Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
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Showing 1 to 20 of 63 for “"clinical success"”.
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Probabilistic modeling of the drug development domain: A Bayesian domain-knowledge application for pharmacovigilance
… a single new chemical entity (NCE) into a successful therapeutic agent is $802 million. This figure is largely dependent on the expense of investigating NCEs that ultimately fail to be approved for use: between 70 - 90% of NCEs do not achieve New Drug Application (NDA) approval, and many of …
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Biomechanical Analysis of Femoral Neck Strength with Respect to Femoral Head Core Decompression
… of core decompression that show similar clinical success. The objective of this study is to assess the difference in femoral neck strength between the single large bore core decompression and multiple small bore core decompression techniques.
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Development of new bioorganometallic metallodendrimers as in vitro anticancer agents
The clinical success of cisplatin and its derivatives for the treatment of different cancers has had a profound effect on the use of metal-containing agents in medicine. Despite the successes, the drawbacks of platinum-based therapy, such as drug resistance, toxicity and the emergence of unwanted …
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Silver Doped Hydroxyapatite Coating on Titanium Surfaces and its Effect on Early Bone Response and Osseointegration
<p>The clinical success of dental implants is determined mostly by surface properties of implants and interactions with surrounding tissues. Furthermore, clinical success of dental implants is directed by implant surfaces and bone cell responses that promote osseointegration and long-term …
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Development and characterization of immunogenic genetically engineered mouse models of pancreatic cancer
… into mechanisms of immune escape have fueled the clinical success of immunotherapy in many cancers. However, pancreatic cancer has remained largely refractory to checkpoint immunotherapy. To uncover mechanisms of immune escape, we have characterized two preclinical models of immunogenic pancreatic …
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Investigation of endogenous and adoptively transferred T cell function in a genetic mouse model of lung adenocarcinoma
The clinical success of immune checkpoint blockade, including in patients with lung cancer, has clearly demonstrated that the body's immune system is capable of tumor cytotoxicity if modulated appropriately. Unfortunately, only a minority of patients with solid tumors respond to checkpoint …
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Identification of genotype-specific dependencies in Keap1-deficient lung adenocarcinoma
… LUAD are numerous, but have been met with little clinical success. Importantly, large-scale sequencing studies have defined the genomic complexities of LUAD resulting in the need to functionally characterize frequently mutated genes in the context of tumorigenesis. The development of somatic …
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Flexural strength and shear bond strength of self-etching/self-adhesive resin luting agents
… both of which have much longer histories of clinical success. By comparing the properties of the newer cements to the standards, it may be possible to determine how clinically successful the newer cements may be. The mechanical properties tested were flexural strength (FS) and shear bond …
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Expedient access to C-aryl linked saturated heterocyclic motifs
… greater solubility and an improved likelihood of clinical success. Based on this, a range of methods have been developed to synthesise compounds with high saturation, particularly with respect to sp2-sp3 cross-coupling reactions. Many of these approaches suffer from severe drawbacks, such as a …
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An Adaptive Bayesian Approach to Bernoulli-Response Clinical Trials
Traditional clinical trials have been inefficient in their methods of dose finding and dose allocation. In this paper a four-parameter logistic equation is used to model the outcome of Bernoulli-response clinical trials. A Bayesian adaptive design is used to fit the logistic equation to the …
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Synthesis of Saponin Immunoadjuvants
The clinical success of conjugate anticancer and antiviral vaccines critically depends on the identification of, and access to, novel adjuvants with high potency and attenuated toxicity. The QS-21 fraction of Quillaja saponaria extracts comprises an isomeric mixture of complex triterpene saponins …
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Quantitative analysis of non-viral gene therapy in primary liver culture systems
… decades of research and development efforts, clinical success has yet to be realized. Successful delivery of DNA is a crucial first step in attaining safe and effective gene therapeutics. While vectors based upon recombinant viruses have shown high delivery and transfection efficiencies, they …
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Characterization of pattern recognition receptor responses against materials for cell encapsulation
… to enable donor cell transplantation, but clinical success has remained elusive due to immunological responses to the encapsulated materials. Alginate is the leading material for the microencapsulation of islet cells, successfully creating a barrier between the host immune system and …
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Study of Physiologic and Immunologic Incompatibilities of Pig to Human Transplantation
… More genetic targets must be identified for clinical success. First, this study examines platelet homeostasis incompatibilities leading to acute thrombocytopenia in liver xenotransplantation. Mechanisms for xenogeneic thrombocytopenia were evaluated using liver macrophages, Kupffer cells, …
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Antioxidant PRDX1 limits CD8+ T cell effector function in the tumour microenvironment
… endogenous CD8+ T cell function has had profound clinical success and exemplifies the anti-tumour potential of T cell immunity. Nevertheless, therapeutic efficacy is confined to a subset of patients and responsive cancer types, highlighting additional and poorly defined mechanisms of …
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Development of high-throughput nanoparticle screening technologies to facilitate the delivery of genetic therapies to non-liver cell types
… toxicity profiles. Yet, LNPs have only seen clinical success as delivery methods to liver cells. In order to treat genetic diseases outside the liver, we hypothesized that a novel methodology for LNP discovery must be applied. Utilizing DNA barcodes to allow for the testing of >100 LNPs …
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A Synthetic Lethal shRNA Screen and Genetic Proof of Concept Identifies RAC1 as a Novel Target to Disrupt Plexiform Neurofibroma Formation
… neurofibromas (PN). Historically, little clinical success has been achieved targeting PN through surgery or chemotherapies. I performed an shRNA library screen of patient-derived Schwann cell lines to identify novel therapeutic targets to disrupt PN formation and progression. An shRNA …
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PECVD of silicon and titanium based coatings to enhance the biocompatibility of blood contacting biomedical devices
The clinical success of a surgical implantation depends on various factors including the design and biocompatibility of the biomaterial, surgical procedure adopted, injuries made during implantation and health and condition of the patient. The success of a biomaterial depends on the interaction and …
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Physiological adaptations in mdx mice treated with microdystrophin gene therapy and endurance exercise
… functions. A promising treatment currently in clinical trials is microdystrophin gene therapy, which delivers a truncated version of dystrophin to muscle via a viral vector. Preclinical studies have established efficacy of microdystrophin to improve muscle quality and function. With clinical …
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