Submitted in fulfillment of the requirements of the Degree in Chemistry, Durban University of Technology, 2017. / High prevalence and mortality cases of prostate cancer (PCa) have increased around the world, particularly in developing countries. Several forthcoming factors have been revealed nowadays, one of them is due to the incapability of the diagnostic methods to produce reliable results, which impacts negatively on cancer-treatment. However, a sensitive diagnosis of PCa cells remains a challenge in the field of biosensors. Emerging whole-cell detection as biosensing targets has opened up avenues for successful cancer diagnostics, due to high selectivity among other cells. A switchable and flexible surface-based graphene material is one of the techniques that revolutionized smart biodevice platforms in biosensor technology. In this present study, a covalently linked poly-(N-isopropylacrylamide) (PNIPAM) to graphene oxide surface has been employed as “on/off”-switchable aptamer-based sensor for the detection of PC3 whole-cancer cell. The constructed surface has benefitted from PNIPAM, as the thermal-stimulus agent, which allows the coil-to-globule transitions by triggering temperature changes. When the system is above its lower critical solution temperature (LCST) of 32oC, PNIPAM will exist as hydrophobic -globular state providing an “on” binding region for the whole-cell, reaching the interactions on the biosurface. The “off” binding systems is only possibly when the PNIPAM turns into extended-state by lowering its temperature below LCST. The first principle studies have successfully characterized the electronic behavior with particular emphasis of PNIPAM monomer functions along with the description of the structural energetics of complex through density functional theory (DFT). Docking studies have further been performed to predict a plausible binding aptamer toward the protein-representative PCa cell. To better understand the prospect of an aptamer-based tunable biosensor, molecular dynamics (MD) highlighted the behavior of PNIPAM-grafted GO in exhibiting a globular and extended conformations at above and below LCST, permitting the biomolecules to interact with each other as well as to avoid interactions, respectively. Experimental studies have been included to validate the theoretical predictions by fabricating real-biosensor systems using electrochemical impedance technique, resulting a low-detection limit down to 14 cells/mL. Engagement between theoretical and experimental studies delivered an enhanced tunable-biosensor performance for the detection of whole cell prostate cancer. / M

Indiana University-Purdue University Indianapolis (IUPUI) / Prodromal Alzheimer’s disease (AD) has recently been identified as a disease state where pathophysiological changes may progress despite the absence of significant clinical symptoms. Yet, the specific processes of neural dysfunction occurring during this preclinical phase remain unclear. Resting state fMRI (RS-fMRI) in combination with brain connectomic measurements may be able to provide ways to measure subtle connectivity changes in different neurological disease states. For instance, RS-fMRI scans allow us to determine functionally connected yet spatially distinct brain regions that can then be separated into resting-state networks (RSNs). More recently, the exploration of RSNs in disease states have proved promising since they have been reliably altered when compared to a control population. By using brain connectomic approaches to assess functional connectivity we can evaluate the human connectome from a different and more global perspective to help us better understand and detect prodromal neurodegenerative disease states.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第20272号 / 医博第4231号 / 新制||医||1021(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 山田 泰広, 教授 藤渕 航, 教授 一山 智 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

This thesis aims to examine the current state of oral health promotion with respect to fluoridation, the impact that the lack of dental care has financially on the patient and the overall health system and a discussion of alternative options that could help to improve the current state of oral health care. While acknowledging research and official reports that indicate dental caries as the most prevalent preventable health condition in the lives of children, this thesis is a literature review studying the positive and negative effects of systemic and topical fluoride on both adults and children. Exploring differing perspectives of fluoridation's benefits and efficacy as a preventative oral health care measure, including community water fluoridation and topical fluoride application, this thesis will examine its effects on dental caries nationally and internationally. Although the prevalence of caries has decreased, to date, no systematic reviews have addressed adequately the disparities between incidence, severity, and recurrence of dental caries especially between children and adults. Likewise, substantial research has not yet adequately addressed the differences found in children that may make them more susceptible than adults to over fluoridation through a combination of systemic, topical fluoridation and water consumption. The literature review also includes the breakdown of costs and cost-effectiveness of dental care, including factors that increase cost, as well as suggestions to shift towards an emphasis on preventative care in attempt to reduce overall costs. Improving access to care especially to the underinsured is discussed. Furthermore, a review of the dental therapist occupation utilized successfully in other countries is discussed as this could be a viable solution for the shortage of dental professionals in areas with minimal access of care here in the United States. This is turn may reduce the number of disparities in oral health care, by reducing the severity of oral health disorders that result from an increased delay or neglect in treating the onset of dental caries from a preventative perspective. The primary measure of impact reported in several studies reviewed was the reduction in advanced care restorations, including surgery, needed with increased preventative care measures. Evidence of the effectiveness of preventative oral health care including systemic and topical fluoridation implementation and city-specific school-wide initiatives to administer dental sealants for children covered by government-sponsored programs are growing. Moving forward towards a more prevention-based system with early detection and better access for all, these changes should help lead to increased oral health initiatives and improved oral and healthcare overall.

Cancer is a major cause of morbidity and mortality with increasing incidence worldwide. Early detection of cancers and better treatments would improve the outcome for patients. The overall 5-year survival rates of head and neck squamous cell carcinoma have not improved in the past several decades due to diagnosis at advanced stages and recurrent disease. Early detection and improved chemotherapy drugs are two key areas that are required to help to improve the prognosis for this disease. This thesis focuses on the enzyme telomerase which is known to contribute to one of the hallmarks of cancer (immortality). Elevated telomerase activity has been observed in the majority of cancer cells but not in most normal human cells so there is an opportunity to use telomerase as a biomarker for disease. This first part of this study assessed telomerase activity in saliva and tissues of head and neck squamous cell cancer patients. The Telomerase PCR-ELISA kit was used to assess telomerase activity in the saliva of patients with confirmed oral carcinomas and its expression was analysed in paraffin embedded tissue using immunohistochemistry (IHC). Whilst telomerase was detected in cell lines, no telomerase activity was detected in saliva samples from patients but was detectable in IHC specimens. The second part of the study focused on the pharmacological evaluation of a series of small molecule G–quadruplex DNA binding agents as potential telomerase inhibitors. A total of 19 telomerase inhibitors were identified but of these, only 4 were specific inhibitors of telomerase. These compounds also caused toxicity to cell lines following a 2 hour drug exposure at doses that also inhibit telomerase activity. Further studies are required to explore these compounds further. In conclusion, the results of this study have demonstrated that detection of telomerase activity I the saliva of patients with oral cancers is unlikely to be useful in terms of detecting oral cancers before symptoms of the disease are clinically manifest. A series of novel and specific inhibitors of telomerase have been identified and further studies are required to develop these compounds further.

No description available.

京都大学 / 新制・課程博士 / 博士(医学) / 甲第23758号 / 医博第4804号 / 新制||医||1056(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 今中 雄一, 教授 川上 浩司, 教授 小濱 和貴 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

No description available.

Bedingt durch die Internationalisierung der Märkte, einen sich zuspitzenden Preiswettbewerb, immer kürzere Produktlebenszyklen und nicht zuletzt durch die zunehmende Nutzung innovativer Informations- und Kommunikationstechnologien sehen sich viele Unternehmen einer erhöhten Marktdynamik und einem verschärften Wettbewerb gegenüber. Für die Konzeption von Management Support Systemen (MSS) bedeutet dies, dass neben den internen Informationen auch Informationen aus externen Quellen eingebunden, mit den internen verknüpft und hinsichtlich auffälliger Konstellationen für die Entscheidungsunterstützung aufbereitet werden müssen. Im Rahmen des von der Deutschen Forschungsgemeinschaft geförderten und kooperativ mit dem Bereich Wirtschaftsinformatik I (Prof. Dr. Dr. h. c. mult. Peter Mertens) an der Universität Erlangen-Nürnberg bearbeiteten Forschungsprojektes INTEX („Integration von Controlling- und Marktforschungsdaten in einem Expertisesystem“) wurde dazu ein Konzept entwickelt und prototypisch realisiert [MeUh01].

Demographic data indicate that 60% of 6.7 million annual global cancer mortalities and 54% of 10.8 million new patients are in developing nations, unable or unwilling to avail of invasive screening tests that are the current norm. For most cancers, survival rate is strongly dependent on early detection, highlighting the need for improved screening methods. Studies have shown that cancers can be identified based on distinct sub-cellular morphological features and expression levels of specific molecular markers. Since 85% of cancers are known to originate in the epithelium, portable in vivo imaging techniques providing sub-cellular detail in tissue up to depths of 250 μm could help improve access to biopsy-free examination in low-infrastructure environments. The resultant early detection could dramatically improve patient prognosis, while reducing screening costs, treatment delay, and occurrences of unnecessary and potentially harmful medication. This dissertation investigates handheld instrumentation for laser-scanning confocal microscopy (LSCM) and its applicability to breast cancer detection and subsequent image-guided management. LSCM allows high-resolution mapping of spatial variations in refractive index or tumor marker expression within a single cell layer situated few hundred micrometers beneath the tissue surface. The main challenge facing miniaturization lies in the mechanism of beam deflection across the sample. The first part of the dissertation presents a fast, large-angle, high-reflectivity two-axis vertical comb driven silicon micromirror fabricated by a novel method compatible with complementary metal-oxide-semiconductor processing employed in the semiconductor industry. The process enables integration of rotation sensors on the chip to adaptively correct for aberrations in beam scanning while significantly reducing fabrication costs and barriers to market acceptance. The second part of the dissertation explores the integration of this micromirror with other optical and electronic components into a handheld laser-scanning confocal microscope. Applicability of the probe to epithelial breast cancer screening via reflectance and fluorescence imaging is investigated. Finally, enhanced imaging modalities based on the micromirror are presented. 3D cellular-level in vivo imaging via rapid swept-source optical coherence tomography is demonstrated. A method for “objective-less” microendoscopy, potentially resulting in substantially reduced probe dimensions, employing reflective binary-phase Fresnel zone plates monolithically integrated on the surface of the micromirror is presented. / text