Miracle-dz/UniFAR-FTUs huggingface dataset:
Loss of T cell progenitor checkpoint control underlies leukemia initiation in Rag 1-deficient NOD mice

NOD mice exhibit major defects in the earliest stages of T cell development in the thymus. Genome-wide genetic and transcriptome analyses were used to investigate the origins and consequences of an early T cell developmental checkpoint breakthrough in Rag1-deficient NOD mice. QTL analysis mapped the presence of checkpoint breakthrough cells to several known NOD diabetes susceptibility regions, particularly Idd9/11 on chromosome 4, suggesting common genetic origins for T cell defects affecting this trait and autoimmunity. Genome-wide RNA deepsequencing of NOD and B6 Rag1-deficient thymocytes revealed the effects of genetic background prior to breakthrough, as well as the cellular consequences of the breakthrough. Transcriptome comparison between the two strains showed enrichment in differentially expressed signal transduction genes, prominently tyrosine kinase and actin-binding genes, in accord with their divergent sensitivities to activating signals. Emerging NOD breakthrough cells aberrantly expressed both stem cell-associated proto-oncogenes, such as Lmo2, Hhex, Lyl1, and Kit which are normally repressed at the commitment checkpoint, and post-β-selection checkpoint genes including Cd2 and Cd5. Co-expression of genes characteristic of multi-potent progenitors and more mature T cells persists in the expanding population of thymocytes, and in the thymic leukemias that emerge with age in these mice. These results show that Rag1-deficient NOD thymocytes have T cell defects that can collapse regulatory boundaries at two early T cell checkpoints, which may predispose them to both leukemia and autoimmunity.
Deposited in DRO : 20 July 2015 Version of attached le : Published Version Peer-review status of attached

Placental invasiveness—the number of maternal tissue layers separating fetal tissues from maternal blood—is variable across mammalian species. Although this diversity is likely to be functionally important, variation in placental invasiveness remains unexplained. Here we test the hypothesis that increased risk of transplacental transmission of pathogens from the mother to the fetus promotes the evolution of non-invasive placentation, the most likely derived condition in eutherian mammals. Specifically, we predict that non-invasive placentation is associated with increased microparasite species richness relative to more invasive placental types, based on the assumption that higher numbers of microparasites in a population reflects greater risk of transplacental transmission to fetuses. As predicted, higher bacteria species richness is associated with non-invasive placentation. Protozoa species richness, however, shows the opposite pattern. Because invasive placentae facilitate the transfer of maternal antibodies to the fetus, we propose that the ancestral condition of invasive placentation is retained under selection for protection of newborns from higher risk of postnatal protozoan infection. Hence, our findings suggest that a tradeoff exists between protection against bacterial infection prenatally and protozoan infection postnatally. Future studies are needed to investigate how maternal prevalence of infection and the relative preversus postnatal risk of fetal infection by different microparasite groups vary among mammalian hosts in relation to placental invasiveness.
Análisis de asociación de los polimorfismos -725C>G (rs1233334), -201G>A (rs1233333) y 14 bp deleción/inserción (14-pb del/ins) (rs66554220) del gen HLA-G en mujeres mexicanas con pérdida gestacional recurrente

RESUMEN Antecedentes: El antigeno leucocitario humano (HLA)-G es una molecula inmunomoduladora que contri-buye a la aceptacion del feto semialogenico. Algunos polimorfismos de un solo nucleotido (SNP) en las regiones no codificantes del gen HLA-G inducen a la disminucion de moleculas HLA-G, lo cual contribuye a complicaciones en el embarazo, tales como la preeclampsia o perdida gestacional recurrente. Objetivo: Analizar la asociacion de los polimorfismos -725C>G (rs1233334), -201G>A (rs1233333) y 14 bp delecion/insercion (14-pb del/ins) (rs66554220) del gen HLA-G en mujeres mexicanas con PGR. Metodos: Los polimorfismos -725C>G (rs1233334), -201G>A (rs1233333) y 14-pb del/ins (rs66554220) se identificaron por medio de PCR-SSOP (Polymerase Chain Reaction–sequence-specific oligonucleotide probe) y PCR (Polymerase Chain Reaction), respectivamente, en 58 mujeres con perdida gestacional recurrente (≥ 2 abortos), sin factores de riesgo identificables y 56 mujeres fertiles no relacionadas (≥ 2 nacidos vivos). Resultados: El polimorfismo -725C>G (rs1233334) presento diferencias significativas entre los grupos de estudio pero no se asocio con PGR (p=0,02601; OR=11,484; IC95%=0,617-213,659). Los polimorfismos -201G>A (rs1233333) y 14-pb del/ins (rs66554220) no se distribuyeron de manera diferente entre los grupos de estudio ni se asociaron con perdida gestacional recurrente. Los polimorfismos analizados se encontraron en equilibrio de ligamiento (D’>0,3563; r
On the Investment-Uncertainty Relationship in a Real Option Model with Stochastic Volatility

We consider the classical investment timing problem in a framework where the instantaneous volatility of the project value is itself given by a stochastic process, hence lifting the old question about the investment–uncertainty relationship to a new level. Motivated by the classical cases of Geometric Brownian Motion (GBM) and Geometric Mean Reversion (GMR), we consider processes of similar functional form, but with Heston stochastic volatility replacing the constant volatility in the classical models. We refer to these processes as Heston-GBM and Heston-GMR. For these cases we derive asymptotic solutions for the investment timing problem using the methodology introduced by Fouque et al. (2000). In particular we show that compared to the classical cases with constant volatility, the question of whether additional stochastic volatility increases or decreases the investment threshold depends on the instantaneous correlation between the project value and the stochastic volatility. For the case of Heston-GBM we provide a closed form expression that measures this effect quantitatively; for the case of Heston-GMR we derive the sign of the effect analytically, using a type of maximum principle for ODEs. Various numerical examples are discussed and a comparative analysis is provided.
Association of a common genetic variant in prostate stem‐cell antigen with gastric cancer susceptibility in a Korean population

A recent genome wide association study (GWAS) indentified a significant association between rs2294008 (C > T) polymorphism in prostate stem‐cell antigen (PSCA) and increased risk of gastric cancer in Japanese and Korean populations. The aim of this study was to determine whether rs2294008 polymorphism is associated with risk of gastric cancer in a Korean population. We conducted a large‐scale case–control study of 3,245 gastric cancer patients and 1,700 controls. The frequencies of the CC, CT, and TT genotypes of rs2294008 polymorphism were 17.8%, 49.9%, and 32.3% in the gastric cancer patients; and 24.4%, 48.1%, and 27.5% in the controls, respectively. We found that the CT and TT genotypes were associated with a significantly increased risk of gastric cancer (ORCT = 1.50, 95% confidence intervals, 95% CI: 1.28–1.76; ORTT = 1.71, 95% CI: 1.43–2.04), compared with the CC genotype. Further, stratified by tumor location and histological type, the effect of the rs2294008 T allele was larger in cardia (ORTT = 2.62, 95% CI = 1.42–4.85) than non‐cardia (ORTT = 1.67, 95% CI = 1.40–2.00), in diffuse‐type (ORTT = 2.00, 95% CI: 1.55–2.59) than in intestinal‐type (ORTT = 1.51, 95% CI: 1.22–1.86). Our study showed that rs2294008 in the PSCA gene was associated with increased risks of gastric cancer in a Korean population, suggests that rs2294008 might play an important role in gastric carcinogenesis. © 2011 Wiley Periodicals, Inc.
Risk Factors for Suicide and Attempted Suicide among Young People

Objective: Suicide rates in young people have increased during the past three decades, particularly among young males, and there is increasing public and policy concern about the issue of youth suicide in Australia and New Zealand. This paper summarises current knowledge about risk factors for suicide and suicide attempts in young people. Method: Evidence about risk factors for suicidal behaviour in young people was gathered by review of relevant English language articles and other papers, published since the mid-1980s. Results: The international literature yields a generally consistent account of the risk factors and life processes that lead to youth suicide and suicide attempts. Risk factor domains which may contribute to suicidal behaviour include: social and educational disadvantage; childhood and family adversity; psychopathology; individual and personal vulnerabilities; exposure to stressful life events and circumstances; and social, cultural and contextual factors. Frequently, suicidal behaviours in young people appear to be a consequence of adverse life sequences in which multiple risk factors from these domains combine to increase risk of suicidal behaviour. Conclusions: Current research evidence suggests that the strongest risk factors for youth suicide are mental disorders (in particular, affective disorders, substance use disorders and antisocial behaviours) and a history of psychopathology, indicating that priorities for intervening to reduce youth suicidal behaviours lie with interventions focused upon the improved recognition, treatment and management of young people with mental disorders.
Effect of Slaughtering Methods on Meat Quality Indicators , Chemical Changes and Microbiological Quality of Broiler Chicken Meat during Refrigerated Storage

Slaughtering is a process of bringing an animal to a quick painless death. It involves throat cutting for maximum blood drainage and the amount of blood retained is dependent on the method of slaughter. This study investigated the effect of slaughtering method (Halal and Chinese methods) on meat quality indicators and shelf life of broiler chicken breast meat. Quality indicators such as pH, drip loss and colour (L*, a*, b*) were significantly (P˂0.05) higher for birds slaughtered with the Chinese method (pH= 6.17, L*= 56.42, a*= 8.36, b*= 19.2, drip loss= 0.58) than the halal method. There were no differences in cook loss, thaw loss and toughness obtained from both slaughtering methods. Iron (Fe) content for birds slaughtered using Chinese method was 13.77 mg/kg which was significantly higher than those slaughtered using the halal method (10.00 mg/kg). The haem iron content were 2.55 and 3.25 mg/100g sample respectively for birds slaughtered using both halal and Chinese methods and this decreased during storage at 4 0 C for 9 days. Higher microbial count after 9 days of refrigerated storage (6.28 cfu/g) were recorded for birds slaughtered using Chinese method as compared with the halal method (5.05 cfu/g). Results from this study indicate that method of slaughter for poultry significantly affects the quality and shelf life of meat produced.
A Scalable FPGA-Based Accelerator for High-Throughput MCMC Algorithms

Markov Chain Monte Carlo (MCMC) algorithms are used to obtain samples from any target probability distribution and are widely used in stochastic processing techniques. Stochastic processing techniques such as machine learning and image processing need to compute large amounts of data in real-time, thus high throughput MCMC samplers are of utmost importance. Parallel Tempering (PT) MCMC has proven better mixing and convergence for high-dimensional and multi-modal distributions compared to other popular MCMC algorithms. In this paper, we employ a special case of Dth order Markov chains to modify the PT-MCMC algorithm, named "Multiple Parallel Tempering" (MPT). The modification converts one MCMC sampler into multiple independent samplers that generate and interleave their samples on one output line each clock cycle. A fully scalable and pipelined hardware accelerator for the PT and proposed MPT sampler is designed and implemented on Artix-7 Xilinx FPGA for chain numbers of 1, 2, and 8. The post-place and route FPGA implementation results indicate that the throughput of the proposed MPT sampler for chain numbers 1, 2, and 8 achieves 31x, 31x, and 28x respectively higher as compared to PT sampler with the same chain number configuration.
Effects of Central Bank Intervention in the Foreign Exchange Market

En este articulo se examinan algunas consideraciones teoricas y demostraciones empiricas referentes a los efectos que la intervencion de los bancos centrales en los mercados de divisas produce en las fluctuaciones de los tipos de cambio. El aspecto principal consiste en determinar hasta que punto se puede prever la influencia que ejercera en el tipo de cambio una intervencion cuyo impacto en la oferta monetaria interna haya sido totalmente neutralizado. Las consideraciones teoricas parecen indicar que la intervencion puede influir en el tipo de cambio si los activos denominados en distintas monedas no son del todo intercambiables, con lo cual se crean oportunidades de intervencion para modificar las diferencias de tipo de interes y, por consiguiente, el tipo de cambio, pues el sector privado modifica la composicion de la cartera para reequilibrarla. Por otra parte, la intervencion puede ejercer una influencia sistematica en las expectativas del publico en cuanto al curso que seguira la politica monetaria y, por consiguiente (como resultado de la especulacion), en el tipo de cambio en vigor. Los resultados empiricos sobre la base de uno u otro de estos factores adolecen de deficiencias debido, por una parte, a la dificultad inherente a la medicion de las expectativas y, por otra, a la obtencion de datos exactos sobre monedas utilizadas en la intervencion y tenencias de activos. Los resultados basados en la estimacion de ecuaciones del tipo de cambio no confirman, en general, que se produzcan efectos significativos y estables en lo que respecta al equilibrio de la cartera. Se llega a la misma conclusion al observar los efectos de la intervencion sobre las primas de riesgo en los mercados de divisas, sobre las diferencias entre los tipos de interes externos y los internos y sobre las diferencias cubiertas de los tipos de interes internacionales. La falta de pruebas concluyentes de que los efectos de la intervencion en los mercados de divisas sobre el equilibrio de la cartera influyen de manera previsible en los tipos de cambio parece indicar que desde el punto de vista practico no cabe separar la politica de intervencion de la politica monetaria general. Esto significa que si ambos instrumentos de politica se utilizan independientemente puede que la estabilidad de los tipos de cambio disminuya en vez de aumentar.
γ-Glutamyl Transpeptidase in Transgenic Tobacco Plants. Cellular Localization, Processing, and Biochemical Properties1

γ-Glutamyl transpeptidase (γ-GT) is a ubiquitous enzyme that catalyzes the first step of glutathione (GSH) degradation in the γ-glutamyl cycle in mammals. A cDNA encoding an Arabidopsis homolog for γ-GT was overexpressed in tobacco (Nicotiana tabacum) plants. A high level of the membrane-bound γ-GT activity was localized outside the cell in transgenic plants. The overproduced enzyme was characterized by a high affinity to GSH and was cleaved post-translationally in two unequal subunits. Thus, Arabidopsis γ-GT is similar to the mammalian enzymes in enzymatic properties, post-translational processing, and cellular localization, suggesting analogous biological functions as a key enzyme in the catabolism of GSH.
Performances of Transmit Antenna Selection, Receive Antenna Selection, and Maximal-Ratio-Combining-Based Hybrid Techniques in the Presence of Feedback Errors

In this paper, performances of joint transmit and receive antenna selection (JTRAS), transmit antenna selection/maximal ratio combining (TAS/MRC), and transmit antenna selection/receive antenna selection (TAS/RAS) techniques are examined in a unified manner in the (42) presence of feedback errors. Exact and closed-form outage probability, moments, moment-generating function, ergodic capacity, and symbol error probability (SEP) expressions are derived for flat Nakagami-m fading channels. In addition, to obtain diversity order and array gain of the investigated techniques in the presence of feedback errors, asymptotic outage probability and SEP expressions are also derived. Analytical results are validated by Monte Carlo simulations. Results show that the diversity order is significantly reduced in the presence of feedback errors, whereas all the systems provide full diversity order for a perfect feedback channel.
Effectiveness of real‐time virtual sonography‐guided radiofrequency ablation treatment for patients with hepatocellular carcinomas

Aim: Real‐time virtual sonography (RVS) can synchronize B‐mode ultrasound (US) images with multiplanar reconstruction (MPR)–computed tomography (CT) images on the same screen in real time. The purpose of this study was to evaluate the effectiveness of RVS for radiofrequency ablation therapy (RFA) of hepatocellular carcinomas (HCC) in which it was difficult to identify contours or margins by B‐mode US.
Fetal corticotrophin‐releasing hormone mRNA, but not phosphatidylserine‐exposing microparticles, in maternal plasma are associated with factor VII activity in pre‐eclampsia

Summary. Background: Pre‐eclampsia is associated with increased placental debris circulating in maternal plasma. Objectives: This study related placental debris to maternal markers of coagulation and endothelial activation in pre‐eclampsia. Patients/methods: Circulating fetal corticotrophin‐releasing hormone (CRH) mRNA and phosphatidylserine (PS)‐exposing microparticles were assayed in third trimester plasma from women with pre‐eclampsia (n = 32) and controls (n = 32) matched for age, body mass index, parity, and gestational age at sampling. Markers of maternal hemostasis and endothelial function were assessed. Results: Fetal CRH mRNA levels were higher in pre‐eclampsia [mean 0.75 (SD 2.77) CRH/glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH) mRNA ratio] than in control pregnancies [0.20 (0.74), P = 0.014]. PS‐exposing microparticle levels were not different between the groups. Women with pre‐eclampsia had higher levels of tissue factor pathway inhibitor (TFPI), prothrombin F1+2 fragment (F1+2), factor XIIa, soluble vascular cell adhesion molecule 1, von Willebrand factor and plasminogen activator inhibitor 1 than controls. Fetal CRH mRNA correlated with TFPI in pre‐eclampsia and control groups (r = 0.38, P = 0.031, and r = 0.37, P = 0.039, respectively). Fetal CRH mRNA correlated with FVII activity (r = 0.43, P = 0.017) and PS‐exposing microparticles correlated inversely with F1+2 (r = −0.64, P < 0.001) in pre‐eclampsia. Conclusions: Placental debris, assessed by fetal CRH mRNA levels in maternal blood, is related to coagulation potential, i.e. FVII activity, but not to markers of coagulation or endothelial activation in pre‐eclampsia.
Partitioning of Serpin-Proteinase Reactions between Stable Inhibition and Substrate Cleavage Is Regulated by the Rate of Serpin Reactive Center Loop Insertion into β-Sheet A*

The serpin family of serine proteinase inhibitors is a mechanistically unique class of naturally occurring proteinase inhibitors that trap target enzymes as stable covalent acyl-enzyme complexes. This mechanism appears to require both cleavage of the serpin reactive center loop (RCL) by the proteinase and a significant conformational change in the serpin structure involving rapid insertion of the RCL into the center of an existing β-sheet, serpin β-sheet A. The present study demonstrates that partitioning between inhibitor and substrate modes of reaction can be altered by varying either the rates of RCL insertion or deacylation using a library of serpin RCL mutants substituted in the critical P14 hinge residue and three different proteinases. We further correlate the changes in partitioning with the actual rates of RCL insertion for several of the variants upon reaction with the different proteinases as determined by fluorescence spectroscopy of specific RCL-labeled inhibitor mutants. These data demonstrate that the serpin mechanism follows a branched pathway, and that the formation of a stable inhibited complex is dependent upon both the rate of the RCL conformational change and the rate of enzyme deacylation.
Thrombin Derivatives Obtained by Autolytic or Limited Tryptic Cleavage

Several proteases have the capacity to produce thrombin derivatives by limited proteolysis of surface loops that are exposed in α-thrombin and obviously ac­ cessible, or flexible enough to bind productively to a protease. 1 Autolysis of human thrombin or controlled proteolysis with trypsin yields β-and 7-thrombin deriva­ tives. 2 Elastase converts α-thrombin to ε-thrombin, 3 whereas cathepsin G or chymotrypsin converts a-to ζ-thrombin. 4 The biologic functions of thrombin are not significantly affected by the ζ-cleavage, although the molecule is less stable. 4 Elastase-modified thrombin also retains most of its activity. 3 ' 5 In contrast, (3-and 7-thrombins, which retain most of the activity toward small synthetic substrates, show no or little procoagulant activity. These two derivative forms of α-thrombin ((3-and 7) have therefore been exceedingly useful in the study of the structural features that define specificity and biologic functions of thrombin
Causality and double-negative metamaterials.

The causality of waves propagating in a double-negative (DNG) metamaterial (epsilon (r)<0 and mu(r)<0) has been investigated both analytically and numerically. By considering the one-dimensional electromagnetic problem of a pulsed current sheet radiating into a DNG medium, it is shown that causality is maintained in the presence of a negative index of refraction only if the DNG medium is dispersive. A Drude model DNG medium is used in this study. Spectrograms of the wave phenomena in the dispersive DNG medium show that the higher frequency components, which create the leading edge of the electromagnetic signals and see a double positive (DPS) medium (epsilon (r)>0 and mu(r)>0), arrive causally before the negative index effects germinate completely. Comparisons with approximate analytical results demonstrate the presence of the negative index of refraction properties in the continuous wave portion of the signals. This dynamic pulse reshaping between the positive and negative index of refraction wave components causes an apparent delay in the realization of the negative index of refraction properties. Pulse broadening of the signal tails is associated with both dispersion and a larger negative index of refraction seen by the associated wave components.
Production and Characterization of a Thermostable Alcohol Dehydrogenase That Belongs to the Aldo-Keto Reductase Superfamily

ABSTRACT The gene encoding a novel alcohol dehydrogenase that belongs to the aldo-keto reductase superfamily has been identified in the hyperthermophilic archaeon Pyrococcus furiosus. The gene, referred to as adhD, was functionally expressed in Escherichia coli and subsequently purified to homogeneity. The enzyme has a monomeric conformation with a molecular mass of 32 kDa. The catalytic activity of the enzyme increases up to 100°C, and a half-life value of 130 min at this temperature indicates its high thermostability. AdhD exhibits a broad substrate specificity with, in general, a preference for the reduction of ketones (pH optimum, 6.1) and the oxidation of secondary alcohols (pH optimum, 8.8). Maximal specific activities were detected with 2,3-butanediol (108.3 U/mg) and diacetyl-acetoin (22.5 U/mg) in the oxidative and reductive reactions, respectively. Gas chromatrography analysis indicated that AdhD produced mainly (S)-2-pentanol (enantiomeric excess, 89%) when 2-pentanone was used as substrate. The physiological role of AdhD is discussed.