Miracle-dz/UniFAR-FTUs huggingface dataset:
The Majority of Active Rhodobacteraceae in Marine Sediments Belong to Uncultured Genera: A Molecular Approach to Link Their Distribution to Environmental Conditions

General studies on benthic microbial communities focus on fundamental biogeochemical processes or the most abundant constituents. Thereby, minor fractions such as the Rhodobacteraceae are frequently neglected. Even though this family belongs to the most widely distributed bacteria in the marine environment, their proportion on benthic microbial communities is usually within or below the single digit range. Thus, knowledge on these community members is limited, even though their absolute numbers might exceed those from the pelagic zone by orders of magnitudes. To unravel the distribution and diversity of benthic, metabolically active Rhodobacteraceae, we have now analyzed an already existing library of bacterial 16S rRNA transcripts. The dataset originated from 154 individual sediment samples comprising seven oceanic regions and a broad variety of environmental conditions. Across all samples, a total of 0.7% of all 16S rRNA transcripts was annotated as Rhodobacteraceae. Among those, Sulfitobacter, Paracoccus, and Phaeomarinomonas were the most abundant cultured representatives, but the majority (78%) was affiliated to uncultured family members. To define them, the 45 most abundant Rhodobacteraceae-OTUs assigned as “uncultured” were phylogenetically assembled in new clusters. Their next relatives particularly belonged to different subgroups other than the Roseobacter group, reflecting a large part of the hidden diversity within the benthic Rhodobacteraceae with unknown functions. The general composition of active Rhodobacteraceae communities was found to be specific for the geographical location, exhibiting a decreasing richness with sediment depth. One-third of the Rhodobacteraceae-OTUs significantly responded to the prevailing redox regime, suggesting an adaption to anoxic conditions. A possible approach to predict their physiological properties is to identify the metabolic capabilities of their nearest relatives. Those need to be proven by physiological experiments, as soon an isolate is available. Because many uncultured members of these subgroups likely thrive under anoxic conditions, in future research, a molecular-guided cultivation strategy can be pursued to isolate novel Rhodobacteraceae from sediments.
Evolved Open-Endedness, Not Open-Ended Evolution

Open-endedness is often considered a prerequisite property of the whole evolutionary system and its dynamical behaviors. In the actual history of evolution on Earth, however, there are many examples showing that open-endedness is rather a consequence of evolution. We suggest that this view, which we call evolved open-endedness (EOE), be incorporated more into research on open-ended evolution. This view should allow for systematic investigation of more nuanced, more concrete research questions about open-endedness and its relationship with adaptation and sustainability.
Disorders of neurogenesis and cortical development

The development of the cerebral cortex requires complex sequential processes that have to be precisely orchestrated. The localization and timing of neuronal progenitor proliferation and of neuronal migration define the identity, laminar positioning, and specific connectivity of each single cortical neuron. Alterations at any step of this organized series of events—due to genetic mutations or environmental factors—lead to defined brain pathologies collectively known as malformations of cortical development (MCDs), which are now recognized as a leading cause of drug-resistant epilepsy and intellectual disability. In this heterogeneous group of disorders, macroscopic alterations of brain structure (eg, heterotopic nodules, small or absent gyri, double cortex) can be recognized and probably subtend a general reorganization of neuronal circuits. In this review, we provide an overview of the molecular mechanisms that are implicated in the generation of genetic MCDs associated with aberrations at various steps of neurogenesis and cortical development.
Cathepsin G Activity as a New Marker for Detecting Airway Inflammation by Microscopy and Flow Cytometry

Muco-obstructive lung diseases feature extensive bronchiectasis due to the uncontrolled release of neutrophil serine proteases into the airways. To assess if cathepsin G (CG) is a novel key player in chronic lung inflammation, we developed membrane-bound (mSAM) and soluble (sSAM) FRET reporters. The probes quantitatively revealed elevated CG activity in samples from 46 patients. For future basic science and personalized clinical applications, we developed a rapid, highly informative, and easily translatable small-molecule FRET flow cytometry assay for monitoring protease activity including cathepsin G. We demonstrated that mSAM distinguished healthy from patient cells by FRET-based flow cytometry with excellent correlation to confocal microscopy data.
Dual Role of CD4 in Peripheral T Lymphocytes

The interaction of T-cell receptors (TCRs) with self- and non-self-peptides in the major histocompatibility complex (MHC) stimulates crucial signaling events, which in turn can activate T lymphocytes. A variety of accessory molecules further modulate T-cell signaling. Of these, the CD4 and CD8 coreceptors make the most critical contributions to T cell sensitivity in vivo. Whereas, CD4 function in T cell development is well-characterized, its role in peripheral T cells remains incompletely understood. It was originally suggested that CD4 stabilizes weak interactions between TCRs and peptides in the MHC and delivers Lck kinases to that complex. The results of numerous experiments support the latter role, indicating that the CD4-Lck complex accelerates TCR-triggered signaling and controls the availability of the kinase for TCR in the absence of the ligand. On the other hand, extremely low affinity of CD4 for MHC rules out its ability to stabilize the receptor-ligand complex. In this review, we summarize the current knowledge on CD4 in T cells, with a special emphasis on the spatio-temporal organization of early signaling events and the relevance for CD4 function. We further highlight the capacity of CD4 to interact with the MHC in the absence of TCR. It drives the adhesion of T cells to the cells that express the MHC. This process is facilitated by the CD4 accumulation in the tips of microvilli on the surface of unstimulated T cells. Based on these observations, we suggest an alternative model of CD4 role in T-cell activation.
Large-Scale Production of 119mTe and 119Sb for Radiopharmaceutical Applications

Radionuclides find widespread use in medical technologies for treating and diagnosing disease. Among successful and emerging radiotherapeutics, 119Sb has unique potential in targeted therapeutic applications for low-energy electron-emitting isotopes. Unfortunately, developing 119Sb-based drugs has been slow in comparison to other radionuclides, primarily due to limited accessibility. Herein is a production method that overcomes this challenge and expands the available time for large-scale distribution and use. Our approach exploits high flux and fluence from high-energy proton sources to produce longer lived 119mTe. This parent isotope slowly decays to 119Sb, which in turn provides access to 119Sb for longer time periods (in comparison to direct 119Sb production routes). We contribute the target design, irradiation conditions, and a rapid procedure for isolating the 119mTe/119Sb pair. To guide process development and to understand why the procedure was successful, we characterized the Te/Sb separation using Te and Sb K-edge X-ray absorption spectroscopy. The procedure provides low-volume aqueous solutions that have high 119mTe—and consequently 119Sb—specific activity in a chemically pure form. This procedure has been demonstrated at large-scale (production-sized, Ci quantities), and the product has potential to meet stringent Food and Drug Administration requirements for a 119mTe/119Sb active pharmaceutical ingredient.
Human-induced environmental changes influence habitat use by an ungulate over the long term

Abstract Habitat use and preferences may be subject to spatial and temporal changes. However, long-term studies of species–habitat relationships are the exception. In the present research, long-term trends in habitat use by an alpine ungulate, the Tatra chamois Rupicapra rupicapra tatrica, were analyzed. We examined how environmental changes attributable to climate change, removal of sheep, and habituation to hikers, which took place over the last half-century have changed the spatial distribution of animals. Data on the localities of groups sighted between 1957 and 2013 during autumnal population surveys were used to evaluate habitat associations: these were correlated with year, group size, population size, and climatic conditions. The results indicate that the Tatra chamois is tending, over the long term, to lower its altitude of occurrence, reduce its average distance to hiking trails, and stay less often on slopes with a southerly aspect. These trends are independent of group size, population size, and the weather conditions prevailing during observations, though not for altitude, where increases in air temperature are related to finding chamois at higher elevations. The proportion of alpine meadows and slope in the places used by chamois is correlated with population size, while the proportion of areas with trees and/or shrubs is correlated with group size and air temperature, though long-term changes were not evident for these variables. To the best of our knowledge, this work is the first to document long-term trends in habitat use by ungulates. It shows that a species’ ecology is influenced by human-induced changes: abandonment of pasturage, high-mountain tourism, and climate changes, which constitute the most probable reasons for this aspect of behavioral evolution in the Tatra chamois.
Personality and burnout among primary care physicians: an international study

Purpose Burnout is a syndrome comprised of three major dimensions, namely, emotional exhaustion, depersonalization, and reduced personal accomplishment. Its etiology appears to be multifactorial, involving work-related and personal factors including personality traits. Personality has been associated with burnout among various physician groups; however, this has not been studied well amongst primary care physicians. This study therefore aimed to investigate the association between personality type and burnout in primary care physicians in Canada and Jamaica. Methods This cross-sectional study involved primary care physicians in Canada and Jamaica. Participants completed a questionnaire that included the Maslach Burnout Inventory Human Services Survey and The Big Five Inventory. Responses were analyzed to determine relationships between burnout, personality type, and various demographic factors. Results Seventy-seven physicians participated in the study. Approximately 38% of participants reported low levels of accomplishment, 34% reported high levels of emotional exhaustion, and 20% reported high levels of depersonalization, all equating to high levels of burnout. Neuroticism was negatively correlated with personal accomplishment (P<0.01) and positively correlated with emotional exhaustion (P≤0.001) and depersonalization (P<0.01). Agreeableness (P<0.05) and conscientiousness (P<0.05) were positively correlated with accomplishment and both were negatively correlated with depersonalization (P<0.01 and P<0.05, respectively). Conclusion In this multinational study, we found that burnout was a common problem among primary care physicians. Personality, particularly neuroticism, agreeableness, and conscientiousness, impacts physician burnout. Strategies that modulate the impact of personality on burnout may be beneficial for optimal health care delivery.
Alkylaminophenol Induces G1/S Phase Cell Cycle Arrest in Glioblastoma Cells Through p53 and Cyclin-Dependent Kinase Signaling Pathway

Glioblastoma (GBM) is the most common type of malignant brain tumor in adults. We show here that small molecule 2-[(3,4-dihydroquinolin-1(2H)-yl)(p-tolyl)methyl]phenol (THTMP), a potential anticancer agent, increases the human glioblastoma cell death. Its mechanism of action and the interaction of selective signaling pathways remain elusive. Three structurally related phenolic compounds were tested in multiple glioma cell lines in which the potential activity of the compound, THTMP, was further validated and characterized. Upon prolonged exposer to THTMP, all glioma cell lines undergo p53 and cyclin-dependent kinase mediated cell death with the IC50 concentration of 26.5 and 75.4 μM in LN229 and Snb19, respectively. We found that THTMP strongly inhibited cell growth in a dose and in time dependent manner. THTMP treatment led to G1/S cell cycle arrest and apoptosis induction of glioma cell lines. Furthermore, we identified 3,714 genes with significant changes at the transcriptional level in response to THTMP. Further, a transcriptional analysis (RNA-seq) revealed that THTMP targeted the p53 signaling pathway specific genes causing DNA damage and cell cycle arrest at G1/S phase explained by the decrease of cyclin-dependent kinase 1, cyclin A2, cyclin E1 and E2 in glioma cells. Consistently, THTMP induced the apoptosis by regulating the expression of Bcl-2 family genes and reactive oxygen species while it also changed the expression of several anti-apoptotic genes. These observations suggest that THTMP exerts proliferation activity inhibition and pro-apoptosis effects in glioma through affecting cell cycle arrest and intrinsic apoptosis signaling. Importantly, THTMP has more potential at inhibiting GBM cell proliferation compared to TMZ, the current chemotherapy treatment administered to GBM patients; thus, we propose that THTMP may be an alternative therapeutic option for glioblastoma.
Risk factors with the development of infection with tigecycline- and carbapenem-resistant Enterobacter cloacae

Background Tigecycline is regarded as a last resort treatment for carbapenem-resistant Enterobacter cloacae (CREC) infections, and increasing numbers of tigecycline- and carbapenem-resistant E. cloacae (TCREC) isolates have been reported in recent years. However, risk factors and clinical impacts of these isolates are poorly characterized. Patients and methods We conducted a retrospective case-case-control study of hospitalized patients with TCREC infection during the period 2012–2016 in Chongqing, China. Case patients with TCREC and those with CREC were compared to a control group with no E. cloacae infection. Multivariate logistic regression models were used to identify independent risk factors for acquiring TCREC and CREC. Results A total of 36 TCREC cases, 36 CREC cases, and 100 controls were enrolled in our study. Multivariable analysis indicated that nasal catheter (OR: 8.9; 95% CI: 1.1–75.2), exposure to penicillin (OR: 95.9; 95% CI: 8.9–1038.3), aminoglycosides (OR: 42.1; 95% CI: 2.1–830.6), and fluoroquinolones (OR: 18.6; 95% CI: 1.9–185.6) were independent predictors for acquiring TCREC. In addition, venous catheterization (OR: 12.2; 95% CI: 2.5–58.5), penicillin (OR: 30.8; 95% CI: 7.9–120.0), and broad-spectrum cephalosporin (OR: 5.0; 95% CI: 1.5–17.3) were independently associated with CREC acquisition. Conclusion Reasonable antibiotic stewardship programs and surveillance are necessary to control the tigecycline resistance among high-risk patients.
Molecular Basis of Broad Spectrum N-Glycan Specificity and Processing of Therapeutic IgG Monoclonal Antibodies by Endoglycosidase S2

Immunoglobulin G (IgG) glycosylation critically modulates antibody effector functions. Streptococcus pyogenes secretes a unique endo-β-N-acetylglucosaminidase, EndoS2, which deglycosylates the conserved N-linked glycan at Asn297 on IgG Fc to eliminate its effector functions and evade the immune system. EndoS2 and specific point mutants have been used to chemoenzymatically synthesize antibodies with customizable glycosylation for gain of functions. EndoS2 is useful in these schemes because it accommodates a broad range of N-glycans, including high-mannose, complex, and hybrid types; however, its mechanism of substrate recognition is poorly understood. We present crystal structures of EndoS2 alone and bound to complex and high-mannose glycans; the broad N-glycan specificity is governed by critical loops that shape the binding site of EndoS2. Furthermore, hydrolytic experiments, domain-swap chimeras, and hydrogen–deuterium exchange mass spectrometry reveal the importance of the carbohydrate-binding module in the mechanism of IgG recognition by EndoS2, providing insights into engineering enzymes to catalyze customizable glycosylation reactions.
Noise Robustness in Aspect Extraction Task

Aspect extraction from user reviews is one of the sources to make dialog systems, which are on the rise now. A typical user of a conversation system has no time to check the spelling or grammar in his or her utterances. Due to that user utterances contain typos and spelling errors, so the noise robustness should be considered as a significant feature of an aspect extraction model. We analyze noise-robustness of state-of-the-art Attention-Based Aspect Extraction technique and propose the extensions for this model, which lead to more robust behaviour in presence of typos. Experimental results demonstrate how suitable each of the complements to the model that uses the data containing typos.
Featherlight Reuse-Distance Measurement

Data locality has a profound impact on program performance. Reuse distance—the number of distinct memory locations accessed between two consecutive accesses to the same location—is the de facto, machine-independent metric of data locality in a program. Reuse distance measurement, typically, requires exhaustive instrumentation (code or binary) to log every memory access, which results in orders of magnitude runtime slowdown and memory bloat. Such high overheads impede reuse distance tools from adoption in long-running, production applications despite their usefulness. We develop RDX, a lightweight profiling tool for characterizing reuse distance in an execution; RDX typically incurs negligible time (5%) and memory (7%) overheads. RDX performs no instrumentation whatsoever but uniquely combines hardware performance counter sampling with hardware debug registers, both available in commodity CPU processors, to produce reuse-distance histograms. RDX typically has more than 90% accuracy compared to the ground truth. With the help of RDX, we are the first to characterize memory performance of long-running SPEC CPU2017 benchmarks. Keywords-Reuse distance; locality; hardware performance counters; debug registers; profiling.
An Annotated Corpus of Stories and Gestures for a Robotic Storyteller

This paper describes a system which has been used to automatically create an annotated corpus of stories. This corpus can be exploited by a robotic storyteller. In a first phase stories were retrieved from a repository. The textual content of each story was semantically analyzed in order to locate meaningful terms in the sentences that can be accompanied by proper gestures and possible emotions that can be expressed. Once the whole story is properly labelled, it can be dramatized by a robot storyteller. We discuss a demonstration of the use of this approach with NarRob, a storyteller robot that we have designed within our institute.
Joint Beamforming and Clustering Optimization of Hybrid-Energy-Powered eRRHs in F-RANs

In order to ensure the seamless coverage in places without power grid, wirelessly powered enhanced radio remote heads (eRRHs) using energy harvesting have been proposed in fog radio access networks (F-RANs). In this paper, to achieve efficient scheduling of hybrid energy powered eRRHs, the energy efficiency of a downlink F-RAN with capacity-limited fronthaul links is investigated, where the eRRHs are powered by the power grid or harvest energy from radio frequency signals. To maximize the energy efficiency, the beamforming vector of the transmitter and the user-centric clustering scheme are jointly optimized under fronthaul capacity and transmission power constraints. We apply some approximate techniques and generalize the relationship between weighted-sum-rate and weighted minimum-mean-squared-error problems to obtain a tractable formulation for the optimization problem. Accordingly, an iteratively algorithm is proposed. Simulation results are provided to show the performance of the algorithm.
Multilevel Simulation of Direct Operated Safety Valve

Models (of different completeness) of gasdynamic processes in direct acting safety valves are considered. All the models are based on the control volume method in 3D, axisymmetric or 1D formulation. In 3D simulation, the internal cavity of the valve is divided into two blocks. In each block, a structured difference mesh is constructed. The mesh in the first block is orthogonal. The proposed approach to numerical simulation of nonstationary 3D gas dynamics enables to determine a spatial structure of flow in a safety valve and its quantitative characteristics (pressure, density, velocity, temperature). To determine the spatial structure and calculate the dynamics of quantitative characteristics of the valve, the first (comprehensive) level of simulation must be applied. The axisymmetric formulation of the gas-dynamic problem can be applied at the stage of disc lifting (valve actuation). Assumption of axial symmetry of the flow under the disc is also justified in simulating stationary characteristics of safety valve. It is a good practice to study wave processes in supply and discharge lines using simplified axisymmetric approach, which is comparable with 1D calculation in terms of computational burden. Keywords— safety valve actuation, numerical simulation, finite volume method, spatial structure of flow, gas dynamic force.
A Matching Game Approach for Joint Resource Allocation and User Association in Fog Radio Access Networks

Fog computing based radio access network (F-RAN) has been regarded as a paradigm with great promise to provide high spectral and energy efficiency with edge devices, and has recently attracted lots of attention. In this paper, we focus on joint user association and resource allocation to optimize the user average file download delay in a device-to-device (D2D) enabled F-RAN. The optimization problem is formulated as a mixed-integer nonlinear programming problem, which can be proved as a NP-hard problem. To solve the problem efficiently, a matching game based algorithm is proposed, where D2D users and fog access points (F-APs) can adjust wireless resource allocation autonomously according to the condition of swap matching. Simulation results verify the accuracy of our analysis and show that the proposed algorithm can achieve a near optimal performance with a fast convergence speed. Meanwhile, the impacts of the cache size of F-APs, the number of users, and the fairness are demonstrated as well.
A Review on Real Time Simulation of UPFC

FACTS (Flexible Alternating Current Transmission System) has proved to be very effective and viable in alleviating the problems of power transmission systems. FACTS play an important role to enhance the transient stability and maintain the related parameters such as voltage sag, harmonics, frequency changes, reactive power, active power. It also decreased the generation cost and reduce the transmission line losses. The Unified Power Flow Controller (UPFC) is a mostly used FACTS device due to its reliability and flexibility. It realizes lines parameters adjusting such as node voltages, line impedance, and phase angle. This paper is focused on the recent developed technologies and real time simulators for UPFC in establishing transient stability of electric power system.