An Acoustic Charge Transport Imager for High Definition Television Applications: Low-Voltage SAW Amplifiers on Multilayer GaAs/ZnO Substrates

This thesis addresses the acoustoelectric issues concerning the amplification of surface acoustic waves (SAWs) and the reflection of SAWs from slanted reflector gratings on GaAs, with application to a novel acoustic charge transport (ACT) device architecture. First a simple model of the SAWAMP was developed, which was subsequently used to define the epitaxially grown material structure necessary to provide simultaneously high resistance and high electron mobility. In addition, a segmented SAWAMP structure was explored with line widths on the order of an acoustic wavelength. This resulted in the demonstration of SAWAMPS with an order of magnitude less voltage and power requirements than previously reported devices. A two-dimensional model was developed to explain the performance of devices with charge confinement layers less then 0.5 mm, which was experimentally verified. This model was extended to predict a greatly increased gain from the addition of a ZnO overlay. These overlays were experimentally attempted, but no working devices were reported due to process incompatibilities. In addition to the SAWAMP research, the reflection of SAWs from slanted gratings on GaAs was also studied and experimentally determined reflection coefficients for both 45 deg grooves and Al stripes on GaAs have been reported for the first time. The SAWAMp and reflector gratings were combined to investigate the integrated ring oscillator for application to the proposed ACT device and design parameters for this device have been provided

Loss of ATM/Chk2/p53 Pathway Components Accelerates Tumor Development and Contributes to Radiation Resistance in Gliomas

SummaryMaintenance of genomic integrity is essential for adult tissue homeostasis and defects in the DNA-damage response (DDR) machinery are linked to numerous pathologies including cancer. Here, we present evidence that the DDR exerts tumor suppressor activity in gliomas. We show that genes encoding components of the DDR pathway are frequently altered in human gliomas and that loss of elements of the ATM/Chk2/p53 cascade accelerates tumor formation in a glioma mouse model. We demonstrate that Chk2 is required for glioma response to ionizing radiation in vivo and is necessary for DNA-damage checkpoints in the neuronal stem cell compartment. Finally, we observed that the DDR is constitutively activated in a subset of human GBMs, and such activation correlates with regions of hypoxia

Longitudinal Impedance Measurement in Rhic.

The very clean Schottky spectra of gold beams in RHIC allow an accurate measurement of potential well distortion. By observing the variation in the small amplitude, incoherent synchrotron tune with intensity and bunch length, the intensity dependent longitudinal force can be measured. Dynamical effects associated with coherent motion are not important though some new dynamical effects appear. Measurements were carried out both at injection energy and store, which allowed the space charge and wall contributions to be individually determined

Perivascular Nitric Oxide Activates Notch Signaling and Promotes Stem-like Character in PDGF-Induced Glioma Cells

SummaryeNOS expression is elevated in human glioblastomas and correlated with increased tumor growth and aggressive character. We investigated the potential role of nitric oxide (NO) activity in the perivascular niche (PVN) using a genetic engineered mouse model of PDGF-induced gliomas. eNOS expression is highly elevated in tumor vascular endothelium adjacent to perivascular glioma cells expressing Nestin, Notch, and the NO receptor, sGC. In addition, the NO/cGMP/PKG pathway drives Notch signaling in PDGF-induced gliomas in vitro, and induces the side population phenotype in primary glioma cell cultures. NO also increases neurosphere forming capacity of PDGF-driven glioma primary cultures, and enhances their tumorigenic capacity in vivo. Loss of NO activity in these tumors suppresses Notch signaling in vivo and prolongs survival of mice. This mechanism is conserved in human PDGFR amplified gliomas. The NO/cGMP/PKG pathway's promotion of stem cell-like character in the tumor PVN may identify therapeutic targets for this subset of gliomas

assessment of pain-related fear in individuals with chronic painful conditions

Background: Heightened fear and anxiety related to pain may result in emotional and behavioral avoidance responses causing disability, distress, and depression. Fear and anxiety associated with pain can potentially change the course of the pain experience. It is plausible that fear and anxiety related to pain affect the duration and frequency of pain experienced by the patient. Aim: The study aimed to examine the applicability of the Fear of Pain Questionnaire-III (FPQ-III) in identifying who are likely to report longer duration and greater frequency of pain experience. Methods: To test this hypothesis, a cross-sectional study was conducted with 579 individuals from a community-based sample living with chronic pain. The factor structure and validity of FPQ-III in the community-based sample were also tested. Results: The findings suggest higher fear of severe pain but lower fear of medical pain, associ- ated with longer duration and more frequent pain experience. The analysis also confirmed the three-factor structure of FPQ-III, demonstrating good internal consistency for fear of severe pain (0.71) and fear of medical pain (0.73) and acceptable range for fear of minor pain (0.65). Conclusion: These findings suggest that the FPQ-III can be potentially applied to identify individuals at risk for prolonged continuous pain and as a screening tool to measure fear and anxiety related to pain

Influence of Fear of Pain and Coping Strategies on Health-Related Quality of Life and Patient-Anticipated Outcomes in Patients With Chronic Pain: Cross-Sectional Study Protocol

Background: Fear of pain and coping strategies are emotional-behavioral responses to pain and are known to play an important role in the development and maintenance of pain. It is highly likely that fear of pain and coping strategies influence each other, potentially affecting the course of chronic pain. To our knowledge, the relationship between pain, fear of pain and coping strategies, and how they influence patient-anticipated outcomes and health-related quality of life, have not been investigated. Objective: The aims of this study are to test (1) if both fear of pain and/or coping strategies are sufficient causes for maintaining pain; and (2) whether fear of pain influences coping strategies and pain intensity. The study will also examine the impact of fear of pain and coping strategies on health-related quality of life and patient-anticipated outcomes. Methods: The cross-sectional study will be conducted using an online survey. The Fear of Pain Questionnaire-III (FPQ-III), the Brief Coping Inventory (COPE), and EuroQoL-5d (EQ-5D) validated questionnaires will be used to collect data. Information pertaining to demographic factors, pain-related factors, and patient-anticipated outcomes will also be collected. The study has ethics approval from the Human Research Ethics Committee of the University of Adelaide. Study participants will be individuals aged 18 years and above who are experiencing chronic pain (ie, pain lasting more than 6 months). Effect measure modification technique (EMMM) will be used to examine if fear of pain acts as a moderator or mediator between coping strategies and pain. Simple and multinomial logistic regression analysis will be used to examine the effect of fear of pain and coping strategies on health-related quality of life and patient-anticipated outcomes. Results: Recruitment began July 2017 and it is anticipated that data collection will be completed by October 2017. Findings from this study will help to extend our understanding of fear of pain and coping strategies, their interaction, and their impact on health-related quality of life and patient-anticipated outcomes. Conclusions: Fear of pain and coping strategies have significant influence on the experience of chronic pain and its course. This study will help enhance our understanding of the relationship between fear of pain and coping strategies, which may help in developing patient-centered care practices

Transcriptional diversity of long-term glioblastoma survivors

BACKGROUND: Glioblastoma (GBM) is a highly aggressive type of glioma with poor prognosis. However, a small number of patients live much longer than the median survival. A better understanding of these long-term survivors (LTSs) may provide important insight into the biology of GBM. METHODS: We identified 7 patients with GBM, treated at Memorial Sloan-Kettering Cancer Center (MSKCC), with survival \u3e48 months. We characterized the transcriptome of each patient and determined rates of MGMT promoter methylation and IDH1 and IDH2 mutational status. We identified LTSs in 2 independent cohorts (The Cancer Genome Atlas [TCGA] and NCI Repository for Molecular Brain Neoplasia Data [REMBRANDT]) and analyzed the transcriptomal characteristics of these LTSs. RESULTS: The median overall survival of our cohort was 62.5 months. LTSs were distributed between the proneural (n = 2), neural (n = 2), classical (n = 2), and mesenchymal (n = 1) subtypes. Similarly, LTS in the TCGA and REMBRANDT cohorts demonstrated diverse transcriptomal subclassification identities. The majority of the MSKCC LTSs (71%) were found to have methylation of the MGMT promoter. None of the patients had an IDH1 or IDH2 mutation, and IDH mutation occurred in a minority of the TCGA LTSs as well. A set of 60 genes was found to be differentially expressed in the MSKCC and TCGA LTSs. CONCLUSIONS: While IDH mutant proneural tumors impart a better prognosis in the short-term, survival beyond 4 years does not require IDH mutation and is not dictated by a single transcriptional subclass. In contrast, MGMT methylation continues to have strong prognostic value for survival beyond 4 years. These findings have substantial impact for understanding GBM biology and progression

Assessing the impact of tailored biosecurity advice on farmer behaviour and pathogen presence in beef herds in England and Wales

The term ‘biosecurity’ encompasses many measures farmers can take to reduce the risk of pathogen incursion or spread. As the best strategy will vary between settings, veterinarians play an important role in assessing risk and providing advice, but effectiveness requires farmer acceptance and implementation. The aim of this study was to assess the effectiveness of specifically-tailored biosecurity advice packages in reducing endemic pathogen presence on UK beef suckler farms. One hundred and sixteen farms recruited by 10 veterinary practices were followed for three years. Farms were randomly allocated to intervention (receiving specifically-tailored advice, with veterinarians and farmers collaborating to develop an improved biosecurity strategy) or control (receiving general advice) groups. A spreadsheet-based tool was used annually to attribute a score to each farm reflecting risk of entry or spread of bovine viral diarrhoea virus (BVDV), bovine herpesvirus-1 (BHV1), Mycobacterium avium subsp. paratuberculosis (MAP), Leptospira interrogans serovar hardjo (L. hardjo) and Mycobacterium bovis (M. bovis). Objectives of these analyses were to identify evidence of reduction in risk behaviours during the study, as well as evidence of reductions in pathogen presence, as indications of effectiveness. Risk behaviours and pathogen prevalences were examined across study years, and on intervention compared with control farms, using descriptive statistics and multilevel regression. There were significant reductions in risk scores for all five pathogens, regardless of intervention status, in every study year compared with the outset. Animals on intervention farms were significantly less likely than those on control farms to be seropositive for BVDV in years 2 and 3 and for L. hardjo in year 3 of the study. Variations by study year in animal-level odds of seropositivity to BHV1 or MAP were not associated with farm intervention status. All farms had significantly reduced odds of BHV1 seropositivity in year 2 than at the outset. Variations in farm-level MAP seropositivity were not associated with intervention status. There were increased odds of M. bovis on intervention farms compared with control farms at the end of the study. Results suggest a structured annual risk assessment process, conducted as a collaboration between veterinarian and farmer, is valuable in encouraging improved biosecurity practices. There were some indications, but not conclusive evidence, that tailored biosecurity advice packages have potential to reduce pathogen presence. These findings will inform development of a collaborative approach to biosecurity between veterinarians and farmers, including adoption of cost-effective strategies effective across pathogens

Defining phenotypic and functional heterogeneity of glioblastoma stem cells by mass cytometry

Most patients with glioblastoma (GBM) die within 2 years. A major therapeutic goal is to target GBM stem cells (GSCs), a subpopulation of cells that contribute to treatment resistance and recurrence. Since their discovery in 2003, GSCs have been isolated using single-surface markers, such as CD15, CD44, CD133, and α6 integrin. It remains unknown how these single-surface marker-defined GSC populations compare with each other in terms of signaling and function and whether expression of different combinations of these markers is associated with different functional capacity. Using mass cytometry and fresh operating room specimens, we found 15 distinct GSC subpopulations in patients, and they differed in their MEK/ERK, WNT, and AKT pathway activation status. Once in culture, some subpopulations were lost and previously undetectable ones materialized. GSCs that highly expressed all 4 surface markers had the greatest self-renewal capacity, WNT inhibitor sensitivity, and in vivo tumorigenicity. This work highlights the potential signaling and phenotypic diversity of GSCs. Larger patient sample sizes and antibody panels are required to confirm these findings

Optimizing sequencing protocols for leaderboard metagenomics by combining long and short reads.

As metagenomic studies move to increasing numbers of samples, communities like the human gut may benefit more from the assembly of abundant microbes in many samples, rather than the exhaustive assembly of fewer samples. We term this approach leaderboard metagenome sequencing. To explore protocol optimization for leaderboard metagenomics in real samples, we introduce a benchmark of library prep and sequencing using internal references generated by synthetic long-read technology, allowing us to evaluate high-throughput library preparation methods against gold-standard reference genomes derived from the samples themselves. We introduce a low-cost protocol for high-throughput library preparation and sequencing