Miracle-dz/UniFAR-FTUs huggingface dataset:
Positive and Negative Allosteric Modulation of an α1β3γ2 γ-Aminobutyric Acid Type A (GABAA) Receptor by Binding to a Site in the Transmembrane Domain at the γ+-β− Interface*

Background: For some chiral barbiturates, one isomer potentiates and the other inhibits GABA responses by binding to unknown sites. Results: A photoreactive convulsant barbiturate identifies a transmembrane intersubunit-binding site between the γ and β subunits. Conclusion: Positive and negative allosteric modulators can bind to a common intersubunit site. Significance: This study defines a novel mode of regulation of GABAAR responses. In the process of developing safer general anesthetics, isomers of anesthetic ethers and barbiturates have been discovered that act as convulsants and inhibitors of γ-aminobutyric acid type A receptors (GABAARs) rather than potentiators. It is unknown whether these convulsants act as negative allosteric modulators by binding to the intersubunit anesthetic-binding sites in the GABAAR transmembrane domain (Chiara, D. C., Jayakar, S. S., Zhou, X., Zhang, X., Savechenkov, P. Y., Bruzik, K. S., Miller, K. W., and Cohen, J. B. (2013) J. Biol. Chem. 288, 19343–19357) or to known convulsant sites in the ion channel or extracellular domains. Here, we show that S-1-methyl-5-propyl-5-(m-trifluoromethyl-diazirynylphenyl) barbituric acid (S-mTFD-MPPB), a photoreactive analog of the convulsant barbiturate S-MPPB, inhibits α1β3γ2 but potentiates α1β3 GABAAR responses. In the α1β3γ2 GABAAR, S-mTFD-MPPB binds in the transmembrane domain with high affinity to the γ+-β− subunit interface site with negative energetic coupling to GABA binding in the extracellular domain at the β+-α− subunit interfaces. GABA inhibits S-[3H]mTFD-MPPB photolabeling of γ2Ser-280 (γM2–15′) in this site. In contrast, within the same site GABA enhances photolabeling of β3Met-227 in βM1 by an anesthetic barbiturate, R-[3H]methyl-5-allyl-5-(m-trifluoromethyl-diazirynylphenyl)barbituric acid (mTFD-MPAB), which differs from S-mTFD-MPPB in structure only by chirality and two hydrogens (propyl versus allyl). S-mTFD-MPPB and R-mTFD-MPAB are predicted to bind in different orientations at the γ+-β− site, based upon the distance in GABAAR homology models between γ2Ser-280 and β3Met-227. These results provide an explanation for S-mTFD-MPPB inhibition of α1β3γ2 GABAAR function and provide a first demonstration that an intersubunit-binding site in the GABAAR transmembrane domain binds negative and positive allosteric modulators.
Candida albicans forms biofilms on the vaginal mucosa

Current understanding of resistance and susceptibility to vulvovaginal candidiasis challenges existing paradigms of host defence against fungal infection. While abiotic biofilm formation has a clearly established role during systemic Candida infections, it is not known whether C. albicans forms biofilms on the vaginal mucosa and the possible role of biofilms in disease. In vivo and ex vivo murine vaginitis models were employed to examine biofilm formation by scanning electron and confocal microscopy. C. albicans strains included 3153A (lab strain), DAY185 (parental control strain), and mutants defective in morphogenesis and/or biofilm formation in vitro (efg1/efg1 and bcr1/bcr1). Both 3153A and DAY815 formed biofilms on the vaginal mucosa in vivo and ex vivo as indicated by high fungal burden and microscopic analysis demonstrating typical biofilm architecture and presence of extracellular matrix (ECM) co-localized with the presence of fungi. In contrast, efg1/efg1 and bcr1/bcr1 mutant strains exhibited weak or no biofilm formation/ECM production in both models compared to wild-type strains and complemented mutants despite comparable colonization levels. These data show for the first time that C. albicans forms biofilms in vivo on vaginal epithelium, and that in vivo biotic biofilm formation requires regulators of biofilm formation (BCR1) and morphogenesis (EFG1).
Information Conveyed in Hiring Announcements of Senior Executives Overseeing Enterprise-Wide Risk Management Processes

Enterprise risk management (ERM) is the process of analyzing the portfolio of risks facing the enterprise to ensure that the combined effect of such risks is within an acceptable tolerance. While more firms are adopting ERM, little academic research exists about the costs and benefits of ERM. Proponents of ERM claim that ERM is designed to enhance shareholder value; however, portfolio theory suggests that costly ERM implementation would be unwelcome by shareholders who can use less costly diversification to eliminate idiosyncratic risk. This study examines equity market reactions to announcements of appointments of senior executive officers overseeing the enterprise's risk management processes. Based on a sample of 120 announcements from 1992-2003, we find that the univariate average two-day market response is not significant, suggesting that a general definitive statement about the benefit or cost of implementing ERM is not possible. However, our multiple regression analysis reveals that there are significant relations between the magnitude of equity market returns and certain firm specific characteristics. For nonfinancial firms, announcement period returns are positively associated with firm size and the volatility of prior periods' reported earnings and negatively associated with leverage and the extent of cash on hand relative to liabilities. For financial firms, however, there are fewer statistical associations between announcement returns and firm characteristics. These results suggest that the costs and benefits of ERM are firm-specific.
Scanning Mobility CCN Analysis—A Method for Fast Measurements of Size-Resolved CCN Distributions and Activation Kinetics

We present Scanning Mobility CCN Analysis (SMCA) as a novel method for obtaining rapid measurements of size-resolved cloud condensation nuclei (CCN) distributions and activation kinetics. SMCA involves sampling the monodisperse outlet stream of a Differential Mobility Analyzer (DMA) operated in scanning voltage mode concurrently with CCN and condensation particle counters. By applying the same inversion algorithm as used for obtaining size distributions with a scanning mobility particle sizer (SMPS), CCN concentration and activated droplet size are obtained as a function of mobility size over the timescale of an SMPS scan (typically 60–120 s). Methods to account for multiple charging, particle non-sphericity, and limited counting statistics are presented. SMCA is demonstrated using commercial SMPS and CFSTGC instruments with the manufacturer-provided control software. The method is evaluated for activation of both laboratory aerosol and ambient aerosol obtained during the 2004 NEAQS-ITCT2k4 field campaign. It is shown that SMCA reproduces the results obtained with a DMA operating in voltage “stepping” mode.
Using PU-Learning to Detect Deceptive Opinion Spam

Nowadays a large number of opinion reviews are posted on the Web. Such reviews are a very important source of information for customers and companies. The former rely more than ever on online reviews to make their purchase decisions and the latter to respond promptly to their clients’ expectations. Due to the economic importance of these reviews there is a growing trend to incorporate spam on such sites, and, as a consequence, to develop methods for opinion spam detection. In this paper we focus on the detection of deceptive opinion spam, which consists of fictitious opinions that have been deliberately written to sound authentic, in order to deceive the consumers. In particular we propose a method based on the PU-learning approach which learns only from a few positive examples and a set of unlabeled data. Evaluation results in a corpus of hotel reviews demonstrate the appropriateness of the proposed method for real applications since it reached a f-measure of 0.84 in the detection of deceptive opinions using only 100 positive examples for training.
Bullying involvement and autism spectrum disorders: prevalence and correlates of bullying involvement among adolescents with an autism spectrum disorder.

OBJECTIVES To produce nationally representative estimates for rates of bullying involvement among adolescents with an autism spectrum disorder (ASD), to compare population estimates with adolescents who have other developmental disabilities, and to identify social ecological correlates of bullying involvement. DESIGN Nationally representative surveys from 2001. SETTING United States. PARTICIPANTS Parents of adolescents with an ASD, principals of the schools they attended, and staff members most familiar with their school programs. MAIN EXPOSURE Autism spectrum disorders. MAIN OUTCOME MEASURES Parent report of victimization, perpetration, and victimization/perpetration within the past school year. RESULTS The prevalence rates of bullying involvement for adolescents with an ASD were 46.3% for victimization, 14.8% for perpetration, and 8.9% for victimization/perpetration. Victimization was related to having a non-Hispanic ethnicity, attention-deficit/hyperactivity disorder, lower social skills, some form of conversational ability, and more classes in general education. Correlates of perpetration included being white, having attention-deficit/hyperactivity disorder, and getting together with friends at least once a week. Victimization/perpetration was associated with being white non-Hispanic, having attention-deficit/hyperactivity disorder, and getting together with friends at least once a week. CONCLUSIONS School-based bullying interventions need to target the core deficits of ASD (conversational ability and social skills) and comorbid conditions (eg, attention-deficit/hyperactivity disorder). Future bullying interventions also need to address the higher rates of victimization that occur in general education settings by increasing social integration into protective peer groups and increasing the empathy and social skills of typically developing students toward their peers with an ASD.
Understanding Radar Refractivity: Sources of Uncertainty

AbstractThis study presents a 2-yr-long comparison of Weather Surveillance Radar-1988 Doppler (WSR-88D) refractivity retrievals with Oklahoma Mesonetwork (“Mesonet”) and sounding measurements and discusses some challenges to implementing radar refractivity operationally. Temporal and spatial analyses of radar refractivity exhibit high correlation with Mesonet data; however, periods of large refractivity differences between the radar and Mesonet are observed. Several sources of refractivity differences are examined to determine the cause of large refractivity differences. One source for nonklystron radars includes magnetron frequency drift, which can introduce errors up to 10 N-units if the frequency drift is not corrected. Different reference maps made at different times can “shift” refractivity values. A semiautomated method for producing reference maps is presented, including trade-offs for making reference maps under different conditions. Refractivity from six Mesonet stations within the clutter domain.
Peripancreatic paraganglioma mimics pancreatic/gastrointestinal neuroendocrine tumor on fine needle aspiration: Report of two cases and review of the literature

Cytologic diagnosis of extra‐adrenal paraganglioma presenting as a peripancreatic mass is challenging with a high error rate due to its rarity. We report two cases of peripancreatic masses identified by radiology. Endoscopic ultrasound‐guided fine needle aspiration (FNA) of the masses showed a moderately cellular tumor composed of small to medium sized neoplastic cells with round to oval nuclei, arranged singly and in loose clusters. Focal rosette‐like structures were present. The cells were positive for neuroendocrine markers (synaptophysin and chromogranin). A diagnosis of a neoplasm with neuroendocrine differentiation and neuroendocrine tumor was made respectively on FNA for each case. The subsequent surgical resection of the tumors revealed peripancreatic paraganglioma. Although paraganglioma has been reported in the literature, the detailed comparison of perpancreatic paraganglioma versus pancreatic/gastrointestinal neuroendocrine tumor is still lacking. Therefore using these two cases with literature review, we wish to illustrate the differential diagnosis between these two entities based on cytomorphology and immunohistochemical study.
Study of Resting-State Functional Connectivity Networks Using EEG Electrodes Position As Seed

Electroencephalography (EEG) is the standard diagnosis method for a wide variety of diseases such as epilepsy, sleep disorders, encephalopathies, and coma, among others. Resting-state functional magnetic resonance (rs-fMRI) is currently a technique used in research in both healthy individuals as well as patients. EEG and fMRI are procedures used to obtain direct and indirect measurements of brain neural activity: EEG measures the electrical activity of the brain using electrodes placed on the scalp, and fMRI detects the changes in blood oxygenation that occur in response to neural activity. EEG has a high temporal resolution and low spatial resolution, while fMRI has high spatial resolution and low temporal resolution. Thus, the combination of EEG with rs-fMRI using different methods could be very useful for research and clinical applications. In this article, we describe and show the results of a new methodology for processing rs-fMRI using seeds positioned according to the 10-10 EEG standard. We analyze the functional connectivity and adjacency matrices obtained using 65 seeds based on 10-10 EEG scheme and 21 seeds based on 10-20 EEG. Connectivity networks are created using each 10-20 EEG seeds and are analyzed by comparisons to the seven networks that have been found in recent studies. The proposed method captures high correlation between contralateral seeds, ipsilateral and contralateral occipital seeds, and some in the frontal lobe.
Acupuncture for Pain Management in Cancer: A Systematic Review and Meta-Analysis

Objective. To evaluate the effectiveness and safety of acupuncture for cancer-related pain. Methods. A systematic review of literatures published from database inception to February 2015 was conducted in eight databases. RCTs involving acupuncture for treatment of cancer-related pain were identified. Two researchers independently performed article selection, data extraction, and quality assessment of data. Results. 1,639 participants in twenty RCTs were analyzed. All selected RCTs were associated with high risk of bias. Meta-analysis indicated that acupuncture alone did not have superior pain-relieving effects as compared with conventional drug therapy. However, as compared with the drug therapy alone, acupuncture plus drug therapy resulted in increased pain remission rate, shorter onset time of pain relief, longer pain-free duration, and better quality of life without serious adverse effects. However, GRADE analysis revealed that the quality of all outcomes about acupuncture plus drug therapy was very low. Conclusions. Acupuncture plus drug therapy is more effective than conventional drug therapy alone for cancer-related pain. However, multicenter high-quality RCTs with larger sample sizes are needed to provide stronger evidence for the effectiveness of acupuncture in cancer-related pain due to the low data quality of the studies included in the current meta-analysis.
Training preschoolers on first-order false belief understanding: transfer on advanced ToM skills and metamemory.

This study investigated the relation between theory of mind (ToM) and metamemory knowledge using a training methodology. Sixty-two 4- to 5-year-old children were recruited and randomly assigned to one of two training conditions: A first-order false belief (ToM) and a control condition. Intervention and control groups were equivalent at pretest for age, parents' education, verbal ability, inhibition, and ToM. Results showed that after the intervention children in the ToM group improved in their first-order false belief understanding significantly more than children in the control condition. Crucially, the positive effect of the ToM intervention was stable over 2 months and generalized to more complex ToM tasks and metamemory.
The quantum Hall effect at 5/2 filling factor

Experimental discovery of a quantized Hall state at 5/2 filling factor presented an enigmatic finding in an established field of study that has remained an open issue for more than twenty years. In this review we first examine the experimental requirements for observing this state and outline the initial theoretical implications and predictions. We will then follow the chronology of experimental studies over the years and present the theoretical developments as they pertain to experiments, directed at sets of issues. These topics will include theoretical and experimental examination of the spin properties at 5/2; is the state spin polarized? What properties of the higher Landau levels promote development of the 5/2 state, what other correlation effects are observed there, and what are their interactions with the 5/2 state? The 5/2 state is not a robust example of the fractional quantum Hall effect: what experimental and material developments have allowed enhancement of the effect? Theoretical developments from initial pictures have promoted the possibility that 5/2 excitations are exceptional; do they obey non-abelian statistics? The proposed experiments to determine this and their executions in various forms will be presented: this is the heart of this review. Experimental examination of the 5/2 excitations through interference measurements will be reviewed in some detail, focusing on recent results that demonstrate consistency with the picture of non-abelian charges. The implications of this in the more general physics picture is that the 5/2 excitations, shown to be non-abelian, should exhibit the properties of Majorana operators. This will be the topic of the last review section.
Behind the Robot’s Smiles and Frowns: In Social Context, People Do Not Mirror Android’s Expressions But React to Their Informational Value

Facial actions are key elements of non-verbal behavior. Perceivers’ reactions to others’ facial expressions often represent a match or mirroring (e.g., they smile to a smile). However, the information conveyed by an expression depends on context. Thus, when shown by an opponent, a smile conveys bad news and evokes frowning. The availability of anthropomorphic agents capable of facial actions raises the question of how people respond to such agents in social context. We explored this issue in a study where participants played a strategic game with or against a facially expressive android. Electromyography (EMG) recorded participants’ reactions over zygomaticus muscle (smiling) and corrugator muscle (frowning). We found that participants’ facial responses to android’s expressions reflect their informational value, rather than a direct match. Overall, participants smiled more, and frowned less, when winning than losing. Critically, participants’ responses to the game outcome were similar regardless of whether it was conveyed via the android’s smile or frown. Furthermore, the outcome had greater impact on people’s facial reactions when it was conveyed through android’s face than a computer screen. These findings demonstrate that facial actions of artificial agents impact human facial responding. They also suggest a sophistication in human-robot communication that highlights the signaling value of facial expressions.
β8 integrin is essential for neuroblast migration in the rostral migratory stream

Neurogenesis in the post‐natal brain occurs in two primary locations: the subgranular layer of the hippocampal dentate gyrus and the subventricular zone (SVZ) of the lateral ventricles. Following differentiation, neuroblasts within the SVZ migrate several millimeters to the olfactory bulbs (OBs) via a distinct anatomic route, or rostral migratory stream (RMS). The genes that govern neuroblast directional migration, and particularly those encoding cell adhesion and signaling factors, remain largely uncharacterized. Here, we report that the extracellular matrix adhesion receptor, β8 integrin, is essential for proper neuroblast chain formation and directional navigation in the RMS. Primary neuroblasts isolated from the mouse brain express robust levels of β8 integrin protein, and selective ablation of β8 integrin gene expression in neuroblasts leads to aberrant chain migration and size‐reduced OBs. These integrin‐dependent defects can be recapitulated ex vivo using isolated neurospheres or SVZ explants. Collectively, these data identify essential cell‐intrinsic functions for β8 integrin in regulating neuroblast polarity and directional navigation in the mouse forebrain. © 2011 Wiley‐Liss, Inc.
Critical Success Factors of Implementing Enterprise Portals

The growing demand for packaged portal solutions is leading to an increasing attention in the management of critical success factors (CSFs) across the stages of the engineering process. We identified and analyzed the most important factors, critical for the success of the implementation of enterprise portals. We also relate the CSFs to the different stages of the implementation process and provide advice on how to manage these factors. Based on these findings, instruments that can improve the engineer-ing and management of portals can be proposed and developed.
Prevalence and associated factors of elder mistreatment: a cross sectional study from urban Nepal.

BACKGROUND mistreatment of elderly people is internationally recognised as a serious public health issue. This study aimed at estimating the prevalence and risk factors associated with mistreatment in urban Nepal. METHODS this was a descriptive cross-sectional study of 212 elderly people residing in Butwal sub-metropolitan city, an urban area in Nepal; the study was conducted between March and October 2015. Two-stage cluster design with simple random sampling was adopted for the study. Information was collected using an interviewer administered semi-structured questionnaire of older people. Logistic regression analysis was used to identify factors associated with elder mistreatment. RESULTS this study found a prevalence of 49.1% for mistreatment of the elderly population. Prevalence rates of caregiver neglect, financial, psychological or physical mistreatment and other types (including sexual assault) were 47.2%, 11.8%, 10.8%, 1.42% and 3.3%, respectively. Being a dalit (untouchable backward class in the traditional Hindu caste system), unemployed, widowed, divorced or separated, problems concentrating and smoking were independent factors associated with mistreatment. Smoking was found to be consistently associated with the three most common mistreatment types. CONCLUSIONS mistreatment of older people is common in urban Nepal, with neglect, financial and psychological abuse most common. Along with standard risk factors, specific ethnic issues (membership of dalit community) are associated with increased risk.