867 research outputs found
The Longevity of Behaviour Change: A Case Study of the London 2012 Olympic and Paralympic Games
Travel behaviour change is traditionally regarded as being difficult to achieve, with strategies and initiatives often generating only slow and incremental shifts in behaviour amongst the population. There is an emerging discussion in the literature that more radical approaches to travel behaviour change are needed, to contribute to achieving challenging decarbonisation targets. If a step change is required then one potential source of learning is the study of disruptions to systems of mobility provision, which may provide valuable insights into how more radical travel behaviour change is achieved and, potentially, sustained.
This thesis provides an innovative approach to examining major-event disruption, in this case arising from the London 2012 Olympic and Paralympic Games, to understand the potential for change from such large, disruptive events. A four-wave longitudinal panel survey was applied to establish the extent, and longevity, of change in response to the Games. The research uses the Transtheoretical Model (TTM) to critically examine travel behaviour.
The results show that change was extensive during the Games (54% made at least one change); however change was not often sustained afterwards. Reducing, relocating and re-timing were the most common changes. The key elements of the TTM were not well suited to studying change in such a context, however less commonly used constructs of the model contributed to the identification of four clusters within the sample that provided valuable insight into the behaviour observed.
This research makes a valuable contribution to the growing literature around the potential for learning, and opportunities for change, when there is an imperative to do so. Whilst the longevity of changes to travel were limited, the research provided greater understanding of the adaptability and planning involved in response to major-event disruption, and what this means for future travel planning. The clusters generated helped to show the psychological constructs important for supporting different types of change, which can contribute to approaching and understanding travel behaviour change in broader contexts, when there is an imperative to change
Absolute calibration of the intramolecular site preference of 15N fractionation in tropospheric N2O by FT-IR spectroscopy
Nitrous oxide (N2O) plays important roles in atmospheric chemistry both as a greenhouse gas and in stratospheric ozone depletion. Isotopic measurements of N2O have provided an invaluable insight into understanding its atmospheric sources and sinks. The preference for 15N fractionation between the central and terminal positions (the âsite preferenceâ) is particularly valuable because it depends principally on the processes involved in N2O production or consumption, rather than the 15N content of the substrate from which it is formed. Despite the value of measurements of the site preference, there is no internationally recognized standard reference material of accurately known and accepted site preference, and there has been some lack of agreement in published studies aimed at providing such a standard. Previous work has been based on isotope ratio mass spectrometry (IRMS); in this work we provide an absolute calibration for the intramolecular site preference of 15N fractionation of working standard gases used in our laboratory by a completely independent techniqueâhigh-resolution Fourier transform infrared (FT-IR) spectroscopy. By reference to this absolute calibration, we determine the site preference for 25 samples of tropospheric N2O collected under clean air conditions to be 19.8Ⱐ± 2.1â°. This result is in agreement with that based on the earlier absolute calibration of Toyoda and Yoshida (Toyoda, S. and Yoshida, N. Anal. Chem. 1999, 71, 4711â4718) who found an average tropospheric site preference of 18.7Ⱐ± 2.2â°. We now recommend an interlaboratory exchange of working standard N2O gases as the next step to providing an international reference standard
Regulation of Liver Regeneration by Hepatocyte O-GlcNAcylation in Mice
A grant from the One-University Open Access Fund at the University of Kansas was used to defray the author's publication fees in this Open Access journal. The Open Access Fund, administered by librarians from the KU, KU Law, and KUMC libraries, is made possible by contributions from the offices of KU Provost, KU Vice Chancellor for Research & Graduate Studies, and KUMC Vice Chancellor for Research. For more information about the Open Access Fund, please see http://library.kumc.edu/authors-fund.xml.Background & Aims
The liver has a unique capacity to regenerate after injury in a highly orchestrated and regulated manner. Here, we report that O-GlcNAcylation, an intracellular post-translational modification regulated by 2 enzymes, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), is a critical termination signal for liver regeneration following partial hepatectomy (PHX).
Methods
We studied liver regeneration after PHX on hepatocyte specific OGT and OGA knockout mice (OGT-KO and OGA-KO), which caused a significant decrease (OGT-KO) and increase (OGA-KO) in hepatic O-GlcNAcylation, respectively.
Results
OGA-KO mice had normal regeneration, but the OGT-KO mice exhibited substantial defects in termination of liver regeneration with increased liver injury, sustained cell proliferation resulting in significant hepatomegaly, hepatic dysplasia, and appearance of small nodules at 28 days after PHX. This was accompanied by a sustained increase in expression of cyclins along with significant induction in pro-inflammatory and pro-fibrotic gene expression in the OGT-KO livers. RNA-sequencing studies revealed inactivation of hepatocyte nuclear 4 alpha (HNF4α), the master regulator of hepatic differentiation and a known termination signal, in OGT-KO mice at 28 days after PHX, which was confirmed by both Western blot and immunohistochemistry analysis. Furthermore, a significant decrease in HNFα target genes was observed in OGT-KO mice, indicating a lack of hepatocyte differentiation following decreased hepatic O-GlcNAcylation. Immunoprecipitation experiments revealed HNF4α is O-GlcNAcylated in normal differentiated hepatocytes.
Conclusions
These studies show that O-GlcNAcylation plays a critical role in the termination of liver regeneration via regulation of HNF4α in hepatocytes
Health and wellbeing amongst older people research in Northamptonshire
The Ageing Research Centre of the University of Northampton (2014-current), in collaboration with the East Midlands Research into Ageing Network (EMRAN) is pleased to compile this brochure on research activity associated with older people across the county of Northamptonshire. This provides a comprehensive overview of activity that is relevant and of value to practice, identifying research outcomes that have real significance to age-related health and wellbeing. The brochure provides a summary of research activity over the last five years from academic, clinical and professional colleagues and demonstrates cross sector networks of collaboration around the common agenda of aging. Such collaboration will enhance the capacity of research understanding across the county and provide information and support for the needs of older people, their families and carers. The translation of research outcomes into practice is essential if we are to promote wellness, independence and healthy aging within the county and beyond and I would like to thank all contributors for their commitment and hard work in the production of this brochure
Localization of type 1 diabetes susceptibility to the MHC class I genes HLA-B and HLA-A
The major histocompatibility complex (MHC) on chromosome 6 is associated with susceptibility to more common diseases than any other region of the human genome, including almost all disorders classified as autoimmune. In type 1 diabetes the major genetic susceptibility determinants have been mapped to the MHC class II genes HLA-DQB1 and HLA-DRB1 (refs 1-3), but these genes cannot completely explain the association between type 1 diabetes and the MHC region. Owing to the region's extreme gene density, the multiplicity of disease-associated alleles, strong associations between alleles, limited genotyping capability, and inadequate statistical approaches and sample sizes, which, and how many, loci within the MHC determine susceptibility remains unclear. Here, in several large type 1 diabetes data sets, we analyse a combined total of 1,729 polymorphisms, and apply statistical methods - recursive partitioning and regression - to pinpoint disease susceptibility to the MHC class I genes HLA-B and HLA-A (risk ratios >1.5; Pcombined = 2.01 à 10-19 and 2.35 à 10-13, respectively) in addition to the established associations of the MHC class II genes. Other loci with smaller and/or rarer effects might also be involved, but to find these, future searches must take into account both the HLA class II and class I genes and use even larger samples. Taken together with previous studies, we conclude that MHC-class-I-mediated events, principally involving HLA-B*39, contribute to the aetiology of type 1 diabetes. ©2007 Nature Publishing Group
HLA-DQA1*05 carriage associated with development of anti-drug antibodies to infliximab and adalimumab in patients with Crohn's Disease
Anti-tumor necrosis factor (anti-TNF) therapies are the most widely used biologic drugs for treating immune-mediated diseases, but repeated administration can induce the formation of anti-drug antibodies. The ability to identify patients at increased risk for development of anti-drug antibodies would facilitate selection of therapy and use of preventative strategies.This article is freely available via Open Access. Click on Publisher URL to access the full-text
Bristol advisory committee on climate change: One City climate strategy progress review - February 2023
This report from the Bristol Advisory Committee on Climate Change (BACCC) reviews citywide progress on tackling the climate crisis and concludes that, although there is some positive progress, the city is still way off meeting its 2030 carbon neutral and climate resilient targets.BACCC is an independent committee which provides expert advice on reducing greenhouse gas emissions and adapting to the impacts of a changing climate. Their latest report is an assessment of progress against the One City Climate Strategy which was launched by the Environment Board in March 2020, setting out the pathway for the city to reduce carbon emissions and build resilience to a changing climate by 2030
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