Performance Evaluation of Global Reading of Entire Databases

Using simulation and probabilistic analysis, we study the performance of an algorithm to read entire databases with locking concurrency control allowing multiple readers or an exclusive writer. The algorithm runs concurrently with the normal transaction processing (on-the-fly) and locks the entities in the database one by one (incremental). The analysis compares different strategies to resolve the conflicts between the global read algorithm and update. Since the algorithm is parallel in nature, its interference with normal transactions is minimized in parallel and distributed databases. A simulation study shows that one variant of the algorithm can read the entire database with very little overhead and interference with the updates

Cryo-electron tomography of Kaposi\u27s sarcoma-associated herpesvirus capsids reveals dynamic scaffolding structures essential to capsid assembly and maturation.

Kaposi\u27s sarcoma-associated herpesvirus (KSHV) is a recently discovered DNA tumor virus that belongs to the gamma-herpesvirus subfamily. Though numerous studies on KSHV and other herpesviruses, in general, have revealed much about their multilayered organization and capsid structure, the herpesvirus capsid assembly and maturation pathway remains poorly understood. Structural variability or irregularity of the capsid internal scaffolding core and the lack of adequate tools to study such structures have presented major hurdles to earlier investigations employing more traditional cryo-electron microscopy (cryoEM) single particle reconstruction. In this study, we used cryo-electron tomography (cryoET) to obtain 3D reconstructions of individual KSHV capsids, allowing direct visualization of the capsid internal structures and systematic comparison of the scaffolding cores for the first time. We show that B-capsids are not a structurally homogenous group; rather, they represent an ensemble of B-capsid-like particles whose inner scaffolding is highly variable, possibly representing different intermediates existing during the KSHV capsid assembly and maturation. This information, taken together with previous observations, has allowed us to propose a detailed pathway of herpesvirus capsid assembly and maturation

Influence of organic and mineral amendments on microbial soil properties and processes

Microbial diversity in soils is considered important for maintaining sustainability of agricultural production systems. However, the links between microbial diversity and ecosystem processes are not well understood. This study was designed to gain better understanding of the effects of short-term management practices on the microbial community and how changes in the microbial community affect key soil processes. The effects of different forms of nitrogen (N) on soil biology and N dynamics was determined in two soils with organic and conventional management histories that varied in soil microbial properties but had the same fertility. The soils were amended with equal amounts of N (100 kg ha⁻¹) in organic (lupin, Lupinus angustifolius L.) and mineral form (urea), respectively. Over a 91-day period, microbial biomass C and N, dehydrogenase enzyme activity, community structure of pseudomondas (sensu stricto), actinomycetes and α proteobacteria (by denaturing gradient gel electrophoresis (DGGE) following PCR amplification of 16S rDNA fragments) and N mineralisation were measured. Lupin amendment resulted in a two- to five-fold increase in microbial biomass and enzyme activity, while these parameters did not differ significantly between the urea and control treatments. The PCR–DGGE analysis showed that the addition of mineral and organic compounds had an influence on the microbial community composition in the short term (up to 10 days) but the effects were not sustained over the 91-day incubation period. Microbial community structure was strongly influenced by the presence or lack of substrate, while the type of amendment (organic or mineral) had an effect on microbial biomass size and activity. These findings show that the addition of green manures improved soil biology by increasing microbial biomass and activity irrespective of management history, that no direct relationship existed among microbial structure, enzyme activity and N mineralisation, and that microbial community structure (by PCR–DGGE) was more strongly influenced by inherent soil and environmental factors than by short-term management practices

Pharmacy Adherence Measures to Assess Adherence to Antiretroviral Therapy: Review of the Literature and Implications for Treatment Monitoring

Prescription or pill-based methods for estimating adherence to antiretroviral therapy (ART), pharmacy adherence measures (PAMs), are objective estimates calculated from routinely collected pharmacy data. We conducted a literature review to evaluate PAMs, including their association with virological and other clinical outcomes, their efficacy compared with other adherence measures, and factors to consider when selecting a PAM to monitor adherence. PAMs were classified into 3 categories: medication possession ratio (MPR), pill count (PC), and pill pick-up (PPU). Data exist to recommend PAMs over self-reported adherence. PAMs consistently predicted patient outcomes, but additional studies are needed to determine the most predictive PAM parameters. Current evidence suggests that shorter duration of adherence assessment (≤6 months) and use of PAMs to predict future outcomes may be less accurate. PAMs which incorporate the number of days for which ART was prescribed without the counting of remnant pills, are reasonable minimum-resource methods to assess adherence to AR

Four Levels of Hierarchical Organization, Including Noncovalent Chainmail, Brace the Mature Tumor Herpesvirus Capsid against Pressurization

SummaryLike many double-stranded DNA viruses, tumor gammaherpesviruses Epstein-Barr virus and Kaposi’s sarcoma-associated herpesvirus withstand high internal pressure. Bacteriophage HK97 uses covalent chainmail for this purpose, but how this is achieved noncovalently in the much larger gammaherpesvirus capsid is unknown. Our cryoelectron microscopy structure of a gammaherpesvirus capsid reveals a hierarchy of four levels of organization: (1) Within a hexon capsomer, each monomer of the major capsid protein (MCP), 1,378 amino acids and six domains, interacts with its neighboring MCPs at four sites. (2) Neighboring capsomers are linked in pairs by MCP dimerization domains and in groups of three by heterotrimeric triplex proteins. (3) Small (∼280 amino acids) HK97-like domains in MCP monomers alternate with triplex heterotrimers to form a belt that encircles each capsomer. (4) One hundred sixty-two belts concatenate to form noncovalent chainmail. The triplex heterotrimer orchestrates all four levels and likely drives maturation to an angular capsid that can withstand pressurization

Estimating entropies from molecular dynamics simulations

The methods to compute the excess entropy and the entropy of solvation using liquid water as a test system were studied. The accuracy and convergence behavior of five methods based on thermodynamic integration and perturbation techniques was evaluated. Through the thermodynamic integration accurate entropy differences were obtained in which many copies of a solute were desolvated. Only two methods yield useful results, the calculation of solute-solvent entropy through thermodynamic integration and the calculation of solvation entropy through the temperature derivative of the corresponding free-energy difference, when one solute molecule is involved

The processing of number scales beyond whole numbers in development: Dissociations in arithmetic in Turner’s syndrome

The arithmetical skills in two children with Turner’s syndrome (TS), each the focus of a case study, were analysed in whole numbers and other number scales that have not been systematically explored previously, fractions, decimals, percentages, and negative numbers. The intention was to identify the fractionation of arithmetical skills. The two girls with TS showed dissociations of arithmetical skill in the calculation system of whole numbers that support its modular organization. Fractionation of skills was observed in some components of the other number scales, suggesting an analogous organization within these scales. The operational specificity of impairment within number scales but not others argued against a unitary arithmetical system but rather for autonomous operational scales within distinct number scales. A general model of arithmetic is proposed

Comparison of normalisation methods for surface-enhanced laser desorption and ionisation (SELDI) time-of-flight (TOF) mass spectrometry data

<p>Abstract</p> <p>Background</p> <p>Mass spectrometry for biological data analysis is an active field of research, providing an efficient way of high-throughput proteome screening. A popular variant of mass spectrometry is SELDI, which is often used to measure sample populations with the goal of developing (clinical) classifiers. Unfortunately, not only is the data resulting from such measurements quite noisy, variance between replicate measurements of the same sample can be high as well. Normalisation of spectra can greatly reduce the effect of this technical variance and further improve the quality and interpretability of the data. However, it is unclear which normalisation method yields the most informative result.</p> <p>Results</p> <p>In this paper, we describe the first systematic comparison of a wide range of normalisation methods, using two objectives that should be met by a good method. These objectives are minimisation of inter-spectra variance and maximisation of signal with respect to class separation. The former is assessed using an estimation of the coefficient of variation, the latter using the classification performance of three types of classifiers on real-world datasets representing two-class diagnostic problems. To obtain a maximally robust evaluation of a normalisation method, both objectives are evaluated over multiple datasets and multiple configurations of baseline correction and peak detection methods. Results are assessed for statistical significance and visualised to reveal the performance of each normalisation method, in particular with respect to using no normalisation. The normalisation methods described have been implemented in the freely available MASDA R-package.</p> <p>Conclusion</p> <p>In the general case, normalisation of mass spectra is beneficial to the quality of data. The majority of methods we compared performed significantly better than the case in which no normalisation was used. We have shown that normalisation methods that scale spectra by a factor based on the dispersion (e.g., standard deviation) of the data clearly outperform those where a factor based on the central location (e.g., mean) is used. Additional improvements in performance are obtained when these factors are estimated locally, using a sliding window within spectra, instead of globally, over full spectra. The underperforming category of methods using a globally estimated factor based on the central location of the data includes the method used by the majority of SELDI users.</p

Impact Assessment Modeling of Low-Water Management Policy

International audienceWe briefly present the main steps involved in designing and developing a platform for the numerical simulation of environmental and social impacts of the implementation of new environmental norms related to low-water management in France (MAELIA Project: multi-agents for environmental norms impact assessment). Some results are highlighted concerning in particular the structure of the underlying low-water management model and the process and agents' activity modeling

Rare deleterious germline variants and risk of lung cancer

Recent studies suggest that rare variants exhibit stronger effect sizes and might play a crucial role in the etiology of lung cancers (LC). Whole exome plus targeted sequencing of germline DNA was performed on 1045 LC cases and 885 controls in the discovery set. To unveil the inherited causal variants, we focused on rare and predicted deleterious variants and small indels enriched in cases or controls. Promising candidates were further validated in a series of 26,803 LCs and 555,107 controls. During discovery, we identified 25 rare deleterious variants associated with LC susceptibility, including 13 reported in ClinVar. Of the five validated candidates, we discovered two pathogenic variants in known LC susceptibility loci, ATM p.V2716A (Odds Ratio [OR] 19.55, 95%CI 5.04–75.6) and MPZL2 p.I24M frameshift deletion (OR 3.88, 95%CI 1.71–8.8); and three in novel LC susceptibility genes, POMC c.*28delT at 3′ UTR (OR 4.33, 95%CI 2.03–9.24), STAU2 p.N364M frameshift deletion (OR 4.48, 95%CI 1.73–11.55), and MLNR p.Q334V frameshift deletion (OR 2.69, 95%CI 1.33–5.43). The potential cancer-promoting role of selected candidate genes and variants was further supported by endogenous DNA damage assays. Our analyses led to the identification of new rare deleterious variants with LC susceptibility. However, in-depth mechanistic studies are still needed to evaluate the pathogenic effects of these specific alleles