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Gene and Cell-Replacement Therapy in the Treatment of Type 1 Diabetes : How High Must the Standards Be Set?

Recent advances in molecular and cell biology may allow for the development of novel strategies for the treatment and cure of type 1 diabetes. In particular, it is now possible to envisage restoration of insulin secretion by gene or cell-replacement therapy. The β-cell is, however, remarkably sophisticated, and many of the features of this highly differentiated secretory cell will have to be faith

Autoimmune type 1 diabetes : Resolved and unresolved issues

Based on the presence of autoantibodies and a strong HLA linkage, type 1 diabetes is now classified as a chronic autoimmune disease. Many issues, however, remain unresolved. Although autoantibodies to GAD65, IA-2, and insulin are clearly markers for this disease, it is not known whether they contribute to pathogenesis or are simply the response to an existing underlying destructive process. Based

Prediction of diabetes with body mass index, oral glucose tolerance test and islet cell autoantibodies in a regional population

Objective. Our aim was to test the hypothesis that a combination of markers for Type 1 diabetes (glutamate decarboxylase and IA-2 autoantibodies) and for Type 2 diabetes [oral glucose tolerance test (OGTT) and body mass index (BMI)], would predict clinical diabetes in a regional population. Design. A population-based follow-up cohort study. Setting. Participants visited the primary health care cen

A novel monoclonal antibody specific for the N-terminal end of GAD65

We describe a novel monoclonal antibody raised towards the N-terminus of the 65 kDa isoform of glutamate decarboxylase (GAD65). This N-GAD65 mAb is highly specific for GAD65 and can be used in a wide range of applications such as Western blot analysis, immunoprecipitation and immunocytochemistry. Full-length cDNAs coding for N-GAD65 mAb heavy and light chains were cloned and characterized by nucle

Induction of islet allotolerance in nonhuman primates

Recent clinical trials have pioneered the successful use of a nonsteroidal immunosuppressive regimen and established a basis for application in a routine clinical setting. In this study, a single islet transplant was not sufficient to regulate blood glucose levels, and a second transplant became necessary. A similar observation was made in our macaque islet transplant study, where animals after th

Proportional–Integral Controller Design for Combustion-Timing Feedback, from n-Heptane to iso-Octane in Compression-Ignition Engines

The problem of designing robust and noise-insensitive PI controllers for pressure-sensor based combustion-timing control was studied through simulation. Different primary reference fuels (PRF) and operating conditions were studied. The simulations were done using a physics-based, control-oriented model with an empirical ignition-delay correlation. It was found that the controllable region, in-betwThe problem of designing robust and noise-insensitive PI controllers for pressure-sensor based combustion-timing control was studied through simulation. Different primary reference fuels (PRF) and operating conditions were studied. The simulations were done using a physics-based, control-oriented model with an empirical ignition-delay correlation. It was found that the controllable region, in-betw

Increased galanin expression in the celiac ganglion of BB diabetic rats

BB rats lose >50% of their islet sympathetic nerve terminals soon after diabetes onset, markedly impairing the glucagon response to activation of these nerves. In this study, we sought evidence that this degree of disease-induced nerve terminal damage affected their neuronal cell bodies. Increased galanin expression was used as a marker of the change of phenotype that occurs in neuronal cell bodie

Evidence of a functional role for mast cells in the development of type 1 diabetes mellitus in the biobreeding rat

Human type 1 diabetes mellitus (T1DM) arises through autoimmune destruction of pancreatic β cells and is modeled in many respects by the lymphopenic and spontaneously diabetic BioBreeding (BB) DRlyp-lyp rat Previously, preonset expression profiling of whole DRlyp-lyp pancreatic lymph nodes (PLN) revealed innate immune activity, specifically that of mast cells and eosinophils. Furthermore, we obser

An extension of digital volume correlation for multimodality image registration

The question of registering two images (or image volumes) acquired with different modalities, and thus exhibiting different contrast, at different positions is addressed based on an extension of global digital image (or volume) correlation. A specific comparison metric is introduced allowing the signature of the different phases to be related. A first solution consists of a Gaussian mixture to des

Oxidation of a Dimethoxyhydroquinone by Ferrihydrite and Goethite Nanoparticles : Iron Reduction versus Surface Catalysis

Hydroquinones are important mediators of electron transfer reactions in soils with a capability to reduce Fe(III) minerals and molecular oxygen, and thereby generating Fenton chemistry reagents. This study focused on 2,6-dimethoxy hydroquinone (2,6-DMHQ), an analogue to a common fungal metabolite, and its reaction with ferrihydrite and goethite under variable pH and oxygen concentrations. Combined

Stages of PPP and principal–agent conflicts : the Swedish water and sewerage sector

The focus of this article is on public–private partnerships (PPPs). The aim is to both theoretically and empirically illustrate PPP agency problems in four PPP stages, as well as to identify potentially relevant solutions to the agency problems. The study employed a longitudinal case study of one PPP in a municipality in southern Sweden. Through an analysis based on interviews, observations, and d

Translating sustainable and smart city strategies into performance measurement systems

This paper shows how sustainable and smart strategies can be implemented in cities and how these strategies influence, and are influenced by, performance measurement systems. Drawing upon the Foucauldian notion of governmentality, the authors present the case of Gothenburg in Sweden, where they interviewed the key actors involved in a new sustainability strategy. Translating strategy into performa

Accuracy and predictive value of classification schemes for ketosis-prone diabetes

OBJECTIVE - Ketosis-prone diabetes (KPD) is an emerging, heterogeneous syndrome. A sound classification scheme for KPD is essential to guide clinical practice and pathophysiologic studies. Four schemes have been used and are based on immunologic criteria, immunologic criteria and insulin requirement, BMI, and immunologic criteria and β-cell function (Aβ classification). The aim of the present stud

On the Maximum Burst-Correcting Capability of Cyclic Hsu–Kasami–Chien Codes

Hsu–Kasami–Chien (HKC) are a class of cyclic codes that can correct either burst or random errors. This paper studies the maximum burst-correcting capability of HKC codes. A necessary and sufficient condition for a b- burst-correcting cyclic HKC code is given and simplified as a generalized one for Fire codes. An upper bound on the burstcorrecting capability of HKC codes is derived, which improves

Antigen presentation of detergent-free glutamate decarboxylase (GAD65) is affected by human serum albumin as carrier protein

The smaller isoform of glutamate decarboxylase (GAD65) is a major autoantigen in type 1 diabetes (TID). Its hydrophobic character requires detergent to keep the protein in solution, which complicates studies of antigen processing and presentation. In this study an attempt was made to replace detergent with human serum albumin (HSA) for in vitro antigen presentation. Different preparations of recom

HLA class II alleles specify phenotypes of ketosis-prone diabetes

OBJECTIVE - Ketosis-prone diabetes (KPD) comprises four subgroups based on the presence or absence of β-cell autoantibodies (A+ or A-) and β-cell functional reserve (β + or β-). Genetic factors could contribute to their distinctive phenotypes. Our aim was to specify the role of HLA class II alleles associated with susceptibility or resistance to autoimmune type 1 diabetes in determining KPD phenot

Prototyping inom ABC och BSc : Erfarenheter från aktionsforskning i tre organisationer

This dissertation focuses on how to use prototyping as a method for developing models in Management Accounting and Control Systems, a field in Business Administration. It combines three emerging theories: prototyping, Activity Based Costing (ABC) and the Balanced Scorecard (BSc). Prototyping is an alternative to the traditional systems development method. In prototyping end-users play an important