Miracle-dz/UniFAR-FTUs huggingface dataset:
The ns12.9 Accessory Protein of Human Coronavirus OC43 Is a Viroporin Involved in Virion Morphogenesis and Pathogenesis

ABSTRACT An accessory gene between the S and E gene loci is contained in all coronaviruses (CoVs), and its function has been studied in some coronaviruses. This gene locus in human coronavirus OC43 (HCoV-OC43) encodes the ns12.9 accessory protein; however, its function during viral infection remains unknown. Here, we engineered a recombinant mutant virus lacking the ns12.9 protein (HCoV-OC43-Δns12.9) to characterize the contributions of ns12.9 in HCoV-OC43 replication. The ns12.9 accessory protein is a transmembrane protein and forms ion channels in both Xenopus oocytes and yeast through homo-oligomerization, suggesting that ns12.9 is a newly recognized viroporin. HCoV-OC43-Δns12.9 presented at least 10-fold reduction of viral titer in vitro and in vivo. Intriguingly, exogenous ns12.9 and heterologous viroporins with ion channel activity could compensate for the production of HCoV-OC43-Δns12.9, indicating that the ion channel activity of ns12.9 plays a significant role in the production of infectious virions. Systematic dissection of single-cycle replication revealed that ns12.9 protein had no measurable effect on virus entry, subgenomic mRNA (sgmRNA) synthesis, and protein expression. Further characterization revealed that HCoV-OC43-Δns12.9 was less efficient in virion morphogenesis than recombinant wild-type virus (HCoV-OC43-WT). Moreover, reduced viral replication, inflammatory response, and virulence in HCoV-OC43-Δns12.9-infected mice were observed compared to the levels for HCoV-OC43-WT-infected mice. Taken together, our results demonstrated that the ns12.9 accessory protein functions as a viroporin and is involved in virion morphogenesis and the pathogenesis of HCoV-OC43 infection. IMPORTANCE HCoV-OC43 was isolated in the 1960s and is a major agent of the common cold. The functions of HCoV-OC43 structural proteins have been well studied, but few studies have focused on its accessory proteins. In the present study, we demonstrated that the ns12.9 protein is a newly recognized viroporin, and the ns12.9 gene knockout virus (HCoV-OC43-Δns12.9) presents a growth defect in vitro and in vivo. We identified the important functions of the ns12.9 viroporin in virion morphogenesis during HCoV-OC43 infection. Furthermore, mice infected with HCoV-OC43-Δns12.9 exhibited reduced inflammation and virulence accompanied by a lower titer in the brain than that of wild-type-infected mice, suggesting the ns12.9 viroporin influences virus pathogenesis. Therefore, our findings revealed that the ns12.9 viroporin facilitates virion morphogenesis to enhance viral production, and these results provided a deeper understanding of HCoV-OC43 pathogenesis.
Phage-Type RNA Polymerase RPOTmp Performs Gene-Specific Transcription in Mitochondria of Arabidopsis thaliana[W][OA]

Transcription of mitochondrial genes in animals, fungi, and plants relies on the activity of T3/T7 phage-type RNA polymerases. Two such enzymes, RPOTm and RPOTmp, are present in the mitochondria of eudicotyledonous plants; RPOTmp is additionally found in plastids. We have characterized the transcriptional role of the dual-targeted RNA polymerase in mitochondria of Arabidopsis thaliana. Examination of mitochondrial transcripts in rpoTmp mutants revealed major differences in transcript abundances between wild-type and rpoTmp plants. Decreased levels of specific transcripts were correlated with reduced abundances of the respiratory chain complexes I and IV. Altered transcript levels in rpoTmp were found to result from gene-specific transcriptional changes, establishing that RPOTmp functions in distinct transcriptional processes within mitochondria. Decreased transcription of specific genes in rpoTmp was not associated with changes in promoter utilization; therefore, RPOTmp function is not promoter specific but gene specific. This implies that additional gene-specific elements direct the transcription of a subset of mitochondrial genes by RPOTmp.
Cytometry of DNA replication and RNA synthesis: Historical perspective and recent advances based on “click chemistry”

This review covers progress in the development of cytometric methodologies designed to assess DNA replication and RNA synthesis. The early approaches utilizing autoradiography to detect incorporation of 3H‐ or 14C‐labeled thymidine were able to identify the four fundamental phases of the cell cycle G1, S, G2, and M, and by analysis of the fraction of labeled mitosis (FLM), to precisely define the kinetics of cell progression through these phases. Analysis of 3H‐uridine incorporation and RNA content provided the means to distinguish quiescent G0 from cycling G1 cells. Subsequent progress in analysis of DNA replication was based on the use of BrdU as a DNA precursor and its detection by the quenching of the fluorescence intensity of DNA‐bound fluorochromes such as Hoechst 33358 or acridine orange as measured by flow cytometry. Several variants of this methodology have been designed and used in studies to detect anticancer drug‐induced perturbations of cell cycle kinetics. The next phase of method development, which was particularly useful in studies of the cell cycle in vivo, including clinical applications, relied on immunocytochemical detection of incorporated halogenated DNA or RNA precursors. This approach however was hampered by the need for DNA denaturation, which made it difficult to concurrently detect other cell constituents for multiparametric analysis. The recently introduced “click chemistry” approach has no such limitation and is the method of choice for analysis of DNA replication and RNA synthesis. This method is based on the use of 5‐ethynyl‐2′deoxyuridine (EdU) as a DNA precursor or 5‐ethynyluridine (EU) as an RNA precursor and their detection with fluorochrome‐tagged azides utilizing a copper (I) catalyzed [3+2] cycloaddition. Several examples are presented that illustrate incorporation of EdU or EU in cells subjected to DNA damage detected as histone H2AX phosphorylation that have been analyzed by flow or laser scanning cytometry. © 2011 International Society for Advancement of Cytometry
Structure and solid solution properties of Cu–Ag nanoalloys

The nanoparticle phase diagram of an immiscible system is studied at the atomic level. Cu–Ag clusters with sizes 1000 and 2000 atoms, resulting from a global minimum search and belonging to icosahedral and crystalline structural motifs, are considered. We present the statistical analysis of the effect of temperature on the solubility of the two elements based on Metropolis Monte Carlo importance sampling. Our results suggest that the relevance of bulk phase diagrams to nanoparticles is limited to cases where the internal stress distribution does not deviate very much from uniform (e.g. sufficiently large crystalline clusters). In the general case, the principal interdependence between partial phase compositions and the overall cluster composition in nanoparticle phase diagrams need to be taken into account.
Co‐Transplantation of Adipose Tissue‐Derived Stromal Cells and Olfactory Ensheathing Cells for Spinal Cord Injury Repair

Patients suffering from spinal cord injury (SCI) still have a dismal prognosis. Despite all the efforts developed in this area, currently there are no effective treatments. Therefore, cell therapies have been proposed as a viable alternative to the current treatments used. Adipose tissue‐derived stromal cells (ASCs) and olfactory ensheathing cells (OECs) have been used with promising results in different models of SCI, namely due to the regenerative properties of the secretome of the first, and the guidance capability of the second. Using an in vitro model of axonal growth, the dorsal root ganglia explants, we demonstrated that OECs induce neurite outgrowth mainly through cell‐cell interactions, while ASCs' effects are strongly mediated by the release of paracrine factors. A proteomic analysis of ASCs' secretome revealed the presence of proteins involved in VEGF, PI3K, and Cadherin signaling pathways, which may be responsible for the effects observed. Then, the cotransplantation of ASCs and OECs showed to improve motor deficits of SCI‐rats. Particular parameters of movement such as stepping, coordination, and toe clearance were improved in rats that received the transplant of cells, in comparison to nontreated rats. A histological analysis of the spinal cord tissues revealed that transplantation of ASCs and OECs had a major effect on the reduction of inflammatory cells close the lesion site. A slight reduction of astrogliosis was also evident. Overall, the results obtained with the present work indicate that the cotransplantation of ASCs and OECs brings important functional benefits to the injured spinal cord. Stem Cells 2018;36:696–708
Occupational exposure to organic solvents and lymphoid neoplasms in men: results of a French case-control study

Objectives Investigating the role of occupational exposure to solvents in the occurrence of lymphoid neoplasms (LNs) in men. Methods The data were generated by a French hospital-based case-control study, conducted in six centres in 2000–2004. The cases were incident cases aged 18–75 years with a diagnosis of LN. During the same period, controls of the same age and gender as the cases were recruited in the same hospitals, mainly in the orthopaedic and rheumatological departments. Exposure to solvents was assessed using standardised occupational questionnaires and case-by-case expert assessment. Specific quantification of benzene exposure was attempted. The analyses included 491 male patients (244 cases of non-Hodgkin's lymphoma (NHL), 87 of Hodgkin's lymphoma, 104 of lymphoproliferative syndrome and 56 of multiple myeloma) and 456 male controls. Unconditional logistic regressions were used to estimate OR and 95% CI. Results Solvent exposure, all solvents considered together, was marginally associated with NHL (OR=1.4 (1.0 to 2.0) p=0.06), but not with other LNs. No association with the main chemical series of solvents was observed. There was no trend with the average intensity or frequency of exposure. Exposure to pure benzene was not significantly related to NHL (OR=3.4 (0.8 to 15.0)). The highest maximum intensities of benzene exposure were associated with diffuse large cell lymphoma (OR=2.1 (1.0 to 4.6)). Conclusion The results of the present study provide estimates compatible with the hypothesis that exposures to pure benzene and high benzene intensities may play a role in some NHL. There was no evidence for a role of other organic solvents in the occurrence of LN.
122 GHz aperture-coupled stacked patch microstrip antenna in LTCC technology

An aperture-coupled stacked patch microstrip antenna based on Low-Temperature Co-fired Ceramic (LTCC) technology is presented in this paper. Inspite of using an antenna substrate with high permittivity of 7.1 and only 200 μm thickness, wide bandwidth characteristic is achieved by means of coupled resonances. The antenna physical features contributing to the coupled resonances include a rectangular aperture, two stacked patches and a double via fence. The influence of various antenna parameters is analyzed in order to optimize the antenna design. The measured antenna reflection coefficient and gain shows good agreement with the simulation results, thus verifying the future potential for integrating this off-chip antenna with a Millimeter-Wave Integrated Circuit (MMIC) placed in an LTCC air cavity, for realization of a 122 GHz fully integrated, low-cost and surface mountable LTCC Antenna-in-Package.
Determinants of Expatriate Knowledge Transfer Performance: A Social Capital Perspective

Although expatriation is increasingly regarded as a vital means for enhancing knowledge diffusion within multinational companies, it has also precluded an in-depth examination of particular inputs to individual performance in knowledge transferring. Drawing upon social capital theory, a model of expatriate knowledge transfer effectiveness in term of knowledge transfer, relational development and task performance, was developed and tested using a sample of 147 expatriate managers working in Hong Kong, Beijing and Shanghai. This model predicts that depth of relationship with host country nationals (HCNs) and access to information and resources (network configuration), trust and instrumental support received (social norm), and HCN's cultural empathy (ability) have direct effects on expatriate knowledge transfer effectiveness. Given the exploratory nature of this research, we hypothesize that all forms of social capital will influence expatriate performance. Results showed the social capital variables were strong predictors of expatriate knowledge transfer performance. Depth of relation, access to information and resources, HCN's cultural empathy had significant direct effects on various dimensions of performance (i.e., knowledge transfer, relational development and knowledge transfer), but the social norm constructs (i.e., trust and instrumental support received) were not found the supports as expected. Implications of these findings and directions for future research are provided
Predictive Value of Individualized Tumor Response Testing by ATP-Based Chemotherapy Response Assay in Ovarian Cancer

The aim of this study is to investigate the correlation between ATP-based chemotherapy response assay (ATP-CRA) results and clinical outcomes in ovarian cancer. Twenty-nine fresh tumor specimens were collected. Tumor cells were isolated and cultured for 48 hrs in medium containing anticancer drugs. The median age of patients was 56 years. The sensitivity, positive predictive value, and accuracy of ATP-CRA were respectively 94.1%, 94.1%, and 90.0%. There was a significant relationship between ATP-CRA results and clinical responses (p = 0.046). This study suggests that ATP-CRA has high sensitivity, positive predictive value, and accuracy for predicting response to chemotherapy in ovarian cancer.
Targeted therapy is required for management of pulmonary arterial hypertension after defect closure in adult patients with atrial septal defect and associated pulmonary arterial hypertension.

BACKGROUND Therapeutic strategies for pulmonary arterial hypertension (PAH) associated with atrial septal defect (ASD) remain a matter of debate. METHODS AND RESULTS We identified 5 outpatients who had been diagnosed with ASD-PAH and undergone ASD closure in combination with targeted therapy with certified PAH drugs. We assessed changes in hemodynamic parameters and exercise capacity. The combination of ASD closure and targeted therapy significantly increased systemic blood flow (Qs) from the baseline (from 3.3 ± 0.6 L/minute to 4.2 ± 1.0 L/minute, P < 0.05) with a significant improvement in the World Health Organization Functional Class (WHO-FC; from 2.8 ± 0.4 to 1.6 ± 0.5, P < 0.05). The hemodynamic data before and after ASD closure without targeted therapy showed further elevation of pulmonary vascular resistance shortly after ASD closure (678 dyne · s/cm(5) to 926 dyne · s/cm(5)) in 1 case, as well as after a long time since ASD closure (491.0 ± 53.7 dyne · s/cm(5) to 1045.0 ± 217.8 dyne · s/cm(5)) in 2 cases. This worsening was reversed after the targeted therapy, accompanied by an increase in Qs and an improvement in WHO-FC in all cases. CONCLUSIONS Targeted therapy should be added to ASD closure in adult patients with ASD-PAH.
Meat and fat intake as risk factors for pancreatic cancer: the multiethnic cohort study.

BACKGROUND Meat intake has been associated with risk of exocrine pancreatic cancer, but previous findings have been inconsistent. This association has been attributed to both the fat and cholesterol content of meats and to food preparation methods. We analyzed data from the prospective Multiethnic Cohort Study to investigate associations between intake of meat, other animal products, fat, and cholesterol and pancreatic cancer risk. METHODS During 7 years of follow-up, 482 incident pancreatic cancers occurred in 190,545 cohort members. Dietary intake was assessed using a quantitative food frequency questionnaire. Associations for foods and nutrients relative to total energy intake were determined by Cox proportional hazards models stratified by gender and time on study and adjusted for age, smoking status, history of diabetes mellitus and familial pancreatic cancer, ethnicity, and energy intake. Statistical tests were two-sided. RESULTS The strongest association was with processed meat; those in the fifth quintile of daily intake (g/1000 kcal) had a 68% increased risk compared with those in the lowest quintile (relative risk = 1.68, 95% confidence interval = 1.35 to 2.07; Ptrend < .01). The age-adjusted yearly incidence rates per 100,000 persons for the respective quintiles were 41.3 and 20.2. Intakes of pork and of total red meat were both associated with 50% increases in risk, comparing the highest with the lowest quintiles (both Ptrend < .01). There were no associations of pancreatic cancer risk with intake of poultry, fish, dairy products, eggs, total fat, saturated fat, or cholesterol. Intake of total and saturated fat from meat was associated with statistically significant increases in pancreatic cancer risk but that from dairy products was not. CONCLUSION Red and processed meat intakes were associated with an increased risk of pancreatic cancer. Fat and saturated fat are not likely to contribute to the underlying carcinogenic mechanism because the findings for fat from meat and dairy products differed. Carcinogenic substances related to meat preparation methods might be responsible for the positive association.
Current and Future Preparative Regimens for Bone Marrow Transplantation in Thalassemia a

Abstract: Preparative regimens for marrow allografts in thalassemia have two objectives. One is eradication of diseased marrow and the other suppression of host‐versus‐graft (HVG) reactions so that the allograft survives. A common regimen to accomplish these goals has combined high‐dose busulfan with cyclophosphamide. Postgrafting immunosuppression with cyclosporine/methotrexate has been used for GVHD prevention. Some patients may die from regimen‐related toxicity. Overall event‐free survival is 75%. Occasional patients have become mixed donor/host hematopoietic chimeras and, yet, disease symptoms have abated. This has raised the possibility of developing safer and less toxic transplant programs that result in stable mixed hematopoietic chimerism. We have devised such a program in dogs consisting of a nonlethal dose of total body irradiation (200 cGy) before and a novel combination of mycophenolate mofetil and cyclosporine after transplant. Mixed donor/host chimerism (≥ 50% donor cells in all lineages) has persisted for > 80 weeks, even though immunosuppression was discontinued after five weeks.
Etomidate is Associated With Longer Seizure Duration, Lower Stimulus Intensity, and Lower Number of Failed Trials in Electroconvulsive Therapy Compared With Thiopental

Objective Induction agents used for electroconvulsive therapy (ECT) may alter seizure parameters. In this study, we aimed to investigate the effects of etomidate and thiopental on seizure-related variables. Methods Registries of patients who received ECT between 2010 and 2013 in a tertiary psychiatry clinic were evaluated retrospectively. The information of patients who were on the same induction agent and muscle relaxant during the whole treatment course was assessed. Primary outcome measures were total number of ECT sessions, mean peripheral and central seizure duration, cumulative stimulus intensity, and the number of adequate seizures per total number of stimuli. Secondary measures were maximum systolic-diastolic and mean blood pressure, peak heart rate, and the frequency of antihypertensive drug use during the sessions. Results Although the total number of ECT sessions is similar between the etomidate (n = 43) and thiopenthal (n = 31) groups, the mean seizure duration per stimuli was significantly longer whereas the cumulative stimulus intensity was lower in the etomidate group. The number of adequate seizures obtained in relation with the number of stimuli was also significantly higher, indicating increased probability of eliciting an adequate seizure with etomidate. During threshold determination, the number of stimuli needed to provide an adequate seizure was marginally less with etomidate. No group difference was observed in hemodynamic changes and the frequency of antihypertensive use. Conclusions Etomidate use, compared with thiopental as an induction agent, is associated with longer seizure duration with less cumulative intensity. The use of etomidate reduces the number of failed trials and may prevent the application of unnecessary electrical stimuli with a possibly safe hemodynamic profile.
Interaction of Notch Signaling Modulator Numb with α-Adaptin Regulates Endocytosis of Notch Pathway Components and Cell Fate Determination of Neural Stem Cells*

Background: Numb/Notch signaling is essential for NSC self-renewal. How Numb works is not well defined. Results: Numb interacts with α-Adaptin through newly defined domains to regulate the endocytosis of Notch pathway components. Conclusion: Endocytosis is critically involved in balancing the self-renewal versus differentiation choice of NSCs. Significance: Aberrant Numb/Notch signaling has been associated with tumorigenesis. Results from this study have important implications for cancer biology. The ability to balance self-renewal and differentiation is a hallmark of stem cells. In Drosophila neural stem cells (NSCs), Numb/Notch (N) signaling plays a key role in this process. However, the molecular and cellular mechanisms underlying Numb function in a stem cell setting remain poorly defined. Here we show that α-Adaptin (α-Ada), a subunit of the endocytic AP-2 complex, interacts with Numb through a new mode of interaction to regulate NSC homeostasis. In α-ada mutants, N pathway component Sanpodo and the N receptor itself exhibited altered trafficking, and N signaling was up-regulated in the intermediate progenitors of type II NSC lineages, leading to their transformation into ectopic NSCs. Surprisingly, although the Ear domain of α-Ada interacts with the C terminus of Numb and is important for α-Ada function in the sensory organ precursor lineage, it was dispensable in the NSCs. Instead, α-Ada could regulate Sanpodo, N trafficking, and NSC homeostasis by interacting with Numb through new domains in both proteins previously not known to mediate their interaction. This interaction could be bypassed when α-Ada was directly fused to the phospho-tyrosine binding domain of Numb. Our results identify a critical role for the AP-2-mediated endocytosis in regulating NSC behavior and reveal a new mechanism by which Numb regulates NSC behavior through N. These findings are likely to have important implications for cancer biology.
Classify Participants in Online Communities

As online communities become increasingly popular, researchers have tried to examine participating activities in online communities as well as how to sustain online communities. However, relatively few studies have tried to understand what kinds of participants constitute online communities. In this study, we try to contribute online community research by developing "common language" to classify different participants in online communities. Specifically, we argue that the previous way to classify participants is not sufficient and accurate, and we propose a continuum to classify participants based on participants' overall trend of posting activities. In order to further online community research, we also propose potential directions for future studies.