Miracle-dz/UniFAR-FTUs huggingface dataset:
A Genome-Wide Association Study for Coronary Artery Disease Identifies a Novel Susceptibility Locus in the Major Histocompatibility Complex

Background— Recent genome-wide association studies (GWAS) have identified several novel loci that reproducibly associate with coronary artery disease (CAD) and/or myocardial infarction risk. However, known common CAD risk variants explain only 10% of the predicted genetic heritability of the disease, suggesting that important genetic signals remain to be discovered. Methods and Results— We performed a discovery meta-analysis of 5 GWAS involving 13 949 subjects (7123 cases, 6826 control subjects) imputed at approximately 5 million single nucleotide polymorphisms, using pilot 1000 Genomes–based haplotypes. Promising loci were followed up in an additional 5 studies with 11 032 subjects (5211 cases, 5821 control subjects). A novel CAD locus on chromosome 6p21.3 in the major histocompatibility complex (MHC) between HCG27 and HLA-C was identified and achieved genome-wide significance in the combined analysis (rs3869109; p discovery=3.3×10−7, p replication=5.3×10−4 p combined=1.12×10−9). A subanalysis combining discovery GWAS showed an attenuation of significance when stringent corrections for European population structure were used (P=4.1×10−10 versus 3.2×10−7), suggesting that the observed signal is partly confounded due to population stratification. This gene dense region plays an important role in inflammation, immunity, and self–cell recognition. To determine whether the underlying association was driven by MHC class I alleles, we statistically imputed common HLA alleles into the discovery subjects; however, no single common HLA type contributed significantly or fully explained the observed association. Conclusions— We have identified a novel locus in the MHC associated with CAD. MHC genes regulate inflammation and T-cell responses that contribute importantly to the initiation and propagation of atherosclerosis. Further laboratory studies will be required to understand the biological basis of this association and identify the causative allele(s).
The Kaufman Ability Battery for Children Mental Processing Scale: A Valid Measure of “Pure” Intelligence?

The Kaufman Ability Battery for Children (K-ABC) is predicated on the distinction between intelligence (measured by the Mental Processing scale) and achievement (measured by the Achievement scale). This article questions the validity of this distinction and the interpretation of the K-ABC’s Mental Processing score as a measure of “pure” intelligence, uncontaminated by schooling. Schooling was found to affect raw scores on all Mental Processing subtests in the Israeli standardization sample of the K-ABC. More-over, for five of the eight subtests, the effect of schooling exceeded the effect of age. No difference was found between the Mental Processing and Achievement scales in the relative magnitude of the age and schooling effects.
Hydrogen bonding in brucinium dihydrogen citrate trihydrate at 130 K.

The structure of brucinium dihydrogen citrate trihydrate (systematic name: 2,3-dimethoxy-10-oxostrychnidinium dihydrogen citrate trihydrate), C(23)H(27)N(2)O(4)(+). C(6)H(7)O(7)(-). 3H(2)O, has been determined at 130 K. The crystallographic asymmetric unit comprises two brucinium cations, two dihydrogen citrate anions and six water molecules of solvation. The two citrate anions, which are conformationally dissimilar, associate through extensive hydrogen-bonding interactions with the common undulating brucinium cation layer substructures and the water molecules, forming a three-dimensional framework polymer.
Learning to wonder together: a group approach to work with parents and infants in a community setting

Abstract This paper describes a group work programme called ‘Together Time’. The group was set up for parents and infants between 10 and 24 months of age, where there was concern about the parents' ability to ‘play’ and difficulties in the parent-infant relationship. The group ran for 10 weeks with four dyads in total. We used the Watch, Wait and Wonder approach in order to heighten parents' observational skills, and to stimulate discussion and thinking with parents about their infants' experiences in the group. Clinical vignettes are inserted throughout this paper, based on my observations of the group and the interactions between each dyad over the course of the 10 sessions.
Topological Analysis of Chlamydia trachomatis L2 Outer Membrane Protein 2

ABSTRACT Using monospecific polyclonal antisera to different parts ofChlamydia trachomatis L2 outer membrane protein 2 (Omp2), we show that the protein is localized at the inner surface of the outer membrane. Omp2 becomes immunoaccessible when Chlamydiaelementary bodies are treated with dithiothreitol, and protease digestions indicate that Omp2 has a possible two-domain structure.
Within-Variable, between Occasion Error Covariances in Models of Educational Achievement

To correct for the effects of measurement error on structural parameter estimates, many researchers are now estimating models of educational achievement with LISREL. In order to estimate such models it is desirable to obtain multiple manifest measures of the latent constructs. Many researchers restrict their models to two manifest measures per latent construct for reasons of economy, but doing so assumes in the absence of external information that all of the covariance between the within-variable measures is reliable covariance. Such an assumption may or may not hold in practice. Using data from High School and Beyond, the present study empirically investigates the extent of within-variable, between-occasion error covariances among variables typically included in models of educational achievement.
Locus of control and efficacy in healthy children and those with diabetes

Abstract Eight-five healthy children (mean age = 11.5 years) and 61 with diabetes completed measures of health locus of control and health-related self-efficacy. Those with diabetes also completed a diabetes specific self-efficacy scale. Low but significant correlations were found between locus of control and both efficacy measures. Factor analysis of the health efficacy scale yielded three factors (personal responsibility, safety and communication). Three factors were also derived for the diabetes efficacy scale (personal responsibility, social communication and minimization of threat). In terms of locus of control, children with diabetes expressed weaker beliefs in powerful others and personal control than healthy children, and weaker beliefs in the personal responsibility sub-scale of general health efficacy. Results are discussed in terms of the theoretical and practical implications of locus of control and efficacy in diabetes management.
Incremental motion-based location recognition

This paper describes a method to recognize the current location of a user using a few simple sensors. The proposed method is based on the integration of incremental motions (e.g., walking) over time to determine location transitions. To handle uncertainty, a fuzzy reasoning method is introduced. The paper also describes a prototype location recognition system that uses a set of inexpensive and wearable sensors, a bi-axial accelerometer and a digital compass. The system uses a reliable motion recognition method featuring only two directional acceleration measurements. The effectiveness of the proposed method is demonstrated by experiments at six locations in an indoor environment.
The Mitochondrial Translocator Protein, TSPO, Inhibits HIV-1 Envelope Glycoprotein Biosynthesis via the Endoplasmic Reticulum-Associated Protein Degradation Pathway

ABSTRACT The HIV-1 Env glycoprotein is folded in the endoplasmic reticulum (ER), which is necessary for viral entry and replication. Currently, it is still unclear how this process is regulated. The glycoprotein folding in the ER is controlled by the ER-associated protein degradation (ERAD) pathway, which specifically targets misfolded proteins for degradation. Previously, we reported that HIV-1 replication is restricted in the human CD4+ T cell line CEM.NKR (NKR). To understand this mechanism, we first analyzed cellular protein expression in NKR cells and discovered that levels of the mitochondrial translocator protein TSPO were upregulated by ∼64-fold. Notably, when NKR cells were treated with TSPO antagonist PK-11195, Ro5-4864, or diazepam, HIV restriction was completely disrupted, and TSPO knockdown by short hairpin RNAs (shRNAs) achieved a similar effect. We next analyzed viral protein expression, and, interestingly, we discovered that Env expression was specifically inhibited. Both TSPO knockdown and treatment with TSPO antagonist could restore Env expression in NKR cells. We further discovered that Env proteins were rapidly degraded and that kifunensine, an ERAD pathway inhibitor, could restore Env expression and viral replication, indicating that Env proteins were misfolded and degraded through the ERAD pathway in NKR cells. We also knocked out the TSPO gene in 293T cells using CRISPR/Cas9 (clustered, regularly interspaced, short palindromic repeat [CRISPR]/CRISPR-associated-9) technology and found that TSPO could similarly inhibit Env expression in these cells. Taken together, these results demonstrate that TSPO inhibits Env protein expression through the ERAD pathway and suggest that mitochondria play an important role in regulating the Env folding process. IMPORTANCE The HIV-1 Env glycoprotein is absolutely required for viral infection, and an understanding of its expression pathway in infected cells will identify new targets for antiretroviral therapies. Env proteins are folded in the ER and secreted through the classical secretory pathway. The Env folding process involves extensive cross-linking of 10 Cys residues by disulfide bond formation and heavy N-glycosylation on ∼30 Asn residues. Currently, it is still unclear how this process is regulated. Here, we studied this mechanism in the HIV nonpermissive human CD4+ T cell line CEM.NKR. We found that Env proteins were rapidly degraded through a cellular pathway that specifically targets misfolded proteins, resulting in inhibition of Env expression. Importantly, we have identified a mitochondrial translocator protein, TSPO, which could trigger this degradation by interfering with the Env folding process. Further characterization of TSPO antiviral activity will reveal a novel antiretroviral mechanism that targets the Env protein.
A 3-axis PZT-based MEMS gyroscope in 0.18μm CMOS

A 3-axis interface for a PZT-based MEMS gyroscope uses a PLL-less architecture and does not require high-voltage devices nor charge-pumps. The use of PZT in the MEMS enables a low-cost package which does not require the MEMS to be vacuum sealed. A single amplifier is used to simultaneously amplify actuation and Coriolis signals, thereby maintaining orthogonal phase between the signals. The ASIC has an inherent Allan variance of 0.13 °/s/√Hz, and 1, 0.35, and 0.66 °/s/√Hz for the ASIC plus x, y, and z axes respectively. The ASIC utilizes 6.2mA of current and 6.22mm2 of total area (including I/Os).
Kinetic Structure of Large-Conductance Ca2+-activated K+ Channels Suggests that the Gating Includes Transitions through Intermediate or Secondary States

Mechanisms for the Ca2+-dependent gating of single large-conductance Ca2+-activated K+ channels from cultured rat skeletal muscle were developed using two-dimensional analysis of single-channel currents recorded with the patch clamp technique. To extract and display the essential kinetic information, the kinetic structure, from the single channel currents, adjacent open and closed intervals were binned as pairs and plotted as two-dimensional dwell-time distributions, and the excesses and deficits of the interval pairs over that expected for independent pairing were plotted as dependency plots. The basic features of the kinetic structure were generally the same among single large-conductance Ca2+-activated K+ channels, but channel-specific differences were readily apparent, suggesting heterogeneities in the gating. Simple gating schemes drawn from the Monod- Wyman-Changeux (MWC) model for allosteric proteins could approximate the basic features of the Ca2+ dependence of the kinetic structure. However, consistent differences between the observed and predicted dependency plots suggested that additional brief lifetime closed states not included in MWC-type models were involved in the gating. Adding these additional brief closed states to the MWC-type models, either beyond the activation pathway (secondary closed states) or within the activation pathway (intermediate closed states), improved the description of the Ca2+ dependence of the kinetic structure. Secondary closed states are consistent with the closing of secondary gates or channel block. Intermediate closed states are consistent with mechanisms in which the channel activates by passing through a series of intermediate conformations between the more stable open and closed states. It is the added secondary or intermediate closed states that give rise to the majority of the brief closings (flickers) in the gating.
Electrically tunable half mode substrate integrated waveguide resonator

This paper presents a novel electronically tunable half mode substrate integrated waveguide (HMSIW) cavity resonator at microwave frequency. The resonant frequency of the cavity is tuned with different DC biasing voltages applied over a varactor coupled to the cavity. This structure has been analyzed with a full-wave software Ansoft-HFSS12. To validate our analyses, an X-band reflective tunable HMSIW cavity resonator is designed and fabricated as an experimental example. According to simulated and measured results, an equivalent circuit of the resonator with the varactor is obtained. Measured results show that the tuning range of the resonator is about 360 MHz with the loaded QL of 85 and the unloaded QU of 150. The proposed resonator can be used to design tunable devices such as microwave and millimeter-wave voltage controlled oscillator (VCO).
Retrotransposon Proliferation Coincident with the Evolution of Dioecy in Asparagus

Current phylogenetic sampling reveals that dioecy and an XY sex chromosome pair evolved once, or possibly twice, in the genus Asparagus. Although there appear to be some lineage-specific polyploidization events, the base chromosome number of 2n = 2× = 20 is relatively conserved across the Asparagus genus. Regardless, dioecious species tend to have larger genomes than hermaphroditic species. Here, we test whether this genome size expansion in dioecious species is related to a polyploidization and subsequent chromosome fusion, or to retrotransposon proliferation in dioecious species. We first estimate genome sizes, or use published values, for four hermaphrodites and four dioecious species distributed across the phylogeny, and show that dioecious species typically have larger genomes than hermaphroditic species. Utilizing a phylogenomic approach, we find no evidence for ancient polyploidization contributing to increased genome sizes of sampled dioecious species. We do find support for an ancient whole genome duplication (WGD) event predating the diversification of the Asparagus genus. Repetitive DNA content of the four hermaphroditic and four dioecious species was characterized based on randomly sampled whole genome shotgun sequencing, and common elements were annotated. Across our broad phylogenetic sampling, Ty-1 Copia retroelements, in particular, have undergone a marked proliferation in dioecious species. In the absence of a detectable WGD event, retrotransposon proliferation is the most likely explanation for the precipitous increase in genome size in dioecious Asparagus species.
Identification of Signal Bias in the Variable Flip Angle Method by Linear Display of the Algebraic Ernst Equation

A novel linear parameterization for the variable flip angle method for longitudinal relaxation time T1 quantification from spoiled steady state MRI is derived from the half angle tangent transform, τ, of the flip angle. Plotting the signal S at coordinates x = Sτ and y = S/τ, respectively, establishes a line that renders signal amplitude and relaxation term separately as y‐intercept and slope. This representation allows for estimation of the respective parameter from the experimental data. A comprehensive analysis of noise propagation is performed. Numerical results for efficient optimization of longitudinal relaxation time and proton density mapping experiments are derived. Appropriate scaling allows for a linear presentation of data that are acquired at different short pulse repetition times, TR << T1 thus increasing flexibility in the data acquisition by removing the limitation of a single pulse repetition time. Signal bias, like due to slice‐selective excitation or imperfect spoiling, can be readily identified by systematic deviations from the linear plot. The method is illustrated and validated by 3T experiments on phantoms and human brain. Magn Reson Med, 2011. © 2011 Wiley‐Liss, Inc.
KernelGen -- The Design and Implementation of a Next Generation Compiler Platform for Accelerating Numerical Models on GPUs

GPUs are becoming pervasive in scientific computing. Originally served as peripheral accelerators, now they are gradually turning into central computing nodes. However, most current directive-based approaches for parallelizing sequential legacy code such as OpenACC and HMPP simply off-load "hot" CPU code onto GPUs, entailing a lot of limitations such as unsupported external calls and coarse-grained data dependence analysis. This paper introduces KernelGen, which is a parallelization framework with a robust parallelism detection mechanism and a novel GPU-centric execution model. KernelGen supports the major scientific programming languages including C and Fortran, and has multiple backends that can generate target code for both X86 CPUs and NVIDIA GPUs. The efficiency of KernelGen has been demonstrated by the performance improvement up to 5.4× compared with three major commercial OpenACC compilers over a benchmark suite of numerical kernels.
Analysis of Pools of Targeted Salmonella Deletion Mutants Identifies Novel Genes Affecting Fitness during Competitive Infection in Mice

Pools of mutants of minimal complexity but maximal coverage of genes of interest facilitate screening for genes under selection in a particular environment. We constructed individual deletion mutants in 1,023 Salmonella enterica serovar Typhimurium genes, including almost all genes found in Salmonella but not in related genera. All mutations were confirmed simultaneously using a novel amplification strategy to produce labeled RNA from a T7 RNA polymerase promoter, introduced during the construction of each mutant, followed by hybridization of this labeled RNA to a Typhimurium genome tiling array. To demonstrate the ability to identify fitness phenotypes using our pool of mutants, the pool was subjected to selection by intraperitoneal injection into BALB/c mice and subsequent recovery from spleens. Changes in the representation of each mutant were monitored using T7 transcripts hybridized to a novel inexpensive minimal microarray. Among the top 120 statistically significant spleen colonization phenotypes, more than 40 were mutations in genes with no previously known role in this model. Fifteen phenotypes were tested using individual mutants in competitive assays of intraperitoneal infection in mice and eleven were confirmed, including the first two examples of attenuation for sRNA mutants in Salmonella. We refer to the method as Array-based analysis of cistrons under selection (ABACUS).
Purinergic Modulation of Neuronal Activity in Developing Auditory Brainstem

In the developing nervous system, spontaneous neuronal activity arises independently of experience or any environmental input. This activity may play a major role in axonal pathfinding, refinement of topographic maps, dendritic morphogenesis, and the segregation of axonal terminal arbors. In the auditory system, endogenously released ATP in the cochlea activates inner hair cells to trigger bursts of action potentials (APs), which are transferred to the central auditory system. Here we show the modulatory role of purinergic signaling beyond the cochlea, i.e., the developmentally regulated and cell-type-specific depolarizing effects on auditory brainstem neurons of Mongolian gerbil. We assessed the effects of P2X receptors (P2XRs) on neuronal excitability from prehearing to early stages of auditory signal processing. Our results demonstrate that in neurons expressing P2XRs, extracellular ATP can evoke APs in sync with Ca2+ signals. In cochlear nucleus (CN) bushy cells, ATP increases spontaneous and also acoustically evoked activity in vivo, but these effects diminish with maturity. Moreover, ATP not only augmented glutamate-driven firing, but it also evoked APs in the absence of glutamatergic transmission. In vivo recordings also revealed that endogenously released ATP in the CN contributes to neuronal firing activity by facilitating AP generation and prolonging AP duration. Given the enhancing effect of ATP on AP firing and confinement of P2XRs to certain auditory brainstem nuclei, and to distinct neurons within these nuclei, it is conceivable that purinergic signaling plays a specific role in the development of neuronal brainstem circuits.
An Adaptive Score Model for Effective Bandwidth Prediction and Provisioning in the Cloud Network

The collocation of applications in the cloud each with unique traffic characteristics presents provisioning challenges to providers. Furthermore, the volatility present in traffic sent & received by these applications necessitates a predictive solution for effective QoS strategies. To comprehend the tasks faced by cloud providers in this regard, we undertook statistical analysis of traffic traces measured periodically over a week, taking into account its nonstationarity. Henceforth, we developed a model to predict bandwidth utilization applicable in maintaining SLAs for multiple traffic flows at the cloud network edge and core. The developed univariate forecast model employs the Auto-Regressive Integrated Moving Average (ARIMA) model augmented with a general class of Adaptive Conditional Score Models (ACS). Our motivation for employing the ACS stems from its robust adaptation to outliers & transients more efficiently with increased computational accuracy than current methods; one of such methods being the recently adopted Generalized Auto-Regressive Conditional Heteroskedasticity (GARCH) to model volatility. These are observable typically as flash-crowds, time-of-day load spikes and DDoS events. The model offers improvements in forecasts over ARIMA/GARCH models with a 10-15% increase in predictive accuracy. Based on this model, we present 2 novel bandwidth adaptive algorithms which find application in the cloud network. The first is resident in the application layer of the SDN stack as a controller integrated into the OpenStack cloud environment. It was tested for effectiveness in a small test-bed where it sustains SLAs at 95%. The second methodology has been adapted in ns-2 where we present it as R2CP: Robust Rate Control Protocol, an extension to the Rate Control Protocol (RCP). R2CP offers a 25% reduction in flow completion time over XCP/RCP & over 60% reduction compared to TCP.