Hyperglycemia: causes and consequences

Dekker, J.M. [Promotor]Nijpels, M.G.A.A.M. [Promotor]Alssema, M.J. [Copromotor

Domain walls inside localised orientifolds

The equations of motion of toroidal orientifold compactifications with fluxes are in one-to-one correspondence with gauged supergravity if the orientifold (and D-brane) sources are smeared over the compact space. This smeared limit is identical to the approximation that ignores warping. It is therefore relevant to compare quantities obtained from the gauged supergravity with the true 10d solution with localised sources. In this paper we find the correspondence between BPS domain walls in gauged SUGRA and 10D SUGRA with localised sources. Our model is the simplest orientifold with fluxes we are aware of: an O6/D6 compactification on T^3/Z_2 in massive IIA with H_3-flux. The BPS domain walls correspond to a O6/D6/NS5/D8 bound state. Our analysis reveals that the domain wall energy computed in gauged SUGRA is unaffected by the localisation of the O6/D6 sources.Comment: 26 pages, 1 figur

Combatting infectious diseases: nanotechnology as a platform for rational vaccine design

Drug Delivery Technolog

Matrix metalloproteinase 13 modulates intestinal epithelial barrier integrity in inflammatory diseases by activating TNF

Several pathological processes, such as sepsis and inflammatory bowel disease (IBD), are associated with impairment of intestinal epithelial barrier. Here, we investigated the role of matrix metalloproteinase MMP13 in these diseases. We observed that MMP13(-/-) mice display a strong protection in LPS- and caecal ligation and puncture-induced sepsis. We could attribute this protection to reduced LPS-induced goblet cell depletion, endoplasmic reticulum stress, permeability and tight junction destabilization in the gut of MMP13(-/-) mice compared to MMP13(+/+) mice. Both in vitro and in vivo, we found that MMP13 is able to cleave pro-TNF into bioactive TNF. By LC-MS/MS, we identified three MMP13 cleavage sites, which proves that MMP13 is an alternative TNF sheddase next to the TNF converting enzyme TACE. Similarly, we found that the same mechanism was responsible for the observed protection of the MMP13(-/-) mice in a mouse model of DSS-induced colitis. We identified MMP13 as an important mediator in sepsis and IBD via the shedding of TNF. Hence, we propose MMP13 as a novel drug target for diseases in which damage to the gut is essential

A 'civilized' drink and a 'civilizing' industry: wine growing and cultural imagining in colonial New South Wales

My starting point for this thesis was the absence of a foundation history of Australian wine growing conducted by an historian rather than researchers in other disciplines or the media. I have used existing work on wine history in New South Wales from 1788 to 1901 alongside a significant body of new research to create an historical argument suitable for incorporation into more broadly-themed narratives of Australian history and to inform studies of wine growing in other academic fields. My main argument is that although wine growing proved of little economic value in colonial primary production compared with nation-building commodities - such as pastoralism, wheat growing and gold - advocates of the cultivation of wine grapes believed wine growing embodied beneficial, even transformative, cultural value so they persisted in attempting to create a ‘civilizing’ industry producing a ‘civilized’ drink despite lacklustre consumption of their product and very modest profits. Several times, from 1788 to 1901, these advocates spoke out or wrote about wine and wine growing as capable of creating order in a wild or ‘savage’ landscape and within a settler society shaped culturally by shifting adaptations to both imported and ‘native’ influences in agriculture as well as alcohol production, consumption and distribution. While the methodological framework employed here falls mainly within cultural and economic history, sociological theories have contributed to findings on causation. The result is a comprehensive narrative of colonial wine growing in New South Wales enriched by links to key developments in Australian colonial history and with reference to wine growing in other British colonies or former territories

Peer support to decrease diabetes-related distress in patients with type 2 diabetes mellitus:Design of a randomised controlled trial

BACKGROUND: Many type 2 diabetes mellitus patients face difficulties self-managing their illness, which can lead to high levels of diabetes-related distress. Diabetes distress may be decreased by peer support, as peers understand and have dealt with similar problems, and can help motivate each other. A recent systematic review concluded that evidence of benefits of peer support in patients with type 2 diabetes mellitus is too inconsistent due to weak theoretical foundation of the interventions. This study describes the design of a trial evaluating the effectiveness of a group-based, peer support programme with a strong theoretical foundation on diabetes-related distress in type 2 diabetes patients. METHODS: This is a parallel group randomised controlled trial of a six session group-based peer support intervention, delivered by peer leaders and group psychotherapists, compared with one educational meeting on diabetes. At least 152 patients with a type 2 diabetes duration of three years or more and between 50 and 70 years of age, recruited via their general practitioner, will be randomised to receive the peer support intervention or one educational meeting. The intervention is developed in line with three key stages of research development of the Medical Research Council framework. The primary outcome measure for this study is diabetes-related distress. Secondary outcomes include self-management behaviour, well-being and health-related quality of life. Perceived social support is a process measure. Outcomes will be measured one month before, and 6, and 12 months after the intervention by means of self-reported questionnaires. Analysis will be on an intention-to-treat basis. DISCUSSION: This article contains a description of the design of a study that will investigate the effect of a group-based, peer support intervention on diabetes-related distress in type 2 diabetes patients. The intervention was developed in recognition of the limited evidence, and the importance of a theoretical foundation and its implementation. Findings will contribute to knowledge in the field of peer support and patient-important outcomes in type 2 diabetes patients. TRIAL REGISTRATION: Dutch Trial Registry: NTR347

Dynamics of Generalized Assisted Inflation

We study the dynamics of multiple scalar fields and a barotropic fluid in an FLRW-universe. The scalar potential is a sum of exponentials. All critical points are constructed and these include scaling and de Sitter solutions. A stability analysis of the critical points is performed for generalized assisted inflation, which is an extension of assisted inflation where the fields mutually interact. Effects in generalized assisted inflation which differ from assisted inflation are emphasized. One such a difference is that an (inflationary) attractor can exist if some of the exponential terms in the potential are negative.Comment: 27 page

Role of Adiposity and Lifestyle in the Relationship Between Family History of Diabetes and 20-Year Incidence of Type 2 Diabetes in U.S. Women

OBJECTIVE - To evaluate to what extent the association between family history of diabetes and risk of type 2 diabetes can be explained by excess adiposity and lifestyle risk factors. RESEARCH DESIGN AND METHODS - We analyzed data from 73,227 women who participated in the Nurses' Health Study cohort. A family history of diabetes was defined as having at least one first-degree family member with diabetes. Lifestyle factors, weight, and height were assessed by using validated questionnaires, and BMI was calculated. The relative risk of type 2 diabetes was estimated using Cox proportional hazards analysis. RESULTS - We documented 5,101 cases of type 2 diabetes during 20 years of follow-up. The age-adjusted relative risk of type 2 diabetes in participants with a family history was 2.27 (95% CI 2.14-2.40) compared with the risk in those without a family history of diabetes. Participants with a family history of diabetes had a higher BMI and were more likely to have a parental history of obesity. BMI explained 21.1% (19.4-22.9) of the association between family history of diabetes and risk of type 2 diabetes. Intakes of red meat, alcohol, and sugar-sweetened beverages explained 1.1% (0.8-1.3), 4.8% (4.3-5.3), and 2.8% (2.4-3.2) of this association, respectively. CONCLUSIONS - These results suggest that excess adiposity and, to a lesser extent, specific dietary habits can explain a substantial part of the association between having a family history of diabetes and risk of type 2 diabetes. © 2010 by the American Diabetes Association

Scaling solutions and geodesics in moduli space

In this paper we consider cosmological scaling solutions in general relativity coupled to scalar fields with a non-trivial moduli space metric. We discover that the scaling property of the cosmology is synonymous with the scalar fields tracing out a particular class of geodesics in moduli space - those which are constructed as integral curves of the gradient of the log of the potential. Given a generic scalar potential we explicitly construct a moduli metric that allows scaling solutions, and we show the converse - how one can construct a potential that allows scaling once the moduli metric is known.Comment: 10 pages, 3 figure