Giant suppression of the Drude conductivity due to quantum interference in disordered two-dimensional systems

Temperature and magnetic field dependences of the conductivity in heavily doped, strongly disordered two-dimensional quantum well structures GaAs/In$_x$Ga$_{1-x}$As/GaAs are investigated within wide conductivity and temperature ranges. Role of the interference in the electron transport is studied in the regimes when the phase breaking length $L_\phi$ crosses over the localization length $\xi\sim l\exp{(\pi k_Fl/2)}$ with lowering temperature, where $k_F$ and $l$ are the Fermi quasimomentum and mean free path, respectively. It has been shown that all the experimental data can be understood within framework of simple model of the conductivity over delocalized states. This model differs from the conventional model of the weak localization developed for $k_Fl\gg 1$ and $L_\phi\ll\xi$ by one point: the value of the quantum interference contribution to the conductivity is restricted not only by the phase breaking length $L_\phi$ but by the localization length $\xi$ as well. We show that just the quantity $(\tau_\phi^\ast)^{-1}=\tau_\phi^{-1}+\tau_\xi^{-1}$ rather than $\tau_\phi^{-1}$, where $\tau_\phi\propto T^{-1}$ is the dephasing time and $\tau_\xi\sim\tau\exp(\pi k_F l)$, is responsible for the temperature and magnetic field dependences of the conductivity over the wide range of temperature and disorder strength down to the conductivity of order $10^{-2} e^2/h$.Comment: 11 pages, 15 figure

Human Adenovirus come indicatore di contaminazione biologica in matrici idriche

In Italia la normativa vigente non prevede virus come indicatori di contaminazione biologica. Nello specifico per le acque reflue, in uscita dall’impianto di recupero, gli unici indicatori presi in considerazione sono E. Coli e Salmonella (Allegato D.M. 185/03). Mentre per le acque di balneazione sono E. Coli ed Enterococchi (2006/7/CE), così come per le acque destinate al consumo umano (D.lgs. n. 31/2001). Per aerosol e superfici non vi sono normative a riguardo. Numerosi studi hanno però fatto emergere che la presenza di questi indicatori non è esaustiva per predire la contaminazione biologica delle matrici idriche in esame. Se da un lato sono in grado di rivelare una contaminazione e quindi un rischio per la salute, dall’altro non sono parametri correlabili con la presenza di virus e protozoi. Infatti, laddove E. Coli ed Enterococchi sono assenti, possono essere presenti virus umani come Human Adenovirus, Rotavirus, Epatite A (HAV), Enterovirus, Norovirus GII. Tra questi Human Adenovirus risulta essere ritrovato con maggior frequenza nelle matrici. In studi effettuati su acqua di mare tale virus risulta presente nel 21% dei campioni in cui invece erano totalmente assenti E. Coli ed Enterococchi (patogeni indice suggeriti dalla normativa). Tale dato si è riscontrato anche nelle acque di fiume dove il 72% dei campioni, negativo per E. Coli ed Enterococchi, è per il 63% positivo per Human Adenovirus. Nelle acque trattate il 46% dei campioni che è negativo per E. Coli ed Enterococchi è invece positivo invece per il 57% a Human Adenovirus. Questo lavoro si è concentrato appunto su Human Adenovirus, un virus della famiglia di Adenoviridae, genere Mastadenovirus, che conta 51 diversi sierotipi in grado di infettare l’uomo, divisi in 6 sottogeneri ( indicati con le lettere da A a F) e 51 sierotipi ( indicati con i numeri). E’ un virus a doppio filamento di DNA, formato da un capside icosaedrico privo di envelope e con un diametro di circa 35-40 nm. La trasmissione del virus avviene per via oro-fecale e respiratoria, mediante secrezioni respiratorie e oculari. Si localizza a livello di del tratto respiratorio, intestinale e della congiuntiva provocando molte patologie come: gastroenteriti, congiuntiviti, patologie respiratorie e infezioni del tratto urinario. E’ eliminato all’esterno mediante feci, urina, secrezioni oro-faringee e liquido congiuntivale. Lo scopo di questo lavoro è proporre Human Adenovirus come patogeno indice di contaminazione biologica in differenti matrici idriche da affiancare agli indicatori tradizionali. Tale scelta deriva dal fatto che Human Adenovirus è ubiquitario, ha elevata resistenza ambientale e ai trattamenti di disinfezione chimico-fisici. Inoltre ha elevata specificità per l’ospite umano il quale rilascia nell’ambiente un’alta concentrazione di particelle virali anche dopo molto tempo dall’infezione. Sono stati analizzati campioni di liquame in entrata e uscita dal depuratore, acqua sperimentalmente trattata, acqua di mare e acqua di fiume. I campioni successivamente sono stati esaminati con procedure standardizzate in house per passare poi all’analisi molecolare mediante la qPCR (Real Time PCR) con protocollo specifico per Human Adenovirus. Nella maggior parte dei campioni analizzati si è riscontrata la presenza del genoma di Human Adenovirus a concentrazioni variabili (liquame in entrata(1,7 x 1010 ± 7,9) e uscita dal depuratore(4,7 x 108 ± 11), acqua sperimentalmente trattata(1,6 x 102 ± 31), acqua di mare(9,3 x 103 ± 2,4) e acqua di fiume(8,5 x 102 ± 27), confermando la sua diffusione ubiquitaria nell’ambiente. I risultati ottenuti con questo lavoro concordano con quelli di precedenti monitoraggi confermano che Human Adenovirus potrebbe essere un ottimo candidato come indicatore di contaminazione biologica da affiancare a quelli tradizionali, per diverse matrici idriche, grazie anche alla facilità con cui, tramite qPCR, si può rilevare e quantificare la sua presenza

Impact of digestive and oropharyngeal decontamination on the intestinal microbiota in ICU patients

Selective digestive microbial decontamination (SDD) is hypothesized to benefit patients in intensive care (ICU) by suppressing Gram-negative potential pathogens from the colon without affecting the anaerobic intestinal microbiota. The purpose of this study was to provide more insight to the effects of digestive tract and oropharyngeal decontamination on the intestinal microbiota by means of a prospective clinical trial in which faecal samples were collected from ICU patients for intestinal microbiota analysis. The faecal samples were collected from ICU patients enrolled in a multicentre trial to study the outcome of SDD and selective oral decontamination (SOD) in comparison with standard care (SC). Fluorescent in situ hybridization (FISH) was used to analyze the faecal microbiota. The numbers of bacteria from different bacterial groups were compared between the three regimens. The total counts of bacteria per gram faeces did not differ between regimens. The F. prausnitzii group of bacteria, representing an important group among intestinal microbiota, was significantly reduced in the SDD regimen compared to the SC and SOD. The Enterobacteriaceae were significantly suppressed during SDD compared to both SOD and SC; enterococci increased in SDD compared to both other regimens. The composition of the intestinal microbiota is importantly affected by SDD. The F. prausnitzii group was significantly suppressed during SDD. This group of microbiota is a predominant producer of butyrate, the main energy source for colonocytes. Reduction of this microbiota is an important trade-off while reducing gram-negative bacteria by SDD

Quantum Gravity in 2+1 Dimensions: The Case of a Closed Universe

In three spacetime dimensions, general relativity drastically simplifies, becoming a ``topological'' theory with no propagating local degrees of freedom. Nevertheless, many of the difficult conceptual problems of quantizing gravity are still present. In this review, I summarize the rather large body of work that has gone towards quantizing (2+1)-dimensional vacuum gravity in the setting of a spatially closed universe.Comment: 61 pages, draft of review for Living Reviews; comments, criticisms, additions, missing references welcome; v2: minor changes, added reference

Glutamic Acid Decarboxylase-Derived Epitopes with Specific Domains Expand CD4+CD25+ Regulatory T Cells

BACKGROUND:CD4(+)CD25(+) regulatory T cell (Treg)-based immunotherapy is considered a promising regimen for controlling the progression of autoimmune diabetes. In this study, we tested the hypothesis that the therapeutic effects of Tregs in response to the antigenic epitope stimulation depend on the structural properties of the epitopes used. METHODOLOGY/PRINCIPAL FINDINGS:Splenic lymphocytes from nonobese diabetic (NOD) mice were stimulated with different glutamic acid decarboxylase (GAD)-derived epitopes for 7-10 days and the frequency and function of Tregs was analyzed. We found that, although all expanded Tregs showed suppressive functions in vitro, only p524 (GAD524-538)-expanded CD4(+)CD25(+) T cells inhibited diabetes development in the co-transfer models, while p509 (GAD509-528)- or p530 (GAD530-543)-expanded CD4(+)CD25(+) T cells had no such effects. Using computer-guided molecular modeling and docking methods, the differences in structural characteristics of these epitopes and the interaction mode (including binding energy and identified domains in the epitopes) between the above-mentioned epitopes and MHC class II I-A(g7) were analyzed. The theoretical results showed that the epitope p524, which induced protective Tregs, possessed negative surface-electrostatic potential and bound two chains of MHC class II I-A(g7), while the epitopes p509 and p530 which had no such ability exhibited positive surface-electrostatic potential and bound one chain of I-A(g7). Furthermore, p524 bound to I-A(g7) more stably than p509 and p530. Of importance, we hypothesized and subsequently confirmed experimentally that the epitope (GAD570-585, p570), which displayed similar characteristics to p524, was a protective epitope by showing that p570-expanded CD4(+)CD25(+) T cells suppressed the onset of diabetes in NOD mice. CONCLUSIONS/SIGNIFICANCE:These data suggest that molecular modeling-based structural analysis of epitopes may be an instrumental tool for prediction of protective epitopes to expand functional Tregs

Mutagenesis Objective Search and Selection Tool (MOSST): an algorithm to predict structure-function related mutations in proteins

<p>Abstract</p> <p>Background</p> <p>Functionally relevant artificial or natural mutations are difficult to assess or predict if no structure-function information is available for a protein. This is especially important to correctly identify functionally significant non-synonymous single nucleotide polymorphisms (nsSNPs) or to design a site-directed mutagenesis strategy for a target protein. A new and powerful methodology is proposed to guide these two decision strategies, based only on conservation rules of physicochemical properties of amino acids extracted from a multiple alignment of a protein family where the target protein belongs, with no need of explicit structure-function relationships.</p> <p>Results</p> <p>A statistical analysis is performed over each amino acid position in the multiple protein alignment, based on different amino acid physical or chemical characteristics, including hydrophobicity, side-chain volume, charge and protein conformational parameters. The variances of each of these properties at each position are combined to obtain a global statistical indicator of the conservation degree of each property. Different types of physicochemical conservation are defined to characterize relevant and irrelevant positions. The differences between statistical variances are taken together as the basis of hypothesis tests at each position to search for functionally significant mutable sites and to identify specific mutagenesis targets. The outcome is used to statistically predict physicochemical consensus sequences based on different properties and to calculate the amino acid propensities at each position in a given protein. Hence, amino acid positions are identified that are putatively responsible for function, specificity, stability or binding interactions in a family of proteins. Once these key functional positions are identified, position-specific statistical distributions are applied to divide the 20 common protein amino acids in each position of the protein's primary sequence into a group of functionally non-disruptive amino acids and a second group of functionally deleterious amino acids.</p> <p>Conclusions</p> <p>With this approach, not only conserved amino acid positions in a protein family can be labeled as functionally relevant, but also non-conserved amino acid positions can be identified to have a physicochemically meaningful functional effect. These results become a discriminative tool in the selection and elaboration of rational mutagenesis strategies for the protein. They can also be used to predict if a given nsSNP, identified, for instance, in a genomic-scale analysis, can have a functional implication for a particular protein and which nsSNPs are most likely to be functionally silent for a protein. This analytical tool could be used to rapidly and automatically discard any irrelevant nsSNP and guide the research focus toward functionally significant mutations. Based on preliminary results and applications, this technique shows promising performance as a valuable bioinformatics tool to aid in the development of new protein variants and in the understanding of function-structure relationships in proteins.</p

Analysis of the Effects of Polymorphism on Pollen Profilin Structural Functionality and the Generation of Conformational, T- and B-Cell Epitopes

An extensive polymorphism analysis of pollen profilin, a fundamental regulator of the actin cytoskeleton dynamics, has been performed with a major focus in 3D-folding maintenance, changes in the 2-D structural elements, surface residues involved in ligands-profilin interactions and functionality, and the generation of conformational and lineal B- and T-cell epitopes variability. Our results revealed that while the general fold is conserved among profilins, substantial structural differences were found, particularly affecting the special distribution and length of different 2-D structural elements (i.e. cysteine residues), characteristic loops and coils, and numerous micro-heterogeneities present in fundamental residues directly involved in the interacting motifs, and to some extension these residues nearby to the ligand-interacting areas. Differential changes as result of polymorphism might contribute to generate functional variability among the plethora of profilin isoforms present in the olive pollen from different genetic background (olive cultivars), and between plant species, since biochemical interacting properties and binding affinities to natural ligands may be affected, particularly the interactions with different actin isoforms and phosphoinositides lipids species. Furthermore, conspicuous variability in lineal and conformational epitopes was found between profilins belonging to the same olive cultivar, and among different cultivars as direct implication of sequences polymorphism. The variability of the residues taking part of IgE-binding epitopes might be the final responsible of the differences in cross-reactivity among olive pollen cultivars, among pollen and plant-derived food allergens, as well as between distantly related pollen species, leading to a variable range of allergy reactions among atopic patients. Identification and analysis of commonly shared and specific epitopes in profilin isoforms is essential to gain knowledge about the interacting surface of these epitopes, and for a better understanding of immune responses, helping design and development of rational and effective immunotherapy strategies for the treatment of allergy diseases. [EN]This study was supported by the following European Regional Development Fund co-financed grants: MCINN BFU 2004-00601/BFI, BFU 2008-00629, BFU2011-22779, CICE (Junta de Andalucía) P2010-CVI15767, P2010-AGR6274 and P2011-CVI-7487, and by the coordinated project Spain/Germany MEC HA2004-0094. JCJ-L thanks Spanish CSIC and the European Marie Curie research program for his I3P-BPD-CSIC, and PIOF-GA-2011-301550 grants, respectively.Peer reviewe