Miracle-dz/UniFAR-FTUs huggingface dataset:
Discovery of Novel Allosteric Modulators of Metabotropic Glutamate Receptor Subtype 5 Reveals Chemical and Functional Diversity and In Vivo Activity in Rat Behavioral Models of Anxiolytic and Antipsychotic Activity

Modulators of metabotropic glutamate receptor subtype 5 (mGluR5) may provide novel treatments for multiple central nervous system (CNS) disorders, including anxiety and schizophrenia. Although compounds have been developed to better understand the physiological roles of mGluR5 and potential usefulness for the treatment of these disorders, there are limitations in the tools available, including poor selectivity, low potency, and limited solubility. To address these issues, we developed an innovative assay that allows simultaneous screening for mGluR5 agonists, antagonists, and potentiators. We identified multiple scaffolds that possess diverse modes of activity at mGluR5, including both positive and negative allosteric modulators (PAMs and NAMs, respectively). 3-Fluoro-5-(3-(pyridine-2-yl)-1,2,4-oxadiazol-5-yl)benzonitrile (VU0285683) was developed as a novel selective mGluR5 NAM with high affinity for the 2-methyl-6-(phenylethynyl)-pyridine (MPEP) binding site. VU0285683 had anxiolytic-like activity in two rodent models for anxiety but did not potentiate phencyclidine-induced hyperlocomotor activity. (4-Hydroxypiperidin-1-yl)(4-phenylethynyl)phenyl)methanone (VU0092273) was identified as a novel mGluR5 PAM that also binds to the MPEP site. VU0092273 was chemically optimized to an orally active analog, N-cyclobutyl-6-((3-fluorophenyl)ethynyl)nicotinamide hydrochloride (VU0360172), which is selective for mGluR5. This novel mGluR5 PAM produced a dose-dependent reversal of amphetamine-induced hyperlocomotion, a rodent model predictive of antipsychotic activity. Discovery of structurally and functionally diverse allosteric modulators of mGluR5 that demonstrate in vivo efficacy in rodent models of anxiety and antipsychotic activity provide further support for the tremendous diversity of chemical scaffolds and modes of efficacy of mGluR5 ligands. In addition, these studies provide strong support for the hypothesis that multiple structurally distinct mGluR5 modulators have robust activity in animal models that predict efficacy in the treatment of CNS disorders.
Recognition of Facial Affect in individuals scoring high and low on Psychopathic Personality Characteristics

The accuracy of perception of facial emotion expressions was studied in individuals with low and high psychopathic personality characteristics in a sample of 21 male and 39 female university students. Participants completed the Psychopathic Personality Inventory (PPI), and the Behavioural Inhibition Scale and the Behavioural Activation Scale (BIS/BAS) as measures of psychopathy. Participants completed a computerised emotion recognition task containing six emotions of facial expressions (each emotion had five different intensities). The results showed that participants scoring low on the BIS and high on the BAS scores showed significant impairments in the recognition of both sad and fearful expressions. On the other hand, group scoring high on the PPI, showed significant impairment in the recognition of angry, but not fearful or sad expressions in the total sample. Males with high psychopathic personality characteristics showed significant impairments in the recognition of sad, fearful and angry expressions compared to males with low psychopathic personality characteristics. On the other hand females with high psychopathic personality characteristics showed significant impairment in recognising the expression of disgust only compared to females with low psychopathic personality characteristics. The PPI and the BIS/BAS scales showed reasonable alpha reliabilities with some exceptions for one subscale in each measure. Correlations between the PPI and the BIS/BAS scales were weak to moderate. The current findings suggest that different dimensions of psychopathy may be associated with selective impairments in recognising unpleasant emotion expressions in others.
Study of prescribing patterns of hypolipidemic agents in a tertiary care teaching hospital in North India

Background: Lipid-lowering agents are now the cornerstone of treatment used to reduce the risk of coronary events. Since there is wide variation in selection and use of these drugs, drug utilization studies help to evaluate and analyze drug therapy from time to time. This in turn can guide physicians prescribing practices and help in minimizing adverse drug reactions. Aims and Objectives: To evaluate the prescribing pattern of hypolipidemic drugs in a tertiary care teaching hospital in Jammu. Materials and Methods: An observational study was carried out in patients attending the departments of cardiology and general medicine for 6 months. Prescription of the patients who were prescribed at least one hypolipidemic drug as monotherapy or in combination was evaluated. Hypolipidemic and other classes of drugs prescribed and the World Health Organization prescribing indicators were analyzed. Monthly cost of the hypolipidemic drugs prescribed was also determined. Results: Nearly, two-third (63.7%) patients with increased plasma lipids and 36.2% patients in spite of having normal lipid profile were prescribed hypolipidemic drugs as well. Hypertension with comorbid conditions (39.63%) was the most common diseases, for which hypolipidemic drugs were prescribed. The average number of drugs per prescription was 6.21 ± 1.6. Atorvastatin was the most common hypolipidemic drug prescribed as monotherapy (59.16%), whereas atorvastatin with ramipril was the most common drugs prescribed as combination therapy (14.69%). Conclusion: This study depicts the widespread use of statins in various disease conditions, both as primary and secondary preventive measures. Such studies should be done to educate the physicians on good prescribing practices and on rational use of hypolipidemic drugs.
Secrets and Misperceptions: The Creation of Self-Fulfilling Illusions

This study examines who hears what secrets, comparing two similar secrets-one that is highly stigmatized and one that is less so. Using a unique survey representative of American adults and intake forms from a medical clinic, I document marked differences in who hears these secrets. People who are sympathetic to the stigmatizing secret are more likely to hear of it than those who may react negatively. This is a consequence of people not just selectively disclosing their own secrets but selectively sharing others’ as well. As a result, people in the same social network will be exposed to and influenced by different information about those they know and hence experience that network differently. When people effectively exist in networks tailored by others not to offend, then the information they hear tends to be that of which they already approve. Were they to hear secrets they disapproved of, then their attitudes might change, but they are less likely to hear those secrets. As such, the patterns of secret hearing contribute to a stasis in public opinion.
Group I Metabotropic Glutamate Receptors in the Monkey Striatum: Subsynaptic Association with Glutamatergic and Dopaminergic Afferents

Group I metabotropic glutamate receptors (mGluRs) are involved in long-term synaptic plasticity and neuroprotection in the striatum, but the specific role(s) of mGluR1 and mGluR5 remain poorly understood. In this study, we used electron-microscopic immunocytochemistry to compare the pattern of subsynaptic and subcellular distribution of mGluR1a and mGluR5 in relation to putative glutamatergic and dopaminergic inputs to the monkey striatum. At the light-microscopic level, both group I mGluRs are expressed in the striatal neuropil. In addition, numerous perikarya of striatal output neurons are immunostained for mGluR5, but much less frequently for mGluR1a. At the electron-microscopic level, immunoreactivity for both receptor subtypes is primarily expressed postsynaptically in dendrites and spines, although presynaptic mGluR1a labeling of glutamatergic thalamostriatal boutons and, less frequently, dopaminergic and corticostriatal terminals is also seen. In contrast to mGluR1a, mGluR5 immunoreactivity is rarely encountered presynaptically. In postsynaptic elements, 40-70% of immunoreactivity for both receptor subtypes is expressed intracellularly, whereas 30-60% is apposed to the plasma membrane. More than 80% of the labeling apposed to the plasma membrane is extrasynaptic. The remaining 20% is located at the edges of putative glutamatergic synapses or in the active zone of symmetric synapses. In mGluR5-, but not mGluR1a-immunostained sections, ∼70% of dopaminergic symmetric synapses are labeled perisynaptically. These data emphasize the differential pattern of subsynaptic localization of the two group I mGluRs and provide various presynaptic and postsynaptic sites whereby mGluR1 and mGluR5 could mediate different, but complementary, effects on glutamatergic and dopaminergic transmission in the primate striatum.
Five Faces of Trust: An Empirical Confirmation in Urban Elementary Schools

After an extensive review of the literature on trust, a multi-faceted definition of faculty trust was developed at three organizational levels: trust in principal, trust in colleagues, and trust in clients. Along with a general willingness to risk vulnerability, five faces of trust emerged: benevolence, reliability, competence, honesty, and openness. This conceptual formulation of faculty trust was then subjected to empirical test, which supported the theoretical underpinnings of the construct. Finally, three trust scales with substantial validity and reliability are offered to researchers and practitioners to analyze antecedents and consequences of faculty trust in other schools.
The Role of Data and Feedback Error in Inference and Prediction

Abstract : The present research investigates two forms of uncertainty, defined operationally as error in the data, at two places within the information flow between the person and the environment. The two kinds were measurement error and system failure error. The former involved adding a random variable to the data. The latter involved the sort of error which occurs when an environmental source of data gives information unrelated to the causal or predictive process under study. These forms of error were studied in the data and also in the feedback of subjects.
Women's Health Care Utilization among Harder-to-Reach HIV-Infected Women ever on Antiretroviral Therapy in British Columbia

Background. HIV-infected women are disproportionately burdened by gynaecological complications, psychological disorders, and certain sexually transmitted infections that may not be adequately addressed by HIV-specific care. We estimate the prevalence and covariates of women's health care (WHC) utilization among harder-to-reach, treatment-experienced HIV-infected women in British Columbia (BC), Canada. Methods. We used survey data from 231 HIV-infected, treatment-experienced women enrolled in the Longitudinal Investigations into Supportive and Ancillary Health Services (LISA) study, which recruited harder-to-reach populations, including aboriginal people and individuals using injection drugs. Independent covariates of interest included sociodemographic, psychosocial, behavioural, individual health status, structural factors, and HIV clinical variables. Logistic regression was used to generate adjusted estimates of associations between use of WHC and covariates of interest. Results. Overall, 77% of women reported regularly utilizing WHC. WHC utilization varied significantly by region of residence (P value <0.01). In addition, women with lower annual income (AOR (95% CI) = 0.14 (0.04–0.54)), who used illicit drugs (AOR (95% CI) = 0.42 (0.19–0.92)) and who had lower provider trust (AOR (95% CI) = 0.97 (0.95–0.99)), were significantly less likely to report using WHC. Conclusion. A health service gap exists along geographical and social axes for harder-to-reach HIV-infected women in BC. Women-centered WHC and HIV-specific care should be streamlined and integrated to better address women's holistic health.
A CONCEPTUAL NETWORK APPROACH TO STRUCTURING OF MEANINGS IN DESIGN

This paper proposes the viewpoint of design as a process of ‘structuring of meanings’. This is a framework which is directly related to the synthesis of concepts and to creativity during the early stages of design. In the presented approach three factors – Sum of Meanings, Relatedness by Path and Standard Deviation of Relatedness by Path – assessing meanings are established in connection with results of design. Furthermore, those assumptions are tested in a case study, resulting in a model of the influence of the proposed factors assessing meanings on the evaluation of design. The validity of this model supports the proposed framework. This understanding of the structuring process of meanings and the utilization of the proposed descriptive factors are important considerations towards further support of conceptual design.
Comparison of ciliary wave disorders measured by image analysis and electron microscopy

Conclusion We have developed a simple, reliable method for the simultaneous determination of the ciliary wave disorder (CWD) and ciliary beat frequency (CBF) of actively beating cilia. Objective The CBF and the directions of beating cilia are two important components of mucociliary transport. Although lots of studies have been performed on the measurement of the CBF, there have been few studies on the direction of cilia, with the exception of those using electron microscopy (EM). EM takes too long to determine the directions of cilia, and it cannot determine the direction of actively beating cilia. The aim of this study was to develop an image analysis (IA) system to conveniently determine the wave directions of multiple actively beating cilia as well as the CBF. Material and methods Sphenoid sinus mucosae obtained from 10 patients undergoing pituitary tumor removal via a trans-septal trans-sphenoidal approach were divided into two 4×4 mm2-sized pieces. One piece was studied using IA, the other with EM. Using IA, ciliary wave directions were determined from 5 20×20 μm2 regions of interest and the mean of 5 consecutive values was regarded as the CWD of each sample. The CBF was also measured. CWD was also measured using EM. Results The average number of cilia analyzed by EM was 102.50 (range 48–136). The mean CWDs determined using IA and EM were 28.25±4.84° and 23.59±8.16°, respectively. There was a significant correlation between the CWDs determined using these two methods (Spearman's correlation coefficient =0.648; p=0.043). The mean CBF of sphenoid mucosa was 10.50±2.20 Hz.
Estimating the density of Blainville's beaked whale (Mesoplodon densirostris) in the Tongue of the Ocean (TOTO) using passive acoustics

Techniques to detect and localize marine mammals including Blainville's beaked whales (Mesoplodon densirostris) using the bottom-mounted hydrophones of the Atlantic Undersea Test and Evaluation Center have been developed. A series of verification tests using these passive acoustics techniques to determine the presence and position of vocalizing animals are being conducted. These acoustic "sightings" are verified by a team of surface observers. Based on Woods Hole Oceanographic Institution tag data and the ongoing verification tests, vocalizations associated with M. densirostris appear to be distinct in type, frequency, and repetition rate. Group size estimates have been derived from these tests and from previous long-term observations. By acoustically mapping the distribution of animals and applying estimates of average group size an initial density estimate for M. densirostris is derived
Effect of a Novel Low‐Energy Pulsed‐Light Device for Home‐Use Hair Removal

BACKGROUND Removal of unwanted hair is the most popular skin treatment worldwide. Over the past decade, various lasers and light sources for epilation have been advocated for use in an office setting, although most people continue to treat unwanted hair with a variety of temporary physical methods (e.g., waxing, shaving) in a home setting, presumably due to cost and convenience factors. OBJECTIVES To evaluate the safety and efficacy of a low‐energy pulsed‐light device intended for home‐use hair removal. MATERIALS AND METHODS Twenty women (skin phototypes I‐IV) with dark terminal hair in nonfacial sites (axilla, forearms, inguinal region, legs) self‐administered three treatments at 2‐week intervals using a handheld intense‐pulsed‐light device. Matched untreated skin sites were also studied. Hair counts and clinical photographs were obtained pretreatment and at 1, 3, and 6 months after the third treatment. Side effects and patient satisfaction scores were recorded. RESULTS All patients showed a positive clinical response to treatment, with reduction of unwanted hair. No reduction of hair was noted in untreated matched areas. Hair counts were reduced 37.8% to 53.6% 6 months after the three treatments. Skin region influenced clinical response, with lower legs exhibiting greater hair reduction than arms and inguinal and axillary areas. Mild erythema was experienced in 25% of patients, but no other side effects or complications were encountered. Patient satisfaction scores were high, with all patients stating that they would purchase the device for future home use. CONCLUSIONS Low‐energy pulsed light can be applied safely and effectively for at‐home hair removal in a variety of nonfacial locations and skin phototypes I‐IV. The device was loaned by Home Skinovations. Dr. Alster purchased stock options after completion of the study.
Fish Oil for the Treatment of Cardiovascular Disease

Omega-3 fatty acids, which are found abundantly in fish oil, are increasingly being used in the management of cardiovascular disease. It is clear that fish oil, in clinically used doses (typically 4 g/d of eicosapentaenoic acid and docosahexaenoic acid) reduce high triglycerides. However, the role of omega-3 fatty acids in reducing mortality, sudden death, arrhythmias, myocardial infarction, and heart failure has not yet been established. This review will focus on the current clinical uses of fish oil and provide an update on their effects on triglycerides, coronary artery disease, heart failure, and arrhythmia. We will explore the dietary sources of fish oil as compared with drug therapy, and discuss the use of fish oil products in combination with other commonly used lipid-lowering agents. We will examine the underlying mechanism of fish oil's action on triglyceride reduction, plaque stability, and effect in diabetes, and review the newly discovered anti-inflammatory effects of fish oil. Finally, we will examine the limitations of current data and suggest recommendations for fish oil use.
Turning Over Turnover

This article applies the methodology of Bai and Ng (2002, 2004) for decomposing panel data into systematic and idiosyncratic components to both stock returns and turnover panels. This approach works well for both returns and turnover, despite the presence of severe heteroscedasticity and nonstationarity of individual stocks' turnover. We test the mutual fund separation model of Lo and Wang (2000). Trading due to systematic risk in returns can account for 66% of systematic turnover. Thus, portfolio rebalancing due to systematic risk is a very important motive for stock trading. Finally, several common turnover measures may understate the impact of stock trading.
New infrared detector on a silicon chip

We report a single-crystal Si-Ge structure which works as an efficient photodetector in the wavelength region of up to 1.5 µm. The multilevel structure is grown by molecular-beam epitaxy on an n-type 3-in silicon substrate and consists of the following layers: n+silicon (1000 Å), n+GexSi1 - xalloy (1800 Å, graded in ten steps fromx = 0tox = 1), n+germanium (1.25 µm), undoped germanium (2.0 µm), and p+germanium (2500 Å). Top three layers form a germanium p-i-n diode, which is removed from the Ge-Si interface by a buffer layer of high conductivity. An advantage of this structure is that its performance is insensitive to material defects in the buffer layers. Moreover, transmission electron microscopy shows that the density of dislocations introduced by lattice mismatch at the Ge-Si interface falls off with the separation from the interface. Our first experimental structures do exhibit the characteristics of a germanium p-i-n diode. The spectral response curves agree with those given in the literature for germanium, both at room and liquid nitrogen temperatures. For the incident light wavelength of 1.45 µm we have measured a quantum efficiency of 41 percent at T = 300 K. we believe that our approach opens an attractive possibility of fabricating complete infrared optoelectronic systems on a silicon chip.
Attempted suicide as an operant behavior.

In the light of the increased incidence of attempted suicide and the stress this imposes on medical resources, alternative approaches to management need to be considered. Where it can be established that the suicidal behavior has an operant component, management according to behavioral principles would appear relevant. The behavior of a 20-year-old woman who exhibited repeated suicidal behavior was managed within a ward program by means of operant principles. After 27 months of follow-up, there has been no recurrence for 18 months.
Loss Analysis of High Order Modes in Photonic Crystal Vertical-Cavity Surface-Emitting Lasers

A new technique for analyzing the loss of high order modes in photonic crystal VCSEL is reported. The technique proposed is a semi-empirical approach that uses comparison to experimental data. For that purpose, photonic crystal VCSEL devices of single mode and multi mode are fabricated and measured for device characteristics comparison. The fabricated devices are modeled using finite difference frequency domain technique for the purpose of investigating the photonic crystal guided modes and loss analysis. In order to verify the findings, full three dimensional analyses are performed based on the fabricated single mode and multi mode devices structures using common finite difference time domain technique. The results show close agreement between the computed and experiment findings, justifying the used of the proposed semi-empirical technique for analyzing the loss of high order modes in photonic crystal VCSEL. Results for guided modes and near- and far-field are also presented for the photonic crystal VCSEL.
On consensus of nonlinear multi-agent systems under directed interaction topologies

In a consensus problem, autonomous agents constituting a dynamical system communicate with one another to reach agreement on certain quantities of interest. By merging control theory and spectral graph theory, we generalize the previous consensus problems under nonlinear protocols for networks with undirected graphs to directed graphs. We prove that, when the nonlinear protocol is strictly increasing, consensus can be achieved if and only if the underlying directed interaction graph has a spanning tree. Numerical examples are taken to show the effectiveness of our theoretical results.