1,285 research outputs found

    ā€œDouble Jeopardy for $1000 Alexā€ - What It Is and How to Apply It

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    PresentationProcess hazards analyses, such as Hazard and Operability studies (HAZOPs) and Layer of Protection Analyses (LOPAs), are structured, team-based exercises focused on hazard identification, risk assessment, and risk management. In order to manage the complexity associated with these analyses, recognized and generally accepted rules are imposed to manage and limit the review of hazard scenarios involving simultaneous failures. One of these rules has been dubbed ā€œdouble jeopardyā€. Based on the authors experience via direct observation and review of PHA documentation, PHA teams continue to struggle to understand double jeopardy and how to effectively address simultaneous failures when applying PHA methodologies, such as HAZOP and LOPA. In addition, more widely accepted emergence and use of enabling conditions and conditional modifiers when developing hazard scenarios has blurred the legacy definition of double jeopardy. In this paper, the authors provide an overview of double jeopardy along with specific PHA examples regarding credible as well as inappropriate applications of double jeopardy. They also present tools and recommendations to enhance PHA teamsā€™ performances regarding the application of double jeopardy. More specifically, they address issues regarding latent failures (revealed vs. unrevealed conditions), concurrent incidence of failures, and independence of initiating events. The target audience for this paper is anyone whose responsibilities include (1) leading within an organization that uses PHAs, (2) establishing PHA guidance documents, (3) applying PHA methodologies, and (4) reviewing PHA outputs and reports

    Als3 is a Candida albicans invasin that binds to cadherins and induces endocytosis by host cells.

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    Candida albicans is the most common cause of hematogenously disseminated and oropharyngeal candidiasis. Both of these diseases are characterized by fungal invasion of host cells. Previously, we have found that C. albicans hyphae invade endothelial cells and oral epithelial cells in vitro by inducing their own endocytosis. Therefore, we set out to identify the fungal surface protein and host cell receptors that mediate this process. We found that the C. albicans Als3 is required for the organism to be endocytosed by human umbilical vein endothelial cells and two different human oral epithelial lines. Affinity purification experiments with wild-type and an als3delta/als3delta mutant strain of C. albicans demonstrated that Als3 was required for C. albicans to bind to multiple host cell surface proteins, including N-cadherin on endothelial cells and E-cadherin on oral epithelial cells. Furthermore, latex beads coated with the recombinant N-terminal portion of Als3 were endocytosed by Chinese hamster ovary cells expressing human N-cadherin or E-cadherin, whereas control beads coated with bovine serum albumin were not. Molecular modeling of the interactions of the N-terminal region of Als3 with the ectodomains of N-cadherin and E-cadherin indicated that the binding parameters of Als3 to either cadherin are similar to those of cadherin-cadherin binding. Therefore, Als3 is a fungal invasin that mimics host cell cadherins and induces endocytosis by binding to N-cadherin on endothelial cells and E-cadherin on oral epithelial cells. These results uncover the first known fungal invasin and provide evidence that C. albicans Als3 is a molecular mimic of human cadherins

    Venous bullet embolism and subsequent endovascular retrieval ā€“ A case report and review of the literature

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    AbstractINTRODUCTIONVascular bullet embolism is a rare phenomenon with fewer than 200 cases reported in the literature.PRESENTATION OF CASEA 22 year-old male presented with a gunshot wound to the right lower quadrant. Imaging demonstrated a bullet lodged in his left lower quadrant. Upon operative exploration, a single hole was found in the right external iliac vein without injury into the left lower quadrant. The bullet was found to have migrated intravascularly from the right external to the left common iliac vein, and was subsequently removed endovascularly.DISCUSSIONBullet embolism occurs infrequently, with arterial more common than venous. Arterial embolization usually requires emergency operative intervention due to ischemia. While venous embolization is often asymptomatic, removal of the bullet is recommended to avoid delayed complications when possible.CONCLUSIONVenous bullet emboli should be removed endovascularly whenever technically possible

    Functional insights from the structure of the 30S ribosomal subunit and its interactions with antibiotics

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    The 30S ribosomal subunit has two primary functions in protein synthesis. It discriminates against aminoacyl transfer RNAs that do not match the codon of messenger RNA, thereby ensuring accuracy in translation of the genetic message in a process called decoding. Also, it works with the 50S subunit to move the tRNAs and associated mRNA by precisely one codon, in a process called translocation. Here we describe the functional implications of the high-resolution 30S crystal structure presented in the accompanying paper, and infer details of the interactions between the 30S subunit and its tRNA and mRNA ligands. We also describe the crystal structure of the 30S subunit complexed with the antibiotics paromomycin, streptomycin and spectinomycin, which interfere with decoding and translocation. This work reveals the structural basis for the action of these antibiotics, and leads to a model for the role of the universally conserved 16S RNA residues A1492 and A1493 in the decoding process

    Detection Of KOI-13.01 Using The Photometric Orbit

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    We use the KOI-13 transiting star-planet system as a test case for the recently developed BEER algorithm (Faigler & Mazeh 2011), aimed at identifying non-transiting low-mass companions by detecting the photometric variability induced by the companion along its orbit. Such photometric variability is generated by three mechanisms, including the beaming effect, tidal ellipsoidal distortion, and reflection/heating. We use data from three Kepler quarters, from the first year of the mission, while ignoring measurements within the transit and occultation, and show that the planet's ephemeris is clearly detected. We fit for the amplitude of each of the three effects and use the beaming effect amplitude to estimate the planet's minimum mass, which results in M_p sin i = 9.2 +/- 1.1 M_J (assuming the host star parameters derived by Szabo et al. 2011). Our results show that non-transiting star-planet systems similar to KOI-13.01 can be detected in Kepler data, including a measurement of the orbital ephemeris and the planet's minimum mass. Moreover, we derive a realistic estimate of the amplitudes uncertainties, and use it to show that data obtained during the entire lifetime of the Kepler mission, of 3.5 years, will allow detecting non-transiting close-in low-mass companions orbiting bright stars, down to the few Jupiter mass level. Data from the Kepler Extended Mission, if funded by NASA, will further improve the detection capabilities.Comment: Accepted to AJ on October 4, 2011. Kepler Q5 Long Cadence data will become publicly available on MAST by October 23. Comments welcome (V2: minor changes, to reflect proof corrections

    The Streets of Laredo

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    One of the best-known of the old cowboy folksongs has a Butler County connection. In his memoir of his days as an open-range cowboy throughout the 1870s, Frank Maynard, whose home was Towanda in the western edge of the Flint Hills, told how he came to write the lyrics to the song we know as ā€œThe Cowboyā€™s Lamentā€ or ā€œThe Streets of Laredo,ā€ which he set at the doorway of Tom Shermanā€™s barroom in Dodge City
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