Miracle-dz/UniFAR-FTUs huggingface dataset:
Cell Surface CD4 Inhibits HIV-1 Particle Release by Interfering with Vpu Activity*

One of the hallmarks of human immunodeficiency virus type I (HIV-1) infection is the rapid removal of the viral receptor CD4 from the cell surface. This remarkably efficient receptor interference requires the activity of three separate viral proteins: Env, Vpu, and Nef. We have investigated whether this unusually tight interference on cell surface CD4 expression had a more essential function during the viral life cycle than simply preventing superinfection. We now report that the removal of cell surface CD4 is required for optimal virus production by HIV-1. Indeed, maintenance of CD4 surface expression in infected cells lead to a 3–5-fold decrease in viral particle production. This effect was not due to the formation of intracellular complexes between CD4 and the gp160 viral envelope precursor but instead required the presence of CD4 at the cell surface and was specifically mediated by CD4 but not closely related plasma membrane receptors. The finding that CD4 had no significant effect on particle release by a Vpu-deficient variant indicates that CD4 acts by inhibiting the particle release-promoting activity of Vpu. Co-immunoprecipitation experiments further showed that CD4 and Vpu physically interact at the cell surface, suggesting that CD4 might inhibit Vpu activity by disrupting its oligomeric structure.
Impact of cultural distance on international destination choices: The case of Chinese outbound travelers

Given the rapid growth of China outbound market, research pertaining to the specificities of this market bears significance to destination marketers and academicians. The focus of this research is on the impact of cultural distance on outbound tourist destination choices with Chinese travelers as the case in point. Based on outbound tourism statistics of China over the 1995–2014 periods, this research has developed an inverted U-curve model to account for the relationship between cultural distance and tourists' destination choice. Results show that the optimal cultural distance for Chinese outbound tourists' destination choice is 2.8757. Through evaluating the positions, potential destinations are located relative to the optimal cultural distance. The preference tourists place on potential destinations can be measured. This research bears valuable theoretical contributions and implications for destination marketing practices.
Adenosine and a related carbocyclic nucleoside analogue selectively inhibit tumor necrosis factor-alpha production and protect mice against endotoxin challenge.

Adenosine (ADO) and its structurally related analogues are known to regulate the activities of immune and inflammatory cells, including a number of key functions of mononuclear phagocytes. In this study ADO and the synthetic ADO analogue MDL201112 inhibited TNF-alpha, but not IL-1, production by activated mouse peritoneal macrophages and the macrophage-like cell lines J774 and RAW-264. Northern blot analysis indicated that MDL201112 selectively inhibited the expression of steady-state TNF-alpha RNA in LPS+IFN-gamma-activated J774 and RAW-264 cells. This effect could not be attributed to changes in TNF-alpha RNA stability. In contrast, ADO had no effect on RNA levels for TNF-alpha and IL-1, suggesting that ADO acts at a post-transcriptional biosynthetic step. To determine whether either compound inhibited TNF-alpha-mediated inflammatory responses, mice were treated with ADO or MDL201112 and challenged with a lethal dose of endotoxic LPS and D-galactosamine, an hepatotoxin that sensitizes mice to lethal LPS challenge. A single i.p. injection of MDL201112 (100 mg/kg) protected over 90% of the mice, whether injected 1 h before or at the time of LPS challenge. MDL201112 also inhibited the appearance of TNF-alpha in the serum of LPS-challenged animals. The compound did not block D-galactosamine sensitization nor did it prevent lethality caused by the injection of rTNF-alpha. ADO failed to protect animals against endotoxin lethality, most likely due to the rapid metabolism of the nucleoside in vivo. These results establish ADO and MDL201112 as potent inhibitors of TNF-alpha biosynthesis and suggest that MDL201112 or similar analogues warrant further study as potential agents for the treatment of endotoxin shock and other diseases in which TNF-alpha plays an important pathogenic role.
The contingent value of the dedicated alliance function

Scholars have underscored the merits of a dedicated alliance function that promotes standardization, formalization, and centralization of alliance management practices, but some recent research finds no support for the claim that a dedicated alliance function creates value. We contribute to this debate by offering a contingency approach. Specifically, we conjecture that the contribution of the dedicated alliance function to value creation in an alliance increases with general partnering experience that the firm has accumulated with its various partners but declines with partner-specific experience that the firm has accumulated in recurrent alliances with the same partner. Our analysis of more than 15,000 alliances involving US-based software firms supports these conjectures and identifies boundary conditions for this function’s effects. We conclude that instituting an organizational infrastructure that is meant to enhance a firm’s ability to leverage its experience with various partners can restrict its gains from experience with specific partners. Nevertheless, by appropriately leveraging its dedicated alliance function, the firm can manage conflicting routines and overcome the tradeoff between efficient use of alliance management practices and responsiveness to partners in its alliance portfolio.
The Empire Strikes Back: French‐African Trade after Independence

This paper studies the effects of foreign influence on trade, focusing on the close relations between France and its former colonies in Sub-Saharan Africa (SSA). It shows that between 1960 and 1989 - the golden age of French-African relations - France exported more to its former SSA colonies than to any comparable countries, while they did not export more to France. This excess of French exports concerned a large variety of products, and particularly luxury goods and products in which France was least competitive. An investigation of the underlying mechanisms shows that migration explains most of this additional trade.
Prevalence, Risk Factors, and Preference-Based Health States of Low Back Pain in a Turkish Population

Study Design. A community-based cross-sectional survey was conducted using face-to-face interviews. Objectives. To estimate the point, 12-month period, and lifetime prevalence of low back pain (LBP) in the general population of Turkey, and to determine the factors associated with LBP. We also aim to determine self-reported health states differences between patients and the general population by the EuroQol-5D & Visual Analogue Scale (EQ5D-VAS). Summary of Background Data. LBP as a major public health problem has been unquestionably the most serious pain problem. LBP generally appears between 35 and 64 years of age. Little was known about the prevalence and determinants of LBP among populations from developing areas; information mostly comes from industrialized countries. This epidemiologic study reported the prevalence of LBP in the general population in Turkey. In Turkey, community-based trials on the prevalence of LBP were scarce. Methods. A total of 7,000 participants selected by randomly sampling from seven regions of Turkey. A comprehensive questionnaire on demographics, physical and emotional stress, LBP, and EQ5D-VAS was administered to 4,990 men and women (age range, 18–70 years). Results. The lifetime, 12-month period, and point prevalence of LBP were 44.1%, 34.0%, and 19.7%, respectively. The prevalence of LBP in women was consistently higher than in men across all age groups. The proportion of specific LBP was 10.2%, and most common etiology of specific LBP was disc hernia. In regression analysis, occupation, physical, and emotional stress showed significant associations with having LBP. The EQ5D-VAS scores of patients with LBP were significantly lower than self-reported assessments of the population without LBP (64.6, 63.0 vs. 73.8, P < 0.05). Conclusions. In comparison with other developing countries, the prevalence of LBP is higher in Turkey and approximates prevalence estimates of LBP in developed countries. LBP is associated with occupation. Smoking is not associated with having LBP. This study also shows that LBP influences disability and quality of life.
A second eukaryotic group with mitochondrion-encoded tmRNA

In bacteria, stalled ribosomes are rescued by transfer-mRNA (tmRNA) that catalyzes two steps. First, a non-encoded alanine is added to the incomplete polypeptide chain by the tRNAAla-like portion of tmRNA, and second, the ribosome switches to the mRNA-like domain of tmRNA, thus resuming protein synthesis. Mitochondrial DNA (mtDNA)-encoded mt-tmRNA is so far only known from jakobid protists, but we posit that the corresponding ssrA gene may also reside in other mtDNAs. Here we present a highly sensitive covariance model built from jakobid ssrA genes that identifies previously unrecognized ssrA homologs in mtDNAs of oomycetes. These genes, located in previously unassigned genomic regions, are circular permuted as in α-Protobacteria, implying that pre-tmRNA is processed and the two pieces are held together by non-covalent interactions. RNA-Seq data from Phytophthora sojae confirm predicted processing sites as well as post-transcriptional addition of 3′ CCA, a prerequisite for tmRNAs to be charged with alanine by alanyl-tRNA synthetase. Structure modeling of oomycete tmRNAs infers that the mRNA-like domain is lacking as in jakobids. Features of mitochondrial tmRNAs include the G-U pair at position three of the acceptor stem, a hallmark of bacterial tmRNAs, and a T-loop sequence that differs from that of standard tRNAs and most bacterial tmRNAs, forming alternative, virtually isosteric tertiary interactions with the D-loop. The anticodon stem has two additional G-A base pairs formed between the D-loop and the variable region, shortening the length of the variable region to a single nucleotide.
Phase I study of PKC412 (N-benzoyl-staurosporine), a novel oral protein kinase C inhibitor, combined with gemcitabine and cisplatin in patients with non-small-cell lung cancer.

BACKGROUND PKC412 (N-benzoyl-staurosporine), an oral inhibitor of protein kinase C, is capable of cell cycle inhibition and is endowed with anti-angiogenic properties. This dose-finding phase I study was designed to establish the maximum tolerated dose (MTD) of PKC412 when combined with cisplatin-gemcitabine. PATIENTS AND METHODS Escalating doses of PKC412 were given every day of a 4 week cycle with cisplatin 100 mg/m2 on day 2 and gemcitabine 1000 mg/m2 on days 1, 8 and 15 in patients with non-small-cell lung cancer. Dose escalation was based on a modified continuous reassessment method. RESULTS Twenty-three patients, assigned to four cohorts receiving PKC412 at a dose ranging from 25 to 150 mg/day were evaluable. Grade 3 diarrhea occurring in 3/4 patients at cycle 1 led us to define 150 mg/day as the MTD. The MTD based on multiple cycles was redefined as 100 mg/day, since prolonged grade 2-3 nausea/vomiting leading to treatment discontinuation occurred in 3/7 patients after repeated cycles. The next lower dose tested of 50 mg/day was therefore considered as the recommended dose for phase II trials. Among 33 cycles in eight patients, toxicity consisted of grade 1-2 diarrhea (12.5%) and asthenia (50%) with only one patient experiencing grade 3 headache at this dose level. A partial response was observed in three patients. CONCLUSIONS The results of the present study indicate that PKC412 at a dose of 50 mg/day can be safely added to cisplatin and gemcitabine in patients with advanced non-small-cell lung cancer.
hTERT-targeted RNA interference inhibits tumorigenicity and motility of HCT116 cells

Telomerase is proposed as an anticancer target. Increasing evidence suggests that telomerase is involved in functions independent of telomere-extension activity. In this study, we designed a small interfering RNA (siRNA) targeting human telomerase reverse transcriptase (hTERT), the catalytic subunit of telomerase. Using transient and persistent transfection of hTERT siRNA into telomerase-positive human colon carcinoma HCT116 cells, we demonstrated that hTERT siRNA suppresses hTERT expression and leads to inhibition of telomerase activity and HCT116 cell growth and in vivo tumorigenicity in nude mice. Further analysis indicated that depletion of hTERT reduces cell adhesion, migration, and invasion prior to inhibition of cell proliferation. Downregulation of hTERT also decreased the expression levels of adhesion- and motility-related proteins, in particular c-Met and integrins. The lack of detectable changes in telomere length showed that downregulation of hTERT in the present system had no significant effect on telomere-extension activity. Taken together, our results highlight the therapeutic potential of a novel hTERT siRNA and suggest that hTERT is involved in the regulation of cell motility in a telomere-independent manner.
Effects of tidal volume and positive end-expiratory pressure during resuscitation of very premature lambs.

BACKGROUND Guidelines recommend neonatal resuscitation without controlling tidal volume or positive end-expiratory pressure (PEEP). However, these may improve gas exchange, lung volume and outcome. AIM To investigate resuscitation of very premature lambs with a Laerdal bag without PEEP versus volume guarantee ventilation with PEEP. METHODS Anaesthetized lambs (n=20) delivered at 125 d gestation were randomized to three groups receiving 15 min resuscitation: (1) Laerdal bag and no PEEP; (2) ventilation with a tidal volume of 5 ml/kg and 8 cm H(2)O PEEP; (3) ventilation with 10 ml/kg and 8 cm H(2)O PEEP. They were then all ventilated for 2 h with tidal volumes of 5 or 10 ml/kg, and 8 cm H(2)O PEEP. Ventilation parameters and blood gases were recorded. RESULTS Different tidal volumes affected PaCO(2) within minutes, with 10 ml/kg causing severe hypocarbia. PEEP had little effect on PaCO(2). Oxygenation improved significantly with PEEP of 8 cm H(2)O, irrespective of tidal volume. CONCLUSION Very premature lambs can be resuscitated effectively using volume-guarantee ventilation and PEEP. Tidal volumes affected PaCO(2) within minutes but had little effect on oxygenation. PEEP halved the oxygen requirement compared with no PEEP. Resuscitating premature babies with controlled tidal volumes and PEEP might improve their outcome.
A case–control study to assess the effectiveness of pertussis vaccination during pregnancy on newborns, Valencian community, Spain, 1 March 2015 to 29 February 2016

In the Valencian Community (Spain), the programme of maternal pertussis vaccination during pregnancy started in January 2015. The objective of this study was to estimate in this region the vaccine effectiveness (VE) in protecting newborns against laboratory-confirmed pertussis infection. A matched case–control study was undertaken in the period between 1 March 2015 and 29 February 2016. Twenty-two cases and 66 controls (+/− 15 days of age difference) were included in the study. Cases were non-vaccinated infants < 3 months of age at disease onset testing positive for pertussis by real-time PCR. For every case three unvaccinated controls were selected. Odds ratios (OR) were calculated by multiple conditional logistic regression for association between maternal vaccination and infant pertussis. Other children in the household, as well as mother- and environmental covariates were taken into account. The VE was calculated as 1 − OR. Mothers of five cases (23%) and of 41 controls (62%) were vaccinated during pregnancy. The adjusted VE was 90.9% (95% confidence interval (CI): 56.6 to 98.1). The only covariate in the final model was breastfeeding (protective effect). Our study provides evidence in favour of pertussis vaccination programmes for pregnant women in order to prevent whooping cough in infants aged less than 3 months.
The Effect of Preoperative Oral Immunonutrition on Complications and Length of Hospital Stay After Elective Surgery for Pancreatic Cancer–A Randomized Controlled Trial

ABSTRACT Major gastrointestinal surgery is associated with immune suppression and a high risk of postoperative complications. The aim of this open, randomized controlled trial was to examine the effect of supplementary per oral immunonutrition (IN) seven days before surgery for pancreatic cancer (PC) on postoperative complications and length of hospital stay (LOS). Secondary outcomes were the changes in functional capability and body weight (BW). Consecutive patients referred for surgery for diagnosed or plausible PC were included. The patients in the intervention group received supplementary IN (Oral Impact®, Nestlé) to reach a goal of 1.5 g protein/kg BW. The control group continued their habitual diet. Complications and LOS were independently assessed by the surgical staff. Secondary outcomes were measured 10, 20, and 30 days postoperatively. Thirty-five patients were included, of whom 19 (54%) were allocated to the intervention group. The doses of IN ranged from 250 to 1000 ml per day and the median compliance was 100 (0–100%). Based on the principle of intention-to-treat, no significant differences were found between the groups. We conclude that the lack of effect could be due to the limited dosage of IN, and/or because only 40% of the patients were at nutritional risk.
Dynamics of locking of peptides onto growing amyloid fibrils

Sequence-dependent variations in the growth mechanism and stability of amyloid fibrils, which are implicated in a number of neurodegenerative diseases, are poorly understood. We have carried out extensive all-atom molecular dynamics simulations to monitor the structural changes that occur upon addition of random coil (RC) monomer fragments from the yeast prion Sup35 and Aβ-peptide onto a preformed fibril. Using the atomic resolution structures of the microcrystals as the starting points, we show that the RC → β-strand transition for the Sup35 fragment occurs abruptly over a very narrow time interval, whereas the acquisition of strand content is less dramatic for the hydrophobic-rich Aβ-peptide. Expulsion of water, resulting in the formation of a dry interface between 2 adjacent sheets of the Sup35 fibril, occurs in 2 stages. Ejection of a small number of discrete water molecules in the second stage follows a rapid decrease in the number of water molecules in the first stage. Stability of the Sup35 fibril is increased by a network of hydrogen bonds involving both backbone and side chains, whereas the marginal stability of the Aβ-fibrils is largely due to the formation of weak dispersion interaction between the hydrophobic side chains. The importance of the network of hydrogen bonds is further illustrated by mutational studies, which show that substitution of the Asn and Gln residues to Ala compromises the Sup35 fibril stability. Despite the similarity in the architecture of the amyloid fibrils, the growth mechanism and stability of the fibrils depend dramatically on the sequence.
IO in I-O: Competition and Volatility in Input-Output Networks

There is a growing literature suggesting that firm level productivity shocks can help understandmacroeconomic level outcomes. However, existingmodels are very restrictive regarding the nature of competition within sector and its implication for the propagation of shocks across the input-output (I-O) network. The goal of this paper is to offer amore comprehensive understanding of how firm level shocks can shape aggregate dynamics. To this end, I build a tractablemulti-sector heterogeneous firm general equilibrium model featuring oligopolistic competition and an I-O network. It is shown that a positive shock to a large firm increases both the average productivity and the Herfindahl Index in its sector. By reducing the sector price, the change in average productivity propagates only to downstream sectors. Conversely, the change in the Herfindahl Index, by increasing price and reducing demand for intermediate inputs, propagates both to downstream and upstream sectors. The sensitivity of aggregate volatility to firms’ shocks is determined by the sector’s (i) Herfindahl Index, which measures the volatility of the sector, (ii) position in the input-output network, which measures the direct and indirect importance of this sector for the household, and (iii) relativemarket power in the supply chain, which relates to the changes in demand to upstreamsectors.
Action recognition by learning pose representations

Pose detection is one of the fundamental steps for the recognition of human actions. In this paper we propose a novel trainable detector for recognizing human poses based on the analysis of the skeleton. The main idea is that a skeleton pose can be described by the spatial arrangements of its joints. Starting from this consideration, we propose a trainable pose detector, that can be configured on a prototype skeleton in an automatic configuration process. The result of the configuration is a model of the position of the joints in the concerned skeleton. In the application phase, the joint positions contained in the model are compared with the ones of their homologous joints in the skeleton under test. The similarity of two skeletons is computed as a combination of the position scores achieved by homologous joints. In this paper we describe an action classification method based on the use of the proposed trainable detectors to extract features from the skeletons. We performed experiments on the publicly available MSDRA data set and the achieved results confirm the effectiveness of the proposed approach.
The enduring mental health impact of mass violence: A community comparison study of Cambodian civilians living in Cambodia and Thailand

Background: No population-based studies have directly compared the long-term health and mental health outcomes of conflict- versus non-conflict-affected communities from the same ethnic background. Aims: To identify and compare levels of psychiatric morbidity between a traumatized and non-traumatized civilian community; to investigate the long-term impact of mass violence. Methods: Double-stratified community surveys in Siem Reap and Surin provinces were conducted by highly qualified Cambodian interviewers using culturally validated survey instruments with known psychometric properties. These included Cambodian versions of the Hopkins Symptom Checklist-25, the Harvard Trauma Questionnaire and the Medical Outcome Study Short Form. Results: Siem Reap and Surin respondents experienced 12,266 and 621 major trauma events, respectively; 745 (76.2%) Siem Reap respondents and six (0.6%) Surin respondents reported torture events; 499 (49.5%) Siem Reap respondents and 203 (19.7%) Surin respondents met the clinical threshold for depression (OR 4.01, 95% CI 3.29–4.88); 204 (20.6%) Siem Reap respondents and 23 (2.2%) Surin respondents met the clinical threshold for post-traumatic stress disorder (PTSD) (OR 11.39, 95% CI 7.3–17.7). The MOS physical disability was higher in Siem Reap versus Surin respondents (74 (7.5%) vs 13 (1.3%), χ2 = 47.4 df = 1, p < . 001). Health status was poorest among Siem Reap respondents when compared with Surin respondents (mean score 1.59 vs 0.59, respectively; t = 19.85 df = 2018, p < .001). Path analysis reveals that recent and past extreme violence are associated with the health and mental health status of the Siem Reap community. Conclusion: After 25 years, the Khmer civilian population that experienced the Pol Pot genocide continues to suffer psychiatric morbidity and poor health.