Miracle-dz/UniFAR-FTUs huggingface dataset:
Nitrogenase metalloclusters: structures, organization, and synthesis

The catalyst for this reaction is nitrogenase, a metalloenzyme which comprises two component proteins usually referred to as Fe protein and MoFe protein. These designations originate from the metal compositions of the respective component proteins of the conventional, Mo-dependent nitrogenase. Namely, the Fe protein is a Y2 homodimer (Mr 60,000; encoded by nifH) which contains 4 Fe atoms organized into a single Fe4S4 cluster, whereas the MoFe protein is an (r2 heterotetramer (Mr 250,000; encoded by nifDK) which contains 30 Fe atoms and 2 Mo atoms organized into two pairs of novel metalloclusters, called P clusters and FeMo-cofactors. Alternative nitrogenases which do not contain Mo, but which are otherwise structurally and functionally quite similar to the conventional Mo-containing nitrogenase, have also been described (for a review, see reference 2). During catalysis, electrons are delivered one at a time from the Fe protein to the MoFe protein in a gated process involving the association and dissociation of the component proteins and the hydrolysis of at least two MgATP molecules for each electron transfer. These features are schematically shown in Fig. 1. Because the Fe protein is the obligate electron donor to the MoFe protein, which in turn contains the sites for substrate reduction, the individual component proteins are sometimes designated dinitrogenase reductase and dinitrogenase, respectively ( 13). It has been known for many years that the nitrogenase metalloclusters play critical roles in electron transfer and substrate reduction. Thus, elucidation of the structures, organization, and biosynthesis of these metalloclusters and determination of their specific functions in electron transfer and substrate reduction have represented major challenges in nitrogen fixation research. Recent reports on the crystallographic structures of the nitrogenase component proteins and their metalloclusters are significant advances in this area of research (3, 4, 6, 12, 28, 29, 35, 39). These structures now provide a basis for a more sophisticated evaluation of several decades' worth of biophysical, biochemical, and genetic investigations and also permit
Mitral Valve Reconstruction and Mitral Valve Replacement for Ischemic Mitral Insufficiency

Abstract Background: Patients with ischemic mitral incompetence have a high operative risk whether the valve is repaired or replaced. The advantage of repair over replacement is unclear in this group of patients. Methods: Between April 1986 and December 1994, 232 patients underwent surgery for ischemic mitral valve insufficiency; mitral valve replacement was performed in 98 of them. Operative mortality was 13.3%. The actuarial survival rate after 5 years was 73.3%. The surgical risk in patients whose left ventricular ejection fraction (LVEF) was 10%‐30% (operative mortality 50.0%) was higher than in those whose LVEF was greater than 30%. Valve reconstruction was performed in 102 patients. Operative mortality in this patient group was 14.7%. The surgical risk in patients whose LVEF was 30% was higher (operative mortality 42.9%). Results: The total actuarial survival rate of all patients was 64.4% after 5 years. Mortality during follow‐up was higher in patients with residual mitral valve insufficiency greater than grade I after mitral valve reconstruction. Twenty‐four patients with severly impaired left ventricular function underwent heart transplantation. Operative mortality in this group was 12.5%. Eight patients received left ventricular aneurysmectomy in addition to valve surgery, three of them died early. Conclusions: We conclude that patients with highly impaired left ventricular function and ischemic mitral insufficiency are at too great a risk for either valve reconstruction or replacement. Cardiac transplantation should be considered for this patient group. However, patients with ischemic mitral insufficiency and moderately impaired left ventricular function can undergo valve reconstruction or replacement with an acceptable prognosis. The goal of mitral valve reconstruction should be reducing mitral valve insufficiency to at least grade I. If this is not achieved, the prognosis after repair is worse than after valve replacement, therefore, the surgeon should replace the valve without delay.
More on ascitic fluid analysis

My recent review of pharmacogenetics (1) quoted a misleading statement that a block in the metabolism of encainide would result in an absence of pharmacological effects from the drug. This statement, originally made in a paper from the United Kingdom ( 2 ) , indicated that the poor metabolizer phenotype is resistant to the antiarrhythmic effects of encainide because pharmacological activity resides in the principal metabolites of encainide rather than in the parent drug. As shown recently (3), the facts are that at sufficiently high plasma concentrations, encainide itself exerts antiarrhythmic effects (3) . Antiarrhythmic activity occurs even in the poor metabolizer phenotype, albeit at several-fold higher plasma concentrations than usually develop in the extensive metabolism phenotype ( 3 ) . Because these observations were published recently, after my review on pharmacogenetics was submitted, it is important to update the matter and indicate that encainide can be used effectively in the poor metabolizer phenotype.
Glycosphingolipids as Novel Targets for T-Cell Suppression by the B Subunit of Recombinant Heat-Labile Enterotoxin

ABSTRACT Heat-labile enterotoxin subunit B (LTB) is a noncatalytic protein derived from Escherichia coli that binds to ganglioside GM1, a glycosphingolipid on the surface of mammalian cells. In this study, the effects of recombinant LTB (rLTB) on murine lymphocytes were examined in vitro. T and B cells readily bound fluorescein isothiocyanate-labeled rLTB. CD8+ T cells bound twice as much as CD4+ T cells and B cells. Exposure of T-cell subsets and B cells to rLTB abrogated mitogen-driven proliferation. CD8+ T cells were more susceptible to rLTB than either CD4+ T cells or B cells. There were differences in the sensitivity of lymphocytes from various strains of mice to rLTB. This was attributed to qualitative and quantitative differences in the CD4+ T cells. rLTB induced apoptosis in both T-cell subsets, but the level was significantly higher in CD8+ T cells. Apoptosis peaked at around 8 h after exposure to rLTB and incubation at 37°C. Binding to ganglioside GM1 was essential for suppression, since rLTB/G33D, a mutant which does not bind GM1, failed to inhibit proliferation or induce apoptosis. Naive T cells, which were acutely sensitive to rLTB, became more resistant after activation. Conversely, activated T cells regained their sensitivity to rLTB when they reverted back to a resting state. A 1-h pulse with rLTB was sufficient to inhibit T-cell proliferation and cytotoxic-T-lymphocyte generation in primary mixed lymphocyte reaction cultures. CD8+ T cells were preferentially depleted in these cultures. rLTB also induced functional modifications in T cells as indicated by inhibition of gamma interferon secretion after polyclonal activation. Thus, rLTB may have immunomodulatory properties independent of its ability to induce apoptosis.
CONVERGENCE OR CAPABILITIES? EXPLAINING FIRM HETEROGENEITY IN LEARNING BY EXPORTING

An interesting theoretical debate arises with respect to learning-by-exporting when considering macro-economic convergence and firm capability arguments side-by-side. Convergence theory intimates that technologically lagging firms stand to benefit most from exporting because exposure to the advanced technological knowledge in foreign markets allows them to make up for the disparity in capabilities and close the gap with their technologically endowed counterparts. By contrast, the capabilities literature posits that technologically superior firms stand to benefit most from trade since they are better equipped to translate knowledge inputs derived from foreign markets into innovative outcomes. In this paper, we focus on the effect of exporting on innovation and empirically explore whether technologically leading or lagging firms benefit disproportionately. Using a sample of Spanish manufacturing firms from 1990-1997, we empirically investigate how exporting differentially influences the patent output of technologically leading and lagging firms. We find that exporting is associated with the ex post increase in innovative productivity for both technologically leading and lagging firms. Moreover, the results provide support for the firm capability claim. Notably, technologically leading firms apply for more patents subsequent to exporting than technologically lagging firms.
Simulation of a Microturbine Generation System for Grid Connected and Islanding Operations

This paper presents the modeling and simulation of a high-speed single-shift micro turbine generation system. This unit has four parts: a compressor-turbine, a permanent magnet generator, a three phases bridge rectifier and inverter. The model is built from the dynamics of each part with their interconnections, and two different control strategies suitable respectively for isolated and grid-connected operation were developed. Finally, simulation studies have been carried out under a stepped load. The model is developed in the MATLAB/Simulink (Matlab 2007a) and implemented in power system toolboxes. This model is a useful tool for studying the various operational aspects of micro turbines.
Effects of leg resistance training on arterial function in older men

Background: Little information is available on the effect of strength training on vascular function, particularly in older people. Objective: To determine the effect of resistance training on arterial stiffness and endothelial function in older adults. Method: Eleven healthy men (mean (SEM) age 64 (1) years) performed 12 weeks of resistance training involving knee flexion and extension (three sets a day, two days a week). Results: Resistance training increased maximal muscle power by 16% (p<0.0001). Arterial stiffness as assessed by aortic pulse wave velocity did not change with resistance training. Plasma concentration of nitric oxide (NO), measured as its stable end product (nitrite/nitrate), had increased (p<0.05) after resistance training (61.2 (10.4) v 39.6 (3.2) μmol/l). There was no change in plasma concentration of endothelin-1. Conclusion: The results suggest that short term resistance training may increase NO production without stiffening central arteries in healthy older men.
Some drinking-water disinfectants and contaminants, including arsenic. Monographs on chloramine, chloral and chloral hydrate, dichloroacetic acid, trichloroacetic acid and 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone.

No specific studies on chlorinated drinking-water are available in the literature. However, a number of studies that address the risk of several cancers associated with drinking-water also evaluate the risk linked to chlorinated compounds, and are described below. 1. Cohort studies Wilkins and Comstock (1981) (Tables 1 and 2) followed up 14 553 men and 16 227 women over 25 years of age, who were residents of Washington County, MD (USA), using data from a census conducted in 1963. Cancer incidence and mortality rates in 1963–75 were assessed in two subcohorts: people who were exposed to chlorinated surface water (average chloroform concentration, 107 µg/L) and those who used water from deep wells that had not been chlorinated. After adjusting for potential confounders, incidence rates were reported for several subsites of cancer. A slightly elevated but non-significant risk for urinary bladder cancer was observed for both men and women. There were no differences in risk for cancers of the kidney or liver between exposed and non-exposed cases, but a risk for liver cancer was suggested in women. Koivusalo et al. (1997) (Tables 1 and 2) reported a historical cohort study of 621 431 persons in 56 towns in Finland with different water sources and practices of water treatment and thus different levels of exposure to chlorination by-products. The cohort was restricted to persons who, in 1970, were living in their town of birth. Information from 1970 onwards on occupation, migration, death, place of residence and water-pipe connection was obtained from Statistics Finland. Cancer incidence for 26 organ sites among these individuals in 1971–93 was ascertained by record linkage with the Finnish National Cancer Registry.
Open or Laparoscopic Living Donor Liver Hepatectomy: Still a Challenging Operation!

I would like to thank our colleagues because they allow us to clarify a very important concept (1). Donor safety is indeed the major concern independent of laparoscopic or open approach. Even an open approach and the presence of anatomical variations can be a challenging procedure as we highlighted in our article. The development of laparoscopic liver surgery in general was not with the aim of esthetic result or less pain but with the aim of reducing the rate of complications.
[A prospective study of FOLFOX7 scheme as neoadjuvant chemotherapy for stage III gastric adenocarcinoma].

OBJECTIVE To evaluate the efficacy and safety of FOLFOX7 scheme as neoadjuvant chemotherapy in patients with stage III gastric adenocarcinoma. METHODS From May 2005 to May 2007, 27 patients with stage III gastric adenocarcinoma were given neoadjuvant chemotherapy with FOLFOX7 scheme. Gastroscopy, endoscopic ultrasonography, abdominal B ultrasonography and abdominal CT was taken before chemotherapy and after 2 - 4 cycles of neoadjuvant chemotherapy to evaluate the objective response rate of the tumor. Then operations were carried out and the pathological responses was evaluated in those cases. The safety, objective response rate and pathological rate of neoadjuvant chemotherapy was assessed according to NCI-CTC v3.0, RECIST 2000, and the criteria established by Japanese Research Society for Gastric Cancer, respectively. R0 resection rate and surgery-related complications was also assessed in this group. RESULTS The treatment was well tolerated, no grade 3 - 5 toxicity was observed. Complete response was obtained in 1 case, and partial response in 18 patients, overall response rate was 70.4% (19/27). Twenty-six patients received operation and R0 resection rate was 88.4% (23/26); no patient died in the perioperative period. The pathological response rate of patients had R0 excision was 60.9% (14/23). CONCLUSION FOLFOX7 scheme as neoadjuvant chemotherapy for selected patients with stage III gastric adenocarcinoma can be well tolerated, it could induce tumor down-staging and improve R0 resection rate, although the long term efficacy remains to be evaluated.
Uptake of transforming DNA in Gram‐positive bacteria: a view from Streptococcus pneumoniae

In a working model for the uptake of transforming DNA based on evidence taken from both Bacillus subtilis and Streptococcus pneumoniae, the ComG proteins are proposed to form a structure that provides access for DNA to the ComEA receptor through the peptidoglycan. DNA would then be delivered to the ComEC–ComFA transport complex. A DNA strand would be degraded by a nuclease, while its complement is pulled into the cell by ComFA through an aqueous pore formed by ComEC. The nuclease is known in S. pneumoniae only as EndA. We have examined the processing (i.e. binding, degradation and internalization) of DNA in S. pneumoniae strains lacking candidate uptake proteins. Mutants were generated by transposon insertion in endA, comEA/C, comFA/C, comGA and dprA. Processing of DNA was abolished only in a comGA mutant. As significant binding was measured in comEA mutants, we suggest the existence of two stages in binding: surface attachment (abolished in a comGA mutant) required for and preceding deep binding (by ComEA). Abolition of degradation in comGA and comEA mutants indicated that, despite its membrane location, EndA cannot access donor DNA by itself. We propose that ComEA is required to deliver DNA to EndA. DNA was still bound and degraded in comEC and comFA mutants. We conclude that recruitment of EndA can occur in the absence of ComEC or ComFA and that EndA is active even when the single strands it produces are not pulled into the cell. Finally, inactivation of dprA had no effect on the internalization of DNA, indicating that DprA is required at a later stage in transformation.
A Bayesian partition model for case‐control studies on highly polymorphic candidate genes

We present a new statistical model for the analysis of case‐control or cohort studies examining a highly polymorphic candidate disease susceptibility gene. Many genotypes are possible for such a gene. Consequently, the average number of subjects having each genotype will be modest. If analyzed separately, the risks associated with most genotypes will be estimated imprecisely. Our Bayesian partition model clusters genotypes according to risk, only allowing partitions that satisfy a particular assumption about the joint effect of the two alleles making up a genotype. This assumption is genetically plausible, imposes structure on the set of genotype risks, and still leaves a highly flexible model. By Bayesian model averaging over partitions, the model becomes, in effect, a semiparametric model for genotype risk. It allows borrowing of strength, i.e., estimates of risk for one genotype are informed by the risk estimates of all the genotypes. We present the results of fitting the model to two datasets, one simulated and one genuine case‐control study of the NAT1 gene and lung cancer, and compare it in a simulation study with a haplotype relative risk model. The partition model enables genotype risks to be estimated more accurately and the alleles to be ranked according to risk. Genet. Epidemiol. 22:356–368, 2002. © 2002 Wiley‐Liss, Inc.
Diurnal variation of choroidal thickness in normal, healthy subjects measured by spectral domain optical coherence tomography.

PURPOSE To describe the pattern and magnitude of diurnal variation of choroidal thickness (CT), its relation to systemic and ocular factors, and to determine the intervisit reproducibility of diurnal patterns. METHODS A prospective study was conducted on 12 healthy volunteers who each underwent sequential ocular imaging on two separate days at five fixed, 2-hour time intervals. Spectral domain optical coherence tomography (OCT) with enhanced depth imaging and image tracking was performed using a standardized protocol. Choroidal and retinal thicknesses were independently assessed by two masked graders. CT diurnal variation was assessed using repeated-measures ANOVA. RESULTS A significant diurnal variation in CT was observed, with mean maximum CT of 372.2 μm, minimum of 340.6 μm (P < 0.001), and mean diurnal amplitude of 33.7 μm. Retinal thickness (mean, 235.0 μm) did not exhibit significant diurnal variation (P = 0.621). The amplitude of CT variation was significantly greater for subjects with thicker morning baseline CT compared with those with thin choroids (43.1 vs. 10.5 μm, P < 0.001). There were significant correlations between amplitude of CT and age (P = 0.032), axial length (P < 0.001), and spherical equivalent (P < 0.001). The change in CT also correlated with change in systolic blood pressure (P = 0.031). Comparing CT on two different days, a similar diurnal pattern was observed, with no significant difference between corresponding measurements at the same time points (P = 0.180). CONCLUSIONS There is significant diurnal variation of CT, with good intervisit reproducibility of diurnal patterns on two different days. The amplitude of variation varies with morning baseline CT, and is correlated with age, axial length, refractive error, and change in systolic blood pressure.
Vitamin D3 Supplemental Treatment for Mania in Youth with Bipolar Spectrum Disorders.

OBJECTIVE We aimed to determine the effect of an open-label 8 week Vitamin D3 supplementation on manic symptoms, anterior cingulate cortex (ACC) glutamate, and γ-aminobutyric acid (GABA) in youth exhibiting symptoms of mania; that is, patients with bipolar spectrum disorders (BSD). We hypothesized that an 8 week Vitamin D3 supplementation would improve symptoms of mania, decrease ACC glutamate, and increase ACC GABA in BSD patients. Single time point metabolite levels were also evaluated in typically developing children (TD). METHODS The BSD group included patients not only diagnosed with BD but also those exhibiting bipolar symptomology, including BD not otherwise specified (BD-NOS) and subthreshold mood ratings (Young Mania Rating Scale [YMRS] ≥8 and Clinical Global Impressions - Severity [CGI-S] ≥3). Inclusion criteria were: male or female participants, 6-17 years old. Sixteen youth with BSD exhibiting manic symptoms and 19 TD were included. BSD patients were asked to a take daily dose (2000 IU) of Vitamin D3 (for 8 weeks) as a supplement. Neuroimaging data were acquired in both groups at baseline, and also for the BSD group at the end of 8 week Vitamin D3 supplementation. RESULTS Baseline ACC GABA/creatine (Cr) was lower in BSD than in TD (F[1,31]=8.91, p=0.007). Following an 8 week Vitamin D3 supplementation, in BSD patients, there was a significant decrease in YMRS scores (t=-3.66, p=0.002, df=15) and Children's Depression Rating Scale (CDRS) scores (t=-2.93, p=0.01, df=15); and a significant increase in ACC GABA (t=3.18, p=0.007, df=14). CONCLUSIONS Following an 8 week open label trial with Vitamin D3, BSD patients exhibited improvement in their mood symptoms in conjunction with their brain neurochemistry.
Current strategies for knee cartilage repair

Defects in knee articular cartilage (AC) can cause pain and disability and present the clinician with an extremely challenging clinical situation. This article describes the most up‐to‐date surgical techniques that aim to repair and/or regenerate symptomatic focal defects in AC, which include arthroscopic debridement, microfracture bone marrow stimulation and autologous osteochondral allografting, with an emphasis on autologous chondrocyte implantation. In the future, refinement of tissue‐engineering approaches promises to further improve outcome for these patients.
p75NTR-dependent Rac1 activation requires receptor cleavage and activation of an NRAGE and NEDD9 signaling cascade

ABSTRACT The p75 neurotrophin receptor (p75NTR, also known as tumor necrosis factor receptor superfamily member 16) is implicated in diverse cellular events, but fundamental aspects of its signaling mechanisms remain unclear. To address this, we have established a novel bioassay to characterize signaling cascades activated by p75NTR. We show that in COS7 cells, p75NTR expression causes a large increase in cell surface area that relies on the activation of Rac1, and we demonstrate that the p75NTR-dependent COS7 phenotype is dependent on ADAM17- and &ggr;-secretase-dependent cleavage of p75NTR and generation of the p75NTR intracellular domain (p75NTRICD). We show that the p75NTR adaptor protein NRAGE (also known as MAGED1) acts downstream of the p75NTRICD in this cascade and, through a yeast two-hybrid screen, identify NEDD9, a Cas family adaptor protein, as a novel NRAGE-binding partner that mediates p75NTR-dependent Rac1 activation and cell spreading. Our results demonstrate a crucial role for p75NTR cleavage in small GTPase activation and define a novel Rac1 activation pathway involving the p75NTRICD, NRAGE and NEDD9.