Miracle-dz/UniFAR-FTUs huggingface dataset:
Expression and purification of a functional heteromeric GABAA receptor for structural studies

The multi-subunit GABA-gated chloride channels of the Cys-loop receptor family, known as GABAA receptors, function as the primary gatekeepers of fast inhibitory neurotransmission in the central nervous system. In addition to their role in controlling synaptic tone, these receptors are the targets of a vast array of therapeutic compounds that potentiate channel gating. Importantly, functional activity and pharmacological efficacy of GABAA receptors is coupled directly to the subunit composition. However, the absence of high resolution structural information precludes an explicit determination of the molecular mechanism of ligand binding to ion channel gating and modulation. Efforts to obtain this data are hindered largely by the lack of heterologous expression and purification protocols for high expressing receptor constructs. To address this issue, we describe a unique approach to identify bona fide functional GABAA receptor subunit combinations by using the Xenopus oocyte as an expression host in combination with fluorescence detection size exclusion chromatography. The results demonstrate that formation of a defined pentameric species is dependent on subunit composition. Furthermore, receptor subunits can tolerate large truncations in non-conserved M3/M4 cytoplasmic loop, although removal of N-linked glycosylation sites is negatively correlated with expression level. Additionally, we report methods to improve GABAA receptor expression in mammalian cell culture that employ recombinant baculovirus transduction. From these methods we have identified a well-behaving minimal functional construct for the α1/β1 GABAA receptor subtype that can be purified in milligram quantities while retaining high affinity agonist binding activity.
3D Non-Stationary GBSMs for High-Speed Train Tunnel Channels

This paper proposes 3D non-stationary multipleinput multiple-output (MIMO) geometry-based stochastic models (GBSMs) for high-speed train (HST) tunnel channels. Considering the line-of-sight (LoS), single-bounced (SB), and double-bounced (DB) components from the geometrical tunnel scattering model, a reference HST tunnel channel model under the assumption that scatterers are uniformly distributed on the tunnel walls is first derived. Then, by using the modified method of equal areas (MMEA), the corresponding simulation model is developed. Based on the proposed tunnel channel models, the correlation properties in time and space domains are investigated. A good agreement of statistical properties between the reference model and simulation model can be obtained. Furthermore, the simulation results show that the proposed model can be applied to mimic the nonstationarity of HST tunnel channels.
Novel Magnetic Burn-In for Retention and Magnetic Tolerance Testing of STTRAM

Spin-transfer torque RAM (STTRAM) is considered as one of the most promising candidates among the emerging memory technologies. However, it brings new test challenges such as characterizing retention time and magnetic tolerance. STTRAM retention time needs to range from few seconds to years depending on its application. This is further aggravated by a significant shift in retention time under static (process variation) and dynamic (voltage, temperature fluctuation) variations. Conventional test-flows lack the capability to characterize STTRAM retention time while maintaining a reasonable test time. We propose the magnetic burn-in (MBI) test, which can be incorporated in the existing test flow with minimal changes to enable STTRAM retention testing with shorter test times (<inline-formula> <tex-math notation="LaTeX">$3.71\times 10^{{^{13}}}\text{X}$ </tex-math></inline-formula> reduction with 220 Oe at 25 °C). MBI is also combined with standard thermal burn-in (MBI+BI) for further compression of retention time and test time (<inline-formula> <tex-math notation="LaTeX">$1.97\times 10^{^{14}}\text{X}$ </tex-math></inline-formula> reduction with 220 Oe at 125 °C). We also propose MBI to certify the magnetic tolerance of STTRAM bits during write/read/retention modes with minimal changes in the existing test flow. For the STTRAM employed in this paper, we have found 86, 370, and 319 Oe to be the write, the read, and the retention tolerance, respectively.
Enhanced Handover Signaling through Integrated MME-SDN Controller Solution

The future wireless networks are expected to be extremely dense and heterogeneous, with the users experiencing multi-connectivity through the multiple available radio access technologies (RATs). These prevalent characteristics, along with the strict QoS requirements, renders the handover (HO) process optimization as a critical objective for future networks. Along side the evolving network characteristics and methodologies, an evolving network architecture needs to be considered as well. Such evolution should not only facilitate HO process enhancement, i.e., reduction in HO delay and signaling, but it should also allow for a smooth transition from current to future wireless networks. Hence, in this work we firstly present an evolutionary core network entity called the Integrated MME-SDN Controller and the associated network architecture. The proposed architecture provides a migratory path for the existing 3GPP cellular architectures towards the 5G networks. Next, we discuss the benefits and challenges of such an architectural approach, with one of the benefits being a manageable CAPEX for the network operators through its transitional nature. Subsequently, utilizing the aforementioned proposed architecture, we present the handover process enhancement for the current 3GPP defined HO processes. We quantify the improvements achieved in terms of latency, transmission and processing cost for the different 3GPP HO processes. We also show that the proposed HO mechanism leads to a significant reduction in latency and signaling for certain types of HOs which, as a consequence, will critically benefit any dense and heterogeneous wireless system, such as 5G.
Thermal Expansion Investigation of Liquid Cold Plate with Varying Ambient Temperature at Storage

Depending on the heat flux increment in recent two decades, liquid cooling techniques in thermal management became one of the most preferred choices for electronics cooling technique, especially in military applications. As the complexity and numbers of cold plate increase, it necessitates examining the design of cold plate in details to prevent catastrophic failures both during operation and storage. In liquid cooling applications, there are many precautions taken to prevent mechanical failures caused by liquid thermal expansion. It is well known that liquids cannot be compressed or very small compression can take place due to their nature. In thermal expansion problems, there is an interaction between stagnant fluid and solid. They expand together because of increase in temperature. As a result, hydrostatic pressure increases due to thermal expansion of trapped liquid even at small temperature increment. Therefore, in liquid cooling applications, one of the easiest measures is the usage of relief valves to release excess pressure to protect the system or design from overpressure. In this study, one cold plate has been selected as a case study to investigate the behavior of cold plate in terms of hydrostatic pressure and stress variation depending on the alternating ambient temperature. In addition, before performing tests, FEM structural analysis has been carried out to design the experiment. Finally, hydrostatic pressure values exerted by trapped liquid have been measured at different locations depending on the temperature.
BMI control of a third arm for multitasking

A brain-machine interface allowed participants to do a task with a robotic arm while performing a different task with their own arms. Brain-machine interface (BMI) systems have been widely studied to allow people with motor paralysis conditions to control assistive robotic devices that replace or recover lost function but not to extend the capabilities of healthy users. We report an experiment in which healthy participants were able to extend their capabilities by using a noninvasive BMI to control a human-like robotic arm and achieve multitasking. Experimental results demonstrate that participants were able to reliably control the robotic arm with the BMI to perform a goal-oriented task while simultaneously using their own arms to do a different task. This outcome opens possibilities to explore future human body augmentation applications for healthy people that not only enhance their capability to perform a particular task but also extend their physical capabilities to perform multiple tasks simultaneously.
Oxybenzone Alters Mammary Gland Morphology in Mice Exposed During Pregnancy and Lactation

Abstract Hormones and endocrine-disrupting chemicals are generally thought to have permanent “organizational” effects when exposures occur during development but not adulthood. Yet, an increasing number of studies have shown that pregnant females are disrupted by endocrine-disrupting chemical exposures, with some effects that are permanent. Here, we examined the long-term effects of exposure to oxybenzone, an estrogenic chemical found in sunscreen and personal care products, on the morphology of the mammary gland in mice exposed during pregnancy and lactation. Female mice were exposed to vehicle or 30, 212, or 3000 µg oxybenzone/kg/d, from pregnancy day 0 until weaning. A nulliparous group, receiving vehicle treatment, was also evaluated. Mammary glands were collected 5 weeks after involution for whole-mount, histological, immunohistochemical, and molecular analyses. Exposure to 3000 µg oxybenzone/kg/d induced permanent changes to ductal density that was significantly different from both the nulliparous and vehicle groups. The two highest doses of oxybenzone similarly induced an intermediate phenotype for expression of progesterone receptor. A monotonic, dose-dependent increase in cell proliferation was also observed in the oxybenzone-treated females, becoming statistically significant at the highest dose. Finally, oxybenzone exposure induced an intermediate phenotype for Esr1 expression in all oxybenzone-treated groups. These data suggest that oxybenzone, at doses relevant to human exposures, produces long-lasting alterations to mammary gland morphology and function. Further studies are needed to determine if exposure to this chemical during pregnancy and lactation will interfere with the known protection that pregnancy provides against breast cancer.
Predicting and Understanding Unexpected Respiratory Decompensation in Critical Care Using Sparse and Heterogeneous Clinical Data

Hospital intensive care units (ICUs) care for severely ill patients, many of whom require some form of organ support. Clinicians in ICUs are often challenged with integrating large volumes of continuously recorded physiological and clinical data in order to diagnose and treat patients. In this work, we focus on developing interpretable models for predicting unexpected respiratory decompensation requiring intubation in ICU patients. Predicting need for intubation could have important implications for the patient and medical staff and potentially enable timely interventions for improved patient outcome. Using data from adult ICU patients from the Medical Information Mart for Intensive Care (MIMIC)-III database, we developed gradient boosting models for predicting intubation onset. In a cohort of 12,470 patients, of whom 1,067 were intubated (8.55%), we achieved an area under the receiver operating characteristic curve (AUROC) of 0.89, with 95% confidence interval (CI) 0.87 - 0.91, when predicting intubation 3 hours ahead of time, a significant increase (p<0.001) over the AUROC achieved using several baselines, including logistic regression (0.81, 95% CI 0.78 - 0.84) and neural networks (0.80, 95% CI 0.77 - 0.83]). Finally, we conducted feature importance analysis using gradient boosting and derived useful insights in understanding the relative importance of clinical vs. biological variables in predicting impending respiratory decompensation in ICUs.
Dynamic condensates activate transcription

Transcriptional components exhibit transient phase separation to drive gene activation Every aspect of human function, from proper cell differentiation and development to normal cellular maintenance, requires properly timed activation of the necessary genes. This requires transcription of genomic DNA into messenger RNA (mRNA), accomplished by RNA polymerase II (RNA Pol II), which initiates transcription at gene promoters. This highly regulated process requires hundreds of proteins that must go to the promoter in a coordinated manner. Although many of these proteins are already organized into large and stable protein complexes, and so travel as a group, the process still requires coordination of many individual proteins and preformed complexes so that they are all in the same place on genomic DNA at the same time. This problem has been appreciated for years and has led to models such as “transcription factories,” where components are organized and ready to act on a gene that goes to the cellular location of the factory (1). On pages 378, 379, and 412 of this issue, Chong et al. (2), Sabari et al. (3), and Cho et al. (4), respectively, argue that special protein domains, which interact with each other to form fleeting or more persistent interactions, form biomolecular condensates that concentrate the transcription machinery. Some of these condensates might even form droplets, generating a liquid phase separated from the rest of the nucleus. Phase separation is a phenomenon familiar to anyone who has made a salad dressing: The oil and vinegar exist as two separated liquids. Phase separation in cells creates membraneless organelles that, in this case, provide the organization necessary for productive transcription (5).
Clustering trees: a visualization for evaluating clusterings at multiple resolutions

Clustering techniques are widely used in the analysis of large data sets to group together samples with similar properties. For example, clustering is often used in the field of single-cell RNA-sequencing in order to identify different cell types present in a tissue sample. There are many algorithms for performing clustering and the results can vary substantially. In particular, the number of groups present in a data set is often unknown and the number of clusters identified by an algorithm can change based on the parameters used. To explore and examine the impact of varying clustering resolution we present clustering trees. This visualisation shows the relationships between clusters at multiple resolutions allowing researchers to see how samples move as the number of clusters increases. In addition, meta-information can be overlaid on the tree to inform the choice of resolution and guide in identification of clusters. We illustrate the features of clustering trees using a series of simulations as well as two real examples, the classical iris dataset and a complex single-cell RNA-sequencing dataset. Clustering trees can be produced using the clustree R package available from CRAN (https://CRAN.R-project.org/package=clustree) and developed on GitHub (https://github.com/lazappi/clustree).
Comparing the Effect of Immediate versus Delayed Initiation of Tacrolimus on Delayed Graft Function in Kidney Transplant Recipients: A Randomized Open-label Clinical Trial

Objective: Delayed graft function (DGF) is an early complication after kidney transplantation with negative impact on allograft outcomes. This study assessed the effect of delayed initiation of tacrolimus as a nephrotoxic drug, on DGF occurrence and allograft function. Methods: This randomized, open-label clinical trial was conducted on kidney transplant recipients with the age of at least 14 years who underwent the first kidney transplantation from deceased or living donor. Patients were randomly allocated to immediate (n = 26) or delayed tacrolimus (n = 27) groups. All patients received thymoglobulin as induction therapy and similar maintenance immunosuppression including tacrolimus, mycophenolate, and prednisolone with the difference in the time of initiation of tacrolimus either on the day of transplantation (immediate tacrolimus group) or day 3 after transplant (delayed tacrolimus group). Findings: DGF incidence (46.15% vs. 37.04%; P = 0.501) and duration (9.75 ± 6.41 vs. 8.6 ± 6.16 days; P = 0.675) were not different between the immediate and delayed tacrolimus groups. Estimated creatinine clearance using Cockcroft–Gault equation (63.14 ± 18.81 vs. 58.19 ± 19.42 mL/min in immediate and delayed tacrolimus groups respectively; P = 0.373) and estimated acute rejection-free survival were also comparable between the groups over the 3 months of follow-up. Compared with the immediate group, the delayed tacrolimus group showed higher estimated 3-month grafts' survival (100% vs. 84.27%; P = 0.072). Conclusion: Delayed initiation of tacrolimus after kidney transplantation under the umbrella of thymoglobulin induction did not result in either lower incidence or duration of DGF or improved the level of graft function in kidney transplant recipients but non-statistically significant increased 3-month grafts' survival.
A note on internet use and the 2016 U.S. presidential election outcome

We use data from the American National Election Studies from 1996 to 2016 to study the role of the internet in the 2016 U.S. presidential election outcome. We compare trends in the Republican share of the vote between likely and unlikely internet users, and between actual internet users and non-users. Relative to prior years, the Republican share of the vote in 2016 was as high or higher among the groups least active online.
Factorial validity and invariance of the Patient Health Questionnaire (PHQ)-9 among clinical and non-clinical populations

The Patient Health Questionnaire-9 (PHQ-9) is commonly used to screen for depressive disorder and for monitoring depressive symptoms. However, there are mixed findings regarding its factor structure (i.e., whether it has a unidimensional, two-dimensional, or bi-factor structure). Furthermore, its measurement invariance between non-clinical and clinical populations and that between patients with major depressive disorder (MDD) and MDD with comorbid anxiety disorder (AD) is unknown. Japanese adults with MDD (n = 406), MDD with AD (n = 636), and no psychiatric disorders (non-clinical population; n = 1,163) answered this questionnaire on the Internet. Confirmatory factor analyses showed that the bi-factor model had a better fit than the unidimensional and two-dimensional factor models did. The results of a multi-group confirmatory factor analysis indicated scalar invariance between the non-clinical and only MDD groups, and that between the only MDD and MDD with AD groups. In conclusion, the bi-factor model with two specific factors was supported among the non-clinical, only MDD, and MDD with AD groups. The scalar measurement invariance model was supported between the groups, which indicated the total or sub-scale scores were comparable between groups.
Global “worming”: Climate change and its projected general impact on human helminth infections

1 Department of Surgery, Baylor College of Medicine, Houston, Texas, United States of America, 2 Texas Children’s Hospital Center for Vaccine Development, Houston, Texas, United States of America, 3 National School of Tropical Medicine, Baylor College of Medicine, Houston, Texas, United States of America, 4 Department of Pediatrics, Baylor College of Medicine, Houston, Texas, United States of America, 5 Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, United States of America, 6 Department of Biology, Baylor University, Waco, Texas, United States America, 7 James A. Baker III Institute of Public Policy, Rice University, Houston, Texas, United States America, 8 Scowcroft Institute of International Affairs, Bush School of Government and Public Policy, Texas A&M University, College Station, Texas, United States of America
Human Plasma Levels of Vascular Endothelial Growth Factor, Matrix Metalloproteinase 9, and Tissue Inhibitor of Matrix Metalloproteinase 1 and Their Applicability as Tumor Markers in Diagnoses of Cervical Cancer Based on ROC Analysis

Cervical cancer (CC) remains a major diagnostic problem. The introduction of human papillomavirus vaccination significantly reduced the number of new cases; however, the search for new methods that would earlier indicate the development of cancerous changes is vital. The aim of this study was to investigate the diagnostic power of those parameters in comparison to Cancer Antigen 125 (CA 125) and Squamous Cell Carcinoma Antigen (SCC-Ag) in patients with CC and in relation to the control group. The study included 100 patients with CC and 50 healthy women. Plasma levels of tested parameters were determined by enzyme-linked immunosorbent assay, CA 125, and SCC-Ag by chemiluminescent microparticle immunoassay. Plasma levels of all parameters in the total cancer group showed statistical significance (in all cases P < .05). In stage I cancer, only vascular endothelial growth factor (VEGF) and tissue inhibitors of metalloproteinase 1; in stage II, all the tested parameters and CA 125; and in stage III + IV, VEGF, matrix metalloproteinase 9 (MMP-9), and CA 125 showed statistical significance when compared to the healthy volunteers group. Vascular endothelial growth factor showed the highest value of sensitivity from all tested parameters (I: 75%, II: 76%, III + IV: 94%, and 82% in total CC group). The highest specificity was obtained by MMP-9 (94%). In the total CC, stage I, and stage II groups, all tested parameters showed statistically significant area under the receiver operating characteristics curve (AUC), but maximum range was obtained for the combination VEGF + SCC-Ag (I: 0.9146, II: 0.8941, III + IV: 0.9139, total CC group: 0.9347). The combined analysis of tested parameters and tumor markers resulted in an increase in sensitivity and AUC values, which provides hope for developing new panel of biomarkers that may be used in the diagnosis of CC in the future.
The Mucosal Vaccine Adjuvant LT(R192G/L211A) or dmLT

Perhaps the best-studied mucosal adjuvants are the bacterially derived ADP-ribosylating enterotoxins. This adjuvant family includes heat-labile enterotoxin of Escherichia coli (LT), cholera toxin (CT), and mutants or subunits of LT and CT. ABSTRACT Perhaps the best-studied mucosal adjuvants are the bacterially derived ADP-ribosylating enterotoxins. This adjuvant family includes heat-labile enterotoxin of Escherichia coli (LT), cholera toxin (CT), and mutants or subunits of LT and CT. These proteins promote a multifaceted antigen-specific response, including inflammatory Th1, Th2, Th17, cytotoxic T lymphocytes (CTLs), and antibodies. However, more uniquely among adjuvant classes, they induce antigen-specific IgA antibodies and long-lasting memory to coadministered antigens when delivered mucosally or even parenterally. The purpose of this minireview is to describe the general properties, history and creation, preclinical studies, clinical studies, mechanisms of action, and considerations for use of the most promising enterotoxin-based adjuvant to date, LT(R192G/L211A) or dmLT. This review is timely due to completed, ongoing, and planned clinical investigations of dmLT in multiple vaccine formulations by government, nonprofit, and industry groups in the United States and abroad.