Non-Universality in Semi-Directed Barabasi-Albert Networks

In usual scale-free networks of Barabasi-Albert type, a newly added node selects randomly m neighbors from the already existing network nodes, proportionally to the number of links these had before. Then the number N(k) of nodes with k links each decays as 1/k^gamma where gamma=3 is universal, i.e. independent of m. Now we use a limited directedness in the construction of the network, as a result of which the exponent gamma decreases from 3 to 2 for increasing m.Comment: 5 pages including 2 figures and computer progra

Immunogenetic novelty confers a selective advantage in host–pathogen coevolution

The major histocompatibility complex (MHC) is crucial to the adaptive immune response of vertebrates and is among the most polymorphic gene families known. Its high diversity is usually attributed to selection imposed by fast-evolving pathogens. Pathogens are thought to evolve to escape recognition by common immune alleles, and, hence, novel MHC alleles, introduced through mutation, recombination, or gene flow, are predicted to give hosts superior resistance. Although this theoretical prediction underpins host–pathogen “Red Queen” coevolution, it has not been demonstrated in the context of natural MHC diversity. Here, we experimentally tested whether novel MHC variants (both alleles and functional “supertypes”) increased resistance of guppies (Poecilia reticulata) to a common ectoparasite (Gyrodactylus turnbulli). We used exposure-controlled infection trials with wild-sourced parasites, and Gyrodactylus-naïve host fish that were F2 descendants of crossed wild populations. Hosts carrying MHC variants (alleles or supertypes) that were new to a given parasite population experienced a 35–37% reduction in infection intensity, but the number of MHC variants carried by an individual, analogous to heterozygosity in single-locus systems, was not a significant predictor. Our results provide direct evidence of novel MHC variant advantage, confirming a fundamental mechanism underpinning the exceptional polymorphism of this gene family and highlighting the role of immunogenetic novelty in host–pathogen coevolution

Probabilistic Reuse of Past Search Results

International audienceIn this paper, a new Monte Carlo algorithm to improve precision of information retrieval by using past search results is presented. Experiments were carried out to compare the proposed algorithm with traditional retrieval on a simulated dataset. In this dataset, documents, queries, and judgments of users were simulated. Exponential and Zipf distributions were used to build document collections. Uniform distribution was applied to build the queries. Zeta distribution was utilized to simulate the Bradford’s law representing the judgments of users. Empirical results show a better performance of our algorithm compared with traditional retrieval

A cost effectiveness analysis of salt reduction policies to reduce coronary heart disease in four Eastern Mediterranean countries.

BACKGROUND: Coronary Heart Disease (CHD) is rising in middle income countries. Population based strategies to reduce specific CHD risk factors have an important role to play in reducing overall CHD mortality. Reducing dietary salt consumption is a potentially cost-effective way to reduce CHD events. This paper presents an economic evaluation of population based salt reduction policies in Tunisia, Syria, Palestine and Turkey. METHODS AND FINDINGS: Three policies to reduce dietary salt intake were evaluated: a health promotion campaign, labelling of food packaging and mandatory reformulation of salt content in processed food. These were evaluated separately and in combination. Estimates of the effectiveness of salt reduction on blood pressure were based on a literature review. The reduction in mortality was estimated using the IMPACT CHD model specific to that country. Cumulative population health effects were quantified as life years gained (LYG) over a 10 year time frame. The costs of each policy were estimated using evidence from comparable policies and expert opinion including public sector costs and costs to the food industry. Health care costs associated with CHDs were estimated using standardized unit costs. The total cost of implementing each policy was compared against the current baseline (no policy). All costs were calculated using 2010 PPP exchange rates. In all four countries most policies were cost saving compared with the baseline. The combination of all three policies (reducing salt consumption by 30%) resulted in estimated cost savings of $235,000,000 and 6455 LYG in Tunisia;$39,000,000 and 31674 LYG in Syria; $6,000,000 and 2682 LYG in Palestine and$1,3000,000,000 and 378439 LYG in Turkey. CONCLUSION: Decreasing dietary salt intake will reduce coronary heart disease deaths in the four countries. A comprehensive strategy of health education and food industry actions to label and reduce salt content would save both money and lives

Metformin reduces airway glucose permeability and hyperglycaemia-induced Staphylococcus aureus load independently of effects on blood glucose

Background Diabetes is a risk factor for respiratory infection, and hyperglycaemia is associated with increased glucose in airway surface liquid and risk of Staphylococcus aureus infection. Objectives To investigate whether elevation of basolateral/blood glucose concentration promotes airway Staphylococcus aureus growth and whether pretreatment with the antidiabetic drug metformin affects this relationship. Methods Human airway epithelial cells grown at air–liquid interface (±18 h pre-treatment, 30 μM–1 mM metformin) were inoculated with 5×105 colony-forming units (CFU)/cm2 S aureus 8325-4 or JE2 or Pseudomonas aeruginosa PA01 on the apical surface and incubated for 7 h. Wild-type C57BL/6 or db/db (leptin receptor-deficient) mice, 6–10 weeks old, were treated with intraperitoneal phosphate-buffered saline or 40 mg/kg metformin for 2 days before intranasal inoculation with 1×107 CFU S aureus. Mice were culled 24 h after infection and bronchoalveolar lavage fluid collected. Results Apical S aureus growth increased with basolateral glucose concentration in an in vitro airway epithelia–bacteria co-culture model. S aureus reduced transepithelial electrical resistance (RT) and increased paracellular glucose flux. Metformin inhibited the glucose-induced growth of S aureus, increased RT and decreased glucose flux. Diabetic (db/db) mice infected with S aureus exhibited a higher bacterial load in their airways than control mice after 2 days and metformin treatment reversed this effect. Metformin did not decrease blood glucose but reduced paracellular flux across ex vivo murine tracheas. Conclusions Hyperglycaemia promotes respiratory S aureus infection, and metformin modifies glucose flux across the airway epithelium to limit hyperglycaemia-induced bacterial growth. Metformin might, therefore, be of additional benefit in the prevention and treatment of respiratory infection

Određivanje donepezil hidroklorida u humanoj plazmi i ljekovitim oblicima pomoću HPLC s detekcijom fluorescencije

A sensitive, isocratic reversed-phase high performance liquid chromatographic method involving fluorescence detection was developed for the determination of donepezil hydrochloride in tablets and in human plasma. Pindolol was successfully used as an internal standard. Good chromatographic separation was achieved by using analytical column C18. The system operated at room temperature using a mobile phase consisting of methanol, phosphate buffer (0.02 mol L1) and triethyl amine (pH 3.5) (55: 45: 0.5 V/V/V) at a flow rate 0.9 mL min1. The analyte and internal standard were extracted from human plasma via liquid-liquid extraction. The proposed method was validated for selectivity, linearity, accuracy and precision. The calibration curve was linear over the range of 5-2000 ng mL1 of donepezil with detection limit of 1.5 ng mL1. Intra- and inter-day relative standard deviations were less than 2.5 %. The method was found to be suitable for the quality control of donepezil hydrochloride in bulk drug as well as in human plasma.Ovaj rad opisuje HPLC metodu određivanja donepezil hidroklorida (DP) u tabletama i u ljudskoj plazmi u nano području. Postavljena je osjetljiva metoda izokratične HPLC s fluorescencijskom detekcijom. Kao unutarnji standard upotrebljen je pindolol. Dobro kromatografsko odjeljivanje postignuto je primjenom analitičke kolone C18. Radna temperatura bila je sobna, a kao mobilna faza upotrebljena je smjesa metanola, fosfatnog pufera (0,02 mol L1) i trietilamina (pH 3,5) (55:45:0.5 V/V/V). Analit i unutarnji standard su ekstrahirani iz ljudske plazme ekstrakcijom tekuće-tekuće. Predložena metoda je validirana s obzirom na selektivnost, područje linearnosti, ispravnost i preciznost. Kalibracijska funkcija bila je linearna u području od 5-2000 ng mL1 donepezila, a granica detekcije iznosila je 2 ng mL1. Relativna standardna devijacija za repetabilnost i intermedijarnu preciznost bila je manja od 2,5 %. Metoda je primjenljliva u kontroli kvalitete ljekovitih formulacija s DP-om i u praćenju DP-a u ljudskoj plazmi

The UfM and the Middle East 'Peace Process': An Unhappy Symbiosis

This contribution explores differing theories on how the failure of the ‘peace process’ featured in the design and goals of the UfM, drawing on lessons from the period when the EMP was pursued in parallel with the peace process. In each case, institutional overlaps are identified, as well as commonalities in the approaches of the actors to both pursuits. Crucially, however, the persistence and intensification of the Arab–Israeli conflict, in combination with the shift from multilateralism to bilateralism embodied in the UfM, has politicized the latter at the expense of the functionalist aspirations of its architects

Female responses to experimental removal of sexual selection components in Drosophila melanogaster

Despite the common assumption that multiple mating should in general be favored in males, but not in females, to date there is no consensus on the general impact of multiple mating on female fitness. Notably, very little is known about the genetic and physiological features underlying the female response to sexual selection pressures. By combining an experimental evolution approach with genomic techniques, we investigated the effects of single and multiple matings on female fecundity and gene expression. We experimentally manipulated the opportunity for mating in replicate populations of Drosophila melanogaster by removing components of sexual selection, with the aim of testing differences in short term post-mating effects of females evolved under different mating strategies

Predictors of job satisfaction among pharmacists: A regional workforce survey

Background: Job satisfaction affects organizational outcomes including performance and retention. The pharmacy job satisfaction literature points to several predictors of job satisfaction, but educational debt and various work settings have not been previously examined. Objectives: To identify predictors of Virginia pharmacists\u27 job satisfaction. Methods: This cross-sectional study used data from the 2018 Virginia Pharmacist Workforce Survey. Of 15,424 registered pharmacists, 13,962 (90.5%) completed the survey. Pharmacists who reported being employed and working in Virginia in the previous year (2017) were included in the analysis (n = 6042). Data were summarized using descriptive statistics. Multiple logistic regression identified predictors of job satisfaction. Results: Respondents were primarily female (66.3%), Pharm.D. degree holders (65.5%), with a 14.8-year average work experience. Most pharmacists (86%) reported being very/somewhat satisfied with their job. Educational debt was not significantly associated with job satisfaction. Significant predictors of job satisfaction included: being female (aOR = 1.28, 95% CI 1.08, 1.52); working \u3c30 (aOR = 1.80, 95% CI 1.14, 2.84), 30–39 (aOR = 1.47, 95% CI 1.02, 2.11), or 40–49 (aOR = 1.42, 95% CI 1.02, 1.98) versus ≥50 h per week; earning an annual income of \u3c$50,000 (aOR = 0.60, 95$150,000 (aOR = 2.05, 95% CI 1.30, 3.23) versus $100,000–$149,999; working in an independent community pharmacy (aOR = 3.72, 95% CI 2.54, 5.44), health system (aOR = 3.81, 95% CI 2.78, 5.22), clinic-based pharmacy (aOR = 4.39, 95% CI 2.18, 8.83), academia (aOR = 5.20, 95% CI 1.97, 13.73), benefits administration (aOR = 3.64, 95% CI 1.71, 7.74), long-term home and home health/infusion (aOR = 1.71, 95% CI 1.10, 2.67), mass merchandiser community (aOR = 0.79, 95% CI 0.62, 0.99), or manufacturer and wholesale distributor (aOR = 3.46, 95% CI 1.97, 6.08) versus chain community pharmacy. Conclusions: Overall, Virginia pharmacists reported high job satisfaction. Pharmacists working in chain community pharmacy reported lower satisfaction relative to other settings. Being female, having a high annual income, and working for less hours was associated with improved job satisfaction

Quantitative RT-PCR analysis of differentially expressed genes in Quercus suber in response to Phytophthora cinnamomi infection

cDNA-AFLP methodology was used to gain insight into gene fragments differentially present in the mRNA profiles of Quercus suber roots infected with zoospores of Phytophthora cinnamomi at different post challenge time points. Fifty-three transcript-derived fragments (TDFs) were identified and sequenced. Six candidate genes were selected based on their expression patterns and homology to genes known to play a role in defence. They encode a cinnamyl alcohol dehydrogenase2 (QsCAD2), a protein disulphide isomerase (QsPDI), a CC-NBS-LRR resistance protein (QsRPc), a thaumatin-like protein (QsTLP), a chitinase (QsCHI) and a 1,3-β-glucanase (QsGlu). Evaluation of the expression of these genes by quantitative polymerase chain reaction (qPCR) revealed that transcript levels of QsRPc, QsCHI, QsCAD2 and QsPDI increased during the first 24 h post-inoculation, while those of thaumatin-like protein decreased. No differential expression was observed for 1,3-β-glucanase (QsGlu).Four candidate reference genes, polymerase II (QsRPII), eukaryotic translation initiation factor 5A (QsEIF-5A), β-tubulin (QsTUB) and a medium subunit family protein of clathrin adaptor complexes (QsCACs) were assessed to determine the most stable internal references for qRT-PCR normalization in the Phytophthora-Q. suber pathosystem in root tissues. Those found to be more stable, QsRPII and QsCACs, were used as internal reference in the present work.Knowledge on the Quercus defence mechanisms against biotic stress is scarce. This study provides an insight into the gene profiling of a few important genes of Q. suber in response to P. cinnamomi infection contributing to the knowledge of the molecular interactions involving Quercus and root pathogens that can be useful in the future to understand the mechanisms underlying oak resistance to soil-borne oomycetes.Peer Reviewe