Miracle-dz/UniFAR-FTUs huggingface dataset:
SPR-5 is a histone H3K4 demethylase with a role in meiotic double-strand break repair

Regulation of histone methylation levels has long been implicated in multiple cellular processes, many of which involve transcription. Here, however, we report a unique role for the Caenorhabditis elegans histone demethylase SPR-5 in meiotic DNA double-strand break repair (DSBR). SPR-5 shows enzymatic activity toward H3K4me2 both in vitro and in the nematode germline, and spr-5 mutants show several phenotypes indicating a perturbation of DSBR, including increased p53-dependent germ cell apoptosis, increased levels of the DSBR marker RAD-51, and sensitivity toward DSB-inducing treatments. spr-5 mutants show no transcriptional misregulation of known DSBR involved genes. Instead, SPR-5 shows a rapid subcellular relocalization upon DSB-inducing treatment, which suggests that SPR-5 may function directly in DSBR.
High-Throughput Identification and Validation of In Situ-Expressed Genes of Lactococcus lactis

ABSTRACT Understanding the functional response of bacteria to their natural environment is one of the current challenges in microbiology. Over the past decades several techniques have been developed to study gene expression in complex natural habitats. Most of these methods, however, are laborious, and validation of results under in situ conditions is cumbersome. Here we report the improvement of the recombinase-based in vivo expression technology (R-IVET) by the implementation of two additional reporter genes. The first one is an α-galactosidase gene (melA), which facilitates the rapid identification of in vivo-induced genes. Second, the bacterial luciferase genes (luxAB) are transcriptionally coupled to the resolvase gene, which allows rapid validation and characterization of in vivo-induced genes. The system is implemented and validated in the industrially important lactic acid bacterium Lactococcus lactis. We demonstrate the applicability of the advanced R-IVET system by the identification and validation of lactococcal promoter elements that are induced in minimal medium compared to the commonly used rich laboratory medium M17. R-IVET screening led to the identification of 19 promoters that predominantly control expression of genes involved in amino acid and nucleotide metabolism and in transport functions. Furthermore, the luciferase allows high-resolution transcription analysis and enabled the identification of complex medium constituents and specific molecules involved in promoter control. Rapid target validation exemplifies the high-throughput potential of the extended R-IVET system. The system can be applied to other bacterial species, provided that the reporter genes used are functional in the organism of interest.
Governance and Productivity: Microeconomic Evidence from Ethiopia

We used household survey data from the rural Ethiopia to investigate the importance of governance for agricultural productivity. We argued that the impact of governance is household speci c and identi ed some governance indicators accordingly. Trust in government and government o¢ cials, strength of property rights and personal contact with local authorities are identi ed as governance indicators. A stochastic frontier production function is speci ed and estimated to capture the e¤ects of governance on productivity or technical e¢ ciency of households. Our results show that improvement in governance could reduce technical ine¢ ciencies signi cantly and hence could considerably boost productivity.
Adoptive T-cell therapies for refractory/relapsed leukemia and lymphoma: current strategies and recent advances

Despite significant advancements in the treatment and outcome of hematologic malignancies, prognosis remains poor for patients who have relapsed or refractory disease. Adoptive T-cell immunotherapy offers novel therapeutics that attempt to utilize the noted graft versus leukemia effect. While CD19 chimeric antigen receptor (CAR)-modified T cells have thus far been the most clinically successful application of adoptive T immunotherapy, further work with antigen specific T cells and CARs that recognize other targets have helped diversify the field to treat a broad spectrum of hematologic malignancies. This article will focus primarily on therapies currently in the clinical trial phase as well as current downfalls or limitations.
Dyspepsia in NSAID Users: The Size of the Problem

Gastroduodenal intolerance is one of the major factors limiting the use of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) in patients with rheumatic diseases. We previously demonstrated that dyspepsia was not a marker for ulcer in NSAID users. We have now evaluated dyspeptic symptoms in 245 arthritic patients (receiving 13 different NSAIDs) from the practices of two rheumatologists. Fifty-seven patients (23%) gave a history of previous peptic ulcers. Heartburn, indigestion, or sour stomach at least once within the past year was present in 62.5%; 36.7% had experienced these symptoms within the previous 2 months and 28.6% within the previous week. Only 39 patients (15.9%) had experienced dyspepsia more than once daily within the previous month, and 8 (3.3%) had dyspepsia >5 times/day. Thirtyfour of the 39 patients with daily dyspepsia claimed to obtain relief with cimetidine or antacids (34 patients) or food (2 patients), whereas 3 had not discovered anything that provided relief. Women smokers were more likely than nonsmokers to experience dyspepsia (p < 0.001). Neither men smokers nor those with a history of previous ulcer were more likely to have dyspepsia than nonsmokers or those without a history of ulcer (p > 0.5). We were not able to find a statistical association between any NSAID, or combination of NSAIDs, and the frequency of dyspepsia.
Follicle characteristics, seasonal changes in ®bre cross-sectional area and ellipticity in Australasian specialty carpet wool sheep, Romneys and Merinos

Data was collected on secondary:primary follicle ratio, relative follicle density, and seasonal changes in ®bre cross-sectional area and ®bre ellipticity (ratio of major-to-minor ®bre cross-sectional axis) in the Australasian specialty carpet wool breeds (Carpetmaster, Drysdale, Elliottdale, Tukidale), Romneys and Merinos. Merinos had a higher secondary:primary follicle ratio (p<0.001), relative primary follicle density (p<0.05), relative secondary and relative total follicle density (p<0.01) than the other breeds. Both breed and follicle type (primary or secondary) had a signi®cant effect on ®bre cross-sectional area (p<0.05). While both ®bre types (primary and secondary) showed changes in cross-sectional area during the experiment, a more distinct seasonal pattern was seen in the secondary ®bres with summer maxima and winter minima in all breeds. Relative change in ®bre diameter was higher in secondary ®bres than in primary ®bres. Changes in ®bre ellipticity were also noted throughout the duration of the experiment. It is apparent that there are differences between primary and secondary follicle populations in the way the ®bres produced contribute to seasonal changes in average ®bre diameter of ̄eeces. The changes suggest there are separate control mechanisms for each follicle type and that the number, size and arrangement of the cells in each type of ®bre vary independently of one another throughout the year, bringing about dynamic changes in ®bre growth and form. Further work is required to examine the in ̄uence of feed quality on these factors and to determine the mechanisms through which these changes in ®bre structure are brought about. # 2000 Elsevier Science B.V. All rights reserved.
Lupus nephritis: prognostic factors in children.

As newer treatment modalities become available for patients with severe lupus nephritis, it becomes increasingly important to identify patients at risk for renal failure. In this study, the records of 90 children presenting with systemic lupus erythematosus over a 13-year period were reviewed. Nineteen were lost to follow-up prior to completion of the study. Of the 71 remaining children, 16 (22%) progressed to chronic renal failure. Persistent hypertension lasting greater than 4 months, anemia, abnormalities of the urinalysis, and elevated serum creatinine level were significantly associated with progression to renal failure. Sex, race, age, abnormalities of creatinine clearance, and 24-hour urine protein collection were not associated with progression to renal failure. Renal biopsies were obtained in 45 children. Biopsies were initially classified according to World Health Organization criteria. Diffuse proliferative glomerulonephritis was significantly associated with progression to renal failure. The 45 biopsies available were reviewed by one of the authors and categorized by activity and chronicity indices. Both the active lesions of fibrinoid necrosis, synechiae, tubular casts, and vasculitic lesions and the chronic lesion of glomerular sclerosis correlated with progression to renal failure. Of the 16 children who progressed to renal failure, 2 had cadaver kidney transplants and are well 5 years posttransplant; 4 had fulminant lupus and died within 1 month of commencing dialysis; 10 began chronic dialysis. Five of the 10 children on chronic dialysis died from sepsis. These data suggest that children with systemic lupus erythematosus who undergo dialysis do poorly. (ABSTRACT TRUNCATED AT 250 WORDS)
The Cytoplasmic Tail of Glycoprotein M (gpUL100) Expresses Trafficking Signals Required for Human Cytomegalovirus Assembly and Replication

ABSTRACT The virion envelope of human cytomegalovirus (HCMV) is complex and consists of an incompletely defined number of glycoproteins. The gM/gN protein complex is the most abundant protein component of the envelope. Studies have indicated that deletion of the viral gene encoding either gM or gN is a lethal mutation. Analysis of the amino acid sequence of gM disclosed a C-terminal acidic cluster of amino acids and a tyrosine-containing trafficking motif, both of which are well-described trafficking/sorting signals in the cellular secretory pathway. To investigate the roles of these signals in the trafficking of the gM/gN complex during virus assembly, we made a series of gM (UL100 open reading frame) mutants in the AD169 strain of HCMV. Mutant viruses that lacked the entire C-terminal cytoplasmic tail of gM were not viable, suggesting that the cytoplasmic tail of gM is essential for virus replication. In addition, the gM mutant protein lacking the cytoplasmic domain exhibited decreased protein stability. Mutant viruses with a deletion of the acidic cluster or alanine substitutions in tyrosine-based motifs were viable but exhibited a replication-impaired phenotype suggestive of a defect in virion assembly. Analysis of these mutant gMs using static immunofluorescence and fluorescence recovery after photobleaching demonstrated delayed kinetics of intracellular localization of the gM/gN protein to the virus assembly compartment compared to the wild-type protein. These data suggest an important role of the glycoprotein gM during virus assembly, particularly in the dynamics of gM trafficking during viral-particle assembly.
Emergence and Localized Circulation of a Vaccine-Derived Poliovirus in an Isolated Mountain Community in Guangxi, China

ABSTRACT From March to May 2006, type 1 circulating vaccine-derived poliovirus (cVDPV) was isolated from one case patient with acute flaccid paralysis (AFP) and six unimmunized healthy contacts in isolated mountain villages in Guangxi, China. We conducted epidemiological investigations in the affected communities and nucleotide sequence analyses of the cVDPV isolates. The results of the investigations showed that the AFP patient, an unimmunized 10-year-old boy, and five laboratory-confirmed contacts lived in the same village; one contact lived in a neighboring village. Only ∼27% of children 5 to 10 years of age in the affected villages had received three or more doses of the trivalent oral poliovirus vaccine (OPV). Nucleotide sequence analyses revealed that the cVDPV isolates differed from the Sabin 1 (S1) isolate at 1.4 to 2.2% of VP1 nucleotide positions and shared 12 nucleotide substitutions within VP1. All isolates were S1/S2/S1/S3 recombinants sharing common recombination junctions. Key determinants of attenuation were replaced. Phylogenetic analysis suggested that the cVDPV circulated locally for ∼12 months following the initiating OPV dose. No VDPVs were found after mass OPV immunizations, conducted from May to June 2006, that targeted all children <12 years of age. Our findings reinforce the point that VDPVs can emerge and spread in isolated communities with immunity gaps. Maintenance of sensitive AFP and poliovirus surveillance is essential to permit early detection and a rapid response to VDPV circulation.
Review of mannequin‐based high‐fidelity simulation in emergency medicine

The spectrum of uses of high‐fidelity simulation in emergency medicine has increased in the past 10 years and ranges from teaching isolated skills to improving complex team behaviours in critical situations. This review will describe these published uses and explore the evidence supporting the use of high‐fidelity simulation, as well as the future directions and difficulties of using this technology in our specialty.
Group identity and positive deviance in work groups

ABSTRACT This study examines why and how identity cognitions, including group identification and individual differentiation, influence the positive deviance of employees. We identify the risk-taking intention of employees as a critical psychological mechanism to overcome stigma-induced identity threat of positive deviance. The analysis of data collected from 293 members comprising 66 work teams reveals that the relationship between individual differentiation and positive deviance is partially mediated by risk-taking intention. The indirect effect of group identification on positive deviance through risk-taking intention is also significant and positive in groups with low conformity pressure, whereas the same indirect effect is neutralized in groups with high conformity pressure. The current analysis offers new insights into the way the group context and the identity cognition of members explain the development of positive deviance and workplace creativity.
Nanoparticle Dynamics in Polymer Melts

Adding solid particles to polymeric materials is a common way to reduce the costs and to impart desired mechanical and transport properties. This makes polymers potential substitutes for more expensive non-polymeric materials. The advantages of filled polymers are normally offset by the increased complexity in the rheological behaviour of the resulting composite. Usually, a compromise has to be made between the benefits ensured by the filler, the increased difficulties in melt processing, the problems in achieving a uniform dispersion of the solid particulate, and the economics of the process due to the added step of compounding [Shenoy, 1999]. Filled polymers can be described as a suspension of particles and particle aggregates dispersed in the polymer matrix. Interactions between individual particles or aggregates and the matrix, as well as between particles, hinder the material deformability modifying both the solidand melt-state behaviour of the host polymer. In polymer-based microcomposites, these effects only become significant at relatively high filler contents, i.e. when the filler particles are sufficiently close to each other to form a network that spans large sections of the polymer matrix. Over the last fifteen years, the same reinforcing and thixotropic effects have been observed with the use of very small amounts of inorganic nanoparticles, which has resulted in extensive research in the field of polymer-based nanocomposites (PNCs) [Usuki et al., 1993; Kojima et al., 1993]. In order to fully understand the exceptional properties of PNCs, the morphological and structural implications stemming from the nanometric sizes of the filler have to be taken into account. With respect to traditional microcomposites, nanocomposites show very high specific interface area, typically of order of ~102 m2 g-1. The matrix properties are significantly affected in the vicinity of the reinforcement, varying continuously from the interface towards the bulk polymer. As a consequence, the large amount of reinforcement surface area means that a relatively small amount of nanoscale reinforcement can have remarkable effects on the macroscale properties of the composite material.
What have positron emission tomography and ‘Zippy’ told us about the neuropharmacology of drug addiction?

Translational molecular imaging with positron emission tomography (PET) and allied technologies offer unrivalled applications in the discovery of biomarkers and aetiological mechanisms relevant to human disease. Foremost among clinical PET findings during the past two decades of addiction research is the seminal discovery of reduced dopamine D2/3 receptor expression in the striatum of drug addicts, which could indicate a predisposing factor and/or compensatory reaction to the chronic abuse of stimulant drugs. In parallel, recent years have witnessed significant improvements in the performance of small animal tomographs (microPET) and a refinement of animal models of addiction based on clinically relevant diagnostic criteria. This review surveys the utility of PET in the elucidation of neuropharmacological mechanisms underlying drug addiction. It considers the consequences of chronic drug exposure on regional brain metabolism and neurotransmitter function and identifies those areas where further research is needed, especially concerning the implementation of PET tracers targeting neurotransmitter systems other than dopamine, which increasingly have been implicated in the pathophysiology of drug addiction. In addition, this review considers the causal effects of behavioural traits such as impulsivity and novelty/sensation‐seeking on the emergence of compulsive drug‐taking. Previous research indicates that spontaneously high‐impulsive rats – as exemplified by ‘Zippy’– are pre‐disposed to escalate intravenous cocaine self‐administration, and subsequently to develop compulsive drug taking tendencies that endure despite concurrent adverse consequences of such behaviour, just as in human addiction. The discovery using microPET of pre‐existing differences in dopamine D2/3 receptor expression in the striatum of high‐impulsive rats suggests a neural endophenotype that may likewise pre‐dispose to stimulant addiction in humans.
Development of a secure system for distributed data storage and processing in the clouds based on the concept of active security in RNS

Addresses the question of application of the concept of active security to a distributed system of data storage in multicloud environment. We show that secret sharing schemes, methods of periodical update of keys and authentication methods allow to minimize the risks of cloud conspiracy and provide secure and reliable data storage for a long time. We research the question of control of results of computations in multicloud environment with the use of arithmetic properties of RNS. It is shown in the paper that RNS allows to provide the authenticity of results of computations with a given proba-bility
Contraintes sur la fonctionnelle de la densite d'energie nucleaire et nouvelles formes analytiques possibles

La methode dite de la fonctionnelle de la densite d'energie (EDF) est l'outil theorique de reference pour l'etude systematique de la structure des noyaux atomiques de masse A>20. La methode EDF est formulee en deux etapes successives consistant a briser puis a restaurer les symetries du Hamiltonien nucleaire sous-jacent. La technique de restauration des symetries n'est cependant rigoureusement formulee que si la fonctionnelle d'energie derive explicitement d'une interaction effective, i.e. d'un pseudo-potentiel, ce qui constitue un cas particulier de la methode EDF plus generale. Ainsi, et comme cela a ete demontre recemment, l'utilisation des parametrisations existantes des fonctionnelles d'energie conduit a l'obtention de resultats non physiques. Le pouvoir predictif limite des fonctionnelles d'energie existantes et leur inocuite relative a la restauration des symetries, necessitent aujourd'hui de repenser leur methode de construction. La premiere partie de ce travail a ete dedie a l'analyse approfondie du probleme associe a la restauration de symetrie et a l'identification de pistes permettant de contraindre la forme analytique des fonctionnelles d'energie ne derivant pas d'un pseudo-potentiel independant du systeme. La seconde partie a consiste a developper un pseudo-potentiel rendant la restauration des symetries automatiquement bien definie. Les difficultes de ce travail ont reside dans (i) l'identification de la complexite minimale du pseudo-potentiel necessaire a l'obtention d'une fonctionnelle d'energie assez flexible pour egaler, et si possible ameliorer, les performances des parametrisations existantes, (ii) la derivation analytique de la fonctionnelle et des champs a un corps decoulant de celle ci, (iii) l'implementation de ces derniers dans les codes de calculs, et dans (iv) le developpement d'un protocole d'ajustement des parametres adapte a la nouvelle fonctionnelle d'energie ainsi developpee. Les premiers resultats obtenus ont permis de valider l'approche en demontrant la flexibilite suffisante du pseudo-potentiel au niveau des calculs realises sans restauration des symetries.
A Longitudinal Investigation of Egoistic and Moralistic Self-Enhancement

This study used a 3-wave longitudinal design to investigate stability and change of egoistic and moralistic self-enhancement. Participants (n = 195) were followed for 6 years, from late adolescence (age 15) to emerging adulthood (age 21). A significant degree of rank-order stability was found that reveals a reasonable continuity in the individuals’ relative standing on measures of egoistic and moralistic self-enhancement. Latent growth curve analysis was used to track the developmental trajectories of the examined constructs. Findings revealed that egoistic self-enhancement is stable from 15 to 21 years, whereas moralistic self-enhancement slightly decreases during the same developmental period. Cross-lagged models were used to examine the reciprocal relations between self-enhancement and the Big Five personality traits. No prospective effects were found between the constructs, which develop independently from late adolescence to young adulthood, showing only synchronous associations. Implications for personality research and assessment are discussed.