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Search Results: 1 - 10 of 168576 matches for " Kari E. Hacker "
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Development and Characterization of a Reverse Genetic System for Studying Dengue Virus Serotype 3 Strain Variation and Neutralization
William B. Messer,Boyd Yount,Kari E. Hacker,Eric F. Donaldson,Jeremy P. Huynh,Aravinda M. de Silva ,Ralph S. Baric
PLOS Neglected Tropical Diseases , 2012, DOI: 10.1371/journal.pntd.0001486
Abstract: Dengue viruses (DENV) are enveloped single-stranded positive-sense RNA viruses transmitted by Aedes spp. mosquitoes. There are four genetically distinct serotypes designated DENV-1 through DENV-4, each further subdivided into distinct genotypes. The dengue scientific community has long contended that infection with one serotype confers lifelong protection against subsequent infection with the same serotype, irrespective of virus genotype. However this hypothesis is under increased scrutiny and the role of DENV genotypic variation in protection from repeated infection is less certain. As dengue vaccine trials move increasingly into field-testing, there is an urgent need to develop tools to better define the role of genotypic variation in DENV infection and immunity. To better understand genotypic variation in DENV-3 neutralization and protection, we designed and constructed a panel of isogenic, recombinant DENV-3 infectious clones, each expressing an envelope glycoprotein from a different DENV-3 genotype; Philippines 1982 (genotype I), Thailand 1995 (genotype II), Sri Lanka 1989 and Cuba 2002 (genotype III) and Puerto Rico 1977 (genotype IV). We used the panel to explore how natural envelope variation influences DENV-polyclonal serum interactions. When the recombinant viruses were tested in neutralization assays using immune sera from primary DENV infections, neutralization titers varied by as much as ~19-fold, depending on the expressed envelope glycoprotein. The observed variability in neutralization titers suggests that relatively few residue changes in the E glycoprotein may have significant effects on DENV specific humoral immunity and influence antibody mediated protection or disease enhancement in the setting of both natural infection and vaccination. These genotypic differences are also likely to be important in temporal and spatial microevolution of DENV-3 in the background of heterotypic neutralization. The recombinant and synthetic tools described here are valuable for testing hypotheses on genetic determinants of DENV-3 immunopathogenesis.
VHL Type 2B Mutations Retain VBC Complex Form and Function
Kathryn E. Hacker, Caroline Martz Lee, W. Kimryn Rathmell
PLOS ONE , 2008, DOI: 10.1371/journal.pone.0003801
Abstract: Background von Hippel-Lindau disease is characterized by a spectrum of hypervascular tumors, including renal cell carcinoma, hemangioblastoma, and pheochromocytoma, which occur with VHL genotype-specific differences in penetrance. VHL loss causes a failure to regulate the hypoxia inducible factors (HIF-1α and HIF-2α), resulting in accumulation of both factors to high levels. Although HIF dysregulation is critical to VHL disease-associated renal tumorigenesis, increasing evidence points toward gradations of HIF dysregulation contributing to the degree of predisposition to renal cell carcinoma and other manifestations of the disease. Methodology/Principal Findings This investigation examined the ability of disease-specific VHL missense mutations to support the assembly of the VBC complex and to promote the ubiquitylation of HIF. Our interaction analysis supported previous observations that VHL Type 2B mutations disrupt the interaction between pVHL and Elongin C but maintain partial regulation of HIF. We additionally demonstrated that Type 2B mutant pVHL forms a remnant VBC complex containing the active members ROC1 and Cullin-2 which retains the ability to ubiquitylate HIF-1α. Conclusions Our results suggest that subtypes of VHL mutations support an intermediate level of HIF regulation via a remnant VBC complex. These findings provide a mechanism for the graded HIF dysregulation and genetic predisposition for cancer development in VHL disease.
Using Appreciative Inquiry as a Tool to Instigate Transformational Change in Recruiting and Developing Women Faculty in STEM Disciplines
Jill E. Nemiro,Barbara Hacker,Mary Lucero Ferrel,Ruth Guthrie
International Journal of Gender, Science and Technology , 2009,
Abstract: The intent of Cal Poly Pomona's (CPP) NSF ADVANCE program is to create a university-wide system of recruitment and career development that will enable women faculty in STEM disciplines to be successful and advance into leadership positions. To begin the organizational transformation at CPP, eight Appreciative Inquiry focus groups were held with tenure-track and tenured faculty in the Colleges of Science and Engineering, with the goal of ascertaining current strengths in recruitment and career development efforts for new STEM female faculty at CPP. Findings revealed an array of recruitment strategies utilized to solicit good applicant pools, and career development practices that have assisted female faculty during the tenure and promotion process. Focus group participants also designed useful actions for further improvement of the recruiting and career development efforts for women STEM faculty at CPP. Out of the focus group findings, a variety of best practices for recruiting and developing women faculty in STEM disciplines are suggested.
De l’économie du don à l’économie de l’échange en Europe. L’amélioration de la situation de l’usager au dépens de l’administration
Violaine Hacker
Pyramides : Revue du Centre d'Etudes et de Recherches en Administration Publique , 2011,
Abstract: L’Union européenne tente de trouver un compromis entre la libéralisation du Marché unique et la conception fran aise duguiste du service public. De nombreux projets européens envisagent d’améliorer la relation entre l’usager et l’administration. La Commission européenne s’inspire notamment des administrations nationales pour améliorer la qualité des services rendus. Or, la notion de service public diffère selon les états membres. La notion d’usager devient inconsistante en droit communautaire. Les nouveaux moyens qui lui sont reconnus lui permettent d’améliorer sa situation mais ont pour contrepartie une aggravation de la situation des services publics. L’usager européen, considéré comme un administré-consommateur-client du service public, bouleverse les équilibres de l’économie du don . L’autorité publique de l’agent administratif est alors mise à mal par le droit à la bonne administration . La relation de l’usager-consommateur avec le service public étant devenue subjective, il dispose d’une légitimité différente. Cela traduit l’évolution de l’économie du don vers une économie d’échange au détriment de l’agent du service public.
Modernidad, búsqueda de sentido y resistencias más allá de la hermenéutica del poder
Andreas HACKER
Relaciones Internacionales , 2012,
Abstract: Review Essay de :Karatzogianni, Athina y Robinson, Andrew. Power, Resistance and Conflict in the Contemporary World: Social movements, networks and hierarchies, Routledge, Nueva York, 2010, 324 páginas.La di, Zaki. Un monde privé de sens, Fayard, Paris, 1994, 333 páginas.Shilliam, Robbie (ed.). International Relations and Non-Western Thought: Imperialism, colonialism and investigations of global modernity, Routledge, Nueva York, 2011, 272 páginas.
The television, an instrument old-fashioned or critical for the future of the European Union ?
Violaine HACKER
Essachess : Journal for Communication Studies , 2011,
Abstract: In a globalized information society, the institutional machinery - willing to promote media policy in the framework of the “knowledge economy” - may stand only wishful-thinking, if media literacy is not utilized as a boon for citizens facing new forms of Medias. Communication on TV in the public sphere is no longer located in the industrial era, described by J. Habermas with his notion of “discursive democracy”. In a more complex and subject to conflict public space, policy-makers have to integrate and manage contradictions as regards the economic vision of global public goods and the ethical vision of the common good. In a competitive industrial environment, the notion of cultural diversity - seen in Europe as a common good (before the WTO and UNESCO) - is supposed to combine the promotion of European citizenship, to respect local identities and to implement national industries in a global context. The EU tries timidly to fit into globalization as a soft power in order to collude with new cultural players, but remains a fragmented power among nations searching for a direction.
Safety and tolerability of bosentan in the management of pulmonary arterial hypertension
Kari E Roberts, Ioana R Preston
Drug Design, Development and Therapy , 2009, DOI: http://dx.doi.org/10.2147/DDDT.S3786
Abstract: fety and tolerability of bosentan in the management of pulmonary arterial hypertension Review (6283) Total Article Views Authors: Kari E Roberts, Ioana R Preston Published Date March 2009 Volume 2009:3 Pages 111 - 118 DOI: http://dx.doi.org/10.2147/DDDT.S3786 Kari E Roberts, Ioana R Preston Pulmonary, Critical Care and Sleep Medicine, Tufts Medical Center, Boston, Massachusetts, USA Abstract: Endothelin receptor antagonism has emerged as an important therapeutic approach in pulmonary arterial hypertension (PAH). Bench to bedside scientific research has clearly shown that endothelin-1 (ET-1) is over-expressed in several forms of pulmonary vascular disease and plays an important pathogenetic role in the development and progression of PAH. Oral endothelin receptor antagonists (ERAs) have been shown to improve exercise capacity, functional status, pulmonary hemodynamics, and delay the time to clinical worsening in several randomized placebo-controlled trials. Bosentan, the first oral ERA, was approved in 2001 and since that time it has established a strong record of safety and efficacy in PAH. More recently, two additional ERAs, ambrisentan and sitaxsentan, have been approved for use. The objective of this review is to evaluate the available evidence supporting the efficacy, pharmacology, safety and tolerability, and patient-focused perspectives for bosentan, the first approved ERA for PAH. Ongoing and forthcoming randomized trials are also highlighted including the application of bosentan in combination with other PAH therapies.
Safety and tolerability of bosentan in the management of pulmonary arterial hypertension
Kari E Roberts,Ioana R Preston
Drug Design, Development and Therapy , 2009,
Abstract: Kari E Roberts, Ioana R PrestonPulmonary, Critical Care and Sleep Medicine, Tufts Medical Center, Boston, Massachusetts, USAAbstract: Endothelin receptor antagonism has emerged as an important therapeutic approach in pulmonary arterial hypertension (PAH). Bench to bedside scientific research has clearly shown that endothelin-1 (ET-1) is over-expressed in several forms of pulmonary vascular disease and plays an important pathogenetic role in the development and progression of PAH. Oral endothelin receptor antagonists (ERAs) have been shown to improve exercise capacity, functional status, pulmonary hemodynamics, and delay the time to clinical worsening in several randomized placebo-controlled trials. Bosentan, the first oral ERA, was approved in 2001 and since that time it has established a strong record of safety and efficacy in PAH. More recently, two additional ERAs, ambrisentan and sitaxsentan, have been approved for use. The objective of this review is to evaluate the available evidence supporting the efficacy, pharmacology, safety and tolerability, and patient-focused perspectives for bosentan, the first approved ERA for PAH. Ongoing and forthcoming randomized trials are also highlighted including the application of bosentan in combination with other PAH therapies.Keywords: bosentan, endothelin receptor antagonists, pulmonary arterial hypertension
Division of Labour and Self-Reported Mental Requirements in Human Services: Retail Sale Jobs  [PDF]
Ulrike Pietrzyk, Sarah Rodehacke, Winfried Hacker
Psychology (PSYCH) , 2014, DOI: 10.4236/psych.2014.510135
Abstract:

Significant associations between self-reported “whole units” of work and self-reported mental task requirements as well as personal outcomes are well known. Also of interest is, however, whether a significant association also exists between the underlying objective assignment of tasks, i.e. the division of labour, and self-reported mental requirements. Such an association would represent a concrete starting point for job design or redesign. We analyzed this question for retail sale jobs as an example of the numerous human service jobs, which usually consist of customer- and object-centred tasks. The study (N = 558 employees) evaluated the potential association between documented assignments of customer-centred and goods-centred activities and employees’ perceived mental requirements, skill utilisation, and learning on the job, as well as mental difficulties. A significant association of moderate effect size between the objective division of labour and self-reported mental job requirements was shown. Theoretical and practical consequences of this association are also discussed.

A collaborative narrative inquiry: Two teacher educators learning about narrative inquiry
Gary Barkhuizen,Penny Hacker
Per Linguam : A Journal of Language Learning , 2011, DOI: 10.5785/25-1-25
Abstract: With its capacity to unharness the power of narrative to promote meaning-making of lived experience, narrative inquiry is developing as a credible approach to research in several areas in the field of language teaching (Johnson, 2006). This article tells the story of two narrative researchers working in language teacher education who engaged in a collaborative narrative inquiry as both participants and inquirers, in order to learn more about narrative inquiry. The ‘bounded’ nature of their inquiry design provided a feasible way for them to explore their focus of research (i.e. their learning about narrative inquiry), and led them, through an iterative and reflexive process of analysing their narrative data, to formulate what they believe are essential ingredients of principled narrative inquiry work. Four narrative inquiry variables became the scaffolding which enabled them to answer their research questions, and are offered here as a heuristic for teaching practitioners, whether they be teachers, teacher educators or researchers, to guide them in narrative inquiries into their own work.
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