977 resultados para America--Discovery and exploration--Early works to 1800
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Vol. 1 of NUMRF copy is 1904 ed.
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Mode of access: Internet.
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v. 4. revised notes.
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Mode of access: Internet.
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Mode of access: Internet.
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Review date: Review period January 1992-December 2001. Final analysis July 2004-January 2005. Background and review context: There has been no rigorous systematic review of the outcomes of early exposure to clinical and community settings in medical education. Objectives of review: (1) Identify published empirical evidence of the effects of early experience in medical education, analyse it, and synthesize conclusions from it. (2) Identify the strengths and limitations of the research effort to date, and identify objectives for future research. Search strategy: Ovid search of. BEI, ERIC, Medline, CIATAHL and EMBASE Additional electronic searches of: Psychinfo, Timelit, EBM reviews, SIGLE, and the Cochrane databases. Hand-searches of: Medical Education, Medical Teacher, Academic Medicine, Teaching and Learning in Medicine, Advances in Health Sciences Education, Journal of Educational Psychology. Criteria: Definitions: Experience: Authentic (real as opposed to simulated) human contact in a social or clinical context that enhances learning of health, illness and/or disease, and the role of the health professional. Early: What would traditionally have been regarded as the preclinical phase, usually the first 2 years. Inclusions: All empirical studies (verifiable, observational data) of early experience in the basic education of health professionals, whatever their design or methodology, including papers not in English. Evidence from other health care professions that could be applied to medicine was included. Exclusions: Not empirical; not early; post-basic; simulated rather than 'authentic' experience. Data collection: Careful validation of selection processes. Coding by two reviewers onto an extensively modified version of the standard BEME coding sheet. Accumulation into an Access database. Secondary coding and synthesis of an interpretation. Headline results: A total of 73 studies met the selection criteria and yielded 277 educational outcomes; 116 of those outcomes (from 38 studies) were rated strong and important enough to include in a narrative synthesis of results; 76% of those outcomes were from descriptive studies and 24% from comparative studies. Early experience motivated and satisfied students of the health professions and helped them acclimatize to clinical environments, develop professionally, interact with patients with more confidence and less stress, develop self-reflection and appraisal skill, and develop a professional identity. It strengthened their learning and made it more real and relevant to clinical practice. It helped students learn about the structure and function of the healthcare system, and about preventive care and the role of health professionals. It supported the learning of both biomedical and behavioural/social sciences and helped students acquire communication and basic clinical skills. There were outcomes for beneficiaries other than students, including teachers, patients, populations, organizations and specialties. Early experience increased recruitment to primary care/rural medical practice, though mainly in US studies which introduced it for that specific purpose as part of a complex intervention. Conclusions: Early experience helps medical students socialize to their chosen profession. It. helps them acquire a range of subject matter and makes their learning more real and relevant. It has potential benefits for other stakeholders, notably teachers and patients. It can influence career choices.
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The slow down in the drug discovery pipeline is, in part, owing to a lack of structural and functional information available for new drug targets. Membrane proteins, the targets of well over 50% of marketed pharmaceuticals, present a particular challenge. As they are not naturally abundant, they must be produced recombinantly for the structural biology that is a prerequisite to structure-based drug design. Unfortunately, however, obtaining high yields of functional, recombinant membrane proteins remains a major bottleneck in contemporary bioscience. While repeated rounds of trial-and-error optimization have not (and cannot) reveal mechanistic details of the biology of recombinant protein production, examination of the host response has provided new insights. To this end, we published an early transcriptome analysis that identified genes implicated in high-yielding yeast cell factories, which has enabled the engineering of improved production strains. These advances offer hope that the bottleneck of membrane protein production can be relieved rationally.
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This dissertation reports an investigation of the utility of two intervention programs to facilitate identity formation by way of exploration, one designed from an explicitly self-construction point of view and the other designed from an explicitly self-discovery point of view. The self-construction program was implemented using cognitive skills and orientations derived from Berzonsky (1989), Grotevant (1987), and Kurtines (1999). The self-discovery program was implemented using affective insight development strategies derived from Csikszentmihalyi (1990), Maslow (1968), and Waterman (1990). Three sets of measures were used: (a) cognitive identity measures, (b) affective identity measures, and (c) overall identity measures. Ninety undergraduates from Florida International University completed the intervention. Participants were assigned to one of three intervention conditions (Cognitive, Affective, and Control) and were pretested and posttested on cognitive, affective, and overall identity measures. Intervention strategies were introduced and discussed in the context of specific goals and choices that participants brought to group. Intervention results were then analyzed in terms of the effectiveness of the intervention conditions in promoting their respective developmental domains. The intervention was effective in promoting identity development in comparison to the control condition, with the cognitive condition facilitating cognitive competence and the affective condition facilitating affective insight. Results are discussed in the context of the constructivist and discovery perspectives, as well as in light of the broadened view of exploration offered in this paper. ^
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This dissertation examines the ideological development of the Catholic University Student (JUC) movements in Cuba and Brazil during the Cold War and their organizational predecessors and intellectual influences in interwar Europe. Transnational Catholicism prioritized the attempt to influence youth and in particular, university students, within the context of Catholic nations within Atlantic civilization in the middle of the twentieth century. This dissertation argues that the Catholic university movements achieved a relatively high level of social and political influence in a number of countries in Latin America and that the experience of the Catholic student activists led them to experience ideological conflict and in some cases, rupture, with the conservative ideology of the Catholic hierarchy. Catholic student movements flourished after World War II in the context of an emerging youth culture. The proliferation of student organizations became part of the ideological battlefield of the Cold War. Catholic university students also played key roles in the Cuban Revolution (1957-1959) and in the attempted political and social reforms in Brazil under President João Goulart (1961-1964). ^ The JUC, under the guidance of the Church hierarchy, attempted to avoid aligning itself with either ideological camp in the Cold War, but rather to chart a Third Way between materialistic capitalism and atheistic socialism. Thousands of students in over 70 nations were intensively trained to think critically about pressing social issues. This paper will to place the Catholic Student movement in Cuba in the larger context of transnational Catholic university movements using archival evidence, newspaper accounts and secondary sources. Despite the hierarchy's attempt to utilize students as a tool of influence, the actual lived experience of students equipped them to think critically about social issues, and helped lay a foundation for the progressive student politics of the late 1960s and the rise of liberation theology in the 1970s. ^
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During oncogenesis, cancer cells go through metabolic reprogramming to maintain their high growth rates and adapt to changes in the microenvironment and the lack of essential nutrients. Several types of cancer are dependent on de novo fatty acid synthesis to sustain their growth rates by providing precursors to construct membranes and produce vital signaling lipids. Fatty acid synthase (FASN) catalyze the terminal step of de novo fatty acid synthesis and it is highly expressed in many types of cancers where it’s up-regulation is correlated with cancer aggressiveness and low therapeutic outcome. Many FASN inhibitors were developed and showed potent anticancer activity however, only one inhibitor advanced to early stage clinical trials with some dose limiting toxicities. Using a modified fluorescence-linked enzyme chemoproteomic strategy (FLECS) screen, we identified HS-106, a thiophenopyrimiden FASN inhibitor that has anti-neoplastic activity against breast cancer in vitro and in vivo. HS-106 was able to inhibit both; purified human FASN activity and cellular fatty acid synthesis activity as evaluated by radioactive tracers incorporation into lipids experiments. In proliferation and apoptosis assays, HS-106 was able to block proliferation and induce apoptosis in several breast cancer cell lines. Several rescue experiment and global lipidome analysis were performed to probe the mechanism by which HS-106 induces apoptosis. HS-106 was found to induce several changes in lipids metabolism: (i) inhibit fatty acids synthesis. (ii) Inhibit fatty acids oxidation as indicated by the ability of inhibiting Malonyl CoA accumulation to block HS-106 induced apoptosis and the increase in the abundance of ceramides. (iii) Increase fatty acids uptake and neutral lipids formation as confirmed 14C Palmitate uptake assay and neutral lipids staining. (iv)Inhibit the formation of phospholipids by inhibiting de novo fatty acid synthesis and diverting exogenous fatty acids to neutral lipids. All of these events would lead to disruption in membranes structure and function. HS-106 was also tested in Lapatinib resistant cell lines and it was able to induce apoptosis and synergizes Lapatinib activity in these cell lines. This may be due the disruption of lipid rafts based on the observation that HS-106 reduces the expression of both HER2 and HER3. HS-106 was found to be well tolerated and bioavailable in mice with high elimination rate. HS-106 efficacy was tested in MMTV neu mouse model. Although did not significantly reduced tumor size (alone), HS-106 was able to double the median survival of the mice and showed potent antitumor activity when combined with Carboplatin. Similar results were obtained when same combinations and dosing schedule was used in C3Tag mouse model except for the inability of HS-106 affect mice survival.
From the above, HS-106 represent a novel FASN inhibitor that has anticancer activity both in vivo and in vitro. Being a chemically tractable molecule, the synthetic route to HS-106 is readily adaptable for the preparation of analogs that are similar in structure, suggesting that, the pharmacological properties of HS-106 can be improved.