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 region Ser333-Arg356 of the alpha-chain of human C4b-binding protein is involved in the binding of complement C4b

Human C4b-binding protein (C4BP) functions as a cofactor to factor I in the degradation of C4b and accelerates the decay rate of the C4b2a complex. In this study we describe a monoclonal antibody directed against the alpha-chain of C4BP that inhibits the binding of C4b to C4BP. In order to identify the structural domain of the alpha-chain of C4BP that interacts with C4b, tryptic fragments of C4BP were generated. Amino acid sequence analysis of the fragments revealed that the residues Ser333-Arg356 of the alpha-chain of C4BP contain the epitope of this antibody, and as a consequence, that this part of the alpha-chain of C4BP is likely to be involved in the interaction with C4b.     

Collection of biological materials in biodiversity prospecting in India: problems and solutions

Forests are the chief resource for the collection and exploration of biological materials. The past few decades have witnessed a large scale deforestation in India due to substantial pressures generated by population growth, leading to demand for more land for agriculture, urbanization and industrial activities, in addition to increased demand for fuel wood and timber. This has resulted in the loss of soil cover, habitat destruction, environmental degradation and ecological imbalance. This scenario has created a progressive awareness for the conservation and restoration of habitats and, thus, the declaration of many forest areas into protected zones, such as national parks, biosphere reserves, etc., including the protection of some marine areas, by both the National and State Governments. Normally, permission for biological collecting is not granted in these protected areas. In India, forests are a State subject and grant for collection permission is vested with the State Forest Departments. In the absence of any rules, regulations and guidelines, either from National or State Governments, forest authorities impose their terms and conditions, which are arbitrary and even contradictory at times, in the process of granting collecting permits. A set of new rules to be applied throughout the country is needed.     

Performance Optimizations for Deploying VoIP Services in Mesh Networks

In the recent past, there has been a tremendous increase in the popularity of VoIP services as a result of huge growth in broadband access. The same voice-over-Internet protocol (VoIP) service poses new challenges when deployed over a wireless mesh network, while enabling users to make voice calls using WiFi phones. Packet losses and delay due to interference in a multiple-hop mesh network with limited capacity can significantly degrade the end-to-end VoIP call quality. In this work, we discuss the basic requirements for efficient deployment of VoIP services over a mesh network. We present and evaluate practical optimizing techniques that can enhance the network capacity, maintain the VoIP quality and handle user mobility efficiently. Extensive experiments conducted on a real testbed and ns-2 provide insights into the performance issues and demonstrate the level of improvement that can be obtained by the proposed techniques. Specifically, we find that packet aggregation along with header compression can increase the number of supported VoIP calls in a multihop network by 2-3 times. The proposed fast path switching is highly effective in maintaining the VoIP quality. Our fast handoff scheme achieves almost negligible disruption during calls to roaming clients     

Characteristics of microstrip transmission lines withhigh-dielectric-constant substrates

An efficient numerical code is developed from a full-wave analysis in the Fourier transform domain to determine the characteristics of a single-strip or multistrip coplanar transmission line. Modes of both even and odd symmetries are included. The impedance of the transmission line is calculated using the power-current equivalent model. Coupling constants between the even and the odd modes are also calculated. Results are provided for a shielded two-strip coupled microstrip transmission line on high-dielectric-constant substrate such as lanthanum aluminate with applications to superconducting transmission lines     

Antibody- and cell-mediated immune responses of Actinobacillus pleuropneumoniae-infected and bacterin-vaccinated pigs

The number involved in and the rate of migration of donor leucocytes into the following recipient organs (spleen, thymus, bone marrow, lung and mesenteric lymph nodes) were measured in two rat models of orthotopic liver transplantation (OLT) using donor-specific MHC class I antibodies. The first OLT model is one that does not require immunosuppression in order to achieve tolerance and involved the transplantation of DA (MHC haplotype, RT1a) livers into PVG (RT1c) recipients. The second model was one that required a 7-day (10 mg/kg) treatment with cyclosporin A (CsA) to achieve tolerance and used DA donors into Lewis (RT1(1)) recipients. Recipient organs were biopsied on days 3, 20 and 87 following OLT and donor leucocyte migration was quantified by immunohistochemistry and computer densitometry of immunoblots of detergent-solublized tissues in order to resolve both membrane-bound and soluble donor MHC class I antigen. In a separate experiment, spleen biopsies were taken following OLT on days 3 and 15 from the naturally tolerizing OLT model (DA into PVG), treated with and without CsA for 7 days and compared with the (DA into Lewis) model. The initial rate of leucocyte migration between days 3 and 21 following OLT was found to be the most rapid into the spleen, followed by the bone marrow and mesenteric lymph nodes in the naturally tolerant (DA into PVG) model when compared with the (DA into Lewis) model. The number of donor leucocytes in the spleen and mesenteric lymph nodes in both models was, however, approximately the same by 87 days. No real difference in the rate of leucocyte migration was seen in the thymus or the lung for both transplant models over the time course assayed. CsA was found to lower the rate of donor leucocyte migration only over the period it was administered. The rate of donor leucocyte migration into the spleen was still much lower 15 days after OLT in the (DA into Lewis) model compared with the (DA into PVG) model treated with and without CsA. Thus the differences in the rate of donor leucocyte migration into the spleen, bone marrow and mesenteric lymph nodes immediately following OLT may offer an explanation as to why the (DA into PVG) combination is able to accept a transplanted liver without immunosuppressive therapy.     

Evaluation of hot hardness and creep of a 350 grade commercial maraging steel

The hardening response and the indentation creep of a 350 grade commercial maraging steel were evaluated using a hot hardness tester. The hardness versus temperature plot exhibited three distinct regions. Hardness response was noted between 500–800 K. The unusually high values of activation energy and stress exponent obtained during the creep experiment could be rationalized by a novel concept of introducing a back stress term in the indentation creep relation. The corrected value of the activation energy was found to be reasonably in agreement with the activation energy for diffusion of Ni in iron. Results are supplemented with microstructural observation.