Miracle-dz/UniFAR-FTUs huggingface dataset:
Treatment with HC-070, a potent inhibitor of TRPC4 and TRPC5, leads to anxiolytic and antidepressant effects in mice

Background Forty million adults in the US suffer from anxiety disorders, making these the most common forms of mental illness. Transient receptor potential channel canonical subfamily (TRPC) members 4 and 5 are non-selective cation channels highly expressed in regions of the cortex and amygdala, areas thought to be important in regulating anxiety. Previous work with null mice suggests that inhibition of TRPC4 and TRPC5 may have anxiolytic effects. HC-070 in vitro To assess the potential of TRPC4/5 inhibitors as an avenue for treatment, we invented a highly potent, small molecule antagonist of TRPC4 and TRPC5 which we call HC-070. HC-070 inhibits recombinant TRPC4 and TRPC5 homomultimers in heterologous expression systems with nanomolar potency. It also inhibits TRPC1/5 and TRPC1/4 heteromultimers with similar potency and reduces responses evoked by cholecystokinin tetrapeptide (CCK-4) in the amygdala. The compound is >400-fold selective over a wide range of molecular targets including ion channels, receptors, and kinases. HC-070 in vivo Upon oral dosing in mice, HC-070 achieves exposure levels in the brain and plasma deemed sufficient to test behavioral activity. Treatment with HC-070 attenuates the anxiogenic effect of CCK-4 in the elevated plus maze (EPM). The compound recapitulates the phenotype observed in both null TRPC4 and TRPC5 mice in a standard EPM. Anxiolytic and anti-depressant effects of HC-070 are also observed in pharmacological in vivo tests including marble burying, tail suspension and forced swim. Furthermore, HC-070 ameliorates the increased fear memory induced by chronic social stress. A careful evaluation of the pharmacokinetic-pharmacodynamic relationship reveals that substantial efficacy is observed at unbound brain levels similar to, or even lower than, the 50% inhibitory concentration (IC50) recorded in vitro, increasing confidence that the observed effects are indeed mediated by TRPC4 and/or TRPC5 inhibition. Together, this experimental data set introduces a novel, high quality, small molecule antagonist of TRPC4 and TRPC5 containing channels and supports the targeting of TRPC4 and TRPC5 channels as a new mechanism of action for the treatment of psychiatric symptoms.
Reformulating Level Sets as Deep Recurrent Neural Network Approach to Semantic Segmentation

Variational Level Set (LS) has been a widely used method in medical segmentation. However, it is limited when dealing with multi-instance objects in the real world. In addition, its segmentation results are quite sensitive to initial settings and highly depend on the number of iterations. To address these issues and boost the classic variational LS methods to a new level of the learnable deep learning approaches, we propose a novel definition of contour evolution named <italic>Recurrent Level Set (RLS)</italic><xref ref-type="fn" rid="fn1"><sup>1</sup></xref> to employ Gated Recurrent Unit under the energy minimization of a variational LS functional. The curve deformation process in RLS is formed as a hidden state evolution procedure and updated by minimizing an energy functional composed of fitting forces and contour length. By sharing the convolutional features in a <italic>fully end-to-end trainable framework</italic>, we extend RLS to <italic>Contextual RLS (CRLS)</italic> to address semantic segmentation in the wild. The experimental results have shown that our proposed RLS improves both computational time and segmentation accuracy against the classic variational LS-based method whereas the fully end-to-end system CRLS achieves competitive performance compared to the state-of-the-art semantic segmentation approaches. <fn id="fn1"><label><sup>1</sup></label><p>Source codes will be publicly available. </p></fn>
Spatially Resolved Spectroscopy and Coronagraphic Imaging of the TW Hydrae Circumstellar Disk

We present the first spatially resolved spectrum of scattered light from the TW Hydrae protoplanetary disk. This nearly face-on disk is optically thick, surrounding a classical T Tauri star in the nearby 10 Myr old TW Hya association. The spectrum was taken with the Hubble Space Telescope (HST) STIS CCD, providing resolution R ~ 360 over the wavelength range 5250-10300 Å. Spatially resolved spectroscopy of circumstellar disks is difficult because of the high contrast ratio between the bright star and faint disk. Our novel observations provide optical spectra of scattered light from the disk between 40 and 155 AU from the star. The scattered light has the same color as the star (gray scattering) at all radii except the innermost region. This likely indicates that the scattering dust grains are larger than about 1 μm all the way out to large radii. From the spectroscopic data, we also obtained radial profiles of the integrated disk brightness at two position angles, over almost the same region as previously observed in HST WFPC2 and NICMOS coronagraphic images (35 to 173 AU from the star). The profiles have the same shape as the earlier ones, but show a small azimuthal asymmetry in the disk not previously noted. Our STIS broadband coronagraphic images of TW Hya confirm the reality of this asymmetry, and show that the disk surface brightness inside 140 AU has a sinusoidal dependence on azimuthal angle. The maximum brightness occurs at a position angle of 233. °6 ± 5. °7 east of north. This might be caused by the combination of forward scattering and an increase in inclination in the inner region of the disk, suggesting that the TW Hya disk has a warp like that seen in the β Pictoris debris disk.
Does training with traditionally presented and virtually simulated tasks elicit differing changes in object interaction kinematics in persons with upper extremity hemiparesis?

Abstract Objective: To contrast changes in clinical and kinematic measures of upper extremity movement in response to virtually simulated and traditionally presented rehabilitation interventions in persons with upper extremity hemiparesis due to chronic stroke. Design: Non-randomized controlled trial. Setting: Ambulatory research facility. Participants: Subjects were a volunteer sample of twenty one community-dwelling adults (mean age: 51 ± 12 years) with residual hemiparesis due to stroke more than 6 months before enrollment (mean: 74 ± 48 months), recruited at support groups. Partial range, against gravity shoulder movement and at least 10° of active finger extension were required for inclusion. All subjects completed the study without adverse events. Interventions: A 2 weeks, 24-hour program of robotic/virtually simulated, arm and finger rehabilitation activities was compared to the same dose of traditionally presented arm and finger activities. Results: Subjects in both groups demonstrated statistically significant improvements in the ability to interact with real-world objects as measured by the Wolf Motor Function Test (P = 0.01). The robotic/virtually simulated activity (VR) group but not the traditional, repetitive task practice (RTP) group demonstrated significant improvements in peak reaching velocity (P = 0.03) and finger extension excursion (P = 0.03). Both groups also demonstrated similar improvements in kinematic measures of reaching and grasping performance such as increased shoulder and elbow excursion along with decreased trunk excursion. Conclusions: Kinematic measurements identified differing adaptations to training that clinical measurements did not. These adaptations were targeted in the design of four of the six simulations performed by the simulated activity group. Finer grained measures may be necessary to accurately depict the relative benefits of dose matched motor interventions.
Internet-Based Cognitive Behavioral Therapy for Patients With Chronic Somatic Conditions: A Meta-Analytic Review

Background Patients with chronic somatic conditions face unique challenges accessing mental health care outside of their homes due to symptoms and physical limitations. Internet-based cognitive behavioral therapy (ICBT) has shown to be effective for various psychological conditions. The increasing number of recent trials need to be systematically evaluated and quantitatively analyzed to determine whether ICBT is also effective for chronic somatic conditions and to gain insight into the types of problems that could be targeted. Objective Our goal was to describe and evaluate the effectiveness of guided ICBT interventions for chronic somatic conditions on general psychological outcomes, disease-related physical outcomes, and disease-related impact on daily life outcomes. The role of treatment length was also examined. Methods PubMed, PsycINFO, and Embase were searched from inception until February 2012, by combining search terms indicative of effect studies, Internet, and cognitive behavioral therapy. Studies were included if they fulfilled the following six criteria: (1) randomized controlled trial, (2) Internet-based interventions, (3) based on cognitive behavioral therapy, (4) therapist-guided, (5) adult (≥18 years old) patients with an existing chronic somatic condition, and (6) published in English. 23 randomized controlled trials of guided ICBT were selected by 2 independent raters after reviewing 4848 abstracts. Demographic, clinical, and methodological variables were extracted. Standardized mean differences were calculated between intervention and control conditions for each outcome and pooled using random effects models when appropriate. Results Guided ICBT was shown to improve all outcome categories with small effect sizes for generic psychological outcomes (effect size range 0.17-0.21) and occasionally larger effects for disease-specific physical outcomes (effect size range 0.07 to 1.19) and disease-related impact outcomes (effect size range 0.17-1.11). Interventions with a longer treatment duration (>6 weeks) led to more consistent effects on depression. Conclusions Guided ICBT appears to be a promising and effective treatment for chronic somatic conditions to improve psychological and physical functioning and disease-related impact. The most consistent improvements were found for disease-specific outcomes, which supports the possible relevance of tailoring interventions to specific patient groups. Explorative analyses revealed that longer treatment length holds the promise of larger treatment effects for the specific outcome of depression. While the current meta-analysis focused on several chronic somatic conditions, future meta-analyses for separate chronic somatic conditions can further consolidate these results, also in terms of cost-effectiveness.
Differing roles of CD1d2 and CD1d1 proteins in type I natural killer T cell development and function

Significance Natural killer T (NKT) cells are selected by CD1d molecules in the thymus. Two homologous genes in the mouse genome encode for CD1d proteins. The two CD1d isoforms are not equivalent in their lipid antigen presentation capabilities, affecting the development and the T cell antigen receptor repertoire of NKT cells. MHC class I-like CD1 molecules have evolved to present lipid-based antigens to T cells. Differences in the antigen-binding clefts of the CD1 family members determine the conformation and size of the lipids that are presented, although the factors that shape CD1 diversity remain unclear. In mice, two homologous genes, CD1D1 and CD1D2, encode the CD1d protein, which is essential to the development and function of natural killer T (NKT) cells. However, it remains unclear whether both CD1d isoforms are equivalent in their antigen presentation capacity and functions. Here, we report that CD1d2 molecules are expressed in the thymus of some mouse strains, where they select functional type I NKT cells. Intriguingly, the T cell antigen receptor repertoire and phenotype of CD1d2-selected type I NKT cells in CD1D1−/− mice differed from CD1d1-selected type I NKT cells. The structures of CD1d2 in complex with endogenous lipids and a truncated acyl-chain analog of α-galactosylceramide revealed that its A′-pocket was restricted in size compared with CD1d1. Accordingly, CD1d2 molecules could not present glycolipid antigens with long acyl chains efficiently, favoring the presentation of short acyl chain antigens. These results indicate that the two CD1d molecules present different sets of self-antigen(s) in the mouse thymus, thereby impacting the development of invariant NKT cells.
Low-Crosstalk Simultaneous 16-Channel × 25 Gb/s Operation of High-Density Silicon Photonics Optical Transceiver

We successfully developed a high-density broadband 16-channel × 25 Gb/s on-package silicon photonics optical transceiver. The flip chip bonded bridge structure realized high density of about 363 Gb/s/cm2 . We demonstrated simultaneously on all 16 channels error-free operations with low crosstalk penalties of Tx-to-Tx 1.4 dB, Rx-to-Rx 1.4 dB, and Tx-to-Rx <0.1 dB.
Associations between retirement reasons, chronic pain, athletic identity, and depressive symptoms among former professional footballers

Abstract Background: Retirement from professional sport has been recognised as a major psychological stressor, and there is a need to identify factors that increase the risk of mental health problems after career termination. The current study examined associations between career-ending injury, chronic pain, athletic identity, and depressive symptomology in retired professional footballers. Methods: A cross-sectional study was performed with 307 retired male footballers who had played within a professional United Kingdom league. Participants completed measures of depressive symptoms (Short Depression-Happiness Scale), chronic pain (Pain Intensity Numerical Rating Scale), and athletic identity (Athletic Identity Measurement Scale), and reported their reasons for retirement. Results: A total of 48 participants (16%) met the cut-off score for possible cases of clinically relevant depression. These participants were more recently retired, and had higher athletic identity than those without depressive symptoms. Former players with depressive symptoms were more likely to cite injury as a retirement reason, and report higher levels of ongoing injury-related pain. Multivariate logistic regression revealed that the presence of depressive symptoms was independently associated with retirement through injury (OR = 3.44; 95% CI = 1.39, 8.51), higher pain levels (OR = 1.38; 95% CI = 1.02, 1.86), and increased athletic identity (OR = 1.28; 95% CI = 1.14, 1.44). Conclusions: Career-ending injury is strongly associated with higher odds of depressive symptomology during retirement, while experiencing chronic pain, and maintaining a high sense of athletic identity, are additional potential contributors.
Effects of maternal investment, temperament, and cognition on guide dog success

Significance A successful guide dog must navigate a complex world, avoid distractions, and respond adaptively to unpredictable events. What leads to success? We followed 98 puppies from birth to adulthood. Puppies were enrolled in a training program where only ∼70% achieved success as guide dogs. More intense mothering early in life was associated with program failure. In addition, mothers whose nursing style required greater effort by puppies produced more successful offspring. Among young adult dogs, poor problem-solving abilities, perseveration, and apparently greater anxiety when confronted with a novel object were also associated with program failure. Results mirror the results from rodents and humans, reaffirming the enduring effects on adult behavior of maternal style and individual differences in temperament and cognition. A continuing debate in studies of social development in both humans and other animals is the extent to which early life experiences affect adult behavior. Also unclear are the relative contributions of cognitive skills (“intelligence”) and temperament for successful outcomes. Guide dogs are particularly suited to research on these questions. To succeed as a guide dog, individuals must accomplish complex navigation and decision making without succumbing to distractions and unforeseen obstacles. Faced with these rigorous demands, only ∼70% of dogs that enter training ultimately achieve success. What predicts success as a guide dog? To address these questions, we followed 98 puppies from birth to adulthood. We found that high levels of overall maternal behavior were linked with a higher likelihood of program failure. Furthermore, mothers whose nursing style required greater effort by puppies were more likely to produce successful offspring, whereas mothers whose nursing style required less effort were more likely to produce offspring that failed. In young adults, an inability to solve a multistep task quickly, compounded with high levels of perseveration during the task, was associated with failure. Young adults that were released from the program also appeared more anxious, as indicated by a short latency to vocalize when faced with a novel object task. Our results suggest that both maternal nursing behavior and individual traits of cognition and temperament are associated with guide dog success.
Stock Photographs Do Not Comply With Infant Safe Sleep Guidelines

We evaluated images in popular stock photography websites for adherence with American Academy of Pediatrics (AAP) guidelines for safe infant sleep practices. Three top stock photo websites were used to collect photographs generated from key phrases. All images depicting an infant sleep environment were analyzed for consistency with AAP guidelines. Descriptive statistics, chi-square and z test of proportions, were conducted. A total of 1233 of 1947 stock photographs showed sleeping infants on a flat surface. In all, 627 (50.8%) photographs showed the infant in the supine position and 79 (5%) of all infant sleep environments were adherent with AAP recommendations. Bedding inconsistent with safe sleep recommendations was identified in 1133 images (71.3%), with blankets noted in 49.5%. Images depicting sleeping infants on stock photography sites do not routinely adhere to AAP recommendations. Media messages inconsistent with health care messages create confusion and misinformation about infant sleep safety and may lead inadvertently to unsafe practices.
Mechanical Properties of Cellulose Fibers Reinforced Thermoplastics

Cellulose fibers are selected as a reinforced filler for thermoplastics due to their superior mechanical properties and lower price compared to the thermoplastics. In the present study chemithermomechanical pulp of hard wood (aspen) fibers having selected aspect ratio (length/diameter) were first encapsulated with polystyrene and then mixed with polystyrene polymer at various concentrations. Mechanical properties were measured on compression molded samples containing between 10 and 40 weight percent of cellulose fibers. Experimental results show a signifi cant increase in tensile stress and modulus with fiber concentration. Using the constituent properties, an efficiency factor of stress transfer between fiber and polymer matrix was calculated and was shown to be constant for the various fiber concentrations. Theoretical predictions of tensile stress and modulus using the basic composite theory have been made. Large differences between experimental results and theoretical predictions have been observed and will be discussed in terms of fiber orientation and fiber aspect ratio.
Early Numerical Studies on the Peristaltic Flow through the Pharynx

The flow through the pharynx from the GPJ to the UES has been numerically investigated with a non-Newtonian fluid obeying the power law with similar rheological indices to a contrast medium used in videofluroscopy. Flow fields revealed the occurrence of reflux regions in the beginning, being this effect stronger at low entrance pressure, which could be related to abnormal swallowing. As a consequence, the bolus travels preferably along the walls. It has been also observed that the bolus head travels faster than the bolus tail, which indicates that the bolus is elongated. Results from this work can be further used for a rheological characterization of oral nutritional supplements for patients suffering from swallowing disorders. Practical Applications The flow through the pharynx has been numerically investigated with a non-Newtonian fluid to get insight about causes leading to abnormal swallowing. Reflux has been observed in the beginning as result of a central stream and two symmetric loops generated along the walls, being this effect at low peristaltic pressure. Velocity fields revealed that the bolus head travels faster than the bolus tail, which is a result of the geometry and conservation of mass. Under these conditions, extensional stresses are generated by the flexion of the pharynx walls. Shear rate fields allowed establishing the shear rate range at which the bolus is subjected along the pharynx, which is useful for the rheological characterization of supplements for patients suffering from swallowing disorders.
Effect of sample preparation techniques on the concentrations and distributions of elements in biological tissues using µSRXRF: a comparative study

Routine tissue sample preparation using chemical fixatives is known to preserve the morphology of the tissue being studied. A competitive method, cryofixation followed by freeze drying, involves no chemical agents and maintains the biological function of the tissue. The possible effects of both sample preparation techniques in terms of the distribution of bio-metals (calcium (Ca), copper (Cu) zinc (Zn), and iron (Fe) specifically) in human skin tissue samples was investigated. Micro synchrotron radiation x-ray fluorescence (μSRXRF) was used to map bio-metal distribution in epidermal and dermal layers of human skin samples from various locations of the body that have been prepared using both techniques. For Ca, Cu and Zn, there were statistically significant differences between the epidermis and dermis using the freeze drying technique (p = 0.02, p < 0.01, and p < 0.01, respectively). Also using the formalin fixed, paraffin embedded technique the levels of Ca, Cu and Zn, were significantly different between the epidermis and dermis layers (p = 0.03, p < 0.01, and p < 0.01, respectively). However, the difference in levels of Fe between the epidermis and dermis was unclear and further analysis was required. The epidermis was further divided into two sub-layers, one mainly composed of the stratum corneum and the other deeper layer, the stratum basale. It was found that the difference between the distribution of Fe in the two epidermal layers using the freeze drying technique resulted in a statistically significant difference (p = 0.012). This same region also showed a difference in Fe using the formalin fixed, paraffin embedded technique (p < 0.01). The formalin fixed, paraffin embedded technique also showed a difference between the deeper epidermal layer and the dermis (p < 0.01). It can be concluded that studies involving Ca, Cu and Zn might show similar results using both sample preparation techniques, however studies involving Fe would need more special attention.