Memory

School of Art and Design: Integrative Project ThesisArt and Design, School ofUniversity of MichiganUniversity of Michiganhttp://deepblue.lib.umich.edu/bitstream/2027.42/60493/1/IPThesis_Lee.pd

Medical Billing Application Development Project

The following report gives a detailed description of the internship carried out by Ji Yoon Lee throughout the duration of the 2019-2020 internship cohort at the Illinois Mathematics and Science Academy. The final product created, the process followed in order to create the product, as well as the research and methods are explained. The report documents the imitations and constraints encountered throughout the project creation and development duration. An inclusion of values, skills, and information resulting from the internship experience are detailed below as well as recommendations on how to improve the results for both the business and for future interns. The final product created is an application that can take billing information about a medical procedure or treatment, whether it is billing information given by the medical provider or the insurance provider, and show an overview of the budgeting information in an easy to interpret manner.https://digitalcommons.imsa.edu/intern_reports_2020/1028/thumbnail.jp

Investigation of the SH3BP2 Gene Mutation in Cherubism

Cherubism is a rare developmental lesion of the jaw that is generally inherited as an autosomal dominant trait. Recent studies have revealed point mutations in the SH3BP2 gene in cherubism patients. In this study, we examined a 6-year-old Korean boy and his family. We found a Pro418Arg mutation in the SH3BP2 gene of the patient and his mother. A father and his 30-month-old younger brother had no mutations. Immunohistochemically, the multinucleated giant cells proved positive for CD68 and tartrate-resistant acid phosphatase (TRAP). Numerous spindle-shaped stromal cells expressed a ligand for receptor activator of nuclear factor kB (RANKL), but not in multinucleated giant cells. These results provide evidence that RANKL plays a critical role in the differentiation of osteoclast precursor cells to multinucleated giant cells in cherubism. Additionally, genetic analysis may be a useful method for differentiation of cherubism.</p

A instituição regulatória setorial e os arranjos contratuais em alianças para pesquisa clínica de medicamentos experimentais no Brasil

O setor farmacêutico, cujo investimento em atividade de P&D de novos medicamentos é determinante da competitividade, vive um contínuo processo de internacionalização de pesquisas, sobretudo por países emergentes. Por questões de estratégia de custo, know-how e eficiência, as indústrias farmacêuticas firmam alianças com as chamadas ORPCs – Organizações Representativas de Pesquisa Clínica, que são empresas especializadas em gestão de pesquisas clínicas (estudo de novos medicamentos conduzido em seres humanos), em um movimento de offshoring, para realizar atividades de gestão e monitoramento das pesquisas. Nesse cenário, destaca-se o Brasil que, de um lado, por possuir diversos fatores atrativos para a realização de pesquisas devido à sua quantidade e heterogeneidade populacional, tamanho do mercado e qualidade em pesquisa, vem crescendo no segmento de pesquisas clínicas. Por outro lado, as particularidades da regulação setorial do Brasil para pesquisa clínica caracterizam-na como ineficaz, morosa e desestimulante de investimentos. Diante desse quadro, o presente trabalho teve por objetivo investigar qual a relação entre a regulação setorial e os arranjos contratuais nessas alianças entre as indústrias e as ORPCs, ou seja, verificar de que forma se comportam contratualmente os agentes da aliança em face do formato da regulação do setor. Para tanto, adotou-se uma metodologia qualitativa exploratória, diante da escassez de estudos anteriores nesse sentido para esse setor, sob a estratégia de estudo de casos múltiplos. Foram estudadas 2 indústrias farmacêuticas, 2 ORPCs e ouvida também a percepção de outros agentes ligados ao segmento, como entidades associativas e o órgão de aprovação ética das pesquisas. Os dados foram coletados por entrevistas semiestruturadas e de documentos públicos como a legislação disponível. Aplicou-se análise temática categorial com uso de categorias definidas a priori e fez-se análise cruzada dos dados. Os resultados evidenciaram a relação entre as características da regulação setorial e o desenho dos arranjos contratuais, levando à reflexão de que a ineficiência do sistema regulatório impõe a adoção de mecanismos compensatórios das falhas institucionais para garantia das transações. Revelaram, nesse sentido, a insuficiência do sistema institucional na garantia das transações, induzindo à necessidade de expansão da teoria sob a perspectiva da Nova Economia Institucional e Economia dos Custos de Transação. Uma regulação burocrática, ineficaz, morosa e instável agrava a incerteza das transações e, consequentemente, estimula a adoção de mecanismos de coordenação entre as partes, contratual e extra contratualmente. Compreender o modo como os contratos podem ser arranjados e coordenados seguindo as características do ambiente institucional é importante, porque influi nas diferentes escolhas, ações e resultados para as organizações, justificando-se daí a relevância do assunto para o estudo estratégico.In the pharmaceutical industry, investments in R&D on new drugs are determinant of competitiveness and it is going through a continuous process of research internationalization, especially over emerging countries. Due to cost strategy, know-how and efficiency reasons, pharmaceutical companies have set alliances with CRO`s - Clinical Research Organizations, which are companies specializing in clinical trials management (study of new drugs conducted in humans) in an outsourcing movement, to perform management activities and monitoring of trials. In this context, Brazil, on one hand, is growing in the segment of clinical trials in virtue of its many attractive factors for the development of research such as population quantity and heterogeneity, market size and quality in research. On the other hand, particularities of the Brazilian sectoral regulation to clinical trials define it as an ineffective and lengthy system, discouraging investments. Given this situation, this study aimed to investigate the relationship between sectoral regulation and contractual arrangements in such alliances among industries and CRO’s, that is, verify how contractually agents behave in these alliances considering the format of sectoral regulation. Therefore, the study adopted an exploratory qualitative methodology, given the lack of previous similar studies for this industry, under the strategy of multiple case study. Two pharmaceutical companies and two CRO’s have been studied as well as heard the perception of other actors from the segment, such as associative entities and government ethical approval body. Data were collected by semi structured interviews and public documents as available legislation. Thematic categorical analysis was used by categories defined a priori, and then a cross-analysis of the data was applied. The results show the relationship between the characteristics of the sectoral regulation and the design of contractual arrangements, inducing to reflection that the inefficiency of the regulatory system requires the adoption of compensatory mechanisms to the institutional failures in transactions. They revealed in that sense the inadequacy of the institutional system in guarantee of transactions, leading to the need for expansion of the theory from the perspective of New Institutional Economics and Transaction Costs Economics. A bureaucratic, inefficient, lengthy and unstable regulation compounds the uncertainty of the transactions and stimulates the adoption of contractual and extra contractual coordination mechanisms between the parties. Understanding how contracts can be arranged and coordinated in accordance to the institutional environment characteristics is important as it influences the different decisions, actions and result for organizations, justifying hence its relevance for the strategic study.Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorFundo Mackenzie de Pesquis

Unleashing the full potential of Hsp90 inhibitors as cancer therapeutics through simultaneous inactivation of Hsp90, Grp94, and TRAP1

Cancer therapeutics: Extending a drug&apos;s reach A new drug that blocks heat shock proteins (HSPs), helper proteins that are co-opted by cancer cells to promote tumor growth, shows promise for cancer treatment. Several drugs have targeted HSPs, since cancer cells are known to hijack these helper proteins to shield themselves from destruction by the body. However, the drugs have had limited success. Hye-Kyung Park and Byoung Heon Kang at Ulsan National Institutes of Science and Technology in South Korea and coworkers noticed that the drugs were not absorbed into mitochondria, a key cellular compartment, and HSPs in this compartment were therefore not being blocked. They identified a new HSP inhibitor that can reach every cellular compartment and inhibit all HSPs. Testing in mice showed that this inhibitor effectively triggered death of tumor cells, and therefore shows promise for anti-cancer therapy. The Hsp90 family proteins Hsp90, Grp94, and TRAP1 are present in the cell cytoplasm, endoplasmic reticulum, and mitochondria, respectively; all play important roles in tumorigenesis by regulating protein homeostasis in response to stress. Thus, simultaneous inhibition of all Hsp90 paralogs is a reasonable strategy for cancer therapy. However, since the existing pan-Hsp90 inhibitor does not accumulate in mitochondria, the potential anticancer activity of pan-Hsp90 inhibition has not yet been fully examined in vivo. Analysis of The Cancer Genome Atlas database revealed that all Hsp90 paralogs were upregulated in prostate cancer. Inactivation of all Hsp90 paralogs induced mitochondrial dysfunction, increased cytosolic calcium, and activated calcineurin. Active calcineurin blocked prosurvival heat shock responses upon Hsp90 inhibition by preventing nuclear translocation of HSF1. The purine scaffold derivative DN401 inhibited all Hsp90 paralogs simultaneously and showed stronger anticancer activity than other Hsp90 inhibitors. Pan-Hsp90 inhibition increased cytotoxicity and suppressed mechanisms that protect cancer cells, suggesting that it is a feasible strategy for the development of potent anticancer drugs. The mitochondria-permeable drug DN401 is a newly identified in vivo pan-Hsp90 inhibitor with potent anticancer activity