Miracle-dz/UniFAR-FTUs huggingface dataset:
Asymptotic behaviour of the posterior distribution in overfitted mixture models

Summary. We study the asymptotic behaviour of the posterior distribution in a mixture model when the number of components in the mixture is larger than the true number of components: a situation which is commonly referred to as an overfitted mixture. We prove in particular that quite generally the posterior distribution has a stable and interesting behaviour, since it tends to empty the extra components. This stability is achieved under some restriction on the prior, which can be used as a guideline for choosing the prior. Some simulations are presented to illustrate this behaviour.
A genetic risk score is significantly associated with statin therapy response in the elderly population

The ability of statins to strongly reduce low‐density lipoprotein cholesterol (LDL‐C) varies interindividually and is partially influenced by genetic variants. Based on a comprehensive analysis of 23 single nucleotide polymorphisms (SNPs) known to be associated with pharmacokinetics and dynamics of statins, we developed a genetic risk score to study its impact on the therapy outcome in elderly individuals under at least 5 years statin therapy. The study was performed in a population‐based cohort of 1016 elderly individuals, which comprised 168 statin users investigated at age 75 and 80. Using random forest models, the major variants influencing LDL‐C levels were summarized in a weighted GRS (wGRS). The wGRS was tested with lipid and glucose outcomes and validated in an independent population‐based cohort including 221 statin users. Four SNPs within the APOE cluster (rs7412, rs4420638), ABCC2 (rs2002042) and CELSR/SORT1/PSRC1 (rs646776), displayed a major impact on statin efficacy. The wGRS was significantly associated with lower LDL‐C at age 75 and 80. This association was replicated displaying similar results. GRS analysis is a powerful tool to evaluate the additive effects of genetic variants on statin response and to estimate the magnitude of LDL‐C reduction to a considerable extent in the older population.
Adenosine receptor expression and gene reference evaluation in human leukocytes.

BACKGROUND Peripheral blood mononuclear cells and isolated polymorphonuclear neutrophilis were used to evaluate gene expression studies. Unfortunately, there are many methodological problems related to these cellular models, limiting their use. The aim was to evaluate a fast and easy procedure for the extraction of total RNA from leukocytes obtained from human whole blood (WB) < 10 mL; to determine adenosine receptor (AR) mRNA expression in WB samples of normal subjects and to establish the most stable reference genes for data normalization. METHODS mRNA expression was performed by Real-Time PCR. RESULTS The most stably expressed genes were TPT1, EEF1A, and RPL13A. Similar levels of mRNA expression were observed for A2aR, A2bR, and A3R while lower levels were measured for A1R (p = 0.02 A1R vs. A2aR; p = 0.04 A1R vs. A3R). CONCLUSIONS Our study represents an important and useful starting point for future investigations devoted to evaluate the expression of ARs in human diseases.
The relationship between combat‐related posttraumatic stress disorder and the 5‐HTTLPR/rs25531 polymorphism

Background: Empirical evidence suggests that there is a significant genetic influence in the development of posttraumatic stress disorder (PTSD). The serotonin transporter (5‐HTT) gene (SLC6A4) has been identified as a prime candidate for the development of the disorder, as 5‐HTT is a working target for selective serotonin reuptake inhibitors (SSRIs), first line treatment agents for PTSD. Several studies have reported associations between 5‐HTT‐linked promoter region (5‐HTTLPR) polymorphism variants and increased rates of PTSD in civilian samples. This study investigated the role of the 5‐HTTLPR polymorphism, triallelically classified, in a sample of combat veterans with and without PTSD. Methods: Rates of PTSD were examined across three genotypes in a sample of 388 combat veterans. The short/long polymorphism of 5‐HTTLPR and the A‐G polymorphism within the 5‐HTTLPR (rs25531) were genotyped, and statistical analyses were conducted. Results: There were significant intergroup (PTSD versus non‐PTSD) differences in the genotype frequencies of 5‐HTTLPR/rs25531 (χ2[1, n = 388] = 16.23, P = 5.62 × 10−5). The 5‐HTTLPR S′/S′ (low transcriptionally efficient) genotype was also associated with the PTSD severity score in the 228 participants who had combat severity data (r = .15, P = 0.03). Conclusions: The findings are consistent with previous research among civilian populations that have indicated that the low transcriptionally efficient S′/S′ genotype of 5‐HTTLPR is a risk factor for the development of PTSD after trauma exposure. Our findings are the first to examine this polymorphism and PTSD in a military sample. Additional large‐scale investigations are needed to replicate these findings. Depression and Anxiety, 2011. © 2011 Wiley Periodicals, Inc.
Population pharmacokinetics and renal function-sparing effects of amphotericin B colloidal dispersion in patients receiving bone marrow transplants

The purpose of this study was to evaluate the pharmacokinetics of amphotericin B colloidal dispersion and its effect on creatinine clearance in bone marrow transplant patients with systemic fungal infections. Seventy-five patients (42 females and 33 males) with a median age of 34.5 years and a median weight of 70.0 kg were enrolled in the study. Patients received 1 of 15 dose levels (range, 0.5 to 8.0 mg/kg of body weight) daily for a mean duration of 28 days and a mean cumulative dose amount of 8 g. Plasma samples for amphotericin B determination (median number, 4; range, 2 to 30) and daily serum creatinine values were obtained for each patient. Iterative two-stage analysis, one of several approaches to population pharmacokinetic and pharmacodynamic modelling, was employed for the pharmacokinetic analysis. The plasma data were available for 51 of 75 patients and were best described by a two-compartment model. Both plasma clearance and volume of distribution increased with escalating doses; the overall average terminal elimination half-life was 29 h. Of the covariates studied, only body weight and dose size were significant. Serum creatinine values over the duration of therapy were available for 59 of 75 patients. Overall, there was no net change in renal function over the duration of therapy; 12 patients had > 30% increases in creatinine clearance, whereas 13 had > 30% decreases. No measure of amphotericin B colloidal dispersion exposure, demographic values, or concomitant treatment with other medications was related to changes in the creatinine clearance.
Why the numbers are dropping in general surgery: the answer no one wants to hear--lifestyle!

America is captivated by the surgeon-perhaps more so than by any other servant in medicine. Channel surfing through daytime soap operas and prime-time television shows, for instance, inevitably displays the drama of the operating room, a domain otherwise foreign to the lay public. Surgery's allure likewise extends to most medical students; many are fascinated by their operating room experiences during the surgery clerkship and enjoy the combination of procedures, teamwork, and patient care. If medical students continue to be intrigued by surgery as a discipline, though, why do they not appear to be as interested in general surgery as a career?
Global phylogenetic community structure and β-diversity patterns in surface bacterioplankton metacommunities

We aimed to identify phylogenetic community patterns in abundant planktonic bacteria (Alpha-, Beta-, and Gammaproteobacteria, Actinobac- teria, Cyanobacteria, and Bacteroidetes) from a world- wide range of surface waters (lakes and seas — 34 sites and ca. 4500 16S rRNA gene sequences). At each site we assessed the number of observed bacterial groups and the genetic relatedness of the most abun- dant groups through a community phylogenetic meta- analysis approach in order to (1) explore which poten- tial ecological processes were consistent with the observed phylogenetic patterns in community assem- bly and (2) disentangle the effects of space and envi- ronment in β-diversity patterns for the different bacte- rial groups. Inland waters had significantly more bacterial groups and were more diverse than marine waters. Marine habitats showed a higher percentage of clustered sites than lakes, and bacterial communi- ties were more closely related than expected by chance. Phylogenetic β-diversity analyses revealed different patterns to both salt composition (marine vs. inland salt lakes) and salt concentration for the domi- nant bacteria. We observed that while β-diversity pat- terns for Bacteroidetes were mostly shaped by salinity concentration, patterns in Alphaproteobacteria and Gammaproteobacteria were controlled by salt compo- sition. Actinobacteria, Betaproteobacteria and Sphin- gobacteria were largely absent from marine habitats and from saline continental sites. In general and despite the lack of contextual metadata, environmen- tal similarity was more relevant than spatial distribu- tion for bacterial β-diversity patterns. However, we detected a geographic signal for some inland waters' groups (i.e. Actinobacteria, Beta-, and Gammapro- teobacteria). Overall, the analyses indicated differ- ences among phylogenetic groups and reflected pat- terns upon which further exploration of community assembly theory could be based.
Winter survival of larvae and pupae of the blowfly, Lucilia sericata (Diptera: Calliphoridae)

Abstract The mortality of larvae and pupae of the blowfly Lucilia sericata (Meigen) were examined during winter and spring, for two or three years. In soil cores in the field, 70–95% of the larvae died overwinter. Larvae congregated in the top 10 cm of the soil core and did not move extensively throughout the column during the winter. Larvae and pupae at greater depth were less likely to pupariate and emerge successfully than larvae closer to the surface. Under semi-natural conditions, where pupae were placed outside in sawdust filled tubes, in the absence of the usual biotic mortality factors, the mortality of larvae was considerably lower and was also unaffected by low winter temperatures. Hence, low temperatures did not appear to be the primary cause of high overwintering mortality in the field which, it is suggested, is more likely to be the result of the action of biotic mortality factors, such as entomopathogenic nematodes and fungi.
Design of a 30-GHz high gain quasi-Yagi antenna

A low-cost, high gain and broadband 30 GHz quasi_Yagi antenna with a corrugated substrate is presented. The corrugation design parameters provide a high flexibility to enhance antenna characteristics. The proposed antenna provides a gain of 17.7 dB at 30 GHz, a high total radiation efficiency of ∼94.4%, an impedance bandwidth covers the 24–31.6 GHz band and in-band crosspolarization of less than 37 dB. With these features, this antenna is suitable for various millimeter-wave applications.
Subnuclear Compartmentalization of Immunoglobulin Loci During Lymphocyte Development

Immunoglobulin (Ig) loci are selectively activated for transcription and rearrangement during B lymphocyte development. Using fluorescence in situ hybridization, we show that Ig heavy (H) and Igκ loci are preferentially positioned at the nuclear periphery in hematopoietic progenitors and pro-T cells but are centrally configured in pro-B nuclei. The inactive loci at the periphery do not associate with centromeric heterochromatin. Upon localization away from the nuclear periphery in pro-B cells, the IgH locus appears to undergo large-scale compaction. We suggest that subnuclear positioning represents a novel means of regulating transcription and recombination of IgH and Igκ loci during lymphocyte development.
A Model of Dynamics of Leaves and Nitrogen in a Plant Canopy: An Integration of Canopy Photosynthesis, Leaf Life Span, and Nitrogen Use Efficiency

A model of dynamics of leaves and nitrogen is developed to predict the effect of environmental and ecophysiological factors on the structure and photosynthesis of a plant canopy. In the model, leaf area in the canopy increases by the production of new leaves, which is proportional to the canopy photosynthetic rate, with canopy nitrogen increasing with uptake of nitrogen from soil. Then the optimal leaf area index (LAI; leaf area per ground area) that maximizes canopy photosynthesis is calculated. If leaf area is produced in excess, old leaves are eliminated with their nitrogen as dead leaves. Consequently, a new canopy having an optimal LAI and an optimal amount of nitrogen is obtained. Repeating these processes gives canopy growth. The model provides predictions of optimal LAI, canopy photosynthetic rates, leaf life span, nitrogen use efficiency, and also the responses of these factors to changes in nitrogen and light availability. Canopies are predicted to have a larger LAI and a higher canopy photosynthetic rate at a steady state under higher nutrient and/or light availabilities. Effects of species characteristics, such as photosynthetic nitrogen use efficiency and leaf mass per area, are also evaluated. The model predicts many empirically observed patterns for ecophysiological traits across species.
Milk secretion in the rabbit: changes during lactation and the mechanism of ion transport.

Changes in the yield and composition of milk and in the permeability of the mammary epithelium to labelled disaccharides and ions have been studied during lactation in rabbits of the Dutch breed. 2. Milk yield increased to reach a peak on day 20 of lactation and then declined, but by 30‐32 days the yield was still relatively high. Milk [protein] and [fat] increased in late lactation; [Na] and [Cl] decreased from early to established lactation (11‐14 days) and then increased, whereas milk [K] and [lactose] showed an inverse pattern to that displayed by[Na] and [Cl]. 3. At all stages of lactation [Na] and [Cl] were both inversely related to milk [lactose] while [K] showed a positive correlation. 4. Labelled lactose and sucrose were found to cross the mammary epithelium at all stages but in increased amounts during late lactation. Sucrose entry from blood into milk was positively correlated with milk [Na], and inversely correlated with [K] and [lactose]. 5. The entry of (24)Na and (36)Cl into milk from blood paralleled the changes in milk [Na] and [Cl]. 6. Intracellular ionic composition determined in vitro was similar for [Na] and [K] in both established (11‐14 days) and late (25‐28 days) lactation, but [Cl] was higher in late lactation. 7. Intracellular potentials recorded in vivo were ‐31 mV (mean) and ‐36 mV in established and late lactation respectively. Transepithelial p.d. was close to zero at both stages. 8. It is suggested that ions and lactose and other small molecules can cross the mammary epithelium by a paracellular, as well as by a transcellular route, throughout lactation and that the paracellular pathway is increased in late lactation. 9. The site of the proposed paracellular pathway and the implications of such a pathway's presence on ion transport are discussed, and a scheme is suggested to account for the ionic composition of milk in this species.
Influence of absorbent layer on nonlinear microwave properties of HTS-based coplanar waveguide

The paper presents the results of continuing experimental studies of a coplanar waveguide on the basis of YBCO thin film (75 nm) depending on the input power and DC level. It is shown that use of a highly absorbent material on the back side of the substrate changes HTS transition characteristics in a strongly dissipative state. Apparently it is caused by a changing in the heat transfer between the structure and the helium gas filling the structure chamber. This fact leads to a decreasing the value of DC corresponding to a structure transition to a highly dissipative state.
Successional Development of Sulfate-Reducing Bacterial Populations and Their Activities in a Wastewater Biofilm Growing under Microaerophilic Conditions

ABSTRACT A combination of fluorescence in situ hybridization, microprofiles, denaturing gradient gel electrophoresis of PCR-amplified 16S ribosomal DNA fragments, and 16S rRNA gene cloning analysis was applied to investigate successional development of sulfate-reducing bacteria (SRB) community structure and in situ sulfide production activity within a biofilm growing under microaerophilic conditions (dissolved oxygen concentration in the bulk liquid was in the range of 0 to 100 μM) and in the presence of nitrate. Microelectrode measurements showed that oxygen penetrated 200 μm from the surface during all stages of biofilm development. The first sulfide production of 0.32 μmol of H2S m−2 s−1 was detected below ca. 500 μm in the 3rd week and then gradually increased to 0.70 μmol H2S m−2 s−1 in the 8th week. The most active sulfide production zone moved upward to the oxic-anoxic interface and intensified with time. This result coincided with an increase in SRB populations in the surface layer of the biofilm. The numbers of the probe SRB385- and 660-hybridized SRB populations significantly increased to 7.9 × 109 cells cm−3 and 3.6 × 109 cells cm−3, respectively, in the surface 400 μm during an 8-week cultivation, while those populations were relatively unchanged in the deeper part of the biofilm, probably due to substrate transport limitation. Based on 16S rRNA gene cloning analysis data, clone sequences that related to Desulfomicrobium hypogeium (99% sequence similarity) and Desulfobulbus elongatus (95% sequence similarity) were most frequently found. Different molecular analyses confirmed that Desulfobulbus, Desulfovibrio, and Desulfomicrobium were found to be the numerically important members of SRB in this wastewater biofilm.
Deep–diving behaviour of the northern bottlenose whale, Hyperoodon ampullatus (Cetacea: Ziphiidae)

Using suction–cup attached time–depth recorder/VHF radio tags, we have obtained the first diving data on northern bottlenose whales (Hyperoodon ampullatus), the first such data on any species within the family Ziphiidae. Two deployments in 1997 on northern bottlenose whales in a submarine canyon off Nova Scotia demonstrated their exceptional diving ability, with dives approximately every 80 min to over 800 m (maximum 1453 m), and up to 70 min in duration. Sonar traces of non–tagged, diving bottlenose whales in 1996 and 1997 suggest that such deep dives are not unusual. This combined evidence leads us to hypothesize that these whales may make greater use of deep portions of the water column than any other mammal so far studied. Many of the recorded dives of the tagged animals were to, or close to, the sea floor, consistent with benthic or bathypelagic foraging. A lack of correlation between dive times and surface intervals suggests that the dives were predominately aerobic.
TNF-dependent BALB/c murine macrophage apoptosis following Mycobacterium tuberculosis infection inhibits bacillary growth in an IFN-gamma independent manner.

SETTING In vitro model of murine macrophage M. tuberculosis infection. OBJECTIVE To evaluate the association and cytokine control of host cell apoptosis and bacillary killing in M. tuberculosis -infected murine peritoneal macrophage (PM). DESIGN Murine PM from different strains of mice were infected with H37Ra. Bacillary growth and macrophage apoptosis were evaluated under different cytokine conditions. RESULTS Like human alveolar macrophages, PM from BALB/c mice were found to undergo apoptosis after infection with M. tuberculosis in a TNF-dependent manner. Neutralizing TNF with anti-TNF antibody inhibited PM apoptosis following infection, and resulted in increased bacillary growth. Pre-treatment of PM with interferon (IFN-gamma) resulted in significant killing of the infecting bacilli, which was not dependent on TNF or apoptosis of the cells. In contrast to BALB/c mice, PM from C3H/HeJ mice did not undergo apoptosis following infection and did not undergo TNF- and apoptosis-dependent inhibition of bacillary growth. CONCLUSION These findings suggest that TNF contributes to macrophage inhibition of M. tuberculosis growth by a mechanism that is dependent on apoptosis and independent of IFN-gamma activity. This protective phenotype was not seen in all strains of mice and merits investigation as a marker of mycobacterial host susceptibility.
Design of low inductive busbar for fast switching SiC modules verified by 3D FEM calculations and laboratory measurements

This paper explains the importance of low inductive busbar for utilizing the fast switching feature of SiC modules. A 3D FEM model of the busbar is built using Ansys Q3D extractor. The simulation results give insight into the physical behaviour of the current flow which aids in the identification of the parts of the structure that must be considered coplanar. The simulated busbar inductance is compared with analytical values and laboratory measurements, and possible reasons for deviations are discussed. Based on this knowledge, different alternative low inductive busbar designs are presented through FEM simulations along with the laboratory measurements for one of the simulated solutions, which are the main contributions of the paper.
Structure of Salmonella Effector Protein SopB N-terminal Domain in Complex with Host Rho GTPase Cdc42*

Background: Salmonella effector protein SopB binds host Rho GTPase Cdc42. Results: Structural characterization of SopB with Cdc42 reveals that SopB contains a CRIB-like motif and contacts Cdc42 switch regions. Conclusion: SopB structurally mimics contacts between Cdc42 switch regions and human guanine dissociation inhibitor (GDI) and slows nucleotide exchange. Significance: This is the first structure of SopB and provides further insight into Salmonella regulation of Cdc42. SopB is a type III secreted Salmonella effector protein with phosphoinositide phosphatase activity and a distinct GTPase binding domain. The latter interacts with host Cdc42, an essential Rho GTPase that regulates critical events in eukaryotic cytoskeleton organization and membrane trafficking. Structural and biochemical analysis of the SopB GTPase binding domain in complex with Cdc42 shows for the first time that SopB structurally and functionally mimics a host guanine nucleotide dissociation inhibitor (GDI) by contacting key residues in the regulatory switch regions of Cdc42 and slowing Cdc42 nucleotide exchange.
Appropriate Use of Screening and Diagnostic Tests to Foster High-Value, Cost-Conscious Care

Unsustainable rising health care costs in the United States have made reducing costs while maintaining high-quality health care a national priority. The overuse of some screening and diagnostic tests is an important component of unnecessary health care costs. More judicious use of such tests will improve quality and reflect responsible awareness of costs. Efforts to control expenditures should focus not only on benefits, harms, and costs but on the value of diagnostic tests-meaning an assessment of whether a test provides health benefits that are worth its costs or harms. To begin to identify ways that practicing clinicians can contribute to the delivery of high-value, cost-conscious health care, the American College of Physicians convened a workgroup of physicians to identify, using a consensus-based process, common clinical situations in which screening and diagnostic tests are used in ways that do not reflect high-value care. The intent of this exercise is to promote thoughtful discussions about these tests and other health care interventions to promote high-value, cost-conscious care.