Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification and Characterization of a Novel and Specific Inhibitor of the Ataxia-Telangiectasia Mutated Kinase ATM

The serine/threonine protein kinase ATM signals to cell cycle and DNA repair components by phosphorylating downstream targets such as p53, CHK2, NBS1, and BRCA1. Mutation of ATM occurs in the human autosomal recessive disorder ataxia-telangiectasia, which is characterized by hypersensitivity to ionizing radiation and a failure of cells to arrest the cell cycle after the induction of DNA double-strand breaks. It has thus been proposed that ATM inhibition would cause cellular radio- and chemosensitization. Through screening a small molecule compound library developed for the phosphatidylinositol 3′-kinase–like kinase family, we identified an ATP-competitive inhibitor, 2-morpholin-4-yl-6-thianthren-1-yl-pyran-4-one (KU-55933), that inhibits ATM with an IC50 of 13 nmol/L and a Ki of 2.2 nmol/L. KU-55933 shows specificity with respect to inhibition of other phosphatidylinositol 3′-kinase–like kinases. Cellular inhibition of ATM by KU-55933 was demonstrated by the ablation of ionizing radiation-dependent phosphorylation of a range of ATM targets, including p53, γH2AX, NBS1, and SMC1. KU-55933 did not show inhibition of UV light DNA damage induced cellular phosphorylation events. Exposure of cells to KU-55933 resulted in a significant sensitization to the cytotoxic effects of ionizing radiation and to the DNA double-strand break-inducing chemotherapeutic agents, etoposide, doxorubicin, and camptothecin. Inhibition of ATM by KU-55933 also caused a loss of ionizing radiation-induced cell cycle arrest. By contrast, KU-55933 did not potentiate the cytotoxic effects of ionizing radiation on ataxia-telangiectasia cells, nor did it affect their cell cycle profile after DNA damage. We conclude that KU-55933 is a novel, specific, and potent inhibitor of the ATM kinase.
Modulation of spontaneous Ca2+‐activated Cl− currents in the rabbit corpus cavernosum by the nitric oxide–cGMP pathway

The whole‐cell perforated patch clamp technique was used to study membrane currents in isolated rabbit corpus cavernosum smooth muscle cells. Depolarization from –80 mV to the range –40 to –10 mV evoked a nifedipine‐sensitive Ca2+ current that was followed by a slower inward current that activated over several hundred milliseconds. The slow current reversed near the Cl− equilibrium potential (ECl) and was reduced by anthracene‐9‐carboxylic acid (A9C; 1 mm) and niflumic acid (100 μm), suggesting that it was a Ca2+‐activated Cl− current. When held constantly at –60 mV, over 70% of cells fired spontaneous transient inward currents (STICs), the amplitudes of which were reduced by A9C and niflumic acid. STICs reversed near ECl in a symmetrical Cl− gradient and when [Cl−]o was substituted with glutamate or I−, the reversal potential shifted to more positive or more negative values, respectively, confirming that STICs were mediated by Cl− channels. STICS were also blocked by cyclopiazonic acid, 2‐aminoethoxydiphenyl borate (2‐APB) and 2‐nitro‐4‐carboxyl‐N,N‐diphenylcarbamate (NCDC), suggesting that they depended on IP3‐mediated Ca2+‐release from the sarcoplasmic reticulum. Modulation by the NO–cGMP pathway was investigated by applying nitrosocysteine, 3‐(5‐hydroxymethyl‐2‐furyl)‐1‐benzyl indazole (YC‐1), and 8‐bromo cGMP, all three of which abolished STIC activity. YC‐1 also reduced noradrenaline‐evoked inward currents, but had no effect on similar currents evoked by caffeine, suggesting that cGMP selectively inhibited IP3‐mediated Ca2+ release. We propose that Ca2+‐activated Cl− currents underlie detumescent tone in the corpus cavernosum, and that modulation of this mechanism by the NO–cGMP pathway is important during penile erection.
Efficient coding of spectrotemporal binaural sounds leads to emergence of the auditory space representation

To date a number of studies have shown that receptive field shapes of early sensory neurons can be reproduced by optimizing coding efficiency of natural stimulus ensembles. A still unresolved question is whether the efficient coding hypothesis explains formation of neurons which explicitly represent environmental features of different functional importance. This paper proposes that the spatial selectivity of higher auditory neurons emerges as a direct consequence of learning efficient codes for natural binaural sounds. Firstly, it is demonstrated that a linear efficient coding transform—Independent Component Analysis (ICA) trained on spectrograms of naturalistic simulated binaural sounds extracts spatial information present in the signal. A simple hierarchical ICA extension allowing for decoding of sound position is proposed. Furthermore, it is shown that units revealing spatial selectivity can be learned from a binaural recording of a natural auditory scene. In both cases a relatively small subpopulation of learned spectrogram features suffices to perform accurate sound localization. Representation of the auditory space is therefore learned in a purely unsupervised way by maximizing the coding efficiency and without any task-specific constraints. This results imply that efficient coding is a useful strategy for learning structures which allow for making behaviorally vital inferences about the environment.
Simple and Efficient Microwave Assisted N-Alkylation of Isatin

We present herein the results of microwave promoted N-alkylations of isatin (1) with different alkyl, benzyl and functionalized alkyl halides. Reactions were carried out under different conditions, always employing methodologies compatible with MW assisted chemistry. Generation of isatin anion employing diverse bases and solvents or using the preformed isatin sodium salt was tested. The best results were achieved using K2CO3 or Cs2CO3 and a few drops of N,N-dimethylformamide or N-methyl-2-pyrrolidinone. These reactions present noteworthy advantages over those carried out employing conventional heating.
MATERNAL EDUCATION, MATERNAL LANGUAGE ACCULTURATION, PARENTAL INVOLVEMENT, AND MATERNAL SOCIAL SUPPORT AS PREDICTORS OF THE ACADEMIC ACHIEVEMENT AND SOCIOEMOTIONAL DEVELOPMENT OF ASIAN AMERICAN CHILDREN

Title of Dissertation: MATERNAL EDUCATION, MATERNAL LANGUAGE ACCULTURATION, PARENTAL INVOLVEMENT, AND MATERNAL SOCIAL SUPPORT AS PREDICTORS OF THE ACADEMIC ACHIEVEMENT AND SOCIOEMOTIONAL DEVELOPMENT OF ASIAN AMERICAN CHILDREN Xiaofang Wang, Doctor of Philosophy, 2009 Directed By: Professor Sally A. Koblinsky Department of Family Science Asian American families are one of the fastest growing groups of the American population. Although multiple studies point to the importance of parents in children’s development, there are few empirical studies of the role of mothers and family members in the academic achievement and socioemotional development of Asian American children. Therefore, this study examined the role of maternal education, maternal language acculturation, maternal and family member involvement in home and school activities, and maternal social support in predicting the reading skills, mathematical thinking skills, peer relations, externalizing behavior problems, and internalizing behavior problems of Asian American children. The sample included 311 third grade Asian American children who had biological mothers of Asian heritage and whose families were participants in the Early Childhood Longitudinal Study-Kindergarten Class of 1998-1999 (ECLS-K). Mothers were interviewed by telephone or in person, and direct assessments were made of children’s academic skills, peer relations, and behavior problems. Secondary data analyses included descriptive statistics, bivariate correlations, and hierarchical multiple regressions. Findings revealed that higher maternal education predicted better child reading and mathematical skills, poorer peer relations, and fewer internalizing behavior problems. Higher maternal language acculturation predicted poorer child mathematical thinking skills and better peer relations. Greater maternal and family involvement in school activities predicted fewer child internalizing problems. Maternal social support was not a significant predictor of any child outcomes in this group of Asian American children. Implications of the findings for developing interventions aimed at mothers of Asian heritage to enhance their children’s academic achievement and socioemotional development are discussed. MATERNAL EDUCATION, MATERNAL LANGUAGE ACCULTURATION, PARENTAL INVOLVEMENT, AND MATERNAL SOCIAL SUPPORT AS PREDICTORS OF THE ACADEMIC ACHIEVEMENT AND SOCIOEMOTIONAL DEVELOPMENT OF ASIAN AMERICAN CHILDREN
Differential processing of binocular and monocular gloss cues in human visual cortex

The visual impression of an object's surface reflectance (“gloss”) relies on a range of visual cues, both monocular and binocular. Whereas previous imaging work has identified processing within ventral visual areas as important for monocular cues, little is known about cortical areas involved in processing binocular cues. Here, we used human functional MRI (fMRI) to test for brain areas selectively involved in the processing of binocular cues. We manipulated stereoscopic information to create four conditions that differed in their disparity structure and in the impression of surface gloss that they evoked. We performed multivoxel pattern analysis to find areas whose fMRI responses allow classes of stimuli to be distinguished based on their depth structure vs. material appearance. We show that higher dorsal areas play a role in processing binocular gloss information, in addition to known ventral areas involved in material processing, with ventral area lateral occipital responding to both object shape and surface material properties. Moreover, we tested for similarities between the representation of gloss from binocular cues and monocular cues. Specifically, we tested for transfer in the decoding performance of an algorithm trained on glossy vs. matte objects defined by either binocular or by monocular cues. We found transfer effects from monocular to binocular cues in dorsal visual area V3B/kinetic occipital (KO), suggesting a shared representation of the two cues in this area. These results indicate the involvement of mid- to high-level visual circuitry in the estimation of surface material properties, with V3B/KO potentially playing a role in integrating monocular and binocular cues.
The influence of a 12-week program of physical activity on changes in body composition and lipid and carbohydrate status in postmenopausal women

Introduction For years there have been studies on what kind of physical activity is optimal for maintaining proper health condition. Besides well known and approved endurance training of moderate intensity, an importance of interval exercise where short term, sudden intensification of work is performed at low endurance load is emphasized. The aim of the work was to assess the effects of a program of physical activity applied to postmenopausal women regarding improvement of their body composition and biochemical indices of lipid and carbohydrate status. Material and methods The program of physical activity contained 12-week trainings of Nordic walking (NW) and gymnastic-dance classes (G-D). The intensity of effort during the NW training was at the level of 60% HRmax, whereas intensity of G-D exercises was selected based on a subjective assessment of effort according to the scale of American College of Sports Medicine. Results The 12-week program of physical activity resulted in statistically significant lowering of total cholesterol and low density lipoprotein (LDL) fraction levels. An increase in high density lipoprotein (HDL) cholesterol level was observed, whereas the values of triacylglycerols (TG) did not change. The average fasting blood glucose level decreased significantly. Similar changes were noted for the insulin level. The analysed body biometrical-structural indices did not change significantly. Conclusions The applied 12-week program of physical activity without changes of dietary habits contributed to an improvement in plasma lipid profile and an increased insulin sensitivity, but it did not affect significantly body composition.
Parkin and PINK1 function in a vesicular trafficking pathway regulating mitochondrial quality control

Mitochondrial dysfunction has long been associated with Parkinson's disease (PD). Parkin and PINK1, two genes associated with familial PD, have been implicated in the degradation of depolarized mitochondria via autophagy (mitophagy). Here, we describe the involvement of parkin and PINK1 in a vesicular pathway regulating mitochondrial quality control. This pathway is distinct from canonical mitophagy and is triggered by the generation of oxidative stress from within mitochondria. Wild‐type but not PD‐linked mutant parkin supports the biogenesis of a population of mitochondria‐derived vesicles (MDVs), which bud off mitochondria and contain a specific repertoire of cargo proteins. These MDVs require PINK1 expression and ultimately target to lysosomes for degradation. We hypothesize that loss of this parkin‐ and PINK1‐dependent trafficking mechanism impairs the ability of mitochondria to selectively degrade oxidized and damaged proteins leading, over time, to the mitochondrial dysfunction noted in PD.
Monitoring of minimal residual disease by quantitative WT1 gene expression following reduced intensity conditioning allogeneic stem cell transplantation in acute myeloid leukemia

Candoni A, Toffoletti E, Gallina R, Simeone E, Chiozzotto M, Volpetti S, Fanin R. Monitoring of minimal residual disease by quantitative WT1 gene expression following reduced intensity conditioning allogeneic stem cell transplantation in acute myeloid leukemia. Clin Transplant 2011: 25: 308–316. © 2010 John Wiley & Sons A/S.
A Model-Based Sequence Similarity with Application to Handwritten Word Spotting

This paper proposes a novel similarity measure between vector sequences. We work in the framework of model-based approaches, where each sequence is first mapped to a Hidden Markov Model (HMM) and then a measure of similarity is computed between the HMMs. We propose to model sequences with semicontinuous HMMs (SC-HMMs). This is a particular type of HMM whose emission probabilities in each state are mixtures of shared Gaussians. This crucial constraint provides two major benefits. First, the a priori information contained in the common set of Gaussians leads to a more accurate estimate of the HMM parameters. Second, the computation of a similarity between two SC-HMMs can be simplified to a Dynamic Time Warping (DTW) between their mixture weight vectors, which significantly reduces the computational cost. Experiments are carried out on a handwritten word retrieval task in three different datasets-an in-house dataset of real handwritten letters, the George Washington dataset, and the IFN/ENIT dataset of Arabic handwritten words. These experiments show that the proposed similarity outperforms the traditional DTW between the original sequences, and the model-based approach which uses ordinary continuous HMMs. We also show that this increase in accuracy can be traded against a significant reduction of the computational cost.
Model-Based Predictive Direct Control Strategies for Electrical Drives: An Experimental Evaluation of PTC and PCC Methods

Model-based predictive direct control methods are advanced control strategies in the field of power electronics. To control an induction machine (IM), the predictive torque control (PTC) method evaluates the electromagnetic torque and stator flux in the cost function. The switching vector selected for the use in the insulated gate bipolar transistors (IGBTs) minimizes the error between references and the predicted values. The system constraints can be easily included. The predictive current control (PCC) strategy assesses the stator current in the cost function. The weighting factor is not necessary. Both the PTC and PCC methods are very useful direct control methods that do not require the use of a modulator. In this paper, the PTC and PCC methods are carried out experimentally for an IM on the same test bench. The behaviors and the robustness in steady state and the performances in transient state are evaluated.
Regulation of ompA mRNA stability: the role of a small regulatory RNA in growth phase‐dependent control

The Escherichia coli ompA mRNA, encoding a highly abundant outer membrane protein, has served as a model for regulated mRNA decay in bacteria. The half‐life of this transcript correlates inversely with the bacterial growth rate and is growth stage‐dependent. The stability of the messenger is determined by the 5′‐untranslated region which possesses cleavage sites for RNase E. Hfq binds to this region, is essential for controlling the stability and has been suggested to directly regulate ompA mRNA decay. Here we report that the 78 nucleotide SraD RNA, which is highly conserved among Enterobacteriaceae, acts in destabilizing the ompA transcript when rapidly grown cells enter the stationary phase of growth. During this growth‐stage the expression of SraD RNA becomes strongly increased. The SraD‐mediated decay of ompA mRNA depends on Hfq and in vitro studies revealed that Hfq facilitates binding of the regulatory RNA to the translational initiation region of the messenger. Deletion of sraD, however, does not significantly affect the stability of the ompA mRNA in slowly growing cells. Our results indicate that distinct regulatory circuits are responsible for growth phase‐ and growth rate‐dependent control of the ompA mRNA stability.
Evaluation of the haemopoietic reservoir in de novo haemolytic paroxysmal nocturnal haemoglobinuria

Summary. Paroxysmal nocturnal haemoglobinuria (PNH) is an acquired clonal disorder of the haemopoietic stem cell (HSC). The pathogenetic link with bone marrow failure is well recognized; however, the process of clonal expansion of the glycosylphosphatidylinositol (GPI)‐deficient cells over normal haemopoiesis remains unclear. We have carried out detailed analysis of the stem cell population in 10 patients with de novo haemolytic PNH using the long‐term culture‐initiating cells (LTC‐IC) assay in parallel with measurements of CD34+ cells and mature haemopoietic progenitors, granulocyte–macrophage colony‐forming unit (CFU‐GM) and CFU‐erythroid [burst‐forming units erythroid (BFU‐E) + CFU granulocyte/erythroid/macrophage/megakaryocyte (GEMM)]. All patients had hypercellular bone marrows with erythroid hyperplasia, normal blood counts or mild peripheral blood cytopenias, increased reticulocyte counts and evidence of deficient GPI‐anchored proteins. We found a significant reduction in the LTC‐IC frequency in the CD34+ compartment of PNH patients (mean 2, range 1·3–3·0; n = 6) compared with normal donors (mean 13, range 5·2–45·5; n = 21) (P < 0·0001). Furthermore, there was a significant reduction in the erythroid compartment [CFU‐E/105 bone marrow mononuclear cells (BMMC) and CFU‐E/105 CD34+ cells] of PNH patients, but no significant difference in the granulocyte–monocyte precursors (CFU‐GM/105 BMMC or CFU‐GM/105 CD34+ cells) compared with normal donors, suggesting that there is a defect in the early stem cell pool in PNH patients without clinical or haematological evidence of bone marrow failure.
DNA Strand Exchange Promoted by RecA K72R

Replacement of lysine 72 in RecA protein with arginine produces a mutant protein that binds but does not hydrolyze ATP. The protein nevertheless promotes DNA strand exchange (Rehrauer, W. M., and Kowalczykowski, S. C.(1993) J. Biol. Chem. 268, 1292-1297). With RecA K72R protein, the formation of the hybrid DNA product of strand exchange is greatly affected by the concentration of Mg in ways that reflect the concentration of a Mg•dATP complex. When Mg is present at concentrations just sufficient to form the Mg•dATP complex, substantial generation of completed product hybrid DNAs over 7 kilobase pairs in length is observed (albeit slowly). Higher levels of Mg are required for optimal uptake of substrate duplex DNA into the nucleoprotein filament, indicating that the formation of joint molecules is facilitated by Mg levels that inhibit the subsequent migration of a DNA branch. We also show that the strand exchange reaction promoted by RecA K72R, regardless of the Mg concentration, is bidirectional and incapable of bypassing structural barriers in the DNA or accommodating four DNA strands. The reaction exhibits the same limitations as that promoted by wild type RecA protein in the presence of adenosine 5′-O-(3-thio)triphosphate. The Mg effects, the limitations of RecA-mediated DNA strand exchange in the absence of ATP hydrolysis, and unusual DNA structures observed by electron microscopy in some experiments, are interpreted in the context of a model in which a fast phase of DNA strand exchange produces a discontinuous three-stranded DNA pairing intermediate, followed by a slow phase in which the discontinuities are resolved. The mutant protein also facilitates the autocatalytic cleavage of the LexA repressor, but at a reduced rate.
The impact of cytomegalovirus infection on new-onset diabetes mellitus after kidney transplantation: a review on current findings

Context: New onset diabetes mellitus after transplantation (NODAT) increases the risk of cardiovascular disease, rate of infections, graft rejection and graft loss as well as decreases patient and graft survival rates. There is a controversy surrounding the impact of cytomegalovirus (CMV) infection in the development of NODAT. This meta-analysis aims to identify the role of CMV infection leading to the development of NODAT in kidney recipient patients. Evidence Acquisitions: We searched several electronic databases, including PubMed, Embase, Medline, Scopus, Trip Database and Google Scholar for studies that completely fulfill our criteria between January 1990 and January 2014 Results: Seven studies with 1389 kidney transplant patients were included in this metaanalysis.The mean age of patients ranged from 42.8 to 48.8 years and males made up 53% to 75% of patients in the cohort studies. The incidence of NODAT varies from 14.3% to 27.1% in these studies. Overall adj OR was 1.94 [exp (0.66)] with a 95% CI of 1.26-2.98 [exp (0.23) and (1.09)]. There was no significant publication bias based on the Begg’s and Egger’s test (p value = 0.17 and 0.54, respectively). Conclusions: Our study showed that CMV infection is a risk factor for increasing incidence of NODAT. Thus, prophylaxis against CMV infection after kidney transplantation is strongly suggested. However, further clinical trials and cohorts are needed to confirm this association.
Application-centric security policies on unmodified Android

AbstractGoogle’s Android platform uses a fairly standard resource-centric permission model toprotect resources such as the camera, GPS, and Internet connection. We claim that a much bet-ter permission model for developers and users would be application-centric, with a vocabularythat directly relates to application-level functionality, e.g., one permission could allow camerause, but only for barcode scanning; another could allow Internet access, but only to certain do-mains. Despite the large apparent gap between resource- and application-centric permissions,we argue that Android already provides the necessary mechanisms to support an expressiveand practical form of application-centric policies. Speciﬁcally, each application-centric per-mission can be represented by a new Android permission and can be enforced by coupling thepermission with a trusted service running in its own process. We present a survey of the top 24free Android apps and show that a small vocabulary of application-centric permissions coversmuch of the functionality of those apps. We also describe a prototype implementation of ourapproach.