Predicting the Risk of Lung Cancer in Never-smokers

Despite being considered a disease of smokers, approximately 10-15% of lung cancer cases occur in never-smokers. Lung cancer risk prediction models have demonstrated excellent ability to discriminate cases from non-cases, and have been shown to be more efficient at selecting individuals for future screening than current criteria. Existing models have primarily been developed in populations of smokers, thus there was a need to develop an accurate model in never-smokers. This study focused on developing and validating a model using never-smokers from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Cox regression analysis, with six-year follow-up, was used for model building. Predictors included: age, body mass index, education level, personal history of cancer, family history of lung cancer, previous chest X-ray, and secondhand smoke exposure. This model achieved fair discrimination (optimism corrected c-statistic = 0.6645) and good calibration. This represents an improvement on existing neversmoker models, but is not suitable for individual-level risk prediction.

Genetic association study of plasma creatine kinase levels in the Montreal Heart Institute Hospital Cohort

Il a déjà été démontré que les statines (ou inhibiteurs de la HMG-CoA réductase) sont efficaces pour réduire le LDL-cholestérol et elles se sont depuis établies comme étant le pilier dans le traitement de la dyslipidémie. Toutefois, environ 10 pourcent des utilisateurs de statines souffrent d'effets indésirables, généralement sous forme de myopathie qui est souvent accompagnée d’un taux élevé de la créatine kinase (CK) plasmatique. Il est fréquent que les patients doivent arrêter les statines à cause d’un taux de CK dépassant un seuil de référence. Nous avons examiné le taux de CK de près de 6000 participants de la biobanque de l’ICM, qui ont récemment été génotypés à l'aide de la micropuce d'ADN ExomChip d'Illumina. Des études antérieures ont démontré une association significative entre le taux de CK plasmatique et des polymorphismes génétiques et nous avons cherché à répliquer ces résultats par association génétique et à l'aide du test SKAT pour les polymorphismes rares. Nous avons répliqué les résultats dans le gène CKM (rs11559024, p=1.59x10-23) et le gène LILRB5 (rs12975366, p=1.44x10-26) dans le chromosome 19. Nous espérons que ces résultats seront éventuellement utilisés en clinique pour la prédiction des taux de référence de CK personnalisés selon le profil génétique des patients utilisateurs de statines.

A description of the FAMOUS (version XDBUA) climate model and control run

FAMOUS is an ocean-atmosphere general circulation model of low resolution, capable of simulating approximately 120 years of model climate per wallclock day using current high performance computing facilities. It uses most of the same code as HadCM3, a widely used climate model of higher resolution and computational cost, and has been tuned to reproduce the same climate reasonably well. FAMOUS is useful for climate simulations where the computational cost makes the application of HadCM3 unfeasible, either because of the length of simulation or the size of the ensemble desired. We document a number of scientific and technical improvements to the original version of FAMOUS. These improvements include changes to the parameterisations of ozone and sea-ice which alleviate a significant cold bias from high northern latitudes and the upper troposphere, and the elimination of volume-averaged drifts in ocean tracers. A simple model of the marine carbon cycle has also been included. A particular goal of FAMOUS is to conduct millennial-scale paleoclimate simulations of Quaternary ice ages; to this end, a number of useful changes to the model infrastructure have been made.

A maternal influence on the conditioning to plant cues of Aphidius colemani Viereck, parasitizing the aphid Myzus persicae Sulzer

The offspring of parasitoids, Aphidius colemani Viereck, reared on Brussels sprouts and emerging from Myzus persicae Sulzer on a fully defined artificial diet, show no preferences in a four-way olfactometer, either for the odour of the diet, the odour of Brussels sprouts, or the odour of two other crucifers (cabbage and Chinese cabbage). A similar lack of odour preferences is shown when the host aphids are exposed for parasitization (for 48 h) on cabbage, Chinese cabbage or wheat. However, if parasitization occurs on Brussels sprouts, a weak but statistically highly significant response to Brussels sprout odour is observed. Although as many as 30-35% of the parasitoids show no response to any odour, another 35% respond positively to the odour of Brussels sprout compared with responses to the odours of cabbage, Chinese cabbage or wheat of only approximately 10%. An analagous result is obtained when the parent parasitoids are reared on cabbage. In this case, significant positive responses of their offspring to cabbage odour occur only if the 48-h parasitization has occurred also on cabbage. However, with parasitoids from Brussels sprouts parasitizing the aphids for 48 h also on Brussels sprouts, the offspring subsequently emerging from pupae excised from the mummies show no preference for Brussels sprout odour. Thus, although the Brussels sprout cue had been experienced early in the development of the parasitoids, they only become conditioned to it when emerging from the mummy. Both male and female parasitoids respond very similarly in all experiments. It is proposed that the chemical cue (probably glucosinolates in these experiments) is most likely in the silk surrounding the parasitoid pupa, and that the mother may leave the chemical in or around the egg at oviposition, inducing chemical defences in her offspring to the secondary plant compounds that the offspring are likely to encounter.

An investigation of the impact of time of generation on carbon savings from PV systems in Great Britain

PV only generates electricity during daylight hours and primarily generates over summer. In the UK, the carbon intensity of grid electricity is higher during the daytime and over winter. This work investigates whether the grid electricity displaced by PV is high or low carbon compared to the annual mean carbon intensity using carbon factors at higher temporal resolutions (half-hourly and daily). UK policy for carbon reporting requires savings to be calculated using the annual mean carbon intensity of grid electricity. This work offers an insight into whether this technique is appropriate. Using half hourly data on the generating plant supplying the grid from November 2008 to May 2010, carbon factors for grid electricity at half-hourly and daily resolution have been derived using technology specific generation emission factors. Applying these factors to generation data from PV systems installed on schools, it is possible to assess the variation in the carbon savings from displacing grid electricity with PV generation using carbon factors with different time resolutions. The data has been analyzed for a period of 363 to 370 days and so cannot account for inter-year variations in the relationship between PV generation and carbon intensity of the electricity grid. This analysis suggests that PV displaces more carbon intensive electricity using half-hourly carbon factors than using daily factors but less compared with annual ones. A similar methodology could provide useful insights on other variable renewable and demand-side technologies and in other countries where PV performance and grid behavior are different.

Up-regulation of c-jun mRNA in cardiac myocytes requires the extracellular signal-regulated kinase cascade, but c-Jun N-terminal kinases are required for efficient up-regulation of c-Jun protein.

Cardiac hypertrophy, an important adaptational response, is associated with up-regulation of the immediate early gene, c- jun, which encodes the c-Jun transcription factor. c-Jun may feed back to up-regulate its own transcription and, since the c-Jun N-terminal kinase (JNK) family of mitogen-activated protein kinases (MAPKs) phosphorylate c-Jun(Ser-63/73) to increase its transactivating activity, JNKs are thought to be the principal factors involved in c- jun up-regulation. Hypertrophy in primary cultures of cardiac myocytes is induced by endothelin-1, phenylephrine or PMA, probably through activation of one or more of the MAPK family. These three agonists increased c- jun mRNA with the rank order of potency of PMA approximately endothelin-1>phenylephrine. Up-regulation of c- jun mRNA by endothelin-1 was attenuated by inhibitors of protein kinase C (GF109203X) and the extracellular signal-regulated kinase (ERK) cascade (PD98059 or U0126), but not by inhibitors of the JNK (SP600125) or p38-MAPK (SB203580) cascades. Hyperosmotic shock (0.5 M sorbitol) powerfully activates JNKs, but did not increase c- jun mRNA. These data suggest that ERKs, rather than JNKs, are required for c- jun up-regulation. However, endothelin-1 and phenylephrine induced greater up-regulation of c-Jun protein than PMA and phosphorylation of c-Jun(Ser-63/73) correlated with the level of c-Jun protein. Up-regulation of c-Jun protein by endothelin-1 was attenuated by inhibitors of protein kinase C and the ERK cascade, probably correlating with a primary input of ERKs into transcription. In addition, SP600125 inhibited the phosphorylation of c-Jun(Ser-63/73), attenuated the increase in c-Jun protein induced by endothelin-1 and increased the rate of c-Jun degradation. Thus whereas ERKs are the principal MAPKs required for c- jun transcription, JNKs are necessary to stabilize c-Jun for efficient up-regulation of the protein.

Reduction of NO by CO on Cu/ZrO(2)/Al(2)O(3) catalysts: Characterization and catalytic activities

ZrO(2), gamma-Al(2)O(3) and ZrO(2)/gamma-Al(2)O(3)-supported copper catalysts have been prepared, each with three different copper loads (1, 2 and 5 wt%), by the impregnation method. The catalysts were characterized by nitrogen adsorption (BET), X-ray diffraction (XRD), temperature programmed reduction (TPR) with H(2), Raman spectroscopy and electronic paramagnetic resonance (EPR). The reduction of NO by CO was studied in a fixed-bed reactor packed with these catalysts and fed with a mixture of 1% CO and 1% NO in helium. The catalyst with 5 wt% copper supported on the ZrO(2)/gamma-Al(2)O(3) matrix achieved 80% reduction of NO. Approximately the same rate of conversion was obtained on the catalyst with 2 wt% copper on ZrO(2). Characterization of these catalysts indicated that the active copper species for the reduction of NO are those in direct contact with the oxygen vacancies found in ZrO(2). (C) 2009 Published by Elsevier Ltd.

Recombinant expression of glycerol-3-phosphate dehydrogenase using the Pichia pastoris system

In the present study, the GPD2 gene from Saccharomyces cerevisiae, which codifies for the enzyme glycerol-3-phosphate dehydrogenase (GPDH), was cloned from the pPICZ-alpha expression vector and used with the purpose of inducing the extracellular expression of the glycerol-3-phosphate dehydrogenase under the control of the methanol-regulated AOX promoter. The presence of the GPD2 insert was confirmed by PCR analysis. Pichia pastoris X-33 (Mut(+)) was transformed with linearized plasmids by electroporation and transformants were selected on YPDS plates containing 100 mu g/mL of zeocin. Several clones were selected and the functionality of this enzyme obtained in a culture medium was assayed. Among the mutants tested, one exhibited 3.1 x 10(-2) U/mg of maximal activity. Maximal enzyme activity was achieved at 6 days of growth. Medium composition and pre-induction osmotic stress influenced protein production. Pre-induction osmotic stress (culturing cells in medium with either 0.35 M sodium chloride or 1.0 M sorbitol for 4h prior to induction) led to an increase in cell growth with sorbitol and resulted in a significant increase in GPDH productivity with sodium chloride in 24h of induction approximately fivefold greater than under standard conditions (without pre-induction). (C) 2010 Elsevier B.V. All rights reserved.

Dynamical erosion of asteroid groups in the region of the Phocaea family

In a previous paper, the current state of knowledge of the region containing the Phocaea dynamical family was revised. Here, the dynamical evolution and possible origin of the Phocaea dynamical family and asteroid groups in the region are investigated. First, I study the case of asteroids at high eccentricity (e > 0.31). I find that these objects are unstable because of encounters with Mars on time-scales of up to 270 Myr. The minimum time needed by members of the Phocaea classical family to reach the orbital locations of these objects, 370 Myr, can be used to set a lower limit on the age of the Phocaea family.Next, attention is focused on the chaotic layer previously identified near the nu(6) secular resonance border. Using analytical and numerical tools, I find that the presence of the nu(6) secular resonance forces asteroids with vertical bar g-g(6)vertical bar < 2.55 arcsec yr(-1) to reach eccentricities high enough to allow them to experience deep, close encounters with Mars. Results of the analytical model of Yoshikawa and of my numerical simulations fully explain the low-inclination chaotic region found by Carruba.Finally, I investigate the long-term stability of the minor families and clumps identified in the previous paper, with particular emphasis on a clump only identifiable in the domain of proper frequencies (n, g, g - s) around (6246) Komurotoru. I find that while the clumps identified in the space of proper elements quickly disperse when the Yarkovsky effect is considered, the family around (19536) is still observable for time-scales of more than 50 Myr. The (6246) clump, characterized by its interaction with the nu(5) + nu(16) and 2 nu(6) - nu(16) secular resonances, is robust on time-scales of 50 Myr. I confirm that this group may be the first clump ever detected in the frequency domain that can be associated with a real collisional event.

Comparative assessment of the flow rate of root canal sealers

OBJETIVO: Este estudo avaliou o escoamento do Acroseal, AH Plus, Endomethasone N, Sealapex e ActiV GP de acordo com a especificação ISO 6876/2001. METODOLOGIA: Um volume de 0,05 mL do cimento manipulado de acordo com as recomendações do fabricante foi colocado numa placa de vidro. Aos 180±5 s após o início da espatulação, uma segunda placa de vidro foi colocada sobre o cimento, seguida por um peso de massa de 100 g para fazer um total de 120±2 g. Dez minutos após o começo da manipulação o peso foi removido e o valor do diâmetro do disco de cimento foi mensurado. A média de 3 mensurações para cada cimento foi tomada como o escoamento do material. Os dados foram comparados estatisticamente pelos testes ANOVA e Tukey. RESULTADOS: Os escoamentos obtidos foram: Acroseal 21.,4 mm, AH Plus 22,72 mm, ActiV GP 24,90 mm, Endomethasone N 18,76 mm e Sealapex 25,15 mm. CONCLUSÃO: Apenas o Endomethasone N não se enquadrou na especificação ISO a qual requer que o cimento tenha um diâmetro não inferior a 20 mm. O Sealapex alcançou o melhor escoamento, mas não foi estatisticamente diferente do Activ GP e AH Plus (P>0,05).

Immunodominant Antigens of Leishmania chagasi Associated with Protection against Human Visceral Leishmaniasis

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Protease inhibition activity of extracts from Salicaceae species from Brazilian Cerrado and Atlantic Rain Forest and of an enriched fraction of clerodane diterpenes (casearins)

Considerando o uso popular de Casearia sylvestris Sw., Salicaceae, para o tratamento de problemas gástricos e resultados pré-clínicos que mostraram potencial atividade anti-ulcerogênica, foi realizado um screening farmacológico para avaliar a atividade biológica de outras espécies de Salicaceae. Para isso, foi utilizado um ensaio de inibição de proteases como um modelo farmacológico molecular para screening de extratos com atividade anti-ulcerogênica. Os extratos etanólico e aquoso dos galhos e folhas de C. gossypiosperma, C. decandra e C. rupestris mostraram inibição da atividade da pepsina em aproximadamente 50% com a concentração de 1 μg/mL. Curiosamente, C. obliquoa e Flacourtia ramontchi não apresentaram atividade sobre a pepsina, mas seus extratos mais apolares mostraram atividade inibitória sobre a subtilisina. A fração enriquecida de diterpenos clerodânicos mostrou atividade inibitória (42,75%) sobre a pepsina com a concentração de 1 μg/mL, mas não sobre a subtilisina (23,76%). Os resultados obtidos com os extratos e folhas das espécies testadas mostraram um padrão de atividade diferente sobre os dois tipos de proteases, a pepsina e a subtilisina, as quais estão relacionadas com diferentes tipos de atividades biológicas. Ainda mais, os resultados com a fração enriquecida de diterpenos clerodânicos sugerem que estas substâncias podem estar relacionadas com a atividade do extrato bruto de C. sylvestris.

The effects of soil fumigation on the growth and mineral nutrition of weeds and crops

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Developmental anatomy of Cyperus laxus (non-Nranz) and Fimbristylis dichotoma (Kranz) (Cyperaceae, Poales) and tissue continuity

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Role of metabolic control on diabetic nephropathy

OBJETIVO: Os autores relatam a influência do controle metabólico do diabetes, experimentalmente induzido no rato, sobre a nefropatia diabética. Eles observaram o efeito da insulina, da acarbose, um inibidor da glicosidase, e de dois agentes combinados sobre o controle metabólico e o desenvolvimento da expansão mesangial de glomérulos renais, no diabetes induzido pela aloxana no rato. MÉTODOS: Usando 5 grupos de ratos Wistar assim definidos: Normal(N), diabéticos não-tratados (D), diabéticos tratados com acarbose (AD); diabéticos tratados com insulina (ID) e diabéticos tratados com insulina associada à acarbose (IAD) foram avaliados os seguintes parâmetros: peso corporal, ingestão alimentar, ingestão hídrica, diurese, níveis de glicose sanguínea e urinária e as lesões renais: alargamento mesangial e vacuolização de células tubulares, usando contagem semi-quantitativa 1, 3, 6, 9 e 12 meses após a indução do diabetes. RESULTADOS: Houve acentuado aumento da glicemia, dos níveis de glicose na urina, da diurese, da ingestão hídrica e alimentar, e progressiva perda de peso nos ratos diabéticos, enquanto que os ratos diabéticos tratados exibiram melhora significativa destes parâmetros, sendo os ratos tratados com insulina + acarbose os que apresentaram controle metabólico mais satisfatório. Houve um significativo alargamento mesangial nos ratos diabéticos quando comparado ao observado nos ratos normais, desde o 3º até o 12º mês após a indução do diabetes, sendo observada diferença significativa entre os animais tratados com acarbose + insulina e os ratos diabéticos não-tratados. Não houve diferença significativa entre os animais tratados somente com acarbose ou com insulina quando comparados com ratos diabéticos não-tratados. CONCLUSÃO: Os autores discutem os resultados abordando o papel do controle metabólico do diabetes na prevenção da nefropatia diabética.