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Firenze, Italy

The University of Florence is an Italian public research university located in Florence, Italy. It comprises 12 schools and has about 60,000 students enrolled. Wikipedia.


Baccari M.C.,University of Florence
Current Protein and Peptide Science | Year: 2010

Orexin A (OXA) and orexin B (OXB) are recently discovered neuropeptides that appear to play a role in various distinct functions such as arousal and the sleep-wake cycle as well as on appetite and regulation of feeding and energy homeostasis. Orexins were first described as neuropeptides expressed by a specific population of neurons in the lateral hypothalamic area, a region classically implicated in feeding behaviour. Orexin neurons project to numerous brain regions, where orexin receptors have been shown to be widely distributed: both OXA and OXB act through two subtypes of receptors (OX1R and OX2R) that belong to the G protein-coupled superfamily of receptors. Growing evidence indicates that orexins act in the central nervous system also to regulate gastrointestinal functions: animal studies have indeed demonstrated that centrally-injected orexins or endogenously released orexins in the brain stimulates gastric secretion and influence gastrointestinal motility. The subsequent identification of orexins and their receptors in the enteric nervous system (including the myenteric and the submucosal plexuses) as well as in mucosa and smooth muscles has suggested that these neuropeptides may also play a local action. In this view, emerging studies indicate that orexins also exert region-specific contractile or relaxant effects on isolated gut preparations. The aim of the proposed review is to summarize both centrally- and peripherally-mediated actions of orexins on gastrointestinal functions and to discuss the related physiological role on the basis of the most recent findings. © 2010 Bentham Science Publishers Ltd. Source


Brandi M.-L.,University of Florence
Current Medical Research and Opinion | Year: 2010

Objective: Vertebral fractures are common in women with postmenopausal osteoporosis, a chronic condition requiring long-term treatment with anti-osteoporotic treatments. Therefore, it is important to assess sustainability of antifracture efficacy. Methods: A review of the literature to determine pivotal vertebral fracture studies for oral bisphosphonates (ibandronate, risedronate and alendronate), strontium ranelate, and raloxifene and to evaluate vertebral antifracture efficacy over time. Results: Data from the BONE trial showed that ibandronate sustained vertebral antifracture efficacy over time (58 vertebral fracture risk reduction in first year p0.0561, increased to 62 for years 03; p<0.001). The Vertebral Efficacy with Risedronate TherapyNorth America (VERT-NA) and VERTmulti-national (VERT-MN) studies demonstrated that the relative risk reduction (RRR) with risedronate versus placebo decreased over time (VERT-NA: 65 for first year to 41 for years 03; VERT-MN: 61 for first year to 49 for years 03). Data from the Fracture Intervention Trial (FIT) I trial with alendronate showed that the RRR in the cumulative incidence of new vertebral fractures versus placebo decreased from 62 for years 02 to 47 for years 03. Similar decreases in RRR over time were reported with strontium ranelate in the Spinal Osteoporosis Therapeutic Intervention study (SOTI; 49 for first year to 33 for years 04) and Treatment of Peripheral Osteoporosis Study (TROPOS; 45 for first year to 24 for years 05). No clear trend exists for sustained efficacy over time with raloxifene. Conclusions: Vertebral fracture protection could be interpreted to decrease over time with alendronate, risedronate and strontium ranelate, and may be due to multiple factors. Ibandronate sustained vertebral antifracture efficacy over time. © 2010 Informa UK Ltd All rights reserved. Source


An α-carbonic anhydrases (CAs, EC 4.2.1.1) was recently discovered, cloned and characterized in the genome of the protozoan parasite Trypanosoma cruzi, the causative agent of Chagas disease, a neglected but widespread tropical disease. Inhibition of this α-CAs (TcCA) with anions, sulfonamides, sulfamates, thiols and hydroxamates has been investigated in detail, with several low nanomolar in vitro inhibitors. Although the sulfonamides were the best in vitro inhibitors, they showed no ex vivo anti-T. cruzi activity, due to poor penetration. However, some thiols and hydroxamates acting as low nanomolar TcCA inhibitors also showed significant antitrypanosomal ex vivo activity, making this enzyme an attractive yet underexplored drug target for the management of Chagas disease. © 2016 Future Science Ltd. Source


Moretti S.,University of Florence
Journal of the European Academy of Dermatology and Venereology : JEADV | Year: 2012

Current studies have treated a limited portion of the subjective aspects of vitiligo patients and have yet to elucidate possible psychological differences between those with autoimmune markers (AIM) with respect to those without autoimmune markers (NAIM). To perform an age and gender-matched 1:1 case-control study through a comparison of non-segmental vitiligo patients with autoimmune features vs. those without autoimmune features in regards to psychiatric features, psychosomatic aspects and social parameters. A total of 112 non-segmental vitiligo patients have been examined at the Florence University dermatology outpatient service (2nd dermatology unit). Vitiligo with an autoimmune background was defined by the presence of autoimmune antibodies and/or autoimmune diseases. Psychiatric screening was performed by dermatologists using the modified Middlesex Healthcare Questionnaire (MHQ); psychosomatic aspects and social impact were analysed with a standardized, Florentine questionnaire. Upon performing a conditional regression model, age, phobia and obsession were significantly predictive of the presence of AIM and a low total MHQ score was significantly predictive of NAIM in vitiligo patients. With univariate analysis, we found significant differences in: identifiable stress related to the onset of vitiligo, vitiligo triggered by stress, and modified interpersonal relationships related to vitiligo, which were associated with the subgroup containing autoimmunity markers. We found a higher prevalence of age, obsession and phobia among vitiligo patients AIM as compared to vitiligo patients NAIM. Thus, in the presence of demonstrated autoimmunity, screening for particular psychiatric aspects may be useful in the clinical practice of vitiligo. © 2011 The Authors. Journal of the European Academy of Dermatology and Venereology © 2011 European Academy of Dermatology and Venereology. Source


Bonacchi A.,University of Florence
2013 International Symposium on Software Testing and Analysis, ISSTA 2013 - Proceedings | Year: 2013

A challenging problem for model checking is represented by railway interlocking systems. It is a well known fact that interlocking systems, due to their inherent complexity related to the high number of variables involved, are not readily amenable to automatic verification, typically incurring in state space explosion problems. The study described in this paper aims at evaluating and experimenting the industrial application of verification by model checking for this class of systems. The choices made at the beginning of the study, also on the basis of specific requirements from the industrial partner, are presented, together with the advancement status of the project and the plans for its completion. © 2013 ACM. Source


Parsons D.F.,Australian National University | Bostrom M.,University of Cagliari | Nostro P.L.,University of Florence | Ninham B.W.,Australian National University
Physical Chemistry Chemical Physics | Year: 2011

The classical Derjaguin-Landau-Verwey-Overbeek (DLVO) theory of colloids, and corresponding theories of electrolytes, are unable to explain ion specific forces between colloidal particles quantitatively. The same is true generally, for surfactant aggregates, lipids, proteins, for zeta and membrane potentials and in adsorption phenomena. Even with fitting parameters the theory is not predictive. The classical theories of interactions begin with continuum solvent electrostatic (double layer) forces. Extensions to include surface hydration are taken care of with concepts like inner and outer Helmholtz planes, and "dressed" ion sizes. The opposing quantum mechanical attractive forces (variously termed van der Waals, Hamaker, Lifshitz, dispersion, nonelectrostatic forces) are treated separately from electrostatic forces. The ansatz that separates electrostatic and quantum forces can be shown to be thermodynamically inconsistent. Hofmeister or specific ion effects usually show up above ≈10-2 molar salt. Parameters to accommodate these in terms of hydration and ion size had to be invoked, specific to each case. Ionic dispersion forces, between ions and solvent, for ion-ion and ion-surface interactions are not explicit in classical theories that use "effective" potentials. It can be shown that the missing ionic quantum fluctuation forces have a large role to play in specific ion effects, and in hydration. In a consistent predictive theory they have to be included at the same level as the nonlinear electrostatic forces that form the skeletal framework of standard theory. This poses a challenge. The challenges go further than academic theory and have implications for the interpretation and meaning of concepts like pH, buffers and membrane potentials, and for their experimental interpretation. In this article we overview recent quantitative developments in our evolving understanding of the theoretical origins of specific ion, or Hofmeister effects. These are demonstrated through an analysis that incorporates nonelectrostatic ion-surface and ion-ion dispersion interactions. This is based on ab initio ionic polarisabilities, and finite ion sizes quantified through recent ab initio work. We underline the central role of ionic polarisabilities and of ion size in the nonelectrostatic interactions that involve ions, solvent molecules and interfaces. Examples of mechanisms through which they operate are discussed in detail. An ab initio hydration model that accounts for polarisabilities of the tightly held hydration shell of "cosmotropic" ions is introduced. It is shown how Hofmeister effects depend on an interplay between specific surface chemistry, surface charge density, pH, buffer, and counterion with polarisabilities and ion size. We also discuss how the most recent theories on surface hydration combined with hydrated nonelectrostatic potentials may predict experimental zeta potentials and hydration forces. © the Owner Societies 2011. Source


Ciancio O.,Accademia Italiana di Science Forestali | Nocentini S.,University of Florence
Plant Biosystems | Year: 2011

Classic silviculture and management, with the aim of predicting regeneration rate and producing a constant yield of merchantable wood, have simplified many forests, often transforming natural forests into plantations or coppices. To conserve forest complexity and biodiversity, silviculture and forest management should change the reference paradigm and consider forest ecosystems as complex biological systems characterized by the inherent unpredictability of their trajectories in a continuously changing environment. The new Management Plan for the Vallombrosa Forest (Florence, Italy), a State Nature Reserve and a Natura 2000 Site, is based on this approach. The aim is the gradual evolution of the pure silver fir stands toward mixed stands with a complex structure. Most of the species considered by Natura 2000 depend on an increase of structural diversity at different space and time scales. The management approach proposed by the new plan is coherent with this aim and thus biodiversity conservation is not in conflict with forest management but is, instead, a direct consequence of the systemic approach. © 2011 Società Botanica Italiana. Source


Papini A.,University of Florence
Microscopy Research and Technique | Year: 2012

All microscopical images contain noise, increasing when (e.g., transmission electron microscope or light microscope) approaching the resolution limit. Many methods are available to reduce noise. One of the most commonly used is image averaging. We propose here to use the mode of pixel values. Simple Python programs process a given number of images, recorded consecutively from the same subject. The programs calculate the mode of the pixel values in a given position (a, b). The result is a new image containing in (a, b) the mode of the values. Therefore, the final pixel value corresponds to that read in at least two of the pixels in position (a, b). The application of the program on a set of images obtained by applying salt and pepper noise and GIMP hurl noise with 10-90% standard deviation showed that the mode performs better than averaging with three-eight images. The data suggest that the mode would be more efficient (in the sense of a lower number of recorded images to process to reduce noise below a given limit) for lower number of total noisy pixels and high standard deviation (as impulse noise and salt and pepper noise), while averaging would be more efficient when the number of varying pixels is high, and the standard deviation is low, as in many cases of Gaussian noise affected images. The two methods may be used serially. © 2011 Wiley Periodicals, Inc. Source


Ugolini A.,University of Florence
Behavioral Ecology and Sociobiology | Year: 2016

Abstract: The difficulties to use the moon as a compass cue are well known: in the same lunar month, the moon never rises at the same hour, it does not show the same shape, and it is not always visible at night. At the equator, the use of the moon as an orienting cue is even more difficult than in the temperate latitudes. In addition to the difficulties listed above, it should be added (1) the relevant variation in its hourly azimuthal speed when the moon approaches the zenith, (2) the zenithal culmination (i.e., no angle on the horizontal plane), and (3) its changes in the culmination (from North to South and vice versa). Here, I present some experiments carried out using the equatorial sandhopper Talorchestia martensii during the zenithal culmination of the moon to clarify its use as an orienting cue taking into account the already demonstrated use of the magnetic field in the orientation of this species. Experiments were carried out in confined environment, with the magnetic sNorth deflected to East, in nights of zenithal culmination of the full moon. The results indicate that the moon is used together with the magnetic field by T. martensii when the azimuthal variation of the moon is ≤10°/h and its zenithal distance is >10°. However, when the moon’s azimuthal variation is >10°/h and its zenithal distance is ≤10°, the moon is no longer used as an orientating cue. The sole compass reference is now the magnetic field. Therefore, equatorial sandhoppers use the same relationship between orienting mechanisms to overcome the difficulties with astronomical orientation to the sun or the moon. Significant statement: At the equator, the use of the moon as an orienting cue is difficult. Sandhoppers use the moon and the magnetic field only when the moon is far from the zenith; otherwise, they use the magnetic compass alone. © 2016 Springer-Verlag Berlin Heidelberg Source


la Marca G.,University of Florence
Journal of Pharmaceutical and Biomedical Analysis | Year: 2014

Newborn screening (NBS) program is a complex and organized system consisting of family and personnel education, biochemical tests, confirmatory biochemical and genetic tests, diagnosis, therapy, and patient follow up. The program identifies treatable metabolic disorders possibly when asymptomatic by using dried blood spot (DBS). During the last 20 years tandem mass spectrometry (TMS) has become the leading technology in NBS programs demonstrating to be versatile, sensitive and specific. There is consistent evidence of benefits from NBS for many disorders detected by TMS as well as for congenital hypothyroidism, cystic fibrosis, congenital adrenal hyperplasia by immune-enzymatic methods.Real time PCR tests have more recently been proposed for the detection of some severe combined immunodeficiences (SCID) along with the use of TMS for ADA and PNP SCID; a first evaluation of their cost-benefit ratio is still ongoing. Avoiding false negative results by using specific biomarkers and reducing the false positive rate by using second tier tests, is fundamental for a successful NBS program. The fully integration of NBS and diagnostic laboratories with clinical service is crucial to have the best effectiveness in a comprehensive NBS system. © 2014 Elsevier B.V. Source


Tesi C.,University of Florence
Advances in Experimental Medicine and Biology | Year: 2010

Tropomyosin (Tm) is an essential component in the regulation of striated muscle contraction. Questions about Tm functional role have been difficult to study because sarcomere Tm content is not as easily manipulated as Troponin (Tn). Here we describe the method we recently developed to replace Tm-Tn of skeletal and cardiac myofibrils from animals and humans to generate an experimental model of homogeneous Tm composition and giving the possibility to measure a wide range of mechanical parameters of contraction (e.g. maximal force and kinetics of force generation). The success of the exchange was determined by SDS-PAGE and by mechanical measurements of calcium dependent force activation on the reconstituted myofibrils. In skeletal and cardiac myofibrils, the percentage of Tm replacement was higher than 90%. Maximal isometric tension was 30-35% lower in the reconstituted myofibrils than in control myofibrils but the rate of force activation (kACT) and that of force redevelopment (kTR) were not significantly changed. Preliminary results show the effectiveness of Tm replacement in human cardiac myofibrils. This approach can be used to test the functional impact of Tm mutations responsible for human cardiomyopathies. © Springer Science+Business Media, LLC 2010. Source


Bemporad F.,University of Cambridge | Chiti F.,University of Florence
Chemistry and Biology | Year: 2012

The conversion of proteins from their native state to misfolded oligomers is associated with, and thought to be the cause of, a number of human diseases, including Alzheimer's disease, Parkinson's disease, and systemic amyloidoses. The study of the structure, mechanism of formation, and biological activity of protein misfolded oligomers has been challenged by the metastability, transient formation, and structural heterogeneity of such species. In spite of these difficulties, in the past few years, many experimental approaches have emerged that enable the detection and the detailed molecular study of misfolded oligomers. In this review, we describe the basic and generic knowledge achieved on protein oligomers, describing the mechanisms of oligomer formation, the methodologies used thus far for their structural determination, and the structural elements responsible for their toxicity. © 2012 Elsevier Ltd. Source


Ravera E.,University of Florence
Concepts in Magnetic Resonance Part A: Bridging Education and Research | Year: 2014

Sample preparation for solid-state NMR of soluble proteins is all but a trivial accomplishment and often represents the factor that determines the success of the experiments, despite the dramatic methodological and technological improvements in the field of SSNMR. Several different sample preparation have been proposed and applied over the years, with varied results. Among those methods we have proposed the use of sedimentation for obtaining samples with high sensitivity and resolution. This review aims at covering the applications of NMR to sedimented solutes from its first description to the latest developments with implications in the field of DNP. © 2015 Wiley Periodicals, Inc. Source


Purpose: To compare surgical results, morbidity and positive surgical margins rate of patients undergoing robotic partial nephrectomy (RPN) versus open partial nephrectomy (OPN). Methods: This is an observational multicenter study promoted by the "Associazione GIovani Laparoscopisti Endoscopisti" (AGILE) no-Profit Foundation, which involved six Italian urologic centers. All clinical, surgical, and pathological variables of patients treated with OPN or RPN for renal tumors were gathered in a prospectively maintained database. Tumor nephrometry was measured with PADUA score, and complications were stratified with modified Clavien system. Differences between RPN and OPN group were assessed with univariate analysis. Perioperative variables independently associated with complications were assessed with multivariate analysis. Results: A total of 198 and 105 patients were enrolled in OPN and RPN group, respectively. Both had similar demographics, indications to surgery, tumor nephrometry, renal function, WIT (18.7 vs. 18.2 min; p = NS), positive margin rate (5.6 vs. 5.7 %; p = NS), intraoperative complications, and postoperative medical complications. Compared to OPN, RPN group was significantly more morbid (p = 0.04), included tumors with smaller size (p = 0.002), had longer operative time (p < 0.001), lower blood loss, surgical postoperative complications (5.7 vs. 21.2 %, p < 0.001), Clavien 3-4 surgical complications (1 vs. 9.1 %, p = 0.001), and shorter hospitalization. The surgical approach resulted independently correlated with surgical complications on multivariate analysis. Conclusion: In the present series, RPN was associated with a significant reduction of blood loss, surgical complications, including the reintervention rate for urinary fistula and postoperative bleeding, and with a shorter hospitalization. © 2013 Springer-Verlag Berlin Heidelberg. Source


Background: Minerals, metals, clays and rocks were widely used by physicians in the past. However, it was and it is well known that some inorganic elements at high dosage may have curative effects but also serious toxicity. The effects at low or ultra-low concentrations, on the contrary, are less documented, but the idea that low dosage supplementation might be beneficial to human health is widespread even in the present period. Methods: The main information about aluminium, bismuth, cobalt, gold, lithium, nickel and silver was selected and evaluated from a vast body of medical literature. Results: In modern times, most elements are proposed for human use at levels comparable with normal dietary intake, probably for precautionary considerations. Conclusion: Some inorganic trace compounds might have unexpected effects at extremely low dosages, but scientific demonstrations of beneficial effects of supplementation are mostly not available in the medical literature. © 2014 Informa UK Ltd. Source


Santini V.,University of Florence
The oncologist | Year: 2011

Myelodysplastic syndromes (MDS) are heterogeneous clonal diseases characterized by cytopenias resulting from ineffective hemopoiesis. Anemia affects the vast majority of patients with MDS and contributes substantially to their symptoms. For more than 20 years, recombinant human erythropoietin has been available for clinical use, and it has been employed in an attempt to relieve MDS-related anemia. Erythropoietin-alpha, erythropoietin-beta, and more recently darbepoetin have been found to increase hemoglobin levels and abolish transfusion dependence in 19%-68% of MDS cases. This wide range in clinical response depends on several biological and clinical variables that allow the selection of patients with the highest probability of successful treatment. These agents are a mainstay in MDS therapy, but many issues are still open in terms of the initiation of therapy, the optimal dosage of erythropoietic stimulating agents (ESAs), the most efficient type of ESA, and the duration and outcome of such treatments. In this review, the mechanisms of response and predictive factors as well as an analysis of the clinical activity of ESAs in MDS therapy are presented. Source


Menchetti M.,University of Florence | Mori E.,University of Turin
Ethology Ecology and Evolution | Year: 2014

More than 16% of parrot species (Aves Psittaciformes) of the world have currently established at least one breeding population outside their natural distribution ranges. Though including the most introduced bird species all over the world, their interactions with native biodiversity and environments are still poorly known. In this paper, we summarize current knowledge about impacts of introduced Psittaciformes and we identify possible gaps to be filled with future research. Breeding site requirements of alien parrots, e.g. trunk cavities, indicate potential routes of direct and indirect competition with native hole-nesting bird species. Interactions with arboreal rodents, bats and insects are poorly documented, but appear to be limited. Psittaciformes potentially affect economy and human wellness, being responsible for damage to crops and to electrical infrastructures. Association with noise pollution has also been suggested, as many alien populations breed in urban parks or close to human settlements. Psittaciformes are potential reservoirs of Chlamydophila psittaci, the etiological agent of human psittacosis, and other diseases transmittable to humans and wildlife. Less is known about impact on native flora as well as on ecosystem functions. Predictive research and information on ecosystem recovery after parrot removal are scarce too, as eradication programs are often hampered by the emotional affiliation linked to these birds. © 2014 Dipartimento di Biologia, Università di Firenze, Italia. Source


Mura P.,University of Florence
Journal of Pharmaceutical and Biomedical Analysis | Year: 2014

Cyclodextrins are cyclic oligosaccharides endowed with a hydrophilic outer surface and a hydrophobic inner cavity, able to form inclusion complexes with a wide variety of guest molecules, positively affecting their physicochemical properties. In particular, in the pharmaceutical field, cyclodextrin complexation is mainly used to increase the aqueous solubility and dissolution rate of poorly soluble drugs, and to enhance their bioavailability and stability. Analytical characterization of host-guest interactions is of fundamental importance for fully exploiting the potential benefits of complexation, helping in selection of the most appropriate cyclodextrin. The assessment of the actual formation of a drug-cyclodextrin inclusion complex and its full characterization is not a simple task and often requires the use of different analytical methods, whose results have to be combined and examined together.The purpose of the present review is to give, as much as possible, a general overview of the main analytical tools which can be employed for the characterization of drug-cyclodextrin inclusion complexes in solution, with emphasis on their respective potential merits, disadvantages and limits. Further, the applicability of each examined technique is illustrated and discussed by specific examples from literature. © 2014 Elsevier B.V. Source


Supuran C.T.,University of Florence
Bioorganic and Medicinal Chemistry Letters | Year: 2010

Carbonic anhydrases (CAs, EC 4.2.1.1) are widespread enzymes in all organisms, catalyzing CO2 hydration to bicarbonate and protons. Their inhibition is exploited clinically for decades for various classes of diuretics and systemically acting antiglaucoma agents. In the last years novel applications of CA inhibitors (CAIs) emerged, such as topically acting antiglaucoma, anticonvulsants, antiobesity, antipain, and antitumor agents/diagnostic tools. Such CAIs target diverse isozymes of the 13 catalytically active α-CA isoforms present in mammals. CAs belonging to the α-, β-, γ-, δ-, and ζ-families are found in many organisms all over the phylogenetic tree, and their inhibition was studied ultimately for some pathogenic protozoa (Plasmodium falciparum), fungi (Cryptococcus neoformans, Candida albicans, Candida glabrata, and Saccharomyces cerevisiae), and bacteria (Helicobacter pylori, Mycobacterium tuberculosis, and Brucella suis). Novel interesting chemotypes, in addition to the sulfonamide and sulfamate CAIs, such as coumarins, phenols, and fullerenes, were also reported recently, together with their mechanism of inhibition. This class of enzyme inhibitors shows promise for designing interesting pharmacological agents and understanding in detail protein-drug interactions at molecular level. © 2010 Elsevier Ltd. Source


Lagendijk R.L.,Technical University of Delft | Erkin Z.,University of California at Irvine | Barni M.,University of Florence
IEEE Signal Processing Magazine | Year: 2013

The solutions for processing encrypted data are designed using cryptographic primitives like homomorphic cryptosystems and secure multiparty computation (MPC). Research by the signal processing community has given rise to a variety of signal recording, storage, processing, analysis, retrieval, and display techniques. The design of a particular signal processing solution is commonly driven by objective or perceptual quality requirements on the processing result and by the tolerable computational complexity of the solution. The important privacy threats are associated with the provider of a particular service. The service provider might learn a lot about a user's preferences, past behavior, and biometrics when offering a service that depends on personal information. Biometric techniques, such as face recognition, are increasingly deployed as a means to unobtrusively verify the identity of a person. Digitized photos also allow the automatizing of identity checks at border crossings using face recognition. Source


Franchi A.,University of Florence
Head and Neck Pathology | Year: 2016

The sinonasal cavities host a wide variety of undifferentiated malignancies with round cell morphology, including neoplasms of epithelial, mesenchymal, neuroectodermal, and hematolymphoid lineage. The differential diagnosis may be difficult, especially in small biopsy material, due to overlapping morphology, but their correct classification is clinically relevant. The aim of this review is to provide practical guidelines for the differential diagnosis of these malignancies, with emphasis on recently described entities and special reference to the role of ancillary techniques. © 2016, Springer Science+Business Media New York. Source


Morfini M.,University of Florence
European Journal of Haematology | Year: 2014

The development of a new recombinant factor VIII was designed and implemented to answer a number of unmet needs of patients affected by hemophilia A. Turoctocog alfa is bioengineered in a specific Chinese hamster ovary clone to present translational and posttranslational characteristics (sulphation, glycosylation) biosimilar to natural circulating forms of FVIII, with the aim to devoid any minimal change which may impact immunogenicity and antigenicity of recombinant protein. Both producer cell line and media are maintained free of any animal or human plasma derivative. Downstream processes of purification are performed by five steps (immunoaffinity chromatography, ion-exchange chromatography, virus inactivation by means of solvent-detergent treatment and nanofiltration, and to end with gel filtration), to provide the best possible margin of safety from known and unknown infectious agents. Large clinical trials seem to confirm the expectations placed in Turoctocog alfa in terms of high quality and safety of recombinant FVIII toward the goal of overcoming actual and future challenges of hemophilia therapy. © 2014 John Wiley & Sons A/S. Source


Parri M.,Externautics | Chiarugi P.,University of Florence
Cell Communication and Signaling | Year: 2010

Rho GTPases represent a family of small GTP-binding proteins involved in cell cytoskeleton organization, migration, transcription, and proliferation. A common theme of these processes is a dynamic reorganization of actin cytoskeleton which has now emerged as a major switch control mainly carried out by Rho and Rac GTPase subfamilies, playing an acknowledged role in adaptation of cell motility to the microenvironment. Cells exhibit three distinct modes of migration when invading the 3 D environment. Collective motility leads to movement of cohorts of cells which maintain the adherens junctions and move by photolytic degradation of matrix barriers. Single cell mesenchymal-type movement is characterized by an elongated cellular shape and again requires extracellular proteolysis and integrin engagement. In addition it depends on Rac1-mediated cell polarization and lamellipodia formation. Conversely, in amoeboid movement cells have a rounded morphology, the movement is independent from proteases but requires high Rho GTPase to drive elevated levels of actomyosin contractility. These two modes of cell movement are interconvertible and several moving cells, including tumor cells, show an high degree of plasticity in motility styles shifting ad hoc between mesenchymal or amoeboid movements. This review will focus on the role of Rac and Rho small GTPases in cell motility and in the complex relationship driving the reciprocal control between Rac and Rho granting for the opportunistic motile behaviour of aggressive cancer cells. In addition we analyse the role of these GTPases in cancer progression and metastatic dissemination. © 2010 Parri and Chiarugi; licensee BioMed Central Ltd. Source


On the small island of Montecristo, in the Tuscan archipelago (Northern Tyrrhenian Sea, Italy), a wild goat population, Capra aegagrus Erxleben, 1777, of very ancient origin continues to display the phenotypic patterns of its wild ancestors, despite the fact that, in recent decades, questionable management by the authorities in charge of its protection may have favoured its radical impoverishment through randomized selective shootings and the illegal introduction of domestic individuals. In the period between 2010 and 2014, this population has been drastically reduced, if not almost entirely eliminated, following the implementation of the EEC LIFE Project+ Montecristo 2010, aimed at redefining the ecological equilibrium of the small Tyrrhenian island, mainly focused on the eradication of the local population of black rats, Rattus rattus (L., 1758) using poison pellets, with the primary purpose of protecting a single species of marine bird. © 2016 by De Gruyter 2016. Source


Pucci F.,University of Florence | Pucci F.,Jet Propulsion Laboratory | Velli M.,Jet Propulsion Laboratory
Astrophysical Journal Letters | Year: 2014

A strong indication that fast reconnection regimes exist within resistive magnetohydrodynamics was given by the proof that the Sweet-Parker current sheet, maintained by a flow field with an appropriate inflow-outflow structure, could be unstable to a reconnecting instability which grows without bound as the Lundquist number, S, tends to infinity. The requirement of a minimum value for S in order for the plasmoid instability to kick in does little to resolve the paradoxical nature of the result. Here we argue against the realizability of Sweet-Parker current sheets in astrophysical plasmas with very large S by showing that an "ideal" tearing mode takes over before current sheets reach such a thickness. While the Sweet-Parker current sheet thickness scales as S -1/2, the tearing mode becomes effectively ideal when a current sheet collapses to a thickness of the order of S -1/3, up to 100 times thicker than S -1/2, when (as happens in many astrophysical environments) S is as large as 1012. Such a sheet, while still diffusing over a very long time, is unstable to a tearing mode with multiple x-points: here we detail the characteristics of the instability and discuss how it may help solve the flare trigger problem and effectively initiate the turbulent disruption of the sheet. © 2014. The American Astronomical Society. All rights reserved. Source


Cavalieri D.,University of Florence
Wiley Interdisciplinary Reviews: Systems Biology and Medicine | Year: 2010

Saccharomyces cerevisiae is the most thoroughly studied eukaryote at the cellular, molecular, and genetic level. Recent boost in whole-genome sequencing, arraybased allelic variation mapping, and genome-wide transcriptional profiling have unprecedentedly advanced knowledge on cell biology and evolution of this organism. It is now possible to investigate how evolution shapes the functional architecture of yeast genomes and how this architecture relates to the evolution of the regulatory networks controlling the expression of genes that make up an organism. A survey of the information on genetic and whole-genome expression variations in yeast populations shows that a significant score of gene expression variation is dependent on genotype-by-environment interaction. In some cases, large trans effects are the result of mutations in the promoters of key master regulator genes. Yet trans-variation in environmental sensor proteins appears to explain the majority of the expression patterns differentiating strains in natural populations. The challenge is now to use this information to model how individual genetic polymorphisms interact in a condition-dependent fashion to produce phenotypic change. In this study, we show how fruitful application of systems biology to the progress of science and medicine requires the use of evolution as a lens to reconstruct the hierarchical structure of regulation of biological systems. The lessons learned in yeast can be of paramount importance in advancing the application of genomics and systems biology to emerging fields including personalized medicine. © 2009 John Wiley & Sons, Inc. Source


A great deal must still be learnt on the structural features of amyloid assemblies, particularly prefibrillar aggregates, and the relationship of the latter with amyloid cytotoxicity. Presently, it is recognized that the population of unstable, heterogeneous amyloid oligomers and protofibrils is mainly responsible for amyloid cytotoxicity. Conversely, mature fibrils are considered stable, harmless reservoirs of molecular species devoid of toxicity in the polymerized state. This view has been modified by recent reports showing that mature fibrils grown at different conditions can display different structural features and stabilities, possibly leading them to undergo disassembly with the leak of toxic oligomers. Fibril polymorphism is paralleled by oligomer polymorphism and both can be traced back to amyloid growth from differently destabilized monomers with distinct structural features at differing conditions. Recent research has started to unravel oligomer structural and biophysical features and the relationship between the latter and oligomer cytotoxicity. These data have led to the proposal that, together, both oligomer and membrane physical features determine the extent of oligomer-membrane interaction with the resulting disruption of membrane integrity and cell impairment. Such a view can help to explain the variable vulnerability of different cell types to the same amyloids and the lack of relationship between amyloid load and the severity of clinical symptoms. It also stresses the importance, for cell/tissue impairment, of the presence, in tissue, in addition to toxic oligomers, of fibrils conformers of reduced stability as a possible source of toxic oligomers, whose leakage can be favoured upon interaction with suitable surfaces or by other environmental conditions. Journal compilation © 2010 FEBS. No claim to original Italian government works. Source


Gandini S.,Italian National Cancer Institute | Massi D.,University of Florence | Mandala M.,Unit of Medical Oncology
Critical Reviews in Oncology/Hematology | Year: 2016

Background: Despite the success of immunotherapy directed at inhibiting of programmed death-1 (PD-1)/PD-ligand (L)1 signaling, it is not established whether PD-L1 expression correlates with the clinical response and outcome in different tumors. The present meta-analysis investigates whether the PD-L1 status, detected by immunohistochemistry, is associated with clinical response and mortality in patients treated with anti-PD-1/PD-L1 therapy. Methods: A systematic literature search and quantitative analysis were planned, conducted and reported following CONSORT and QUORUM checklists, up to December 2015, to identify clinical trials with information on cancer outcome by PD-L1 immunohistochemical expression in tumor tissues. We used random effects models to estimate Summary Objective Response Rates (SORRs) and Summary Odd Ratio (SOR) for the comparison of PD-L1 positive and negative patients. Results: We summarized 20 trials carried out in metastatic melanoma (MM), non-small cell lung cancer (NSCLC), and renal cell carcinoma (RCC) patients receiving anti-PD-1/PD-L1 antibodies (4230 MM, 1417 NSCLC and 312 RCC patients). Positive PD-L1 MM patients showed a significant decrease (53%) in the risk of mortality vs. negative cases with no heterogeneity. Furthermore, SORRs were 45% and 27% in PD-L1 positive and negative patients, respectively, and SOR indicates a significant difference in term of responses: 2.14 (95% CI: 1.65, 2.77), with low between-study heterogeneity (I2 = 35%). Furthermore, results from randomized clinical trials on MM showed that PD-L1 expression is significantly associated with greater clinical response rates to anti-PD1 treatments (SOR 1.89; 95%CI: 1.35, 2.64) but not to other treatments (SOR 0.96; 95%CI: 0.5, 1.87).In non-squamous NSCLC SORRs were 29% and 11% in PD-L1 positive and negative patients, respectively, and SOR indicates a significant difference between responses: 3.78 (1.54, 9.24), with no between-study heterogeneity. Squamous NSCLC and RCC did not show any significant difference in response according to the PD-L1 status. Conclusion: PD-L1 expression is significantly associated with mortality and clinical response to anti-PD-1/PD-L1 antibodies in MM patients and with clinical response in patients with non-squamous NSCLC. © 2016 Elsevier Ireland Ltd. Source


Karevski D.,CNRS Jean Lamour Institute | Popkov V.,University of Florence | Popkov V.,Max Planck Institute for Complex Systems | Schutz G.M.,Julich Research Center
Physical Review Letters | Year: 2013

We demonstrate that the exact nonequilibrium steady state of the one-dimensional Heisenberg XXZ spin chain driven by boundary Lindblad operators can be constructed explicitly with a matrix product ansatz for the nonequilibrium density matrix where the matrices satisfy a quadratic algebra. This algebra turns out to be related to the quantum algebra U q[SU(2)]. Coherent state techniques are introduced for the exact solution of the isotropic Heisenberg chain with and without quantum boundary fields and Lindblad terms that correspond to two different completely polarized boundary states. We show that this boundary twist leads to nonvanishing stationary currents of all spin components. Our results suggest that the matrix product ansatz can be extended to more general quantum systems kept far from equilibrium by Lindblad boundary terms. © 2013 American Physical Society. Source


Lehto J.,VTT Technical Research Center of Finland | Oasmaa A.,VTT Technical Research Center of Finland | Solantausta Y.,VTT Technical Research Center of Finland | Kyto M.,Metso Power Oy | Chiaramonti D.,University of Florence
Applied Energy | Year: 2014

Fast pyrolysis bio-oils are completely different from petroleum fuels and other bio-fuels available in the market, as regards both to their physical properties and chemical composition. When the unusual properties of these bio-oils are carefully taken into account in system and burner design, their combustion without a pilot flame or support fuel is possible on an industrial scale. The aim of the paper is to review the work done on combustion of fast pyrolysis bio-oils and highlight the latest and most important findings of its combustion from laboratory fundamentals to industrial scale. The main focus of the paper is on the bio-oil burner applications.In recent industrial scale bio-oil combustion tests, bio-oil has been found to be technically suitable for replacing heavy fuel oil in district heating. In addition, it has also been found out that limited possibilities for further lowering particulate emissions exist, since the majority of the particulates are typically incombustible matter. Curves for NO. x-emissions of fast pyrolysis bio-oil combustion for air-assisted atomization burners are presented in the paper.Current burner designs are quite sensitive to the changes in the quality of the bio-oil, which may cause problems in ignition, flame detection and flame stabilization. Therefore, in order to be able to create reliable bio-oil combustion systems that operate at high efficiency, bio-oil grades should be standardized for combustion applications. Careful quality control, combined with standards and specifications, all the way from feedstock harvesting through production to end-use is recommended in order to make sure that emission targets and limits in combustion applications are achieved. Also the cost-effectiveness of the total package is extremely important. © 2013 Elsevier Ltd. Source


New light is shed on the evolutionary affinities and generic diversity in Alysseae (Brassicaceae) by means of nuclear DNA sequences. Internal transcribed spacer analysis was used to assess the relationships and the monophyletic status of Aurinia and Ptilotrichum, when defined to include three poorly known taxa from southeast Europe. The alpine Ptilotrichum rupestre from central Appennines and its Balkan and Anatolian relative Ptilotrichum cyclocarpum clustered together as sister to Bornmuellera and Leptoplax, while their evident lack of affinity with the Asian type species of Ptilotrichum (Arabideae) leads to the definitive exclusion of the latter from the European flora. To accommodate the two species mentioned above, the so far neglected genus Phyllolepidum is accepted. The rare pontic endemic Aurinia uechtritziana resulted closely related to Berteroa and Galitzkya and is treated here as the sole member of Lepidotrichum. Comparative scanning electron micrograph analyses of trichome morphology are consistent with the phylogenetic evidence. The new combinations Phyllolepidum cyclocarpum and P. cyclocarpum subsp. pindicum are proposed, and a key for the identification of all European genera of the Alysseae is presented. © 2011 Societá Botanica Italiana. Source


Mariano P.M.,University of Florence
Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences | Year: 2016

This article introduces the collection of papers in this issue of the Philosophical Transactions of the Royal Society A and offers a perspective view on the description of the mechanics of material characterized by a prominent influence of small-scale phenomena on the gross mechanical behaviour. © 2016 The Author(s) Published by the Royal Society. All rights reserved. Source


To face the severe loss in biodiversity recorded in freshwater crayfish (Crustacea, Decapoda, Astacidea), there is an increasing awareness that the CBD's concept of the sustainable use of natural resources should be applied also to this large assemblage of species. This review paper will synthesize the several uses we make or have made of crayfish with the purpose of pinpointing where sustainability is desirable and feasible. Uses are here classified as direct (i.e. consumption and production) and indirect. The latter uses refer to the recreational, cultural, ethical, aesthetic, scientific and education values of crayfish. An additional indirect use regards the environmental key role this taxon plays. Several examples, mostly related to Europe, will be provided to illustrate the importance of crayfish to human societies, culture and history. The potential of assigning a non-use value to them will be finally discussed. © 2011 ONEMA. Source


Gualtieri G.,CNR Institute for Biometeorology | Zappitelli G.,University of Florence
International Journal of Green Energy | Year: 2015

Wind energy potential and turbulence characteristics on four mountain locations in Southern Italy have been analyzed based on a 2 year wind dataset composed of 10 min averaged records collected at 30 m. These sites have been identified as eligible areas to be exploited, being representative of the typical mid-altitude Apennine rural ridges running the length of the country, as well as quite easily accessed and free from any environmental constraint. Wind resource has been assessed through wind roses, wind speed frequency distributions, and Weibull probability density function. Turbulence intensity and gust factor variation by month, hour of day, and wind direction has been also assessed. In addition, the Counihan and Wieringa models to calculate turbulence intensity and gust factor, respectively, have been implemented and compared to observations. © 2015 Taylor & Francis Group, LLC. Source


Vannucchi A.M.,University of Florence
Current Hematologic Malignancy Reports | Year: 2010

The clinical course of the classic myeloproliferative neoplasms (MPNs) is burdened by an increased rate of cardiovascular events, which are the major cause of mortality. Age and history of thrombosis are the criteria used to stratify patients to the most appropriate therapeutic options. However, the mechanisms ultimately responsible for the increased thrombotic tendency have not yet been elucidated; abnormalities of blood cell count, neutrophil and platelet activation, and a state of hypercoagulability can all occur. Recurrent mutations in JAK2 or MPL have been described in MPNs and serve as disease markers. There is also evidence that a JAK2V617F mutant state represents an independent factor associated with thrombosis, and abnormalities of cell function attributable to JAK2V617F have been characterized. It is hoped that elucidation of the role mutant JAK2 plays in MPNs will improve our understanding of the pathophysiology of thrombosis and eventually result in improved patient treatment using molecularly targeted drugs. © 2010 Springer Science+Business Media, LLC. Source


D'Ambrisi A.,University of Florence | Focacci F.,University eCampus | Caporale A.,University of Cassino and Southern Lazio
Composite Structures | Year: 2013

Many existing railway bridges have been designed for live loads significantly lower than those produced by the present day train traffic. The most part of them are masonry arch bridges whose load carrying capacity needs to be verified with respect to the current traffic loads in order to define the necessary strengthening interventions. In the last two decades innovative strengthening techniques based on the use of polymeric and, more recently, cementitious fiber reinforced composite materials have been adopted. The design criteria adopted for the strengthening intervention with a poliparafenilenbenzobisoxazole (PBO) fiber reinforced cementitious matrix (FRCM) material of a railway bridge on the ancient Rome-Naples railway line are presented in the paper. The structure is constituted by unreinforced concrete barrel vaults supported by masonry piers. The bridge is analyzed both in its original and in its strengthened configuration following the approach of the collapse mechanisms. This approach allows to capture the strengthening effect of the PBO-FRCM material in terms of modification of the collapse mechanism and increase of the load collapse multiplier. The analyses evidence a lack of load carrying capacity of about 40% with respect to that required by current codes. The proposed strengthening intervention allows to overcome this lack. © 2013 Elsevier Ltd. Source


Carrara P.,University of Florence | Ferretti D.,University of Parma
Composites Part B: Engineering | Year: 2013

In the last years the strengthening of existing structures by means of externally glued fiber-reinforced polymer has become increasingly popular. This stimulated the study of new numerical and analytical models to understand the ultimate behavior of this reinforcement technique. Simultaneously, many experimental tests permitted to identify the main parameters involved in the failure process, which often occurs by debonding (i.e. with a crack propagating into the support underneath the reinforcement). Recent studies clarified the role of the coupling between normal and tangential stresses, pointing out that tensile stresses orthogonal to the bonding plane (peeling stresses) could be detrimental to the bond behavior. The effects of the peeling stresses are substantially related to a local reduction of the shear strength along the bonded length and to a variation of the failure mechanism. To investigate these issues, here a numerical model for debonding of FRP reinforcements is proposed by adding the effects of normal stresses to the classic pure shear cohesive zone model. The interaction between the reinforcement and the support is accounted for using an interface cohesive law, coupling tangential and normal behaviors. Finally, comparisons with experimental evidences and already validated models are presented to assess the capabilities of the proposed approach. © 2013 Elsevier Ltd. All rights reserved. Source


Carrara P.,University of Florence | Ferretti D.,University of Parma | Freddi F.,University of Parma
Composites Part B: Engineering | Year: 2013

Strengthening of ancient masonry constructions by means of composite materials is strongly influenced by the properties of the substrate where the reinforcement is applied. Therefore, ageing and damaging processes affecting the masonry can play an important role in the effectiveness of the reinforcement and failure behavior. Presented in this paper is the study of the bond behavior of different ancient clay bricks and masonry specimens reinforced by carbon fiber composite sheets. Obtained results of single-lap shear tests, particularly in terms of bond resistance, pull-out curve, detachment mechanism, strain and stress distributions, are discussed to show different peculiarities of the detachment process. Moreover, the fracture energy has been computed using experimental data and then compared with the expression proposed by the Italian design code. © 2012 Elsevier Ltd. All rights reserved. Source


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

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


Dei A.,University of Florence | Bernardini S.,Research Unit
Homeopathy | Year: 2015

This paper summarizes the results of investigations showing how molecular biological tools, such as DNA-microarrays, can provide useful suggestions about the behaviour of human organisms treated with microamounts of drugs or homeopathic medicines. The results reviewed here suggest firstly that the action of drugs is not quenched by ultra-high dilution and proceeds through modulation of gene expressions. The efficacy of drug solutions seems to be maintained in ultra-highly diluted preparations, a fact which constitutes a challenge to the dogma of quantization of matter.The second and more important result is that the different gene expression profiles of cell systems treated with the same drugs at different dilutions suggest the existence of hormetic mechanisms. The gene expression profiles of cells treated with copper(II) sulfate, Gelsemium sempervirens and Apis mellifica, are characterized by the same common denominator of the concentration-dependent inversion of gene expression, which can justify at a molecular level the concept of simile adopted in homeopathy.The main conclusion we draw from these results is that these procedures provide new kinds of information and a tool for disclosing the mechanisms involved in hormetic effects. The application of these effects to modern medicine may allow researchers to conceive unprecedented therapeutic applications or to optimize the currently used ones in the framework of a low-dose pharmacology based on a reliable experimental platform. © 2015 The Faculty of Homeopathy. Source


Monti S.M.,CNR Institute of Biostructure and Bioimaging | Supuran C.T.,University of Florence | De Simone G.,CNR Institute of Biostructure and Bioimaging
Current Medicinal Chemistry | Year: 2012

Carbonic anhydrase IX (CA IX) is a tumor associated protein, since it is highly expressed in a multitude of carcinomas, while it is present in a limited number of normal tissues. It is a multi-domain protein consisting of an N-terminal proteoglycan-like (PG) domain, a catalytic domain, a trans-membrane portion (TM) and an intracytoplasmatic (IC) segment. These domains have peculiar biochemical and physiological features. Among these, only the PG domain is unique among the CA family. This review focuses on the most recent molecular and catalytic features uncovered of this enzyme, the role of its different domains in tumor physiology, and its three dimensional structure which has recently been solved. In addition, we present recent advances in the development of antibodies and small inhibiting molecules able to target CA IX for diagnostic and therapeutic applications. © 2012 Bentham Science Publishers. Source


Angeli D.,Imperial College London | Angeli D.,University of Florence | Amrit R.,Royal Dutch Shell | Rawlings J.B.,University of Wisconsin - Madison
IEEE Transactions on Automatic Control | Year: 2012

Control performance and cost optimization can be conflicting goals in the management of industrial processes. Even when optimal or optimization-based control synthesis tools are applied, the economic cost associated with plant operation is often only optimized according to static criteria that pick, among all feasible steady states, those with minimal cost. In mathematical terms, an economic cost functional differs from stage costs commonly adopted in model predictive control (MPC) as it need not be minimal at its best equilibrium. This note collects and illustrates some recent advances in receding horizon optimization of nonlinear systems that allow the control designer to simultaneously and dynamically optimize transient and steady-state economic performance. In particular, we show that average performance of economic MPC is never worse than the optimal steady-state operation. We introduce a dissipation inequality and supply function that extend previous sufficient conditions for asymptotic stability of economic MPC. Dissipativity is also shown to be a sufficient condition for concluding that steady-state operation is optimal. We show how to modify an economic cost function so that steady-state operation is asymptotically stable when that feature is deemed desirable. Finally, for the case when steady-state operation is not optimal, we develop two modified MPC controllers that asymptotically guarantee 1) improved performance compared to optimal periodic control and 2) satisfaction of constraints on average values of states and inputs. © 2011 IEEE. Source


Volta U.,University of Bologna | Bardella M.T.,University of Milan | Calabro A.,University of Florence | Troncone R.,University of Naples Federico II | Corazza G.R.,University of Pavia
BMC Medicine | Year: 2014

Background: Non-celiac gluten sensitivity (NCGS) is still an undefined syndrome with several unsettled issues despite the increasing awareness of its existence. We carried out a prospective survey on NCGS in Italian centers for the diagnosis of gluten-related disorders, with the aim of defining the clinical picture of this new syndrome and to establish roughly its prevalence compared with celiac disease. Methods: From November 2012 to October 2013, 38 Italian centers (27 adult gastroenterology, 5 internal medicine, 4 pediatrics, and 2 allergy) participated in this prospective survey. A questionnaire was used in order to allow uniform and accurate collection of clinical, biochemical, and instrumental data. Results: In total, 486 patients with suspected NCGS were identified in this 1-year period. The female/male ratio was 5.4 to 1, and the mean age was 38 years (range 3-81). The clinical picture was characterized by combined gastrointestinal (abdominal pain, bloating, diarrhea and/or constipation, nausea, epigastric pain, gastroesophageal reflux, aphthous stomatitis) and systemic manifestations (tiredness, headache, fibromyalgia-like joint/muscle pain, leg or arm numbness, 'foggy mind,' dermatitis or skin rash, depression, anxiety, and anemia). In the large majority of patients, the time lapse between gluten ingestion and the appearance of symptoms varied from a few hours to 1 day. The most frequent associated disorders were irritable bowel syndrome (47%), food intolerance (35%) and IgE-mediated allergy (22%). An associated autoimmune disease was detected in 14% of cases. Regarding family history, 18% of our patients had a relative with celiac disease, but no correlation was found between NCGS and positivity for HLA-DQ2/-DQ8. IgG anti-gliadin antibodies were detected in 25% of the patients tested. Only a proportion of patients underwent duodenal biopsy; for those that did, the biopsies showed normal intestinal mucosa (69%) or mild increase in intraepithelial lymphocytes (31%). The ratio between suspected NCGS and new CD diagnoses, assessed in 28 of the participating centers, was 1.15 to 1. Conclusions: This prospective survey shows that NCGS has a strong correlation with female gender and adult age. Based on our results, the prevalence of NCGS seems to be only slightly higher than that of celiac disease. Please see related article http://www.biomedcentral.com/1741-7015/12/86. © 2014 Volta et al.; licensee BioMed Central Ltd. Source


Barzagli F.,CNR Institute of Neuroscience | Mani F.,CNR Institute of Neuroscience | Mani F.,University of Florence | Peruzzini M.,CNR Institute of Neuroscience
International Journal of Greenhouse Gas Control | Year: 2013

In the present study, an efficient process for CO2 capture using some AMP-alkanolamine blends, namely DEA, MDEA, MMEA, DIPA, in non-aqueous solvents has been described. The solvents used are mixtures of ethylene glycol or 1,2-propandiol with either methanol or ethanol. Additionally, either pure 1-propanol or diethylene glycol monomethyl ether have been also employed. Throughout the whole set of experiments, the amine solutions were continuously circulated in a closed cycle between the absorber (set at 20°C) and the desorber (set at 65, 70, 75, 80°C). The CO2 absorption efficiency at equilibrium is in the range 73.1-95.9%. The carbon containing species in the amine-CO2-alcohol equilibria were analyzed by 13C NMR spectroscopy showing that they originate from alcohol and/or amine carboxylation. The AMP-DEA-1-propanol-CO2 system gives a solid compound that has been identified as the carbamate derivative of AMP, [(AMPH)(AMPCO2)], from its 13C solid state NMR spectrum and confirmed by single crystal X-ray structure determination. [(AMPH)(AMPCO2)] instantaneously dissolves in methanol, ethanol and ethylene glycol affording the respective monoalkyl carbonate. The lower stripping temperature of the studied absorbents offers several potential advantages with respect to conventional aqueous solutions of the same alkanolamines, yet preserving comparable efficiency. © 2013 Elsevier Ltd. Source


Focardi M.,University of Florence
Mathematical Methods in the Applied Sciences | Year: 2012

De Giorgi's Γ-convergence is a variational theory modelled upon the convergence of families of (perturbed) minimum problems and of the corresponding minimizers. In these notes, after reviewing briefly the basic theory and accounting for some recent new insights, we discuss three examples of static mechanical models, which can be analysed by means of Γ-convergence arguments. Copyright © 2012 John Wiley & Sons, Ltd. Source


Valensin D.,University of Siena | Gabbiani C.,University of Pisa | Messori L.,University of Florence
Coordination Chemistry Reviews | Year: 2012

Alzheimer's disease (AD) is a widespread neurodegenerative disease with a very high medical, social and economic burden. The etiopathogenesis of AD is still largely obscure; however, there is growing evidence that aggregation of β-amyloid peptides (Aβ) into a variety of supramolecular structures is critically involved in its insurgence and progression (the so called " amyloid cascade hypothesis" ). Recent results point to oligomeric Aβ aggregates rather than mature Aβ fibrils as the major culprit for neurotoxicity; details of the inherent aggregation processes are being progressively clarified. In view of these achievements, early stages of Aβ aggregation are considered today a realistic " druggable" target for the development of new anti-AD agents. Notably, a variety of organic compounds that are able to inhibit effectively Aβ aggregation represent promising drug candidates. Metal based compounds capable of interacting with the N-terminal metal binding site of amyloid peptides might similarly contrast metal-induced Aβ aggregation and serve as potential drugs for AD. In a recent pioneering study Barnham et al. showed that platinum(II) phenanthroline complexes strongly inhibit Aβ oligomerisation and attenuate its neurotoxicity in vitro. A number of additional examples involving metal complexes as inhibitors of Aβ aggregation were reported afterward. On the ground of those results it may be proposed that metal based compounds constitute today a suitable and rich source for novel anti-AD agents. The potential and the limits of this therapeutic option are comprehensively and critically discussed as well as the perspectives for future research. © 2012 Elsevier B.V. Source


Noskov B.A.,Saint Petersburg State University | Loglio G.,MPI fur Kolloid und Grenzflachenforschung | Miller R.,University of Florence
Advances in Colloid and Interface Science | Year: 2011

Recent application of the methods of surface dilational rheology to solutions of the complexes between synthetic polyelectrolytes and oppositely charged surfactants (PSC) gave a possibility to determine some steps of the adsorption layer formation and to discover an abrupt transition connected with the formation of microaggregates at the liquid surface. The kinetic dependencies of the dynamic surface elasticity are always monotonous at low surfactant concentrations but can have one or two local maxima in the range beyond the critical aggregation concentration. The first maximum is accompanied by the generation of higher harmonics of induced surface tension oscillations and caused by heterogeneities in the adsorption layer. The formation of a multilayered structure at the surface for some systems leads to the second maximum in the dynamic surface elasticity. The hydrophobicity and charge density of a polymer chain influence strongly the surface structure, resulting in a variety of dynamic surface properties of PSC solutions. Optical methods and atomic force microscopy give additional information for the systems under consideration. Experimental results and existing theoretical frameworks are reviewed with emphasis on the general features of all studied PSC systems. © 2011 Elsevier B.V. All rights reserved. Source


Supuran C.T.,University of Florence
Expert Review of Neurotherapeutics | Year: 2016

Introduction: Neuropathic pain affects up to 8% of the population with few therapeutic options for its management. No specific drugs are approved for its treatment. Areas covered: Recent advances in understanding the pathological mechanisms of this syndrome and the biochemical/pharmacological characterization of novel drug targets, evidenced carbonic anhydrase (CA, EC 4.2.1.1) inhibition as a new approach for designing antineuropathic pain agents. Expert commentary: Peripheral nerve injury negatively influences spinal γ-aminobutyric (GABA)-ergic networks via a reduction in the neuron-specific potassium-chloride (K+-Cl−) cotransporter (KCC2), which leads to neuropathic allodynia. CA inhibitors (CAIs) reduce the bicarbonate-dependent depolarization of GABAA receptors, showing analgesic effects. Novel classes of selective sulfonamide CA II/VII inhibitors showed highly improved efficacy in animal models of neuropathic pain, compared to acetazolamide, offering the basis for the development of specific therapies of this syndrome based on selective CA isoforms inhibition. © 2016 Informa UK Limited, trading as Taylor & Francis Group. Source


Radi E.,University of Modena and Reggio Emilia | Mariano P.M.,University of Florence
Proceedings of the Royal Society A: Mathematical, Physical and Engineering Sciences | Year: 2011

We analyse the steady propagation at constant speed, lower than the shear wave-speed, of a straight dislocation in an unbounded elastic quasi-crystal with five-fold symmetry. We discuss only the ideal elastic behaviour, neglecting the dissipation associated with the atomic rearrangements. Under these conditions, we provide the expressions of phonon and phason fields in closed form. Both phonon and phason stresses appear to be singular near to the dislocation core. We also find the explicit expression of the energy per unit length around a moving dislocation. © 2011 The Royal Society. Source


Time can be considered the fourth dimension in dento-facial orthopedics. Treatment timing can play a significant role in the outcomes of treatment aimed to produce an orthopedic effect in the craniofacial structures. The results of methodologically-sound cephalometric studies of both the past and the recent history of orthodontics clearly indicate that optimal treatment timing for Class II skeletal disharmony with a functional appliance (e.g. twin block) is during or slightly after the peak in mandibular growth as revealed by a reliable biologic indicator of individual skeletal maturity such as the cervical vertebral maturation method. © EDP Sciences, SFODF, 2010. Source


Camporesi M.,University of Florence
International journal of paediatric dentistry / the British Paedodontic Society [and] the International Association of Dentistry for Children | Year: 2010

To evaluate the prevalence of dental abnormalities of the primary and permanent maxillary dentitions in children affected by unilateral (UCLP) and bilateral (BCLP) cleft of the lip and palate. One hundred and fifty-six Caucasian patients (64 females and 92 males) affected by non-syndromic UCLP or BLCP were selected. A control sample of 1000 subjects (482 males and 518 females) without CLP was selected. All comparisons were carried out by means of z-tests on proportions. The prevalence rate for missing primary lateral incisors in UCLP subjects was 8.1% and it was 27.9% for the permanent lateral incisors. In BLCP subjects, the prevalence rates were 17% for the primary lateral incisors and 60% for the permanent lateral incisors. The second premolar was absent in 5.4% of UCLP subjects and in 8.8% in the BCLP sample. The statistical analysis revealed significant differences for the prevalence rates of all dental anomalies compared with the control group except for second premolar agenesis. In both UCLP and BCLP subjects the most prevalent missing teeth were the lateral incisors. The dental anomalies occurred predominantly in the cleft area, thus suggesting that the effect of the cleft disturbance is more local than general on the dentition. © 2010 The Authors. International Journal of Paediatric Dentistry © 2010 BSPD, IAPD and Blackwell Publishing Ltd. Source


Alessandri A.,Genova Engineering, LLC. | Baglietto M.,niversity of Genoa | Battistelli G.,University of Florence
Automatica | Year: 2010

State estimation is addressed for a class of discrete-time systems that may switch among different modes taken from a finite set. The system and measurement equations of each mode are assumed to be linear and perfectly known, but the current mode of the system is unknown. Moreover, additive, independent, normally distributed noises are assumed to affect the dynamics and the measurements. First, relying on a well-established notion of mode observability developed "ad hoc" for switching systems, an approach to system mode estimation based on a maximum-likelihood criterion is proposed. Second, such a mode estimator is embedded in a Kalman filtering framework to estimate the continuous state. Under the unique assumption of mode observability, stability properties in terms of boundedness of the mean square estimation error are proved for the resulting filter. Simulation results showing the effectiveness of the proposed filter are reported. © 2010 Elsevier Ltd. All rights reserved. Source


Multiple sclerosis is an autoimmune inflammatory demyelinating disease of the central nervous system and represents one of the most common causes of chronic neurologic disability in young adults. All the current disease-modifying drugs are administered parenterally, and can be associated with varying degrees of injection site or infusion-related reactions. Together with other side effects, the parenteral route of administration is one of the key factors affecting adherence to therapy in multiple sclerosis. Fingolimod (FTY720) is an immunomodulator that acts on sphingosine 1-phosphate (S1P) receptors and is the first oral drug approved by the US Food and Drug Administration for the treatment of relapsing-remitting multiple sclerosis. Downmodulation of S1P receptor type 1 (S1P1) slows the egress of lymphocytes from lymph nodes and recirculation to the central nervous system, reduces astrogliosis, and inhibits angiogenesis during chronic neuroinflammation. Fingolimod also regulates the migration of B cells and dendritic cells, and enhances endothelial barrier function. Results from Phase II and III clinical trials provide robust evidence of the efficacy of fingolimod in relapsing-remitting multiple sclerosis. While some caution should be exercised in terms of safety issues, the introduction of fingolimod represents a great advance in the treatment of relapsing-remitting multiple sclerosis. The pharmacologic data on fingolimod and its efficacy and safety in multiple sclerosis are reviewed in this paper. © 2011 Portaccio. Source


Domenichini F.,University of Florence
Journal of Fluid Mechanics | Year: 2011

The vortex formation behind an orifice is a widely investigated phenomenon, which has been recently studied in several problems of biological relevance. In the case of a circular opening, several works in the literature have shown the existence of a limiting process for vortex ring formation that leads to the concept of critical formation time. In the different geometric arrangement of a planar flow, which corresponds to an opening with straight edges, it has been recently outlined that such a concept does not apply. This discrepancy opens the question about the presence of limiting conditions when apertures with irregular shape are considered. In this paper, the three-dimensional vortex formation due to the impulsively started flow through slender openings is studied with the numerical solution of the Navier'Stokes equations, at values of the Reynolds number that allow the comparison with previous two-dimensional findings. The analysis of the three-dimensional results reveals the two-dimensional nature of the early vortex formation phase. During an intermediate phase, the flow evolution appears to be driven by the local curvature of the orifice edge, and the time scale of the phenomena exhibits a surprisingly good agreement with those found in axisymmetric problems with the same curvature. The long-time evolution shows the complete development of the three-dimensional vorticity dynamics, which does not allow the definition of further unifying concepts. © 2011 Cambridge University Press. Source


Martelli F.,University of Florence
Journal of Near Infrared Spectroscopy | Year: 2012

In this paper, the theories commonly used for the study of photon migration through biological tissues and for biomedical applications are reviewed. The concepts of absorption and scattering are introduced with particular reference to biological tissues and to the near infrared wavelength range. In particular, the basic definitions of optical properties and their statistical meaning, the Beer-Lambert law, the modified Beer-Lambert law, the radiative transfer equation and the diffusion equation are examined and described. The main frame of the theories is provided in the time domain, in the continuous wave domain and in the frequency domain and the principal solutions of the radiative transfer equation and of the diffusion equation are reviewed. The propagation of photons through biological tissue can be accurately described with solutions of the radiative transfer equation, while solutions of the diffusion equation are subjected to intrinsic approximations that limit their range of validity. Whenever the solutions of the diffusion equation provide a suffciently accurate description of photon migration, we have a diffusive regime of propagation and the media where this happens can be denoted as diffusive as well. A rule to identify the diffusive regime of propagation has been provided. For many biological tissues, the diffusive regime of propagation can be established, even near the source, provided the photons have travelled trajectories with lengths greater than four times the transport mean free path. © IM Publications LLP 2012. Source


Colli S.,AGMIN | Mariano P.M.,University of Florence
Physics Letters, Section A: General, Atomic and Solid State Physics | Year: 2011

In static setting, the standard formulation of quasicrystal linear elasticity, obtained neglecting phason diffusion in addition to inertia, implies - it is shown here - non-physical results for common choices of the constitutive tensors. Two examples of this type are presented: they involve a 2D-quasicrystal filling half-plane, subjected to in-plane concentrated forces. © 2011 Elsevier B.V. All rights reserved. Source


Pratesi S.,University of Florence
The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians | Year: 2012

to monitor the incidence of cases of kernicterus and severe hyperbilirubinemia in Italy over time, and to describe each single registered event with sufficient information in order to identify one or more possible failures in the management of jaundice. the Task Force on hyperbilirubinemia of the Italian Society of Neonatology will draw up national guidelines for management of jaundice in the newborn and a national registry of kernicterus and hyperbilirubinemia for newborns with a gestational age greater than 34. the choice of the inclusion criteria for the registry and the minimum information necessary to describe each single event registered are reported and will be discussed at the national congress of the Italian Society of Neonatology next October 2012. Source


Cassioli A.,University of Florence | Locatelli M.,University of Parma
Computers and Operations Research | Year: 2011

In this paper we propose a heuristic approach for the problem of packing equal rectangles within a convex region. The approach is based on an Iterated Local Search scheme, in which the key step is the perturbation move. Different perturbation moves, both combinatorial and continuous ones, are proposed and compared through extensive computational experiments on a set of test instances. The overall results are quite encouraging. © 2010 Elsevier Ltd. All rights reserved. Source


Messori L.,University of Florence | Merlino A.,CNR Institute of Neuroscience | Merlino A.,University of Naples Federico II
Dalton Transactions | Year: 2014

A crystallographic study of the adduct formed between hen egg white lysozyme (HEWL) and NAMI-A, an established ruthenium(iii) anticancer agent in clinical trials, is presented here. The X-ray structure reveals that NAMI-A coordinates the protein, as a naked ruthenium ion, at two distinct sites (namely Asp101 or Asp119) after releasing all its original ligands (DMSO, imidazole and Cl-). Structural data of the HEWL/NAMI-A adduct are compared with those previously obtained for the HEWL adduct of AziRu, a NAMI-A analogue bearing a pyridine in place of imidazole. The present results further support the view that NAMI-A exerts its biological effects acting as a classical "prodrug" first undergoing activation and then causing extensive metalation of relevant protein targets. It is also proposed that the original Ru-ligands, although absent in the final adduct, play a major role in directing the ruthenium center to its ultimate anchoring site on the protein surface. This journal is © the Partner Organisations 2014. Source


Bateni S.M.,Massachusetts Institute of Technology | Entekhabi D.,Massachusetts Institute of Technology | Castelli F.,University of Florence
Water Resources Research | Year: 2013

A variational data assimilation model is developed to estimate surface energy fluxes from remotely sensed land surface temperature (LST). Components of the surface energy balance (sensible, latent, and ground heat fluxes) have different degrees of efficiency in dissipating available energy. LST is the state variable of the surface energy balance (SEB). Land surface models that capture the exchange and storage of energy in the soil and vegetation media use LST as a prognostic variable. Sequences of LST measurements implicitly contain information on partitioning of available energy among the components of SEB. In this study, we focus on the estimation of the sum of the turbulent fluxes as well as the partitioning among them. Two dimensionless parameters are used to characterize the sum and the partitioning. Using LST observations from a constellation of satellites, these parameters are mapped over a large region. The remotely sensed LST is assimilated to the heat diffusion equation within the SEB framework. In addition, a model error term is added to the SEB equation such that the variational data assimilation scheme includes model uncertainty as well as observation error. The framework is tested over the Southern Great Plains region. The mapped results of the surface evaporation estimation are used to study the surface control on evaporation. Independent mapped soil moisture estimates from an airborne microwave campaign are used. The dependence of the evaporation control-soil moisture relationship on vegetation cover and plant functional types over large regions is examined in this first and exploratory study. © 2013. American Geophysical Union. All Rights Reserved. Source


Baccini M.,University of Florence | Carreras G.,Cancer Prevention and Research Institutte ISPO
Substance Use and Misuse | Year: 2014

This paper describes the methods used to investigate variations in total alcoholic beverage consumption as related to selected control intervention policies and other socioeconomic factors (unplanned factors) within 12 European countries involved in the AMPHORA project. The analysis presented several critical points: presence of missing values, strong correlation among the unplanned factors, long-term waves or trends in both the time series of alcohol consumption and the time series of the main explanatory variables. These difficulties were addressed by implementing a multiple imputation procedure for filling in missing values, then specifying for each country a multiple regression model which accounted for time trend, policy measures and a limited set of unplanned factors, selected in advance on the basis of sociological and statistical considerations are addressed. This approach allowed estimating the "net" effect of the selected control policies on alcohol consumption, but not the association between each unplanned factor and the outcome. © 2014 Informa Healthcare USA, Inc. Source


Mundici D.,University of Florence
Journal of Logic and Computation | Year: 2011

By an MV-set, we understand a pair (E,X) where X is a set of unit vectors in a Hilbert space E such that the linear span of X is dense in E, and 〈v,w〉 ≥ 0 for all v,w ∈ X. The scalar product 〈v,w〉 ∈ [0,1] is the identity degree of v and w. Building on MV-sets and continuous functions and relations defined on them, we construct a compact [0,1]-valued first-order Łukasiewicz logic, whose set of unsatisfiable formulas is recursively enumerable. In the particular case when X is an orthonormal basis of E we recover classical Skolem first-order logic with identity, constants, functions and relations. Our main tools are the Kolmogorov dilation theorem for positive semidefinite kernels, and the TarskiSeidenberg decision method for elementary algebra and geometry. © The Author, 2009. Published by Oxford University Press. All rights reserved. Source


Bencini A.,University of Florence | Lippolis V.,University of Cagliari
Coordination Chemistry Reviews | Year: 2010

This review will cover the developments in the chemistry of phenanthroline-based ligands in the last 10-15 years. 1,10-Phenanthroline (phen) is a classic ligand in coordination chemistry, which couples versatility in metal ion binding with peculiar properties of its complexes. For instance, metal complexes with phenanthroline can be featured by an intense luminescence or can interact with DNA in an intercalative fashion inducing, in some cases, DNA cleavage. For this reason a number of phenanthroline-containing ligands has been recently synthesized by inserting phenanthroline within open-chain or macrocyclic backbone, in order to develop new molecular chemosensors for metal cations and anions, ionophores as well as new intercalating agents for polynucleotides. Furthermore, phenanthroline is rigid and its insertion within cyclic or acyclic structures can impart to the resulting ligand a high degree of pre-organization, affording selective complexing agents. This review will discuss on the coordination, luminescence and intercalating and/or DNA cleaving properties as well as on analytical applications of metal complexes with phenanthroline-based ligands. Particular attention will be devoted to macrocyclic receptors or open-chain ligands that, beside the phenanthroline nitrogen atoms, contain other donor atoms able to interact with the metal cations or anions. © 2010 Elsevier B.V. Source


Sacchelli S.,University of Florence | De Meo I.,Italian Agricultural Research Council | Paletto A.,Italian Agricultural Research Council
Applied Energy | Year: 2013

Environmental assessment needs of Decision Support Systems (DSSs) able to consider several aspects in a unique analysis framework. The complexity of interaction among ecological, economic and political variables and a widespread lack of data availability lead to difficulty in bringing together large scale analysis and local planning systems. This loop can be solved through flexible tools able to relate large scale environmental assessment with medium and small scale DSS, useful for local decisions makers.The present research aims at creating a spatial model, based on Geographic Information Systems (GISs), capable to quantify the potential amount of woody biomass from forest sector at several evaluation scales, to consider the theoretical impact of biomass removal on forest multifunctionality and to estimate the potential trade-off between forest functions in case of bioenergy chain development.The model is carried out basing on multifunctionality aspects and their potential relationship with biomass energy production. The forest functions considered in the model are: (i) soil and water protection, (ii) biodiversity and habitat conservation, (iii) fire risk prevention, (iv) tourist and recreational function and (v) economic evaluation related to timber and bioenergy processing. The structure of the model is based on sub-models that enable biomass chain analysis from large scale to small scale. Large scale analysis is developed using forest yield data, protected areas and main and forest roads localization, geomorphological variables and fire risk maps. An increase of input data (economic and logistic variables) is requested for medium and small scale analysis. The model is tested from national (Italy) to regional (Tuscany region in Central Italy) and provincial scale (province of Trento in North-Eastern Italian Alps). Results stress how the model can be able to depict territorial differences in several contexts and to consider respective influence on estimation of biomass availability. Finally, the Compromise Programming (CP) methodology permits defining the optimal quantity of residues removal in different compartments according to priority forest function. © 2012 Elsevier Ltd. Source


Santi A.,University of Florence
Journal of Geometry and Physics | Year: 2010

Let M0 = G0 / H be a (n + 1)-dimensional Cahen-Wallach Lorentzian symmetric space associated with a symmetric decomposition g0 = h + m and let S (M0) be the spin bundle defined by the spin representation ρ : H → GLR (S) of the stabilizer H. This article studies the superizations of M0, i.e. its extensions to a homogeneous supermanifold M = G / H whose sheaf of superfunctions is isomorphic to Λ (S* (M0)). Here, G is a Lie supergroup which is the superization of the Lie group G0 associated with a certain extension of the Lie algebra g0 to a Lie superalgebra g = gover(0, -) + gover(1, -) = g0 + S, via the Kostant construction. The construction of the superization g consists of two steps: extending the spin representation ρ : h → g lR (S) to a representation ρ : g0 → g lR (S) and constructing appropriate ρ (g0)-equivariant bilinear maps on S. Since the Heisenberg algebra h e i s is a codimension one ideal of the Cahen-Wallach Lie algebra g0, first we describe spin representations of h e i s and then determine their extensions to g0. There are two large classes of spin representations of h e i s and g0: the zero charge and the non-zero charge ones. The description strongly depends on the dimension n + 1 (mod 8). Some general results about superizations g = gover(0, -) + gover(1, -) are stated and examples are constructed. © 2009 Elsevier B.V. All rights reserved. Source


Fortuny C.,University of Florence
Pediatric Infectious Disease Journal | Year: 2015

Worldwide, the benefits of combined antiretroviral therapy in morbidity and mortality due to perinatally-acquired human immunodeficiency virus infection are beyond question and outweigh the toxicity these drugs have been associated with in HIV-infected children and adolescents to date. In puberty, abnormal body fat distribution is stigmatizating and leads to low adherence to antiretroviral treatment. The other metabolic co-morbidities (mitochondrial toxicity, dyslipidemias, insulin resistance and low bone mineral density) and renal toxicity, albeit non-symptomatic in most children, are increasingly being reported and potentially put this population at risk for early cardiovascular or cerebrovascular atherosclerotic disease, diabetes, pathologic fractures or premature renal failure in the 3 and 4 decades of life. Evidence from available studies is limited because of methodological limitations and also because of several HIV-unrelated factors influencing, to some degree, the development of these conditions. Current recommendations for the prevention, diagnosis, monitoring and treatment of metabolic and renal adverse effects in HIV-children and adolescents are based on adult studies, observational pediatric studies and experts’ consensus. Healthy lifestyle habits (regarding diet, exercise and refraining from toxic substances) and wise use of antiretroviral options are the only preventive tools for the majority of patients. Should abnormal findings arise, switches in one or more antiretroviral drugs have proved useful. Specific therapies are also available for some of these co-morbidities, although the experience in the pediatric age is still very scarce. We aim to summarize the epidemiological, clinical and therapeutic aspects of metabolic and renal adverse effects in vertically-HIV-infected children and adolescents. © 2015 by Lippincott Williams & Wilkins, Inc. Source


Maddio S.,University of Florence
Progress in Electromagnetics Research Letters | Year: 2015

This paper presents the design and development of a circularly polarized microstrip antenna array for C-band application. The proposed antenna has a convenient trade-off between bandwidth and dimension. The array design is based on the sequential phase arrangement (SPA) of 2×2 non-identical disc-based patch elements, operating in modal degeneration. Exploiting the properties of the SPA, capable of forcing CP even when operating on linear polarized elements, each disc is independently detuned to operate on non-perfectly overlapping bands. When properly fed by a sequential phase network (SPN), the set of four discs seamlessly covers the wide cumulative bandwidth which is the combination of the four sub-channels. To verify the design, a single-layer via-less array was fabricated in a compact printed square board of side 40mm, meaning a surface of 0.64λ2 0 at the center frequency of 6.0GHz, assembling the elements with a compact space-filling SPN. Measurements show a wide 10 dB return loss bandwidth of 28.5%, a 3 dB axial ratio (AR) bandwidth exceeding 1 GHz, and a realized gain ranging from 4.1 dB to 7.25 dB inside the AR bandwidth. The global bandwidth of the proposed array, almost coincident with the AR bandwidth, is 17.0%. © 2015, Electromagnetics Academy. All Rights Reserved. Source


Coccia M.E.,University of Florence | Rizzello F.,University of Rome La Sapienza
Annals of the New York Academy of Sciences | Year: 2011

Modern imaging techniques allow for the noninvasive diagnosis of endometriosis. Preoperative staging of pelvic endometriosis helps the gynecologist plan therapy and offer a prognosis to patients. The challenge of creating a satisfactory classification of endometriosis remains. The ability of the current classification schemes to predict pregnancy outcome, or aid in the management of pelvic pain, is recognized to be inadequate. The study of deeply infiltrating endometriosis and adenomyosis is greatly hampered by a lack of clear terminology and the absence of a consensus classification of the lesions. A reviewed consensus classification of endometriosis in general, with a more detailed consideration on deep endometriosis, is urgently required. We suggest a new staging system for deep, infiltrating endometriosis based on ultrasonographic findings. Prospective data collection and review in large centers may provide a larger clinical base from which to derive empirical point scores and breakpoints in the classification scheme. © 2011 New York Academy of Sciences. Source


Minguzzi E.,University of Florence
Communications in Mathematical Physics | Year: 2010

Every time function on spacetime gives a (continuous) total preordering of the spacetime events which respects the notion of causal precedence. The problem of the existence of a (semi-)time function on spacetime and the problem of recovering the causal structure starting from the set of time functions are studied. It is pointed out that these problems have an analog in the field of microeconomics known as utility theory. In a chronological spacetime the semi-time functions correspond to the utilities for the chronological relation, while in a K-causal (stably causal) spacetime the time functions correspond to the utilities for the K+ relation (Seifert's relation). By exploiting this analogy, we are able to import some mathematical results, most notably Peleg's and Levin's theorems, to the spacetime framework. As a consequence, we prove that a K-causal (i. e. stably causal) spacetime admits a time function and that the time or temporal functions can be used to recover the K+ (or Seifert) relation which indeed turns out to be the intersection of the time or temporal orderings. This result tells us in which circumstances it is possible to recover the chronological or causal relation starting from the set of time or temporal functions allowed by the spacetime. Moreover, it is proved that a chronological spacetime in which the closure of the causal relation is transitive (for instance a reflective spacetime) admits a semi-time function. Along the way a new proof avoiding smoothing techniques is given that the existence of a time function implies stable causality, and a new short proof of the equivalence between K-causality and stable causality is given which takes advantage of Levin's theorem and smoothing techniques. © 2010 Springer-Verlag. Source


Piccini L.,University of Florence | Iandelli N.,IUAV University of Venice
Earth Surface Processes and Landforms | Year: 2011

The St. Paul karst (Palawan, Philippines) is a tropical coastal karst, consisting of towers, cones, huge depressions and large caves. This area hosts the Puerto Princesa Subterranean River (PPSR, 24km long), whose main entrance is a large spring along the coast and which is one of the largest cave complexes in eastern Asia. A geomorphological study performed by several field surveys and a morphometric analysis of the digital terrain model (DTM) and 3D cave models, allowed formulation of a first evolutionary framework of the karst system. The DTM was extracted from maps and aerial photographs in order to find different generations of 'relict' landforms, through the morphometric analysis of topographic surface and karst landforms. Several features suggest a long and multi-stage evolution of the karst, whose age ranges from Pliocene to present. The southern and northern sectors of the area differ in their altimetric distribution of caves. In the southern sector, some large caves lie between 300 and 400masl and were part of an ancient system that developed at the base level of a past river network. In the northern sector, some mainly vadose caves occur, with a phreatic level at 120-130masl. An important phase of base-level cave development is well documented in the inactive passages of PPSR at 50-80masl. Morphological features, such as horizontal solution passages and terraced deposits, suggest a phase of stillstand of the base level, which is recorded in the topography as low-relief surfaces at 40-50masl. The age of this phase is probably Early Pleistocene, on the basis of assumed uplift rates. The more recent caves are still active, being located at the current sea level, but they show more than one cycle of flooding and dewatering (with calcite deposition). In the PPSR, several morphologic features, such as two main water level notches at +12·4 and +7·7masl and terraced alluvial deposits, suggest that the lower and active level passed through more than two high-stands of sea level and so it could have formed throughout most of the Middle-Late Pleistocene. © 2010 John Wiley & Sons, Ltd. Source


Conti C.,University of Florence | Romani L.,University of Milan Bicocca
BIT Numerical Mathematics | Year: 2010

A general affine combination of B-spline subdivision masks is here considered with the aim of generating new subdivision schemes with enhanced properties. This will be done using either stationary or non-stationary coefficients combining both B-splines and their non-stationary counterparts. © Springer Science + Business Media B.V. 2010. Source


Spadea L.,University of LAquila | Mencucci R.,University of Florence
Clinical Ophthalmology | Year: 2012

Background: The purpose of this paper was to report the results of transepithelial corneal collagen cross-linking (CXL) with modified riboflavin and ultraviolet A irradiation in patients affected by keratoconus, each with thinnest pachymetry values of less than 400 μm (with epithelium) and not treatable using standard de-epithelialization techniques. Methods: Sixteen patients affected by progressive keratoconus with thinnest pachymetry values ranging from 331 μm to 389 μm underwent transepithelial CXL in one eye using a riboflavin 0.1% solution in 15% Dextran T500 containing ethylenediamine tetra-acetic acid 0.01% and trometamol to enhance epithelial penetration. The patients underwent complete ophthalmological examination, including endothelial cell density measurements and computerized videokeratography, before CXL and at one day, one week, and one, 6, and 12 months thereafter. Results: Epithelial healing was complete in all patients after one day of use of a soft bandage contact lens. No side effects or damage to the limbal region was observed during the follow-up period. All patients showed slightly improved uncorrected and spectacle-corrected visual acuity; keratometric astigmatism showed reductions (up to 5.3 D) and apical ectasia power decreased (Kmax values reduced up to 4.3 D). Endothelial cell density was unchanged. Conclusion: Application of transepithelial CXL using riboflavin with substances added to enhance epithelial permeability was safe, seemed to be moderately effective in keratoconic eyes with ultrathin corneas, and applications of the procedure could be extended to patients with advanced keratoconus. © 2012 Simpson et al. Source


Esposito R.,University of Naples Federico II | Martelli F.,University of Florence | De Nicola S.,CNR Institute of Neuroscience
Optics Letters | Year: 2014

We have developed a theoretical model for photon migration through scattering media in the presence of an absorbing in homogeneity. A closed-form solution for the average diffuse intensity has been obtained through an iterative approximation scheme of the steady-state diffusion equation. The model describes absorbing defects in a wide range of values. Comparisons with the results of Monte Carlo simulations show that the error of the model is lower than 3% for size inclusion lower than 4 mm and absorption contrast up to the threshold value of the "black defect." The proposed model provides a tractable mathematical basis for diffuse optical and photoacoustic tomographic reconstruction techniques. © 2014 Optical Society of America. Source


D'Elios M.M.,University of Florence | Czinn S.J.,University of Maryland Baltimore County
Helicobacter | Year: 2014

Helicobacter pylori colonizes mucosa, activates Toll-like and Nod-like receptors, and usually elicits a gastric T-helper 1/17 (Th1/Th17) type of immune response. Among several bacterial factors, the secreted peptidyl prolyl cis, trans-isomerase of H. pylori represents a key factor driving Th17 inflammation. A complex and fascinating balance between H. pylori and host factors takes part in the gastric niche and is responsible for the chronicity of the infection. Novel insights into the innate and adaptive responses against H. pylori, dealing with gastric epithelial cells, cytokines, and immune evasion have been elucidated over the past year and are discussed for the development of an effective vaccine. © 2014 John Wiley & Sons Ltd. Source


Zambelli B.,University of Bologna | Musiani F.,University of Bologna | Benini S.,Sudan University of Science and Technology | Ciurli S.,University of Bologna | Ciurli S.,University of Florence
Accounts of Chemical Research | Year: 2011

Transition metals are both essential to enzymatic catalysis and limited in environmental availability. These two biological facts have together driven organisms to evolve mechanisms for selective metal ion sensing and utilization. Changes in metal ion concentrations are perceived by metal-dependent transcription factors and transduced into appropriate cellular responses, which regulate the machineries of competitive metal ion homeostasis and metallo-enzyme activation. The intrinsic toxicity of the majority of metal ions further creates a need for regulated intracellular trafficking, which is carried out by specific chaperones.The Ni2+-dependent urease enzymatic system serves as a paradigm for studying the strategies that cells use to handle an essential, yet toxic, metal ion. Although the discovery of urease as the first biological system for which nickel is essential for activity dates to 1975, the rationale for Ni2+ selection, as well as the cascade of events involving metal-dependent gene regulation and protein-protein interactions leading to enzyme activation, have yet to be fully unraveled. The past 14 years since the Account by Hausinger and co-workers (Karplus, P. A.; Pearson, M. A.; Hausinger, R. P. Acc. Chem. Res. 1997, 30, 330-337) have witnessed impressive achievements in the understanding of the biological chemistry of Ni2+ in the urease system. In our Account, we discuss more recent advances in the comprehension of the specific role of Ni2+ in the catalysis and the interplay between Ni2+ and other metal ions, such as Zn2+ and Fe2+, in the metal-dependent enzyme activity. Our discussion focuses on work carried out in our laboratory.In particular, the structural features of the enzyme bound to inhibitors, substrate analogues, and transition state or intermediate analogues have shed light on the catalytic mechanism. Structural and functional information has been correlated to understand the Ni2+ sensing effected by NikR, a nickel-dependent transcription factor. The urease activation process, involving insertion of Ni2+ into the urease active site, has been in part dissected and analyzed through the investigation of the molecular properties of the accessory proteins UreD, UreF, and UreG. The intracellular trafficking of Ni2+ has been rationalized through a deeper understanding of the structural and metal-binding properties of the metallo-chaperone UreE. All the while, a number of key general concepts have been revealed and developed. These include an understanding of (i) the overall ancillary role of Zn2+ in nickel metabolism, (ii) the intrinsically disordered nature of the GTPase responsible for coupling the energy consumption to the carbon dioxide requirement for the urease activation process, and (iii) the role of the accessory proteins regulating this GTPase activity. © 2011 American Chemical Society. Source


Vannucchi A.M.,University of Florence
Internal and Emergency Medicine | Year: 2010

The classic myeloproliferative neoplasms (MPNs) include polycythemia vera and essential thrombocythemia; their molecular basis has been described only recently with the demonstration of recurrent mutations in JAK2 or MPL. While life expectancy may not be significantly shortened, arterial and venous thrombosis constitute the major causes of morbidity and mortality, together with disease evolution to myelofibrosis or transformation to acute leukemia. Therapy is currently aimed at reducing the rate of thrombosis without increasing the risk of hematologic transformation by inappropriate exposure to cytotoxic drugs. Nevertheless, the mechanism(s) finally responsible for the increased thrombotic tendency have not been clearly elucidated, although risk factors for thrombosis have been identified, and are currently employed for stratifying patients to the most appropriate therapeutic options. Abnormalities of blood cells, activation of neutrophils and platelets, and a hypercoagulability state, can all act in conjunction to lead to thrombosis. Intriguing data also point to the JAK2V617F mutation as both a marker and a mechanism for thrombosis. Better knowledge in the pathophysiology of these disorders, and the introduction of molecularly targeted drugs in clinical trials, anticipate the possibility of more specific and efficacious treatment of classic MPN, particularly as concerns the reduction of risk associated with vascular events. © 2009 SIMI. Source


Manca S.,National Research Council Italy | Ranieri M.,University of Florence
Internet and Higher Education | Year: 2016

This study aims at providing empirical evidence on how higher education scholars are using Social Media for personal, teaching and professional purposes. A survey tool was addressed to the entire Italian academic staff, with a response rate of 10.5% corresponding to 6139 responses. The study takes into account a number of socio-demographic variables such as gender, age, numbers of years of teaching, academic title, and academic discipline. It also explores the relationship between the different kinds of use, the relationship between frequency of use of Social Media and online and/or blended teaching, as well as the use of institutional e-learning systems. The results show that Social Media use is still rather limited and restricted and that the variable most associated with frequency of use is scientific discipline. In addition, age and seniority seem to influence the adoption of Social Media. The results also revealed that frequency of personal use is mostly associated with the frequency of professional use more than with the frequency of teaching use. They also show that prior experience with e-learning or blended learning is greatly associated with Social Media use. Overall, the study emphasises a generally more favourable attitude towards personal sharing and connecting with peers in professional networks rather than integrating these devices into their teaching practices. © 2015 Elsevier Inc. All rights reserved. Source


Calusi S.,University of Florence
Microscopy and Microanalysis | Year: 2011

Ion beam analysis (IBA) techniques are a powerful analytical tool used to investigate the composition and structure of precious materials principally because they can be applied in atmosphere. Thus, the sample can be analyzed as is, and heating and charging effects are strongly diminished. Since IBA measurements can be made with low ion currents and acquisition time, the damage risk is limited. At the microbeam line of the LABEC laboratory, it is possible to exploit the potentials of IBA techniques in an external set up to reconstruct the distribution maps of all the detected elements over the analyzed area with spatial resolutions as low as 10 μm. This is an important feature when objects with inhomogeneous structures-on a scale of hundred microns or so-are investigated, as happens in some cases with artworks. The detection set up installed on our external microbeam allows us to use different IBA techniques simultaneously. Thus, in a single measurement run, it is possible to obtain complementary information on both sample composition and structure. Some applications to works of art are presented here as examples of the analytical capabilities of the external scanning microbeam in the cultural heritage field. © Microscopy Society of America 2011. Source


Cirri P.,University of Florence
Cell communication and signaling : CCS | Year: 2013

Solid tumors are composed of both cancer cells and various types of accessory cells, mainly fibroblasts, that collectively compose the so called tumor-microenvironment. Cancer-associated fibroblasts have been described to actively participate in cancer progression by establishing a cytokine-mediated as well as metabolic crosstalk with cancer cells. In the present paper we show that activated human fibroblasts are able to boost tumor cells proliferation and that this effect is greatly dependent on stromal carbonic anhydrase IX (CA IX) activity. In fact fibroblasts show a strong upregulation of CA IX expression upon activation by cancer cells, while CA IX products, protons and bicarbonate, exert differential effects on cancer cells proliferation. While acidification of extracellular pH, a typical condition of rapidly growing solid tumors, is detrimental for tumor cells proliferation, bicarbonate, through its organication, supplies cancer cells with intermediates useful to sustain their high proliferation rate. Here we propose a new kind of fibroblasts/tumor cells crosstalk within tumor microenvironment, mediated by stromal CA IX products, aimed to favor cancer cells growth, opening new perspectives on CA IX role in tumor microenvironment. Source


Mura P.,University of Florence
Journal of Pharmaceutical and Biomedical Analysis | Year: 2015

Cyclodextrins are cyclic oligosaccharides able to form inclusion complexes with a variety of hydrophobic guest molecules, positively modifying their physicochemical properties. A thorough analytical characterization of cyclodextrin complexes is of fundamental importance to provide an adequate support in selection of the most suitable cyclodextrin for each guest molecule, and also in view of possible future patenting and marketing of drug-cyclodextrin formulations. The demonstration of the actual formation of a drug-cyclodextrin inclusion complex in solution does not guarantee its existence also in the solid state. Moreover, the technique used to prepare the solid complex can strongly influence the properties of the final product. Therefore, an appropriate characterization of the drug-cyclodextrin solid systems obtained has also a key role in driving in the choice of the most effective preparation method, able to maximize host-guest interactions. The analytical characterization of drug-cyclodextrin solid systems and the assessment of the actual inclusion complex formation is not a simple task and involves the combined use of several analytical techniques, whose results have to be evaluated together. The objective of the present review is to present a general prospect of the principal analytical techniques which can be employed for a suitable characterization of drug-cyclodextrin systems in the solid state, evidencing their respective potential advantages and limits. The applications of each examined technique are described and discussed by pertinent examples from literature. © 2015 Elsevier B.V.. Source


Pierucci L.,University of Florence
IEEE Wireless Communications | Year: 2015

Quality of experience (QoE) is the subjective acceptability of the quality of a telecommunication service perceived by the user. This paper expands the vision to new QoE acceptability for the future 5G networks and analyzes the impact of the main challenges of 5G on QoE. An efficient QoE estimation method tailored for 5G systems is also proposed based on the neural network (NN) approach. Due to their ability to fully learn the causal relationship between network parameters of quality of services (QoS) and the resulting QoE, NN can be suitable to gain QoE self-optimization for 5G. Again, new increasingly smart user devices will be delegated to handle the most burdensome tasks of ensuring user satisfaction. © 2002-2012 IEEE. Source


Materassi D.,University of Minnesota | Innocenti G.,University of Florence
IEEE Transactions on Automatic Control | Year: 2010

The paper deals with the problem of reconstructing the tree-like topological structure of a network of linear dynamical systems. A distance function is defined in order to evaluate the closeness of two processes and some useful mathematical properties are derived. Theoretical results to guarantee the correctness of the identification procedure for networked linear systems characterized by a tree topology are provided as well. The paper also suggests the approximation of a complex connected network with a tree in order to detect the most meaningful interconnections. The application of the techniques to the analysis of an actual complex network, i.e., to high frequency time series of the stock market, is extensively illustrated. © 2010 IEEE. Source


Locatelli M.,University of Parma | Schoen F.,University of Florence
Mathematical Programming | Year: 2014

In this paper we discuss convex envelopes for bivariate functions, satisfying suitable assumptions, over polytopes. We first propose a technique to compute the value and a supporting hyperplane of the convex envelope over a general two-dimensional polytope through the solution of a three-dimensional convex subproblem with continuously differentiable constraint functions. Then, for quadratic functions as well as for some polynomial and rational ones, again satisfying suitable assumptions, we show how the same computations can be carried out through the solution of a single semidefinite problem. © 2012 Springer-Verlag Berlin Heidelberg and Mathematical Optimization Society. Source


Adams D.C.,Iowa State University | Nistri A.,University of Florence
BMC Evolutionary Biology | Year: 2010

Background. A major goal in evolutionary biology is to understand the evolution of phenotypic diversity. Both natural and sexual selection play a large role in generating phenotypic adaptations, with biomechanical requirements and developmental mechanisms mediating patterns of phenotypic evolution. For many traits, the relative importance of selective and developmental components remains understudied. Results. We investigated ontogenetic trajectories of foot morphology in the eight species of European plethodontid cave salamander to test the hypothesis that adult foot morphology was adapted for climbing. Using geometric morphometrics and other approaches, we found that developmental patterns in five species displayed little morphological change during growth (isometry), where the extensive interdigital webbing in adults was best explained as the retention of the juvenile morphological state. By contrast, three species exhibited significant allometry, with an increase in interdigital webbing during growth. Phylogenetic analyses revealed that multiple evolutionary transitions between isometry and allometry of foot webbing have occurred in this lineage. Allometric parameters of foot growth were most similar to those of a tropical species previously shown to be adapted for climbing. Finally, interspecific variation in adult foot morphology was significantly reduced as compared to variation among juveniles, indicating that ontogenetic convergence had resulted in a common adult foot morphology across species. Conclusions. The results presented here provide evidence of a complex history of phenotypic evolution in this clade. The common adult phenotype exhibited among species reveals that selection plays an important part in generating patterns of foot diversity in the group. However, developmental trajectories arriving at this common morphology are distinct; with some species displaying developmental stasis (isometry), while others show an increase in foot webbing during growth. Thus, multiple developmental solutions exist to the same evolutionary challenge. Our findings underscore the importance of examining morphological adaptations from multiple perspectives, and emphasize that both selective hypotheses and developmental processes must be considered for a more comprehensive understanding of phenotypic evolution. © 2010 Adams and Nistri; licensee BioMed Central Ltd. Source


The potential use of protection forests to combat shallow slope instabilities is becoming increasingly important and considerable, especially in the light of the recent landslides and debris/mud flows in regions triggered by rainfalls with increased intensity. Tree vegetation has been constantly subjected to silvicultural activity both in exclusively productive forest areas and in more conservative ones meant to contrasthydrogeological risk. It is important to quantify the root system dynamics in order to correctly evaluate the impact of wood felling or plants death on slope stability. Based on field investigation (on experimental plots and 29 occurred landslides) and numerical modelling (on slope stability and root distribution), the aim of this work is to determine the effects of the evolution of the mechanical characteristics of root systems (and consequently on landslide probability). The paper investigates variations over time in the hazard of rainfall-triggered landslides as a result of root degradation after forest cutting (or death). The case under study is related to experimental investigations aimed at determining the tensile strength and elasticity of root samples of trees dead within a decade, which correspond to decreasing values of soil cohesion (root reinforcement). Two kinds of samples were taken into account: living beech roots from protected wood areas to determine the current characteristics and roots from dead beeches (felled in previous years and at present in degradation) to analyse the evolution of root mechanical characteristics. To analyse the stability of representative slopes, we calculated the return time associated with a rainfall event, which in saturated conditions would lead to the attainment of the limit value of the safety factor and the associated hazard for different rainfall durations during a fixed period of time. Information about the increasing risk of collapse with the degradation of root system was obtained and compared with land slides occurrence in forested slopes of the study area. The results of the present paper show that such slopes may remain stable if they are covered with intact protective vegetation, but they will become unstable if the conditions of the forest deteriorate or after a wooded area dies off: within a decade of tree death the root system of protection forests loses most of its soil-stabilising function. © 2012 Elsevier B.V. Source


Gallo M.,University of Naples "LOrientale" | Buccianti A.,University of Florence
Environmetrics | Year: 2013

Data collected for the investigation of the environmental and ecological characteristics of a river basin are often in the form of a large three-way array; hence, a particular version of the Tucker model could be applied to gather more information contained in such complex geochemical systems. Indeed, when the data are in compositional form, more attention must be given to the analysis of the numerical data. Recently, the Tucker3 model has been proposed to analyze compositional data characterized by a three-way structure. In this work, a particular version of the Tucker model, known as the weighted principal component analysis, was used to analyze water samples collected from the Arno river (Tuscany, central Italy) in order to evaluate the method's effectiveness. Several graphical displays have been developed to allow an accurate and complete interpretation of results. © 2013 John Wiley & Sons, Ltd. Source


Messori L.,University of Florence | Merlino A.,University of Naples Federico II
Inorganic Chemistry | Year: 2014

The crystal structure of the main adduct formed in the reaction between cisplatin and bovine pancreatic ribonuclease is reported here. Notably, in both of the protein molecules present in the asymmetric unit, platinum(II) binding takes place exclusively at the level of Met29. In one of the two molecules, the Gln28 side chain completes the platinum coordination sphere, anchoring the cisplatin fragment to the protein in a bidentate fashion. These results contain interesting implications for understanding the biological chemistry of this important drug. © 2014 American Chemical Society. Source


AIM: The aim of this study was to evaluate differences in the inflammatory profile of young ( Source


Huang Y.J.,Rutgers University | Rosato A.,University of Florence | Singh G.,Rutgers University | Montelione G.T.,Rutgers University | Montelione G.T.,Johnson University
Nucleic Acids Research | Year: 2012

We describe the RPF web server, a quality assessment tool for protein NMR structures. The RPF server measures the 'goodness-of-fit' of the 3D structure with NMR chemical shift and unassigned NOESY data, and calculates a discrimination power (DP) score, which estimates the differences between the fits of the query structures and random coil structures to these experimental data. The DP-score is an accuracy predictor of the query structure. The RPF server also maps local structure quality measures onto the 3D structure using an online molecular viewer, and onto the NMR spectra, allowing refinement of the structure and/or NOESY peak list data. © 2012 The Author(s). Source


Bencini A.,University of Florence | Lippolis V.,University of Cagliari
Coordination Chemistry Reviews | Year: 2012

The reciprocal influence of the thermodynamic (binding) selectivity and the sensing (optical response) selectivity of fluorescent chemosensors in determining their efficiency in probing biologically and environmentally important metal ions in real matrices will be discussed on the basis of some study cases from the work of the authors. © 2011 Elsevier B.V.. Source


Tricarico E.,University of Florence
Fisheries Management and Ecology | Year: 2012

The Mediterranean region is considered one of the six global invasion hotspots, with non-native freshwater fishes representing more than a quarter of all fish species in drainage basins. Existing literature is reviewed to identify the main pathways and drivers of non-native fish introductions. In the Mediterranean region, non-native fishes were introduced through aquaculture and stocking activities for commercial and angling purposes. Introductions doubled from the 1950s, involving mostly Perciformes and Cypriniformes, with species coming from other parts of Europe, Asia and North America. Some differences between the northern and the south-eastern areas of the Mediterranean region were found, although data from the latter area were scanty. Greater effort should be exerted to improve controls on aquaculture and stocking activities, as well as public awareness of the risks posed by non-native species introductions. © 2012 Blackwell Publishing Ltd. Source


Arcangeli A.,University of Florence
American Journal of Physiology - Cell Physiology | Year: 2011

The traditional view of cancer as a collection of proliferating cells must be reconsidered, and cancer must be viewed as a "tissue" constituted by both transformed cells and a heterogeneous microenvironment, that tumor cells construct and remodel during multistep tumorigenesis. The "tumor microenvironment" (TM) is formed by mesenchymal, endothelial, and immune cells immersed in a network of extracellular matrix (ECM) proteins and soluble factors. The TM strongly contributes to tumor progression, through long distance, cell-to-cell or cell-to-matrix signals, which influence different aspects of tumor cell behavior. Understanding the relationships among the different components of the cancer tissue is crucial to design and develop new therapeutic strategies. Ion channels are emerging as relevant players in the cross talk between tumor cells and their TM. Ion channels are expressed on tumor cells, as well as in the different cellular components of the TM. In all these cells, ion channels are in a strategic position to sense and transmit extracellular signals into the intracellular machinery. Often, this transmission is mediated by integrin adhesion receptors, which can be functional partners of ion channels since they form molecular complexes with the channel protein in the context of the plasma membrane. The same relevant role is exerted by ion transporters, which also contribute to determine two facets of the cancer tissue: hypoxia and the acidic extracellular pH. On the whole, it is conceivable to prospect the targeting of ion channels for new therapeutic strategies aimed at better controlling the malignant progression of the cancer tissue. © 2011 the American Physiological Society. Source


Nannicini A.,University of Florence
Journal of Geometry and Physics | Year: 2010

We study a class of complex structures on the generalized tangent bundle of a smooth manifold M endowed with a torsion free linear connection, {down triangle, open}. We introduce the concept of {down triangle, open}-integrability and we study integrability conditions. In the case of the generalized complex structures introduced by Hitchin (2003) in [2], we compare the two concepts of integrability. Moreover, as an application, we describe almost complex structures on the cotangent bundle of M induced by complex structures on the generalized tangent bundle of M. © 2010 Elsevier B.V. Source


Battilotti G.,University of Florence
International Journal of Theoretical Physics | Year: 2010

We introduce an interpretation of quantum superposition in predicative sequent calculus, in the framework of basic logic. Then we introduce a new predicative connective for the entanglement. Our aim is to represent quantum parallelism in terms of logical proofs. © 2009 Springer Science+Business Media, LLC. Source


Tino G.M.,University of Florence
Proceedings of the International School of Physics "Enrico Fermi" | Year: 2014

We developed two types of atom interferometer for gravitational physics experiments: The first is a double Raman interferometer with Rb atoms that we operate as a gravity gradiometer. The second is based on Bloch oscillations of Sr atoms in optical lattices. As in my lectures at the 2013 'E. Fermi' School in Varenna, the aim of these notes is to describe the characteristics of the two interferometers taking as examples the experiments that we performed. I present the schemes of the interferometers, the key steps that allowed us to optimize the setups, their operation and performances. I discuss experiments that we carried out, namely, a precision measurement of the value of the gravitational constant G using the Rb Raman interferometer and the measurement of gravity at small spatial scale using the Sr apparatus, with implications in the search for deviations from Newtonian gravity and as tests of general relativity. I also discuss prospects and possible ideas for future experiments in laboratories on ground and in space. © Societa Italiana di Fisica. Source


Becucci M.,University of Florence | Melandri S.,University of Bologna
Chemical Reviews | Year: 2016

A wealth of structural and dynamical information has been obtained in the last 30 years from the study of high-resolution spectra of molecular clusters generated in a cold supersonic expansion by means of highly resolved spectroscopic methods. The data obtained, generally lead to determination of the structures of stable conformations. In addition, in the case of weakly bound molecular complexes, it is usual to observe the effects of internal motions due to the shallowness of the potential energy surfaces involved and the flexibility of the systems. In the case of electronic excitation experiments, also the effect of electronic distribution changes on both equilibrium structures and internal motions becomes accessible. The structural and dynamical information that can be obtained by applying suitable theoretical models to the analysis of these unusually complex spectra allows the determination and understanding of the driving forces involved in formation of the molecular complex. In this way, many types of non-covalent interactions have been characterized, from pure van der Waals interactions in complexes of rare gases to moderate-strength and weak hydrogen bonds and to the most recent halogen bonds and n-π interactions. The aim of this review is to underline how the different experimental and theoretical methods converge in giving a detailed picture of weak interactions in small molecular adducts involving medium-size molecules. The conclusions regarding geometries and energies can contribute to understanding of the different driving forces involved in the dynamics of the processes and can be exploited in all fields of chemistry and biochemistry, from design of new materials with novel properties to rational design of drugs. © 2016 American Chemical Society. Source


Meeus L.,University of Florence | Meeus L.,Catholic University of Leuven
Energy Economics | Year: 2011

Implicit auctioning in Europe is about eliminating cross-border trade inefficiencies by internalizing cross-border trade into the day-ahead auction procedures of the Power Exchanges that are already organizing trade nationally. On the Kontek Cable, implicit auctioning has first been implemented with "no coupling" between the relevant Power Exchanges, followed by a "volume coupling" implementation, and finally a "one way price coupling" implementation that is still operational today. The main contribution of this paper is to compare the theoretical properties of these three implementations and to analyze their performance empirically. We find that the third implementation is significantly outperforming the previous two implementations, but in this third implementation stakeholders partly abandoned the "volume coupling" approach they initially believed to be a viable alternative and institutionally easier to implement. © 2010 Elsevier B.V. Source


Cosci F.,University of Florence
General Hospital Psychiatry | Year: 2013

Objective: The bowel obsession syndrome (BOS) is a psychosomatic disorder which often remains at the intersection of somatic and psychological domains without being adequately diagnosed and treated. Case report: A 32-year-old man with chronic constipation presented with restricted diet, compulsions on evacuation, social isolation and depressed mood, thus satisfying the diagnosis of BOS. Cognitive behavioral therapy led to complete remission of symptoms, and results were maintained after 1 year of follow-up. Conclusion: Although BOS is not frequently diagnosed, it is probably more prevalent than thought. Clinicians should be aware of its existence in order to assess, diagnose and properly treat it. © 2013 Elsevier Inc. Source


Di Donato M.,CNR Institute of Applied Physics Nello Carrara | Di Donato M.,University of Florence | Groot M.L.,VU University Amsterdam
Biochimica et Biophysica Acta - Bioenergetics | Year: 2015

In recent years visible pump/mid-infrared (IR) probe spectroscopy has established itself as a key technology to unravel structure-function relationships underlying the photo-dynamics of complex molecular systems. In this contribution we review the most important applications of mid-infrared absorption difference spectroscopy with sub-picosecond time-resolution to photosynthetic complexes. Considering several examples, such as energy transfer in photosynthetic antennas and electron transfer in reaction centers and even more intact structures, we show that the acquisition of ultrafast time resolved mid-IR spectra has led to new insights into the photo-dynamics of the considered systems and allows establishing a direct link between dynamics and structure, further strengthened by the possibility of investigating the protein response signal to the energy or electron transfer processes. This article is part of a Special Issue entitled: Vibrational spectroscopies and bioenergetic systems. © 2014 Elsevier B.V. All rights reserved. Source


Palchetti I.,University of Florence
Bioanalysis | Year: 2014

The use of cancer biomarkers is emerging as one of the most promising strategies for early detection and management of cancer. Biosensors can provide advanced platforms for biomarker analysis with the advantages of being easy to use, inexpensive, rapid and offering multi-analyte testing capability. The intention of this article is to discuss recent advances and trends in affinity biosensors for cancer diagnosis, prognosis and even theragnosis. The different types of affinity biosensors will be reviewed in terms of molecular recognition element. Current challenges and trends for this technology will be also discussed, with a particular emphasis on recent developments in miRNA detection. © 2014 Future Science Ltd. Source


Vignozzi L.,University of Florence
Journal of endocrinological investigation | Year: 2010

Puberty is the developmental period during which rapid somatic changes and attainment of reproductive capacity take place. The sine qua non event for the onset of puberty is the increase in pulsatile GnRH release from GnRH neurons. GnRH neurons originate in the nasal placode and migrate, from the nasal compartment through the basal forebrain, before they attain their positions in the hypothalamus. Failure of GnRH neurons to migrate, mainly due to genetic alterations, leads to a clinical condition defined congenital hypogonadotropic hypogonadism. Other important factors demonstrated a permissive role for GnRH secretion at time of puberty, such as the kisspeptin G-protein-coupled receptor 54 (GPR54, now called KISS-1R) and its ligand, as well as neurokinin B (NKB) and the neurokinin 3 (NK3) receptor. Kisspeptin and neurokinin B colocalized in a subset of hypothalamic neurons that regulate GnRH secretion by GnRH neurons. Indeed, loss of function mutations in the above-mentioned and other genes result in hypogonadotrophic hypogonadism with absence of pubertal development. In males, pubertal increase of androgens levels seems to be required for the attainment of a normal bone density and male-specific body composition. However, also genetic variants of genes involved in bone metabolism as well as in osteoblast/osteoclast activation are associated to bone mineral density. Source


Meeus L.,University of Florence | Meeus L.,Catholic University of Leuven
Energy Policy | Year: 2011

The European Union (EU) market integration is leading to increasingly monopolistic electricity market infrastructures, which has opened a debate on the regulation of these so-called power exchanges. In this paper, we start by stating that there are two types of power exchanges in Europe, i.e. "merchant" and "cost-of-service regulated" power exchanges. We then discuss how regulation can be used to better align their incentives with the main power exchange tasks. We conclude that adopting the cost-of-service regulated model for all power exchanges in Europe could be counterproductive in the current context, but that regulation can help ensure that the benefits of the EU market integration materialize. Promising regulatory actions include tempering the reinforced market power of power exchanges, and quality-of-service regulation for the ongoing cooperation among power exchanges to organize trade across borders. © 2010 Elsevier Ltd. Source


Certini G.,University of Florence | Scalenghe R.,University of Palermo | Scalenghe R.,University of Poitiers
Holocene | Year: 2011

We propose that the Anthropocene be defined as the last c. 2000 years of the late Holocene and characterized on the basis of anthropogenic soils. This contrasts with the original definition of the Anthropocene as the last c. 250 years (since the Industrial Revolution) and more recent proposals that the Anthropocene began some 5000 to 8000 years ago in the early to mid Holocene (the early-Anthropocene hypothesis). Anthropogenic soil horizons, of which several types are recognized, provide extensive terrestrial stratigraphic markers for defining the start of the Anthropocene. The pedosphere is regarded as the best indicator of the rise to dominance of human impacts on the total environment because it reflects strongly the growing impact of early civilisations over much of the Earth's surface. Hence, the composition of anthropogenic soils is deemed more appropriate than atmospheric composition in providing 'golden spikes' for the Anthropocene. © SAGE Publications 2011. Source


Mariano P.M.,University of Florence
Physics Letters, Section A: General, Atomic and Solid State Physics | Year: 2010

It is proven that magnetizable quasicrystals undergoing large deformations admit elastic ground states characterized by a net of linear topological defects for the magnetic spin field. © 2010 Elsevier B.V. Source


Rostagno C.,University of Florence
Cardiovascular and Hematological Agents in Medicinal Chemistry | Year: 2012

Atrial fibrillation occurs in 20-50% of patients after surgical revascularization (40% have more than 1 episode), with a peak between 2nd and 3rd postoperative days. Postoperative atrial fibrillation (POAF) has been associated with an increase in adverse events, length of hospital stay and, therefore, cost of care, and late mortality. A higher risk profile in patients who develop POAF may contribute to the higher late mortality rate. The pathogenesis of PAOF is multi factorial: transient ischemia during surgical procedure, neurohormonal activation, electrolyte imbalance, fluid overload and finally an exaggerated inflammatory response have been associated with POAF. Advanced age, an history of AF or heart failure and, finally, COPD are clinically independent risk factors related to POAF. The lower incidence of POAF reported after off-pump CABG in comparison to conventional cardiopulmonary by-pass CABG techniques has not been confirmed. The administration of antiarrhythmic drugs (amiodarone, metoprolol, sotalol and recently propafenone and landiolol) before and /or after surgical procedure has been extensively investigated and most of the investigators have demonstrated a favorable effect on POAF incidence. The decreased incidence of POAF and related shorter hospital stay by PUFA administration during hospitalization needs to be confirmed. Preliminary results suggest that pre-treatment with the antianginal drug ranolazine may significantly decrease POAF incidence. Treatments directed to antagonize inflammation are presently under investigation. Recently, a randomized study with naproxen, although effective on POAF, was interrupted due to increased risk of nephrotoxicty. Despite different action mechanisms, both hydrocortisone and statins have been shown to decrease post-operative AF risk. No data at present exist on the effects of association of these drugs. Aim of the present review was to update the current practice and report the recent results of research in the prophylaxis of atrial fibrillation in patients undergoing CABG. © 2012 Bentham Science Publishers. Source


La Mela M.,University of Florence
Scandinavian Economic History Review | Year: 2014

Wild berries became a valuable export article in Sweden and Finland at the end of the nineteenth century. At the time, property rights over wild berries were not explicitly defined, and in both countries, proposals were made to subject the berries to the landowner. The proposals did not pass and wild berry-picking on another's land continued, as seen from today's perspective, to be available to everyone. This paper looks at the socioeconomic context of wild berry-picking, and asks whether the principle of allemansrätt – a Nordic tradition of public access to nature – played a role in why wild berries did not become private property. By focusing on the Finnish penal code debate of 1888 and the process of stabilising the property rights, the paper rejects the idea of continuity. It argues that (1) the traditional allemansrätt is debatable as a historical concept and shows how (2) the contingent political process created the conditions, and economic imagination the impetus, that wild berries were not privatised but turned into an open resource. © 2014 Taylor & Francis. Source


Gacci M.,University of Florence
Prostate cancer and prostatic diseases | Year: 2013

Epidemiological data indicate that lower urinary tract symptoms (LUTS)/BPH can be associated with metabolic syndrome (MetS). Chronic inflammation has been proposed as a candidate mechanism at the crossroad between these two clinical entities.Aim of study is to examine the correlation among pre-operatory LUTS/BPH severity, MetS features and inflammatory infiltrates in prostatectomy specimens. A total of 271 consecutive men treated with simple prostatectomy were retrospectively selected for this study in two tertiary referral centers for LUTS/BPH. Prostate diameters and volume were measured by transrectal ultrasound, LUTS scored by International Prostate Symptom Score (IPSS) and obstruction by uroflowmetry. The International Diabetes Federation and American Heart Association and the National Heart, Lung and Blood Institute was used to define MetS. The inflammatory infiltrate was investigated combining anatomic location, grade and extent of flogosis into the overall inflammatory score (IS); the glandular disruption (GD) was used as a further marker. Eighty-six (31.7%) men were affected by MetS. Prostatic volume and anterior-posterior (AP) diameter were positively associated to the number of MetS components. Among MetS determinants, only dyslipidaemia (increased serum triglycerides and reduced serum high-density lipoprotein) was associated with an increased risk of having a prostatic volume >60 cm(3) (hazard ratio (HR) = 3.268, P < 0.001). A significant positive correlation between the presence of MetS and the IS was observed. MetS patients presented lower uroflowmetric parameters as compared with those without MetS (Maximum flow rate (Q(max)): 8.6 vs 10.1, P = 0.008 and average flow rate (Q(ave)): 4.6 vs 5.3, P = 0.033, respectively), and higher obstructive urinary symptoms score (P = 0.064). A positive correlation among both IS-GD and IPSS Score was also observed (adjusted r = 0.172, P = 0.008 and adjusted r = 0.128, P = 0.050). MetS is associated with prostate volume, prostatic AP diameter and intraprostatic IS. The significantly positive association between MetS and prostatic AP diameter could support the observation that MetS patients presented lower uroflowmetric parameters. In conclusion, MetS can be regarded as a new determinant of prostate inflammation and BPH progression. Source


Modugno G.,University of Florence
Reports on Progress in Physics | Year: 2010

The understanding of disordered quantum systems is still far from being complete, despite many decades of research on a variety of physical systems. In this review we discuss how Bose-Einstein condensates of ultracold atoms in disordered potentials have opened a new window for studying fundamental phenomena related to disorder. In particular, we direct our attention to recent experimental studies on Anderson localization and on the interplay of disorder and weak interactions. These realize a very promising starting point for a deeper understanding of the complex behaviour of interacting, disordered systems. © 2010 IOP Publishing Ltd. Source


Cianchi A.,University of Florence | Maz'ya V.G.,Linkoping University | Maz'ya V.G.,University of Liverpool
Archive for Rational Mechanics and Analysis | Year: 2014

Gradient boundedness up to the boundary for solutions to Dirichlet and Neumann problems for elliptic systems with Uhlenbeck type structure is established. Nonlinearities of possibly non-polynomial type are allowed, and minimal regularity on the data and on the boundary of the domain is assumed. The case of arbitrary bounded convex domains is also included. © 2014, Springer-Verlag Berlin Heidelberg. Source


Carobbi C.F.M.,University of Florence
IEEE Transactions on Electromagnetic Compatibility | Year: 2013

Analytical formulas derived here are capable of predicting the measurement error of the parameters of the standard unidirectional impulse waveforms due to the distortion induced by the limited bandwidth of the measuring system. The parameters subject to analysis are the rise time and the peak value. The standard waveforms considered are those defined in the IEC 61000-4-2 (electrostatic discharge), -4-4 (electrical fast transient/burst) and -4-5 (surge 1,2/50 μs and 8/20 μs) standards. The results obtained are of importance for the evaluation of the calibration uncertainty of the standard unidirectional impulse generators and associated coupling/decoupling networks as well as for the design of the corresponding measuring systems. Analytical predictions are confirmed by numerical simulations. © 1964-2012 IEEE. Source


The Mt. Corchia karst system is one of the most important and famous caves in the World. Different from many other large caves, here the geological structure has had only a minor role on the vertical, multi-level pattern of the cave. A detailed geomorphic and morphometric analysis of the cave and a preliminary study of cave sediments, along with new datings of speleothems, allow us now to depict the multistage evolution of this cave, which produced at least three major paleo-phreatic levels related to different base-level stages. The analysis of the directions of cave passages shows that the three main phases have different orientations, which can be attributed to the different surface morphology during speleogenesis in former times.Chronological constraints and geomorphic features suggest that the upper part of Mt. Corchia Cave developed during the end of Pliocene in a stage of favourable climatic conditions and with a moderate tectonic uplift-rate. The morphological features and the nature of sediments in the upper paleo-phreatic level at 1350-1450. m above present sea level (apsl) imply the occurrence of a wide allogenic catchment area. This drainage pattern persisted also in the following stage, during a significant but slow lowering of the base level, which allowed the formation and the intense vadose rearrangement of the epi-phreatic network around 1100-1250. m apsl. An uplift stage in the Early Pleistocene caused the capture of the basins and the loss of allogenic feeding. A third epi-phreatic level was formed at around 900. m (apsl) when the catchment area was reduced to the present extent of carbonate rock, more than 1. Ma ago. The recent evolution is due to rapid uplift and to the progressive incision of surrounding basins, which led to the lowering of the local base level and to a readjustment of the cave system in order to adapt to a new equilibrium with the present elevation of the springs. © 2011 Elsevier B.V. Source


This paper is designed to provide the reader with some guidelines towards understanding the importance of the log-ratio approach in geochemistry. An application example is presented with an analysis of the water chemistry from the Arno river basin (Tuscany, central Italy). Simple graphical alternatives are proposed using ilr (isometric log-ratio) transformation on compositional data (constrained support), which are generally used to build up molar-ratio diagrams. If the variables are suitably chosen from a geochemical standpoint, relationships among samples in space and time, as well as compositional changes attributable to different natural or anthropogenic processes, can be analysed on a sound statistical basis. Classical statistics can be applied to ilr diagrams to evaluate differences among groups of data, presence of outliers, or significant changes in time (monitoring). The final aim is to demonstrate that through simple principles of univariate or bivariate statistics, valuable results can be obtained, both from a geochemical and a statistical point of view. The approach can be extended to the analysis of different geochemical data matrices. Source


Rostagno C.,University of Florence
Cardiovascular and Hematological Agents in Medicinal Chemistry | Year: 2013

Deep venous thrombosis (DVT) is a common cause of morbidity after orthopedic surgery, both in the early post operative period when pulmonary embolism may complicate in hospital clinical course or occur after discharge and later due to development of post thrombotic syndrome. At present, clear evidence has been provided that pharmacological primary prophylaxis of venous thromboembolism (VTE) is associated with an impressive decrease in the incidence of DVT and related complications. The main limitation of VTE prophylaxis with anticoagulant drug is the risk of bleeding. Both pharmacological and non pharmacological measures are available and indication, clinical results and limitations will be discussed for each. For drug prophylaxis at present mainly are used as parenteral agents, low dose un fractionated heparin, low molecular weight heparin and fondaparinux; however, limited compliance may be a concern. Newer oral anticoagulants, dabigatran, rivaroxaban and apixiban, may be indicated in elective surgery in particular in patients with expected poor adherence to parenteral route. Non pharmacological treatment includes measures directed to decrease the effects of blood stasis, intermittent pneumatic compression device (IPCD) and graduated compression stockings, mechanical devices, inferior caval vein filters. Aim of the present review was to suggest practical approach to DVT prophylaxis in patients undergoing major orthopedic surgery. © 2013 Bentham Science Publishers. Source


Schade M.,Humboldt University of Berlin | Berti D.,University of Florence | Huster D.,University of Leipzig | Herrmann A.,Humboldt University of Berlin | Arbuzova A.,Humboldt University of Berlin
Advances in Colloid and Interface Science | Year: 2014

Lipophilic nucleic acids have become a versatile tool for structuring and functionalization of lipid bilayers and biological membranes as well as cargo vehicles to transport and deliver bioactive compounds, like interference RNA, into cells by taking advantage of reversible hybridization with complementary strands. This contribution reviews the different types of conjugates of lipophilic nucleic acids, and their physicochemical and self-assembly properties. Strategies for choosing a nucleic acid, lipophilic modification, and linker are discussed. Interaction with lipid membranes and its stability, dynamic structure and assembly of lipophilic nucleic acids upon embedding into biological membranes are specific points of the review. A large diversity of conjugates including lipophilic peptide nucleic acid and siRNA provides tailored solutions for specific applications in bio- and nanotechnology as well as in cell biology and medicine, as illustrated through some selected examples. © 2014 Elsevier B.V. Source


Based on an analysis of individual claims for provision of medicines brought by users of the Unified National Health System (SUS) against the State of Rio de Janeiro, Brazil, in the year 2005, this study aims to discuss the action and behavior of the court system in ruling on these suits. The study adopted a semi-qualitative exploratory documental research design, analyzing key aspects related to the claims, such as type of medication claimed by the plaintiff, wording of the court rulings, and the key elements used by judges in trying the cases. According to the analysis of the lawsuits and the concepts of judicialization and official standardization of medicines, the study concludes that when ruling on the provision of medicines, the court system grants the claims as submitted without considering the standardization of medicines adopted by the Ministry of Health, thus exercising excessive court intervention in health policy. Source


Fantechi A.,University of Florence
Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics) | Year: 2014

Since more than 25 years, railway signalling is the subject of successful industrial application of formal methods in the development and verification of its computerized equipment. However the evolution of the technology of railways signalling systems in this long term has had a strong influence on the way formal methods can be applied in their design and implementation. At the same time important advances had been also achieved in the formal methods area. The scope of the formal methods discipline has enlarged from the methodological provably correct software construction of the beginnings to the analysis and modelling of increasingly complex systems, always on the edge of the ever improving capacity of the analysis tools, thanks to the technological advances in formal verification of both qualitative and quantitative properties of such complex systems. The thesis we will put forward in this paper is that the complexity of future railway systems of systems can be addressed with advantage only by a higher degree of distribution of functions on local interoperable computers - communicating by means of standard protocols - and by adopting a multi-level formal modelling suitable to support the verification at different abstraction levels, and at different life-cycle times, of the safe interaction among the distributed functions. © 2014 Springer International Publishing. Source


Muniz-Miranda M.,University of Florence | Muniz-Miranda M.,CNR Institute of Applied Physics Nello Carrara
Journal of Raman Spectroscopy | Year: 2013

The adsorption of 4-nitroanisole on silver colloidal nanoparticles was investigated by surface-enhanced Raman spectroscopy (SERS). Actually, the chemical binding with a metal substrate may play a role in changing the electronic structure of this molecule, which can be considered a push-pull chromophore, because an internal charge-transfer occurs between methoxy and nitrogroup. A SERS signal could be detected only in chloride-activated silver colloids, but the spectrum recorded with green-light excitation was not related to adsorbed 4-nitroanisole, but to its azoderivative, formed by photoreduction of the nitrogroup on the surface of the silver substrate. Copyright © 2013 John Wiley & Sons, Ltd. Source


Schulz H.,Free University of Berlin | Salzarulo P.,University of Florence
Sleep Medicine Reviews | Year: 2012

The development of sleep research can be divided into two main periods. The first one was initiated in 1863 by the first systematic measurement of the depth of sleep, the second in 1953 by the discovery of recurrent episodes of rapid eye movements in sleep. The main methodological procedure in the first of these two periods was the measurement of a single physiological variable, while beginning with long-term measurements of the electroencephalogram (EEG) in sleep, multi-channel, polygraphic recording became the method of choice for sleep studies. Although rhythmic changes in the ultradian frequency range of one to 2h were observed early in many variables during sleep (movements, autonomic functions, penile erections), the recognition of the existence of two different states of sleep (rapid eye movement (REM) and non-rapid eye movement (NREM sleep)) was contingent upon a 'synthetic' view, which focus on the coalescence of multiple variables. The dual concept of sleep organization evolved stepwise in parallel to the rapid growth of neurophysiological knowledge and techniques in the first half of the 20th century, culminating in the discovery of REM sleep. © 2011 Elsevier Ltd. Source


Virgili G.,University of Florence
Cochrane database of systematic reviews (Online) | Year: 2010

BACKGROUND: Orientation and mobility (O&M) training is provided to people who are visually impaired to help them maintain travel independence. It teaches them new orientation and mobility skills to compensate for reduced visual information. OBJECTIVES: The objective of this review was to assess the effects of O&M training, with or without associated devices, for adults with low vision. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library, 2010, Issue 3), MEDLINE (January 1950 to March 2010), EMBASE (January 1980 to March 2010), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to March 2010), System for Information on Grey Literature in Europe (OpenSIGLE) (March 2010), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com) (March 2010), ClinicalTrials.gov (http://clinicaltrials.gov) (March 2010), ZETOC (March 2010) and the reference lists of retrieved articles. There were no language or date restrictions in the search for trials. The electronic databases were last searched on 31 March 2010. SELECTION CRITERIA: We planned to include randomised or quasi-randomised trials comparing O&M training with no training in adults with low vision. DATA COLLECTION AND ANALYSIS: Two authors independently assessed the search results for eligibility, evaluated study quality and extracted the data. MAIN RESULTS: Two small studies satisfied the inclusion criteria. They were consecutive phases of development of the same training curriculum and assessment tool. The intervention was administered by a volunteer on the basis of written and oral instruction. In both studies the randomisation technique was inadequate, being based on alternation, and masking was not achieved. Training had no effect in the first study but tended to be beneficial in the second but not to a statistically significant extent. Reasons for differences between studies may have been: the high scores obtained in the first study, suggestive of little need for training and small room for further improvement (a ceiling effect), and the refinement of the curriculum allowing better tailoring to patients' specific needs and characteristics, in the second study. AUTHORS' CONCLUSIONS: The review found two small quasi-randomised trials with similar methods, comparing training to physical exercise and assessing O&M physical performance by means of a volunteer or a professional, which were unable to demonstrate a difference. Therefore, there is little evidence on which type of O&M training is better for people with low vision who have specific characteristics and needs. Orientation and mobility instructors and scientists should plan randomised controlled trials (RCTs) to compare the effectiveness of different types of O&M training. A consensus is needed on the adoption of standard measurement instruments of mobility performance which are proven to be reliable and sensitive to the diverse mobility needs of people with low vision. For this purpose, questionnaires and performance-based tests may represent different tools that explore people with low vision's subjective experience or their objective functioning, respectively. In fact, it has to be observed that low vision rehabilitation research is increasingly shifting towards the use of quality of life questionnaires as an outcome measure, sometimes with the aim to study complex and multidisciplinary interventions including different types of education and support, of which O&M can be a component. An example of this is an ongoing cluster RCT conducted by Zijlstra et al. in The Netherlands. This trial is designed to compare standardised O&M training with usual O&M care not only for its effectiveness, but also its applicability and acceptability. This study adopts validated questionnaires for patients' subjective assessment of performance during activities of daily living. As performance assessment does not need to be made by an O&M trainer, this allows for masking of assessors and a patient-centred outcome measure. Source


Brandi M.L.,University of Florence
Expert Opinion on Investigational Drugs | Year: 2012

Introduction: The biological process of fracture healing is complex with influences that are both patient-dependent and related to the trauma experienced and stability of the fracture. Fracture healing complications negatively affect the patient's quality of life, even more when fractures occur in the elderly osteoporotic patients. Areas covered: In the polytherapy for bone regeneration, a high success rate was obtained with the use of growth factors, osteogenic cells, and osteoconductive factors. There have been high expectations that treatment with drugs active on bone remodeling would be efficient for acceleration of fracture healing. A literature search was undertaken using wording like "drug or pharmacology of fracture healing." This report will review the systemic pharmacological agents for which clinical trials documenting their efficacy on bone healing have been carried out or are underway. Expert opinion: At present the use of systemic pharmacological agents to enhance fracture healing in the clinical setting is still controversial. However, future clinical trials will offer the possibility to obtain data that will make possible the registration of a drug as a "healer." © Informa UK, Ltd. Source


In Italy, between the end of the "long nineteenth century" and the beginning of the "age of extremes", ways, places and languages of riots and manifestations deeply changed. Therefore, in the field of history of Social conflict, the First World War is also a strong switch. Many researchers underlined that former ways of protestation had then disappeared - particularly in the field of resources control and price policies - while new forms of social arbitration and mass industrialized societies born. According to them, the mobilisation the institutions and parties were organizing did substitute the former and traditional protestations. Actually, during the 20th century, many large-scale food riots happened. In 1919, many forms of revolts, usually associated to several historical periods, do intersect. For a long time, Italian historiography has associated that kind of mob to archaic riot forms, not compatible with a more modern kind of mob such as strike or factories occupations. It is not a primitive rebellion resurgence, but a renewal of traditional forms of collective actions, and their respective declinations, according to 20th century's typical protestations whose influence on contemporary Italian social and conflicts history will be a fundamental point. © 2013 Taylor & Francis. Source


Locatelli M.,University of Turin | Schoen F.,University of Florence
Journal of Global Optimization | Year: 2015

In this paper we derive a lower bound, independent from the number of atoms N, for the minimal interatomic distances between atoms in a cluster whose total energy is modelled by means of the so called Morse potential. A similar result was previously proven for Lennard–Jones clusters but the proof can not be extended to Morse clusters. Besides the theoretical interest, the derivation of this lower bound is important for the definition of efficient procedures for the computation of the total energy of clusters with a large number of atoms. © 2002Kluwer Academic Publishers. Printed in the Netherlands. Source


Caneschi A.,University of Florence | Casu M.B.,University of Tubingen
Chemical Communications | Year: 2014

We deposit a paramagnetic pyrene derivative of the nitronyl nitroxide radical on Si(111). The molecules experience a strong chemical interaction with the substrate that influences the film growth. We also study the time evolution of the nitronyl nitroxide radical under a micro-focused soft X-ray beam, observing a stable radical as a product. This result hints at the possibility of using this class of materials in dosimeters and sensors. © the Partner Organisations 2014. Source


Landi S.,University of Florence | Matteini L.,Imperial College London | Pantellini F.,University Paris Diderot
Astrophysical Journal Letters | Year: 2014

Using statistically significant data at 1 AU, it has recently been shown (Bale et al.) that in the solar wind, when the Knudsen number K T (the ratio between the electron mean free path and the electron temperature scale height) drops below about 0.3, the electron heat flux q intensity rapidly approaches the classical collisional Spitzer-Härm limit. Using a fully kinetic model including the effect of Coulomb collisions and the expansion of the solar wind with heliocentric distance, we observe that the heat flux strength does indeed approach the collisional value for Knudsen numbers smaller than about 0.3 in very good agreement with the observations. However, closer inspection of the heat flux properties, such as its variation with the heliocentric distance and its dependence on the plasma parameters, shows that for Knudsen numbers between 0.02 and 0.3 the heat flux is not conveniently described by the Spitzer-Härm formula. We conclude that even though observations at 1 AU seem to indicate that the electron heat flux intensity approaches the collisional limit when the Knudsen drops below 0.3, the collisional limit is not a generally valid closure for a Knudsen larger than 0.01. Moreover, the good agreement between the heat flux from our model and the heat flux from solar wind measurements in the high-Knudsen number regime seems to indicate that the heat flux at 1 AU is not constrained by electromagnetic instabilities as both wave-particle and wave-wave interactions are neglected in our calculations. © 2014. The American Astronomical Society. All rights reserved.. Source


Moriondo M.,CNR Institute for Biometeorology | Giannakopoulos C.,Institute for Environmental Research and Sustainable Development | Bindi M.,University of Florence
Climatic Change | Year: 2011

This work was aimed at assessing the role of climate extremes in climate change impact assessment of typical winter and summer Mediterranean crops by using Regional Circulation Model (RCM) outputs as drivers of a modified version of the CropSyst model. More specifically, climate change effects were investigated on sunflower (Helianthus annuus L.) and winter wheat (Triticum aestivum L.) development and yield under the A2 and B2 scenarios of the IPCC Special Report on Emissions Scenarios (SRES). The direct impact of extreme climate events (i. e. heat stress at anthesis stage) was also included. The increase in both mean temperatures and temperature extremes under A2 and B2 scenarios (2071-2100) resulted in: a general advancement of the main phenological stages, shortening of the growing season and an increase in the frequency of heat stress during anthesis with respect to the baseline (1961-1990). The potential impact of these changes on crop yields was evaluated. It was found that winter and summer crops may possess a different fitting capacity to climate change. Sunflower, cultivated in the southern regions of the Mediterranean countries, was more prone to the direct effect of heat stress at anthesis and drought during its growing cycle. These factors resulted in severe yield reduction. In contrast, the lower frequency of heat stress and drought allowed the winter wheat crop to attain increased yields with respect to the baseline period. It can be concluded that the impact of extreme events should be included in crop-modelling approaches, otherwise there is the risk of underestimating crop yield losses, which in turn would result in the application of incorrect policies for coping with climate change. © 2010 Springer Science+Business Media B.V. Source


Monami M.,University of Florence | Mannucci E.,Diabetes Agency
Current Medical Research and Opinion | Year: 2013

Objectives: Degludec is a novel long-acting insulin analogue, providing an adequate supply of basal insulin over 24 hours with one daily injection, with a supposed greater reproducibility and flexibility than other basal insulins. Methods: An extensive search of Medline and the Cochrane Library for 'degludec' was performed, up to July 1st, 2012, collecting all randomised trials with a duration of at least 16 weeks and enrolling patients with diabetes. The principal outcome was the effect of degludec, compared with other basal insulins, on endpoint HbA1c and hypoglycaemia. Secondary outcomes included BMI, FPG at endpoint, and the incidence of cardiovascular events and cancer. Results: In the four trials comparing degludec with glargine, endpoint HbA1c was similar in the two groups, whereas FPG was significantly lower in degludec-treated patients. Degludec was associated with a lower rate of overall and nocturnal hypoglycaemia in type 2 and type 1 diabetes, respectively. No differences were observed for cardiovascular events and cancer. Study limitations: The number of available trials and the duration of exposure were limited, so the results obtained should be considered preliminary. Conclusions: Degludec appears to be associated with a lower incidence of hypoglycaemia in comparison with glargine, for similar levels of glycaemic control. The use of this agent could represent one step further in insulin therapy. © 2013 Informa UK Ltd All rights reserved. Source


Virgili G.,University of Florence
The Cochrane database of systematic reviews | Year: 2013

The purpose of low-vision rehabilitation is to allow people to resume or to continue to perform daily living tasks, with reading being one of the most important. This is achieved by providing appropriate optical devices and special training in the use of residual-vision and low-vision aids, which range from simple optical magnifiers to high-magnification video magnifiers. To assess the effects of reading aids for adults with low vision. We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2013, Issue 1), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE, (January 1950 to January 2013), EMBASE (January 1980 to January 2013), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to January 2013), OpenGrey (System for Information on Grey Literature in Europe) (www.opengrey.eu/), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov/) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 31 January 2013. We searched the reference lists of relevant articles and used the Science Citation Index to find articles that cited the included studies and contacted investigators and manufacturers of low-vision aids. We handsearched the British Journal of Visual Impairment from 1983 to 1999 and the Journal of Visual Impairment and Blindness from 1976 to 1991. This review includes randomised and quasi-randomised trials in which any device or aid used for reading had been compared to another device or aid in people aged 16 or over with low vision as defined by the study investigators. At least two authors independently assessed trial quality and extracted data. We included nine small studies with a cross-over-like design (181 people overall) and one study with three parallel arms (243 participants) in the review. All studies reported the primary outcome, results for reading speed.Two studies including 92 participants found moderate- or low-quality evidence suggesting that reading speed is higher with stand-mounted electronic devices or electronic devices with the camera mounted in a 'mouse' than with optical magnifiers, which in these trials were generally stand-mounted or, less frequently, hand-held magnifiers or microscopic lenses. In another study of 20 participants there was moderate-quality evidence that optical devices are better than head-mounted electronic devices (four types).There was low-quality evidence from three studies (93 participants) that reading using head-mounted electronic devices is slower than with stand-based electronic devices. The technology of electronic devices may have changed and improved since these studies were conducted.One study suggested no difference between a diffractive spectacle-mounted magnifier and either refractive (15 participants) or aplanatic (15 participants) magnifiers.One study of 10 people suggested that several overlay coloured filters were no better and possibly worse than a clear filter.A parallel-arm study including 243 participants with age-related macular degeneration found that custom or standard prism spectacles were no different from conventional reading spectacles, although the data did not allow precise estimates of performance to be made. There is insufficient evidence on the effect of different types of low-vision aids on reading performance. It would be necessary to investigate which patient characteristics predict performance with different devices, including costly electronic devices. Better-quality research should also focus on assessing sustained long-term use of each device. Authors of studies testing several devices on the same person should consider design and reporting issues related to their sequential presentation and to the cross-over-like study design. Source


Rook L.,University of Florence | Martinez-Navarro B.,Rovira i Virgili University
Quaternary International | Year: 2010

European continental mammal biochronology has been developed in Italy since the pioneering work of Augusto Azzaroli. The Villafranchian is a Mammal Age, a biochronological unit. Biochronology is a sub-division of geological time on the basis of the succession of evolutionary stage of faunal assemblages and dispersal events. The Villafranchian Mammal Age is based on European large mammals and corresponds, in the International Stratigraphic Scale, to a time span from Late Pliocene to most of the Early Pleistocene. Within these limits the Villafranchian spans from around 3.5 Ma to about 1.0-1.1 Ma. " Villafranchian" is a concept relatively common within the scientific literature of continental stratigraphers in Europe. Unfortunately, it is sometimes used in the wrong way or in wrong contexts, especially because the term Villafranchian has been used with the meaning of a continental stage, totally misunderstanding its significance as a biochronologic unit. The authors provide an update of the Villaranchian Mammal Age and its present significance. © 2010 Elsevier Ltd and INQUA. Source


Gherardini L.,CNR Institute of Neuroscience | Gennaro M.,CNR Institute of Neuroscience | Pizzorusso T.,CNR Institute of Neuroscience | Pizzorusso T.,University of Florence
Cerebral Cortex | Year: 2015

Ischemic stroke insults may lead to chronic functional limitations that adversely affect patient movements. Partial motor recovery is thought to be sustained by neuronal plasticity, particularly in areas close to the lesion site. It is still unknown if treatments acting exclusively on cortical plasticity of perilesional areas could result in behavioral amelioration. We tested whether enhancing plasticity in the ipsilesional cortex using local injections of chondroitinase ABC (ChABC) could promote recovery of skilled motor function in a focal cortical ischemia of forelimb motor cortex in rats. Using the skilled reaching test, we found that acute and delayed ChABC treatment induced recovery of impaired motor skills in treated rats. vGLUT1, vGLUT2, and vGAT staining indicated that functional recovery after acute ChABC treatment was associated with local plastic modification of the excitatory cortical circuitry positive for VGLUT2. ChABC effects on vGLUT2 staining were present only in rats undergoing behavioral training. Thus, the combination of treatments targeting the CSPG component of the extracellular matrix in perilesional areas and rehabilitation could be sufficient to enhance functional recovery from a focal stroke. © 2013 The Author. Source


Tognini P.,Normal School of Pisa | Tognini P.,CNR Institute of Neuroscience | Pizzorusso T.,CNR Institute of Neuroscience | Pizzorusso T.,University of Florence
International Journal of Biochemistry and Cell Biology | Year: 2012

MicroRNAs (miRNAs) are small non-coding RNAs that mediate post-transcriptional gene silencing. It is increasingly clear that miRNAs are key regulatory factors for a tight gene expression control. MiRNAs are involved in many aspects of organism development and function, in physiological and pathological conditions. MiRNA expression varies with cell type, tissue and developmental stages. The microRNA212/132 family is one of the most studied miRNA family due to the involvement of miR132 and miR212 in important cellular processes, especially in the brain. MiR132 and miR212 have been implicated in tissue development and in the formation and plasticity of neuronal connections. The main aim of this review is to highlight recent discoveries about miR212/132 family functions and its possible involvement in pathological processes. © 2011 Elsevier Ltd. All rights reserved. Source


Bertini A.,University of Florence | Martinetto E.,University of Turin
Palaeogeography, Palaeoclimatology, Palaeoecology | Year: 2011

The first comprehensive and comparative analysis of the main micro (pollen) - and macro (leaves, fruits and seeds) - palaeobotanical data from northern and central Italian sites, allows four transects of ancient vegetation for the Messinian to Piacenzian interval to be constructed. Standard criteria for the reconstruction of vegetation transects are established, so that our approach could be extended to other basins or regions bearing Neogene palaeofloras, and would permit readily comparable reconstructions of past vegetation to be obtained. Messinian to Piacenzian lowland plant communities, as reconstructed by means of this integrated and standardized approach, show the dominance of warm temperate forest taxa in northern and central Italy, with the highest floristic affinity to present day forests of the eastern part of central China. Some panholartic conifers, usually interpreted as "cool temperate" taxa in Neogene assemblages, are assigned to the upland vegetation; they are scarcely represented in Messinian and Zanclean pollen records (with the exception of some intervals characterized by increases in Picea and Cedrus) and almost completely lacking in leaf and carpological ones; during the Piacenzian, notably from 2.8. Ma, the pollen percentage of such taxa, in particular Picea, progressively increased. The overall scantiness of non-aquatic herbs, not only in the macrofossil record, but also in the pollen one, indicates the absence of dry conditions and excludes long-lasting expansion of open vegetation. The type of vegetation ("subtropical humid forest") reconstructed for the evaporitic Messinian (ca. 5.9 to 5.6. Ma) suggests that the Adriatic-Padane basin would have been under predominant moist conditions, even during the deposition of evaporites. Slightly drier phases in the post-evaporitic Messinian are suggested at first by the short period of increase of Lygeum, a steppe plant, close to 5.5. Ma, then by the ecological preferences of some unusual macrofossil taxa (Cupressus, Medicago, Vitex). These are, however, still associated with arboreal plants which require humid conditions, definitely indicating that forested environments persisted ("subtropical sub-humid forest"). The Zanclean and Piacenzian transects are extremely similar to the evaporitic Messinian one, and the mesic lowland (zonal) vegetation can still be defined as "subtropical humid forest". © 2010 Elsevier B.V. Source


Apollaro T.J.G.,University of Florence | Di Franco C.,University College Cork | Plastina F.,University of Calabria | Paternostro M.,Queens University of Belfast
Physical Review A - Atomic, Molecular, and Optical Physics | Year: 2011

Using recently proposed measures for non-Markovianity, we study the dynamics of a qubit coupled to a spin environment via an energy-exchange mechanism. We show the existence of a point, in the parameter space of the system, where the qubit dynamics is effectively Markovian and that such a point separates two regions with completely different dynamical behaviors. Indeed, our study demonstrates that the qubit evolution can in principle be tuned from a perfectly forgetful one to a deep non-Markovian regime where the qubit is strongly affected by the dynamical backaction of the environmental spins. By means of a theoretical quantum process tomography analysis, we provide a complete and intuitive characterization of the qubit channel. © 2011 American Physical Society. Source


Baluska F.,University of Bonn | Mancuso S.,University of Florence
Frontiers in Cellular and Infection Microbiology | Year: 2013

In the course of plant evolution, there is an obvious trend toward an increased complexity of plant bodies, as well as an increased sophistication of plant behavior and communication. Phenotypic plasticity of plants is based on the polar auxin transport machinery that is directly linked with plant sensory systems impinging on plant behavior and adaptive responses. Similar to the emergence and evolution of eukaryotic cells, evolution of land plants was also shaped and driven by infective and symbiotic microorganisms. These microorganisms are the driving force behind the evolution of plant synapses and other neuronal aspects of higher plants; this is especially pronounced in the root apices. Plant synapses allow synaptic cell-cell communication and coordination in plants, as well as sensory-motor integration in root apices searching for water and mineral nutrition. These neuronal aspects of higher plants are closely linked with their unique ability to adapt to environmental changes. © 2013 Baluška and Mancuso. Source


Sorace S.,University of Udine | Terenzi G.,University of Florence
Bulletin of Earthquake Engineering | Year: 2014

The study of two motion control-based seismic retrofit solutions for a low-rise reinforced concrete school building is presented in this paper. The building was assumed as a benchmark structure for a Research Project financed by the Italian Department of Civil Protection, and is representative of several similar public edifices designed with earlier Technical Standards editions, in Italy as well as in other earthquake-prone European countries. The two solutions refer to the alternative earthquake protection strategies based on the concepts of supplemental damping and seismic isolation, respectively. Namely, they consist in the installation of: (1) a dissipative bracing system incorporating pressurized fluid viscous spring-dampers; and (2) a base isolation system including double friction pendulum sliding bearings. The structural characteristics of the building, and a synthesis of the investigation campaigns developed on it, are initially presented. The mechanical parameters, dimensions, locations and installation details of the constituting elements of the two protective systems are then illustrated, along with the performance assessment analyses carried out in original and rehabilitated conditions according to a full non-linear dynamic approach. The results of the analyses show a remarkable enhancement of the seismic response capacities of the structure for both retrofit hypotheses. This allows reaching the mutual high performance levels postulated in the two rehabilitation designs with remarkably lower costs and architectural intrusion as compared to traditional rehabilitation interventions designed for the same objectives. © 2014, Springer Science+Business Media Dordrecht. Source


Bartolini F.,University of Florence | Barausse A.,University of Padua | Portner H.-O.,Alfred Wegener Institute for Polar and Marine Research | Giomi F.,Alfred Wegener Institute for Polar and Marine Research
Global Change Biology | Year: 2013

Integrating long-term ecological observations with experimental findings on species response and tolerance to environmental stress supports an understanding of climate effects on population dynamics. Here, we combine the two approaches, laboratory experiments and analysis of multi-decadal time-series, to understand the consequences of climate anomalies and ongoing change for the population dynamics of a eurythermal littoral species, Carcinus aestuarii. For the generation of cause and effect hypotheses we investigated the thermal response of crab embryos at four developmental stages. We first measured metabolic rate variations in embryos following acute warming (16-24 °C) and after incubation at 20 and 24 °C for limited periods. All experiments consistently revealed differential thermal responses depending on the developmental stage. Temperature-induced changes in metabolic activity of early embryonic stages of blastula and gastrula suggested the onset of abnormal development. In contrast, later developmental stages, characterized by tissue and organ differentiation, were marginally affected by temperature anomalies, indicating enhanced resilience to thermal stress. Then, we extended these findings to a larger, population scale, by analyzing a time-series of C. aestuarii landings in the Venice lagoon from 1945 to 2010 (ripe crabs were recorded separately) in relation to temperature. Landings and extreme climatic events showed marked long-term and short-term variations. We found negative relationships between landings and thermal stress indices on both timescales, with time lags consistent with an impact on crab early life stages. When quantitatively evaluating the influence of thermal stress on population dynamics, we found that it has a comparable effect to that of the biomass of spawners. This work provides strong evidence that physiological responses to climatic anomalies translate into population-level changes and that apparently tolerant species may be impacted before the ontogeny of eurythermy. These ontogenetic bottlenecks markedly shape population dynamics and require study to assess the effects of global change. copy; 2012 Blackwell Publishing Ltd. Source


The aim of this review is to characterize the functional results and "anterior resection syndrome" (ARS) after sphincter-saving surgery for rectal cancer. The purpose of sphincter-saving operations is to save the anal sphincters by avoiding the need for rectal abdomino-perineal resection with a permanent stoma. A variety of alternative techniques have been proposed and, today, ultra-low anterior resections of the rectum are commonplace. Inevitably rectal resections modify anorectal physiology. The backdrop of the functional asset for ultralow anterior resections is related to a small neorectal capacity with high endo-neorectal pressures that act together on a weakened sphincteric mechanism. Sometimes a defecation disorder called ARS may be induced and the patient experiences an extremely low quality of life. Impaired bowel function is usually provoked either by colonic dysmotility, neorectal reservoir dysfunction, anal sphincter damage or by a combination of these factors. Surgical technique defects can contribute to these possible causes: anastomotic ischemia, short length of the descending colon and stretching of neorectal mesentery may play a role. Unfortunately, there is no therapeutic algorithm or gold standard treatment that may be used for ARS. Nevertheless, it is rational to use conservative therapy first and then resort to surgery. Drugs, rehabilitative treatment and sacral neuromodulation may be used; after failure of conservative methods, surgical treatment can be considered. © 2013 Springer-Verlag Italia. Source


Rovida E.,University of Florence
Cellular and molecular life sciences : CMLS | Year: 2014

Receptor tyrosine kinases (RTK) have long being studied with respect to the "canonical" signaling. This includes ligand-induced activation of a receptor tyrosine kinase at the cell surface that leads to receptor dimerization, followed by its phosphorylation in the intracellular domain and activation. The activated receptor then recruits cytoplasmic signaling molecules including other kinases. Activation of the downstream signaling cascade frequently leads to changes in gene expression following nuclear translocation of downstream targets. However, RTK themselves may localize within the nucleus, as either full-length molecules or cleaved fragments, with or without their ligands. Significant differences in this mechanism have been reported depending on the individual RTK, cellular context or disease. Accumulating evidences indicate that the colony-stimulating factor-1 receptor (CSF-1R) may localize within the nucleus. To date, however, little is known about the mechanism of CSF-1R nuclear shuttling, as well as the functional role of nuclear CSF-1R. Source


Gallori E.,University of Florence
Rendiconti Lincei | Year: 2011

The formation of primordial genetic material, whatever it was, would have required the presence on early Earth of the starting organic material for the synthesis of the building blocks of the genetic molecules, the nucleotides. Recent observations indicated that the majority of the organic compounds have been introduced on Earth by the interstellar dust particles (IDPs) that are considered the principal agents in the formation of complex molecules, thanks to their peculiar surface-catalytic activities. Results obtained in the last years, in different fields, strengthen the hypothesis, originally proposed by Bernal (The Physical basis of life, 1951) of a clay-surface-mediated origin of genetic material. © Springer-Verlag 2011. Source


Landi S.,University of Florence | Bettarini L.,Observatoire Royale de Belgique
Space Science Reviews | Year: 2012

The properties of spontaneous reconnection of a current sheet analyzed via direct three-dimensional simulations are presented. In particular the non-linear dynamics of resistive instabilities has been studied in absence or in presence of velocity shears. It is shown that full three-dimensional simulations allow the inclusion of a rich variety of (ideal) secondary instabilities which, depending on the initial equilibrium magnetic field configuration, determine the final fate of the system in the fully non linear regime. In particular in presence of a guide-field the dynamic is similar to what observed in two-dimensional simulations with energy driven toward both smaller and larger scales and energy spectra anisotropy. For different magnetic field configurations, the final state is characterized by the disruption of the coalesced structure created during the resistive phase and the system is characterized by a more chaotic state. A discussion on the importance of high-order numerical techniques in numerical simulations of magnetic reconnection is also present. © 2011 Springer Science+Business Media B.V. Source


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

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


Marie P.J.,French Institute of Health and Medical Research | Marie P.J.,University Paris Diderot | Felsenberg D.,Center for Muscle and Bone Research | Brandi M.L.,University of Florence
Osteoporosis International | Year: 2011

Oestrogen deficiency increases the rate of bone remodelling which, in association with a negative remodelling balance (resorption exceeding formation), results in impaired bone architecture, mass and strength. Current antiosteoporotic drugs act on bone remodelling by inhibiting bone resorption or by promoting its formation. An alternative therapeutic approach is based on the concept of inducing opposite effects on bone resorption and formation. One therapeutic agent, strontium ranelate, was shown to induce opposite effects on bone resorption and formation in pre-clinical studies and to reduce fracture risk in postmenopausal osteoporotic patients. How strontium ranelate acts to improve bone strength in humans remains a matter of debate, however. This review of the most recent pre-clinical and clinical studies is a critical analysis of strontium ranelate's action on bone resorption and formation and how it increases bone mass, microarchitecture and strength in postmenopausal osteoporotic women. © International Osteoporosis Foundation and National Osteoporosis Foundation 2010. Source


Marin-Valencia I.,University of Texas Southwestern Medical Center | Guerrini R.,University of Florence | Gleeson J.G.,Howard Hughes Medical Institute
Epilepsia | Year: 2014

Focal cortical dysplasias (FCDs) constitute a prevalent cause of intractable epilepsy in children, and is one of the leading conditions requiring epilepsy surgery. Despite recent advances in the cellular and molecular biology of these conditions, the pathogenetic mechanisms of FCDs remain largely unknown. The purpose if this work is to review the molecular underpinnings of FCDs and to highlight potential therapeutic targets. A systematic review of the literature regarding the histologic, molecular, and electrophysiologic aspects of FCDs was conducted. Disruption of the mammalian target of rapamycin (mTOR) signaling comprises a common pathway underlying the structural and electrical disturbances of some FCDs. Other mechanisms such as viral infections, prematurity, head trauma, and brain tumors are also posited. mTOR inhibitors (i.e., rapamycin) have shown positive results on seizure management in animal models and in a small cohort of patients with FCD. Encouraging progress has been achieved on the molecular and electrophysiologic basis of constitutive cells in the dysplastic tissue. Despite the promising results of mTOR inhibitors, large-scale randomized trials are in need to evaluate their efficacy and side effects, along with additional mechanistic studies for the development of novel, molecular-based diagnostic and therapeutic approaches. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here. © Wiley Periodicals, Inc. © 2014 International League Against Epilepsy. Source


Procacci P.,University of Florence
Journal of Chemical Information and Modeling | Year: 2016

We present a new release (6.0β) of the ORAC program [Marsili et al. J. Comput. Chem. 2010, 31, 1106-1116] with a hybrid OpenMP/MPI (open multiprocessing message passing interface) multilevel parallelism tailored for generalized ensemble (GE) and fast switching double annihilation (FS-DAM) nonequilibrium technology aimed at evaluating the binding free energy in drug-receptor system on high performance computing platforms. The production of the GE or FS-DAM trajectories is handled using a weak scaling parallel approach on the MPI level only, while a strong scaling force decomposition scheme is implemented for intranode computations with shared memory access at the OpenMP level. The efficiency, simplicity, and inherent parallel nature of the ORAC implementation of the FS-DAM algorithm, project the code as a possible effective tool for a second generation high throughput virtual screening in drug discovery and design. The code, along with documentation, testing, and ancillary tools, is distributed under the provisions of the General Public License and can be freely downloaded at www.chim.unifi.it/orac. © 2016 American Chemical Society. Source


Cevenini E.,University of Bologna | Monti D.,University of Florence | Franceschi C.,University of Bologna
Current Opinion in Clinical Nutrition and Metabolic Care | Year: 2013

PURPOSE OF REVIEW: Inflamm-ageing, defined as the chronic low-grade inflammation typical of ageing, seems to be the common biological factor responsible for the decline and the onset of disease in the elderly. The major age-related diseases share a common inflammatory pathogenesis, giving rise to the so-called 'diseasome of inflamm-ageing'. Main objective of this review is to provide a comprehensive view of the complex interactions responsible for inflamm-ageing, underlining its relationship with metaflammation and the role of senescent cells, gut microbiota and nutrition in determining when, where and how much this phenomenon impacts on the health status during human lifespan. RECENT FINDINGS: The ageing process and the health status of elderly people may be improved by facing and slowing down inflamm-ageing. Among the inflammation modulators, gut microbiota and nutrition should be exploited as potential powerful tools to promote healthy ageing and to extend the lifespan in humans. SUMMARY: The possibility to control inflamm-ageing represents a powerful tool to modulate and counteract the major age-related pathologies and it is urgent to clarify the shady areas of the complex mechanisms underpinning inflamm-ageing in order to carry out targeted therapeutic interventions towards an improvement of the health status in the elderly population. © Lippincott Williams & Wilkins. Source


Becattini F.,University of Florence
Journal of Physics: Conference Series | Year: 2014

In this talk we briefly review some of the achievements in the study of the QCD matter at high temperature produced in the nuclear collisions at very high energies. We focus on its bulk properties: hydrodynamical and thermodynamical. © Published under licence by IOP Publishing Ltd. Source


Brandi M.L.,University of Florence | Minisola S.,University of Rome La Sapienza
Current Medical Research and Opinion | Year: 2013

Objective: Osteoporosis is a skeletal disorder characterized by diminished bone strength, which results in an increased risk of fracture. Currently, osteoporosis is a public health priority due to the large number of individuals affected and the detrimental effect on quality of life. Primary osteoporosis, the most common form, usually results from age-related reduction in bone mineral strength. Over time, the individual's capacity to build bone is impaired, as the synthesis of vitamin D, the hormone responsible for calcium absorption, tends to decline. As serum calcium levels decrease, metabolic control serves to increase the removal of calcium from the skeleton to make up for the deficit. The synthesis of the 'hormone' vitamin D and its control therefore become central to intervention in involutional osteoporosis syndromes. In humans, plain vitamin D (cholecalciferol), also called parental or native vitamin D, is photosynthesized in the skin and then hydroxylated in the liver into the vitamin D analog calcidiol [25(OH)D3], which is hydroxylated again in the kidney into the vitamin D analog calcitriol [1,25(OH)2D3]. The advantage of administering vitamin D analogs is that the pro-drug calcidiol avoids the effect of declines in hepatic function, while calcitriol avoids the effect of declines in hepatic and kidney function. A strategy to enhance [25(OH)D3] levels to the optimal threshold of vitamin D is supplementation with the calcidiol metabolite itself. The goal of this paper is to review published studies on the efficacy of the calcidiol metabolite in increasing 25(OH)D3 serum levels and improving skeletal health parameters in humans. Methods: A library search of published papers in the area of use of calcidiol in humans from 1967 to 2013 was performed (key words: calcidiol, 25-hydroxy-vitamin D3, vitamin D supplementation, vitamin D metabolism, osteomalacia). Results and conclusion: The results of the survey made it possible to conclude that calcidiol is characterized by a number of features that make the compound ideal in conditions that require supplementation with a 25-hydroxylated metabolite. © 2013 Informa UK Ltd. Source


Pellegrino E.,University of Florence
Annali di igiene : medicina preventiva e di comunità | Year: 2013

Listening to music through portable MP3 players has become a very popular mode among young people and adolescents. The aim of this study is to investigate the behaviors of adolescents engaged in listening to music with MP3 player and the attendance at clubs (pubs, discotheques) where music is played at high volume. Among the 1470 students attending a secondary school in Scandicci (FI) during the school year 2009/2010, 1278 (86.9%) were at school the day of the examination and 1276 completely filled in the questionnaire. Descriptive analysis and univariate and multivariate logistic regression were performed to calculate the degree of association (OR) among the sociodemographic characteristics, listening habits and some factors identified as risky or protective as regards the possibility of developing health disorders. MP3 player users are 88.2% of the sample. Among these, a high proportion engaged behaviours that increase the risk of presenting disorders, including the exposure to high-volume (27.4%). Furthermore, 44.6% use the MP3 while driving. From the regression analysis it emerges that MP3 users showed a sort of addiction: by increasing the time and the occasions of exposure to music, they increased the volume, used maximum or medium-high volume, did not take breaks and did not decrease the volume. The study points out the spread of risky behavior in music listening, so it is necessary to better inform especially the youngsters and achieve specific preventive interventions. Source


Mazzinghi A.,University of Florence
Nuovo Cimento della Societa Italiana di Fisica C | Year: 2014

Beato Angelico is one of the most important Italian painters of the Renaissance period, in particular he was a master of the so-called " buon fresco" technique for mural paintings. A wide diagnostic campaign with X-Ray Fluorescence (XRF) analyses has been carried out on three masterworks painted by Beato Angelico in the San Marco monastery in Florence: the Crocifissione con Santi, the Annunciazione and the Madonna delle Ombre. The latter is painted by mixing fresco and secco techniques, which makes it of particular interest for the study of two different paintings techniques of the same artist. Then the aim of the study was focused on the characterization of the painting palette, and therefore the painting techniques, used by Beato Angelico. Moreover, the conservators were interested in the study of degradation processes and old restoration treatments. Our analyses have been carried out by means of the XRF spectrometer developed at LABEC laboratory at Istituto Nazionale di Fisica Nucleare in Florence (Italy). XRF is indeed especially suited for such a kind of study, allowing for multi-elemental, nondestructive, non-invasive analyses in a short time, with portable instruments. In this paper the first results concerning the XRF analysis are presented. © Società Italiana di Fisica. Source


Gomis J.,University of Barcelona | Longhi G.,University of Florence
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2016

We study the canonical realization of Bondi-Metzner-Sacks symmetry for a massive scalar field introduced by Longhi and Materassi [J. Math. Phys. 40, 480 (1999)]. We construct an invariant scalar product for the generalized momenta. As a consequence we introduce a quadratic Casimir with the supertranslations. © 2016 American Physical Society. Source


The objective of this study was to prospectively verify if diffusion-weighted magnetic resonance (DwMR)-related parameters such as perfusion fraction (f) and slow diffusion coefficient (D), according to Le Bihan theory, are more effective than apparent diffusion coefficient (ADC) for classification and characterization of the more frequent focal liver lesions (FLLs) in noncirrhotic liver. Sixty-seven patients underwent standard liver magnetic resonance imaging (MRI) and free-breath multi-b DwMR study. Two regions of interest were defined by 2 observers, including 1 FLL for each patient (21 hemangiomas, 21 focal nodular hyperplasias, 25 metastases) and part of surrounding parenchyma, respectively. For every FLL, D, f, and ADC were estimated both as absolute value and as ratio between FLL and surrounding parenchyma by fitting the reduced equation of the bicompartmental model to experimental data; t test, analysis of variance, and receiver operating characteristic analysis were performed. t Test showed significant differences in ADClesion, f lesion, D lesion, ADCratio, and D ratio values between benign and malignant FLLs, more pronounced for ADClesion (P < 0.0009) and ADCratio (P = 0.001). Applying cutoff values of 1.55 × 10 mm/s (ADClesion) and 0.89 (ADCratio), the DwMR study presented sensitivities and specificities, respectively, of 84% and 80% (for ADClesion), 72% and 80% (ADCratio). Apparent diffusion coefficient (by fitting procedures) better performs than do D and f in FLL classification, especially when its values are less than 1.30 or greater than 2.00 × 10 mm/s. Source


Li Y.,Zhejiang University | Ranieri M.,University of Florence
Computers and Education | Year: 2013

Over the last decades, the issue of digital divide has received particular attention from international bodies and researchers in Western countries. One of the main reasons for this growing interest is related to the implications that digital inequalities have for social development and particularly for education. Despite the relevance of the issue, there are still few studies on the digital divide in China and even less on Chinese K-12 schools' students. This paper aims at exploring the digital divide issues among Chinese children from an educational and social perspective. Four schools were selected, involving 658 students aged 10-14. Nine hypotheses on Internet inequality indicators (DiMaggio & Hargittai, 2001) and their possible outcomes were tested. The study found that: (1) students' Internet access at home is better than that at school; (2) compared with parents, teachers have more positive influence on students' Internet behaviour; (3) students from rural or migrant schools score lower on all the Internet inequality indicators (digital access, autonomy of use, social support, Internet use and self-efficacy) and are therefore more disadvantaged in Internet usage status than their urban peers; (4) there are no significant gender differences; (5) the more education parents have received, the better the conditions of their children according to the listed Internet inequality indicators; (6) the dimensions of the Internet inequality indicators (technical apparatus, autonomy of use, availability of social support, variation of use) are significantly correlated to students' Internet self-efficacy; (7) there is high correlation between students' Internet self-efficacy and their exploring behaviours of Internet use and their academic performance. Overall, these results are consistent with data from OECD countries and confirm that the digital divide represents a big social challenge, revealing that schools still have to develop effective strategies to balance social and learning opportunities among students. © 2012 Elsevier Ltd. All rights reserved. Source


Mandala M.,Unit of Medical Oncology | Merelli B.,Unit of Medical Oncology | Massi D.,University of Florence
Critical Reviews in Oncology/Hematology | Year: 2014

RAS belongs to the guanosine 5'-triphosphate (GTP)-binding proteins' family, and oncogenic mutations in codons 12, 13, or 61 of RAS family occur in approximately one third of all human cancers with N-RAS mutations found in about 15-20% of melanomas. The importance of RAS signaling as a potential target in cancer is emphasized not only by the prevalence of RAS mutations, but also by the high number of RAS activators and effectors identified in mammalian cells that places the RAS proteins at the crossroads of several, important signaling networks. Ras proteins are crucial crossroads of signaling pathways that link the activation of cell surface receptors with a wide variety of cellular processes leading to the control of proliferation, apoptosis and differentiation. Furthermore, oncogenic ras proteins interfere with metabolism of tumor cells, microenvironment's remodeling, evasion of the immune response, and finally contributes to the metastatic process. After 40 years of basic, translational and clinical research, much is now known about the molecular mechanisms by which these monomeric guanosine triphosphatase-binding proteins promote cellular malignancy, and it is clear that they regulate signaling pathways involved in the control of cell proliferation, survival, and invasiveness. In this review we summarize the biological role of RAS in cancer by focusing our attention on the biological rational and strategies to target RAS in melanoma. © 2014 Elsevier Ireland Ltd. Source


Rook L.,University of Florence | Martinez-Navarro B.,Institute Catala Of Paleoecologia Humana Iphes
Palaeontographica, Abteilung A: Palaozoologie - Stratigraphie | Year: 2013

In 2004 by Rook and co-authors have been described the cervical vertebrae of a large primate from the Early Pleistocene record of Pirro Nord (Apulia, Italy). These specimens have been attributed to a large cercopithecoid on the basis of the overall morphology. According the European biochronological framework the authors proposed attribution of these fossils to the genus Theropithecus.The Rook et al. (2004) paper has been recently criticized by Patel et al. (2007) who questioned the relevance of the fossil primate cervical vertebrae for taxonomic identification. We offer here our view on the morphological evidence and we discuss the Early Pleistocene scenario of mammal faunals dispersal from Africa into Eurasia.© 2013 E. Schweizerbartsche Verlagsbuchhandlung, Stuttgart, Germany. Source


Merelli B.,Unit of Medical Oncology | Massi D.,University of Florence | Cattaneo L.,Papa Giovanni XXIII Hospital | Mandala M.,Unit of Medical Oncology
Critical Reviews in Oncology/Hematology | Year: 2014

A dynamic interplay exists between host and tumor, and the ability of the tumor to evade immune recognition often determines the clinical course of the disease. Significant enthusiasm currently exists for a new immunotherapeutic strategy: the use of immunomodulatory monoclonal antibodies that directly enhance the function of components of the anti-tumor immune response such as T cells, or block immunologic checkpoints that would otherwise restrain effective anti-tumor immunity. This strategy is based on the evidence that development of cancer is facilitated by the dis-regulation and exploitation of otherwise physiological pathways that, under normal circumstances, down-regulate immune activation and maintain tolerance to self. Among these pathways an important role is covered by the Programmed death-1 (PD-1)/PD-Ligand (L) 1 axis. An emerging concept in cancer immunology is that inhibitory ligands such as PD-L1 are induced in response to immune attack, a mechanism termed "adaptive resistance". This potential mechanism of immune resistance by tumors suggests that therapy directed at blocking the interaction between PD-1 and PD-L1 might synergize with other treatments that enhance endogenous antitumor immunity. The anti-PD-1 strategy can be effective in several solid tumors such as renal cell carcinoma (RCC) or non-small cell lung cancer (NSCLC), however in this review we summarize the biological role of PD-1/PD-L1 on cancer by focusing our attention in the biological rationale, clinical challenges and opportunities to target the PD-1/PD-L1 axis in melanoma. © 2013 Elsevier Ireland Ltd. Source


Social enterprise has become a key phenomenon in providing public services in many developed countries. The debate on the evaluation of the socio-economic impact generated by this kind of organization has gone hand in hand with the growth of social entrepreneurship. This study provides an exploratory analysis of the emerging practice of measuring the socio-economic impact of social enterprises using the theoretic construct called "Blended Value Accounting" (BVA). Among the models and tools proposed by BVA, we examine in particular the Social Return on Investment (SROI)-an instrument of causal contribution analysis-conducting a literature review on its application to the evaluation of socio-economic impact of social enterprises and on its implications for BVA. Finally, we reach a conclusion as to the role that these tools of mixed accounting and assessment might play-particularly the one examined-with respect to the positivist, critical, and interpretative theories of accounting, thus identifying the areas for further research. © 2012 International Society for Third-Sector Research and The Johns Hopkins University. Source


Santini V.,University of Florence
Hematology / the Education Program of the American Society of Hematology. American Society of Hematology. Education Program | Year: 2012

The treatment of symptomatic and high-risk myelodysplastic syndrome (MDS) spans several therapeutic goals and options. Key to the successful therapy of these heterogeneous diseases is careful characterization and diagnosis, including clinical, cytogenetic, biological, and molecular evaluation of individual patients. Any novel management strategy in MDS must be based on accepted and validated prognostic scoring systems, such as the International Prognostic Scoring System (IPSS), and should take into account predictive parameters of response to the available therapeutic agents and individual comorbidities. For IPSS lower-risk MDS patients, several first-line options are available, including erythropoietic stimulating agents, lenalidomide, and immunosuppressive drugs. Sequential therapy is advisable whenever response is lost, and the activity of azacitidine and decitabine in first- or second-line therapy is relevant, especially in patients with symptomatic cytopenias and anemia. Hypomethylating agents have a central role in therapy of IPSS higher-risk MDS patients. These agents include azacitidine and decitabine, which allow treatment of very elderly and frail patients, resulting in hematological improvement and transfusion independency in roughly half, and for azacitidine a demonstrated significant prolongation of survival. Because hypomethylating agents are not curative, they are not satisfactory for younger MDS patients, for whom a transplantation strategy should be planned. Although hypomethylating agent therapy is used extensively, a growing number of MDS patients fail to respond or progress. The future challenge is not only to find treatment regimens that target the dysplastic clone(s) so that durable remissions are achieved (particularly in high-risk patients with short survival and/or increased leukemic transformation rates), but also to also identify active salvage regimens. Source


Carloni V.,University of Florence | Luong T.V.,University College London | Rombouts K.,University College London
Liver International | Year: 2014

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the third leading cause of cancer death. Recent epidemiological data indicate that the mortality rate of HCC will double over the next decades in the USA and Europe. Liver cancer progresses in a large percentage of cases during the clinical course of chronic fibro-inflammatory liver diseases leading to cirrhosis. Therefore, HCC development is regarded as the result of different environmental risk factors each involving different genetic, epigenetic- and chromosomal alterations and gene mutations. During tumour progression, the malignant hepatocytes and the activated hepatic stellate cells are accompanied by cancer-associated fibroblasts, myofibroblasts and immune cells generally called tumour stromal cells. This new and dynamic milieu further enhances the responsiveness of tumour cells towards soluble mediators secreted by tumour stromal cells, thus directly affecting the malignant hepatocytes. This results in altered molecular pathways with cell proliferation as the most important mechanism of liver cancer progression. Given this contextual complexity, it is of utmost importance to characterize the molecular pathogenesis of HCC, and to identify the dominant pathways/drivers and aberrant signalling pathways. This will allow an effective therapy for HCC that should combine strategies affecting both cancer and the tumour stromal cells. This review provides an overview of the recent challenges and issues regarding hepatic stellate cells, extracellular matrix dynamics, liver fibrosis/cirrhosis and therapy, tumour microenvironment and HCC. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. Source


Hinderer M.,TU Darmstadt | Kastowski M.,TU Darmstadt | Kamelger A.,OMV Austria Exploration and Production GmbH | Bartolini C.,University of Florence | Schlunegger F.,University of Bern
Earth-Science Reviews | Year: 2013

This paper presents the first comprehensive analysis of sediment and dissolved load across an entire mountain range. We investigate patterns and rates of modern denudation of the European Alps based on a compilation of data about river loads and reservoir sedimentation from 202 drainage basins that are between ca. 1 to 10,000km2 large. The study basins cover about 50% of the total area of the Alps. Modern glaciated basins have the highest sediment yields of up to 7000tkm-2a-1, which are on average 5 to 10 times higher than in non-glaciated basins. Likewise sediment yield and glacial cover are positively correlated. Instead, relief is a relatively weak predictor of sediment yield. The strong glacial impact in the correlations is due to glacier recession since the 19th century as well as due to glacial conditioning during repeated Quaternary glaciations which have produced the strong transient state of the Alpine landscape. We suggest that this is the major cause for ca. 3 fold enhanced denudation of the western compared to the eastern Alps. Chemical denudation rates are highest in the external Alps dominated by carbonate sedimentary rocks, where they make up about one third of total denudation. The high rates cannot be explained without anhydrite dissolution. We estimated that only 45% of the sediments mobilized in headwaters are exported out off the Alps, most sediments being trapped in artificial reservoirs. The total amount of sediment annually trapped within the Alps equates to 43Mt. When corrected for sediment storage, we obtain an area-weighted mean total denudation rate for the Alps of about 0.32mma-1. The pre-dam rate might be as high as 0.42mma-1. In total, ca. 35 plus 23Mt of mass are exported each year out of the Alps as solids and solutes, respectively. These rates are not enough to out pace modern rock uplift. Nevertheless, pattern of sediment yield across the Alps coincides roughly with the intensity of glacial conditioning and modern rock uplift, supporting the hypothesis of an erosion-driven uplift of the Alps. © 2013 Elsevier B.V. Source


Ciampolini M.,University of Florence
International Journal of General Medicine | Year: 2012

Background: Scheduled meals are considered to be equivalent to those requested by the infant (null hypothesis). In adults, we have found high blood glucose before scheduled meals and low blood glucose after recognition of validated initial hunger. Low preprandial blood glucose is associated with a decrease in energy intake and body weight both in adults who are overtly overweight and in those who are of normal weight with insulin resistance (hidden overweight). In this study, we investigated the validity of the null hypothesis between scheduled and requested meals in 2-year-old infants with chronic nonspecific diarrhea. Methods: We trained a "recognizing request" meal pattern in 70 mother-infant pairs. The trained meal pattern consisted of administering food after a first request that we validated by blood glucose measurement in the hospital laboratory. Using a 7-day food diary, mothers reported preprandial blood glucose measurements for their infants three times a day. We assessed mean preprandial blood glucose, daily energy intake, days with diarrhea, blood parameters, and anthropometry before training and 4 months after training, and compared the results with measurements in 73 randomly selected untrained controls. Results: In the trained group, there was a decrease in mean blood glucose from 86.9 ± 9.4 mg/dL to 76.4 ± 6.7 mg/dL (P < 0.0001), as well as a decrease in energy intake and days with diarrhea in comparison with control infants who maintained scheduled meals. Only two of 21 infants who had a mean blood glucose lower than 81.2 mg/dL at recruitment showed a statistically significant decrease in mean blood glucose, whereas 36 of 49 infants above this cutoff level showed a statistically significant decrease after training (Chi-square test, P < 0.0001). Conclusion: Requested meals are associated with low preprandial blood glucose, significantly lower energy intake, and recovery from diarrhea, whereas scheduled meals are associated with high blood glucose, higher energy intake, and persistence of diarrhea. The disparities in blood glucose levels and energy intake disprove the null hypothesis, suggesting the need for a change from scheduled to requested meals early on in food administration, ie, during the neonatal period. © 2012 Ciampolini, publisher and licensee Dove Medical Press Ltd. Source


John Camm A.,St Georges, University of London | Colombo A.,EMO Centro Cuore Columbus | Corbucci G.,Boston Scientific Italy | Padeletti L.,University of Florence
Heart Rhythm | Year: 2014

Background/Objective Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. It is associated with increased risk for stroke mainly due to cardiac embolism from the left atrial appendage (LAA). Occlusion of the LAA by means of a device represents a valid alternative to oral anticoagulation, mainly in patients who cannot tolerate this therapy because of a high bleeding risk. Recent data on the endocardial device WATCHMAN show encouraging results for this patient population in terms of stroke risk reduction compared to the expected rate as well as in terms of implant success. This article reviews all relevant publications related to the main surgical and transcatheter devices used for LAA closure (LAAC). Methods/Results PROTECT-AF, the first prospective randomized trial conducted on this technique, showed that LAA occlusion using the WATCHMAN was noninferior to warfarin for a combined end-point in patients with nonvalvular AF. There is a lack of large-scale randomized trials on long-term stroke risk in patients submitted to LAAC. Most studies are relatively small and focus on the comparison of different surgical techniques with regard to complete/incomplete closure success. More recently, PROTECT-AF long-term results (4-year follow-up) demonstrated that LAAC was statistically superior to warfarin in terms of efficacy. Conclusion This review concludes that it is now appropriate to consider these techniques for patients with AF who are at high risk for stroke for whom effective conventional or novel anticoagulant therapy is not available or who present problems in managing drug treatment. © 2014 Heart Rhythm Society. Source


Lavorini F.,University of Florence
Journal of Aerosol Medicine and Pulmonary Drug Delivery | Year: 2014

Asthma and chronic obstructive pulmonary disease (COPD) are both diseases with an increasing prevalence worldwide. Inhaled therapy for these conditions has a number of advantages over systemic therapy, but requires the patients to use, and to master the use of, an inhaler device. However, many patients cannot use inhalers correctly, and over 50% of patients struggle to use a metered-dose inhaler properly. Poor inhaler technique is associated with a reduced asthma control, worst COPD outcomes, and wastage of economic resources. Of perhaps more concern is the fact that many health professionals also do not know how to use inhalers correctly and are therefore not in a position to coach patients effectively. Training patients and caregivers in the correct inhaler preparation and use is an essential component in the process toward achieving reliable and repeatable medication delivery. Instructions should be inhaler-specific, and they include instruction on how to load or prime the device. Providing only the leaflet that comes with the medicines does not lead to adequate inhalation technique, not even immediately after the patient has read the instructions and practiced with the inhaler. One-on-one sessions with health-care professionals probably represent the most effective educational method. However, it appears that, by itself, even repeated instruction could be insufficient to achieve improved adherence in the long term, as there is a tendency for patients or caregivers to forget what they have learned as time elapses since the training event. Thus, despite the development of several new and improved types of inhaler device, the evidence currently available points to little or no progress having been made with patients' ability to use their inhalers. As the range of drugs delivered by inhalation increases, inhaler technique checks and training need to be an integral part of the routine management of any patient with either asthma or COPD. © Mary Ann Liebert, Inc. 2014. Source


Massi D.,University of Florence | Panelos J.,General Hospital of Ioannina G. Hatzikosta
Advances in Experimental Medicine and Biology | Year: 2012

The innermost (basal) layer of the skin epidermis consists of proliferative progenitors which give rise to multiple differentiating layers providing a barrier that keeps the inside of the body moist and protects the body from outside assaults by physical, environmental and biological factors. The epidermis is maintained throughout life through the proliferation of stem cells and differentiation of their progeny. Notch signaling pathway is a highly conserved molecular network that plays an essential role in cell fate determination during embryogenesis and also in postnatal life. Data from ongoing studies indicate that Notch signaling orchestrates the process of epidermal differentiation and proliferation through the sequential activity of different Notch ligands, receptors and downstream pathways. © 2012 Landes Bioscience and Springer Science+Business Media. Source


Conti A.A.,University of Florence
Clinica Terapeutica | Year: 2012

The heart is an essential and central organ in human beings. The heart is a muscular pump which contracts approximately a hundred thousand times a day for a life time, and in the last few decades it has been scientifically documented that it also produces hormones. The symbolic role of the heart has been established from time immemorial; more recently, and intriguingly, modern biomedical evidence has proved that historical knowledge and common language expressions referring to the heart are, in many cases, correct. In this perspective it is interesting to consider that already in the remote past the heart was "at the heart" of the attention of great western and eastern civilizations. From the brief panorama presented in this paper, connections between popular historical knowledge and current biomedical evidence emerge, proving the relevance of the symbolic role of the heart and of its perceived functions from pre-Christian to contemporary times, and documenting how the heart continues to remain strategically central, and epistemologically and linguistically crucial in the physical, psychological and social context of human life. © Società Editrice Universo (SEU). Source


Minguzzi E.,University of Florence
Classical and Quantum Gravity | Year: 2016

A simple proof (based on results in Chruściel et al 2015 Ann. Henri Poincaré arXiv:1301.2909) is given that every globally hyperbolic spacetime admits a smooth Cauchy steep time function. This result is useful in order to show that globally hyperbolic spacetimes can be isometrically embedded in Minkowski spacetimes and that they split as a product. The proof is based on a recent result on the differentiability of Geroch's volume functions. © 2016 IOP Publishing Ltd. Source


Valenti R.,University of Florence | Pantoni L.,Stroke Unit and Neurology | Markus H.S.,University of Cambridge
BMC Medicine | Year: 2014

Background: Increasing evidence suggests vascular risk factors (VRF) play a role in the pathogenesis of Alzheimer's disease (AD). Epidemiological studies have found associations between VRF and risk of AD. Treating VRF in patients with AD offers a potential treatment option but ineffective treatments should be avoided in this group who are frequently on multiple medications and in whom compliance may be challenging. Methods: Studies containing information on the treatment of VRF in patients with a diagnosis of AD were identified using a defined search strategy. Randomised controlled trials and observational studies were included. Results: The pre-specified search strategy retrieved 11,992 abstract articles, and 25 papers including those identified on review of reference lists and reviews met the inclusion criteria. Of these, 11 were randomised controlled trials (RCTs) and 14 observational studies. Observational studies suggested that a VRF package and treatment of hypertension and statin therapy may be associated with improved outcome but these studies suffered from potential bias. The few RCTs performed were mostly small with short duration follow-up, and do not provide clear evidence either way. Conclusions: Observational data raises the possibility that treating VRF could alter the rate of decline in AD. However RCT data are not yet available to support this hypothesis and to alter clinical practice. RCTs in larger numbers of individuals with longer follow-up, ideally in the early stages of AD, are required to address this potentially important treatment question. © 2014 Valenti et al. Source


De Carlo F.,University of Florence
International Journal of Engineering and Technology | Year: 2013

This paper enlightens Bayesian Networks (BNs) potentialities as a support tool, thanks to their capability of providing a graphic and intuitive representation of any process. As an engineering tool, BNs are sometimes used for reliability evaluation and in maintenance management of complex systems, but, as a matter of fact, they could be applied nearly to any field. This paper aims at illustrating how BNs can be applied to nonconformities (NCs) management. By means of a case study, we built an expert system that showed improvements both from the operations and from the strategic side. BNs were operated as an intelligent system: starting from a set of data, they were used not just as an inferential tool but the model created encoded also some human knowledge and experience, showing the added value of BN modelling. In addition to the ability of being used as an expert system, the BN was continuously improved and refined, making the model closer and closer to reality, without any amazing effort, thanks to their flexibility. As a result, we could verify the advantages of the BNs, with the addition of some information not found in the database and with the ability to quickly formalize new logical relationships of cause -effect. Source


Bogelein V.,Friedrich - Alexander - University, Erlangen - Nuremberg | Duzaar F.,Friedrich - Alexander - University, Erlangen - Nuremberg | Marcellini P.,University of Florence
Archive for Rational Mechanics and Analysis | Year: 2013

We consider the evolution problem associated with a convex integrand f: ℝNn → [0,∞) satisfying a non-standard p, q-growth assumption. To establish the existence of solutions we introduce the concept of variational solutions. In contrast to weak solutions, that is, mappings u: ΩT → ↠n which solve ∂tu- div Df(Du)=0 weakly in ΩT, variational solutions exist under a much weaker assumption on the gap q - p. Here, we prove the existence of variational solutions provided the integrand f is strictly convex and 2n/n+2 < p ≦ q < p+1. These variational solutions turn out to be unique under certain mild additional assumptions on the data. Moreover, if the gap satisfies the natural stronger assumption 2 ≦ p ≦ q < p+ min{1,4/n}, we show that variational solutions are actually weak solutions. This means that solutions u admit the necessary higher integrability of the spatial derivative Du to satisfy the parabolic system in the weak sense, that is, we prove that u ∈ Lq loc(0,T; W1,q loc(Ω,ℝN)). © 2013 Springer-Verlag Berlin Heidelberg. Source


Muniz-Miranda M.,University of Florence | Muniz-Miranda M.,European Laboratory for Nonlinear Spectroscopy LENS
Applied Catalysis B: Environmental | Year: 2014

Nitrophenols represent common environmental pollutants because of their toxicity and resistance to microbial degradation. In the present work the SERS (surface-enhanced Raman scattering) spectroscopy has been applied to Ag/titania colloidal nanocomposites to monitor the catalytic reduction of 4-nitrophenol under UV irradiation and identify the reaction products. © 2013 Elsevier B.V. Source


Sorace S.,University of Udine | Terenzi G.,University of Florence
Engineering Structures | Year: 2013

A structural assessment study on " Palazzo del Lavoro" in Turin, a masterpiece by Pier Luigi Nervi, was carried out within a National Research Project dedicated to the analysis of modern heritage architecture in Italy. Based on the original design documentation collected through records, a complete finite element model of the building was generated. The study included detailed models of the main structural members, represented by monumental reinforced concrete columns, a mushroom-type steel roof and reinforced concrete ribbed gallery slabs, and the main non-structural systems, constituted by continuous gallery-to-roof glazed façades. The results of the linear and non-linear analyses developed by these models, aimed at fully understanding the original design concept of the various members, as well as at evaluating their current static and seismic safety conditions, are reported in this paper. The non-linear computations include a buckling analysis of the slender steel beams constituting the roof, and an " integral" seismic pushover analysis of the monumental columns. The results of the analyses highlight safe conditions and good performance objectives in general, but for some important exceptions. Indeed, the roof beams failed to pass the verifications on global and local panel flexural-torsional buckling, and some cantilever beams of the gallery floors showed poor shear resistance. Retrofit hypotheses are also formulated for these elements, so as to help the entire structure to comply with the requirements of the new Italian Technical Standards. © 2012 Elsevier Ltd. Source


Guerrini R.,University of Florence | Oguni H.,Tokyo Womens Medical University
Epilepsia | Year: 2011

The term "borderline" severe myoclonic epilepsy of infancy (SMEIB) has been used to designate patients in whom myoclonic seizures or generalized spike and wave activity are absent. It has also been used loosely to indicate mild forms of the syndrome. It is now acknowledged that the course and outcome of patients with SMEIB are the same as in the core syndrome. The rate of patients exhibiting SCN1A gene mutations is also similar, and it has been observed that the same mutations can cause both typical and " borderline" forms, indicating causal homogeneity. Defining a borderline form of a syndrome would mean setting the criteria of semiology and severity whereby a given phenotype falls within and outside the core syndrome. Such process has never been made for Dravet syndrome and is of course unrealistic in view its polymorphic expression. The eponym Dravet syndrome has been preferred to designate a syndrome spectrum that also embraces SMEIB. Therefore the term "borderline" Dravet syndrome is improper. The definition "mild form" of Dravet syndrome would certainly be more suitable to indicate those patients exhibiting a less severe or incomplete form of the syndrome. Variability in severity favors the concept that SCN1A loss of function causes a spectrum of epilepsy phenotypes in which seizures, often prolonged and precipitated by fever, are the prominent feature and schematic subdivisions would be inappropriate, at least in the early stages. An initial definition of SCN1A gene-related epilepsy would perhaps be more suitable when a mutation of this gene is ascertained and the clinical picture is still ill defined. © Wiley Periodicals, Inc. 2011 International League Against Epilepsy. Source


Vangi D.,University of Florence
Proceedings of the Institution of Mechanical Engineers, Part D: Journal of Automobile Engineering | Year: 2013

In a collision between vehicles, the post-impact phase, where they translate and rotate, often has significant importance in the analysis and reconstruction of road accidents. Indeed, the calculation of errors made in this analysis will be reflected in later stages, compromising the correct identification of the accident scenario. Because of the uncertainty in the initial data as well the lack of data, simplified models are used in order to calculate the kinematic parameters of the vehicles. The literature offers some of these simplified models, even though the most reliable models require iterative calculations or numerical integration of the equations of motion. In the present work a model for the calculation of both the linear velocity and the angular velocity of the vehicle, which are useful for analysing the post-impact phase between vehicles, is built. The model is based on the schematization of the trajectory of the individual wheels with a cycloid, which is lengthened or shortened depending on the magnitude of the ratio of the translational velocity to the rotational velocity of the vehicle. The work dissipated by friction along this trajectory is calculated and then made equal to the loss in kinetic energy, assuming that the ratio of the angular velocity to the linear velocity during motion is constant. The model gives results comparable with the numerical integration of the equations of motion, when schematizing the vehicle as a rigid body with three degrees of freedom. The model is suitable in the field of road accident reconstruction owing to its simplicity of use. Indeed, it is necessary to consider only the friction coefficient between the tyre and the road, and to use only two uncoupled equations to find the values of the angular velocity and the translation. © IMechE 2013. Source


Poli D.,Thrombosis Center | Antonucci E.,University of Florence | Testa S.,Haemostasis and Thrombosis Center | Lip G.Y.H.,University of Birmingham
Internal and Emergency Medicine | Year: 2014

Stroke prevention, achieved with oral anticoagulation therapy (OAT), is central to the management of patients with atrial fibrillation (AF). Well-managed OAT, as reflected by a long time in therapeutic range (TTR), is associated with good clinical outcomes. The SAME-TT2R2 score has been proposed to identify patients who will maintain a high average TTR on vitamin K antagonists (VKA) treatment. The objective of the study was to validate this score in a cohort of AF patients followed by an anticoagulation clinic. We applied the SAME-TT2R2 score to 1,089 patients with AF on VKAs followed by two anticoagulation clinics. The median TTR overall for the whole cohort was 73.0 %. There was a significant decline in mean (or median) TTR in relation to the SAME-TT2R2 score (p = 0.042). When the SAME-TT2R2 scores were categorized we find a TTR 74.0 % for score ≤2 and 68.0 % for score >2 (p = 0.006). The rate of major bleeding events and stroke/TIA was 1.78 × 100 patient-years (pt-yrs) and 1.26 × 100 pt-yrs, respectively. No relationship exists between the SAME-TT2R2 score and adverse events. We describe the first validation of the SAME-TT2R2 score in AF patients where, despite an overall good quality of anticoagulation, the SAME-TT2R2 score is able to identify the patients who are less likely to do well on VKA therapy if this is the chosen OAT. © 2014 SIMI. Source


Certini G.,University of Florence | Scalenghe R.,University of Palermo | Woods W.I.,University of Kansas
Earth-Science Reviews | Year: 2013

One of the most dramatic ways humans can affect soil properties is through the performance of military activities. Warfare-induced disturbances to soil are basically of three types - physical, chemical, and biological - and are aimed at causing direct problems to enemies or, more often, are indirect, undesired ramifications. Physical disturbances to soil include sealing due to building of defensive infrastructures, excavation of trenches or tunnels, compaction by traffic of machinery and troops, or cratering by bombs. Chemical disturbances consist of the input of pollutants such as oil, heavy metals, nitroaromatic explosives, organophosphorus nerve agents, dioxins from herbicides, or radioactive elements. Biological disturbances occur as unintentional consequences of the impact on the physical and chemical properties of soil or the deliberate introduction of microorganisms lethal to higher animals and humans such as botulin or anthrax. Soil represents a secure niche where such pathogens can perpetuate their virulence for decades.Soil morphology, composition, and biology can be profoundly modified by warfare activities in either wartime or peacetime (e.g. at test-firing facilities), and complete recovery of some characteristics can require years or even centuries. A few soil functions can be definitively compromised, if appropriate reclaiming techniques are not carried out. Such techniques often are extremely expensive, as in the case of contamination by dioxins or radionuclides, and remediation can even impel the complete removal of the polluted soil and its substitution with soil material from elsewhere. Taking into account how much of the pedosphere is currently and was in the past involved in warfare, warfare is actually a major means by which humans play a recognized role as a soil forming factor, as well as the parent material, topography, time, climate, and organisms not endowed with the power of reason. The variegated impact of warfare on the soil environment is reviewed here. © 2013 Elsevier B.V. Source


Balan V.,Michigan State University | Chiaramonti D.,University of Florence | Kumar S.,Old Dominion University
Biofuels, Bioproducts and Biorefining | Year: 2013

Advanced biofuels produced from lignocellulosic biomass offer an exciting opportunity to produce renewable liquid transportation fuels, biochemicals, and electricity from locally available agriculture and forest residues. The growing interest in biofuels from lignocellulosic feedstock in the United States (US) and the European Union (EU) can provide a path forward toward replacing petroleum-based fuels with sustainable biofuels which have the potential to lower greenhouse gas (GHG) emissions. The selection of biomass conversion technologies along with feedstock development plays a crucial role in the commercialization of next-generation biofuels. There has been synergy and, even with similar basic process routes, diversity in the conversion technologies chosen for commercialization in the EU and the US. The conversion technologies for lignocellulosic biomass to advanced biofuels can be broadly classified in three major categories: biochemical, thermochemical, and hybrid conversions. The objective of this review is to discuss the US and EU biofuel initiatives, feedstock availability, and the state-of-art conversion technologies that are potentially ready or are already being deployed for large-scale applications. The review covers and compares the developments in these areas in the EU and the USA and provides a comprehensive list of the most relevant ongoing development, demonstration, and commercialization activities in various companies, along with the different processing strategies adopted by these projects. © 2013 Society of Chemical Industry and John Wiley & Sons, Ltd. Source


Drabowicz T.,University of Florence | Drabowicz T.,University of Lodz
Computers and Education | Year: 2014

The paper investigates how gender exerts its influence on contemporary adolescents with respect to their access to the Information and Communication Technologies (ICTs). The focus here is on the so-called usage access. The paper's empirical basis is that of information on the ICTs usage collected for 39 countries in the framework of the 2006 wave of the Program for International Student Assessment (PISA) study. Ordinal regression modelling is used as a method for data investigation. The analysis points to the persistence of gender inequality seemingly in favour of boys. In all countries under investigation, boys report using computers and the Internet for educational purposes more often than girls. Controlling for the 2006 value of the national GDP per capita, the level of a country's gender inequality measured by the Gender Gap Index does not have any statistically significant effect on gender gap in educational use of ICTs. A sign of the gender coefficient suggest, however, that the increase in society's gender-neutrality is associated with the increase in boys' advantage over girls as regards the frequency of ICT/Internet educational use. The possibility that this advantage of boys is in fact a sign of their educational underperformance is discussed. Another possibility is also discussed, namely, that girls' decreased (in comparison with boys) frequency of using computers and the Internet for playing computer games might, counterintuitively, be the source of girls' disadvantage in the future. © 2014 Elsevier Ltd. All rights reserved. Source


Tosetto A.,Hemophilia and Thrombosis Center | Castaman G.,University of Florence
Blood | Year: 2015

Type 2 von Willebrand disease (VWD) includes a wide range of qualitative abnormalities of von Willebrand factor structure and function resulting in a variable bleeding tendency. According to the current classification, 4 different subtypes can be identified, each with distinctive phenotypic and therapeutic characteristics. Current available laboratory methods allow a straightforward approach to VWD subtyping, and although the precise molecular characterization remains complex, it is not required for appropriate treatment of the vast majority of cases. Desmopressin can be useful only in a few type 2 cases compared with patients with actual quantitative deficiency (type 1), most often in variants with a nearly normal multimeric pattern (type 2M). However, since no laboratory test accurately predicts response to desmopressin, a trial test should always be performed in all type 2 VWD patients, with the exception of type 2B ones. Replacement therapy with plasma-derived von Willebrand factor-factor VIII concentrates represents the safe mainstay of treatment of all patients, particularly those not responding to desmopressin or requiring a sustained hemostatic correction because of major surgery or bleeding. A significant patient bleeding history correlates with increased bleeding risk and should be considered in tailoring the optimal antihemorrhagic prophylaxis in the individual patient. © 2015 by The American Society of Hematology. Source


Maddio S.,University of Florence
IEEE Antennas and Wireless Propagation Letters | Year: 2015

In this letter, we present a compact single-layer microstrip antenna array for applications in the C-band. The device is designed and fabricated with an overall volume of 45mm 45mm 1.6mm, (0.86 λ0 0.86 λ0 × 0.03 λ0 at a frequency of 5.75 GHz), a suitable dimension for compact handhelds. The proposed array is based on a modified sequential phase network, composed of nonuniform curved transmission lines, feeding a set of 2 × 2 disc based patch elements. The proposed network has space-filling properties, and is arranged in the unoccupied area between the elements, minimizing the overall dimensions without sacrificing the operating bandwidth. Adequate agreements between the simulated and measured results validate the proposed design: a 3-dB axial ratio band of 900 MHz, meaning 15.5%, a peak gain of 8.25 dB maintained within 3 dB for 1.2 GHz, and a very wide 10-dB return loss bandwidth of 29%. This performance is unmatched for the given dimensional constraint with a single-layer via-less technology. © 2015 IEEE. Source


Poli D.,Struttura Operativa Dipartimentale SOD Malattie Aterotrombotiche | Miniati M.,University of Florence
Current Opinion in Pulmonary Medicine | Year: 2011

Purpose of Review: Pulmonary embolism is the most serious complication of venous thromboembolism, with an elevated case/fatality rate. Patients who survived a first episode of pulmonary embolism should be evaluated for the risk of recurrence and of chronic thromboembolic pulmonary hypertension (CTEPH). Recent Findings: The risk of recurrence is higher in patients with unprovoked pulmonary embolism than in those with transient risk factors. Persistent risk factors, such as active cancer and antiphospholipid antibodies, are associated with high risk of recurrence. Recently, elevated D-dimer levels after discontinuation of therapy have been identified as a risk factor for recurrence. CTEPH is characterized by intravascular organization of emboli and occurs in 0.5-1% of cases. Some patients with CTEPH have impaired fibrinolysis, likely due to a structural abnormality of fibrin or fibrin clot. Echocardiography often reveals signs of pulmonary hypertension. This should be confirmed by direct measurement of pulmonary artery pressures at right heart catheterization. Summary: CTEPH patients should receive life-long anticoagulation for preventing recurrent pulmonary embolism. Pulmonary endarterectomy is the treatment of choice for patients with proximal pulmonary vascular occlusion. Patients with predominantly distal pulmonary vascular occlusion are candidates for pharmacological treatment. All patients with unprovoked pulmonary embolism should be evaluated for long-term anticoagulation. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins. Source


We report the design, synthesis, and immunological evaluation of a series of glycopeptide analogues of the previously described antigenic probe CSF114(Glc), with the aim of understanding the importance of N-glycosylation on Asn residue in multiple sclerosis antibody recognition. The glucopeptide, characterized by a β-turn conformation which is fundamental for a correct presentation of the epitope, has been modified by introducing various natural glycoamino acids in position 7. The new glycopeptides were evaluated by measuring the IgG and IgM antibody titer in multiple sclerosis patients' and normal blood donors' sera. Moreover, we achieved the efficient synthetic strategy of new Asn derivative bearing N-acetylneuraminic acid (Neu5Ac), linked by an N-glycosidic bond, on the side chain of the Asn residue orthogonally protected for Fmoc/tBu SPPS. 2010 Wiley Periodicals, Inc. Source


Vannucchi A.M.,University of Florence
Hematology / the Education Program of the American Society of Hematology. American Society of Hematology. Education Program | Year: 2011

Myelofibrosis (MF), either primary or arising from previous polycythemia vera (PV) or essential thrombocythemia (ET), is the worst among the chronic myeloproliferative neoplasms in terms of survival and quality of life. Patients with MF have to face several clinical issues that, because of the poor effectiveness of medical therapy, surgery or radiotherapy, represent largely unmet clinical needs. Powerful risk stratification systems, applicable either at diagnosis using the International Prognostic Scoring System (IPSS) or during the variable course of illness using the Dynamic International Prognostic Scoring System (DIPSS) and DIPSS Plus, allow recognition of categories of patients with survival times ranging from decades to < 2 years. These scores are especially important for therapeutic decisions that include allogeneic stem cell transplantation (allogeneic SCT), the only curative approach that still carries a nonnegligible risk of morbidity and mortality even with newest reduced intensity conditioning (RIC) regimens. Discovery of JAK2V617F mutation prompted the development of clinical trials using JAK2 inhibitors; these agents overall have resulted in meaningful symptomatic improvement and reduction of splenomegaly that were otherwise not achievable with conventional therapy. Intriguing differences in the efficacy and tolerability of JAK2 inhibitors are being recognized, which could lead to a nonoverlapping spectrum of activity/safety. Other agents that do not directly target JAK2 and have shown symptomatic efficacy in MF are represented by inhibitors of the mammalian target of rapamycin (mTOR) and histone deacetylases (HDACs). Pomalidomide appears to be particularly active against MF-associated anemia. However, because these agents are all poorly effective in reducing the burden of mutated cells, further advancements are needed to move from enhancing our ability to palliate the disease to arriving at an actual cure for MF. Source


Becattini F.,University of Florence | Bleicher M.,Frankfurt Institute for Advanced Studies FIAS | Kollegger T.,Frankfurt Institute for Advanced Studies FIAS | Schuster T.,Yale University | And 3 more authors.
Physical Review Letters | Year: 2013

We study particle production in ultrarelativistic nuclear collisions at CERN SPS and LHC energies and the conditions of chemical freeze-out. We determine the effect of the inelastic reactions between hadrons occurring after hadronization and before chemical freeze-out employing the ultrarelativistic quantum molecular dynamics hybrid model. The differences between the initial and the final hadronic multiplicities after the rescattering stage resemble the pattern of data deviation from the statistical equilibrium calculations. By taking these differences into account in the statistical model analysis of the data, we are able to reconstruct the original hadrochemical equilibrium points in the (T, μB) plane which significantly differ from chemical freeze-out ones and closely follow the parton-hadron phase boundary recently predicted by lattice quantum chromodynamics. © 2013 American Physical Society. Source


Harris A.J.L.,CNRS Magmas and Volcanoes Laboratory | Ripepe M.,University of Florence | Hughes E.A.,CNRS Magmas and Volcanoes Laboratory
Journal of Volcanology and Geothermal Research | Year: 2012

Using high frame rate (33Hz) thermal video data we describe and parameterize the emission and ascent dynamics of a mixed plume of gas and particles emitted during a normal explosion at Stromboli (Aeolian Islands, Italy). Analysis of 34 events showed that 31 of them were characterized by a first phase characterized by an initial diffuse spray of relatively small (lapilli-sized) particles moving at high velocities (up to 213ms -1; average 66-82ms -1). This was followed, typically within 0.1s, by a burst comprising a mixture of ash and lapilli, but dominated by larger bomb-sized particles, moving at lower exit velocities of up to 129ms -1, but typically 46ms -1. We interpret these results as revealing initial emission of a previously unrecorded high velocity gas-jet phase, to which the lapilli are coupled. This is followed by emission of slower moving larger particles that are decoupled from the faster moving gas-phase. Diameters for particles carried by the gas phase are typically around 4cm, but can be up to 9cm, with the diameter of the particles carried by the gas jet (D) decreasing with increased density and velocity of the erupted gas cloud (ρ gas and U gas). Data for 101 particles identified as moving with the gas jet during 32 eruptions allow us to define a new relation, whereby U gas=U particle+a [ρ gas D] b. Here, U particle is the velocity of bombs whose motion is decoupled from that of the gas cloud, and a and b are two empirically-derived coefficients. This replaces the old relation, whereby U gas=U particle+k D; a relation that requires a constant gas density for each eruption. This is an assumption that we show to be invalid, with gas density potentially varying between 0.04kgm -3 and 9kgm -3 for the 32 cases considered, so that k varies between 54m 1/2s -1 and 828m 1/2s -1, compared with the traditionally used constant of 150m 1/2s -1. © 2012 Elsevier B.V. Source


Burr D.,University of Florence | Burr D.,CNR Institute of Neuroscience | Thompson P.,University of York
Vision Research | Year: 2011

This review traces progress made in the field of visual motion research from 1985 through to 2010. While it is certainly not exhaustive, it attempts to cover most of the major achievements during that period, and speculate on where the field is heading. © 2011 Elsevier Ltd. Source


Romagnani P.,University of Florence | Crescioli C.,Foro Italico University of Rome
Clinica Chimica Acta | Year: 2012

Interferon (IFN) γ-induced protein 10. kDa (IP-10) or C-X-C motif chemokine 10 (CXCL10) is a small cytokine belonging to the CXC chemokine family. This family of signaling molecules is known to control several biological functions and to also play pivotal roles in disease initiation and progression. By binding to its specific cognate receptor CXCR3, CXCL10 critically regulates chemotaxis during several immune-inflammatory processes. In particular, this chemokine controls chemotaxis during the inflammatory response resulting from allograft rejection after transplantation.Interestingly, a strong association has been described between CXCL10 production, immune response and the fate of the graft following allotransplantation. Enhanced CXCL10 production has been observed in recipients of transplants of different organs. This enhanced production likely comes from either the graft or the immune cells and is correlated with an increase in the concentration of circulating CXCL10. Because CXCL10 can be easily measured in the serum and plasma from a patient, the detection and quantitation of circulating CXCL10 could be used to reveal a transplant recipient's immune status.The purpose of this review is to examine the critical role of CXCL10 in the pathogenesis of allograft rejection following organ transplantation. This important role highlights the potential utilization of CXCL10 not only as a therapeutic target but also as a biomarker to predict the severity of rejection, to monitor the inflammatory status of organ recipients and, hopefully, to fine-tune patient therapy in transplantation. © 2012 Elsevier B.V.. Source


Angioni M.,University of Florence | Chachamis G.,Paul Scherrer Institute | Madrigal J.D.,Institute Fisica Teorica UAM CSIC | Sabio Vera A.,Institute Fisica Teorica UAM CSIC | Sabio Vera A.,University of California at Santa Barbara
Physical Review Letters | Year: 2011

Ratios of azimuthal angle correlations between two jets produced at large rapidity separation are studied in the N=4 maximally supersymmetric Yang-Mills (MSYM) theory. It is shown that these observables, which directly prove the SL(2,C) symmetry present in gauge theories in the Regge limit, exhibit an excellent perturbative convergence. They are compared to those calculated in QCD for different renormalization schemes concluding that the momentum-substraction scheme with the Brodsky-Lepage-Mackenzie scale-fixing procedure captures the bulk of the MSYM results. © 2011 American Physical Society. Source


Bartolini C.,University of Florence
Bollettino di Geofisica Teorica ed Applicata | Year: 2012

The paper tries to investigate whether tectonics played or not a significant role in shaping a few selected relief forms, as reported in the literature. All reviewed case histories, except for the last one, deal with fault-connected relief features. It may be stated that, in general, the pervasive role of differential erosion induced by lithologic hetereogeneities is often overlooked. © 2012-OGS. Source


Morgentaler A.,Beth Israel Deaconess Medical Center | Khera M.,Baylor College of Medicine | Maggi M.,University of Florence | Zitzmann M.,University Clinics
Journal of Sexual Medicine | Year: 2014

Introduction: Despite increasing use of testosterone therapy (TTh) for men with testosterone deficiency (TD), there remains uncertainty determining who is a candidate for treatment. Aim: The aim if this study was to report the opinions of international experts on TTh, as initially presented at the meeting of the World Meeting on Sexual Medicine in Chicago, United States in August 2012. Methods: Expert responses to questions regarding the diagnosis of TD based on their own clinical and research experience. Results: All experts emphasized the primacy of symptoms for the diagnosis of TD. Total testosterone (T) thresholds used to identify TD ranged from 350ng/dL to 400ng/dL (12-14nmol/L); however, experts emphasized the diagnostic limitations of this test. Free T was obtained by all, with some valuing this test more than total T for clinical decision making. Only one expert routinely used a screening questionnaire. None used age-adjusted values. Bioavailable T and the free androgen index were not used. Luteinizing hormone (LH) and sex hormone-binding globulin levels were routinely obtained at evaluation. Additional supportive evidence for TD diagnosis included small testicular volume, high androgen receptor CAG repeats, elevated LH, and presence of diabetes or metabolic syndrome. Two T tests were generally obtained but not always required. Some experts did not require morning testing in men 50 years and older. All monitored prostate-specific antigen and hematocrit after initiation of TTh. All but one expert would consider a trial of TTh to a symptomatic man with total T within the normal range. Recent studies suggesting increased cardiovascular risk with T therapy were not found to be credible. Conclusions: Determining who is a candidate for TTh requires clinical assessment based on symptoms and signs, with confirmatory laboratory evaluation. These expert opinions differed from some published guidelines by the emphasis on symptoms as paramount, recognition of the limitations of total T as a diagnostic test, and the potential utility of a therapeutic trial in symptomatic cases with normal total T concentrations. © 2014 International Society for Sexual Medicine. Source


To compare the efficacy and safety of adalimumab versus infliximab in an open-label prospective, comparative, multicenter cohort study of childhood noninfectious chronic uveitis. Thirty-three patients (22 females, 11 males, median age 9.17 years) with refractory, vision-threatening, noninfectious active uveitis were enrolled, and received for at least 1 year infliximab (5 mg/kg at weeks 0, 2, and 6, and then every 6-8 weeks) or adalimumab (24 mg/m2 every 2 weeks). The primary outcome was to assess, once remission was achieved, the time of a first relapse. Time to remission, time to steroid discontinuation, and the number of relapses were also considered. Sixteen children (12 with juvenile idiopathic arthritis [JIA], 3 with idiopathic uveitis, and 1 with Behçet's disease) were recruited in the adalimumab cohort and 17 children (10 with JIA, 5 with idiopathic uveitis, 1 with early-onset sarcoidosis, and 1 with Behçet's disease) were recruited in the infliximab group. Cox regression analysis did not show statistically significant differences between the two groups with regard to time to achieve remission and time to steroid discontinuation, whereas a higher probability of uveitis remission on adalimumab during the time of treatment was shown (Mantel-Cox χ2=6.83, P<0.001). At 40 months of followup, 9 (60%) of 15 children receiving adalimumab compared to 3 (18.8%) of 16 children receiving infliximab were still in remission on therapy (P<0.02). Even if limited to a relatively small group, our study suggests that over 3 years of treatment, adalimumab is more efficacious than infliximab in maintaining remission of chronic childhood uveitis. Copyright © 2011 by the American College of Rheumatology. Source


Saberi R.-S.,Sharif University of Technology | Shahrokhian S.,Sharif University of Technology | Marrazza G.,University of Florence
Electroanalysis | Year: 2013

In this work, an electrochemical DNA biosensor, based on a dual signal amplified strategy by employing a polyaniline film and gold nanoparticles as a sensor platform and enzyme-linked as a label, for sensitive detection is presented. Firstly, polyaniline film and gold nanoparticles were progressively grown on graphite screen-printed electrode surface via electropolymerization and electrochemical deposition, respectively. The sensor was characterized by scanning electron microscopy (SEM), cyclic voltammetry and impedance measurements. The polyaniline-gold nanocomposite modified electrodes were firstly modified with a mixed monolayer of a 17-mer thiol-tethered DNA probe and a spacer thiol, 6-mercapto-1-hexanol (MCH). An enzyme-amplified detection scheme, based on the coupling of a streptavidin-alkaline phosphatase conjugate and biotinylated target sequences was then applied. The enzyme catalyzed the hydrolysis of the electroinactive α-naphthyl phosphate to α-naphthol; this product is electroactive and has been detected by means of differential pulse voltammetry. In this way, the sensor coupled the unique electrical properties of polyaniline and gold nanoparticles (high surface area, fast heterogeneous electron transfer, chemical stability, and ease of miniaturisation) and enzymatic amplification. A linear response was obtained over a concentration range (0.2-10nM). A detection limit of 0.1nM was achieved. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Source


Buccianti A.,University of Florence | Magli R.,University of Milan
Computers and Geosciences | Year: 2011

The paper is designed to give the reader an outline that is useful for understanding the importance of distance, as a metric concept, and its implications when compositional (geochemical) data are managed from a statistical point of view in a given sample space. Application examples are shown by considering the construction of confidence regions and mixing models. The analyzed data are related to the chemistry of the most important rivers of the world as referring to the GEMS/WATER Global Register of River Inputs when each sample (river) is represented as a composition. A compositional vector of d parts, x=[x1,x2,...,xd], is defined as a vector in which the only relevant information is contained in the ratios between its components. All the components of the vector are assumed positive and are called parts (variables), while the whole compositional vector, with the sum of the parts equal to a constant, represents the composition. In this case data are not represented by variables free to vary from -∞ to +∞ within a Euclidean space but occupy a restricted part of it called the simplex. The d-part simplex, Sd, is a subset of a d-dimensional real space. In this context the metric of the R space, with the definition of basic algebraic operations and of inner product, norm and distance, thus giving an Euclidean vector space structure, cannot be applied since the scale is relative and not absolute. © 2011 Elsevier Ltd. Source


Crawford Camiciottoli B.,University of Florence
Journal of Pragmatics | Year: 2010

As multi-functional devices, discourse connectives have provided fertile ground for language researchers, regardless of theoretical orientation, methodological approach or context of analysis. This study investigates the use of selected discourse connectives in texts produced by companies for purposes of financial disclosure, representing a vital component of corporate communication. The analysis is based on two specially designed corpora of financial disclosure genres mediated by Information and Communication Technology (ICT): earnings presentations, i.e., oral presentations of financial results given by company executives to investment analysts via teleconferencing, and earnings releases, i.e., the written counterpart published on the Internet. Text analysis software was used to generate the quantitative profile of the discourse connectives, while follow-up qualitative analysis in the context of usage provided additional interpretive insights. Overall, the discourse connectives were found to be more frequent in the earnings presentations as compared to the earnings releases, even if they are more typically associated with written prose. Across both corpora, discourse connectives served a range of functions, often foregrounding the positive while attenuating the negative. These findings shed light on the pragmatic uses of discourse connectives by corporate speakers and writers as a way to influence the interpretation of the message, and thus succeed in achieving their professional aims. © 2009 Elsevier B.V. All rights reserved. Source


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

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


Supuran C.T.,University of Florence
Frontiers in Pharmacology | Year: 2011

Carbonic anhydrases (CAs, EC 4.2.1.1) are metalloenzymes which catalyze the hydration of carbon dioxide to bicarbonate and protons. Many pathogenic bacteria encode such enzymes belonging to the α-, β , and/or gamma;-CA families. In the last decade, the a-CAs from Neisseria spp. and Helicobacter pylori as well as the β-class enzymes from Escherichia coli, H. pylori, Mycobacterium tuberculosis, Brucella spp., Streptococcus pneumoniae, Salmonella enterica, and Haemophilus influenzae have been cloned and characterized in detail. For some of these enzymes the X-ray crystal structures were determined, and in vitro and in vivo inhibition studies with various classes of inhibitors, such as anions, sulfonamides and sulfamates reported. Although efficient inhibitors have been reported for many such enzymes, only for Neisseria spp., H. pylori, B. suis, and S. pneumoniae enzymes it has been possible to evidence inhibition of bacterial growth in vivo. Thus, bacterial CAs represent promising targets for obtaining antibacterials devoid of the resistance problems of the clinically used such agents but further studies are needed to validate these and other less investigated enzymes as novel drug targets. © 2011 Supuran. Source


Minguzzi E.,University of Florence
Classical and Quantum Gravity | Year: 2015

The Raychaudhuri equation and its consequences for chronality are studied in the context of Finsler spacetimes. It is proved that the notable singularity theorems of Lorentzian geometry extend to the Finslerian domain. Indeed, so do the theorems by Hawking, Penrose, Hawking and Penrose, Geroch, Gannon, Tipler and Kriele, and also the Topological Censorship theorem and so on. It is argued that the notable results in causality theory connected to achronal sets, future sets, domains of dependence, limit curve theorems, length functional, Lorentzian distance and geodesic connectedness, extend to the Finslerian domain. Results concerning the spacetime asymptotic structure, horizons differentiability and conformal transformations are also included. © 2015 IOP Publishing Ltd. Source


Conti A.A.,University of Florence
Clinica Terapeutica | Year: 2011

Cardiac rehabilitation is an interdisciplinary and multidimensional process aimed at preventing and containing cardiovascular mortality, morbidity and disability, and promoting health in subjects with cardiocirculatory pathologies. A body of scientifi c evidence is today available with regard to the benefi ts of cardiac rehabilitation in terms of the containment of the progression of atherosclerosis, the increase in physical work ability, the reduction in symptomatology, the improvement in psychological well being and social re-adaptation, and the lowering in hospitalization rates and in recurrent clinical cardiac events. Cardiac rehabilitation derives its origin from the application of physical activity to the therapy of ischemic heart disease, and in this paper the historical evolution of the concept of angina pectoris and myocardial infarction as also the major progress in therapeutic exercise are discussed. Cardiac rehabilitation has become through time a multi-faceted process implemented in hospitals, in outpatient clinics and at home in a variety of models. However, recent data indicate that, in the USA, no more than 20% of eligible patients per year enter cardiac rehabilitation programs, and in Europe no more than 30% participate in them. The historical perception of cardiac rehabilitation provides knowledge of the fact that, through a long and articulated process, this health intervention has achieved relevant medical and social results and it also generates the awareness of the further advantages to be obtained in future cardiovascular patients. Source


Minguzzi E.,University of Florence
European Journal of Physics | Year: 2015

Abstract It is shown that Rayleigh's dissipation function can be successfully applied in the solution of mechanical problems involving friction non-linear in the velocities. Through the study of surfaces at contact we arrive at a simple integral expression which gives directly the Rayleigh dissipation function in terms of generalized coordinates. In this way the solutions of Lagrangian problems with friction are reduced to often elementary calculations of the kinetic energy, the potential energy, and the Rayleigh dissipation function. Some examples of pedagogical interest are given. © 2015 IOP Publishing Ltd. Source


Minguzzi E.,University of Florence
General Relativity and Gravitation | Year: 2015

A version of the vacuum conservation theorem is proved which does not assume the existence of a time function nor demands stronger properties than the dominant energy condition. However, it is shown that a stronger stable version plays a role in the study of compact Cauchy horizons. © 2015, Springer Science+Business Media New York. Source


Pela I.,University of Florence
Clinical Cases in Mineral and Bone Metabolism | Year: 2012

Recently a number of studies have reported worldwide recrudescence of biochemical and clinical rickets, despite continuous revisions of the experts about the adequate intake of vitamin D for infants and children to maintain an adequate 25-hydroxyvitamin D status and assure the achievement of peak bone mass during the growth. The aim of this review is to illustrate the current opinions and controversies about what should be considered the normal range for serum 25-hydroxyvitamin D concentrations and which doses of vitamin D supplements should be recommended in the various pediatric ages and in different contests as climatic regions, colour of skin and sunlight exposure. Source


Brandi M.L.,University of Florence
Expert Opinion on Pharmacotherapy | Year: 2013

Introduction: Fracture healing is a complex process that leads to the restoration of tissue integrity through bone repair and represents a unique physiological characteristic of bone. Developing a better understanding of a fracture is essential to plan best noninvasive treatment for the patient. In osteoporosis, the patient who suffers of a fragility fracture is recommended to initiate a treatment with compounds active in preventing other low-energy skeletal trauma. Pharmaceutical industries are developing controlled clinical trials aiming to evaluate the capability of osteoporosis drugs to accelerate fracture healing. Areas covered: In preparing this review, a search was made with key words encompassing 'osteoporosis anti-fracture drugs and bone repair/healing', 'antiresorptives and bone repair/healing', 'bone-forming agents and bone repair/healing', and 'osteoporosis/anti-fracture drugs in fractures'. The results published in the area of the use of registered anti-fracture drugs to improve fracture repair and the efforts made to recommend measures for clinical outcomes in fracture healing acceleration are described in this report. Expert opinion: At present, the use of systemic pharmacological agents active to improve fracture healing by the clinicians is controversial and clinicians and scientists must do a better job in determining the methods of assessment for fracture healing. © 2013 Informa UK, Ltd. Source


This study assessed the capability of magnetic resonance (MR) diffusion-weighted imaging (DwI) with measurement of apparent diffusion coefficient (ADC) in both predicting and evaluating the response to chemotherapy (CHT) of liver metastases by itself and along with preliminary dimensional assessment. Patients affected by liver metastases from cancers of the digestive tract and breast were prospectively enrolled and underwent computed tomography and MR-DwI before CHT (time 0) and 20-25 days after the beginning of the second cycle (time 3). Moreover, MR-DwI was performed 10-15 (time 1) and 20-25 days (time 2) after the beginning of the first cycle. Maximum diameter and mean ADC value (×10(-3) mm(2)/s) of metastases were evaluated. Lesions were classified as progressive disease (PD), stable disease (SD) or partial response (PR) according to dimensional changes between time 0 and time 3, following RECIST 1.1 indications. Clinically, PD lesions were defined as nonresponding (NR), and SD and PR lesions as responding (R). Analysis of variance and ROC analyses were performed (significance at p < 0.05). Eighty-six metastases (33 patients) were classified as follows: 15 PD, 39 SD and 32 PR without significant differences in mean ADC values among the groups before CHT and at all corresponding times. The mean ADC values of SD and PR groups at times 1 (respectively 1.66 ± 0.36 and 1.59 ± 0.23), 2 (1.72 ± 0.42 and 1.68 ± 0.37) and 3 (1.86 ± 0.44 and 1.73 ± 0.39) were significantly higher than the corresponding values at time 0 (1.50 ± 0.30 and 1.39 ± 0.33). An accurate cutoff value of ADC increase or diameter decrease for the early identification of R or NR lesions was not found. The pretreatment ADC value of a liver metastasis does not seem useful in predicting the CHT outcome. A trend towards early ADC increase, alone or occurring with dimensional decrease, may be a good indicator of a responding lesion. Source


Valtancoli P.,University of Florence | Valtancoli P.,National Institute of Nuclear Physics, Italy
Annals of Physics | Year: 2015

The decomposition in normal modes of a scalar field conformally coupled to an AdS black hole leads to a Heun equation with simple coefficients thanks to conformal invariance. By applying the Damour-Ruffini method we can relate the critical exponent of the radial part at the horizon surface to the Hawking radiation of scalar particles. © 2015 Elsevier Inc.. Source


Gherardi F.,University of Florence
OIE Revue Scientifique et Technique | Year: 2010

After habitat destruction, invasive alien species are the second leading cause of biodiversity loss, particularly in freshwater ecosystems. They also alter the structure and functioning of ecosystems, lead to biotic homogenisation, and eventually threaten human economies and health. This review aims to synthesise some of the existing information about the world distribution, vectors of spread, and impacts of two important components of freshwater ecosystems, crayfish and fishes. Analysis of the available literature shows that crayfish and fish species, once moved outside their native range, are likely to establish selfreproducing populations, spread from the point of introduction and become invasive. Efforts to manage these populations are difficult and expensive, which warrants the provision of effective preventative measures. Unfortunately, the state of our knowledge of the mechanisms in play in crayfish and fish invasions is still limited, which suggests that much greater attention and investment should be directed to studies in this field. Source


Stanghellini G.,University of Chieti Pescara | Ballerini M.,University of Florence
Psychopathology | Year: 2011

This is a critical review of research on the subjective experience of social dysfunction in persons with schizophrenia. Studies from the phenomenological and cognitive paradigms are examined, and significant outcomes and shortcomings are pointed out. Clinical phenomenologists have mainly interpreted schizophrenic dissociality as an anomaly of prereflexive attunement. The main shortcoming of phenomenological research is that it lacks adequate methodology to collect reliable data since most studies are based on the analysis of a few typical cases. Cognitivism has reliably documented disorders of social functioning in large-scale experimental studies. The main shortcoming of most cognitive paradigms is that they do not properly investigate the personal level of experience in real-world functioning. We conclude that there is a need to reliably collect data through quantitative as well as qualitative methodology as established and accepted by the scientific community in the area of schizophrenic dissociality, reflecting the subjective experiences of people with schizophrenia in the real world. Copyright © 2011 S. Karger AG, Basel. Source


Romagnani P.,University of Florence
Contributions to Nephrology | Year: 2011

Chronic kidney disease is a leading cause of mortality and morbidity in western countries which affects about 11% of the adult population. With the increasing rate of chronic kidney disease and limited alternatives for its treatment, potential regenerative approaches for kidney damage are urgently needed, but are limited by the complexity of this organ. Bone marrow-derived stem cells as well as mesenchymal stem cells were envisioned for the development of this type of treatment. However, most studies suggested that these cells cannot differentiate into renal epithelial cells, and concluded that their beneficial effects are probably related to secretion of growth factors. In addition, a long-term partial maldifferentiation of injected mesenchymal stem cells into adipocytes accompanied by glomerular sclerosis was reported. The incapacity of bone marrow-derived stem cells to differentiate into renal cells suggested that turnover of resident renal epithelial cells may be related to the existence of potential stem/progenitor cells within the adult human kidney. Consistently, renal progenitors with the potential to differentiate into podocytes as well as tubular cells were recently identified at the urinary pole of the Bowman's capsule in adult kidneys. The discovery of renal progenitors that encourage regeneration and promote functional repair of glomerular injury demonstrates that prevention and treatment of glomerulosclerosis may be possible. In addition, converging evidence suggests that the outcome of glomerular disorders depends on a balance between injury and regeneration provided by renal progenitors. In summary, understanding how self-renewal and fate decision of renal progenitors may be perturbed or modulated will be of crucial importance to obtain novel pharmacological tools for prevention and treatment of diabetic nephropathy, as well as other causes of glomerulosclerosis. Copyright © 2011 S. Karger AG, Basel. Source


Romagnani P.,University of Florence
Contributions to Nephrology | Year: 2011

Parietal epithelial cells of Bowman's capsules were first described by Sir William Bowman in 1842 in his paper On the Structure and Use of the Malpighian Bodies of the Kidney [London, Taylor, 1842], but since then their functions have remained poorly understood. A large body of evidence has recently suggested that parietal epithelial cells represent a reservoir of renal progenitors in adult human kidney which generate novel podocytes during childhood and adolescence, and can regenerate injured podocytes. The discovery that parietal epithelial cells represent a potential source for podocyte regeneration suggests that podocyte injury can be repaired. However, recent results also suggest that an abnormal proliferative response of renal progenitors to podocyte injury can generate hyperplastic glomerular lesions that are observed in crescentic glomerulonephritis and other types of glomerular disorders. Taken together, these results establish an entirely novel view that changes the way of thinking about renal physiology and pathophysiology, and suggest that understanding how self-renewal and fate decision of parietal epithelial cells in response to podocyte injury may be perturbed or modulated will be crucial for obtaining novel tools for prevention and treatment of glomerulosclerosis. Copyright © 2011 S. Karger AG, Basel. Source


Capasso C.,CNR Institute of Protein Biochemistry | Supuran C.T.,University of Florence
Journal of Enzyme Inhibition and Medicinal Chemistry | Year: 2014

Recent advances in microbial genomics, synthetic organic chemistry and X-ray crystallography provided opportunities to identify novel antibacterial targets for the development of new classes of antibiotics and to design more potent antimicrobial compounds derived from existing antibiotics in clinical use for decades. The antimetabolites, sulfa drugs and trimethoprim (TMP)-like agents, are inhibitors of three families of enzymes. One family belongs to the carbonic anhydrases, which catalyze a simple but physiologically relevant reaction in all life kingdoms, carbon dioxide hydration to bicarbonate and protons. The other two enzyme families are involved in the synthesis of tetrahydrofolate (THF), i.e. dihydropteroate synthase (DHPS) and dihydrofolate reductase. The antibacterial agents belonging to the THF and DHPS inhibitors were developed decades ago and present significant bacterial resistance problems. However, the molecular mechanisms of drug resistance both to sulfa drugs and TMP-like inhibitors were understood in detail only recently, when several X-ray crystal structures of such enzymes in complex with their inhibitors were reported. Here, we revue the state of the art in the field of antibacterials based on inhibitors of these three enzyme families. © 2014 Informa UK Ltd. Source


Gensini G.F.,University of Florence
Neurological Sciences | Year: 2011

On March 15th 2010, Italy adopted the Law no. 38 "Disposizioni per garantire l'accesso alle cure palliative e alla terapia del dolore'' (Provisions aimed at ensuring access to palliative care and pain therapy). The aim of pain therapy is to enable patients with chronic diseases to achieve pain control. Palliative care, as defined by the World Health Organization, aims at "improving the quality of life of patients and families, who face the problems associated with incurable diseases, through prevention and relief from suffering, achieved through an early identification and treatment of pain by pharmacological medication and other physical, psychosocial and spiritual techniques''. The main issues addressed by the law concern the monitoring of pain (the doctors will have to record on the clinical report form every level of pain intensity suffered by the patient, the appropriate therapy administered, and the pain relief achieved. This report must be kept accurately in all settings: Hospital, day hospital and in outpatients). The law also suggests the establishment of two kinds of regional networks. One network (including Hospices) ensures the administration of palliative care to terminally ill patients; the other, including clinics and centers of pain therapy, provides assistance to patients with chronic pain. These networks involve general practitioners, hospital specialists and pain therapy specialists in order to ensure the best patient care. Simplification of the prescription of opiate drugs is also included in the law. In the prescription of opiates, the National Health Service medical staff can use the normal prescription form, and opiates will reimbursed by the NHS, like all other drugs. In addition, the technical papers provide precise indications of the appropriate modality of administration. The law allocates (art. 12, paragraph 2) 100 million euros per year and £ 2,450,000 in the biennium 2010-2011 to implement experimental regional projects: "hospital-territory without pain''. The Ministry of Health has established a deadline within which this law must be implemented at the regional level, and further establishes a specific National Observatory, an annual report on the use of drugs in the treatment of pain, and other provisions. The levels of spending by region will also be monitored in compliance with this law; university courses and masters are required to update professionals involved in pain treatment. In July 2010, in Florence, during the interdisciplinary IMPACT 2010 summit, Institutions and Scientific Societies met to define the concrete implementation of Law No. 38, in terms of the arrangements to ensure access to palliative care and pain management. Subsequently, last November, a new meeting was held bringing together medical directors from public hospitals; further meetings are planned with Regional Health Authorities to reaffirm the importance of this law and to implement it. The most important molecules in the opioids are traditionally divided into two groups: Weak and strong. Among the strong analgesics are morphine, methadone, buprenorphine, fentanyl, oxycodone, hydromorphone. Among the weak are codeine and tramadol, or opiates administered at low doses, such as oxycodone combined with acetaminophen. IMPACT's aim is also to stimulate scientific association to consider with attention and continuous medical education on the appropriates of diagnosis and administration of these medications according to data flow sheets approved in Italy. Regarding the headaches, it should be noted that the law 38 cited above includes all forms of pain, and headaches should be integrated into the care networks. In this context, several multi-disciplinary professionals within the centers (hub and spoke) or territory (GPs, specialists from neurologists and other professionals involved) should be integrated to offer the best response to the needs of the citizen. The diagnosis and treatment of various forms of headache have to be integrated into the path of pain, both National and Regional, in line with the rest of the organization. © Springer-Verlag 2011. Source


Santini V.,University of Florence
Seminars in Hematology | Year: 2015

Myelodysplastic syndromes (MDS) are a constellation of different diseases sharing anemia in the great majority of cases, and this cytopenia defines these pathologies and their most dramatic clinical manifestations. Anemia in MDS is due to ineffective erythropoiesis, with a high degree of apoptosis of marrow erythroid progenitors. These progenitors show distinctive dysplastic features that consent diagnosis, and are recognizable and differentiated, although not easily, from other morphologic alterations present in other types of anemia. Reaching the diagnosis of MDS in a macrocytic anemia and alleviating the symptoms of anemia are therefore an essential objective of the treating physician. In this work, the signs and symptoms of anemia in MDS, as well as its peculiar pathophysiology, are discussed. Erythopoietic stimulating agents (ESAs) are providing the best treatment for anemic MDS patients, but their use is still not approved by health agencies. While still waiting for this waiver, their clinical use is widespread and their effectivness is well known, as well as the dismal prognosis of patients who do not respond to ESAs and require transfusions. MDS with del5q constitute a unique model of anemia whose complex pathophysiology has been clarified at least partially, defining its link to ribosomal alterations likewise what observed in hereditary anemias like Blackfan Diamond anemia. Lenalidomide is the agent that has shown striking and specific erythropoietic activity in del5q MDS, and the basis of this response is starting to be understood. Several new agents are under evaluation for ESA refractory/relapsed MDS patients, targeting different putative mechanisms of ineffective erythropoiesis, and are here reviewed. © 2015 Elsevier Inc. Source


Camici P.G.,San Raffaele Scientific Institute | Olivotto I.,University of Florence | Rimoldi O.E.,National Research Council Italy
Journal of Molecular and Cellular Cardiology | Year: 2012

Two distinct types of left ventricular hypertrophy (LVH) have been described: the so called "physiologic" hypertrophy, which is normally found in professional athletes, and "pathologic" LVH which is found in patients with inherited heart muscle disease such as hypertrophic cardiomyopathy (HCM) or patients with cardiac and systemic diseases characterized by pressure or volume overload. Patients with pathologic LVH have often symptoms and signs suggestive of myocardial ischemia despite normal coronary angiograms. Under these circumstances ischemia is due to coronary microvascular dysfunction (CMD). The abnormalities of the coronary microcirculation may be unrelated to the degree of LVH and cause a reduction in maximum myocardial blood flow which, in the absence of epicardial stenoses, is suggestive of CMD. There is no technique that enables direct visualization of coronary microcirculation in vivo in humans. Therefore, its assessment relies on the measurement of parameters which reflect its functional status, such as myocardial blood flow and coronary flow reserve which is an integrated measure of flow through both the large epicardial coronary arteries and the microcirculation. In this review article we discuss the pathophysiological mechanisms responsible for CMD in patients with primary and secondary LVH and how the recognition of this phenomenon is providing new important information on patient stratification and prognosis. Finally, we discuss how assessment of CMD may be used as a valuable surrogate marker to test the efficacy of old and new drugs. This article is part of a Special Issue entitled "Coronary Blood Flow". © 2011 Elsevier Ltd. Source


The author has studied plentiful material collected in Taiwan by Aleš Smetana during the years 1990-1998. Eleven new species (Metolinus liseae sp. n., Atopolinus tenchi sp. n., A. subtiliphallus sp. n., A. diaphanus sp. n., A. anma sp. n., A. ilan sp. n., A. peitawu sp. n., A. kuai sp. n., A. smetanai sp. n., A. silvanus sp. n., A. tona sp. n.) are described. The current knowledge on the population of Xantholinini in the island is summarized. Comment on geographical distribution, particularly of the many endemic species, including those of the genus Atopolinus Coiffait, 1982, are presented. Thyreocephalus hongkongensis (Redtenbacher, 1867) and Erymus gracilis (Fauvel, 1895) are new for Taiwan. Source


Nativi S.,University of Florence | Craglia M.,European Commission - Joint Research Center Ispra | Pearlman J.,Ocean Research Coordination Network
IEEE Journal of Selected Topics in Applied Earth Observations and Remote Sensing | Year: 2013

For disciplinary and domain applications, systems interoperability largely deals with the adoption of agreed technologies, standards, specifications and interfaces with a disciplinary/domain service bus or means of information exchange, if available. However, multi-disciplinary efforts make more complex demands on the type of systems and arrangements needed to support cross-domain activities. Thus, interoperability among diverse disciplinary and domain systems must be pursued adopting more flexible and sustainable approaches. This paper discusses the challenges for multi-disciplinary interoperability. The recent Brokering approach is introduced; this solution aims at interconnecting the heterogeneous disciplinary and domain service buses, avoiding the imposition of any federated or common specification. It can deliver a range of services such as discovery and access through a Broker Framework. The Brokering approach has been successfully introduced by the EuroGEOSS research project and recently adopted by the GEOSS Common Infrastructure (GCI). US NSF EarthCube initiative also has recognized the importance of brokering for its reference architecture. The GI-* technology, empowering the EuroGEOSS and the GCI brokering frameworks, is presented and discussed. © 2013 IEEE. Source


Rossin A.,CNR Institute of Chemistry of organometallic Compounds | Giambastiani G.,CNR Institute of Chemistry of organometallic Compounds | Peruzzini M.,CNR Institute of Chemistry of organometallic Compounds | Sessoli R.,University of Florence
Inorganic Chemistry | Year: 2012

The novel polymeric formates of general formula [(Fmd)Ln III(HCOO) 4] ∞ (Fmd + = NH 2-CH +-NH 2; Ln = Eu (1), Gd (2), Tb (3), Dy (4)] were synthesized through solvothermal methods in formamide solutions. The compounds are isotructural; they crystallize in the orthorhombic C222 1 chiral space group. The coordination geometry at the metal centers is square antiprismatic (coordination number eight), with each formate ligand bridging adjacent lanthanide ions. The overall negative three-dimensional (3D) framework charge is balanced by the formamidinium cations sitting inside the channels along the a axis, forming extensive N-H⋯O hydrogen bonding with the surrounding cage. All the compounds have been characterized through single-crystal/powder X-ray diffraction, IR spectroscopy, and TG-MS analysis. Finally, their luminescence and magnetic properties have been assessed, leading to remarkable emission intensities, especially for the Tb(III) compound (φ = 0.83), with corresponding lifetime decays in the micro (Dy) and millisecond (Tb, Eu) time scale. A weak but sizable antiferromagnetic interaction has been observed for the Gd(III) derivative. © 2012 American Chemical Society. Source


Pieraccini M.,University of Florence
The Scientific World Journal | Year: 2013

Ground-based radar interferometry is an increasingly popular technique for monitoring civil infrastructures. Many research groups, professionals, and companies have tested it in different operative scenarios, so it is time for a first systematic survey of the case studies reported in the literature. This review is addressed especially to the engineers and scientists interested to consider the applicability of the technique to their practice, so it is focused on the issues of the practical cases rather than on theory and principles, which are now well consolidated. © 2013 Massimiliano Pieraccini. Source