Miracle-dz/UniFAR-FTUs huggingface dataset:
The Calcilytic Agent NPS 2143 Rectifies Hypocalcemia in a Mouse Model With an Activating Calcium-Sensing Receptor (CaSR) Mutation: Relevance to Autosomal Dominant Hypocalcemia Type 1 (ADH1)

Autosomal dominant hypocalcemia type 1 (ADH1) is caused by germline gain-of-function mutations of the calcium-sensing receptor (CaSR) and may lead to symptomatic hypocalcemia, inappropriately low serum PTH concentrations and hypercalciuria. Negative allosteric CaSR modulators, known as calcilytics, have been shown to normalize the gain-of-function associated with ADH-causing CaSR mutations in vitro and represent a potential targeted therapy for ADH1. However, the effectiveness of calcilytic drugs for the treatment of ADH1-associated hypocalcemia remains to be established. We have investigated NPS 2143, a calcilytic compound, for the treatment of ADH1 by in vitro and in vivo studies involving a mouse model, known as Nuf, which harbors a gain-of-function CaSR mutation, Leu723Gln. Wild-type (Leu723) and Nuf mutant (Gln723) CaSRs were expressed in HEK293 cells, and the effect of NPS 2143 on their intracellular calcium responses was determined by flow cytometry. NPS 2143 was also administered as a single ip bolus to wild-type and Nuf mice and plasma concentrations of calcium and PTH, and urinary calcium excretion measured. In vitro administration of NPS 2143 decreased the intracellular calcium responses of HEK293 cells expressing the mutant Gln723 CaSR in a dose-dependent manner, thereby rectifying the gain-of-function associated with the Nuf mouse CaSR mutation. Intraperitoneal injection of NPS 2143 in Nuf mice led to significant increases in plasma calcium and PTH without elevating urinary calcium excretion. These studies of a mouse model with an activating CaSR mutation demonstrate NPS 2143 to normalize the gain-of-function causing ADH1 and improve the hypocalcemia associated with this disorder.
.05: A Case of the Tail Wagging the Distribution

After a brief review of the origins of the . 05 criterion for judging statistical significance, this article challenges the management discipline's rigid adherence to conventional levels of significancefor differentiating reliable from unreliable results. Arguing instead that there is no right or wrong level of significance, it contends that the selection of a significance level should be treated as one more research parameter. In this respect, the appropriateness of a specific level of significance should be based on such considerations as sample size and research design rather than a priori declarations of . 05, . 01, or whatever.
Polycystin-1 Mediates Mechanical Strain-Induced Osteoblastic Mechanoresponses via Potentiation of Intracellular Calcium and Akt/β-Catenin Pathway

Mechanical regulation of bone formation involves a complex biophysical process, yet the underlying mechanisms remain poorly understood. Polycystin-1 (PC1) is postulated to function as a mechanosensory molecule mediating mechanical signal transduction in renal epithelial cells. To investigate the involvement of PC1 in mechanical strain-induced signaling cascades controlling osteogenesis, PKD1 gene was stably silenced in osteoblastic cell line MC3T3-E1 by using lentivirus-mediated shRNA technology. Here, our findings showed that mechanical tensile strain sufficiently enhanced osteogenic gene expressions and osteoblastic proliferation. However, PC1 deficiency resulted in the loss of the ability to sense external mechanical stimuli thereby promoting osteoblastic osteogenesis and proliferation. The signal pathways implicated in this process were intracellular calcium and Akt/β-catenin pathway. The basal levels of intracellular calcium, phospho-Akt, phospho-GSK-3β and nuclear accumulation of active β-catenin were significantly attenuated in PC1 deficient osteoblasts. In addition, PC1 deficiency impaired mechanical strain-induced potentiation of intracellular calcium, and activation of Akt-dependent and Wnt/β-catenin pathways, which was able to be partially reversed by calcium ionophore A23187 treatment. Furthermore, applications of LiCl or A23187 in PC1 deficient osteoblasts could promote osteoblastic differentiation and proliferation under mechanical strain conditions. Therefore, our results demonstrated that osteoblasts require mechanosensory molecule PC1 to adapt to external mechanical tensile strain thereby inducing osteoblastic mechanoresponse, partially through the potentiation of intracellular calcium and downstream Akt/β-catenin signaling pathway.
Parental Conditional Regard, Subjective Well-Being and Self-Esteem: The Mediating Role of Perfectionism

The present study investigated the relationship between parental conditional regard, perfectionism, subjective well-being and self-esteem, and the role of perfectionism as a mediator in the relationship between parental conditional regard and both subjective well-being and self-esteem. Using a convenience sampling, 500 Turkish university students (M age = 20.83 years old, SD age = 2.05) completed questionnaires. The results showed positive links between parental conditional regard and perfectionism, negative links between parental conditional regard and both subjective well-being and self-esteem and negative links between perfectionism and both subjective well-being and self-esteem. While perfectionism was a partial mediator between parental conditional regard and self-esteem, perfectionism was not a mediator between parental conditional regard and subjective well-being.
Vhlh Gene Deletion Induces Hif-1-Mediated Cell Death in Thymocytes

ABSTRACT The von Hippel-Lindau gene product (pVHL) targets the α subunit of basic helix-loop-helix transcription factor hypoxia-inducible factor (HIF) for proteasomal degradation. Inactivation of pVhl in the mouse germ line results in embryonic lethality, indicating that tight control of Hif-mediated adaptive responses to hypoxia is required for normal development and tissue function. In order to investigate the role of pVhl in T-cell development, we generated mice with thymocyte-specific inactivation of Vhlh resulting in constitutive transcriptional activity of Hif-1, as well as mice with thymocyte-specific repression of Hif-1 in a wild-type and Vhlh-deficient background. Thymi from Vhlh-deficient mice were small due to a severe reduction in the total number of CD4/CD8-double-positive thymocytes which was associated with increased apoptosis in vivo and in vitro. Increased apoptosis was a result of enhanced caspase 8 activity, while Bcl-2 and Bcl-XL transgene expression had little effect on this phenotype. Inactivation of Hif-1 in Vhlh-deficient thymocytes restored thymic cellularity as well as thymocyte viability in vitro. Our data suggest that tight regulation of Hif-1 via pVhl is required for normal thymocyte development and viability and that an increase in Hif-1 transcriptional activity enhances caspase 8-mediated apoptosis in thymocytes.
GPCR-controlled membrane recruitment of negative regulator C2GAP1 locally inhibits Ras signaling for adaptation and long-range chemotaxis

Significance Eukaryotic cells migrate through a gradient with a huge concentration range of chemoattractant stimuli by employing “adaptation,” in which cells no longer respond to the present stimuli, but remain sensitive to stronger stimuli. Many models agree on the “temporal adaptation”: a rapid “excitation” that triggers cellular responses and a temporally delayed “inhibition” that terminates the responses to reach adaptation. The inhibitory mechanism largely remains elusive, although many molecules of the excitatory signaling pathway have been identified. In the present study, we showed that GPCR-activated Ras negative regulator C2GAP1 locally inhibits Ras signaling for adaptation and long-range chemotaxis. Eukaryotic cells chemotax in a wide range of chemoattractant concentration gradients, and thus need inhibitory processes that terminate cell responses to reach adaptation while maintaining sensitivity to higher-concentration stimuli. However, the molecular mechanisms underlying inhibitory processes are still poorly understood. Here, we reveal a locally controlled inhibitory process in a GPCR-mediated signaling network for chemotaxis in Dictyostelium discoideum. We identified a negative regulator of Ras signaling, C2GAP1, which localizes at the leading edge of chemotaxing cells and is activated by and essential for GPCR-mediated Ras signaling. We show that both C2 and GAP domains are required for the membrane targeting of C2GAP1, and that GPCR-triggered Ras activation is necessary to recruit C2GAP1 from the cytosol and retains it on the membrane to locally inhibit Ras signaling. C2GAP1-deficient c2gapA− cells have altered Ras activation that results in impaired gradient sensing, excessive polymerization of F actin, and subsequent defective chemotaxis. Remarkably, these cellular defects of c2gapA− cells are chemoattractant concentration dependent. Thus, we have uncovered an inhibitory mechanism required for adaptation and long-range chemotaxis.
Logos: a system for translating queries into narratives

This paper presents Logos, a system that provides natural language translations for relational queries expressed in SQL. Our translation mechanism is based on a graph-based approach to the query translation problem. We represent various forms of structured queries as directed graphs and we annotate the graph edges with template labels using an extensible template mechanism. Logos uses different graph traversal strategies for efficiently exploring these graphs and composing textual query descriptions. The audience may interactively explore Logos using various database schemata and issuing either sample or ad hoc queries.
Hidden Markov model topology optimization for handwriting recognition

In this paper we present a method to optimize the topology of linear left-to-right hidden Markov models. These models are very popular for sequential signals modeling on tasks such as handwriting recognition. Many topology definition methods select the number of states for a character model based on character length. This can be a drawback when characters are shorter than the minimum allowed by the model, since they can not be properly trained nor recognized. The proposed method optimizes the number of states per model by automatically including convenient skip-state transitions and therefore it avoids the aforementioned problem. We discuss and compare our method with other character length-based methods such the Fixed, Bakis and Quantile methods. Our proposal performs well on off-line handwriting recognition task.
Modern techniques for automatic classification of products

Researches throughout the past few years, having as a goal the automatic classification of products, via calculus systems implementation, as well as machine vision techniques, and artificial intelligence field methods, have lead to very promising results. Using them allowed for the assessment of some parameters such as shape, colour and the integrity degree of the products analyzed, having much more superior results than the classical classification installations. Still, due to these techniques particularities, the classification process implies going through some more phases. Both the experimental methodology for classifying vegetal products and some original algorithms are presented in this paper. A new original program for algorithms implementation was developed and used during the tests.
VIABILITY SELECTION ON SEASONALLY POLYPHENIC TRAITS: WING MELANIN PATTERN IN WESTERN WHITE BUTTERFLIES

Wing melanin pattern varies seasonally among generations in many populations of the butterfly Pontia occidentalis, leading to distinctly different wing phenotypes during spring and summer generations. Estimates of directional selection on wing pattern can therefore quantify the imperfection of this phenotypically plastic (polyphenic) response in generating “optimal” phenotypes for each seasonal generation. Mark‐release‐recapture (MRR) studies were used to estimate directional selection on six wing traits in a natural population of P. occidentalis during both spring and summer weather conditions. Estimated survival and recapture probabilities varied substantially among the four MRR studies. When differences between males and females were detected, the survival and recapture probabilities were higher for males than for females. Estimated selection coefficients suggested that the direction of selection on one wing trait important for thermoregulation, melanin on the base of the dorsal hindwings (trait hb), fluctuated seasonally; there was evidence of directional selection for increased hb in the spring studies and for decreased hb in the summer studies. Such fluctuating seasonal selection on hb implies that the seasonal polyphenic response may not be sufficient to eliminate selection on this trait; the slope of the reaction‐norm mapping hb onto seasonal environmental cues is too shallow, resulting in further selection on the reaction norm. Adaptive evolution of the reaction norm may be constrained by phenotypic and genetic correlations with other wing traits that experience different patterns of selection and by variable weather conditions within seasons and among years.
Children's God Concepts: Influences of Denomination, Age, and Gender

Children (N = 968, ages 3-18) from eight Christian groups drew pictures of God. Analyses investigated their use of symbols and deity gender. Age-related results indi- cate a linear increase in the use of symbols with age. Also, youngest and oldest partici- pants drew more neuter figures in contrast to the masculine images of the middle children. Group membership was not found to directly influence symbolism. Explora- tory analyses suggest denominational differences in how girls perceive the deity.
The Case for Using the Repeatability Coefficient When Calculating Test–Retest Reliability

The use of standardised tools is an essential component of evidence-based practice. Reliance on standardised tools places demands on clinicians to understand their properties, strengths, and weaknesses, in order to interpret results and make clinical decisions. This paper makes a case for clinicians to consider measurement error (ME) indices Coefficient of Repeatability (CR) or the Smallest Real Difference (SRD) over relative reliability coefficients like the Pearson’s (r) and the Intraclass Correlation Coefficient (ICC), while selecting tools to measure change and inferring change as true. The authors present statistical methods that are part of the current approach to evaluate test–retest reliability of assessment tools and outcome measurements. Selected examples from a previous test–retest study are used to elucidate the added advantages of knowledge of the ME of an assessment tool in clinical decision making. The CR is computed in the same units as the assessment tool and sets the boundary of the minimal detectable true change that can be measured by the tool.
Ja n 20 02 Quantum-Corrected Cardy Entropy for Generic 1 + 1-Dimensional Gravity by

Various studies have explored the possibility of explaining the Bekenstein-Hawking (black hole) entropy by way of some suitable state-counting procedure. Notably, many of these treatments have used the well-known Cardy formula as an intermediate step. Our current interest is a recent calculation in which Carlip has deduced the leading-order quantum correction to the (otherwise) classical Cardy formula. In this paper, we apply Carlip's formulation to the case of a generic model of two-dimensional gravity with coupling to a dilaton field. We find that the corrected Cardy entropy includes the anticipated logarithmic " area " term. Such a term is also evident when the entropic correction is derived independently by thermodynamic means. However, there is an apparent discrepancy between the two calculations with regard to the factor in front of the logarithm. In fact, the two values of this prefactor can only agree for very specific two-dimensional models, such as that describing Jackiw-Teitelboim theory.
Physiological and Gene Expression Analysis of Inhibition of Desulfovibrio vulgaris Hildenborough by Nitrite

ABSTRACT A Desulfovibrio vulgaris Hildenborough mutant lacking the nrfA gene for the catalytic subunit of periplasmic cytochrome c nitrite reductase (NrfHA) was constructed. In mid-log phase, growth of the wild type in medium containing lactate and sulfate was inhibited by 10 mM nitrite, whereas 0.6 mM nitrite inhibited the nrfA mutant. Lower concentrations (0.04 mM) inhibited the growth of both mutant and wild-type cells on plates. Macroarray hybridization indicated that nitrite upregulates the nrfHA genes and downregulates genes for sulfate reduction enzymes catalyzing steps preceding the reduction of sulfite to sulfide by dissimilatory sulfite reductase (DsrAB), for two membrane-bound electron transport complexes (qmoABC and dsrMKJOP) and for ATP synthase (atp). DsrAB is known to bind and slowly reduce nitrite. The data support a model in which nitrite inhibits DsrAB (apparent dissociation constant Km for nitrite = 0.03 mM), and in which NrfHA (Km for nitrite = 1.4 mM) limits nitrite entry by reducing it to ammonia when nitrite concentrations are at millimolar levels. The gene expression data and consideration of relative gene locations suggest that QmoABC and DsrMKJOP donate electrons to adenosine phosphosulfate reductase and DsrAB, respectively. Downregulation of atp genes, as well as the recorded cell death following addition of inhibitory nitrite concentrations, suggests that the proton gradient collapses when electrons are diverted from cytoplasmic sulfate to periplasmic nitrite reduction.
Prototyping symbolic execution engines for interpreted languages

Symbolic execution is being successfully used to automatically test statically compiled code. However, increasingly more systems and applications are written in dynamic interpreted languages like Python. Building a new symbolic execution engine is a monumental effort, and so is keeping it up-to-date as the target language evolves. Furthermore, ambiguous language specifications lead to their implementation in a symbolic execution engine potentially differing from the production interpreter in subtle ways. We address these challenges by flipping the problem and using the interpreter itself as a specification of the language semantics. We present a recipe and tool (called Chef) for turning a vanilla interpreter into a sound and complete symbolic execution engine. Chef symbolically executes the target program by symbolically executing the interpreter's binary while exploiting inferred knowledge about the program's high-level structure. Using Chef, we developed a symbolic execution engine for Python in 5 person-days and one for Lua in 3 person-days. They offer complete and faithful coverage of language features in a way that keeps up with future language versions at near-zero cost. Chef-produced engines are up to 1000 times more performant than if directly executing the interpreter symbolically without Chef.
Reproducibility of two electrical stimulation techniques to assess neuromuscular fatigue

Abstract The main aim of this study was to compare the reliability of percutaneous electrical stimulation over the muscle (MES) and electrical stimulation over the nerve (NES) to assess quadriceps muscle voluntary activation and muscle contractile properties. A secondary aim was to determine whether MES detects the fatigue induced by prolonged exercise in the heat. For the first purpose, eight participants performed on three non-consecutive days: quadriceps maximal voluntary contractions (MVC) with superimposed electrical stimulation to assess voluntary activation, and electrically evoked contractions to assess peak force (PEVO), using NES (ball-shaped cathode) or MES (adhesive electrodes). For the second purpose, the same participants pedalled for 2 h at 60% VO2max in a 36°C environment. Quadriceps maximal voluntary contractions, voluntary activation, and PEVO were measured before and just after the completion of exercise using MES. Voluntary activation assessed with MES presented lower intra-day (1.3±0.2 vs. 2.5±0.5%) and inter-day (1.7±0.3 vs. 2.9 ±0.4%) coefficients of variation than with NES. PEVO had lower intra-day and inter-day coefficients of variation (5.6±1.0 vs. 17.0±3.3%) and higher intraclass correlation values (ICC 0.95 vs. 0.85) when using MES than with NES either when stimulating at 20 or 80 Hz. Prolonged exercise in the heat reduced MVC (11±2%) and quadriceps muscle voluntary activation (5.2±0.5%) from pre-exercise values (P<0.05), as previously found. PEVO was unaffected by exercise in the heat. In conclusion, MES is more reliable than NES to assess quadriceps muscle voluntary activation and PEVO. In addition, MES readily detects the reduction in voluntary activation induced by prolonged exercise in the heat.
Safe Passage for Passwords and Other Sensitive Data

The prevalence of malware such as keyloggers and screen scrapers has made the prospect of providing sensitive information via web pages disconcerting for security-conscious users. We present Bumpy, a system to exclude the legacy operating system and applications from the trusted computing base for sensitive input, without requiring a hypervisor or VMM. Bumpy allows the user to specify strings of input as sensitive when she enters them, and ensures that these inputs reach the desired endpoint in a protected state. The inputs are processed in an isolated code module on the user’s system, where they can be encrypted or otherwise processed for a remote webserver. We present a prototype implementation of Bumpy.
Idiocentrism‐allocentrism and academics' self‐efficacy for research in Beijing universities

Purpose – This article aims to explore how self‐efficacy is related to academic research activities and how intra‐culturally relevant factors may play a role in self‐efficacy in the context of higher education in Beijing. In particular, relationships of self‐efficacy for research with research productivity and idiocentrism‐allocentrism are to be examined.Design/methodology/approach – A survey was administered to academics in ten randomly selected universities in Beijing and generated 296 valid questionnaires. Data were analysed using factor analysis and multiple regression.Findings – Gender and discipline are identified as predictors of self‐efficacy. Specifically, female academics reported lower levels of self‐efficacy for research than males. Academics in the social sciences reported lower levels of self‐efficacy for research than those in the natural sciences. Moreover, relationships are also found between self‐efficacy for research and idiocentrism‐allocentrism.Originality/value – The study makes an e.
Spirituality and Substance Abuse Recovery

Researchers explored patient and staff perceptions of spiritual well-being and the spiritual needs of patients enrolled in a residential substance abuse treatment program. The Spiritual Well-Being Scale was used to gather quantitative data. Additionally, a brief questionnaire containing one qualitative and two quantitative questions was completed by both clients and staff. A statistically significant difference was found, indicating a more positive sense of spiritual well-being among patients upon discharge. Although the staff and clients of the residential program have similar perceptions regarding the concept of spiritual well-being, their definitions do not appear identical.