40 research outputs found

    Close and Allosteric Opening of the Polypeptide-Binding Site in a Human Hsp70 Chaperone BiP

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    SummaryBinding immunoglobulin protein (BiP), an essential and ubiquitous Hsp70 chaperone in the ER, plays a key role in protein folding and quality control. BiP contains two functional domains: a nucleotide-binding domain (NBD) and a substrate-binding domain (SBD). NBD binds and hydrolyzes ATP; the substrates for SBD are extended polypeptides. ATP binding allosterically accelerates polypeptide binding and release. Although crucial to the chaperone activity, the molecular mechanisms of polypeptide binding and allosteric coupling of BiP are poorly understood. Here, we present crystal structures of an intact human BiP in the ATP-bound state, the first intact eukaryotic Hsp70 structure, and isolated BiP-SBD with a peptide substrate bound representing the ADP-bound state. These structures and our biochemical analysis demonstrate that BiP has a unique NBD-SBD interface that is highly conserved only in eukaryotic Hsp70s found in the cytosol and ER to fortify its ATP-bound state and promote the opening of its polypeptide-binding pocket

    Attitude towards Workforce Immigration in Latvia

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    Maģistra darba nosaukums ir „Attieksme pret darbaspēka imigrāciju Latvijā”. Kopš Latvija ir ES dalībvalsts, lielāka daļa Latvijas ekonomiski aktīvo iedzīvotāju emigrē uz citām valstīm darba nolūkos, kas, ņemot vērā lielo novecojošo iedzīvotāju īpatsvaru Latvijā, palielina sociālo un ekonomisko slogu, nākotnē apgrūtinās sociālo pabalstu izmaksāšanu un veicinās kopējās labklājības līmeņa samazināšanos valsts ietvaros. Problēmas risināšanai autore izpēta faktorus, kas ietekmē iedzīvotāju attieksmi pret darbaspēka imigrāciju, jo tā ietekmē imigrantu vēlmi atrasties valstī. Darbs iekļauj teorētiskas nodaļas par imigrāciju un to ietekmējošiem faktoriem, attieksmju teoriju analīzi, empīrisko materiālu analīzi par Eiropas un Latvijas iedzīvotāju attieksmi pret darbaspēka imigrāciju, kā arī vadošo imigrācijas ekspertu interviju rezultātus.The title of the diploma paper is "Attitude towards Workforce Immigration in Latvia”. Since Latvia's accession to the EU, a large part of Latvia's economically active population migrates abroad in search of jobs, which, given the rapid ageing of population, increases the social and economical burden, and will impede the payments of social benefits in future, and reduce the total welfare level in the country. Seeking solutions to those problems, the author of the paper has studied the attitude of Latvia’s and European Union’s inhabitants towards workforce immigration. The paper contains chapters of theoretical discourse on migration, on the influencing factors, empirical analysis of materials about the attitude towards workforce immigration in Europe and Latvia, the analysis of the answers gained at interviews with immigration experts

    Rapid Cloning For Protein Crystallography Using Type IIS Restriction Enzymes

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    Recombinant proteins are used routinely in macromolecular crystallographic experiments. Efficiency in cloning thus becomes a valuable resource to a macromolecular crystallographer. The use of type IIS restriction enzymes (outside cutters) concurrent with ligation allows for rapid cloning. A vector can be modified easily to incorporate sites for outside cutters, such as BspQI or BsaI. Critical and unique to our cloning method is the upshift of reaction incubations to 50 °C where the ligase is inactivated while the restriction enzyme is still active. The result is that very low background of undesired cloning intermediates is observed. Multiple DNA molecules can be simultaneously joined with a simplicity and effectiveness that rivals overlap PCR when BsaI is used. Using type IIS enzymes thus provides great control, flexibility, and simplicity in cloning strategies

    Jezik govora, jezik pesmi: Med narečjem, nadnarečjem in standardnim jezikom

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    The article discusses the language switching from dialect to supra-dialect / standard language in three positions of language use in a folklore event, which represents the relationship between the singing of a song, the speech between the informant and the scholar and the adaptation to the different speech positions of both participants in the event. Author finds this on the basis of an analysis of three variants of the folk ballad “Suicide of a Nun” from three dialect environments and one prayer, and an analysis of speech. He also discusses the symbolic meaning of the use of language in the linguistic and social situation and the issue of the identity use of an individual language code.V članku je obravnavano jezikovno preklapljanje iz narečja v nadnarečje oz. standardni jezik v treh položajih rabe jezika v folklornem dogodku. Ta označuje razmerje med petjem pesmi, govorom med informatorjem ali informatorko in spraševalcem ali spraševalko ter prilagajanje obeh različnim govornim položajem v dogodku. Ugotovitve temeljijo na analizi treh variant ljudske balade »Samomor nune« iz treh narečnih okolij in ene molitve ter analize govora. Ob tem avtorica razpravlja še o simbolnem pomenu rabe jezika v jezikovno-socialnem položaju ter vprašanju identitetne rabe obravnavanih jezikovnih kodov

    Introduction to Of This Brave Time

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    Contemporary Irish Documentary Theatre is the first anthology of Irish documentary drama. It features five challenging plays by Irish writers, and one by an international author, interrogating and commenting on crucial events of Irish history and of the diaspora, with introductory essays by established academics. Together these plays represent the most innovative development in contemporary Irish theatre and illuminate the social and political realities of contemporary Ireland.The first two plays, of 2010 and 2013, deal with scandals of clerical and institutional abuse, and use as source material the Ryan Report of 2009, and the documents from the 2008 Irish Bank Guarantee. The next two, of 2014 and 2013, concern interpretations of the most iconic moment of Irish history: the Easter Rising. The first of these is based on published statements of participants in the event and the second on the lived experiences of those in the contemporary Republic whose founding ideals have not been realized . The last two plays, of 2015 and 2016, widen the view to the history of the Irish in the diaspora: one retelling the history of emigration to England based on published research material; and the other tracing Roger Casement's experiences in the Amazon and his subsequent participation in the Easter Rising using extracts from his diaries and other writings.The plays included and discussed are:No Escape by Mary RafteryGuaranteed by Colin MurphyOf This Brave Time by Jimmy MurphyHistory by Grace DyasMy English Tongue, My Irish Heart by Martin LynchThe Two Deaths of Roger Casement by Domingos Nune

    A poética do horror em Amândio Sobral

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    Este trabalho tem a finalidade de pesquisar o restrito campo da literatura do terror no Brasil; para isso, analisamos os efeitos de terror presentes em três contos do autor Amândio Sobral: O homem que matou um morto, A estranha cavalgada de Ivan Palinskye A podridão viva, contos esses presentes na obra Contos Exóticos, publicada em 1934. Para a realização de tal intento, a dissertação está dividida em quatro capítulos. No primeiro deles, Conto: um gênero que diz muito em poucas palavras, analisamos as teorias sobre o conto, a fim de apontarmos as principais características desse gênero. Baseamo-nos, aqui, nas considerações feitas por teóricos como Julio Cortázar, Ricardo Piglia e Edgar Allan Poe. No segundo capítulo, Variações da estética do horror, analisamos o gênero fantástico e sua relação com o insólito, o gótico, o terror, o grotesco e o sublime. Para isso, fizemos uso das teorias de Marcelo Briseno Marques de Melo, Maurício Cesar Menon, Wolfgang Kayser, Tzvetan Todorov e Lainister de Oliveira Esteves. O terceiro capítulo, Amândio Sobral: um texto aparentemente fora do contexto, por seu turno, tem a finalidade de apresentar o autor e seu contexto, bem como apontar algumas de suas predecessoras influências literárias no que concerne ao uso do horror e do fantástico na literatura brasileira, recorrendo, neste aspecto, às reflexões de Antônio Candido, Alfredo Bosi, Randal Johnson e Luís Bueno. No último, Suspense, medo e horror: os contos de Amândio Sobral, apresentamos a análise das obras e as estratégias empregadas pelo autor para gerar o efeito de horrore medo em seus contos, utilizando, para isso, das considerações de H.P. Lovecraft, Alcídes Ribeiro, Gaston Bachelard e Benedito NunesThis work aims to find the restricted terror literature field in Brazil; for this, we analyzed the horror effects present in three tales of the author Amândio Sobral: O homem que matou um morto, A estranha cavalgada de Ivan Palinskyand A podridão viva, these stories present in the work Contos Exóticos, published in 1934. For the realization such intent, the dissertation is divided into four chapters. In the first, Tale: a genre that says a lot in a few words, we analyze the theories of the story in order to point out the main characteristics of this genre. We rely here on considerations made by theorists such as Julio Cortazar, Ricardo Piglia and Edgar Allan Poe. In the second chapter, horror aesthetic variations, we analyze the fantastic genre and its relationship with the unusual, gothic, horror, the grotesque and the sublime. For this we use the theories of Marcelo Briseno Marques de Melo, Maurício Cesar Menon, Wolfgang Kayser, Tzvetan Todorov and Lainister de Oliveira Esteves. The third chapter, Amândio Sobral: a seemingly text out of context, in turn, has the purposeof presenting the author and his context and point out some of its predecessors literary influences regarding the use of the horror and the fantastic in literature Brazil, using this aspect, the reflections of Antonio Candido, Alfredo Bosi, Randal Johnsonand Luis Bueno. At last, Suspense, fear and horror: the tales of Amândio Sobral, we present the analysis of the works and the strategies employed by the author to generate the horror effect and fear in his short stories, using, for this, the H.P. Lovecraft considerations, Alcides Ribeiro, Gaston Bachelard and Benedito Nune

    Evidence of W gamma gamma Production in pp Collisions at root s=8 TeV and Limits on Anomalous Quartic Gauge Couplings with the ATLAS Detector

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    Published by the American Physical Society under the terms of the Creative Commons Attribution 3.0 License. Further distribution of this work must maintain attribution to the author(s) and the published article’s title, journal citation, and DOISCOAP
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