New Haplotype and Genealogical Data Give Important Implications for the Origins and Prevalence of the American Founder Mutation of MSH2

Top Student Presentation, 2007 American Assoc. of Anthropological GeneticsHighest Honors, OSU College of Biological Sciences Research Colloquium2nd Place, 2007 Denman Research Forum- Health Professions- Laboratory / CellularLynch syndrome, which is also known as hereditary nonpolyposis colorectal cancer (HNPCC), is estimated to account for approximately half of all heritable colon cancers and perhaps upward of 3% of all colon cancers in the western world. This amounts to approximately 4500 cases a year in the US alone. Lynch syndrome arises as a result of mutations in genes of the mismatch repair pathway, conferring an autosomal dominant cancer predisposition with an ~80% lifetime risk of HNPCC-associated cancers. Four mismatch repair (MMR) genes, MLH1, MSH2, PMS2 and MSH6, are typically implicated in the transmission of Lynch syndrome. Large scale germline deletions within the mismatch repair gene MSH2 account for a significant proportion of all deleterious mutations in this gene, and are associated with the onset of HNPCC. A recently characterized deletion of exons 1 through 6 of MSH2 has been associated with a founder event within the United States which genealogical studies have previously dated to 1727. The sequencing of the breakpoints completed the characterization of the “American Founder Mutation” (AFM) and allowed for the separation of this deletion from that of other similar, but distinct, deletions via long-range PCR and sequencing. Here, we report the development of a robust multiplex PCR which has assisted in the detection of 24 new families who carry the AFM and the subsequent characterization of 20 patient haplotypes which flank the deletion. New genealogical data has identified a likely erroneous connection in the original pedigree analysis. As such, three further families have been linked to the original pedigree and we have now identified an alternative founding family dating to 1764, as well as five further “subfounder” groups, all of which date to the eighteenth century. The use of molecular data, combined with extensive pedigree analysis, provides independent measures of the origins of the AFM, with significant implications for the mutation’s modern prevalence in America, which has been estimated to be nearly 19,000 individuals. In this study, I have sought to gain further insight into the origin, occurrence, and spread of the AFM through improved genealogical and molecular genetic studies.A three-year embargo was granted for this item

APPLYING COMMERCIAL PROCEDURES AND TECHNOLOGY TO NAVY AUDIT READINESS

The Department of the Navy (DON) does not have sufficient record keeping, processes, or controls in place for the management of physical assets, and this has a negative impact on our readiness. There are multiple technologies available, which have demonstrated inventory accuracy improvement. We address current practices, current regulations, and possible alternatives that could be implemented to improve compliance with applicable directives and inventory accuracy. We conduct a cost benefit analysis to determine which of these methods are feasible and provide recommendations on implementing the technologies.Lieutenant Commander, United States NavyLieutenant Commander, United States NavyApproved for public release. Distribution is unlimited

Deep Ocean Vehicle (DOV) Scientific Payload

This report aims to provide technical insight into the Deep Ocean Vehicle project performed by the Barrel Eye Explorers. The project was a part of the 2021-2022 Interdisciplinary Senior Project class at California Polytechnic State University, San Luis Obispo. The team consisted of Nikki Arm, Mason Gariepy, Brianna Roberts, and Kyle Walsh who were engineering students in the Mechanical, Materials, General, and Industrial engineering departments, respectively. This project was sponsored by Dr. Crow White and overseen by Karla Carichner

Online supplement for: Changes in otoacoustic emissions during selective auditory and visual attention

This is an online supplement for the article, Changes in otoacoustic emissions during selective auditory and visual attention, published in The Journal of the Acoustical Society of America.PACS (Physics & Astronomy Classification Scheme) numbers associated with this article supplement: 43.64.Jb, 43.64.Kc, 43.64.Bt, 43.64.Nf, 43.66.LjPsycholog

Deep Ocean Vehicle (DOV) Scientific Payload

This report aims to provide technical insight into the Deep Ocean Vehicle project performed by the Barrel Eye Explorers. The project was a part of the 2021-2022 Interdisciplinary Senior Project class at California Polytechnic State University, San Luis Obispo. The team consisted of Nikki Arm, Mason Gariepy, Brianna Roberts, and Kyle Walsh who were engineering students in the Mechanical, Materials, General, and Industrial engineering departments, respectively. This project was sponsored by Dr. Crow White and overseen by Karla Carichner

VALIDATION OF A PORTABLE FORCE PLATE TO ASSESSING JUMPING AND LANDING PERFORMANCE

Jumping and landing tasks are commonly used! to examine various parameters regarding performance (Arampatziz et al. 2001) and injury (Hewitt et al. 2005). Traditionally jumping tasks have been used to measure a variety of neuromuscular factors regarding performance. Landings have been studied extensively with r~$pect to factors related to injury. It is commonly accepted that the standard force platform is the most commonly used and considered the 'gold standard' for measuring ground reaction force during jumping and landing tasks. One potential aspect which limits the use of a force platform is that they are typically mounted to the ground to prevent any unrelated vibrations from affecting the force measurement. The portability of these devices is difficult and measurements are normally restricted to a laboratory setting. Another possible factor that could affect the data collected by a portable force plate is the difference in surface height between the ground and the force plate. Therefore, the dimensions of a portable force platform should be large enough to accommodate the given maneuver without changes in performance. Therefore, the purpose of this study was to validate the force measurements of a new portable force platform during two jumping/landing tasks by comparing the measurements to a traditional laboratory mounted force platform. A secondary purpose was to establish the reliability of the portable force platform. If the validity and reliability of the portable force platform are confirmed, this will provide a device that can assess a variety of measurements in field (non laboratory) situations. We hypothesize that the force and temporal measurements between the two instruments would not be different

Compact and Lightweight Sabatier Reactor for Carbon Dioxide Reduction

The utilization of CO2 to produce life support consumables, such as O2 and H2O, via the Sabatier reaction is an important aspect of NASA s cabin Atmosphere Revitalization System and In-Situ Resource Utilization architectures for both low-earth orbit and long-term manned space missions. In the current International Space Station (ISS) and other low orbit missions, metabolically-generated CO2 is removed from the cabin air and vented into space, resulting in a net loss of O2. This requires a continuous resupply of O2 via water electrolysis, and thus highlights the need for large water storage capacity. For long-duration space missions, the amount of life support consumables is limited and resupply options are practically nonexistent, thus atmosphere resource management and recycle becomes crucial to significantly reduce necessary O2 and H2O storage. Additionally, the potential use of the Martian CO2-rich atmosphere and Lunar regolith to generate life support consumables and propellant fuels is of interest to NASA. Precision Combustion, Inc. (PCI) has developed a compact, lightweight Microlith(Registered TradeMark)-based Sabatier (CO2 methanation) reactor which demonstrates the capability of achieving high CO2 conversion and near 100% CH4 selectivity at space velocities of 30,000-60,000 hr-1. The combination of the Microlith(Registered TradeMark) substrates and durable, novel catalyst coating permitted efficient Sabatier reactor operation that favors high reactant conversion, high selectivity, and long-term durability. This paper presents the reactor development and performance results at various operating conditions. Additionally, results from 100-hr durability tests and mechanical vibration tests are discussed

Clonal and microclonal mutational heterogeneity in high hyperdiploid acute lymphoblastic leukemia.

High hyperdiploidy (HD), the most common cytogenetic subtype of B-cell acute lymphoblastic leukemia (B-ALL), is largely curable but significant treatment-related morbidity warrants investigating the biology and identifying novel drug targets. Targeted deep-sequencing of 538 cancer-relevant genes was performed in 57 HD-ALL patients lacking overt KRAS and NRAS hotspot mutations and lacking common B-ALL deletions to enrich for discovery of novel driver genes. One-third of patients harbored damaging mutations in epigenetic regulatory genes, including the putative novel driver DOT1L (n=4). Receptor tyrosine kinase (RTK)/Ras/MAPK signaling pathway mutations were found in two-thirds of patients, including novel mutations in ROS1, which mediates phosphorylation of the PTPN11-encoded protein SHP2. Mutations in FLT3 significantly co-occurred with DOT1L (p=0.04), suggesting functional cooperation in leukemogenesis. We detected an extraordinary level of tumor heterogeneity, with microclonal (mutant allele fraction <0.10) KRAS, NRAS, FLT3, and/or PTPN11 hotspot mutations evident in 31/57 (54.4%) patients. Multiple KRAS and NRAS codon 12 and 13 microclonal mutations significantly co-occurred within tumor samples (p=4.8x10-4), suggesting ongoing formation of and selection for Ras-activating mutations. Future work is required to investigate whether tumor microheterogeneity impacts clinical outcome and to elucidate the functional consequences of epigenetic dysregulation in HD-ALL, potentially leading to novel therapeutic approaches

CO2 Reduction Assembly Prototype Using Microlith-Based Sabatier Reactor for Ground Demonstration

The utilization of CO2 to produce life support consumables, such as O2 and H2O, via the Sabatier reaction is an important aspect of NASA's cabin Atmosphere Revitalization System (ARS) and In-Situ Resource Utilization (ISRU) architectures for both low-earth orbit and long-term manned space missions. Carbon dioxide can be reacted with H2, obtained from the electrolysis of water, via Sabatier reaction to produce methane and H2O. Methane can be stored and utilized as propellant while H2O can be either stored or electrolyzed to produce oxygen and regain the hydrogen atoms. Depending on the application, O2 can be used to replenish the atmosphere in human-crewed missions or as an oxidant for robotic and return missions. Precision Combustion, Inc. (PCI), with support from NASA, has previously developed an efficient and compact Sabatier reactor based on its Microlith catalytic technology and demonstrated the capability to achieve high CO2 conversion and CH4 selectivity (i.e., 90% of the thermodynamic equilibrium values) at high space velocities and low operating temperatures. This was made possible through the use of high-heat-transfer and high-surface-area Microlith catalytic substrates. Using this Sabatier reactor, PCI designed, developed, and demonstrated a stand-alone CO2 Reduction Assembly (CRA) test system for ground demonstration and performance validation. The Sabatier reactor was integrated with the necessary balance-of-plant components and controls system, allowing an automated, single "push-button" start-up and shutdown. Additionally, the versatility of the test system prototype was demonstrated by operating it under H2-rich (H2/CO2 of >4), stoichiometric (ratio of 4), and CO2-rich conditions (ratio of <4) without affecting its performance and meeting the equilibrium-predicted water recovery rates. In this paper, the development of the CRA test system for ground demonstration will be discussed. Additionally, the performance results from testing the system at various operating conditions and the results from durability testing will be presented