Classifying the embedded young stellar population in Perseus and Taurus & the LOMASS database

Context. The classification of young stellar objects (YSOs) is typically done using the infrared spectral slope or bolometric temperature, but either can result in contamination of samples. More accurate methods to determine the evolutionary stage of YSOs will improve the reliability of statistics for the embedded YSO population and provide more robust stage lifetimes. Aims. We aim to separate the truly embedded YSOs from more evolved sources. Methods. Maps of HCO+ J=4-3 and C18O J=3-2 were observed with HARP on the James Clerk Maxwell Telescope (JCMT) for a sample of 56 candidate YSOs in Perseus and Taurus in order to characterize emission from high (column) density gas. These are supplemented with archival dust continuum maps observed with SCUBA on the JCMT and Herschel PACS to compare the morphology of the gas and dust in the protostellar envelopes. The spatial concentration of HCO+ J=4-3 and 850 micron dust emission are used to classify the embedded nature of YSOs. Results. Approximately 30% of Class 0+I sources in Perseus and Taurus are not Stage I, but are likely to be more evolved Stage II pre-main sequence (PMS) stars with disks. An additional 16% are confused sources with an uncertain evolutionary stage. Conclusions. Separating classifications by cloud reveals that a high percentage of the Class 0+I sources in the Perseus star forming region are truly embedded Stage I sources (71%), while the Taurus cloud hosts a majority of evolved PMS stars with disks (68%). The concentration factor method is useful to correct misidentified embedded YSOs, yielding higher accuracy for YSO population statistics and Stage timescales. Current estimates (0.54 Myr) may overpredict the Stage I lifetime on the order of 30%, resulting in timescales of 0.38 Myr for the embedded phase.Comment: 33 pages, 21 figures, 6 tables, Accepted to be published in A&

Reliability of Quality Assessments in Research Synthesis: Securing the Highest Quality Bioinformation for HIT.

Current trends in bio-medicine include research synthesis and dissemination of bioinformation by means of health (bio) information technology (H[b] IT). Research must secure the validity and reliability of assessment tools to quantify research quality in the pursuit of the best available evidence. Our concerted work in this domain led to the revision of three instruments for that purpose, including the stringent characterization of inter-rater reliability and coefficient of agreement. It is timely and critical to advance the methodological development of the science of research synthesis by strengthening the reliability of existing measure of research quality in order to ensure H[b] IT efficacy and effectiveness

Towards a Notion of Distributed Time for Petri Nets

We set the ground for research on a timed extension of Petri nets where time parameters are associated with tokens and arcs carry constraints that qualify the age of tokens required for enabling. The novelty is that, rather than a single global clock, we use a set of unrelated clocks --- possibly one per place --- allowing a local timing as well as distributed time synchronisation. We give a formal definition of the model and investigate properties of local versus global timing, including decidability issues and notions of processes of the respective models

Genome-wide association studies of the self-rating of effects of ethanol (SRE).

The level of response (LR) to alcohol as measured with the Self-Report of the Effects of Alcohol Retrospective Questionnaire (SRE) evaluates the number of standard drinks usually required for up to four effects. The need for a higher number of drinks for effects is genetically influenced and predicts higher risks for heavy drinking and alcohol problems. We conducted genome-wide association study (GWAS) in the African-American (COGA-AA, N = 1527 from 309 families) and European-American (COGA-EA, N = 4723 from 956 families) subsamples of the Collaborative Studies on the Genetics of Alcoholism (COGA) for two SRE scores: SRE-T (average of first five times of drinking, the period of heaviest drinking, and the most recent 3 months of consumption) and SRE-5 (the first five times of drinking). We then meta-analyzed the two COGA subsamples (COGA-AA + EA). Both SRE-T and SRE-5 were modestly heritable (h2 : 21%-31%) and genetically correlated with alcohol dependence (AD) and DSM-IV AD criterion count (rg : 0.35-0.76). Genome-wide significant associations were observed (SRE-T: chromosomes 6, rs140154945, COGA-EA P = 3.30E-08 and 11, rs10647170, COGA-AA+EA P = 3.53E-09; SRE-5: chromosome13, rs4770359, COGA-AA P = 2.92E-08). Chromosome 11 was replicated in an EA dataset from the National Institute on Alcohol Abuse and Alcoholism intramural program. In silico functional analyses and RNA expression analyses suggest that the chromosome 6 locus is an eQTL for KIF25. Polygenic risk scores derived using the COGA SRE-T and SRE-5 GWAS predicted 0.47% to 2.48% of variances in AD and DSM-IV AD criterion count in independent datasets. This study highlights the genetic contribution of alcohol response phenotypes to the etiology of alcohol use disorders

Priprava i vrednovanje biorazgradljivih implantata s kontroliranim oslobađanjem za postoperativnu primjenu

Biodegradable implants of ciprofloxacin hydrochloride for post operative site delivery were prepared using glyceryl monostearate and different concentrations of polyethylene glycol (PEG 6000) glycerol and Tween 80 as erosion enhancers by compression and molding technique. Formulations were subjected to in vitro drug release by the USP dissolution method, while promising formulations were subjected to in vitro drug release by the agar gel method and also to stability studies. It was observed that glyceryl monostearate formed hydrophobic matrix and delayed the drug delivery. Antibiotic release profile was controlled by using different combinations of erosion enhancers. The formulation prepared by compression method showed more delayed release as compared to formulations prepared by molding method.Biorazgradljivi implantati ciprofloksacin hidroklorida za postoperativnu primjenu pripravljeni su pomoću gliceril monostearata (GMS) i različitih koncentracija polietilen glikola (PEG 6000), glicerola i Tween 80 kao promotora erozije metodom kompresije i lijevanja. Oslobađanje ljekovite tvari iz pripravaka praćeno je in vitro prema USP metodi. Pripravci koji su dali dobre rezultate ispitani su i in vitro metodom s agarom te su podvrgnuti testovima stabilnosti. Primijećeno je da gliceril monostearat tvori hidrofobni matriks i usporava oslobađanje lijeka. Koristeći različite kombinacije promotora erozije postignuto je kontrolirano oslobađanje antibiotika. Oslobađanje iz implantata dobivenih metodom kompresije sporije je od implantata dobivenih metodom lijevanja

The derivation of performance expressions for communication protocols from timed Petri net models

Petri Net models have been extended in a variety of ways and have been used to prove the correctness and evaluate the performance of communication protocols. Several extensions have been proposed to model time. This work uses a form of Timed Petri Nets and presents a technique for symbolically deriving expressions which describe system performance. Unlike past work on performance evaluation of Petri Nets which assumes a priori knowledge of specific time delays, the technique presented here applies to a wide range of time delays so long as the delays satisfy a set of timing constraints. The technique is demonstrated using a simple communication protocol

The glucagon-like peptide-1 receptor as a potential treatment target in alcohol use disorder: evidence from human genetic association studies and a mouse model of alcohol dependence

The hormone glucagon-like peptide-1 (GLP-1) regulates appetite and food intake. GLP-1 receptor (GLP-1R) activation also attenuates the reinforcing properties of alcohol in rodents. The present translational study is based on four human genetic association studies and one preclinical study providing data that support the hypothesis that GLP-1R may have a role in the pathophysiology of alcohol use disorder (AUD). Case–control analysis (N=908) was performed on a sample of individuals enrolled in the National Institute on Alcohol Abuse and Alcoholism (NIAAA) intramural research program. The Study of Addiction: Genetics and Environment (SAGE) sample (N=3803) was used for confirmation purposes. Post hoc analyses were carried out on data from a human laboratory study of intravenous alcohol self-administration (IV-ASA;N=81) in social drinkers and from a functional magnetic resonance imaging study in alcohol-dependent individuals (N=22) subjected to a Monetary Incentive Delay task. In the preclinical study, a GLP-1R agonist was evaluated in a mouse model of alcohol dependence to demonstrate the role of GLP-1R for alcohol consumption. The previously reported functional allele 168Ser (rs6923761) was nominally associated with AUD (P=0.004) in the NIAAA sample, which was partially replicated in males of the SAGE sample (P=0.033). The 168Ser/Ser genotype was further associated with increased alcohol administration and breath alcohol measures in the IV-ASA experiment and with higher BOLD response in the right globus pallidus when receiving notification of outcome for high monetary reward. Finally, GLP-1R agonism significantly reduced alcohol consumption in a mouse model of alcohol dependence. These convergent findings suggest that the GLP-1R may be an attractive target for personalized pharmacotherapy treatment of AUD

Maternal corticotropin-releasing hormone is associated with LEP DNA methylation at birth and in childhood: an epigenome-wide study in Project Viva

BackgroundCorticotropin-releasing hormone (CRH) plays a central role in regulating the secretion of cortisol which controls a wide range of biological processes. Fetuses overexposed to cortisol have increased risks of disease in later life. DNA methylation may be the underlying association between prenatal cortisol exposure and health effects. We investigated associations between maternal CRH levels and epigenome-wide DNA methylation of cord blood in offsprings and evaluated whether these associations persisted into mid-childhood.MethodsWe investigated mother-child pairs enrolled in the prospective Project Viva pre-birth cohort. We measured DNA methylation in 257 umbilical cord blood samples using the HumanMethylation450 Bead Chip. We tested associations of maternal CRH concentration with cord blood cells DNA methylation, adjusting the model for maternal age at enrollment, education, maternal race/ethnicity, maternal smoking status, pre-pregnancy body mass index, parity, gestational age at delivery, child sex, and cell-type composition in cord blood. We further examined the persistence of associations between maternal CRH levels and DNA methylation in children's blood cells collected at mid-childhood (n = 239, age: 6.7-10.3 years) additionally adjusting for the children's age at blood drawn.ResultsMaternal CRH levels are associated with DNA methylation variability in cord blood cells at 96 individual CpG sites (False Discovery Rate <0.05). Among the 96 CpG sites, we identified 3 CpGs located near the LEP gene. Regional analyses confirmed the association between maternal CRH and DNA methylation near LEP. Moreover, higher maternal CRH levels were associated with higher blood-cell DNA methylation of the promoter region of LEP in mid-childhood (P < 0.05, β = 0.64, SE = 0.30).ConclusionIn our cohort, maternal CRH was associated with DNA methylation levels in newborns at multiple loci, notably in the LEP gene promoter. The association between maternal CRH and LEP DNA methylation levels persisted into mid-childhood

Trimethoprim resistance in <em>Escherichia coli</em> exhibits an allele-specific growth advantage

\ua9 2025 The Authors.Introduction. The antibiotic trimethoprim has been used to treat urinary tract infection (UTI) since ~1962. Alongside the nitrofurantoin, there are still justified reasons for trimethoprim use, especially in non-pregnant women. Trimethoprim resistance is commonly the result of acquiring the trimethoprim-insensitive dihydrofolate reductase gene: dfrA. Assessment of clinical Escherichia coli isolates from two clinical trials, AnTIC and ALTAR, identified carriage of two copies of dfrA. Hypothesis. The hypothesis tested here was that dual dfrA carriage provided E. coli with a growth advantage. Methodology. Two hundred and seventy-eight clinical isolates from AnTIC/ALTAR were assessed for dfrA carriage. Microplate-based growth assays assessed growth behaviour with and without 64 mg l−1 trimethoprim. Allelic replacement of dfrA5 with five other alleles was also performed. Results. One hundred and four isolates (37%) were identified to carry a total of 112 dfrA genes. Eight isolates (2.9%) carried two copies of dfrA. Comparison of dfrA+ to dual dfrA carriage could be differentiated by their growth behaviour when exposed to trimethoprim but had comparable MIC (&gt;512 mg l−1). Analysis of all dfrA+ isolates determined that the growth behaviour exhibited an allelic bias. Allelic replacement of dfrA5 with dfrA1, dfrA7, dfrA8, dfrA14 and dfrA17 demonstrated that the growth behaviour was dfrA specific. Conclusion. This analysis determined that the dual carriage of two dfrA alleles generated a growth advantage to E. coli. However, the growth behaviour was dictated by allele carriage and not specifically dual carriage, as single carriage isolates also possessed the identified phenotype. This data suggests that there is a potential clinical impact dictated by dfrA allele carriage that could improve clinical decisions on management strategies of UTI