Somatic mutations render human exome and pathogen DNA more similar

Immunotherapy has recently shown important clinical successes in a substantial number of oncology indications. Additionally, the tumor somatic mutation load has been shown to associate with response to these therapeutic agents, and specific mutational signatures are hypothesized to improve this association, including signatures related to pathogen insults. We sought to study in silico the validity of these observations and how they relate to each other. We first addressed whether somatic mutations typically involved in cancer may increase, in a statistically meaningful manner, the similarity between common pathogens and the human exome. Our study shows that common mutagenic processes increase, in the upper range of biologically plausible frequencies, the similarity between cancer exomes and pathogen DNA at a scale of 12-16 nucleotide sequences and established that this increased similarity is due to the specific mutation distribution of the considered mutagenic processes. Next, we studied the impact of mutation rate and showed that increasing mutation rate generally results in an increased similarity between the cancer exome and pathogen DNA, at a scale of 4-5 amino acids. Finally, we investigated whether the considered mutational processes result in amino-acid changes with functional relevance that are more likely to be immunogenic. We showed that functional tolerance to mutagenic processes across species generally suggests more resilience to mutagenic processes that are due to exposure to elements of nature than to mutagenic processes that are due to exposure to cancer-causing artificial substances. These results support the idea that recognition of pathogen sequences as well as differential functional tolerance to mutagenic processes may play an important role in the immune recognition process involved in tumor infiltration by lymphocytes

The Sweet Efforts of Hershey\u27s Chocolate Corporation During WWII

Undergraduate Textual or Investigativ

An Assessment if Institutional Relationships at the Olympic Coast National Marine Sanctuary

Collaborative and coordinated management is necessary for successful ecosystem management, especially in marine ecosystems that cross jurisdictional lines. Agencies at the state and federal level recognize the need for effective institutional relationships. The Olympic Coast National Marine Sanctuary (OCNMS) identified collaborative and coordinated management as a priority in its 2011 Final Management Plan and Environmental Assessment. To reach its goal of achieving effective collaborative and coordinated management, OCNMS commissioned an external assessment of its institutional relationships. This assessment consisted of a literature review of standards for measuring collaboration in natural resource contexts, interviews with OCNMS staff and current key institutional partners, and a survey of individuals, organizations and tribes that work with OCNMS. The assessment determined that OCNMS has built a strong foundation for collaboration through two collaborative forums, projects and policies that address important issues for partners, and positive interactions between partners and OCNMS staff. Individuals feel they are working on issues important to their organizations and for the most part they value opportunities to share their priorities and learn about emerging issues, and they appreciate the efforts of OCNMS staff. Individuals in the network of relationships represent a wide range of institutions with different expectations for engagement and different criteria for what characterizes successful collaboration. OCNMS has complex and sometimes strained relationships with the four Coastal Treaty Tribes. OCNMS also faces challenges commonly found in other collaborative processes – constraints on individuals’ time, shortages of funding and staff support, communication challenges, and divergent goals among individuals. Still, the relationships have enabled notable accomplishments that include regulations to protect marine resources, joint projects related to research and education, and a ready network for communication and feedback.Master of ScienceNatural Resources and EnvironmentUniversity of Michiganhttp://deepblue.lib.umich.edu/bitstream/2027.42/90863/1/OCNMSAssessment_FINAL2012.pd

Detecting Long-Duration Narrow-Band Gravitational Wave Transients Associated with Soft Gamma Repeater Quasi-Periodic Oscillations

We have performed an in-depth concept study of a gravitational wave data analysis method which targets repeated long quasi-monochromatic transients (triggers) from cosmic sources. The algorithm concept can be applied to multi-trigger data sets in which the detector-source orientation and the statistical properties of the data stream change with time, and does not require the assumption that the data is Gaussian. Reconstructing or limiting the energetics of potential gravitational wave emissions associated with quasi-periodic oscillations (QPOs) observed in the X-ray lightcurve tails of soft gamma repeater flares might be an interesting endeavour of the future. Therefore we chose this in a simplified form to illustrate the flow, capabilities, and performance of the method. We investigate performance aspects of a multi-trigger based data analysis approach by using O(100 s) long stretches of mock data in coincidence with the times of observed QPOs, and by using the known sky location of the source. We analytically derive the PDF of the background distribution and compare to the results obtained by applying the concept to simulated Gaussian noise, as well as off-source playground data collected by the 4-km Hanford detector (H1) during LIGO's fifth science run (S5). We show that the transient glitch rejection and adaptive differential energy comparison methods we apply succeed in rejecting outliers in the S5 background data. Finally, we discuss how to extend the method to a network containing multiple detectors, and as an example, tune the method to maximize sensitivity to SGR 1806-20 flare times.Comment: 11 pages, 8 figure

SLIDES: Taking the Long View: Doing Something About Climate Change

Presenter: Maggie Fox, President, America Votes, Boulder, CO. Presenter: Susan Avery, Interim Provost and Executive Vice-Chancellor for Academic Affairs, University of Colorado. Presenter: Roger Pielke, Jr., Professor, Environmental Studies, Center for Science and Technology Policy Research, University of Colorado. 4 slides

Senior Recital: David W. Reece, Tenor; Maggie Mooha, Piano/Harpsichord; April 25, 1976

Centennial East Recital HallSunday AfternoonApril 25, 19762:00 p.m

Harnessing Technology Schools Survey 2009: data report – part 1, descriptive analysis

This document, the data report, is a reference document which presents the data in tabular form for anyone who wants to examine the findings of the Harnessing Technology Schools Survey (HTSS) in depth, for example in relation to specific areas of technology or policy, or by school sector. The findings for each question are also set out by school sector by primary, secondary and special school sub-samples

Estimation of Bounds on Potential Outcomes For Decision Making

Estimation of individual treatment effects is commonly used as the basis for contextual decision making in fields such as healthcare, education, and economics. However, it is often sufficient for the decision maker to have estimates of upper and lower bounds on the potential outcomes of decision alternatives to assess risks and benefits. We show that, in such cases, we can improve sample efficiency by estimating simple functions that bound these outcomes instead of estimating their conditional expectations, which may be complex and hard to estimate. Our analysis highlights a trade-off between the complexity of the learning task and the confidence with which the learned bounds hold. Guided by these findings, we develop an algorithm for learning upper and lower bounds on potential outcomes which optimize an objective function defined by the decision maker, subject to the probability that bounds are violated being small. Using a clinical dataset and a well-known causality benchmark, we demonstrate that our algorithm outperforms baselines, providing tighter, more reliable bounds

Using the theory of planned behaviour to explore the multicultural nursing workforces' behavioural intentions to comply with nursing policies and procedures in Prince Military Medical City (PSMMC) in Kingdom of Saudi Arabia

Background & aims: mBarrett's esophagus (BE) increases risk for esophageal adenocarcinoma (EAC). Increased risk for BE has been associated with single nucleotide polymorphisms (SNPs) on chromosome 6p21 (within the HLA region) and on 16q23, where the closest protein-coding gene is FOXF1. The Barrett's and Esophageal Adenocarcinoma Consortium (BEACON) identified risk loci for BE and esophageal adenocarcinoma in CRTC1 and BARX1, and within 100 kb FOXP1. We aimed to identify SNPs that increased risk for BE in a genome-wide association study (GWAS) and to validate previously reported associations.Methods: we performed a GWAS to identify variants associated with BE and further analyzed promising variants identified by the BEACON. We performed genotype analysis of 10,158 patients with BE and 21,062 controls.Results: we identified 2 SNPs not previously associated with BE: rs3072 (2p24.1; odds ratio [OR] = 1.14; 95% CI: 1.09–1.18; P = 1.8 × 10?11) and rs2701108 (12q24.21; OR = 0.90; 95% CI: 0.86–0.93; P = 7.5 × 10?9). The closest protein-coding genes were GDF7 (rs3072), which encodes a ligand in the bone morphogenetic protein pathway, and TBX5 (rs2701108), which encodes a transcription factor that regulates esophageal and cardiac development. We also identified 3 SNPS already identified by the BEACON (rs2687201, rs11789015, and rs10423674). Meta-analysis of all data identified another SNP associated with BE and esophageal adenocarcinoma: rs3784262, near ALDH1A2 (OR = 0.90; 95% CI: 0.87–0.93; P = 3.72 × 10?9).Conclusions: we identified 2 loci associated with risk for BE and provide data to support a locus previously associated with risk in the BEACON. The genes we found to be associated with risk for BE encode transcription factors involved in thoracic, diaphragmatic, and esophageal development or proteins involved in the inflammatory respons