Miracle-dz/UniFAR-FTUs huggingface dataset:
TMP21 Transmembrane Domain Regulates γ-Secretase Cleavage*

TMP21 has been shown to be associated with the γ-secretase complex and can specifically regulate γ-cleavage without affecting ϵ-mediated proteolysis. To explore the basis of this activity, TMP21 modulation of γ-secretase activity was investigated independent of ϵ-cleavage using an amyloid-β precursor proteinϵ (APPϵ) construct which lacks the amyloid intracellular domain domain. The APPϵ construct behaves similarly to the full-length precursor protein with respect to α- and β-cleavages and is able to undergo normal γ-processing. Co-expression of APPϵ and TMP21 resulted in the accumulation of membrane-embedded higher molecular weight Aβ-positive fragments, consistent with an inhibition of γ-secretase cleavage. The APPϵ system was used to examine the functional domains of TMP21 through the investigation of a series of TMP21-p24a chimera proteins. It was found that chimeras containing the transmembrane domain bound to the γ-secretase complex and could decrease γ-secretase proteolytic processing. This was confirmed though investigation of a synthetic peptide corresponding to the TMP21 transmembrane helix. The isolated TMP21 TM peptide but not the homologous p24a domain was able to reduce Aβ production in a dose-dependent fashion. These observations suggest that the TMP21 transmembrane domain promotes its association with the presenilin complex that results in decreased γ-cleavage activity.
NMF-based multimodal image indexing for querying by visual example

This paper proposes a method for image indexing that allows to retrieve related images under the query-by-example paradigm. The proposed strategy exploits multimodal interactions between text annotations and visual contents in the image database to build a semantic index. We achieve this using a Non-negative Matrix Factorization algorithm to construct a latent semantic space in which visual features and text terms are represented together. The proposed system was evaluated using a standard benchmark dataset. The experimental evaluation shows a significant improvement on the system performance using the proposed multimodal indexing approach.
Increased Secretion and Expression of Myostatin in Skeletal Muscle From Extremely Obese Women

OBJECTIVE—Obesity is associated with endocrine abnormalities that predict the progression of insulin resistance to type 2 diabetes. Because skeletal muscle has been shown to secrete proteins that could be used as biomarkers, we characterized the secreted protein profile of muscle cells derived from extremely obese (BMI 48.8 ± 14.8 kg/m2; homeostasis model assessment [HOMA] 3.6 ± 1.0) relative to lean healthy subjects (BMI 25.7 ± 3.2 kg/m2; HOMA 0.8 ± 0.2). RESEARCH DESIGN AND METHODS—We hypothesized that skeletal muscle would secrete proteins that predict the severity of obesity. To test this hypothesis, we used a “bottom-up” experimental design using stable isotope labeling by amino acids in culture (SILAC) and liquid chromatography/mass spectometry/mass spectometry (LC-MS/MS) to both identify and quantify proteins secreted from cultured myotubes derived from extremely obese compared with healthy nonobese women. RESULTS—Using SILAC, we discovered a 2.9-fold increase in the secretion of myostatin from extremely obese human myotubes. The increased secretion and biological activity of myostatin were validated by immunoblot (3.16 ± 0.18, P < 0.01) and a myoblast proliferation assay using conditioned growth medium. Myostatin was subsequently shown to increase in skeletal muscle (23%, P < 0.05) and plasma (35%, P < 0.05) and to correlate (r2 = 0.6, P < 0.05) with the severity of insulin resistance. CONCLUSIONS—Myostatin is a potent antianabolic regulator of muscle mass that may also play a role in energy metabolism. These findings show that increased expression of myostatin in skeletal muscle with obesity and insulin resistance results in elevated circulating myostatin. This may contribute to systemic metabolic deterioration of skeletal muscle with the progression of insulin resistance to type 2 diabetes.
Acute Humanin Therapy Attenuates Myocardial Ischemia and Reperfusion Injury in Mice

Objective—Humanin (HN), an endogenous antiapoptotic peptide, has previously been shown to protect against Alzheimer's disease and a variety of cellular insults. We evaluated the effects of a potent analog of HN (HNG) in an in vivo murine model of myocardial ischemia and reperfusion. Methods and Results—Male C57BL6/J mice (8 to 10 week old) were subjected to 45 minutes of left coronary artery occlusion followed by a 24-hour reperfusion. HNG or vehicle was administered IP 1 hour prior or at the time of reperfusion. The extent of myocardial infarction per area-at-risk was evaluated at 24 hours using Evans Blue dye and 2-3-5-triphenyl tetrazolium chloride staining. Left ventricular function was evaluated at 1 week after ischemia using high-resolution, 2D echocardiography (VisualSonics Vevo 770). Myocardial cell signaling pathways and apoptotic markers were assessed at various time points (0 to 24 hours) following reperfusion. Cardiomyocyte survival and apoptosis in response to HNG were assessed in vitro. HNG reduced infarct size relative to the area-at-risk in a dose-dependent fashion, with a maximal reduction at the dose of 2 mg/kg. HNG therapy enhanced left ventricular ejection fraction and preserved postischemic left ventricular dimensions (end-diastolic and end-systolic), resulting in improved cardiac function. Treatment with HNG significantly increased phosphorylation of AMPK and phosphorylation of endothelial nitric oxide synthase in the heart and attenuated Bcl-2-associated X protein and B-cell lymphoma-2 levels following myocardial ischemia and reperfusion. HNG improved cardiomyocyte survival and decreased apoptosis in response to daunorubicin in vitro. Conclusion—These data show that HNG provides cardioprotection in a mouse model of myocardial ischemia and reperfusion potentially through activation of AMPK-endothelial nitric oxide synthase-mediated signaling and regulation of apoptotic factors. HNG may represent a novel agent for the treatment of acute myocardial infarction.
Remarks on a paper of Ballot and Luca concerning prime divisors of a f ( n ) − 1

Let a be an integer with |a| > 1. Let f(T ) ∈ Q[T ] be a nonconstant, integer-valued polynomial with positive leading term, and suppose that there are infinitely many primes p for which f does not possess a root modulo p. Under these hypotheses, Ballot and Luca showed that almost all primes p do not divide any number of the form a−1. More precisely, assuming the Generalized Riemann Hypothesis (GRH), their argument gives that the number of primes p ≤ x which do divide numbers of the form a − 1 is at most (as x→∞) π(x) (log log x)f , where rf is the density of primes p for which the congruence f(n) ≡ 0 (mod p) is insoluble. Under GRH, we improve this upper bound to x(log x)−1−rf , which we believe is the correct order of magnitude.
Comparison of Methyl-capture Sequencing vs. Infinium 450K methylation array for methylome analysis in clinical samples

ABSTRACT Interindividual variability in the epigenome has gained tremendous attention for its potential in pathophysiological investigation, disease diagnosis, and evaluation of clinical intervention. DNA methylation is the most studied epigenetic mark in epigenome-wide association studies (EWAS) as it can be detected from limited starting material. Infinium 450K methylation array is the most popular platform for high-throughput profiling of this mark in clinical samples, as it is cost-effective and requires small amounts of DNA. However, this method suffers from low genome coverage and errors introduced by probe cross-hybridization. Whole-genome bisulfite sequencing can overcome these limitations but elevates the costs tremendously. Methyl-Capture Sequencing (MC Seq) is an attractive intermediate solution to increase the methylome coverage in large sample sets. Here we first demonstrate that MC Seq can be employed using DNA amounts comparable to the amounts used for Infinium 450K. Second, to provide guidance when choosing between the 2 platforms for EWAS, we evaluate and compare MC Seq and Infinium 450K in terms of coverage, technical variation, and concordance of methylation calls in clinical samples. Last, since the focus in EWAS is to study interindividual variation, we demonstrate the utility of MC Seq in studying interindividual variation in subjects from different ethnicities.
Emergence from anaesthesia: Have we got it all smoothened out?

Emergence from general anaesthesia implies liberation of the patient from the state of anaesthesia. The indication for anaesthetic state no longer exists at the end of surgery; the patient should ideally be free from effects of anaesthetics and only analgesia needs to be continued. The emergence should happen in a short-time, smooth and free from undesirable effects, a consequence of residual effects of anaesthesia and altered physiology related to airway, respiration, autonomic, metabolic and endocrine functions. Along with the advent of newer anaesthetic agents, reversal agents/antidotes and monitoring devices, there have been improved understanding of arousal pathways in the nervous system contributing to faster and smoother emergence from anaesthesia. Variability in patient population and pathology however, still poses challenges to the Anaesthesiologist who has to juggle with the available agents, and longer emergence times are still encountered. Attempts at early recovery may be associated with autonomic stimulation and precipitation of airway spasm and hence special care must be taken in patients with cardiac disease, hyper reactive airways and those undergoing brain surgeries.
Design based analog testing by characteristic observation inference

In this paper, a new approach to analog test design based on the circuit design process, called Characteristic Observation Inference (COI), is presented. In many situations, it is prohibitive to directly verify the circuit specifications due to the test equipment costs. Our approach considers a given universal set of reasonable input stimuli and measurements that can be performed with the given test equipment. From this universal set, a minimal number of measurements is automatically selected that represent a set of observations characterizing the state of the circuit under test with respect to parametric faults. A parametric fault model is introduced which is related to the individual circuit specifications. For each given circuit specification, a corresponding test inference criterion is computed, based on logistic discrimination analysis. By applying these criteria, the satisfaction or violation of the given circuit specifications can be inferred from the observations of the circuit under test. The COI method applied to a complex operational amplifier yields very encouraging simulated results with respect to parametric faults as well as to catastrophic faults.
Changes in Hepatitis C Virus (HCV) Viral Load and Interferon-&agr; Levels in HIV/HCV-Coinfected Patients Treated With Highly Active Antiretroviral Therapy

Background: Reports are mixed as to whether highly active antiretroviral therapy (HAART) increases liver transaminase levels or hepatitis C virus (HCV) titers in HIV/HCV-coinfected individuals. It is hypothesized that increases in HCV RNA titers may result from changes in endogenous interferon-&agr; (IFN-&agr;) production. Methods: HIV/HCV-coinfected patients receiving HAART were tested at baseline, 1, 2, 3, 6, and 9 months for liver transaminase levels, HIV and HCV viral loads, and IFN-&agr;. Linear regression analysis was used to determine the effect of HAART on liver transaminase levels, HCV viral load, and IFN-&agr;. Results: Initiating HAART did not increase liver transaminase levels in majority of cases. In patients (n = 30) with baseline HIV titer >10,000 copies/mL, HCV titers increased 0.69 log10 and IFN-&agr; decreased −0.96 log10 during HAART, in association with a ≥0.5 log10 decrease in HIV titer. As HIV titers reached their nadir approximately 4 months after initiation of HAART, HCV titers remained 0.54 log10 and IFN-&agr; −0.71 log10 above and below baseline levels, respectively. HCV titers and IFN-&agr; levels did not change from baseline in patients with baseline HIV titer ≤10,000 copies/mL. Conclusions: Coinfected patients did not have evidence of hepatoxicity HAART. In patients with baseline HIV titer >10,000 copies/mL, suppression of HIV replication by HAART was associated with an increase in HCV titer and a decrease in endogenous IFN-&agr; levels.
Analysis of the Contribution of Wind Drift Factor to Oil Slick Movement under Strong Tidal Condition: Hebei Spirit Oil Spill Case

The purpose of this study is to investigate the effects of the wind drift factor under strong tidal conditions in the western coastal area of Korea on the movement of oil slicks caused by the Hebei Spirit oil spill accident in 2007. The movement of oil slicks was computed using a simple simulation model based on the empirical formula as a function of surface current, wind speed, and the wind drift factor. For the simulation, the Environmental Fluid Dynamics Code (EFDC) model and Automatic Weather System (AWS) were used to generate tidal and wind fields respectively. Simulation results were then compared with 5 sets of spaceborne optical and synthetic aperture radar (SAR) data. From the present study, it was found that highest matching rate between the simulation results and satellite imagery was obtained with different values of the wind drift factor, and to first order, this factor was linearly proportional to the wind speed. Based on the results, a new modified empirical formula was proposed for forecasting the movement of oil slicks on the coastal area.
Evaluation of a Major Surface Antigen of Babesia microti Merozoites as a Vaccine Candidate against Babesia Infection

Babesia species are tick-borne intraerythrocytic protozoa that cause babesiosis in humans worldwide. No vaccine has yet proven effective against Babesia infection. Surface antigens of merozoites are involved in the invasion of erythrocytes by Babesia. Surface antigens may be presented by both babesial sporozoites and merozoites and provide a general target for antibody-mediated inhibition of erythrocyte invasion. Here we evaluated a major surface antigen of B. microti merozoites, BMSA, as a potential vaccine to prevent babesiosis. Our data indicated that bmsa is transcribed during different phases, including ring form, amoeboid form, and merozoites, and that its expression is significantly increased in mature merozoites. The protein was found to be located in the membrane of B. microti and in the cytoplasm of infected erythrocytes. The immune response induced by BMSA had a significant inhibitory effect on parasite invasion of the host erythrocytes (83.3% inhibition of invasion) and parasite growth in vivo. The levels of parasitemia significantly decreased after BMSA vaccination when mice were infected with babesia parasite. Importantly, protective immunity was significantly related to the upregulation of the Th17 cytokine interleukin-17, the Th1 cytokine interleukin-12p70 and the Th2 cytokines, such as interleukin-4, -6, and -10. Ingenuity Pathway Analysis indicated that interleukin-17 facilitated the secretion of Th2 cytokines, such as interleukin-10, -4, and -6, thereby inducing a predominately Th2 protective immune response and promoting the expression a high level of special IgG1 against Babesia infection. Further, an anti-BMSA monoclonal antibody successfully protected NOD/SCID mice from a challenge with B. microti. Taken together, our results indicated that BMSA induces a protective immune response against Babesia infection and may serve as a potential vaccine.
Chandra point-source counts in distant galaxy clusters

Context. With the superb angular resolution of the Chandra Observatory, it is now possible to detect X‐ray point sources, either e mbedded in galaxy clusters or along the cluster line of sight, which cou ld not be resolved by previous instruments. This now allows studies of source counts in distant cluster fields. Aims. We want to analyze the inner region of clusters of galaxies to check for the presence of any overdensity of X-ray point sources embedded in the gas diffuse emission. These point sources are possible AGN belonging to the clusters and could contaminate the cluster emission. Methods. We used a sample of 18 distant (0.25 < z < 1.01) galaxy clusters from the Chandra archive to construct the log N− log S , in both the soft and hard energy bands, for the X‐ray point sources detected in the central cluster region to be compared with the counts of point sources detected in similarly deep fields without clusters. Results. We find a ∼ 2 � excess of cluster region sources at the bright end of the log N− log S . The radial distribution of the brightest X‐ray point sources confirms this excess and indicates that it is co nfined to the inner 0.5 Mpc of the cluster region. Conclusions. The results suggest the possible existence of X‐ray sources belonging to the cluster (most probably AGN, given their 0.5‐10 keV luminosity ranging from 10 43 to 10 44 erg s −1 ): on average one every three clusters. Unlike previous studies, which have mainly investigated the point-source population in the vicinity of the galaxy clust ers, the present study analyzes the content of point sources within the 1 Mpc region covered by the cluster extent. Our work confirms the findings o f other investigators who analyzed the central 1 Mpc region of more massive clusters and/or groups in a similar redshift range. The X‐ray source excess found here is much smaller than the excess of radio galaxies found recently in high-z X‐ray selected clusters, possibly due to the better sensitivity of the radio observations.
Sense and sensibility: evaluation and interactive art

HCI evaluation methods are useful for improving the design of interactive systems, yet they may be rejected by nontraditional technology disciplines such as media art. We have developed a two-tiered evaluation model that responds to the concerns of interactive artists and have used it to improve the design of an interactive artwork, the Influencing Machine, exploring issues in affective computing. The method was interpretive, focusing on giving the artists a grounded feeling for how the machine was interpreted and their message was communicated. We describe the resulting design of the Influencing Machine and the reactions of users. The study itself is part of the art piece - together these activities achieve the goal of the artists: to provoke our cultural notions of whether a machine can "have emotions".
Male Involvement in Maternal Health Care at Anomabo, Central Region, Ghana

Background Globally, male involvement in maternal health care services remains a challenge to effective maternal health care accessibility and utilization. Objective This study assessed male involvement in maternal health care services and associated factors in Anomabo in the Central Region of Ghana. Methods Random sampling procedures were employed in selecting 100 adult male respondents whose partners were pregnant or had given birth within twelve months preceding the study. Pearson Chi-Square and Fisher's exact tests were conducted to assess the association of sociodemographic and enabling/disenabling factors with male involvement in maternal health care services. Results Some 35%, 44%, and 20% of men accompanied their partners to antenatal care, delivery, and postnatal care services, respectively. Male involvement in antenatal care and delivery was influenced by sociodemographic (partner's education, type of marriage, living arrangements, and number of children) and enabling/disenabling (distance to health facility, attitude of health workers, prohibitive cultural norms, unfavourable health policies, and gender roles) factors. Conclusion The low male involvement in maternal health care services warrants interventions to improve the situation. Public health interventions should focus on designing messages to diffuse existing sociocultural perceptions and health care provider attitudes which influence male involvement in maternal health care services.
Freezing of Water in a Differentially Heated Cubic Cavity

An experimental and numerical study has been made of transient natural convection of water freezing in a cube-shaped cavity. The effect of the heat transfer through the side walls is studied in two configurations: with the cavity surrounded by air and with the cavity immersed in an external water bath of constant temperature. The experimental data for the velocity and temperature fields are obtained using liquid crystal tracers. The transient development of the ice/water interface is measured. The collected data are used as an experimental benchmark and compared with numerical results obtained from a Finite-difference code with boundary fitted grid generation. The computational model has been adopted to simulate as closely as possible the physical experiment. Hence, fully variable fluid properties are implemented in the code, and, to improve modelling of the thermal boundary conditions, the energy equation is also solved inside the bounding walls. Although the general behaviour of the calculated ice front.
Backbone dynamics of barstar: A 15N NMR relaxation study

Backbone dynamics of uniformly 15N‐labeled barstar have been studied at 32°C, pH 6.7, by using 15N relaxation data obtained from proton‐detected 2D {1H}‐15N NMR spectroscopy. 15N spin‐lattice relaxation rate constants (R1), spin‐spin relaxation rate constants (R2), and steady‐state heteronuclear {1H}‐15N NOEs have been determined for 69 of the 86 (excluding two prolines and the N‐terminal residue) backbone amide 15N at a magnetic field strength of 14.1 Tesla. The primary relaxation data have been analyzed by using the model‐free formalism of molecular dynamics, using both isotropic and axially symmetric diffusion of the molecule, to determine the overall rotational correlation time (τm), the generalized order parameter (S2), the effective correlation time for internal motions (τe), and NH exchange broadening contributions (Rex) for each residue. As per the axially symmetric diffusion, the ratio of diffusion rates about the unique and perpendicular axes (D‖/D⟂) is 0.82 ± 0.03. The two results have only marginal differences. The relaxation data have also been used to map reduced spectral densities for the NH vectors of these residues at three frequencies: 0, ωH, and ωN, where ωH,N are proton and nitrogen Larmor frequencies. The value of τm obtained from model‐free analysis of the relaxation data is 5.2 ns. The reduced spectral density analysis, however, yields a value of 5.7 ns. The τm determined here is different from that calculated previously from time‐resolved fluorescence data (4.1 ns). The order parameter ranges from 0.68 to 0.98, with an average value of 0.85 ± 0.02. A comparison of the order parameters with the X‐ray B‐factors for the backbone nitrogens of wild‐type barstar does not show any considerable correlation. Model‐free analysis of the relaxation data for seven residues required the inclusion of an exchange broadening term, the magnitude of which ranges from 2 to 9.1 s−1, indicating the presence of conformational averaging motions only for a small subset of residues. Proteins 2000;41:460–474. © 2000 Wiley‐Liss, Inc.