Miracle-dz/UniFAR-FTUs huggingface dataset:
1 1 Contractile dysfunction in muscle may underlie androgen-dependent 2 motor dysfunction in spinal bulbar muscular atrophy 3 4 running title : Contractile dysfunction underlies motor dysfunction in SBMA 5 6

33 34 Spinal and bulbar muscular atrophy (SBMA) is characterized by progressive muscle 35 weakness linked to a polyglutamine expansion in the androgen receptor (AR). Current evidence 36 indicates that mutant AR causes SBMA by acting in muscle to perturb its function. However, 37 information about how muscle function is impaired is scant. One fundamental question is 38 whether the intrinsic strength of muscles, an attribute of muscle independent of its mass, is 39 affected. In the current study, we assess the contractile properties of hindlimb muscles in vitro 40 from chronically diseased males of three different SBMA mouse models: a transgenic (Tg) 41 model that broadly expresses a full length human AR with 97 CAGs (97Q), a knock-in (KI) 42 model that expresses a ‘humanized’ AR containing a CAG expansion in the first exon and a Tg 43 myogenic model that overexpresses wildtype AR only in skeletal muscle fibers. We find that 44 hindlimb muscles in the two Tg models (97Q and myogenic) show marked losses in their 45 intrinsic strength and resistance to fatigue, but were minimally affected in KI males. However, 46 diseased muscles of all three models showed symptoms consistent with myotonic dystrophy 47 type 1; namely, reduced resting membrane potential and deficits in chloride channel mRNA. 48 These data indicate that muscle dysfunction is a core feature of SBMA caused by at least some 49 of the same pathogenic mechanisms as myotonic dystrophy. Thus, mechanisms controlling 50 muscle function per se independent of mass are prime targets for SBMA therapeutics. 51
Kohonen neural networks for optimal colour quantization

We present a self-organizing Kohonen neural network for quantizing colour graphics images. The network is compared with existing algorithmic methods for colour quantization. It is shown experimentally that, by adjusting a quality factor, the network can produce images of much greater quality with longer running times, or slightly better quality with shorter running times than the existing methods. This confounds the frequent observation that Kohonen neural networks are necessarily slow. The continuity of the colour map produced can be exploited for further image compression, or for colour palette editing.
Effects of Peripherally Restricted κ Opioid Receptor Agonists on Pain-Related Stimulation and Depression of Behavior in Rats

κ Opioid receptor agonists that do not readily cross the blood-brain barrier are peripherally restricted and distribute poorly to the central nervous system after systemic administration. Peripherally restricted κ agonists have promise as candidate analgesics, because they may produce antinociception mediated by peripheral κ receptors more potently than they produce undesirable sedative and psychotomimetic effects mediated by central κ receptors. The present study used assays of pain-related stimulation and depression of behavior in rats to compare effects of 1) two peripherally restricted κ agonists [the tetrapeptide d-Phe-d-Phe-d-Ile-d-Arg-NH2 (ffir) and the nonpeptidic compound ((R,S)-N-[2-(N-methyl-3,4-dichlorophenylacetamido)-2-(3-carboxyphenyl)-ethyl]pyrrolidine hydrochloride (ICI204448)], 2) a centrally penetrating κ agonist (salvinorin A), and 3) several reference drugs, including a nonsteroidal anti-inflammatory drug (NSAID; ketoprofen). Intraperitoneal injection of dilute lactic acid served as a noxious stimulus to stimulate a stretching response and depress intracranial self-stimulation (ICSS) maintained by the delivery of electrical brain stimulation to the medial forebrain bundle. Acid-stimulated stretching was blocked by ketoprofen, the peripherally restricted κ agonists, and salvinorin A. However, acid-induced depression of ICSS was blocked only by ketoprofen. The peripherally restricted κ agonists had little effect, and salvinorin A exacerbated acid-induced depression of ICSS. These results suggest that peripherally restricted κ agonists may be safer than centrally penetrating κ agonists but less efficacious than NSAIDS or μ opioid receptor agonists to block pain-related depression of behavior; however, the peripheral selectivity of ffir and ICI204448 is limited, and future studies with κ agonists capable of greater peripheral selectivity are warranted.
Glucocorticoid receptor gene polymorphisms and childhood adversity are associated with depression: New evidence for a gene–environment interaction

The hypothalamic‐pituitary‐adrenal (HPA)‐axis regulates the response to stressful events and is expected to be involved in the pathogenesis of depression. The glucocorticoid receptor (GR) regulates the activity of the HPA‐axis. Both GR gene polymorphisms and childhood adversity are known to be associated with increased risk for depression. In the Longitudinal Aging Study Amsterdam, a large population based sample of older men and women, 906 subjects were genotyped. An association study was performed to determine the relationship between GR gene polymorphisms, childhood adversity, HPA‐axis markers and depressive symptoms. A gene–environment interaction between the GR polymorphisms 22/23EK and 9beta and childhood adversity resulted in an increased risk of clinically relevant depressive symptoms. Without childhood adversity no increased risk was present. The 22/23EK variant was also associated with a lower Free Cortisol Index in the presence of childhood adversity. Persons that are heterozygous for the BclI variant, in contrast with wild‐type and BclI‐homozygotes, had lower serum levels of cortisol binding globulin and had no increased risk of recurrent depressive symptoms in the presence of childhood adversity. We found a gene–environment (G × E) interaction between common variants of the GR gene and childhood adversity, demonstrating a vulnerable phenotype for developing clinically relevant depressive symptoms at old age. This G × E interaction also influenced HPA‐axis markers providing support for the involvement of the HPA‐axis in both stress regulation and the pathogenesis of depression. © 2008 Wiley‐Liss, Inc.
MNC Staffing policies for the managing director position in foreign subsidiaries: the results of an innovative research method

This research note draws the attention to the harmful consequence of a serious lack of empirical research in the field of International Human Resource Management: myth-building on the basis of one or two publications. The apparent myth of high expatriate failure rates is shortly discussed. To prevent another myth from appearing, this time in the field of staffing policies, this research note provides an empirical test of the framework proposed by Meredith Downes (1996) for making decisions about staffing foreign subsidiaries. The propositions set forward by Downes are tested using a database of nearly 1800 subsidiaries located in twenty-two different countries. Headquarters of these subsidiaries are located in nine different countries and operate in eight different industries. Although the variables suggested by Downes have a fair explanatory power, some of the specific propositions had to be rejected.
The human oncoprotein MDM2 arrests the cell cycle: elimination of its cell‐cycle‐inhibitory function induces tumorigenesis

The human oncoprotein MDM2 (hMDM2) overexpresses in various human tumors. If amplified, the mdm2 gene can enhance the tumorigenic potential of murine cells. Here, we present evidence to show that the full‐length human or mouse MDM2 expressed from their respective cDNA can inhibit the G0/G1–S phase transition of NIH 3T3 and normal human diploid cells. The protein harbors more than one cell‐cycle‐inhibitory domain that does not overlap with the p53‐interaction domain. Deletion mutants of hMDM2 that lack the cell‐cycle‐inhibitory domains can be stably expressed in NIH 3T3 cells, enhancing their tumorigenic potential. The tumorigenic domain of hMDM2 overlaps with the p53‐interaction domain. Some tumor‐derived cells, such as Saos‐2, H1299 or U‐2OS, are relatively insensitive to the growth‐inhibitory effects of hMDM2. These observations suggest that hMDM2 overexpression in response to oncogenic stimuli would induce growth arrest in normal cells. Elimination or inactivation of the hMDM2‐induced G0/G1 arrest may contribute to one of the steps of tumorigenesis.
The Fundamentals of Minimum Wage Fixing

This manual draws on the ILO's comprehensive database containing the principal legal provisions and minimum wage fixing mechanisms in 100 countries. The minimum wage has had a long and turbulent history, and this study sheds light on its intricacies by providing a thorough overview of the institutions and practices in different countries. It outlines the main topics for debate concerning the effects of minimum wages on major social and economic variables such as employment, wage inequality, and poverty. The book considers the various procedures countries use for implementation, including the criteria employed to fix the minimum wage, and how they are linked to specific country objectives. It then measures the efficiency of the minimum wage, and focuses on its impact on employment as a major political issue. For the benefit of non-specialists, the validity of econometric models and their results are examined.
Hematological Parameters and Hemozoin-Containing Leukocytes and Their Association with Disease Severity among Malaria Infected Children: A Cross-Sectional Study at Pawe General Hospital, Northwest Ethiopia

Hematological parameter changes are the most common complications in malaria. We aimed to determine the hematological parameters and hemozoin-containing leukocytes and their association with disease severity in malaria infected children aged between 1 and 15 years. A facility-based cross-sectional study was conducted at Pawe General Hospital from July 31 to December 30, 2014. Demographic and clinical data were collected using structured questionnaire. Blood specimen was collected from each study participant for hematological investigations. Data were analyzed using SPSS version 20. The overall prevalence of anemia was 40.3%, most of which were mildly anemic. Leukocytosis was found in 15.4% of study participants. More than a fourth (27%) of the children had severe malaria. Hemozoin-containing monocytes and neutrophils were found in 80.1% and 58.9% of the study participants, respectively. Under-five years of age (AOR = 3.01, 95% CI: 1.83–7.39, P < 0.001), leukocytosis (AOR = 3.20, 95% CI: 1.65–6.24, P = 0.001), mean hemozoin-containing monocytes >5% (AOR = 6.26, 95% CI: 2.14–14.29, P < 0.001), mean hemozoin-containing neutrophils >5% (AOR = 7.93, 95% CI: 3.09–16.86, P < 0.001), and high density parasitemia (AOR = 1.90, 95% CI: 1.13–3.18, P = 0.015) were associated with severe malaria. Hemozoin-containing leukocytes, leukocytosis, and other identified associated factors should be considered for proper management of children with severe malaria.
Quantitative tomographic imaging of intermolecular FRET in small animals

Forster resonance energy transfer (FRET) is a nonradiative transfer of energy between two fluorescent molecules (a donor and an acceptor) in nanometer range proximity. FRET imaging methods have been applied to proteomic studies and drug discovery applications based on intermolecular FRET efficiency measurements and stoichiometric measurements of FRET interaction as quantitative parameters of interest. Importantly, FRET provides information about biomolecular interactions at a molecular level, well beyond the diffraction limits of standard microscopy techniques. The application of FRET to small animal imaging will allow biomedical researchers to investigate physiological processes occurring at nanometer range in vivo as well as in situ. In this work a new method for the quantitative reconstruction of FRET measurements in small animals, incorporating a full-field tomographic acquisition system with a Monte Carlo based hierarchical reconstruction scheme, is described and validated in murine models. Our main objective is to estimate the relative concentration of two forms of donor species, i.e., a donor molecule involved in FRETing to an acceptor close by and a nonFRETing donor molecule.
SCHOOL REPETITION, DROPOUTS, AND THE RATES OF RETURN TO SCHOOLING: THE CASE OF INDONESIA

Standard Estimates of the rates of return to primary schooling in most developing countries are high, and have been used to support advocacy of increased investments in primary schooling. But the standard estimates ignore repetition and dropout experience. This paper develops a procedure for estimating the impact of repetition and dropout rates and applies it to Indonesian data. The results are striking, suggesting that standard procedures overstate substantially the economic returns to schooling in Indonesia (eg. by 38 to 78 percent for primary schooling), distort the pattern of estimated returns across schooling levels by overestimating especially the returns to the lower schooling levels, and misrepresent the relative returns to schooling investments among groups identified by sex, rural-urban residence, and age. Copyright 1991 by Blackwell Publishing Ltd
Evaluating cash benefits as real options for a commodity producer in an emerging market

The amount of cash a firm should maintain is an old problem tackled by finance literature. The recent advances in finance, mainly in the derivatives area, has opened the opportunity to revisit this subject. Cossin and Hricko (2004) studied the benefits of cash holdings using the Real Options approach. We follow their ideas extending the problem to a specific commodity producer firm in an emerging economy. We evaluate the benefits considering that raising capital takes time (timing benefit) and also the benefit of avoiding the issue of securities at unfavorable moments (underpricing benefit). We use numerical procedures to solve the problem. Despite the fact that the results are not totally intuitive, we verify that the timing benefit is much more relevant than that of avoiding the underpricing benefit and that firms in emerging economies have greater advantage holding cash than those in developed economies. There is empirical evidence of this last result in the literature.
Nationally Representative Medical Costs of Diabetes by Time Since Diagnosis

OBJECTIVE—This study provides nationally representative estimates for the U.S. of medical expenditures associated with diabetes by years since initial diagnosis. RESEARCH DESIGN AND METHODS—Expenditures are estimated using cross-sectional regression analysis on the 2000–2004 Medical Expenditure Panel Survey linked to the 1998–2003 National Health Interview Survey (n = 46,203). The primary variables of interest are an indicator for self-reported diabetes and the years since diabetes diagnosis. RESULTS—Under the base specification, a 50-year-old person just diagnosed with diabetes has medical expenditures that are 4,174 USD higher than an identical person without diabetes. On average, each additional year with diabetes increases annual medical expenditures by $158 (standard error = $38) above and beyond increases in medical expenditures due to aging. Conditional on diabetes complications, each additional year with diabetes increases annual medical expenditures by $75 (standard error = $55). Diabetes increases medical expenditures at any age, and the cumulative effect grows over time. CONCLUSIONS—The results show the expected trajectory of medical expenditures after diagnosis of diabetes, highlighting the benefits of prevention and control as well as informing cost-effectiveness models of diabetes interventions.
Programming Education with a Blocks-Based Visual Language for Mobile Application Development.

The aim of this study is to assess the impact upon academic success of the use of a reference block-based visual programming tool, namely the MIT App Inventor for Android, as an educational instrument for teaching object-oriented GUI-application development (CS2) concepts to students; who have previously completed a fundamental programming course that involved education of structured programming concepts using C# (CS1). It has also been studied whether impacts upon CS2 success of factors such as previous success in CS1 and prior high school experience in programming, have a relationship with the impact upon CS2 success from the use of the blocks-based instructional tool. The research; which has a post-test only quasi-experimental design; has a sample comprised of 101 Undergraduate students who are taking up the CS2 course at a Department of Computer Education and Instructional Technologies (CEIT).
On Graphical Models via Univariate Exponential Family Distributions

Undirected graphical models, or Markov networks, are a popular class of statistical models, used in a wide variety of applications. Popular instances of this class include Gaussian graphical models and Ising models. In many settings, however, it might not be clear which subclass of graphical models to use, particularly for non-Gaussian and non-categorical data. In this paper, we consider a general sub-class of graphical models where the node-wise conditional distributions arise from exponential families. This allows us to derive multivariate graphical model distributions from univariate exponential family distributions, such as the Poisson, negative binomial, and exponential distributions. Our key contributions include a class of M-estimators to fit these graphical model distributions; and rigorous statistical analysis showing that these M-estimators recover the true graphical model structure exactly, with high probability. We provide examples of genomic and proteomic networks learned via instances of our class of graphical models derived from Poisson and exponential distributions.
L'impact de la participation aux pôles de compétitivité sur les PMe et les eTi

[fre] Mise en place a partir de 2005, la politique des poles de competitivite a cherche a developper des ecosystemes locaux d’innovation et des reseaux plus vastes en selectionnant des thematiques et des territoires biens definis. Ces poles ont utilise plusieurs outils, en particulier des subventions accordees pour financer des projets collaboratifs de R& D comprenant des entreprises et des organismes de recherche et de formation. Cet article presente une evaluation des effets de la participation aux poles des Petites et Moyennes Entreprises (PME) et des Entreprises de Taille Intermediaire (ETI). Ces entreprises n’ont pas toutes participe a un projet subventionne, aussi cette evaluation mesure-t-elle un melange de l’effet de la participation a un projet collaboratif et de l’effet de la seule participation a un pole de competitivite. La mise en place des poles s’est deroulee dans un contexte de fort developpement du soutien a la R& D : le passage du montant du credit d’impot recherche (CIR) de 1 a 5 milliards d’euros entre 2005 et 2009 a joue un role preponderant. La participation aux poles ne peut etre dissociee de l’evolution du CIR car les entreprises ont pu cumuler les subventions et le CIR pour monter le financement de leurs projets de R& D. Les effets mesures dans cette etude correspondent a ceux de la participation aux poles et de leur possible amplification par la forte augmentation du CIR. En 2009, les PME et ETI des poles auraient en moyenne realise 116 000 euros de R& D de plus que les entreprises similaires restees hors du dispositif. Ce montant equivaut a peu pres au surcroit d’aides publiques qu’elles ont recu sous forme de subventions et de CIR : il n’y aurait eu ni effet d’aubaine ni effet d’entrainement sur les depenses privees de R& D. Cette hausse des depenses de R& D se traduit par une augmentation de l’emploi consacre a la R& D. En revanche, a ce stade, il n’y aurait pas eu d’augmentation du chiffre d’affaires ou de hausse du nombre de depots de brevets.
Holographic flavor in N=4 gauge theories in 3d from wrapped branes

We study the addition of flavor to the gravity dual of N=4 three-dimensional gauge theories obtained by wrapping $N_c$ D4-branes on a two-cycle of a non-compact Calabi-Yau two-fold. In this setup the flavor is introduced by adding another set of D4-branes that are extended along the non-compact directions of the Calabi-Yau which are normal to the cycle which the color branes wrap. The analysis is performed both in the quenched and unquenched approximations. In this latter case we compute the backreacted metric and we show that it reproduces the running of the gauge coupling. The meson spectrum and the behavior of Wilson loops are also discussed and the holographic realization of the Higgs branch is analyzed. Other aspects of this system studied are the entanglement entropy and the non-relativistic version of our backgrounds.
Human CYP2C8 Is Post-Transcriptionally Regulated by MicroRNAs 103 and 107 in Human Liver

The CYP2C genes are extensively regulated at the transcriptional stage. The present study shows for the first time that CYP2Cs are also regulated post-transcriptionally by microRNAs (miRNAs). By using online search engines, we found potential miRNA response elements (MREs) in the 3′-untranslated region (3′-UTR) of the CYP2C mRNAs. Among these were a MRE for the miRNAs miR-103 and miR-107 in the 3′-UTR of human CYP2C8. CYP2C8 protein levels (measured through immunoblot analyses) did not correlate with CYP2C8 mRNA levels (measured through quantitative polymerase chain reaction analyses) in human liver samples. The translation efficiency (protein/mRNA ratio) for CYP2C8 was inversely correlated with the expression of miR-103 and miR-107. When three copies of the putative MRE from CYP2C8 were inserted downstream from a luciferase expression reporter, transfection with precursors for miR-103 or miR-107 decreased luciferase activity in primary hepatocytes, whereas transfection with antisense oligonucleotides (AsOs) for miR-103/miR-107 increased luciferase activity. As expected, there was no effect of the precursors or AsOs when three copies of the putative MRE were inserted in the reverse orientation. When precursors for miR-103/miR-107 were transfected into primary human hepatocytes, CYP2C8 protein levels were decreased, whereas AsOs increased CYP2C8 protein levels. Neither precursors nor AsOs affected CYP2C8 mRNA levels, which indicated that the effect was post-transcriptional. Putative MRE motifs were also found in the 3′-UTRs of CYP2C9 and CYP2C19, which suggested that the same miRNAs could regulate translation of other members of the CYP2C family, although to a lesser degree than CYP2C8. These results clearly show that CYP2Cs are regulated post-transcriptionally by miR-103 and miR-107.