982 resultados para Proteïnes ras
Resumo:
A necessidade de mudança no projeto político-pedagógico das escolas médicas vem sendo discutida, especialmente, em resposta ao amadurecimento da reflexão acerca do perfil do egresso desejado. Reconhece- se que o ensino médico tradicional - centrado, prioritariamente, na transmissão de conhecimentos - tem levado à formação de profissionais despreparados para responder aos agravos à saúde mais encontrados na população. Para tentar mudar esse panorama, vêm sendo privilegiadas, a partir das Diretrizes Curriculares Nacionais do Curso de Graduação em Medicina do Ministério da Educação (MEC), as metodologias ativas de ensino-aprendizagem, entre as quais se destaca a Aprendizagem Baseada em Problemas (ABP), que permite maior participação do estudante na construção do conhecimento. Tal encaminhamento é realizado a partir da inclusão do graduando na comunidade desde os primeiros períodos do curso médico, promovendo a contextualização dos constructos teóricos adquiridos por meio de buscas individuais e do compartilhamento do conhecimento. Desta forma, cria-se uma parceria entre instituições de ensino superior, serviços de saúde e a comunidade, a partir da qual se espera formar médicos com uma visão integral do ser humano, comprometidos com a sociedade.
Resumo:
The study examines the signalling of text organisation in research articles (RA) in French. The work concentrates on a particular type of organisation provided by text sequences, i.e. structures organising text to items of which at least some are signalled by markers of addition or order: First… 0… The third point… In addition… / Premièrement… 0… Le troisième point… De plus… By indicating the way the text is organised, these structures guide the reader in the reading process so that he doesn’t need to interpret the text structure himself. The aim of the work is to study factors affecting the marking of text sequences. Why is their structure sometimes signalled explicitly by markers such as secondly, whereas in other places such markers are not used? The corpus is manually XML-annotated and consists of 90 RAs (~800 000 words) in French from the fields of linguistics, education and history. The analysis highlights several factors affecting the marking of text sequences. First, exact markers (such as fist ) seem to be more frequent in sequences where all the items are explicitly signalled by a marker, whereas additive markers (such as moreover) are used in sequences with both explicitly signalled and unmarked items. The marking of explicitly signalled sequences seems thus to be precise and even repetitive, whereas the signalling of sequences with unmarked items is altogether more vague. Second, the marking of text sequences seems to depend on the length of the text. The longer the text segment, the more vague the marking. Additive markers and unmarked items are more frequent in longer sequences possibly covering several pages, whereas shorter sequences are often signalled explicitly by exact markers. Also the marker types vary according to the sequence length. Anaphoric expressions, such as first, are fairly close to their referents and are used in short sequences, connectors, such as secondly, are frequently used in sequences of intermediate length, whereas the longest sequences are often signalled by constructions composed of an ordinal and a noun acting as a subject of the sentence: The first item is… Finally, the marking of text organisation depends also on the discipline the RA belongs to. In linguistics, the marking is fairly frequent and precise; exact markers such as second are the most used, and structures with unmarked items are less common. Similarly, the marking is fairly frequent in education. In this field, however, it is also less precise than in linguistics, with frequent unmarked items and additive markers. History, on the other hand, is characterised by less frequent marking. In addition, when used, the marking in this field is also less precise and less explicit.
Resumo:
O processo de curtimento do couro gera resíduos com potencial de uso como corretivo e fertilizante, no entanto alguns de seus constituintes são tóxicos quando presentes em elevado teor no solo, o que limita sua utilização nos sistemas de produção. O objetivo deste trabalho foi avaliar as alterações nos atributos químicos de um Cambissolo Húmico e o crescimento e teor de Cr em clones de Eucalyptus urophylla após a adição de doses de lodo de curtume (LCT). O experimento foi realizado em casa de vegetação, no período de março a julho de 2009. Os tratamentos consistiram da adição de doses de lodo de curtume (0; 1,5; 3,0; 4,5; e 6,0 g dm-3) ao solo, que recebeu, de forma complementar, calcário e adubação NPK em dose única. O pH, a condutividade elétrica, a relação de adsorção de sódio e a porcentagem de sódio trocável, relacionadas com a salinidade do solo, aumentaram com o incremento das doses do lodo de curtume, porém os valores observados ficaram abaixo dos níveis salinos. O teor de Cr solúvel no solo, extraído pela água, decresceu linearmente com o aumento das doses de LCT, correlacionando-se negativamente com o pH do solo. O aumento da dose do LCT proporcionou incremento na altura dos clones de Eucalyptus urophylla em até 11,5% em relação à testemunha. A produção de massa das raízes secas decresceu, em média, 28,3%, em relação à testemunha, com a maior dose (6 g dm-3). As plantas de eucalipto, em todos os tratamentos, continham o Cr somente no sistema radicular, e, quanto maior a dose de LCT, maior o teor desse metal nas raízes.
Resumo:
Para avaliar o risco de salinidade e de sodicidade do solo pelo manejo da irrigação, desenvolveu-se estudo comparativo entre os valores de CEes e RAS de área irrigada com os da mata nativa. A investigação ocorreu nos Distritos Irrigados Baixo Acaraú (DIBAU) e Araras Norte (DIPAN), localizados na Bacia do Acaraú. As amostras de solo foram coletadas bimestralmente, de maio/2003 a set./2005, nas camadas de 0-0,30 m; 0,30-0,60 m; 0,60-0,90 m e 0,90-1,20 m, sendo as análises efetuadas no Laboratório de Solo e Água da Embrapa Agroindústria Tropical. Para identificar se os incrementos dos parâmetros estudados eram estatisticamente significativos, aplicou-se o teste de Wilcoxon. Os incrementos de CEes foram maiores no DIPAN, com média de 250%, enquanto no DIBAU, a média atingiu 50%. Em 2004, as precipitações pluviométricas levaram a área irrigada do DIBAU à condição de mata nativa, não ocorrendo o mesmo no DIPAN. Para a RAS, os incrementos médios situaram-se em torno de 200% (DIBAU) e não houve incremento no DIPAN. Portanto, os solos do DIBAU apresentaram maior predisposição à sodicidade, e os do DIPAN, maior risco de salinização. Apesar dos incrementos, os valores da CEes e RAS apresentaram-se inferiores ao limite de classificação de solos salinos e sódicos, respectivamente. No DIBAU, a chuva teve maior influência no processo de lixiviação devido à predominância da textura arenosa dos solos.
Resumo:
Segregering eller segregation är ett fenomen som kan förekomma inom olika områden av samhället. Inom samhällsvetenskaperna kan segregering definieras som det rumsliga åtskiljandet av befolkningsgrupper på urval av ras eller etniskt ursprung, kön, social härkomst, religion, ålder, yrke, osv. Segregering av befolkningsgrupper sker ofta mer eller mindre frivilligt och är motsatsen till integration. Inom partikelteknologi definieras segregering oftast som det rumsliga åtskiljandet av beståndsdelarna i en blandning av olika partiklar. Segregering sker då på urval av bl.a. partiklarnas storlek, densitet, form, elektrostatiska eller mekaniska egenskaper, och kan beskrivas som motsatsen till blandning. Segregeringsmekanismer används för att förklara hur och varför en partikelblandning segregerar samt vad slutresultatet i form av den rumsliga fördelningen av partiklarna blir till följd av att blandningen utsetts för en viss behandling. I denna avhandling har segregering av partikelblandningar och speciellt torra mineralbaserade byggmaterial (t.ex. murbruk) till följd av lagring i siloer studerats. Vid industriell produktion av mineralbaserade byggmaterial används siloer för korttidslagring av slutprodukterna precis innan förpackning. Segregering leder till kraftiga variationer i sammansättningen för partikelströmmen ut ur silon, vilket gör att slutprodukterna inte uppfyller kvalitetskraven och kan därmed inte säljas till kunder. Detta leder till arbetsam och dyr bearbetning (återcirkulation) av produkterna med påföljder för produktionsekonomin samt hållbara utvecklingen. I avhandlingen identifierades de väsentligaste segregeringsmekanismerna för torra mineralbaserade byggmaterial i siloer. Dessutom klargjordes effekterna av materialegenskaper, processbetingelser och siloparametrar. Slutligen behandlas möjliga åtgärder för minskning av partikelsegregering i siloer samt tillämpning av matematiska metoder för simulering av partikelflöden med hjälp av datorer.
Resumo:
A utilização do efluente de esgoto tratado para poupar os corpos d'água utilizados para irrigação tem sido de grande interesse na agricultura, e o uso não regulamentado desta prática pode acarretar mudanças no comportamento físico-químico do solo. Sua prática tem sido de grande interesse em vista da redução da quantidade de água retirada dos mananciais, preservando-os. Objetivou-se, neste trabalho, a avaliação dos atributos físico-químicos de um Latossolo Vermelho-Amarelo após aplicação de água de reúso. O experimento foi realizado em uma condição de casa de vegetação onde foram cultivados dois ciclos da alface-crespa (Lactuca sativa, L) com dois tratamentos, com três repetições cada: testemunhas (água de abastecimento proveniente de poço) e reúso (proveniente de esgoto local). Os resultados mostraram que não ocorreram aumentos em alguns atributos químicos de fertilidade, como ferro, magnésio, zinco, boro, potássio, nitrato, sódio e cálcio; decréscimo nos valores de matéria orgânica e manganês, além de diminuição da condutividade hidráulica e aumento na condutividade elétrica do solo. Observou-se, ainda, redução do pH no solo, além do aumento da RAS e PST. Desta forma, concluiu-se que a utilização de água de reúso para fins agronômicos deve ser de forma racional, monitorando-se, principalmente, a elevação do teor de sais no solo.
Resumo:
A qualidade da água de irrigação é de fundamental importância para não comprometer a qualidade dos produtos e o funcionamento dos equipamentos de irrigação, especialmente quando são diluídos outros compostos. O objetivo deste trabalho foi avaliar a influência do lançamento de efluente de abate de bovinos tratado sobre a qualidade da água para fins de irrigação do Córrego Jurubatuba, Anápolis-GO. As amostras de efluente e água foram obtidas em seis diferentes dias e nos seguintes locais: na descarga do efluente tratado antes do lançamento no córrego -P1, 50 m a montante do ponto de descarga -P2, 50 m a jusante do ponto de descarga -P3 e 120 m a jusante do ponto de descarga -P4. Analisaram-se os sólidos dissolvidos, pH, ferro, dureza, sódio, cálcio, magnésio, manganês, RAS, boro e DBO. Constatou-se risco médio ou alto de entupimento de emissores pelo uso do efluente na irrigação localizada, quando foram considerados pH, sólidos dissolvidos, ferro, dureza e manganês. A água dos locais avaliados no Córrego Jurubatuba apresentou risco médio de entupimento e restrição de uso moderada em relação a problemas de infiltração de água no solo. Em todos os pontos avaliados, as concentrações de DBO foram superiores aos limites para irrigação de vegetais consumidos in natura e cozidos.
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This overview examines some selected genetic mechanisms of cancer development. Strong evidence has been accumulated suggesting that alteration in either the struture or activity of proto-oncogene contributes to the development and for the maintenance of the malignant phenotype. Many factors are known to interfere with both normal and pathological controls of growth and differentiation of thyroid cells. Among them, some are oncogenes, like those encoding g-proteins (ras, gsp, TSH-R), encoding thyrosino kinases receptors (RET, trk, c-met, c-erb, BRAF) and encoding nuclear proteins (c-myc, e-fós). Others are anti-oncogenes (p53, p15, RB), by loss of the growth suppression ativity of the suppressive gene. Cancer cell invasion and metastasis are the major causes of morbidity and mortality in cancer patients. Many genes are involved in the mechanism of invasion and metastasis of thyroid tumors, like Nis, b-catenina, E-caderina, galectina-3, GLUT, telomerase, VEGT, nm-23. All these oncogenes, antioncogenes and tumor invasion and metastasis-related genes are analysed. Several clinical and prognostic factors have been proposed to identify patients at risk for the development of metastasis and death. The role of molecular genetics in this issue is discussed. However, other studies are needed to validate molecular alterations as an independent prognostic factor in thyroid cancer.
Resumo:
Neurofibromatosis type 1 (NF1) is an autosomal dominant cancer predisposition syndrome that affects about 1 in 3500 individuals worldwide. NF1 is caused by mutations in the NF1 gene that encodes the tumor suppressor protein neurofibromin, an inactivator of the Ras oncogene. The hallmarks of NF1 include pigmentary lesions of the skin, Lisch nodules of the iris and cutaneous neurofibromas. Cutaneous neurofibromas are benign tumors composed of all the cell types of normal peripheral nerve. The traditional view of neurofibroma development has been that cutaneous neurofibromas arise from the disruption of the small nerve tributaries of the skin and subsequent proliferation of the resident cells. The second hit mutation in the NF1 gene has been considered as a prerequisite for neurofibroma development. The second hit is detectable in a subpopulation of primary Schwann cells cultured from neurofibromas. This thesis challenges the traditional concept of neurofibroma development. The results show that cutaneous neurofibromas are intimately associated with hair follicular structures and contain multipotent precursor cells (NFPs), suggesting that neurofibromas may arise from the multipotent cells which reside in hair follicles. Furthermore, this study presents that neurofibroma-derived Schwann cells that harbor bi-allelic inactivation in the NF1 gene express HLA class II genes and may act as nonprofessional antigen presenting cells. The CD4- and FoxP3-positive cells detected in cutaneous neurofibromas suggest that these cells may represent regulatory T cells (Tregs) which interact with HLA II –positive cells and aid the tumor cells in hiding from the immune system and are thus mediators of immune tolerance. This thesis also investigated neurofibroma development in the oral cavity and the use of different biomarkers to characterize cellular differentiation in neurofibromas. The results revealed that oral neurofibromas are not rare, but they usually appear as solitary lesions contrary to multiple cutaneous neurofibromas and present high heterogeneity within and between tumors. The use of class III beta-tubulin as a marker for neuronal differentiation led to an unexpected finding showing that multiple cell types express class III beta-tubulin during mitosis. The increased understanding of the multipotency of tumor cells, cellular differentiation and ability to hide from immune system will aid in the development of future treatments. Specifically, targeting Tregs in NF1 patients could provide a novel therapeutic approach to interfere with the development of neurofibromas.
Resumo:
Då aktivister i den sydafrikanska organisationen Treatment Action Campaign - TAC- demonstrerar för tillgång till bromsmediciner för den fattiga delen av världen, iklädda T-skjortor med texten "HIV-POSITIV", är de offer samtidigt som de är globala aktörer för en rättvisare värld. Denna typ av aktivism, och särskilt mobiliseringen av kvinnor som lever med hiv och kämpar för tillgång till bromsmediciner, utmanar aktuell, hälso- och hiv-forskning. Vidare kastar hiv-aktivismen ljus på globaliseringens effekter på sjukdom och hälsa. TAC är en hälsorörelse som fokuserar på hiv på såväl ett personligt, nationellt som globalt plan. Genom sitt breda perspektiv förskjuter TAC frågan om hiv från att handla om individuell sjukdom till att beröra ett brett spektrum av politiska frågor. Studien "Long Live! HIV-aktivism, knowledge and power", som grundar sig på ett rikt etnografisk material insamlat i Sydafrika under åren 200-2006, visar hur hiv-aktivisterna utmanar dikotomier mellan socialt och medicinskt, mellan behandling och prevention samt mellan aktör och offer. I TAC:s arbete dekonstrueras också de ofta skarpa konstrasterna mellan expert- och lekmannakunskap, eftersom organisationen belyser hur läkare, patienter och aktivister kan samarbeta för en fungerande hälsovård. Studien granskar hur TAC-aktivister, som lever med hiv, agerar som globala aktörer i sitt arbete för förändring. Studien visar vidare hur TAC-aktivister utmanar hur hiv-prevention och -behandling sätts i motsatsförhållande till varandra och hävdar att man inte kan ha det ena utan det andra. Man kan säga att aktivisternas kritik av hälsopolitik synliggör hur teorier om hälsa och sjukdom, måste ta i beaktande det komplexa förhållandet mellan kön, ras, klass och globala maktstrukturer.
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The integrin family of transmembrane receptors are important for cell-matrix adhesion and signal transmission to the interior of the cell. Integrins are essential for many physiological processes and defective integrin function can consequently result in a multitude of diseases, including cancer. Integrin traffic is needed for completion of cytokinesis and cell division failure has been proposed to be an early event in the formation of chromosomally aberrant and transformed cells. Impaired integrin traffic and changes in integrin expression are known to promote invasion of malignant cells. However, the direct roles of impaired integrin traffic in tumorigenesis and increased integrin expression in oncogene driven invasion have not been examined. In this study we have investigated both of these aspects. We found that cells with reduced integrin endocytosis become binucleate and subsequently aneuploid. These aneuploid cells display characteristics of transformed cells; they are anchorage-independent, resistant to apoptosis and invasive in vitro. Importantly, subcutaneous injection of the aneuploid cells into athymic nude mice produced highly malignant tumors. Through gene expression profiling and analysis of integrin-triggered signaling pathways we have identified several molecules involved in the malignancy of these cells, including Src kinase and the transcription factor Twist2. Thus, even though chromosomal aberrations are associated with reduced cell fitness, we show that aneuploidy can facilitate tumor evolution and selection of transformed cells. Invasion and metastasis are the primary reason for deaths caused by cancer and the molecular pathways responsible for invasion are therefore attractive targets in cancer therapy. In addition to integrins, another major family of adhesion receptors are the proteoglycans syndecans. Integrins and syndecans are known to signal in a synergistic manner in controlling cell adhesion on 2D matrixes. Here we explored the role of syndecans as α2β1 integrin co-receptors in 3D collagen. We show that in breast cancer cells harbouring mutant K-Ras, increased levels of integrins, their co-receptors syndecans and matrix cleaving proteases are necessary for the invasive phenotype of these cells. Together, these findings increase our knowledge of the complicated changes that occur during tumorigenesis and the pathways that control the ability of cancer cells to invade and metastasize.
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Uskelanjoki virtaa Salon kaupungin läpi ja varsinkin jääpato tulvatilanteissa tulvavedenkorkeudet uhkaavat nousta maa-alueille. Tässä työssä tutkittiin valittujen tulvasuojelutoimenpiteiden vaikutuksia tulvavedenkorkeuksiin Uskelanjoessa sekä Salon kaupungin keskusta-alueella. Tavoitteena oli löytää Uskelanjoen tulvimisen ehkäisyyn kustannustehokas ratkaisu. Työssä mallinnettiin Uskelanjoen vedenkorkeuksia yksidimensionaalisesti käyttäen HEC-RAS -mallia. Mallinnus suoritettiin mitoitustulvalla tulvasuojelutoimenpiteille, jotka olivat jäidenpidätysrakennelmien rakentaminen, ruoppaus, pengerrys sekä näiden vaihtoehtojen yhdistelmät. Mallinnuksesta saatujen tulvavedenkorkeuksien avulla laadittiin tarkastellulta uomaosuudelta tulvavaarakartat sekä tulvavahinkoarviot. Näiden tietojen pohjalta voitiin vaihtoehtojen hyötyjä vertailla käyttämällä kustannus-hyötyanalyysia. Kustannus-hyötyanalyysin tuloksista havaittiin, että jäidenpidätysrakennelmat osoittautuivat parhaaksi tulvasuojeluvaihtoehdoksi Uskelanjoessa. Muutkin työssä tutkitut vaihtoehdot osoittautuivat kannattaviksi. Epävarmuuden kumuloituminen vedenkorkeuksien mallinnuksesta hyötyjen ja haittojen arviointiin luo oman epävarmuutensa tässä työssä laskettuihin arvoihin. Tätä epävarmuutta on tutkittu työssä käyttämällä herkkyysanalyysia. Herkkyysanalyysin tuloksia tarkastelemalla jäidenpidätysrakennelmien rakentaminen osoittautui kaikkein riskivapaimmaksi vaihtoehdoksi Uskelanjoen tulvasuojelussa.
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Realizou-se um levantamento das plantas daninhas de mandiocais na região Mineradora de Diamantina (Alto do Jequitinhonha) em Minas Gerais, avaliando-se a composição florística e a estrutura da flora daninha. Percorreram-se os municípios mais representativos desta microregião - Carbonita, Itamarandiba e Capelinha - amostrando as lavou ras indicadas pelos técnicos da EMATER - Empresa de Assistência Técnica e Extensão Rural, coletando e anotando o grau de abundância e a frequência das espécies invasoras, as quais, posteriormente, foram identificadas e na sua maioria depositadas no Herbarium ESAL, da Escola Superior de Agricultura de Lavras, MG. Constatou-se a presença de 45 espécies pertencentes a 19 famílias, sendo 16 dicotiledôneas, 2 monocotiledôneas e 1 pteridóphyta. Destacaram-se as famílias Compositae, Gramineae, Malvaceae, Leguminosae, Rubiaceae e Convolvulaceae e as espécies Acanthospermum australe, Sida rhombifolia e Borreria alata.
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Information gained from the human genome project and improvements in compound synthesizing have increased the number of both therapeutic targets and potential lead compounds. This has evolved a need for better screening techniques to have a capacity to screen number of compound libraries against increasing amount of targets. Radioactivity based assays have been traditionally used in drug screening but the fluorescence based assays have become more popular in high throughput screening (HTS) as they avoid safety and waste problems confronted with radioactivity. In comparison to conventional fluorescence more sensitive detection is obtained with time-resolved luminescence which has increased the popularity of time-resolved fluorescence resonance energy transfer (TR-FRET) based assays. To simplify the current TR-FRET based assay concept the luminometric homogeneous single-label utilizing assay technique, Quenching Resonance Energy Transfer (QRET), was developed. The technique utilizes soluble quencher to quench non-specifically the signal of unbound fraction of lanthanide labeled ligand. One labeling procedure and fewer manipulation steps in the assay concept are saving resources. The QRET technique is suitable for both biochemical and cell-based assays as indicated in four studies:1) ligand screening study of β2 -adrenergic receptor (cell-based), 2) activation study of Gs-/Gi-protein coupled receptors by measuring intracellular concentration of cyclic adenosine monophosphate (cell-based), 3) activation study of G-protein coupled receptors by observing the binding of guanosine-5’-triphosphate (cell membranes), and 4) activation study of small GTP binding protein Ras (biochemical). Signal-to-background ratios were between 2.4 to 10 and coefficient of variation varied from 0.5 to 17% indicating their suitability to HTS use.
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There is increasing evidence that angiotensin-(1-7) (Ang-(1-7)) is an endogenous biologically active component of the renin-angiotensin system (RAS). In the present study, we investigated the effects of Ang-(1-7) on reperfusion arrhythmias in isolated rat hearts. Isolated rat hearts were perfused with two different media, i.e., Krebs-Ringer (2.52 mM CaCl2) and low-Ca2+ Krebs-Ringer (1.12 mM CaCl2). In hearts perfused with Krebs-Ringer, Ang-(1-7) produced a concentration-dependent (27-210 nM) reduction in coronary flow (25% reduction at highest concentration), while only slight and variable changes in contraction force and heart rate were observed. Under the same conditions, angiotensin II (Ang II; 27 and 70 nM) produced a significant reduction in coronary flow (39% and 48%, respectively) associated with a significant increase in force. A decrease in heart rate was also observed. In low-Ca2+ Krebs-Ringer solution, perfusion with Ang-(1-7) or Ang II at 27 nM concentration produced similar changes in coronary flow, contraction force and heart rate. In isolated hearts perfused with normal Krebs-Ringer, Ang-(1-7) produced a significant enhancement of reperfusion arrhythmias revealed by an increase in the incidence and duration of ventricular tachycardia and ventricular fibrillation (more than 30-min duration). The facilitation of reperfusion arrhythmias by Ang-(1-7) was associated with an increase in the magnitude of the decreased force usually observed during the post-ischemic period. The effects of Ang-(1-7) were abolished in isolated rat hearts perfused with low-Ca2+ Krebs-Ringer. The effect of Ang II (27 nM) was similar but less pronounced than that of Ang-(1-7) at the same concentration. These results indicate that the heart is a site of action for Ang-(1-7) and suggest that this heptapeptide may be involved in the mediation of the cardiac effects of the RAS