Design summary of the magnet support structures for the proton storage ring injection line upgrade

This report summarizes the technical engineering and design issues associated with the Proton Storage Ring (PSR) Injection Line upgrade of the Los Alamos Neutron Science Center (LANSCE). The main focus is on the engineering design calculations of several magnet support structures. The general procedure based upon a set number of design criteria is outlined, followed by a case-by-case summary of the engineering design analyses, reutilization or fabrication callouts and design safety factors

Neuroendocrine Responses to Cold Pressor Stimuli in Midshipmen Participating in the Naval Special Warfare Screener.

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The β-isoform of BCCIP promotes ADP release from the RAD51 presynaptic filament and enhances homologous DNA pairing

Homologous recombination (HR) is a template-driven repair pathway that mends DNA double-stranded breaks (DSBs), and thus helps to maintain genome stability. The RAD51 recombinase facilitates DNA joint formation during HR, but to accomplish this task, RAD51 must be loaded onto the single-stranded DNA. DSS1, a candidate gene for split hand/split foot syndrome, provides the ability to recognize RPA-coated ssDNA to the tumor suppressor BRCA2, which is complexed with RAD51. Together BRCA2-DSS1 displace RPA and load RAD51 onto the ssDNA. In addition, the BRCA2 interacting protein BCCIP normally colocalizes with chromatin bound BRCA2, and upon DSB induction, RAD51 colocalizes with BRCA2-BCCIP foci. Down-regulation of BCCIP reduces DSB repair and disrupts BRCA2 and RAD51 foci formation. While BCCIP is known to interact with BRCA2, the relationship between BCCIP and RAD51 is not known. In this study, we investigated the biochemical role of the β-isoform of BCCIP in relation to the RAD51 recombinase. We demonstrate that BCCIPβ binds DNA and physically and functionally interacts with RAD51 to stimulate its homologous DNA pairing activity. Notably, this stimulatory effect is not the result of RAD51 nucleoprotein filament stabilization; rather, we demonstrate that BCCIPβ induces a conformational change within the RAD51 filament that promotes release of ADP to help maintain an active presynaptic filament. Our findings reveal a functional role for BCCIPβ as a RAD51 accessory factor in HR

RICE Limits on the Diffuse Ultra-High Energy Neutrino Flux

We present new limits on ultra-high energy neutrino fluxes above 100 PeV based on data collected by the Radio Ice Cherenkov Experiment (RICE) at the South Pole from 1999-2005. We discuss estimation of backgrounds, calibration and data analysis algorithms (both on-line and off-line), procedures used for the dedicated neutrino search, and refinements in our Monte Carlo (MC) simulation, including recent in situ measurements of the complex ice dielectric constant. An enlarged data set and a more detailed study of hadronic showers results in a sensitivity improvement of more than one order of magnitude compared to our previously published results. Examination of the full RICE data set yields zero acceptable neutrino candidates, resulting in 95% confidence-level model dependent limits on the flux (E_\nu)^2(d\phi/dE_\nu)<10^{-6} GeV/(cm^2s~sr}) in the energy range 10^{17}< E_\nu< 10^{20} eV. The new RICE results rule out the most intense flux model projections at 95% confidence level.Comment: Submitted to Astropart. Phy

Analytic philosophy for biomedical research: the imperative of applying yesterday's timeless messages to today's impasses

The mantra that "the best way to predict the future is to invent it" (attributed to the computer scientist Alan Kay) exemplifies some of the expectations from the technical and innovative sides of biomedical research at present. However, for technical advancements to make real impacts both on patient health and genuine scientific understanding, quite a number of lingering challenges facing the entire spectrum from protein biology all the way to randomized controlled trials should start to be overcome. The proposal in this chapter is that philosophy is essential in this process. By reviewing select examples from the history of science and philosophy, disciplines which were indistinguishable until the mid-nineteenth century, I argue that progress toward the many impasses in biomedicine can be achieved by emphasizing theoretical work (in the true sense of the word 'theory') as a vital foundation for experimental biology. Furthermore, a philosophical biology program that could provide a framework for theoretical investigations is outlined

Immune-mediated mechanisms influencing the efficacy of anticancer therapies

Conventional anticancer therapies, such as chemotherapy, radiotherapy, and targeted therapy, are designed to kill cancer cells. However, the efficacy of anticancer therapies is not only determined by their direct effects on cancer cells but also by off-target effects within the host immune system. Cytotoxic treatment regimens elicit several changes in immune-related parameters including the composition, phenotype, and function of immune cells. Here we discuss the impact of innate and adaptive immune cells on the success of anticancer therapy. In this context we examine the opportunities to exploit host immune responses to boost tumor clearing, and highlight the challenges facing the treatment of advanced metastatic disease