Miracle-dz/UniFAR-FTUs huggingface dataset:
Inhibitory Effect of Adefovir on Viral DNA Synthesis and Covalently Closed Circular DNA Formation in Duck Hepatitis B Virus-Infected Hepatocytes In Vivo and In Vitro

ABSTRACT The elimination of viral covalently closed circular DNA (CCC DNA) from the nucleus of infected hepatocytes is an obstacle to achieving sustained viral clearance during antiviral therapy of chronic hepatitis B virus (HBV) infection. The aim of our study was to determine whether treatment with adefovir, a new acyclic nucleoside phosphonate, the prodrug of which, adefovir dipivoxil, is in clinical evaluation, is able to suppress viral CCC DNA both in vitro and in vivo using the duck HBV (DHBV) model. First, the effect of adefovir on viral CCC DNA synthesis was examined with primary cultures of DHBV-infected fetal hepatocytes. Adefovir was administered for six consecutive days starting one day before or four days after DHBV inoculation. Dose-dependent inhibition of both virion release in culture supernatants and synthesis of intracellular viral DNA was observed. Although CCC DNA amplification was inhibited by adefovir, CCC DNA was not eliminated by antiviral treatment and the de novo formation of CCC DNA was not prevented by pretreatment of the cells. Next, preventive treatment of experimentally infected ducklings with lamivudine or adefovir revealed that both efficiently suppressed viremia and intrahepatic DNA. However, persistence of viral DNA even when detectable only by PCR was associated with a recurrence of viral replication following drug withdrawal. Taken together, our results demonstrate that adefovir is a potent inhibitor of DHBV replication that inhibits CCC DNA amplification but does not effectively prevent the formation of CCC DNA from incoming viral genomes.
The Relationship Between Cerebral Blood Flow and Transcranial Doppler Blood Flow Velocity During Hypothermic Cardiopulmonary Bypass in Adults

A noninvasive, simple, and continuous method to assess cerebral perfusion during cardiopulmonary bypass (CPB) could help prevent cerebral ischemia.Transcranial Doppler sonography (TCD) allows a noninvasive, on-line measurement of blood flow velocity in cerebral arteries. The correlation of TCD-estimated and actual cerebral blood flow (CBF) has not been well studied during CPB. We determined the correlation of middle cerebral artery (MCA) mean velocity and CBF determined by the Kety-Schmidt method during nonbypass and two hypothermic bypass flow conditions. Sixteen patients undergoing hypothermic (27 degrees C) CPB for coronary artery bypass grafting and/or valve replacement surgery were enrolled in the study. We were able to determine MCA velocity in only 12 patients. We determined CBF and MCA velocity in each patient during four 15-min study periods: 1) prebypass after sternotomy before aortic cannulation; 2) hypothermic (27 degrees C) CPB with 1.2 L centered dot min-1 centered dot m-2 pump flow; 3) hypothermic CPB with 2.4 L centered dot min-1 centered dot m-2 pump flow, and 4) 30 min after weaning from CPB. There was no difference in the mean arterial pressure between the two CPB pump blood flows. The pooled change in MCA velocity and CBF as percentage of baseline (prebypass) for all patients and at all time points had a correlation of 0.33 (r). A decrease or increase in MCA velocity did not necessarily indicate a corresponding decrease or increase in CBF. This technology may be of limited usefulness during the circulatory condition of hypothermic, nonpulsatile CPB. (Anesth Analg 1996;82:1146-51)
Temporal changes in the incidence and 30-day mortality associated with bacteremia in hospitalized patients from 1992 through 2006: a population-based cohort study.

BACKGROUND Little is known about temporal trends in the incidence and mortality associated with bacteremia in the general population. METHODS We conducted a population-based cohort study in Northern Denmark to examine changes in bacteremia occurrence and 30-day mortality from 1992 through 2006. All patients who received a diagnosis of bacteremia were identified in a population-based bacteremia database and followed up for mortality through the Danish Civil Registry System. We determined the overall annual age- and sex-standardized rates of bacteremia episodes, the incidence of first-time episodes, and the adjusted 30-day mortality by place of acquisition and study period. RESULTS We identified 14,303 bacteremia episodes, 11,703 (81.8%) of which were incident. The age- and sex-standardized overall rate of bacteremia increased by 68% from 1992 through 2006, and the incidence increased by 46% (from 114 to 166 episodes per 100,000 person-years). Community-acquired and nosocomial bacteremia incidence rates peaked at 92.1 and 77.2 episodes per 100,000 person-years in 2004 and 2002, respectively, whereas the incidence of health care-associated bacteremia increased steadily from 2.9 to 39.8 episodes per 100,000 person-years. Total number of deaths increased from 742 during 1992-1996 to 926 during 2002-2006. The 30-day mortality decreased in patients with community-acquired bacteremia (19.0% during 1992-1996 vs 15.4% during 2002-2006) but remained nearly unchanged for health care-associated (23.4% and 22.0%, respectively) and nosocomial bacteremia (27.9% and 27.7%, respectively). CONCLUSIONS The occurrence of bacteremia in Northern Denmark, regardless of the place of acquisition, increased considerably in the past 15 years, and bacteremia was associated with persistently high 30-day mortality. Thus, bacteremia remains a clinical and public health concern.
On the Performance of a One-way Car Sharing System in Suburban Areas: A Real-world Use Case

In recent years, one-way car sharing systems have gained momentum across the world with their promise to encourage more sustainable urban mobility models. However, economic viability of car sharing is still uncertain due to high investment cost for station and fleet deployment, as well as high operation cost for fleet management and rebalancing. Furthermore, existing car sharing are typically confined to city centres with significant business and residential concentrations. In this study, we evaluate the performance of a novel oneway car sharing system that will be deployed in a suburban area of the city of Lyon using a detailed multi-agent and multi-modal transport simulation model. Data from a recent large-scale household travel survey is used to determine the travel demands on different transportation alternatives. We analyse the impact of different coverage constraints on the system capacity in terms of number of trips and vehicle availability. We also investigate the potential of user-based relocation strategies to increase the efficiency of the car sharing service. The model shows that: (i) the car sharing system is most sensitive to the infrastructure and fleet sizes, and (ii) user-based relocation does not have a significant impact on the total number of car sharing trips.
Biotic ligand model of the acute toxicity of metals. 2. Application to acute copper toxicity in freshwater fish and Daphnia

The biotic ligand model (BLM) was developed to explain and predict the effects of water chemistry on the acute toxicity of metals to aquatic organisms. The biotic ligand is defined as a specific receptor within an organism where metal complexation leads to acute toxicity. The BLM is designed to predict metal interactions at the biotic ligand within the context of aqueous metal speciation and competitive binding of protective cations such as calcium. Toxicity is defined as accumulation of metal at the biotic ligand at or above a critical threshold concentration. This modeling framework provides mechanistic explanations for the observed effects of aqueous ligands, such as natural organic matter, and water hardness on metal toxicity. In this paper, the development of a copper version of the BLM is described. The calibrated model is then used to calculate LC50 (the lethal concentration for 50% of test organisms) and is evaluated by comparison with published toxicity data sets for freshwater fish (fathead minnow, Pimephales promelas) and Daphnia.
Activation of cytokine genes during primary and anamnestic immune response to inactivated C. albicans

Recent evidence suggests that after repeated stimulations with inactivated C. albicans (CA) cells, CD2F1 mice respond with a cytokine pattern typical of T‐helper 1 (Th1) subset development. The purpose of this study was to analyse the sequence of immunological events which, soon after priming mice with CA, lead to the development of primary and anamnestic response. A comprehensive kinetics analysis of cytokine mRNA expression was performed by Northern blot assay, in peritoneal exudate cells (PEC), at different phases of immune response to CA: after priming (one i.p. injection of 2×107 CA cells/mouse), during development of the primary immune response (five progressive CA i.p. injections over a 2‐week period) and in the anamnestic response (CA booster 30days after the primary response). In vitro assays were performed 2 and 24hr after every CA stimulation. The response to CA priming was characterized by an early and high expression of interleukin‐2 (IL‐2) and IL‐1β mRNAs. At 24hr, IL‐2 mRNA was still at a high level, while IL‐1β had greatly decreased. A weak expression of IL‐10 was only induced at 2hr, whereas IL‐12 p40 subunit, interferon‐γ (IFN‐γ), IL‐4 and IL‐5 mRNAs were undetectable. In this phase no in vitro proliferative response of PEC to CA was observed, whereas a significant natural killer (NK) activity was induced. From the second CA injection, the IFN‐γ mRNA was already induced at 2hr. Its expression level increased progressively with the number of CA injections persisting up to 24hr after the fifth stimulation. A progressive increase of IL‐2 mRNA expression was also induced whereas IL‐1β and IL‐10 mRNAs were always transiently expressed at 2hr at levels similar to those observed after the priming. IL‐12 p40 subunit, IL‐4 and IL‐5 mRNAs were never detectable. The expression of this selected cytokine pattern typical of Th1 response was correlated with the development of CA‐specific T lymphocytes as confirmed by the in vitro proliferative response of CA‐5d‐induced PEC to CA. NK activity also increased progressively with the number of CA injections and after the fifth stimulation lymphokine‐activated killer (LAK) activity was also induced. The anamnestic response to CA was characterized by a very quick induction of high levels of IL‐2, IFN‐γ and IL‐1β mRNAs. IL‐2 and IFN‐γ mRNAs remained high up to 24hr while IL‐1β mRNA decreased strongly. A weak, transient expression of IL‐10 mRNA was induced at 2hr whereas the IL‐12 p40 subunit, IL‐4 and IL‐5 mRNAs were not detectable. The presence of CA‐specific memory lymphocytes was confirmed by the in vitro specific proliferative response of PEC to CA. CA booster caused also a very rapid and high level of NK/LAK activation. In conclusion, these results indicate that CA is able to progressively trigger differentiation of the Th1 subset which develops in the absence of IL‐12, and that Th memory cells retain the same selected Th1 cytokine profile developed in the primary immune response.
Polymerase chain reaction for diagnosis of enterohemorrhagic Escherichia coli infection and hemolytic-uremic syndrome

Two pairs of oligonucleotide primers were designed to amplify fragments of the genes for Shiga-like toxin I (SLT-I) and SLT-II in a single reaction. A 370-bp segment and a 283-bp segment were amplified for SLT-I and SLT-II, respectively. The specificities of the polymerase chain reaction (PCR) amplification products were confirmed by using radioactively labeled oligonucleotide probes. SLT sequences were amplified from DNA isolated from 13 previously characterized enterohemorrhagic Escherichia coli (EHEC) strains. No amplification product was produced by using DNA from 20 non-EHEC strains. As little as one bacterial genome was detectable. PCR was then applied to DNA isolated directly from stool samples. We had to remove inhibitors of PCR that were present in lysates prepared from stool samples before amplification was achieved. First, we evaluated the sensitivity of PCR for the detection of known numbers of EHEC added to normal stools. Second, three children with SLT in their stools were shown to have SLT sequences in their stools by PCR. Two of these children had hemolytic-uremic syndrome, and a third child was asymptomatic. Stool specimens collected from another 26 asymptomatic children were negative by PCR for SLT sequences. PCR can be used to diagnose EHEC infections without prior culture of stool specimens.
Caffeate Respiration in the Acetogenic Bacterium Acetobacterium woodii: a Coenzyme A Loop Saves Energy for Caffeate Activation

ABSTRACT The anaerobic acetogenic bacterium Acetobacterium woodii couples reduction of caffeate with electrons derived from molecular hydrogen to the synthesis of ATP by a chemiosmotic mechanism with sodium ions as coupling ions. Caffeate is activated to caffeyl coenzyme A (caffeyl-CoA) prior to its reduction, and the caffeate reduction operon encodes an ATP-dependent caffeyl-CoA synthetase that is thought to catalyze the initial caffeate activation. The operon also encodes a potential CoA transferase, the product of carA, which was thought to be involved in subsequent ATP-independent caffeate activation. To prove the proposed function of carA, we overproduced its protein in Escherichia coli and then purified it. Purified CarA drives the formation of caffeyl-CoA from caffeate with hydrocaffeyl-CoA as the CoA donor. The dependence of the reaction on caffeate and hydrocaffeyl-CoA followed Michaelis-Menten kinetics, with apparent Km values of 75 ï¿½ 5 μM for caffeate and 8 ï¿½ 2 μM for hydrocaffeyl-CoA. The enzyme activity had broad ranges of pH and temperature optima. In addition to being able to use caffeate, CarA could use p-coumarate and ferulate but not cinnamate, sinapate, or p-hydroxybenzoate as a CoA acceptor. Neither acetyl-CoA nor butyryl-CoA served as the CoA donor for CarA. The enzyme uses a ping-pong mechanism for CoA transfer and is the first classified member of a new subclass of family I CoA transferases that has two catalytic domains on one polypeptide chain. Apparently, CarA catalyzes an energy-saving CoA loop for caffeate activation in the steady state of caffeate respiration.
Mechanical and Electronic Amplitude-Limiting Techniques in a MEMS Resonant Accelerometer

Two methods for limiting the oscillation amplitude in micromechanical resonators, typically used in many kinds of MEMS sensors, are discussed and compared. First, it is shown how the presence of parasitic capacitances sets several constraints on the design of the oscillating circuit gain and bandwidth. The paper specifically focuses on the case of a transimpedance based oscillator coupled to a clamped-clamped beam, that forms the sensing element of a resonant accelerometer. Experimental results then show that the oscillating amplitude can be limited either using an electronic limiting stage, or exploiting the mechanical nonlinearities of the beam for large displacements. Though the latter approach is advantageous in terms of power dissipation, it is shown that the sensitivity of the resonant accelerometer is strongly compromised.
Analytical Model for Coexistence Performance Evaluation of WiFi and LTE Licensed-Assisted Access to Unlicensed Spectrum

 —LTE Licensed-Assisted Access (LAA) to unlicensed spectrum has been considered as an effective complement in offloading growing traffic since its emergence at 3GPP. Since 2015, 3GPP has launched standardization to develop LAA as a key technology for LTE-Advanced unlicensed spectrum deployment in Rel-13. In this paper, an analytical model is built for the performance evaluation of typical coexistence of Licensed-Assisted Access (LAA) LTE and WiFi IEEE 802.11. Assuming that LAA eNode-B performs Channel Clear Assessment (CCA) in a manner similar to Carrier Sense Multiple Access (CSMA) of WiFi, we use a two dimensional Markov chain to help analyzing not only the affected performance of WiFi but also the relation between the joint system performance and LAA maximum transmission time. After analytical analysis and simulations, it is shown that under certain system configuration joint system performance is approximately inversely proportional to a monomial of the maximum LAA transmission time.
Amplification of the Benefits of a Reliable and Maintainable Design by Adequate Maintenance and Support Concepts

Abstract : A reliable and maintainable design has obvious benefits with respect to Life Cycle Cost However, in order to make fell use of these design features, adequate alternative maintenance & support concepts - which are only viable in case of excellent Reliability and Maintainability of the Weapon System - must be considered. The traditional 4-level maintenance concept does not saflsf' the requirement for low Life Cycle Cost if a Weapon System featuring a reliable and maintainable design is to be supported. This requirement is flilfilled if the more advanced 2-level maintenance concept which is characterised by the limitation of base level maintenance to on A/C tasks and transfer of the remaining activities to a single source supplier, i.e. industry. In order to make the 2-level maintenance concept a viable solution, aircraft availability and Airforce self-sufficiency need special attention but can be ensured via an adequate support concept and integration of military personnel in industry maintenance. The 2-level maintenance concept was analysed for the Eurofighter/Typhoon to be operated by the German Airforce. A thorough comparison with traditional maintenance concepts revealed that the 2-level maintenance concept is much more cost-effective, therefore this advanced concept is now applied by the German Airforce.
Community drinking water quality monitoring data: utility for public health research and practice.

CONTEXT Environmental Public Health Tracking (EPHT) tracks the occurrence and magnitude of environmental hazards and associated adverse health effects over time. The EPHT program has formally expanded its scope to include finished drinking water quality. OBJECTIVES Our objective was to describe the features, strengths, and limitations of using finished drinking water quality data from community water systems (CWSs) for EPHT applications, focusing on atrazine and nitrogen compounds in 8 Midwestern states. METHODS Water quality data were acquired after meeting with state partners and reviewed and merged for analysis. RESULTS Data and the coding of variables, particularly with respect to censored results (nondetects), were not standardized between states. Monitoring frequency varied between CWSs and between atrazine and nitrates, but this was in line with regulatory requirements. Cumulative distributions of all contaminants were not the same in all states (Peto-Prentice test P < .001). Atrazine results were highly censored in all states (76.0%-99.3%); higher concentrations were associated with increased measurement frequency and surface water as the CWS source water type. Nitrate results showed substantial state-to-state variability in censoring (20.5%-100%) and in associations between concentrations and the CWS source water type. CONCLUSIONS Statistical analyses of these data are challenging due to high rates of censoring and uncertainty about the appropriateness of parametric assumptions for time-series data. Although monitoring frequency was consistent with regulations, the magnitude of time gaps coupled with uncertainty about CWS service areas may limit linkage with health outcome data.
Social Media and Public Opinion

Communication is used to develop identity. In digital communication identity building is based on different tools than in a real world setting. Reputation and social authority are therefore based on different aspects. Social Media is human communication mediated through social software. Social software facilitate the creation of social networks in digital environment. Networks are a form of organization that increases the effectiveness of the individual and the whole network. During the last years Social Media, social networks, and Web 2.0 have been studied with the result that they are better understood nowadays. It now seems as if these phenomena are more than a technological advancement, rather a paradigm shift. Opinion building is strongly connected to the process of shaping human society. Social communication, social networks, and reputation play a key role in this process. Opinion is a result of cultural, political, ideological, and social believes and desires and public opinion is the aggregate of dominant opinions within a society, communicated in public sphere. Social communication through social media is increasing. The way public opinion is formed is strongly influenced by these new media.
HBV NAT positive [corrected] blood donors in the early and late stages of HBV infection: analyses of the window period and kinetics of HBV DNA.

BACKGROUND AND OBJECTIVES The Japanese Red Cross (JRC) carries out nucleic acid amplification testing (NAT) for hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus-1 (HIV-1) by using a multiplex (MPX) reagent. Screening is undertaken on serologically negative units. In this study we characterized HBV NAT-positive donations individually and analysed the window period and kinetics of HBV DNA, during acute infection, in follow-up studies. MATERIALS AND METHODS Two hundred and seventy-seven HBV DNA-positive donations have been identified in Japan since the introduction of NAT screening of 50-donation minipools. The viral loads and genotypes of these HBV DNA-positive donations were characterized. The doubling time and half-life of HBV was estimated from the data of 123 follow-up donors. The sensitivity of the NAT system (based on 50-donation minipools) was compared with the sensitivities of the enzyme immunoassay (EIA) and the chemiluminescence immunoassay (CLIA). Samples that were CLIA negative, but with > 10(4) copies/ml of HBV DNA, were analysed by sequencing the hepatitis B surface antigen (HBsAg) region. RESULTS Out of 277 HBV NAT-positive samples, 125 (45%) were found to have an increasing viral load and 45 (16%) a decreasing viral load. Forty per cent of HBV NAT-positive samples with an increasing viral load, and 33% of those with a decreasing viral load, were negative when tested by using the CLIA. No mutations related to escape mutants were found in the samples that were CLIA negative but with HBV DNA loads of > 10(4) copies/ml. The median HBV doubling time was 2.6 days (n = 93, 1.3-15.2 days) and the half-life was 1.6 days (n = 55, 0.9-6.3 days). Some kinetic difference was observed between genotypes A and B. CONCLUSIONS HBV NAT screening detected HBV DNA in both early (the so-called serological window period) and late stages of acute HBV infection.
The Effect of Efficiency Improvement and Technological Progress on Green Productivity Growth: An Empirical Analysis for 36 Sub-industrial Sectors in China

Global DEA approach and Malmquist-Luenberger index are applied to measure subindustrial green TFP growth and its components in presence of energy and carbon emissions.From the result of calculating,it is concluded that industrial green TFP growth is mainly driven by technological progress and drawn back by efficiency change.It is also found that the sub-industrial carbon productivity shows a constantly rising trend.The different impact of technical efficiency and technological progress is confirmed by empirical test on the rising sub-industrial carbon productivity.The impact of efficiency change is stronger than that of technological progress on industrial carbon productivity and the impact of technical efficiency and technological progress on the carbon productivity of weight industry is stronger than that of light industry.Therefore,Low-carbon technological progress should be strengthened to promote the subindustrial carbon productivity growth,while more attention should be paid to exert the role of technical efficiency in promoting sub-industrial carbon productivity.