4,403 research outputs found

    Prognostic Launch Vehicle Probability of Failure Assessment Methodology for Conceptual Systems Predicated on Human Causal Factors

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    Lessons learned from past failures of launch vehicle developments and operations were used to create a new method to predict the probability of failure of conceptual systems. Existing methods such as Probabilistic Risk Assessments and Human Risk Assessments were considered but found to be too cumbersome for this type of system-wide application for yet-to-be-flown vehicles. The basis for this methodology were historic databases of past failures, where it was determined that various faulty human-interactions were the predominant root causes of failure rather than deficient component reliabilities evaluated through statistical analysis. This methodology contains an expert scoring part which can be used in either a qualitative or a quantitative mode. The method produces two products: a numerical score of the probability of failure or guidance to program management on critical areas in need of increased focus to improve the probability of success. In order to evaluate the effectiveness of this new method, data from a concluded vehicle program (USAF's Titan IV with the Centaur G-Prime upper stage) was used as a test case. Although the theoretical vs. actual probability of failure was found to be in reasonable agreement (4.46% vs. 6.67% respectively) the underlying sub-root cause scoring had significant disparities attributable to significant organizational changes and acquisitions. Recommendations are made for future applications of this method to ongoing launch vehicle development programs

    Time-resolved velocity map imaging of methyl elimination from photoexcited anisole

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    To date, H-atom elimination from heteroaromatic molecules following UV excitation has been extensively studied, with the focus on key biological molecules such as chromophores of DNA bases and amino acids. Extending these studies to look at elimination of other non-hydride photoproducts is essential in creating a more complete picture of the photochemistry of these biomolecules in the gas-phase. To this effect, CH3 elimination in anisole has been studied using time resolved velocity map imaging (TR-VMI) for the first time, providing both time and energy information on the dynamics following photoexcitation at 200 nm. The extra dimension of energy afforded by these measurements has enabled us to address the role of πσ* states in the excited state dynamics of anisole as compared to the hydride counterpart (phenol), providing strong evidence to suggest that only CH3 fragments eliminated with high kinetic energy are due to direct dissociation involving a 1πσ* state. These measurements also suggest that indirect mechanisms such as statistical unimolecular decay could be contributing to the dynamics at much longer times

    Targeting colorectal cancer with anti-epidermal growth factor receptor antibodies: focus on panitumumab

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    The tumor biology targeted therapies have improved outcomes in colorectal cancer (CRC). The epidermal growth factor receptor (EGFR) inhibitors represent one of these successful strategies. EGFR is frequently overexpressed in CRCs and associated with a malignant phenotype. Two EGFR inhibitors have shown efficacy in metastatic CRC, cetuximab and panitumumab. Cetuximab is a human–mouse chimeric monoclonal antibody that binds to the extracellular domain of the EGF-receptor. Similarly, panitumumab is a fully humanized monoclonal IgG2 antibody, directed against EGFR. Being fully humanized, panitumumab does not contain mouse protein reducing the risk of hypersensitivity. In a pivotal clinical trial, panitumumab was well tolerated and effective, demonstrating an objective response rate of 10% vs best supportive care (ORR = 0%; P < 0.0001). Panitumumab was approved for the treatment of mCRC by the FDA in 2006. Studies combining panitumumab with cytotoxic chemotherapy and other targeted therapies have been completed while others are ongoing to further evaluate the clinical utility of this agent. Recently it has been demonstrated that mutations in KRAS predict the efficacy of panitumumab and cetuximab, limiting their use to CRC patients with wild-type KRAS, and moving the clinical field towards personalized cancer care

    Mapping Low-Density Intergalactic Gas: a Third Helium Lyman-alpha Forest

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    We present a new HST/STIS spectrum of the z=3.18 quasar PKS 1935-692 and summarize the spectral features shortwards of 304A in the rest frame likely to be caused by foreground HeII Lyman-alpha absorption. In accord with previous results on two other quasars at similar redshifts, we demonstrate a correlation with the HI Lyman-alpha forest absorption, and show that much of the helium absorption is caused by a comparable quantity of more diffuse gas with Omega~0.01, that is not detected in HI. The helium ionization zone around the quasar is detected as well as a void seen in both HI and HeII. The properties of the absorption are in broad agreement with those of the other quasars and with models of the protogalactic gas distribution and ionization at this redshift.Comment: 17 pages including 5 figures. As accepted for publication in The Astronomical Journal (minor revisions

    A Prognostic Launch Vehicle Probability of Failure Assessment Methodology for Conceptual Systems Predicated on Human Causal Factors

    Get PDF
    Lessons learned from past failures of launch vehicle developments and operations were used to create a new method to predict the probability of failure of conceptual systems. Existing methods such as Probabilistic Risk Assessments and Human Risk Assessments were considered but found to be too cumbersome for this type of system-wide application for yet-to-be-flown vehicles. The basis for this methodology were historic databases of past failures, where it was determined that various faulty human-interactions were the predominant root causes of failure rather than deficient component reliabilities evaluated through statistical analysis. This methodology contains an expert scoring part which can be used in either a qualitative or a quantitative mode. The method produces two products: a numerical score of the probability of failure and guidance to program management on critical areas in need of increased focus to improve the probability of success. In order to evaluate the effectiveness of this new method, data from a concluded vehicle program (USAF's Titan IV with the Centaur G-Prime upper stage) was used as a test case. The theoretical vs. actual probability of failure was found to be 4.46% vs. 6.67% respectively. Recommendations are made for future applications of this method to ongoing launch vehicle development programs

    Health Services Management Education On-Site At A Military Medical Center

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    A cooperative educational program with the U.S. military is described to illustrate a unique opportunity that confronted a graduate healthcare management program. The resulting degree program supported the military’s operational medical mission but also presented interesting and unexpected challenges resulting from the wars in Iraq and Afghanistan. Pressure to provide cost-effective services has been mounting for many years. Civilian and military cooperative ventures can be highly successful. The program addressed the need for enhanced managerial skills. Program content focused on traditional business and healthcare content with applications tailored to military settings. While instruction was provided primarily by civilian faculty, active duty military instructors were also incorporated into specific course content areas. Program pricing and marketing were critical to success. Technical course delivery issues raised additional challenges due to work obligations and deployments. Academic institutions need to assist military commands in achieving their training objectives and can benefit from the experience. The views expressed in this article are those of the authors and do not reflect the official policy or position of the Department of the Navy, Department of Defense, or the United States Government

    The anti-adhesive effect of curcumin on Candida albicans biofilms on denture materials

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    The use of natural compounds as an alternative source of antimicrobials has become a necessity given the growing concern over global antimicrobial resistance. Polyphenols, found in various edible plants, offers one potential solution to this. We aimed to investigate the possibility of using curcumin within the context of oral health as a way of inhibiting and preventing the harmful development of Candida albicans biofilms. We undertook a series of adsorption experiments with varying concentrations of curcumin, showing that 50 ug/ml could prevent adhesion. This effect could be further synergised by the curcumin pretreatment of yeast cells to obtain significantly greater inhibition (&gt;90, p&lt;0.001). Investigation of the biological impact of curcumin showed that it preferentially affected immature morphological forms (yeast and germlings), and actively promoted aggregation of the cells. Transcriptional analyses showed that key adhesins were down-regulated (ALS1 and ALS3), whereas aggregation related genes (ALS5 and AAF1) were up-regulated. Collectively, these data demonstrated that curcumin elicits anti-adhesive effects and that induces transcription of genes integrally involved in the processes related to biofilm formation. Curcumin and associated polyphenols therefore have the capacity to be developed for use in oral healthcare to augment existing preventative strategies for candidal biofilms on the denture surface

    Raman scattering mediated by neighboring molecules

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    Raman scattering is most commonly associated with a change in vibrational state within individual molecules, the corresponding frequency shift in the scattered light affording a key way of identifying material structures. In theories where both matter and light are treated quantum mechanically, the fundamental scattering process is represented as the concurrent annihilation of a photon from one radiation mode and creation of another in a different mode. Developing this quantum electrodynamical formulation, the focus of the present work is on the spectroscopic consequences of electrodynamic coupling between neighboring molecules or other kinds of optical center. To encompass these nanoscale interactions, through which the molecular states evolve under the dual influence of the input light and local fields, this work identifies and determines two major mechanisms for each of which different selection rules apply. The constituent optical centers are considered to be chemically different and held in a fixed orientation with respect to each other, either as two components of a larger molecule or a molecular assembly that can undergo free rotation in a fluid medium or as parts of a larger, solid material. The two centers are considered to be separated beyond wavefunction overlap but close enough together to fall within an optical near-field limit, which leads to high inverse power dependences on their local separation. In this investigation, individual centers undergo a Stokes transition, whilst each neighbor of a different species remains in its original electronic and vibrational state. Analogous principles are applicable for the anti-Stokes case. The analysis concludes by considering the experimental consequences of applying this spectroscopic interpretation to fluid media; explicitly, the selection rules and the impact of pressure on the radiant intensity of this process
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