Miracle-dz/UniFAR-FTUs huggingface dataset:
Mechanism of Inhibition of TRPC Cation Channels by 2-Aminoethoxydiphenylborane

We investigated the actions of the organoborane, 2-aminoethoxydiphenylborane (2APB), on Ca2+ signaling in wild-type human embryonic kidney (HEK) 293 cells and in HEK293 cells stably expressing canonical transient receptor potential (TRPC) channels. Previous reports have suggested that 2APB inhibits agonist activation of TRPC channels because of its ability to act as a membrane-permeant inhibitor of inositol 1,4,5-trisphosphate (IP3) receptors. 2APB was specifically said to inhibit TRPC3 channels when activated through a phospholipase C-linked receptor but not when activated more directly by a synthetic diacylglycerol, oleyl-acetyl-glycerol (OAG) [Science (Wash DC) 287:1647-1651, 2000]. However, we subsequently reported that IP3 does not activate TRPC3; rather the mechanism of activation by phospholipase C-linked receptors seemed to result from diacylglycerol [J Biol Chem 278:16244-16252, 2003]. Thus, the current study was carried out to address the mechanism of action of 2APB in inhibiting TRPC channels. We found that, although the release of Ca2+ by a muscarinic agonist was reduced by high concentrations of 2APB, this effect was indistinguishable from that seen when stores were discharged by thapsigargin, which does not involve IP3 receptors. This indicates that 2APB is incapable of significant inhibition of IP3 receptors when applied to intact cells. We found that 2APB partially inhibits divalent cation entry in cells expressing TRPC3, TRPC6, or TRPC7 and that this partial inhibition was observed whether the channels were activated by a muscarinic agonist or by OAG. Thus, as concluded for store-operated channels, 2APB seems to inhibit TRPC channels by a direct mechanism not involving IP3 receptors.
Relationship Between Pacemaker Dependency and the Effect of Pacing Mode on Cardiovascular Outcomes

Background—A recently completed trial, the Canadian Trial of Physiological Pacing (CTOPP), showed that physiological pacing did not significantly reduce mortality, stroke, or heart failure hospitalization, but it did show that atrial fibrillation occurred less frequently in patients with physiological pacing. Many pacemaker patients experience only transient bradyarrhythmias with an adequate unpaced heart rate (UHR) and are not pacemaker-dependent. The purpose of the present analysis was to determine if pacemaker-dependent patients have an increased benefit from physiological pacing compared with non–pacemaker-dependent patients. Methods and Results—Of 2568 patients included in the CTOPP trial, 2244 patients had a pacemaker dependency test performed at the first follow-up visit. The yearly event rate of cardiovascular death or stroke steadily increased with decreasing UHR in the ventricular pacing group, but it remained constant in the physiological pacing group. When the patients were subdivided to UHR ≤60 bpm or >60 bpm, there was an interaction between pacing mode treatment and UHR subgroup. The Kaplan-Meier plot confirmed a physiological pacing advantage only in the UHR ≤60 bpm subgroup. This differential effect was also present for the outcomes of cardiovascular death and total mortality. Conclusions—This study demonstrated that UHR at first follow-up has an important influence on how pacing mode selection affects cardiovascular death and total mortality. Pacemaker-dependent patients with low UHR will probably be paced frequently and will likely benefit from physiological pacing. In contrast, non–pacemaker-dependent patients will likely be paced infrequently and may not benefit from physiological pacing.
Environmental Transmission Electron Microscopy in an Aberration-Corrected Environment

Abstract The increasing use of environmental transmission electron microscopy (ETEM) in materials science provides exciting new possibilities for investigating chemical reactions and understanding both the interaction of fast electrons with gas molecules and the effect of the presence of gas on high-resolution imaging. A gaseous atmosphere in the pole-piece gap of the objective lens of the microscope alters both the incoming electron wave prior to interaction with the sample and the outgoing wave below the sample. Whereas conventional TEM samples are usually thin (below 100 nm), the gas in the environmental cell fills the entire gap between the pole pieces and is thus not spatially localized. By using an FEI Titan environmental transmission electron microscope equipped with a monochromator and an aberration corrector on the objective lens, we have investigated the effects on imaging and spectroscopy caused by the presence of the gas.
THE COMPLEX EVOLUTIONARY HISTORY OF SEEING RED: MOLECULAR PHYLOGENY AND THE EVOLUTION OF AN ADAPTIVE VISUAL SYSTEM IN DEEP‐SEA DRAGONFISHES (STOMIIFORMES: STOMIIDAE)

The vast majority of deep‐sea fishes have retinas composed of only rod cells sensitive to only shortwave blue light, approximately 480–490 nm. A group of deep‐sea dragonfishes, the loosejaws (family Stomiidae), possesses far‐red emitting photophores and rhodopsins sensitive to long‐wave emissions greater than 650 nm. In this study, the rhodopsin diversity within the Stomiidae is surveyed based on an analysis of rod opsin‐coding sequences from representatives of 23 of the 28 genera. Using phylogenetic inference, fossil‐calibrated estimates of divergence times, and a comparative approach scanning the stomiid phylogeny for shared genotypes and substitution histories, we explore the evolution and timing of spectral tuning in the family. Our results challenge both the monophyly of the family Stomiidae and the loosejaws. Despite paraphyly of the loosejaws, we infer for the first time that far‐red visual systems have a single evolutionary origin within the family and that this shift in phenotype occurred at approximately 15.4 Ma. In addition, we found strong evidence that at approximately 11.2 Ma the most recent common ancestor of two dragonfish genera reverted to a primitive shortwave visual system during its evolution from a far‐red sensitive dragonfish. According to branch‐site tests for adaptive evolution, we hypothesize that positive selection may be driving spectral tuning in the Stomiidae. These results indicate that the evolutionary history of visual systems in deep‐sea species is complex and a more thorough understanding of this system requires an integrative comparative approach.
The skinny on physical activity interventions among Hispanic youth

Background: Hispanic youth are a high-risk population that does not meet the recommended amount of physical activity for their age group. Additionally previous research indicates that as Hispanic youth grow older, physical activity significantly decreases overtime. Therefore the purpose of this article is to review physical activity components in previously conducted interventions and examine evidence-based strategies for promoting physical activity behaviors among Hispanic youth. Methods: In March of 2012, a literature search was performed and a total of nine articles were found describing nine intervention programs that met the following inclusion criteria. The present review conducted in 2012 included previous intervention studies that were published in the English language, conducted in the United States, published between the years 2002 and 2012, and focused on Hispanic youth under 18 years of age. Results: Most of the interventions were comprehensive and focused on physical activity, nutrition behaviors, and obesity prevention and ranged from seven weeks to three years duration. Of these interventions, most were school-based and fostered individual-level behavior change. The majority of interventions utilized a behavioral theory. A summary of each was developed, and commonly used physical activity promotion components were identified. More than half of the interventions had a significant impact on the outcomes. Conclusions: Effective strategies and lessons learned from research regarding physical activity promotion and Hispanic youth involvement in physical activity could be more clearly discussed. Recommendations for future programming for Hispanic youth should incorporate culturally appropriate learning materials and physical activities by degree of acculturation. Additionally, family-based strategies and religious-based strategies should be further explored in future interventions to try and increase the success of promoting physical activity behaviors among the Hispanic youth population.
Addiction and Present-Biased Preferences

We investigate the role that self-control problems modeled as time-inconsistent, present-biased preferences and a person's awareness of those problems might play in leading people to develop and maintain harmful addictions. Present-biased preferences create a tendency to over-consume addictive products, and awareness of future self-control problems can mitigate or exacerbate this over-consumption, depending on the environment. Our central concern is the welfare consequences of this over-consumption. Our analysis suggests that for realistic environments self-control problems are a plausible source of severely harmful addictions only in conjunction with some unawareness of future self- control problems.
A Genomewide Association Study of Nicotine and Alcohol Dependence in Australian and Dutch Populations

Persistent tobacco use and excessive alcohol consumption are major public health concerns worldwide. Both alcohol and nicotine dependence (AD, ND) are genetically influenced complex disorders that exhibit a high degree of comorbidity. To identify gene variants contributing to one or both of these addictions, we first conducted a pooling-based genomewide association study (GWAS) in an Australian population, using Illumina Infinium 1M arrays. Allele frequency differences were compared between pooled DNA from case and control groups for: (1) AD, 1224 cases and 1162 controls; (2) ND, 1273 cases and 1113 controls; and (3) comorbid AD and ND, 599 cases and 488 controls. Secondly, we carried out a GWAS in independent samples from the Netherlands for AD and for ND. Thirdly, we performed a meta-analysis of the 10, 000 most significant AD- and ND-related SNPs from the Australian and Dutch samples. In the Australian GWAS, one SNP achieved genomewide significance (p < 5 x 10-8) for ND (rs964170 in ARHGAPlOon chromosome 4, p = 4.43 x 10”8) and three others for comorbid AD/ND (rs7530302 near MARK1 on chromosome 1 (p = 1.90 x 10-9), rs1784300 near DDX6 on chromosome 11 (p = 2.60 x 10-9) and rs12882384 in KIAA1409 on chromosome 14 (p = 4.86 x 10-8)). None of the SNPs achieved genomewide significance in the Australian/Dutch meta-analysis, but a gene network diagram based on the top-results revealed overrepre-sentation of genes coding for ion-channels and cell adhesion molecules. Further studies will be requirec before the detailed causes of comorbidity between AC and ND are understood.
Outdated interference alignment based transmit precoding for MU-MIMO

We present a simple transmit precoding scheme which exploits the delayed interference state information (INTSI) and the concept of interference alignment (IA). We design the precoding such that the inter-cell interference subspace from the previous transmission is aligned at the desired receiver with the intra-cell interference subspace of current transmission. Due to this fact, the alignment is not perfect for current transmission and causes leakage interference in the desired signal space. However, we show that with the help of proper receiver design, we can minimize this leakage interference and get substantial gains. We also consider the practical limitations of the current receivers and provide a modified solution to overcome these limits. With the help of extensive system level simulations we compare our scheme with other baseline MU-MIMO transmit precoding schemes in terms of mean user rates. The simulation results show that our proposed scheme provides considerable gains over the baseline transmission schemes.
Ca2+/Calmodulin-Dependent Protein Kinase II Phosphorylation Regulates the Cardiac Ryanodine Receptor

Abstract— The cardiac ryanodine receptor (RyR2)/calcium release channel on the sarcoplasmic reticulum is required for muscle excitation-contraction coupling. Using site-directed mutagenesis, we identified the specific Ca2+/calmodulin-dependent protein kinase II (CaMKII) phosphorylation site on recombinant RyR2, distinct from the site for protein kinase A (PKA) that mediates the “fight-or-flight” stress response. CaMKII phosphorylation increased RyR2 Ca2+ sensitivity and open probability. CaMKII was activated at increased heart rates, which may contribute to enhanced Ca2+-induced Ca2+ release. Moreover, rate-dependent CaMKII phosphorylation of RyR2 was defective in heart failure. CaMKII-mediated phosphorylation of RyR2 may contribute to the enhanced contractility observed at higher heart rates. The full text of this article is available online at http://circres.ahajournals. org.
Relating Nominal and Higher-Order Pattern Unification

Higher-order pattern unification and nominal unification are two approaches to unifying modulo some form of α-equivalence (consistent renaming of bound names). The higher-order and nominal approaches seem superficially dissimilar. However, we show that a natural concretion (or name-application) operation for nominal terms can be used to simulate the behavior of higher-order patterns. We describe a form of nominal terms called nominal patterns that includes concretion and for which unification is equivalent to a special case of higher-order pattern unification, and then show that full higher-order pattern unification can be reduced to nominal unification via nominal patterns.
Freeze-Dried Human Platelet-Rich Plasma Retains Activation and Growth Factor Expression after an Eight-Week Preservation Period

Study Design Controlled laboratory study. Purpose This study aimed to evaluate the efficacy of platelet-rich plasma (PRP) stored at room temperature (RT), frozen, or after freeze-drying. Overview of Literature PRP enriches tissue repair and regeneration, and is a novel treatment option for musculoskeletal pathologies. However, whether biological activity is preserved during PRP storage remains uncertain. Methods PRP was prepared from blood of 12 healthy human volunteers (200 mL/person) and stored using three methods: PRP was stored at RT with shaking, PRP was frozen and stored at −80℃, or PRP was freeze-dried and stored at RT. Platelet counts and growth factor content were examined immediately after preparation, as well as 2, 4, and 8 weeks after storage. Platelet activation rate was quantified by flow cytometry. Results Platelet counts were impossible to determine in many RT samples after 2 weeks, but they remained at constant levels in frozen and freeze-dried samples, even after 8 weeks of storage. Flow cytometry showed approximately 80% activation of the platelets regardless of storage conditions. Almost no growth factors were detected in the RT samples after 8 weeks, while low but significant expression was detected in the frozen and freeze-dried PRP. Over time, the mean relative concentrations of various growth factors decreased significantly or disappeared in the RT group. In the frozen group, levels were maintained for 4 weeks, but decreased significantly by 8 weeks (p <0.05). The freeze-dried group maintained baseline levels of growth factors for the entire 8-week duration. Conclusions Freeze-drying enables PRP storage while maintaining bioactivity and efficacy for extended periods.
Stabilization of Sampled-Data Control Systems With Control Inputs Missing

This note is concerned with the stabilization problem for sampled-data control systems with control inputs missing. A sufficient condition is derived for the existence of exponentially stabilizing state feedback controllers via the switched system approach. The obtained condition establishes several quantitative relations among some system parameters (such as the sampling period and the exponential decay rate), the actual data missing rate, and the admissible data missing rate bound. Two illustrative examples are given to show the effectiveness of the proposed results.
Speech timing and rhythmic structure in arabic dialects: a comparison of two approaches

This paper raises questions about the discrete or continuous nature of rhythm classes. Within this framework, our study investigates speech rhythm in the different Arabic dialects that have been constantly described as stress-timed compared with other languages belonging to different rhythm categories. Preliminary evidence from perceptual experiments revealed that listeners use speech rhythm cues to distinguish speakers of Arabic from North Africa from those of the Middle East. In an attempt to elucidate the reasons for this perceptual discrimination, an acoustic investigation based on duration measurement was carried out (i.e. percentages of vocalic intervals (%V) and the standard deviation of consonantal intervals (∆C)). This experiment reveals that despite their rhythmic differences, all Arabic dialects still cluster around stress-timed languages exhibiting a different distribution from languages belonging to other rhythm categories such as French and Catalan. Besides, our study suggests that there is no such thing as clear-cut rhythm classes but rather overlapping categories. As a means of comparison, we also used Pairwise Variability Indices so as to validate the reliability of our findings.
Determinants of Business Success of Small and Medium Enterprises

The small and medium enterprises (SMEs) play critical role in the development of the country. The success of SMEs depends on number of factors. This study examines the role of key factors in the success of SMEs in Pakistan. The study also investigates the relationship between SMEs success and its determinants. Target population of the study was SMEs operating in different lines of business from service to manufacturing. Sample size of this study was 520 small and medium lines of businesses. Responses of the subjects were collected through questionnaires. SPSS software is used for analysis. This study concludes that there is a significant relationship between business success and its determinants. The result also shows that financial resources are the most important factor in the success of business perceived by small and medium enterprises. The success of small and medium enterprises can contribute significantly in the development of the country.
A small-molecule inhibitor suppresses the tumor-associated mitochondrial NAD(P)+-dependent malic enzyme (ME2) and induces cellular senescence

Here, we found a natural compound, embonic acid (EA), that can specifically inhibit the enzymatic activity of mitochondrial NAD(P)+-dependent malic enzyme (m-NAD(P)-ME, ME2) either in vitro or in vivo. The in vitro IC50 value of EA for m-NAD(P)-ME was 1.4 ± 0.4 μM. Mutagenesis and binding studies revealed that the putative binding site of EA on m-NAD(P)-ME is located at the fumarate binding site or at the dimer interface near the site. Inhibition studies reveal that EA displayed a non-competitive inhibition pattern, which demonstrated that the binding site of EA was distinct from the active site of the enzyme. Therefore, EA is thought to be an allosteric inhibitor of m-NAD(P)-ME. Both EA treatment and knockdown of m-NAD(P)-ME by shRNA inhibited the growth of H1299 cancer cells. The protein expression and mRNA synthesis of m-NAD(P)-ME in H1299 cells were not influenced by EA, suggesting that the EA-inhibited H1299 cell growth occurs through the suppression of in vivo m-NAD(P)-ME activity EA treatment further induced the cellular senescence of H1299 cells. However, down-regulation of the enzyme-induced cellular senescence was not through p53. Therefore, the EA-evoked senescence of H1299 cells may occur directly through the inhibition of ME2 or a p53-independent pathway.
Perspectives in Laryngopharyngeal Reflux: An International Survey

Objectives Although data exists to support the relationship between laryngopharyngeal reflux (LPR) and laryngitis, there is variability among otolaryngologists regarding the methods and criteria used to make the diagnosis. This study was undertaken to discern the current attitudes and practices of a select cohort of otolaryngologists in regards to LPR.
The Pervasive Effects of an Antibiotic on the Human Gut Microbiota, as Revealed by Deep 16S rRNA Sequencing

The human intestinal microbiota is essential to the health of the host and plays a role in nutrition, development, metabolism, pathogen resistance, and regulation of immune responses. Antibiotics may disrupt these coevolved interactions, leading to acute or chronic disease in some individuals. Our understanding of antibiotic-associated disturbance of the microbiota has been limited by the poor sensitivity, inadequate resolution, and significant cost of current research methods. The use of pyrosequencing technology to generate large numbers of 16S rDNA sequence tags circumvents these limitations and has been shown to reveal previously unexplored aspects of the “rare biosphere. ” We investigated the distal gut bacterial communities of three healthy humans before and after treatment with ciprofloxacin, obtaining more than 7,000 full-length rRNA sequences and over 900,000 pyrosequencing reads from two hypervariable regions of the rRNA gene. A companion paper in PLoS Genetics (see Huse et al., doi: 10.1371/journal.pgen.1000255) shows that the taxonomic information obtained with these methods is concordant. Pyrosequencing of the V6 and V3 variable regions identified 3,300–5,700 taxa that collectively accounted for over 99% of the variable region sequence tags that could be obtained from these samples. Ciprofloxacin treatment influenced the abundance of about a third of the bacterial taxa in the gut, decreasing the taxonomic richness, diversity, and evenness of the community. However, the magnitude of this effect varied among individuals, and some taxa showed interindividual variation in the response to ciprofloxacin. While differences of community composition between individuals were the largest source of variability between samples, we found that two unrelated individuals shared a surprising degree of community similarity. In all three individuals, the taxonomic composition of the community closely resembled its pretreatment state by 4 weeks after the end of treatment, but several taxa failed to recover within 6 months. These pervasive effects of ciprofloxacin on community composition contrast with the reports by participants of normal intestinal function and with prior assumptions of only modest effects of ciprofloxacin on the intestinal microbiota. These observations support the hypothesis of functional redundancy in the human gut microbiota. The rapid return to the pretreatment community composition is indicative of factors promoting community resilience, the nature of which deserves future investigation.