Miracle-dz/UniFAR-FTUs huggingface dataset:
Synaptotagmins form a hierarchy of exocytotic Ca2+ sensors with distinct Ca2+ affinities

Synaptotagmins constitute a large family of membrane proteins implicated in Ca2+‐triggered exocytosis. Structurally similar synaptotagmins are differentially localized either to secretory vesicles or to plasma membranes, suggesting distinct functions. Using measurements of the Ca2+ affinities of synaptotagmin C2‐domains in a complex with phospholipids, we now show that different synaptotagmins exhibit distinct Ca2+ affinities, with plasma membrane synaptotagmins binding Ca2+ with a 5‐ to 10‐fold higher affinity than vesicular synaptotagmins. To test whether these differences in Ca2+ affinities are functionally important, we examined the effects of synaptotagmin C2‐domains on Ca2+‐triggered exocytosis in permeabilized PC12 cells. A precise correlation was observed between the apparent Ca2+ affinities of synaptotagmins in the presence of phospholipids and their action in PC12 cell exocytosis. This was extended to PC12 cell exocytosis triggered by Sr2+, which was also selectively affected by high‐affinity C2‐domains of synaptotagmins. Together, our results suggest that Ca2+ triggering of exocytosis involves tandem Ca2+ sensors provided by distinct plasma membrane and vesicular synaptotagmins. According to this hypothesis, plasma membrane synaptotagmins represent high‐affinity Ca2+ sensors involved in slow Ca2+‐dependent exocytosis, whereas vesicular synaptotagmins function as low‐affinity Ca2+ sensors specialized for fast Ca2+‐dependent exocytosis.
CHRONIC AUTOIMMUNE URTICARIA: WHERE WE STAND?

It is well-recognized that 30-40% of chronic idiopathic urticaria is autoimmune in nature. Chronic autoimmune urticaria is caused by anti-FcεRI and less frequently, by anti-IgE autoantibodies that lead to mast cell and basophil activation, thereby giving rise to the release of histamine and other proinflammatory mediators. Activation of the classical complement pathway and formation of C5a are important in dermal mast cell activation. C5a is also a neutrophil and eosinophil chemoattractant. Chronic autoimmune urticaria has been found to be associated with autoimmune thyroid disease. The autologous serum skin test is used as a screening test for chronic autoimmune urticaria and has a sensitivity and specificity of about 70 and 80%, respectively. The current gold standard diagnostic test is the basophil histamine release assay. The treatment of chronic autoimmune urticaria, as in chronic idiopathic urticaria, is with H1 antihistamines. Oral corticosteroids may be used during acute flares. Refractory cases have been shown to respond to cyclosporine and other immunomodulators. The prevalence of chronic autoimmune urticaria in Singapore is similar to that reported in Western countries at about 42%. The presence of thyroid autoimmunity appears to be higher than reported, with 22.5% of patients with chronic idiopathic urticaria here, exhibiting presence of thyroid autoantibodies.
The genetic epidemiology of osteoarthritis

Purpose of reviewOsteoarthritis is the most common form of arthritis in the elderly and is influenced by both genetic and environmental risk factors. The scope of the present article is to offer an overview of recent developments in the genetic epidemiology of knee and hip osteoarthritis, with particular emphasis on published genomewide association studies (GWAS). Recent findingsCandidate gene studies and genomewide linkage studies have identified genes in the bone morphogenetic pathway (e.g. GDF5), the thyroid regulation pathway (DIO2) and apoptotic pathways as involved in genetic risk of large joint osteoarthritis. GWAS have reported structural genes (COL6A4), inflammation-related genes (PTGS2/PLA2G4A) and a locus on chr 7q22 (GPR22 and four other genes in the same linkage disequilibrium block) associated with osteoarthritis. SummaryGenetic studies have identified polymorphisms associated with osteoarthritis and related end-points. These include genes in signaling cascades involved in joint and bone biology, as well as genes in inflammatory pathways and a cluster of five genes in perfect linkage disequilibrium in the 7q22 region.
FinFET SRAM Cell Optimization Considering Temporal Variability Due to NBTI/PBTI, Surface Orientation and Various Gate Dielectrics

This paper analyzes the impacts of intrinsic process variations and negative bias temperature instability (NBTI)/positive BTI (PBTI)-induced time-dependent variations on the stability/variability of 6T FinFET static random access memory (SRAM) cells with various surface orientations and gate dielectrics. Due to quantum confinement, (110)-oriented pull down n-channel FETs with fin line-edge roughness (LER) show larger Vread,0 and Vtrip variations, thus degrading READ static noise margin (RSNM) and its variability. Pull-up p-channel FETs with fin LER that are (100)-oriented show larger Vwrite,0 and Vtrip variations, hence degrade the variability of WRITE SNM. The combined effects of intrinsic process variations and NBTI/PBTI-induced statistical variations have been examined to optimize the FinFET SRAM cells. Worst-case stress scenario for SNM stability/variability is analyzed. With the presence of both NBTI and PBTI in high-fe metal-gate FinFET SRAM, the RSNM suffers significant degradation as Vread,0 increases, whereas Vtrip simultaneously decreases. Variability comparisons for FinFET SRAM cells with different gate stacks (SiO2 and SiO2/HfO2) are also examined. Our paper indicates that the consideration of NBTI/PBTI-induced temporal variation changes the optimal choice of FinFET SRAM cell surface orientations in terms of the μ/σ ratio in RSNM.
MATERIALS AND METHODS RESULTS

λ= Pi · Pt · r Mating experiments. They were carried out using the E. coli strain Bw27783 (NxR) as a donor strain of the conjugative plasmid (either R388 (TpR), or pOX38 (a KmR derivative of the plasmid F)) and Bw27783 (RifR) as a recipient strain. Different ratios of donor and recipient strains were used, estimated by OD600 measurements. Donor and recipients were mixed and plated onto LB-agar surfaces in a 24-well plate, at 37oC, for periods ranging from 1-3h. After mating, the cells were resuspended in PBS to avoid subsequent growth and dilutions were plated in appropiate antibiotics. Conjugation frequency was calculated as the proportion of transconjugants per donor or recipient cell. Some mating experiments were carried out with serial dilutions from the original cultures of donor and recipient cells. Charts indicate the average and confidence interval (significance level: 0.05) for n=9 replicates. They were calculated taking into account that rates of conjugation follow a log-Normal Distribution.
CD1d1 Displayed on Cell Size Beads Identifies and Enriches an NK Cell Population Negatively Regulated by CD1d11

NK cells destroy microbe-infected cells while sparing healthy cells, and are controlled, in part, by inhibitory receptors specific for class I Ag-presenting molecules. CD1d1, a β2-microglobulin-associated class I-like molecule, binds glycolipids and stimulates NKT cells. We previously demonstrated that target cell lysis by IL-2-activated mouse NK cells is inhibited by target cell expression of CD1d1, suggesting that IL-2-activated NK cells may express a CD1d1-specific inhibitory receptor. We now report that a significant subset of mouse IL-2-activated NK cells specifically binds cell size beads displaying either naturally expressed or recombinant CD1d1. In contrast, although tetramers of soluble recombinant CD1d1 loaded with α-galactosylceramide identify NKT cells, binding of this reagent to resting or IL-2-activated NK cells was undetectable, even with activated NK cells sorted with CD1d1 beads. Cytotoxicity by the CD1d1 bead-separated NK subset was strongly inhibited by CD1d1, compared with the NK cell subset not bound to CD1d1 beads. An Ab that blocks NKT cell recognition of CD1d1 also reverses CD1d1 inhibition of NK lysis, suggesting that TCRs of NKT cells and NK inhibitory receptor(s) may interact with a similar site on CD1d1. These results provide direct evidence for a physical interaction of NK cells with CD1d1, mediated by a functional, CD1d1-specific low-affinity inhibitory NK receptor. Display of ligands on cell size beads to maximize multivalent interaction may offer an alternative approach to examine NK cell receptor-ligand interactions, particularly those of lower expression and/or lower affinity/avidity that may go undetected using tetrameric reagents.
Social Skills Interventions for Students With Challenging Behavior

This study provides results on a methodological quality review of the single-case research literature from 1998 to 2014 on the use of social skills interventions for students with challenging behavior. A systematic review of the social skills literature was conducted with the intent of updating the Mathur et al. study of social skills interventions. Twenty-four studies, published between 1998 and 2014, were identified and coded for methodological quality. Findings indicated half the studies failed to meet single-case design standards. Many studies did not sufficiently report reliability, implementation fidelity, or provide adequate opportunities to demonstrate intervention effect. The three most common behaviors across all studies were noncompliance, negative verbal interactions, and class disruptions. The majority of studies were conducted in early elementary grades. Results are discussed in the context of the need for greater methodological rigor for future single-case research studies in the area of social skills instruction.
Toxicity of Metals to a Freshwater Ostracod: Stenocypris major

Adults of freshwater ostracod Stenocypris major (Crustacea, Candonidae) were exposed for a four-day period in laboratory conditions to a range of copper (Cu), cadmium (Cd), zinc (Zn), lead (Pb), nickel (Ni), iron (Fe), aluminium (Al), and manganese (Mn) concentrations. Mortality was assessed, and median lethal times (LT50) and concentrations (LC50) were calculated. LT50 and LC50 increased with the decrease in mean exposure concentrations and times, respectively, for all metals. LC50s for 96 hours for Cu, Cd, Zn, Pb, Ni, Fe, Al, and Mn were 25.2, 13.1, 1189.8, 526.2, 19743.7, 278.9, 3101.9, and 510.2 μg/L, respectively. Metals bioconcentration in S. major increases with exposure to increasing concentrations, and Cd was the most toxic to S. major, followed by Cu, Fe, Mn, Pb, Zn, Al, and Ni (Cd>Cu>Fe>Mn>Pb>Zn>Al>Ni). Comparison of LC50 values for metals for this species with those for other freshwater crustacean reveals that S. major is equally or more sensitive to metals than most other tested crustacean.
Dynamics and Drivers of Consumption and Multidimensional Poverty: Evidence from Rural Ethiopia

This study aims to explore poverty measures, its dynamics and determinants using Multidimensional Poverty Index (MPI) and consumption poverty. Our results show that the two measures assign similar poverty status to about 52 percent of households and that both approaches confirm poverty is mainly transient in rural Ethiopia. However, we find that the trend in adjusted head count poverty is different when using these two poverty measures. In terms of determinants of poverty dynamics, we find that household size matters in consumption poverty while we do not find significant effects on multidimensional poverty. Amongst the shocks, drought shock is found to affect consumption poverty but not multidimensional poverty. This implies that short-term shocks are more reflected in consumption poverty while the effect of simultaneous shocks is exhibited significantly on multidimensional poverty. Overall, our result provides empirical evidence on the importance of using both measures as complementary to get a full picture of poverty measure, dynamics and determinants.
Multilevel Analysis of Fifth Gr ade Teacher Qualific ations and Their S tudents' Science Achievement

The No Child Left Behind Act mandated every student be taught by a highly qualified teacher (HQT). Criteria to determine if teachers meet the HQT mandate fail to account for differences in grade levels, subject areas, and student demographics. This study posited that the relationship between measures of teacher quality and student achievement vary according to contextual factors. Fifth grade is unique in that it marks students’ transition from upper elementary to middle school grade levels; thus, fifth grade may be classified as either an upper elementary grade or middle grade. This classification determines HQT requirements; specifically, classification affects the level of content knowledge teachers must demonstrate to satisfy the HQT mandate. Middle level teachers are specialists and required to demonstrate content knowledge (CK) in the subjects they teach. However, the relationship between teachers’ level of content knowledge and fifth grade student science achievement is poorly understood.
Analyzing Data Locality in Numeric Applications

In this article, we introduce SPLAT (Static and Profiled Data Locality Analysis Tool). The tool's purpose is to provide a fast study of memory behavior without the necessity of a costly memory simulator. SPLAT consists of a static locality analysis enhanced by simple profiling data. Its overhead is low because it performs most of the analysis at compile time, and because the required profiling support is just a basic-block-execution count. Many commercial compilers support this profiling option. Compared with simulation techniques, SPLAT's estimation technique is highly accurate for numeric codes.
Sulfated is a negative feedback regulator of wingless in Drosophila

Drosophila Wingless (Wg) acts as a morphogen to control pattern formation in a concentration dependent manner. Previous studies demonstrated important roles of heparan sulfate proteoglycans (HSPGs) in controlling Wg signaling and distribution. Here, we examined the role of Sulfated (Sulf1), a Drosophila homolog of vertebrate heparan sulfate 6‐O endosulfatase, in Wg signaling and distribution. We show that sulf1 is specifically up‐regulated by Wg signaling in the wing disc. We found that expression of Wg target gene senseless (sens) was elevated in the sulf1 mutant wing discs. Sulf1 also negatively regulate extracellular levels of Wg. Genetic interaction experiments indicate that Wg antagonist Notum may work synergistically with Sulf1 to restrict Wg signaling, and Dally, a member of Drosophila HSPGs, is a potential target of Sulf1. Our results demonstrate that sulf1 is a novel Wg target gene and by a feedback mechanism, it negatively regulated Wg signaling and distribution in vivo. Developmental Dynamics 240:640–648, 2011. © 2011 Wiley‐Liss, Inc.
Effects of artifact rejection and bayesian weighting on the auditory brainstem response during quiet and active behavioral conditions.

PURPOSE To evaluate the effects of 2 noise reduction techniques on the auditory brainstem response (ABR). METHOD ABRs of 20 normal hearing adults were recorded during quiet and active behavioral conditions using 2 stimulus intensity levels. Wave V amplitudes and residual noise root-mean-square values were measured following the offline application of artifact rejection and Bayesian weighting. Repeated measures analysis of variance and Bonferroni adjusted pairwise t tests were utilized to evaluate significant main effects and interactions between the 2 noise reduction techniques. RESULTS ABRs recorded during the quiet behavioral condition resulted in minimal differences in wave V amplitude and noise reduction improvement, suggesting that the 2 techniques were equally effective under ideal recording situations. During the active behavioral condition, however, the techniques differed significantly in the ability to preserve the evoked potential and reduce noise. Consequently, strict artifact rejection levels resulted in an inherent underestimation of wave V amplitudes when compared with the Bayesian approach. CONCLUSION Artifact rejection had a detrimental effect on waveform morphology of the ABR. This could lead to difficulty in ABR interpretation when patients are active and ultimately result in diagnostic errors.
Murine cardiac function: a cautionary tail.

The capacity to selectively mutate genes or create excessive or deleted gene expression in mice has yielded a powerful new approach to structure-function studies of cardiac proteins and their role in heart disease.1 As it happened, the molecular techniques required to generate such animals developed more rapidly than did the methods for studying the chamber physiological phenotype. Mainly because of these methodological limitations, studies to date have often presented hemodynamic data that would fail the standards usually applied in larger species. In particular, heart rates (HRs) and basal levels of systolic contraction are frequently depressed to a substantial degree. It has required a major leap of faith to assume that the physiological differences measured between genetically modified and wild-type animals under such conditions translate to the healthy heart or intact animal. Furthermore, in the understandable rush to assess the impact of molecular manipulations, the careful assessment of normal murine cardiac physiology has been left shortchanged. Only now are we beginning to see the results of such analysis, with evidence growing to support potentially important differences between mice and other mammalian species.2 Such data may be very important for properly interpreting the physiological consequences of targeted genetic manipulations, as reviewed by James et al3 in this issue of Circulation Research . As with larger animals, compromises can and often must be made to balance the need for adequate control to precisely assess cardiac mechanics and physiological intactness to maintain near-normal physiology. Although conscious animal data are often considered the gold standard in larger species, they are not necessarily required to provide relevant or valuable hemodynamic insights. However, awareness of more intact normal physiology has always been critical to properly interpret data obtained in more invasive or isolated heart studies. Rarely has the discrepancy between conscious animal and anesthetized …
Vesicular Stomatitis Virus-Based Vaccine Protects Hamsters against Lethal Challenge with Andes Virus

ABSTRACT Andes virus (ANDV) is a highly pathogenic South American hantavirus that causes hantavirus pulmonary syndrome (HPS). A high case fatality rate, the potential for human-to-human transmission, the capacity to infect via aerosolization, and the absence of effective therapies make it imperative that a safe, fast-acting, and effective ANDV vaccine be developed. We generated and characterized a recombinant vesicular stomatitis virus (VSV) vector expressing the ANDV surface glycoprotein precursor (VSVΔG/ANDVGPC) as a possible vaccine candidate and tested its efficacy in the only lethal-disease animal model of HPS. Syrian hamsters immunized with a single injection of VSVΔG/ANDVGPC were fully protected against disease when challenged at 28, 14, 7, or 3 days postimmunization with a lethal dose of ANDV; however, the mechanism of protection seems to differ depending on when the immunization occurs. At 28 days postimmunization, a lack of detectable ANDV RNA in lung, liver, and blood tissue samples, as well as a lack of seroconversion to the ANDV nucleocapsidprotein in nearly all animals, suggested largely sterile immunity. The vaccine was able to generate high levels of neutralizing anti-ANDV GN/GC antibodies, which seem to play a role as a mechanism of vaccine protection. Administration of the vaccine at 7 or 3 days before challenge also resulted in full protection but with no specific neutralizing humoral immune response, suggesting a possible role of innate responses in protection against challenge virus replication. Administration of the vaccine 24 h postchallenge was successful in protecting 90% of hamsters and again suggested the induction of a potent antiviral state by the recombinant vector as a potential mechanism. Overall, our data suggest the potential for the use of the VSV platform as a fast-acting and effective prophylaxis/postexposure treatment against lethal hantavirus infections.
Morphometric age and mortality after liver transplant.

IMPORTANCE Morphometric assessment has emerged as a strong predictor of postoperative morbidity and mortality. However, a gap exists in translating this knowledge to bedside decision making. We introduced a novel measure of patient-centered surgical risk assessment: morphometric age. OBJECTIVE To investigate the relationship between morphometric age and posttransplant survival. DATA SOURCES Medical records of recipients of deceased-donor liver transplants (study population) and kidney donors/trauma patients (morphometric age control population). STUDY SELECTION A retrospective cohort study of 348 liver transplant patients and 3313 control patients. We assessed medical records for validated morphometric characteristics of aging (psoas area, psoas density, and abdominal aortic calcification). We created a model (stratified by sex) for a morphometric age equation, which we then calculated for the control population using multivariate linear regression modeling (covariates). These models were then applied to the study population to determine each patient's morphometric age. DATA EXTRACTION AND SYNTHESIS All analytic steps related to measuring morphometric characteristics were obtained via custom algorithms programmed into commercially available software. An independent observer confirmed all algorithm outputs. Trained assistants performed medical record review to obtain patient characteristics. RESULTS Cox proportional hazards regression model showed that morphometric age was a significant independent predictor of overall mortality (hazard ratio, 1.03 per morphometric year [95% CI, 1.02-1.04; P < .001]) after liver transplant. Chronologic age was not a significant covariate for survival (hazard ratio, 1.02 per year [95% CI, 0.99-1.04; P = .21]). Morphometric age stratified patients at high and low risk for mortality. For example, patients in the middle chronologic age tertile who jumped to the oldest morphometric tertile have worse outcomes than those who jumped to the youngest morphometric tertile (74.4% vs 93.2% survival at 1 year [P = .03]; 45.2% vs 75.0% at 5 years [P = .03]). CONCLUSIONS AND RELEVANCE Morphometric age correlated with mortality after liver transplant with better discrimination than chronologic age. Assigning a morphometric age to potential liver transplant recipients could improve prediction of postoperative mortality risk.
Story detection using generalized concepts and relations

A major challenge in automated text analysis is that different words are used for related concepts. Analyzing text at the surface level would treat related concepts (i.e. actors, actions, targets, and victims) as different objects, potentially missing common narrative patterns. Shallow parsers reveal semantic roles of words leading to subject-verb-object triplets. We developed a novel algorithm to extract information from triplets by clustering them into generalized concepts by utilizing syntactic criteria based on common contexts and semantic corpus-based statistical criteria based on "contextual synonyms". We show that generalized concepts representation of text (1) overcomes surface level differences (which arise when different keywords are used for related concepts) without drift, (2) leads to a higher-level semantic network representation of related stories, and (3) when used as features, they yield a significant 36% boost in performance for the story detection task.