Fast Statistical Alignment

We describe a new program for the alignment of multiple biological sequences that is both statistically motivated and fast enough for problem sizes that arise in practice. Our Fast Statistical Alignment program is based on pair hidden Markov models which approximate an insertion/deletion process on a tree and uses a sequence annealing algorithm to combine the posterior probabilities estimated from these models into a multiple alignment. FSA uses its explicit statistical model to produce multiple alignments which are accompanied by estimates of the alignment accuracy and uncertainty for every column and character of the alignment—previously available only with alignment programs which use computationally-expensive Markov Chain Monte Carlo approaches—yet can align thousands of long sequences. Moreover, FSA utilizes an unsupervised query-specific learning procedure for parameter estimation which leads to improved accuracy on benchmark reference alignments in comparison to existing programs. The centroid alignment approach taken by FSA, in combination with its learning procedure, drastically reduces the amount of false-positive alignment on biological data in comparison to that given by other methods. The FSA program and a companion visualization tool for exploring uncertainty in alignments can be used via a web interface at http://orangutan.math.berkeley.edu/fsa/, and the source code is available at http://fsa.sourceforge.net/

Copper(I) complexes of modified nucleobases and vitamin B3 as potential chemotherapeutic agents: In vitro and in vivo studies

Three new complexes of Cu(I) have been synthesized using ancillary ligands like thiopyrimidine (tp) a modified nucleobase, and nicotinamide (nie) or vitamin B3, and characterized by spectroscopy and X-ray crystallography. In vitro cytotoxicity studies of the complexes on various human cancer cell lines such as Colo295, H226, HOP62, K562, MCF7 and T24 show that Cu(PPh3)(2)(tp)Cl] and Cu(PPh3)(2)(tp)ClO4 (2) have in vitro cytotoxicity comparable to cisplatin. Complex Cu(nic)(3)PPh3]ClO4 (3) is non-toxic and increases the life span by about 55 % in spontaneous breast tumor model. DNA binding and cleavage studies show that complex (3) binds to calf thymus DNA with an apparent binding constant of 5.9 x 10(5)M and completely cleaves super-coiled DNA at a concentration of 400 mu M, whereas complexes (1) and (2) do not bind DNA and do not show any cleavage even at 1200 mu M. Thus, complex (3) may exhibit cytotoxicity Via DNA cleavage whereas the mechanism of cytotoxicity of (1) and (2) probably involves a different pathway

Evaluation of some plant extracts for standardization and anticancer activity

682-687<span style="letter-spacing:-.1pt;mso-ansi-language: EN-US;mso-fareast-language:EN-IN" lang="EN-US">In recent times, the trend in cancer research is shifting towards identifying new medicines from natural resources for management of cancer.<span style="letter-spacing:-.1pt; mso-ansi-language:EN-US" lang="EN-US"> <span style="letter-spacing:-.1pt; mso-ansi-language:EN-US;mso-fareast-language:EN-IN" lang="EN-US">Medicinal plants such as Sthauneyaka (<i style="mso-bidi-font-style: normal">Taxus baccata L.) and compound formulations like Triphala ghrita, <i style="mso-bidi-font-style: normal">Khadirarista, Madhusnuhi rasayana, Maha triphaladya ghrita, Panchatikta guggulu ghrita are indicated in the Ayurvedic texts for management of cancer/ tumour. <span style="letter-spacing:-.1pt;mso-fareast-language:EN-IN;mso-bidi-font-weight: bold" lang="EN-GB">The anti-proliferative activities of hydro-alcoholic extracts of some standardized plant materials were screened against a panel of 14 human cancer cell lines representing different tissues (lung, pancreas, colon, cervix, oral, bladder, prostate, breast, leukaemia, etc.) through Sulforhodamine-B (SRB) assay. The findings revealed that <span style="letter-spacing:-.1pt;mso-fareast-language:EN-IN;mso-bidi-font-weight: bold" lang="EN-GB">Cedrus deodara (Roxb.) ex Lamb. and <span style="letter-spacing:-.1pt;mso-fareast-language:EN-IN;mso-bidi-font-weight: bold" lang="EN-GB">Berberis aristata (Roxb.) ex DC. have maximum anticancer activity against 3 cell lines while <span style="letter-spacing:-.1pt; mso-fareast-language:EN-IN;mso-bidi-font-weight:bold" lang="EN-GB">Withania somnifera<span style="letter-spacing:-.1pt;mso-fareast-language:EN-IN;mso-bidi-font-weight: bold" lang="EN-GB"> Dunal. showed activity against two cell lines. In addition to these, <span style="letter-spacing:-.1pt; mso-fareast-language:EN-IN;mso-bidi-font-weight:bold" lang="EN-GB">Picrorhiza kurroa<span style="letter-spacing:-.1pt;mso-fareast-language:EN-IN;mso-bidi-font-weight: bold" lang="EN-GB"> Royle ex Benth. and Piper longum L. were found active against only one cell line. These results indicate the potential of Ayurvedic medicinal herbs as anti-neoplastic agents mentioned in the Ayurvedic texts. However, further studies are needed for evaluating their mechanism of action and to isolate the active anticancer compounds responsible for this activity. </span

Unemployment in chronic airflow obstruction (CAO) around the world: results from the Burden of Obstructive Lung Disease (BOLD) study

Objectives: We aimed to examine associations between CAO and unemployment across the world. Methods: Cross-sectional data from 26 sites in the Burden of Obstructive Lung Disease (BOLD) Study were used to analyze effects of CAO on unemployment. Odds ratios (OR) for unemployment in subjects 40-65 years old were estimated with multilevel mixed-effects generalized linear model with study site as random effect. Site-by-site heterogeneity was assessed using individual participant data meta-analyses. Results: Of 18710 participants, 11.3% had CAO. Ratio of unemployed subjects with CAO divided by unemployed subjects without CAO showed large discrepancies between sites, particularly in low-to-middle income countries with ratio from 0.5 (lower unemployment among CAO cases) in the Philippines to 5.8 (higher unemployment among CAO cases) in India. Site-adjusted OR for unemployment (95% confidence interval) was 1.79 (1.41, 2.27) for participants with CAO, decreasing to 1.43 (1.14, 1.79) after adjusting for gender, age, smoking, comorbidities, education and forced vital capacity (FVC). Risk factors for unemployment in high-income sites were age (OR (95%CI) 4.02 (3.53, 4.57), and primary education vs university education 3.86 (2.80, 5.30). Female gender was the most important factor for unemployment in low-to-middle-income sites (OR 3.23 (2.66, 3.91). Conclusions: CAO was associated with unemployment even after adjusting for sociodemographic factors, comorbidities and FVC. We observed that the association was particularly strong in high-income sites

Unemployment in chronic airflow obstruction around the world: Results from the BOLD study

Objectives: We aimed to examine associations between chronic airflow obstruction (CAO) and unemployment across the world. Methods: Cross-sectional data from 26 sites in the Burden of Obstructive Lung Disease (BOLD) Study were used to analyze effects of CAO on unemployment. Odds ratios (OR) for unemployment in subjects 40-65 years old were estimated with multilevel mixed-effects generalized linear model with study site as random effect. Site-by-site heterogeneity was assessed using individual participant data meta-analyses. Results: Of 18710 participants, 11.3% had CAO. Ratio of unemployed subjects with CAO divided by subjects without CAO showed large site discrepancies, though these were no longer significant after adjusting for age, sex, smoking and education. Site-adjusted OR for unemployment (95%CI) was 1.79 (1.41, 2.27) for CAO cases, decreasing to 1.43 (1.14, 1.79) after adjusting for sociodemographic factors, comorbidities and forced vital capacity. Of other covariates that were associated with unemployment, age and education were important risk factors in high-income sites (OR (95%CI) 4.02 (3.53, 4.57) and 3.86 (2.80, 5.30) respectively), while female gender was important in low-to-middle-income sites (OR 3.23 (2.66, 3.91)). Conclusions: In the global BOLD study, CAO was associated with increased levels of unemployment, even after adjusting for sociodemographic factors, comorbidities and lung function

Airflow obstruction and use of solid fuels for cooking or heating: BOLD results

Rationale: Evidence supporting the association of COPD or airflow obstruction with use of solid fuels is conflicting and inconsistent. Objective: To assess the association of airflow obstruction with self-reported use of solid fuels for cooking or heating. Methods: We analysed 18,554 adults from the BOLD study, who had provided acceptable post-bronchodilator spirometry measurements and information on use of solid fuels. The association of airflow obstruction with use of solid fuels for cooking or heating was assessed by sex, within each site, using regression analysis. Estimates were stratified by national income and meta-analysed. We carried out similar analyses for spirometric restriction, chronic cough and chronic phlegm. Measurements and main results: We found no association between airflow obstruction and use of solid fuels for cooking or heating (ORmen=1.20, 95%CI 0.94-1.53; ORwomen=0.88, 95%CI 0.67-1.15). This was true for low/middle and high income sites. Among never smokers there was also no evidence of an association of airflow obstruction with use of solid fuels (ORmen=1.00, 95%CI 0.57-1.76; ORwomen=1.00, 95%CI 0.76-1.32). Overall, we found no association of spirometric restriction, chronic cough or chronic phlegm with the use of solid fuels. However, we found that chronic phlegm was more likely to be reported among female never smokers and those who had been exposed for ≥20 years. Conclusion: Airflow obstruction assessed from post-bronchodilator spirometry was not associated with use of solid fuels for cooking or heating

Social factors and overweight : evidence from nine Asian INDEPTH Network sites

BACKGROUND: Overweight/obesity increases the risk of morbidity and mortality from a number of chronic conditions, including heart disease, stroke, diabetes and some cancers. This study examined the distribution of body mass index (BMI) in nine Health and Demographic Surveillance System (HDSS) sites in five Asian countries and investigated the association between social factors and overweight. DATA AND METHODS: This cross-sectional study was conducted in nine HDSS sites in Bangladesh, India, Indonesia, Thailand and Vietnam. The methodology of the WHO STEPwise approach to Surveillance with core risk factors (Step 1) and physical measurements for weight, height and waist circumference (Step 2) were included. In each site, about 2,000 men and women aged 25-64 years were selected randomly using the HDSS database. Weight was measured using electronic scales, height was measured by portable stadiometers and waist circumference was measured by measuring tape. Overweight/obesity was assessed by BMI defined as the weight in kilograms divided by the square of the height in metres (kg/m(2)). RESULTS: At least 10% people were overweight (BMI &gt;/= 25) in each site except for the two sites in Vietnam and WATCH HDSS in Bangladesh where few men and women were overweight. After controlling for all the variables in the model, overweight increases with age initially and then declines, with increasing education, and with gender with women being heavier than men. People who eat vegetables and fruits below the recommended level and those who do high level of physical activity are, on the whole, less heavy than those who eat more and do less physical activity. CONCLUSIONS: As the proportion of the population classified as being overweight is likely to increase in most sites and overweight varies by age, sex, and social and behavioural factors, behavioural interventions (physical exercise, healthy diet) should be developed for the whole population together with attention to policy around nutrition and the environment, in order to reduce the adverse effects of overweight on health