Miracle-dz/UniFAR-FTUs huggingface dataset:
A Role for Bone Morphogenetic Protein-4 in Adipocyte Development

Obesity is characterized by increases in the number of mature adipocytes. Nascent adipocytes arise from mesenchymal stem cells (MSCs) by a multi-step process — MSCs are recruited to the adipocyte lineage forming determined preadipocytes, these committed progenitors proliferate, undergo growth arrest, and finally differentiate into mature adipocytes. Although the genetic mechanisms that control the differentiation of preadipocytes into mature adipocytes are understood to a large extent, the earliest events in adipogenesis — especially the commitment of MSCs into preadipocytes — are largely unknown. Recently, bone morphogenetic protein-4 (BMP-4) has been implicated in the commitment of pluripotent MSCs to the adipocyte lineage by two independent lines of investigation. First, growth-arrested 10T1/2 cells do not normally respond to a hormonal cocktail that causes various growth-arrested preadipocyte cell lines to differentiate into adipocytes, but if 10T1/2 cells are first treated with BMP-4 they will respond to these hormonal inducers by undergoing terminal adipocyte differentiation. Second, a preadipocyte cell line, A33 cells, derived from 10T1/2 cells after exposing the cells to the DNA methyltransferase inhibitor 5-azacytidine was shown to express BMP-4, and this endogenous BMP-4 expression is required for acquisition of the preadipocyte phenotype of these cells. A role for the BMP-4 signaling pathway in adipogenesis is discussed.
Predictive value of ALT levels for histologic findings in chronic hepatitis C: A European collaborative study

The aim of this retrospective study was to determine the predictive value of alanine aminotransferase (ALT) levels for histologic findings in patients with chronic hepatitis C virus (HCV) infection. Data on 864 HCV RNA–positive patients were collected. ALT values were obtained at the time of biopsy (before treatment), and normal ALT values were defined as normal values obtained at serial evaluations during a 6‐month period. Histologic results were scored using the METAVIR system. Among all patients, 99% of those with elevated ALT levels had a score of at least F1 (positive predictive value [PPV], 99%) and 88% had a score greater than A1F1. Among patients with persistently normal ALT values, 65% had a score of at least F1 (negative predictive value [NPV], 35%) and 26% had a score greater than A1F1. The receiver operating characteristics analysis indicates that the ALT threshold for the best compromise sensitivity‐specificity was about 2.25 times the upper limit of normal (ULN). In conclusion, almost all HCV RNA–positive patients with elevated ALT levels have some degree of fibrosis. However, an important proportion of patients with persistently normal ALT levels also show some histologic signs of fibrosis; the degree of fibrosis is usually mild but is sometimes more marked, and in rare cases cirrhosis may be present. In this subset of patients, the indication of liver biopsy and the potential benefit of therapy need to be further evaluated. These results suggest the need to revisit the algorithm for liver biopsy practice.
The 4 percent Strategy Revisited: A Pre-Commitment Optimal Mean-Variance Approach to Wealth Management

In contrast to single-period mean-variance portfolio allocation, optimal multi-period mean-variance allocation can be modified slightly to be effectively a down-side risk measure. With this in mind, we consider optimal multi-period mean-variance portfolio allocation in the presence of periodic withdrawals. The investment portfolio can be allocated between a risk-free investment and a risky asset. The risky asset is assumed to follow a jump diffusion process. We consider two wealth management applications, namely optimal de-accumulation rates for a defined contribution pension plan, and sustainable withdrawal rates for an endowment. Compared with a constant proportions strategy, the optimal mean-variance policy achieves the same expected wealth at the end of the investment horizon, while significantly reducing the standard deviation and probability of shortfall.
Alcohol Cirrhosis Alters Nuclear Receptor and Drug Transporter Expression in Human Liver

Unsafe use of alcohol results in approximately 2.5 million deaths worldwide, with cirrhosis contributing to 16.6% of reported deaths. Serum insulin levels are often elevated in alcoholism and may result in diabetes, which is why alcoholic liver disease and diabetes often are present together. Because there is a sizable population with these diseases alone or in combination, the purpose of this study was to determine whether transporter expression in human liver is affected by alcoholic cirrhosis, diabetes, and alcoholic cirrhosis coexisting with diabetes. Transporters aid in hepatobiliary excretion of many drugs and toxic chemicals and can be determinants of drug-induced liver injury. Drug transporter expression and transcription factor–relative mRNA and protein expression in normal, diabetic, cirrhotic, and cirrhosis with diabetes human livers were quantified. Cirrhosis significantly increased ABCC4, 5, ABCG2, and solute carrier organic anion (SLCO) 2B1 mRNA expression and decreased SLCO1B3 mRNA expression in the liver. ABCC1, 3–5, and ABCG2 protein expression was also upregulated by alcoholic cirrhosis. ABCC3-5 and ABCG2 protein expression was also upregulated in diabetic cirrhosis. Cirrhosis increased nuclear factor E2–related factor 2 mRNA expression, whereas it decreased pregnane-X-receptor and farnesoid-X-receptor mRNA expression in comparison with normal livers. Hierarchical cluster analysis indicated that expressions of ABCC2, 3, and 6; SLCO1B1 and 1B3; and ABCC4 and 5 were more closely related in the livers from this cohort. Overall, alcoholic cirrhosis altered transporter expression in human liver.
ACUTE CARDIOPULMONARY EFFECTS OF A DUAL–ENDOTHELIN RECEPTOR ANTAGONIST ON OLEIC ACID–INDUCED PULMONARY ARTERIAL HYPERTENSION IN DOGS

The objective of this study was to evaluate the cardiopulmonary effects of a dual–endothelin (ET) receptor antagonist, Tezosentan, on oleic acid (OA)-induced acute lung injury with pulmonary arterial hypertension in dogs. Twelve pentobarbital-anesthetized dogs with intravenous OA-induced acute lung injury (ALI) were divided into 2 groups. The control group (n = 6) received saline treatment, whereas the treatment group (n = 6) received the ET receptor antagonist, Tezosentan (1 mg/kg intravenous [IV] + 1 mg/kg/h IV infusion). Cardiopulmonary parameters were monitored continuously for 1 hour. OA administration resulted in a significant increase in mean pulmonary arterial pressure (MPAP) and pulmonary vascular resistance (PVR) and a decrease in mean systemic arterial pressure (MSAP), systemic vascular resistance (SVR), and cardiac output (CO) in all dogs. Tezosentan treatment markedly attenuated the pulmonary hypertension, with a 32% decrease in MPAP (from 23±2 mm Hg to 15±2 mm Hg; P < .01) and a 22% decrease in PVR (from 860±105 dyn · s · cm−5to 670±96 dyn · s · cm−5; P < .01) at the end of study. MSAP and SVR were unchanged after Tezosentan treatment, and there was an increase in cardiac output and a decline in peak inspiratory pressure (PIP) in the Tezosentan group compared with the control group. These results indicate that the dual–ET receptor antagonist, Tezosentan, can attenuate the pulmonary hypertension induced by OA. Thus, dual–ET receptor antagonists such as Tezosentan may be useful in the management of acute pulmonary arterial hypertension, complicating the course of OA-induced lung injury.
Epoxyeicosatrienoic Acids Regulate Trp Channel–Dependent Ca2+ Signaling and Hyperpolarization in Endothelial Cells

Objective—An initial step in endothelium-derived hyperpolarizing factor-mediated responses is endothelial cell hyperpolarization. Here we address the mechanisms by which cytochrome P450 (CYP)-derived epoxyeicosatrienoic acids (EETs) contribute to this effect in native and cultured endothelial cells. Methods and Results—In native CYP2C-expressing endothelial cells, bradykinin elicited a Ca2+ influx that was potentiated by the soluble epoxide hydrolase inhibitor, 1-adamantyl-3-cyclohexylurea (ACU), and attenuated by CYP inhibition. Similar effects were observed in cultured endothelial cells overexpressing CYP2C9, but not in CYP2C9-deficient cells, and were prevented by the EET antagonist 14,15-epoxyeicosa-5(Z)-enoic acid as well as by the cAMP antagonist, Rp-cAMPS. The effects on Ca2+ were mirrored by prolongation of the bradykinin-induced hyperpolarization. Ruthenium red and the combination of charybdotoxin and apamin prevented the latter effect, suggesting that Trp channel activation increases Ca2+ influx and prolongs the activation of Ca2+-dependent K+ (KCa) channels. Indeed, overexpression of CYP2C9 enhanced the agonist-induced translocation of a TrpC6-V5 fusion protein to caveolin-1–rich areas of the endothelial cell membrane, which was prevented by Rp-cAMPS and mimicked by 11,12-EET. Conclusions—Elevated EET levels regulate Ca2+ influx into endothelial cells and the subsequent activation of KCa channels, via a cAMP/PKA-dependent mechanism that involves the intracellular translocation of Trp channels.
10kV SiC-based isolated DC-DC converter for medium voltage-connected Solid-State Transformers

Silicon-carbide semiconductor technology offers the possibility to synthesize power devices with unprecedented blocking voltage capabilities while achieving outstanding switching and conduction performances. Accordingly, this new semiconductor technology is especially interesting for Solid-State Transformer concepts and is utilized in this paper for designing a 25 kW/50 kHz prototype based on 10 kV SiC devices, featuring a 400V DC output. The focus is on the DC-DC converter stage while special attention is placed on the large step-down medium frequency transformer, whereby the impact of the rather high operating frequency and high number of turns with respect to the transformer's resonance frequency is analyzed This leads to useful scaling laws for the resonance frequency of transformers in dependence of the operating frequency and construction parameters. Finally, a transformer prototype and efficiency and power density values for the DC-DC stage are presented.
Do no harm: Balancing the costs and benefits of patient outcomes in health psychology research and practice

This article analyses research exploring medication adherence, help-seeking behaviour, screening and behaviour change to argue that all interventions have the potential for both benefit and harm. Accordingly, health psychology may have inadvertently contributed to psychological harms (e.g. lead times, anxiety, risk compensation and rebound effects); medical harms (e.g. medication side effects, unnecessary procedures) and social harms (e.g. financial costs, increased consultations rates). Such harms may result from medicalisation or pharmaceuticalisation. Or, they may reflect the ways in which we manage probabilities and an optimistic bias that emphasises benefit over cost.
Impact of an Education Program on the Incidence of Central Line-Associated Bloodstream Infection in 2 Medical-Surgical Intensive Care Units in Brazil

An intervention study was undertaken to evaluate the impact of an education program on the incidence of central line–associated bloodstream infection (CLABSI) in 2 intensive care units. There was a nonsignificant reduction in the incidence of CLABSI (odds ratio, 0.46 [95% confidence interval, 0.21–1.02]; P = .04) despite a significant increase in knowledge of CLABSI prevention by the staff of both intensive care units after the education program.
Cholinergic and nitrergic interneurones in the myenteric plexus of the human colon

Background: Myenteric interneurones are involved in the reflexes that control the motility of the human colon. Aims: The distribution of choline acetyltransferase (ChAT) and nitric oxide synthase (NOS) immunoreactivity in myenteric interneurones was investigated in this study. Methods: DiI (1,1`- didodecyl 3,3,3`,3`-indocarbocyanine perchlorate) was applied to the myenteric plexus of the human colon followed by organotypic culture. Retrogradely labelled neurones, with projections longer than motor neurones (>10 mm), were studied to exclude motor neurone populations. ChAT and NOS immunoreactivity was then determined in the interneurones. Results: We found that 90% of interneurones projecting orally contained ChAT and none contained NOS. Ninety five per cent of descending interneurones were labelled with ChAT and/or NOS antisera; 46% contained NOS immunoreactivity alone, 20% contained ChAT immunoreactivity alone, and 29% contained both ChAT and NOS. Anally directed interneurones had significantly longer projections than orally projecting interneurones. Conclusions: Nearly all interneurones contain either NOS or ChAT immunoreactivity. Orally projecting interneurones are of two types: 90% contain ChAT alone and the remainder contain immunoreactivity for neither ChAT nor NOS. There are three main types of anally projecting interneurones: the largest, which contains NOS but not ChAT, and the two smaller classes which contain ChAT and NOS, and CHAT alone.
A 16-Year Experience in Minimally Invasive Aortic Valve Replacement

Objective The aim of this study was to evaluate short- and long-term morbidity and mortality in patients with aortic valve disease who had minimally invasive aortic valve replacement (AVR) through upper hemisternotomy. Methods From July 1996 to June 2012, a total of 1639 patients underwent minimally invasive aortic valve surgery (AVR). Patient data were extracted from hospital electronic records after institutional review board approval. Outcomes of interest included postoperative complication rates, perioperative mortality, and long-term survival. Results The mean age was 67 years (SD, 14 years; range, 22–95 years). Of the total cohort, 211 (13%) underwent reoperative AVR. Postoperatively, 2.3% (37/1639) had reoperations to correct bleeding, 2.7% (44/1639) had strokes, 20.4% (334/1639) had new-onset atrial fibrillation, and 1.5% (24/1639) required permanent pacemakers. Only 34% (571/1639) of the patients received packed red blood cells. The median discharge was on day 6 (5–8), and 72.2% of the patients (1184/1639) were discharged home. Operative mortality was 2.9% (48/1639), and long-term survival at 1, 5, 10, and 15 years was 96%, 93%, 92%, and 92%, respectively. Operative mortality was 5.7% (12/208) for the reoperative patients. Conclusions The upper hemisternotomy approach for AVR is safe and reliable, especially for patients undergoing reoperations and those older than 80 years.
Estrogen-receptor status and outcomes of modern chemotherapy for patients with node-positive breast cancer.

CONTEXT Breast cancer estrogen-receptor (ER) status is useful in predicting benefit from endocrine therapy. It may also help predict which patients benefit from advances in adjuvant chemotherapy. OBJECTIVE To compare differences in benefits from adjuvant chemotherapy achieved by patients with ER-negative vs ER-positive tumors. DESIGN, SETTING, AND PATIENTS Trial data from the Cancer and Leukemia Group B and US Breast Cancer Intergroup analyzed; patient outcomes by ER status compared using hazards over time and multivariate models. Randomized trials comparing (1): 3 regimens of cyclophosphamide, doxorubicin, and fluorouracil (January 1985 to April 1991); (2) 3 doses of doxorubicin concurrent with cyclophosphamide, with or without subsequent paclitaxel (May 1994 to April 1997); (3) sequential doxorubicin, paclitaxel, and cyclophosphamide with concurrent doxorubicin and cyclophosphamide followed by paclitaxel, and also 3-week vs 2-week cycles (September 1997 to March 1999). A total of 6644 node-positive breast cancer patients received adjuvant treatment. MAIN OUTCOME MEASURES Disease-free and overall survival. RESULTS For ER-negative tumors, chemotherapy improvements reduced the relative risk of recurrence by 21%, 25%, and 23% in the 3 studies, respectively, and 55% comparing the lowest dose in the first study with biweekly cycles in the third study. Corresponding relative risk reductions for ER-positive tumors treated with tamoxifen were 9%, 12%, and 8% in the 3 studies, and 26% overall. The overall mortality rate reductions associated with chemotherapy improvements were 55% and 23% among ER-negative and ER-positive patients, respectively. All individual ER-negative comparisons and no ER-positive comparisons were statistically significant. Absolute benefits due to chemotherapy were greater for patients with ER-negative compared with ER-positive tumors: 22.8% more ER-negative patients survived to 5 years disease-free if receiving chemotherapy vs 7.0% for ER-positive patients; corresponding improvements for overall survival were 16.7% vs 4.0%. CONCLUSION Among patients with node-positive tumors, ER-negative breast cancer, biweekly doxorubicin/cyclophosphamide plus paclitaxel lowers the rate of recurrence and death by more than 50% in comparison with low-dose cyclophosphamide, doxorubicin, and fluorouracil as used in the first study.
TAXONOMIC ANALYSIS OF NONPIGMENTED, RAPIDLY GROWING MYCOBACTERIA

Strains of mycobacteria capable of growth in 1 to 3 days of incubation from small inocula in L6wenstein-Jensen medium or in glycerolnutrient-agar are grouped under the name of rapidly growing mycobacteria. This group includes both pigmented and nonpigmented strains. The purpose of the present paper is to review only the characteristics of the nonpigmented strains for taxonomic purposes, utilizing the method proposed by Sneath (1957a, b) based on the Adansonian principles (i) every feature is of equal importance in creating taxa, (ii) organisms are classified according to their over-all similarity, (iii) over-all similarity is the proportion of features possessed in common by two organisms, and (iv) divisions between taxa are based on correlated features. Preliminary studies directed toward specific taxonomic identification of some mycobacteria have been reported (Frey and Hagan, 1931; Thompson, 1932; Pinner, 1932; Gordon, 1937; Gordon and Hagan, 1938; McMillen and Kushner, 1959). The only well-defined species among the rapidly growing, nonpigmented strains of acid-fast bacilli is Mycobacterium fortuitum Cruz (Gordon and Smith, 1955) but there are also a certain number of related strains of unsettled taxonomic position. The present study was undertaken in an attempt to clarify the taxonomic position of the last mentioned group of strains.
Aberrant expression of transmembrane mucins, MUC1 and MUC4, in human prostate carcinomas

Mucins are considered important markers for early diagnosis and targeted therapy due to their aberrant and unique expression pattern during malignant progression of carcinomas. Recent findings have provided substantial evidence for the involvement of transmembrane mucins, MUC1 and MUC4, in altered cell signaling, tumor growth, and metastasis.
Ordered ferrimagnetic form of ferrihydrite reveals links among structure, composition, and magnetism

The natural nanomineral ferrihydrite is an important component of many environmental and soil systems and has been implicated as the inorganic core of ferritin in biological systems. Knowledge of its basic structure, composition, and extent of structural disorder is essential for understanding its reactivity, stability, and magnetic behavior, as well as changes in these properties during aging. Here we investigate compositional, structural, and magnetic changes that occur upon aging of “2-line” ferrihydrite in the presence of adsorbed citrate at elevated temperature. Whereas aging under these conditions ultimately results in the formation of hematite, analysis of the atomic pair distribution function and complementary physicochemical and magnetic data indicate formation of an intermediate ferrihydrite phase of larger particle size with few defects, more structural relaxation and electron spin ordering, and pronounced ferrimagnetism relative to its disordered ferrihydrite precursor. Our results represent an important conceptual advance in understanding the nature of structural disorder in ferrihydrite and its relation to the magnetic structure and also serve to validate a controversial, recently proposed structural model for this phase. In addition, the pathway we identify for forming ferrimagnetic ferrihydrite potentially explains the magnetic enhancement that typically precedes formation of hematite in aerobic soil and weathering environments. Such magnetic enhancement has been attributed to the formation of poorly understood, nano-sized ferrimagnets from a ferrihydrite precursor. Whereas elevated temperatures drive the transformation on timescales feasible for laboratory studies, our results also suggest that ferrimagnetic ferrihydrite could form naturally at ambient temperature given sufficient time.
Modeling of subgrid effects in coarse‐scale simulations of transport in heterogeneous porous media

A methodology for incorporating subgrid effects in coarse‐scale numerical models of flow in heterogeneous porous media is presented. The method proceeds by upscaling the deterministic fine‐grid permeability description and then solving the pressure equation over the coarse grid to obtain coarse‐scale velocities. The coarse‐grid saturation equation is formed through a volume average of the fine‐scale equations and includes terms involving both the average and fluctuating components of the velocity field. The terms involving the fluctuating components are subgrid effects that appear as length‐ and time‐dependent dispersivities. A simplified model for the coarse‐scale dispersivity, in terms of these subgrid velocity fluctuations, is proposed, and a numerical scheme based on this model is implemented. Results using the new method are presented for a variety of two‐dimensional heterogeneous systems characterized by moderate permeability correlation length in the dominant (horizontal) flow direction and small correlation length in the vertical direction. The new method is shown to provide much more accurate results than comparable coarse‐grid models that do not contain the subgrid treatment. Extensions of the overall methodology to handle more general systems are discussed.
Naphthalene plasmids in pseudomonads

A rapid method beginning with the direct lysis of bacteria in alkaline sodium dodecyl sulfate was used to detect naphthalene plasmids in pseudomonads. The strains NCIB 9816, PG, ATCC 17483, and ATCC 17484, which can grow on naphthalene as the sole source of carbon and energy, were examined. All except ATCC 17483 contained more than one plasmid. ATCC 17483 did not contain any plasmids. The largest pair of plasmids found in each of NCIB 9816 and PG(NAH2 and NAH3, respectively) determined naphthalene metabolism and could be transferred by conjugation. This also transferred the unusually regulated meta pathway enzymes for catechol metabolism. NAH2 determines the constitutive production of low concentrations of catechol 2,3-dioxygenase and 2-hydroxymuconic acid semialdehyde dehydrogenase, and NAH3 determines the constitutive production of high concentration of these. NAH2 and NAH3 gave identical fragments on digestion with BamHI or HindIII, but these were quite different from those of NAH. Nonetheless, NAH2 and NAH3 hybridized with NAH.