Miracle-dz/UniFAR-FTUs huggingface dataset:
Highlight article: Rs1982809 is a functional biomarker for the prognosis of severe post-traumatic sepsis and MODs

BTLA is a useful biomarker to characterize the immune states of sepsis patients. We investigated the association between genetic variations of BTLA and morbidity of sepsis and MODS in severe traumatic patient. Three tag single nucleotide polymorphisms of BTLA were genotyped in 562 severe trauma patients. To further elucidate the mechanism, mRNA stability, BTLA 3ʹ-UTR activity, and its expression on T lymphocytes were measured. Only rs1982809 which located in 3ʹ-UTR of BTLA showed a significant clinical relevance with the incidence rate of sepsis and MOD scores. The sepsis incidence and MOD score of rs1982809 CC genotype carriers were higher than TT carriers. The percentage of circulating BTLA + CD4 + CD3 + T lymphocytes was markedly lower in CC genotype carriers. Luciferase activity in plasmids containing C allele was lower than that of T allele. Thus, the differential expression of BTLA on T lymphocytes might be caused by the different 3ʹ-UTR activity induced by rs1982809 T/C. Therefore, rs1982809 is a useful clinical biomarker in the prognosis evaluating of sepsis and subsequent MODS. Moreover, it is also a functional single nucleotide polymorphism affecting the activity of BTLA 3ʹ-UTR and the expression of BTLA in peripheral blood T lymphocytes. Impact statement This work is useful in the field of genetic mechanism of severe post-traumatic complications, as it provides important evidence for the influence of BTLA gene polymorphism on sepsis and MODS susceptibility. The results are useful and of importance because rs1982809 is a useful clinical biomarker in the prognosis evaluating of sepsis and subsequent MODS. It is also a functional single nucleotide polymorphism affecting the activity of BTLA 3ʹ-UTR and the expression of BTLA in peripheral blood T lymphocytes.
A thiazole-derived oridonin analogue exhibits antitumor activity by directly and allosterically inhibiting STAT3

Constitutive activation of signal transducer and activator of transcription 3 (STAT3) occurs in ∼70% of human cancers, and STAT3 is regarded as one of the most promising targets for cancer therapy. However, specific direct STAT3 inhibitors remain to be developed. Oridonin is an ent-kaurane plant-derived diterpenoid with anti-cancer and anti-inflammatory activities. Here, using an array of cell-based and biochemical approaches, including cell proliferation and apoptosis assays, pulldown and reporter gene assays, site-directed mutagenesis, and molecular dynamics analyses, we report that a thiazole-derived oridonin analogue, CYD0618, potently and directly inhibits STAT3. We found that CYD0618 covalently binds to Cys-542 in STAT3 and suppresses its activity through an allosteric effect, effectively reducing STAT3 dimerization and nuclear translocation, as well as decreasing expression of STAT3-targeted oncogenes. Remarkably, CYD0618 not only strongly inhibited growth of multiple cancer cell lines that harbor constitutive STAT3 activation, but it also suppressed in vivo tumor growth via STAT3 inhibition. Taken together, our findings suggest Cys-542 as a druggable site for selectively inhibiting STAT3 and indicate that CYD0618 represents a promising lead compound for developing therapeutic agents against STAT3-driven diseases.
Research and Application for Power-Grid Comprehensive Distribution Decision System

High-efficiency power-grid planning is used to ensure the benefits and smooth operation of power-grid companies and industries. In order to solve the planning management business, such as the enterprise overall planning, power-grid planning and early planning, and its decision analysis issues, such as comprehensive planning, investment planning, production planning, etc. This paper proposes some statistical data models for power-grid planning decision and its applications. With some quantitative and data information analysis, the different decisions are designed for different plans and mathematical analysis methods are provided to decision makers. Taking the common decision analysis model as the carrier, a specific and applicable logic model is proposed with power-grid companies' business characteristics and decision-making requirements. The experimental results show that this power-grid planning method has the features of robust reregulation and universal adaptation with same types, which implied that the optimization constraints of this model are matching with the actual conditions and further ensuring the credibility and practicality of the power-grid planning. Keywords—power-grid planning; statistical data model; decision-making requirements; robust reregulation; universal adaptation
Two novel proteins, TtpB2 and TtpD2, are essential for iron transport in the TonB2 system of Vibrio vulnificus

In gram‐negative bacteria, energy‐dependent active transport of iron‐bound substrates across the outer membrane is achieved through the TonB systems of proteins. Three TonB systems have been identified in the human pathogen Vibrio vulnificus. The TonB1 system contains three proteins: TonB1, ExbB1, and ExbD1. Both the TonB2 and TonB3 systems have been shown to also contain a fourth protein, TtpC2 and TtpC3, respectively. Here, we report and begin to characterize two additional proteins in the TonB2 and TonB3 systems: TtpB and TtpD. Both TtpB2 and TtpD2 are absolutely required for the function of the TonB2 system in V. vulnificus. However, although both TtpB3 and TtpD3 in the TonB3 system are related to the proteins in the TonB2 system, neither are active in iron transport. All six protein components of the TonB2 system—TonB2, ExbB2, ExbD2, TtpB2, TtpC2, and TtpD2—are essential for the uptake of both endogenously produced iron‐bound siderophores and exogenous siderophores produced from other organisms. Through complementation, we have shown that V. vulnificus is capable of using different TtpD2 proteins from other Vibrio species to bring in multiple siderophores. In contrast, we also demonstrate that TtpB2 must come from V. vulnificus, and not other species within the genus, to complement mutations in the TonB2 system.
Human virome in nasopharynx and tracheal secretion samples

BACKGROUND In Brazil the implementation of the Sentinel Surveillance System of Influenza began in 2000. Central public health laboratories use reverse transcription-quantitative polymerase chain reaction (RT-qPCR) for diagnosis of respiratory viruses, but this protocol identifies only specific targets, resulted in inconclusive diagnosis for many samples. Thus, high-throughput sequencing (HTS) would be complementary method in the identification of pathogens in inconclusive samples for RT-qPCR or other specific detection protocols. OBJECTIVES This study aimed to detect unidentified viruses using HTS approach in negative samples of nasopharynx/tracheal secretions by the standard RT-qPCR collected in the Federal District, Brazil. METHODS Nucleic acids were extracted from samples collected in winter period of 2016 and subjected to HTS. The results were confirmed by the multiplex PR21 RT-qPCR, which identifies 21 respiratory pathogens. FINDINGS The main viruses identified by HTS were of families Herpesviridae, Coronaviridae, Parvoviridae and Picornaviridae, with the emphasis on rhinoviruses. The presence of respiratory viruses in the samples was confirmed by the PR21 multiplex RT-qPCR. Coronavirus, enterovirus, bocavirus and rhinovirus were found by multiplex RT-qPCR as well as by HTS analyses. MAIN CONCLUSIONS Wide virus diversity was found by different methodologies and high frequency of rhinovirus occurrence was confirmed in population in winter, showing its relevance for public health.
Dual-Ligand Porous Coordination Polymer Chemiresistor with Modulated Conductivity and Porosity.

Single-ligand-based electronically conductive porous coordination polymers / metal organic frameworks (EC-PCPs/MOFs) fail to meet the requirements in numerous electronic applications due to their limited turnabilities in terms of both conductivity and topology. In this work, a new 2D π-conjugated EC-MOFs containing mixed trigonal-liganded copper units was developed: Cu3(HHTP)(THQ) (HHTP = 2,3,6,7,10,11-hexahydrotriphenylene, THQ = tetrahydroxy-1,4-quinone). The modulated conductivity (σ = ~2.53 × 10-5 S cm-1 with an activation energy of 0.30 eV) and high porosity (∼441.2 m2 g-1) of the Cu3(HHTP)(THQ) semiconductive nanowires provided the proper resistance baseline and highly accessible areas for the development of an excellent chemiresistive gas sensor.
Realist approach to evaluating an interprofessional education program for medical students in clinical practice at a community hospital

Abstract Introduction: We examined the interrelationships between context, mechanism, and outcome using a realist approach following the introduction of interprofessional education (IPE) to clinical practice for medical students in the community. Methods: Through participant observation and interviews, a working hypothesis was developed. To evaluate IPE in clinical practice, medical students’ reports were thematically analyzed, and configuration on contexts, mechanisms, and outcomes were identified using a realist approach. Results: Influential contexts were medical students’ experience of clinical practice and learning characteristics, the capacity of other professionals, interprofessional relationships, and characteristics of the community hospital. One key mechanism was observational learning. Others were self-regulated learning, legitimate peripheral participation, experiential learning, contact hypotheses, awareness of social structure, and cognitive empathy. As faculties supported these key mechanisms, medical students became aware of the legitimacy of community-oriented primary care, noting the roles of physicians who support patients’ and/or their family’s life in collaboration with other professionals, and reflecting the necessity of shifting from physician-centered perspectives. As a result, medical students deepened their empathic understanding for other professionals. Conclusion: Faculties should develop IPE programs in clinical practice based on the ‘mechanism’, ‘context’, ‘outcome’ pattern and ‘context-mechanism-outcome’ configuration in primary care settings.
Opioids differentially modulate two synapses important for pain processing in the amygdala

Pain is a subjective experience involving sensory discriminative and emotionally aversive components. Consistent with its role in pain processing and emotions, the amygdala modulates the aversive component of pain. The laterocapsular region of the central nucleus of the amygdala (CeLC) receives nociceptive information from the parabrachial nucleus (PB) and polymodal, including nociceptive, inputs from the basolateral nucleus of the amygdala (BLA). Opioids are strong analgesics and reduce both the sensory discriminative and the affective component of pain. However, it is unknown whether opioids regulate activity at the two nociceptive inputs to the amygdala.
Functionally critical residues in the aminoglycoside resistance-associated methyltransferase RmtC play distinct roles in 30S substrate recognition

Methylation of the small ribosome subunit rRNA in the ribosomal decoding center results in exceptionally high-level aminoglycoside resistance in bacteria. Enzymes that methylate 16S rRNA on N7 of nucleotide G1405 (m7G1405) have been identified in both aminoglycoside-producing and clinically drug-resistant pathogenic bacteria. Using a fluorescence polarization 30S-binding assay and a new crystal structure of the methyltransferase RmtC at 3.14 Å resolution, here we report a structure-guided functional study of 30S substrate recognition by the aminoglycoside resistance-associated 16S rRNA (m7G1405) methyltransferases. We found that the binding site for these enzymes in the 30S subunit directly overlaps with that of a second family of aminoglycoside resistance-associated 16S rRNA (m1A1408) methyltransferases, suggesting that both groups of enzymes may exploit the same conserved rRNA tertiary surface for docking to the 30S. Within RmtC, we defined an N-terminal domain surface, comprising basic residues from both the N1 and N2 subdomains, that directly contributes to 30S-binding affinity. In contrast, additional residues lining a contiguous adjacent surface on the C-terminal domain were critical for 16S rRNA modification but did not directly contribute to the binding affinity. The results from our experiments define the critical features of m7G1405 methyltransferase–substrate recognition and distinguish at least two distinct, functionally critical contributions of the tested enzyme residues: 30S-binding affinity and stabilizing a binding-induced 16S rRNA conformation necessary for G1405 modification. Our study sets the scene for future high-resolution structural studies of the 30S-methyltransferase complex and for potential exploitation of unique aspects of substrate recognition in future therapeutic strategies.
Bitopertin, a selective oral GLYT1 inhibitor, improves anemia in a mouse model of beta-thalassemia.

Anemia of β-thalassemias is caused by ineffective erythropoiesis and reduced red cell survival. Several lines of evidence indicate that iron/heme restriction is a potential therapeutic strategy for the disease. Glycine is a key initial substrate for heme and globin synthesis. We provide evidence that bitopertin, a glycine transport inhibitor administered orally, improves anemia, reduces hemolysis, diminishes ineffective erythropoiesis, and increases red cell survival in a mouse model of β-thalassemia (Hbbth3/+ mice). Bitopertin ameliorates erythroid oxidant damage as indicated by a reduction in membrane-associated free α-globin chain aggregates, in reactive oxygen species cellular content, in membrane-bound hemichromes and in HRI activation and elF2α phosphorylation. The improvement of β-thalassemic ineffective erythropoiesis is associated with diminished mTOR activation, Rab5, Lamp1, and p62 accumulation, indicating an improved autophagy. Bitopertin also upregulates liver hepcidin and diminishes liver iron overload. The hematologic improvements achieved by bitopertin are blunted by the concomitant administration of the iron chelator deferiprone, suggesting that an excessive restriction of iron availability might negate the beneficial effects of bitopertin. These data provide important and clinically relevant insights into glycine restriction and reduced heme synthesis strategies for the treatment of β-thalassemia.
Dimensional reduction in networks of non-Markovian spiking neurons: Equivalence of synaptic filtering and heterogeneous propagation delays

Message passing between components of a distributed physical system is non-instantaneous and contributes to determine the time scales of the emerging collective dynamics. In biological neuron networks this is due in part to local synaptic filtering of exchanged spikes, and in part to the distribution of the axonal transmission delays. How differently these two kinds of communication protocols affect the network dynamics is still an open issue due to the difficulties in dealing with the non-Markovian nature of synaptic transmission. Here, we develop a mean-field dimensional reduction yielding to an effective Markovian dynamics of the population density of the neuronal membrane potential, valid under the hypothesis of small fluctuations of the synaptic current. Within this limit, the resulting theory allows us to prove the formal equivalence between the two transmission mechanisms, holding for any synaptic time scale, integrate-and-fire neuron model, spike emission regimes and for different network states even when the neuron number is finite. The equivalence holds even for larger fluctuations of the synaptic input, if white noise currents are incorporated to model other possible biological features such as ionic channel stochasticity.
Triggered all-active metal organic framework: Ferroptosis machinery contributes to the apoptotic photodynamic antitumor therapy.

Nanoscale photodynamic therapy (PDT) is an appealing antitumor modality for which apoptosis is the major mechanism of toxicity induction. It was postulated that the highly reactive singlet oxygen in PDT could deplete glutathione (GSH) and activate ferroptosis, the extent to which could be further manipulated by a redox-responsive nanocarrier. To validate this, a disulfide-bearing imidazole ligand coordinated with zinc to form an all-active metal organic framework (MOF) nanocarrier where a photosensitizer (chlorin e6/Ce6) was encapsulated. Regardless of light irradiation, the Ce6-loaded nanocarrier caused the depletion of intracellular GSH via the disulfide-thiol exchange reaction in a murine mammary carcinoma cell line (4T1). The GSH depletion further caused the inactivation of glutathione peroxide 4 (GPX4) and the enhancement of cytotoxicity that was alleviated by ferroptosis inhibitors. The superior in vivo antitumor efficacy of the all-active nanocarrier was corroborated in a 4T1 tumor-bearing mice model regarding tumor growth suppression and animal survival rate. The co-administration of an iron chelator weakened the antitumor potency of nanocarrier due to ferroptosis inhibition, which was supported by the fact of tumor growth upsurge and the recovered GPX4 activity. The current work highlights the contribution of ferroptotic machinery to antitumor PDT via an activatable, adaptable, all-active MOF nanocarrier.
State School Policies as Predictors of Physical and Mental Health: A Natural Experiment in the REGARDS Cohort.

We used differences in state school policies as natural experiments to evaluate the joint influence of educational quantity and quality on late-life physical and mental health. Using US census microsample data, historical measures of state compulsory schooling and school quality (term length, student-teacher ratio, and attendance rates) were combined via regression modeling on a scale corresponding to years of education (Policy Predicted Years of Education [PPYEd]). PPYEd values were linked to individual-level records for 8,920 black and 14,605 white participants aged 45+ in the REasons for Geographic and Racial Differences in Stroke study (2003-2007). Linear and quantile regression models estimated the association between PPYEd and Physical Component Summary (PCS) and Mental Component Summary (MCS) from the Short Form Health Survey. Models examined interactions by race and included adjustment for sex, birth year, state-of-residence at age 6, and year of study enrollment. Higher PPYEd was associated with better median PCS (β=1.28; 95%CI: 0.40,1.49) and possibly better median MCS (β=0.46; 95%CI:-0.01,0.94). Effect estimates were higher in blacks than whites (PCS x race interaction-β=0.22; 95%CI:-0.62,1.05) (MCS x race interaction-β=0.18; 95%CI:-0.08,0.44). When incorporating both school quality and duration, this quasi-experimental analysis found mixed evidence for a causal effect of education on health decades later.
Surface Processing Facilities for Superconducting RF Cavities at ANL

New SRF cavity processing systems at ANL, including those for electropolishing (EP), high-pressure water rinsing (HPR), and single-cavity clean room assembly have been developed and operated at ANL for use with cavities for a range of electron and ion linac applications. Jointly with FNAL, systems for 1.3 GHz singleand multi-cell elliptical cavities for the linear collider effort have been developed. New systems for use with low-beta TEM-class cavities have also been built and used to process a set of six quarter-wave resonators as part of an upgrade to the ATLAS heavy-ion accelerator at ANL. All of the new hardware is located in a 200 m joint ANL/FNAL Superconducting Cavity Surface Processing Facility (SCSPF) consisting of two separate chemical processing rooms, a clean anteroom, and a pair of class 10 and 100 clean rooms for HPR and cavity assembly. First cold tests results for elliptical cavities processed in these facilities are discussed.
A Gesture Recognition System Based on Time Domain Features and Linear Discriminant Analysis

Surface electromyogram (sEMG) signals have been used to control multifunctional prosthetic hands. Researchers usually focused on the use of several channels with sEMG signals to identify more gestures without limiting the number of sEMG sensors. However, the residual muscles of an amputee are limited. Therefore, the point of a successful recognition system is to decrease the channels of sEMG signals to classify more gestures. To achieve this goal, we proposed a novel gesture recognition system, in which three channels of sEMG signals can classify nine gestures. In this recognition system, the time domain features, root mean square ratio, and autoregressive model, were selected to extract the features of the sEMG signals as compared with the time–frequency domain features. Furthermore, the linear discriminant analysis was adopted as the classifier. Consequently, the average accuracy rate of the presented system was 91.7%. Therefore, the proposed gesture recognition system is feasible to identify more gestures with less sensors.
Performance analysis of K-tier cellular networks with time-switching energy harvesting

Dense heterogeneous cellular networks (HCNs) with energy harvesting nodes are promising solutions to meet both the capacity and energy efficiency needs in the next generation cellular networks. This paper studies the system performance of both energy harvesting and information receiving in a K-tier cellular networks with time-switching simultaneous wireless information and power transfer (SWIPT). Based on stochastic geometry theory, we derive the closed-form formulas for the average harvested energy, the average transmission rate and the total power and information gains. Moreover, we propose a scheme that can optimally adjust the bias factors of tier selection while leveraging the system between energy harvesting and information receiving.
Non-Linear Control Strategies for Musculoskeletal Robots

Recently, focus has shifted to more human-friendly robots, especially in the field of service or rehabilitation robotics, where research aims at bringing robots into increasingly unstructured environments. In this work, modern techniques from non-linear control are employed to develop a control framework for the class of musculoskeletal robots. The developed control framework, comprising several different controller types, was evaluated on a robot arm that was developed to cover the control challenges of this type of robot.
Design of Wide-band Power Amplifier based on Power Combiner Technique with Low Intermodulation Distortion

RF power amplifiers are one of challenging blocks in designing radio frequency transceivers, this is due to non-linearity behavior of power amplifiers that leads to inter-modulation distortion. This paper presents the design of wide-band power amplifier which combined with parallel coupled line band pass filter at the input and output of power amplifier to allow the only required frequency band to pass through the power amplifier. Class-A topology and ATF-511P8 transistor are used in this design. Advanced Design System software used as a simulation tool to simulate the designed wide-band power amplifier. The simulation results showed an input return loss (S11) which less than -10dB, and gain (S21) is higher than 10 dB over the entire frequency band and considers as flat as well. The designed amplifier is stable over the bandwidth (K>1). Inter-modulation distortion is -56.919dBc which is less than -50dBc with 10dBm input power. The designed amplifier can be used for the microwave applications which include weather radar, satellite communication, wireless networking, mobile, and TV.