O sistema brasileiro de avaliação de programas de pós-graduação vem evoluindo desde 1976, sendo considerado como um dos mais eficientes do mundo. Este sistema tem se mostrado essencial para a formação de recursos humanos de alto nível e para o desenvolvimento efetivo da ciência e tecnologia no País, pois, por meio de seus critérios e indicadores, ele permite avaliar a qualidade dos programas e apontar as áreas que o Estado deseja desenvolver. Este trabalho tem por objetivo propor contribuições à gestão dos programas de pós-graduação stricto sensu em Administração do Brasil, com base nos sistemas de avaliação de pós-graduação norte-americano e brasileiro. Para tanto, procedeu-se uma pesquisa em oito programas: quatro nos Estados Unidos, credenciados pela Association to Advance Collegiate School of Business (AACSB), e quatro no Brasil, reconhecidos e recomendados pela Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES). O método de pesquisa foi o estudo de casos múltiplos, baseado nos trabalhos de Eisenhardt (1989) e Yin (2003). A análise de dados seguiu as técnicas de agrupamento e de cluster sugeridas por Miles e Huberman (1994). Os principais resultados indicam diferenças na concepção e no uso dos sistemas pelos programas brasileiros e americanos. Por exemplo, nos Estados Unidos, os programas utilizam o sistema para assegurar o cumprimento da própria missão e atender a um padrão mínimo de qualidade. No Brasil, entretanto, os programas investem no aprimoramento da produção intelectual (qualidade e quantidade), na formação de alunos e na inserção social para cumprir com as exigências do sistema e obter maior nota. Contudo, propõe-se um o modelo de gestão que - além de atender aos requisitos do sistema de avaliação da CAPES - leve em consideração a realidade do programa e demais elementos importantes para seu contínuo aprimoramento, dentre eles, o plano estratégico, que abrange a missão e a visão; o egresso e as estratégias de acesso a recursos para melhor atender a seus stakeholders. / The Brazilian evaluation (or accreditation) system of graduate programs has been evolving since 1976 and it is considered as one of the most efficient in the world. This system has been shown to be essential for the formation of high-level human resources for the effective development of science and technology in the country. By means of its criteria and quality indicators, the newer system is capable of evaluating the quality of programs and to point to the areas that the State desires to develop. The goal of this research is to propose possible extensions to the current system to manage graduate programs in business field in Brazil, by comparing USA and Brazilian evaluation systems. This research was conducted in eight business school programs: four programs in the USA that are accredited by the Association to Advance Collegiate School of Business (AACSB) and four Brazilian programs recognized by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES). The method used was multiple case study analyses based on the work of Eisenhard (1989) and Yin (2003). For the analysis, we followed the cluster techniques of Miles and Huberman (1994). The results point to the conceptual difference in the use of evaluation systems among program in the USA and Brazil. For example, in the USA, programs use the system to assure that mission and minimum quality standards are met. In Brazil the evaluation system is used as a guide to increase and maintain the programs\' overall evaluations. Further, in Brazil, the system is used to focus on areas of improvement in the quality and the quantity of intellectual production, students\' rates or performance, and social development to achieve the stated goals of the programs and to increase the evaluate score. However, the model of management proposed in this study is intended to reach the requirements of CAPES evaluate system, but also to considerate the program reality and the other important elements for the program\'s continuous improvement. Among the suggestions are: a Strategic Plan, that encloses the mission and the vision of each program. Also, inclusion of the alumni (former students), and the strategies to develop and access financial resources to attend the various needs of the stakeholders.

O principal objetivo deste trabalho é compreender como se deu o desenvolvimento da econometria no programa de pós-graduação em economia da FEA/USP e averiguar se havia ou não grandes atrasos no ensino e pesquisas desse referencial metodológico com relação ao exterior, no período entre a criação do programa de pós-graduação (meados dos anos 1960) e o fim dos anos 1970. Outro objetivo é com relação à importância do Professor Delfim Netto nesse processo. O trabalho tenta inserir estes desenvolvimentos tanto na história institucional da FEA/USP como na evolução da econometria na academia internacional, notadamente a norte-americana. Foi efetuada uma pesquisa nos arquivos da FEA, onde encontramos as ementas dos cursos. Adicionalmente, foram efetuadas entrevistas com professores que ministraram cursos de econometria no início da pós-graduação e professores que orientaram trabalhos econométricos nesse mesmo período. As principais conclusões que pudemos chegar é que nesse período a literatura era, dentro do possível, atualizada em relação ao exterior, sendo que os próprios cursos já alcançavam grau de sofisticação comparável ao dos cursos dos EUA. Com relação à influência do professor Delfim, não há indícios de que sua participação para o desenvolvimento dos cursos de pós-graduação de econometria da FEA tenha sido grande, mas podemos argumentar que ele foi importante para o desenvolvimento da pós-graduação em economia como um todo. / The main objective of this work is to understand how econometrics courses developed in the Economics graduate program at FEA/USP and to analyze whether there was a significant time gap between the courses taught and the research done using this methodological reference in Brazil versus what was made abroad. Another objective is to assess how important Professor Delfim Netto was in that process. With this we hope to place the development of econometrics at FEA/USP within the broad developments wordwide, with a focus in the United States, and within the institutional history of FEA/USP. Through an archival research, we found the courses syllaby. Additionally, we interviewed professors who taught econometric courses at the begining of the graduate program and professors who were advisors of theses that used econometrics. The main conclusions we reached are that at that time the reading list of the courses was, as far as possible, up to date in relation to what existed abroad at the time: the courses were in a level of sophistication comparable to those courses taught in the US. With respect of the influence of professor Delfim, there is not evidence to show that his participation on the development of the econometrics courses at FEA graduate school was great, but we can argue that he was important to the development of the economics program at FEA as a whole.

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As a novel therapy for neurodegenerative diseases, transplantation of multipotent mesenchymal stromal cells (MSCs) requires extensive optimization in animal models before being implemented in clinical trials. It is a goal of our laboratory to understand the mechanism of action of these cells and to improve their therapeutic efficacy. To address these goals, this study aims to optimize the cell dosage, cell type, administration route and timing, and/or donor age for stem cell therapy in two mouse models of demyelinating diseases: globoid cell leukodystrophy (GLD; Krabbe’s disease) and experimental autoimmune encephalomyelitis (EAE). GLD is a neurodegenerative lysosomal storage disease caused by the deficiency of galactocerebrosidase (GALC). Accumulation of toxic byproducts in myelin producing oligodendrocytes leads to the demyelination of neurons and increase in brain inflammation. The twitcher mouse model of GLD was used to test the therapeutic effects of MSCs after injection through intracerebroventricular (ICV) or intraperitoneal (IP) routes. Weekly MSC IP injections and single IP GALC-transduced MSC injections were performed. Other twitcher mouse cohorts received temporal vein (TV) or intracerebral (IC) injections of GALC-containing adeno-associated virus serotype 9 (AAV9-GALC) with or without IP MSC injections. All GLD affected mice treated with peripheral MSC and/or vector therapy had extended lifespans with improved motor function. The ameliorating effects of MSCs were related to their potent anti-apoptotic and anti-inflammatory effects on the peripheral and central nervous systems. These results indicate a promising future for peripheral administration of MSCs and vectors as non-invasive, adjunct therapies for patients affected with GLD. A similar study was performed using the EAE mouse model of multiple sclerosis (MS), which is a demyelinating disease due to an autoimmune reaction to myelin. The results demonstrated that biological age of the donor reduces the ability of MSCs to alleviate symptoms and improve pathology in the EAE mouse model. Upon transplantation, the young, but not old, MSCs provided neuroprotective effects through immunomodulation and remyelination in the central nervous system (CNS). The age-related therapeutic differences corroborate recent findings that biologic aging occurs in stem cells and highlight the potential need for allogeneic transplantation of MSCs in older MS patients. / acase@tulane.edu

Human Immunodeficiency Virus -1 infects CD4+ cells, and the subsequent loss of these cells cause Acquired Immune Deficiency Syndrome. Highly active antiretroviral therapy (HAART) is crucial to control viremia in the clinical management of AIDS/HIV infection; however, drug regimens are complex, expensive, and require life-long intervention with potential side effects. Current conventional anti-HIV drugs target different phases of the HIV life cycle and can be categorized as nucleoside or nucleotide reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors, entry inhibitors (co-receptor antagonists and fusion inhibitors), and integrase inhibitors(II). Enfuvirtide (Fuzeon, or T-20) is the first fusion inhibitor approved by the FDA and has substantial side effects and drug delivery issues with most patients developing some local injection site reaction. The subcutaneous application of enfuvirtide and its short half-life, which requires twice daily administration, has disadvantages in patients who are already burdened by complex oral therapy. To overcome these drug issues, we propose an alternative method to administer the HIV-1 peptide fusion inhibitor C46. Stem cells can be a vehicle for delivering genes to specific tissues in the body and their therapeutic delivery systems are extensively used in cancer research. For many years, restoration of blood and immune system function has been used as a component in the care of cancer patients who have been treated with chemotherapeutic agents. Mesenchymal Stem Cells (MSCs) have been demonstrated as a delivery vehicle for gene therapy applications based on their ability to engraft and home to inflamed tissues. MSCs are multi-potent and have immunological function in several human diseases. To investigate MSCs immune suppressive ability in HIV infection system, we will evaluate the crosstalk between MSCs and HIV infection immune-modulatory network. / acase@tulane.edu

Triple-negative breast cancer (TNBC) accounts for 15% of all diagnosed breast cancers nationally and affects African-American women 3 times more likely than any other ethnic group. Locally, African-American women in the New Orleans area see higher incidence of TNBC cases versus African-American women from the rest of the state of Louisiana, which represents an area of heightened public health interest for the metropolitan area. TNBC is a highly metastatic disease, and targeted therapies such as tamoxifen and herceptin are ineffective due to the lack of estrogen receptor (ER) and HER2/neu target expression in TNBC tumors. Chemotherapy remains the only effective drug therapy in TNBC cases. Evaluating new classes of drugs for clinical use against TNBC as well as furthering our understanding of underlying regulatory mechanisms in TNBC is a priority. Pan-deacetylase inhibitors (DACi), like panobinostat, have shown promise in clinical trials as therapies in other cancers. Pre-clinical data of panobinostat treatment in TNBC cell lines published by this lab has been positive so far, exhibiting a reduction in TNBC metastatic potential. DACi can alter multiple signaling pathways and are known to restore dysregulated microRNA (miRNA) expression patterns (miRnome) in cancers. MiRNA are a relatively new class of non-protein coding regulatory biomolecules that exhibit a variety of cancer-related properties, many still unknown in TNBC. Pan-DACi treatment combined with miRnome analysis in TNBC cell lines can be used to identify previously unknown miRNA cancer-related properties in TNBC. The specific aim of this project consists of using DACi treatment on TNBC cell lines in conjunction with miRnome analysis to identify previously undescribed anti-cancer miRNAs and elucidate their cancer-related properties in TNBC while uncovering affected cancer pathways, detecting miRNA targets, and revealing affected downstream components. Initial miRNA expression analysis of MDA-MB-231 TNBC cells treated with panobinostat or trichostatin A versus controls produced a list of potential anti-cancer miRNA candidates for further study. Among them, investigations into miR-203 and miR-335 produced unclear results as these were theorized to have anti-metastatic properties in TNBC yet enhanced cancer properties in our models and assays. Overexpression of mir-215 (a tumor suppressor in other cancers) unexpectedly enhanced tumor growth five fold in SCID mice xenografted with lentivirally-transduced MDA-MB-231 breast cancer cells stably overexpressing miR-215 (231/215+). Further qPCR analysis of 231/215+ cells uncovered upregulation of the breast cancer-associated lncRNA, HOTAIR; the breast cancer-associated miRNA, miR-196a; as well as the entire HOXC cluster in which they reside. This represents a previously unidentified regulatory mechanism of the HOXC cluster in humans. Additionally, miR-200b overexpression in MDA-MB-231 cells induced a change in cell morphology to an epithelial-like phenotype, reduced migration by 50%, and re-expressed the epithelial marker CDH1. This demonstrates a partial reversal of epithelial-mesenchymal transition (EMT), which indicates a reduction in metastatic potential by miR-200b overexpression in MDA-MB-231 cells. Additionally, these cells exhibited increased estrogen receptor alpha and related signaling pathways while also being susceptible to reduced proliferation with the anti-estrogen drug fulvestrant at high doses. Using pan-DACi treatment of TNBC cells to analyze changes in the miRnome for unknown cancer-related miRNA candidates suitable for further investigation in TNBC, we identified miR-215 overexpression in MDA-MB-231 cells as an oncogenic event that enhances tumor growth, cell proliferation, and HOXC cluster transcription while miR-200b is an anti-metastatic miRNA that partially reverses EMT and reduces fulvestrant resistance through re-expression of estrogen receptor signaling. / acase@tulane.edu

acase@tulane.edu

There are not enough donor lungs available to meet the increasing demand for lung transplantation. To compound the problem, transplant recipients have a projected survival time of only 5.7 years despite life-long immunosuppression. An alternative approach for acquiring transplantable lungs and reducing post-operative complications may be possible through tissue engineering. Perfusion-decellularization generates natural, three-dimensional extracellular matrix (ECM) scaffolds of an organ that are apt for tissue engineering. Decellularization of the heart, lung, liver, kidney, and pancreas has been reported in animal models and from human tissue. Decellularization of fibrotic and emphysematic lungs indicated that this technique can efficiently remove cells from diseased tissue—a potential source of materials for engineering of transplantable lung tissue. Pulmonary hypertension (PHT) is a vascular disease characterized by increased pulmonary vascular resistance leading to right heart failure and death. Lungs damaged by PHT are unsuitable for transplantation; however, decellularization of these organs may provide scaffolds appropriate for ex vivo lung engineering. Monocrotaline-induced PHT (MCT-PHT) is a well-established model of this disease in rats closely resembling the clinical presentation of PHT in humans. Thus, decellularization and recellularization of hypertensive lungs was evaluated using the MCT-PHT model. Decellularization of control and MCT-PHT Sprague-Dawley rat lungs was accomplished by treating the lungs with Triton X-100, sodium deoxycholate (SDC), NaCl, and DNase. The resulting acellular matrices were extensively characterized by molecular, mechanical, and structural analyses revealing that decellularization was able to remove cells while leaving the ECM components and lung ultrastructure intact; however, the vasculature of MCT-PHT acellular lung scaffolds was narrower than control scaffolds—a hallmark of PHT. To evaluate the effect of narrowed vasculature on the use of hypertensive lungs for tissue engineering, an optimal vascular recellularization technique was developed. Gravity-based seeding of endothelial cells followed by bioreactor-based whole-organ culture resulted in efficient vascular recellularization of control lung scaffolds. However, this method led to heterogeneous re-endothelialization of the vasculature of MCT-PHT matrices suggesting that additional manipulation or optimization is required. / acase@tulane.edu

The active human retrotransposon L1 is the most prevalent human retroelement, constituting 17% of the mass of the human genome and contributing significantly to mutagenesis. L1 mutagenizes human genomes in a number of ways including insertional mutagenesis of itself and other retrotransposons, creating of DNA double strand breaks, and induction of non-allelic homologous recombination. Through these processes, the activity of L1 is responsible for approximately 0.5% of all new genetic diseases. All L1-derived mutagenesis stems from the activity of a small number of intact full-length L1 loci that remain capable of mobilization. A smaller subset of these active L1s are called hot L1s and are responsible for the vast majority of all L1 activity. Hot L1s are polymorphic in the population and represent evolutionarily recent L1 insertion events. Here, we show that potentially active full length L1 elements are more prevalent in individual genomes than previously believed. We find that the typical individual likely harbors approximately 60 active and 50 hot L1s. However, we also find that there is significant variation between individuals in numbers of potentially active L1s. As a result, the mutagenic burden associated with L1 likely varies between individuals. / acase@tulane.edu