This study seeks to understand public and institutional uptake of the public hearing genre. More specifically, this study examines how public hearing genre conventions are established and how those conventions inform and often govern tensions that arise in public discourse about a contested environmental project. In my research, I analyzed a corpus of public comments from two Mountain Valley Pipeline (MVP) 401 Water Quality Certification public hearings that were held in August 2017 and hosted by Virginia Department of Environmental Quality (VA DEQ). Additionally, I conducted interviews with 13 community members and two state representatives who spoke at one of the two hearings. This approach led me to several important findings. Most significantly, I found that while many community members understood VA DEQ's stated purpose of the public hearings, they prepared comments that spoke to an entirely different purpose because they were responding to a different kind of problem than that of VA DEQ. This finding is crucial to understanding the other tensions and ideas of consensus that occur among citizens and VA DEQ representatives since the kind of problem informs the uptake of the public hearing and the overall interpretation of the public hearing genre. My dissertation thus argues that there are ways we might reimagine ideas of effectiveness, consensus, and the public hearing genre, specifically in the case of the 401 Public Hearings and more generally in other public hearings where public discourses center on a contested environmental project like the MVP. / Doctor of Philosophy / This study examines the role and effect of public hearings and the tensions that sometimes arise within them. More specifically, I analyze transcripts from the two 401 Water Quality public hearings about the Mountain Valley Pipeline (MVP). These hearings occurred in August 2017 and were hosted by Virginia Department of Environmental Quality (VA DEQ). Additionally, I conducted interviews with 13 community members and 2 state representatives who spoke at one of the two hearings. This approach led me to several important findings. Most significantly, I found that while many community members understood VA DEQ's stated purpose of the public hearings, they prepared comments that spoke to an entirely different purpose because they were responding to a different kind of problem than that of VA DEQ. This finding is crucial to understanding the other tensions and ideas of consensus that occur among citizens and VA DEQ representatives since the kind of problem informs how people prepare for and engage with the public hearing and the overall interpretation of the public hearing as a genre. My dissertation thus argues that there are ways we might reimagine ideas of effectiveness, consensus, and the public hearing genre, specifically in the case of the 401 Public Hearings and more generally in other public hearings where public discourses center on a contested environmental project like the MVP.

Yes / Living well with dementia is promoted nationally and internationally (Department of Health, 2009: Global Action Against Dementia, 2013). UK health policy recommends post-diagnostic support to enable people to live well in the community for as long as possible (Department of Health, 2015; NHS England, 2017; Scottish Government, 2017; Welsh Government, 2017). This is important given that a cure for dementia is not imminent. A growing evidence base demonstrates that psychosocial interventions can benefit people with mild to moderate dementia, by improving cognition, performance in valued activities or daily living skills, maintaining quality of life or carer coping. (Clare et al., 2011;2017; Graff et al.,2006,2007; Streater et al.,2016). Occupational therapists offer interventions to people living with mild to moderate dementia and family carers (Swinson et al.,2016;Streater et al.,2016;Yuill and Hollis,2011). The National Institute for Clinical Excellence and Social Care Institute for Excellence (2006) recommended occupational therapists provide skills training for activities of daily living. Also, the Memory Services National Accreditation Programme recommends people with dementia have access to occupational therapy and other psychosocial interventions such as reminiscence, life story work or cognitive stimulation therapy, for the cognitive, emotional, occupational and functional aspects of dementia (Hodge et al.,2016). Such interventions can be delivered by occupational therapists. The focus on the benefits of non-pharmacological interventions provides occupational therapists with an opportunity, to deliver services that improve lives and the experience of dementia (Collier and Pool, 2016). Understanding what may influence uptake of such interventions is important if people with dementia and their carers are to benefit from what occupational therapists can offer. Yet what supports the uptake of such interventions, specifically by people with mild to moderate dementia and their family carers, living in the community is poorly understood and limited research about this topic exists. ‘Uptake’, in this paper, is defined as initial acceptance of an offer, of intervention, support or services, rather than continued engagement or adherence to an intervention over time. / National Institute for Health Research’s Programme Grants for Applied Research Programme (RP-PG 0610-10108)

The growing epidemic of antimicrobial resistance has caused significant morbidity rates worldwide as well as increasing probabilities of cancer recurrence. Efforts to address this epidemic have turned to immunomodulators, a class of molecules which modify the immune system in order to fight off infection. Muramyl dipeptide (MDP) is an immunomodulator of interest due to its specificity for NOD2, a primary receptor involved in immunoregulation. However, use of MDP in vivo causes an overly strong immunostimulatory effect; furthermore, MDP is rapidly cleared from the body due to high solubility and low molecular weight. In order to improve the clinical outlook of MDP, multiple analogues and delivery methods have been explored, with mixed success. MDP analogues have found the most success as adjuvants, although strict FDA approval guidelines limit this approach. Delivery methods for MDP are costly and also induce cytotoxicity, thereby emphasizing the clinical challenges of MDP. Introduced in 1996, Spherical Nucleic Acids (SNAs) are radially oriented oligonucleotides on a nanoparticle surface. SNAs have been shown to readily enter cells with little to no cytotoxicity and in fact, they have found clinical success in a variety of gene delivery and vaccine applications, making them a versatile platform for drug delivery. Herein, we demonstrate that SNAs can be applied as cellular delivery vehicles for MDP. To achieve this, we synthesized dual-layer SNAs whereby two unique oligonucleotides were functionalized onto a gold nanoparticle core. We show that by modulating the surface charge of the SNAs, faster cellular uptake can be achieved, which presents promise for increasing drug delivery and reaching cell compartments of interest. Additionally, we show early evidence that conjugation of MDP to the SNA corona retains MDP activity. Taken together, this work proposes effective SNA designs to deliver muramyl-based immunostimulants, which show promise in the expansion of SNA utility into immunomodulation. / Thesis / Master of Science (MSc) / The growing epidemic of antimicrobial resistance has been linked to deaths, weakened immune systems, and even cancer recurrence. To address this, immunomodulators have become an area of interest. Immunomodulators are capable of modifying the immune system to restore its normal function and fight off infection. Muramyl dipeptide (MDP) is a well-known immunomodulator, however, free MDP is too potent for clinical use. Attempts to modify or deliver MDP have had mixed success. Spherical Nucleic Acids (SNAs) are a 3D orientation of short DNA strands, SNAs are able to readily enter cells with little harmful effects on the cell. Herein, we demonstrate the development of SNAs for MDP delivery. We incorporate two unique DNA strands onto the SNA and leverage charge to enhance cellular uptake. Furthermore, we show early efforts in using the modified SNA as a delivery vehicle for MDP.

This study examined the relationship between selective serotonin reuptake inhibitor (SSRI) medication and auditory measures in clinically depressed women. Experimental subjects were tested in both a medicated and unmedicated condition. Experimental subjects were compared to a normal control group; additionally intrasubject comparison was made within the experimental group. Test measures included: audiometry, tympanometry, otoacoustic emissions, uncomfortable loudness level, masking level difference, SCAN-A, Synthetic Sentence Identification (SSI), and the low predictability section of the Revised Speech in noise (RSPIN). The unmedicated group scored significantly less favorably than the control group on the following tests; SCAN-A (composite, filtered words, and auditory figure ground), R-SPIN (0MCR condition in both the right and left ears). Additionally, the unmedicated group scored significantly less favorably than the medicated group on the SSI (-20MCR condition right ear only) and of the R-SPIN (0MCR condition right ear only). Other test measures indicated consistent trends but did reach significance.

Black Cottonwood (Populus trichocarpa) is a fast-growing, economically important tree species. P. trichocarpa was the first tree to have its genome fully sequenced and is considered the model organism for genomic research in trees. Of the macronutrients in plants, Nitrogen (N) is required in the greatest amounts and is generally the limiting nutrient in terrestrial ecosystems. Inorganic N-transport is performed by four families of transporter proteins, AMT1 and AMT2 for ammonium (NH4+) and NRT1 and NRT2 for nitrate (NO3-). I have created phylogenetic reconstructions of each of these transporter families in 22 members of Viridiplantae whose genomes have been fully sequenced. Based on these phylogenies, I have introduced a new classification system for the transporter families that better represents the evolutionary and functional relatedness of the proteins. These phylogenies were supplemented with topology predictions, subcellular localization predictions, and in silico expression profiling in order to suggest functional characterization of the groups. This facilitated candidate gene selection for NH4+ and NO3- uptake transporters from P. trichocarpa. Expression profiling was performed on two of these candidates. Results suggest that PtAMT1-1 may be a high-affinity, root-localized NH4+ transporter. In contrast, PtNRT2-6 is a high-affinity NO3- transporter localized to the dormant bud, but its physiological functions remain largely enigmatic. Flux profiles of NH4+, NO3-, and H+ in the first 1.4 cm of root tips of three-week-old P. trichocarpa seedlings and cuttings were measured using the Microelectrode Ion Flux mEasurement (MIFE) system to demonstrate the activity of AMTs and NRTs under nutrient-abundant and nutrient-deficient conditions. I found mainly N-efflux from roots of cuttings while seedling roots exhibited N-uptake. This is the first report of such a difference. This highlights an unexpected but clear physiological difference between seedling and cutting roots, which are frequently used in experimental setups. / Graduate / 0817 / 0369 / 0715 / neilvonw@gmail.com

Over the years, biological drugs have evolved and have made breakthroughs in diseases associated with extracellular proteins. However, intracellular proteins that cause disease progression are still largely inaccessible. Examples of diseases that are caused by an intracellular aggregation of proteins are neurodegenerative diseases such as Parkinson's disease, Huntington's disease (HD), and Alzheimer's disease (AD). The purpose of the work is to find a strategy to reach the neurons intracellularly. The goal is to be able to design a biological drug that enters the neuron by investigating different uptake mechanisms. A systematic review of 43 published studies was reviewed, and the results could be obtained. All result presents data from different receptors, cell-penetrating peptides, and adeno-associated viruses (AAV) that were examined. It showed that there are advantages and disadvantages with all the uptake mechanisms. There are risks of side effects for each uptake mechanism, and further studies are required to consider the risk. AAV2 and the neuron-specific receptors lack specific information about their mechanism, but there is a high potential to develop these strategies. Both AVV and the neuron-specific receptors provide specific uptake into tissues.

No description available.

No description available.

Diss. (sammanfattning) Linköping : Univ., 2003. / Härtill 4 uppsatser.

Molibdênio é um elemento traço envolvido na fixação de nitrogênio, enxofre e carbono. Oligopeptídeos estão envolvidos na nutrição bacteriana e diversos outros processos de sinalização intercelular. O objetivo do presente estudo foi investigar o papel funcional das proteínas ligadoras dos sistemas de captação de molibdato (ModA) e oligopeptídeo (OppA) em Xanthomonas axonopodis pv. citri em condições in vitro e in vivo. O mutante ModA mostrou uma produção diminuída de goma xantana, alteração do biofilme e adesão prejudicada em condições in vitro. In vivo a interação do mutante modA mostrou alterações nas lesões causadas em folhas de grapefruit possivelmente resultado da baixa expressão do gene gumB. O mutante na proteína OppA apresentou células mais co-agregadas alterando a estrutura do biofilme e consequentemente diminuindo sua capacidade de adesão. In vivo, a linhagem mutante não alterou o fenótipo de patogenicidade, mas a sua capacidade de crescimento foi afetada no início da fase estacionária sugerindo que o sistema Opp desempenha um papel nutricional. / Molybdenum is a trace element involved in nitrogen fixation, sulfur and carbon. Oligopeptides are involved in bacterial nutrition and several other intercellular signaling processes. The aim of this study was to investigate the functional role of binding proteins of molybdate (ModA) and oligopeptide (OppA) uptake systems of Xanthomonas campestris pv. citri in in vitro and in vivo conditions. ModA mutant showed a decreased production of xanthan gum, altered biofilm and adhesion impaired in vitro conditions. In vivo ModA mutant interaction showed changes in injuries on leaves of grapefruit possibly due to low expression of the gumB gene. The OppA mutant showed more cells co-aggregated by changing the structure of the biofilm and consequently reducing their capacity to adhere. In vivo, the mutant strain did not modify the phenotype of pathogenicity, but its ability for growth was affected at the early stationary phase suggesting that the Opp system plays a nutritional role.