Miracle-dz/UniFAR-FTUs huggingface dataset:
Monocyte-Derived Dendritic Cells Differentiated in the Presence of Lenalidomide Display a Semi-Mature Phenotype, Enhanced Phagocytic Capacity, and Th1 Polarization Capability

Lenalidomide is an analog of thalidomide, with potent anticancer activity demonstrated in several hematological malignancies. It has immunomodulatory properties, being able to enhance the activation of different types of immune cells, which results in antitumor activities. Dendritic cells (DCs) are pivotal in the immune response, and different immunotherapeutic approaches targeting these cells are being developed. Since little is known about the effect of lenalidomide on DCs, the goal of the present work was to investigate the phenotype and function of human monocyte-derived DCs differentiated in the presence of lenalidomide (L-DCs). Our results showed that L-DCs display a unique phenotype, with increased cell surface expression of some maturation markers such as CD1d, CD83, CD86, and HLA-DR. This phenotype correlates with a lower expression of the E3 ubiquitin-ligase MARCH-I in L-DCs, upregulating the cell surface expression of CD86 and HLA-DR. In addition, immature L-DCs express higher amounts of DC-SIGN on the cell surface than control immature DCs. After LPS stimulation, production of IL-6 and TNF-α was severely decreased, whereas IL-12 and IL-10 secretion was dramatically upregulated in L-DCs, compared to that in the controls. Functionally, L-DCs are more effectively recognized by NKT cells in cytotoxicity experiments. Furthermore, L-DCs display higher opsonin-independent antigen uptake capability than control DCs. Mixed lymphocyte reaction experiments showed that L-DCs could stimulate naïve CD4 T-cells, polarizing them toward a predominant Th1 phenotype. In summary, DCs derived from monocytes in the presence of lenalidomide present a semi-mature phenotype, increased phagocytic capacity, reduced production of proinflammatory cytokines, and the ability to polarize T-cells toward predominant Th1-type responses; these are qualities that might be useful in the development of new immunotherapeutic treatments.
TGF-β/Smad3 pathway enhances the cardio-protection of S1R/SIPR1 in in vitro ischemia-reperfusion myocardial cell model

Ischemia-reperfusion (IR) injury is usually associated with a high risk of cardiomyocyte death in patients with acute myocardial infarction. Sphingosine 1-phosphate (S1P) and transforming growth factor (TGF)-β are thought to be involved in the protection of cardiomyocyte and heart function following IR-induced injury. However, the possible association of S1P and S1P receptor 1 (S1PR1) with the TGF-β/Smad3 pathway as the potential protective mechanism has remained to be investigated. In the present study, an in vitro ischemia/reperfusion injury model was established and evaluated by analysis of apoptosis, lactate dehydrogenase (LDH) release and caspase3 activity. The mRNA and protein levels of S1PR1, TGF-β and Smad3 after treatment with 1 µM S1P alone or combined with 0.4 µM W146 (a specific S1PR1 antagonist) were assessed. The mRNA expression of five S1PRs (S1PR1-5) and the protein levels of S1PR1 were also assayed following treatment with 1 ng/ml TGF-β for 0, 4 or 24 h. The mRNA expression of S1PR1 and the levels of S1P were further assessed following exposure to 10 µM SB4 (TGFβR1 inhibitor) plus 1 ng/ml TGF-β and 2 µM SIS3 (Smad3 inhibitor) plus 1 ng/ml TGF-β. The results indicated that apoptosis, LDH release and caspase3 activity were all increased in the established IR model. Exogenous S1P increased the mRNA and protein levels of S1PR1, TGF-β and Smad3, which was abolished by addition of W146. Extraneous TGF-β resulted in the stimulation of several S1PRs, most prominently of S1PR1, while supplementation with SB4 and SIS3 offset the stimulation by TGF-β. These results suggested that the TGF-β/Smad3 pathway was closely associated with S1P/S1PR1 in the protection of myocardial cells from IR injury.
Lyman α-emitting galaxies in the epoch of reionization

With a total integration time of 168 h and a narrowband filter tuned to Lyα emission from z = 8.8, the UltraVISTA survey has set out to find some of the most distant galaxies, on the verge of the epoch of reionization. Previous calculations of the expected number of detected Lyα-emitting galaxies (LAEs) at this redshift based for example on extrapolation of lower-redshift luminosity functions did not explicitly take into account the radiative transfer of Lyα. In this work we have combined a theoretical model for the halo mass function, that is, the expected number of haloes per volume, with numerical results from high-resolution cosmological hydro-simulations post-processed with radiative transfer of ionizing UV and Lyα radiation, assessing the visibility of LAEs residing in these haloes. We have taken into account uncertainties such as cosmic variance and the anisotropic escape of Lyα, and predict that once the survey has finished, the probabilities of detecting none, one, or more than one are roughly 90%, 10%, and 1%, respectively. This is a significantly smaller success rate than in earlier predictions, due to the combined effect of a highly neutral intergalactic medium (IGM) scattering Lyα to such large distances from the galaxy that they fall outside the observational aperture, and to the actual depth of the survey being less than predicted. Because the IGM affects narrowband (NB) and broadband (BB) magnitudes differently, we argue for a relaxed colour selection criterion of mNB − mBB ≃ +0.85 in the AB system. Since the flux is dominated by the continuum, however, even if a galaxy is detectable in the NB, its probability of being selected as a narrowband excess object is ≲35%. Various additional properties of galaxies at this redshift are predicted, for example, the Lyα and UV luminosity functions, the stellar mass–halo mass relation, the spectral shape, the optimal aperture, as well as the anisotropic escape of Lyα through both the dusty, interstellar medium and through the partly neutral IGM. Finally, we describe and make public a fast numerical code for adding numbers with asymmetric uncertainties (“x+σ+−σ−”) which proves significantly more precise than the standard, but wrong, way of separately adding upper and lower uncertainties in quadrature.
Compromised function of the ESCRT pathway promotes endolysosomal escape of tau seeds and propagation of tau aggregation

Intercellular propagation of protein aggregation is emerging as a key mechanism in the progression of several neurodegenerative diseases, including Alzheimer's disease and frontotemporal dementia (FTD). However, we lack a systematic understanding of the cellular pathways controlling prion-like propagation of aggregation. To uncover such pathways, here we performed CRISPR interference (CRISPRi) screens in a human cell-based model of propagation of tau aggregation monitored by FRET. Our screens uncovered that knockdown of several components of the endosomal sorting complexes required for transport (ESCRT) machinery, including charged multivesicular body protein 6 (CHMP6), or CHMP2A in combination with CHMP2B (whose gene is linked to familial FTD), promote propagation of tau aggregation. We found that knocking down the genes encoding these proteins also causes damage to endolysosomal membranes, consistent with a role for the ESCRT pathway in endolysosomal membrane repair. Leakiness of the endolysosomal compartment significantly enhanced prion-like propagation of tau aggregation, likely by making tau seeds more available to pools of cytoplasmic tau. Together, these findings suggest that endolysosomal escape is a critical step in tau propagation in neurodegenerative diseases.
cis- and trans-Acting Factors Influence Expression of the norM-Encoded Efflux Pump of Neisseria gonorrhoeae and Levels of Gonococcal Susceptibility to Substrate Antimicrobials

The gonococcal NorM efflux pump exports substrates with a cationic moiety, including quaternary ammonium compounds such as berberine (BE) and ethidium bromide (EB) as well as antibiotics such as ciprofloxacin and solithromycin. The norM gene is part of a four-gene operon that is transcribed from a promoter containing a polynucleotide tract of 6 or 7 thymidines (T's) between the −10 and −35 hexamers; the majority of gonococcal strains analyzed in this study contained a T-6 sequence. ABSTRACT The gonococcal NorM efflux pump exports substrates with a cationic moiety, including quaternary ammonium compounds such as berberine (BE) and ethidium bromide (EB) as well as antibiotics such as ciprofloxacin and solithromycin. The norM gene is part of a four-gene operon that is transcribed from a promoter containing a polynucleotide tract of 6 or 7 thymidines (T's) between the −10 and −35 hexamers; the majority of gonococcal strains analyzed in this study contained a T-6 sequence. Primer extension analysis showed that regardless of the length of the poly(T) tract, the same transcriptional start site (TSS) was used for expression of norM. Interestingly, the T-6 tract correlated with a higher level of both norM expression and gonococcal resistance to NorM substrates BE and EB. Analysis of expression of genes downstream of norM showed that the product of the tetR-like gene has the capacity to activate expression of norM as well as murB, which encodes an acetylenolpyroylglucosamine reductase predicted to be involved in the early steps of peptidoglycan synthesis. Moreover, loss of the TetR-like transcriptional regulator modestly increased gonococcal susceptibility to NorM substrates EB and BE. We conclude that both cis- and trans-acting regulatory systems can regulate expression of the norM operon and influence levels of gonococcal susceptibility to antimicrobials exported by NorM.
Four Weeks of Off-Season Training Improves Peak Oxygen Consumption in Female Field Hockey Players

The purpose of the study was to examine the changes in peak oxygen consumption (V˙O2peak) and running economy (RE) following four-weeks of high intensity training and concurrent strength and conditioning during the off-season in collegiate female field hockey players. Fourteen female student-athletes (age 19.29 ± 0.91 years) were divided into two training groups, matched from baseline V˙O2peak: High Intensity Training (HITrun; n = 8) and High Intensity Interval Training (HIIT; n = 6). Participants completed 12 training sessions. HITrun consisted of 30 min of high-intensity running, while HIIT consisted of a series of whole-body high intensity Tabata-style intervals (75–85% of age predicted maximum heart rate) for a total of four minutes. In addition to the interval training, the off-season training included six resistance training sessions, three team practices, and concluded with a team scrimmage. V˙O2peak was measured pre- and post-training to determine the effectiveness of the training program. A two-way mixed (group × time) ANOVA showed a main effect of time with a statistically significant difference in V˙O2peak from pre- to post-testing, F(1, 12) = 12.657, p = 0.004, partial η2 = 0.041. Average (±SD) V˙O2peak increased from 44.64 ± 3.74 to 47.35 ± 3.16 mL·kg−1·min−1 for HIIT group and increased from 45.39 ± 2.80 to 48.22 ± 2.42 mL·kg−1·min−1 for HITrun group. Given the similar improvement in aerobic power, coaches and training staff may find the time saving element of HIIT-type conditioning programs attractive.
Clonal Background, Resistance Gene Profile, and Porin Gene Mutations Modulate In Vitro Susceptibility to Imipenem-Relebactam in Diverse Enterobacteriaceae

Treatment options for carbapenem-resistant Enterobacteriaceae (CRE) are limited. While Klebsiella pneumoniae strains harboring blaKPC account for most CRE, recent evidence points to increasing diversification of CRE. ABSTRACT Treatment options for carbapenem-resistant Enterobacteriaceae (CRE) are limited. While Klebsiella pneumoniae strains harboring blaKPC account for most CRE, recent evidence points to increasing diversification of CRE. We determined whether the CRE species and antibiotic resistance genotype influence the response to relebactam (REL), a novel beta-lactamase inhibitor with class A/C activity, combined with imipenem-cilastatin (IMI). We carried out broth microdilution testing with IMI alone or in the presence of 4 μg/ml REL against 154 clinical isolates collected at a New York City hospital with a high prevalence of organisms carrying blaKPC, including Enterobacter spp. (n = 96), K. pneumoniae (n = 44), Escherichia coli (n = 1), Serratia marcescens (n = 9), and Citrobacter spp. (n = 4). Resistance gene profiles and the presence of major porin gene disruptions were ascertained by whole-genome sequencing. Addition of REL decreased the IMI MIC to the susceptible range (≤1 μg/ml) against 88% of isolates. However, S. marcescens IMI-REL MICs were 4- to 8-fold higher than those for other organisms. Most blaKPC-positive isolates had IMI-REL MICs of ≤1 μg/ml (88%), including isolates of Enterobacter cloacae ST171 (93%) and K. pneumoniae ST258 (82%). Nineteen isolates had IMI-REL MICs of ≥2 μg/ml, among which 84% harbored blaKPC and one was blaNDM-1 positive. Isolates with IMI-REL MICs of ≥2 μg/ml versus those with MICs of ≤1 μg/ml were significantly more likely to demonstrate disruption of at least one porin gene (42% versus 19%; P = 0.04), although most S. marcescens isolates (67%) had intact porin genes. In conclusion, while REL reduced IMI MICs in a majority of diverse CRE isolates, including high-risk clones, chromosomal factors had an impact on IMI-REL susceptibilities and may contribute to elevated MICs for S. marcescens.
Sclerosing encapsulating peritonitis after living-donor liver transplantation: A case series, Kyoto experience

Sclerosing encapsulating peritonitis (SEP), or abdominal cocoon is a rare cause of intestinal obstruction, and still etiology remains unknown. We report a series of 4 patients with abdominal cocoon, and all the 4 patients had previously undergone living-donor liver transplantation (LDLT). There was no evidence of SEP before and during LDLT. At the time of diagnosis of SEP, 3 out of 4 patients had ascites. First and fourth patients had multiple episodes or attacks of cholangitis, which were managed by percutaneous transhepatic biliary drainage and hepaticojejunostomy, respectively. All 4 patients presented with intestinal obstruction and 3 of them underwent a successful operation. The fourth patient died due to liver failure and complications of the SEP. The first 3 patients are doing well without SEP recurrence. Our experience suggest that the prognosis of SEP is poor in patients with poor graft liver functions after LDLT.
Fully Solution-Processed Tandem White Quantum-Dot Light-Emitting Diode with an External Quantum Efficiency Exceeding 25.

Solution-processed electroluminescent tandem white quantum-dot light-emitting diodes (TWQLEDs) have the advantages of being low-cost and high-efficiency and having a wide color gamut combined with color filters, making this a promising backlight technology for high-resolution displays. However, TWQLEDs are rarely reported due to the challenge of designing device structures and the deterioration of film morphology with component layers that can be deposited from solutions. Here, we report an interconnecting layer with the optical, electrical, and mechanical properties required for fully solution-processed TWQLED. The optimized TWQLEDs exhibit a state-of-the-art current efficiency as high as 60.4 cd/A and an extremely high external quantum efficiency of 27.3% at a luminance of 100 000 cd/m2. A high color gamut of 124% NTSC 1931 standard can be achieved when combined with commercial color filters. These results represent the highest performance for solution-processed WQLEDs, unlocking the great application potential of TWQLEDs as backlights for new-generation displays.
Transgenerational inheritance of chronic adolescent stress: Effects of stress response and the amygdala transcriptome

Adolescent stress can impact health and well‐being not only during adulthood of the exposed individual but even in future generations. To investigate the molecular mechanisms underlying these long‐term effects, we exposed adolescent males to stress and measured anxiety behaviors and gene expression in the amygdala—a critical region in the control of emotional states—in their progeny for two generations, offspring and grandoffspring. Male C57BL/6 mice underwent chronic unpredictable stress (CUS) for 2 weeks during adolescence and were used to produce two generations of offspring. Male and female offspring and grandoffspring were tested in behavioral assays to measure affective behavior and stress reactivity. Remarkably, transgenerational inheritance of paternal stress exposure produced a protective phenotype in the male, but not the female lineage. RNA‐seq analysis of the amygdala from male offspring and grandoffspring identified differentially expressed genes (DEGs) in mice derived from fathers exposed to CUS. The DEGSs clustered into numerous pathways, and the “notch signaling” pathway was the most significantly altered in male grandoffspring. Therefore, we show that paternal stress exposure impacts future generations which manifest in behavioral changes and molecular adaptations.
Negative regulation of cationic nanoparticle-induced inflammatory toxicity through the increased production of prostaglandin E2 via mitochondrial DNA-activated Ly6C+ monocytes

Rationale: Cationic nanocarriers present with well-known toxicities, including inflammatory toxicity, which limit their clinical application. How the cationic nanocarrier-induced inflammatory response is negatively regulated is unknown. Herein, we found that following a sublethal dose of cationic nanocarriers, the induced inflammatory response is characterized by early neutrophil infiltration and spontaneous resolution within 1 week. Methods: C57BL/6 mice were intravenously injected with a dosage of 1-100 mg/kg cationic DOTAP liposomes as well as other cationic materials. Cell necrosis was detected by flow cytometry. Release of mitochondrial DNA was quantified by qPCR via Taqman probes. Signal proteins were detected by Western blotting. PGE2 production in the supernatant was quantitated using an enzyme immunoassay (EIA). The infiltrated inflammatory cells were observed in WT mice, Ccr2-/- mice, Sting-/-mice and Tlr9-/-mice. Results: The early stage (24-48 h) inflammatory neutrophil infiltration was followed by an increasing percentage of monocytes; and, compared with WT mice, Ccr2-/- mice presented with more severe pulmonary inflammation. A previously uncharacterized population of regulatory monocytes expressing both inflammatory and immunosuppressive cytokines was identified in this model. The alteration in monocyte phenotype was directly induced by mtDNA release from cationic nanocarrier-induced necrotic cells via a STING- or TLR9-dependent pathway. Neutrophil activation was specifically inhibited by PGE2 from Ly6C+ inflammatory monocytes, and intravenous injections of dual-phenotype monocytes beneficially modified the immune response; this inhibitory effect was abolished after treatment with indomethacin. Moreover, we provide clear evidence that mitochondrial DNA activated Ly6C+ monocytes and increased PGE2 production through TLR9- or STING-mediated MAPK-NF-κB-COX2 pathways. Conclusion: Our findings suggest that Ly6C+ monocytes and mtDNA-induced Ly6C+ monocyte PGE2 production may be part of a feedback mechanism that contributes to the resolution of cationic nanocarrier-induced inflammatory toxicity and may have important implications for understanding nanoparticle biocompatibility and designing better, safer drug delivery systems.
Meta-Learning for Stochastic Gradient MCMC

Stochastic gradient Markov chain Monte Carlo (SG-MCMC) has become increasingly popular for simulating posterior samples in large-scale Bayesian modeling. However, existing SG-MCMC schemes are not tailored to any specific probabilistic model, even a simple modification of the underlying dynamical system requires significant physical intuition. This paper presents the first meta-learning algorithm that allows automated design for the underlying continuous dynamics of an SG-MCMC sampler. The learned sampler generalizes Hamiltonian dynamics with state-dependent drift and diffusion, enabling fast traversal and efficient exploration of neural network energy landscapes. Experiments validate the proposed approach on both Bayesian fully connected neural network and Bayesian recurrent neural network tasks, showing that the learned sampler out-performs generic, hand-designed SG-MCMC algorithms, and generalizes to different datasets and larger architectures.
A Novel Security Scheme Based on Instant Encrypted Transmission for Internet of Things

Internet of Things (IoT) is a research field that has been continuously developed and innovated in recent years and is also an important driving force for the improvement of people’s life in the future. There are lots of scenarios in IoT where we need to collaborate through devices to complete tasks; that is, a device sends data to other devices, and other devices operate on the aid of the data. These transmitted data are often users’ privacy data, such as medical data and grid data. We propose an instant encrypted transmission based security scheme for such scenarios in IoT. The analysis in this paper indicates that our scheme can guarantee the security of users’ data while ensuring rapid transmission and acquisition of instant IoT data.
Projecting Embeddings for Domain Adaption: Joint Modeling of Sentiment Analysis in Diverse Domains

Domain adaptation for sentiment analysis is challenging due to the fact that supervised classifiers are very sensitive to changes in domain. The two most prominent approaches to this problem are structural correspondence learning and autoencoders. However, they either require long training times or suffer greatly on highly divergent domains. Inspired by recent advances in cross-lingual sentiment analysis, we provide a novel perspective and cast the domain adaptation problem as an embedding projection task. Our model takes as input two mono-domain embedding spaces and learns to project them to a bi-domain space, which is jointly optimized to (1) project across domains and to (2) predict sentiment. We perform domain adaptation experiments on 20 source-target domain pairs for sentiment classification and report novel state-of-the-art results on 11 domain pairs, including the Amazon domain adaptation datasets and SemEval 2013 and 2016 datasets. Our analysis shows that our model performs comparably to state-of-the-art approaches on domains that are similar, while performing significantly better on highly divergent domains. Our code is available at https://github.com/jbarnesspain/domain_blse
Tensions in the adoption and evolution of software quality management systems

This paper reports some results from a project to uncover the non-technical factors that affect the adoption and evolution of Software Quality Management Systems (referred to here as 'the quality effort'). The data which the paper discusses comes from interviews with people involved in the quality effort in four different companies. Our approach to data collection was to use semistructured interviews and to encourage interviewees to talk about their experiences of quality management in their own organisations. We analysed this data using discourse analysis, informed by ethnographic observation, and identified a number of themes, one of which was the tensions that exist between developers and the quality effort. In this paper, we present and discuss some data which illustrates the tensions we found. 1. BACKGROUND This paper describes the collection and analysis of qualitative empirical data to investigate the non-technical factors influencing the adoption and evolution of software quality management systems (SQMS). We collected a variety of data through our project, but in this paper we concentrate on data from semi-structured interviews conducted with quality managers.