Miracle-dz/UniFAR-FTUs huggingface dataset:
Regulation of transferrin recycling kinetics by PtdIns[4,5]P2 availability

Phosphatidylinositol 4,5‐bisphosphate (PtdIns[4,5]P2) is a phosphoinositide involved in a variety of cellular functions, including signal transduction, organelle trafficking, and actin dynamics. Although the role of PtdIns[4,5]P2 in endocytosis is well established, the precise trafficking steps relying on normal PtdIns[4,5]P2 balance in the endosomal pathway have not yet been elucidated. Here we show that decrease in intracellular PtdIns[4,5]P2 levels achieved by the overexpression of the 5‐phosphatase domain of synaptojanin 1 or by siRNA knock‐down of PIP5Ks expression lead to severe defects in the internalization of transferrin as well as in the recycling of internalized transferrin back to the cell surface in COS‐7 cells. These defects suggest that PtdIns[4,5]P2 participates in multiple trafficking and/or sorting events during endocytosis. Coexpression of the PtdIns[4,5]P2 synthesizing enzyme, PIP5KI, was able to rescue these endocytic defects. Furthermore, decreased levels of PtdIns[4,5]P2 caused delays in rapid and slow membrane recycling pathways as well as a severe backup of endocytosed membrane. Taken together, our results demonstrate that PtdIns[4,5]P2 availability regulates multiple steps in the endocytic cycle in non‐neuronal cells. —Kim, S. , Kim, H. , Chang, B. , Ahn, N. , Hwang, S. , Di Paolo, G. , Chang, S. Regulation of transferrin recycling kinetics by PtdIns[4,5]P2 availability. FASEB J. 20, E1753–E1762 (2006)
Regulation of myocyte contraction via neuronal nitric oxide synthase: role of ryanodine receptor S‐nitrosylation

The sarcoplasmic reticulum (SR) Ca2+ release channel (ryanodine receptor, RyR2) has been proposed to be an end target of neuronal nitric oxide synthase (NOS1) signalling. The purpose of this study is to investigate the mechanism of NOS1 modulation of RyR2 activity and the corresponding effect on myocyte function. Myocytes were isolated from NOS1 knockout (NOS1−/−) and wild‐type mice. NOS1−/− myocytes displayed a decreased fractional SR Ca2+ release, NOS1 knockout also led to reduced RyR2 S‐nitrosylation levels. RyR2 channels from NOS1−/− hearts had decreased RyR2 open probability. Additionally, knockout of NOS1 led to a decrease in [3H]ryanodine binding, Ca2+ spark frequency (CaSpF) and a rightward shift in the SR Ca2+ leak/load relationship. Similar effects were observed with acute inhibition of NOS1. These data are indicative of decreased RyR2 activity in myocytes with NOS1 knockout or acute inhibition. Interestingly, the NO donor and nitrosylating agent SNAP reversed the depressed RyR2 open probability, the reduced CaSpF, and caused a leftward shift in the leak/load relationship in NOS1−/− myocytes. SNAP also normalized Ca2+ transient and cell shortening amplitudes and SR fractional release in myocytes with NOS1 knockout or acute inhibition. Furthermore, SNAP was able to normalize the RyR2 S‐nitrosylation levels. These data suggest that NOS1 signalling increases RyR2 activity via S‐nitrosylation, which contributes to the NOS1‐induced positive inotropic effect. Thus, RyR2 is an important end target of NOS1.
Evaluation of the circulating CD34+, CD309+, and endothelial progenitor cells in patients with first attack of optic neuritis

Background: Endothelial progenitor cells (EPCs) are present in circulation and contribute to vasculogenesis in adults. The aim of the present study was to determine the number of circulating EPCs in patients with optic neuritis (ON). Materials and Methods : Fifty patients with ON were diagnosed by expert neurologist and optometrist at the Feiz Hospital, Isfahan, Iran (2012-2013). Blood samples were collected from ON patients in the first attack. The number of EPCs was measured by flow cytometry through the assessment of CD34 + and CD309 + in patients and healthy individuals. Results : With using flow cytometry, CD34 + and CD309 + cells detected in peripheral blood cells of patients (n = 50) with ON, and healthy individuals (n = 30). Patients with ON had (mean = 66.71 ± 17.82) CD34 + and CD309 + cells compared with healthy controls (mean = 28.72 ± 22.46). In addition, there was no significant difference in CD309 + cells in both groups. Conclusion: This study showed elevated CD34 + and CD309 + cells in the early stage of the disease. Regarded to EPC increment in neural repair, it expected the EPC level be increased in these patients, but no detectable differences were observed among both markers in healthy and patient with first attack.
Material for : Empirical estimates suggest most published medical research is true

A common model for p-values from multiple hypothesis tests is the “two-groups” model[1], where the p-values are assumed to be drawn from the mixture distribution: p ∼ π0f0 + (1− π0)f1 where π0 is the proportion of p-values corresponding to tests where the null hypothesis is true, f0(·) is the density of the p-values under the null hypotheses and f1(·) is the density of p-values under the alternative hypothesis. In general, each test may have a corresponding null and alternative distribution, in which case both f0 and f1 may be represented by mixture distributions. This model is frequently used in genomics [2], or brain imaging studies [3], where thousands of variables are measured simultaneously with the goal of estimating the statistical significance of a group of variables [4]. This model simultaneously estimates π0, the fraction of results that are drawn from the null distribution. Alternatively, 1 − π0 represents the fraction of p-values from the alternative distribution.
Two Standards: One for the Media and One for the School

This paper argues that young Danes are in the process of changing the notion of Standard Danish, partly by 'moving' it in the direction of what used to be perceived as 'low' Copenhagen speech, partly by 'splitting' it in two. Verbal guise data gathered in the town of Næstved not far from Copenhagen in 1989 indicated that 'low' Copenhagen features were far from alien to young Næstveders' representations of Standard Danish. Furthermore, the upgrading of speakers with such features was found to be stronger on 'dynamism' traits than on 'superiority' traits. A replication of the study in 1998 showed that the notion of Standard Danish continues to move in the direction of 'low' Copenhagen speech, and also that considerations of 'dynamism' and 'superiority' continue to play a decisive role in young Næstveders' attitudinal relationship to the phonetic variation in Copenhagen speech. The paper suggests that the evaluative distinction between 'dynamism' and 'superiority' reflects different notions of 'excellence' within traditional public institutions like school and business, on the one hand, and the modern media, on the other.
PARTIAL OBSERVABILITY

We present and explore the agent programming language TEAMGOLOG, which is a novel approach to programming a team of cooperative agents under partial observability. Every agent is associated with a partial control program in Golog, which is completed by the TEAMGOLOG interpreter in an optimal way by assuming a decision-theoretic semantics. The approach is based on the key concepts of a synchronization state and a communication state, which allow the agents to passively resp. actively coordinate their behavior, while keeping their belief states, observations, and activities invisible to the other agents. We show the practical usefulness of the TEAMGOLOG approach in a rescue simulated domain. We describe the algorithms behind the TEAMGOLOG interpreter and provide a prototype implementation. We also show through experimental results that the TEAMGOLOG approach outperforms a standard greedy one in the rescue simulated domain. 1Electronic and Computer Science Department, University of Southampton, Southampton SO17 1BJ, UK; e-mail: af2@ecs.soton. ac.uk. Dipartimento di Informatica e Sistemistica, Sapienza Università di Roma, Via Ariosto 25, 00185 Rome, Italy; e-mail: farinelli@dis.uniroma1. it. 2Institut für Informationssysteme, TU Wien, Favoritenstraße 9-11, 1040 Vienna, Austria. Dipartimento di Scienze Fisiche, Università di Napoli Federico II, Via Cinthia, 80126 Naples, Italy; e-mail: finzi@na.infn. it. 3Computing Laboratory, University of Oxford, Wolfson Building, Parks Road, Oxford OX1 3QD, UK; e-mail: thomas.lukasiewicz@comlab.ox. ac.uk. Institut für Informationssysteme, TU Wien, Favoritenstraße 9-11, 1040 Vienna, Austria; e-mail: lukasiewicz@kr.tuwien. ac.at. Acknowledgements: This work has been partially supported by the Austrian Science Fund (FWF) under the Project P18146-N04 and by the German Research Foundation (DFG) under the Heisenberg Programme. We thank the reviewers of the IJCAI-2007 abstract of this paper for their constructive comments, which helped to improve this work. Copyright c © 2008 by the authors INFSYS RR 1843-08-04 I
The student teacher and the school community of practice: an exploration of the contribution of the legitimate peripheral participant

Relentless reform and increased accountability in education in England have led to increasing attention on the effectiveness of teachers’ professional development (PD). A shift away from top-down approaches to PD has led to more emphasis placed on in-house, collaborative models. This paper reports on qualitative research conducted in the south of England, which explored the notion of postgraduate certificate in education (PGCE) student teachers on school placements as legitimate peripheral participants in communities of practice. It focuses on the benefits to the “old-timer” of training a “newcomer” rather than the original approach of examining how the community shapes the apprentice. It was found that school stake holders recognized the positive contribution made to teachers’ PD by the student teachers. This paper suggests that schools should be encouraged to build upon communities of practice to realize the benefits to themselves of engaging in training student teachers.
CD4 is retained in the endoplasmic reticulum by the human immunodeficiency virus type 1 glycoprotein precursor

We analyzed coexpression of the human immunodeficiency virus type 1 glycoprotein precursor, gp160, and its cellular receptor CD4 in HeLa cells to determine whether the two molecules can interact prior to transport to the cell surface. Results of studies employing coprecipitation, analysis of oligosaccharide processing, and immunocytochemistry showed that newly synthesized CD4 and gp160 form a complex prior to transport from the endoplasmic reticulum (ER). CD4 expressed by itself was transported efficiently from the ER to the cell surface, but the complex of CD4 and gp160 was retained in the ER. This retention of CD4 within the ER is probably a consequence of the very inefficient transport of gp160 itself (R. L. Willey, J. S. Bonifacino, B. J. Potts, M. A. Martin, and R. D. Klausner, Proc. Natl. Acad. Sci. USA 85:9580-9584, 1988). Retention of CD4 in the ER by gp160 may partially explain the down regulation of CD4 in human immunodeficiency virus type 1-infected T cells. Inhibition of CD4 transport appears to be a consequence of the interaction of two membrane-bound molecules, because a complex of CD4 and gp120 (the soluble extracellular domain of gp160) was transported rapidly and efficiently from the ER.
Covert Planning for Social Transformation in Indonesia

Public engagement in planning can be viewed as a continuum ranging from local inclusion in synoptic planning schemes devised by the state to participation in grassroots social movements that seek broader social transformation. This continuum is incomplete because it does not elucidate how local people plan for social transformation within highly restrictive political environments where responses to social activism encompass real physical and social harm. The article draws on historical and contemporary analysis of social change in Indonesia and Malaysia together with a case study from Indonesia to demonstrate that social transformation does occur within environments where overt radical action is dangerous. In these circumstances, it takes a more subtle and nuanced form of collective action, here referred to as covert planning.
Regional Variations in Health Status

Context.Knowledge about variations in the health status of patients seeking primary care in different parts of the United States is limited. Objective.To examine regional variations in the physical and mental health of patients receiving primary care in the largest integrated health care system in the United States which is operated by the Department of Veteran Affairs (VA). Study design and setting. We performed a mailed, cross sectional survey of 54,844 patients who were enrolled in seven VA General Internal Medicine clinics. Results.Among the 30,690 patients who returned an initial set of screening questionnaires, the prevalence of common chronic conditions varied by as much as 60% among the seven clinics. Moreover, patients’ general health (measured by the SF-36) also varied significantly in a pattern that mirrored the observed differences in the prevalence of chronic conditions. After adjustment for important comorbid illnesses and sociodemographic factors, geographic site accounted for a small percentage of the explained variance in patient assessed health status. Conclusions.The substantial differences in the health of patients enrolled in different VA primary clinics have important implications for the evaluation of clinical performance and health outcomes. Most of these differences can be attributed to sociodemographic and comorbid factors.
The International Journal of Biostatistics A Nearly Exhaustive Search for CpG Islands on Whole Chromosomes

CpG islands are genome subsequences with an unexpectedly high number of CG dinucleotides. They are typically identified using filtering criteria (e.g., G+C% expected vs. observed CpG ratio and length) and are computed using sliding window methods. Most such studies illusively assume an exhaustive search of CpG islands are achieved on the genome sequence of interest. We devise a Lexis diagram and explicitly show that filtering criteria-based definitions of CpG islands are mathematically incomplete and non-operational. These facts imply that the sliding window methods frequently fail to identify a large percentage of subsequences that meet the filtering criteria. We also demonstrate that an exhaustive search is computationally expensive. We develop the Hierarchical Factor Segmentation (HFS) algorithm, a pattern recognition technique with an adaptive model selection device to overcome the incompleteness and non-operational drawbacks, and to achieve effective computations for identifying CpGislands. The concept of a CpG island “core" is introduced and computed using the HFS algorithm, which is independent from any specific filtering criteria. Upon such a CpG island “core," a CpGisland is constructed using a Lexis diagram. This two-step computational approach provides a nearly exhaustive search for CpG islands that can be practically implemented on whole chromosomes. In a simulation study realistically mimicking CpG-island dynamics through a Hidden Markov Model we demonstrate that this approach retains very high sensitivity and specificity, that is, very low rates of false positives and false negatives. Finally, we apply the HFS algorithm to identify CpG island cores on human chromosome 21.
Approximation Algorithms Going Online

In an online linear optimization problem, on each period t, an online algorithm chooses st ∈ S from a fixed (possibly infinite) setS of feasible decisions. Nature (who may be adversarial) choo ses a weight vector wt ∈ R, and the algorithm incurs cost c(st, wt), wherec is a fixed cost function that is linear in the weight vector. In thefull-information setting, the vector wt is then revealed to the algorithm, and in the banditsetting, only the cost experienced, c(st, wt), is revealed. The goal of the online algorithm is to perform ne arly as well as the best fixed s ∈ S in hindsight. Many repeated decision-making problems with weights fit natural ly into this framework, such as online shortest-path, onlin e TSP, online clustering, and online weighted set cover. Previously, it was shown how to convert any efficient xactoffline optimization algorithm for such a problem into an efficient online bandit algorithm in both the full-informat ion and the bandit settings, with average cost nearly as good as that of the best fixed s ∈ S in hindsight. However, in the case where the offline algorith m is an approximation algorithm with ratioα > 1, the previous approach only worked for special types of appr oximation algorithms. We show how to convert any efficient offline α-approximation algorithm for a linear optimization proble m into an efficient algorithm for the corresponding online problem, w ith average cost not much larger than α times that of the bests ∈ S, in both the full-information and the bandit settings. Our m ain innovation is in the full-information setting: we combine Zinkevich’s algorithm for convex optimization w ith a geometric transformation that can be applied to any approximation algorithm. In the bandit setting, standard t echniques apply, except that a “Barycentric Spanner” for th e problem is also (provably) necessary as input. Our algorithm can also be viewed as a method for playing a larg e repeated games, where one can only compute approximatebest-responses, rather than best-responses. TTI-C. sham@tti-c.org Georgia Tech. atk@cc.gatech. edu Carnegie Mellon. katrina@cs.cmu. edu
Study of Computational Issues in Simulation of Transient Flow in Continuous Casting

Unsteady three‐dimensional turbulent flow and heat transport in the liquid pool during continuous casting of steel slabs has been computed using several different computational models, domains, grids, and inlet conditions. The most advanced computations employ a large‐eddy simulation code, UIFLOW with a second‐order central‐differencing scheme, 1.6 million nodes and a realistic simulation domain including the complete submerged entry nozzle. The model has been validated in previous work through comparison with PIV measurements in caster water models, and with velocity and temperature measurements in an operating steel caster. The present computations are compared with flow measurements in a full‐scale water model and with heat flux measurements in a jet impingement test problem. Results are compared between model domains of the full caster with symmetric half‐caster and two‐fold symmetric quarter‐caster simulations. The effects of thermal buoyancy and the solidifying steel shell walls are studied independently. The effect of different inlet conditions is investigated by comparing results including nozzle simulations that are both coupled and uncoupled with the mold domain and a simplified nozzle geometry. The importance of the Sub‐grid scale (SGS) model for treating the small turbulent eddies is investigated through simulations with and without the Horiuti SGS K model. A rigorous grid refinement study is undertaken, which indicates criteria for choosing the element size near the walls. Accurate heat transfer predictions are more difficult to attain than accurate velocities. Finally, comparisons are made with Reynolds‐averaged approaches, including standard K‐ε and low Re‐number K‐ε model computations of the same system. The relative advantages and disadvantages of the different flow simulation methods are evaluated.
A 13-year follow-up of an adolescent psychiatric clientele

A follow-up of an adolescent psychiatric patient group, interviewed on the average 12 years after discharge, included scorings on the basis of the Global Assessment Scale. The four diagnostic groups (DSM-III) had different outcomes: for neurotic conditions a gradually increasing curve on the basis of GAS scores was seen? from the week before admission, the week before discharge, at termination of the outpatient treatment, and at follow-up. The curve indicates a GAS score of 78.3 at the time of follow-up, corresponding to cured or symptom-free. The outcome for the group of schizophrenics was unfavourable, with a GAS score at the time of follow-up of 36.5. A good outcome was seen for the group other psychoses, ending up with a GAS score of 68.5. The same outcome was found for the group of drug abusers, with a GAS score of 67.9 at the time of follow-up.
Multipotent Mesenchymal Stromal Cells for the Prophylaxis of Acute Graft-versus-Host Disease—A Phase II Study

The efficacy and the safety of the administration of multipotent mesenchymal stromal cells (MMSCs) for acute graft-versus-host disease (aGVHD) prophylaxis following allogeneic hematopoietic cell transplantation (HSCT) were studied. This prospective clinical trial was based on the random patient allocation to the following two groups receiving (1) standard GVHD prophylaxis and (2) standard GVHD prophylaxis combined with MMSCs infusion. Bone marrow MMSCs from hematopoietic stem cell donors were cultured and administered to the recipients at doses of 0.9–1.3 × 106/kg when the blood counts indicated recovery. aGVHD of stage II–IV developed in 38.9% and 5.3% of patients in group 1 and group 2, respectively, (P = 0.002). There were no differences in the graft rejection rates, chronic GVHD development, or infectious complications. Overall mortality was 16.7% for patients in group 1 and 5.3% for patients in group 2. The efficacy and the safety of MMSC administration for aGVHD prophylaxis were demonstrated in this study.
Simulating crowd phenomena in African markets

Crowd simulation is an important feature in the computer graphics field. Typical implementations simulate battle scenes, emergency situations, safety issues or add content to virtual environments. The problem stated in this paper falls in the last category. We present a crowd simulation behavioural model which allows us to simulate identified phenomena in popular local African markets such as narrow street flows and crowd formation around street performances. We propose a three-tier architecture model enable to produce intentions, perform path planning and control movement. We demonstrate that this approach produces the desired behaviour associated with crowds in an African market, which includes navigation, flow formation and circle creation.