julilili42/papers huggingface dataset:
Integrin activation enables simultaneous and sensitive detection of functional virus-specific CD4+ and CD8+ T cells
2020-08-28

<title>Abstract</title> We have previously shown that beta<sub>2</sub>-integrin conformational change is a very early activation marker that can be detected with fluorescent multimers of its ligand ICAM-1 for a rapid assessment of antigen-specific CD8<sup>+ </sup>T cells. Here, we describe a modified protocol of this assay for sensitive detection of functional antigen-specific CD4<sup>+</sup> T cells using a monoclonal antibody (clone m24) specific for the open, high affinity conformation of the beta<sub>2</sub>-integrin. Kinetics of beta<sub>2</sub>-integrin activation were different on CD4<sup>+</sup> and CD8<sup>+</sup> T cells (several hours vs. few minutes, respectively), however, m24 antibody readily stained both cell types 4-6 hours after antigen stimulation. With this protocol, we were able to monitor CD4<sup>+</sup> and CD8<sup>+</sup> virus-specific T cells specific for CMV, EBV, HBV, and SARS-CoV-2 in whole blood or cryopreserved PBMCs of infected or vaccinated individuals. By costaining with m24 and CD154 antibodies, we assessed extremely low frequencies of polyfunctional CD4<sup>+</sup> T cell responses to SARS-CoV-2 derived peptides. Our novel assay thus allows very sensitive and simultaneous screening of both CD4<sup>+</sup> and CD8<sup>+</sup> T cell reactivities with versatile applicability in clinical and vaccination studies, and for epitope discovery.
CTLA-4-IG PROLONGS GRAFT SURVIVAL SPECIFICALLY IN YOUNG BUT NOT IN OLD RECIPIENTS
2020-08-28

Introduction: The proportion of older transplant recipients has increased dramatically. Age-specific effects of established immunosuppressants are poorly understood. Here, we assessed the impact of CTLA4-Ig, a fusion protein blocking costimulatory signaling between APCs and T cells through CD28. We hypothesized that the immunosuppressive capacity of CTLA4-Ig will depend on an age-specific expression of CD28 on alloreactive T-cells. Methods: Heart and skin grafts from young DBA2/J mice were transplanted into either young or old (2-3 and 18 mths, resp.) allogeneic C57BL/6 recipients treated with CTLA4-Ig or PBS; T-cell frequencies and subsets in addition to cytokine expression were assessed by flow cytometry and ELISA; expression of CD28 was assessed on young and old T-cell subsets. To delineate the age-specific immunosuppressive potential of CTL4-Ig, T-cells were transfected with a lentiviral vector inducing CD28 expression; transfected T-cells were subsequently transferred into young RAG2-/- mice receiving a fully mismatched skin graft. Results: Treatment with CTLA4-Ig prolonged skin graft survival only in young (p<0.01) but not in old recipients (p=0.33). Age-specific immunosuppressive effects of CTLA4-Ig were also confirmed in a SOT model: cardiac allografts in young mice treated with CTLA4-Ig survived indefinitely. In contrast, 80% of old recipients treated with CTLA4-Ig had lost their graft by 100 days. CTLA4-Ig reduced CD4+ central-memory and effector-memory T cells and diminished systemic IFN-γ levels only in young (p<0.05), but not old recipients (p=0.8). These differences correlated with a reduced expression of CD28 on antigen-experienced CD4+ T cells in old mice (p<0.001). Interestingly, Tregs displayed an increased expression of CD28 with age making them more prone to be targeted by CTLA4-Ig. Strikingly, adoptive transfer of old CD4+ T cells that were transfected with a lentiviral vector augmenting the expression of CD28 accelerated the rejection of allogeneic skin grafts in young RAG2-/- recipient mice (p<0.01 vs. controls animals that received adoptively transferred, non-transfected old T cells) demonstrating the cardinal role of CD28 expression on alloreactive CD4+ T cells. Conclusion: Immunosuppressive effects of CTLA4-Ig showed distinct age-dependent effects in both skin and cardiac transplantation linked to a reduced CD28 expression of alloreactive old T-cells in parallel to an augmented CD28 expression on old T-regs. Transfection experiments confirmed the critical role of CD28 in mounting robust alloimmune responses. These findings carry relevant clinical consequences.
Meta-analysis of the effects of transcranial direct current stimulation (tDCS) on inhibitory control
2020-08-28

Background: Inhibitory control refers to a central cognitive capacity involved in the interruption and correction of actions. Dysfunctions in these cognitive control processes have been identified as major maintaining mechanisms in a range of mental disorders such as ADHD, binge eating disorder, obesity, and addiction. Improving inhibitory control by transcranial direct current stimulation (tDCS) could ameliorate symptoms in a broad range of mental disorders. Objective: The primary aim of this pre-registered meta-analysis was to investigate whether inhibitory control can be improved by tDCS in healthy and clinical samples. Additionally, several moderator variables were investigated.Methods: A comprehensive literature search was performed on PubMed/MEDLINE database, Web of Science, and Scopus. To achieve a homogenous sample, only studies that assessed inhibitory control in the go-/no-go (GNG) or stop-signal task (SST) were included, yielding a total of 75 effect sizes from 45 studies. Results: Results of the meta-analysis indicate a small but significant overall effect of tDCS on inhibitory control (g = 0.21) which was moderated by target and return electrode placement as well as by the task. The small effect size was further reduced after correction for publication bias.
Cathodal tDCS &amp; Implicit Associations
2020-08-29

Implicit associations can interfere with cognitive operations and behavioural decisions without direct intention. Enhancement of neural activity with anodal transcranial direct current stimulation (tDCS) was proposed to reduce implicit associations by means of improved cognitive control. However, the notion of a direct inhibition of implicit associations by cathodal tDCS has not yet been addressed. Here, we introduce a cathodal tDCS configuration with extracephalic return electrode to reduce implicit associations. Based on previous studies on implicit spatial-numerical associations, we generalize the stimulation rationale by demonstrating efficacy in the standardized implicit association task (IAT). In this double-classification task, insect vs. flower pictures and negative vs. positive words are mapped together onto two shared response keys with crossed response assignments in separate blocks. Responses were faster when insect + negative and flower + positive stimuli required the same answer (IAT effect). Most critically, the IAT effect was reduced during 1 mA prefrontal cathodal tDCS as compared to sham stimulation. Results are consistent with the proposed stimulation rationale, with our previous observations, and complementary to previous attempts to modulate IAT effects with (medial) prefrontal anodal tDCS configurations. Limited by the validity of the IAT in general, results suggest transferability to other implicit biases.
A novel method to measure T1‐relaxation times of macromolecules and quantification of the macromolecular resonances
2020-08-30

Purpose Macromolecular peaks underlying metabolite spectra influence the quantification of metabolites. Therefore, it is important to understand the extent of contribution from macromolecules (MMs) in metabolite quantification. However, to model MMs more accurately in spectral fitting, differences in T 1 relaxation times among individual MM peaks must be considered. Characterization of T 1 ‐relaxation times for all individual MM peaks using a single inversion recovery technique is difficult due to eventual contributions from metabolites. On the contrary, a double inversion recovery (DIR) technique provided flexibility to acquire MM spectra spanning a range of longitudinal magnetizations with minimal metabolite influence. Thus, a novel method to determine T 1 ‐relaxation times of individual MM peaks is reported in this work. Methods Extensive Bloch simulations were performed to determine inversion time combinations for a DIR technique that yielded adequate MM signal with varying longitudinal magnetizations while minimizing metabolite contributions. MM spectra were acquired using DIR‐metabolite‐cycled semi‐LASER sequence. LCModel concentrations were fitted to the DIR signal equation to calculate T 1 ‐relaxation times. Results T 1 ‐relaxation times of MMs range from 204 to 510 ms and 253 to 564 ms in gray‐ and white‐matter rich voxels respectively at 9.4T. Additionally, concentrations of 13 MM peaks are reported. Conclusion A novel DIR method is reported in this work to calculate T 1 ‐relaxation times of MMs in the human brain. T 1 ‐relaxation times and relaxation time corrected concentrations of individual MMs are reported in gray‐ and white‐matter rich voxels for the first time at 9.4T.
DeepLabCut: markerless pose estimation of user-defined body parts with deep learning
2020-08-30

This data entry contains <strong>annotated mouse data from the DeepLabCut Nature Neuroscience paper</strong>. This data entry contains a public release of annotated mouse data from the DeepLabCut paper. The trail-tracking behavior is part of an investigation into odor guided navigation, where one or multiple wildtype (C57BL/6J) mice are running on a paper spool and following odor trails. These experiments were carried out by Alexander Mathis &amp; Mackenzie Mathis in the Murthy lab at Harvard University. Data was recorded by two different cameras (640×480 pixels with Point Grey Firefly (FMVU-03MTM-CS), and at approximately 1,700×1,200 pixels with Grasshopper 3 4.1MP Mono USB3 Vision (CMOSIS CMV4000-3E12)) at 30 Hz. The latter images were cropped around mice to generate images that are approximately 800×800. Here we share 1066, frames from multiple experimental sessions observing 7 different mice. Pranav Mamidanna labeled the snout, the tip of the left and right ear as well as the base of the tail in the example images. The data is organized in DeepLabCut 2.0 project structure with images and annotations in the labeled-data folder. The names are pseudocodes indicating mouse id and session id, e.g. m4s1 = mouse 4 session 1. Code for loading, visualizing &amp; training deep neural networks available at https://github.com/DeepLabCut/DeepLabCut.
Controlling the Dipole Blockade and Ionization Rate of Rydberg Atoms in Strong Electric Fields
2020-08-31

We study a hitherto unexplored regime of the Rydberg excitation blockade using highly Stark-shifted, yet long-living, states of Rb atoms subject to electric fields above the classical ionization limit. Such states allow tuning the dipole-dipole interaction strength while their ionization rate can be changed over 2 orders of magnitude by small variations of the electric field. We demonstrate laser excitation of the interacting Rydberg states followed by their detection using controlled ionization and magnified imaging with high spatial and temporal resolution. Our work reveals new possibilities to engineer the interaction strength and dynamically control the ionization and detection of Rydberg atoms, which can be useful for realizing and assessing quantum simulators that vary in space and time.
Geochemical, biological and clumped isotopologue evidence for substantial microbial methane production under carbon limitation in serpentinites of the Samail Ophiolite, Oman
2020-08-31

In high-pH ( ) fluids that have participated in low-temperature ( ) serpentinization, the dominant form of C is often methane (CH ), but the origin of this CH is uncertain. To assess CH origin during low-temperature serpentinization, we pumped fluids from aquifers within the Samail Ophiolite, Oman. We determined fluid chemical compositions, analyzed taxonomic profiles of fluid-hosted microbial communities, and measured isotopic compositions of hydrocarbon gases. We found that 16S rRNA gene sequences affiliated with methanogens were widespread in the aquifer. We measured clumped isotopologue ( CH D and CH D ) relative abundances less than equilibrium, consistent with substantial microbial CH production. Further, we observed an inverse relationship between dissolved inorganic C concentrations and across fluids bearing microbiological evidence of methanogenic activity, suggesting that the apparent C isotope effect of microbial methanogenesis is modulated by C availability. A second source of CH is evidenced by the presence of CH -bearing fluid inclusions in the Samail Ophiolite and our measurement of high values of ethane and propane, which are similar to those reported in studies of CH -rich inclusions in rocks from the oceanic lithosphere. In addition, we observed 16S rRNA gene sequences affiliated with aerobic methanotrophs and, in lower abundance, anaerobic methanotrophs, indicating that microbial consumption of CH in the ophiolite may further enrich CH in C. We conclude that substantial microbial CH is produced under varying degrees of C limitation and mixes with abiotic CH released from fluid inclusions. This study lends insight into the functioning of microbial ecosystems supported by water/rock reactions.
The potential of induced pluripotent stem cells for discriminating neurodevelopmental disorders
2020-08-31

Abstract Studying human disease-specific processes and mechanisms in vitro is limited by a lack of valid human test systems. Induced pluripotent stem cells (iPSCs) evolve as an important and promising tool to better understand the molecular pathology of neurodevelopmental disorders. Patient-derived iPSCs enable analysis of unique disease mechanisms and may also serve for preclinical drug development. Here, we review the current knowledge on iPSC models for schizophrenia and autism spectrum disorders with emphasis on the discrimination between them. It appears that transcriptomic analyses and functional read-outs are the most promising approaches to uncover specific disease mechanisms in vitro.
Optimized Birch Bark Extract-Loaded Colloidal Dispersion Using Hydrogenated Phospholipids as Stabilizer
2020-08-31

This study investigated the formulation and processing of aqueous colloidal dispersions containing a birch bark dry extract (TE) as the active substance and hydrogenated phospholipids (Phospholipon 90H) as stabilizer, which can be used in the preparation of electrospun wound dressings. Colloidal dispersions manufactured using a two-stage homogenization process had a bimodal particle size distribution, which was most significantly (p &lt; 0.0001) affected by the phospholipid content. The size of the single particles decreased from an average particle size of about 4 μm to a particle size of approximately 400 nm. Dynamic interfacial tension studies performed using a profile analysis tensiometer (PAT) showed that the phospholipids strongly declined the interfacial tension, whereas a further decrease was observed when phospholipids were combined with birch bark extract. Interfacial viscoelasticity properties analyzed using the oscillating drop technique resulted in an increase of both interfacial elasticity and viscosity values. These results indicated that the phospholipids are preferentially located at the lipophilic/water interface and a stable film is formed. Furthermore, the results point to a synergistic interaction between phospholipids and TE. Confocal Raman microscopy (CRM) suggested that the TE is predominantly located in the oil phase and the phospholipids at the interface.
Employee Identification and Wages: On the Economics of
2020-08-31

We study the role of employees' identification to the employer for wage growth. We first show in a formal model that identification implies countervailing effects: Employees with higher identification are more valuable as they exert higher efforts, but have weaker bargaining positions, and less outside options as they search less. Analyzing a novel representative panel dataset, we find that stronger identification is associated with less job search and turnover. Workers that have higher identification exhibit significantly lower wage growth. In line with the model, this pattern tends to be reversed conditional on having obtained an external offer.
Life Satisfaction in Families with A Child in an Unresponsive Wakefulness Syndrome
2020-08-31

<title>Abstract</title> <bold>Background: </bold>The article examines life conditions in families living together with a child in an Unresponsive Wakefulness Syndrome (UWS). Such families experience severe stress at financial, logistical, and existential level.<bold>Methods: </bold>We investigated a large sample of families living with a UWS child (comprising 13% of the total population) and compared these families with families without a chronically ill child. A set of four questionnaires aimed to evaluate life conditions entails a total of 204 items. One of the questionnaires was developed by the corresponding author specifically for this study. The questionnaires were positively accepted by the persons concerned and permitted us to test six specific hypotheses. <bold>Results: </bold>Life satisfaction (LS) in families with a UWS child was significantly lower than in control families. LS was significantly affected by the positive anamnestic situation (everyday support, home visits, support by a doctor, nursing service, health insurance, etc.). Self-management skills were on average lower in families with a UWS child than in controls. These skills strongly and directly correlated with LS. Further, LS was not significantly related to the acceptance of feelings and negatively correlated with the floods of emotions. The relationship with the own child was equally satisfactory in families with and without a UWS child indicating that the families regard their UWS child as a full family member.<bold>Conclusions: </bold>The data show that happy life is possible in families living together with a UWS child. They further specify conditions for satisfactory life under multiple highly severe challenges. Personal self-management skills, coping strategies, and resilience, as well as outside social support, appear to be critical factors.
Synergistic targeting and resistance to PARP inhibition in DNA damage repair-deficient pancreatic cancer
2020-09-01

Objective ATM serine/threonine kinase (ATM) is the most frequently mutated DNA damage response gene, involved in homologous recombination (HR), in pancreatic ductal adenocarcinoma (PDAC). Design Combinational synergy screening was performed to endeavour a genotype-tailored targeted therapy. Results Synergy was found on inhibition of PARP, ATR and DNA-PKcs (PAD) leading to synthetic lethality in ATM-deficient murine and human PDAC. Mechanistically, PAD-induced PARP trapping, replication fork stalling and mitosis defects leading to P53-mediated apoptosis. Most importantly, chemical inhibition of ATM sensitises human PDAC cells toward PAD with long-term tumour control in vivo. Finally, we anticipated and elucidated PARP inhibitor resistance within the ATM-null background via whole exome sequencing. Arising cells were aneuploid, underwent epithelial-mesenchymal-transition and acquired multidrug resistance (MDR) due to upregulation of drug transporters and a bypass within the DNA repair machinery. These functional observations were mirrored in copy number variations affecting a region on chromosome 5 comprising several of the upregulated MDR genes. Using these findings, we ultimately propose alternative strategies to overcome the resistance. Conclusion Analysis of the molecular susceptibilities triggered by ATM deficiency in PDAC allow elaboration of an efficient mutation-specific combinational therapeutic approach that can be also implemented in a genotype-independent manner by ATM inhibition.
Hepatitis E virus genome detection in commercial pork livers and pork meat products in Germany
2020-09-01

Abstract The hepatitis E virus (HEV) is one of the most common causes of hepatitis worldwide. HEV is also widespread in many developed countries, where the number of infections is steadily increasing. In those countries, the virus is transmitted mainly through consumption of undercooked or raw food or through contact with animals. Especially, pigs serve as a main reservoir of HEV. Here, we investigated the prevalence of HEV RNA in pork livers and pork meat products to assess the actual risk of HEV infection through food consumption in Germany. A total of 131 pork products were collected from grocery stores and butcher shops between October 2019 and February 2020 and screened for HEV RNA using nested PCR and subsequent sequencing. Overall, 10% of the samples were positive for HEV, including pork livers (5%), spreadable liver sausages (13%) and liver pâté samples (15%). Sequence analyses indicated that the large majority of HEV strains belonged to subtype HEV‐3c, representing the most frequent subtype in Germany. One sample belonged to subtype HEV‐3f. Further sequence analysis revealed large sequence variation between the samples; however, most of the mutations identified were synonymous. Although infectivity of the virus was not tested, the results suggest a considerable risk of HEV infection through food consumption. Therefore, preventive measures should be taken according to a One Health approach.
High School Teachers’ Self-efficacy in Teaching Computer Science
2020-09-01

Self-efficacy is an important construct for CS teachers’ professional development, because it can predict both teaching behaviors as well as student outcomes. Research has shown that teachers’ self-efficacy can be as influential as their actual level of knowledge and abilities. However, there has been very limited research on CS teachers’ self-efficacy. This study describes the development and implementation of an instrument that measures secondary school teachers’ self-efficacy in teaching computer science. Teachers attended a nine-week hybrid professional development program and completed the computer science teaching self-efficacy instrument. Confirmatory factor analysis validated the self-efficacy instrument, which can be potentially used in other CS education settings. The results also indicated that teachers’ self-efficacy in the content knowledge and pedagogical content knowledge dimensions of teaching computer science significantly increased from participating in the professional development program.
Grounding the Consolationist Concept of Mood in the African Vital Force Theory
2020-09-01

ABSTRACT The concept of vital force in African philosophy received its first full articulation in Placide Tempels’s Bantu Philosophy (1959) and has evolved over time from the ontological dimension of a universal actuation and energizing principle to an element of mind, notably in the work of Kwame Gyekye. In this essay, I present the concept of vital force and trace its evolution from the time of its first full articulation by Tempels up to its identification with spirit, or mind, in Gyekye’s thought. I try to defend the thesis that the concept of vital force can ground the notion of mood that takes a pivotal position in the twenty-first century philosophy of consolationism. I adopt an analytical and constructive method in this paper.