A C-terminally-anchored Golgi protein is inserted into the endoplasmic reticulum and then transported to the Golgi apparatus.

Unlike conventional membrane proteins of the secretory pathway, proteins anchored to the cytoplasmic surface of membranes by hydrophobic sequences near their C termini follow a posttranslational, signal recognition particle-independent insertion pathway. Many such C-terminally-anchored proteins have restricted intracellular locations, but it is not known whether these proteins are targeted directly to the membranes in which they will ultimately reside. Here we have analyzed the intracellular sorting of the Golgi protein giantin, which consists of a rod-shaped 376-kDa cytoplasmic domain followed by a hydrophobic C-terminal anchor sequence. Unexpectedly, we find that giantin behaves like a conventional secretory protein in that it inserts into the endoplasmic reticulum (ER) and then is transported to the Golgi. A deletion mutant lacking a portion of the cytoplasmic domain adjacent to the membrane anchor still inserts into the ER but fails to reach the Golgi, even though this mutant has a stable folded structure. These findings suggest that the localization of a C-terminally-anchored Golgi protein involves at least three steps: insertion into the ER membrane, controlled incorporation into transport vesicles, and retention within the Golgi.

Folate receptors targeted to clathrin-coated pits cannot regulate vitamin uptake.

Potocytosis is an endocytic process that is specialized for the internalization of small molecules. Recent studies on the uptake of 5-methyltetrahydrofolate by the folate receptor have suggested that the glycosyl-phosphatidylinositol anchor on this protein causes it to cluster and be internalized by caveolae instead of coated pits. To test this hypothesis directly, we have constructed a chimeric folate receptor that has the glycosyl-phosphatidylinositol anchor replaced with the transmembrane domain and cytoplasmic tail of the low density lipoprotein receptor. The cells with wild-type receptors delivered 5-methyltetrahydrofolate to the cytoplasm more rapidly than did cells expressing the chimeric receptor. This suggests that efficient delivery to the cytoplasm depends on caveolae. In sharp contrast to cells with wild-type folate receptors, cells internalizing folate by clathrin-coated pits were unable to decrease vitamin uptake when they were either folate replete or confluent.

Forças, momentos e coeficiente de atrito em teste de três pontos e em teste de resistência ao deslizamento com braquetes autoligáveis e fios 0.014\" utilizando um novo dispositivo

O objetivo principal do estudo é comparar o teste em 3 pontos com braquetes com o teste de resistência ao deslizamento utilizando um novo dispositivo que realiza a mensuração simultânea do coeficiente de atrito, das forças e dos momentos nos braquetes de ancoragem e da força de desativação no braquete desalinhado, exercidos por fios ortodônticos. Os objetivos secundários foram desenvolver o dispositivo e comparar, no teste em 3 pontos: (i) a influência, nas grandezas e no coeficiente de atrito cinético, da variação da simetria nas distâncias inter-braquetes, do tipo de braquete de ancoragem (canino ou 2º pré-molar), do deslocamento (3 ou 5mm) do braquete central, do sentido do desalinhamento (vestibular ou lingual) do braquete central e da marca de fio-braquete; (ii) as 3 formas de cálculo do coeficiente de atrito cinético; (iii) os 10 ciclos, para vestibular ou lingual, para verificar se eles são semelhantes ou não entre si. Foram utilizados braquetes autoligáveis (dentes 13, 14 e 15) e fios 0.014\'\' NiTi e CuNiTi das marcas Aditek e Ormco. O teste de resistência ao deslizamento foi realizado no desalinhamento lingual, nos dois deslocamentos e na configuração simétrica. O teste em 3 pontos com braquetes foi realizado no desalinhamento lingual e vestibular, nos dois deslocamentos e na configuração simétrica e assimétrica. Por meio da ANOVA, foram comparados, entre os dois tipos de teste: (A) as grandezas e o coeficiente de atrito e (B) o coeficiente de atrito gerado apenas no braquete de 2º pré-molar. Utilizando-se do mesmo teste estatístico foram comparados, no teste em 3 pontos com braquetes: (A) na configuração simétrica, algumas grandezas e o coeficiente de atrito advindos da variação da marca de fio-braquete, do deslocamento, do desalinhamento e do tipo de braquete; (B) algumas grandezas e o coeficiente de atrito gerados na configuração simétrica e assimétrica; (C) os valores das 3 formas de cálculo do coeficiente de atrito na configuração simétrica; e (D) algumas grandezas e o coeficiente de atrito encontrados nos 10 ciclos. Resultados: (A) a maioria dos valores das grandezas e do coeficiente de atrito gerados pelos dois tipos de teste foram diferentes estatisticamente; (B) o braquete de 2º pré-molar apresentou valores de coeficiente de atrito diferentes entre os dois tipos de teste; (C) na configuração simétrica, as variáveis foram estatisticamente significantes na maioria dos casos para as grandezas analisadas e para o coeficiente de atrito; (D) houve diferença entre a configuração simétrica e assimétrica; (E) o coeficiente de atrito baseado nas duas normais e na força de atrito se aproximou mais da realidade clínica e foi sensível à variação da geometria da relação fio-braquete; e (F) os 10 ciclos para lingual foram semelhantes entre si em 70% dos casos e os 10 ciclos para vestibular foram diferentes em 57% dos casos. Conclusões: o teste em 3 pontos com braquetes é diferente do teste de resistência ao deslizamento; a variação das configurações geométricas e da marca de fio-braquete pode influenciar nos valores das grandezas e do coeficiente de atrito cinético; os 10 ciclos para lingual foram mais semelhantes entre si que os 10 ciclos para vestibular.

Influência do uso de amostras de referência no julgamento perceptivo-auditivo da oclusiva glotal

Objetivos: estabelecer amostras de referência constituídas por gravações julgadas com consenso como representativas da presença ou ausência da oclusiva glotal (OG) e comparar julgamentos perceptivo-auditivos da presença e ausência da OG com e sem o uso de amostras de referência. Metodologia: o estudo foi dividido em duas etapas. Durante a ETAPA 1, 480 frases referentes aos sons oclusivos e fricativos produzidas por falantes com história de fissura labiopalatina foram julgadas por três fonoaudiólogas experientes quanto à identificação da OG. As frases foram julgadas individualmente e aquelas que não apresentaram consenso inicial foram julgadas novamente de maneira simultânea. As amostras julgadas com consenso com relação à presença ou ausência da OG durante produção das seis consoantes-alvo oclusivas e seis fricativas foram selecionadas para estabelecer um Banco de Amostras Representativas da OG. A ETAPA 2 consistiu na seleção de 48 amostras de referência referentes aos 12 sons de interesse e 120 amostras experimentais e, o julgamento dessas amostras experimentais por três grupos de juízes, cada grupo com três juízes com experiências distintas com relação ao julgamento de fala na fissura de palato. Os juízes julgaram as amostras experimentais duas vezes, primeiro sem acesso às referências e, após uma semana, com acesso às referências. Resultados: os julgamentos realizados na ETAPA 1 evidenciaram consenso com relação a OG em 352 amostras, sendo 120 frases com produção adequada para os sons de interesse e 232 representativas do uso da OG. Essas 352 amostras constituíram o Banco de amostras Representativas da OG. Os resultados da ETAPA 2 indicaram que ao comparar a média do valor de Kappa obtida para os 12 sons de interesse em cada um dos grupos nos julgamentos sem e com acesso às amostras de referência a concordância para o grupo 1 (G1) passou de regular (K=0,35) para moderada (K=0,55), para o grupo 2 (G2) passou de moderada (K=0,44) para substancial (K=0,76) e para o grupo 3 (G3) passou de substancial (K=0,72) para quase perfeita (K=0,83). Observou-se que as melhores concordâncias ocorreram para o grupo dos fonoaudiólogos experientes (G3), seguido dos fonoaudiólogos recém-formados (G2), com as piores observadas para o grupo de alunos de graduação (G1). Conclusão: um Banco de Amostras de Referência Representativas da OG foi estabelecido e os julgamentos perceptivo-auditivos de juízes com uso das amostras de referência foram obtidos com concordância inter-juízes e porcentagem de acertos melhor do que os julgamentos sem acesso às referências. Os resultados sugerem a importância do uso de amostras de referência para minimizar a subjetividade da avaliação perceptivo auditiva da fala.

Partial collapse of a ventilated stone façade: Diagnosis and analysis of the anchorage system

The mechanical behaviour of transventilated façades performed by natural stone is necessarily based on the correct execution of both anchoring elements on the stone cladding as in the ones corresponding to the enclosure support, either with brick masonry walls or reinforced concrete walls. In the case studied in the present work, the origin of the damages suffered on the façade of a building located in Alcoy has been analyzed, where the detachment of part of the outer enclosure occurred. This enclosure is a transventilated façade formed by Bateig Blue stone tiles. To this end, “in situ” tests of the anchoring systems employed have been performed, as well as laboratory tests of mechanical characterization of the material and of different types of anchor, comparing these results with those obtained in both the simplified analytical models of continuum mechanics as developed by the Finite Element Method (FEM).

Specific and reversible immobilization of proteins tagged to the affinity polypeptide C-LytA on functionalized graphite electrodes

We have developed a general method for the specific and reversible immobilization of proteins fused to the choline-binding module C-LytA on functionalized graphite electrodes. Graphite electrode surfaces were modified by diazonium chemistry to introduce carboxylic groups that were subsequently used to anchor mixed self-assembled monolayers consisting of N,N-diethylethylenediamine groups, acting as choline analogs, and ethanolamine groups as spacers. The ability of the prepared electrodes to specifically bind C-LytA-tagged recombinant proteins was tested with a C-LytA-β-galactosidase fusion protein. The binding, activity and stability of the immobilized protein was evaluated by electrochemically monitoring the formation of an electroactive product in the enzymatic hydrolysis of the synthetic substrate 4-aminophenyl β-D-galactopyranoside. The hybrid protein was immobilized in an specific and reversible way, while retaining the catalytic activity. Moreover, these functionalized electrodes were shown to be highly stable and reusable. The method developed here can be envisaged as a general, immobilization procedure on the protein biosensor field.

Salem, Marblehead, Beverly and Manchester harbors, Massachusetts, 1806 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: Chart of the harbours of Salem, Marblehead, Beverly, and Manchester : from a survey taken in the years 1804, 5 & 6, by Nathl. Bowditch, AM. AAS. ; assisted by Geo. Burchmore & Wm. Ropes, 3d. ; Hooker & Fairman, sc. Scale [ca. 1:20,500]. The image inside the map neatline is georeferenced to the surface of the earth and fit to the Massachusetts State Plane Coordinate System, Mainland Zone (in Feet) (Fipszone 2001). All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, or other information associated with the principal map. This nautical chart shows coastal features such as lighthouses, rocks, shoals, channels, points, coves, harbors, anchor points, islands, and more. Depths are shown by soundings and shading. Land features include settlements, selected buildings and roads, and more. Relief is shown pictorially. This layer is part of a selection of digitally scanned and georeferenced historic maps of Massachusetts from the Harvard Map Collection. These maps typically portray both natural and manmade features. The selection represents a range of regions, originators, ground condition dates (1755-1922), scales, and purposes. The digitized selection includes maps of: the state, Massachusetts counties, town surveys, coastal features, real property, parks, cemeteries, railroads, roads, public works projects, etc.

Provincetown Harbor, Cape Cod, Massachusetts, 1799 (Raster Image)

This layer is a georeferenced raster image of the historic paper map entitled: This chart of Cape Cod and Harbour is dedicated to the Boston Marine Society by their friend & brother, John Foster Williams. It was published in 1799. Scale [ca. 1:6,450]. Covers Cape Cod from Truro to Provincetown including Provincetown Harbor, Massachusetts. The image inside the map neatline is georeferenced to the surface of the earth and fit to the Massachusetts State Plane Coordinate System, Mainland Zone (in Feet) (Fipszone 2001). All map collar and inset information is also available as part of the raster image, including any inset maps, profiles, statistical tables, directories, text, illustrations, or other information associated with the principal map. This map is a nautical chart showing coastal features such as anchor points, currents, points, inlets, coves, and more. Shows also land features: windmills, lighthouse, and buildings pictorially. Harbor depths are shown by soundings. Includes text "Directions for sailing by Cape-Cod Light-House and into Cape-Harbour." This layer is part of a selection of digitally scanned and georeferenced historic maps of Massachusetts from the Harvard Map Collection. These maps typically portray both natural and manmade features. The selection represents a range of regions, originators, ground condition dates (1755-1922), scales, and purposes. The digitized selection includes maps of: the state, Massachusetts counties, town surveys, coastal features, real property, parks, cemeteries, railroads, roads, public works projects, etc.

Rebalancing the EU-Russia-Ukraine gas relationship. Bruegel Policy Contribution ISSUE 2014/15, DECEMBER 2014

The October 2014 agreement on gas supplies between Russia, Ukraine and the European Union did not resolve the Ukraine-Russia conflict over gas. The differences between parties in terms of objectives, growing mistrust and legacy issues make it unlikely that a long-term stable arrangement will be achieved without further escalation. Without EU pressure and support, Ukraine is likely to enter a new unfavourable gas arrangement with Russia, which could have repercussions beyond the energy sector. Key highlights: To reduce prices and increase the security of imports, the EU as a bloc should redefine its gas relationship with Russia and Ukraine and overcome the diverging interests of EU member states on second-order issues. Implementation of a joint strategy rests on enforcement of EU competition and gas market rules, a strengthened role for the Energy Community and the establishment of a market-based instrument for supply security. For Ukraine, the EU should serve as an anchor for comprehensive gas sector reform. Contingent on Ukraine’s reform efforts, EU financial and technical assistance, the enabling of reverse flows from the EU to Ukraine and pressure on Gazprom, should eventually enable Ukraine to obtain a sustainable gas-supply contract with Russia. This should make a sustainable and mutually beneficial Russia-Ukraine-EU gas relationship possible. However, during the transition, the EU should be prepared for possible frictions.

Russia and Turkey - What does their partnership mean for the EU? EPC Policy Brief, 13 February 2015

Russia and Turkey have, over the past two decades, developed a very constructive relationship across a wide variety of policy areas. Imperial rivals during much of the Cold War, both countries have since then found common interests in matters of energy, trade and even defence. Besides their growing interdependence, it is hard not to notice the similarities between the two leaders of these countries, especially when it comes to the conspiracy mind-set of blaming dissent at home on foreign meddling. But does this mean that Turkey is fundamentally realigning its foreign policy strategy, away from the EU and towards Russia? And is the EU facing the emergence of an “axis of the excluded”? Not so according to Dimitar Bechev. In this Policy Brief, he argues that the ties between Russia and Turkey are driven by pragmatism and realpolitik. Contentious issues – such as the war in Syria - may be insulated from areas of overlapping interest, but deeper examination shows the glue holding the two countries together – their energy interdependence – is slowly weakening. Bechev believes the EU should take advantage of this divergence and try to (re-)anchor Turkey to its own initiatives and policies.

Doença cardiovascular: contribuição do Vascepa®, medicamento de origem marinha, no combate à hipertrigliceridemia

Dissertação para obtenção do grau de Mestre no Instituto Superior de Ciências da Saúde Egas Moniz

Efeitos dos choques de políticas monetária e fiscal sobre as expectativas de inflação no Brasil

In the past few years, uncertainty regarding fiscal situation in Brazil has raised concerns about Central Bank’s ability to anchor inflation expectations. This work examines the impact of monetary and fiscal policy shocks in inflation expectations in Brazil from 2003 to 2015, using VAR models. The results show that unexpected increases in the overnight interest rate lower 12 and 24-months-ahead inflation expectations. However when we reestimate the model using only the late sample (2010-2015), the effects of monetary shocks in inflation expectations are not statistically significant. On the other hand, negative shocks in primary balance expectations have a positive and stronger effect on inflation expectations for recent years. These results suggest that the deanchoring of inflation expectations in Brazil over the past five years is no longer a monetary phenomenon but a fiscal phenomenon.

Sir Thomas Elyots̓ The defence of good women,

"The defence of good women was first published in 1540. The only known copy of this edition is in the Henry E. Huntington library; this copy is here reproduced in a line-for-line and letter-for-letter reprint."--Introd., p. viii.

Of the knowledge which maketh a wise man,

A page-for-page reprint of the Henry E. Huntington library copy of the 1533 edition. cf. Introd.

Pleasant quippes for upstart newfangled gentlewomen,

"This edition is limited to two hundred copies; this is no. 13."