Miracle-dz/UniFAR-FTUs huggingface dataset:
4E-BP2/SH2B1/IRS2 Are Part of a Novel Feedback Loop That Controls β-Cell Mass

The mammalian target of rapamycin complex 1 (mTORC1) regulates several biological processes, although the key downstream mechanisms responsible for these effects are poorly defined. Using mice with deletion of eukaryotic translation initiation factor 4E-binding protein 2 (4E-BP2), we determine that this downstream target is a major regulator of glucose homeostasis and β-cell mass, proliferation, and survival by increasing insulin receptor substrate 2 (IRS2) levels and identify a novel feedback mechanism by which mTORC1 signaling increases IRS2 levels. In this feedback loop, we show that 4E-BP2 deletion induces translation of the adaptor protein SH2B1 and promotes the formation of a complex with IRS2 and Janus kinase 2, preventing IRS2 ubiquitination. The changes in IRS2 levels result in increases in cell cycle progression, cell survival, and β-cell mass by increasing Akt signaling and reducing p27 levels. Importantly, 4E-BP2 deletion confers resistance to cytokine treatment in vitro. Our data identify SH2B1 as a major regulator of IRS2 stability, demonstrate a novel feedback mechanism linking mTORC1 signaling with IRS2, and identify 4E-BP2 as a major regulator of proliferation and survival of β-cells.
B7–CD28 Costimulatory Signals Control the Survival and Proliferation of Murine and Human γδ T Cells via IL-2 Production

γδ T cells play key nonredundant roles in immunity to infections and tumors. Thus, it is critical to understand the molecular mechanisms responsible for γδ T cell activation and expansion in vivo. In striking contrast to their αβ counterparts, the costimulation requirements of γδ T cells remain poorly understood. Having previously described a role for the TNFR superfamily member CD27, we since screened for other nonredundant costimulatory receptors in γδ T cell activation. We report in this article that the Ig superfamily receptor CD28 (but not its related protein ICOS) is expressed on freshly isolated lymphoid γδ T cells and synergizes with the TCR to induce autocrine IL-2 production that promotes γδ cell survival and proliferation in both mice and humans. Specific gain-of-function and loss-of-function experiments demonstrated a nonredundant function for CD28 interactions with its B7 ligands, B7.1 (CD80) and B7.2 (CD86), both in vitro and in vivo. Thus, γδ cell proliferation was significantly enhanced by CD28 receptor agonists but abrogated by B7 Ab-mediated blockade. Furthermore, γδ cell expansion following Plasmodium infection was severely impaired in mice genetically deficient for CD28. This resulted in the failure to mount both IFN-γ–mediated and IL-17–mediated γδ cell responses, which contrasted with the selective effect of CD27 on IFN-γ–producing γδ cells. Our data collectively show that CD28 signals are required for IL-2–mediated survival and proliferation of both CD27+ and CD27− γδ T cell subsets, thus providing new mechanistic insight for their modulation in disease models.
On the generality of leadership style measures across cultures

It is proposed that cross-cultural studies of leadership style have failed to distinguish adequately between global characterizations of style and the specific behaviours which leaders need to use in a given culture if a particular style is to be attributed to them. A study is reported of perceptions of electronics plant supervisors in Britain, the USA, Japan and Hong Kong, derived from Misumi's PM leadership theory. The findings indicate that characterizations of P(Performance) and M(Maintenance) leader style have a similar factor structure in each culture. However, the specific behaviours associated with those styles differ markedly, in ways which are comprehensible within the cultural norms of each setting. The study illustrates how a series of emic correlations within each culture sample may be used to test the validity of etic models of leader style.
Dementia and Rapid Mortality: Who is at Risk?

BACKGROUND Dementia is typically known for its insidious onset and slowly progressive course, but a subgroup deteriorates fast and dies within years or even months. OBJECTIVE The purpose of this study was to characterize dementia patients with a rapidly progressive course to death and evaluate their cause of death. METHODS We retrospectively included all patients from the Amsterdam Dementia Cohort who died within two years after diagnosis. We evaluated the characteristics of these rapid progressors and compared them to patients known to be alive two years after diagnosis ('non-rapid mortality'). RESULTS We included 129 dementia patients (13% of our total cohort with known follow-up) with rapid mortality (age 72±10 y [29% <65 y], 70[55%]M, MMSE 20±5). Mean(SD) survival was 12±7 months. Compared to non-rapid mortality patients (n = 892; age 68±9, 503(56%)M, MMSE 22±5), patients with rapid mortality were slightly older at time of diagnosis, had lower MMSE scores, more depressive symptoms and higher prevalence of a cardiovascular history (all p < 0.05). Alzheimer's disease (AD, 43%) was most frequent in patients with rapid mortality, but the occurrence was much lower compared to non-rapid mortality patients (71%), while all other dementia diagnoses, especially Creutzfeldt-Jakob disease (CJD), vascular dementia (VaD), and frontotemporal dementia (FTD), were more frequent (p < 0.001). There were no specific characteristics for AD patients with rapid versus non-rapid mortality, especially APOE genotypes and CSF-profiles were comparable (p > 0.70). Cause of death was highly variable without a clear relation to dementia diagnosis, with exception of dementia itself in CJD, intracerebral hematoma in VaD, and motor neuron disease in FTD. CONCLUSIONS Short survival is relatively common (∼13% in our cohort) and occurs in all different types of dementia, with overrepresentation of non-AD dementias like CJD, VaD, and FTD.
Diagnostic tests in urology: magnetic resonance imaging (MRI) for the staging of prostate cancer

The use of MRI for prostate cancer diagnosis and staging is increasing. Indications for prostate MRI are not defined and many clinicians are unsure of how best to use MRI to aid clinical decisions. This evidence‐based medicine article addresses the clinical utility of prostate MRI for preoperative staging. Based on a common patient scenario, a guide to calculating the probability of extraprostatic extension is provided.
Personal Hypothesis Testing: The Role of Consistency and Self-Schema

We report the results of two experiments that examined the way individuals test hypotheses about themselves. Both experiments were based on the work of Snyder (e.g., Snyder, 1981; Snyder & Skrypnek, 1981), which suggests that individuals have a confirmatory bias when testing hypotheses about others and about themselves. In Experiment 1, we examined the extent to which this bias toward confirmation persists when a negative (e.g., depression) or nonconsistent (not consistent with the individual's evaluation of him- or herself) personal hypothesis is tested. Results suggest that the negative or positive nature of a personal hypothesis does not directly influence the way individuals test their hypothesis. However, the way individuals tested personal hypotheses was influenced by hypothesis consistency. In Experiment 2, we examined the relation of a cognitive schematic variable (i.e., vulnerability for depression) and hypothesis testing. Results suggest that vulnerability is related to the way individuals test a personal hypothesis about depression. Vulnerable, low-depression participants were confirmatory when testing a depression hypothesis, whereas nonvulnerable, low-depression participants were disconfirmatory. We discuss implications for counseling and future directions for research.
Controlling processing usage at user level: a way to make resource sharing more flexible

General purpose Operating Systems do not provide effective mechanisms for application processing reservation. To overcome this limitation, some initiatives aim at guaranteeing processing by instrumenting kernels or by isolating the performance through the creation of virtual machines. However, these proceedings may be impractical if the kernel code is not available or high overheads should be avoided. As will be described in this paper, CPUReserve works differently from these approaches. It is a processing reservation system that runs at user level. CPUReserve allows the configuration of the active scheduling policy and simplifies the development of new ones. Thus, it can be used in many computing scenarios such as distributed and shared environments. Copyright © 2009 John Wiley & Sons, Ltd.
The Effect of Switching between Sequential and Repetitive Movements on Cortical Activation

We used whole-head functional magnetic resonance imaging (fMRI) to investigate the effect of switching between different sequential and repetitive movements in the context of conditional and fixed tasks. Four different movement tasks were applied: (1) unpredictable switching between two movement sequences comprising six submovements each according to visual cues (SEQ-VC); (2) unpredictable switching between repetitive movement of one finger according to visual cues (REP-VC); (3) performance of the same sequential movements used for SEQ-VC but in a fixed mode triggered by a visual stimulus (SEQ-FIX); (4) performance of the repetitive movements used for REP-FIX but in a fixed mode by a visual stimulus (REP-FIX). The statistical group analysis of the hemodynamic responses revealed the following results: (1) the SEQ-VC compared to the SEQ-FIX condition (switching between movement sequences) engendered stronger activations in the left rostral supplementary motor area (pre-SMA), bilaterally in the posterior parietal lobule, the left ventral premotor area, and the visual cortices; (2) the REP-VC compared to the REP-FIX condition (switching between repetitive movements) only revealed stronger activation in extra-striate areas. We hypothesize that during switching of movement sequences higher motor control aspects are involved including movement selection, updating of motor plans, as well as recalling and restoring motor plans. The repetitive movements are too simple in order to evoke additional activations in the medial and lateral premotor areas, as well as in parietal areas.
Information flow and influence in collective choice

If decision-relevant information is distributed among team members, the group is inclined to focus on common information and to neglect unique information. This classical finding is robust in experimental settings, in which the distribution of information is created by experimental design. The current paper examines information sharing when access to information is not restricted. We analyzed archival search and discussion data obtained from business executives completing a personnel selection exercise. Information popularity in the population from which groups were composed predicted both the number of group members accessing items during information searches and whether the group discussed the items. The number of group members who accessed an item predicted whether information was repeated during discussion, and repetition predicted which items were included on an executive summary. Moreover, cognitively central group members were more influential than cognitively peripheral members. One implication is that collective information search and discussion highlights information that is perceived as relevant in the population from which groups are composed.
Genomic Prediction in Maize Breeding Populations with Genotyping-by-Sequencing

Genotyping-by-sequencing (GBS) technologies have proven capacity for delivering large numbers of marker genotypes with potentially less ascertainment bias than standard single nucleotide polymorphism (SNP) arrays. Therefore, GBS has become an attractive alternative technology for genomic selection. However, the use of GBS data poses important challenges, and the accuracy of genomic prediction using GBS is currently undergoing investigation in several crops, including maize, wheat, and cassava. The main objective of this study was to evaluate various methods for incorporating GBS information and compare them with pedigree models for predicting genetic values of lines from two maize populations evaluated for different traits measured in different environments (experiments 1 and 2). Given that GBS data come with a large percentage of uncalled genotypes, we evaluated methods using nonimputed, imputed, and GBS-inferred haplotypes of different lengths (short or long). GBS and pedigree data were incorporated into statistical models using either the genomic best linear unbiased predictors (GBLUP) or the reproducing kernel Hilbert spaces (RKHS) regressions, and prediction accuracy was quantified using cross-validation methods. The following results were found: relative to pedigree or marker-only models, there were consistent gains in prediction accuracy by combining pedigree and GBS data; there was increased predictive ability when using imputed or nonimputed GBS data over inferred haplotype in experiment 1, or nonimputed GBS and information-based imputed short and long haplotypes, as compared to the other methods in experiment 2; the level of prediction accuracy achieved using GBS data in experiment 2 is comparable to those reported by previous authors who analyzed this data set using SNP arrays; and GBLUP and RKHS models with pedigree with nonimputed and imputed GBS data provided the best prediction correlations for the three traits in experiment 1, whereas for experiment 2 RKHS provided slightly better prediction than GBLUP for drought-stressed environments, and both models provided similar predictions in well-watered environments.
School Improvement Plans in Schools on Probation: A Comparative Content Analysis across Three Accountability Systems

This article explores school improvement planning under conditions of high-stakes accountability by means of a content analysis of school improvement plans. The schools examined here were identified by their accountability agencies as low performing and were put on probation to reverse their decline. Schools in three accountability systems are compared. Content analyses indicated that school improvement plans across the three jurisdictions were very similar, suggesting institutional isomorphism. However, certain policy design features prompted variation in the levels of internalization of external demands by school sites.
Essential role for Atox1 in the copper-mediated intracellular trafficking of the Menkes ATPase

The metallochaperone Atox1 directly interacts with the copper-transporting ATPases and plays a critical role in perinatal copper homeostasis. To determine the cell biological mechanisms of Atox1 function, intracellular copper metabolism, and Menkes ATPase abundance, localization and trafficking were examined in immortalized fibroblast cell lines derived from Atox1+/+ and Atox1−/− embryos. Consistent with the proposed role for Atox1 in copper delivery to the secretory pathway, a marked increase in intracellular copper content secondary to impaired copper efflux was observed in Atox1-deficient cells. Although the localization of the Menkes ATPase was identical in Atox1+/+ and Atox1−/− cells under conditions of equivalent intracellular copper content, a significant impairment in copper-mediated Menkes ATPase trafficking was observed in the absence of Atox1. When quantitative confocal immunofluorescence was used, significant differences in the time and dose-dependent trafficking of the Menkes ATPase from the Golgi compartment in response to copper were observed between Atox1+/+ and Atox1−/− cells. These data reveal an essential role for Atox1 in establishing the threshold for copper-dependent movement of the copper-transporting ATPases within the secretory compartment and that, in the absence of Atox1, this movement alone is not sufficient to restore normal copper efflux. Taken together, these findings provide a cell biological model for the role of this metallochaperone under the physiological conditions of copper limitation in mammalian cells.
Cooperation and Control in Japanese Nursery Schools

permanent employment have been attributed to Japanese child rearing. Yet, there is remarkably little English-language evidence on early socialization in Japan. This article provides observational data from 15 Japanese nursery schools. It is not my intention here to draw generalizations about Japanese nursery schools or to demonstrate differences between Japanese and American schools. The substantial variability in nursery schools within each country makes such systematic comparison an ambitious undertaking. Rather, the behavioral and ethnopsychological data of the present paper are intended to identify potentially interesting areas for future research on nursery school socialization and to stimulate American thinking about two aspects of early education: school practices which influence the development of cooperative behavior in children and adult strategies for controlling children's behavior.
DSNotify: handling broken links in the web of data

The Web of Data has emerged as a way of exposing structured linked data on the Web. It builds on the central building blocks of the Web (URIs, HTTP) and benefits from its simplicity and wide-spread adoption. It does, however, also inherit the unresolved issues such as the broken link problem. Broken links constitute a major challenge for actors consuming Linked Data as they require them to deal with reduced accessibility of data. We believe that the broken link problem is a major threat to the whole Web of Data idea and that both Linked Data consumers and providers will require solutions that deal with this problem. Since no general solutions for fixing such links in the Web of Data have emerged, we make three contributions into this direction: first, we provide a concise definition of the broken link problem and a comprehensive analysis of existing approaches. Second, we present DSNotify, a generic framework able to assist human and machine actors in fixing broken links. It uses heuristic feature comparison and employs a time-interval-based blocking technique for the underlying instance matching problem. Third, we derived benchmark datasets from knowledge bases such as DBpedia and evaluated the effectiveness of our approach with respect to the broken link problem. Our results show the feasibility of a time-interval-based blocking approach for systems that aim at detecting and fixing broken links in the Web of Data.
Computer-based Test Interpretations: Advice to the Consumer

Actuarial systems for computer-based test interpretation (C.B.T.I.) are distinguished from those based on clinical judgement. It is noted that most C.B. T.I. systems are of the latter type. Clinical judgement has proven superior to both types of C.B. T.I. system in the interpretation of neuropsychological tests and in several areas of medicine. Similar data on the automated clinical systems for the interpretation of personality instruments are sparse and methodologically weak. Studies of the validity of C.B. T.I. systems for the most popular personality inventory–the Minnesota Multiphasic Personality Inventory–are reviewed in detail. Fourteen criteria are proposed for evaluating the adequacy of these and similar studies. Four additional suggestions are made for the benefit of those trying to choose a C.B. T.I. system for practical use: Check the bona fides of the system author; check to ensure that scoring and interpretation are orthodox; read scholarly reviews of the system; and evaluate the system using a set of cases with known outcomes. Finally, five situations are described that should lead one to be especially sceptical about the accuracy of C.B. T.I. s: Inferences about low probability events (e.g. suicide); rare score combinations; extreme scores; scores near cut-offs; and unusual response sets or styles. Les systemes actuariels d' interpretation de tests par ordinateur (C.B.T.I.) doivent etre distingues de ceux fondes sur le jugement clinique. La plupart des systemes C.B. T.I. sont du second type. Le jugement clinique s'est revele superieur aux deux categories de systemes C.B. T.I. dans l'interpretation des tests neuropsychologiques ainsi que dans d'autres domaines de la medecine. Les donnees analogues sur les systemes cliniques automatises d'interpretation des epreuves de personnalite sont rares et methodologiquement contestables. Les etudes de validite des systemes C.B. T.I. appliques a l'inventaire de personnalite le plus repandu (le M.M.P.I.) sont recensees en detail. On propose 14 criteres pour apprecier la valeur de ce genre d'etudes. Quatre suggestions complementaires sont destinees a ceux qui souhaitent selectionner un systeme C.B. T.I. pour leur pratique: Controlez la bonne foi de l'auteur du systeme; verifiez l'orthodoxie de la cotation et de l'interpretation; lisez ce qui a eteecrit sur le systeme; eprouvez-le en utilisant une serie de cas dont vous connaissez l'interpretation. Enfin, on decrit cinq situations dans lesquelles s'impose le scepticisme en ce qui concerne la validite des C.B. T.I. : La prediction devene-ments a faible probabilitye comme le suicide, la combinaison de scores rares, les scores extremes, les scores proches des limites de classes, les series ou styles de reponses inhabituelles.
Conformation and packing of porphyrin polymer chains deposited using electrospray on a gold surface.

Conjugated porphyrin polymers have stimulated great interest due to their potential applications in nonlinear optics, light harvesting and nanoscale charge transport. As with many other organic materials, interfacial properties are likely to play an important role in their applications in molecular electronics. However, it has not so far been possible to study these effects due to the difficulty in preparing suitable monolayers, since the relevant polymers and oligomers cannot be sublimed. A question of particular interest relates to the influence of the flexibility of such a large molecule on the ordering within interfacial regions. We have investigated the adsorption of two oligomers, a porphyrin tetramer (P4, N= 4; see Figure 1 for structural diagrams), a hexamer (P6, N= 6), and a polymer Pn (N = 30–50) on the Au(111) surface using scanning tunneling microscopy (STM). The porphyrin units have long octyloxy side chains to promote solubility in organic solvents. Our experiments are performed at room temperature under ultrahigh vacuum (UHV) conditions (base pressure 5 10 11 Torr) and we use UHV electrospray deposition (UHV-ESD) to transfer the oligomers and polymers directly from solution onto a surface. In our approach to UHV-ESD, a volatilized mixture of solvent and solute molecules is produced in atmosphere by electrospray. This mixture enters the UHV system through a small aperture and is passed through a series of differentially pumped chambers, to the Au(111) substrate (for further details see Supporting Information). UHV-ESD and related approaches have been used to introduce nanotubes, fullerenes, dye molecules, and polymers into a UHV environment. Images acquired after deposition of a sub-monolayer coverage of P6 (Figure 2) show that, despite their large size, the porphyrin oligomers diffuse on the surface and form Figure 1. a) Structure of porphyrin oligomers and polymers. b) P6 molecule with the trihexylsilyl end groups truncated to trimethylsilyl groups for clarity.