32,493 research outputs found

    Purified human BRCA2 stimulates RAD51-mediated recombination.

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    Mutation of the breast cancer susceptibility gene, BRCA2, leads to breast and ovarian cancers. Mechanistic insight into the functions of human BRCA2 has been limited by the difficulty of isolating this large protein (3,418 amino acids). Here we report the purification of full-length BRCA2 and show that it both binds RAD51 and potentiates recombinational DNA repair by promoting assembly of RAD51 onto single-stranded DNA (ssDNA). BRCA2 acts by targeting RAD51 to ssDNA over double-stranded DNA, enabling RAD51 to displace replication protein-A (RPA) from ssDNA and stabilizing RAD51-ssDNA filaments by blocking ATP hydrolysis. BRCA2 does not anneal ssDNA complexed with RPA, implying it does not directly function in repair processes that involve ssDNA annealing. Our findings show that BRCA2 is a key mediator of homologous recombination, and they provide a molecular basis for understanding how this DNA repair process is disrupted by BRCA2 mutations, which lead to chromosomal instability and cancer

    Organizational Conflict Resolution and Strategic Choice: Evidence from a Survey of Fortune 1000 Companies

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    In this paper we develop the argument that a firm’s ADR strategies are likely to be associated with a firm’s use of one conflict resolution option or the other. More specifically, we examine whether a firm’s use of either arbitration or mediation is a function of (1) the extent to which the use of either of these dispute resolution processes aligns with the goals and objectives management is seeking to advance, and (2) the extent of the firm’s commitment to the use of these practices. We expect to find that an organization’s use of either mediation or arbitration may be governed by different underlying strategic objectives as well as the firm’s broader commitment to ADR. In what follows, we further develop this strategic choice argument

    Organizational Strategies for the Adoption of Electronic Medical Records: Toward an Understanding of Outcome Variation in Nursing Homes

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    [Excerpt] An important element in president-elect Obama\u27s economic stimulus proposal is his plan to invest a significant proportion of federal dollars in installing electronic medical records (EMR) in U.S. healthcare institutions. In emphasizing the need for EMR, Obama is following the advice of numerous healthcare experts who have pointed out that the healthcare sector lags behind other industries in the use of computer technology. They believe the widespread use of EMR would help reduce medical errors, control the costs of healthcare, and lead to significant improvements in the quality of care Americans receive. In this paper we present preliminary results of an ongoing study of the introduction of EMR in 20 nursing homes in the New York City area. Although most observers believe EMR holds great promise for the improvement of healthcare, in fact recent studies have found mixed evidence regarding the effect of EMR on patient outcomes. The evidence we have gathered to date suggests that whether EMR has beneficial effects on the costs and quality of healthcare depends very much on the purposes and objectives nursing home managers and administrators intend to achieve through its use. That is, management strategy and style, we believe, strongly influences healthcare outcomes associated with technological innovation

    Neutrinoless double-beta decay. A brief review

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    In this brief review we discuss the generation of Majorana neutrino masses through the see-saw mechanism, the theory of neutrinoless double-beta decay, the implications of neutrino oscillation data for the effective Majorana mass, taking into account the recent Daya Bay measurement of theta_13, and the interpretation of the results of neutrinoless double-beta decay experiments.Comment: 22 page

    Geophysical and astronomical models applied in the analysis of very long baseline interferometry

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    Very long baseline interferometry presents an opportunity to measure at the centimeter level such geodetic parameters as baseline length and instantaneous pole position. In order to achieve such precision, the geophysical and astronomical models used in data analysis must be as accurate as possible. The Mark-3 interactive data analysis system includes a number of refinements beyond conventional practice in modeling precession, nutation, diurnal polar motion, UT1, solid Earth tides, relativistic light deflection, and reduction to solar system barycentric coordinates. The algorithms and their effects on the recovered geodetic, geophysical, and astrometric parameters are discussed

    The Mark 3 data base handler

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    A data base handler which would act to tie Mark 3 system programs together is discussed. The data base handler is written in FORTRAN and is implemented on the Hewlett-Packard 21MX and the IBM 360/91. The system design objectives were to (1) provide for an easily specified method of data interchange among programs, (2) provide for a high level of data integrity, (3) accommodate changing requirments, (4) promote program accountability, (5) provide a single source of program constants, and (6) provide a central point for data archiving. The system consists of two distinct parts: a set of files existing on disk packs and tapes; and a set of utility subroutines which allow users to access the information in these files. Users never directly read or write the files and need not know the details of how the data are formatted in the files. To the users, the storage medium is format free. A user does need to know something about the sequencing of his data in the files but nothing about data in which he has no interest

    Mark 3 interactive data analysis system

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    The interactive data analysis system, a major subset of the total Mark 3 very long baseline interferometry (VLBI) software system is described. The system consists of two major and a number of small programs. These programs provide for the scientific analysis of the observed values of delay and delay rate generated by the VLBI data reduction programs and product the geophysical and astrometric parameters which are among the ultimate products of VLBI. The two major programs are CALC and SOLVE. CALC generates the theoretical values of VLBI delay rate as well as partial derivatives based on apriori values of the geophysical and astronometric parameters. SOLVE is a least squares parameters estimation program which yields the geophysical and astrometric parameters using the observed values by the data processing system and theoretical values and partial derivatives provided by CALC. SOLVE is a highly interactive program in which the user selects the exact form of the recovered parameters and the data to be accepted into the solution

    Dune field pattern formation and recent transporting winds in the Olympia Undae Dune Field, north polar region of Mars

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    High-Resolution Imaging Science Experiment (HiRISE) imagery of the central Olympia Undae Dune Field in the north polar region of Mars shows a reticulate dune pattern consisting of two sets of nearly orthogonal dune crestlines, with apparent slipfaces on the primary crests, ubiquitous wind ripples, areas of coarse-grained wind ripples, and deflated interdune areas. Geomorphic evidence and dune field pattern analysis of dune crest length, spacing, defect density, and orientation indicates that the pattern is complex, representing two constructional generations of dunes. The oldest and best-organized generation forms the primary crestlines and is transverse to circumpolar easterly winds. Gross bed form-normal analysis of the younger pattern of crestlines indicates that it emerged with both circumpolar easterly winds and NE winds and is reworking the older pattern. Mapping of secondary flow fields over the dunes indicates that the most recent transporting winds were from the NE. The younger pattern appears to represent an influx of sediment to the dune field associated with the development of the Olympia Cavi reentrant, with NE katabatic winds channeling through the reentrant. A model of the pattern reformation based upon the reconstructed primary winds and resulting secondary flow fields shows that the development of the secondary pattern is controlled by the boundary condition of the older dune topography

    Movement and habitat use of two aquatic turtles (\u3cem\u3eGraptemys geographic\u3c/em\u3e and \u3cem\u3eTrachemys scripta\u3c/em\u3e) in an urban landscape

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    Our study focuses on the spatial ecology and seasonal habitat use of two aquatic turtles in order to understand the manner in which upland habitat use by humans shapes the aquatic activity, movement, and habitat selection of these species in an urban setting. We used radiotelemetry to follow 15 female Graptemys geographica (common map turtle) and each of ten male and female Trachemys scripta (red-eared slider) living in a man-made canal within a highly urbanized region of Indianapolis, IN, USA. During the active season (between May and September) of 2002, we located 33 of the 35 individuals a total of 934 times and determined the total range of activity, mean movement, and daily movement for each individuals. We also analyzed turtle locations relative to the upland habitat types (commercial, residential, river, road, woodlot, and open) surrounding the canal and determined that the turtles spent a disproportionate amount of time in woodland and commercial habitats and avoided the road-associated portions of the canal. We also located 21 of the turtles during hibernation (February 2003), and determined that an even greater proportion of individuals hibernated in woodland-bordered portions of the canal. Our results clearly indicate that turtle habitat selection is influenced by human activities; sound conservation and management of turtle populations in urban habitats will require the incorporation of spatial ecology and habitat use data

    Defining the content and delivery of an intervention to Change AdhereNce to treatment in BonchiEctasis (CAN-BE): a qualitative approach incorporating the Theoretical Domains Framework, behavioural change techniques and stakeholder expert panels

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    BACKGROUND: Low patient adherence to treatment is associated with poorer health outcomes in bronchiectasis. We sought to use the Theoretical Domains Framework (TDF) (a framework derived from 33 psychological theories) and behavioural change techniques (BCTs) to define the content of an intervention to change patients' adherence in bronchiectasis (Stage 1 and 2) and stakeholder expert panels to define its delivery (Stage 3). METHODS: We conducted semi-structured interviews with patients with bronchiectasis about barriers and motivators to adherence to treatment and focus groups or interviews with bronchiectasis healthcare professionals (HCPs) about their ability to change patients' adherence to treatment. We coded these data to the 12 domain TDF to identify relevant domains for patients and HCPs (Stage 1). Three researchers independently mapped relevant domains for patients and HCPs to a list of 35 BCTs to identify two lists (patient and HCP) of potential BCTs for inclusion (Stage 2). We presented these lists to three expert panels (two with patients and one with HCPs/academics from across the UK). We asked panels who the intervention should target, who should deliver it, at what intensity, in what format and setting, and using which outcome measures (Stage 3). RESULTS: Eight TDF domains were perceived to influence patients' and HCPs' behaviours: Knowledge, Skills, Beliefs about capability, Beliefs about consequences, Motivation, Social influences, Behavioural regulation and Nature of behaviours (Stage 1). Twelve BCTs common to patients and HCPs were included in the intervention: Monitoring, Self-monitoring, Feedback, Action planning, Problem solving, Persuasive communication, Goal/target specified:behaviour/outcome, Information regarding behaviour/outcome, Role play, Social support and Cognitive restructuring (Stage 2). Participants thought that an individualised combination of these BCTs should be delivered to all patients, by a member of staff, over several one-to-one and/or group visits in secondary care. Efficacy should be measured using pulmonary exacerbations, hospital admissions and quality of life (Stage 3). CONCLUSIONS: Twelve BCTs form the intervention content. An individualised selection from these 12 BCTs will be delivered to all patients over several face-to-face visits in secondary care. Future research should focus on developing physical materials to aid delivery of the intervention prior to feasibility and pilot testing. If effective, this intervention may improve adherence and health outcomes for those with bronchiectasis in the future
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