Miracle-dz/UniFAR-FTUs huggingface dataset:
A Phase 1c Trial Comparing the Efficacy and Safety of a New Aqueous Formulation of Alphaxalone with Propofol

BACKGROUND: Phaxan™ (PHAX, Chemic Labs, Canton, MA) is an aqueous solution of 10 mg/mL alphaxalone and 13% 7-sulfobutylether &bgr;-cyclodextrin (betadex). In preclinical studies, PHAX is a fast onset–offset IV anesthetic like propofol, but causes less cardiovascular depression. This first-in-man study was designed to find the anesthetic dose of PHAX and to compare it with an equivalent dose of propofol for safety, efficacy, and quality of recovery from anesthesia and sedation. METHODS: The study adhered to compliance with Good Clinical Practices regulations (clinical trials registry number, ACTRN12611000343909). This randomized, double-blind study compared PHAX and propofol using a Bayesian algorithm to determine dose equivalence for effects on the bispectral index (BIS). Male volunteers, ASA physical status I, gave written informed consent (n = 12 per group; PHAX or propofol). Parameters assessed for 80 minutes after drug injection (single bolus dose) were pain on injection, involuntary movement, BIS, blood pressure, need for airway support, and, as measures of recovery from sedation, the Richmond Agitation and Sedation Scale and the Digit Symbol Substitution Test. Arterial blood was withdrawn for biochemistry, hematology, and complement levels. RESULTS: No subject complained of pain on injection with PHAX, whereas 8 of the 12 subjects given propofol did. Nine PHAX and 8 propofol subjects reached BIS values of ⩽50: median (interquartile range [IQR]) mg/kg dose = 0.5 (0.5–0.6) for PHAX and 2.9 (2.4–3.0) for propofol. The lowest median BIS reached was 27 to 28 for both agents with no significant differences between them for timing of onset and recovery of BIS. The concomitant median changes in systolic and diastolic blood pressures were −11% vs −19% for systolic and −25% vs −37% for diastolic in PHAX- and propofol-treated subjects, respectively. Nine of the 12 propofol-treated subjects and none of 12 PHAX-treated subjects required airway support. For subjects reaching an equivalent BIS of ⩽50: a Richmond Agitation and Sedation Scale score of 0 was reached at a median of 5 (IQR, 5–10) and 15 (IQR, 10–20) minutes after PHAX and propofol, respectively; BIS returned to 90 at a mean of 21 (SD, 10.1) and 21 (SD, 9.2) minutes after PHAX and propofol, respectively; and Digit Symbol Substitution Test scores returned to predrug injection values at median of 50 (IQR, 35–72.5) and 42.5 (IQR, 35–76.3) minutes after PHAX and propofol, respectively. There was no increase in C3 and C4 complement fractions after either drug. CONCLUSIONS: PHAX causes fast-onset, short-duration anesthesia with fast cognitive recovery similar to propofol, but with less cardiovascular depression, or airway obstruction and no pain on injection.
Always Gamble on an Empty Stomach: Hunger Is Associated with Advantageous Decision Making

Three experimental studies examined the counterintuitive hypothesis that hunger improves strategic decision making, arguing that people in a hot state are better able to make favorable decisions involving uncertain outcomes. Studies 1 and 2 demonstrated that participants with more hunger or greater appetite made more advantageous choices in the Iowa Gambling Task compared to sated participants or participants with a smaller appetite. Study 3 revealed that hungry participants were better able to appreciate future big rewards in a delay discounting task; and that, in spite of their perception of increased rewarding value of both food and monetary objects, hungry participants were not more inclined to take risks to get the object of their desire. Together, these studies for the first time provide evidence that hot states improve decision making under uncertain conditions, challenging the conventional conception of the detrimental role of impulsivity in decision making.
Coding exon-structure aware realigner (CESAR) utilizes genome alignments for accurate comparative gene annotation

Abstract Identifying coding genes is an essential step in genome annotation. Here, we utilize existing whole genome alignments to detect conserved coding exons and then map gene annotations from one genome to many aligned genomes. We show that genome alignments contain thousands of spurious frameshifts and splice site mutations in exons that are truly conserved. To overcome these limitations, we have developed CESAR (Coding Exon-Structure Aware Realigner) that realigns coding exons, while considering reading frame and splice sites of each exon. CESAR effectively avoids spurious frameshifts in conserved genes and detects 91% of shifted splice sites. This results in the identification of thousands of additional conserved exons and 99% of the exons that lack inactivating mutations match real exons. Finally, to demonstrate the potential of using CESAR for comparative gene annotation, we applied it to 188 788 exons of 19 865 human genes to annotate human genes in 99 other vertebrates. These comparative gene annotations are available as a resource (http://bds.mpi-cbg.de/hillerlab/CESAR/). CESAR (https://github.com/hillerlab/CESAR/) can readily be applied to other alignments to accurately annotate coding genes in many other vertebrate and invertebrate genomes.
Birds of a Feather: Homophily in Social Networks

Similarity breeds connection. This principle—the homophily principle—structures network ties of every type, including marriage, friendship, work, advice, support, information transfer, exchange, comembership, and other types of relationship. The result is that people's personal networks are homogeneous with regard to many sociodemographic, behavioral, and intrapersonal characteristics. Homophily limits people's social worlds in a way that has powerful implications for the information they receive, the attitudes they form, and the interactions they experience. Homophily in race and ethnicity creates the strongest divides in our personal environments, with age, religion, education, occupation, and gender following in roughly that order. Geographic propinquity, families, organizations, and isomorphic positions in social systems all create contexts in which homophilous relations form. Ties between nonsimilar individuals also dissolve at a higher rate, which sets the stage for the formation of niches (localize.
[Expression of interleukin-1beta and tumor necrosis factor-alpha in the synovium and synovial fluid of patients with Kashin-Beck disease and osteoarthritis].

OBJECTIVE To investigate the role of interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) in the pathogenesis and progression of Kashin-Beck disease (KBD) and primary osteoarthritis (OA). METHODS The synovium and synovial fluid of the knee joint were collected from 20 adult patients with KBD, 18 with OA and 19 with meniscus injury (controls). The expression of IL-1beta and TNF-alpha in the synovium were analyzed by immunohistochemistry staining, and the levels of IL-1beta and TNF-alpha in the synovial fluid were determined by enzyme-linked immunosorbent assay. RESULT IL-1beta and TNF-alpha expressions in the synovium and their levels in the synovial fluid were significantly higher in patients with KBD and OA than in patients with meniscus injury (P<0.05), but comparable between KBD and OA groups (P>0.05). CONCLUSION IL-1beta and TNF-alpha may play an important role in the pathogenesis and progression of KBD and OA.
Metalloproteinase-mediated release of human Fas ligand

Fas ligand (FasL) is a type II integral membrane protein homologous with tumor necrosis factor (TNF). Recent studies indicate that TNF is processed to yield the soluble cytokine by metalloproteinases at the cell surface of activated macrophages and T cells. In the present study, we investigated whether FasL is also released by metalloproteinases. Treatment with hydroxamic acid inhibitors of matrix metalloproteinases specifically led to accumulation of membrane-type FasL (p40) on the surface of human FasL cDNA transfectants and activated human T cells, as estimated by surface immunofluorescence and immunoprecipitation with newly established anti-human FasL monoclonal antibodies. This surface accumulation of mFasL was associated with the decrease of soluble FasL (p27) in the supernatant as estimated by quantitative ELISA and immunoprecipitation with anti-human FasL monoclonal antibodies. These results indicate that human FasL is efficiently released from the cell surface by metalloproteinases like TNF.
Laboratory simulations of acid-sulfate weathering under volcanic hydrothermal conditions: Implications for early Mars

We have completed laboratory experiments and thermochemical equilibrium models to investigate secondary mineral formation under conditions akin to volcanic, hydrothermal acid‐sulfate weathering systems. Our research used the basaltic mineralogy at Cerro Negro Volcano, Nicaragua, characterized by plagioclase, pyroxene, olivine, and volcanic glass. These individual minerals and whole‐rock field samples were reacted in the laboratory with 1 molal sulfuric acid at varying temperatures (65, 150, and 200°C), fluid:rock weight ratios (1:1, 4:1, and 10:1), and durations (1–60 days). Thermochemical equilibrium models were developed using Geochemist's Workbench. To understand the reaction products and fluids, we employed scanning electron microscopy/energy dispersive spectroscopy, X‐ray diffraction, and inductively coupled plasma‐atomic emission spectroscopy. The results of our experiments and models yielded major alteration minerals that include anhydrite, natroalunite, minor iron oxide, and amorphous Al‐Si gel. We found that variations in experimental parameters did not drastically change the suite of minerals produced; instead, abundance, size, and crystallographic shape changed. Our results also suggest that it is essential to separate phases formed during experiments from those formed during fluid evaporation to fully understand the reaction processes. Our laboratory reacted and model predicted products are consistent with the mineralogy observed at places on Mars. However, our results indicate that determination of the formation conditions requires microscopic imagery and regional context, as well as a thorough understanding of contributions from both experiment precipitation and fluid evaporation minerals.
Innovation in a global consulting firm: when the problem is too much diversity

This paper explores how individual managers in multinational firms utilize their informal relations to create new knowledge. Specifically, how does the density of informal networks affect an actor's ability to access and integrate diverse information and consequently that actor's innovation performance? The arguments are developed using the setting of 79 senior partners in a global management consulting firm and tested on a dataset of 1,449 informal relationships. I distinguish between internal, external, local, and global relations and find that this separation permits a more nuanced understanding of the effect of network structure on innovation performance. Specifically, I argue that the most effective network strategy is contingent upon the context in which the partners operate. The findings show that partners operating in homogeneous contexts, where the primary challenge is to access diverse information, benefit from low-density networks. In contrast, when crossing both firm and geographic boundaries, partners with dense networks have higher innovation performance. I argue that in such heterogeneous contexts, dense network interactions facilitate partners' ability to integrate the diverse information to which they are exposed. Copyright © 2010 John Wiley & Sons, Ltd.
Androgen Receptor in the Ovary Theca Cells Plays a Critical Role in Androgen-Induced Reproductive Dysfunction

Androgen and its receptor (AR) play a critical role in reproductive function under both physiological and pathophysiological conditions. Female AR global knockout mice are subfertile due to both neuroendocrine and ovarian defects. Female offspring from prenatally androgenized heterozygous AR pregnant mice showed rescued estrous cyclicity and fertility. Ar is expressed in granulosa cells, theca interstitial cells, and oocytes in the ovary. We created mice with theca-specific deletion of Ar (ThARKO) by crossing Cyp17-iCre mice that express Cre recombinase under cytochrome P450 17A1 (Cyp17) promoter with Arfl/fl mice. ThARKO mice exhibited no significant differences in pubertal onset or fertility compared with control littermates, and neither estrogen or testosterone levels were different between these groups. Therefore, Ar expression in theca cells likely does not influence fertility nor androgen levels in female mice. We then tested the role of AR in theca cells under hyperandrogenemic condition. After treatment with a pathophysiological level of dihydrotestosterone (DHT), control mice (control-DHT) showed acyclicity and infertility. However, estrous cycles and fertility were altered to a significantly less degree in ThARKO-DHT mice than in control-DHT mice. Messenger RNA (mRNA) levels of Lhcgr (luteinizing hormone receptor) and Timp1 (tissue inhibitor of metalloproteinase 1, and inhibitor of matrix metalloproteinase) were significantly lower in control-DHT ovary compared with control-no DHT ovaries, whereas mRNA levels of Fshr (follicle-stimulating hormone receptor) were significantly higher. Timp1 gene expression was comparable in the ThARKO-DHT and the control-no DHT ovary. We speculate that the preserved level of Timp1 in ThARKO-DHT mice contributes to retained reproductive function.
The Genetics of Extreme Longevity: Lessons from the New England Centenarian Study

The New England Centenarian Study (NECS) was founded in 1994 as a longitudinal study of centenarians to determine if centenarians could be a model of healthy human aging. Over time, the NECS along with other centenarian studies have demonstrated that the majority of centenarians markedly delay high mortality risk-associated diseases toward the ends of their lives, but many centenarians have a history of enduring more chronic age-related diseases for many years, women more so than men. However, the majority of centenarians seem to deal with these chronic diseases more effectively, not experiencing disability until well into their nineties. Unlike most centenarians who are less than 101 years old, people who live to the most extreme ages, e.g., 107+ years, are generally living proof of the compression of morbidity hypothesis. That is, they compress morbidity and disability to the very ends of their lives. Various studies have also demonstrated a strong familial component to extreme longevity and now evidence particularly from the NECS is revealing an increasingly important genetic component to survival to older and older ages beyond 100 years. It appears to us that this genetic component consists of many genetic modifiers each with modest effects, but as a group they can have a strong influence.
Consequents of functional and technical quality: evidence from electronic and mobile service industry in China

The growing market potential of China's service industry requires an in-depth understanding of factors leading to consumers' loyalty towards e-service and mobile services providing websites. The growth of e-service and mobile services has changed the manner in which firms and consumers interact. A conceptual model that examines the relationship between service quality, trust, satisfaction, and loyalty in electronic and mobile environment is proposed. The analysis of data from 415 Chinese consumers reveals that both technical and functional quality of e-services and mobile services have a strong impact on consumers' trust and satisfaction, which in turn positively influence their loyalty towards service providers in electronic and mobile environment. We conclude our paper with a discussion of our findings and possible future research alternatives.
Collecting, organizing, and sharing pins in pinterest: interest-driven or social-driven?

Pinterest, a popular social curating service where people collect, organize, and share content (pins in Pinterest), has gained great attention in recent years. Despite the increasing interest in Pinterest, little research has paid attention to how people collect, manage, and share pins in Pinterest. In this paper, to shed insight on such issues, we study the following questions. How do people collect and manage pins by their tastes in Pinterest? What factors do mainly drive people to share their pins in Pinterest? How do the characteristics of users (e.g., gender, popularity, country) or properties of pins (e.g., category, topic) play roles in propagating pins in Pinterest? To answer these questions, we have conducted a measurement study on patterns of pin curating and sharing in Pinterest. By keeping track of all the newly posted and shared pins in each category (e.g., animal, kids, women's fashion) from June 5 to July 18, 2013, we built 350 K pin propagation trees for 3 M users. With the dataset, we investigate: (1) how users collect and curate pins, (2) how users share their pins and why, and (3) how users are related by shared pins of interest. Our key finding is that pin propagation in Pinterest is mostly driven by pin's properties like its topic, not by user's characteristics like her number of followers. We further show that users in the same community in the interest graph (i.e., representing the relations among users) of Pinterest share pins (i) in the same category with 94% probability and (ii) of the same URL where pins come from with 89% probability. Finally, we explore the implications of our findings for predicting how pins are shared in Pinterest.
Prevalence of suicidal feelings in a sample of non‐consulting medical students

Five hundred and sixteen final‐year non‐consulting medical students were studied as to the occurrence of different degrees of suicidal feelings. A total of 12.6 % reported some degree of suicidal feelings during the past year. Responses ranged along a continuum such that subjects reporting the more intense feelings also reported the less intense feelings.
Mycalamide A Shows Cytotoxic Properties and Prevents EGF-Induced Neoplastic Transformation through Inhibition of Nuclear Factors

Mycalamide A, a marine natural compound previously isolated from sponges, is known as a protein synthesis inhibitor with potent antitumor activity. However, the ability of this compound to prevent malignant transformation of cells has never been examined before. Here, for the first time, we report the isolation of mycalamide A from ascidian Polysincraton sp. as well as investigation of its cancer preventive properties. In murine JB6 Cl41 P+ cells, mycalamide A inhibited epidermal growth factor (EGF)-induced neoplastic transformation, and induced apoptosis at subnanomolar or nanomolar concentrations. The compound inhibited transcriptional activity of the oncogenic nuclear factors AP-1 and NF-κB, a potential mechanism of its cancer preventive properties. Induction of phosphorylation of the kinases MAPK p38, JNK, and ERK was also observed at high concentrations of mycalamide A. The drug shows promising potential for both cancer-prevention and cytotoxic therapy and should be further developed.
Prevalence of Specific Helicobacter PyloricagA, vacA, iceA, ureC Genotypes and its Clinical Relevance in the Patients with Acid-Peptic Diseases.

INTRODUCTION Virulent markers of H. pylori, the vacuolating cytotoxin (vacA), cytotoxin-associated gene A (cagA), induced by contact with epithelium factor antigen (iceA gene) and the urease C gene (ureC) may plays a major role in determining the clinical outcome of Helicobacter infections. AIM To detect the prevalence of the cagA, vacA, ureC and iceA genotypes of H. pylori from antral biopsy specimens of patients and to associate its role in specific disease. MATERIALS AND METHODS The study was conducted at Department of Microbiology of Shree P.M. Patel College of Paramedical Sciences, Anand, Gujarat, India. Seventy one antral biopsies of symptomatic patients referred for endoscopy from October 2012 to September 2013 were subjected to Multiplex PCR. DNA isolation from 71 biopsy samples was done by using "QIAamp DNA mini kit" from QIAGEN (GmbH, Hilden, Germany). Data was analysed using Chi square (χ2) test and p-value<0.05 was considered significant. RESULTS Out of the 71 biopsies screened, 22(31%) samples were positive for H. pylori by PCR, with high proportion of cagA positive (17/22 specimen; 77.27%), followed by ureC positive (4/22 specimen; 18.18%) and vacA positive (1/22 specimen; 4.54%) strains. Significant association was found between cagA and female gender (p-value=0.042). Out of 17 cagA positive strains, 9(52.94%) were found in patients with gastritis, 5(29.41%) in reflux oesophagitis and 3(17.64%) in patients with diodenal ulcer. We found 0% prevalence of iceA gene; conversely we had three peptic ulcer patients with only cagA positivity. CONCLUSION The cagA positive strain mainly affects the patients with gastritis specifically of female gender and iceA genotype is not a useful marker associated with peptic ulcer disease. Patients should be screened for cagA genotype when reported to be a case of gastritis for early treatment to prevent further complications such as cancer.
A comprehensive overview of Infinium HumanMethylation450 data processing

Infinium HumanMethylation450 beadarray is a popular technology to explore DNA methylomes in health and disease, and there is a current explosion in the use of this technique. Despite experience acquired from gene expression microarrays, analyzing Infinium Methylation arrays appeared more complex than initially thought and several difficulties have been encountered, as those arrays display specific features that need to be taken into consideration during data processing. Here, we review several issues that have been highlighted by the scientific community, and we present an overview of the general data processing scheme and an evaluation of the different normalization methods available to date to guide the 450K users in their analysis and data interpretation.
Chemical Yields from Supernovae and Hypernovae

Abstract We review the final stages of stellar evolution, supernova properties, and chemical yields as a function of the progenitor's mass. (1) 8 - 10 M⊙ stars are super-AGB stars when the O+Ne+Mg core collapses due to electron capture. These AGB-supernovae may constitute an SN 2008S-like sub-class of Type IIn supernovae. These stars produce little α-elements and Fe-peak elements, but are important sources of Zn and light p-nuclei. (2) 10 - 90 M⊙ stars undergo Fe-core collapse. Nucleosynthesis in aspherical explosions is important, as it can well reproduce the abundance patterns observed in extremely metal-poor stars. (3) 90 - 140 M⊙ stars undergo pulsational nuclear instabilities at various nuclear burning stages, including O and Si-burning. (4) Very massive stars with M ≳ 140 M⊙ either become pair-instability SNe, or undergo core-collapse to form intermediate mass black holes if the mass loss is small enough.
A New Approach to the Extraction of ANN Rules and to Their Generalization Capacity Through GP

Various techniques for the extraction of ANN rules have been used, but most of them have focused on certain types of networks and their training. There are very few methods that deal with ANN rule extraction as systems that are independent of their architecture, training, and internal distribution of weights, connections, and activation functions. This article proposes a methodology for the extraction of ANN rules, regardless of their architecture, and based on genetic programming. The strategy is based on the previous algorithm and aims at achieving the generalization capacity that is characteristic of ANNs by means of symbolic rules that are understandable to human beings.