Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of cytochrome P450 (CYP) 2A6 gene deletion and CYP2E1 genotypes on gastric adenocarcinoma

Cytochrome P450 (CYP) 2A6 and CYP2E1 are enzymes with a high ability to activate a nitrosamine, 4‐(methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanone (NNK), to its potent and ultimate carcinogens. The polymorphic CYP2A6 and CYP2E1 have been implicated in increased susceptibility to certain malignancies. In our study, 120 Japanese patients with gastric adenocarcinoma and 158 healthy controls were compared for frequencies of CYP2A6 and CYP2E1 genotypes. The frequency with which the subjects carried homozygotes of the CYP2A6 gene deletion allele, which causes lack of the enzyme activity, was significantly higher in the gastric cancer patients than in the healthy control subjects (OR = 3.14, 95% confidence interval (95% CI) = 1.05–9.41). Subdividing gastric adenocarcinoma according to tumor differentiation, patients with the well‐differentiated type were 4.9‐fold more likely to have the CYP2A6 homozygote deletion genotype (OR = 4.91, 95% CI 1.17–20.52). Stratifying by smoking status, we did not find the risk of CYP2A6 gene deletion allele in gastric adenocarcinoma. The CYP2E1 polymorphism detected by RsaI was not significantly different between gastric adenocarcinoma patients (40.8%) and the control population (44.3%). No statistically significant changes were observed when the CYP2E1 genotype was examined relative to tumor differentiation and smoking status. These results suggest that the CTY2A6 deletion is associated with gastric adenocarcinoma among Japanese populations. © 2002 Wiley‐Liss, Inc.
Immature Dendritic Cells Suppress Collagen-Induced Arthritis by In Vivo Expansion of CD49b+ Regulatory T Cells1

Dendritic cells (DCs) are specialized APCs with an important role in the initiation and regulation of immune responses. Immature DCs (iDCs) reportedly mediate tolerance in the absence of maturation/inflammatory stimuli, presumably by the induction of regulatory T cells. In this study, we show for the first time that repetitive iDC injections trigger the expansion of a novel regulatory population with high immunomodulatory properties, able to protect mice from collagen-induced arthritis. These regulatory T cells are characterized by the expression of the CD49b molecule and correspond to a CD4+ α-galactosylceramide/CD1d-nonrestricted T cell population producing IL-10. Adoptive transfer of <105 TCRβ+CD49b+ cells isolated from the liver of iDCs-vaccinated mice, conferred a complete protection against arthritis. This protection was associated with an attenuation of the B and T cell response associated with a local secretion of IL-10. Thus, together these data demonstrate that iDCs can expand and activate a novel regulatory population of CD49b+ T cells, with high immunosuppressive potential able to mediate protection against a systemic autoimmune disease.
Optimal routings in communication networks with linearly bounded forwarding index

In a given graph with n vertices, a routing is defined as a set of n(n - 1) routes, one route connecting each ordered pair of vertices. The load of a vertex is the number of routes going through it. The forwarding index of the graph is the minimum of the largest load taken over all routings. We construct undirected graphs with a high degree of symmetry and specified diameter, in which the load of every vertex is at most constant times the number of vertices. This gives a partial solution to a problem of Chung et al.
What Intelligence Tests Miss

It is a profound historical irony of the behavioural sciences that the Nobel Prize was awarded for studies of cognitive characteristics (rational thinking skills) that are entirely missing from the most well-known mental assessment device in the behavioral sciences – the intelligence test. Intelligence tests measure important things, but not these – they do not assess the extent of rational thought. This might not be such an omission if it were the case that intelligence was an exceptionally strong predictor of rational thinking. However, research has found that it is a moderate predictor at best and that some rational thinking skills can be quite dissociated from intelligence. I n psychology and among the lay public alike, high scores on intelligence tests are considered a mark of good thinking. This is not unreasonable. It is now over 100 years since Spearman first reported a single general intelligence factor, known as g or 'the positive manifold' – the tendency for scores on different cognitive tests to correlate. Indeed, it is rare that a cognitive process or phenomenon is found to be independent of g (Carroll, 1993), so it is reasonable to assume that the construct of general intelligence encompasses most of cognition. It is revealing that when critics of IQ tests try to argue that such tests fail to assess many essential domains of psychological functioning, they often point to non-cognitive domains, including: socio-emotional abilities, motivation, empathy, morality and interpersonal skills. By targeting these non-cognitive domains, these critics indirectly bolster the assumption that IQ tests exhaustively encompass the cognitive domain. Our research group has challenged IQ tests much more fundamentally than the average critic. Our argument is that intelligence, as conventionally measured, leaves out critical cognitive domains – domains of thinking itself. We were led to this conclusion through our long-standing interest in the heuristics and biases research programme inaugurated by Kahneman and Tversky several decades ago A press release from the Royal Swedish Academy of Sciences drew attention to the roots of the award-winning work in 'the analysis of human judgment and decision-making by cognitive psychologists'. Kahneman was cited for discovering 'how human judgment may take heuristic shortcuts that systematically depart from basic principles of probability. His work has inspired a new generation of researchers in economics and finance to enrich economic theory using insights from cognitive psychology into intrinsic human motivation. ' One reason that the Kahneman and Tversky work was …
Continuing medical education and the physician as a learner: guide to the evidence.

One faculty member in a professional school referred to continuing education as “shouting out of windows,” and an analysis of the programs at his institution shows the aptness of his metaphor: Faculty members who can be persuaded to do so give lectures on subjects of their own choosing to audiences they do not know, who have assembled only because they want to put in enough hours of classroom attendance so that they can meet a relicensure requirement. As a result, every profession now has members who vigorously oppose what they regard as the excessive promotion of continuing education. Cyril O. Houle, 1980 RESEARCHERS OF THE PAST DEcade produced systematic reviews of continuing medical education (CME) and other strategies intended to change physician behavior and improve patient outcomes. The subjects of the reviews included such concepts as audit and feedback, chart-based reminders, clinical practice guidelines, and formal lectures. Defined as interventions to change the behavior of physicians, the effects of those strategies were inconsistent across practitioners, settings, and behaviors. As a result, in the midst of contemporary discussions about quality improvement and the effects of continuing education, there is no singularly effective method for improving physician performance. Physicians must accept responsibility for their own continuous learning: setting goals and selecting educational activities to achieve those goals. We searched the Research and Development Resource Base in Continuing Medical Education and the Specialised Register of the Cochrane Effective Practice and Organization of Care group, supplemented by searches of MEDLINE from 1992 to February 2002 for systematic reviews and evidence of CME and its effect on both physicians and CME planners.
Quadratic permutation polynomial interleaver for LTE turbo coding

Interleaver is an important component of turbo code and has a strong impact on its error correcting performance. Quadratic permutation polynomial (QPP) interleaver is a contention-free interleaver which is suitable for parallel turbo decoder implementation. To improve the performance of LTE QPP interleaver, largest-spread and maximum-spread QPP interleavers are analyzed for Long Term Evolution (LTE) turbo codes in this paper. Compared with LTE QPP interleaver, those algorithms have low computing complexity and better performances from simulation results.
Mesenchymal Stem Cell-Derived Molecules Reverse Fulminant Hepatic Failure

Modulation of the immune system may be a viable alternative in the treatment of fulminant hepatic failure (FHF) and can potentially eliminate the need for donor hepatocytes for cellular therapies. Multipotent bone marrow-derived mesenchymal stem cells (MSCs) have been shown to inhibit the function of various immune cells by undefined paracrine mediators in vitro. Yet, the therapeutic potential of MSC-derived molecules has not been tested in immunological conditions in vivo. Herein, we report that the administration of MSC-derived molecules in two clinically relevant forms-intravenous bolus of conditioned medium (MSC-CM) or extracorporeal perfusion with a bioreactor containing MSCs (MSC-EB)-can provide a significant survival benefit in rats undergoing FHF. We observed a cell mass-dependent reduction in mortality that was abolished at high cell numbers indicating a therapeutic window. Histopathological analysis of liver tissue after MSC-CM treatment showed dramatic reduction of panlobular leukocytic infiltrates, hepatocellular death and bile duct duplication. Furthermore, we demonstrate using computed tomography of adoptively transferred leukocytes that MSC-CM functionally diverts immune cells from the injured organ indicating that altered leukocyte migration by MSC-CM therapy may account for the absence of immune cells in liver tissue. Preliminary analysis of the MSC secretome using a protein array screen revealed a large fraction of chemotactic cytokines, or chemokines. When MSC-CM was fractionated based on heparin binding affinity, a known ligand for all chemokines, only the heparin-bound eluent reversed FHF indicating that the active components of MSC-CM reside in this fraction. These data provide the first experimental evidence of the medicinal use of MSC-derived molecules in the treatment of an inflammatory condition and support the role of chemokines and altered leukocyte migration as a novel therapeutic modality for FHF.
A Concurrent IFDS Dataflow Analysis Algorithm Using Actors

There has recently been a resurgence in interest in techniques for effective programming of multi-core computers. Most programmers find general-purpose concurrent programming to be extremely difficult. This difficulty severely limits the number of applications that currently benefit from multi-core computers. There already exist many concurrent solutions for the class of regular applications, which include various algorithms for linear algebra. For the class of irregular applications, which operate on dynamic and pointerand graph-based structures, efficient concurrent solutions have so far remained elusive. Dataflow analysis applications, which are often found in compilers and program analysis tools, have received particularly little attention with regard to execution on multi-core machines. Operating on the theory that the Actor model, which structures computations as systems of asynchronously-communicating entities, is a more appropriate method for representing irregular algorithms than the shared-memory model, this work presents a concurrent Actor-based formulation of the IFDS, or Interprocedural Finite Distributive Subset, dataflow analysis algorithm. The implementation of this algorithm is done using the Scala language and its Actors library. This algorithm achieves significant speedup on multi-core machines without using any optimistic execution. This work contributes to Actor research by showing how the Actor model can be practically applied to a dataflow analysis problem. This work contributes to static analysis research by showing how a dataflow analysis algorithm can effectively make use of multi-core machines, allowing the possibility of faster and more precise analyses.
Glycine antagonist in neuroprotection for patients with acute stroke: GAIN Americas: a randomized controlled trial.

CONTEXT Elucidation of the ischemic cascade has helped stimulate development of neuroprotective drugs aimed at limiting brain injury in the hours following an ischemic stroke. To date, none of these drugs has shown clinical efficacy. OBJECTIVE To examine the efficacy of gavestinel (GV150526), an antagonist of the glycine site of the N-methyl-D-aspartate receptor, as a neuroprotective therapy for acute ischemic stroke when administered within 6 hours of symptom onset. DESIGN The Glycine Antagonist in Neuroprotection (GAIN) Americas trial, a randomized, double-blind placebo-controlled trial with enrollment from April 1998 to October 1999. SETTING One hundred thirty-two hospital centers across the United States and Canada. PATIENTS The primary efficacy population consisted of 1367 ischemic stroke patients with a predefined level of limb weakness and functional independence prior to stroke, stratified at randomization by age (</=75 vs >75 years) and initial stroke severity (National Institutes of Health [NIH] Stroke Scale scores of 2-5, 6-13, or >/=14). INTERVENTION Patients were randomly assigned to receive an intravenous loading dose (800 mg) plus 5 maintenance doses (200 mg every 12 hours) of gavestinel (n = 701) or placebo (n = 666) for 3 days. MAIN OUTCOME MEASURE Functional capability at 3 months, measured by the Barthel Index (BI), with scores trichotomized as dead/0-55, 60-90, and 95-100, compared between the gavestinel and placebo groups. RESULTS Treatment groups were well matched for baseline characteristics. For each group, median NIH Stroke Scale was 12, median age was 72 years, and median time to treatment was 5.2 hours. No statistically significant improvement on the 3-month BI trichotomy was demonstrated for gavestinel (P =.79). The proportion who were functionally independent (BI score = 95-100) was 39% in the gavestinel group and 37% in the placebo group. No statistically significant difference in 3-month survival was observed using Kaplan-Meier curves (P =.11). No other secondary end point suggested an advantage for gavestinel. Among the 333 patients (24%) who received recombinant tissue-type plasminogen activator, there was also no benefit for gavestinel (P =.53). There were no serious safety issues. CONCLUSION In this study, gavestinel administered up to 6 hours after an acute ischemic stroke did not improve functional outcome at 3 months.
Teaching psychodynamic formulation to psychiatric trainees: Part 1: Basics of formulation

All psychiatrists should be able to construct a psychodynamic formulation of a case. A key advantage of formulation over diagnosis is that it can be used to predict how an individual might respond in certain situations and to various psychotherapies. This article looks in some depth at what psychiatric trainees need to be taught about psychodynamic formulation. We introduce formulation in terms of four levels, each level corresponding to a different degree of theoretical and clinical sophistication and therefore to different trainees’ needs. We use a case vignette to illustrate how a clinical situation might be formulated at each of these levels.
Physical activity, motor function, and white matter hyperintensity burden in healthy older adults

Objective: To test the hypothesis that physical activity modifies the association between white matter hyperintensity (WMH) burden and motor function in healthy older persons without dementia. Methods: Total daily activity (exercise and nonexercise physical activity) was measured for up to 11 days with actigraphy (Actical; Philips Respironics, Bend, OR) in 167 older adults without dementia participating in the Rush Memory and Aging Project. Eleven motor performances were summarized into a previously described global motor score. WMH volume was expressed as percent of intracranial volume. Linear regression models, adjusted for age, education, and sex, were performed with total WMH volume as the predictor and global motor score as the outcome. Terms for total daily physical activity and its interaction with WMH volume were then added to the model. Results: Higher WMH burden was associated with lower motor function (p = 0.006), and total daily activity was positively associated with motor function (p = 0.002). Total daily activity modified the association between WMH and motor function (p = 0.007). WMH burden was not associated with motor function in persons with high activity (90th percentile). By contrast, higher WMH burden remained associated with lower motor function in persons with average (50th percentile; estimate = −0.304, slope = −0.133) and low (10th percentile; estimate = −1.793, slope = −0.241) activity. Conclusions: Higher levels of physical activity may reduce the effect of WMH burden on motor function in healthy older adults.
Inferring Disease-Related Pathways Using A Probabilistic Epistasis Model

MOTIVATION We present a probabilistic model called a Joint Intervention Network (JIN) for inferring interactions among a chosen set of regulator genes. The input to the method are expression changes of downstream indicator genes observed under the knock-out of the regulators. JIN can use any number of perturbation combinations for model inference (e.g. single, double, and triple knock-outs). RESUITS/CONCLUSIONS: We applied JIN to a Vibrio cholerae regulatory network to uncover mechanisms critical to its environmental persistence. V. cholerae is a facultative human pathogen that causes cholera in humans and responsible for seven pandemics. We analyzed the expression response of 17 V. cholerae biofilm indicator genes under various single and multiple knock-outs of three known biofilm regulators. Using the inferred network, we were able to identify new genes involved in biofilm formation more accurately than clustering expression profiles.
Structural Basis for Regulation of the Human Acetyl-CoA Thioesterase 12 and Interactions with the Steroidogenic Acute Regulatory Protein-related Lipid Transfer (START) Domain

Background: The regulation of ACOT12 by ADP and ATP is thought to occur through oligomerization. Results: The structures of apo-ACOT12 and ADP-bound ACOT12 reveal new insights into regulation. Conclusion: ACOT12 is a homotrimer and neither ADP nor ATP alter the oligomeric state of the protein. Significance: These findings provide the first structural insights in the regulation of this enzyme family. Acetyl-CoA plays a fundamental role in cell signaling and metabolic pathways, with its cellular levels tightly controlled through reciprocal regulation of enzymes that mediate its synthesis and catabolism. ACOT12, the primary acetyl-CoA thioesterase in the liver of human, mouse, and rat, is responsible for cleavage of the thioester bond within acetyl-CoA, producing acetate and coenzyme A for a range of cellular processes. The enzyme is regulated by ADP and ATP, which is believed to be mediated through the ligand-induced oligomerization of the thioesterase domains, whereby ATP induces active dimers and tetramers, whereas apo- and ADP-bound ACOT12 are monomeric and inactive. Here, using a range of structural and biophysical techniques, it is demonstrated that ACOT12 is a trimer rather than a tetramer and that neither ADP nor ATP exert their regulatory effects by altering the oligomeric status of the enzyme. Rather, the binding site and mechanism of ADP regulation have been determined to occur through two novel regulatory regions, one involving a large loop that links the thioesterase domains (Phe154-Thr178), defined here as RegLoop1, and a second region involving the C terminus of thioesterase domain 2 (Gln304-Gly326), designated RegLoop2. Mutagenesis confirmed that Arg312 and Arg313 are crucial for this mode of regulation, and novel interactions with the START domain are presented together with insights into domain swapping within eukaryotic thioesterases for substrate recognition. In summary, these experiments provide the first structural insights into the regulation of this enzyme family, revealing an alternate hypothesis likely to be conserved throughout evolution.
Manufacture and Experimental Analysis of a Concentrated Strain Based Deployable Truss Structure

Abstract : A truss structure was built and tested to advance deployable structures technology based on the concentrated strain approach. In 3rd order hierarchy systems, this architecture has the potential to provide a 10 fold improvement in mass efficiency, and demonstrate a linear compaction ratio that is five times better than current technology. A 101.6 cm x 12.7 cm x 12.7 cm test article was fabricated, and a buckling test and analysis was performed. The total mass of the deployable truss structure was 28 grams. This structure was constructed of piecewise constant cross section elements. One of the components consisted of high modulus pull-truded carbon fiber rods (CFRs) for the majority of the length. The other components were compliant flexure joints made of Nitinol NiTi, a shape memory alloy (SMA) capable of a repeatable superelastic strain of 5.0% at either boundary. The results of this research provide a contribution to the deployable structures science by improving the compaction ratio and the mass efficiency of deployable structures without decreasing the truss performance limits.
Flotillins Are Involved in the Polarization of Primitive and Mature Hematopoietic Cells

Background Migration of mature and immature leukocytes in response to chemokines is not only essential during inflammation and host defense, but also during development of the hematopoietic system. Many molecules implicated in migratory polarity show uniform cellular distribution under non-activated conditions, but acquire a polarized localization upon exposure to migratory cues. Methodology/Principal Findings Here, we present evidence that raft-associated endocytic proteins (flotillins) are pre-assembled in lymphoid, myeloid and primitive hematopoietic cells and accumulate in the uropod during migration. Furthermore, flotillins display a polarized distribution during immunological synapse formation. Employing the membrane lipid-order sensitive probe Laurdan, we show that flotillin accumulation in the immunological synapse is concomittant with membrane ordering in these regions. Conclusions Together with the observation that flotillin polarization does not occur in other polarized cell types such as polarized epithelial cells, our results suggest a specific role for flotillins in hematopoietic cell polarization. Based on our results, we propose that in hematopoietic cells, flotillins provide intrinsic cues that govern segregation of certain microdomain-associated molecules during immune cell polarization.
Metastability of R-charged black holes

The global stability of R-charged AdS black holes in a grand canonical ensemble is examined by eliminating the constraints from the action, but without solving the equations of motion, thereby constructing the reduced action of the system. The metastability of the system is found to set in at a critical value of the chemical potential which is conjugate to the R-charge. The relation among the small black hole, large black hole and the instability is discussed. The result is consistent with the metastability found in the AdS/CFT-conjectured dual field theory. The ‘renormalized’ temperature of AdS black holes, which has been rather ad hoc, is suggested to be the boundary temperature in the sense of AdS/CFT correspondence. As a byproduct of the analysis, we find a more general solution of the theory and its properties are briefly discussed.