Miracle-dz/UniFAR-FTUs huggingface dataset:
HBsAg retention sensitizes the hepatocyte to injury by physiological concentrations of interferon‐γ

The role that inflammatory cytokines may play in the life cycle of the hepatitis B virus and in the pathogenesis of its associated liver disease has not been carefully delineated. In this report, we demonstrate that bacterial lipopolysaccharide, a potent inducer of inflammatory cytokines in vivo, causes a severe acute liver disease in transgenic mice whose hepatocytes produce the hepatitis B virus large envelope polypeptide and retain HBsAg within the endoplasmic reticulum. In contrast, 100‐fold higher doses of bacterial lipopolysaccharide do not induce liver cell injury in nontransgenic littermate controls or in transgenic mice whose hepatocytes secrete HBsAg rather than retain it. Coincident with the hepatocellular injury and the influx of inflammatory cells into the liver, a marked reduction occurs in the intrahepatic content of hepatitis B virus steady‐state messenger RNA, thereby confirming the selectivity of this process for the HBsAg‐positive hepatocyte. Bacterial lipopolysaccharide‐induced hepatocellular injury appears to be principally mediated by interferon‐γ because it can be markedly reduced by the prior administration of neutralizing interferon‐γ–specific monoclonal antibodies and because recombinant interferon‐γ is also selectively cytotoxic for the HBsAg‐positive transgenic hepatocyte in vivo. Tumor necrosis factor–α is also involved in this process because bacterial lipopolysaccharide‐induced liver cell injury is significantly reduced by tumor necrosis factor–α specific monoclonal antibodies. The role of tumor necrosis factor–α in bacterial lipopolysaccharide–induced liver cell injury is less clear than interferon‐γ, however, because unlike interferon‐γ it is also toxic for nontransgenic hepatocytes. These results demonstrate that the HBsAg‐positive transgenic mouse hepatocyte is selectively sensitive to destruction by interferon‐γ in vivo. Because this cytokine has been shown to be produced by intrahepatic lymphocytes during viral hepatitis in humans, these results raise the possibility that a similar pathway may contribute to the clearance of HBsAg‐positive hepatocytes and to the pathogenesis of liver cell injury in human HBV infection as well. (HEPATOLOGY 1992;16:655–663.)
Memory editing mechanisms

This special issue of the journal Memory is devoted to an investigation of those mechanisms by which memory is edited for inaccuracies and inconsistencies. In the past 20 years false memories have been investigated from a variety of different angles. Substantial evidence indicates that false memories can be created in a number of different situations, including word learning (Deese, 1959; Payne, Elie, Blackwell, & Neuschatz, 1996; Roediger & McDermott, 1995), sentence and story memory (Bower, Black, & Turner, 1979; Bransford & Franks, 1971; Reyna & Kiernan, 1994), eyewitness memory (Lindsay & Johnson, 1989; Loftus, 1979a, 1979b), memory for faces (Hannigan & Reinitz, 2000; Read, Vokey, & Hammersley, 1990; Reinitz & Hannigan, 2001; Sommer, Heinz, Leuthold, Matt, & Schweinberger, 1995), and memory for naturalistic scenes (Brewer & Treyens, 1981; Lampinen, Copeland, & Neuschatz, 2001; Pezdek, Whetstone, Reynolds, Askari, & Dougherty, 1989). In each of these cases, it has been found that memory is subject to a range of distortions. But there has also been an increasing recognition that this is only half the story. For although memory is subject to distortion, there are also editing mechanisms that are utilised which allow our memories to be relied on as reasonably accurate under most circumstances (Brainerd & Reyna, 2002; Brainerd, Reyna, & Kneer, 1995; Dodson & Schacter, 2002; Gallo, Weiss, & Schacter, 2004; Lampinen, Odegard, & Neuschatz, 2004; Odegard, Lampinen, & Toglia, 2005; Schacter, Israel, & Racine, 1999). The focus of this special issue of Memory, then, is on the interplay between those mechanisms that distort memory and those mechanisms that protect memory against distortion. Natural selection did not produce in humans a memory system that acts as a video-recorder, faithfully recording all events in detail for mental examination into perpetuity (Loftus, 1979b). This tells us something important about memory, namely that memory serves survival functions that do not typically require verbatim-level recall of details (Reyna & Brainerd, 1995). However, memory is also not wanton in the way in which it stores and recovers past events. Memories are sometimes inaccurate, but provide a good first approximation of the events that make up our personal past. This first-order faithfulness also tells us something important about memory. Errors in memory are errors that ‘‘make sense’’ in terms of constructing a more or less accurate rendition of the gist of past events (Scheflin, 1999). Martin Enns (2004), in writing about visual perception, points out that although visual stimuli are typically ambiguous and open to multiple
Uma revisão sistemática sobre medição da experiência do usuário

In scenarios of measuring user experience (UX) identified in the literature of the last 8 years, the interaction between the user and the system is evaluated in different ways. This article presents a systematic review of the factors considered when measuring UX, with 22 studies. As a result, usability still arouses much interest, and not only the other factors of UX. We also identified the interest in measuring UX, although the purpose of this measurement is unclear.
Telerehabilitation implementation and routine clinical use: Preliminary findings from a case study across three rehabilitation centers

Integrating innovations such as telerehabilitation (TR) into routine clinical care is a complex process. This study aimed to identify the factors which impact on TR implementation and routine use. Methods. A mixed-method prospective single-case study with multiple embedded units of analysis was conducted. Interviews (implementation leaders, clinical champions and upper management) and focus groups with users and non-users of TR were conducted, and TR use was recorded. The Consolidated Framework for Implementation Research and Normalization Process Theory were used to examine factors which impacted on TR implementation and routine use. Results. Over 18 months, 155 TR sessions were carried out by 12 clinicians (6% of potential staff), eight of which continued using TR routinely clinical activities. During implementation, deviations to the intended implementation and unexpected delays impacted on TR use. TR continued to be used for some clinical activities. Facilitators and barriers were related to the intervention, the organisations and the health care context. Discussion. Comprehensive frameworks and theories used in long term studies of TR use can help identify factors which impact on implementation and routine clinical use.
Human interleukin‐6 induces human herpesvirus‐8 replication in a body cavity‐based lymphoma cell line

Human herpesvirus‐8 (HHV‐8) is etiologically associated with Kaposi's sarcoma (KS), body cavity‐based lymphoma (BCBL), and multicentric Castleman's disease (MCD). These HHV‐8‐associated diseases arise predominantly in acquired immunodeficiency syndrome (AIDS) patients. Human interleukin‐6 (huIL‐6) elevated in the serum of AIDS patients is suggested to stimulate the growth of KS and BCBL and to augment the symptoms of MCD. To determine whether huIL‐6 stimulates HHV‐8 replication directly, expression of the HHV‐8 ORF‐50 immediate‐early gene (transcription activator) and ORF‐26 late lytic gene (a capsid protein) was assessed in a BCBL‐1 cell line stimulated by huIL‐6 by means of real‐time reverse transcription‐polymerase chain reaction. huIL‐6 induced both ORF‐50 and ORF‐26 expression, and the maximal ORF‐50 expression appeared earlier than that of ORF‐26. The data indicate that huIL‐6 reactivates HHV‐8 in BCBL‐1 cells through inducing ORF‐50. We also confirmed the previously reported activities of HHV‐8‐encoded huIL‐6 homologue (viral interleukin‐6 [vIL‐6]) on human immunodeficiency virus (HIV) replication in U1 cell line and huIL‐6 production by MT‐4 T cells, and utilizing monoclonal antibodies to the huIL‐6 receptor components, we elucidated that gp130 is the signaling molecule necessary for these vIL‐6 activities. These data suggest the possible existence of interaction between HIV and HHV‐8 via IL‐6, and that the blockade of IL‐6 signal by anti‐IL‐6R antibody or anti‐gp130 antibody can constitute a strategy to treat HIV/HHV‐8 dually infected patients. J. Med. Virol. 68:404–411, 2002. © 2002 Wiley‐Liss, Inc.
Bubble-seq analysis of the human genome reveals distinct chromatin-mediated mechanisms for regulating early- and late-firing origins

We have devised a method for isolating virtually pure and comprehensive libraries of restriction fragments that contained replication initiation sites (bubbles) in vivo. We have now sequenced and mapped the bubble-containing fragments from GM06990, a near-normal EBV-transformed lymphoblastoid cell line, and have compared origin distributions with a comprehensive replication timing study recently published for this cell line. We find that early-firing origins, which represent ∼32% of all origins, overwhelmingly represent zones, associate only marginally with active transcription units, are localized within large domains of open chromatin, and are significantly associated with DNase I hypersensitivity. Origin “density” falls from early- to mid-S-phase, but rises again in late S-phase to levels only 17% lower than in early S-phase. Unexpectedly, late origin density calculated on the 1-Mb scale increases as a function of increasing chromatin compaction. Furthermore, the median efficiency of origins in late-replicating, heterochromatic domains is only 25% lower than in early-replicating euchromatic loci. Thus, the activation of early- and late-firing origins must be regulated by quintessentially different mechanisms. The aggregate data can be unified into a model in which initiation site selection is driven almost entirely by epigenetic factors that fashion both the long-range and local chromatin environments, with underlying DNA sequence and local transcriptional activity playing only minor roles. Importantly, the comprehensive origin map we have prepared for GM06990 overlaps moderately well with origin maps recently reported for the genomes of four different human cell lines based on the distributions of small nascent strands.
Small and Micro Business Enterprises (SMBEs) in Addis Ababa, Ethiopia : development and poverty reduction through Information and Communication Technologies (ICTs), with particular reference to the hotel industry and associated businesses

The role of Information and Communication Technologies (ICTs) as a facilitator and enabler for development and poverty reduction has been increasingly recognised by many international organisations. ICTs need to be diffused in society to have their effects realised. The diffusion of ICTs in developing countries is lagging behind the developed countries creating the digital divide. Although the divide is reducing in many sub-Saharan countries, in Ethiopia it is increasing. The purpose of this study is to find the factors that affect the adoption and nonadoption of ICTs in small and micro businesses in Addis Ababa, Ethiopia. A number of sectors were explored and the hotel and tour operator sector was found to have both adopters and non-adopters. The hotel and tour operator business in Addis Ababa was selected to be the study population. The main research question was to find the connection between the political, economic, and social factors and the adoption and use of ICT in this sector. While cultural, social-economic, political and legal factors affect the adoption of innovation in both developed and developing countries, these factors are more pronounced in the developing countries. Rogers’ diffusion of innovation theory is a good initial theoretical candidate for understanding the ICT diffusion factors. However, to include the national level factors, a theoretical framework was proposed based on Rogers’ diffusion of innovation theory. An exploratory research method was used to shed light on the adoption and non-adoption factors. It uses mixed methods research methodology in two phases to collect data from owners/managers. In the first phase in-depth interviews were conducted with 16 hoteliers who adopted ICT in their businesses. In the second phase survey questionnaires were used to collect data from 128 hoteliers and 57 tour operators. In this phase both adopters and non-adopters of ICT were included. Data were analysed using NVivo and Statistical Package for Social Sciences (SPSS) software packages. This study argues that the telecommunications monopoly, the non-affordability of ICT products and services, the general economic situation, lack of knowledge and awareness of the technology, and lack of legal protection for small hotels affect the adoption negatively. On the other hand, network externalities, competition among hoteliers, and major customers (foreign) act as a facilitator agent and have a positive impact on the adoption of ICT. The researcher argues that the political, social, economic, technological and legal policies are the sources of the adoption and non-adoption factors of ICTs in the hotel and tour operator business.
Effects of parental radiation exposure on developmental instability in grasshoppers

Mutagenic and epigenetic effects of environmental stressors and their transgenerational consequences are of interest to evolutionary biologists because they can amplify natural genetic variation. We studied the effect of parental exposure to radioactive contamination on offspring development in lesser marsh grasshopper Chorthippus albomarginatus. We used a geometric morphometric approach to measure fluctuating asymmetry (FA), wing shape and wing size. We measured time to sexual maturity to check whether parental exposure to radiation influenced offspring developmental trajectory and tested effects of radiation on hatching success and parental fecundity. Wings were larger in early maturing individuals born to parents from high radiation sites compared to early maturing individuals from low radiation sites. As time to sexual maturity increased, wing size decreased but more sharply in individuals from high radiation sites. Radiation exposure did not significantly affect FA or shape in wings nor did it significantly affect hatching success and fecundity. Overall, parental radiation exposure can adversely affect offspring development and fitness depending on developmental trajectories although the cause of this effect remains unclear. We suggest more direct measures of fitness and the inclusion of replication in future studies to help further our understanding of the relationship between developmental instability, fitness and environmental stress.
Kainic Acid-Induced Post-Status Epilepticus Models of Temporal Lobe Epilepsy with Diverging Seizure Phenotype and Neuropathology

The aim of epilepsy models is to investigate disease ontogenesis and therapeutic interventions in a consistent and prospective manner. The kainic acid-induced status epilepticus (KASE) rat model is a widely used, well-validated model for temporal lobe epilepsy (TLE). As we noted significant variability within the model between labs potentially related to the rat strain used, we aimed to describe two variants of this model with diverging seizure phenotype and neuropathology. In addition, we evaluated two different protocols to induce status epilepticus (SE). Wistar Han (Charles River, France) and Sprague-Dawley (Harlan, The Netherlands) rats were subjected to KASE using the Hellier kainic acid (KA) and a modified injection scheme. Duration of SE and latent phase were characterized by video-electroencephalography (vEEG) in a subgroup of animals, while animals were sacrificed 1 week (subacute phase) and 12 weeks (chronic phase) post-SE. In the 12 weeks post-SE groups, seizures were monitored with vEEG. Neuronal loss (neuronal nuclei), microglial activation (OX-42 and translocator protein), and neurodegeneration (Fluorojade C) were assessed. First, the Hellier protocol caused very high mortality in WH/CR rats compared to SD/H animals. The modified protocol resulted in a similar SE severity for WH/CR and SD/H rats, but effectively improved survival rates. The latent phase was significantly shorter (p < 0.0001) in SD/H (median 8.3 days) animals compared to WH/CR (median 15.4 days). During the chronic phase, SD/H rats had more seizures/day compared to WH/CR animals (p < 0.01). However, neuronal degeneration and cell loss were overall more extensive in WH/CR than in SD/H rats; microglia activation was similar between the two strains 1 week post-SE, but higher in WH/CR rats 12 weeks post-SE. These neuropathological differences may be more related to the distinct neurotoxic effects of KA in the two rat strains than being the outcome of seizure burden itself. The divergences in disease progression and seizure outcome, in addition to the histopathological dissimilarities, further substantiate the existence of strain differences for the KASE rat model of TLE.
Low-Noise Single-Frequency 1.5- $\mu$ m Fiber Laser With a Complex Optical-Feedback Loop

A low-noise narrow-linewidth distributed Bragg reflector (DBR) single frequency 1.5- $\mu \text{m}$ fiber laser with a complex optical-feedback loop (COFL) is demonstrated. The COFL is used to reduce the relative intensity noise (RIN) and narrow the linewidth, which is composed of an erbium-doped fiber amplifier (EDFA), an unpumped Er80 fiber and a sagnac loop mirror. The COFL combines the nonlinear amplification effect of saturated optical amplifiers, the standing-wave saturation effects of saturable absorber (SA), and the self-injection locking technology at the same time. The effects of self-injection locking give a sufficient proof, which the RIN is reduced and the resonance peak shifts to lower frequency. The RIN of low frequency is greatly reduced by the EDFA. In addition, the SA narrows the linewidth. After the COFL suppression, the RIN of relaxation oscillation is reduced by 24.5 dB from 80.3 dB/Hz at 219 kHz to 104.8 dB/Hz at 87 kHz. Furthermore, the linewidth narrows from 7.47 kHz to 720 Hz. Even after two-stage fiber amplification, the RIN does not increase significantly, and a spectral linewidth well below 1.8 kHz is also achieved at the output power of 11.1 W.
The duration of action of bupivacaine, prilocaine and lignocaine.

SUMMARY The duration of analgesia and of hypoaesthesia produced by a variety of solutions has been examined by skin weal testing; each separate study was carried out in twenty female volunteers under double-blind conditions. First, bupivacaine, lignocaine and prilocaine were compared with and without 1 in 200,000 adrenaline. Bupivacaine was found to give significantly longer analgesia than prilocaine and significantly longer hypoaesthesia than both the other agents. Adrenaline significantly lengthened the action of all three drugs, this prolongation being greatest with lignocaine. The second part of the trial compared the duration of action of hospital-prepared and commercially prepared solutions of the three local analgesics plus adrenaline. The commercial ampoule preparations provided significantly longer action than the corresponding drugs in hospital-prepared multidose vials. The third group of experiments studied the effect of doubling the concentrations of the solutions; there was no great increase in duration of analgesia but the duration of hypoaesthesia was lengthened, significantly so with bupivacaine. Throughout all the above studies the individual results with bupivacaine showed a greater range of variation than those with the other agents. Finally the analgesic effect of saline (with and without adrenaline) was investigated; it was found that both agents generally produced a similar brief period of hypoaesthesia. The findings and their practical implications are discussed.
Generation of free radicals and induction of DNA adducts by activation of heterocyclic aromatic amines via different metabolic pathways in vitro

Food‐derived heterocyclic aromatic amines (HCAs) have proved to be carcinogenic in both rodents and nonhuman primates. Two different metabolic pathways are suggested for the metabolic activation of HCA. The hepatic pathway proceeds via a two‐step process involving N‐hydroxylation by cytochrome P4501A2 and subsequent O‐acetylation by N‐acetyltransferase‐2. An alternative pathway may be of particular interest in extrahepatic tissues and proceeds via one‐electron oxidation catalyzed by prostaglandin H synthase (PHS), rendering free‐radical metabolites. In this study, we investigated the metabolic activation of two HCAs, 2‐amino‐3‐methylimidazo[4,5‐f]quinoline (IQ) and 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine (PhIP), by two different enzyme systems in vitro, generating different primary and secondary reactive metabolites. Rat liver S9 mix and PHS were used as the activating system and represent the hepatic and extrahepatic pathways, respectively. Electron‐spin resonance spectroscopy showed that both IQ and PhIP exerted inhibiting effects on PHS‐mediated formation of hydroxyl radicals during the conversion of arachidonic acid to prostaglandins. Evidence for the formation of HCA free radicals was presented in an indirect way by the formation of glutathione‐derived thiyl radicals, with purified PHS as the activating system. Activation by S9 mix did not result in the formation of detectable radical metabolites, showing that the two metabolic routes primarily led to the formation of different metabolites. In all electron‐spin resonance experiments, IQ appeared to be more effective than PhIP. In contrasts, DNA adduct analysis by means of 32P‐postlabeling showed similar adduct patterns for S9 and PHS in single‐stranded and double‐stranded salmon testes DNA after incubation with PhIP, indicating the ultimate formation of a common reactive intermediate. For IQ, activation by PHS led to an additional adduct spot that was not present after S9 activation. Furthermore, activation of IQ resulted in higher adduct levels compared with PhIP for both activation pathways. Overall, adduct levels were higher in single‐stranded DNA than double‐stranded DNA. Our results showed that the hepatic and extrahepatic pathways resulted in different primary metabolites, while the ultimate formation of a similar reactive intermediate for PhIP, possibly an arylnitrenium ion, suggested that both pathways could play an important role in the onset of carcinogenesis. © 2002 Wiley‐Liss, Inc.