51,181 research outputs found
Minimising train delays in a mixed traffic railway network with consideration of passenger delay
No full textHeterogeneous and tissue-specific regulation of effector T cell responses by IFN-gamma during Plasmodium berghei ANKA infection.
No full textIFN-γ and T cells are both required for the development of experimental cerebral malaria during Plasmodium berghei ANKA infection. Surprisingly, however, the role of IFN-γ in shaping the effector CD4(+) and CD8(+) T cell response during this infection has not been examined in detail. To address this, we have compared the effector T cell responses in wild-type and IFN-γ(-/-) mice during P. berghei ANKA infection. The expansion of splenic CD4(+) and CD8(+) T cells during P. berghei ANKA infection was unaffected by the absence of IFN-γ, but the contraction phase of the T cell response was significantly attenuated. Splenic T cell activation and effector function were essentially normal in IFN-γ(-/-) mice; however, the migration to, and accumulation of, effector CD4(+) and CD8(+) T cells in the lung, liver, and brain was altered in IFN-γ(-/-) mice. Interestingly, activation and accumulation of T cells in various nonlymphoid organs was differently affected by lack of IFN-γ, suggesting that IFN-γ influences T cell effector function to varying levels in different anatomical locations. Importantly, control of splenic T cell numbers during P. berghei ANKA infection depended on active IFN-γ-dependent environmental signals--leading to T cell apoptosis--rather than upon intrinsic alterations in T cell programming. To our knowledge, this is the first study to fully investigate the role of IFN-γ in modulating T cell function during P. berghei ANKA infection and reveals that IFN-γ is required for efficient contraction of the pool of activated T cells
A Bíblia da farmacologia e os antidepressivos: análise do livro texto de Goodman e Gilman - as bases farmacológicas da terapêutica de 1941 a 2006
No full textTese (doutorado) - Universidade Federal de Santa Catarina, Centro de Filosofia e Ciências Humanas, Programa de Pós-Graduação em Ciências Humanas, Florianópolis, 2010Se a dor e o sofrimento são inerentes à condição humana, a forma como lidamos com essas condições tem sido diversa em diferentes contextos socioculturais e históricos. O uso de medicamentos chamados antidepressivos para tratar situações relacionadas à tristeza com sintomas que caracterizam sofrimento físico e psíquico é uma estratégia terapêutica na biomedicina desde o surgimento dessas drogas. O uso abusivo desses medicamentos tem sido questionado. Estão sendo levantadas questões como a redução do sofrimento a aspectos puramente biológicos, excluindo desse modo uma abordagem compreensiva de problemas de saúde que não estariam restritos apenas à intervenção em alterações bioquímicas endógenas. O objetivo deste estudo é conhecer o modo como a armacologia e os medicamentos antidepressivos foram apresentados a profissionais e estudantes de medicina ao longo da segunda metade do século XX e analisar quais as estratégias argumentativas utilizadas para justificar o uso dessas drogas a partir do discurso científico. Para atingir esse objetivo, foram analisadas as diferentes edições do principal livro-texto de farmacologia, utilizado no século XX em diferentes países como modo de divulgação do conhecimento científico: o livro Goodman e Gilman: as bases farmacológicas da terapêutica, conhecido como a #bíblia da farmacologia#. Inicialmente foi feita uma abordagem dos quadros relacionados à depressão, categoria médica que deu origem aos #antidepressivos#, a partir da melancolia nos primórdios da biomedicina. Foram abordados textos de médicos como Pinel, Esquirol e Dagonet, do início do período em que #nasce# a medicina moderna, a segunda metade do século XVIII e o século XIX, com uma breve passagem pelo início do século XX, quando surgem os trabalhos de autores como Kraepelin e Freud, trazendo a questão da imprecisão dos diagnósticos médicos na área do sofrimento psíquico. Os livros-texto de Goodman e Gilman, desde sua 1ª edição (em 1941) até a 11ª edição (em 2006), foram analisados a partir de uma perspectiva histórica, utilizando como estratégia metodológica a análise de discurso. Buscou-se identificar questões que influenciaram tanto o desenvolvimento da farmacologia quanto o desenvolvimento dos medicamentos chamados antidepressivos. A partir da análise dos textos, pode-se concluir que: existe dificuldade para especificar as situações em que os antidepressivos são utilizados, por causa das incertezas do iagnóstico clínico; as tentativas realizadas a partir do conhecimento farmacológico para estabelecer uma relação causal entre diferentes substâncias endógenas e os sintomas clínicos não são comprovadas até a última edição do livro-texto; os avanços na área do conhecimento técnico-científico no sentido de controle dos sintomas têm obtido um êxito relativo (pelo menos em curto prazo, como, por exemplo, no controle dos efeitos colaterais e na facilidade de administração dos medicamentos), sendo esse um aspecto que tem dado força à expansão do uso dos antidepressivos; esses medicamentos, inicialmente utilizados para tratar sintomas depressivos (no sentido de pouca ou baixa atividade corporal) vêm tendo seu uso ampliado progressivamente para situações que não estão relacionadas aos sintomas que inicialmente lhes deram esse nome (antidepressivos); o desenvolvimento das pesquisas em farmacologia está vinculado a saberes e práticas de outras áreas do conhecimento, que, por sua vez, determinam o desenvolvimento de medicamentos; e, por fim, a industria farmacêutica está ligada ao desenvolvimento da farmacologia desde os primórdios desta.If pain and suffering are inherent to the human condition, the manner in which we deal with such conditions has been diverse in different sociocultural and historical contexts. The use of antidepressive medication to cure conditions related to sadness, which can demonstrate symptoms characterized by physical and psychic suffering, is a biomedicinal therapeutic strategy used since the emergence of such drugs. The abuse of such medication has become highly questioned. Inquiries have surfaced in relation to the reduction of suffering to purely biological aspects, thereby excluding a comprehensive approach of health problems that would not be solely restricted to an intervention of endogenous biochemical alterations. The aim of this study is to identify how pharmacology and the antidepressant drugs were introduced to physicians and medical students in the second half of XX century and to analyze which argumentative strategies are utilized in justifying the use of such drugs via scientific discourse. In order to achieve this aim, we have analyzed the different editions of the primary textbook of pharmacology, used in various countries during the XX century as a means of disseminating scientific knowledge: Goodman and Gilman: The Pharmacological Basis of Therapeutics, the commonly recognized #bible of Pharmacology#. Initially examined are the clinical conditions related to depression, a medical category that gave origin to #antidepressants#, by means of melancholia in the early days of biomedicine. Analyzed were texts from doctors such as Pinel, Esquirol, and Dagonet from earlier periods, in which modern medicine was #born#, the second half of the XVIII century, the XIX century, and a brief passage through the beginning of the XX century, when works from such authors as Kraeplin and Freud brought forth questions regarding the imprecision of medical diagnosis in the area of psychological distress. Goodman and Gilman#s textbooks, from the first edition (in 1941) through the eleventh edition (in 2006), have been analyzed from a historical perspective, using discourse analysis as a methodological strategy. We tried to identify issues that influenced both the development of knowledge in the area of pharmacology as well as the development of such medications labeled antidepressants. From the analysis of texts, one can conclude that: difficulties exist when specifying the situations in which the antidepressants are utilized, via the uncertainties of clinical diagnosis; the attempts, from de pharmacological knowledge, to establish a causal relationship between various endogenous substances and clinical symptoms are not supported in any of the textbook editions; the advances in the field of technicalscientific knowledge in order to control the symptoms have obtained a relative amount of success (at least short-term, for example, in the control of side effects and in the ease of administering medication), this being one aspect that has given strength to the expansion of antidepressants being used; these drugs, originally used to treat depressive symptoms (in the sense of little or low body activity), have had their use extended progressively to situations that are not related to the symptoms that initially gave them that name (antidepressants); the development of research in pharmacology is linked to understandings and practices from other areas of knowledge, which in turn determine the development of such drugs as antidepressants; and finally, that the pharmaceutical industry is associated to the development of pharmacology since its inception
Dose-response relationship between serum 2,3,7,8-tetrachlorodibenzo-p-dioxin and diabetes mellitus: A meta-analysis
No full textWe systematically evaluated studies published through May 2014 in which investigators assessed the dose-response relationship between serum levels of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and the occurrence of diabetes mellitus (DM), and we investigated the extent and sources of interstudy heterogeneity. The dose-response relationship between serum TCDD and DM across studies was examined using 2 dependent variables: an exposure level-specific proportion of persons with DM and a corresponding natural log-transformed ratio measure of the association between TCDD and DM. Regression slopes for each dependent variable were obtained for each study and included in a random-effects meta-analysis. Sensitivity analyses were used to assess the influence of inclusion and exclusion decisions, and sources of heterogeneity were explored using meta-regression models and a series of subanalyses. None of the summary estimates in the main models or in the sensitivity analyses indicated a statistically significant association. We found a pronounced dichotomy: a positive dose-response in cross-sectional studies of populations with low-level TCDD exposures (serum concentrations <10 pg/g lipid) and heterogeneous, but on balance null, results for prospective studies of persons with high prediagnosis TCDD body burdens. Considering the discrepancy of results for low current versus high past TCDD levels, the available data do not indicate that increasing TCDD exposure is associated with an increased risk of DM. © The Author 2015. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health
Wave turbulence of a rotating array of quantized vortices in the T → 0 temperature limit
No full textThe dynamics of quantized vortices in the zero temperature limit is currently of great interest, particularly in the case of the Fermi superfluid He-B. Here we study wave turbulence, generated by the librating motion of a rotating cylindrical container filled with He-B, in the limit of vanishing viscous forces at temperatures . The polarization of the quantized vortices with respect to the axis of rotation is measured using non-invasive NMR techniques. We observe a decrease of the polarization when the librating motion is started, and a two-stage relaxation process when the modulation of the rotation velocity is stopped. The first relaxation process is associated with the dissipation of large-scale flow stored in inertial waves and the solid body rotation of the vortex array. From the decay of these energy reservoirs we determine the rate of energy dissipation of large-scale flow. The later second process is related to the relaxation of Kelvin waves on individual vortices. This process is monitored by the recovery of the polarization. The existence of a Kelvin wave cascade at the lowest temperatures is currently a central open question. We supply some evidence for the cascade
Evaluation of the effectiveness of API-modified Goodman diagram in sucker rod fatigue analysis
No full textIn petroleum engineering applications an understanding of the fatigue behavior of metals is of great importance primarily in the selection of sucker rods. Of all the components of the oil-well pumping mechanism, sucker rods have the greatest effect on the action and performance of the whole pumping system. The behavior of the sucker rods in the transfer of forces and loads determines the action of the pump. Their inherent characteristics affect the loads imposed on the surface equipment. For years, the Goodman diagram is the basis of analyzing the endurance (fatigue) life of ferrous material. Goodman published the diagram during the year 1908. An American Petroleum Institute (API) Committee suggested several design factors for Goodman Diagram in order to adapt it specifically to specifically sucker-rod pumping installations. The diagram is known as the API Modified Goodman diagram. The committee had suggested the following revisions to original Goodman Diagram. They are: (1) The apex of the diagram should be set at the tensile strength of the material. (2) The >^-intercept should have a factor of safety of two. (3) The safety factor on the material tensile strength apex should be 1.75.
The result was the creation of API Modified Goodman Diagram. The design formula for the allowable stress line is given as:
S,={T/4+MSmin)SF…………………………………………………………………………………(1) where
Sa = Allowable maximum stress, psi,
T= Minimum tensile strength, psi,
M= Slope of the allowable stress line = 0.5625,
Smin = Minimum stress, measured or calculated, psi,
SF = Design Safety Factor.
Since this diagram is used for the design of permissible stresses for sucker rod installations, it is imperative that the design engineer understands the loads imposed on the sucker rods; however, conventional polish rod dynamometer analysis does not provide sufficient information regarding down-hole load conditions.
Since the rods available today is superior due to the improved manufacturing processes and testing facilities, this thesis is an experimental study the effectiveness and accuracy of the "API Modified Goodman Diagram." Tests conducted at 160% of the stress range as specified in the API Modified Goodman Diagram on 5/8 inch. Grade 'D' sucker rod specimens resulted in the following findings:
1. The Y-intercept of the diagram can be changed to r/2.5 as compared to T/4 given by the API Modified diagram.
2. The slope of the allowable stress line is found to be 0.3 as compared to the 0.5625 given by the Modified Goodman diagram.
In effect, the test results indicate that the present API Modified Goodman diagram is conservative and the formula for the allowable stress line could be revised to
Sa =(T/2.5+ MSmin)SF………………………………………………………………………(2) where,
Sa = Allowable stress, psi,
T = Minimum Tensile Strength, psi,
M= Slope of the allowable stress line = 0.3,
Smin= Minimum Stress, psi,
SF= Safety Factor
E-book : Industrial Transformation In The Developing World (author: Michael T. Rock & David P. Angel)
No full textArsip Kuliah Online 2010: E-book : Industrial Transformation In The Developing World (author: Michael T. Rock & David P. Angel
Letter from Carl Hayden to P. J Moran
No full textLetter from Carl T. Hayden to P. J. Moran concerning the alignment of the road to Bright Angel Trail
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