On coherent sheaves of small length on the affine plane

We classify coherent modules on $k[x,y]$ of length at most $4$ and supported at the origin. We compare our calculation with the motivic class of the moduli stack parametrizing such modules, extracted from the Feit-Fine formula. We observe that the natural torus action on this stack has finitely many fixed points, corresponding to connected skew Ferrers diagrams

Monte Carlo study of kink effect in isolated-gate InAs/AlSb high electron mobility transistors

A semiclassical two-dimensional ensemble Monte Carlo simulator is used to perform a physical analysis of the kink effect in InAs/AlSb high electron mobility transistors (HEMTs). Kink effect, this is, an anomalous increase in the drain current I-D when increasing the drain-to-source voltage V-DS, leads to a reduction in the gain and a rise in the level of noise, thus limiting the utility of these devices for microwave applications. Due to the small band gap of InAs, InAs/AlSb HEMTs are very susceptible to suffer from impact ionization processes, with the subsequent hole transport through the structure, both implicated in the kink effect. The results indicate that, when V-DS is high enough for the onset of impact ionization, holes thus generated tend to pile up in the buffer (at the gate-drain side) due to the valence-band energy barrier between the buffer and the channel. Due to this accumulation of positive charge the channel is further opened and I-D increases, leading to the kink effect in the I-V characteristics and eventually to the device electrical breakdown. The understanding of this phenomenon provides useful information for the development of kink-effect-free InAs/AlSb HEMTs

Glyphosate resistance by engineering the flavoenzyme glycine oxidase.

Glycine oxidase from Bacillus subtilis is a homotetrameric flavoprotein of great potential biotechnological use because it catalyzes the oxidative deamination of various amines and D-isomer of amino acids to yield the corresponding \u3b1-keto acids, ammonia/amine, and hydrogen peroxide. Glyphosate (N-phosphonomethylglycine), a broad spectrum herbicide, is an interesting synthetic amino acid: this compound inhibits 5-enolpyruvylshikimate-3-phosphate synthase in the shikimate pathway, which is essential for the biosynthesis of aromatic amino acids in plants and certain bacteria. In recent years, transgenic crops resistant to glyphosate were mainly generated by overproducing the plant enzyme or by introducing a 5-enolpyruvylshikimate-3-phosphate synthase insensitive to this herbicide. In this work, we propose that the enzymatic oxidation of glyphosate could be an effective alternative to this important biotechnological process. To reach this goal, we used a rational design approach (together with site saturation mutagenesis) to generate a glycine oxidase variant more active on glyphosate than on the physiological substrate glycine. The glycine oxidase containing three point mutations (G51S/A54R/H244A) reaches an up to a 210-fold increase in catalytic efficiency and a 15,000-fold increase in the specificity constant (the kcat/Km ratio between glyphosate and glycine) as compared with wild-type glycine oxidase. The inspection of its three-dimensional structure shows that the \u3b12-\u3b13 loop (comprising residues 50-60 and containing two of the mutated residues) assumes a novel conformation and that the newly introduced residue Arg54 could be the key residue in stabilizing glyphosate binding and destabilizing glycine positioning in the binding site, thus increasing efficiency on the herbicide

The determinants of individual health care expenditures in prison: evidence from Switzerland.

Prison health systems are subject to increasing pressures given the specific health needs of a growing and aging prison population. Identifying the drivers of medical spending among incarcerated individuals is therefore key for health care governance in prisons. This study assesses the determinants of individual health care expenditures within the prisons of the canton of Vaud, a large region of Switzerland. We use a unique dataset linking demographic and prison stay characteristics as well as objective measures of morbidity to detailed medical invoice data. We adopt a multivariate regression approach to model total, somatic and psychiatric outpatient health care expenditures. We find that chronic infectious, musculoskeletal and skin diseases are strong predictors of total and somatic costs. Schizophrenia, neurotic and personality disorders as well as the abuse of illicit drugs and pharmaceuticals drive total and psychiatric costs. Furthermore, cumulating psychiatric and somatic comorbidities has an incremental effect on costs. By identifying the characteristics associated with health care expenditures in prison, this study constitutes a key step towards a more efficient use of medical resources in prison

Exploring differences in healthcare utilization of prisoners in the Canton of Vaud, Switzerland.

Prison healthcare is an important public health concern given the increasing healthcare needs of a growing and aging prison population, which accumulates vulnerability factors and suffers from higher disease prevalence than the general population. This study identifies the key factors associated with outpatient general practitioner (GP), nursing or psychiatric healthcare utilization (HCU) within prisons. Cross-sectional data systematically collected by the prison medical staff were obtained for a sample of 1664 adult prisoners of the Canton of Vaud, Switzerland, for the year 2011. They contain detailed information on demographics (predisposing factors), diagnosed chronic somatic and psychiatric disorders (needs factors), as well as prison stay characteristics (contextual factors). For GP, nurse and psychiatric care, two-part regressions are used to model separately the probability and the volume of HCU. Predisposing factors are generally not associated with the probability to use healthcare services after controlling for needs factors. However, female inmates use higher volumes of care, and the volume of GP consultations increases with age. Chronic somatic and psychiatric conditions are the most important predictors of the probability of HCU, but associations with volumes differ in their magnitude and significance across disease groups. Infectious, musculoskeletal, nervous and circulatory diseases actively mobilize GP and nursing staff. Schizophrenia, illicit drug and pharmaceuticals abuse are strongly positively associated with psychiatric and nurse HCU. The occupancy rate displays positive associations among contextual factors. Prison healthcare systems face increasingly complex organizational, budgetary and ethical challenges. This study provides relevant insights into the HCU patterns of a marginalized and understudied population

An innovative method to produce green table olives based on "pied de cuve" technology

The technology of "pied de cuve" (PdC) is applied in food process only to produce wines with an enriched community of pro-technological yeasts. PdC promotes the growth of the desirable microbial strains in a small volume of grape must acting as a starter inoculums for higher volumes. The aim of the present work was to investigate the use of partially fermented brines, a technology known as PdC, developed with lactic acid bacteria (LAB) on the microbiological, chemical and sensory characteristics of green fermented table olives during two consecutive campaigns. The experimental plan included two trials based on different PdCs: trial A, PdC obtained with Lactobacillus pentosus OM13; trial B, PdC obtained through a spontaneous fermentation. Two control additional trials without PdC were included for comparison: trial C, spontaneous fermentation; trial D, direct inoculation of L. pentosus OM13. The use of PdCs favoured the rapid increase of LAB concentrations in both trials A and B. These trials showed levels of LAB higher than trial C and almost superimposable to that of trial D. Trial B was characterized by a certain diversity of L. pentosus strains and some of them dominated the manufacturing process. These results indicated PdC as a valuable method to favour the growth of autochthonous L. pentosus strains. Hierarchical cluster analysis (HCA) and principal component analysis (PCA) visibly discriminated olive processes fermented with the two experimental PdCs. Interestingly, on the basis of microbial and pH variables, both approaches showed that the olives produced with PdC technology are closely related to those of trial D, with the advantages of reducing the amount of starter to inoculate (trial A) and a higher LAB biodiversity (trial B). Volatile organic compound (VOC) composition and sensory analysis showed trials A and B different from the trials with no PdC added, in both years. Furthermore, the trial B showed the highest scores of green olive aroma and taste complexity. Spoilage microorganisms were estimated at very low levels in all trials. Undesired off-odours and off-flavours were not revealed at the end of the process

Engineering Archeal Surrogate Systems for the Development of Protein-Protein Interaction Inhibitors against Human RAD51

Protein-protein interactions (PPIs) are increasingly important targets for drug discovery. Efficient fragment-based drug discovery approaches to tackle PPIs are often stymied by difficulties in the production of stable, unliganded target proteins. Here, we report an approach that exploits protein engineering to "humanise" thermophilic archeal surrogate proteins as targets for small-molecule inhibitor discovery and to exemplify this approach in the development of inhibitors against the PPI between the recombinase RAD51 and tumour suppressor BRCA2. As human RAD51 has proved impossible to produce in a form that is compatible with the requirements of fragment-based drug discovery, we have developed a surrogate protein system using RadA from $\textit{Pyrococcus furiosus}$. Using a monomerised RadA as our starting point, we have adopted two parallel and mutually instructive approaches to mimic the human enzyme: firstly by mutating RadA to increase sequence identity with RAD51 in the BRC repeat binding sites, and secondly by generating a chimeric archaeal human protein. Both approaches generate proteins that interact with a fourth BRC repeat with affinity and stoichiometry comparable to human RAD51. Stepwise humanisation has also allowed us to elucidate the determinants of RAD51 binding to BRC repeats and the contributions of key interacting residues to this interaction. These surrogate proteins have enabled the development of biochemical and biophysical assays in our ongoing fragment-based small-molecule inhibitor programme and they have allowed us to determine hundreds of liganded structures in support of our structure-guided design process, demonstrating the feasibility and advantages of using archeal surrogates to overcome difficulties in handling human proteins.Wellcome Trust Translational (Grant ID: 080083/Z/06/Z) and Seeding Drug Discovery Initiative (Grant ID: 91050/Z/10/Z) award

Development of a multipurpose scaffold for the display of peptide loops

Protein–protein interactions (PPIs) determine a wide range of biological processes and analysis of these dynamic networks is increasingly becoming a mandatory tool for studying protein function. Using the globular ATPase domain of recombinase RadA as a scaffold, we have developed a peptide display system (RAD display), which allows for the presentation of target peptides, protein domains or full-length proteins and their rapid recombinant production in bacteria. The design of the RAD display system includes differently tagged versions of the scaffold, which allows for flexibility in the protein purification method, and chemical coupling for small molecule labeling or surface immobilization. When combined with the significant thermal stability of the RadA protein, these features create a versatile multipurpose scaffold system. Using various orthogonal biophysical techniques, we show that peptides displayed on the scaffold bind to their natural targets in a fashion similar to linear parent peptides. We use the examples of CK2β/CK2α kinase and TPX2/Aurora A kinase protein complexes to demonstrate that the peptide displayed by the RAD scaffold can be used in PPI studies with the same binding efficacy but at lower costs compared with their linear synthetic counterparts.This work was funded by the Wellcome Trust Strategic Award (090340/Z/09/Z)

Spatially self-similar spherically symmetric perfect-fluid models

Einstein's field equations for spatially self-similar spherically symmetric perfect-fluid models are investigated. The field equations are rewritten as a first-order system of autonomous differential equations. Dimensionless variables are chosen in such a way that the number of equations in the coupled system is reduced as far as possible and so that the reduced phase space becomes compact and regular. The system is subsequently analysed qualitatively with the theory of dynamical systems.Comment: 21 pages, 6 eps-figure

Plutonium and surrogate fission products in a composite ceramic waste form.

Argonne National Laboratory is developing a ceramic waste form to immobilize salt containing fission products and transuranic elements. Preliminary results have been presented for ceramic waste forms containing surrogate fission products such as cesium and the lanthanides. In this work results from scanning electron microscopy/energy dispersive spectroscopy and x-ray diffraction are presented in greater detail for ceramic waste forms containing surrogate fission products. Additionally, results for waste forms containing plutonium and surrogate fission products are presented. Most of the surrogate fission products appear to be silicates or aluminosilicates whereas the plutonium is usually found in an oxide form. There is also evidence for the presence of plutonium within the sodalite phase although the chemical speciation of the plutonium is not known