Characterizing the Load Environment of Ferry Landings for Washington State Ferries and the Alaska Marine Highway System

INE/AUTC 13.0

Characterizing the berthing load environment of the Seattle ferry teminal, Bremerton slip

Thesis (M.S.) University of Alaska Fairbanks, 2012This manuscript characterizes and presents design recommendations for berthing demands on ferry landing structures. There is a lack of research focused on the berthing load demand imparted by ferry class vessels, therefore the load criteria used for design is often based on a number of assumptions. This study involved a one-year field study of the structural load environment of wingwalls at the Bremerton Slip of the Seattle Ferry Terminal, located in Elliott Bay adjacent to Seattle, Washington. Measurements of marine fender displacement, vessel approach distance with respect to time, and. pile strain were used to determine berthing demands. Berthing event parameters were characterized using the Python programming language, compiled, and analyzed statistically. Probability theory was used to provide design value recommendations for berthing energy, force, approach velocity, berthing factor, and berthing coefficient. This study presents a number of engineering design aids intended to quantify the berthing load environment of wingwalls in the Washington State Ferry System

HST Observations of Heavy Elements in Metal-Poor Galactic Halo Stars

We present new abundance determinations of neutron-capture elements Ge, Zr, Os, Ir, and Pt in a sample of 11 metal-poor (-3.1 <= [Fe/H] <= -1.6) Galactic halo giant stars, based on Hubble Space Telescope UV and Keck I optical high-resolution spectroscopy. The stellar sample is dominated by r-process-rich stars such as the well-studied CS 22892-052 and bd+173248, but also includes the r-process-poor, bright giant HD 122563. Our results demonstrate that abundances of the 3rd r-process peak elements Os, Ir and Pt in these metal-poor halo stars are very well-correlated among themselves, and with the abundances of the canonical r-process element Eu (determined in other studies), thus arguing for a common origin or site for r-process nucleosynthesis of heavier (Z>56) elements. However, the large (and correlated) scatters of [Eu,Os,Ir,Pt/Fe] suggests that the heaviest neutron-capture r-process elements are not formed in all supernovae. In contrast, the Ge abundances of all program stars track their Fe abundances, very well. An explosive process on iron-peak nuclei (e.g., the alpha-rich freeze-out in supernovae), rather than neutron capture, appears to have been the dominant synthesis mechanism for this element at low metallicities -- Ge abundances seem completely uncorrelated with Eu.Comment: 35 pages, 5 tables, 7 figures; To appear in the Astrophysical Journa

High-Content, High-Throughput Analysis of Cell Cycle Perturbations Induced by the HSP90 Inhibitor XL888

BACKGROUND: Many proteins that are dysregulated or mutated in cancer cells rely on the molecular chaperone HSP90 for their proper folding and activity, which has led to considerable interest in HSP90 as a cancer drug target. The diverse array of HSP90 client proteins encompasses oncogenic drivers, cell cycle components, and a variety of regulatory factors, so inhibition of HSP90 perturbs multiple cellular processes, including mitogenic signaling and cell cycle control. Although many reports have investigated HSP90 inhibition in the context of the cell cycle, no large-scale studies have examined potential correlations between cell genotype and the cell cycle phenotypes of HSP90 inhibition. METHODOLOGY/PRINCIPAL FINDINGS: To address this question, we developed a novel high-content, high-throughput cell cycle assay and profiled the effects of two distinct small molecule HSP90 inhibitors (XL888 and 17-AAG [17-allylamino-17-demethoxygeldanamycin]) in a large, genetically diverse panel of cancer cell lines. The cell cycle phenotypes of both inhibitors were strikingly similar and fell into three classes: accumulation in M-phase, G2-phase, or G1-phase. Accumulation in M-phase was the most prominent phenotype and notably, was also correlated with TP53 mutant status. We additionally observed unexpected complexity in the response of the cell cycle-associated client PLK1 to HSP90 inhibition, and we suggest that inhibitor-induced PLK1 depletion may contribute to the striking metaphase arrest phenotype seen in many of the M-arrested cell lines. CONCLUSIONS/SIGNIFICANCE: Our analysis of the cell cycle phenotypes induced by HSP90 inhibition in 25 cancer cell lines revealed that the phenotypic response was highly dependent on cellular genotype as well as on the concentration of HSP90 inhibitor and the time of treatment. M-phase arrest correlated with the presence of TP53 mutations, while G2 or G1 arrest was more commonly seen in cells bearing wt TP53. We draw upon previous literature to suggest an integrated model that accounts for these varying observations

Localization of type 1 diabetes susceptibility to the MHC class I genes HLA-B and HLA-A

The major histocompatibility complex (MHC) on chromosome 6 is associated with susceptibility to more common diseases than any other region of the human genome, including almost all disorders classified as autoimmune. In type 1 diabetes the major genetic susceptibility determinants have been mapped to the MHC class II genes HLA-DQB1 and HLA-DRB1 (refs 1-3), but these genes cannot completely explain the association between type 1 diabetes and the MHC region. Owing to the region's extreme gene density, the multiplicity of disease-associated alleles, strong associations between alleles, limited genotyping capability, and inadequate statistical approaches and sample sizes, which, and how many, loci within the MHC determine susceptibility remains unclear. Here, in several large type 1 diabetes data sets, we analyse a combined total of 1,729 polymorphisms, and apply statistical methods - recursive partitioning and regression - to pinpoint disease susceptibility to the MHC class I genes HLA-B and HLA-A (risk ratios >1.5; Pcombined = 2.01 × 10-19 and 2.35 × 10-13, respectively) in addition to the established associations of the MHC class II genes. Other loci with smaller and/or rarer effects might also be involved, but to find these, future searches must take into account both the HLA class II and class I genes and use even larger samples. Taken together with previous studies, we conclude that MHC-class-I-mediated events, principally involving HLA-B*39, contribute to the aetiology of type 1 diabetes. ©2007 Nature Publishing Group

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity.

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant

Pf7: an open dataset of Plasmodium falciparum genome variation in 20,000 worldwide samples

We describe the MalariaGEN Pf7 data resource, the seventh release of Plasmodium falciparum genome variation data from the MalariaGEN network.  It comprises over 20,000 samples from 82 partner studies in 33 countries, including several malaria endemic regions that were previously underrepresented.  For the first time we include dried blood spot samples that were sequenced after selective whole genome amplification, necessitating new methods to genotype copy number variations.  We identify a large number of newly emerging crt mutations in parts of Southeast Asia, and show examples of heterogeneities in patterns of drug resistance within Africa and within the Indian subcontinent.  We describe the profile of variations in the C-terminal of the csp gene and relate this to the sequence used in the RTS,S and R21 malaria vaccines.  Pf7 provides high-quality data on genotype calls for 6 million SNPs and short indels, analysis of large deletions that cause failure of rapid diagnostic tests, and systematic characterisation of six major drug resistance loci, all of which can be freely downloaded from the MalariaGEN website