BRCA1 and BRCA2 germline mutation analysis among Indian women from south India: identification of four novel mutations and high-frequency occurrence of 185delAG mutation

Mutations in the BRCA1 and BRCA2 genes profoundly increase the risk of developing breast and/or ovarian cancer among women. To explore the contribution of BRCA1 and BRCA2 mutations in the development of hereditary breast cancer among Indian women, we carried out mutation analysis of the BRCA1 and BRCA2 genes in 61 breast or ovarian cancer patients from south India with a positive family history of breast and/or ovarian cancer. Mutation analysis was carried out using conformation-sensitive gel electrophoresis (CSGE) followed by sequencing. Mutations were identified in 17 patients (28.0%); 15 (24.6%) had BRCA1 mutations and two (3.28%) had BRCA2 mutations. While no specific association between BRCA1 or BRCA2 mutations with cancer type was seen, mutations were more often seen in families with ovarian cancer. While 40% (4/10) and 30.8% (4/12) of families with ovarian or breast and ovarian cancer had mutations, only 23.1% (9/39) of families with breast cancer carried mutations in the BRCA1 and BRCA2 genes. In addition, while BRCA1 mutations were found in all age groups, BRCA2 mutations were found only in the age group of <= 40 years. Of the BRCA1 mutations, there were three novel mutations (295delCA; 4213T -> A; 5267T -> G) G) and three mutations that have been reported earlier. Interestingly, 185delAG, a BRCA1 mutation which occurs at a very high frequency in Ashkenazi Jews, was found at a frequency of 16.4% (10/61). There was one novel mutation (4866insT) and one reported mutation in BRCA2. Thus, our study emphasizes the importance of mutation screening in familial breast and/or ovarian cancers, and the potential implications of these findings in genetic counselling and preventive therapy.

Four generations: SUSY and SUSY breaking

We revisit four generations within the context of supersymmetry. Wecompute the perturbativity limits for the fourth generation Yukawa couplings and show that if the masses of the fourth generation lie within reasonable limits of their present experimental lower bounds, it is possible to have perturbativity only up to scales around 1000 TeV. Such low scales are ideally suited to incorporate gauge mediated supersymmetry breaking, where the mediation scale can be as low as 10-20 TeV. The minimal messenger model, however, is highly constrained. While lack of electroweak symmetry breaking rules out a large part of the parameter space, a small region exists, where the fourth generation stau is tachyonic. General gauge mediation with its broader set of boundary conditions is better suited to accommodate the fourth generation.

Static balancing of a four-bar linkage and its cognates

Motivated by the need to statically balance the inherent elastic forces in linkages, this paper presents three techniques to statically balance a four-bar linkage loaded by a zero-free-length spring attached between its coupler point and an anchor point on the ground. The number of auxiliary links and balancing springs required for the three techniques is less than or equal to that of the only technique currently in the literature. One of the three techniques does not require auxiliary links. In these techniques, the set of values for the spring constants and the ground-anchor point of the balancing springs can vary over a one-parameter family. Thrice as many balancing choices are available when the cognates are considered. The ensuing numerous options enable a user to choose the most practical solution. To facilitate the evaluation of the balancing choices for all the cognates, Roberts-Chebyshev cognate theorem is extended to statically balanced four-bar linkages. (C) 2011 Elsevier Ltd. All rights reserved.

The physics of ENSO-monsoon connection

The physical mechanism through which Ei-Nino and Southern Oscillation (ENSO) tends to produce deficient precipitation over Indian continent is investigated using both observations as well as a general circulation model. Both analysis of observations and atmospheric general circulation model (AGCM) study show that the planetary scale response associated with ENSO primarily influences the equatorial Indian Ocean region. Through this interaction it tends to favour the equatorial heat source, enhance precipitation over the equatorial Indian Ocean and indirectly cause a decrease in continental precipitation through induced subsidence. This situation is further complicated by the fact the regional tropospheric quasi biennial oscillation (QBO) has a bimodal structure over this region with large amplitude over the Indian continent. While the ENSO response has a quasi-four year periodicity and tends peak during beginning of the calendar year, the QBO mode tends to peak during northern summer. Thus, the QBO mode exerts a stronger influence on the interannual variability of the monsoon. The strength of the Indian monsoon in a given year depends on the combined effect of the ENSO and the QBO mode. Sines the two oscillations have disparate time scales, exact phase information of the two modes during northern summer is important in determining the Indian summer monsoon. The physical mechanism of the interannual variations of the Indian monsoon precipitation associated with ENSO presented here is similar to the physical process that cause intraseasonal 'active', 'break' oscillations of the monsoon.