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141	Local moment phases in quantum impurity problems Tucker, Adam Philip January 2014 (has links) This thesis considers quantum impurity models that exhibit a quantum phase transition (QPT) between a Fermi liquid strong coupling (SC) phase, and a doubly-degenerate non-Fermi liquid local moment (LM) phase. We focus on what can be said from exact analytic arguments about the LM phase of these models, where the system is characterized by an SU(2) spin degree of freedom in the entire system. Conventional perturbation theory about the non-interacting limit does not hold in the non-Fermi liquid LM phase. We circumvent this problem by reformulating the perturbation theory using a so-called `two self-energy' (TSE) description, where the two self-energies may be expressed as functional derivatives of the Luttinger-Ward functional. One particular paradigmatic model that possesses a QPT between SC and LM phases is the pseudogap Anderson impurity model (PAIM). We use infinite-order perturbation theory in the interaction, U, to self-consistently deduce the exact low-energy forms of both the self-energies and propagators in each of the distinct phases of the model. We analyse the behaviour of the model approaching the QPT from each phase, focusing on the scaling of the zero-field single-particle dynamics using both analytical arguments and detailed numerical renormalization group (NRG) calculations. We also apply two `conserving' approximations to the PAIM. First, second-order self-consistent perturbation theory and second, the fluctuation exchange approximation (FLEX). Within the FLEX approximation we develop a numerical algorithm capable of self-consistently and coherently describing the QPT coming from both distinct phases. Finally, we consider a range of static spin susceptibilities that each probe the underlying QPT in response to coupling to a magnetic field. 541
142	[en] DATA SCIENCE AND SOLID STATE CHEMISTRY: A PLATFORM FOR THE COMPETITIVENESS OF THE PHARMACEUTICAL INDUSTRY IN EMERGING MARKETS / [pt] CIÊNCIA DE DADOS E QUÍMICA DO ESTADO SÓLIDO: UMA PLATAFORMA PARA COMPETITIVIDADE DA INDÚSTRIA FARMOQUÍMICA E FARMACÊUTICA EM MERCADO EMERGENTES RONALDO PEDRO DA SILVA 28 November 2018 (has links) [pt] A área de química do estado sólido ocupa uma posição cada vez mais importante nas atividades de pesquisa e desenvolvimento farmacêuticas. A compreensão das propriedades do estado sólido de um insumo farmacêutico ativo (IFA) mostra-se crítica no desenvolvimento de formulações em função de seus impactos na biodisponibilidade e solubilidade dos fármacos, sendo essencial para garantir o benefício terapêutico, otimizar o desenvolvimento e garantir a proteção da propriedade intelectual. Esta tese investiga indicadores científicos e tecnológicos na área de química do estado sólido utilizando ferramentas de ciência dos dados a partir de publicações científicas e depósitos de patentes, visando contribuir para o aumento da competitividade da indústria farmoquímica e farmacêutica brasileira e de outros mercados emergentes. A partir da utilização de ferramentas de ciência dos dados é proposta uma metodologia baseada em técnicas de text mining associadas a relações fuzzy. Essa metodologia de identificação de competências específicas aplicada na área de química do estado sólido tem como estudo de caso a descoberta de uma nova forma polimórfica para o IFA acetato de dexametasona. Os resultados revelam que existem competências científicas em química do estado sólido no Brasil. Contudo, quando comparada com a interação universidade-empresa mundial, a indústria farmoquimica e farmacêutica local perde em estágio de competitividade e desenvolvimento. Por outro lado, os resultados demonstram a robustez da metodologia e sua capacidade de identificar pesquisadores em área específicas, oferecendo soluções para apoio a tomada de decisão e identificação de pesquisadores relevantes para o desenvolvimento do setor farmoquímico e farmacêutico. / [en] The solid-state chemistry area has received increased attention in the pharmaceutical research and development activities. The comprehension of the solid-state properties of an active pharmaceutical ingredient (API) is critical in the development of formulations due to their impact on the bioavailability and solubility of the final drug, being essential to ensure therapeutic benefit, optimize development and allow a proper intellectual property protection. This research investigates science and technology indicators in the solid-state chemistry area using data science tools applied to scientific publications and patent documents, aiming to contribute to the increase of the competitiveness of the pharmaceutical industry in Brazil and in other emerging markets. Through data science tools, a methodology based on text mining techniques associated to fuzzy relations is proposed. This methodology for identifying specific competencies is applied in the solid-state chemistry area exploring a case study of the discovery of a new polymorphic form of the API dexamethasone acetate. The results reveal the existence of scientific competencies in solid-state chemistry in Brazil. However, when compared to the global university-company interaction, the local pharmaceutical industry shows a lower stage of competitiveness and development. On the other hand, the results indicates the robustness of the methodology and its ability to identify researchers in specific areas, offering solutions to support the decision making and identification of researchers relevant to the development of the pharmaceutical sector. [pt] PARCERIA PUBLICO-PRIVADA [en] PRIVATE-PUBLIC PARTNERSHIP [pt] CIENCIA DOS DADOS [en] DIGITAL COMMUNICATION [pt] QUIMICA DO ESTADO SOLIDO [en] SOLID STATE CHEMISTRY [pt] TEXT MINING [en] TEXT MINING [pt] RELACOES FUZZY [en] FUZZY RELATION [pt] GESTAO DE P E D [en] R AND D MANAGEMENT [pt] INTERACAO UNIVERSIDADE-EMPRESA [en] UNIVERSITY-COMPANY INTERACTION
143	TARGETED DELIVERY OF BONE ANABOLICS TO BONE FRACTURES FOR ACCELERATED HEALING Jeffery J H Nielsen (8787002) 21 June 2022 (has links) <div>Delayed fracture healing is a major health issue involved with aging. Therefore, strategies to improve the pace of repair and prevent non-union are needed in order to improve patient outcomes and lower healthcare costs. In order to accelerate bone fracture healing noninvasively, we sought to develop a drug delivery system that could safely and effectively be used to deliver therapeutics to the site of a bone fracture. We elected to pursue the promising strategy of using small-molecule drug conjugates that deliver therapeutics to bone in an attempt to increase the efficacy and safety of drugs for treating bone-related diseases.</div><div>This strategy also opened the door for new methods of administering drugs. Traditionally, administering bone anabolic agents to treat bone fractures has relied entirely on local surgical application. However, because it is so invasive, this method’s use and development has been limited. By conjugating bone anabolic agents to bone-homing molecules, bone fracture treatment can be performed through minimally invasive subcutaneous administration. The exposure of raw hydroxyapatite that occurs with a bone fracture allows these high-affinity molecules to chelate the calcium component of hydroxyapatite and localize primarily to the fracture site.</div><div>Many bone-homing molecules (such as bisphosphonates and tetracycline targeting) have been developed to treat osteoporosis. However, many of these molecules have toxicity associated with them. We have found that short oligopeptides of acidic amino acids can localize to bone fractures with high selectivity and with very low toxicity compared to bisphosphonates and tetracyclines.</div><div>We have also demonstrated that these molecules can be used to target peptides of all chemical classes: hydrophobic, neutral, cationic, anionic, short, and long. This ability is particularly useful because many bone anabolics are peptidic in nature. We have found that acidic oligopeptides have better persistence at the site of the fracture than bisphosphonate-targeted therapeutics. This method allows for a systemic administration of bone anabolics to treat bone fractures, which it achieves by accumulating the bone anabolic at the fracture site. It also opens the door for a new way of treating the prevalent afflictions of broken bones and the deaths associated with them.</div><div>We further developed this technology by using it to deliver anabolic peptides derived from growth factors, angiogenic agents, neuropeptides, and extracellular matrix fragments. We found several promising therapeutics that accelerated the healing of bone fractures by improving the mineralization of the callus and improving the overall strength. We optimized the performance of these molecules by improving their stability, targeting ligands, linkers, dose, and dosing frequency.</div><div>We also found that these therapeutics could be used to accelerate bone fracture repair even in the presence of severe comorbidities (such as diabetes and osteoporosis) that typically slow the repair process. We found that, unlike the currently approved therapeutic for fracture healing (BMP2), our therapeutics improved functionality and reduced pain in addition to strengthening the bone. These optimized targeted bone anabolics were not only effective at healing bone fractures but they also demonstrated that they could be used to speed up spinal fusion. Additionally, we demonstrated that acidic oligopeptides have potential to be used to treat other bone diseases with damaged bone.</div><div>With these targeted therapeutics, we no longer have to limit bone fracture healing to casts or invasive surgeries. Rather, we can apply these promising therapeutics that can be administered non-invasively to augment existing orthopedic practices. As these therapeutics move into clinical development, we anticipate that they will be able to reduce the immobilization time that is the source of so many of the deadly complications associated with bone fracture healing, particularly in the elderly.</div> Genetics not elsewhere classified Nanobiotechnology Animal behaviour Clinical microbiology Endocrinology Nanomedicine Regenerative medicine (incl. stem cells) Solid state chemistry Molecular medicine Proteins and peptides Solution chemistry Radiation and matter Biomaterials Biomechanical engineering bone fracture healing Anabolic Agents/pharmacology Targeted Drug DeliveryDesign Bone fracture targeted drugs Bone theapeutics targeted therapies Growth factors Neuropepetides Extracellular matrix Extracellular matrix fragments spinal fusion Angiogensis Acidic oligopeptides osteoporosic fractures diabetic bone fractures Integrin alpha 5 Acelerated Bone fracture healing Hydroxyapatite Hydroxyapatite targeting Targeting peptides Peptide drugs osteomyelitis (OM) Rheumatoid arthritis Bone fractures osteogenic therapies osteotropic osteotropic nanomedicines osteoinductive capacity Molecular Medicine Organic Chemistry Proteins and Peptides Radiochemistry Solid State Chemistry Solution Chemistry Biochemistry Animal Behaviour Biological Engineering Biotechnology Genetics Medicine Pharmacology Biomaterials Biomechanical Engineering Biomechanics Endocrinology Nanobiotechnology Nanomedicine

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