2,373 research outputs found
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Small cities for a small country: Sustaining the cultural renaissance?
Copyright @ 2006 RoutledgeThis chapter explores the implications for smaller cities of adopting culture-led
regeneration strategies. It is suggested that there is a divergence between cultural
planning for long term sustainable urban cultural renaissance and culture-led
makeovers which rely on externally orientated projects devised to draw in new
visitors, residents and enterprises. Drawing on evidence from Sheffield, an industrial
city in South Yorkshire, northern England, it is suggested that small cities by thinking
big, have been seduced into entering a culture-led city competition in which the
stakes are high and the prospects of success limited
Recommended from our members
Rich mix cities: From multicultural experience to cosmopolitan engagement
Copyright @ 2004 Museum Tusculanum Press and ScanOC
Evaluating Conservation Effectiveness and Adaptation in Dynamic Landscapes
Rissman talks about evaluating conservation easement effectiveness requires interdisciplinary research that reaches beyond legal analysis to examine how easements influence human behaviors, which subsequently influence environmental conditions. Conservation easement effectiveness is not a fixed target, but is influenced over time by social and ecological landscape change. The promise of perpetuity is central to the appeal of conservation easements within the conservation movement
Pitting and film thickness in rolling contact
Imperial Users onl
Bridging the Gap Between Traditional Metadata and the Requirements of an Academic SDI for Interdisciplinary Research
Metadata has long been understood as a fundamental component of any Spatial Data Infrastructure, providing information relating to discovery, evaluation and use of
datasets and describing their quality. Having good metadata about a dataset is fundamental to using it correctly and to understanding the implications of issues such as missing data or incorrect attribution on the results obtained for any analysis carried out.
Traditionally, spatial data was created by expert users (e.g. national mapping agencies), who created metadata for the data. Increasingly, however, data used in spatial analysis comes from multiple sources and could be captured or used by nonexpert users â for example academic researchers â many of whom are from nonâGIS disciplinary backgrounds, not familiar with metadata and perhaps working in geographically dispersed teams. This paper examines the applicability of metadata in this academic context, using a multiânational coastal/environmental project as a case study. The work to date highlights a number of suggestions for good practice, issues and research questions relevant to Academic SDI, particularly given the increased levels of research data sharing and reuse required by UK and EU funders
Mapping the immune landscape in solid tumors : implications for immunotherapy
Our cells are programmed with various safety mechanisms to avoid transformation into tumor cells. In case these fail, we have a guarding immune system ready to recognize and eliminate these cells. Despite these safety measurements, cancer is one of the leading causes of death worldwide. The tumor cells find ways to escape the immune system. Paradoxically, components of the immune system can contribute to the progression of tumors by the use of various immunosuppressive pathways. However, the immune system can also be harnessed, and the anti-tumor functions restored to regain control of the tumor development. This has been highlighted in the past decade, with the introduction of novel immunotherapeutic approaches, such as checkpoint blockade, to target the naturally occurring brakes called co-inhibitory receptors.
The work presented in this thesis consists of four papers which contribute with knowledge on infiltrating immune cells in prostate cancer (Paper I) and ovarian cancer (Paper II-IV). In the work of Paper I-IV, we have looked into tumor-infiltrating lymphocytes and mapped the presence, composition, expression pattern and functionality of various T cell subsets in these two solid tumor types. The work was performed by retrieving material from cancer patients undergoing surgery, isolating immune cells and performing phenotypic descriptions by flow cytometry. We also have assessed the soluble environment in which the immune infiltrates reside and assessed T cell functionality by looking into cytokine secretion, cytotoxicity and/or proliferation by various readouts.
In Paper I, we performed phenotyping of immune infiltrates in peripheral blood and prostates with malignant, benign or healthy histology. In Paper II, we assessed the immunophenotype in peripheral blood, ascites and metastasized tumor tissue of advanced ovarian cancer patients. The results in Paper I and II showed lymphocyte infiltration to be common in both tumor types, in particular of CD8+ effector memory T cells. PD-1, which enables inhibition of effector functions by binding to its ligands, was the most abundantly expressed co-inhibitory receptor in both tumor types. However, in Paper I, PD-1 expression was also common in healthy prostates indicating a role in the homeostasis of the prostate environment. In Paper II, we correlated our findings to patient outcome and identified eight immune-related risk factors (both cellular and soluble) in ascites and/or tumor associated with overall patient survival.
In Paper III, we investigated the functionality of infiltrating T cells isolated from ovarian cancer patients. We wanted to explore if functionality, in terms of cytokine responsiveness, could be enhanced using immunotherapeutic PD-1-targeting conventional monoclonal antibodies (mAbs) nivolumab/pembrolizumab and novel scaffold proteins called DARPinÂź proteins. The results showed improved secretion of several important effector cytokines using the PD-1 targeting reagents. A bivalent PD-1 targeting DARPinÂź protein showed comparable results to the clinically approved mAbs which warrants further investigation. However, despite boosted cytokine responsiveness, our results indicated that tumor-derived T cells are still highly dysfunctional, presenting challenges in restoring anti-tumor responses.
In Paper IV, we investigated the features of the unconventional subset γΎ T cells in ovarian cancer. Our aim was to investigate their features and contribution in this cancer type. We profiled their T cell receptor (TCR) characteristics, their phenotype and functional response to various stimuli. We found the ascites-derived and tumor-derived γΎ T cell repertoires to be distinct from one another. We suggested the ascites γΎ T cells to be driven by adaptive TCR-driven pathways due to the observed clonal focusing in this compartment, while tumor γΎ T cells displayed a high diversity and likely respond through innate pathways. In summary, we found the γΎ T cells to be beneficial for the patients by anti-tumor functions including cytotoxicity and production of important effector cytokines. Importantly, we identified their functionality to be associated to outcome, where higher functionality was linked to increased patient survival. We observed a negative impact of CD39 on γΎ functionality, which warrants further investigation to understand how γΎ T cell functionality can be boosted.
Future optimization of immunotherapeutic approaches requires basic understanding of immune infiltrates in tumors. By learning more about these tumor-infiltrating immune cells, what they express and how their functionality can be affected, new strategies can be outlined based on this knowledge. I hope that by reading this thesis, you will obtain insight into this exciting research field and how the presented work has contributed.
Idealized Slab Plasma approach for the study of Warm Dense Matter
Recently, warm dense matter (WDM) has emerged as an interdisciplinary field
that draws increasing interest in plasma physics, condensed matter physics,
high pressure science, astrophysics, inertial confinement fusion, as well as
materials science under extreme conditions. To allow the study of well-defined
WDM states, we have introduced the concept of idealized-slab plasmas that can
be realized in the laboratory via (i) the isochoric heating of a solid and (ii)
the propagation of a shock wave in a solid. The application of this concept
provides new means for probing the dynamic conductivity, equation of state,
ionization and opacity. These approaches are presented here using results
derived from first-principles (density-functional type) theory, Thomas-Fermi
type theory, and numerical simulations.Comment: 37 pages, 21 figures, available, pdf file only. To appear in: Laser
and Particle beams. To appear more or less in this form in Laser and Particle
beam
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