Local Source Tsunami Inundation Modelling for Poverty Bay, Gisborne

After the Boxing Day 2004 Sumatran Tsunami, a review of tsunami hazard and risk for New Zealand identified Gisborne as the urban area with the greatest risk. Gisborne could experience gt;500 fatalities and extensive damage to infrastructure during a severe tsunami. The severity of a tsunami is likely to be low for distance sources given the effectiveness of the Pacific Tsunami Warning System. However, there is a substantial risk from local sources, as no local warning system of any kind exists. Prompt evacuation is probably the most cost-effective tsunami mitigation strategy available for New Zealand coastal locations, including Gisborne. This requires both knowledge of the extent of tsunami inundation, and sufficient warning of the tsunami arrival. Hence, there are two main objectives for this investigation: 1. Determine the likely extent of tsunami inundation for Gisborne City and surrounding populated coastal locations in Poverty Bay, using a combination of hydrodynamic tsunami modelling and GIS. The modelling will simulate historical events, particularly the largest historical tsunami, the May 1947 local tsunami. Modelling will consider potential events based on the Maximum Credible Earthquake for local sources associated with the Hikurangi Deformation Front. 2. Create inundation maps of Poverty Bay that can be used for future town planning and emergency plans

Effects of load and task duration on selected kinematic variables during a manual materials handling task on an inclined surface.

The purpose of this study was to examine the effects of bath load and task duration on stride length, stride period, velocity (calculated in m/s and statures/second), cadence, elbow angle, arm angle and hip angle of the human body during a manual materials handling task on an inclined surface. Eight male subjects (mean age 22.58 $\pm$ 2.42 years) were used as subjects in this study. Each subject was required to repeatedly ascend and descend a 7.47 m runway inclined to a 9.41\sp\circ slope, carrying a load on each ascent, for a period of fifteen minutes. Ascents began at thirty second intervals. The three load conditions used in this study were 6.25 kg, 11.25 kg and 18.25 kg. The subjects\u27 stride lengths and stride periods decreased significantly when ascending a 9.41\sp\circ inclined surface with the 18.25 kg load. The subjects\u27 cadence increased significantly when ascending the inclined surface with the 18.25 kg load. The elbow angles of the subjects significantly increased as they ascended the inclined surface with the 18.25 kg load. The elbow angles of the subjects were also significantly different when measured at 0, 50 and 100 percent of the subjects\u27 stride length. The arm angles of the subjects significantly decreased as they ascended the inclined surface with the 18.25 kg load. The arm angles of the subjects were also significantly different when measured at 0, 50 and 100 percent of the subjects\u27 stride length. The results of this study suggest that changes in stride length, stride period, cadence, elbow angle, arm angle and hip angle occurred when completing a manual materials handling task on a 9.41\sp\circ inclined surface. The results indicate that these changes are dependent on the mass of the load being handled. Based on the results of this study in the completions of the required task, which was 15 minutes in duration, time does not affect any of the reported gait characteristics or body positions.Dept. of Kinesiology. Paper copy at Leddy Library: Theses & Major Papers - Basement, West Bldg. / Call Number: Thesis1993 .H46. Source: Masters Abstracts International, Volume: 32-06, page: 1645. Adviser: G. W. Marino. Thesis (M.H.K.)--University of Windsor (Canada), 1993

Interplay between Single Resistance-Associated Mutations in the HIV-1 Protease and Viral Infectivity, Protease Activity, and Inhibitor Sensitivity

ABSTRACT Resistance-associated mutations in the HIV-1 protease modify viral fitness through changes in the catalytic activity and altered binding affinity for substrates and inhibitors. In this report, we examine the effects of 31 mutations at 26 amino acid positions in protease to determine their impact on infectivity and protease inhibitor sensitivity. We found that primary resistance mutations individually decrease fitness and generally increase sensitivity to protease inhibitors, indicating that reduced virion-associated protease activity reduces virion infectivity and the reduced level of per virion protease activity is then more easily titrated by a protease inhibitor. Conversely, mutations at more variable positions (compensatory mutations) confer low-level decreases in sensitivity to all protease inhibitors with little effect on infectivity. We found significant differences in the observed effect on infectivity with a pseudotype virus assay that requires the protease to cleave the cytoplasmic tail of the amphotropic murine leukemia virus (MuLV) Env protein. Additionally, we were able to mimic the fitness loss associated with resistance mutations by directly reducing the level of virion-associated protease activity. Virions containing 50% of a D25A mutant protease were 3- to 5-fold more sensitive to protease inhibitors. This level of reduction in protease activity also resulted in a 2-fold increase in sensitivity to nonnucleoside inhibitors of reverse transcriptase and a similar increase in sensitivity to zidovudine (AZT), indicating a pleiotropic effect associated with reduced protease activity. These results highlight the interplay between enzyme activity, viral fitness, and inhibitor mechanism and sensitivity in the closed system of the viral replication complex

Kidney single-cell atlas reveals myeloid heterogeneity in progression and regression of kidney disease

BACKGROUND: Little is known about the roles of myeloid cell subsets in kidney injury and in the limited ability of the organ to repair itself. Characterizing these cells based only on surface markers using flow cytometry might not provide a full phenotypic picture. Defining these cells at the single-cell, transcriptomic level could reveal myeloid heterogeneity in the progression and regression of kidney disease. METHODS: Integrated droplet– and plate-based single-cell RNA sequencing were used in the murine, reversible, unilateral ureteric obstruction model to dissect the transcriptomic landscape at the single-cell level during renal injury and the resolution of fibrosis. Paired blood exchange tracked the fate of monocytes recruited to the injured kidney. RESULTS: A single-cell atlas of the kidney generated using transcriptomics revealed marked changes in the proportion and gene expression of renal cell types during injury and repair. Conventional flow cytometry markers would not have identified the 12 myeloid cell subsets. Monocytes recruited to the kidney early after injury rapidly adopt a proinflammatory, profibrotic phenotype that expresses Arg1, before transitioning to become Ccr2(+) macrophages that accumulate in late injury. Conversely, a novel Mmp12(+) macrophage subset acts during repair. CONCLUSIONS: Complementary technologies identified novel myeloid subtypes, based on transcriptomics in single cells, that represent therapeutic targets to inhibit progression or promote regression of kidney disease

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Torture Approval in Comparative Perspective

Torture is (almost) universally condemned as barbaric and ineffective, yet it persists in the modern world. What factors influence levels of support for torture? Public opinion data from 31 countries in 2006 and 2008 (a total of 44 country-years) are used to test three hypotheses related to the acceptability of torture. The findings, first, show that outright majorities in 31 country-years reject the use of torture. Multiple regression results show that countries with high per capita income and low domestic repression are less likely to support torture. Constraints on the executive have no significant effect on public opinion on torture