Miracle-dz/UniFAR-FTUs huggingface dataset:
Discontinuation of secondary prophylaxis against Pneumocystis carinii pneumonia in patients with HIV infection who have a response to antiretroviral therapy. Eight European Study Groups.

BACKGROUND Patients with human immunodeficiency virus (HIV) infection and a history of Pneumocystis carinii pneumonia are at high risk for relapse if they are not given secondary prophylaxis. Whether secondary prophylaxis against P. carinii pneumonia can be safely discontinued in patients who have a response to highly active antiretroviral therapy is not known. METHODS We analyzed episodes of recurrent P. carinii pneumonia in 325 HIV-infected patients (275 men and 50 women) in eight prospective European cohorts. Between October 1996 and January 2000, these patients discontinued secondary prophylaxis during treatment with at least three anti-HIV drugs after they had at least one peripheral-blood CD4 cell count of more than 200 cells per cubic millimeter. RESULTS Secondary prophylaxis was discontinued at a median CD4 cell count of 350 per cubic millimeter; the median nadir CD4 cell count had been 50 per cubic millimeter. The median duration of the increase in the CD4 cell count to more than 200 per cubic millimeter after discontinuation of secondary prophylaxis was 11 months. The median follow-up period after discontinuation of secondary prophylaxis was 13 months, yielding a total of 374 person-years of follow-up; for 355 of these person-years, CD4 cell counts remained at or above 200 per cubic millimeter. No cases of recurrent P. carinii pneumonia were diagnosed during this period; the incidence was thus 0 per 100 patient-years (99 percent confidence interval, 0 to 1.2 per 100 patient-years, on the basis of the entire follow-up period, and 0 to 1.3 per 100 patient-years, on the basis of the follow-up period during which CD4 cell counts remained at or above 200 per cubic millimeter). CONCLUSIONS It is safe to discontinue secondary prophylaxis against P. carinii pneumonia in patients with HIV infection who have an immunologic response to highly active antiretroviral therapy.
Testosterone Pathway Genetic Polymorphisms in Relation to Primary Open-Angle Glaucoma: An Analysis in Two Large Datasets

Purpose Sex hormones may be associated with primary open-angle glaucoma (POAG), although the mechanisms are unclear. We previously observed that gene variants involved with estrogen metabolism were collectively associated with POAG in women but not men; here we assessed gene variants related to testosterone metabolism collectively and POAG risk. Methods We used two datasets: one from the United States (3853 cases and 33,480 controls) and another from Australia (1155 cases and 1992 controls). Both datasets contained densely called genotypes imputed to the 1000 Genomes reference panel. We used pathway- and gene-based approaches with Pathway Analysis by Randomization Incorporating Structure (PARIS) software to assess the overall association between a panel of single nucleotide polymorphisms (SNPs) in testosterone metabolism genes and POAG. In sex-stratified analyses, we evaluated POAG overall and POAG subtypes defined by maximum IOP (high-tension [HTG] or normal tension glaucoma [NTG]). Results In the US dataset, the SNP panel was not associated with POAG (permuted P = 0.77), although there was an association in the Australian sample (permuted P = 0.018). In both datasets, the SNP panel was associated with POAG in men (permuted P ≤ 0.033) and not women (permuted P ≥ 0.42), but in gene-based analyses, there was no consistency on the main genes responsible for these findings. In both datasets, the testosterone pathway association with HTG was significant (permuted P ≤ 0.011), but again, gene-based analyses showed no consistent driver gene associations. Conclusions Collectively, testosterone metabolism pathway SNPs were consistently associated with the high-tension subtype of POAG in two datasets.
Shape optimized struts made of ultra-high performance concrete

Motivation Particularly due to high formwork and scaffolding costs in comparison to the material costs, mainly massive concrete structures with plane surfaces and rectangular geometries have been built in the last few decades. In most cases a low material consumption only played a minor role. However, in the meantime by further development and research on the building material concrete, e.g. ultra-high performance concrete (UHPC), combined with the almost unlimited shaping possibilities, the basis for the realization of more elegant and “lighter” concrete construction methods also for a wide range of applications has been created. So, under Priority Program 1542 “Concrete light. Future concrete structures using bionic, mathematical and engineering formfinding principles”, funded by the German Research Foundation (DFG), a subproject has been carried out at the Chair of Concrete and Masonry Structures of TUM, which focused on the development of shape optimized struts made of UHPC in accordance with the principle “form follows force”. In comparison to “usual” compression members the optimized struts are characterized by weight reduction at equal load capacity, a more slender and aesthetical shape and an optimized material distribution, which results in a higher resource efficiency.
Matching Watershed and Otolith Chemistry to Establish Natal Origin of an Endangered Desert Lake Sucker

AbstractStream habitat restoration and supplemental stocking of hatchery-reared fish have increasingly become key components of recovery plans for imperiled freshwater fish; however, determining when to discontinue stocking efforts, prioritizing restoration areas, and evaluating restoration success present a conservation challenge. In this study, we demonstrate that otolith microchemistry is an effective tool for establishing natal origin of the June Sucker Chasmistes liorus, an imperiled potamodromous fish. This approach allows us to determine whether a fish is of wild or hatchery origin in order to assess whether habitat restoration enhances recruitment and to further identify areas of critical habitat. Our specific objectives were to (1) quantify and characterize chemical variation among three main spawning tributaries; (2) understand the relationship between otolith microchemistry and tributary chemistry; and (3) develop and validate a classification model to identify stream origin using otolith micro.
Association of Polyaminergic Loci With Anxiety, Mood Disorders, and Attempted Suicide

Background The polyamine system has been implicated in a number of psychiatric conditions, which display both alterations in polyamine levels and altered expression of genes related to polyamine metabolism. Studies have identified associations between genetic variants in spermidine/spermine N1-acetyltransferase (SAT1) and both anxiety and suicide, and several polymorphisms appear to play important roles in determining gene expression. Methodology/Principal Findings We genotyped 63 polymorphisms, spread across four polyaminergic genes (SAT1, spermine synthase (SMS), spermine oxidase (SMOX), and ornithine aminotransferase like-1 (OATL1)), in 1255 French-Canadian individuals who have been followed longitudinally for 22 years. We assessed univariate associations with anxiety, mood disorders, and attempted suicide, as assessed during early adulthood. We also investigated the involvement of gene-environment interactions in terms of childhood abuse, and assessed internalizing and externalizing symptoms as endophenotypes mediating these interactions. Overall, each gene was associated with at least one main outcome: anxiety (SAT1, SMS), mood disorders (SAT1, SMOX), and suicide attempts (SAT1, OATL1). Several SAT1 polymorphisms displayed disease-specific risk alleles, and polymorphisms in this gene were involved in gene-gene interactions with SMS to confer risk for anxiety disorders, as well as gene-environment interactions between childhood physical abuse and mood disorders. Externalizing behaviors demonstrated significant mediation with regards to the association between OATL1 and attempted suicide, however there was no evidence that externalizing or internalizing behaviors were appropriate endophenotypes to explain the associations with mood or anxiety disorders. Finally, childhood sexual abuse did not demonstrate mediating influences on any of our outcomes. Conclusions/Significance These results demonstrate that genetic variants in polyaminergic genes are associated with psychiatric conditions, each of which involves a set of separate and distinct risk alleles. As several of these polymorphisms are associated with gene expression, these findings may provide mechanisms to explain the alterations in polyamine metabolism which have been observed in psychiatric disorders.
Revised Rates of Stellar Disruption in Galactic Nuclei

We compute rates of tidal disruption of stars by supermassive black holes in galactic nuclei, using downwardly revised black hole masses from the MBH-σ relation. In galaxies with steep nuclear density profiles, which dominate the overall event rate, the disruption frequency varies inversely with assumed black hole mass. We compute a total rate for nondwarf galaxies of ~10-5 yr-1 Mpc-3, about a factor of 10 higher than in earlier studies. Disruption rates are predicted to be highest in nucleated dwarf galaxies, assuming that such galaxies contain black holes. Monitoring of a rich galaxy cluster for a few years could rule out the existence of intermediate-mass black holes in dwarf galaxies.
The Effects Of Controlling Parameters On Polymer Enhanced Foam (PEF) Stability

In the present study, four surfactants including AOS, SDS, SDBS, and TX100 were used as the foaming agent and a PHPA polymer with relatively low to high concentrations was added to the solutions prepared in both fresh water and 8 wt. % NaCl. Also, paraffin and vaseline oils with different viscosities were used to investigate the effect of oil on PEF stability. Polymer addition to foam can effectively improve foam stability compared with conventional foam stability. In addition, the polymer concentration increase could lead to foam stability increase; thus, the maximum polymer concentration in solutions could produce the most stable foam. Solutions with 8 wt. % NaCl had destabilizing effect, that is, unlike solutions with fresh water, it slightly reduced foam stability. Contacted oil in the solutions could substantially reduce foam stability. Also, the destabilizing effect was more severe with paraffin oil rather than vaseline oil. Of all the four surfactants used in this research, SDS had the highest compatibility with PHPA and produced the most stable foam, while AOS, SDBS, and finally TX100 surfactants were in next orders. In addition, microscopic photos showed that the type of solution has a significant effect on bubble size and foam stability.
DNA topoisomerase VIII: a novel subfamily of type IIB topoisomerases encoded by free or integrated plasmids in Archaea and Bacteria

Type II DNA topoisomerases are divided into two families, IIA and IIB. Types IIA and IIB enzymes share homologous B subunits encompassing the ATP-binding site, but have non-homologous A subunits catalyzing DNA cleavage. Type IIA topoisomerases are ubiquitous in Bacteria and Eukarya, whereas members of the IIB family are mostly present in Archaea and plants. Here, we report the detection of genes encoding type IIB enzymes in which the A and B subunits are fused into a single polypeptide. These proteins are encoded in several bacterial genomes, two bacterial plasmids and one archaeal plasmid. They form a monophyletic group that is very divergent from archaeal and eukaryotic type IIB enzymes (DNA topoisomerase VI). We propose to classify them into a new subfamily, denoted DNA topoisomerase VIII. Bacterial genes encoding a topoisomerase VIII are present within integrated mobile elements, most likely derived from conjugative plasmids. Purified topoisomerase VIII encoded by the plasmid pPPM1a from Paenibacillus polymyxa M1 had ATP-dependent relaxation and decatenation activities. In contrast, the enzyme encoded by mobile elements integrated into the genome of Ammonifex degensii exhibited DNA cleavage activity producing a full-length linear plasmid and that from Microscilla marina exhibited ATP-independent relaxation activity. Topoisomerases VIII, the smallest known type IIB enzymes, could be new promising models for structural and mechanistic studies.
Differential susceptibility to rearing environment depending on dopamine-related genes: New evidence and a meta-analysis

Abstract In the current paper we present new empirical data and meta-analytic evidence for the role of dopamine-related genes as a susceptibility factor interacting with the rearing environment for better and for worse, that is, increasing children's susceptibility to both the adverse effects of unsupportive environments and the beneficial effects of supportive rearing. In Study 1 we examined the readiness of 91 7-year-old children to donate their money to a charity (UNICEF). We tested whether the association between attachment and donating behavior was moderated by the presence of the dopamine receptor D4 (DRD4) 7-repeat allele. The attachment story completion task was used to assess attachment as an index of the quality of the rearing environment. Children with secure attachment representations donated more but only if they had the DRD4 7-repeat allele. In Study 2 we present the results of a meta-analysis of gene–environment studies on children up to 10 years of age involving dopamine-related genes (dopamine receptor D2, DRD4, dopamine transporter). The cumulative negative effects of these “risk genes” and adverse rearing environments have been stressed, but potentially cumulative positive effects of these same genes interacting with positive rearing environments remained largely unnoticed. We examined the associations between negative and positive rearing environments and developmental outcomes as moderated by dopamine-related gene polymorphisms. Children with the less efficient dopamine-related genes did worse in negative environments than the comparisons without the “genetic risk,” but they also profited most from positive environments. Findings are discussed in light of evolutionary theory, and illustrated with some practical implications of differential susceptibility.
Evaluation of membrane physiology following fluorescence activated or magnetic cell separation.

BACKGROUND Over the past decade, cell separation technology has become an important tool in various fields of cell biology allowing for the analysis or subsequent cultivation of specific cell subsets. The objective of the present study was to evaluate if the established sorting techniques fluorescence-activated (FACS) and magnetic cell separation (MACS) affect cell membrane physiology in order to define the most non-perturbing application for the separation of tumor and stromal cells. MATERIALS AND METHODS Membrane physiology was monitored in single cell suspensions of adherently grown BT474 breast tumor cells and N1 normal skin fibroblasts using flow cytometry. Cell membrane integrity was evaluated by propidium iodide (PI) staining. Microviscosity within the lipophilic membrane layer was determined by a monomer/excimer method utilizing pyrene decanoic acid, membrane potential measurements were carried out using the fluorescence indicator DiBAC4(3), and Annexin-V-staining reflected transversal membrane asymmetry, and an altered phospholipid distribution. RESULTS Not only the number of preparative cycles prior to cell separation but also the sort conditions during FACS resulted in loss of membrane integrity of a certain cell fraction. If these PI-positive cells were excluded from further analysis, neither MACS nor FACS affected membrane microviscosity while a clear hyperpolarization in both cell types after MACS resulting from exposure to the ferromagnetic matrix of the depletion column and the inhomogeneous magnetic field was shown. In addition, cell sorting of BT474 tumor cells by MACS and FACS was accompanied by the generation of an Annexin-V-positive/PI-negative cell fraction with altered phospholipid distribution. Data were discussed with regard to the sort-induced "stress" conditions such as exposure to hydrodynamic forces or magnetic fields. CONCLUSIONS Both separation procedures modify cell membrane with neither technique being physiologically preferable for subsequent analysis or recultivation of the sorted cells.
Impact of Orphanhood on Underweight Prevalence in Sub-Saharan Africa

Background In Africa, approximately 25 million people live with HIV/AIDS and 12 million children are orphaned. Although evidence indicates that orphans risk losing opportunities for adequate education, health care, and future employment, the immediate effects of orphanhood on child nutritional status remain poorly understood. Objective This paper assesses the nutritional impact of orphanhood, with particular emphasis on taking account of various factors potentially confounding or masking these impacts. Methods Child anthropometry and orphan status were examined in 23 Multiple Indicator Cluster Surveys and Demographic and Health Surveys throughout sub-Saharan Africa, which were subsequently merged into larger, region-specific datasets (East, West, and Southern Africa). To compare orphans and nonorphans, linear regression and probit models were developed, taking account of orphan status and type, presence of a surviving parent in the household, household structure, child age and sex, urban versus rural residence, and current wealth status. Results Few differences emerged between orphans and nonorphans in controlled and uncontrolled comparisons, regardless of orphan type, presence of surviving parent, or household structure. Age differentials did confound nutritional comparisons, although in the counterintuitive direction, with orphans (who were 8 months older on average) becoming less malnourished when age differences were taken into account. Wealth did appear to be associated with orphanhood status, although it did not significantly confound nutritional comparisons. Conclusions Orphans were not consistently more malnourished than nonorphans, even when potential confounding variables were examined. Since household wealth status is likely to change after becoming affected by HIV, ruling out wealth as a potential confounder would require more detailed, prospective studies.
Modeling Bursty Temporal Pattern of Rumors

Online social networks enable fast and wide diffusion of rumors, which could be potential threats to the society. Understanding the rumor spreading mechanism is therefore essential. This demo presents an agent-pattern based model that can explain the spiky temporal diffusion pattern of rumors. The demo platform provides an interface allowing users to check a wide set of parameters contribute to the characteristic temporal pattern of rumors.
Author ' s personal copy PARADOXICAL FACILITATION OF PENTYLENETETRAZOLE-INDUCED CONVULSION SUSCEPTIBILITY IN MICE LACKING NEURONAL NITRIC OXIDE SYNTHASE

The major aim of this study was to elucidate the relationship between nitric oxide (NO) and generalized epilepsy. Mice lacking the neuronal nitric oxide synthase (nNOS) gene (nNOS / ) were used in this study to determine the relationship between nNOS and NO in pentylentetrazole (PTZ)-induced convulsions. nNOS / mice exhibited severe convulsions following injection with a subconvulsive dose of PTZ (40 mg/kg i.p.) and convulsive doses were lethal in all of the mice (60 mg/kg i.p.) following tonic convulsions. The results were confirmed by using selective nNOS inhibitors in wild-type (nNOS / ) mice. The higher doses of the nNOS inhibitors 1-[2-(trifluoromethyl)phenyl] imidazole (TRIM) and 3-bromo-7-nitroindazole (3Br7NI) inhibited clonic–tonic convulsions induced by a convulsive dose of PTZ (60 mg/kg) in nNOS / mice. In contrast, either TRIM or 3Br7NI at lower doses enhanced convulsions following injection with a subconvulsive dose of PTZ (40 mg/kg) in nNOS / mice similar to nNOS / mice treated with PTZ. Such a proconvulsant effect was observed in nNOS / mice pretreated with nNOS inhibitors but not other NOS inhibitors. These results indicate that NO may be regarded as an anticonvulsant or a proconvulsant substance in relation to convulsions induced by PTZ in mice. Pretreatment with N-methylD-aspartate (NMDA) receptor antagonists (5S,10R)-( )-5methyl-10,11-dihydro-5H-dibenzo[a,d]-cyclohepten-5,10-imine maleate (MK-801), (E)-( )-2-amino-4-methyl-5-phospho no-3pentenoic acid ethyl ester, CGP39551) and DL-alpha-amino3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist (2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide, NBQX) inhibited a subconvulsive dose of PTZ-induced convulsions in nNOS / mice, demonstrating that convulsions induced by PTZ are modulated by endogenous NO production and ionotropic glutamate receptor–mediated stimulation. These results suggest a negative or positive modulation of neuronal interactions by basal or enhanced NO production, respectively. © 2009 IBRO. Published by Elsevier Ltd. All rights reserved.
Association of aortic-valve sclerosis with cardiovascular mortality and morbidity in the elderly.

BACKGROUND Although aortic-valve stenosis is clearly associated with adverse cardiovascular outcomes, it is unclear whether valve sclerosis increases the risk of cardiovascular events. METHODS We assessed echocardiograms obtained at base line from 5621 men and women 65 years of age or older who were enrolled in a population-based prospective study. On echocardiography, the aortic valve was normal in 70 percent (3919 subjects), sclerotic without outflow obstruction in 29 percent (1610), and stenotic in 2 percent (92). The subjects were followed for a mean of 5.0 years to assess the risk of death from any cause and of death from cardiovascular causes. Cardiovascular morbidity was defined as new episodes of myocardial infarction, angina pectoris, congestive heart failure, or stroke. RESULTS There was a stepwise increase in deaths from any cause (P for trend, <0.001) and deaths from cardiovascular causes (P for trend, <0.001) with increasing aortic-valve abnormality; the respective rates were 14.9 and 6.1 percent in the group with normal aortic valves, 21.9 and 10.1 percent in the group with aortic sclerosis, and 41.3 and 19.6 percent in the group with aortic stenosis. The relative risk of death from cardiovascular causes among subjects without coronary heart disease at base line was 1.66 (95 percent confidence interval, 1.23 to 2.23) for those with sclerotic valves as compared with those with normal valves, after adjustment for age and sex. The relative risk remained elevated after further adjustment for clinical factors associated with sclerosis (relative risk, 1.52; 95 percent confidence interval, 1.12 to 2.05). The relative risk of myocardial infarction was 1.40 (95 percent confidence interval, 1.07 to 1.83) among subjects with aortic sclerosis, as compared with those with normal aortic valves. CONCLUSIONS Aortic sclerosis is common in the elderly and is associated with an increase of approximately 50 percent in the risk of death from cardiovascular causes and the risk of myocardial infarction, even in the absence of hemodynamically significant obstruction of left ventricular outflow.