Boosting of Replication Competent NYVAC Primed HIV-1-Specific T-Cell Responses by HIV Synthetic Long Peptides (SLP)

Background: To enhance the induction of insert specific immune responses, a new generation of replication competent poxvirus vectors was designed and evaluated against non-replicating poxvirus vectors in a HIV vaccine study in non human primates.Methods: Rhesus macaques were immunized with either the non-replicating variant NYVAC-GagPolNef HIV-1 clade C or the replicating NYVAC-GagPolNef-C-KC, boosted with HIVGag- PolEnv-SLP and immune responses were monitored.Results: Gag-specific T-cell responses were only detected in animals immunized with the replicating NYVAC-GagPolNef-C-KC variant. Further enhancement and broadening of the immune response was studied by boosting the animals with novel T-cell immunogens HIVconsv synthetic long peptides (SLP), which direct vaccine-induced responses to the most conserved regions of HIV and contain both CD4 T-helper and CD8 CTL epitopes. The adjuvanted (Montanide ISA-720) SLP divided into subpools and delivered into anatomically separate sites enhanced the Gag-specific T-cell responses in 4 out of 6 animals, to more than 1000 SFC/106 PBMC in some animals. Furthermore, the SLP immunization broadened the immune response in 4 out of 6 animals to multiple Pol epitopes. Even Env-specific responses, to which the animals had not been primed, were induced by SLP in 2 out of 6 animals.Conclusion: This new immunization strategy of priming with replicating competent poxvirus NYVAC-HIVGagPolNef and boosting with HIVGagPolEnv-SLP, induced strong and broad Tcell responses and provides a promising new HIV vaccine approach. This study was performed within the Poxvirus T-cell Vaccine Discovery Consortium (PTVDC) which is part of the CAVD program.

Densidade relativa ótima de Latossolos Vermelhos para a produtividade de soja

A compactação do solo tem causado decréscimos na produtividade de soja, e os valores de densidade do solo a partir dos quais a produtividade decresce são pouco conhecidos. Assim, este trabalho objetivou avaliar a produtividade de soja (cv. Embrapa 48) em relação à densidade relativa (Dsr) de Latossolo Vermelho textura média (LVd) e argilosa (LVef). Em 2001/2002, foi realizado um experimento em casa de vegetação, com amostras coletadas nos dois solos na camada de 0,0-0,2 m, peneirados a 4,0 mm, adubados e compactados em camadas de 3,0 cm, em vasos de 20 cm de altura e 25 cm de diâmetro. Foram estabelecidos quatro níveis de compactação e dois de água no solo (tensão de 0,01 e 0,05 MPa), com três repetições. A soja foi semeada em novembro (duas plantas por vaso) e irrigada duas vezes ao dia. No segundo experimento, no campo (2002/2003), utilizou-se apenas o LVd que foi compactado por meio de passadas de trator com quatro pneus de mesma largura, estabelecendo-se cinco níveis de compactação, com quatro repetições. A soja foi semeada, em dezembro de 2002, no espaçamento de 0,45 m entre linhas e 20 plantas por metro. Foram determinadas a densidade do solo (Ds) e a Ds máxima pelo teste de Proctor, sendo a Dsr obtida por divisão da Ds pela Ds máxima. Na colheita, foi avaliada a produtividade de grãos. A Dsr ótima para a produtividade de soja, em casa de vegetação, foi superior no Latossolo Vermelho eutroférrico argiloso (0,84), comparada à do Latossolo Vermelho caulinítico de textura média (0,75), na tensão de água no solo de 0,01 MPa. No campo, a Dsr ótima para soja foi de 0,80.

Atributos físicos nos tempos de adoção de manejos em Latossolo cultivado com soja

A condução das operações de preparo de forma inadequada ocasiona sérios problemas de conservação do solo, destacando-se a compactação, que acarreta a redução do espaço poroso, principalmente dos macroporos, e altera os atributos físico-hídricos. Este trabalho teve como objetivo verificar a influência dos diferentes sistemas e tempos de adoção de manejos em Latossolo Vermelho de Jaboticabal, Estado de São Paulo, por meio da densidade máxima, e correlacioná-la com a produtividade da soja, a densidade relativa e a umidade crítica de compactação. O delineamento experimental foi o inteiramente casualizado com parcelas subdivididas (cinco sistemas de uso e três camadas), com quatro repetições. Os cinco sistemas de uso foram: plantio direto por cino anos (SPD5), plantio direto por sete anos (SPD7), plantio direto por nove anos (SPD9), preparo convencional (SPC) e uma área adjacente de mata nativa (MN). As camadas do solo avaliadas foram as de 0-0,10, 0,10-0,20 e 0,20-0,30 m, nas quais foram determinados a densidade máxima do solo (Ds máx), a umidade crítica de compactação (Ugc), a densidade relativa do solo (Dsr), a composição granulométrica, a porosidade e o teor de matéria orgânica do solo. Os resultados mostraram que o comportamento das curvas de compactação do solo foi o mesmo em todas as camadas dos diferentes manejos e que os teores de matéria orgânica não justificaram as pequenas alterações da Ds máx. Para o Latossolo Vermelho, as operações mecanizadas nos sistemas de manejo podem ser executadas na faixa de 0,13 a 0,19 kg kg-1 de umidade sem causar degradação física. Verificou-se que a Dsr ótima e a umidade crítica de compactação foram de 0,86 e 0,15 kg kg-1, respectivamente, embora os diferentes sistemas e tempos de adoção de manejo tenham apresentado comportamento semelhante quanto à produtividade da soja.

Multicenter phase II trial of gefitinib first-line therapy followed by chemotherapy in advanced non-small-cell lung cancer (NSCLC): SAKK protocol 19/03.

BACKGROUND: Gefitinib is active in patients with pretreated non-small-cell lung cancer (NSCLC). We evaluated the activity and toxicity of gefitinib first-line treatment in advanced NSCLC followed by chemotherapy at disease progression. PATIENTS AND METHODS: In all, 63 patients with chemotherapy-naive stage IIIB/IV NSCLC received gefitinib 250 mg/day. At disease progression, gefitinib was replaced by cisplatin 80 mg/m(2) on day 1 and gemcitabine 1250 mg/m(2) on days 1, 8 for up to six 3-week cycles. Primary end point was the disease stabilization rate (DSR) after 12 weeks of gefitinib. RESULTS: After 12 weeks of gefitinib, the DSR was 24% and the response rate (RR) was 8%. Median time to progression (TtP) was 2.5 months and median overall survival (OS) 11.5 months. Never smokers (n = 9) had a DSR of 56% and a median OS of 20.2 months; patients with epidermal growth factor receptor (EGFR) mutation (n = 4) had a DSR of 75% and the median OS was not reached after the follow-up of 21.6 months. In all, 41 patients received chemotherapy with an overall RR of 34%, DSR of 71% and median TtP of 6.7 months. CONCLUSIONS: First-line gefitinib monotherapy led to a DSR of 24% at 12 weeks in an unselected patients population. Never smokers and patients with EGFR mutations tend to have a better outcome; hence, further trials in selected patients are warranted.

Estudio Clínico aleatorio, controlado, paralelo, para evaluar la eficacia del ejercicio físico progresivo como tratamiento en los pacientes diagnosticados del Síndrome de Fatiga Crónica

Antecedentes: El Síndrome de Fatiga Crónica (SFC) es una enfermedad que presenta disfunción multidimensional. Se recomienda tratamiento multidisciplinario que incluya el ejercicio. Material y métodos: Diseñamos un proyecto unicéntrico, experimental, prospectivo partiendo de la hipótesis siguiente: El ejercicio físico progresivo (EFP) enseñado por fisioterapeutas, puede beneficiar a los enfermos de SFC mejorando sus síntomas. Resultados: Evidencian la eficacia del EFP con SFC valorando las variables sintomáticas con escalas y cuestionarios. Conclusiones: El estudio, valora sintomatología relevante antes de iniciar el tratamiento para comparar los resultados obtenidos, mediante tres seguimientos, constatando la eficacia del tratamiento multidisciplinar con EFP a corto y largo plazo.

Syndrome de fatigue chronique [Chronic fatigue syndrome].

Le syndrome de fatigue chronique (SFC) est une pathologie invalidante, moins rare qu'on ne le pense (prévalence de l'ordre de 0,3-0,9 %), qui associe un épuisement physique persistant et inexpliqué à des douleurs diffuses, des troubles du sommeil, des troubles neurocognitifs et neurovégétatifs. Sa physiopathologie est controversée, mais les pistes de recherche actuelles convergent vers une atteinte dysimmunitaire, dans laquelle le stress oxydatif et un dysfonctionnement des mitochondries semblent jouer un rôle. Il n'existe pas de médication ayant démontré une efficacité spécifique pour le traitement du SFC. La prise en charge consiste à limiter les investigations superflues et à encourager le patient vers un reconditionnement à l'effort très progressif, dans le cadre d'un counselling empathique visant à prévenir les pensées négatives. Chronic fatigue syndrome (CFS) is a debilitating disorder, characterized by a severe, persistant and unexplained fatigue, which can be associated with diffuse pain, sleep difficulties, neurocognitive and neurovegetative troubles. Its prevalence has been estimated between 0.3 and 0.9%. Though its physiopathology remains controversial, evidence is growing that dysimmunity, oxidative stress and mitochondrial dysfunction are involved in its pathogeny. No medication has demonstrated specifc efficacy in the CFS. The management of CFS involves limiting unnecessary investigations, promoting graded exercice therapy, and providing empathic counselling in order to prevent negative thoughts.

Fast and sensitive supercritical fluid chromatography - tandem mass spectrometry multi-class screening method for the determination of doping agents in urine.

This study shows the possibility offered by modern ultra-high performance supercritical fluid chromatography combined with tandem mass spectrometry in doping control analysis. A high throughput screening method was developed for 100 substances belonging to the challenging classes of anabolic agents, hormones and metabolic modulators, synthetic cannabinoids and glucocorticoids, which should be detected at low concentrations in urine. To selectively extract these doping agents from urine, a supported liquid extraction procedure was implemented in a 48-well plate format. At the tested concentration levels ranging from 0.5 to 5 ng/mL, the recoveries were better than 70% for 48-68% of the compounds and higher than 50% for 83-87% of the tested substances. Due to the numerous interferences related to isomers of steroids and ions produced by the loss of water in the electrospray source, the choice of SFC separation conditions was very challenging. After careful optimization, a Diol stationary phase was employed. The total analysis time for the screening assay was only 8 min, and interferences as well as susceptibility to matrix effect (ME) were minimized. With the developed method, about 70% of the compounds had relative ME within the range ±20%, at a concentration of 1 and 5 ng/mL. Finally, limits of detection achieved with the above-described strategy including 5-fold preconcentration were below 0.1 ng/mL for the majority of the tested compounds. Therefore, LODs were systematically better than the minimum required performance levels established by the World anti-doping agency, except for very few metabolites.

Fluidos supercríticos em química analítica. I. Cromatografia com fluido supercrítico: conceitos termodinâmicos

Under the chromatographic point of view, the physico-chemical properties of a supercritical fluid are intermediate to those of the gases and liquids. Many times they approach the best features of each one, as for example, the solubilization power of liquids and low viscosity of gases. The thermodynamic definitions and main physico-chemical features of a supercritical fluid will be presented in this article. The use of supercritical fluids in analytical chemistry has been extremely modest in Brazil, even considering the enormous potential of their applications, and their use in several techniques, such as chromatography (SFC) and supercritical fluid extration (SFE). This article series is intended to discuss the historical evolution, instrumentation features and potential and limitations of the supercritical fluid use in analytical chemistry. A special focus will be centered on chromatography and extration techniques using supercritical fluids.

Fluidos supercríticos em química analítica. II. Cromatografia com fluido supercrítico: instrumentação

The first paper in this series discussed the basic theory involved in supercritical fluid chromatography (SFC) and how the technique progressed from gas and liquid chromatography. The first SFC instruments were simple adaptations of the commercially available liquid chromatographs with packed columns followed by modifications in gas chromatographs using open tubular capillary columns. In this paper, the most important aspects regarding instrumentation are covered, including practical, simple, and the most important, inexpensive solutions to build a home-made SFC system.

Fluidos supercríticos em química analítica. III.: aplicações

The first two papers in this series described the basic theory involved in supercritical fluid chromatography (SFC), how the technique evolved from gas and liquid chromatography and how the instrumentation was developed. Over the last two years, a commercial, dedicated packed-column SFC/MS instrument appeared on the market. The SFC continues to grow in use, with fundamental developments, coupled with a steady rise in the number of industrial users and applications.

Super/subcritical fluid chromatography with packed columns: state of the art and applications

Separations using supercritical fluid chromatography (SFC) with packed columns have been re-discovered and explored in recent years. SFC enables fast and efficient separations and, in some cases, gives better results than high performance liquid chromatography (HPLC). This paper provides an overview of recent advances in SFC separations using packed columns for both achiral and chiral separations. The most important types of stationary phases used in SFC are discussed as well as the most critical parameters involved in the separations and some recent applications.

Efeito da concentração de coagulantes e do pH da solução na turbidez da água, em recirculação, utilizada no processamento dos frutos do cafeeiro

Com o objetivo de determinar a dose e a faixa de pH dos coagulantes sulfato de alumínio (SA), sulfato ferroso clorado (SFC), cloreto férrico (CF) e extrato de semente de moringa (ESM), que proporcionassem maior eficiência na remoção da turbidez na água residuária da despolpa de frutos do cafeeiro (ARDC), após serem efetuadas cinco recirculações, foram conduzidos ensaios de coagulação/floculação utilizando o aparelho "Jar-test". Todos esses coagulantes foram avaliados nas concentrações de 0; 0,5; 1,0; 1,5; 2,0; 2,5 e 3,0 g L-1. No caso da solução preparada com ESM, as doses utilizadas foram: 0; 10; 20; 30; 40; 50 e 60 mL L-1. O pH da solução em teste foi alterado, utilizando-se do hidróxido de sódio (NaOH), na concentração de 0,3 mol L-1, sendo avaliadas as faixas de 4,0 a 5,0; 5,0 a 6,0; 6,0 a 7,0 e 7,0 a 8,0. No ensaio de coagulação/floculação, o ESM proporcionou maior remoção de SS (sólidos em suspensão) da ARDC com a dose de 10 mL L-1 e pH de 4,27 (natural). Para os coagulantes SA e CF, os melhores resultados foram obtidos com a concentração de 3 g L-1 e pH de 7,27 e, para o coagulante SFC, com a concentração de 3 g L-1 e pH de 4,27.

The Effect of Different Weed Management Strategies on the Growth and Yield of Direct-Seeded Dry Rice (Oryza sativa)

Weed management is a primary concern in direct seeded rice (DSR) cropping because weed growth becomes a major constraint on crop yield. A two year field study was set up to evaluate the effect of various weed control measures on crop growth, grain yield and grain quality of DSR. The experiment involved five different weed control measures: hand weeding, hoeing, inter-row tine cultivation, inter-row spike hoeing and herbicide treatment (Nominee 100 SC). The extent of weed control (compared to a non-weeded control) ranged from 50-95%. The highest crop yield was obtained using hand weeding. Hand weeding, tine cultivation and herbicide treatment raised the number of fertile rice tillers formed per unit area and the thousand grain weight. Tine cultivation provided an effective and economical level of weed control in the DSR crop.

On advancing business intelligence in the electricity retail market

In recent decades, business intelligence (BI) has gained momentum in real-world practice. At the same time, business intelligence has evolved as an important research subject of Information Systems (IS) within the decision support domain. Today’s growing competitive pressure in business has led to increased needs for real-time analytics, i.e., so called real-time BI or operational BI. This is especially true with respect to the electricity production, transmission, distribution, and retail business since the law of physics determines that electricity as a commodity is nearly impossible to be stored economically, and therefore demand-supply needs to be constantly in balance. The current power sector is subject to complex changes, innovation opportunities, and technical and regulatory constraints. These range from low carbon transition, renewable energy sources (RES) development, market design to new technologies (e.g., smart metering, smart grids, electric vehicles, etc.), and new independent power producers (e.g., commercial buildings or households with rooftop solar panel installments, a.k.a. Distributed Generation). Among them, the ongoing deployment of Advanced Metering Infrastructure (AMI) has profound impacts on the electricity retail market. From the view point of BI research, the AMI is enabling real-time or near real-time analytics in the electricity retail business. Following Design Science Research (DSR) paradigm in the IS field, this research presents four aspects of BI for efficient pricing in a competitive electricity retail market: (i) visual data-mining based descriptive analytics, namely electricity consumption profiling, for pricing decision-making support; (ii) real-time BI enterprise architecture for enhancing management’s capacity on real-time decision-making; (iii) prescriptive analytics through agent-based modeling for price-responsive demand simulation; (iv) visual data-mining application for electricity distribution benchmarking. Even though this study is from the perspective of the European electricity industry, particularly focused on Finland and Estonia, the BI approaches investigated can: (i) provide managerial implications to support the utility’s pricing decision-making; (ii) add empirical knowledge to the landscape of BI research; (iii) be transferred to a wide body of practice in the power sector and BI research community.

Design and evaluation of web interface signs to improve web usability : a semiotic framework

Technological innovations, the development of the internet, and globalization have increased the number and complexity of web applications. As a result, keeping web user interfaces understandable and usable (in terms of ease-of-use, effectiveness, and satisfaction) is a challenge. As part of this, designing userintuitive interface signs (i.e., the small elements of web user interface, e.g., navigational link, command buttons, icons, small images, thumbnails, etc.) is an issue for designers. Interface signs are key elements of web user interfaces because ‘interface signs’ act as a communication artefact to convey web content and system functionality, and because users interact with systems by means of interface signs. In the light of the above, applying semiotic (i.e., the study of signs) concepts on web interface signs will contribute to discover new and important perspectives on web user interface design and evaluation. The thesis mainly focuses on web interface signs and uses the theory of semiotic as a background theory. The underlying aim of this thesis is to provide valuable insights to design and evaluate web user interfaces from a semiotic perspective in order to improve overall web usability. The fundamental research question is formulated as What do practitioners and researchers need to be aware of from a semiotic perspective when designing or evaluating web user interfaces to improve web usability? From a methodological perspective, the thesis follows a design science research (DSR) approach. A systematic literature review and six empirical studies are carried out in this thesis. The empirical studies are carried out with a total of 74 participants in Finland. The steps of a design science research process are followed while the studies were designed and conducted; that includes (a) problem identification and motivation, (b) definition of objectives of a solution, (c) design and development, (d) demonstration, (e) evaluation, and (f) communication. The data is collected using observations in a usability testing lab, by analytical (expert) inspection, with questionnaires, and in structured and semi-structured interviews. User behaviour analysis, qualitative analysis and statistics are used to analyze the study data. The results are summarized as follows and have lead to the following contributions. Firstly, the results present the current status of semiotic research in UI design and evaluation and highlight the importance of considering semiotic concepts in UI design and evaluation. Secondly, the thesis explores interface sign ontologies (i.e., sets of concepts and skills that a user should know to interpret the meaning of interface signs) by providing a set of ontologies used to interpret the meaning of interface signs, and by providing a set of features related to ontology mapping in interpreting the meaning of interface signs. Thirdly, the thesis explores the value of integrating semiotic concepts in usability testing. Fourthly, the thesis proposes a semiotic framework (Semiotic Interface sign Design and Evaluation – SIDE) for interface sign design and evaluation in order to make them intuitive for end users and to improve web usability. The SIDE framework includes a set of determinants and attributes of user-intuitive interface signs, and a set of semiotic heuristics to design and evaluate interface signs. Finally, the thesis assesses (a) the quality of the SIDE framework in terms of performance metrics (e.g., thoroughness, validity, effectiveness, reliability, etc.) and (b) the contributions of the SIDE framework from the evaluators’ perspective.