Endogenous Presentation of CD8+ T Cell Epitopes from Epstein-Barr Virus–encoded Nuclear Antigen 1

Epstein-Barr virus (EBV)-encoded nuclear antigen (EBNA)1 is thought to escape cytotoxic T lymphocyte (CTL) recognition through either self-inhibition of synthesis or by blockade of proteasomal degradation by the glycine-alanine repeat (GAr) domain. Here we show that EBNA1 has a remarkably varied cell type-dependent stability. However, these different degradation rates do not correspond to the level of major histocompatibility complex class I-restricted presentation of EBNA1 epitopes. In spite of the highly stable expression of EBNA1 in B cells, CTL epitopes derived from this protein are efficiently processed and presented to CD8(+) T cells. Furthermore, we show that EBV-infected B cells can readily activate EBNA1-specific memory T cell responses from healthy virus carriers. Functional assays revealed that processing of these EBNA1 epitopes is proteasome and transporter associated with antigen processing dependent. We also show that the endogenous presentation of these epitopes is dependent on the newly synthesized protein rather than the long-lived stable EBNA1. Based on these observations, we propose that defective ribosomal products, not the full-length antigen, are the primary source of endogenously processed CD8(+) T cell epitopes front EBNA1.

Cost-effectiveness of combination peginterferon alpha-2a and ribavirin compared with interferon alpha-2b and ribavirin in patients with chronic hepatitis C

BACKGROUND: Sustained virological response (SVR) is the primary objective in the treatment of chronic hepatitis C (CHC). Results from a recent clinical trial of patients with previously untreated CHC demonstrate that the combination of peginterferon alpha-2a and ribavirin produces a greater SVR than interferon alpha-2b and ribavirin combination therapy. However, the cost-effectiveness of peginterferon alpha-2a plus ribavirin in the U.S. setting has not been investigated. METHODS: A Markov model was developed to investigate cost-effectiveness in patients with CHC using genotype to guide treatment duration. SVR and disease progression parameters were derived from the clinical trials and epidemiologic studies. The impact of treatment on life expectancy and costs were projected for a lifetime. Patients who had an SVR were assumed to remain virus-free for the rest of their lives. In genotype 1 patients, the SVRs were 46% for peginterferon alpha-2a plus ribavirin and 36% for interferon alpha-2b plus ribavirin. In genotype 2/3 patients, the SVRs were 76% for peginterferon alpha-2a plus ribavirin and 61% for interferon alpha-2b plus ribavirin. Quality of life and costs were based on estimates from the literature. All costs were based on published U.S. medical care costs and were adjusted to 2003 U.S. dollars. Costs and benefits beyond the first year were discounted at 3%. RESULTS: In genotype 1, peginterferon alpha-2a plus ribavirin increases quality-adjusted life expectancy (QALY) by 0.70 yr compared to interferon alpha-2b plus ribavirin, producing a cost-effectiveness ratio of $2,600 per QALY gained. In genotype 2/3 patients, peginterferon alpha-2a plus ribavirin increases QALY by 1.05 yr in comparison to interferon alpha-2b plus ribavirin. Peginterferon alpha-2a combination therapy in patients with HCV genotype 2 or 3 is dominant (more effective and cost saving) compared to interferon alpha-2b plus ribavirin. Results weighted by genotype prevalence (75% genotype 1; 25% genotype 2 or 3) also show that peginterferon alpha-2a plus ribavirin is dominant. Peginterferon alpha-2a and ribavirin remained cost-effective (below $16,500 per QALY gained) under sensitivity analyses on key clinical and cost parameters. CONCLUSION: Peginterferon alpha-2a in combination with ribavirin with duration of therapy based on genotype, is cost-effective compared with conventional interferon alpha-2b in combination with ribavirin when given to treatment-naive adults with CHC.

Choosing organics: A path analysis of factors underlying the selection of organic food among Australian consumers

Path analysis of attitudinal, motivational, demographic and behavioural factors influencing food choice among Australian consumers who had consumed at least some organic food in the preceding 12 months showed that concern with the naturalness of food and the sensory and emotional experience of eating were the major determinants of increasing levels of organic consumption. Increasing consumption was also related to other 'green consumption' behaviours such as recycling and to lower levels of concern with convenience in the purchase and preparation of food. Most of these factors were, in turn, strongly affected by gender and the level of responsibility taken by respondents for food provisioning within their households, a responsibility dominated by women. Education had a slightly negative effect on the levels of concern for sensory and emotional appeal due to lower levels of education among women. Income, age, political and ecological values and willingness to pay a premium for safe and environmentally friendly foods all had extremely minor effects. (C) 2004 Elsevier Ltd. All rights reserved.

Lessons learned . . . about curriculum: Five years on and half a world away

The knowledge, skills, and attitudes manifested in health and physical education school curricula are an arbitrary selection of that which is known and valued at a particular place and time. Bernstein's (2000) theories of the social construction of knowledge offer a way to better understand the relationship among the production, selection, and reproduction of curricular knowledge. This article overviews contemporary knowledge in the primary field (production) on which curriculum writers in the recontextualizing field might draw. It highlights tensions in the knowledge generated within the primary field and, using a case of the USXs National Standards for Physical Education (NASPE), demonstrates how particular discourses become privileged when translated into curriculum documents in the recontextualizing field

Diffuse optical light in galaxy clusters. I. Abell 3888

We are undertaking a program to measure the characteristics of the intracluster light ( ICL; total flux, profile, color, and substructure) in a sample of 10 galaxy clusters with a range of cluster mass, morphology, and redshift. We present here the methods and results for the first cluster in that sample, A3888. We have identified an ICL component in A3888 in V and r that contains 13% +/- 5% of the total cluster light and extends to 700 h(70)(-1) kpc (similar to 0.3r(200)) from the center of the cluster. The ICL color in our smallest radial bin is V - r 0.3 +/- 0.1, similar to the central cluster elliptical galaxies. The ICL is redder than the galaxies at 400 h(70)(-1) kpc < r < 700 h(70)(-1) kpc, although the uncertainty in any one radial bin is high. Based on a comparison of V - r color with simple stellar models, the ICL contains a component that formed more than 7 Gyr ago ( at z less than 1) with a high-metallicity ( 1.0 Z(circle dot) < Z(ICL) less than or similar to 2.5 Z(circle dot)) and a more centralized component that contains stars formed within the past 5 Gyr ( at z similar to 1). The profile of the ICL can be roughly fitted by a shallow exponential in the outer regions and a steeper exponential in the central region. We also find a concentration of diffuse light around a small group of galaxies 1.4 h(70)(-1) Mpc from the center of the cluster. In addition, we find three low surface brightness features near the cluster center that are blue ( V - r 0.0) and contain a total flux of 0.1M*. Based on these observations and X-ray and galaxy morphology, we suggest that this cluster is entering a phase of significant merging of galaxy groups in the core, whereupon we expect the ICL fraction to grow significantly with the formation of a cD galaxy, as well as the infall of groups.

Re-treatment of chronic hepatitis C patients after relapse: efficacy of peginterferon-alpha-2a (40 kDa) and ribavirin

SUMMARY. We conducted a randomized multinational study to determine whether 48 weeks of re-treatment with peginterferon- alpha-2a (40 kDa) plus ribavirin would induce a sustained virological response (SVR) in relapsed chronic hepatitis C patients. Patients who had previously relapsed during 24 weeks of untreated follow-up, after having achieved an end-of-treatment virological response with 24 weeks of peginterferon-alpha-2a (40 kDa)/ribavirin combination therapy, within a phase III trial, were studied. Although the recommended dosage was the same as that used at the end of the initial trial, adjustments were permitted. Data on serious adverse events, or adverse events that resulted in dose reductions or discontinuations, were collected. Following re-treatment, the overall SVR rate in the 64 patients was 55%. The SVR rates in patients infected with hepatitis C virus (HCV) genotype 1 and non-1 genotypes were 51% and 63%, respectively. Early (week 12) virological responses were seen in 39 patients (61%) and were predictive of an SVR. Re-treatment was well tolerated. The most frequent adverse events recorded were fatigue (5%) and abdominal pain (3%). Dosages of peginterferon-alpha-2a (40 kDa) and/or ribavirin were modified because of adverse events in 3% and 13% of patients, and because of laboratory abnormalities in 23% and 5% of patients, respectively. Thus, a 48-week course of peginterferon-alpha-2a (40 kDa) plus ribavirin induces an SVR in 55% of patients who relapsed during follow-up after 24 weeks of combination therapy. Physicians should not hesitate to offer re-treatment to patients who relapse after an initial, 24-week course of combination therapy, or who have prematurely stopped treatment because, for example, of laboratory abnormalities.

Queer enough? Contested terrains of identity deployment in the context of gay and lesbian public activism in Poland

Gay and lesbian prides and marches are of crucial relevance to the way in which non-heterosexual lives are imagined internationally despite regional and national differences. Quite often, these events are connected not only with increased activist mobilisation, but also with great controversy, which is the case of Poland, where gay and lesbian marches have been attacked by right-wing protesters and cancelled by right-wing city authorities on a number of occasions. Overall, the scholars analysing these events have largely focused on the macro-context of the marches, paying less attention to the movement actors behind these events. The contribution of this thesis lies not only in filling a gap when it comes to research on sexual minorities in Eastern Europe/Poland, but also in its focus on micro-level movement processes and engagement with theories of collective identity and citizenship. Furthermore, this thesis challenges the inscription of Eastern European/Polish movements into the narrative of victimhood and delayed development when compared to LGBT movements in the Global North. This thesis is grounded in qualitative research including participant observation of public activist events as well as forty semi-structured interviews with the key organisers of gay and lesbian marches in Warsaw, Poznan and Krakow between 2001 and 2007, and five of these interviews were further accompanied by photo-elicitation (self-directed photography) methods. Starting from the processes whereby from 2001 onwards, marches, pride parades and demonstrations became the most visible and contested activity of the Polish lesbian and gay movement, this thesis examines how the activists redefined the meanings of citizenship in the post-transformation context, by incorporating the theme of sexual minorities' rights. Using Bernstein's (1997, 2002, 2005, 2008) concept of identity deployment, I show how and when movement actors use identity tactically, depending on their goals. Specifically, in the context of movement-media interactions, I examine the ways in which the activists use marches to challenge the negative representations of sexual minorities in Poland. I also broaden Bernstein's framework to include the discussion of emotion work as relevant to public LGBT activism in Poland. Later, I discuss how the emotions of protests allowed the activists to inscribe their efforts into the "revolutionary" narrative of the Polish Solidarity movement and by extension, the frame of citizenship. Finally, this thesis engages with the dilemmas of identity deployment strategies, and seeks to problematise the dichotomy between identity-based gay and lesbian assimilationist strategies and the anti-identity queer politics.

Truthiness and falsiness of trivia claims depend on judgmental contexts

When people rapidly judge the truth of claims presented with or without related but nonprobative photos, the photos tend to inflate the subjective truth of those claims-a "truthiness" effect (Newman et al., 2012). For example, people more often judged the claim "Macadamia nuts are in the same evolutionary family as peaches" to be true when the claim appeared with a photo of a bowl of macadamia nuts than when it appeared alone. We report several replications of that effect and 3 qualitatively new findings: (a) in a within-subjects design, when people judged claims paired with a mix of related, unrelated, or no photos, related photos produced truthiness but unrelated photos had no significant effect relative to no photos; (b) in a mixed design, when people judged claims paired with related (or unrelated) and no photos, related photos produced truthiness and unrelated photos produced "falseness;" and © in a fully between design, when people judged claims paired with either related, unrelated, or no photos, neither truthiness nor falsiness occurred. Our results suggest that photos influence people's judgments when a discrepancy arises in the expected ease of processing, and also support a mechanism in which-against a backdrop of an expected standard-related photos help people generate pseudoevidence to support claims. (PsycINFO Database Record)

Semantic patterns for sentiment analysis of Twitter

Most existing approaches to Twitter sentiment analysis assume that sentiment is explicitly expressed through affective words. Nevertheless, sentiment is often implicitly expressed via latent semantic relations, patterns and dependencies among words in tweets. In this paper, we propose a novel approach that automatically captures patterns of words of similar contextual semantics and sentiment in tweets. Unlike previous work on sentiment pattern extraction, our proposed approach does not rely on external and fixed sets of syntactical templates/patterns, nor requires deep analyses of the syntactic structure of sentences in tweets. We evaluate our approach with tweet- and entity-level sentiment analysis tasks by using the extracted semantic patterns as classification features in both tasks. We use 9 Twitter datasets in our evaluation and compare the performance of our patterns against 6 state-of-the-art baselines. Results show that our patterns consistently outperform all other baselines on all datasets by 2.19% at the tweet-level and 7.5% at the entity-level in average F-measure.

Stretching the life of Twitter classifiers with time-stamped semantic graphs

Social media has become an effective channel for communicating both trends and public opinion on current events. However the automatic topic classification of social media content pose various challenges. Topic classification is a common technique used for automatically capturing themes that emerge from social media streams. However, such techniques are sensitive to the evolution of topics when new event-dependent vocabularies start to emerge (e.g., Crimea becoming relevant to War Conflict during the Ukraine crisis in 2014). Therefore, traditional supervised classification methods which rely on labelled data could rapidly become outdated. In this paper we propose a novel transfer learning approach to address the classification task of new data when the only available labelled data belong to a previous epoch. This approach relies on the incorporation of knowledge from DBpedia graphs. Our findings show promising results in understanding how features age, and how semantic features can support the evolution of topic classifiers.

EPCIS Event-Based traceability in pharmaceutical supply chains via automated generation of linked pedigrees

In this paper we show how event processing over semantically annotated streams of events can be exploited, for implementing tracing and tracking of products in supply chains through the automated generation of linked pedigrees. In our abstraction, events are encoded as spatially and temporally oriented named graphs, while linked pedigrees as RDF datasets are their specific compositions. We propose an algorithm that operates over streams of RDF annotated EPCIS events to generate linked pedigrees. We exemplify our approach using the pharmaceuticals supply chain and show how counterfeit detection is an implicit part of our pedigree generation. Our evaluation results show that for fast moving supply chains, smaller window sizes on event streams provide significantly higher efficiency in the generation of pedigrees as well as enable early counterfeit detection.

Теглови апроксимации с оператори от тип на Гудман–Шарма

P. E. Parvanov - The uniform weighted approximation errors of the Goodman–Sharma operators are characterized for functions.

On Optimal Quadratic Lagrange Interpolation: Extremal Node Systems with Minimal Lebesgue Constant via Symbolic Computation

ACM Computing Classification System (1998): G.1.1, G.1.2.

Sobolev Type Decomposition of Paley-Wiener-Schwartz Space with Application to Sampling Theory

2000 Mathematics Subject Classification: 94A12, 94A20, 30D20, 41A05.