of A. lixula and natural density of P. lividus; (3) total removal of A. lixula and natural density of P. lividus; (4) 50 % of the natural density of P. lividus and natural density of A. lixula; (5) total removal of P. lividus and natural density of A. lixula; (6) 50 % of the natural densities of both A. lixula and P. lividus; (7) total removal of both A. lixula and P. lividus. The effects of the herbivore treatments were evaluated either in the presence or the absence of encrusting corallines. The partial or total removal of A. lixula, P. lividus or both favored the proliferation of filamentous macroalgae at the margins of barren patches. The presence of encrusting corallines reduced the development of these macroalgae. The results of this study suggest that a moderate decrease in the density of just one of the two species can decrease the ability of the herbivore assemblage to control the proliferation of filamentous macroalgae at the margins of barren patches. The extent of barren areas appears, therefore, to be regulated by the outcome of density-dependent interactions between the two species of sea urchins. © 2013 Springer-Verlag Berlin Heidelberg.


Rossi M.,University of Pisa
Clinical hemorheology and microcirculation | Year: 2013

Vascular oscillation (vasomotion) occurs in the microcirculation and is thought to be a significant contributor to tissue perfusion. Our aim was to assess skin vasomotion (SV) of type 1 diabetic patients (T1D-pts) and its relationship with clinical or laboratory variables of the studied T1D-pts. Forearm endothelial-, sympathetic- and myogenic-dependent SV were assessed basally and after 3 min of forearm ischemia in 40 T1D-pts and 50 healthy controls, by spectral analysis of laser-Doppler (LD) signal at the frequency ranges of 0.009-0.02 Hz, 0.021-0.06 Hz and 0.061-0.2 Hz, respectively. Post-ischemic per cent increase (PI%-increase) in power spectral density (PSD) of skin endothelial- and sympathetic-dependent VS was significantly reduced in T1D-pts compared to controls (p < 0.0005, p < 0.0001, respectively). Linear regression analysis showed a significant positive relationship between PI%-increase of endothelial-dependent SV and heart rate variation during laying-standing test (R = 0.65, p = 0.00001), and a negative relationship between PI%-increase in PSD of skin LD signal 0.009-1.6 Hz spectrum and glycated haemoglobin serum levels (R = 0.44, p = 0.0036) in T1D-pts. These results are consistent with reduced skin endothelial- and sympathetic-dependent stimulated SV and with relationships between some clinical or laboratory variables and SV parameters in the T1D-pts studied.


Franco A.,University of Pisa | Royer-Carfagni G.,University of Parma
International Journal of Non-Linear Mechanics | Year: 2014

The problem of an elastic bar bonded to an elastic half space and pulled at one end is considered to model the performance of FRP strips glued to concrete or masonry substrates. If the bond is perfect, stress singularities at both bar-extremities do appear. These can be removed by assuming cohesive contact forces à là Baranblatt that annihilate the stress intensity factor. We show that the presence of such cohesive zones is crucial to predict the experimentally measured effective bond length (EBL), i.e., the bond length beyond which no apparent increase of strength is attained. In particular, it is the cohesive zone at the loaded end of the stiffener, rather than that at the free end, that governs the phenomenon because the EBL coincides with the maximal length of such a zone. The proposed approach provides better estimates than formulas proposed in technical standards. © 2013 Elsevier Ltd.


This paper proposes a swarm intelligence approach based on a disjunctive graph model in order to schedule a manufacturing system with resource flexibility and separable setup times. Resource flexibility assigns each operation to one of the alternative resources (assigning sub-problem) and, consequently, arranges the operation in the right sequence of the assigned resource (sequencing sub-problem) in order to minimize the makespan. Resource flexibility is mandatory for rescheduling a manufacturing system after unforeseen events which modify resource availability. The proposed method considers parallel (related) machines and enforces in a single step both the assigning and sequencing sub-problems. A neighboring function on the disjunctive graph is enhanced by means of a reinforced relation-learning model of pheromone involving more effective machine-sequence constraints and a dynamic visibility function. It also considers the overlap between the jobs feeding and the machine (anticipatory) setup times. It involves separable sequence-independent and dependent setup phases. The algorithm performance is evaluated by modifying the well-known benchmark problems for job shop scheduling. Comparison with other systems and lower bounds of benchmark problems has been performed. Statistical tests highlight how the approach is very promising. The performance achieved when the system addresses the complete problem is quite close to that obtained in the case of the classical job-shop problem. This fact makes the system effective in coping with the exponential complexity especially for sequence dependent setup times. © 2014 Elsevier B.V. All rights reserved.


Anselmi D.,University of Pisa
European Physical Journal C | Year: 2013

In all nontrivial cases renormalization, as it is usually formulated, is not a change of integration variables in the functional integral, plus parameter redefinitions, but a set of replacements, of actions and/or field variables and parameters. Because of this, we cannot write simple identities relating bare and renormalized generating functionals, or generating functionals before and after nonlinear changes of field variables. In this paper we investigate this issue and work out a general field-covariant approach to quantum field theory, which allows us to treat all perturbative changes of field variables, including the relation between bare and renormalized fields, as true changes of variables in the functional integral, under which the functionals Z and W=lnZ behave as scalars. We investigate the relation between composite fields and changes of field variables, and we show that, if J are the sources coupled to the elementary fields, all changes of field variables can be expressed as J-dependent redefinitions of the sources L coupled to the composite fields. We also work out the relation between the renormalization of variable-changes and the renormalization of composite fields. Using our transformation rules it is possible to derive the renormalization of a theory in a new variable frame from the renormalization in the old variable frame, without having to calculate it anew. We define several approaches, useful for different purposes, in particular a linear approach where all variable changes are described as linear source redefinitions. We include a number of explicit examples. © 2013 Springer-Verlag Berlin Heidelberg and Società Italiana di Fisica.


Gudnason S.B.,University of Pisa
Nuclear Physics B | Year: 2010

In this paper we study fractional as well as semi-local Chern-Simons vortices in G=U(1)×SO(2M) and G=U(1)×USp(2M) theories. The master equations are solved numerically using appropriate Ansätze for the moduli matrix field. In the fractional case the vortices are solved in the transverse plane due to the broken axial symmetry of the configurations (i.e. they are non-rotational invariant). It is shown that unless the fractional vortex-centers are all coincident (i.e. local case) the ring-like flux structure, characteristic of Chern-Simons vortices, will become bell-like fluxes - just as those of the standard Yang-Mills vortices. The asymptotic profile functions are calculated in all cases and the effective size is identified. © 2010 Elsevier B.V.


Lencioni R.,University of Pisa
Clinical Cancer Research | Year: 2013

The modified Response Evaluation Criteria in Solid Tumors (mRECIST) guideline has introduced specific amendments to standard RECIST to address the unique complexities involved in the evaluation of tumor response in hepatocellular carcinoma. A growing amount of data suggests that mRECIST, designed for response assessment in clinical trials, may translate into a tool for clinical practice. © 2013 AACR.


Del Prato S.,University of Pisa
Expert Opinion on Pharmacotherapy | Year: 2011

Dipeptidyl peptidase-4 (DPP-4) inhibitors are a new class of antidiabetic agents that have been rapidly adopted since their introduction in 2006. There are now five agents in global use, with three approved for treatment of patients with type 2 diabetes (T2D) in the USA. The results of Phase III clinical trials for linagliptin, a new addition to this class of inhibitors (approved by the FDA on 2 May 2011), have now been published. We reported on a 24-week Phase III trial of linagliptin administered as monotherapy in patients with T2D. This agent is characterized by a pharmacokinetic and metabolic profile that may have important implications for the choice of treatment in certain patient populations. © 2011 Informa UK, Ltd.


Mennucci B.,University of Pisa
Journal of Physical Chemistry Letters | Year: 2010

Molecular modeling is nowadays a well-established analytical tool exactly as spectroscopies or other experimental methodologies, and we expect that its impact on many research fields in chemistry, biology, material science, and even medicine will enormously increase in the near future. The real spread and success of this expectation will be strictly linked to different factors, among which a fundamental one will be the capacity of simulations of (supra)molecular systems to include environment effects. It is in fact well-known that molecular responses and processes are strongly affected or, in some cases, completely determined by the surrounding environment (either a solvent, a protein, a membrane, a polymer, or a composite matrix). This Perspective highlights recent achievements and suggests possible future developments of one of the most popular approaches to include environmental effects in molecular calculations, the continuun solvation model. © 2010 American Chemical Society.


DeFronzo R.A.,University of Texas Health Science Center at San Antonio | Davidson J.A.,University of Texas at Dallas | del Prato S.,University of Pisa
Diabetes, Obesity and Metabolism | Year: 2012

The maintenance of normal glucose homeostasis requires a complex, highly integrated interaction among the liver, muscle, adipocytes, pancreas and neuroendocrine system. Recent studies have showed that the kidneys also play a central role in glucose homeostasis by reabsorbing all the filtered glucose, an adaptive mechanism that ensures sufficient energy is available during fasting periods. This mechanism becomes maladaptive in diabetes, however, as hyperglycaemia augments the expression and activity of the sodium-glucose cotransporter (SGLT) 2 in the proximal tubule of the kidney. As a result, glucose reabsorption may be increased by as much as 20% in individuals with poorly controlled diabetes. SGLT2 is a low-affinity, high-capacity glucose transport protein that reabsorbs 90% of filtered glucose, while the high-affinity, low-capacity SGLT1 transporter reabsorbs the remaining 10%. SGLT2 represents a novel target for the treatment of diabetes. In animal studies, SGLT2 inhibition reduces plasma glucose levels, resulting in improved β-cell function and enhanced insulin sensitivity in liver and muscle. Human studies have confirmed the efficacy of SLGT2 inhibitors in improving glucose control and reducing the A1c. Because the mechanism of SGLT2 inhibition is independent of circulating insulin levels or insulin sensitivity, these agents can be combined with all other antidiabetic classes, including exogenous insulin. Although the long-term efficacy and safety of SGLT2 inhibitors remain under study, the class represents a novel therapeutic approach with potential for the treatment of both type 2 and 1 diabetes. © 2011 Blackwell Publishing Ltd.


Pellegrini M.,CNR Institute for Informatics and Telematics | Renda M.E.,CNR Institute for Informatics and Telematics | Vecchio A.,University of Pisa
Bioinformatics | Year: 2010

Motivation: Genomes in higher eukaryotic organisms contain a substantial amount of repeated sequences. Tandem Repeats (TRs) constitute a large class of repetitive sequences that are originated via phenomena such as replication slippage and are characterized by close spatial contiguity. They play an important role in several molecular regulatory mechanisms, and also in several diseases (e.g. in the group of trinucleotide repeat disorders). While for TRs with a low or medium level of divergence the current methods are rather effective, the problem of detecting TRs with higher divergence (fuzzy TRs) is still open. The detection of fuzzy TRs is propaedeutic to enriching our view of their role in regulatory mechanisms and diseases. Fuzzy TRs are also important as tools to shed light on the evolutionary history of the genome, where higher divergence correlates with more remote duplication events. Results: We have developed an algorithm (christened TRStalker) with the aim of detecting efficiently TRs that are hard to detect because of their inherent fuzziness, due to high levels of base substitutions, insertions and deletions. To attain this goal, we developed heuristics to solve a Steiner version of the problem for which the fuzziness is measured with respect to a motif string not necessarily present in the input string. This problem is akin to the 'generalized median string' that is known to be an NP-hard problem. Experiments with both synthetic and biological sequences demonstrate that our method performs better than current state of the art for fuzzy TRs and that the fuzzy TRs of the type we detect are indeed present in important biological sequences. Availability: TRStalker will be integrated in the web-based TRs Discovery Service (TReaDS) at bioalgo.iit.cnr.it. Contact: marco.pellegrini@iit.cnr.it. Supplementary information: Supplementary data are available at Bioinformatics online. © The Author(s) 2010. Published by Oxford University Press.


Marcucci L.E.,University of Pisa | Marcucci L.E.,National Institute of Nuclear Physics, Italy | Schiavilla R.,Old Dominion University | Schiavilla R.,Jefferson Lab | Viviani M.,National Institute of Nuclear Physics, Italy
Physical Review Letters | Year: 2013

The astrophysical S factor for proton-proton weak capture is calculated in chiral effective field theory over the center-of-mass relative-energy range 0-100 keV. The chiral two-nucleon potential derived up to next-to-next-to-next- to leading order is augmented by the full electromagnetic interaction including, beyond Coulomb, two-photon and vacuum-polarization corrections. The low-energy constants entering the weak current operators are fixed so as to reproduce the A=3 binding energies and magnetic moments and the Gamow-Teller matrix element in tritium β decay. Contributions from S and P partial waves in the incoming two-proton channel are retained. The S factor at zero energy is found to be S(0)=(4.030±0.006)×10-23 MeV fm2, with a P-wave contribution of 0.020×10-23 MeV fm2. The theoretical uncertainty is due to the fitting procedure of the low-energy constants and to the cutoff dependence. © 2013 American Physical Society.


Field investigations at Castel di Guido revealed a Middle Pleistocene open-air site containing macrofaunal remains associated with Acheulean industry. The large majority of the remains lay at the bottom of a depressed area, which probably evolved into a low energy freshwater basin after the deposition of the assemblage.To quantify the importance of the natural processes compared to the anthropogenic ones in the formation of the site, a full taphonomic analysis of the macromammal assemblage was carried out. A geoarchaelogical study, together with a taphonomic analysis of the lithic and bone implements, is ongoing.This paper discusses the results of the study of elephant bones. The taphonomic analysis has documented traces of different modifying agents on the specimens, indicating the important role of syn- and post-depositional factors in the accumulation and modification of bones. Nevertheless, evidence of utilization of carcasses for subsistence and for tool production was detected. The study provides new data for the exploitation of elephants by hominins during the Lower Palaeolithic. © 2012 Elsevier Ltd and INQUA.


Peruzzi L.,University of Pisa
Atti della Societa Toscana di Scienze Naturali, Memorie Serie B | Year: 2011

After critical analysis of the available systematic and phylogenetic literature, some adjustment to the current Gagea infrageneric classification is proposed, including the two nomenclatural novelties sect. Triflorae Peruzzi and sect. Persicae (Levichev) Peruzzi. The new setting is made up by at least 14 sections. © 2011, Societa Toscana di Scienze Naturali. All rights reserved.


We conducted an open-label trial to evaluate whether simvastatin therapy was, or was not, associated in systemic sclerosis hypercholesterolemic patients (SSc-Ps) with beneficial changes in finger skin microvascular function. 13 females SSc-Ps and 15 females healthy control subjects (CSs), age-matched with SSc-Ps, underwent finger skin post-occlusive reactive hyperaemia (PORH), using laser Doppler flowmetry (LDF). This test was repeated in SSc-Ps after about 10 weeks of simvastatin (20 mg/day) therapy (ST). At baseline and after ST, finger skin vasomotion was evaluated using spectral Fourier analysis of the LDF tracings. Endothelin-1 and cholesterol serum levels were also determined in SSc-Ps at baseline and after ST. At baseline, SSc-Ps had significantly lower basal finger skin blood flow (basal flow) and PORH, compared to CSs (18.9 ± 11.7 PU vs. 28.5 ± 17.5 PU, 58.6 ± 31.0 PU vs. 93. 1 ± 37.3; P < 0.05). After ST, SSc-Ps had a significant increase in basal flow and PORH compared to baseline (42.7 ± 35.7 PU vs. 18.9 ± 11.7 PU, 111.0 ± 66.6 PU vs. 58.6 ± 31.0 PU, respectively; P < 0.05), as well as a significant reduction in endothelin-1, total- and LDL-cholesterol serum levels. After ST, SSc-Ps also showed a partially restored post-ischaemic amplification in finger skin blood flow oscillations within 0.06-0.6 Hz, related to myogenic vasomotion. This study showed that a short time period of ST in hypercholesterolemic SSc-Ps resulted in increased finger skin vasoreactivity and in partially restored post-ischaemic amplification of finger skin vasomotion, suggesting that ST affects positively finger skin microvascular dysfunction in SSc-Ps.


Logoteta D.,University of Coimbra | Bombaci I.,University of Pisa
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2013

A phase of strong interacting matter with deconfined quarks is expected in the core of massive neutron stars. In this article, we perform a study of the hadron-quark phase transition in cold (T=0) neutron star matter and we calculate various structural properties of hybrid stars. For the quark phase, we make use of an equation of state (EOS) derived with the field correlator method (FCM) recently extended to the case of nonzero baryon density. For the hadronic phase, we consider both pure nucleonic and hyperonic matter, and we derive the corresponding EOS within a relativistic mean field approach. We make use of measured neutron star masses, and particularly the mass M=1.97±0.04M ⊙ of PSR J1614-2230 to constrain the values of the gluon condensate G2, which is one of the EOS parameters within the FCM. We find that the values of G2 extracted from the mass measurement of PSR J1614-2230 are consistent with the values of the same quantity derived within the FCM from recent lattice QCD calculations of the deconfinement transition temperature at zero baryon chemical potential. The FCM thus provides a powerful tool to link numerical calculations of QCD on a space-time lattice with measured neutron star masses. © 2013 American Physical Society.


Coppede F.,University of Pisa
Expert Review of Gastroenterology and Hepatology | Year: 2014

Colorectal cancer (CRC) results from a stepwise accumulation of genetic and epigenetic alterations that transform the normal colonic epithelium into cancer. DNA methylation represents one of the most studied epigenetic marks in CRC, and three common epigenotypes have been identified characterized by high, intermediate and low methylation profiles, respectively. Combining DNA methylation data with gene mutations and cytogenetic alterations occurring in CRC is nowadays allowing the characterization of different CRC subtypes, but the crosstalk between DNA methylation and other epigenetic mechanisms, such as histone tail modifications and the deregulated expression of non-coding RNAs is not yet clearly defined. Epigenetic biomarkers are increasingly recognized as promising diagnostic and prognostic tools in CRC, and the potential of therapeutic applications aimed at targeting the epigenome is under investigation. © 2014 Informa UK Ltd.


Calabrese P.,University of Pisa | Le Doussal P.,Ecole Normale Superieure de Paris
Physical Review Letters | Year: 2011

We provide the first exact calculation of the height distribution at arbitrary time t of the continuum Kardar-Parisi-Zhang (KPZ) growth equation in one dimension with flat initial conditions. We use the mapping onto a directed polymer with one end fixed, one free, and the Bethe ansatz for the replicated attractive boson model. We obtain the generating function of the moments of the directed polymer partition sum as a Fredholm Pfaffian. Our formula, valid for all times, exhibits convergence of the free energy (i.e., KPZ height) distribution to the Gaussian orthogonal ensemble Tracy-Widom distribution at large time. © 2011 American Physical Society.


Pannocchia G.,University of Pisa | Calosi M.,Aspen Technology
Journal of Process Control | Year: 2010

In this paper, we present a novel subspace identification algorithm in which all non-causal terms are removed, and the specific Toeplitz structure of the Markov parameter's matrices is fully exploited in the spirit of the so-called PARSIMonious algorithms. We use the state-space formulation in predictor form, and we show that consistent estimates of the Markov parameters are granted both for open-loop and closed-loop data. Furthermore, we propose to evaluate the system matrices (BK = B - KD, D, K) and the initial condition by a single Least Squares problem, which is well conditioned even for unstable systems. We present identification results for two multi-variable systems to show the main features of the proposed method, and to assess its performance against that achieved by other subspace methods. Furthermore, we compare the performance of Model Predictive Controllers, based on models identified from closed-loop data using the different subspace algorithms, in the control of the Wood-Berry distillation column. Results indicate that the proposed method is suitable for MPC design purposes, and compares favorably with the other subspace algorithms. © 2010 Elsevier Ltd. All rights reserved.


Guidi L.,University of Pisa | Calatayud A.,Instituto Valenciano Of Investigaciones Agrarias Ivia
Environmental and Experimental Botany | Year: 2014

In Mediterranean areas, plants are concomitantly exposed to various abiotic stresses such as light intensity, water deficit, extremes in air temperature, air pollutants, etc. These environmental pressures adversely affect plant development. Changes in photosystem activity are an early response of plants to abiotic stresses. Therefore, chlorophyll (Chl) fluorescence and gas exchange, two non-invasive, rapid and inexpensive techniques for measuring photosynthesis in leaves, have been widely used by plant ecophysiologists to analyse plant responses to stressful conditions. Chl a fluorescence and gas exchange parameters can be indeed used to evaluate changes in photochemical and non-photochemical processes in photosystems associated with electron transport, CO2 fixation, and heat dissipation.In this review, we focus our analysis on the effects of different abiotic stresses on the photochemistry of Mediterranean plants using Chl a fluorescence and gas exchange measurements. Since changes in photosynthetic parameters are observed in the absence of visual injuries, these methodologies constitute fundamental tools to predict and evaluate the extent to which abiotic stresses damage photosynthesis. © 2014 Elsevier B.V.


Peruzzi L.,University of Pisa | Conti F.,University of Camerino | Bartolucci F.,University of Camerino
Phytotaxa | Year: 2014

For the purpose of the present study we considered as Italian endemics those specific and subspecific taxa occurring in Italy that are not found elsewhere with the exception of Corsica (France) and Malta. This study presents an updated list of the endemic taxa in the Italian flora, including their geographical distribution at regional level. Italy is characterized by 1371 endemic species and subspecies (18.9% of the total vascular flora): three taxa belong to Lycopodiidae, one to Polypodiidae, two to Pinidae and 1365 to Magnoliidae (three paleoherbs, 221 monocots and 1144 eudicots). The endemic flora belongs to 29 orders, 67 families and 304 genera. Sicily, Sardinia, Calabria and Abruzzo are the four regions richest in endemics. About 58% of endemics are confined to a single administrative region. The most represented orders, families and genera are: Asterales, Caryophyllales and Asparagales, Asteraceae, Plumbaginaceae and Caryophyllaceae, Limonium, Centaurea and Hieracium, respectively. The phytogeographic isolation of Sardinia and Sicily and the separation of peninsular Italy from Northern Italy is confirmed. The relative isolation of Puglia with respect the remaining southern Italian pensinsular regions is also confirmed. Alpine region endemics (from northern Italy) are underrepresented. © 2014 Magnolia Press.


Bactrocera oleae is a worldwide olive fruit pest. In late afternoon males form swarms on the windward side of trees. Within the swarm, each male occupies a leaf and aggressively excludes male conspecifics before starting courtship displays. Females display aggressive interactions each other too, particularly when they are in close proximity of oviposition sites. In this research, the aggressive behavior displayed by both sexes was quantified. Aggressions were composed by wing waving, fast running towards the opponent, pouncing and boxing on the head and thorax of the foe. High-speed videos highlighted that the parameters characterizing the aggressions did not strongly differ between sexes and between residents and intruders. Resident flies won more combats, both in male-male and female-female aggressive interactions. In both sexes, aggressions were more frequent in the late morning than in the afternoon. Among males, aggressions could be functional to maintain single leaf territories in which each fly can perform courtship displays. Through aggressions females could gain and maintain single oviposition sites. Lastly, by favorable fight outcomes B. oleae could also get access to food sources on olive leaves and fruits. © 2013 Springer Science+Business Media New York.


Pezzullo G.,University of Pisa
Nuovo Cimento della Societa Italiana di Fisica C | Year: 2014

Lepton flavor violation in the neutrino mixing is so far a fact. This means that also charged-lepton-flavor-violation (cLFV) must exists. Mu2e searches for a particular process, the neutrino-less conversion of muons into electrons in the field of an aluminum nucleus. The sensitivity expected for Mu2eis ~ 10 -17, which represents an improvement of a factor of 10 3-104 over existing limits. If no conversion events will be seen, it will set an upper limit on the conversion rate of Rμe < 6 × 10-17 90% C.L. Mu2e collaboration has received CD1 approval in 2012 and will start data taking in 2019. © Società Italiana di Fisica.


Porzi C.,SantAnna School of Advanced Studies | Bogoni A.,University of Pisa | Contestabile G.,SantAnna School of Advanced Studies
IEEE Photonics Technology Letters | Year: 2012

We investigate and experimentally demonstrate a simple method for phase-preserving amplitude regeneration of constant envelope phase-coded signals. This scheme exploits nonlinear interaction between noisy data and a continuous wave beam at a different wavelength in a saturated semiconductor optical amplifier (SOA). We show that proper balancing of the input signals' power allows us to exploit the amplitude limiting effect of SOA saturated gain without introducing significant excess phase noise due to suppression of the α-factor in the amplifier. In a 10-Gb/s nonreturn-to-zero differential phase-shift-keying experiment, both four-wave-mixing (FWM) and pass-through signals are remarkably improved with respect to input data in terms of Q-factor and bit error ratio threshold margin, demonstrating wavelength preserving and wavelength converting regeneration. In particular, the FWM signal exhibits better regenerative performance over a broader range of degraded input data and for lower input overall power levels. © 1989-2012 IEEE.


In the present paper, a preliminary in vitro analysis of biocompatibility of newly-synthesised acrylic copolymers is reported. In particular, with the aim to obtain coatings for drug-eluting stents, blood protein absorption and cytocompatibility were studied. For protein absorption tests, bovine serum albumin and bovine plasma fibrinogen were considered. Cytocompatibility was tested using C2C12 cell line as model, analysing the behaviour of polymeric matrices and of drug-eluting systems, obtained loading polymeric matrices with paclitaxel, an anti-mitotic drug, in order to evaluate the efficacy of a pharmacological treatment locally administered from these materials. Results showed that the amount of albumin absorbed was greater than the amount of fibrinogen (comprised in the range of 70%-85% and 10%-22% respectively) and it is a good behaviour in terms of haemocompatibility. Cell culture tests showed good adhesion properties and a relative poor proliferation. In addition, a strong effect related to drug elution and a correlation with the macromolecular composition were detected. In this preliminary analysis, tested materials showed good characteristics and can be considered possible candidates to obtain coatings for drug-eluting stents. © 2012 Elsevier B.V.


Giulietti D.,University of Pisa
Physics Procedia | Year: 2015

The propagation of super-intense and ultra-short laser pulses in plasmas is a main concern in several applications of the laserplasma interactions, from Inertial Confinement Fusion (ICF) to High Energy Physics (HEP). During the propagation in the plasma the light beam deeply changes its parameters due the onset of non-linear effects, among them the relativistic regime of the electron quivering motion. These extreme conditions are suitable for the electron acceleration in high field gradient, opening the way for the realization of compact secondary sources of X-gamma rays. © 2015 The Authors. Published by Elsevier B.V.


Di Marco P.,University of Pisa
Journal of Heat Transfer | Year: 2012

Recent experimentation of boiling in different environments, namely in reduced or enhanced gravity and/or in the presence of electric fields, have shed new light on the comprehension of boiling phenomena and have focused the objectives of future investigation. The recent results achieved by the author and other research groups around the world are reported and discussed in the paper. After a short introduction on some fundamental phenomena and their dependence on force fields, pool, and flow boiling are dealt with. In particular, it is stressed that due to increased coalescence peculiar flow regimes take place in reduced gravity, influencing the heat transfer performance. The application of an electric field may, in some instances, delay or avoid these regime transitions. In boiling at high flowrate, the phenomena are dominated by inertia and thus gravity-independent; however, the threshold at which this occurs has still to be determined. © 2012 American Society of Mechanical Engineers.


To identify perinatal factors associated with sub-optimal neuromotor outcome in infants without evident central nervous system lesions (intraventricular hemorrhage/ periventricular leukomalacia), with gestational age ≤30 (group I) and of 31-32 weeks (group II). A total of 102 premature infants admitted to the Neonatal Intensive Care Unit of Pisa, at 26-32 weeks of gestation, were studied. Data about perinatal factors and TSH values at 3-4 days of life were collected. The assessment of neuromotor development was performed at 18 months of corrected age, using the locomotor subscale of the Griffiths Scales of Mental Development. Risk factors supposed to be predictive of sub-optimal neuromotor outcome (odds ratio >1) were at ≤30 weeks: male sex, small for gestational age, patent duct arterious, respiratory distress syndrome, and at 31-32 weeks: Apgar at 5 min <7, respiratory distress syndrome, patent duct arterious and birth weight <1500 g. A strong correlation was also found between TSH screening values >4,3 mU/l and suboptimal neuromotor outcome in both groups. Several perinatal factors, acting on an immature and more vulnerable nervous system, such as the pre-term one, different for different gestational ages, are associated with a sub-optimal neuromotor outcome. Higher, but within the normal range, TSH values at screening seem to be a strong risk factor for neuromotor outcome in preterm infants without intraventricular hemorrhage or periventricular leukomalacia.


Giordano M.,Hungarian Academy of Sciences | Meggiolaro E.,University of Pisa
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2015

We determine the large-distance behavior of the static dipole-dipole potential for a wide class of gauge theories on nonperturbative grounds, exploiting only general properties of the theory. In the case of QCD, we recover the known results in the regime of small dipole sizes and discuss recent nonperturbative calculations. Moreover, we discuss the case of pure-gauge theories and compare our prediction with the available lattice results. © 2015 American Physical Society.


Rascio N.,University of Padua | Navari-Izzo F.,University of Pisa
Plant Science | Year: 2011

The term "hyperaccumulator" describes a number of plants that belong to distantly related families, but share the ability to grow on metalliferous soils and to accumulate extraordinarily high amounts of heavy metals in the aerial organs, far in excess of the levels found in the majority of species, without suffering phytotoxic effects. Three basic hallmarks distinguish hyperaccumulators from related non-hyperaccumulating taxa: a strongly enhanced rate of heavy metal uptake, a faster root-to-shoot translocation and a greater ability to detoxify and sequester heavy metals in leaves. An interesting breakthrough that has emerged from comparative physiological and molecular analyses of hyperaccumulators and related non-hyperaccumulators is that most key steps of hyperaccumulation rely on different regulation and expression of genes found in both kinds of plants. In particular, a determinant role in driving the uptake, translocation to leaves and, finally, sequestration in vacuoles or cell walls of great amounts of heavy metals, is played in hyperaccumulators by constitutive overexpression of genes encoding transmembrane transporters, such as members of ZIP, HMA, MATE, YSL and MTP families. Among the hypotheses proposed to explain the function of hyperaccumulation, most evidence has supported the "elemental defence" hypothesis, which states that plants hyperaccumulate heavy metals as a defence mechanism against natural enemies, such as herbivores. According to the more recent hypothesis of "joint effects", heavy metals can operate in concert with organic defensive compounds leading to enhanced plant defence overall.Heavy metal contaminated soils pose an increasing problem to human and animal health. Using plants that hyperaccumulate specific metals in cleanup efforts appeared over the last 20 years. Metal accumulating species can be used for phytoremediation (removal of contaminant from soils) or phytomining (growing plants to harvest the metals). In addition, as many of the metals that can be hyperaccumulated are also essential nutrients, food fortification and phytoremediation might be considered two sides of the same coin. An overview of literature discussing the phytoremediation capacity of hyperaccumulators to clean up soils contaminated with heavy metals and the possibility of using these plants in phytomining is presented. © 2010 Elsevier Ireland Ltd.


Anselmi D.,University of Pisa
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2015

Using the Batalin-Vilkovisky formalism, we study the Ward identities and the equations of gauge dependence in potentially anomalous general gauge theories, renormalizable or not. A crucial new term, absent in manifestly nonanomalous theories, is responsible for interesting effects. We prove that gauge invariance always implies gauge independence, which in turn ensures perturbative unitarity. Precisely, we consider potentially anomalous theories that are actually free of gauge anomalies thanks to the Adler-Bardeen theorem. We show that when we make a canonical transformation on the tree-level action, it is always possible to re-renormalize the divergences and re-fine-tune the finite local counterterms, so that the renormalized Γ functional of the transformed theory is also free of gauge anomalies, and is related to the renormalized Γ functional of the starting theory by a canonical transformation. An unexpected consequence of our results is that the beta functions of the couplings may depend on the gauge-fixing parameters, although the physical quantities remain gauge independent. We discuss nontrivial checks of high-order calculations based on gauge independence and determine how powerful they are. © 2015 American Physical Society.


Grammatico S.,ETH Zurich | Blanchini F.,University of Udine | Caiti A.,University of Pisa
IEEE Transactions on Automatic Control | Year: 2014

Given two control Lyapunov functions (CLFs), a 'merging' is a new CLF whose gradient is a positive combination of the gradients of the two parents CLFs. The merging function is an important trade-off since this new function may, for instance, approximate one of the two parents functions close to the origin, while being close to the other far away. For nonlinear control-affine systems, some equivalence properties are shown between the control-sharing property, i.e., the existence of a single control law which makes simultaneously negative the Lyapunov derivatives of the two given CLFs, and the existence of merging CLFs. It is shown that, even for linear time-invariant systems, the control-sharing property does not always hold, with the remarkable exception of planar systems. The class of linear differential inclusions is also discussed and similar equivalence results are presented. For this class of systems, linear matrix inequalities conditions are provided to guarantee the control-sharing property. Finally, a constructive procedure, based on the recently considered "R-functions," is defined to merge two smooth positively homogeneous CLFs. © 2013 IEEE.


Ardagna D.,Polytechnic of Milan | Panicucci B.,University of Modena and Reggio Emilia | Passacantando M.,University of Pisa
IEEE Transactions on Services Computing | Year: 2013

In recent years, the evolution and the widespread adoption of virtualization, service-oriented architectures, autonomic, and utility computing have converged letting a new paradigm to emerge: cloud computing. Clouds allow the on-demand delivering of software, hardware, and data as services. Currently, the cloud offer is becoming wider day by day because all the major IT companies and service providers, like Microsoft, Google, Amazon, HP, IBM, and VMWare, have started providing solutions involving this new technological paradigm. As cloud-based services are more numerous and dynamic, the development of efficient service provisioning policies becomes increasingly challenging. In this paper, we take the perspective of Software as a Service (SaaS) providers that host their applications at an Infrastructure as a Service (IaaS) provider. Each SaaS needs to comply with quality-of-service requirements, specified in service-level agreement (SLA) contracts with the end users, which determine the revenues and penalties on the basis of the achieved performance level. SaaS providers want to maximize their revenues from SLAs, while minimizing the cost of use of resources supplied by the IaaS provider. Moreover, SaaS providers compete and bid for the use of infrastructural resources. On the other hand, the IaaS wants to maximize the revenues obtained providing virtualized resources. In this paper, we model the service provisioning problem as a generalized Nash game and we show the existence of equilibria for such game. Moreover, we propose two solution methods based on the best-reply dynamics, and we prove their convergence in a finite number of iterations to a generalized Nash equilibrium. In particular, we develop an efficient distributed algorithm for the runtime allocation of IaaS resources among competing SaaS providers. We demonstrate the effectiveness of our approach by simulation and performing tests on a real prototype environment deployed on Amazon EC2. Results show that, compared to other state-of-the-art solutions, our model can improve the efficiency of the cloud system evaluated in terms of Price of Anarchy by 50-70 percent. © 2013 IEEE.


Oberhof B.,University of Pisa | Oberhof B.,National Institute of Nuclear Physics, Italy
Nuclear and Particle Physics Proceedings | Year: 2015

We perform a measurement of the branching fractions for τ→lγνν-, (l=e, μ) decays for a minimum photon energy of 10 MeV in the τ rest frame using 430 fb-1 of e+e- collisions collected at the center-of-mass energy of the ϒ{hooked}(4S) resonance with the BaBar detector at the PEP-II storage rings. We find B(τ→μγνν)=(3.69±0.03±0.10)×10-3 and B(τ→eγνν)=(1.847±0.015±0.052)×10-2 where the first quoted error is statistical and the second is systematic. These results represent a substantial improvement with respect to existing measurements for both channels. © 2015 .


Anselmi D.,University of Pisa
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2015

We prove the Adler-Bardeen theorem in a large class of general gauge theories, including nonrenormalizable ones. We assume that the gauge symmetries are general covariance, local Lorentz symmetry, and Abelian and non-Abelian Yang-Mills symmetries, and that the local functionals of vanishing ghost numbers satisfy a variant of the Kluberg-Stern-Zuber conjecture. We show that if the gauge anomalies are trivial at one loop, for every truncation of the theory there exists a subtraction scheme where they manifestly vanish to all orders, within the truncation. Outside the truncation the cancellation of gauge anomalies can be enforced by fine-tuning local counterterms. The framework of the proof is worked out by combining a recently formulated chiral dimensional regularization with a gauge invariant higher-derivative regularization. If the higher-derivative regularizing terms are placed well beyond the truncation, and the energy scale Λ associated with them is kept fixed, the theory is superrenormalizable and has the property that, once the gauge anomalies are canceled at one loop, they manifestly vanish from two loops onwards by simple power counting. When the Λ divergences are subtracted away and Λ is sent to infinity, the anomaly cancellation survives in a manifest form within the truncation and in a nonmanifest form outside. The standard model coupled to quantum gravity satisfies all the assumptions, so it is free of gauge anomalies to all orders. © 2015 American Physical Society.


Anselmi D.,University of Pisa
Modern Physics Letters A | Year: 2015

The properties of quantum gravity are reviewed from the point of view of renormalization. Various attempts to overcome the problem of non-renormalizability are presented, and the reasons why most of them fail for quantum gravity are discussed. Interesting possibilities come from relaxing the locality assumption, which also can inspire the investigation of a largely unexplored sector of quantum field theory. Another possibility is to work with infinitely many independent couplings, and search for physical quantities that only depend on a finite subset of them. In this spirit, it is useful to organize the classical action of quantum gravity, determined by renormalization, in a convenient way. Taking advantage of perturbative local field redefinitions, we write the action as the sum of the Hilbert term, the cosmological term, a peculiar scalar that is important only in higher dimensions, plus invariants constructed with at least three Weyl tensors. We show that the FRLW configurations, and many other locally conformally flat metrics, are exact solutions of the field equations in arbitrary dimensions d>3. If the metric is expanded around such configurations the quadratic part of the action is free of higher-time derivatives. Other well-known metrics, such as those of black holes, are instead affected in nontrivial ways by the classical corrections of quantum origin. © 2015 World Scientific Publishing Company.


Queiroz F.S.,University of California at Santa Cruz | Sinha K.,Syracuse University | Strumia A.,University of Pisa | Strumia A.,Estonian National Institute of Chemical Physics and Biophysics
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2015

Leptoquarks with mass in the region of 550-650 GeV are a possible candidate for the recent excess seen by CMS in the eejj and eνjj channels. We discuss models where leptoquarks decay primarily to dark matter and jets, thereby giving a branching to charged lepton and jet final states that can match data. The confluence of proton decay constraints, dark matter indirect and direct detection data, and Higgs invisible decay bounds results in a handful of predictive models that will be conclusively verified or excluded in upcoming direct detection experiments. Along the way, we present robust limits on such leptoquark models stemming from the muon magnetic moment using current and projected experiment sensitivities, as well as from K and B meson mixing, and leptonic and semileptonic meson decays. © 2015 American Physical Society.


Solini A.,University of Pisa
Diabetes/Metabolism Research and Reviews | Year: 2015

Type 2 diabetes is a complex and multifaceted disease requiring an individualized approach. A special attention, in treating the patients, should be devoted to the presence of comorbidities like overweight or obesity and arterial hypertension. Among the available anti-hyperglycaemic agents, several are associated with side effects like hypoglycaemia and weight gain. An increasing interest is reported in sodium-glucose co-transporter-2 inhibitors, a relatively novel class of glucose-lowering drugs that act independently of insulin, provide benefits beyond glucose-lowering actions and show a better tolerability compared with traditional medications for type 2 diabetes. This review tries to offer a balanced view on the main extra-glycaemic effects of empagliflozin, also mentioning clinical data obtained with other sodium-glucose co-transporter-2 inhibitors; the role of the proximal tubule in the pathophysiology of diabetic nephropathy and the potential nehroprotection exerted by this compound are also briefly discussed. © 2015 John Wiley & Sons, Ltd.


Martorella M.,University of Pisa
IEEE Transactions on Aerospace and Electronic Systems | Year: 2011

Bistatic inverse synthetic aperture radar (B-ISAR) has the potential to become the radar imaging tool for obtaining noncooperative target images in arbitrary bistatic configurations. A monostatic ISAR processor is used here to form B-ISAR images and its robustness is tested with respect to phase synchronisation errors and rapidly time-varying bistatic configurations. Specifically, the B-ISAR point spread function (PSF) is analytically derived and the problem of B-ISAR image autofocusing is reformulated in such conditions. It is shown that, in most bistatic scenarios, the range-Doppler (RD) based monostatic ISAR processor is able to form focussed B-ISAR images. Simulation results are used to support the theoretical results. © 2011 IEEE.


Bolognesi S.,University of Pisa | Zakrzewski W.,Durham University
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2015

We study the baby Skyrme model as a theory that interpolates between two distinct BPS systems. For this, a near-BPS approximation can be used when there is a small deviation from each of the two BPS limits. We provide analytical explanation and numerical support for the validity of this approximation. We then study the set of all possible supersymmetric extensions of the baby Skyrme model with N=1 and the particular ones with extended N=2 supersymmetries and relate this to the above mentioned almost-BPS approximation. © 2015 American Physical Society.


Kahn S.E.,University of Washington | Cooper M.E.,Baker IDI Heart and Diabetes Institute | Del Prato S.,University of Pisa
The Lancet | Year: 2014

Glucose metabolism is normally regulated by a feedback loop including islet β cells and insulin-sensitive tissues, in which tissue sensitivity to insulin aff ects magnitude of β-cell response. If insulin resistance is present, β cells maintain normal glucose tolerance by increasing insulin output. Only when β cells cannot release suffi cient insulin in the presence of insulin resistance do glucose concentrations rise. Although β-cell dysfunction has a clear genetic component, environmental changes play an essential part. Modern research approaches have helped to establish the important role that hexoses, aminoacids, and fatty acids have in insulin resistance and β-cell dysfunction, and the potential role of changes in the microbiome. Several new approaches for treatment have been developed, but more eff ective therapies to slow progressive loss of β-cell function are needed. Recent fi ndings from clinical trials provide important information about methods to prevent and treat type 2 diabetes and some of the adverse eff ects of these interventions. However, additional long-term studies of drugs and bariatric surgery are needed to identify new ways to prevent and treat type 2 diabetes and thereby reduce the harmful eff ects of this disease.


Del Corso A.,University of Pisa | Vergaro G.,CNR Institute of Neuroscience
CardioVascular and Interventional Radiology | Year: 2013

Purpose: Although the majority of iatrogenic pseudoaneurysms (PSAs) are amenable to ultrasound (US)-guided thrombin injection, patients with those causing neuropathy, claudication, significant venous compression, or soft tissue necrosis are considered poor candidates for this option and referred to surgery. We aimed to test the effectiveness and feasibility of a novel percutaneous cyanoacrylate glue (NBCA-MS)-based technique for treatment of symptomatic and asymptomatic iatrogenic PSA. Material and Methods: During a 3-year period, we prospectively enrolled 91 patients with iatrogenic PSA [total n = 94 (femoral n = 76; brachial n = 11; radial n = 6; axillary n = 1)]. PSA were asymptomatic in 66 % of cases, and 34 % presented with symptoms due to neuropathy, venous compression, and/or soft tissue necrosis. All patients signed informed consent. All patients received NBCA-MS-based percutaneous treatment. PSA chamber emptying was first obtained by US-guided compression; superior and inferior walls of the PSA chamber were then stuck together using NBCA-MS microinjections. Successfulness of the procedure was assessed immediately and at 1-day and 1-, 3-, and 12-month US follow-up. Results: PSA occlusion rate was 99 % (93 of 94 cases). After treatment, mean PSA antero-posterior diameter decrease was 67 ± 22 %. Neuropathy and vein compression immediately disappeared in 91 % (29 of 32) of cases. Patients with tissue necrosis (n = 6) underwent subsequent outpatient necrosectomy. No distal embolization occurred, nor was conversion to surgery necessary. Conclusion: PSA treatment by way of NBCA-MS glue injection proved to be safe and effective in asymptomatic patients as well as those with neuropathy, venous compression, or soft-tissue necrosis (currently candidates for surgery). Larger series are needed to confirm these findings. © 2012 Springer Science+Business Media New York and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE).


Pegoraro F.,University of Pisa
Physics of Plasmas | Year: 2015

Generalisations of the relativistic ideal Ohm's law are presented that include specific dynamical features of the current carrying particles in a plasma. Cases of interest for space and laboratory plasmas are identified where these generalisations allow for the definition of generalised electromagnetic fields that transform under a Lorentz boost in the same way as the real electromagnetic fields and that obey the same set of homogeneous Maxwell's equations. © 2015 AIP Publishing LLC.


Pelaggi G.M.,University of Pisa
Nuclear Physics B | Year: 2015

We consider a model where the weak and the DM scale arise at one loop from the Coleman-Weinberg mechanism. We perform a precision computation of the model predictions for the production cross section of a new Higgs-like scalar and for the direct-detection cross section of the DM particle candidate. © 2015 The Author.


Salvio A.,Autonomous University of Madrid | Strumia A.,University of Pisa | Strumia A.,Estonian National Institute of Chemical Physics and Biophysics
Journal of High Energy Physics | Year: 2014

We explore the possibility that the fundamental theory of nature does not contain any scale. This implies a renormalizable quantum gravity theory where the graviton kinetic term has 4 derivatives, and can be reinterpreted as gravity minus an anti-graviton. We compute the super-Planckian RGE of adimensional gravity coupled to a generic matter sector. The Planck scale and a flat space can arise dynamically at quantum level provided that a quartic scalar coupling and its β function vanish at the Planck scale. This is how the Higgs boson behaves for M h ≈ 125 GeV and M t ≈ 171 GeV. Within agravity, inflation is a generic phenomenon: the slow-roll parameters are given by the β-functions of the theory, and are small if couplings are perturbative. The predictions n s ≈ 0.967 and r ≈ 0.13 arise if the inflaton is identified with the Higgs of gravity. Furthermore, quadratically divergent corrections to the Higgs mass vanish: a small weak scale is natural and can be generated by agravity quantum corrections. © 2014 The Author(s).


Rajabpour M.A.,University of Sao Paulo | Sotiriadis S.,University of Pisa
Physical Review A - Atomic, Molecular, and Optical Physics | Year: 2014

We consider a quantum quench of the trap frequency in a system of bosons interacting through an inverse-square potential and confined in a harmonic trap (the harmonic Calogero model). We determine exactly the initial state in terms of the postquench eigenstates and derive the time evolution of simple physical observables. Since this model possesses an infinite set of integrals of motion that allow its exact solution, a generalized Gibbs ensemble (GGE), i.e., a statistical ensemble that takes into account the conservation of all integrals of motion, can be proposed in order to describe the values of local physical observables long after the quench. Even though, due to the presence of the trap, physical observables do not exhibit equilibration but periodic evolution, such a GGE may still describe correctly their time-averaged values. We check this analytically for the local boson density and find that the GGE conjecture is indeed valid, in the thermodynamic limit. © 2014 American Physical Society.


Giordano M.,Hungarian Academy of Sciences | Meggiolaro E.,University of Pisa
Journal of High Energy Physics | Year: 2014

We show how to obtain the leading energy dependence of hadronic total cross sections, in the framework of the nonperturbative approach to soft high-energy scattering based on Wilson-loop correlation functions, if certain nontrivial analyticity assumptions are satisfied. The total cross sections turn out to be of "Froissart" type, σtothh (s) ~ B log2 s for s → ∞. We also discuss under which conditions the coefficient B is universal, i.e., independent of the hadrons involved in the scattering process. In the most natural scenarios for universality, B can be related to the stable spectrum of QCD, and is predicted to be B th ≠0.22 mb, in fair agreement with experimental results. If we consider, instead, the stable spectrum of the quenched (i.e., pure-gauge) theory, we obtain a quite larger value Bth (Q) ≥ 0.42 mb, suggesting (quite surprisingly) large unquenching effects due to the sea quarks. © 2014 The Author(s).


Elia G.,University of Pisa
Clinica Terapeutica | Year: 2015

Some studies reported that chemokine interferon-γ-inducible protein 10 (IP-10) and its receptor chemokine (C-X-C motif) receptor (CXCR) 3, which is exhibited by T cells, are expressed in several types of cutaneous damages associated with Systemic Lupus Erythematosus (SLE), and that the CXCR3-activating chemokines are produced locally, suggesting their significant role in the recruitment of T cells in these inflammatory lesions. The involvement of IP-10 and CXCR3 has been shown also in several other types of tissue damages associated with SLE, such as glomerulonephritis or central nervous system lupus. Urinary IP-10 is a sensitive and non-invasive diagnostic tool for monitoring lupus nephritis patients, and the response to treatments. Serum levels of IP-10 are increased in SLE patients, showing a strong correlation with disease activity. Levels of IP-10 are also increased in the cerebrospinal fluid samples from neuropsychiatric SLE patients. These data provide increasing evidence that IP-10 may participate in the pathogenesis of a variety of the manifestations of SLE, even if the exact role of IP-10 in the pathogenesis of SLE remains to be clarified. Copyright © Società Editrice Universo (SEU).


Brunetto M.R.,University of Pisa | Lok A.S.,University of Michigan
Antiviral Therapy | Year: 2010

Substantial advances have been made in the treatment of chronic hepatitis B in the past decade. Currently, there are seven approved agents including two forms of interferon (conventional and pegylated), and five oral nucleoside/nucleotide analogues (lamivudine, adefovir, entecavir, telbivudine and tenofovir disoproxil fumarate). The availability of these multiple treatment options has led to expansion of treatment indications. However, the need for a long duration of treatment with some therapies, the high costs of HBV medications, the side effects associated with some treatments and the risks of drug resistance during long-term use of oral antiviral medications necessitate the careful assessment of the risk-benefit ratio prior to initiating treatment, and the evaluation of better strategies to optimize response once treatment is initiated. In this article, we review the current approaches to optimize treatment response to nucleoside/nucleotide analogue- and interferon-based therapies for chronic hepatitis B. ©2010 International Medical Press.


Sotiriadis S.,University of Pisa | Sotiriadis S.,National Institute of Nuclear Physics, Italy | Takacs G.,Budapest University of Technology and Economics | Takacs G.,Momentum | And 2 more authors.
Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics | Year: 2014

We study a quantum quench of the mass and the interaction in the Sinh-Gordon model starting from a large initial mass and zero initial coupling. Our focus is on the determination of the expansion of the initial state in terms of post-quench excitations. We argue that the large energy profile of the involved excitations can be relevant for the late time behaviour of the system and common regularization schemes are unreliable. We therefore proceed in determining the initial state by first principles expanding it in a systematic and controllable fashion on the basis of the asymptotic states. Our results show that, for the special limit of pre-quench parameters we consider, it assumes a squeezed state form that has been shown to evolve so as to exhibit the equilibrium behaviour predicted by the Generalized Gibbs Ensemble. © 2014 The Authors.


Smellie J.L.,University of Leicester | Wilch T.I.,Albion College | Rocchi S.,University of Pisa
Geology | Year: 2013

Lava-fed deltas are extraordinarily useful indicators of fossil water (and ice) levels in glacial, marine, and lacustrine environments. Deltas fed by 'a'ā lava should be at least as common as those sourced in pāhoehoe, yet they have been rarely described. Although facies models for pāhoehoe lava-fed deltas are well established, the architecture and lithofacies of 'a'ā-fed equivalents are substantially different and have thus far largely been unrecognized. This can have profound consequences for paleoenvironmental investigations, particularly those attempting to reconstruct past ice sheets. Essential features of 'a'ā lava-fed deltas include (1) a subaerial 'a'ā lava capping unit comprising massive internal sheet lava overlain by clinkers; (2) a crudely developed subaerial to subaqueous transition (passage zone); (3) a chaotic subaqueous association of abundant lava lobes and hyaloclastite with admixed vesicular, often reddened (oxidized) lava clinkers; and (4) rare subaqueous stratification with predominantly lower dips (̃10o-20o) than in deltas fed by pāhoehoe lava (̃25o-40o). We develop a generic facies model and investigate the emplacement conditions of 'a'ā lava-fed deltas in order to facilitate the recognition and environmental interpretation of these important sequence types in ancient successions. © 2013 Geological Society of America.


Cupisti A.,University of Pisa
Giornale italiano di nefrologia : organo ufficiale della Società italiana di nefrologia | Year: 2011

The pathogenesis of CKD-MBD is multifactorial but the tendency towards phosphorus retention due to an excessive dietary intake for the residual renal function plays a central role. The dietary phosphorus is absorbed in the intestine as inorganic free phosphorus. The share of intestinal absorption (about 60% on average) is negligible for plant phosphorus (in the form of phytate), while it is maximal for phosphate or polyphosphates contained in food additives. The latter represent a dangerous extra load of phosphorus because they are poorly recognized by patients and widely used in modern nutrition, in particular in low-cost food. In a free mixed diet, the phosphorus content is directly related to that of proteins. It follows that protein-rich foods are the main source of phosphorus. This is a favorable condition for CKD patients in conservative therapy when a low-protein diet is implemented, while it represents a huge problem for dialysis patients, who need a high-protein diet. A simple and effective approach to reduce the load of dietary phosphorus without reducing protein intake is to educate patients to avoid foods high in phosphorus (cheese, egg yolk, nuts, etc.), and particularly those containing phosphorus additives. In addition, they should prefer boiling (resulting also in a decrease in sodium and potassium) to other methods of cooking. Counseling by a dietician is important for successful patient care. The dietician provides nutritional education, can help the patient with the choice of food, and may favor the adherence to dietary prescriptions, which is a crucial aspect in an integrated approach to CKD-MBD.


Rovigatti U.,University of Pisa
Critical Reviews in Oncology/Hematology | Year: 2015

It is today indisputable that great progresses have been made in our molecular understanding of cancer cells, but an effective implementation of such knowledge into dramatic cancer-cures is still belated and yet desperately needed. This review gives a snapshot at where we stand today in this search for cancer understanding and definitive treatments, how far we have progressed and what are the major obstacles we will have to overcome both technologically and for disease modelling. In the first part, promising 3rd/4th Generation Sequencing Technologies will be summarized (particularly IonTorrent and OxfordNanopore technologies). Cancer modelling will be then reviewed from its origin in XIX Century Germany to today's NGS applications for cancer understanding and therapeutic interventions. Developments after Molecular Biology revolution (1953) are discussed as successions of three phases. The first, PH1, labelled ". Clonal Outgrowth" (from 1960s to mid 1980s) was characterized by discoveries in cytogenetics (Nowell, Rowley) and viral oncology (Dulbecco, Bishop, Varmus), which demonstrated clonality. Treatments were consequently dominated by a "cytotoxic eradication" strategy with chemotherapeutic agents. In PH2, (from the mid 1980s to our days) the description of cancer as ". Gene Networks" led to targeted-gene-therapies (TGTs). TGTs are the focus of Section 3: in view of their apparent failing (Ephemeral Therapies), alternative strategies will be discussed in review part II (particularly cancer immunotherapy, CIT). Additional Pitfalls impinge on the concepts of tumour heterogeneity (inter/intra; ITH). The described pitfalls set the basis for a new phase, PH3, which is called ". NGS Era" and will be also discussed with ten emerging cancer models in the Review 2nd part. © 2015 Elsevier Ireland Ltd.


Nervi M.,University of Pisa
Biology and Philosophy | Year: 2010

Mechanisms are a way of explaining how biological phenomena work rather than why single elements of biological systems are there. However, mechanisms are usually described as physiological entities, and little or no attention is paid to malfunction as an independent theoretical concept. On the other hand, malfunction is the main focus of interest of applied sciences such as medicine. In this paper I argue that malfunctions are parts of pathological mechanisms, which should be considered separate theoretical entities, conceptually having a priority over physiological sequences. While pathological mechanisms can be described in terms of a Cummins-like mechanistic explanation, they show some unnoticed peculiarities when compared to physiological ones. Some features of pathological mechanisms are considered, such as outcome variability, ambivalence and dependence on a range. © Springer Science+Business Media B.V. 2009.


Iamonico D.,University of Rome La Sapienza | Peruzzi L.,University of Pisa
Taxon | Year: 2014

The typification of the six Linnaean names Gossypium hirsutum, Hibiscus pentacarpos, H. trionum, Lavatera lusitanica, L. micans and Malva crispa var. verticillata is discussed. The names are lectotypified using specimens from Clifford, Linnaeus and Van Royen Herbaria and illustrations from Zannichelli and Morison. © International Association for Plant Taxonomy (IAPT) 2014.


The magnetic connection theorem of ideal magnetohydrodynamics by Newcomb (Newcomb W. A., Ann. Phys. (N.Y.), 3 (1958) 347) and its covariant formulation are rederived and reinterpreted in terms of a time resetting projection that accounts for the loss of simultaneity in different reference frames between spatially separated events. © Copyright EPLA, 2012.


Giudice G.F.,CERN | Rattazzi R.,Ecole Polytechnique Federale de Lausanne | Strumia A.,University of Pisa | Strumia A.,Estonian National Institute of Chemical Physics and Biophysics
Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics | Year: 2012

Dark matter, gauge coupling unification, and the strong CP problem find a common and simple solution (in the absence of naturalness) within axion models. We show that such a solution, even without specifying the details of the model implementation, makes testable predictions for the experimentally measurable axion parameters: the axion mass and its coupling to photons. © 2012 Elsevier B.V.


D'Elia M.,University of Pisa | Negro F.,University of Genoa
Physical Review Letters | Year: 2012

We determine the θ dependence of the deconfinement temperature of SU(3) pure gauge theory, finding that it decreases in the presence of a topological θ term. We do that by performing lattice simulations at imaginary θ, then exploiting analytic continuation. We also give an estimate of such dependence in the limit of a large number of colors N and compare it with our numerical results. © 2012 American Physical Society.


Ipata P.L.,University of Pisa
American Journal of Physiology - Advances in Physiology Education | Year: 2011

The brain relies on the salvage of preformed purine and pyrimidine rings, mainly in the form of nucleosides, to maintain its nucleotide pool in the proper qualitative and quantitative balance. The transport of nucleosides from blood into neurons and glia is considered to be an essential prerequisite to enter their metabolic utilization in the brain. Recent lines of evidence have also suggested that local extracellular nucleoside triphosphate (NTP) degradation may contribute to brain nucleosides. Plasma membranelocated ectonucleotidases, with their active sites oriented toward the extracellular space, catalyze the successive hydrolysis of NTPs to their respective nucleosides. Apart from the well-established modulation of ATP, ADP, adenosine (the purinergic agonists), UTP, and UDP (the pyrimidinergic agonists) availability at their respective receptors, ectonucleotidases may also serve the local reutilization of nucleosides in the brain. After their production in the extracellular space by the ectonucleotidase system, nucleosides are transported into neurons and glia and converted back to NTPs via a set of purine and pyrimidine salvage enzymes. Finally, nucleotides are transported into brain cell vescicles or granules and released back into the extracellular space. The key teaching concepts to be included in a two-to threelecture block on the molecular mechanisms of the local nucleoside recycling process, based on a cross talk between the brain extracellular space and cytosol, are discussed in this article. © 2011 The American Physiological Society.


Becirevic D.,University Paris - Sud | Schneider E.,University Paris - Sud | Schneider E.,University of Pisa
Nuclear Physics B | Year: 2012

We discuss the three independent asymmetries, AT (2)(q2), AT (im)(q2) and AT (re)(q2), that one can build from the amplitudes A⊥(q2) and A{norm of matrix}(q2). These quantities are expected to be accessible from the new B-physics experiments, they are sensitive to the presence of new physics, and they are not very sensitive to hadronic uncertainties. Studying their low q2 dependence can be helpful in discerning among various possible new physics scenarios. All three asymmetries can be extracted from the full angular analysis of B→K*ℓ+ℓ-. Our formulas apply to both the massless and the massive lepton case. © 2011 Elsevier B.V.


Shore S.N.,University of Pisa | Shore S.N.,National Institute of Nuclear Physics, Italy
Bulletin of the Astronomical Society of India | Year: 2012

The spectroscopic development of classical novae is described as a narrative of the various stages of the outburst. The review highlights the multiwavelength aspects of the phenomenology and the recent developments related to structure, inhomogeneity, and dynamics of the ejecta. Special emphasis is placed on the distinct behavior of the symbiotic-like recurrent novae.


Ferrannini E.,University of Pisa | Mari A.,CNR Institute of Biomedical Engineering | Nofrate V.,CNR Institute of Biomedical Engineering | Sosenko J.M.,University of Miami | Skyler J.S.,University of Miami
Diabetes | Year: 2010

OBJECTIVE - Relatives of type 1 diabetic patients are at enhanced risk of developing diabetes. We investigated the mode of onset of hyperglycemia and how insulin sensitivity and β-cell function contribute to the progression to the disease. RESEARCH DESIGN AND METHODS - In 328 islet cell autoantibody-positive, nondiabetic relatives from the observational arms of the Diabetes Prevention Trial-1 Study (median age 11 years [interquartile range 8], sequential OGTTs (2,143 in total) were performed at baseline, every 6 months, and 2.7 years [2.7] later, when 115 subjects became diabetic. β-Cell glucose sensitivity (slope of the insulin-secretion/plasma glucose dose-response function) and insulin sensitivity were obtained by mathematical modeling of the OGTT glucose/C-peptide responses. RESULTS - In progressors, baseline insulin sensitivity, fasting insulin secretion, and total postglucose insulin output were similar to those of nonprogressors, whereas β-cell glucose sensitivity was impaired (median 48 pmol/min per m2 per mmol/l [interquartile range 36] vs. 87 pmol/min per m2 per mmol/l [67]; P < 0.0001) and predicted incident diabetes (P < 0.0001) independently of sex, age, BMI, and clinical risk. In progressors, 2-h glucose levels changed little until 0.78 years before diagnosis, when they started to rise rapidly (∼13 mmol · l-1 · year-1); glucose sensitivity began to decline significantly (P < 0.0001) earlier (1.45 years before diagnosis) than the plasma glucose surge. During this anticipation phase, both insulin secretion and insulin sensitivity were essentially stable. CONCLUSIONS - In high-risk relatives, β-cell glucose sensitivity is impaired and is a strong predictor of diabetes progression. The time trajectories of plasma glucose are frequently biphasic, with a slow linear increase followed by a rapid surge, and are anticipated by a further deterioration of β-cell glucose sensitivity. © 2010 by the American Diabetes Association.


Okawa H.,University of Washington | Hoon M.,University of Washington | Yoshimatsu T.,University of Washington | Santina L.D.,University of Washington | And 2 more authors.
Neuron | Year: 2014

Across the nervous system, neurons form highly stereotypic patterns of synaptic connections that are designed to serve specific functions. Mature wiring patterns are often attained upon the refinement of early, less precise connectivity. Much work has led to the prevailing view that many developing circuits are sculpted by activity-dependent competition among converging afferents, which results in the elimination of unwanted synapses and the maintenance and strengthening of desired connections. Studies of the vertebrate retina, however, have recently revealed that activity can play a role in shaping developing circuits without engaging competition among converging inputs that differ in their activity levels. Such neurotransmission-mediated processes can produce stereotypic wiring patterns by promoting selective synapse formation rather than elimination. We discuss how the influence of transmission may also be limited by circuit design and further highlight the importance of transmission beyond development in maintaining wiring specificity and synaptic organization of neural circuits. © 2014 Elsevier Inc.


Calabrese P.,University of Pisa | Cardy J.,University of Oxford | Cardy J.,All Souls College | Tonni E.,International School for Advanced Studies
Physical Review Letters | Year: 2012

We develop a systematic method to extract the negativity in the ground state of a 1+1 dimensional relativistic quantum field theory, using a path integral formalism to construct the partial transpose ρAT 2 of the reduced density matrix of a subsystem A=A 1A 2, and introducing a replica approach to obtain its trace norm which gives the logarithmic negativity E=lnρAT 2. This is shown to reproduce standard results for a pure state. We then apply this method to conformal field theories, deriving the result E∼(c/4)ln[ 12/( 1+ 2)] for the case of two adjacent intervals of lengths 1, 2 in an infinite system, where c is the central charge. For two disjoint intervals it depends only on the harmonic ratio of the four end points and so is manifestly scale invariant. We check our findings against exact numerical results in the harmonic chain. © 2012 American Physical Society.


Vicari E.,University of Pisa
Physical Review A - Atomic, Molecular, and Optical Physics | Year: 2012

We investigate the entanglement properties of the nonequilibrium dynamics of one-dimensional noninteracting Fermi gases released from a trap. The gas of N particles is initially in the ground state within a hard-wall or a harmonic trap, and then it expands after dropping the trap. We compute the time dependence of the von Neumann and Rényi entanglement entropies and the particle fluctuations of spatial intervals around the original trap in the limit of a large number N of particles. The results for these observables apply to one-dimensional gases of impenetrable bosons as well. We identify different dynamical regimes at small and large times, depending also on the initial condition, i.e., whether it is that of a hard-wall or a harmonic trap. In particular, we show analytically that the expansion from hard-wall traps is characterized by the asymptotic small-time behavior S (1/3)ln(1/t) of the von Neumann entanglement entropy and the relation S π2V/3 (where V is the particle variance), which are analogous to the equilibrium behaviors whose leading logarithms are essentially determined by the corresponding conformal field theory with central charge c=1. The time dependence of the entanglement entropy of extended regions during the expansion from harmonic traps has a remarkable property in that it can be expressed as a global time-dependent rescaling of the space dependence of the initial equilibrium entanglement entropy. © 2012 American Physical Society.


Marcucci L.E.,University of Pisa
International Journal of Modern Physics A | Year: 2012

The present status of theoretical and experimental studies of muon capture reactions on light nuclei is reviewed. In particular, the recent results for the two reactions 2H(μ -,ν μ)nn and 3He(μ -, ν μ) 3H are presented, and the unresolved discrepancies among different measurements and calculations, open problems, and future developments are discussed. © 2012 World Scientific Publishing Company.


Cosottini M.,University of Pisa
Journal of computer assisted tomography | Year: 2013

Primary angiitis of the central nervous system (PACNS) is a rare disease characterized by an inflammatory process of intracranial vessels. Magnetic resonance angiography (MRA) (3 T) offers increased signal-to-noise ratio and background suppression, leading to better depiction of the intracranial vessels. The aim of our work was to compare the sensitivity of 3-T MRA to that of 1.5-T MRA in the diagnosis of PACNS. Eight patients with PACNS and signs of angiitis at digital subtraction angiography (DSA) underwent MRA at 1.5 and 3 T. Magnetic resonance angiograms obtained with time-of-flight (TOF) technique were evaluated for the presence of stenosis with respect to DSA. In PACNS patients, DSA identified 827 intracranial stenoses. Sensitivity for vessel stenosis of 3-T TOF MRA was 47% and 14% for 1.5-T TOF. Time-of-flight MRA at 3 T improved the sensitivity of MRA in the noninvasive preliminary evaluation of patients with PACNS.


Menotti P.,University of Pisa
Journal of High Energy Physics | Year: 2012

We give an implicit equation for the accessory parameter on the torus which is the necessary and sufficient condition to obtain the monodromy of the conformal factor. It is shown that the perturbative series for the accessory parameter in the coupling constant converges in a finite disk and give a rigorous lower bound for the radius of convergence. We work out explicitly the perturbative result to second order in the coupling for the accessory parameter and to third order for the one-point function. Modular invariance is discussed and exploited. At the non perturbative level it is shown that the accessory parameter is a continuous function of the coupling in the whole physical region and that it is analytic except at most a finite number of points. We also prove that the accessory parameter as a function of the modulus of the torus is continuous and real-analytic except at most for a zero measure set. Three soluble cases in which the solution can be expressed in terms of hypergeometric functions are explicitly treated. © 2012 SISSA, Trieste, Italy.


Merlino S.,University of Pisa
Rendiconti Lincei | Year: 2013

After the epochal experience of Friedrich and Knipping suggested and interpreted by Laue, the scene rapidly moved to England where the young Bragg correctly explained the results of the Munich discovery and showed how to use X-rays to determine the arrangement of atoms in crystals and, in few years, actually derived the structures of several inorganic compounds. Their comparison permitted Bragg to assert that crystals are composed of "inelastic spheres in contact" and that "it is possible to assign to the sphere representing an atom. a constant diameter." The development of these concepts by various authors (Wasastjerna, Goldschmidt,.) led to the well-known Table of ionic radii by Pauling, who - at the same time - proposed the rules for the stability of ionic compounds, based on the concept of coordination polyhedra as building elementary modules of inorganic compounds. The stability rules of Pauling, as well as the conception, formulated by Bragg, of the structures of complex oxides as characterized by 'close packing' of oxygen anions, were the main guiding lines in the 'trial and error' procedures to determine the atomic arrangements in minerals and in inorganic compounds in general. The increasing number of known structures raised the need for proper classification schemes, largely based on elementary structural units (as the silicon tetrahedra in silicates) and the various ways of their connection. At the same time the wide basis of structural data and the increased precision and accuracy of those data stimulated the revision of the old compilations of ionic radii as well as a re-formulation of the Pauling's rule of valence-bond balance. Examples are presented of the application of the crystal chemical concepts to some important mineralogical, geochemical and geophysical problems. An explosive growth of structural knowledge in the last decades of the twentieth century was stimulated by the new techniques of data collection, the high speed of computing and the advent of direct methods of structure solution, which resulted not only in an enormous increase in the number of known structures, but also in unraveling very complex arrangements. This increasing structural knowledge accompanied and stimulated the development of a new way to look at the arrangements of inorganic compounds, based on their modular aspects. The concept of assembling different, geometrically compatible modules, mainly structural layers, to build up complex structures has been very productive; in fact it not only consented a deep knowledge of the structural relationships inside wide families of natural and synthetic compounds, but also favored the solution of complex structural problems and permitted careful previsions of new possible structural arrangements. Few lines of future developments of the crystal chemical study of minerals are briefly presented and discussed: 'synergy' between mineralogists and material chemists; computational simulations of structural arrangements; new experimental approach through automated electron diffraction tomography. © 2012 Accademia Nazionale dei Lincei.


Vicari E.,University of Pisa
Physical Review A - Atomic, Molecular, and Optical Physics | Year: 2012

We investigate quantum correlations in the ground state of noninteracting Fermi gases of N particles trapped by an external space-dependent harmonic potential, in any dimension. For this purpose we compute one-particle correlations, particle fluctuations, and bipartite entanglement entropies of extended space regions, and study their large-N scaling behaviors. The half-space von Neumann entanglement entropy is computed for any dimension, obtaining S HSc lN (d -1 )/dlnN analogously to homogenous systems, with c l=1/6,1/(6√2),1/(6√6) in one, two, and three dimensions, respectively. We show that the asymptotic large-N relation S Aπ 2V A/3, between the von Neumann entanglement entropy S A and particle variance V A of an extended space region A, holds for any subsystem A and in any dimension, analogously to homogeneous noninteracting Fermi gases. © 2012 American Physical Society.


Freer G.,University of Pisa
Current Immunology Reviews | Year: 2016

The type of immune response a host can raise against an invading parasite may often be decisive between chronicity or clearance, and in the worst cases between host survival and death. Helper T cells are key to determining whether antibody-mediated, inflammatory or cytolytic responses will be predominant. Interleukin 10 (IL10) is widely recognized to be the most important cytokine for anti-inflammatory reactions and tends to be associated to chronicity in quite a few types of viral infections. On the other hand, it has also been associated to tissue preservation in chronic viral disease. This review summarizes the most recent data available in the literature on this pivotal cytokine during experimental viral infection and in the clinical setting. © 2016 Bentham Science Publishers.


Angst J.,University of Zurich | Azorin J.-M.,Hopital de Sainte Marguerite | Bowden C.L.,University of Texas Health Science Center at San Antonio | Perugi G.,University of Pisa | And 3 more authors.
Archives of General Psychiatry | Year: 2011

Context: Major depressive disorder, the most common psychiatric illness, is often chronic and a major cause of disability. Many patients with major depressive episodes who have an underlying but unrecognized bipolar disorder receive pharmacologic treatment with ineffective regimens that do not include mood stabilizers. Objective: To determine the frequency of bipolar disorder symptoms in patients seeking treatment for a major depressive episode. Design: Multicenter, multinational, transcultural, crosssectional, diagnostic study. The study arose from the initiative Bipolar Disorders: Improving Diagnosis, Guidance and Education (BRIDGE). Setting: Community and hospital psychiatry departments. Patients: Participants included 5635 adults with an ongoing major depressive episode. Main Outcome Measures: The frequency of bipolar disorder was determined by applying both DSM-IV-TR criteria and previously described bipolarity specifier criteria. Variables associated with bipolarity were assessed using logistic regression. Results: A total of 903 patients fulfilled DSM-IV-TR criteria for bipolar disorder (16.0%; 95% confidence interval, 15.1%-17.0%), whereas 2647 (47.0%; 95% confidence interval, 45.7%-48.3%) met the bipolarity specifier criteria. Using both definitions, significant associations (odds ratio>2; P<.001) with bipolarity were observed for family history of mania/hypomania and multiple pastmoodepisodes. The bipolarity specifier additionally identified significant associations for manic/hypomanic states during antidepressant therapy, current mixed mood symptoms, and comorbid substance use disorder. Conclusions: The bipolar-specifier criteria in comparison with DSM-IV-TR criteria were valid and identified an additional 31% of patients with major depressive episodes who scored positive on the bipolarity criteria. Family history, illness course, and clinical status, in addition to DSMIV- TR criteria, may provide useful information for physicians when assessing evidence of bipolarity in patients with major depressive episodes. Such an assessment is recommended before deciding on treatment. ©2011 American Medical Association. All rights reserved.


Franco A.,University of Pisa
Applied Thermal Engineering | Year: 2011

An interesting feature in the design of Combined Cycle Power Plants (CCPP), as the gas turbines become larger and the exhaust temperatures rise, is the use of Heat Recovery Steam Generators (HRSG) with supercritical (SC) steam properties. The paper is orientated at assessing the potential of using supercritical steam cycles in combined cycle power plants. The interaction between gas turbine and HRSG thermodynamic is mainly focused. The analysis is based on minimizing total exergy losses in order to optimise the performance of the HRSG-steam turbine system. In the paper the alternative design of combined cycle power plants in which a supercritical (SC) HRSG is present has been analyzed. The analysis includes a comparison of three different supercritical HRSG configurations with single (SC1RH) and double reheaters (SC2RH) with simple HRSG single pressure configurations and advanced double and triple pressure HRSG structures. The HRSG structures (steam pressure, maximum temperature and mass flow rate) are designed considering as objective function the minimization of the total exergy losses in the system composed by HRSG and steam turbine (ST). The optimization procedure is based on combination of random-search and simplex method. The evaluation shows that even if the use of supercritical HRSG is non particularly convenient in the perspective of efficiency increase it can be a valid technical solution aiming to the development of medium size (50-120 MW) combined cycle power plants. Four different commercially available gas turbine cycles have been tested for this specific purpose obtaining efficiency level approaching in particular cases the state of the art results with simpler technical solutions. © 2010 Elsevier Ltd. All rights reserved.


Several tests have been carried out with two miniature periodic two-phase thermosyphons (PTPTs), which have been developed for thermal control applications. A PTPT is a wickless device which can operates even against gravity. The two PTPTs have the same condenser and accumulator and different evaporators: the evaporator Type A, which can contain a large amount of liquid (20 × 10-6 m3) and which can be tilted up to 90°, and the evaporator Type B, which has an internal volume of 5 × 10-6 m3 and can operate just in horizontal orientation. Their unsteady and their periodic steady state performances have been studied and compared with those of several miniature loop heat pipes quoted in the references. The paper shows that the PTPT thermal resistances are similar to those of miniature LHPs, even those of PTPTs are less influenced by the arrangement of the condenser and the evaporator with respect to the gravity. The thermal resistance, as the PTPT steadily operates, is about 0.55 K/W with a heat load of 110 W. The main experimental observation on the PTPT unsteady behaviour is that their start-ups are rather smooth in the most cases. However the start-up performances does not depend on any configuration and orientation of the loop element. © 2010 Elsevier Ltd. All rights reserved.


Trenti M.,University of Colorado at Boulder | Vesperini E.,Drexel University | Pasquato M.,University of Pisa
Astrophysical Journal | Year: 2010

We present a unified picture for the evolution of star clusters on the two-body relaxation timescale. We use direct N-body simulations of star clusters in a galactic tidal field starting from different multimass King models, up to 10% of primordial binaries and up to N tot = 65, 536 particles. An additional run also includes a central Intermediate Mass Black Hole. We find that for the broad range of initial conditions we have studied the stellar mass function of these systems presents a universal evolution, which depends only on the fractional mass loss. The structure of the system, as measured by the core to half-mass radius ratio, also evolves toward a universal state, which is set by the efficiency of heating on the visible population of stars induced by dynamical interactions in the core of the system. Interactions with dark remnants (white dwarfs, neutron stars, and stellar mass black holes) are dominant over the heating induced by a moderate population of primordial binaries (3%-5%), especially under the assumption that most of the neutron stars and black holes are retained in the system. All our models without primordial binaries undergo a deep gravothermal collapse in the radial mass profile. However, their projected light distribution can be well fitted by medium concentration King models (with parameter W 0 ∼ 8), even though there tends to be an excess over the best fit for the innermost points of the surface brightness. This excess is consistent with a shallow cusp in the surface brightness (μ R -ν with ν ∼ 0.4-0.7), like it has been observed for many globular clusters from high-resolution Hubble Space Telescope imaging. Generally, fitting a King profile to derive the structural parameters yields to larger fluctuations in the core size than defining the core as the radius where the surface brightness is one half of its central value. Classification of core-collapsed globular clusters based on their surface brightness profile may thus fail in systems that appear to have already bounced back to lower concentrations, particularly if the angular resolution of the observations is limited and the core is not well resolved. © 2010. The American Astronomical Society. All rights reserved.


Pacifici G.M.,University of Pisa
Current Pediatric Reviews | Year: 2014

Background: Ibuprofen and indomethacin are potent non-selective cyclo-oxygenase inhibitors and inhibit prostaglandin E2 synthesis. The patent ductus arteriosus (PDA) occurs in more than 70% of preterm infants weighing <1500 g. Prostaglandin E2 relaxes smooth muscle, tends to inhibit the closure of PDA, yields vasodilatation of the afferent renal arterioles and maintains glomerular filtration rate (GFR). Ibuprofen and indomethacin inhibiting prostaglandin E2 synthesis close PDA and reduce GFR with consequent decrease of urine output and increase of serum creatinine concentrations. Aims: The aims of this study are to give the definitive estimates of PDA closure rate following ibuprofen or indomethacin treatment and to evaluate the extent of renal side effects following the administration of these drugs to preterm infants. Other aims are to review the metabolism and the pharmacokinetics of ibuprofen and indomethacin in preterm infants with PDA. Methods: The bibliographic search was performed using PubMed and EMBASE databases as search engines, January 2013 was the cutoff point. Results: The %PDA closed by ibuprofen (n=24) and indomethacin (n=24) is 77.7+14.1 and 77.3+11.0, respectively. For ibuprofen, the gestational age of the infants included in the study ranged from 25.0 to 39.0 weeks (mean+SD=29.3+3.1 weeks). The %PDA did not correlate with the gestational age (p=0.2516). For indomethacin, the gestational age of infants included in the study ranged from 25.0 and 39.0 weeks (mean+SD=29.4+2.9 weeks). The %PDA did not correlate with the gestational age (p=0.3742). The treatment with ibuprofen reduces the urine output and increases the serum creatinine concentrations less extensively than indomethacin. The half-life (t1/2) of ibuprofen and indomethacin is lengthened and the clearance is reduced in preterm infants as compared with fullterm infants. Conclusions. Ibuprofen and indomethacin are equally effective in closing PDA. Treatment with ibuprofen decreases the risk of renal failure. Ibuprofen has the most favourable risk/benefit ratio. The rate of metabolism is reduced and t1/2 is lengthened in prematures as compared with term infants. © 2014 Bentham Science Publishers.


Donadio C.,University of Pisa
American Journal of Physiology - Renal Physiology | Year: 2010

The screening for chronic kidney diseases (CKD) patients with impaired GFR needs the measurement of serum creatinine (SCr) or cystatin C (SCys). GFR can also be predicted from SCr or SCys with different formulas. The aim of this study, performed in a group of CKD patients with different levels of GFR, was to evaluate the possibility to select the patients with a GFR <90 ml·min-1·1.73 m-2 by means of serum levels and urinary excretion of different low-molecular-weight proteins (LMWP), cystatin C (Cys), β2-microglobulin (β2M), retinol-binding protein (RBP), β-trace protein (BTP), and derived prediction equations for GFR. In the 295 CKD patients (137 women), at all stages of GFR impairment a very high correlation was found between GFR (99mTc-DTPA) and serum Cr, Cys, β2M, and BTP. All these serum markers showed a similar accuracy as indicators of different GFR impairments. RBP had the lowest correlation with GFR and was also significantly less accurate. The different prediction formulas derived from gender, anthropometric data and SCr or S-LMWP had a diagnostic accuracy similar to that of serum Cr, Cys, β2M, and BTP. Urinary albumin was inadequate as an indicator of any level of GFR impairment. Urinary excretion of Cys and β2M increased significantly only in patients with a GFR <30 ml·min-1·1.73 m-2, while urinary BTP increased already at GFR <90 ml·min-1·1.73 m -2. In this selected group of CKD patients, the positive predictive value of urinary BTP for a GFR <90 ml·min-1·1.73 m-2 was 85%, indicating that, in CKD patients, a urine-based test can predict a slight GFR impairment. Copyright © 2010 the American Physiological Society.


Mauri R.,University of Pisa
Foundations of Physics | Year: 2016

Analytical models describing the motion of colloidal particles in given force fields are presented. In addition to local approaches, leading to well known master equations such as the Langevin and the Fokker–Planck equations, a global description based on path integration is reviewed. A new result is presented, showing that under very broad conditions, during its evolution a dissipative system tends to minimize its energy dissipation in such a way to keep constant the Hamiltonian time rate, equal to the difference between the flux-based and the force-based Rayleigh dissipation functions. In fact, the Fokker–Planck equation can be interpreted as the Hamilton–Jacobi equation resulting from such minumum principle. At steady state, the Hamiltonian time rate is maximized, leading to a minimum resistance principle. In the unsteady case, we consider the relaxation to equilibrium of harmonic oscillators and the motion of a Brownian particle in shear flow, obtaining results that coincide with the solution of the Fokker–Planck and the Langevin equations. © 2015, Springer Science+Business Media New York.


Pauwels E.K.J.,University of Pisa
Medical Principles and Practice | Year: 2011

The lower occurrence of cancer and cardiovascular disease in the population around the Mediterranean basin has been linked to the dietary habits of the region. Indeed, this so-called Mediterranean diet is essentially different from the diets consumed in Western and Northern European countries and is rich in nuts, fruits, vegetables, legumes, whole-wheat bread, fish, and olive oil, with moderate amounts of red wine, which is mainly consumed during meals. Although a variety of cultural and religious traditions exist among the peoples of the Mediterranean area, olive oil, fish, and red wine hold a traditional and central position in the culinary routines of the region. The components of the diet contain an ample source of molecules with antioxidant and anti-inflammatory actions, among which omega-3 fatty acids, oleic acid, and phenolic compounds hold a prominent place. This review will summarize the results of important epidemiological studies that have investigated the protective effect of fish and olive oil on the risk of breast, prostate, and colorectal cancer and of wine on the risk of cardiovascular disease. The present review also aims to elucidate the various mechanisms by which various dietary components exhibit their beneficial action. In this respect, emphasis will be placed on the properties of omega-3 fatty acids from fish, oleic acid from olive oil, and phenolic compounds from olive oil and red wine. Copyright © 2011 S. Karger AG, Basel.


Mastroeni G.,University of Pisa
Journal of Global Optimization | Year: 2012

In this paper, we extend the image space analysis to a vector quasi-equilibrium problem (VQEP) with a variable ordering relation and we analyse scalar and vector saddle point optimality conditions arising from the existence of a vector separation in the image space associated with VQEP. © Springer Science+Business Media, LLC. 2011.


Spinelli A.,University of Pisa
Biomatter | Year: 2012

In this work we describe the fabrication of a biocompatible hydrophilic scaffold composed of cross-linked gelatin that mimics the porous three-dimensional structure of pulmonary tissue as well as its water content and mechanical properties. The lung replica also reproduces the characteristic sonographic signs of pulmonary interstitial syndrome, the B-lines or ultrasound lung comets.


Hall B.L.,University of Maine, United States | Henderson G.M.,University of Oxford | Baroni C.,University of Pisa | Kellogg T.B.,University of Maine, United States
Earth and Planetary Science Letters | Year: 2010

Southern Ocean radiocarbon reservoir ages (i.e. non-zero radiocarbon ages in seawater) are the highest in the world's surface ocean. Constraining these reservoir ages at present and in the past is important not only because unknown reservoir ages limit the interpretation of Antarctic radiocarbon chronologies, but also because reservoir ages provide information about ocean circulation (as a recorder of past circulation and as an end member for major deep-water masses in today's ocean). In this study, we use paired U/Th and 14C ages of an unusual set of solitary coral samples trapped by fringing ice shelves in the Ross Sea to provide the first detailed study of Holocene reservoir ages for the Southern Ocean. Our results indicate a relatively constant marine radiocarbon reservoir age of 1144±120years for the past 6000years. These results are consistent with extrapolation of the relationship between 14C and alkalinity seen elsewhere, supporting the use of this empirical relationship in high latitudes. The results also suggest constant deep-ocean circulation and air-sea exchange during the Holocene and provide a good target for tuning ocean models of modern circulation. Combining the new ages for corals with their distance from the modern-day ice-shelf grounding line provides some of the first long-term records of ice-shelf velocities for any region and indicates constant flow of the McMurdo Ice Shelf during the Holocene, at a rate similar to that observed today. © 2010 Elsevier B.V.


Cupisti A.,University of Pisa
Journal of Nephrology | Year: 2011

Nephrolithiasis research and care have been focused on biochemical changes in urinary solute excretion leading to stone formation, but abnormalities in urine chemistry alone do not explain many aspects of the condition of patients with kidney stone disease. Evidence exists of an association with metabolic syndrome, obesity, diabetes and hypertension, and of enhanced risk of chronic kidney disease and metabolic bone disease. Very recently also a higher risk of cardiovascular events and damage has been reported in kidney stone formers when compared with non-stone formers. It is time to view nephrolithiasis as a condition predictive of chronic kidney disease and cardiovascular damage, which deserves full metabolic evaluation together with an early prevention care strategy, mainly consisting of dietary and lifestyle changes, in a multi-disciplinary approach. Kidney stone disease should be considered as a systemic disorder with clinical relevance beyond symptomatic urinary tract obstruction. © 2011 Società Italiana di Nefrologia.


Coppede F.,University of Pisa
Advances in Experimental Medicine and Biology | Year: 2012

Hutchinson-Gilford progeria syndrome and Werner syndrome are two of the best characterized human progeroid diseases with clinical features mimicking physiological aging at an early age. Both disorders have been the focus of intense research in recent years since they might provide insights into the pathology of normal human aging. The chapter contains a detailed description of the clinical features of both disorders and then it focuses on the genetics, the resulting biochemical alterations at the protein level and the most recent findings and hypotheses concerning the molecular basis of the premature aging phenotypes. A description of available diagnostic and therapeutic approaches is included. © 2012 Landes Bioscience and Springer Science+Business Media.


Roda C.,University of Pisa
Nuclear and Particle Physics Proceedings | Year: 2016

The rich set of data collected from HERA, Tevatron and LHC collisions offer an extraordinary possibility to test different aspects of perturbative Quantum Chromodynamics. A selection of recent results illustrates the variety and precision of these tests. The comparison of the experimental data with the most recent theoretical predictions demonstrates the advances made in the theoretical field. © 2015 Elsevier B.V.


Biver T.,University of Pisa
Coordination Chemistry Reviews | Year: 2013

A general overview is provided about the recent and state of the art advances in the field of metal ions, metal complexes and small aromatic molecules use as stabilising agents for non-canonical nucleotide forms (non-B duplex, triplexes, quadruplexes). Despite the broad topic, the collection and comparison of the large amount of data available enable some general remarks to be done. The ability of metal ions to stabilise a particular form is discussed on the basis of ion size, charge density, coordination and binding modes and/or dehydration energy. In the case of small molecules (intercalators and/or groove binders) charge, flexibility, hydrophobicity and/or geometry are considered. © 2013 Elsevier B.V.


Shayeganrad G.,University of Pisa
Optics Communications | Year: 2013

A compact diode-end-pumped actively Q-switched Raman laser generating simultaneous dual-wavelength first Stokes Raman scattering at 1178.9 and 1199.9 nm using c-cut Nd:YVO4 and undoped YVO4 crystals in the cavity is reported for the first time to the author's knowledge. The output characteristics versus the incident pump power and the pulse repetition rates are investigated. With the incident pump power of ∼19 W and pulse repetition rate of 20 kHz, a total average output power at 1178.9 and 1199.9 nm up to 0.765 W with a pulse width of 36 ns is obtained from the concave-plane cavity, corresponding to an optical-to-optical conversion efficiency of ∼4%. © 2012 Elsevier B.V. All rights reserved.