Miracle-dz/UniFAR-FTUs huggingface dataset:
TRPC1‐ and TRPC3‐dependent Ca2+ signaling in mouse cortical astrocytes affects injury‐evoked astrogliosis in vivo

Following brain injury astrocytes change into a reactive state, proliferate and grow into the site of lesion, a process called astrogliosis, initiated and regulated by changes in cytoplasmic Ca2+. Transient receptor potential canonical (TRPC) channels may contribute to Ca2+ influx but their presence and possible function in astrocytes is not known. By RT‐PCR and RNA sequencing we identified transcripts of Trpc1, Trpc2, Trpc3, and Trpc4 in FACS‐sorted glutamate aspartate transporter (GLAST)‐positive cultured mouse cortical astrocytes and subcloned full‐length Trpc1 and Trpc3 cDNAs from these cells. Ca2+ entry in cortical astrocytes depended on TRPC3 and was increased in the absence of Trpc1. After co‐expression of Trpc1 and Trpc3 in HEK‐293 cells both proteins co‐immunoprecipitate and form functional heteromeric channels, with TRPC1 reducing TRPC3 activity. In vitro, lack of Trpc3 reduced astrocyte proliferation and migration whereas the TRPC3 gain‐of‐function moonwalker mutation and Trpc1 deficiency increased astrocyte migration. In vivo, astrogliosis and cortex edema following stab wound injury were reduced in Trpc3‐/‐ but increased in Trpc1‐/‐ mice. In summary, our results show a decisive contribution of TRPC3 to astrocyte Ca2+ signaling, which is even augmented in the absence of Trpc1, in particular following brain injury. Targeted therapies to reduce TRPC3 channel activity in astrocytes might therefore be beneficial in traumatic brain injury.
The effects of a simulated occupational kneeling exposure on squat mechanics and knee joint load during gait

Abstract Occupational kneeling is associated with an increased risk for tibiofemoral knee osteoarthritis. Forces on the knee in the kneeling posture, as well as the greater incidence of meniscus tears among workers, likely contribute to the increased risk. We hypothesise that an additional mechanism may contribute – altered neuromuscular control due to prolonged high knee flexion. Forty participants (20 male, 20 female) completed an evaluation of gait and squatting before, immediately following, and 30 min following a 30 min simulated occupational kneeling exposure. An increase in the peak external knee adduction moment and a delay in vastus medialis activation onset during walking were observed post-kneeling, as well as increased frontal plane knee motion during squatting. This was the first investigation to find changes in high flexion transitions as a result of kneeling. Greater frontal plane knee motion may increase the risk for meniscal tears, and subsequently, knee osteoarthritis. Practitioner Summary: A 30 min simulated occupational kneeling exposure resulted in small but significant gait changes. The greatest effect was on frontal plane knee movement during squatting, which is especially relevant to occupations requiring frequent kneeling/squatting. This increased motion may indicate an increased risk of injury, which supports a link to knee osteoarthritis.
[POSTER] AirGestAR: Leveraging Deep Learning for Complex Hand Gestural Interaction with Frugal AR Devices

Hand gestures provide a natural and an intuitive way of user interaction in AR/VR applications. However, the most popular and commercially available devices such as the Google Cardboard and Wearality1 still employ only primitive modes of interaction such as the magnetic trigger, conductive lever and have limited user-input capability. The truly instinctual gestures work only with inordinately priced devices such as the Hololens, Magic Leap, and Meta Glasses2 which use proprietary hardware and are still not commercially available. In this paper, we explore the possibility of leveraging deep learning for recognizing complex 3-dimensional marker-less gestures (Bloom, Click, Zoom-In, Zoom-Out) in real-time using monocular camera input from a single smartphone. This framework can be used with frugal smartphones to build powerful AR/VR systems for large scale deployments that work in real-time, eliminating the need for specialized hardware. We have created a hand gesture dataset to train LSTM networks for gesture classification and published the same online. We also demonstrate the performance of our proposed method in terms of classification accuracy and computational time.
Handling incomplete smoking history data in survival analysis

While data are unavoidably missing or incomplete in most observational studies, consequences of mishandling such incompleteness in analysis are often overlooked. When time-varying information is collected irregularly and infrequently over a long period, even precisely obtained data may implicitly involve substantial incompleteness. Motivated by an analysis to quantitatively evaluate the effects of smoking and radiation on lung cancer risks among Japanese atomic-bomb survivors, we provide a unique application of multiple imputation to incompletely observed smoking histories under the assumption of missing at random. Predicting missing values for the age of smoking initiation and, given initiation, smoking intensity and cessation age, analyses can be based on complete, though partially imputed, smoking histories. A simulation study shows that multiple imputation appropriately conditioned on the outcome and other relevant variables can produce consistent estimates when data are missing at random. Our approach is particularly appealing in large cohort studies where a considerable amount of time-varying information is incomplete under a mechanism depending in a complex manner on other variables. In application to the motivating example, this approach is expected to reduce estimation bias that might be unavoidable in naive analyses, while keeping efficiency by retaining known information.
Evaluation of Ultra Violet Emissions Radiated from Compact Fluorescent Lamps of Iranian Current Brands

Background: Compact fluorescent lamp (CFL) is a developed fluorescent lamp type designed to saving energy. CFLs can cause an increased health risk to humans due to the ultraviolet radiation. Objectives: The current study aimed to assess the ultraviolet radiation emitted from compact fluorescent lamps in highly used Iranian brands. Materials and Methods: This experimental study was conducted on 16 CFLs that were manufactured by four Iranian manufacturers including: Pars Khazar, Parmis, Etehad and Nama Noor. The CFLs were marked as 11, 18, 40 and 60 Watt. Measurement was done in 10, 25, 50, 100, 150 and 200 cm in three angles including 0°, 45° and 90° using a calibrated UV-meter. All the CFLs are aged for one hundred hours in the laboratory. The information was analyzed using SPSS-20 and ANOVA test. Results: Measurement of UV showed that UVC emission was not observed at the distance of 10 cm in all of CFLs lamps. UVB irradiance in most of lamps in 10 and 25 cm was more than occupational exposure limits (OEL), but in 50 cm was less than OEL. One way ANOVA indicated that differences between UVB irradiance of four brands of lamps were not significant statistically (P > 0.05). UVA irradiance of all CFLs lamps in 25 cm was less than OEL. One way ANOVA indicated that differences between UVA statistically were not significant (P > 0.05). Conclusions: Based on the results of this study, authors recommended that CFLs lamps, due to UV radiation, especially in UVB span, be used at distances greater than 25 cm.Compact Fluorescent Lamp (CFL) is a developed fluorescent lamp type designed for saving energy. CFLs can cause the health risk increase in humans due to the ultraviolet radiation.
Inhibition of HIV-1 Maturation via Small-Molecule Targeting of the Amino-Terminal Domain in the Viral Capsid Protein

ABSTRACT The human immunodeficiency virus type 1 (HIV-1) capsid protein is an attractive therapeutic target, owing to its multifunctionality in virus replication and the high fitness cost of amino acid substitutions in capsids to HIV-1 infectivity. To date, small-molecule inhibitors have been identified that inhibit HIV-1 capsid assembly and/or impair its function in target cells. Here, we describe the mechanism of action of the previously reported capsid-targeting HIV-1 inhibitor, Boehringer-Ingelheim compound 1 (C1). We show that C1 acts during HIV-1 maturation to prevent assembly of a mature viral capsid. However, unlike the maturation inhibitor bevirimat, C1 did not significantly affect the kinetics or fidelity of Gag processing. HIV-1 particles produced in the presence of C1 contained unstable capsids that lacked associated electron density and exhibited impairments in early postentry stages of infection, most notably reverse transcription. C1 inhibited assembly of recombinant HIV-1 CA in vitro and induced aberrant cross-links in mutant HIV-1 particles capable of spontaneous intersubunit disulfide bonds at the interhexamer interface in the capsid lattice. Resistance to C1 was conferred by a single amino acid substitution within the compound-binding site in the N-terminal domain of the CA protein. Our results demonstrate that the binding site for C1 represents a new pharmacological vulnerability in the capsid assembly stage of the HIV-1 life cycle. IMPORTANCE The HIV-1 capsid protein is an attractive but unexploited target for clinical drug development. Prior studies have identified HIV-1 capsid-targeting compounds that display different mechanisms of action, which in part reflects the requirement for capsid function at both the efferent and afferent phases of viral replication. Here, we show that one such compound, compound 1, interferes with assembly of the conical viral capsid during virion maturation and results in perturbations at a specific protein-protein interface in the capsid lattice. We also identify and characterize a mutation in the capsid protein that confers resistance to the inhibitor. This study reveals a novel mechanism by which a capsid-targeting small molecule can inhibit HIV-1 replication.
[POSTER] CoVAR: Mixed-Platform Remote Collaborative Augmented and Virtual Realities System with Shared Collaboration Cues

We present CoVAR, a novel Virtual Reality (VR) and Augmented Reality (AR) system for remote collaboration. It supports collaboration between AR and VR users by sharing a 3D reconstruction of the AR user's environment. To enhance this mixed platform collaboration, it provides natural inputs such as eye-gaze and hand gestures, remote embodiment through avatar's head and hands, and awareness cues of field-of-view and gaze cue. In this paper, we describe the system architecture, setup and calibration procedures, input methods and interaction, and collaboration enhancement features.
Accelerating Big Data Infrastructure and Applications (Ongoing Collaboration)

High-performance computing (HPC) systems are increasingly being used for data-intensive, or "Big Data", workloads. However, since traditional HPC workloads are compute-intensive, the HPC-Big Data convergence has created many challenges with optimizing data movement and processing on modern supercomputers. Our collaborative work addresses these challenges using a three-pronged approach: (i) measuring and modeling extreme-scale I/O workloads, (ii) designing a low-latency, scalable, on-demand burst-buffer solution, and (iii) optimizing graph algorithms for processing Big Data workloads. We describe the three areas of our collaboration and report on their respective developments.
Retracted: Anti‐inflammatory properties of tianeptine on lipopolysaccharide‐induced changes in microglial cells involve toll‐like receptor‐related pathways

Accumulating evidence suggests that activation of microglia plays a key role in the pathogenesis of depression. Activated microglia produce a wide range of factors whose prolonged or excessive release may lead to brain disorders. Thus, the inhibition of microglial cells may be beneficial in the treatment of depressive diseases. Tianeptine is an atypical antidepressant drug with proven clinical efficacy, but its mechanism of action remains still not fully understood. In the present study, using microglial cultures we investigated whether tianeptine modifies microglial activation after lipopolysaccharide (LPS) stimulation and which intracellular pathways are involved in the activity of this antidepressant. Our study shows that tianeptine attenuated the LPS‐evoked inflammatory activation of microglia by decreasing the expression of proinflammatory cytokines such as IL‐1β, IL‐18, IL‐6 and tumor necrosis factor α (TNF‐α), the release of nitric oxide (NO) and reactive oxygen species (ROS) as well as the expression of inducible nitric oxide synthase. Analyses of signaling pathways demonstrate that tianeptine led to the suppression of LPS‐induced TLR4 expression and ERK1/2 phosphorylation. Furthermore, our study reveals the inhibitory impact of tianeptine on caspase‐3‐induced PKCδ degradation and consequently on the activation of NF‐κB factor in microglial cells. Taken together, present results show anti‐inflammatory properties of tianeptine in microglial cultures stimulated by LPS. This study provides evidence that the inhibition of microglial activation may underlie the therapeutic activity of tianeptine.
Viral myocarditis: a prime example for endomyocardial biopsy-guided diagnosis and therapy

Purpose of review Myocarditis is an inflammatory disease of the cardiac muscle mainly caused by viral infection. Due to the diverse clinical presentation of myocarditis, accurate diagnosis demands simultaneous histologic, immunohistochemical and molecular biological workup of endomyocardial biopsies (EMBs) as defined by the position statement of the Working Group on Myocardial and Pericardial Diseases of the European Society of Cardiology on myocarditis. Recent findings Endomyocardial biopsy-based analysis of viral transcriptional activity, mRNA expression, epigenetics and region-specific protein expression analysis via imaging mass spectrometry have led to the identification of novel potential diagnostic criteria, markers with prognostic value and therapeutic targets for the treatment of viral myocarditis, opening new avenues for novel therapies, including cell therapies, as well as the use of established treatment options, be it from other indications. Summary Under certain clinical scenarios EMB-based analysis is required to come to a tailored individualized therapy that improves symptoms and prognosis of patients with acute and chronic viral-driven cardiac inflammation.
Use of Synthetic Hybrid Strains To Determine the Role of Replicon 3 in Virulence of the Burkholderia cepacia Complex

ABSTRACT The Burkholderia cepacia complex (Bcc) displays a wealth of metabolic diversity with great biotechnological potential, but the utilization of these bacteria is limited by their opportunistic pathogenicity to humans. The third replicon of the Bcc, megaplasmid pC3 (0.5 to 1.4 Mb, previously chromosome 3), is important for various phenotypes, including virulence, antifungal, and proteolytic activities and the utilization of certain substrates. Approximately half of plasmid pC3 is well conserved throughout sequenced Bcc members, while the other half is not. To better locate the regions responsible for the key phenotypes, pC3 mutant derivatives of Burkholderia cenocepacia H111 carrying large deletions (up to 0.58 Mb) were constructed with the aid of the FLP-FRT (FRT, flippase recognition target) recombination system from Saccharomyces cerevisiae. The conserved region was shown to confer near-full virulence in both Caenorhabditis elegans and Galleria mellonella infection models. Antifungal activity was unexpectedly independent of the part of pC3 bearing a previously identified antifungal gene cluster, while proteolytic activity was dependent on the nonconserved part of pC3, which encodes the ZmpA protease. To investigate to what degree pC3-encoded functions are dependent on chromosomally encoded functions, we transferred pC3 from Burkholderia cenocepacia K56-2 and Burkholderia lata 383 into other pC3-cured Bcc members. We found that although pC3 is highly important for virulence, it was the genetic background of the recipient that determined the pathogenicity level of the hybrid strain. Furthermore, we found that important phenotypes, such as antifungal activity, proteolytic activity, and some substrate utilization capabilities, can be transferred between Bcc members using pC3. IMPORTANCE The Burkholderia cepacia complex (Bcc) is a group of closely related bacteria with great biotechnological potential. Some strains produce potent antifungal compounds and can promote plant growth or degrade environmental pollutants. However, their agricultural potential is limited by their opportunistic pathogenicity, particularly for cystic fibrosis patients. Despite much study, their virulence remains poorly understood. The third replicon, pC3, which is present in all Bcc isolates and is important for pathogenicity, stress resistance, and the production of antifungal compounds, has recently been reclassified from a chromosome to a megaplasmid. In this study, we identified regions on pC3 important for virulence and antifungal activity and investigated the role of the chromosomal background for the function of pC3 by exchanging the megaplasmid between different Bcc members. Our results may open a new avenue for the construction of antifungal but nonpathogenic Burkholderia hybrids. Such strains may have great potential as biocontrol strains for protecting fungus-borne diseases of plant crops.
Exploring Patients’ Experiences of Eating Disorder Treatment Services From a Motivational Perspective

This study employed qualitative methods to explore eating disorder (ED) patients’ perspectives on their treatment experiences to gain insight into those factors that influenced their motivational trajectory. Semistructured interviews were conducted with a purposive female sample of current (N = 11) and discharged (N = 3) ED service users, aged 18 to 31 years (M = 23.21, SD = 4.19). An interpretive thematic analytic approach, comprising both inductive and deductive methods of analysis, was employed to identify key themes in the data. Self-determination theory (SDT) provided a conceptual lens for analyzing data. Participants highlighted that factors such as physical design and nature of the treatment environment, relational aspects of care, and therapeutic methods all played a role in treatment engagement. The findings highlight ways in which current ED services might more effectively meet the needs of service users and support the utility of applying SDT to the study of motivational dynamics in the treatment of EDs.
Composition and microstructural evolution of nonsuperconducting phases in silver-clad (Bi,Pb)_2Sr_2Ca_2Cu_3O_x composite conductors

The composition and microstructural evolution of nonsuperconducting phases during the course of formation of (Bi,Pb)_2Sr_2Ca_2Cu_3O_ x (Bi-2223) in a silver sheath have been investigated by x-ray diffraction (XRD) analysis, scanning electron microscopy (SEM), energy dispersive x-ray spectroscopy (EDX), and digital image analysis. Wire samples fabricated by the oxide-powder-in-tube technique were heat-treated under a variety of conditions (time, temperature, and oxygen pressure). Backscattered images taken on polished but unetched transverse cross sections were subjected to computerized image processing, which allowed determination of the stoichiometry and quantification of microstructural characteristics (such as area fraction, size distribution, position, and orientation) of each nonsuperconducting particle. The dominant nonsuperconducting phases observed by SEM/EDX were CuO, (Ca,Sr)_2CuO_3 (2/1), and (Ca, Sr)_14Cu_24O_41 (14/24) in amounts that varied depending on the annealing temperature, time, and oxygen partial pressure. Time evolution studies performed at 825 °C in 0.075 atm O_2 showed that the area fraction of 2/1 decreased with reaction time, while that for 14/24 increased. In all cases, a substantial amount (>10% area fraction) of nonsuperconducting phases was detected even after all the Bi_2Sr_2CaCu_2O_ y (Bi-2212) in the as-rolled composite conductor was fully converted to Bi-2223, as determined by XRD. High aspect ratio nonsuperconducting particles were initially randomly oriented in the composite conductor core but gradually aligned parallel to the silver/(Bi,Pb)-Sr-Ca-Cu-O interface after extended annealing. They tended to segregate and exhibited a much broader size distribution when processing was carried out at temperatures and oxygen partial pressures on the high end of the normal processing range, most likely as a result of the occurrence of partial melting in the system.
Microsensor and transcriptomic signatures of oxygen depletion in biofilms associated with chronic wounds

Biofilms have been implicated in delayed wound healing, although the mechanisms by which biofilms impair wound healing are poorly understood. Many species of bacteria produce exotoxins and exoenzymes that may inhibit healing. In addition, oxygen consumption by biofilms and by the responding leukocytes, may impede wound healing by depleting the oxygen that is required for healing. In this study, oxygen microsensors to measure oxygen transects through in vitro cultured biofilms, biofilms formed in vivo within scabs from a diabetic (db/db) mouse wound model, and ex vivo human chronic wound specimens was used. The results showed that oxygen levels within mouse scabs had steep gradients that reached minima ranging from 17 to 72 mmHg on live mice and from 6.4 to 1.1 mmHg on euthanized mice. The oxygen gradients in the mouse scabs were similar to those observed for clinical isolates cultured in vitro and for human ex vivo specimens. To characterize the metabolic activities of the bacteria in the mouse scabs, transcriptomics analyses of Pseudomonas aeruginosa biofilms associated with the db/db mice wounds was performed. The results demonstrated that the bacteria expressed genes for metabolic activities associated with cell growth. Interestingly, the transcriptome results also indicated that the bacteria within the wounds experienced oxygen‐limitation stress. Among the bacterial genes that were expressed in vivo were genes associated with the Anr‐mediated hypoxia‐stress response. Other bacterial stress response genes highly expressed in vivo were genes associated with stationary‐phase growth, osmotic stress, and RpoH‐mediated heat shock stress. Overall, the results supported the hypothesis that bacterial biofilms in chronic wounds promote chronicity by contributing to the maintenance of localized low oxygen tensions, through their metabolic activities and through their recruitment of cells that consume oxygen for host defensive processes.
Lateral Thinking for Trustworthy Apps

The growing computerization of critical infrastructure as well as the pervasiveness of computing in everyday life has led to increased interest in secure application development. We observe a flurry of new security technologies like ARM TrustZone and Intel SGX, but a lack of a corresponding architectural vision. We are convinced that point solutions are not sufficient to address the overall challenge of secure system design. In this paper, we outline our take on a trusted component ecosystem of small individual building blocks with strong isolation. In our view, applications should no longer be designed as massive stacks of vertically layered frameworks, but instead as horizontal aggregates of mutually isolated components that collaborate across machine boundaries to provide a service. Lateral thinking is needed to make secure systems going forward.