Miracle-dz/UniFAR-FTUs huggingface dataset:
Multiple inhibitor analysis of the brequinar and leflunomide binding sites on human dihydroorotate dehydrogenase.

Brequinar and the active metabolite of leflunomide, A77 1726, have been clearly shown to inhibit human dihydroorotate dehydrogenase (DHODH), but conflicting mechanisms for their inhibition have been reported. DHODH catalyses the conversion of dihydroorotate (DHO) to orotate concurrent with the reduction of ubiquinone. This study presents data that indicates brequinar is a competitive inhibitor versus ubiquinone; A77 1726 is noncompetitive versus ubiquinone and both are uncompetitive versus DHO. 2-Phenyl 5-quinolinecarboxylic acid (PQC), the core moiety of brequinar also shows competitive inhibition versus ubiquinone. Multiple inhibition experiments indicate that PQC (and thus brequinar) and A77 1726 have overlapping binding sites. Both PQC and A77 1726 are also mutually exclusive with barbituric acid (a competitive inhibitor versus DHO). In addition, we failed to observe brequinar binding to E.orotate by isothermal titration calorimetry (ITC). These results indicate that the E.DHO. inhibitor and E.orotate. inhibitor ternary complexes do not form. The absence of these complexes is consistent with the two-site ping-pong mechanism reported for DHODH. This kinetic data suggests that recent crystal structures of human DHODH complexed with orotate and A77 1726 or brequinar may not represent the relevant physiological binding sites for these inhibitors [Liu, S. , Neidhardt, E. A. , Grossman, T. H. , Ocain, T. , and Clardy J. (2000) Structure 8, 25-33].
Understanding Declining Fluidity in the U.S. Labor Market

In this paper, we first document a clear, downward trend in labor market fluidity that is common across a variety of measures of worker and job turnover. This trend began in the early 1980s, if not somewhat earlier. Next, we present evidence for a variety of hypotheses that might explain this downward trend, which is only partly related to population demographics and is not due to the secular shift in industrial composition. Moreover, this decline in labor market fluidity seems unlikely to have been caused by an improvement in worker–firm matching or by mounting regulatory strictness in the labor or housing markets. Plausible avenues for further exploration include changes in the worker–firm relationship, particularly with regard to compensation adjustment; changes in firm characteristics, such as firm size and age; and a decline in social trust, which may have increased the cost of job searches or made both parties in the hiring process more risk averse.
Experimental Infection of Pigs with Border Disease Virus Isolated from Pyrenean Chamois (Rupicapra Pyrenaica)

Between 2001 and 2007, several outbreaks of disease associated with Border disease virus (BDV) infection were reported in the central Pyrenees (northeast Spain) and were associated with a major reduction in chamois (Rupicapra pyrenaica) populations. At the same time, wild boars (Sus scrofa) from the same area were found to be seropositive to this pestivirus, without showing clinical signs. The present study examines the susceptibility of domestic swine and the course of the infection with a BDV strain isolated from naturally infected chamois. Twenty pigs were inoculated with 1 × 107 TCID50 (50% tissue culture infective dose) by oronasal route, and 16 control pigs received Eagles sterile Minimal Essential Medium. Serologic (enzyme-linked immunosorbent assay and virus neutralization test) and reverse transcription polymerase chain reaction assays were performed on serum samples obtained at 0, 3, 7, 10, 14, 21, and 31 days postinoculation (dpi). All infected pigs were viremic from 3 to 14 dpi. After 14 dpi, all infected animals developed an antibody response against the homologous virus. Clinical signs or histologic lesions were not observed in inoculated pigs. The present work demonstrates the susceptibility of domestic swine to a BDV strain of chamois origin.
Regional inflation, spatial locations and the Balassa-Samuelson effect: Evidence from Japan

We empirically analyse regional inflation using data from Japan where there is no regulation to impede the free movement of labour, capital, goods and services across regions. In particular, our analysis will focus on the geographical location of regions and the productivity (known as the Balassa-Samuelson (BS)) effect as explanations for the dynamics of regional inflation. Based on a spatial model which is consistent with the theoretical specification of the BS, we have confirmed that, while it is a relatively small country in terms of land area, both spatial location and productivity are important determinants of regional inflation.
New epothilone congeners from Sorangium cellulosum strain So0157-2

As a continuous work to find more epothilone congeners produced by the epothilones A and B producing Sorangium cellulosum strain So0157-2 in the large-scale fermentation (5000 L), we reinvestigated the chemical compositions of the fermentation broth. Consequently, two new epothilone variants (1–2) and one new natural epothilone derivative (3) were isolated from the fermentation broth. Their structures were established as 16-ethyl epothilone B (1), 6-desmethyl-16-hydroxymethyl epothilone C (2) and 20-ethyl epothilone A (3), respectively, by an extensive NMR analysis.
Conducting Long-Run Event Studies in Asia-Pacific Security Markets

This paper investigates the robustness of existing long-run event study methodologies using the Asia-Pacific security market data. In doing so, the study employs the buy-and-hold abnormal return approach and the calendar time portfolio method to measure the return anomalies. Since each of these two widely used approaches has a number of potential pitfalls, we also use standardized calendar time approach (SCTA) of Dutta (2015). The empirical analysis shows that all the employed methods are effective in the selected Asia-Pacific security markets. Simulations also show that SCTA documents better specification and power than the conventional methodologies.
Early predictors of adverse left ventricular remodelling after myocardial infarction treated by primary angioplasty.

BACKGROUND Progressive left ventricular dilatation (PLVD) occurs after myocardial infarction (MI), and this may take place in the area of primary percutaneous coronary intervention (PCI). The factors predicting PLVD after primary PCI still need to be clarified. The aim of the study was to assess the prevalence and to define the baseline clinical and echocardiographic predictors of PLVD in patients with STEMI treated by primary PCI. METHODS Of the 90 patients initially selected for the study 88 (29 women and 59 men, mean age 67.1 +/- 5.6 years) with first ST-elevation myocardial infarction (STEMI) treated with primary PCI were examined. Echocardiographic examination was performed in all patients at discharge (M1) and after 6 months (M2). The following factors influencing PLVD were evaluated: type of infarct-related artery (IRA), infarct size expressed as wall motion score index (WMSI) >/= 1.5, left ventricular end-diastolic volume index (LVEDVI) >/= 80 ml/m(2), ejection fraction (EF) </= 45%, restrictive pattern of transmitral flow, time to reperfusion, left ventricular mass index (LVMI) >/= 125 g/m(2) and coronary risk factors. RESULTS The overall prevalence of PLVD (according to the criterion of 20% LVEDVI increase from M1 to M2) was 24%. Univariate regression analysis revealed that the following were the significant baseline M1 predictors of adverse PLVD: left anterior descending as IRA (relative risk: rr = 2.3, p < 0.05), WMSI >/= 1.5 (rr = 4.29, p < 0.005), EF </= 45% (rr = 2.89, p < 0.005) and a restrictive pattern of transmitral flow (rr = 2.4, p < 0.01). Multivariate logistic analysis showed that the only independent determinant of PLVD was WMSI >/= 1.5. CONCLUSIONS Both regional and global left ventricular systolic dysfunction indices as well as severe left ventricular diastolic abnormalities but not left ventricular dilatation at discharge are significant predictors of adverse cardiac remodelling after STEMI in patients treated with primary PCI. However the only independent determinant of PLVD was WMSI >/= 1.5 expressing the infarct size. (Cardiol J 2007; 14: 238-245).
Management of Post-Traumatic Osteomyelitis in the Lower Limb: Current State of the Art

Abstract Osteomyelitis (OM) of the lower limb represents a large unmet global healthcare burden. It often arises from a contiguous focus of infection and is a recognized complication of open fractures or their surgical treatment, arthroplasty, and diabetic foot ulcers. Historically, this debilitating condition is associated with high rates of recurrence and secondary amputation. However, excellent long-term outcomes are now achieved by adopting a multidisciplinary approach with meticulous surgical debridement, skeletal and soft tissue reconstruction, and tailored antimicrobial treatment. This review focuses on the modern evidence-based management of post-traumatic OM in the lower limb from a reconstructive plastic surgery perspective, highlighting the latest developments and areas of controversy.
Dynamics of Pension Reform: The Case of Ontario

Following a decade of pension debate, in order to improve the effectiveness of employment pension plans, the Ontario Government has recently formulated a number of policy initiatives as potential amendments to the Pension Benefits Act of 1965. In this paper the authors undertake a comparative analysis of pension benefits and pension costs associated with these initiatives, as they are added to the "reform package" sequentially, under a number of representative scenarios. Two different modes of analysis are used: (1) a "steady state" analysis of comparing pension benefits and pension costs before the introduction of a reform package with those benefits and costs after the reform package has fully impacted, and (2) a "dynamic" analysis of describing the evolution of pension benefits and costs as the reform package takes effect.
The IMPROVE™ study – a multinational, observational study in type 2 diabetes: baseline characteristics from eight national cohorts

Aims: The IMPROVE™ study is a multinational, open‐label, non‐randomised, 26‐week observational study assessing the safety and effectiveness of biphasic insulin aspart 30 (BIAsp 30) treatment in type 2 diabetes in routine clinical practice. The principal aims of this report were to characterise the baseline population and physicians’ treatment decisions.
Patient-Informant Agreement on Personality Ratings and Self-Awareness after Head Injury

To address concerns about self-awareness deficits and the validity of self-ratings by patients with head injury (HI), the current study examines mean differences and correlations between self-ratings from 52 patients with HI and ratings of the patient by informants using the revised NEO Personality Inventory (NEO-PI-R). Patient self-ratings were significantly lower than informant ratings on neuroticism and extraversion and significantly higher on conscientiousness. Patient-informant correlations ranged from . 42 for conscientiousness to . 67 for agreeableness, and these agreement correlations compare favorably with those obtained from normal adult samples. Hierarchical multiple regression equations for each of the five NEO-PI-R trait domains showed that more severe injuries were associated with higher agreement for extraversion. For all five traits, the strongest predictors of informant personality ratings were the patients' self-ratings. The implications of these findings for clinical assessment and improved research on self-awareness deficits after HI are discussed.
Conservation of polyamine regulation by translational frameshifting from yeast to mammals

Regulation of ornithine decarboxylase in vertebrates involves a negative feedback mechanism requiring the protein antizyme. Here we show that a similar mechanism exists in the fission yeast Schizosaccharomyces pombe. The expression of mammalian antizyme genes requires a specific +1 translational frameshift. The efficiency of the frameshift event reflects cellular polyamine levels creating the autoregulatory feedback loop. As shown here, the yeast antizyme gene and several newly identified antizyme genes from different nematodes also require a ribosomal frameshift event for their expression. Twelve nucleotides around the frameshift site are identical between S.pombe and the mammalian counterparts. The core element for this frameshifting is likely to have been present in the last common ancestor of yeast, nematodes and mammals.
Atopic disorders in ankylosing spondylitis and rheumatoid arthritis

Background: The prevalence of atopic disorders in ankylosing spondylitis (AS) is unknown. AS and rheumatoid arthritis (RA) exhibit divergent T helper (Th) cell cytokine patterns. Objective: To test the hypothesis that Th2 polarised atopic disorders may be decreased in Th1 polarised RA but increased in AS, which is characterised by an impaired Th1 cytokine pattern, by assessing the prevalence of atopic disorders in AS and RA. Methods: 2008 subjects (380 patients with AS, 728 patients with RA, 900 controls) from Berlin, Germany, were considered in this cross sectional study. A questionnaire incorporating questions from the European Community Respiratory Health Service (ECRHS) and the International Study of Asthma and Allergies in Childhood (ISAAC) protocol was mailed to all subjects. Disease severity was assessed by the modified Health Assessment Questionnaire (mHAQ). Results: 1271 (63.3%) people responded to the questionnaire. The prevalence of any atopic disorder was 24.6% (61/248) in patients with AS, 20.7% (111/536) in controls, and 13.1% (64/487) in patients with RA (p=0.0009 for AS v RA; p=0.001 for controls v RA). Hay fever was reported by 40/248 (16.1%) patients with AS, 82/536 (15.3%) controls, and 42/487 (8.6%) patients with RA (p=0.002 for AS v RA; p=0.001 for controls v RA). Atopic dermatitis was reported by 19/248 (7.7%) patients with AS, 26/536 (4.9%) controls, and 14/487 (2.9%) patients with RA (p=0.003 for AS v RA), and asthma by 18/248 (7.3%) patients with AS, 35/536 (6.5%) controls, and 21/487 (4.3%) patients with RA. The differences were related neither to age nor to drugs. Disease severity was less in atopic patients with RA who had the atopic disorder before the onset of RA (median mHAQ 0.75) than in patients in whom RA preceded the atopic disorder (median mHAQ 1.75; p=0.027). Conclusions: Atopic disorders are decreased in RA but only slightly and non-significantly increased in AS. This may imply that atopy confers some protection from RA but only little if any susceptibility to AS. It may further indicate that the cytokine deviation towards an impaired Th1 pattern in AS is less strong than the cytokine deviation towards Th1 in RA, a finding which may affect future therapeutic approaches.
The Incentive to Adopt Cost Reducing Innovation in the Presence of a Non-Linear Demand Curve

The degree to which the structure of an industry rewards the introduction of a process improvement is one consideration which enters into a discussion of the relative merits of monopolistic and competitive industries. There have been conflicting results concerning which industry provides the greater incentive. The incentive to an inventor is the additional profits, resulting from the adoption of the innovation. In the competitive industry a patent or royalty system is established by the government to insure that the inventor is able to appropriate all the profits from the invention. However, in the monopolistic industry it is assumed that the monoplist is the only one capable of the innovation and the subsequent adoption of the innovation. ' Kenneth Arrow demonstrated that "the incentive to invent is less under monopolistic than under competitive conditions. [1, 619]. " This occurs because the profits are initially zero in the competitive industry, while they are positive in the monopolistic industry due to an exploitation of monopoly power. Subsequently, monopoly power is given to the inventor in the competitive industry because the royalty system has been established by the government. This implies that the inventor in the competitive industry is able to reap additional profits, since the inventor would receive the benefits from an exploitation of monoply power as well as from the reduction in cost resulting from the adoption of the new innovation. In a subsequent article Harold Demsetz reversed this conclusion in that "at least in the linear model of two industries of equal output size, the more monopolistic will give the greatest encouragement to invention [4, 19]. " The distinction between Arrow's and Demsetz's results is predicated on Demsetz's assertion that
Prognosis in HIV-1 Infection Predicted by the Quantity of Virus in Plasma

The relation between viremia and clinical outcome in individuals infected with human immunodeficiency virus-type 1 (HIV-1) has important implications for therapeutic research and clinical care. HIV-1 RNA in plasma was quantified with a branched-DNA signal amplification assay as a measure of viral load in a cohort of 180 seropositive men studied for more than 10 years. The risk of acquired immunodeficiency syndrome (AIDS) and death in study subjects, including those with normal numbers of CD4+ T cells, was directly related to plasma viral load at study entry. Plasma viral load was a better predictor of progression to AIDS and death than was the number of CD4+ T cells.
Elevated levels of shed syndecan‐1 correlate with tumour mass and decreased matrix metalloproteinase‐9 activity in the serum of patients with multiple myeloma

Sera from 20 myeloma patients and 12 normal controls were analysed for the presence of syndecan‐1 and matrix metalloproteinase‐9 (MMP‐9). The level of syndecan‐1 in the serum was elevated in 7/20 (35%) myeloma patients whilst 6/19 patients (31%) had decreased serum MMP‐9 activity. The presence of increased syndecan‐1 was associated with decreased serum MMP‐9. Both elevated syndecan‐1 and decreased MMP‐9 were associated with higher marrow plasmacytosis, serum beta‐2 microglobulin and paraprotein levels. These data provide evidence that the syndecan‐1 ectodomain is shed in vivo. Quantitation of serum syndecan‐1 may be a useful measure of tumour mass and may have important implications for myeloma biology.
Drug-eluting stent safety: findings from preclinical studies

After pivotal clinical trials, drug-eluting stents (DES) are now considered the standard of care for the management of acute coronary syndrome. However, late stent thrombosis has emerged as a major concern. Preclinical testing is an important regulatory process that determines the safety and efficacy of devices prior to human clinical trials. Histopathologic analysis following placement of DES has typically been performed in porcine coronary artery models to ensure safety in these devices. The recently issued consensus report from the US FDA, for the approval of DES recommends the use of the porcine model for the safety assessment of these devices in the vascular bed for which they are intended. Other models are also recommended, as vascular responses to stents are much slower in man than in animals, and no animal truly elicits the response seen in humans. The rabbit iliac artery can provide further data, especially regarding endothelialization, which is slower in the rabbit model than in the porcine model. Furthermore, inflammation is not as extensive in the rabbit and may thus be a closer model of humans than the porcine models. The FDA recognizes that it may be more appropriate to test these devices in atherosclerosis. The choice of animal model may mask the serious drawbacks of the devices; therefore, we suggest the use of both models to understand the healing following DES implantation, with emphasis on endothelialization, inflammation and neointimal formation and, whenever possible, to complement the observations in the environment of atherosclerosis.
Clinical anatomy and significance of the thoracic intervertebral foramen: A cadaveric study and review of the literature

Introduction: The literature is lacking information on the anatomy and the osseous dimensions of the thoracic intervertebral foramen (IVF). We describe the anatomy of the broader area, and we proceed with morphometric data of the vertebrae and the foramina. Depiction of these features is provided with imaging and illustrations. The purpose of this paper is to survey and present the anatomy of the foramen as a whole and provide baseline statistical data. Materials and Methods: We review relevant literature, and we present data obtained from skeletal samples of known population and sex. One hundred and nineteen thoracic vertebrae of ten cadaveric spines from the prefecture of Eastern Macedonia and Thrace, Greece, were selected. Statistical analysis measuring the vertical height and the foraminal width of each vertebra was made in accordance with sex. Results: No statistically important differences referring to the descriptive data of both sexes were found. However, statistically, important positive correlation between the vertebral height and the foraminal width was observed, especially for men. The components of the foramen including arteries and veins passing through or neighboring it, and the spinal nerves and roots are described and depicted. Conclusions: The osseous thoracic IVF reveals a glimpse of the in vivo structure and alterations of its width may be present in back pain and other degenerative diseases. Although it is crucial for surgeries and other interventional procedures of the thoracic spine, little is known about the precise anatomy and dimensions of this anatomical landmark.
State-of-the-art vitamin D assays: a comparison of automated immunoassays with liquid chromatography-tandem mass spectrometry methods.

BACKGROUND Vitamin D testing is increasing worldwide. Recently several diagnostic manufacturers including Abbott and Siemens have launched automated 25-hydroxy vitamin D (25OH-D) immunoassays. Furthermore, preexisting assays from DiaSorin and Roche have recently been modified. We compared the performance of 5 automated immunoassays, an RIA and 2 liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods. METHODS Aliquots of 170 randomly selected patient samples were prepared and 25OH-D was measured by 2 LC-MS/MS methods, an RIA (DiaSorin), and automated immunoassays from Abbott (Architect), DiaSorin (LIAISON), IDS (ISYS), Roche (E170, monoclonal 25OH-D(3) assay), and Siemens (Centaur). Within-run and between-run imprecision were evaluated by measurement of 5 replicates of 2 serum pools on 5 consecutive days. RESULTS The LC-MS/MS methods agreed, with a concordance correlation coefficient (CCC) of 0.99 and bias of 0.56 μg/L (1.4 nmol/L). The RIA assay showed a performance comparable to LC-MS/MS, with a CCC of 0.97 and a mean bias of 1.1 μg/L (2.7 nmo/L). All immunoassays measured total 25OH-D (including D(3) and D(2)), with the exception of the Roche assay (D(3) only). Among the immunoassays detecting total 25OH-D, the CCCs varied between 0.85 (Abbott) to 0.95 (LIAISON). The mean bias ranged between 0.2 μg/L (0.5 nmol/L) (LIAISON) and 4.56 μg/L (11.4 nmol/L) (Abbott). The Roche 25OH-D(3) assay demonstrated small mean bias [-2.7 μg/L (-6.7 nmol/L)] [-2.7 μg/L (-6.7 nmol/L)] but a low CCC of just 0.66. Most assays demonstrated good intra- and interassay precision, with CV <10%. CONCLUSIONS Automated immunoassays demonstrated variable performance and not all tests met our minimum performance goals. It is important that laboratories be aware of the limitations of their assay.