Designed protein tetramer zipped together with a hydrophobic Alzheimer homology: A structural clue to amyloid assembly

Limited solubility and precipitation of amyloidogenic sequences such as the Alzheimer peptide (β-AP) are major obstacles to a molecular understanding of protein fibrillation and deposition processes. Here we have circumvented the solubility problem by stepwise engineering a β-AP homology into a soluble scaffold, the monomeric protein S6. The S6 construct with the highest β-AP homology crystallizes as a tetramer that is linked by the β-AP residues forming intermolecular antiparallel β-sheets. This construct also shows increased coil aggregation during refolding, and a 14-mer peptide encompassing the engineered sequence forms fibrils. Mutational analysis shows that intermolecular association is linked to the overall hydrophobicity of the sticky sequence and implies the existence of “structural gatekeepers” in the wild-type protein, that is, charged side chains that prevent aggregation by interrupting contiguous stretches of hydrophobic residues in the primary sequence.

The United States dominates global investment banking: does it matter for Europe? Bruegel Policy Contribution 2016/06, March 2016

In the aftermath of the global financial crisis, the market share of US investment banks is increasing, while that of their European counterparts is declining. We present evidence that US investment banks are on the verge of taking over pole position in European investment banking. Meanwhile, since 2015, Chinese investment banks have overtaken American and European investment banks in the Asia-Pacific market. Credit rating agencies and investment banks are the gatekeepers of the capital markets. The European supervisory institutions can effectively supervise the European operations of these US-managed players. On the political side, we suggest that the European Commission should continue to view its, albeit declining, banking industry as a strategic sector. The Commission, the European Central Bank and the Bank of England should jointly develop a strategic agenda for the EU-US Regulatory Dialogue. Finally, corporates rely on investment banks to issue new securities. We recommend that the big European corporates should cherish the (few) remaining European investment banks, by giving them at least one place in otherwise US- dominated banking syndicates. That could help to avoid complete dependence on US investment banks.

Examining the Relationship Between Secondary Traumatic Stress and Sickness Absenteeism within 9-1-1 Emergency Call Centers

Thesis (Master's)--University of Washington, 2016-06

Inter-organisational networks, value creation and the process of technology integration in research and development

Traditional methods of R&D management are no longer sufficient for embracing innovations and leveraging complex new technologies to fully integrated positions in established systems. This paper presents the view that the technology integration process is a result of fundamental interactions embedded in inter-organisational activities. Emerging industries, high technology companies and knowledge intensive organisations owe a large part of their viability to complex networks of inter-organisational interactions and relationships. R&D organisations are the gatekeepers in the technology integration process with their initial sanction and motivation to develop technologies providing the first point of entry. Networks rely on the activities of stakeholders to provide the foundations of collaborative R&D activities, business-to-business marketing and strategic alliances. Such complex inter-organisational interactions and relationships influence value creation and organisational goals as stakeholders seek to gain investment opportunities. A theoretical model is developed here that contributes to our understanding of technology integration (adoption) as a dynamic process, which is simultaneously structured and enacted through the activities of stakeholders and organisations in complex inter-organisational networks of sanction and integration.

The role of neurotransmission and the Chopper domain in p75 neurotrophin receptor death signaling

The role of p75 neurotrophin receptor (p75(NTR)) in mediating cell death is now well charaterized, however, it is only recently that details of the death signaling pathway have become clearer. This review focuses on the importance of the juxtamembrane Chopper domain region of p75(NTR) in this process. Evidence supporting the involvement of K+ efflux, the apoptosome (caspase-9, apoptosis activating factor-1, APAF-1, and Bcl-(xL)), caspase-3, c-jun kinase, and p53 in the p75(NTR) cell death pathway is discussed and regulatory roles for the p75(NTR) ectodomain and death domain are proposed. The role of synaptic activity is also discussed, in particular the importance of neutrotransmitter-activated K+ channels acting as the gatekeepers of cell survival decisions during development and in neurodegenerative conditions.

The Opinion Editorial: teaching physiology outside the box

Improving the public understanding of science is an important challenge for the future professional scientists who are our current undergraduates. In this paper, we present a conceptual model that explores the role of mass media as community gatekeepers of new scientific findings. This model frames the benefits for undergraduate science students to learn about media genres so that they can learn to communicate science more effectively to nonprofessional audiences. Informed by this Media Role model, we then detail a novel writing task for undergraduate physiology students, the Opinion Editorial (Op-Ed), and an accompanying Peer Review. The Op-Ed genre was directly taught to the students by a professional journalist. As an assessment task, students presented a recent, highly technical paper as an Op-Ed. This was assessed by both faculty members and peers using a detailed assessment rubric. Most students were able to replicate the features of Op-Eds and attained high grades on their writing tasks. Survey data from final-year physiology students (n = 230) were collected before and after the implementation of the Op-Ed/Peer Review. These indicated that most students were aware of the importance of scientists to effectively communicate their knowledge to nonprofessional audiences, that the Op-Ed writing task was challenging, and that they believed that their ability to write to nonprofessional audiences was improved after explicit teaching and feedback.

A COBERTURA EM POLÍTICA NO WEBJORNALISMO: UM ESTUDO DE CASO DA COBERTURA DA POLÍTICA NAS ELEIÇÕES MUNICIPAIS 2012 EM PALMAS-TOCANTINS

O tema desta dissertação é a cobertura jornalística especializada em política em portais na internet durante as eleições municipais de 2012 em Palmas, capital do estado do Tocantins. A importância do estudo está na abordagem da cobertura política regional em período de campanha eleitoral, pouco estudada em algumas cidades como na capital do Tocantins, e de um pleito recente, ocorrido no ano passado. Além disso, o estado (criado com a divisão de Goiás em 1988) possui um perfil político peculiar, com grupos rivais que se perpetuam no poder. O objetivo principal aqui é analisar as rotinas produtivas nesses suportes digitais em tempos de eleições, e como se dão as relações entre fontes e jornalistas especializados em cobertura política. Como referenciais teóricos são apresentados os conceitos do newsmaking, agenda-setting e gatekeepers no cenário da internet e do jornalismo político. Para a pesquisa houve a necessidade de utilizar abordagens quantitativa e qualitativa, com o uso das técnicas de análise de conteúdo e entrevistas semiabertas (ou semiestruturadas) com os jornalistas responsáveis pelos dois principais portais de notícias especializados em política, T1 Notícias e Portal CT, durante o período eleitoral municipal em 2012. O conteúdo analisado abrange as publicações nos portais no período de 19 de outubro a 08 de novembro, momento em que a campanha eleitoral foi mais acirrada entre os candidatos à prefeitura de Palmas. As principais conclusões são que as rotinas produtivas dos veículos sofreram grandes mudanças, com a criação de editoria especial para a cobertura, além de contratação de profissionais de redação para a produção de um volume expressivo de informações sobre as eleições. Alguns aspectos que influenciaram na produção noticiosa, por se tratar de veículos digitais, foram a necessidade de rapidez na geração da informação, além da concorrência entre os portais - e consequentemente da verba publicitária. A quantidade de fontes oficiais e o prestígio dos jornalistas responsáveis pelos portais estudados também interferiram na cobertura, especialmente porque as relações de poder na cidade se dão de maneira mais intensa e mais próxima. Outro destaque na conclusão é que os portais exploram pouco as características do webjornalismo, restringindo-se basicamente a textos, e deixando de usar a linguagem multimídia, a interatividade e o hipertexto.

Industrial new product planning:a study of the sources of new product ideas and the development of new product proposals in the UK computer industry

This thesis presents a study of the sources of new product ideas and the development of new product proposals in an organisation in the UK Computer Industry. The thesis extends the work of von Hippel by showing how the phenomenon which he describes as "the Customer Active Paradigm for new product idea generation" can be observed to operate in this Industry. Furthermore, this thesis contrasts his Customer Active Paradigm with the more usually encountered Manufacturer Active Paradigm. In a second area, the thesis draws a number of conclusions relating to methods of market research, confirming existing observations and demonstrating the suitability of flexible interview strategies in certain circumstances. The thesis goes on to demonstrate the importance of free information flow within the organisation, making it more likely that sought and unsought opportunities can be exploited. It is shown that formal information flows and documents are a necessary but not sufficient means of influencing the formation of the organisation's dominant ideas on new product areas. The findings also link the work of Tushman and Katz on the role of "Gatekeepers" with the work of von Hippel by showing that the role of gatekeeper is particularly appropriate and useful to an organisation changing from Customer Active to Manufacturer Active methods of idea generation. Finally, the thesis provides conclusions relating to the exploitation of specific new product opportunities facing the sponsoring organisation.

Food Swamps, Obesity & Health Zoning Restrictions on Fast Food Restaurants

Protecting public health is the most legitimate use of zoning, and yet there is minimal progress in applying it to the obesity problem. Zoning could potentially be used to address both unhealthy and healthy food retailers, but lack of evidence regarding the impact of zoning and public opinion on zoning changes are barriers to implementing zoning restrictions on fast food on a larger scale. My dissertation addresses these gaps in our understanding of health zoning as a policy option for altering built, food environments.

Chapter 1 examines the relationship between food swamps and obesity and whether spatial mapping might be useful in identifying priority geographic areas for zoning interventions. I employ an instrumental variables (IV) strategy to correct for the endogeneity problems associated with food environments, namely that individuals may self-select into certain neighborhoods and may consider food availability in their decision process. I utilize highway exits as a source of exogenous variation .Using secondary data from the USDA Food Environment Atlas, ordinary least squares (OLS) and IV regression models were employed to analyze cross-sectional associations between local food environments and the prevalence of obesity. I find even after controlling for food desert effects, food swamps have a positive, statistically significant effect on adult obesity rates.

Chapter 2 applies theories of message framing and prospect theory to the emerging discussion around health zoning policies targeting food environments and to explore public opinion toward a list of potential zoning restrictions on fast-food restaurants (beyond moratoriums on new establishments). In order to explore causality, I employ an online survey experiment manipulating exposure to vignettes with different message frames about health zoning restrictions with two national samples of adult Americans age 18 and over (N1=2,768 and N2=3,236). The second sample oversamples Black Americans (N=1,000) and individuals with high school as their highest level of education. Respondents were randomly assigned to one of six conditions where they were primed with different message frames about the benefits of zoning restrictions on fast food retailers. Participants were then asked to indicate their support for six zoning policies on a Likert scale. Subjects also answered questions about their food store access, eating behaviors, health status and perceptions of food stores by type.

I find that a message frame about Nutrition and increasing Equity in the food system was particularly effective at increasing support for health zoning policies targeting fast food outlets across policy categories (Conditional, Youth-related, Performance and Incentive) and across racial groups. This finding is consistent with an influential environmental justice scholar’s description of “injustice frames” as effective in mobilizing supporters around environmental issues (Taylor 2000). I extend this rationale to food environment obesity prevention efforts and identify Nutrition combined with Equity frames as an arguably universal campaign strategy for bolstering public support of zoning restrictions on fast food retailers.

Bridging my findings from both Chapters 1 and 2, using food swamps as a spatial metaphor may work to identify priority areas for policy intervention, but only if there is an equitable distribution of resources and mobilization efforts to improve consumer food environments. If the structural forces which ration access to land-use planning persist (arguably including the media as gatekeepers to information and producers of message frames) disparities in obesity are likely to widen.

El periodismo deportivo condicionado por la gestión comunicativa de los clubes de fútbol: el caso del FC Barcelona

Las relaciones entre los gabinetes de Comunicación de los clubes de fútbol y los periodistas deportivos se enmarcan en el modelo de Gieber y Johnson (1961) por el que el hecho de que ambos compartan objetivos comunes, donde los gabinetes de Comunicación necesitan que los medios publiquen determinadas informaciones y los periodistas precisan de noticias que publicar, provoca una pérdida de independencia por parte de los periodistas, ya que necesitan a esos departamentos como fuentes. En la actualidad, los departamentos de Comunicación de los clubes de fútbol, como el del FC Barcelona, se han constituido en gatekeepers. Esto ha acentuado las históricas diferencias que existen entre los periodistas y los profesionales de la comunicación corporativa, incrementado por el control informativo de estos departamentos lo que provoca constantes tensiones entre ambos.

TIMESCAPES: an architectural process of memory and adaptation

What if the architectural process of making could incorporate time? All designers who impact the physical environment- consciously and unconsciously are gatekeepers of the past, commentators of the present, and speculators of the future. This project proposes the creation of architecture and adaptive public space that looks to historical memories, foster present day cultural formation, and new alternative visions for the city of the future. The thesis asks what it means to design for stasis and change in a variety of scales- urban, architectural, and detail and arrives at a speculated new neighborhood, institutional buildings, and landscape. Central to this project is the idea of the architect as archeologist, anthropologist, and artist. The project focuses on a rapidly changing part of the city of Fort Worth, Texas and assigns a multipurpose institutional buildings and public space as a method of investigation. The thesis hopes to further architectural discourse about into the role of architecture in the preservation of memory, adaptive potential of public spaces, and the role of time in architecture.

Tapes, Transgression and Mundanity: the participatory engenderment of death metal and grindcore

Since its origins in the early 1980s, the popular rise of extreme metal throughout the globe has been phenomenal. The emergence of extreme metal's most sonically transgressive subgenres of death metal and grindcore between the mid 1980s and the early 1990s, however, was not an easy one. Indeed, during this period, the only way for globally dispersed extreme metal fans and unsigned extreme metal bands to stay musically connected was via the underground practice of tape-trading. The aim of this study is to illuminate the impact of tape-trading upon the global spread of extreme metal. The study will situate the historical context of extreme metal tape-trading by exploring how it emerged, and why it was necessary in the first place. Utilising the concept of 'extreme metal scene', the study will focus on the central scenic discourse of transgression and explore how this was negotiated into the mundane scenic practice of tape-trading. In relation to this, and utilising the concept of participatory culture, the study will further explore how the music arose and spread throughout the globe via the socially networked practice of both musician and non-musician tape-traders in relation to the tape cassette technology itself. Ethnographic interviews were undertaken with both types of traders in order to gain a deeper understanding of the phenomenon in question. The research concludes that the tape-traders were able to challenge the status quo of record company gatekeepers, by facilitating the engenderment and global distribution (including the later commercial distribution) of death metal and grindcore. Such powerfully affective music via its continual global spread, offers as it did for the original tape-traders, a pleasurable and empowering communal/personal space for disempowered people throughout the globe. Further research into extreme metal tape-trading would require deeper exploration into other extreme metal subgenres, especially black metal, tape-traders situated outside of North America and Europe, women tape-traders as well as exploration of the phenomenon after the early 1990s.

Tapes, Transgression and Mundanity: the participatory engenderment of death metal and grindcore

Since its origins in the early 1980s, the popular rise of extreme metal throughout the globe has been phenomenal. The emergence of extreme metal's most sonically transgressive subgenres of death metal and grindcore between the mid 1980s and the early 1990s, however, was not an easy one. Indeed, during this period, the only way for globally dispersed extreme metal fans and unsigned extreme metal bands to stay musically connected was via the underground practice of tape-trading. The aim of this study is to illuminate the impact of tape-trading upon the global spread of extreme metal. The study will situate the historical context of extreme metal tape-trading by exploring how it emerged, and why it was necessary in the first place. Utilising the concept of 'extreme metal scene', the study will focus on the central scenic discourse of transgression and explore how this was negotiated into the mundane scenic practice of tape-trading. In relation to this, and utilising the concept of participatory culture, the study will further explore how the music arose and spread throughout the globe via the socially networked practice of both musician and non-musician tape-traders in relation to the tape cassette technology itself. Ethnographic interviews were undertaken with both types of traders in order to gain a deeper understanding of the phenomenon in question. The research concludes that the tape-traders were able to challenge the status quo of record company gatekeepers, by facilitating the engenderment and global distribution (including the later commercial distribution) of death metal and grindcore. Such powerfully affective music via its continual global spread, offers as it did for the original tape-traders, a pleasurable and empowering communal/personal space for disempowered people throughout the globe. Further research into extreme metal tape-trading would require deeper exploration into other extreme metal subgenres, especially black metal, tape-traders situated outside of North America and Europe, women tape-traders as well as exploration of the phenomenon after the early 1990s.

Actores y factores del contexto institucional que permiten entender la discusión y aprobación de la Ley 975 de 2005

El trabajo de investigación es un estudio de caso que pretende analizar la forma en que factores del contexto institucional y la capacidad de influencia de ciertos actores se reflejan en la discusión y aprobación de la Ley 975 de 2005. Factores del contexto institucional y la capacidad de influencia sobre las posiciones asumidas por los actores políticos y sociales en las diferentes etapas del proceso legislativo y sobre las decisiones que se tomaron para la aprobación de la Ley, en torno a dos elementos fundamentales de ésta que son el delito político y la rebaja de penas. Para ello, se tiene en cuenta el enfoque neo-institucional y el concepto de agencia.