Miracle-dz/UniFAR-FTUs huggingface dataset:
Time trends in the use of cholesterol-lowering agents in older adults: the Cardiovascular Health Study.

OBJECTIVES To describe recent temporal patterns of cholesterol-lowering medication use and the characteristics that may have influenced the initiation of cholesterol-lowering therapy among those aged 65 years or older. SUBJECTS AND METHODS A cohort of 5201 adults 65 years or older were examined annually between June 1989 and May 1996. We added 687 African American adults to the cohort in 1992-1993. We measured blood lipid levels at baseline and for the original cohort in the third year of follow-up. We assessed the use of cholesterol-lowering drugs at each visit. RESULTS The prevalence of cholesterol-lowering drug use in 1989-1990 was 4.5% among the men and 5.9% among the women; these figures increased over the next 6 years to 8.1% and 10.0%, respectively, in 1995-1996. There was a 4-fold increase in the use of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors during the 6 years of follow-up, from 1.9% of all participants in 1989-1990 to 7.5% in 1995-1996. The use of bile acid sequestrants, nicotinic acid, and probucol declined from initial levels of less than 1% each. Among the participants who were untreated in 1989-1990, but eligible for cholesterol-lowering therapy after a trial of dietary therapy according to the 1993 guidelines of the National Cholesterol Education Panel, less than 20% initiated drug therapy in the 6 years of follow-up, even among subjects with a history of coronary heart disease. Among participants untreated at baseline but eligible for either cholesterol-lowering therapy or dietary therapy, initiation of cholesterol-lowering drug therapy was directly associated with total cholesterol levels, hypertension, and a history of coronary heart disease, and was inversely related to age, high-density lipoprotein cholesterol levels, and difficulties with activities of daily living. Other characteristics that form the basis of the 1993 National Cholesterol Education Panel guidelines-diabetes, smoking, family history of premature coronary heart disease, and total number of risk factors-were not associated with the initiation of cholesterol-lowering drug therapy. CONCLUSIONS Given the clinical trial evidence for benefit, those aged 65 to 75 years and with prior coronary heart disease appeared undertreated with cholesterol-lowering drug therapy.
Identification and Characterization of Two Genes (MIP-1β, VE-CADHERIN) Implicated in Acute Rejection in Human Heart Transplantation: Use of Murine Models in Tandem With cDNA Arrays

Background—Genes and mechanisms of action involved in human acute rejection after allogeneic heart transplantation remain to be elucidated. The use of a murine allograft model in tandem with cDNA arrays and quantitative real-time polymerase chain reaction (Q-PCR) can greatly help in identifying key genes implicated in human heart acute rejection. Methods and Results—Hearts from Balb/c mice were either not transplanted or transplanted heterotopically in the abdomen of Balb/c (isografts) and C57BL/6 (allografts) mice. Histological analysis showed acute rejection only in allografts. Total RNA was extracted from isografts (n=3), allografts (n=4), and not transplanted hearts (n=4); reverse transcribed; and labeled with P32. Each probe was hybridized to cDNA macroarrays. Eight genes were overexpressed and 7 genes were underexpressed in allografts compared with isografts. Macrophage inflammatory protein-1β (MIP-1β), an overexpressed gene, and VE-cadherin, an underexpressed gene, were validated by immunohistochemistry and Q-PCR in the murine models. Genes of interest, validated in the 3 murine groups, were then investigated in human heart tissues. Immunohistochemistry and Q-PCR performed on endomyocardial biopsies after heart transplantation showing no rejection (n=10) or grade IB (n=10) or IIIA (n=10) rejection, according to International Society of Heart and Lung Transplantation criteria, confirmed the results obtained from the murine model. Conclusions—We have demonstrated that the upregulation of MIP-1β and downregulation of VE-cadherin may strongly participate in human acute heart rejection.
Propagule supply controls grazer community structure and primary production in a benthic marine ecosystem

Early theories of species diversity proposed that communities at equilibrium are saturated with species. However, experiments in plant communities suggest that many communities are unsaturated and species richness can be increased by adding propagules of new species. We experimentally tested for community saturation and measured the effects of propagule supply on community structure in a benthic marine system. We manipulated propagule supply (arrival of individuals of numerous species) of mobile grazers in experimental mesocosms over multiple generations and, unlike previous tests, we examined the cascading effects of propagule supply on prey (macroalgae) biomass. We found little evidence for saturation, despite the absence of processes such as disturbance and predation that are thought to alleviate saturation in nature. Increasing propagule supply increased the total number of species and made rare species more abundant. Perhaps surprisingly, given the strong effect of propagule supply on species richness, supply-related changes in body size and composition suggest that competitive interactions remained important. Grazer supply also had strong cascading effects on primary production, possibly because of dietary complementarity modified by territorial behavior. Our results indicate that propagule supply can directly influence the diversity and composition of communities of mobile animals. Furthermore, the supply of consumer propagules can have strong indirect effects on prey and fundamental ecosystem properties.
Identification and Expression of Immunogenic Proteins of a Disease-Associated Marine Turtle Herpesvirus

ABSTRACT Herpesviruses are associated with several diseases of marine turtles, including lung-eye-trachea disease (LETD) and fibropapillomatosis. Two approaches were used to identify immunodominant antigens of LETV, the LETD-associated herpesvirus. The first approach targeted glycoprotein B, which is known to be immunogenic and neutralizing in other species. The second strategy identified LETV proteins recognized on Western blots by antibodies in immune green turtle plasma. A 38-kDa protein was resolved by two-dimensional gel electrophoresis, sequenced, and identified as a scaffolding protein encoded by the overlapping open reading frames of UL26 and UL26.5. Glycoprotein B and the scaffolding protein were cloned and expressed in Escherichia coli. The expressed proteins were recognized on Western blots by antibodies in immune green turtle plasma. Phylogenetic studies based on UL26, DNA polymerase, and glycoprotein B revealed that LETV clusters with the alphaherpesviruses.
A dynamic test compaction method on low power test generation based on capture safe test vectors

In at-speed scan testing, capture power is a serious problem because the high power dissipation that can occur when the response for a test vector is captured by flip-flops results in circuit-damaging high temperature and timing errors, which may cause significant capture-induced yield loss. A low capture power test generation method based on fault simulation using capture safe test vectors in an initial test set was proposed to resolve a high capture power problem. In this paper, we propose a dynamic test compaction method on the low capture power test generation to reduce the number of capture-safe test vectors. In the dynamic test compaction, faults to satisfy the following conditions are selected as secondary faults. The conditions are that fault excitation cubes of secondary faults are compatible with that of a primary fault and secondary faults are located in fanout-free regions which are sensitized by a test vector for a primary fault. Experimental results show that this method reduces the number of capture-safe test vectors by 18% on average.
Clarification of Taxonomic Status within the Pseudomonas syringae Species Group Based on a Phylogenomic Analysis

The Pseudomonas syringae phylogenetic group comprises 15 recognized bacterial species and more than 60 pathovars. The classification and identification of strains is relevant for practical reasons but also for understanding the epidemiology and ecology of this group of plant pathogenic bacteria. Genome-based taxonomic analyses have been introduced recently to clarify the taxonomy of the whole genus. A set of 139 draft and complete genome sequences of strains belonging to all species of the P. syringae group available in public databases were analyzed, together with the genomes of closely related species used as outgroups. Comparative genomics based on the genome sequences of the species type strains in the group allowed the delineation of phylogenomic species and demonstrated that a high proportion of strains included in the study are misclassified. Furthermore, representatives of at least 7 putative novel species were detected. It was also confirmed that P. ficuserectae, P. meliae, and P. savastanoi are later synonyms of P. amygdali and that “P. coronafaciens” should be revived as a nomenspecies.
The association between different cognitive domains and age in a multi‐centre study of middle‐aged and older European men

We determined levels of cognitive functioning in community dwelling men aged 40–79 (n = 3265) from eight European centres and investigated to what extent cognitive performance varied between centres, the association between different cognitive domains and age, educational level, co‐morbidity and lifestyle factors and the respective contributions of centre and individual factors to cognitive performance.
Protease‐activated receptor 4: from structure to function and back again

Protease‐activated receptors are a family of four GPCRs (PAR1–PAR4) with a number of unique attributes. Nearly two and a half decades after the discovery of the first PAR, an antagonist targeting this receptor has been approved for human use. The first‐in‐class PAR1 antagonist, vorapaxar, was approved for use in the USA in 2014 for the prevention of thrombotic cardiovascular events in patients with a history of myocardial infarction or with peripheral arterial disease. These recent developments indicate the clinical potential of manipulating PAR function. While much work has been aimed at uncovering the function of PAR1 and, to a lesser extent, PAR2, comparatively little is known regarding the pharmacology and physiology of PAR3 and PAR4. Recent studies have begun to develop the pharmacological and genetic tools required to study PAR4 function in detail, and there is now emerging evidence for the function of PAR4 in disease settings. In this review, we detail the discovery, structure, pharmacology, physiological significance and therapeutic potential of PAR4.
Aromatic Amino Acids Are Critical for Stability of the Bicoid Homeodomain*

The Drosophila Bicoid (Bcd) protein plays a dual role as a transcription and translation factor dependent on the unique DNA and RNA binding properties of the homeodomain (HD). We have used circular dichroism and fluorescence spectroscopy to probe the structure and stability of the Bcd-HD, for which a high resolution structure is not yet available. The fluorescence from the single tryptophan residue in the HD (Trp-48) is strongly quenched in the native state but is dramatically enhanced (∼20-fold) upon denaturation. Similar results were obtained with the Ultrabithorax HD (Ubx-HD), suggesting that the unusual tryptophan fluorescence may be a general phenomenon of HD proteins. We have used site-directed mutagenesis to explore the role of aromatic acids in the structure of the Bcd-HD and to evaluate the proposal that interactions between the strictly conserved Trp residue in HDs and nearby aromatic residues are responsible for the fluorescence quenching in the native state. We determined that both Trp-48 and Phe-8 in the N-terminal region of the HD are individually necessary for structural stability of the Bcd-HD, the latter most likely as a factor coordinating the orientation of the N-terminal helix I and the recognition helix for efficient binding to a DNA target.
Submillimeter‐Wave Cloud Ice Radiometer: Simulations of retrieval algorithm performance

[1] The Submillimeter-Wave Cloud Ice Radiometer (SWCIR), developed by the Jet Propulsion Laboratory to fly on the NASA DC-8, has ten channels from four receivers at 183, 325, 448, and 643 GHz. The SWCIR is designed to retrieve upper tropospheric cloud ice water path (IWP) and median mass equivalent sphere diameter (Dme). This paper describes the retrieval algorithm developed for the SWCIR, results from retrieval simulations, and the rationale for choosing the SWCIR frequencies. The retrieval algorithm uses Bayes theorem to combine prior information about atmospheric properties with radiative transfer simulations. The algorithm uses a precalculated database of stochastic cirrus/atmospheric profiles and corresponding simulated SWCIR brightness temperatures. Statistics of cirrus microphysics are derived from in situ cloud probe data obtained during midlatitude winter and tropical field experiments, and include correlations between temperature, particle size, and ice water content. The Bayesian algorithm effectively interpolates between database cases that approximately match the observed SWCIR brightness temperatures. Retrieval experiments are performed for midlatitude winter ice clouds with the SWCIR viewing downward from 12 km and for tropical anvil cirrus with the SWCIR viewing upward from 10 km. Each experiment simulates SWCIR brightness temperatures (with 1 K added noise) from 10000 random cloud/atmosphere profiles. For clouds with IWP greater than 5 g/m2 (which contain 97% of the simulated total ice mass) the overall median retrieval error is about 30% for IWP and 15% for Dme. The effects of liquid clouds just below ice clouds and of nonspherical ice particle shapes are small.
The CAPM and beta in an imperfect market

T he mean-variance rule formulated by Harry Markowitz [13] and James Tobin [16] is a powerful tool for explaining investor behavior. Nevertheless, the Capital Asset Pricing Model (CAPM) developed on the basis of the pioneering work of Markowitz and Tobin-rests on questionable ground. The basis of the CAPM is, indeed, particularly questionable at the critical point where it argues that the well known beta provides an index of the risk of securities. The CAPM was developed independently by William Sharpe [15], John Lintner [lo], and Jack Treynor [17]. Two basic related properties implied by the CAPM are: (a) that all investors hold in their portfolios all the risky securities available in the market, and (b) that investors hold the risky assets in the same proportions as these assets are available in the market, independent of the individual investors’ preference. ’ This latter property of the CAPM makes it possible to draw many conclusions regarding the equilibrium risk-return relationship of risky assets. Properties (a) and (b) contradict the market experience established in’all empirical research. First, investors differ in their investment strategies and do not necessarily adhere to the same risky portfolio. Second, the typical investor usually does not hold many risky assets in his portfolio. Indeed, in a recent study, Marshall Blume, Jean Crockett, and Irwin Friend [4] found that, in the tax year 1971, individuals held highly undiversified portfolios. The sample, which included 17,056 individual income tax returns, revealed that 34.1% of the individuals held only one stock paying dividends,
A Comprehensive Analysis of Common and Rare Variants to Identify Adiposity Loci in Hispanic Americans: The IRAS Family Study (IRASFS)

Obesity is growing epidemic affecting 35% of adults in the United States. Previous genome-wide association studies (GWAS) have identified numerous loci associated with obesity. However, the majority of studies have been completed in Caucasians focusing on total body measures of adiposity. Here we report the results from genome-wide and exome chip association studies focusing on total body measures of adiposity including body mass index (BMI), percent body fat (PBF) and measures of fat deposition including waist circumference (WAIST), waist-hip ratio (WHR), subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT) in Hispanic Americans (nmax = 1263) from the Insulin Resistance Atherosclerosis Family Study (IRASFS). Five SNPs from two novel loci attained genome-wide significance (P<5.00x10-8) in IRASFS. A missense SNP in the isocitrate dehydrogenase 1 gene (IDH1) was associated with WAIST (rs34218846, MAF = 6.8%, PDOM = 1.62x10-8). This protein is postulated to play an important role in fat and cholesterol biosynthesis as demonstrated in cell and knock-out animal models. Four correlated intronic SNPs in the Zinc finger, GRF-type containing 1 gene (ZGRF1; SNP rs1471880, MAF = 48.1%, PDOM = 1.00x10-8) were strongly associated with WHR. The exact biological function of ZGRF1 and the connection with adiposity remains unclear. SNPs with p-values less than 5.00x10-6 from IRASFS were selected for replication. Meta-analysis was computed across seven independent Hispanic-American cohorts (nmax = 4156) and the strongest signal was rs1471880 (PDOM = 8.38x10-6) in ZGRF1 with WAIST. In conclusion, a genome-wide and exome chip association study was conducted that identified two novel loci (IDH1 and ZGRF1) associated with adiposity. While replication efforts were inconclusive, when taken together with the known biology, IDH1 and ZGRF1 warrant further evaluation.
PTB/nPTB switch: a post-transcriptional mechanism for programming neuronal differentiation.

Neuronal differentiation involves extensive reprogramming of gene expression. Many neuronal-specific genes are actively repressed in nonneuronal cells, while many others are induced in response to cell differentiation cues. Together these constitute the transcriptome in neurons to instruct specific neuronal functions (Rosenfeld et al. 2006). The transcriptome in neurons is further diversified by alternative splicing, arising from the expression of a number of neuronal-specific RNA-binding splicing regulators (Black and Grabowski 2003). In this issue of Genes & Development, Boutz et al. (2007b) report a novel switch in the expression of a pair of related splicing regulators that occurs during neuronal differentiation. These proteins, known as polypyrimidine tractbinding proteins (PTB) and neural PTB (nPTB), are structurally and functionally similar, but PTB is widely expressed in nonneuronal cells, and nPTB is restricted to neurons. Remarkably, ∼25% of neuronally induced alternative splicing events detected by mRNA isoform-sensitive splicing arrays are estimated to result from the down-regulation of PTB, and the up-regulation of its neuronal-specific cousin nPTB.
Risk Factors for Criminal Recidivism in Older Sexual Offenders

Sexual offenders constitute a substantial proportion of the older male prison population. Recent research findings, with potential consequences for risk management, indicate that recidivism risk might be lower in older sexual offenders. We followed up all adult male sexual offenders released from prison in Sweden during 1993–1997 (N=1,303) for criminal reconviction for an average of 8.9 years. We studied rates of repeat offending (sexual and any violent) by four age bands (<25, 25–39, 40–54, and 55+years), and examined whether risk factors for recidivism remained stable across age groups. Results showed that recidivism rates decreased significantly in older age bands. In addition, the effect of certain risk factors varied by age band. These findings on recidivism rates in older sexual offenders concur with studies from the United Kingdom, United States, and Canada and may suggest some generalizability in Western settings. Further research is needed to address underlying mechanisms.
Bad News Does Not Always Travel Fast: Evidence from Chapter 11 Bankruptcy Filings

type="main" xml:id="acfi12063-abs-0001"> This paper examines the stock price performances of 275 non-financial, non-utility U.S. industrial firms that continue trading on the main exchanges after filing for Chapter 11 bankruptcy between 1 October 1979 and 17 October 2005. This paper identifies a negative and statistically significant post-bankruptcy drift that lasts for at least 6 months. This finding adds to the literature showing that the market is unable to process bad public news events in a timely manner. Further analysis suggests that the theoretical model proposed by Hong and Stein (1999) can be used to help explain this market-pricing anomaly.
Tests for interest rate convergence and structural breaks in the EMS

We use a new test for cointegration that allows for structural breaks in the cointegrating relationship to test for bilateral interest rate convergence in the European Monetary System. Contrary to previous studies that employed standard cointegration tests, we find strong evidence for convergence between German nominal interest rates and interest rates in four other EMS countries in the 1979-1995 period.
Aerobic conditioning in patients with mitochondrial myopathies: Physiological, biochemical, and genetic effects

Aerobic training has been shown to increase work and oxidative capacity in patients with mitochondrial myopathies, but the mechanisms underlying improvement are not known. We evaluated physiological (cycle exercise, 31P‐MRS), biochemical (enzyme levels), and genetic (proportion of mutant/wild‐type genomes) responses to 14 weeks of bicycle exercise training in 10 patients with heteroplasmic mitochondrial DNA (mtDNA) mutations. Training increased peak work and oxidative capacities (20–30%), systemic arteriovenous O2 difference (20%), and 31P‐MRS indices of metabolic recovery (35%), consistent with enhanced muscle oxidative phosphorylation. Mitochondrial volume in vastus lateralis biopsies increased significantly (50%) and increases in deficient respiratory chain enzymes were found in patients with Complex I (36%) and Complex IV (25%) defects, whereas decreases occurred in 2 patients with Complex III defects (‐20%). These results suggest that the cellular basis of improved oxygen utilization is related to training‐induced mitochondrial proliferation likely resulting in increased levels of functional, wild‐type mtDNA. However, genetic analysis indicated the proportion of wild‐type mtDNA was unchanged (3/9) or fell (6/9), suggesting a trend toward preferential proliferation of mutant genomes. The long‐term implications of training‐induced increases in mutant relative to wild‐type mtDNA, despite positive physiological and biochemical findings, need to be assessed before aerobic training can be proposed as a general treatment option.
EXPRESSION OF UDP-GLUCURONOSYLTRANSFERASE ISOFORM mRNAS DURING INFLAMMATION AND INFECTION IN MOUSE LIVER AND KIDNEY

Inflammation or infection down-regulates the activity and expression of cytochrome P450 (P450) enzymes involved in hepatic drug clearance, possibly altering drug effectiveness and leading to toxicity. The regulation of UDP-glucuronosyltransferases (UGTs) in inflammation and infection is less well characterized. To determine the response of hepatic and renal UGTs during inflammation and infection, mice were administered either saline or 1 mg/kg lipopolysaccharide (LPS) (16 h), or Citrobacter rodentium by oral gavage (6 days). Hepatic mRNA expression of UGT1A1, 1A9, and 2B5 was similarly down-regulated after LPS exposure and C. rodentium infection, whereas UGT1A2 and 1A6 mRNAs were unchanged. Effects of C. rodentium infection did not require a functional Toll-like receptor 4. Conversely, renal UGT isoforms were relatively unaffected, except for UGT2B5 induction after LPS treatment. Regulation of UGTs during the inflammatory response exhibits similarities to and differences from regulation of P450s, and may be cytokine-mediated.