Taking the Evolutionary Road to Developing an In-House Cost Estimate

This slide presentation reviews the process and some of the problems and challenges of developing an In-House Cost Estimate (IHCE). Using as an example the Space Network Ground Segment Sustainment (SGSS) project, the presentation reviews the phases for developing a Cost estimate within the project to estimate government and contractor project costs to support a budget request

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

A Selective Novel Peroxisome Proliferator-Activated Receptor ( PPAR)-alpha Antagonist Induces Apoptosis and Inhibits Proliferation of CLL Cells In Vitro and In Vivo

Tumor-specific metabolic changes can reveal new therapeutic targets. Our findings implicate a supporting role for fatty acid metabolism in chronic lymphocytic leukemia (CLL) cell survival. Peroxisome proliferator-activated receptor (PPAR)-alpha, a major transcriptional regulator of fatty acid oxidation, was recently shown to be upregulated in CLL. To evaluate PPAR alpha as a potential therapeutic target, we developed a highly selective, potent small molecule antagonist of PPAR alpha, NXT629. NXT629 inhibited agonist-induced transcription of PPAR alpha-regulated genes, demonstrating target engagement in CLL cells. Furthermore, NXT629 induced apoptosis of CLL cells even in the presence of a protective microenvironment. To mimic the proliferative lymphoid compartment of CLL, we examined the activity of NXT629 on CLL cells that were stimulated to proliferate in vitro. NXT629 reduced the number of leukemia cells undergoing cell division. In addition, in two xenograft mouse models of CLL (one a model for nondividing and one for dividing CLL), NXT629 reduced the number of viable CLL cells in vivo. Overall, these results suggest that fatty acid metabolism promotes survival and proliferation of primary CLL cells and that inhibiting PPAR alpha gene regulation could be a new therapeutic approach to treating CLL

A dimensão espacial nos estudos sobre saúde: uma trajetória histórica The spatial dimension in health studies: a historical trajectory

Este artigo recupera as concepções de espaço incorporadas pela saúde pública entre final do século XVIII e meados do XX. É proposta uma padronização, com base na produção intelectual da área, iniciando-se com a apresentação da obra de Finke (1792), passando-se então à análise do século XIX, quando geografia e medicina se transformaram em disciplinas científicas. A concepção de espaço como ambiente físico, abstraído da ação humana - consolida-se no interior da geografia, enquanto na medicina prevalece o paradigma biológico-individual. Discute-se a importância da incorporação das noções geográficas de determinismo, gênero de vida e ecologia humana pela saúde pública e apresentam-se as contribuições de Max Sorré e Pavlovsky. Recupera-se a criação, em 1952, da Comissão de Geografia Médica de Saúde e Doença da União Geográfica Internacional e analisa-se o surgimento e a consolidação da New Geography.<br>Focusing on concepts taken from critical geography, this article re-examines the spatial notions that were incorporated by the public health field between the late eighteenth and mid-twentieth centuries. Based on a review and systematization of intellectual production within the field of medical geography, this time span is broken into periods. We begin with a presentation of Finke's work (1792) and then move on to analyze the nineteenth century, when geography and medicine became scientific disciplines. The concept of space as a physical environment, with human action abstracted out, took hold within geography, while the biological-individual paradigm prevailed within the field of medicine. The text discusses the implications of the public health field's decision to embrace the geographic notions of determinism, type of life, and human ecology, and describes the contributions of Max Sorré and Pavlovsky. It also looks at the International Geographical Union's 1952 creation of a Commission on the Medical Geography of Health and Illness and analyzes the emergence and coalescence of the 'new geography'

Riquetsioses no Brasil e Portugal: ocorrência, distribuição e diagnóstico Rickettsial diseases in Brazil and Portugal: occurrence, distribution and diagnosis

O presente artigo é uma atualização sobre a ocorrência e diagnóstico das riquetsioses existentes no Brasil e Portugal, com o objetivo de incentivar e incrementar a vigilância epidemiológica dessas doenças nos dois países. Realizou-se levantamento bibliográfico e foram apresentados dados não publicados de laboratórios e serviços de epidemiologia. Os resultados descreveram a ocorrência das riquetsioses no Brasil e Portugal, inclusive aquelas recém-descritas, advindas de riquétsias de potencial patogênico ainda incerto. Os métodos diagnósticos atualmente empregados foram discutidos. Como em outros países, as riquetsioses parecem assumir crescente importância em saúde pública. Relegadas a um plano secundário por muitas décadas, o interesse por essas infecções tem aumentado nos dois países, mas ainda carece de investigação para esclarecer seu real significado em saúde pública.<br>The present study is an update review on the occurrence and diagnosis of rickettsial diseases in Brazil and Portugal, aiming at promoting their epidemiological surveillance in both countries. A literature review was carried out and unpublished data of laboratories and surveillance systems were presented. The results described the occurrence of rickettsial diseases and infections in Brazil and Portugal, including other new and still poorly understood rickettsial infections. Current diagnostic methods were discussed. As in many other countries, rickettsial diseases and infections seem to be an emerging public health problem. Treated as a minor problem for many decades, the interest in these infections has increased in both countries but further studies are needed to establish their role as a public health problem