Miracle-dz/UniFAR-FTUs huggingface dataset:
BET inhibitor OTX015 targets BRD2 and BRD4 and decreases c-MYC in acute leukemia cells

The bromodomain (BRD) and extraterminal (BET) proteins including BRD2, BRD3 and BRD4 have been identified as key targets for leukemia maintenance. A novel oral inhibitor of BRD2/3/4, the thienotriazolodiazepine compound OTX015, suitable for human use, is available. Here we report its biological effects in AML and ALL cell lines and leukemic samples. Exposure to OTX015 lead to cell growth inhibition, cell cycle arrest and apoptosis at submicromolar concentrations in acute leukemia cell lines and patient-derived leukemic cells, as described with the canonical JQ1 BET inhibitor. Treatment with JQ1 and OTX15 induces similar gene expression profiles in sensitive cell lines, including a c-MYC decrease and an HEXIM1 increase. OTX015 exposure also induced a strong decrease of BRD2, BRD4 and c-MYC and increase of HEXIM1 proteins, while BRD3 expression was unchanged. c-MYC, BRD2, BRD3, BRD4 and HEXIM1 mRNA levels did not correlate however with viability following exposure to OTX015. Sequential combinations of OTX015 with other epigenetic modifying drugs, panobinostat and azacitidine have a synergic effect on growth of the KASUMI cell line. Our results indicate that OTX015 and JQ1 have similar biological effects in leukemic cells, supporting OTX015 evaluation in a Phase Ib trial in relapsed/refractory leukemia patients.
New directions in attachment theory and research

The goal of this special issue is to take stock of attachment theory and research as it applies to adolescent and adult relationships. We briefly summarize and comment on the 12 articles included in the issue, placing them into four thematic categories: (i) attachment theory and research viewed from a life history perspective; (ii) biological bases of attachment processes; (iii) relations between the attachment system and other behavioral systems; and (iv) extensions of attachment research in applied directions. Taken together, the 12 articles provide an exciting foundation for future research on attachment and further development of attachment theory.
Defining neurogenetic phenotypes (or how to compare needles in haystacks).

Accurate diagnosis is the foundation of clinical neurology, providing both the physician and the patient with a guide to the future, hopefully leading to a treatment, and sometimes pointing towards a cure. Unlike many other clinical disciplines, the day-to-day practice of neurology involves a pantheon of symptoms and long lists of differential diagnoses. The challenge is to spot the rarities, especially if this is going to influence clinical management. This should be much easier in 2010, given recent advances in the routine diagnostic armamentarium; but paradoxically it seems more difficult, as we continue to dissect sub-categories of common disorders and overlapping clinical spectrums expand. So what are the distinguishing features of a particular disorder, and how can we reliably define them? This is particularly difficult if they are exceptionally rare ‘once in a lifetime’ diagnoses. Two papers in this edition of Brain tackle this issue for two important genetic neurometabolic disorders (Jinnah et al. , 2010; Leen et al. , 2010), illustrating an emerging approach to this thorny topic. In 1964, the medical student Michael Lesch and the paediatrician Bill Nyhan published the classic description of two brothers, aged 4 and 8, with a new familial disorder of uric acid metabolism and central nervous system dysfunction (Lesch and Nyhan, 1964). The primary biochemical defect was defined within a few years, affecting the enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT) (Seegmiller et al. , 1967), ultimately leading to the identification of recessive mutations in the X-chromosomal disease gene HPRT1 . After a normal pregnancy and birth, Lesch–Nyhan disease typically presents with developmental delay in the first year of life, most noticeably affecting the motor system, and leading to delayed sitting, crawling and walking. Involuntary movements develop before school age, with dystonia and choreoathetosis, leading on to spasticity that prevents affected boys from walking …
Exploring self training for Hindi dependency parsing

In this paper we explore the effect of selftraining on Hindi dependency parsing. We consider a state-of-the-art Hindi dependency parser and apply self-training by using a large raw corpus. We consider two types of raw corpus, one from same domain as of training and testing data and the other from different domain. We also do an experiment, where we add small gold-standard data to the training set. Comparing these experiments, we show the impact of adding small, but gold-standard data to training data versus large, but automatically parsed data on Hindi parser.
ECONOMICS FOR A CREATIVE WORLD* (and a response to comments)

Drawing on current biology, we argue that the phase space of economic evolution is not stable. Thus, there are no entailing laws of economic dynamics. In this sense, economic dynamics are creative and the economy is not a causal system. Because economic dynamics are creative, the implicit frame of analysis for the econosphere changes in unprestatable and non-algorithmic ways. New-venture, social, and political entrepreneurs solve the frame problem of the econosphere. Economic evolution is unpredictable, not entailed, and the number of things traded (‘cambiodiversity’) increases over time. Our metatheoretic framework points out how institutions, entrepreneurs, and disparate actors enable what we call ‘novelty intermediation’. We provide examples of novelty intermediation from Rennaissance Italy to Silicon Valley. Our framework does not automatically provide clear policy prescriptions in part because our main result is negative. It may nevertheless provide a useful prolegomenon to a future economics fit for a creative world. [T]he matter with which the chemist deals is the same always: but economics, like biology, deals with a matter, of which the inner nature and constitution, as well as the outer form, are constantly changing (Alfred Marshall). ∗Email: rkoppl@syr.edu ∗∗Email: stukauffman@gmail.com ∗∗∗Email: teppo.felin@sbs.ox. ac.uk ∗∗∗∗Email: Giuseppe.Longo@ens.fr We thank two anonymous referees for helpful comments. We thank Geoffrey Hodgson and Richard Langlois for help and encouragement. This paper emerged from many conversations each of us has had over the years. We regret that we cannot properly acknowledge everyone who contributed to our efforts through these many conversations.
Meninos e meninas: expectativas corporais e implicações na educação física escolar

In this paper gender is discussed as a social construction which is established by a given culture in relation to men and women. Gender is characterised as a relational construction with reference not only to the other sex but also to categories such as race, age, social class and motor skills. The paper also analyses: (i) boys' and girls' anticipated bodily expectations and how they manifest in school culture; (ii) how this concept of sport can be re-defined by applying this notion of gender to contents in Physical Education; (iii) possibilities for teachers' interventions in the construction of relationships between boys and girls.
Body weight gain rate in patients with Parkinson's disease and deep brain stimulation

We evaluated body weight changes in patients with Parkinson's disease (PD) after electrode implantation for deep brain stimulation (DBS) in the subthalamic nucleus (STN) in relation to clinical improvement. Thirty PD patients who received STN DBS were included (22 men, 8 women; mean age, 60.0 ± 7.1 years; mean PD duration, 13.5 ± 3.7 years; mean body mass index [BMI], 21.6 ± 3.0 kg/m2). Body weight, physical activity, and Unified Parkinson's Disease Rating Scale (UPDRS) scores were noted before and 3 and 12 months after the procedure. Significant weight gain occurred in 29 patients; the mean increase was 14.8 ± 9.8% of initial body weight in 1 year. Of the patients, 46.5% reported weight gain in the first 3 months, 21.4% gradual weight gain in the first 6 months, and 32.1% a slow increase for 1 year. Mean BMI increased up to 24.7 ± 3.7 kg/m2. After 1 year, mean UPDRS motor score improved significantly in off and in on; and therapy complications improved by 91.0 ± 17.0%. BMI changes at 3 and 12 months were significantly correlated to dyskinesia score changes, and levodopa dosage was not. In PD, STN DBS produces not only symptom control, but also weight gain. DBS candidates should be given nutritional counseling before the intervention to prevent rapid and/or excessive weight gain. © 2003 Movement Disorder Society
East—West Differences in Attributions for Company Performance

Prior cross-cultural studies indicate that the self-serving attributional bias is more prevalent in Western cultures than in Eastern cultures. There is, however, a dearth of research looking into cross-cultural differences in attributional patterns that is based on publicly available archival data. This study tries to fill that lacuna. It reports the results based on a content analysis of corporate annual reports from U.S. and Japanese companies. The results reported in this study demonstrate that cross-cultural differences found in experimental settings are not necessarily observed in naturalistic settings. Specifically, this study reveals that both U.S. as well as Japanese companies explain company results in a self-serving fashion. Overall, the results support the notion that the nature of the relationship affects the extent to which cross-cultural differences in attributional patterns emerge.
Moderators of the curvilinear relation between extent of telecommuting and job and life satisfaction: The role of performance outcome orientation and worker type

The purpose of this study is to determine factors that are related to employee satisfaction with telecommuting. Recent research supports the notion of a curvilinear relation between extent of telecommuting and job satisfaction. Drawing on control theory, we find that performance outcome orientation (degree to which objective criteria are used in employee evaluation) moderates the curvilinear relation between extent of telecommuting and job satisfaction. We also find support for a curvilinear (inverted U) relation between extent of telecommuting and life satisfaction, with worker type (defined by work drive and work enjoyment) moderating that relation.
Regulation of Fibroblast Growth Factor-inducible 14 (Fn14) Expression Levels via Ligand-independent Lysosomal Degradation*

Background: Fn14 is a highly inducible TNF superfamily cytokine receptor. Results: Fn14 undergoes rapid, ligand-independent internalization and degradation mediated by the extracellular domain of the receptor. Conclusion: Fn14 expression is regulated through transcription as described previously and through a novel post-translational mechanism. Significance: Receptor trafficking may play an important role in regulating receptor availability, cytokine responses, and ligand-independent signaling. Fibroblast growth factor-inducible 14 (Fn14) is a highly inducible cytokine receptor that engages multiple intracellular signaling pathways, including nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK). Fn14 expression is regulated by several cytokines and growth factors, and Fn14 is transiently up-regulated after injury. In contrast, in states of chronic inflammatory disease and in some solid tumors, Fn14 is persistently up-regulated. However, the post-translational regulation of Fn14 expression has not been directly investigated. Thus, we examined Fn14 proteostasis in the presence and absence of the Fn14 ligand TNF-like weak inducer of apoptosis (TWEAK). Similar to other TNF receptor superfamily members, we found that TWEAK induces Fn14 internalization and degradation. Surprisingly, we also observed rapid, TWEAK-independent, constitutive Fn14 internalization and turnover. Fn14 levels are maintained in cell culture by ongoing synthesis and trafficking of the receptor, leading to subsequent down-regulation by lysosomal degradation. Unexpectedly, the extracellular domain of Fn14 is necessary and sufficient for constitutive turnover. Based on these findings, we propose a model in which constitutive down-regulation of Fn14 facilitates dynamic regulation of Fn14 protein levels and prevents spontaneous or inappropriate receptor signaling.
The prevention of falls in later life. A report of the Kellogg International Work Group on the Prevention of Falls by the Elderly.

Although falls among the elderly carry high costs to individuals and society, the prevention of falls in later life has not received adequate attention from health care professionals. The prevalence of falls appears to involve roughly one-third of persons aged 65 and over, and the risk of falling and suffering serious injury increases substantially up to the eighth decade of life. The proportion of falls which result in fracture is low, but the absolute number of older people who suffer fractures is high and places heavy demands on health care systems. Even falls which result in no physical injury often have serious social and psychological consequences for the elderly, including loss of confidence and restrictions in mobility, and high proportions of older people report fears of falling. There is a need to provide accurate information about the causes and prevention of falls in later life. Falls are not part of the normal aging process. Rather, they are due to underlying physical illnesses, medications, and environmental hazards, often in interaction. This report provides an overview of the elderly population at risk of falling and suffering serious injury, some of the reasons older people fall, and the methods to prevent falls which have been developed in both community and institutional settings. In addition, it suggests some of the practical steps which can be taken by health and social care professionals and by older people and their families in order to prevent falls. Empirical knowledge about the causes of falls by the elderly and the most effective methods of prevention remains limited. Major barriers to research have been the lack of a clear definition of a fall and the fact that falls are not included in medical diagnostic indices. It is recommended that falls be recorded as a disease entity in Index Medicus and in the International Classification of Diseases Xth Revision. To facilitate future comparisons of research findings on falls, a definition of a fall is proposed. The report underscores that the causes of falls are very different for persons of varying ages, health status, and levels of mobility. While the many risk factors for falls are not yet known, poor health status, especially chronic illness, impaired mobility and postural instability, and a history of prior falls have been associated with the risk of falling. Balance, the ability to prevent falls upon displacement, can be impaired by disease or age-related changes in a number of anatomical structures, by medications which reduce their efficient functioning, and by environmental hazards. (ABSTRACT TRUNCATED AT 400 WORDS)
Framework for the analysis of executive information systems based on the perceived usefulness and the perceived ease of use

The acquisition and use of information are key factors in successful executive performance. Although there are various and different media that executives use to obtain information, in the last decade the academic research has emphasised computer-based systems. Inside this group of systems, we can find the Executive Information Systems (EIS), which are tools that can help executives to obtain relevant informationmore efficiently.Recently, EIS have been analyzed through the Technology Acceptance Model (TAM) with significant results. A deeper review of these results, the existing literature, as well as our own experience, suggest there are some factors that affect to the use of EIS indirectly or as moderating variables, instead of directly as recent studies suggest. The objective of our research is to propose a framework based on the TAM, which shows the different types of factors that affect to the Perceived Usefulness (U) and Perceived Ease of Use(EOU) of EIS, as well as how the kind of influence of these factors on U and EOU.
Does Indigeneity Matter? Sentencing Indigenous Offenders in South Australia's Higher Courts

Abstract In Australia, research investigating Indigenous differences in sentencing is limited.This study examines the impact of offenders' Indigenous status on the decision to imprison and length of imprisonment in South Australia's Higher Courts. Results indicate that Indigenous offenders were less likely than their non-Indigenous counterparts to be sentenced to a term of imprisonment when appearing before the court under similar circumstances. However, when sentence length was decided, Indigenous offenders were sentenced to longer periods of imprisonment. The theoretical implications of these research findings are explored including conflict and focal concerns (attribution) perspectives.
Prefrontal Brain Asymmetry: A Biological Substrate of the Behavioral Approach and Inhibition Systems

Resting anterior brain electrical activity, self-report measures of Behavioral Approach and Inhibition System (BAS and BIS) strength, and general levels of positive and negative affect (PA and NA) were collected from 46 unselected undergraduates on two separate occasions Electroencephalogram (EEG) measures of prefrontal asymmetry and the self-report measures showed excellent internal consistency reliability and adequate test-retest stability Aggregate measures across the two assessments were computed for all indices Subjects with greater relative left prefrontal activation reported higher levels of BAS strength, whereas those with greater relative right prefrontal activation reported higher levels of BIS strength Prefrontal EEG asymmetry accounted for more than 25% of the variance in the self-report measure of relative BAS-BIS strength Prefrontal EEG, however, was not significantly correlated with PA or NA, or the relative strength of PA versus NA Posterior asymmetry was unrelated to the self-report measures
ADHD: applying practice guidelines to improve patient outcome and executive function.

T his ACADEMIC HIGHLIGHTS section of The Journal of Clinical Psychiatry presents the highlights of the planning teleconferences “ADHD: Applying Practice Guidelines to Improve Patient Outcome and Executive Function,” which were held in August and September 2006. This report was prepared by the CME Institute of Physicians Postgraduate Press, Inc., and was supported by an educational grant from McNeil Pharmaceuticals. The planning teleconferences were chaired by Joseph Biederman, M.D., Department of Psychiatry, Harvard Medical School and Department of Pediatric Psychopharmacology, Massachusetts General Hospital, Boston. The faculty were Steven A. Safren, Ph.D., Department of Psychiatry, Harvard Medical School and Department of Behavioral Medicine, Massachusetts General Hospital, Boston; Larry J. Seidman, Ph.D., Department of Psychiatry, Harvard Medical School and Department of Pediatric Psychopharmacology, Massachusetts General Hospital, Boston; Thomas J. Spencer, M.D., Department of Psychiatry, Harvard Medical School and Department of Pediatric Psychopharmacology, Massachusetts General Hospital, Boston; and Timothy E. Wilens, M.D., Department of Psychiatry, Harvard Medical School and Department of Pediatric Psychopharmacology, Massachusetts General Hospital, Boston. Faculty disclosure appears at the end of the article. The opinions expressed herein are those of the faculty and do not necessarily reflect the views of the CME provider and publisher or the commercial supporter. An Overview on Advances in the Neurobiology of ADHD
Long-Lived Self-Healing Group Key Distribution Scheme with Backward Secrecy

Self-healing group key distribution schemes allow for the establishment of a secure multicast communication between a group manager and group members through an unreliable broadcast channel. They can be used in multicast networks with centralized management, such as machine-to-machine systems, embedded and sensor networks, cellular networks and wireless networks. Constructions based on the exponential arithmetic are currently the most efficient long-lived schemes, but they lack backward secrecy. In this paper we present a new mechanism, which allows to achieve backward secrecy in this class of schemes and we illustrate its use in a long-lived key distribution scheme. Then, we perform security and performance analyses of the scheme, in order to show that it is efficient, achieves forward and backward secrecy, and resists collusion between the newly joined users and the revoked ones.
Community Colleges and Baccalaureate Attainment.

In recent years, several critics of the community college have raised the cry that baccalaureate aspirants are much less likely to receive a bachelor's degree if they enter a community college rather than a four-year college [11; 14, p. 209; 15, p. 226; 27; and 55, pp. 13-15]. For example, Steven Brint and Jerome Karabel [15, p. 227] recently declared: "The very fact of attending a two-year rather than a four-year institution lowers the likelihood that a student will obtain a bachelor's degree. " This claim has not gone unchallenged. Defenders of the community college have argued that the critics are comparing apples and oranges. Students who enter the community college, they note, are much less likely than four-year college entrants to want a baccalaureate degree. Moreover, even if they have such a desire, they are hampered by weaker academic skills, less certain plans, and shakier confidence than four-year college entrants. Hence, any simple comparison of baccalaureate-attainment rates is highly deceptive [24, p. 44; 72, pp. 11-12]. This debate is important. Despite the community college's strong commitment to occupational, remedial, and community and adult education, it still enrolls many students who aspire to a baccalaureate degree. They still make up 30 to 40 percent of all community college
Tight Coupling of Na+/K+-ATPase with Glycolysis Demonstrated in Permeabilized Rat Cardiomyocytes

The effective integrated organization of processes in cardiac cells is achieved, in part, by the functional compartmentation of energy transfer processes. Earlier, using permeabilized cardiomyocytes, we demonstrated the existence of tight coupling between some of cardiomyocyte ATPases and glycolysis in rat. In this work, we studied contribution of two membrane ATPases and whether they are coupled to glycolysis - sarcoplasmic reticulum Ca2+ ATPase (SERCA) and plasmalemma Na+/K+-ATPase (NKA). While SERCA activity was minor in this preparation in the absence of calcium, major role of NKA was revealed accounting to ∼30% of the total ATPase activity which demonstrates that permeabilized cell preparation can be used to study this pump. To elucidate the contribution of NKA in the pool of ATPases, a series of kinetic measurements was performed in cells where NKA had been inhibited by 2 mM ouabain. In these cells, we recorded: ADP- and ATP-kinetics of respiration, competition for ADP between mitochondria and pyruvate kinase (PK), ADP-kinetics of endogenous PK, and ATP-kinetics of total ATPases. The experimental data was analyzed using a series of mathematical models with varying compartmentation levels. The results show that NKA is tightly coupled to glycolysis with undetectable flux of ATP between mitochondria and NKA. Such tight coupling of NKA to PK is in line with its increased importance in the pathological states of the heart when the substrate preference shifts to glucose.