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101.
Many clinical trials compare two or more treatment groups by using a binary outcome measure. For example, the goal could be to determine whether the frequency of pain episodes is significantly reduced in the treatment group (arm A) as compared to the control group (arm B). However, for ethical or regulatory reasons, group sequential designs are commonly employed. Then, based on a binomial distribution, the stopping boundaries for the interim analyses are constructed for assessing the difference in the response probabilities between the two groups. This is easily accomplished by using any of the standard procedures, e.g., those discussed by Jennison and Turnbull (2000), and using one of the most commonly used software packages, East (2000). Several factors are known to often affect the primary outcome of interest, but their true distributions are not known in advance. In addition, these factors may cause heterogeneous treatment responses among individuals in a group, and their exact effect size may be unknown. To limit the effect of such factors on the comparison of the two arms, stratified randomization is used in the actual conduct of the trial. Then, a stratified analysis based on the odds ratio proposed in Jennison and Turnbull (2000, pages 251-252) and consistent with the stratified design is undertaken. However, the stopping rules used for the interim analyses are those obtained for determining the differences in response rates in a design that was not stratified. The purpose of this paper is to assess the robustness of such an approach on the performance of the odds ratio test when the underlying distribution and effect size of the factors that influence the outcome may vary. The simulation studies indicate that, in general, the stratified approach offers consistently better results than does the unstratified approach, as long as the difference in the weighted average of the response probabilities across strata between the two groups remains closer to the hypothesized values, irrespective of the differences in the (allocation) distributions and heterogeneous response rate. However, if the response probabilities deviate significantly from the hypothesized values so that the difference in the weighted average is less than the hypothesized value, then the proposed study could be significantly underpowered. 相似文献
102.
The role of mitochondria in causing diseases is becoming evident as more and more studies are focusing on this organelle of
the cell. This is largely attributed to its reactive oxygen species (ROS) production property. In the context of diabetes,
ROS is suggested to trigger different forms of insulin resistance involving different mechanisms. The suggestive role of a
mtDNA variant G10398A in increasing ROS production and the impaired response to oxidative stress due to T16189C variant is
worth addressing as genetic susceptibility factors in type 2 diabetes mellitus (T2DM). A case control study on 312 T2DM cases
and ethnically matched 466 controls involving two North Indian populations, referred as cohort 1 and cohort 2 (in a replicative
study), was undertaken to test such a genetic association. A statistically significant association was observed for 10398A
allele in both the cohorts [cohort1 (OR = 2.67 95% CI 1.77–4.00); cohort2 (OR = 1.76 95%CI 1.12–2.77)]. The analysis of G10398A/T16189C
haplotypic combinations revealed that 10398A/16189C haplotype provides a risk in both the cohorts. To sum up the study suggests
that 10398A and 16189C alleles provide susceptiblity to T2DM independently as well as together. 相似文献
103.
Human GMP reductase (hGMPR) enzyme is involved in a cellular metabolic pathway, converting GMP into IMP, and also it is an important target for anti-leukemic agents. Present computational investigations explain dynamical behavior of water molecules during the conformational transition process from GMP to IMP using molecular dynamics simulations. Residues at substrate-binding site of cancerous protein (PDB Id. 2C6Q) are mostly more dynamic in nature than the normal protein (PDB Id. 2BLE). Nineteen conserved water molecules are identified at the GMP/IMP binding site and are classified as (i) conserved stable dynamic and (ii) infrequent dynamic. Water molecules W11, W14, and W16 are classified as conserved stable dynamic due to their immobile character, whereas remaining water molecules (W1, W2, W3, W4, W5, W7, W8, W9, W10, W12, W13, W15, W17, W18, and W19) are infrequent with dynamic nature. Entrance or displacement of these infrequent water molecules at GMP/IMP sites may occur due to forward and backward movement of reference residues involving ligands. Four water molecules of hGMPR-I and nine water molecules of hGMPR-II are observed in repetitive transitions from GMP to IMP pathway, which indicates discrimination between two isoforms of hGMPRs. Water molecules in cancerous protein are more dynamic and unstable compared to normal protein. These water molecules execute rare dynamical events at GMP binding site and could assist in detailed understanding of conformational transitions that influence the hGMPR's biological functionality. The present study should be of interest to the experimental community engaged in leukemia research and drug discovery for CML cancer. 相似文献
104.
Molecular Biology Reports - S100A12, also known as Calgranulin C, is a ligand for the receptor for advanced glycation end products (RAGE) and plays key roles in cardiovascular and other... 相似文献
105.
106.
Minerals can enter the food chain through industrial and mining activities. Soil-to-vegetable transfer is higher than soil-to-cereal, but human consumption of metals is attributable to balanced diets containing both vegetables and cereals and drinking water. However, the impact of location on intakes of metals from predominantly cereal-based Indian diets is not clear. Hence, the present study was undertaken in selected Agricultural, Industrial, and Coal Mining Areas (AA, IA, CMA) around the Allahabad District in Northern India to compare transfer of toxic metals, Pb, Cd, Cr and essential metals, Fe, Zn, Cu, Co in soil and water to common crops: cereals (rice, wheat, maize) and vegetables (spinach, potato), and to assess Daily Intake of Metal (DIM) and consequent Health Risk Index (HRI). The overall content of all metals, except Cu, in water, soils, and crops followed the pattern CMA > IA > AA. Transfer factors (TFs) followed the sequence spinach > potato > cereals. Quantitatively, however, cereals contribute maximally to a balanced diet, so DIM and HRI were higher from cereals than vegetables. Even though spinach had the highest TFs, cereals contributed maximally to HRI. CMA had the highest metal content so locally grown cereals contributed significantly to intake of both toxic and essential metals. 相似文献
107.
Virus‐induced gene silencing of Withania somnifera squalene synthase negatively regulates sterol and defence‐related genes resulting in reduced withanolides and biotic stress tolerance 下载免费PDF全文
108.
Govindan Selvakumar Satya N. Sushil Johnson Stanley Muthugounder Mohan Anu Deol Deepak Rai 《Biocontrol Science and Technology》2011,21(7):821-827
We describe the isolation, biochemical characterization, phylogenetic analysis, and pathogenecity of a novel entomopathogenic bacterium Brevibacterium frigoritolerans to first instar larvae of Anomala dimidiata and Holotrichia longipennis. The almost full length 16S rRNA sequence of the bacterium has 99% identity with the type strain of B. frigoritolerans, while phylogenetic analysis revealed that the isolate formed a tightly linked branch with the type strain of B. frigoritolerans. Under in vitro bioassay conditions, the isolate infected and caused 89±5.4 and 74±7.7% mortality, in first instar larvae of A. dimidiata and H. longipennis, respectively. The infected larvae exhibited bacteremia like symptoms and mortality occurred between the second and fifth weeks after inoculation. This is an early report on the entomopathogenic potential of the hitherto lesser-known bacterium Brevibacterium frigoritolerans. 相似文献
109.
Biotechnological interventions in sea buckthorn (Hippophae L.): current status and future prospects 总被引:1,自引:0,他引:1
Rajwant K. Kalia Rohtas Singh Manoj K. Rai Gyan P. Mishra Sharbati R. Singh A. K. Dhawan 《Trees - Structure and Function》2011,25(4):559-575
Sea buckthorn (Hippophae L., Elaeagnaceae) is an economically and ecologically important medicinal plant comprising of species which are winter hardy,
dioecious, wind-pollinated multipurpose shrubs bearing yellow or orange berries with nitrogen-fixing ability. It grows widely
in cold regions of Indian Himalayas, China, Russia, Europe and many other countries. It is commonly known as ‘cold desert
gold’ due to its high potential as a bio-resource for land reclamation, reducing soil erosion and its multifarious uses. The
wild populations are being used for harvesting economic benefits with negligible plantation efforts. Although this plant has
many excellent traits, it is still in an early phase of domestication. This woody plant is prone to many pests and diseases
which destroy the plants and halt its commercial production. Limited progress has been made for improvement of sea buckthorn
through breeding programs due to long juvenile period and lack of QTL linkage map, which makes screening of mapping populations
a time-consuming and labor-intensive task. Conventional propagation methods, i.e. seeds, softwood and hardwood cuttings, and
suckers are in place but are cumbersome and season dependent. Therefore, application of modern tools of biotechnology needs
to be standardized for harnessing maximum benefits from this nutraceutical plant. Improvement of this genus through genetic
transformation requires an efficient regeneration system, which is yet to be standardized. Taxonomic status of the genus is
controversial and requires more inputs. Taxonomic delineation of species and subspecies and also the breeding programs can
be more robustly addressed using molecular markers. This review summarizes the progress made and suggests some future directions
of research for this important fruit species. 相似文献
110.
Kumar L Sarswat A Lal N Jain A Kumar S Kiran Kumar ST Maikhuri JP Pandey AK Shukla PK Gupta G Sharma VL 《Bioorganic & medicinal chemistry letters》2011,21(1):176-181
We designed a series of 25 3-(azol-1-yl)phenylpropanes which yielded 10 compounds (3, 4, 7, 8, 13, 14, 19, 21, 23, 26) that irreversibly immobilized 100% human sperm at 1% (w/v) concentration in 60 s; 12 compounds (8, 9, 15, 16, 19-21, 23-25, 27, 28) that showed potent microbicidal activity at 12.5-50 μg/mL against Trichomonas vaginalis; and 17 compounds (3-11, 13, 15, 19, 21, 23, 26, 28, 30) that exhibited potent anticandida activity with minimum inhibitory concentration (MIC) of 12.5-50 μg/mL. Almost all the compounds exhibited high level of safety towards normal vaginal flora (Lactobacillus) and human cervical (HeLa) cells in comparison to the marketed spermicide nonoxynol-9 (N-9). All the biological activities were evaluated in vitro. Two compounds (4, 8) with good safety profile exhibited multiple (spermicidal, antitrichomonas and anticandida) activities, warranting further lead optimization for furnishing a prophylactic vaginal contraceptive. 相似文献