Miracle-dz/UniFAR-FTUs huggingface dataset:
Hepatitis B and D viruses exploit sodium taurocholate co-transporting polypeptide for species-specific entry into hepatocytes.

BACKGROUND & AIMS Hepatitis B and D viruses (HBV and HDV) are human pathogens with restricted host ranges and high selectivity for hepatocytes; the HBV L-envelope protein interacts specifically with a receptor on these cells. We aimed to identify this receptor and analyze whether it is the recently described sodium-taurocholate co-transporter polypeptide (NTCP), encoded by the SLC10A1 gene. METHODS To identify receptor candidates, we compared gene expression patterns between differentiated HepaRG cells, which express the receptor, and naïve cells, which do not. Receptor candidates were evaluated by small hairpin RNA silencing in HepaRG cells; the ability of receptor expression to confer binding and infection were tested in transduced hepatoma cell lines. We used interspecies domain swapping to identify motifs for receptor-mediated host discrimination of HBV and HDV binding and infection. RESULTS Bioinformatic analyses of comparative expression arrays confirmed that NTCP, which was previously identified through a biochemical approach is a bona fide receptor for HBV and HDV. NTCPs from rat, mouse, and human bound Myrcludex B, a peptide ligand derived from the HBV L-protein. Myrcludex B blocked NTCP transport of bile salts; small hairpin RNA-mediated knockdown of NTCP in HepaRG cells prevented their infection by HBV or HDV. Expression of human but not mouse NTCP in HepG2 and HuH7 cells conferred a limited cell-type-related and virus-dependent susceptibility to infection; these limitations were overcome when cells were cultured with dimethyl sulfoxide. We identified 2 short-sequence motifs in human NTCP that were required for species-specific binding and infection by HBV and HDV. CONCLUSIONS Human NTCP is a specific receptor for HBV and HDV. NTCP-expressing cell lines can be efficiently infected with these viruses, and might be used in basic research and high-throughput screening studies. Mapping of motifs in NTCPs have increased our understanding of the species specificities of HBV and HDV, and could lead to small animal models for studies of viral infection and replication.
Independent and combined effects of tobacco smoking, chewing and alcohol drinking on the risk of oral, pharyngeal and esophageal cancers in Indian men

Oral, pharyngeal and esophageal cancers are 3 of the 5 most common cancer sites in Indian men. To assess the effect of different patterns of smoking, chewing and alcohol drinking in the development of the above 3 neoplasms and to determine the interaction among these habits, we conducted a case‐control study in Chennai and Trivandrum, South India. The cases included 1,563 oral, 636 pharyngeal and 566 esophageal male cancer patients who were compared with 1,711 male disease controls from the 2 centers as well as 1,927 male healthy hospital visitors from Chennai. We observed a significant dose‐response relationship for duration and amount of consumption of the 3 habits with the development of the 3 neoplasms. Tobacco chewing emerged as the strongest risk factor for oral cancer, with the highest odds ratio (OR) for chewing products containing tobacco of 5.05 [95% confidence internal (CI) 4.26–5.97]. The strongest risk factor for pharyngeal and esophageal cancers was tobacco smoking, with ORs of 4.00 (95% CI 3.07–5.22) and 2.83 (95% CI 2.18–3.66) in current smokers, respectively. An independent increase in risk was observed for each habit in the absence of the other 2. For example, the OR of oral cancers for alcohol drinking in never smokers and never chewers was 2.56 (95% CI 1.42–4.64) and that of esophageal cancers was 3.41 (95% CI 1.46–7.99). Furthermore, significant decreases in risks for all 3 cancer sites were observed in subjects who quit smoking even among those who had quit smoking 2–4 years before the interview. © 2003 Wiley‐Liss, Inc.
Changes in bone mineral density in newly diagnosed testicular cancer patients after anticancer treatment.

CONTEXT Patients with germ cell tumors (GCTs) have an excellent prognosis but are at risk for silent fractures. Data on bone mineral density (BMD) after anticancer treatment are scarce. OBJECTIVE The objective of the study was BMD monitoring in GCT patients treated with or without chemotherapy. DESIGN We prospectively studied 63 newly diagnosed GCT patients with a median age of 33 years (range 16-70 y) within 3 months of unilateral orchidectomy. Twenty-seven patients (42.9%) had no metastases. Thirty-six patients (57.1%) with metastatic disease received combination chemotherapy. SETTING This study was conducted at the outpatient clinic of a single academic institution. INTERVENTIONS We performed dual-energy X-ray absorptiometry scans and collected blood samples on a yearly basis, before and up to 5 years after anticancer treatment. MAIN OUTCOME MEASURES Changes in total hip and lumbar spine BMD, serum concentrations of gonadal hormones, and bone turnover markers were measured. RESULTS BMD remained normal in stage I patients. In patients with metastatic disease, a significant decrease in lumbar spine BMD (-1.52%; P = .004) and total hip BMD (-2.05%; P < .0001) was observed 1 year after chemotherapy and remained stable thereafter for up to 5 years. There was no significant relationship between the observed decrease in BMD and gonadal status, vitamin D status, or cumulative dose of cisplatin or (antiemetic) corticosteroids. CONCLUSIONS Metastatic GCT survivors demonstrate significant bone loss within the first year after curative combination chemotherapy, with no recovery up to 5 years after anticancer treatment. Whether this bone loss is associated with increased fracture risk and whether this could be prevented by bone modifying treatment remains to be established.
Design for testability of FPGA blocks

Reconfigurable logic devices that are based on an FPGA substrate are gaining widespread acceptance. As such devices are used in many different configurations, manufacturers need to ensure that each potential configuration will not fail due to device defects. This flexibility leads to severely increased test time. We show how to use reconfigurability to speed up test and diagnosis times of individual FPGA blocks. We present a scheme to incorporate our test architecture, reducing diagnostic and test times of individual FPGA blocks. The test architecture includes added Feedback Shift Registers (FSRs) that change the circuit configuration during test. Algorithms are presented to produce test and diagnosis test sets with a minimized number of test configurations, along with the creation of an FSR that produces the test and diagnosis sets by dynamic reconfiguration of the device.
Los determinantes de las variaciones en el rendimiento del oro

En este trabajo se caracteriza el comportamiento de los rendimientos logaritmicos del oro entre 1995 y 2017 con base en varios modelos de media y varianza condicionales, que incorporan efectos de asimetria y colas pesadas. Para tal efecto, se lleva a cabo, primero, un analisis basado en vectores autorregresivos con el fin de identificar los principales regresores externos y, luego, una serie de ajustes con distintas especificaciones del tipo AR-GARCH para pronosticar la volatilidad de las fluctuaciones del oro con base en dichos regresores. La conclusion principal es que esas fluctuaciones pueden ser adecuadamente explicadas por el comportamiento de las series de USDEER y SP500 de acuerdo con la especificacion AR(1)-GARCH(1,1) que tiene asociada una distribucion t de Student. Esto quiere decir que los determinantes de largo plazo de las variaciones del rendimiento del oro estan relacionados con las estrategias cambiarias y de proteccion contra el ciclo del mercado de valores por parte de los inversionistas.
Equivalent disturbance observer based discrete-time integral sliding mode control for PMSM speed regulation system

In order to improve the speed-regulation performance of the permanent-magnet synchronous motor (PMSM) system under uncertainties and disturbances, an equivalent disturbance observer (EDO) based discrete-time integral sliding mode control (DISMC) scheme is proposed. To avoid the high-frequency noise caused by the differential terms of conventional sliding mode control (SMC), a discrete-time integral sliding surface is designed, which can eliminate the reaching phase and achieve excellent tracking responses and global robustness. Then, a discretized EDO is proposed to realize the estimation and feed-forward compensation of the disturbances online, so that it can guarantee disturbance rejection ability and high-precision control. Furthermore, stability analysis of the designed system is given. Simulation results demonstrate the validity of the proposed control scheme.
The role of epitope specificity in the human opsonic antibody response to the staphylococcal surface polysaccharide poly N-acetyl glucosamine.

BACKGROUND The staphylococcal surface polysaccharide poly N-acetyl glucosamine (PNAG) is a target for killing and protective antibody in animals. We investigated the human antibody response and specificity of binding and opsonic antibodies for different epitopes on PNAG in serum samples from patients with cystic fibrosis (CF) colonized and not colonized with Staphylococcus aureus. METHODS Serum samples from patients with CF colonized and not colonized with S. aureus were used to compare levels and specificities of binding and opsonic antibodies to native PNAG (>95% acetylation) and deacetylated PNAG (dPNAG, approximately 15% acetylation). RESULTS Colonized patients had higher killing activity mediated by opsonic antibody than did noncolonized patients in a PNAG-specific opsonophagocytic assay (P<.0001) but no difference in average levels of antibody to either PNAG or dPNAG by enzyme-linked immunosorbent assay. Killing activity in serum samples of the colonized patients correlated with the level of IgG specific to dPNAG more than to native PNAG. dPNAG and PNAG shared expression of the epitopes binding opsonic antibody, as evidenced by comparable inhibition of opsonophagocytic killing by both antigens. Affinity-purified antibodies specific to dPNAG were superior in mediating opsonic killing. CONCLUSION Human antibodies to PNAG that mediate opsonic killing bind primarily to the nonacetylated epitopes of this antigen, which indicates that these antigenic determinants are the dominant targets of the functional human antibody response to staphylococcal PNAG.
MECHANISMS OF REDUCTION OF ANTITUMOR DRUG TOXICITY BY LIPOSOME ENCAPSULATION *

Actinomycin D, when encapsulated within liposomes, has been previously shown to be less toxic to mice than nonencapsulated actinomycin D, but to retain its tumoricidal activity. We have compared the toxic effects of Act D encapsulated either in the aqueous phase or in the lipid phase of liposomes (APL and LPL, respectively), and the nonencapsulated Act D on the blood forming system, on cell proliferation in the intestine, and on antibody production by spleen lymphocytes. At a single dose of 0.4 mg/kg, APL-encapsulated Act D wass less toxic to white blood cells and to the nucleated cells and colony-forming stem cells of the bone marrow. During toxicity in the proliferating intestinal cells, measured by 3H-thymidine incorporation, was reduced by about a factor of 4 with encapsulation in APL, particularly 24 hours after Act D administration. The toxiciaty of LPL-encapsulated Act D to both the blood-forming system and the intestinal proliferating cells was, however, not significantly different from that of the nonencapsulated Act D. Effects of Act D on the antibody production by spleen cells, determined by the "limited hemolysis in agar" assay, showed that immunosuppression was most markedly reduced by liposome encapsulation either in APL or in LPL, when the drug was given one day before the antigen. These findings are important for considerations of liposome application in cancer chemotherapy.
[Clinical presentation and complications of Plasmodium falciparum malaria in two populations: travelers and immigrants].

INTRODUCTION Plasmodium falciparum malaria is the most aggressive form of this disease, with 90% of cases occurring in Africa. Only natives of malaria-endemic areas can acquire a certain degree of immunity to the disease. It is not known whether immunity is lost when contact with the parasite is discontinued. PATIENTS AND METHODS Retrospective study of cases of falciparum malaria imported from Africa, performed in Hospital Clinic, Barcelona (Spain), from 1999 to 2005. Clinical, epidemiological and laboratory parameters were compared between travelers and African immigrants. RESULTS Among 187 patients, 85 were immigrants from an endemic area who had been living in a non-endemic area for more than 5 years. These patients presented fewer complications than travelers. DISCUSSION These data may point to a certain persistence of immunity in previously semi-immune persons who migrate to non-endemic areas.
Meta-analysis of depression and substance use and impairment among intravenous drug users (IDUs).

AIMS To evaluate, among intravenous drug users (IDUs), the hypothesized positive association of depression with substance-related behaviors including concurrent drug use and impairment, future drug use and impairment, alcohol use and impairment, needle sharing and substance use treatment participation, and to identify moderators of these associations. DESIGN Meta-analysis of reports on IDUs published in English in peer-reviewed journals since 1986 that contained data on depression and substance use outcome(s) with no restrictions on range of depression scores to select the sample. SETTING Fifty-five reports containing 55 samples met criteria, including 42 (76%) samples from clinical venues and 13 (24%) that were community-based. PARTICIPANTS Mean age was 34.3 (standard deviation = 4.5) years, comprising approximately 68% men and 43% white, non-Hispanic subjects. MEASUREMENTS Depression was assessed with the Beck Depression Inventory, Center for Epidemiological Studies Depression Scale (CES-D) and other validated scales or diagnostic interviews. The Addiction Severity Index was the most frequently used measure of substance-related outcomes. FINDINGS A priori hypotheses pertaining to depression and the substance-related variables were supported, with the exception of the predicted association of depression and future drug use and impairment. Effect sizes were small. Moderating effects of gender were identified, including greater associations of depression with substance use treatment participation and needle sharing among women and a greater association of depression with future drug use and impairment among men. Effect sizes of moderators were large. CONCLUSIONS Depression is associated with several substance-related behaviors, and select associations are stronger according to gender. Prospective associations of depression with future drug use and impairment are not immediately evident, but could be examined in subsequent research.
Growth of Listeria monocytogenes in Camembert and other soft cheeses at refrigeration temperatures

Summary Listeria monocytogenes survived and, under most conditions, multiplied when inoculated directly into the cheese milk of laboratory made Camembert cheeses. The rate and extent of growth was reduced at lower storage temperatures. Significantly higher rates of growth occurred at the surface compared with the centre of the cheeses, and these were probably associated with increased pH and proteolysis at the cheese surface due to the mould ripening process. Similar results were obtained with Camembert cheeses surface inoculated after manufacture. There was also temperature-dependent growth of List, monocytogenes on a range of inoculated commercially manufactured soft cheeses. Significant growth occurred in Cambazola, French and English Brie, blue and white Lymeswold, French Camembert and Brie with garlic. Little if any growth occurred in blue and white Stilton, Mycella, Chaume and full fat soft cheese with garlic and herbs at the temperatures examined.
Real-Time Macroeconomic Forecasting With a Heteroscedastic Inversion Copula

Abstract There is a growing interest in allowing for asymmetry in the density forecasts of macroeconomic variables. In multivariate time series, this can be achieved with a copula model, where both serial and cross-sectional dependence is captured by a copula function, and the margins are nonparametric. Yet most existing copulas cannot capture heteroscedasticity well, which is a feature of many economic and financial time series. To do so, we propose a new copula created by the inversion of a multivariate unobserved component stochastic volatility model, and show how to estimate it using Bayesian methods. We fit the copula model to real-time data on five quarterly U.S. economic and financial variables. The copula model captures heteroscedasticity, dependence in the level, time-variation in higher moments, bounds on variables and other features. Over the window 1975Q1–2016Q2, the real-time density forecasts of all the macroeconomic variables exhibit time-varying asymmetry. In particular, forecasts of GDP growth have increased negative skew during recessions. The point and density forecasts from the copula model are competitive with those from benchmark models—particularly for inflation, a short-term interest rate and current quarter GDP growth. Supplementary materials for this article are available online.
High monthly temperature as a possible risk factor of local vascular bleeding complications during percutaneous coronary interventions evaluated by ultrasonography - retrospective analysis.

BACKGROUND Bleeding complications are a very important issue in the era of percutaneous coronary interventions (PCI). Effective antiplatelet therapy increases the rate of successful interventions but the risk of bleeding complications, among them local vascular complications, may be higher. Other factors may also be important in the development of local bleeding complications. AIM To examine the relationship between air temperature and local haemorrhagic complications. METHODS The retrospective analysis of ultrasonographic examinations performed during the last 5 years (2003-2007) in 10 548 consecutive patients undergoing cardiac catheterisation due to acute coronary syndromes or elective coronary angiography was performed. The relationship between mean monthly temperature, other factors and the rate of local bleeding complications was examined. RESULTS Mean number of treated patients was 2708 +/- 377/year (2113-3089), of whom 1692 +/- 362/year had coronary angiography and 1345 +/- 281/year had PCI. Yearly rate of all femoral bleeding complications was 3.0 +/- 0.5%. There were more haematomas than pseudoaneurysms: 2.2 +/- 0.4 vs. 0.8 +/- 0.1%, p < 0.0001. Higher mean monthly air temperatures were positively correlated with the number of complications (r = 0.11, p < 0.05), both in males and females (r = 0.13, p < 0.05). A positive correlation between number of haematomas and air temperature values was detected in women. Yearly rate of all vascular complications, haematomas and pseudoaneurysms was higher in women than in men 4.3 +/- 0.9 vs. 2.3 +/- 0.3% (p < 0.0001), 3.0 +/- 0.7 vs. 1.7 +/- 0.3% (p < 0.0001) and 1.3 +/- 0.2 vs. 0.6 +/- 0.1% (p < 0.0005) respectively. In spite of more aggressive antiplatelet therapy, higher clopidogrel loading doses and abciximab use introduced during the analysed period, the rate of local vascular bleeding complications did not increase. CONCLUSIONS High air temperature during the post-intervention period, besides female gender and advanced age, may be another risk factor for local bleeding complications. This risk remains low (3%), in spite of growing intensity of antiplatelet treatment.
Bruch's membrane and choroidal macrophages in early and advanced age-related macular degeneration

Aim To determine the sub-macular Bruch's membrane (BrM) macrophage count and the choroidal and BrM macrophage immunophenotype in normal eyes and in eyes with early and advanced age-related macular degeneration (AMD). Methods BrM macrophages were counted in 125 human eyes (normal, normal aged, early AMD and geographical atrophy), and CD68 and inducible nitric oxide synthase (iNOS) immunohistochemistry was performed on 16 human eyes (normal, normal aged, early AMD, geographical atrophy and disciform scarring). All eyes were examined clinically ante mortem. Results were correlated with histopathological features, including basal laminar deposit and membranous debris, and with clinical fundus appearance. Results CD68+ macrophages were found in the choroid of normal human eyes, and did not express iNOS. Expression of iNOS by choroidal macrophages (as well as endothelial cells and pericytes) was associated with: (1) recruitment of macrophages to BrM in early AMD eyes with soft drusen or thick continuous basal laminar deposit, corresponding to clinically detectable soft drusen or pigment changes; and (2) active disciform scarring. iNOS expression was absent in BrM macrophages, suggesting immunomodulatory differences between the choroid and BrM. The highest BrM macrophage counts were found in eyes with subclinical choroidal neovascularisation. Conclusion The presence of extracellular deposits (soft drusen and thick continuous basal laminar deposit) is associated with macrophage recruitment to BrM and alteration in the immunophenotype of resident choroidal macrophages.
Total Focusing Method With Virtual Sources in the Presence of Unknown Geometry Interfaces

Auto-focused virtual source imaging (AVSI) has been recently presented as an alternative method for synthetic aperture focusing through arbitrarily shaped interfaces with arrays. This paper extends the AVSI concept to the case of the total focusing method (TFM-AVSI) using several virtual receivers for each virtual source. This approach overcomes the known contrast limitation of AVSI, while preserving the advantage of performing synthetic focusing in the second medium only [no time-of-flight (TOF) calculations through the interface]. In contrast, equipment with more active channels must be used to digitalize the signals received by all the array elements after each focused emission. When compared with the conventional TFM, the proposed method reduces the processing complexity of the most time consuming task: TOF calculation in the presence of interfaces. This improvement could lead to more efficient real-time implementations of the TFM in non-destructive testing applications where water immersion or flexible wedges are used. In this paper, the mathematical formulation for the new method is given, accounting for the surface slope and the array angular sensitivity. Its performance is evaluated by numerical simulation, experimentally and compared with AVSI and the conventional TFM. It was found that the TFM-AVSI achieves the same resolution and contrast as that of the TFM, although it shows a wider blind zone below the interface due to focusing with normal incidence.