Miracle-dz/UniFAR-FTUs huggingface dataset:
Genetic Polymorphism rs6922269 in the MTHFD1L Gene Is Associated with Survival and Baseline Active Vitamin B12 Levels in Post-Acute Coronary Syndromes Patients

Background and Aims The methylene-tetrahydrofolate dehydrogenase (NADP+ dependent) 1-like (MTHFD1L) gene is involved in mitochondrial tetrahydrofolate metabolism. Polymorphisms in MTHFD1L, including rs6922269, have been implicated in risk for coronary artery disease (CAD). We investigated the association between rs6922269 and known metabolic risk factors and survival in two independent cohorts of coronary heart disease patients. Methods and Results DNA and plasma from 1940 patients with acute coronary syndromes were collected a median of 32 days after index hospital admission (Coronary Disease Cohort Study, CDCS). Samples from a validation cohort of 842 patients post-myocardial infarction (PMI) were taken 24–96 hours after hospitalization. DNA samples were genotyped for rs6922269, using a TaqMan assay. Homocysteine and active vitamin B12 were measured by immunoassay in baseline CDCS plasma samples, but not PMI plasma. All cause mortality was documented over follow-up of 4.1 (CDCS) and 8.8 (PMI) years, respectively. rs6922269 genotype frequencies were AA n = 135, 7.0%; GA n = 785, 40.5% and GG n = 1020, 52.5% in the CDCS and similar in the PMI cohort. CDCS patients with AA genotype for rs6922269 had lower levels of co-variate adjusted baseline plasma active vitamin B12 (p = 0.017) and poorer survival than patients with GG or GA genotype (mortality: AA 19.6%, GA 12.0%, GG 11.6%; p = 0.007). In multivariate analysis, rs6922269 genotype predicted survival, independent of established covariate predictors (p = 0.03). However the association between genotype and survival was not validated in the PMI cohort. Conclusion MTHFD1L rs6922269 genotype is associated with active vitamin B12 levels at baseline and may be a marker of prognostic risk in patients with established coronary heart disease.
Recurrence of Preterm Birth and Early Term Birth

OBJECTIVE: To examine recurrent preterm birth and early term birth in women's initial and immediately subsequent pregnancies. METHODS: This retrospective cohort study included 163,889 women who delivered their first and second liveborn singleton neonates between 20 and 44 weeks of gestation in California from 2005 through 2011. Data from hospital discharge records and birth certificates were used for analyses. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression models adjusted for risk factors. RESULTS: Shorter gestational duration in the first pregnancy increased the risk of subsequent preterm birth (both early, before 32 weeks of gestation, and later, from 32 to 36 weeks of gestation) as well as early term birth (37–38 weeks of gestation). Compared with women with a prior term birth, women with a prior early preterm birth (before 32 weeks of gestation) were at the highest risk for a subsequent early preterm birth (58/935 [6.2%] compared with 367/118,505 [0.3%], adjusted OR 23.3, 95% CI 17.2–31.7). Women with a prior early term birth had more than a twofold increased risk for subsequent preterm birth (before 32 weeks of gestation: 171/36,017 [0.5%], adjusted OR 2.0, 95% CI 1.6–2.3; from 32 to 36 weeks of gestation: 2,086/36,017 [6.8%], adjusted OR 3.0, 95% CI 2.9–3.2) or early term birth (13,582/36,017 [37.7%], adjusted OR 2.2, 95% CI 2.2–2.3). CONCLUSION: Both preterm birth and early term birth are associated with these outcomes in a subsequent pregnancy. Increased clinical attention and research efforts may benefit from a focus on women with a prior early term birth as well as those with prior preterm birth.
Interactions between commensal bacteria and the gut-associated immune system of the chicken

Abstract The chicken gut-associated lymphoid tissue is made up of a number of tissues and cells that are responsible for generating mucosal immune responses and maintaining intestinal homeostasis. The normal chicken microbiota also contributes to this via the ability to activate both innate defense mechanisms and adaptive immune responses. If left uncontrolled, immune activation in response to the normal microbiota would pose a risk of excessive inflammation and intestinal damage. Therefore, it is important that immune responses to the normal microbiota be under strict regulatory control. Through studies of mammals, it has been established that the mucosal immune system has specialized regulatory and anti-inflammatory mechanisms for eliminating or tolerating the normal microbiota. The mechanisms that exist in the chicken to control host responses to the normal microbiota, although assumed to be similar to that of mammals, have not yet been fully described. This review summarizes what is currently known about the host response to the intestinal microbiota, particularly in the chicken.
Partitioned Time Stepping Method for Fully Evolutionary Stokes-Darcy Flow with Beavers-Joseph Interface Conditions

In this report, a partitioned time stepping algorithm for transient flow in a matrix domain coupled to a free flow in embedded conduits is analyzed. The coupled flow is modeled by the fully evolutionary Stokes--Darcy problem. This method requires solving only one, uncoupled Stokes and Darcy subphysics and subdomain per time step. On the interface between the matrix and conduit, Beavers--Joseph interface conditions, instead of the simplified Beavers--Joseph--Saffman condition, are imposed. Under a modest time step restriction of the form $\triangle t\leq C$, where $C=C$ (physical parameters) we prove stability of the method. We also derive error estimates. Numerical tests illustrate the validity of the theoretical results.
Genes of the N-Methylglutamate Pathway Are Essential for Growth of Methylobacterium extorquens DM4 with Monomethylamine

ABSTRACT Monomethylamine (MMA, CH3NH2) can be used as a carbon and nitrogen source by many methylotrophic bacteria. Methylobacterium extorquens DM4 lacks the MMA dehydrogenase encoded by mau genes, which in M. extorquens AM1 is essential for growth on MMA. Identification and characterization of minitransposon mutants with an MMA-dependent phenotype showed that strain DM4 grows with MMA as the sole source of carbon, energy, and nitrogen by the N-methylglutamate (NMG) pathway. Independent mutations were found in a chromosomal region containing the genes gmaS, mgsABC, and mgdABCD for the three enzymes of the pathway, γ-glutamylmethylamide (GMA) synthetase, NMG synthase, and NMG dehydrogenase, respectively. Reverse transcription-PCR confirmed the operonic structure of the two divergent gene clusters mgsABC-gmaS and mgdABCD and their induction during growth with MMA. The genes mgdABCD and mgsABC were found to be essential for utilization of MMA as a carbon and nitrogen source. The gene gmaS was essential for MMA utilization as a carbon source, but residual growth of mutant DM4gmaS growing with succinate and MMA as a nitrogen source was observed. Plasmid copies of gmaS and the gmaS homolog METDI4690, which encodes a protein 39% identical to GMA synthetase, fully restored the ability of mutants DM4gmaS and DM4gmaSΔmetdi4690 to use MMA as a carbon and nitrogen source. Similarly, chemically synthesized GMA, the product of GMA synthetase, could be used as a nitrogen source for growth in the wild-type strain, as well as in DM4gmaS and DM4gmaSΔmetdi4690 mutants. The NADH:ubiquinone oxidoreductase respiratory complex component NuoG was also found to be essential for growth with MMA as a carbon source.
Neural Representations of Relevant and Irrelevant Features in Perceptual Decision Making

Although perceptual decision making activates a network of brain areas involved in sensory, integrative, and motor functions, circuit activity can clearly be modulated by factors beyond the stimulus. Of particular interest is to understand how the network is modulated by top-down factors such as attention. Here, we demonstrate in a motion coherence task that selective attention produces marked changes in the blood oxygen level-dependent (BOLD) response in a subset of regions within a human perceptual decision-making circuit. Specifically, when motion is attended, the BOLD response decreases with increasing motion coherence in many regions, including the motion-sensitive area MT+, the intraparietal sulcus, and the inferior frontal sulcus. However, when motion is ignored, the negative parametric response in a subset of this circuit becomes positive. Through both modeling and connectivity analyses, we demonstrate that this inversion both reflects a top-down influence and segregates attentional from accumulation regions, thereby permitting us to further delineate the contributions of different regions to the perceptual decision.
Neuromuscular function during prolonged pedalling exercise at different cadences.

AIM The purpose of the present work was to assess the strategies set by the central nervous system in order to provide the power output required throughout a prolonged (1-h) pedalling exercise performed at different cadences (50 rpm, 110 rpm and the freely chosen cadence). METHODS Neuromuscular (NM) activity of vastus lateralis, rectus femoris, biceps femoris and gastrocnemius lateralis muscles was studied quantitatively [root-mean square (RMS) and mean power frequency (MPF)] and qualitatively (timing of onset and offset of muscle bursts during crank cycle). RESULTS The present results showed that increased cadence resulted in earlier muscle activation in crank cycle. The influence of cadence on RMS and MPF depended on the considered muscle and its functional role during pedalling. Timing of onset and offset of muscle bursts was not altered by fatigue throughout the prolonged exercise. In contrast, RMS and MPF of some muscles was found to increase during prolonged exercise. CONCLUSION In summary, the present study revealed that tonic aspects of the NM activity (RMS, MPF) are altered during prolonged pedalling exercise, while phasic aspects are remained unchanged. These results suggest that the strategies set by the central nervous system in order to provide the power output required by the exercise are held constant throughout the exercise, but that quantitative aspects of the central drive are increased in order to adapt to the progressive occurrence of the NM fatigue.
Stretching agile to fit CMMI level 3 - the story of creating MSF for CMMI/spl reg/ process improvement at Microsoft corporation

Agile practitioners pride themselves on highly productive, responsive, low ceremony, lightweight, tacit knowledge processes with little waste, adaptive planning and frequent iterative delivery of value. It is often assumed that CMMI compliant processes need to be heavyweight, bureaucratic, slow moving, high ceremony and plan driven. Agile developers often skeptically perceive formal process improvement initiatives as management generated inefficiency that gets in the way of productivity. At Microsoft, we've adopted the teachings of W. Edwards Deming and stretched our MSF for agile software development method to fit the requirements for CMMI level 3. The resultant MSF for CMMI process improvement is a highly iterative, adaptive planning method, light on documentation, and heavily automated through tooling. It enables management and organization of software engineering through use of agile metrics such as velocity and cumulative flow but with an added dimension of an understanding of variation - adapted from Deming's teachings. This is the story of how mixing Deming with Agile produced a lightweight CMMI solution for . Net developers everywhere.
Multi-Element Generalized Polynomial Chaos for Arbitrary Probability Measures

We develop a multi-element generalized polynomial chaos (ME-gPC) method for arbitrary probability measures and apply it to solve ordinary and partial differential equations with stochastic inputs. Given a stochastic input with an arbitrary probability measure, its random space is decomposed into smaller elements. Subsequently, in each element a new random variable with respect to a conditional probability density function (PDF) is defined, and a set of orthogonal polynomials in terms of this random variable is constructed numerically. Then, the generalized polynomial chaos (gPC) method is implemented element-by-element. Numerical experiments show that the cost for the construction of orthogonal polynomials is negligible compared to the total time cost. Efficiency and convergence of ME-gPC are studied numerically by considering some commonly used random variables. ME-gPC provides an efficient and flexible approach to solving differential equations with random inputs, especially for problems related to long-term integration, large perturbation, and stochastic discontinuities.
Plasmonic waves allow perfect transmission through sub-wavelength metallic gratings

We investigate the transmission properties of a metallic layer with narrow slits. Recent measurements and numerical calculations concerning the light transmission through metallic sub-wavelength structures suggest that an unexpectedly high transmission coefficient is possible. We analyze the time harmonic Maxwell's equations in the $H$-parallel case for a fixed incident wavelength. Denoting by $\eta>0$ the typical size of the complex structure, effective equations describing the limit $\eta\to 0$ are derived. For metallic permittivities with negative real part, plasmonic waves can be excited on the surfaces of the channels. When these waves are in resonance with the height of the layer, the result can be perfect transmission through the layer.
The deregulated promoter methylation of the Polo-like kinases as a potential biomarker in hematological malignancies

Abstract Deregulation of Polo-like kinase (PLK) transcription via promoter methylation results in perturbations at the protein level, which has been associated with oncogenesis. Our objective was to further characterize the methylation profile for PLK1–4 in bone marrow aspirates displaying blood neoplasms as well as in cells grown in vitro. Clinically, we have determined that more than 70% of lymphoma and myelodysplastic syndrome (MDS)/leukemia bone marrow extracts display a hypermethylated PLK4 promoter region in comparison to the normal. Decreased PLK4 protein expression due to promoter hypermethylation was negatively correlated with JAK2 overexpression, a common occurrence in hematological malignancies. In vitro examination of the PLKs under biologically relevant condition of 5% O2 revealed that the highly conserved PLKs respond to lower oxygen tension at both the DNA and the protein level. These findings suggest that PLK promoter methylation status correlates with disease and tumorigenesis in blood neoplasms and could serve as a biomarker.
Association of small ubiquitin-like modifier 4 (SUMO4) polymorphisms in a Tunisian population with Behçet's disease.

OBJECTIVES An association of SUMO4 gene, which has recently been shown to be a negative feedback regulator for nuclear factor NF-κB, has been reported in several autoimmune/inflammatory diseases. A case-control study was set up to investigate the contribution of SUMO4 locus to the genetic susceptibility to Behçet's disease (BD). METHODS One hundred and thirty-five Tunisian BD patients and 167 healthy blood donors from the same geographical area were genotyped by polymerase chain reaction for the SUMO4 polymorphisms. RESULTS. The SUMO4+438 C allele frequency is significantly increased in BD patients (p=0.03; χ2=4.71; OR=1.44; 95% CI=1.02-2.04) and highly significantly increased in HLA-B51 positive BD patients (p=3 10-6; χ2=21.62; OR=4.44; 95% CI=2.21-8.98). Similarly, the SUMO4 -847 G allele frequency is significantly increased in BD patients (p=0.03; χ2=4.34; OR=1.41; 95% CI=1.01-1.97). The studied polymorphisms were also associated with disease severity, skin lesions and vascular involvement. CONCLUSIONS SUMO4+438 C and -847 G alleles seem to be associated with susceptibility to BD in Tunisian population. We suggest that SUMO4 gene polymorphisms may be involved in the development of skin lesions, vascular BD, as well as the severity of the disease.
Prosodic transfer in Black South African English

This article reports on a perception study that was carried out with Zulu-English bilinguals in order to investigate how suprasegmental aspects differ in Black South African English compared to White English-speaking South African English. Two prosodic phenomena were investigated: prosodic focus marking on noun phrases (NPs) and prosodic boundary marking. The results support existing claims in the literature that Black South African English falls into at least two distinct groups (van Rooy 2004): L2 English spoken by non-native speakers and “L1 speakers of English whose dialects have developed from non-native varieties” (Da Silva 2008: 96), the speech of the former showing L1 influence in not marking focus prosodically. In contrast, prosodic means are used for boundary marking by all speakers.
Oct4 expression revisited: potential pitfalls for data misinterpretation in stem cell research

Abstract The octamer-binding transcription factor 4 gene encodes a nuclear protein (Oct4, also known as Pou5F1 and Oct3/4) that belongs to a family of transcription factors containing the POU DNA-binding domain. Expression can be detected in embryonic stem cells as well as in adult stem cells, such as bone marrow-derived mesenchymal stem cells. Expression of Oct4 is downregulated coincident with stem cell differentiation and loss of expression leading to differentiation. A role for maintaining pluripotency and self-renewal of embryonic stem cells is ascribed to Oct4 as a pluripotency marker. Results describing Oct4 expression in differentiated cells, including peripheral blood mononuclear cells (PBMCs), neonatal and adult stem cells, as well as cancer cells, must be interpreted with caution. In several publications, Oct4 has been ascribed a function in maintaining self-renewal of adult stem cells. In contrast, other publications reported Oct4 expression in human tumor cells. Here, we summarize the recent findings on Oct4 expression and present possibilities and reasons why several false positive results on Oct4 expression still occur in the recent literature. Also, simple solutions are provided to avoid these positive signals.
Chronic Lymphocytic Leukemia Associated with Myelodysplastic Syndrome and/or Chronic Myeloid Leukemia: Evidence for Independent Clonal Chromosomal Evolution

We describe the cytogenetic findings of three cases with simultaneous or sequential development of a B-chronic lymphocytic leukemia (B-CLL) and either a myelodysplastic syndrome (MDS) in 2 cases or a chronic myeloid leukemia (CML) in one case. The coexistence of these two hematologic malignancies leads to questions about their cell of origin. Through analysis of the cytogenetic abnormalities, we studied the derivation of both malignancies. The cytogenetic analyses of these three patients were simultaneously studied from both peripheral blood and bone marrow. Furthermore unstimulated short-time (USSTC) and long-time (72–96 hours) stimulated cultures (LTSC) were systematically performed. In all cases, we have demonstrated the independent bi-clonal evolution. This is the first report ever described for patients with CLPD and MDS and/or MPD shown to arise from distinct chromosomal abnormalities.
Information Acquisition for Capacity Planning via Pricing and Advance Selling: When to Stop and Act?

This paper investigates a capacity planning strategy that collects commitments to purchase before the capacity decision and uses the acquired advance sales information to decide on the capacity. In particular, we study a profit-maximization model in which a manufacturer collects advance sales information periodically prior to the regular sales season for a capacity decision. Customer demand is stochastic and price sensitive. Once the capacity is set, the manufacturer produces and satisfies customer demand (to the extent possible) from the installed capacity during the regular sales period. We study scenarios in which the advance sales and regular sales season prices are set exogenously and optimally. For both scenarios, we establish the optimality of a control band or a threshold policy that determines when to stop acquiring advance sales information and how much capacity to build. We show that advance selling can improve the manufacturer's profit significantly. We generate insights into how operating conditions (such as the capacity building cost) and market characteristics (such as demand variability) affect the value of information acquired through advance selling. From this analysis, we identify the conditions under which advance selling for capacity planning is most valuable. Finally, we study the joint benefits of acquiring information for capacity planning through advance selling and revenue management of installed capacity through dynamic pricing.
Axotomy-Induced Smad1 Activation Promotes Axonal Growth in Adult Sensory Neurons

Mature neurons have diminished intrinsic regenerative capacity. Axotomy of the peripheral branch of adult dorsal root ganglia (a “conditioning” lesion) triggers a transcription-dependent axon growth program. Here, we show that this growth program requires the function of the transcription factor Smad1. After peripheral axotomy, neuronal Smad1 is upregulated, and phosphorylated Smad1 accumulates in the nucleus. Both events precede the onset of axonal extension. Reducing Smad1 by RNA interference in vitro impairs axonal growth, and the continued presence of Smad1 is required to maintain the growth program. Furthermore, intraganglionic injection of BMP2 or 4, which activates Smad1, markedly enhances axonal growth capacity, mimicking the effect of a conditioning lesion. Thus, activation of Smad1 by axotomy is a key component of the transcriptional switch that promotes an enhanced growth state of adult sensory neurons.
Treadmill exercise alleviates impairment of spatial learning ability through enhancing cell proliferation in the streptozotocin-induced Alzheimer’s disease rats

Alzheimer’s disease is the most common cause of dementia. This disease is a progressive and irreversible brain disorder accompanied with severe learning and memory impairment. Exercise increases cognitive ability, attenuates motor deficits, increases new neuron formation, and ameliorates neurological impairments in several neurodegenerative diseases. This study investigated the effects of treadmill exercise on spatial learning ability in relation with cell proliferation in the hippocampus. The rat model of Alzheimer’s disease was induced by intracerebroventricular (ICV) injection of streptozotocin (STZ) using a stereotaxic instrument. The rats in the exercise groups were forced to run on a treadmill for once 30 min daily for 28 consecutive days starting at 3 days after the ICV injection of STZ. Radial 8-arm maze test was conducted for the spatial learning ability. New neuron formation in the hippocampus was detected by 5-bromo-2’-deoxyuridine (BrdU) immunohistochemistry. Brain-derived neurotrophic factor (BDNF) and tyrosine kinase B (TrkB) expressions were examined by western blot analysis. The present results show that ICV injection of STZ impaired spatial learning ability. Decreased cell proliferation with decrement of BDNF and TrkB expressions in the hippocampus were observed in the STZ-induced Alzheimer’s disease rats. However, treadmill exercise alleviated deficits of spatial learning ability. Treadmill exercise enhanced cell proliferation and increased BDNF and TrkB expressions in the rats with ICV injection of STZ. The present study suggests that treadmill exercise can be a useful strategy for treating memory impairment induced by several neurodegenerative diseases.