Angiogenesis is the formation of new blood vessels from existing vasculature. It is a process fundamental to normal development and tissue repair, and is implicated in many pathological conditions. ...The major pro-angiogenic factor is VEGF, for which the major receptor is VEGFR2. Blood vessels are lined with endothelial cells that express VEGFR2 to detect VEGF in surrounding tissue. This detection mediates cell responses to initiate fOlmation of angiogenic sprouts. VEGFR2 belongs to the family of receptor tyrosine kinases. Ligand binding to the extracellular domain results in receptor dimerisation and autophosphorylation of the intracellular kinase domain. This activates multiple downstream signalling cascades, which in the case of VEGFR2 have four main outcomes: proliferation, migration, permeability and survival. Receptor activation is often followed by internalisation and degradation to downregulate signalling pathways. VEGFR2 has unusual trafficking kinetics for a receptor tyrosine kinase because it constitutively internalises and recycles back to the cell surface in the absence of VEGF. It is distributed such that a significant proportion is localised to an intracellular endosomal storage pool. Moreover, the behaviour of VEGFR2 during angiogenesis depends on the location of the endothelial cell within the growing sprout. The importance of this unusual trafficking in relation to signal transduction is poorly understood. My aim was to elucidate how VEGFR2 trafficking controls angiogenic signalling. I worked to identify sorting proteins required for VEGFR2 trafficking. I investigated proteins that are known to mediate the trafficking of other cargoes. Using an ELISA-based screen, I discovered several potential regulators of VEGFR2, including the motor protein myosin Vb. Myosin Vb traffics organelles along actin filaments and has been described in the recycling of many receptors. I used biochemical methods to establish an essential role for myosin Vb in VEGFR2 recycling in unstimulated conditions. I show that myosin Vb depletion impairs vessel formation in an organotypic angiogenesis assay and disrupts phosphorylation of several kinases activated upon VEGF stimulation in endothelial cells. Furthermore, I show that myosin Vb is required for the polarised distribution of VEGFR2 in endothelial cells to enable chemotactic migration towards VEGF. My data suggest that myosin Vb-dependent constitutive trafficking of inactive VEGFR2 is necessary for angiogenesis.
At the end of the twentieth century, the gradual triumph of liberal democracy and capitalism over “really existing socialism” brought to many West Germans not relief but melancholy. Facing what they ...interpreted as the dissipation of radical social and political alternatives, academics and public intellectuals pronounced the death of ideology, of history, and of utopian ambitions. This dissertation asks how West Germans nevertheless found ways to challenge this resignation by giving voice to new, radical hopes for Germany’s future. For their broad popularity and sustained impact, this study traces the grassroots efforts of three groups. First, it follows the Berlin History Workshop, a collection of amateur and professional historians, as they attempted to liberate the process of researching and writing history from the rigid confines German universities. This group sought, instead, to bring the historian’s craft into Berlin’s local neighborhoods in order to enable ordinary Germans to narrate their own histories. Second, this dissertation analyzes the Green Party, which practiced localized plebiscitary policy making in an effort to endow German citizens with greater political agency. The Greens brought this political practice to numerous cultural projects in an effort to democratize German society by democratizing the cultural encounters of its citizens. Third, this project investigates a loosely-connected group of artists who echoed the investments of the historians and politicians by creating art installations with ordinary objects in ordinary spaces that prompted passersby to reevaluate their relationships to the topography of their daily lives. This dissertation argues that, through these groups, everyday Germans adopted a set of cultural practices in the 1980s and ‘90s that not only critiqued established institutions but also crafted new institutions in their place. Their critical practices followed three conventions. First, they championed radical grassroots democracy by giving citizens opportunities to create socially-significant cultural products like museums and monuments. Second, they decentralized the creative process, locating it in the spaces of everyday life in order to make it widely accessible. Finally, they borrowed from the environmental movement the concept of sustainability, which demanded that any alternative to existing society be both enduring and adaptable. These practices put culture to work in realizing a more democratic, more socially-integrated Germany. In doing so, they permitted their practitioners to reclaim utopian hope from the dustbin of historical ideas. These three case studies span Germany’s academic, political, and aesthetic terrain. As such, together they offer evidence that efforts to battle twentieth-century apathy signaled a broad shift in German cultural sensibilities, not an isolated phenomenon. The first three chapters of the dissertation treat each of these groups individually as they began to advocate for new, more democratic geographies of cultural engagement, or “alternative public spheres,” in the early 1980s. Their focus on Germany’s cultural environment made them particularly receptive to the idea of sustainability popularized after the convening of the World Commission on Environment and Development in the middle of the decade. The next three chapters trace their pursuit of sustainability in culture. A sustainable culture, they came to realize, had to regard its projects as part of an ongoing process rather than as static goals: theirs was a renewable, future-oriented cultural movement in the present, or a “sustainable utopia.” Faced with radical changes to the international political landscape and the rapid expansion of their constituencies to include sixteen million East Germans alongside more pedestrian concerns like funding difficulties and interpersonal conflicts, these groups weathered the last decade of the twentieth century with varying success. The study concludes by underscoring the irony that the most durable component of their cultural programs in the wake of German political reunification was their push for cultural decentralization.
Infection with genital human papillomavirus (HPV) may cause anogenital cancers, oropharyngeal cancers, anogenital warts, and respiratory papillomas. Two prophylactic vaccines (a bivalent and a ...quadrivalent vaccine) are now licensed and currently in use in a number of countries. Both vaccines prevent infection with HPV-16 and HPV-18, which together cause approximately 70% of cervical cancers, and clinical trials have demonstrated 90%-100% efficacy in preventing precancerous cervical lesions attributable to HPV-16 and HPV-18. One vaccine also prevents HPV-6 and HPV-11, which cause 90% of genital warts. A growing literature describes associations between psychosocial, interpersonal, organizational, and societal factors that influence HPV vaccination acceptability. This paper summarizes the current literature and presents an integrated perspective, taking into account these diverse influences. The resulting integrated model can be used as a heuristic tool for organizing factors at multiple levels to guide intervention development and future research.
1 Vermont Lung Center, Departments of Medicine and Molecular Physiology and Biophysics, University of Vermont, Burlington, Vermont 05405; 2 Department of Clinical Physiology, Malmö University ...Hospital, Lund University, 20512 Malmö, Sweden; and 3 Departamento de Engenharia Elétrica, Universidade do Estado de Santa Catarina, Joinville, Brazil
Submitted 22 March 2004
; accepted in final form 21 June 2004
To more precisely measure the mechanical properties of the lung periphery in asthma, we have developed a forced oscillation technique that applies a broad-band flow signal through a wedged bronchoscope. We interpreted the data from four healthy and eight mildly asthmatic subjects in terms of an anatomically accurate computer model of the wedged segment. There was substantial overlap in impedance between the two groups, with resistance (R) showing minimal frequency dependence and elastance (E) showing positive and negative frequency dependence across subjects. After direct instillation of methacholine, R rose in both groups, but compared with healthy subjects, the asthmatic subjects displayed upward, parallel shifts in their dose-response curves. The baseline frequency-response patterns of E were enhanced after methacholine. Frequency dependencies of R and E were well reproduced in two normal subjects by a computational model that employed rigid airways connected to constant-phase tissue units but were better reproduced in the other two normal and three asthmatic subjects when the model employed heterogeneous, peripheral airway narrowing and compliant airways. To capture the frequency dependencies of R and E in the remaining five asthmatic subjects, the model was modified by increasing airway wall stiffness. These results indicate that the lung periphery of mildly asthmatic subjects is not well distinguished from that of healthy subjects by measurement of mechanical impedance at baseline, but group differences are seen after challenge with methacholine. Modeling of the response suggests that variable contributions of airway narrowing and wall compliance are operative in determining overall mechanical impedance of the lung periphery in humans with asthma, likely reflecting the functional consequences of airway inflammation and remodeling.
forced oscillation technique; impedance; airway remodeling
Address for reprint requests and other correspondence: D. A. Kaminsky, Pulmonary Disease and Critical Care Medicine, Univ. of Vermont College of Medicine, Given D-302, Burlington, VT 05405 (E-mail: dkaminsk{at}zoo.uvm.edu ).
So should a country have greater latitude to restrict speech in the aftermath of genocide? Which considerations should it take into account in deciding whether and how to limit speech? How can a ...nation struggling to establish the rule of law provide effective checks on the potential misuse of speech restrictions? This article examines these questions by comparing how legal regimes with a broad range of experiences have answered speech questions for themselves, and how their solutions may or may not work for Rwanda. Part I will discuss the 1994 Rwandan genocide, the role that hate speech played in the rise of violence, and the state of the country post-genocide. Part II will provide a comparative analysis of approaches to hate speech in the United States, Germany, Israel, and the European Union (EU) as starting points for a broad discussion on post-conflict speech restrictions. Finally, Part III will expand on elements to consider in crafting post-conflict speech restrictions, explain how different legal regimes have addressed these elements, and suggest ways in which Rwanda could draw on other countries' examples to strike an effective, workable balance between preserving national stability and protecting its citizens' right to free speech. Adapted from the source document.
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During a week-long celebration of science, run under the federally supported National Science Week umbrella, the Catch a Rising Star: women in Queensland research (CaRS) programme flew scientists who ...identify as women to nine regional and remote communities in the Australian State of Queensland. The aim of the project was twofold: first, to bring science to remote and regional communities in a large, economically diverse state; and second, to determine whether media and public engagement provides career advancement opportunities for women scientists. This paper focuses on the latter goal. The data show: (i) a substantial majority (greater than 80%) of researchers thought the training and experience provided by the programme would help develop her career as a research scientist in the future, (ii) the majority (65%) thought the programme would help relate her research to end users, industry partners or stakeholders in the future, and (iii) analytics can help create a compelling narrative around engagement metrics and help to quantify influence. During the week-long project, scientists reached 600 000 impressions on one social media platform (Twitter) using a program hashtag. The breadth and depth of the project outcomes indicate funding bodies and employers could use similar data as an informative source of metrics to support hiring and promotion decisions. Although this project focused on researchers who identify as women, the lessons learned are applicable to researchers representing a diverse range of backgrounds. Future surveys will help determine whether the CaRS programme provided long-term career advantages to participating scientists and communities.
Painter and Collector Allen, Jennifer
Afterall,
10/2004, Volume:
10, Issue:
10
Journal Article
Peer reviewed
Discusses the work of the Berlin-based artist Monika Baer. The author notes her recent interest in maps, comments on the nature of art collecting with reference to the writing of Walter Benjamin, and ...highlights Baer's use of the symbolic image in paintings such as Mit Chen (2004) and Ohne Titel (2003). She argues that Baer's art practice resembles a form of art collecting, examines her use of Easter egg designs in are (2003), and suggests why Baer collects her own works together with reference to Alice Springs (2004; col. illus.) and Land's End (2001).
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BFBNIB, NMLJ, NUK, PNG, UL, UM, UPUK
500.
Perianesthesia Hand-Off Communication Allen, Jennifer; Weaver, Meghan; Witcher, Kenneth
Journal of perianesthesia nursing,
6/2009, Volume:
24, Issue:
3
Journal Article
Peer reviewed
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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