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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
101

An assessment of metabolic bone disease in the skeletal remains of Chinese indentured mine labourers from the Witwatersrand

Meyer, Anja January 2014 (has links)
An essential part of bioarchaeology is the study of diet and nutrition and its effects on the general health of a person. Interpretation of nutritional and metabolic disease related pathologies often provide additional insight into the daily social and cultural practices of people. It is therefore also an essential part of understanding differences amongst past populations from archaeological contexts and provides an alternative means for cross referencing historical accounts. In this study the skeletal remains of 36 Chinese indentured mine labourers, who worked and died on the Witwatersrand mines during the period AD 1904-1910, were assessed for any signs of metabolic or nutritionally related signs of disease. Historical information suggests that these indentured Chinese labourers came from poverty stricken communities in China where disease and malnutrition were often encountered. Once in South Africa they were again subjected to the harsh living and working conditions associated with mining. Analyses suggest that all 36 individuals were males between the ages of 16 and 45 years, with the majority being of young adult age (20-34 years). Pathology that could be observed included a high prevalence of nutrition-related changes and linear enamel hypoplasia which suggests that the Chinese miners had been subjected to long periods of malnutrition and illness throughout childhood continuing into adulthood. Nevertheless, a large proportion of lesions associated with malnutrition showed some degree of healing. A high frequency of traumatic lesions, specifically peri-mortem fractures, was observed and may have contributed to the death of many of the Chinese miners. It therefore seems that even though the healing of pathological lesions associated with malnutrition indicated a period of improved nutritional intake, possibly during their time on the Witwatersrand mines, the high prevalence of peri-mortem fractures attests to the hazardous working conditions associated with deep-level mining. In order to aid in the interpretation of skeletal pathology associated with metabolic and nutritional diseases non-specific signs of disease observed in a cadaver skeletal sample with known causes of death (related to specific metabolic or nutritional diseases) were compared to pathology observed in the Chinese miners. This provided pathological patterns which enabled a better interpretation of the pathology observed in the Chinese skeletal remains. / Dissertation (MSc)--University of Pretoria, 2014. / am2014 / Anatomy / unrestricted
102

我國金融業審計委員會與內部控制缺失關聯性之探討 / The association between audit committee and internal control deficiencies of Taiwan financial industry

沈宛亭, Shen, Wan Ting Unknown Date (has links)
金融秩序之維持基於金融機構的穩健運作,金融機構穩健運作之關鍵來自內部控制制度的落實,而此一制度係建構在公司治理—強化經營者責任上。2013年底,我國公司治理機制一項重大變革為審計委員會之設置要求。因此本研究即探討審計委員會與內部控制缺失之關聯性。以2013年至2015年上市櫃金融控股公司(包含其銀行和保險子公司)以及上市櫃和興櫃的銀行及保險公司為研究對象。 本研究發現:審計委員會與內部控制缺失具統計上的顯著關聯性。審計委員會的設立與內部控制缺失呈顯著負相關;監督者(獨立董監事及審計委員會成員)會計或財務專業的比例,並未與內部控制缺失成顯著負相關,拆出分獨立董監事和審計委員會兩項不同監督機制,其成員會計或財務專業的比例與內部控制缺失也並未呈現顯著的負相關;金融控股母公司的獨立董事同時兼任子公司獨立董事,則與較多的裁罰件數成顯著正相關。另外研究也發現,部分會計師事務所與金融業者內部控制缺失呈顯著的負相關。 綜上結果隱含以下推論:審計委員會監督功能發揮,將幫助金融業者減少內部控制缺失的發生,不過獨立董事在同一金控體系兼任多家公司獨立董事的情形,並未有較佳的監督效果出現。由於我國金融業者發生的內部控制缺失類型多樣,因此在審計委員的安排上,除了會計或財務專業的審計委員,也可廣納其他專業的專家學者擔任,另外會計師事務所也可扮演完善內部控制制度的一個輔助角色。 / To find out the effect of the audit committee on internal control, this study examines the association between audit committees and internal control deficiencies.The samples are listed financial holding companies including their bank and insurance subsidiaries, bank, and insurance companies in TWSE and OTC in Taiwan over the period from 2013 to 2015. I find that the audit committees are negatively associated with the internal control deficiencies. However, there is no association between the audit committees of accounting or financial expertise and internal control deficiencies. Besides, I find that the circumstances that the independent directors of the financial holding parent companies also serve as an independent directors of the subsidiaries are positively associated with more incidences of penalty cases. Taken together, the empirical result indicates the association between the audit committees and internal control deficiencies in Taiwan financial industry.
103

Natural Killer Cells and Pre-B Acute Lymphoblastic Leukemia : Evidence for an Unconventional Cytotoxicity Pathway / Cellules Natural Killer et leucémies aiguës lymphoblastiques pré-B : éléments de preuve d’une voie de cytotoxicité non conventionnelle

Nicoletti, Simon 06 November 2017 (has links)
Les cellules Natural Killer (NK) représentent une population de cellules innées lymphoïdes aux fonctions anti-infectieuses et antitumorales. Les leucémies aiguës lymphoblastiques pré-B (LAL pré-B) constituent le cancer de l’enfant le plus fréquent et ont été décrites comme résistantes à la cytotoxicité médiée par les NK bien que les bases moléculaires demeurent inconnues.L’objectif de ces travaux a été de caractériser cette résistance. En développant un essai de cytotoxicité par cytométrie en flux et en utilisant des cellules effectrices activées in vitro, nous avons établi la sensibilité retardée des LAL pré-B à la cytotoxicité NK : initialement résistantes après 4h d’incubation, elles sont fortement tuées après 25h.Cette cytotoxicité est contact-dépendante mais ni la voie de l’exocytose des granules cytotoxiques ni celle des récepteurs de mort n’y contribuent. La mort cellulaire des cibles est de profil apoptotique mais indépendante des caspases ; la signalisation mitochondriale l’amplifie partiellement. Interférer avec les dérivés de l’oxygène par un antioxydant diminue la cytotoxicité. Nous montrons que les cellules NK de patients atteints de granulomatose septique chronique liée à l’X présentent un défaut de cette nouvelle cytotoxicité. Nous démontrons l’expression par les NK des composants clefs d’une NADPH oxydase distincte du complexe utilisé par les phagocytes. Nos travaux établissent l’existence d’une voie de cytotoxicité non conventionnelle et en définissent les principaux prérequis moléculaires. / Natural Killer (NK) cells are innate lymphoid cells with anti-infectious and anti-tumoral activities. Among neoplasia, pre-B acute lymphoblastic leukemias (pre-B ALL) represent the most common form of cancer in childhood and were shown to be resistant to NK cell mediated cytotoxicity although the mechanisms explaining this phenomenon are incompletely understood.In the present work, we investigated the relative immune resistance of pediatric pre-B ALL targets to activated NK cells. We developed a flow cytometry based cytotoxicity assay to assess the NK activity and the involvement of long term cytotoxic pathways. Although pre-B ALL blasts were strongly resistant at 4h, we found a considerable delayed NK killing at 25h.Further investigations revealed that cell contact was mandatory for efficient killing but also that neither the granule exocytosis nor the death receptor pathway were involved. Target cell death was caspase independent but mitochondria signaling amplified it. We then showed that NK cells from patients with X-linked chronic granulomatous disease could not kill efficiently ALL blasts and that NK cells expressed key components of a NADPH oxidase complex that was distinct from the phagocyte type. Our work reveals an uncharacterized effector pathway among cytotoxic lymphocytes and establishes key molecular requirements for this unconventional pathway.
104

Exploiting DNA Repair Vulnerabilities to Modulate Anti-Cancer Immunity : a Study of the Immunological Potential of PARP inhibitors / Exploiter les défauts de réparation de l’ADN pour moduler l’immunité anti-cancéreuse : une étude du potentiel immunologique des inhibiteurs de PARP

Chabanon, Roman 31 January 2019 (has links)
Les inhibiteurs de poly(ADP-ribose) polymérase (PARPi) ciblent sélectivement les cellules porteuses de défauts des voies de réparation de l’ADN tels que les mutations de BRCA1/2 et les défauts d’ERCC1. Sur le plan clinique, plusieurs PARPi ont été approuvés pour le traitement des cancers BRCA-mutés ou platine-sensibles du sein et de l’ovaire, et des essais cliniques sont en cours pour évaluer l’efficacité des PARPi dans le cancer bronchique non-à-petites cellules (CBNPC) platine-sensible. Alors que les PARPi ont un fort potentiel thérapeutique dans les cancers comportant des défauts de réparation de l’ADN, de plus en plus d’essais cliniques évaluent également l’efficacité de ces médicaments en combinaison avec les « inhibiteurs d’immune checkpoints » (ICI) dans diverses populations de patients. Dans ce contexte, il est essentiel de mieux comprendre comment les PARPi modulent la réponse immunitaire anti-tumorale, et d’étudier le potentiel immunologique inhérent de ces médicaments.Dans cette étude, nous avons établi que les cellules de CBNPC déficientes en ERCC1 expriment fortement la signature interféron (IFN) de type I, et que les tumeurs de CBNPC ayant une faible expression d’ERCC1 ont un infiltrat lymphocytaire renforcé. En utilisant des lignées cellulaires isogéniques et des xénogreffes dérivées de patients, nous avons montré que plusieurs PARPi, notamment l’olaparib et le rucaparib, ont des propriétés immunomodulatrices dans les modèles de CBNPC ERCC1-déficients et de cancers du sein triple-négatifs (CSTN) BRCA1-mutés. D’un point de vue mécanistique, les PARPi génèrent des fragments d’ADN cytoplasmiques ayant les caractéristiques de micronoyaux ; ceux-ci activent la voie cGAS/STING et déclenchent une réponse IFN de type I, associée à la sécrétion de la cytokine CCL5. De manière importante, ces effets sont largement diminués dans les cellules de CSTN BRCA1-révertantes et les cellules de CBNPC ré-exprimant ERCC1, ce qui suggère que les défauts de réparation de l’ADN amplifient les phénotypes immunitaires associés au traitement par PARPi. En outre, ces effets sont totalement abrogés dans les cellules de CSTN PARP1-neutralisées, ce qui confirme que les phénotypes observés dépendent d’un effet spécifique des PARPi sur leur cible.Au-delà de leur potentiel d’activation d’une immunité spécifique des cellules cancéreuses via cGAS/STING et la signalisation IFN de type I, nous avons également constaté que les PARPi potentialisent les effets inducteurs de l‘IFN de type II sur l’expression de PD-L1 dans des lignées cellulaires et cellules tumorales fraîches de patients CBNPC, surtout en présence de défauts d’ERCC1. De plus, nous avons montré que certains PARPi, utilisés à des concentrations létales, activent de manière indépendante les éléments moléculaires clés de la mort cellulaire immunogénique, dont l’exposition de la calréticuline à la surface des cellules cancéreuses, la sécrétion d’ATP et le relargage d’HMGB1 en grandes quantités dans le milieu extracellulaire.Dans l’ensemble, ces données précliniques suggèrent que les PARPi ont des propriétés immunomodulatrices intrinsèques qui participent à l’activation de réponses immunitaires anti-tumorales ; ce potentiel pourrait être exploité cliniquement en combinaison avec les ICI dans des populations adéquatement sélectionnées au plan moléculaire. / Poly(ADP-ribose) polymerase inhibitors (PARPi) selectively target cancer cells with DNA repair deficiencies such as BRCA1/2 mutations or ERCC1 defects. Clinically, several PARPi are currently approved for the treatment of BRCA-mutant or platinum-sensitive advanced ovarian and breast cancers, and ongoing clinical trials are investigating the efficacy of PARPi in platinum-sensitive Non-Small Cell Lung Cancer (NSCLC). While PARPi constitute potent targeted therapies for the treatment of DNA repair-deficient malignancies, an increasing number of clinical trials are also evaluating their efficacy in combination with immune checkpoint inhibitor (ICI) in various populations. In this context, it is of critical importance to better understand how PARPi might modulate immune responses against cancer, and to investigate the inherent immunological potential of these agents.In this study, we show that ERCC1-defective NSCLC cells exhibit an enhanced type I interferon (IFN) transcriptomic signature and that low ERCC1 expression correlates with increased lymphocytic infiltration in human NSCLC tumours. Using isogenic cell lines and patient-derived xenografts, we further demonstrate that several clinical PARPi, including olaparib and rucaparib, display cell-autonomous immunomodulatory properties in ERCC1-defective NSCLC and BRCA1-mutant triple-negative breast cancer (TNBC) models. Mechanistically, PARPi generate cytoplasmic chromatin fragments with micronuclei characteristics; this activates the cGAS/STING pathway and elicits downstream type I IFN signalling and CCL5 secretion. Importantly, these effects are suppressed in BRCA1-reverted TNBC cells and ERCC1-rescued NSCLC cells, suggesting that DNA repair defects exacerbate the innate immunity-related phenotypes triggered by PARPi. Similarly, these effects are totally abrogated in PARP1-null TNBC cells, supporting the on-target effect of PARPi in mediating such phenotypes. Besides this potential to activate tumour cell-autonomous immunity through cGAS/STING and type I IFN signalling, we also observed that PARPi synergize with type II IFN to induce PD-L1 expression in NSCLC cell lines and fresh patient tumour cells, especially in the ERCC1-deficient setting. Moreover, we show that lethal concentrations of some PARPi independently activate the key damage-associated molecular patterns dictating the immunogenicity of cancer cell death, including calreticulin exposure at the tumour cell surface, ATP secretion and HMGB1 release in the extracellular compartment.Together, these preclinical data suggest that PARPi have intrinsic immunomodulatory properties that activate anti-cancer immune responses; this could be exploited clinically in combination with ICI in appropriately molecularly-selected populations.
105

Brister vid offentlig upphandling av event utifrån ett hållbarhetsperspektiv : En fallstudie av Östersunds kommuns upphandling av “Stadsfesten 2019”

Norell, Louise January 2019 (has links)
Offentlig upphandling kan anpassas mot att vara mer hållbar genom att ta hänsyn till miljömässiga och sociala faktorer. Event kan skapas genom offentlig upphandling. “Stadsfesten 2019” är ett sådant event, beställt av Östersunds kommun. Eventet tillägnades allmänheten och ägde rum i samband med VM i skidskytte 2019 i Östersund stad. En del av detta event var en temporärt uppställd festivalbyggnad, i form av ett så kallat spegeltält.  Syftet med denna studie är att klargöra hur tillämpning av hållbar upphandling ser ut idag, detta med Östersunds kommuns event-upphandling “Stadsfesten 2019” som studieobjekt. Studien lyfter brister i upphandlingsprocessen. Förhoppningen är att denna studie ska inspirera aktörer inblandade i upphandlingsprocessen, i synnerhet vad gäller event-upphandlingar, att tillämpa samtliga delar av upphandlingsprocessen och ta vara på tillgängligt stöd för att tillämpa mer hållbar upphandling.  Studien inleddes med att undersöka vilka steg som ingår i upphandlingsprocessen samt vad tillämpning av hållbar upphandling och skapande av hållbara event kan innebära. Studien utgår från följande sju delar av offentlig upphandling: behovsanalys, marknadsanalys, formulering av förfrågningsunderlag, annonsering/anbud/avtal, genomförande/avtalstid, uppföljning samt utvärdering.  Fokusområden i studien kopplade till hållbarhet är sysselsättning, mat, serveringsmaterial, tillgänglighet för personer med rullstol, källsortering samt återbruk. Dessa områden har valts ut utifrån Region Gävleborgs “Checklista för hållbara konferenser och event” samt Håll Sverige rents dokument “Miljömärkt event - Miljökrav på externa aktörer vid event”.  En granskning av förfrågningsunderlaget för “Stadsfesten 2019”-upphandlingen har genomförts vad gäller kravställande kopplat till ovan nämnda fokusområden. Granskningar har även genomförts av förfrågningsunderlaget för event-upphandlingen, den preliminära miljöplanen (formulerad av leverantörsorganisationen), Östersunds kommuns “Checklista miljöplan för arrangemangsbidrag”, menyerna under eventet, upphandlingsorganisationens upphandlingspolicy, kommunens miljöpolicy samt upphandlingens beslutsprotokoll.  Viss direkt observation vad gäller källsortering och tillgänglighet i spegeltältet under eventet har genomförts. Information kring Stadsfesten-upphandlingen och eventet har samlats in genom i huvudsak personlig kommunikation med utvalda personer inblandade i processen via intervjuer, telefonsamtal och/eller mailkonversationer.  Resultatet har analyserats mot politiska mål för Östersunds kommun, Lag om offentlig upphandling (SFS 2016:1145), Naturvårdsverkets rapport “Miljöanpassade inköp - Verktyg för att nå de nationella miljökvalitetsmålen”, Region Gävleborgs “Checklista för hållbara konferenser och event” samt Håll Sverige rents dokument “Miljömärkt event - Miljökrav på externa aktörer vid event”.  Denna studie visar på att samtliga sju delar av upphandlingsprocessen när det kommer till stadsfesten-upphandlingen innehåller brister, åtminstone när det kommer till miljömässiga faktorer. Östersunds kommun och Upphandlingskontoret som upphandlingsorganisation och leverantören av “Stadsfesten 2019” har visat på en ambition mot skapande av hållbara event men det finns utvecklingspotential. Varken en ingående behovsanalys eller en marknadsanalys har genomförts. Förfrågningsunderlaget kunde ha omfattat fler krav gällande tekniska specifikationer och krav kring uppföljning. Stöd i form av miljökompetens inom kommunens organisation har inte nyttjats till fullo när det kommer till utveckling av den preliminära miljöplanen. En skriftlig utveckling av den slutgiltiga miljöplanen har uteblivit. Kommunens arbetsdokument “Checklista miljöplan för arrangemangsbidrag” har inte följts fullt ut. Utformning av källsorteringshänvisningar under eventet är bristfällig, då det saknas illustrationer och text på fler språk än svenska. Mat som serverats tycks ej vara ekologisk. Vitt och vilt kött har ej prioriterats vid framställning av menyerna. Vid framtagande av menyerna tycks ej heller en minimering av serveringsmaterial ha stått i fokus. Uppföljning kring miljömässiga faktorer har ej genomförts av beställaren eller rapporterats till beställaren av leverantörsorganisationen. Utvärderingen av eventet omfattar ej miljömässiga faktorer eller de sociala faktorer som lyfts i denna studie.   Samtidigt som det i studien framkommer brister i upphandlingsprocessen framkommer det att samtliga inblandade aktörer ställer sig positiva till att utveckla sitt arbete mot en mer hållbar riktning vad gäller upphandling och skapande av event. Förslag till förbättringar mot en mer hållbar upphandlingsprocess som framkommer i studien är att låta testpersoner undersöka tillgängligheten för rullstolsburna innan event börjar, att inleda samarbete mellan Mittuniversitetet och Östersunds kommun, att ställa uppföljningskrav i förfrågningsunderlaget, att formulera slutgiltiga miljöplaner skriftligen samt att ta hjälp av miljökompetens för detta ändamål.​ ​Redan påbörjade organisatoriska hållbarhetsutvecklingar framkommer i form av utveckling av riktlinjer inom eventbranschen och en påbörjad uppföljning av upphandlingar inom upphandlingsorganisationen. / Public procurement can be adjusted to be more sustainable, this through taking in consideration environmental and social factors. Events can be created through public procurement, “Stadsfesten 2019” is one of these events. The event was ordered by the municipality of Östersund, Sweden. This event was dedicated to the general public, and took place during the biathlon world championship in 2019 in Östersund city. Part of this event was the so called mirror tent, a festival building temporary mounted.  The purpose of this study is to clarify whether a sustainable procurement procedure is applied in reality today, this having “Stadsfesten 2019” as a study object.  The study raise deficiencies within the procurement procedure. The aim is that this study will inspire actors involved in the procurement procedure, especially when it comes to the creation of events, to practise all of the steps within the procedure, and also to make use of available competence and support. This to apply a more sustainable public procurement.  Initially the study investigated which steps that are included within the procurement process, and what sustainable procurement and creation of event can involve. The study involves following seven steps within the public procurement: needs analysis, market analysis, formulation of demands within the specifications for the mission, advertising/bid/agreement, implementation/contract period, follow-up and also evaluation.    Focus areas in the study connected to sustainability are employment possibilities for people currently outside the market, food, serving materials, availability for people in wheelchairs, waste sorting and reuse of material. These areas were selected regarding a checklist for creating more sustainable conferences and events by the region of Gävleborg, Sweden, and a document about environmentally certified events by the NGO “Håll Sverige rent”.   A review has been carried out regarding the specifications for the mission for “Stadsfesten 2019”, and the demands connected to the already mentioned focus areas. Reviews have also been carried out regarding the preliminary environmental plan for the event (formulated by the contractor), the municipality’s checklist for environmental plans, the menus presented during the event, the procurement policy of the procurement organsiation, the environment policy of the municipality and of the decision protocol of the Stadsfesten-event.   Some direct observation regarding waste sorting and availability connected to the mirror tent took place during the event.  Information about the event-procurement and the event has been collected mainly through personal communication, involving people connected to the procurement procedure of the event. This communication was made through interviews, phone calls and/or mail conversations.   The result has been analysed against political goals for the municipality of Östersund, the swedish law about public procurement (SFS 2016:1145), a report by the swedish Environmental Protection Agency about environmentally friendly purchases, the checklist by the region of Gävleborg mentioned earlier and also the document by “Håll Sverige rent” already mentioned.  This study shows that all of the seven steps within the procurement procedure includes deficiencies when it comes to the procedure of  the “Stadsfesten 2019”-procurement, at least when it comes to environmental factors. The municipality of Östersund and Upphandlingskontoret (its procurement partner) as a procurement organisation, and the contractor of the event have shown an ambition towards creating a more sustainable event. Still there is a need of further development. Either a thorough need analysis or a market analysis have been carried through. The specifications for the mission could have been including more demands regarding technical specifications and follow-up. Support including competence within the environmental area within the organisation of the municipality has not been used of fully when it comes to the development of the preliminary environmental plan for the specific event. A written version of the final environmental plan has not been formulated. The municipality’s own checklist for creating environmental plans has not been used fully. The layout of the waste sorting instructions connected to the waste bins directed to event visitors is insufficient. It lacks of illustrations and texts in other languages than swedish. The food served within the tent is not ecological. White and wild caught meat have not been prioritised when creating the menus. Also, when creating the menus a minimizing of the serving material needed has not been in focus. A follow-up regarding environmental factors has not been carried through by the municipality or been reported to the municipality by the contractor. The evaluation of the event does not include any environmental or social factors lifted within this study.  At the same time, this study shows that the people involved in this study are positive about developing their work towards a more sustainable direction when it comes to procurement and the creation of events. Suggestions for improvements towards a more sustainable procurement procedure reveals in the study from people involved. These includes having people testing the availability for people in wheelchairs before an event opens, starting a collaboration between the municipality and the local university (Mid Sweden university), including demands about follow-up within the specification for the mission, formulate final environmental plans in written form and make use of environmental competence for this purpose.     Already started organisational developments towards sustainability are revealed in this study. The event branch is developing guidelines about creating more sustainable events, and within the procurement organisation of the municipality of Östersund and Upphandlingskontoret there is an ongoing follow-up regarding their earlier procurement missions. / <p>2019-06-07</p>
106

The Identification and Targeting of Partially-Folded Conformations on the Folding Free-Energy Landscapes of ALS-Linked Proteins for Therapeutic Intervention: A Dissertation

Mackness, Brian C 07 April 2016 (has links)
The hallmark feature of many neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), is the accumulation of cytoplasmic inclusions of key disease-linked proteins. Two of these proteins, TDP-43 and SOD1, represent a significant proportion of sporadic and familial ALS cases, respectively. The population of potentially aggregation-prone partially-folded states on the folding free-energy landscape may serve as a common mechanism for ALS pathogenesis. A detailed biophysical understanding of the folding and misfolding energy landscapes of TDP-43 and SOD1 can provide critical insights into the design of novel therapeutics to delay onset and progression in ALS. Equilibrium unfolding studies on the RNA recognition motif (RRM) domains of TDP-43 revealed the population of a stable RRM intermediate in RRM2, with residual structure localized to the N-terminal half of the domain. Other RRM domains from FUS/TLS and hnRNP A1 similarly populate RRM intermediates, suggesting a possible connection with disease. Mutations, which enhance the population of the RRM2 intermediate, could serve as tools for deciphering the functional and misfolding roles of this partially-folded state in disease models, leading to the development of new biomarkers to track ALS progression. ALS mutations in SOD1 have been shown to destabilize the stable homodimer to result in increased populations of the monomeric and unfolded forms of SOD1. Mechanistic insights into the misfolding of SOD1 demonstrated that the unfolded state is a key species in the initiation and propagation of aggregation, suggesting that limiting these populations may provide therapeutic benefit to ALS patients. An in vitro time-resolved Förster Resonance Energy Transfer assay to screen small molecules that stabilize the native state of SOD1 has identified several lead compounds, providing a pathway to new therapeutics to treat ALS.
107

The Gap Between Engineering Education and Postgraduate Preparedness

Warsame, Abdulla Farah 01 January 2017 (has links)
Engineering students entering the workforce often struggle to meet the competency expectations of their employers. Guided by constructivist theory, the purpose of this case study was to understand engineers' experiences of engineering education, deficiencies in practical skills, and the self-learning methods they employed to advance their technical and professional competencies. Working engineers were asked about their experiences overcoming practical skill deficiencies and bridging the gap between education and practice. Interviews with 15 chemical, civil, mechanical, and electrical engineers were analyzed by coding for common statements and identifying themes. Firsthand experiences of the participants captured 3 themes: overall perceptions of engineering education, deficiencies in skills, and self-learning experiences. According to study findings, engineering education did not supply sufficient practical skills for working engineers. The study also provided descriptions of training and self-learning methods employed by practicing engineers to advance their technical and professional competencies. The study found that although universities might provide some practical skills through industry collaboration, engineering graduates still required professional development to ensure a smooth transition from academic learner to acclimated working engineer. The project is a practical training, developed for recent graduates, that could achieve positive social change by making strides toward bridging the gap between theory and practice for the participants. This study may also incite positive social change as it contributes to the evidence that there is a lack of practical experience in colleges of engineering, which may therefore improve their curriculum.
108

Changes in Adipose Tissue Inflammation following Surgical Weight Loss in Patients with Obesity: The Relationship between the Adipose Tissue Immune Microenvironment and Clinical Outcomes after Bariatric Surgery

Jalilvand, Anahita D. 21 September 2020 (has links)
No description available.
109

pQCT Assessment at the Radius And Tibia: The Effects of Menopause and Breast Cancer Therapy on Trabecular and Cortical Bone

Szabo, Kristina 11 1900 (has links)
<p> This thesis focuses on an examination of cortical and trabecular bone density and geometry at the radius and tibia in postmenopausal women, primarily women with history of breast carcinoma, while also assessing musculoskeletal changes in postmenopausal breast cancer patients after treatment with the Aromatase Inhibitor, Anastrozole. The first sub-study is an investigation of the reproducibility of the pQCT measurement parameters at the radius and tibia in healthy pre-and postmenopausal women. Results indicated that the reproducibility was good at the radius and even better at the tibia for all parameters measured. The second study is an appraisal of the level of osteoporosis knowledge in a cohort of postmenopausal women. The participants were assessed via the Facts on Osteoporosis Quiz, a well validated questionnaire, and the data revealed significantly lower test scores among the breast cancer subjects in comparison with healthy postmenopausal women. In the remaining group of studies, pQCT technology was utilized to describe trabecular and cortical bone at the radius and tibia in postmenopausal women and women with a history of breast carcinoma whom had been prescribed Anastrozole. The following measurement sites were significantly lower in the breast cancer subjects: TOT_DEN and TOT_CNT at the 4% radius; CRT_DEN, TOT_CNT, and CRT_CNT at the 20% radius; TOT_DEN at the 4% tibia; and CRT_DEN at the 38% tibia. With respect to time on Anastrozole, TOT_CNT at the 4% radius (r=-0.36); TOT_CNT (r=-0.33), CRT_CNT (r=-0.34) and CRT_DEN (r=-0.44) at the 20% radius; and CRT_DEN (r=-0.39) and CRT_CNT (r=-0.27) at the 38% tibia were significantly negatively correlated with days on Anastrozole. Furthermore, after two years of Anastrozole treatment in a small cohort of breast cancer subjects, there was a significant decrease in CRT_DEN (p=0.025) at the 20% diaphyseal radius and also at the 38% diaphyseal tibia (p=0.051). Together, the sub-studies that comprise this thesis demonstrate that there are noteworthy deficiencies in osteoporosis knowledge among postmenopausal women, particularly those with a history of breast carcinoma, and yet, these are the same women that have an increased need to understand the preventative and treatment options regarding this disease as they demonstrate reduced bone density at all measurement sites. It also appears that time on Anastrozole primarily affects cortical bone density in these women. In summary, this thesis provides novel details regarding cortical bone in breast cancer subjects and emphasizes the need for a normative database of bone quality parameters at different skeletal sites in order to gain a better understanding of the utility of each skeletal site with regard to fracture risk prediction. </p> / Thesis / Doctor of Philosophy (PhD)
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HOW CAN ICTs AND NEW/SOCIAL MEDIA REMEDY THE PROBLEM OF VITAL STATISTICS DEFICIENCIES IN GHANA? (THE CASE OF GHANA BIRTHS AND DEATHS REGISTRY DEPARTMENT)

BAIDOO, Stephen January 2012 (has links)
De två viktigaste händelserna i varje man jordliv är födelse och död. Varje av dessa händelser händer en gång i en livtid. Varje individ kommer in i världen på en bestämd tid på en särskild dag. På samma sätt lämnar varje person denna värld på en särskild dag på en bestämd tid. Växelverkan av dessa två viktiga händelser definierar, till en stor grad, totalityen av den globala befolkningen på någon given tidsperiod. Huruvida det finns befolkningboom/explosionen, eller kollapsen i världen beror i sin helhet på dessa två naturliga källor. Några demographers, klassificerar emellertid flyttning (dvs. emigration och invandring eller inflyttning och ut-flyttning) som delen av källorna av befolkningtillväxt.Antecknar dessa händelser, som och, när de uppstår, inte för gyckel eller en avsluta till honom, men ganska som hjälpmedel till en avsluta. Befolkningen påverkar varje aspekt av människoliv, namely: ekonomiskt, politiskt, lagligt, socialt, kulturellt, miljö-, vård-, Etc. Det är för dessa, och annat lika viktigt resonerar att folk av vision liksom John Graunt (1620-1674); Thomas Malthus (1766-1834); Herrn James Steuart (1713-1780); William Godwin (1756-1836); och något liknande sökte, i de tidig sortdagar, att ge erkännande till befolkningen utfärdar. Detta upprättar faktumet att, även om de formella sätter in av demography, är en förhållandevis ny innovation, folk long har angå om storleksanpassa och kännetecknen av deras territoriella befolkningar för mycket en lång tid. Trots dess jättelika betydelse, verkar som om det lite tid och resurser kanaliseras in i befolkningledning i samtidaa tider.I Ghana som i många ett u-land mycket lite uppmärksamhet har givits sätta in av på varandra följande regeringar. Denna low-profile inställning in mot befolkning utfärdar, över åren, har motsatt påverkats landets samhällsekonomiska och politiska framsteg. Jag kan inte vara för fel att förutsätta att riktig utveckling har undsluppit mest afrikanska länder och framkallningsvärlden på stort främst, därför att sammanlagt av dessa länder riktig uppmärksamhet inte har varit fallen föra befolkningmaterier. Är det inte riktigt att brist av den riktiga metoden och resurser är det huvudsakligt orsakar av ledare seemingly care-free inställning in mot befolkning utfärdar i dessa ett u-land i förflutnan? Även om det kan verka, att många bevattnar, har passerat under överbrygga, och, att, saker verkar för att ha stupat apart (Chinua Achibe) där är alltid ett fönster av flykten, när alla dörrar är stängda.Informations- och kommunikationsteknologier (ICTs) är den nya utvecklingen av fönster och flyktruttar ut ur många hitherto oöverstigliga problem. Därför i detta te, skulle jag något liknande för att undersöka och undersöka hur ICTs och det berömda nya/sociala massmedia kan hjälpa att lätta problemet av non-registreringen eller den otillräckliga registreringen av livsviktiga händelser i Ghana. / THE two most important events in every man’s Earth life are birth and death. Each of these events happens once in a life time. Every individual comes into the world at a certain time on one particular day. In the same way, every person leaves this world on one particular day at a certain time. The interaction of these two important events define, to a large extent, the totality of global population at any given time period. Whether there is population boom/ explosion or collapse in the world as a whole depends on these two natural sources. Some demographers, however, classify migration (i.e. emigration and immigration or in-migration and out-migration) as part of the sources of population growth.Recording these events as and when they occur is not for fun or an end to itself, but rather as a means to an end. Population affects every aspect of human life, namely: economic, political, legal, social, cultural, environmental, health, etc. It is for these and other equally important reasons that people of vision such as John Graunt (1620-1674); Thomas Malthus (1766-1834); Sir James Steuart (1713-1780); William Godwin (1756-1836); and the like sought, in those early days, to give recognition to population issues. This establishes the fact that although the formal field of demography is a relatively recent innovation, people have long been concerned about the size and characteristics of their territorial populations for a very long time. In spite of its enormous importance, it appears that little time and resources are channeled into population management in contemporary times.In Ghana, as in many developing countries, very little attention has been given the field by successive governments. This low-profile attitude towards population issues has, over the years, adversely affected the country’s socio-economic and political progress. I may not be too wrong to postulate that true development has eluded most African countries and the developing world at large mainly because in all of these countries proper attention has not been given to population matters. Is it not true that lack of proper method and resources are the main causes of leaders’ seemingly care-free attitude towards population issues in these developing countries in the past? Even though it may seem that many waters have passed under the bridge and that, things seem to have fallen apart (Chinua Achibe) there is always a window of escape when all doors are closed.Information and Communication Technologies (ICTs) are the new generation of windows and escape routes out of many hitherto insurmountable problems. Therefore, in this thesis, I would like to explore and examine how ICTs and the famous new/social media may help alleviate the problem of non-registration or inadequate registration of vital events in Ghana.

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