DLC1 as a comparative epigenetic biomarker for radiotherapy of Non-Hodgkin's lymphoma

The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file.Vita.Includes bibliographical references."August 2007"Thesis (Ph. D.) University of Missouri-Columbia 2007.Dissertations, Academic -- University of Missouri--Columbia -- Veterinary pathobiology area program.The American Cancer Society estimates that 58,870 people were diagnosed with non-Hodgkin's lymphoma (NHL) in 2006, and 18,840 people died of the disease. Recent investigation of epigenetic gene regulation has identified the role of DNA methylation of cytosine followed by guanine in silencing gene expression. Such hypermethylated genes may serve as markers of disease, markers of prognostic groups, or targets for therapy. In this series of experiments, evidence of DNA hypermethylation was identified in the gene Deleted in Liver Cancer 1 (DLC1), a tumor suppressor gene, in canine NHL. The structure of the canine form of this gene was further characterized in silico and biologically, and the methylation patterns surrounding its promoter region were defined in 21 cases of naturally occurring NHL. Although the presence of hypermethylation did not result in silencing of the gene in the majority of the dogs, methylation patterns were statistically associated with NHL compared to normal lymphoid tissue. Further experiments discovered a significant synergistic interaction between external irradiation or ¹⁷⁷Lu-labeled 1,4,7,10-tetraazacyclododecane- N,N',N",N'"-tetraacetic acid (DOTA)-tyrosine³-octreotate (TATE) treatment and zebularine, a demethylating agent. Finally, ¹¹¹In-DOTA-TATE was used to successfully image somatostatin receptors of NHL lesions in three dogs with naturally occurring disease. The results of these studies will form the underpinnings of future canine clinical trials, modeling markers for diagnosis, prognosis, and therapy of NHL

Equivariant volumes of non-compact quotients and instanton counting

Motivated by Nekrasov's instanton counting, we discuss a method for calculating equivariant volumes of non-compact quotients in symplectic and hyper-K\"ahler geometry by means of the Jeffrey-Kirwan residue-formula of non-abelian localization. In order to overcome the non-compactness, we use varying symplectic cuts to reduce the problem to a compact setting, and study what happens in the limit that recovers the original problem. We implement this method for the ADHM construction of the moduli spaces of framed Yang-Mills instantons on $\R^{4}$ and rederive the formulas for the equivariant volumes obtained earlier by Nekrasov-Shadchin, expressing these volumes as iterated residues of a single rational function.Comment: 34 pages, 2 figures; minor typos corrected, to appear in Comm. Math. Phy

Centennial-to-millennial hydrologic trends and variability along the North Atlantic Coast, USA, during the Holocene

Author Posting. © American Geophysical Union, 2014. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geophysical Research Letters 41 (2014): 4300–4307, doi:10.1002/2014GL060183.Geophysical and sedimentary records from five lakes in Massachusetts reveal regionally coherent hydrologic variability during the Holocene. All of the lakes have risen since ~9.0 ka, but multicentury droughts after 5.6 ka repeatedly lowered their water levels. Quantified water level histories from the three best-studied lakes share >70% of their reconstructed variance. Four prominent low-water phases at 4.9–4.6, 4.2–3.9, 2.9–2.1, and 1.3–1.2 ka were synchronous across coastal lakes, even after accounting for age uncertainties. The droughts also affected sites up to ~200 km inland, but water level changes at 5.6–4.9 ka appear out of phase between inland and coastal lakes. During the enhanced multicentury variability after ~5.6 ka, droughts coincided with cooling in Greenland and may indicate circulation changes across the North Atlantic region. Overall, the records demonstrate that current water levels are exceptionally high and confirm the sensitivity of water resources in the northeast U.S. to climate change.The National Science Foundation (EAR-0602408, EAR- 1036191, and DEB-0816731 to Shuman; EAR-0602380 to Donnelly) and the Woods Hole Oceanographic Institution, Ocean and Climate Change Institute (Donnelly) funded this research.2014-12-2

Hormonal and Sex Impact on the Epidemiology of Canine Lymphoma

The Surveillance Epidemiology and End Results data demonstrate that the risk of non-Hodgkin lymphoma is lower for women, but that the incidence increases after fifty years of age, at which menopause is regularly reached, suggesting that female hormones may be protective for NHL. This study examines the influence of sex on lymphoma risk in a relevant large animal model. Records for dogs in the Veterinary Medical Database were analyzed from 1964 to 2002. Risk ratios were calculated to evaluate associations between sex, neutering status, and lymphoma occurrence. A total of 14,573 cases and 1,157,342 controls were identified. Intact females had a significantly lower risk of developing lymphoma, Odds Ratio 0.69 (0.63–0.74) with a P < .001. We conclude that there is a sex effect on NHL risk in dogs similar to humans. We hypothesize that the hormone levels of intact females lower the risk of NHL. The possibility of a protective role of endogenous estrogens in the etiology of NHL should be investigated

Pterodactyl: Trade Study for an Integrated Control System Design of a Mechanically Deployable Entry Vehicle

This paper presents the trade study method used to evaluate and downselect from a set of guidance and control (G&C) system designs for a mechanically Deployable Entry Vehicle (DEV). The Pterodactyl project was prompted by the challenge to develop an effective G&C system for a vehicle without a backshell, which is the case for DEVs. For the DEV, the project assumed a specific aeroshell geometry pertaining to an Adaptable, Deployable Entry and Placement Technology (ADEPT) vehicle, which was successfully developed by NASAs Space Technology Mission Directorate (STMD) prior to this study. The Pterodactyl project designed three different entry G&C systems for precision targeting. This paper details the Figures of Merit (FOMs) and metrics used during the course of the projects G&C system assessment. The relative importance of the FOMs was determined from the Analytic Hierarchy Process (AHP), which was used to develop weights that were combined with quantitative design metrics and engineering judgement to rank the G&C systems against one another. This systematic method takes into consideration the projects input while simultaneously reducing unintentional judgement bias and ultimately was used to select a single G&C design for the project to pursue in the next design phase

Astrometry and Photometry for ≈\approx1000 L, T, and Y Dwarfs from the UKIRT Hemisphere Survey

We present positions, proper motions, and near-infrared photometry for 966 known objects with spectral types later than M observed as part of the the UKIRT Hemisphere Survey (UHS). We augment the photometry and astrometry from UHS with information from Gaia DR3, Pan-STARRS DR2, and CatWISE 2020 to produce a database of homogeneous photometry and astrometry for this sample. The multi-epoch survey strategy of UHS allows us to determine proper motions for most sources, with a median proper motion uncertainty of $\sim$3.6 mas yr$^{-1}$. Our UHS proper motion measurements are generally in good agreement with those from Gaia DR3, Pan-STARRS, and CatWISE 2020, with UHS proper motions typically more precise than those from CatWISE 2020 and Pan-STARRS but not Gaia DR3. We critically analyze publicly available spectra for 406 members of this sample and provide updated near-infrared spectral types for $\sim$100 objects. We determine typical colors as a function of spectral type and provide absolute magnitude vs. spectral type relations for UHS $J$- and $K$-band photometry. Using newly determined proper motions, we highlight several objects of interest, such as objects with large tangential velocities, widely separated co-moving companions, and potential members of young nearby associations.Comment: Accepted to A

Metagenomic analysis of DNA viruses with targeted sequence capture of canine lobular orbital adenomas and normal conjunctiva

Our study aims are: (1) to evaluate phenotypically normal canine conjunctival and orbital tissue and tissue from canine lobular orbital adenomas (CLOAs) for the presence of viral genomic material and (2) phylogenetically classify detected DNA viruses to determine if a DNA virus is associated with CLOAs. A total of 31 formalin fixed paraffin embedded CLOA tissue samples, 4 papillomas or sarcoid, and 10 fresh clinically normal conjunctival tissues were included in this study. Genomic DNA was isolated from all samples and sequencing libraries were prepared. The libraries were molecularly indexed and pooled and viral DNA was enriched via targeted sequence capture utilizing ViroCap. The libraries were sequenced on the Illumina HiSeq platform and compared to known viral DNA reference genomes to identify viral DNA. Carnivore parvovirus was identified in 6.4% and 20% of CLOA tissue and normal conjunctival samples, respectively. This study showed that conjunctival tissue from healthy dogs and CLOAs uncommonly harbor DNA viruses, and no DNA virus was associated with these tumors. Further studies are needed to evaluate the etiologic cause of CLOAs

Spatial Transmission of 2009 Pandemic Influenza in the US

The 2009 H1N1 influenza pandemic provides a unique opportunity for detailed examination of the spatial dynamics of an emerging pathogen. In the US, the pandemic was characterized by substantial geographical heterogeneity: the 2009 spring wave was limited mainly to northeastern cities while the larger fall wave affected the whole country. Here we use finely resolved spatial and temporal influenza disease data based on electronic medical claims to explore the spread of the fall pandemic wave across 271 US cities and associated suburban areas. We document a clear spatial pattern in the timing of onset of the fall wave, starting in southeastern cities and spreading outwards over a period of three months. We use mechanistic models to tease apart the external factors associated with the timing of the fall wave arrival: differential seeding events linked to demographic factors, school opening dates, absolute humidity, prior immunity from the spring wave, spatial diffusion, and their interactions. Although the onset of the fall wave was correlated with school openings as previously reported, models including spatial spread alone resulted in better fit. The best model had a combination of the two. Absolute humidity or prior exposure during the spring wave did not improve the fit and population size only played a weak role. In conclusion, the protracted spread of pandemic influenza in fall 2009 in the US was dominated by short-distance spatial spread partially catalysed by school openings rather than long-distance transmission events. This is in contrast to the rapid hierarchical transmission patterns previously described for seasonal influenza. The findings underline the critical role that school-age children play in facilitating the geographic spread of pandemic influenza and highlight the need for further information on the movement and mixing patterns of this age group

Prototype Tool and Focus Group Evaluation for an Advanced Trajectory-Based Operations Concept

Trajectory-based operations (TBO) is a key concept in the Next Generation Air Transportation System transformation of the National Airspace System (NAS) that will increase the predictability and stability of traffic flows, support a common operational picture through the use of digital data sharing, facilitate more effective collaborative decision making between airspace users and air navigation service providers, and enable increased levels of integrated automation across the NAS. NASA has been developing trajectory-based systems to improve the efficiency of the NAS during specific phases of flight and is now also exploring Advanced 4-Dimensional Trajectory (4DT) operational concepts that will integrate these technologies and incorporate new technology where needed to create both automation and procedures to support gate-to-gate TBO. A TBO Prototype simulation toolkit has been developed that demonstrates initial functionality of an Advanced 4DT TBO concept. Pilot and controller subject matter experts (SMEs) were brought to the Air Traffic Operations Laboratory at NASA Langley Research Center for discussions on an Advanced 4DT operational concept and were provided an interactive demonstration of the TBO Prototype using four example scenarios. The SMEs provided feedback on potential operational, technological, and procedural opportunities and concerns. This paper describes an Advanced 4DT operational concept, the TBO Prototype, the demonstration scenarios and methods used, and the feedback obtained from the pilot and controller SMEs in this focus group activity