Predictions from an anisotropic inflationary era

This paper investigates the predictions of an inflationary phase starting from a homogeneous and anisotropic universe of the Bianchi I type. After discussing the evolution of the background spacetime, focusing on the number of e-folds and the isotropization, we solve the perturbation equations and predict the power spectra of the curvature perturbations and gravity waves at the end of inflation. The main features of the early anisotropic phase is (1) a dependence of the spectra on the direction of the modes, (2) a coupling between curvature perturbations and gravity waves and (3) the fact that the two gravity wave polarizations do not share the same spectrum on large scales. All these effects are significant only on large scales and die out on small scales where isotropy is recovered. They depend on a characteristic scale that can, but a priori must not, be tuned to some observable scale. To fix the initial conditions, we propose a procedure that generalizes the one standardly used in inflation but that takes into account the fact that the WKB regime is violated at early times when the shear dominates. We stress that there exist modes that do not satisfy the WKB condition during the shear-dominated regime and for which the amplitude at the end of inflation depends on unknown initial conditions. On such scales, inflation loses its predictability. This study paves the way for the determination of the cosmological signature of a primordial shear, whatever the Bianchi I spacetime. It thus stresses the importance of the WKB regime to draw inflationary predictions and demonstrates that, when the number of e-folds is large enough, the predictions converge toward those of inflation in a Friedmann-Lemaitre spacetime but that they are less robust in the case of an inflationary era with a small number of e-folds.

Anisotropy and chemical composition of ultra-high energy cosmic rays using arrival directions measured by the Pierre Auger Observatory

The Pierre Auger Collaboration has reported. evidence for anisotropy in the distribution of arrival directions of the cosmic rays with energies E > E(th) = 5.5 x 10(19) eV. These show a correlation with the distribution of nearby extragalactic objects, including an apparent excess around the direction of Centaurus A. If the particles responsible for these excesses at E > E(th) are heavy nuclei with charge Z, the proton component of the sources should lead to excesses in the same regions at energies E/Z. We here report the lack of anisotropies in these directions at energies above E(th)/Z (for illustrative values of Z = 6, 13, 26). If the anisotropies above E(th) are due to nuclei with charge Z, and under reasonable assumptions about the acceleration process, these observations imply stringent constraints on the allowed proton fraction at the lower energies.

Effectiveness of commercial inhibitors against subtype F HIV-1 protease

Subtype F wild type HIV protease has been kinetically characterized using six commercial inhibitors (amprenavir, indinavir, lopinavir, nelfinavir, ritonavir and saquinavir) commonly used for HIV/AIDS treatment, as well as inhibitor TL-3 and acetylpepstatin. We also obtained kinetic parameters for two multi-resistant proteases (one of subtype B and one of subtype F) harboring primary and secondary mutations selected by intensive treatment with ritonavir/nelfinavir. This newly obtained biochemical data shows that all six studied commercially available protease inhibitors are significantly less effective against subtype F HIV proteases than against HIV proteases of subtype B, as judged by increased K(i) and biochemical fitness (vitality) values. Comparison with previously reported kinetic values for subtype A and C HIV proteases show that subtype F wild type proteases are significantly less susceptible to inhibition. These results demonstrate that the accumulation of natural polymorphisms in subtype F proteases yields catalytically more active enzymes with a large degree of cross-resistance, which thus results in strong virus viability.

Structure-activity relationships for a class of selective inhibitors of the major cysteine protease from Trypanosoma cruzi

Chagas` disease is a parasitic infection widely distributed throughout Latin America, with devastating consequences in terms of human morbidity and mortality. Cruzain, the major cysteine protease from Trypanosoma cruzi, is an attractive target for antitrypanosomal chemotherapy. In the present work, classical two-dimensional quantitative structure-activity relationships (2D QSAR) and hologram QSAR (HQSAR) studies were performed on a training set of 45 thiosemicarbazone and semicarbazone derivatives as inhibitors of T. cruzi cruzain. Significant statistical models (HQSAR, q2=0.75 and r2=0.96; classical QSAR, q2=0.72 and r2=0.83) were obtained, indicating their consistency for untested compounds. The models were then used to evaluate an external test set containing 10 compounds which were not included in the training set, and the predicted values were in good agreement with the experimental results (HQSAR, [image omitted]=0.95; classical QSAR, [image omitted]=0.91), indicating the existence of complementary between the two ligand-based drug design techniques.

Antioxidant effect of functionalized alkyl-organotellurides: a study in vitro

We evaluated the in vitro antioxidant effect of alkyl-organotellurides A-D on lipid peroxidation and protein carbonylation in rat liver homogenates. The thiol oxidase and thiol peroxidase-like activities of compounds were investigated. delta-Aminolevulinic acid dehydratase (delta-ALA-D) activity was determined in rat liver homogenates. Compounds A-D protected against lipid peroxidation induced by Fe(2+)/EDTA and sodium nitroprusside (SNP). According to the confidence limits of the IC(50) values of compounds A-D, the IC(50) values for organotellurides followed the order: C (0.30 mu M) <= B (0.40 mu M) < D (0.68 mu M) < A (2.90 mu M), for Fe(2+)/EDTA, and B (0.21 mu M) <= C (0.33 mu M) < D (0.43 mu M) < A (1.21 mu M) for SNP-induced lipid peroxidation. Compounds A-D reduced protein carbonyl content to control levels. The results demonstrated an inverse correlation between thiol oxidase and delta-ALA-D activities. This study supports an antioxidant effect of organotellurides A-D on rat liver.

Analys av förvridning vid hålning av rör : Analysis of metal torsion in rotary piercing

Hålningsprocessen är det inledande bearbetningssteget vid varmvalsning av sömlösa rör. Det är en tvärvalsningsprocess i vilken ett cylindriskt ämne valsas mellan två dubbelkoniska val¬sar över en plugg. Valsarna är snedställda med en viss mat¬ningsvinkel, vilken ger upphov till en axiell drivkraft genom ver¬ket. Hela denna pro¬cess är roterande. Detta i kombination med bl.a. de koniska valsarna leder till en förvrid¬ning av röret, dvs. en tänkt rak linje på det ingå¬ende äm¬net övergår till en spiral efter genomförd valsning. Med föreliggande uppgift är målet att studera förvridningen genom teoretisk och experimen¬tell analys. Syftet med detta är dels att få fördjupad kunskap inom området och dels att ut¬veckla en modell för pre¬diktering av förvridningen.Det experimentella arbetet är utfört på ett stål av typ Ovako 280 (SS2142). Denna mjuka stål¬sort valdes i syfte att undvika värmebehandling innan provberedning. För att visuali¬sera för¬vridningen fräs¬tes ett rakt spår längs det ingående äm¬net och hål borrades mot symmetrilinjen. De praktiska undersökningarna utfördes direkt i den löpande produktionen. Genomförda beräkningar uppvisar en längsgående förvridningsvinkel som stämmer väl över¬ens med uppmätt värde. Detta är dock under antagandet att den tangentiella hastighetskoeffi¬cienten varierar linjärt utmed deformationszonen. För en mer utvecklad modell krävs en nog¬grannare analys av kontakten mellan vals/ämne eller en grundligt genomförd uppmätning av ämnets vinkelhastighet.

Effectiveness of artemether-lumefantrine provided by community health workers in under-five children with uncomplicated malaria in rural Tanzania : an open label prospective study

Background: Home-management of malaria (HMM) strategy improves early access of anti-malarial medicines to high-risk groups in remote areas of sub-Saharan Africa. However, limited data are available on the effectiveness of using artemisinin-based combination therapy (ACT) within the HMM strategy. The aim of this study was to assess the effectiveness of artemether-lumefantrine (AL), presently the most favoured ACT in Africa, in under-five children with uncomplicated Plasmodium falciparum malaria in Tanzania, when provided by community health workers (CHWs) and administered unsupervised by parents or guardians at home. Methods: An open label, single arm prospective study was conducted in two rural villages with high malaria transmission in Kibaha District, Tanzania. Children presenting to CHWs with uncomplicated fever and a positive rapid malaria diagnostic test (RDT) were provisionally enrolled and provided AL for unsupervised treatment at home. Patients with microscopy confirmed P. falciparum parasitaemia were definitely enrolled and reviewed weekly by the CHWs during 42 days. Primary outcome measure was PCR corrected parasitological cure rate by day 42, as estimated by Kaplan-Meier survival analysis. This trial is registered with ClinicalTrials.gov, number NCT00454961. Results: A total of 244 febrile children were enrolled between March-August 2007. Two patients were lost to follow up on day 14, and one patient withdrew consent on day 21. Some 141/241 (58.5%) patients had recurrent infection during follow-up, of whom 14 had recrudescence. The PCR corrected cure rate by day 42 was 93.0% (95% CI 88.3%-95.9%). The median lumefantrine concentration was statistically significantly lower in patients with recrudescence (97 ng/mL [IQR 0-234]; n = 10) compared with reinfections (205 ng/mL [114-390]; n = 92), or no parasite reappearance (217 [121-374] ng/mL; n = 70; p <= 0.046). Conclusions: Provision of AL by CHWs for unsupervised malaria treatment at home was highly effective, which provides evidence base for scaling-up implementation of HMM with AL in Tanzania.

Association of soluble tumor necrosis factor receptors 1 and 2 with nephropathy, cardiovascular events, and total mortality in type 2 diabetes

AIMS/HYPOTHESIS: Soluble tumor necrosis factor receptors 1 and 2 (sTNFR1 and sTNFR2) contribute to experimental diabetic kidney disease, a condition with substantially increased cardiovascular risk when present in patients. Therefore, we aimed to explore the levels of sTNFRs, and their association with prevalent kidney disease, incident cardiovascular disease, and risk of mortality independently of baseline kidney function and microalbuminuria in a cohort of patients with type 2 diabetes. In pre-defined secondary analyses we also investigated whether the sTNFRs predict adverse outcome in the absence of diabetic kidney disease. METHODS: The CARDIPP study, a cohort study of 607 diabetes patients [mean age 61 years, 44 % women, 45 cardiovascular events (fatal/non-fatal myocardial infarction or stroke) and 44 deaths during follow-up (mean 7.6 years)] was used. RESULTS: Higher sTNFR1 and sTNFR2 were associated with higher odds of prevalent kidney disease [odd ratio (OR) per standard deviation (SD) increase 1.60, 95 % confidence interval (CI) 1.32-1.93, p < 0.001 and OR 1.54, 95 % CI 1.21-1.97, p = 0.001, respectively]. In Cox regression models adjusting for age, sex, glomerular filtration rate and urinary albumin/creatinine ratio, higher sTNFR1 and sTNFR2 predicted incident cardiovascular events [hazard ratio (HR) per SD increase, 1.66, 95 % CI 1.29-2.174, p < 0.001 and HR 1.47, 95 % CI 1.13-1.91, p = 0.004, respectively]. Results were similar in separate models with adjustments for inflammatory markers, HbA1c, or established cardiovascular risk factors, or when participants with diabetic kidney disease at baseline were excluded (p < 0.01 for all). Both sTNFRs were associated with mortality. CONCLUSIONS/INTERPRETATIONS: Higher circulating sTNFR1 and sTNFR2 are associated with diabetic kidney disease, and predicts incident cardiovascular disease and mortality independently of microalbuminuria and kidney function, even in those without kidney disease. Our findings support the clinical utility of sTNFRs as prognostic markers in type 2 diabetes.

Influence of a prudent diet on circulating cathepsin S in humans

BACKGROUND: Increased circulating cathepsin S levels have been linked to increased risk of cardiometabolic diseases and cancer. However, whether cathepsin S is a modifiable risk factor is unclear. We aimed to investigate the effects of a prudent diet on plasma cathepsin S levels in healthy individuals. FINDINGS: Explorative analyses of a randomized study were performed in 88 normal to slightly overweight and hyperlipidemic men and women (aged 25 to 65) that were randomly assigned to ad libitum prudent diet, i.e. healthy Nordic diet (ND) or a control group (habitual Western diet) for 6 weeks. Whereas all foods in the ND were provided, the control group was advised to consume their habitual diet throughout the study. The ND was in line with dietary recommendations, e.g. low in saturated fats, sugars and salt, but high in plant-based foods rich in fibre and unsaturated fats.The ND significantly decreased cathepsin S levels (from 20.1 (+/-4.0 SD) to 19.7 μg/L (+/-4.3 SD)) compared with control group (from 18.2 (+/-2.9 SD) to 19.1 μg/L (+/-3.8 SD)). This difference remained after adjusting for sex and change in insulin sensitivity (P = 0.03), and near significant after adjusting for baseline cathepsin S levels (P = 0.06), but not for change in weight or LDL-C. Changes in cathepsin S levels were directly correlated with change in LDL-C. CONCLUSIONS: Compared with a habitual control diet, a provided ad libitum healthy Nordic diet decreased cathepsin S levels in healthy individuals, possibly mediated by weight loss or lowered LDL-C. These differences between groups in cathepsin S were however not robust and therefore need further investigation.

Verdi's Settings of Shakespeare : from Play to Liberetto to Opera

As a Senior Scholar pursuing the topic, Verdi's Settings of Shakespeare: From Play to Libretto to Opera, I have endeavoured to study a project relevant to my majors, Music and English. During first semester, I carefully analysed Shakespeare's plays, Macbeth, Othello and Falstaff. The highlight of my project was in January when I travelled to New York City and spent the day working with the Metropolitan Opera Guild. I was also able to see a performance of Verdi's Othello with Jon Vickers in the lead role. During the second semester, I studied the musical aspects of the compositions. I spent time analysing musical passages and relating them to the plays and the operas. I was also able to continue my study of Italian, which I find extremely beneficial while studying Verdi's libretti. On Monday, 13th May, 1974, I gave a lecture presentation of my project. At this time, I showed slides of Metropolitan productions of the operas, presented my own rendition of five arias (in costume) and talked about comparisions between the plays and the operas. I applied for a Rotary Fellowship to take my project to Europe and am presently waiting to hear the results. If I do receive the fellowship, I am planning to spend a year studying the plays and operas in England and Italy. Afterwards, I hope to publish a paper explaining my findings. The paper is divided into six sections. The first section is an introduction which explains the period of Romanticism and its relationship to Shakespeare and Verdi. The second section is devoted to discussing the librettist for Macbeth, Francesco Piave. Following this section the opera Macbeth is discussed. Arrigo Boito, the librettist for Otello and Falstaff is discussed in the fourth section. The last two sections deal with Otello and Falstaff. I have also included a number of musical selections to better explain certain passages. My project has been invaluable to me. My Senior Scholar project has allowed me the freedom of independent study as well as a means of tying my majors together.

Estabilização pozolânica de cinzas volante e pesada com cal dolomítica hidratada e areia, curadas pelos processos de autoclavagem e câmara a temperatura constante

Este trabalho tem como objetivo verificar o comportamento mecânico e físico de pozolanas artifíciais estabilizadas química e granulometricamente, curadas por dois processos de cura denominados de : autoclave(ATC), que utiliza temperaturas na faixa de 149 a 188°C e câmara à temperatura constante(CTC) que utiliza uma temperatura de ± 21°C. Também fez-se análises estatísticas com a finalidade de se determinar o efeito da energia de moldagem, temperatura e tempo de cura sobre os resultados dos ensaios, para cada processo de cura, além de se determinar modelos matemáticos para previsão de resultados de resistência através de regressões múltiplas e simples. As pozolanas artificiais empregadas foram as cinzas volante e pesada da Usina de Candiota, as quais foram estabilizadas com cal dolomítica hidratada e areia do Rio Guaíba. Os ensaios de resistência à compressão simples , absorção e perda de massa basearam-se nas normas da ABNT e DNER e para os estudos de análise estatística, fez-se anteriormente aos ensaios, dois planejamentos experimentais denominados de Split-Splot e Quadrado Latino, que foram utilizados nos processos de autoclavagem e câmara à temperatura constante, representativamente. Os Corpos-de-Prova curados na câmara à temperatura constante, até os 28 dias de cura, apresentaram resultados de resistências inferiores aqueles curados pelo processo de autoclave. Aos 60 dias de cura suas resistências ficaram na faixa dos valores de Corpos-de-Provas curados pela autoclave nas temperaturas de 149 a 188°C, excessão feita na mistura utilizando areia, onde em todos os períodos de cura estudados,os valores de resistência dos Corpos-de-Prova curados pelo câmara à temperatura constante foram inferiores. A proporção da quantidade de cal e cinza na mistura, bem como o valor da superfície específica da cinza influenciam nos resultados de ensaios, independentemente da variação dos fatores principais. Em termos de análise estatística verificou-se que a energia de moldagem e o tempo de cura são os fatores que apresentam os maiores efeitos sobre os resultados da resistência, para os processos de cura ATC e CTC, respectivamente.

Seguimento clinoceletrográfico de criançcas e adolescentes com crise epiléptica única não-provocada

Os fenômenos convulsivos despertaram o interesse de estudiosos e pensadores já na Antigüidade, quando aspectos mágicos e sobrenaturais eram a eles associados. No século XIX foram lançadas as bases dos conceitos atuais sobre a desestruturação funcional cerebral na epilepsia, e Berger, em 1929, marcou definitivamente a história com a descoberta dos ritmos cerebrais. Crise epiléptica e epilepsia não são sinônimos, já que o último termo refere-se a crises recorrentes espontâneas. Ela costuma iniciar na infância, daí a preocupação com o risco de repetição do primeiro episódio e com a decisão de instituir tratamento medicamentoso. Fatores prognósticos são apontados, mas não há consenso. No Brasil existem poucas pesquisas nesta linha, tanto de prevalência da epilepsia como de fatores envolvidos na recorrência de crises. Este estudo teve como objetivo geral avaliar aspectos clinicoeletrográficos capazes de auxiliar no prognóstico e no manejo da epilepsia da criança e do adolescente. Foram objetivos específicos determinar a incidência de crise epiléptica não provocada recorrente; identificar fatores remotos implicados na ocorrência de crise epiléptica; relacionar tipo de crise com achados eletrencefalográficos; relacionar tipo de crise, duração da crise, estado vigília/sono no momento da crise e achados eletrencefalográficos com possibilidade de recorrência; e identificar os fatores de risco para epilepsia. Foram acompanhados 109 pacientes com idades entre 1 mês e 16 anos, com primeira crise não-provocada, em média por 24 meses, a intervalos trimestrais, no Hospital de Clínicas de Porto Alegre (HCPA). Foram realizados eletrencefalogramas (EEG) após a primeira crise; depois, solicitados anualmente. Não foram incluídos casos com epilepsia ou síndrome epiléptica bem definida, ou que fizeram uso prévio de drogas antiepilépticas. A média de idade foi 6 anos, com predomínio da faixa etária de 6 a 12 anos. Setenta eram meninos e 39, meninas. Os indivíduos brancos eram 92, e os não-brancos, 17. O nível de escolaridade dos casos esteve de acordo com a distribuição da idade e, entre os responsáveis, predominaram 8 anos de escolaridade. Foi possível concluir que as crises únicas não-provocadas mais freqüentes foram generalizadas, e sem predomínio significativo do tipo de EEG. A incidência de crise não-provocada recorrente foi 51,4%. História de intercorrências pré-natais maternas aumentou em 2 vezes o risco de repetição de crises. Via de nascimento, escore de Apgar no 5º minuto, relação peso ao nascer/idade gestacional, intercorrências no período pós-natal imediato e desenvolvimento neuropsicomotor não tiveram influência na recorrência. História familiar de crises mostrou tendência à significância estatística para repetição dos episódios, com risco de 1,7. Não foi encontrada associação entre tipo de crise e achado eletrencefalográfico. A maioria das crises foi de curta duração (até 5 minutos), mas este dado não esteve relacionado com a recorrência. Estado de vigília teve efeito protetor na recorrência. Se a primeira crise foi parcial, o risco de repetição foi 1,62, com tendência à significância. Quando o primeiro EEG foi alterado, houve relação significativa com primeira crise tanto generalizada como parcial. O primeiro EEG com alterações paroxísticas focais apontou risco de repetição de 2,90. Quando as variáveis envolvidas na repetição de crises foram ajustadas pelo modelo de regressão de Cox, EEG alterado mostrou risco de 2,48, com riscos acumulados de 50%, 60%, 62% e 68%; com EEG normal, os riscos foram 26%, 32%, 34% e 36% em 6, 12, 18 e 24 meses respectivamente.