Vitamin B1 blocks damage caused by hyperglycemia

Diabetes accelerates the aging process and leads to complications that include blindness, renal failure, nerve damage, stroke, and cardiovascular disease. It has been hypothesized that high plasma glucose concentrations are responsible for increased mitochondrial free radical production and subsequent inactivation of glyceraldehyde phosphate dehydrogenase (GAPDH) in vascular endothelial cells and other cells implicated in these complications. As a result of the decreased ability of GAPDH to process upstream metabolites, three pathways of metabolic damage are activated, which include the advanced glycation end-product formation pathway, the protein kinase C pathway, and the hexosamine pathway. All three pathways have been implicated in abnormal cell signaling in diabetes. A group of German and U.S. scientists has now found that treating diabetic rats with high doses of benfotiamine, a lipid-soluble form of vitamin B1, can prevent diabetic retinopathy and all three forms of metabolic damage by stimulating transketolase activity and thus diverting excess metabolites toward the pentose pathway. Although vitamin B1 is available over the counter, the researchers at this time do not advocate self-treatment without further clinical data.     

TEACHING THE PRODUCTION/OPERATIONS MANAGEMENT CORE COURSE: INTEGRATING LOGISTICS PLANNING ACTIVITIES

This paper discusses the benefits of restructuring the introductory undergraduate production and operations management (pom) course to improve its pedagogical effectiveness and to better convey the importance of integrating logistics planning activities. The introduction of a dynamic integrative semester-long case study which involves students in applying pom concepts and tools through a simulation game is reported.     

The dynamics of hapū research relationships

Abstract

The Whakaki Lake Trust has a long history of being an active kaitiaki of Whakaki Lake and has developed a hapū-based restoration and enhancement programme at the Lake property. Part of this programme has involved working with a range of external agencies and researchers. Research relationships have become an important part of the restoration process to build the capability and capacity of hapū to execute activities associated with restoration. In addition, relationships have provided an opportunity to strengthen and expand the knowledge base that hapū can draw upon to inform ecological restoration and resource management decisions. Some of these relationships have been adversarial and a source of much frustration. As a consequence the Trust has developed very clear expectations and policy around working with others. My experience of developing a doctoral research project with Whakaki Lake Trust is used here to discuss hapū expectations of research and resultant academic dilemmas.     

Penalized Maximum Likelihood Estimator for Normal Mixtures

The estimation of the parameters of a mixture of Gaussian densities is considered, within the framework of maximum likelihood. Due to unboundedness of the likelihood function, the maximum likelihood estimator fails to exist. We adopt a solution to likelihood function degeneracy which consists in penalizing the likelihood function. The resulting penalized likelihood function is then bounded over the parameter space and the existence of the penalized maximum likelihood estimator is granted. As original contribution we provide asymptotic properties, and in particular a consistency proof, for the penalized maximum likelihood estimator. Numerical examples are provided in the finite data case, showing the performances of the penalized estimator compared to the standard one.     

Apoptotic killing of fibroblasts by matrix-bound advanced glycation endproducts

The extracellular matrix accumulates biologically active advanced glycation endproducts such as carboxymethyl-lysine (CML). Alikhani et al. recently reported that CML-rich collagen, representing an artifically aged matrix protein, induces apoptosis in vivo and in fibroblasts. This observation may have profound implications for the biology of cell-matrix interactions during aging.     

中国古代慈善事业的发展特点

中国古代慈善事业在漫长的历史发展过程中不但逐渐形成了庞杂而丰富的思想体系,而且其慈善主体也实现了从最初单纯的国家慈善到以国家慈善为主、宗族慈善和宗教慈善为重要补充的多元化发展过程。另外,中国古代慈善事业的发展轨迹还明显具备与整个中国古代社会兴衰相表里的重要特点。     

Glycation stimulates amyloid formation

Amyloidosis comprises a group of systemic and localized diseases with varied clinical presentations. In these diseases, amyloid forms when proteins with a largely alpha-helical structure lose their original conformation and are converted into a predominantly beta-sheet form, thereby increasing their propensity to form highly insoluble and fibrillar aggregates. Most soluble amyloid precursor proteins have substantial beta-pleated sheet secondary structure, and extensive beta-pleated sheet structure occurs in all of the deposited fibrils. The aberrant deposition of proteins as cellular inclusions or plaques in the form of amyloid fibrils is a characteristic hallmark of all amyloid diseases (or amyloidoses) and of the so-called conformational diseases. Environmental and genetic factors are known to be involved, but the mechanism by which this process happens still is poorly understood. Here we report a new finding from the Dutch group of Gebbink and colleagues, which points to the posttranslational process of glycation as a key mechanism in the formation of amyloid. These researchers showed that glycation causes albumin, a globular protein with a largely alpha-helical structure, to adopt a beta-pleated sheet structure and the quaternary structural element known as the cross-beta conformation. These are features commonly shared by all amyloids. This research is the first to show glycation as a predisposing factor for amyloidosis.     

Wake up and smell the maillard reaction

The chemical reactions that occur when foods are browned during processing at high temperature also occur in the body during the natural aging process. Such reactions proceed at an accelerated rate in certain pathologies, such as diabetes, renal disease, atherosclerosis, and neurodegenerative diseases. A study now reveals that the consumption of foods rich in browned and oxidized products (so-called glycotoxins) induces a chronic inflammatory state in diabetic individuals. The study reveals a novel aspect at the interface between nutrition and disease, which might be especially relevant for the elderly and those with impaired renal function.     

Non-parametric Quantile Regression with Censored Data

Abstract.  Censored regression models have received a great deal of attention in both the theoretical and applied statistics literature. Here, we consider a model in which the response variable is censored but not the covariates. We propose a new estimator of the conditional quantiles based on the local linear method, and give an algorithm for its numerical implementation. We study its asymptotic properties and evaluate its performance on simulated data sets.     

Estimating the Effects of Residential Mobility: A Methodological Note

This article reviews the methodological challenges of estimating a causal association between mobility and children's cognitive, social, emotional, and physical development. Utilizing a comprehensive set of empirical articles published in the past 25 years that employ quantitative methods, it describes the limitations of previous studies and the innovative ways that researchers have attempted to deal with them. The concept of mobility is inconsistently operationalized along four dimensions: school versus residential, distance, timing, and frequency. Imprecise operationalization conflates different forms of mobility, which have differential effects on development. Attempts to estimate a causal association between mobility and development suffer from three sources of bias: selection, contextual shifts, and contemporaneous instigating events. (a) Methods that account for unobserved differences between mobile and nonmobile children have consistently shown smaller or even positive effects of mobility. (b) Moving can have a positive or negative effect on children's ecological contexts in ways that are systematically correlated with child development. (c) Moves are frequently catalyzed by changes in family structure and employment. The article concludes with recommendations for future research. Researchers should continue to engage fixed- and random-effect, matching, and instrumental variable techniques, each of which makes the question of causality explicit.