BRCA1 mutations in women attending clinics that evaluate the risk of breast cancer

BACKGROUND: To define the incidence of BRCA1 mutations among patients seen in clinics that evaluate the risk of breast cancer, we analyzed DNA samples from women seen in this setting and constructed probability tables to provide estimates of the likelihood of finding a BRCA1 mutation in individual families. METHODS: Clinical information, family histories, and blood for DNA analysis were obtained from 263 women with breast cancer. Conformation-sensitive gel electrophoresis and DNA sequencing were used to identify BRCA1 mutations. RESULTS: BRCA1 mutations were identified in 16 percent of women with a family history of breast cancer. Only 7 percent of women from families with a history of breast cancer but not ovarian cancer had BRCA1 mutations. The rates were higher among women from families with a history of both breast and ovarian cancer. Among family members, an average age of less than 55 years at the diagnosis of breast cancer, the presence of ovarian cancer, the presence of breast and ovarian cancer in the same woman, and Ashkenazi Jewish ancestry were all associated with an increased risk of detecting a BRCA1 mutation. No association was found between the presence of bilateral breast cancer or the number of breast cancers in a family and the detection of a BRCA1 mutation, or between the position of the mutation in the BRCA1 gene and the presence of ovarian cancer in a family. CONCLUSIONS: Among women with breast cancer and a family history of the disease, the percentage with BRCA1 coding-region mutations is less than the 45 percent predicted by genetic-linkage analysis. These results suggest that even in a referral clinic specializing in screening women from high-risk families, the majority of tests for BRCA1 mutations will be negative and therefore uninformative.     

The impact of tidal stream turbines on large-scale sediment dynamics

Tidal stream turbines are exploited in regions of high tidal currents. Such energy extraction will alter the hydrodynamics of a tidal region, analogous to increasing the bed friction in the region of extraction. In addition, this study demonstrates that energy extracted with respect to tidal asymmetries due to interactions between quarter (M₄) and semi-diurnal (M₂) currents will have important implications for large-scale sediment dynamics. Model simulations show that energy extracted from regions of strong tidal asymmetry will have a much more pronounced effect on sediment dynamics than energy extracted from regions of tidal symmetry. The results show that energy extracted from regions of strong tidal asymmetry led to a 20% increase in the magnitude of bed level change averaged over the length of a large estuarine system, compared with energy extracted from regions of tidal symmetry. However, regardless of the location of a tidal stream farm within a tidal system, energy extraction reduces the overall magnitude of bed level change in comparison with non-extraction cases. This has practical application to many areas surrounding the UK, including the Irish Sea and the Bristol Channel, that exhibit strong tidal currents suitable for exploitation of the tidal stream resource, but where large variations in tidal asymmetry occur.     

Haplotype and phenotype analysis of six recurrent BRCA1 mutations in 61 families: results of an international study

Central to the Mu transpositional recombination are the two chemical steps; donor DNA cleavage and strand transfer. These reactions occur within the Mu transpososome that contains two Mu DNA end segments bound to a tetramer of MuA, the transposase. To investigate which MuA monomer catalyzes which chemical reaction, we made transpososomes containing wild-type and active site mutant MuA. By pre-loading the MuA variants onto Mu end DNA fragments of different length prior to transpososome assembly, we could track the catalysis by MuA bound to each Mu end segment. The donor DNA end that underwent the chemical reaction was identified. Both the donor DNA cleavage and strand transfer were catalyzed in trans by the MuA monomers bound to the partner Mu end. This arrangement explains why the transpososome assembly is a prerequisite for the chemical steps.     

Neutron radiation effects in GaAs planar doped barrier diodes

The degradation of GaAs planar doped barrier diodes subject to neutron irradiation is discussed. It is shown that for fluences as high as 10¹⁵ cm^-2, the diode characteristics are very well preserved, which strengthens the rationale for using these devices in place of Schottky diodes in harsh working environments such as nuclear instrumentation and space     

Mathematics as Information Technologies

In ancient societies, the development of abstract symbols for quantities of space and time and the formulation of computational strategies were intertwined with major developments in social structure.     

Platelet aggregation, stroke, and transient ischemic attack in middle-aged and elderly patients

Platelet aggregation was studied with optical density methods in a group of 39 patients with stroke or transient ischemic attacks (TIA) and in age, sex, and race-matched controls. The patients were divided at age 60 into young stroke patients and young controls (18 pairs) and old stroke patients and old controls (21 pairs). A semiquantitative measure of the threshold of phase II of platelet aggregation and distinct of disaggregation 3 minutes after peak aggregation were used as an index of platelet aggregability. Aggregability was significantly greater in young stroke patients than in young controls. Aggregability was similar in old stroke patients and old controls. Both old stroke patients and old controls were hyperaggregable compared with young controls, indicating that aggregability rises with age. This suggests that platelet aggregability is significant risk factor for stroke but is relatively more important in the younger than in the older stroke patient.