Miracle-dz/UniFAR-FTUs huggingface dataset:
Role of N-Linked Glycans in the Functions of Hepatitis C Virus Envelope Glycoproteins

ABSTRACT Hepatitis C virus (HCV) encodes two viral envelope glycoproteins. E1 contains 4 or 5 N-linked glycosylation sites and E2 contains up to 11, with most of the sites being well conserved, suggesting that they play an essential role in some functions of these proteins. For this study, we used retroviral pseudotyped particles harboring mutated HCV envelope glycoproteins to study these glycans. The mutants were named with an N followed by a number related to the relative position of the potential glycosylation site in each glycoprotein (E1N1 to E1N4 for E1 mutants and E2N1 to E2N11 for E2 mutants). The characterization of these mutants allowed us to define three phenotypes. For the first group (E1N3, E2N3, E2N5, E2N6, E2N7, and E2N9), the infectivities of the mutants were close to that of the wild type. The second group (E1N1, E1N2, E1N4, E2N1, and E2N11) contained mutants that were still infectious but whose infectivities were reduced to <50% that of the wild type. The third group (E2N2, E2N4, E2N8, and E2N10) contained mutants that had almost totally lost infectivity. The absence of infectivity of the E2N8 and E2N10 mutants was due to the lack of incorporation of the E1E2 heterodimer into HCVpp, which was due to misfolding of the heterodimer, as shown by immunoprecipitation with conformation-sensitive antibodies and by a CD81 pull-down assay. The absence of infectivity of the E2N2 and E2N4 mutants indicated that these two glycans are involved in controlling HCV entry. Altogether, the data indicate that some glycans of HCV envelope glycoproteins play a major role in protein folding and others play a role in HCV entry.
Cerebral Hemodynamic Reserve and Early Neurologic Deterioration in Acute Ischemic Stroke

Early neurological deterioration (END) is associated with increased mortality and morbidity. Although several predictive factors have been reported, there are little data about the hemodynamic factors. Our aim was to determine the capacity of cerebral hemodynamic reserve (CHR) to predict END. We studied 100 hospitalized patients with a first ever ischemic stroke of the middle cerebral artery (MCA) within the first 24 hours of symptoms onset. END was defined as a drop of at least one point in the Canadian Stroke Scale between admission and 72 hours. The mean flow velocity (mV) in the MCA and the CHR were measured by means of transcranial Doppler within the first 24 hours of admission. The CHR was expressed as the percentage increase in the MCA mV divided by the absolute increase in the end-tidal CO2 pressure in mm Hg after carbogen inhalation. END was observed in 23 patients. Reduced values of the mV in the symptomatic MCA (P = 0.043) and of the CHR in the symptomatic hemisphere (P < 0.001) were significantly associated with END. A CHR of less than 2%/1 mm Hg was independently associated with END (OR 8.45, 95% CI 1.82–39.2) after adjusting for potential confounders. CHR impairment within the first 24 hours of acute ischemic stroke is associated with a higher risk of END. This technique may be useful in selecting patients requiring a more intensive management.
Second-line antiretroviral therapy in resource-limited settings: the experience of Médecins Sans Frontières

Objectives:To describe the use of second-line protease-inhibitor regimens in Médecins Sans Frontières HIV programmes, and determine switch rates, clinical outcomes, and factors associated with survival. Design/Methods:We used patient data from 62 Médecins Sans Frontières programmes and included all antiretroviral therapy-naive adults (> 15 years) at the start of antiretroviral therapy and switched to a protease inhibitor-containing regimen with at least one nucleoside reverse transcriptase inhibitor change after more than 6 months of nonnucleoside reverse transcriptase inhibitor first-line use. Cumulative switch rates and survival curves were estimated using Kaplan–Meier methods, and mortality predictors were investigated using Poisson regression. Results:Of 48 338 adults followed on antiretroviral therapy, 370 switched to a second-line regimen after a median of 20 months (switch rate 4.8/1000 person-years). Median CD4 cell count at switch was 99 cells/μl (interquartile ratio 39–200; n = 244). A lopinavir/ritonavir-based regimen was given to 51% of patients and nelfinavir-based regimen to 43%; 29% changed one nucleoside reverse transcriptase inhibitor and 71% changed two nucleoside reverse transcriptase inhibitors. Median follow-up on second-line antiretroviral therapy was 8 months, and probability of remaining in care at 12 months was 0.86. Median CD4 gains were 90 at 6 months and 135 at 12 months. Death rates were higher in patients in World Health Organization stage 4 at antiretroviral therapy initiation and in those with CD4 nadir count less than 50 cells/μl. Conclusion:The rate of switch to second-line treatment in antiretroviral therapy-naive adults on non-nucleoside reverse transcriptase inhibitor-based first-line antiretroviral therapy was relatively low, with good early outcomes observed in protease inhibitor-based second-line regimens. Severe immunosuppression was associated with increased mortality on second-line treatment.
COPD: a multifactorial systemic disease

Chronic obstructive pulmonary disease (COPD) has traditionally been considered a disease of the lungs secondary to cigarette smoking and characterized by airflow obstruction due to abnormalities of both airway (bronchitis) and lung parenchyma (emphysema). It is now well known that COPD is associated with significant systemic abnormalities, such as renal and hormonal abnormalities, malnutrition, muscle wasting, osteoporosis, and anemia. However, it is still unclear whether they represent consequences of the pulmonary disorder, or whether COPD should be considered as a systemic disease. These systemic abnormalities have been attributed to an increased level of systemic inflammation. Chronic inflammation, however, may not be the only cause of the systemic effects of COPD. Recent data from humans and animal models support the view that emphysema may be a vascular disease. Other studies have highlighted the role of repair failure, bone marrow abnormality, genetic and epigenetic factors, immunological disorders and infections as potential causes of COPD systemic manifestations. Based on this new evidence, it is reasonable to consider COPD, and emphysema in particular, as ‘a disease with a significant systemic component’ if not a ‘systemic disease’ per se. The aim of this review is to give an overview of the most relevant and innovative hypothesis about the extrapulmonary manifestations of COPD.
Do immigrants delay retirement and social security claiming?

ABSTRACT We use data from the Health and Retirement Study (HRS) to examine how immigrants’ retirement and Social Security claiming patterns compare to those of natives. We find that immigrants retire and claim Social Security at older ages than natives, an effect that is similar across immigrant ethnic groups and more pronounced among immigrants who arrived in the U.S. after age 40. We discuss and explore possible mechanisms for these differences. Hazard models suggests that these differences arise because immigrants have lower retirement and claiming hazard rates in their early 60s. We do not find evidence of an increase in the rate at which immigrants move abroad or exit the survey, compared to U.S. natives, in their late 50s through 60s, a finding that is consistent with immigrants retiring in the U.S. rather than abroad. These results are important given the rising share of older immigrants living in the U.S., and they have implications for the impact of immigration on government finances as well as the retirement security of an important subgroup of the population.
Efeitos da Avaliação de Desempenho na Performance Gerencial Mediada pelo Feedback e Sistema de Recompensas

Objetivo : Este estudo analisa os efeitos da avaliacao de desempenho na performance gerencial mediada pelo feedback e pelo sistema de recompensas. Metodo : Uma survey foi realizada com 194 gestores de empresas brasileiras listadas entre as Melhores & Maiores da Revista Exame de 2016 e um modelo estrutural foi proposto para testar as hipoteses da pesquisa. Originalidade / relevância : A pesquisa denota que diferentes tipos de controles de um Performance Measurement Systems (PMS) estao associados entre si, e que contribuem de maneiras distintas e complementares na explicacao da performance gerencial. O sistema de recompensas foi o construto que se destacou na explicacao da relacao entre avaliacao de desempenho e performance gerencial. A relevância do estudo esta na investigacao simultânea de multiplos sistemas de controle de um PMS, o que pode contribuir para entender a relacao entre eles e seus efeitos no desempenho. Resultados : Os resultados da pesquisa indicam que a avaliacao de desempenho tem efeito direto no feedback e no sistema de recompensas e indireto na performance dos gestores. O maior efeito indireto da avaliacao de desempenho na performance gerencial via sistema de recompensas pode ser oriundo do desenho do PMS adotado pelas empresas pesquisadas, em que predominam bonus, compensacoes e sancoes. Contribuicoes teoricas / metodologicas : Este estudo contribui para o corpo da literatura que examina os efeitos do PMS no desempenho individual em detrimento do desempenho organizacional. Contribui tambem para a lacuna de pesquisas relativas ao sistema de recompensas e desempenho individual, ja que estudos anteriores apresentaram entendimentos distintos quanto aos seus efeitos.
LocaLisa Catheter Navigation Reduces Fluoroscopy Time and Dosage in Ablation of Atrial Flutter:

Introduction: Catheter ablation has become a well‐established therapy for isthmus‐dependent right atrial flutter (AFL). Recently, mapping and ablation of AFL have been performed using sophisticated three‐dimensional mapping systems, such as electroanatomic and noncontact mapping systems. The LocaLisa system enables nonfluoroscopic navigation of intracardiac electrode catheters based on impedance changes related to catheter movements in transthoracic current fields. The aim of this randomized prospective study was to compare the efficacy of the LocaLisa system with the conventional mapping/ablation approach for radiofrequency ablation of AFL.
Cytomegalovirus viremia associated with death or retransplantation in pediatric lung-transplant recipients

Background. Cytomegalovirus (CMV) infection is a frequent complication of lung transplantation. However, there is limited information regarding the incidence and sequelae of CMV infections in pediatric lung-transplant recipients. On the basis of case series suggesting that CMV infection was associated with excess morbidity and mortality in lung-transplant recipients, we hypothesize that CMV viremia increases the risk of bronchiolitis obliterans (BOS) or death and retransplantation in the first year following transplantation. Methods. A case-cohort study of pediatric primary lung-transplant recipients was performed. Univariate analysis was used to assess whether CMV viremia was associated with BOS or death and retransplantation within 1 year after transplantation. Patients at high risk for CMV infection received ganciclovir prophylaxis for 42 days posttransplantation. Results. From July 1990 to November 2000, 194 pediatric patients received primary lung transplants. Twenty-three percent of patients developed CMV viremia. Eighty percent of CMV viremia episodes occurred before 120 days posttransplant. A first episode of CMV viremia was associated with retransplantation or death between days 90 and 365 (RR=4.1, 95% confidence interval [CI] 1.1–14.5) and was not associated with BOS (RR=1.3, 95% CI 0.5–3.3). Conclusions. CMV viremia in the first year after pediatric primary lung transplantation is associated with increased risk of death or retransplantation between 90 and 365 days posttransplant, when CMV prophylaxis has stopped. A phase II pilot trial is warranted to assess safety and short-term efficacy of increasing the duration of CMV prophylaxis from 42 to 120 days.
Particulate Matter (PM) Exposure Assessment—Horizontal and Vertical PM Profiles in Relation to Agricultural Activities and Environmental Factors in Farm Fields

Reports profiling airborne particulate matter (PM) in farm fields, especially during a Class B biosolids land-injection process, are scarce. Thus, this study characterized PM in such a farm field located in northwest Ohio. For comparison, a control farm field with no biosolids application history was also monitored. During 11 days of varied agricultural activities, the concentrations of particle mass and number (count) and also metal content were monitored in the study field, and their interactions with environmental factors were examined. The monitoring was performed across the farm field at four heights of 0.5, 1.5, 2.5, and 3.5 m from the ground. The overall mean (SD) concentration (μg/m3) of respirable suspended particulate matter (RPM) was 30.8 (23.1) with means ranging from 15.9 (3.80) during post-tilling Event 1, 19.9 (12.4) during biosolids application to 56.1 (11.7) during post-harvest (including baling) activity. The maximum concentration of RPM (μg/m3) was 43 during biosolids application, 90 during post-harvest, and 183 during post-tilling Event 2 activities. Overall, 93.7% (8.98%) of the total suspended particulate matter (TPM) was respirable. The levels of RPM significantly (p < 0.01) correlated with TPM and particle counts of ultrafine particles (UFP) and 0.3 μm particle size. Ambient temperature showed no effect, whereas wind speed and relative humidity had an inverse effect on RPM concentration. Particle concentrations changed minimally during each set of monitoring across the field, except during major activities or sudden weather changes. For particles with sizes of 2, 5, and 10 μm, the counts decreased with increasing height from the ground and were significantly (p < 0.05) higher at 0.5 m than at other heights. The levels of nine metals within particles monitored were well below current recommended occupational exposure criteria. These results suggest that injection of the biosolids into agricultural land provides significant protection against exposure to biosolids particles.
X-ray and Cryo-electron Microscopy Structures of Monalysin Pore-forming Toxin Reveal Multimerization of the Pro-form*

Background: Monalysin is a β-barrel pore-forming toxin secreted by Pseudomonas entomophila. Results: Monalysin structure belongs to the Aerolysin fold family but is devoid of receptor-binding domain; pro-Monalysin forms a stable 18-mer complex. Conclusion: The delivery of 18 subunits may bypass the requirement of receptor-dependent concentration. Significance: The functional mechanism of Monalysin differs from that of described Aerolysin family members. β-Barrel pore-forming toxins (β-PFT), a large family of bacterial toxins, are generally secreted as water-soluble monomers and can form oligomeric pores in membranes following proteolytic cleavage and interaction with cell surface receptors. Monalysin has been recently identified as a β-PFT that contributes to the virulence of Pseudomonas entomophila against Drosophila. It is secreted as a pro-protein that becomes active upon cleavage. Here we report the crystal and cryo-electron microscopy structure of the pro-form of Monalysin as well as the crystal structures of the cleaved form and of an inactive mutant lacking the membrane-spanning region. The overall structure of Monalysin displays an elongated shape, which resembles those of β-pore-forming toxins, such as Aerolysin, but is devoid of a receptor-binding domain. X-ray crystallography, cryo-electron microscopy, and light-scattering studies show that pro-Monalysin forms a stable doughnut-like 18-mer complex composed of two disk-shaped nonamers held together by N-terminal swapping of the pro-peptides. This observation is in contrast with the monomeric pro-form of the other β-PFTs that are receptor-dependent for membrane interaction. The membrane-spanning region of pro-Monalysin is fully buried in the center of the doughnut, suggesting that upon cleavage of pro-peptides, the two disk-shaped nonamers can, and have to, dissociate to leave the transmembrane segments free to deploy and lead to pore formation. In contrast with other toxins, the delivery of 18 subunits at once, nearby the cell surface, may be used to bypass the requirement of receptor-dependent concentration to reach the threshold for oligomerization into the pore-forming complex.
Education Stock and its Implication for Income Inequality: The Case of Asian Economies

This study develops a quadratic relationship between education and income inequality among Asian developing economies for the period from 1960 to 2015. Panel cointegration and fully modified OLS is applied for the estimation of long‐run coefficients. The results show that initial, primary, secondary, and tertiary enrollment increases inequality. However, the effect of education on income inequality becomes negative after a certain threshold level (i.e., 97.5% for primary, 43.5% for secondary, and 11% for tertiary). Thus, this result proves the Kuznets phenomenon of an inverted U‐shape relationship for primary, secondary, and tertiary enrollments.
The International Bank Lending Channel of Monetary Policy Rates and QE: Credit Supply, Reach‐for‐Yield, and Real Effects

We identify the international credit channel of monetary policy by analyzing the universe of corporate loans in Mexico, matched with firm and bank balance-sheet data, and by exploiting foreign monetary policy shocks, given the large presence of European and U.S. banks in Mexico. We find that a softening of foreign monetary policy increases the supply of credit of foreign banks to Mexican firms. Each regional policy shock affects supply via their respective banks (for example, U.K. monetary policy affects credit supply in Mexico via U.K. banks), in turn implying strong real effects, with substantially larger elasticities from monetary rates than QE. Moreover, low foreign monetary policy rates and expansive QE increase disproportionally more the supply of credit to borrowers with higher ex ante loan rates--reach-for-yield--and with substantially higher ex post loan defaults, thus suggesting an international risk-taking channel of monetary policy. All in all, the results suggest that foreign QE increases risk-taking in emerging markets more than it improves the real outcomes of firms.
Identification and characterization of a new disulfide isomerase‐like protein (DsbD) in Escherichia coli.

Previous studies have established that DsbA and DsbC, periplasmic proteins of Escherichia coli, are two key players involved in disulfide bond formation. A search for extragenic mutations able to compensate for the lack of dsbA function in vivo led us to the identification of a new gene, designated dsbD. Lack of DsbD protein leads to some, but not all, of the phenotypic defects observed with other dsb mutations, such as hypersensitivity to dithiothreitol and to benzylpenicillin. In addition, unlike the rest of the dsb genes, dsbD is essential for bacterial growth at temperatures above 42 degrees C. Cloning of the wild‐type gene and sequencing and overexpression of the protein show that dsbD is part of an operon and encodes an inner membrane protein. A 138 amino acid subdomain of the protein was purified and shown to possess an oxido‐reductase activity in vitro. Expressing this subdomain in the periplasmic space helped restore the phenotypic defects associated with a dsbD null mutation. Interestingly, this domain shares 45% identity with the portion of the eukaryotic protein disulfide isomerase carrying the active site. We further show that in dsbD mutant bacteria the dithiol active sites of DsbA and DsbC proteins are mostly oxidized, as compared with wild‐type bacteria. Our results argue that DsbD generates a reducing source in the periplasm, which is required for maintaining proper redox conditions. The finding that overexpression of DsbD leads to a Dsb‐ phenotype, very similar to that exhibited by dsbA null mutants, is in good agreement with such a model.
Credibility, audacity and joy: Brand personalities that connect users to social media

The main purpose of this article is to evaluate the influence brand personality has on customer loyalty in the context of social networks as brands. We conducted a survey of 268 social networks users in Brazil and analyzed data through Structural Equation Modeling. As a result, brand personality dimensions Credibility, Audacity and Joy were found to be predictors of loyalty, the main aspect governing customer relationship perception. Credibility is the main predictor of customer loyalty, shedding light on network trustworthiness, user privacy and personal information safety, while Audacity indicates the power of innovation, and Joy points out the relevance of social networks’ entertainment atmospheres. Together, these dimensions are strategic aspects to be considered in the development of relationships with users in the digital world. Our finding contributes to the body of knowledge interested in relationship marketing and its relation with strategy and sustainable competitive advantage. We also investigated social networks as brands, a topic of major impact in the development of a literature on the digital world. Lastly, the results serve as a source of information about social network user behavior, helping companies enhance their communication strategies and achieve customer loyalty.
Impact of sustained deprenyl (selegiline) in levodopa‐treated Parkinson's disease: A randomized placebo‐controlled extension of the deprenyl and tocopherol antioxidative therapy of parkinsonism trial

Deprenyl (selegiline) delays the need for levodopa therapy in patients with early Parkinson's disease, but the long‐term benefits of this treatment remain unclear. During 1987 to 1988, 800 patients with early Parkinson's disease were randomized in the Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism trial to receive deprenyl, tocopherol, combined treatments, or a placebo and were then placed on active deprenyl (10mg/day). A second, independent randomization was carried out in early 1993 for 368 subjects who by that time had required levodopa and who had consented to continuing the deprenyl treatment (D subjects) or changing to a matching placebo (P subjects) under double‐blind conditions. The first development of wearing off, dyskinesias, or on–off motor fluctuations was the prespecified primary outcome measure. During the average 2‐year follow‐up, there were no differences between the treatment groups with respect to the primary outcome measure (hazard ratio, 0.87; 95% confidence interval, 0.63, 1.19; p = 0.38), withdrawal from the study, death, or adverse events. Although 34% of D subjects developed dyskinesias and only 19% of P subjects did (p = 0.006), only 16% of D subjects developed freezing of gait but 29% of P subjects did (p = 0.0003). Decline in motor performance was less in D subjects than P subjects. Levodopa‐treated Parkinson's disease patients who had been treated with deprenyl for up to 7 years, compared with patients who were changed to a placebo after about 5 years, experienced slower motor decline and were more likely to develop dyskinesias but less likely to develop freezing of gait.
Selling War

Manual for Heavy Artillery, for the uee of Volunteer]? Service of Piece—of Guu on Siege Carriage, 8-inch Siege Howitzer—10-inch Siege Mortar—8-inch Siege Mortar— Cocliom Mortar—10-inch Sea-Coast Mortar—13-inch ScaCoaat Mortar—Stone Mortar—Barbette Gun«—Casemate Guns—3-inch Columbians—24 pdr. Howitzer, &c. 1 voL 12mo, plates, red cloth, 75 cent«. Sent free, bv mail, on receipt of price. D. VAN NOSTRAND, Publisher, 102 Broadway.