Alien Registration- Gormley, Joseph (Portland, Cumberland County)

https://digitalmaine.com/alien_docs/24236/thumbnail.jp

Doctor of Philosophy

dissertationWhen a patient is presented with locally advanced prostate cancer, it is possible to provide treatment with curative intent. However, once the disease has formed distant metastases, the chances of survival drops precipitously. For this reason, proper management of the disease while it remains localized is of critical importance. Treating these malignant cells with cytotoxic agents is effective at cell killing; however, the nonspecific toxicity profiles of these drugs often limit their use until the disease has progressed and symptom palliation is required. Incorporation of these drugs in nanocarriers such as polymers help target them to tumors with a degree of specificity, though major vascular barriers limit their effective delivery. In this dissertation, it is shown that plasmonic photothermal therapy (PPTT) can be used to help overcome some of these barriers and improve delivery to prostate tumors. First, the concept of using PPTT to improve the delivery of macromolecules to solid tumors was validated. This was done by measuring the tumor uptake of albumin. Next, the concept of targeting gold nanorods (GNRs) directly to the tumor's vasculature to better modulate vascular response to heating was tested. Surface conjugation of cyclic RGD (Arg-Gly-Asp) to GNRs improved their binding and uptake to endothelial cells in vitro, but not in vivo. Nontargeted GNRs and PPTT were then utilized to guide the location of polymer therapeutic delivery to prostate tumors. #-(2-hydroxypropyl)methacrylamide (HPMA) copolymers, which were designed to be targeted to cells previously exposed to heat shock, were used in this study. Treatment of tumors with PPTT facilitated a burst accumulation of the copolymers over 4 hours, and heat shock targeting to cells allowed them to be retained for an extended period of time. Finally, the tumor localization of the HPMA copolymers following PPTT was evaluated by magnetic resonance imaging (MRI). These results show that PPTT may be a useful tool to enhance delivery of polymeric drug carriers to locally advanced prostate tumors

First Year GPA and Academic Service Use Among College Students With and Without ADHD

ADHD is a chronic neurodevelopmental disorder characterized by significant impairments in attention and behavioral inhibition typically resulting in academic difficulties that persist into college (Weyandt & DuPaul, 2013). Although most colleges offer support services, students often do not utilize the services they are entitled to or have available to them (Chew et al., 2009). The current study is the first to examine differences in GPA using a rigorously defined, multi-site sample. Second, the current study seeks to identify the predictors of academic performance specifically among college students with ADHD. Third, this study provides data regarding how often students with ADHD utilize academic support services. Finally, the current study investigates the academic outcomes of service use among students with and without ADHD during their first year at a four-year college. Results demonstrated significantly lower GPAs among a rigorously defined, multi-site sample of first year college students with ADHD relative to students without ADHD. Second, this study indicated that traditional predictors of college success may be less meaningful for students with ADHD. Third, ADHD combined with other disorders, but not ADHD alone, predicted higher rates of service use relative to students without ADHD. Finally, the present results suggest that typically available academic services are not independently related to GPA among first-year college students with or without ADHD

Automated Image Analysis of Offshore Infrastructure Marine Biofouling

Supplementary Materials: The following are available online at www.mdpi.com/2077-1312/6/1/2/s1 Acknowledgments: This project was funded by the Natural Environmental Research Council (NERC) project No.: NE/N019865/1. The authors would like to thank Melanie Netherway and Don Orr, from our project partner (company requested to remain anonymous) for the provision of survey footage and for supporting the project. In addition, many thanks to Oscar Beijbom, University California Berkley for providing guidance and support to the project. Additional thanks to Calum Reay, Bibby Offshore; George Gair, Subsea 7; and Alan Buchan, Wood Group Kenny for help with footage collection and for allowing us to host workshops with them and their teams, their feedback and insights were very much appreciated.Peer reviewedPublisher PD

Antigen stimulation of peripheral blood mononuclear cells from Mycobacterium bovis infected cattle yields evidence for a novel gene expression program

<p>Abstract</p> <p>Background</p> <p>Bovine tuberculosis (BTB) caused by <it>Mycobacterium bovis </it>continues to cause substantial losses to global agriculture and has significant repercussions for human health. The advent of high throughput genomics has facilitated large scale gene expression analyses that present a novel opportunity for revealing the molecular mechanisms underlying mycobacterial infection. Using this approach, we have previously shown that innate immune genes in peripheral blood mononuclear cells (PBMC) from BTB-infected animals are repressed <it>in vivo </it>in the absence of exogenous antigen stimulation. In the present study, we hypothesized that the PBMC from BTB-infected cattle would display a distinct gene expression program resulting from exposure to <it>M. bovis</it>. A functional genomics approach was used to examine the immune response of BTB-infected (<it>n </it>= 6) and healthy control (<it>n </it>= 6) cattle to stimulation with bovine tuberculin (purified protein derivative – PPD-b) <it>in vitro</it>. PBMC were harvested before, and at 3 h and 12 h post <it>in vitro </it>stimulation with bovine tuberculin. Gene expression changes were catalogued within each group using a reference hybridization design and a targeted immunospecific cDNA microarray platform (BOTL-5) with 4,800 spot features representing 1,391 genes.</p> <p>Results</p> <p>250 gene spot features were significantly differentially expressed in BTB-infected animals at 3 h post-stimulation contrasting with only 88 gene spot features in the non-infected control animals (<it>P </it>≤ 0.05). At 12 h post-stimulation, 56 and 80 gene spot features were differentially expressed in both groups respectively. The results provided evidence of a proinflammatory gene expression profile in PBMC from BTB-infected animals in response to antigen stimulation. Furthermore, a common panel of eighteen genes, including transcription factors were significantly expressed in opposite directions in both groups. Real-time quantitative reverse transcription PCR (qRT-PCR) demonstrated that many innate immune genes, including components of the TLR pathway and cytokines were differentially expressed in BTB-infected (<it>n </it>= 8) versus control animals (<it>n </it>= 8) after stimulation with bovine tuberculin.</p> <p>Conclusion</p> <p>The PBMC from BTB-infected animals exhibit different transcriptional profiles compared with PBMC from healthy control animals in response to <it>M. bovis </it>antigen stimulation, providing evidence of a novel gene expression program due to <it>M. bovis </it>exposure.</p

Innate gene repression associated with Mycobacterium bovis infection in cattle: toward a gene signature of disease

<p>Abstract</p> <p>Background</p> <p>Bovine tuberculosis is an enduring disease of cattle that has significant repercussions for human health. The advent of high-throughput functional genomics technologies has facilitated large-scale analyses of the immune response to this disease that may ultimately lead to novel diagnostics and therapeutic targets. Analysis of mRNA abundance in peripheral blood mononuclear cells (PBMC) from six <it>Mycobacterium bovis </it>infected cattle and six non-infected controls was performed. A targeted immunospecific bovine cDNA microarray with duplicated spot features representing 1,391 genes was used to test the hypothesis that a distinct gene expression profile may exist in <it>M. bovis </it>infected animals <it>in vivo</it>.</p> <p>Results</p> <p>In total, 378 gene features were differentially expressed at the <it>P </it>≤ 0.05 level in bovine tuberculosis (BTB)-infected and control animals, of which 244 were expressed at lower levels (65%) in the infected group. Lower relative expression of key innate immune genes, including the Toll-like receptor 2 (<it>TLR2</it>) and <it>TLR4 </it>genes, lack of differential expression of indicator adaptive immune gene transcripts (<it>IFNG, IL2, IL4</it>), and lower <it>BOLA </it>major histocompatibility complex – class I (<it>BOLA</it>) and class II (<it>BOLA-DRA</it>) gene expression was consistent with innate immune gene repression in the BTB-infected animals. Supervised hierarchical cluster analysis and class prediction validation identified a panel of 15 genes predictive of disease status and selected gene transcripts were validated (<it>n </it>= 8 per group) by real time quantitative reverse transcription PCR.</p> <p>Conclusion</p> <p>These results suggest that large-scale expression profiling can identify gene signatures of disease in peripheral blood that can be used to classify animals on the basis of <it>in vivo </it>infection, in the absence of exogenous antigenic stimulation.</p

Seven Key Principles of Program and Project Success: A Best Practices Survey

The National Aeronautics and Space Administration (NASA) Organization Design Team (ODT), consisting of 20 seasoned program and project managers and systems engineers from a broad spectrum of the aerospace industry, academia, and government, was formed to support the Next Generation Launch Technology (NGLT) Program and the Constellation Systems Program. The purpose of the ODT was to investigate organizational factors that can lead to success or failure of complex government programs, and to identify tools and methods for the design, modeling, and analysis of new and more-efficient program and project organizations. The ODT conducted a series of workshops featuring invited lectures from seasoned program and project managers representing 25 significant technical programs spanning 50 years of experience. The result was the identification of seven key principles of program success that can be used to help design and operate future program organizations. This paper presents the success principles and examples of best practices that can significantly improve the design of program, project, and performing technical line organizations, the assessment of workforce needs and organization performance, and the execution of programs and projects

Pericyte Seeded Dual Peptide Scaffold with Improved Endothelialization for Vascular Graft Tissue Engineering

At times when rhinoceros are fiercely poached, when some rhinoceros species are closer than ever to extinction, and when the scientific community is in debate over the use of advanced cell technologies as a remaining resort it is time to simplify and improve existing assisted reproduction techniques to enhance breeding and genetic diversity in the living populations under our care. Semen cryopreservation has been performed in all captive rhinoceros species with limited degree of success. Here we tested three freezing extenders, containing different cryoprotectants and various freezing rates for the cryopreservation of rhinoceros sperm from 14 bulls. In experiment I, semen from 9 bulls was used to determine the most suitable diluent, cryoprotectant and freezing rate for the successful cryopreservation of rhinoceros sperm. In experiment II, semen from 5 bulls was used to assess whether the removal of seminal plasma could further improve post thaw sperm quality following cryopreservation with conditions identified in Experiment I. Semen was diluted with Berliner Cryomedia, ButoCrio® or INRA Freeze®, packaged in 0.5 mL straws and frozen 3, 4, and 5 cm over liquid nitrogen (LN) vapour or directly in a dryshipper. It was found that semen extended with ButoCrio® (containing glycerol and methylformamide) and frozen 3cm over LN vapour provided the best protection to rhinoceros spermatozoa during cryopreservation. When pooled over treatments, total and progressive post thaw motility was 75.3 ± 4.2% and 68.5 ± 5.7%, respectively marking a new benchmark for the cryopreservation of rhinoceros sperm. Post thaw total and progressive motility, viability and acrosome integrity of semen diluted in ButoCrio® was significantly higher than semen extended in Berliner Cryomedia or INRA Freeze®. The removal of seminal plasma did not improve post thaw sperm survival (p > 0.05). In conclusion, the cryosurvival of rhinoceros spermatozoa was significantly improved when using a mixture of glycerol and methylformamide in combination with a fast freezing rate at 3 cm. These results describe a new protocol for the improved cryosurvival of rhinoceros spermatozoa and will enable a more successful preservation of genetic diversity between males, especially in donors whose spermatozoa may already be compromised prior to or during collection. The successful reduction of glycerol concentration in favour of methylformamide as a cryoprotectant could be a novel suggestion for the improvement of cryopreservation techniques in other wildlife species

The endoscopic endonasal approach is not superior to the microscopic transcranial approach for anterior skull base meningiomas—a meta-analysis

Object In the past decade, the endonasal transsphenoidal approach (eTSA) has become an alternative to the microsurgical transcranial approach (mTCA) for tuberculum sellae meningiomas (TSMs) and olfactory groove meningiomas (OGMs). The aim of this meta-analysis was to evaluate which approach offered the best surgical outcomes. Methods: A systematic review of the literature from 2004 and meta-analysis were conducted in accordance with the PRISMA guidelines. Pooled incidence was calculated for gross total resection (GTR), visual improvement, cerebrospinal fluid (CSF) leak, intraoperative arterial injury, and mortality, comparing eTSA and mTCA, with p-interaction values. Results: Of 1684 studies, 64 case series were included in the meta-analysis. Using the fixed-effects model, the GTR rate was significantly higher among mTCA patients for OGM (eTSA: 70.9% vs. mTCA: 88.5%, p-interaction < 0.01), but not significantly higher for TSM (eTSA: 83.0% vs. mTCA: 85.8%, p-interaction = 0.34). Despite considerable heterogeneity, visual improvement was higher for eTSA than mTCA for TSM (p-interaction < 0.01), but not for OGM (p-interaction = 0.33). CSF leak was significantly higher among eTSA patients for both OGM (eTSA: 25.1% vs. mTCA: 10.5%, p-interaction < 0.01) and TSM (eTSA: 19.3%, vs. mTCA: 5.81%, p-interaction < 0.01). Intraoperative arterial injury was higher among eTSA (4.89%) than mTCA patients (1.86%) for TSM (p-interaction = 0.03), but not for OGM resection (p-interaction = 0.10). Mortality was not significantly different between eTSA and mTCA patients for both TSM (p-interaction = 0.14) and OGM resection (p-interaction = 0.88). Random-effect models yielded similar results. Conclusion: In this meta-analysis, eTSA was not shown to be superior to mTCA for resection of both OGMs and TSMs. Electronic supplementary material The online version of this article (10.1007/s00701-017-3390-y) contains supplementary material, which is available to authorized users

Macroeconomic Fluctuations, Inequality, and Human Development

This paper examines the two-way relationship between inequality and economic fluctuations, and the implications for human development. For years, the dominant paradigm in macroeconomics, which assumed that income distribution did not matter, at least for macroeconomic behavior, ignored inequality--both its role in causing crises and the effect of fluctuations in general, and crises in particular, on inequality. But the most recent financial crisis has shown the errors in this thinking, and these views are finally beginning to be questioned. Economists who had looked at the average equity of a homeowner--ignoring the distribution--felt comfortable that the economy could easily withstand a large fall in housing prices. When such a fall occurred, however, it had disastrous effects, because a large fraction of homeowners owed more on their homes than the value of the home, leading to waves of foreclosure and economic stress. Policy-makers and economists alike have begun to take note: inequality can contribute to volatility and the creation of crises, and volatility can contribute to inequality. Here, we explore the variety of channels through which inequality affects fluctuations and fluctuations affect inequality, and explore how some of the changes in our economy may have contributed to increased inequality and volatility both directly and indirectly. After describing the two-way relationship, the paper discusses hysteresis--the fact that the consequences of an economic downturn can be long-lived. Then, it examines how policy can either mitigate or exacerbate the inequality consequences of economic downturns, and shows how well-intentioned policies can sometimes be counterproductive. Finally, it links these issues to human development, especially in developing countries