A genome-wide association study identifies susceptibility variants for type 2 diabetes in Han Chinese.

To investigate the underlying mechanisms of T2D pathogenesis, we looked for diabetes susceptibility genes that increase the risk of type 2 diabetes (T2D) in a Han Chinese population. A two-stage genome-wide association (GWA) study was conducted, in which 995 patients and 894 controls were genotyped using the Illumina HumanHap550-Duo BeadChip for the first genome scan stage. This was further replicated in 1,803 patients and 1,473 controls in stage 2. We found two loci not previously associated with diabetes susceptibility in and around the genes protein tyrosine phosphatase receptor type D (PTPRD) (P = 8.54x10(-10); odds ratio [OR] = 1.57; 95% confidence interval [CI] = 1.36-1.82), and serine racemase (SRR) (P = 3.06x10(-9); OR = 1.28; 95% CI = 1.18-1.39). We also confirmed that variants in KCNQ1 were associated with T2D risk, with the strongest signal at rs2237895 (P = 9.65x10(-10); OR = 1.29, 95% CI = 1.19-1.40). By identifying two novel genetic susceptibility loci in a Han Chinese population and confirming the involvement of KCNQ1, which was previously reported to be associated with T2D in Japanese and European descent populations, our results may lead to a better understanding of differences in the molecular pathogenesis of T2D among various populations.

The calculator as an instrument of validation of mathematical knowledge: a case study

En este trabajo se describe una experiencia llevada a cabo con profesores de matemáticas en formación, sobre el papel que pueden desarrollar las nuevas tecnologías para llevar a cabo procesos de demostración y prueba en el aula de secundaria.

Optimizing the operation of straight-grate iron-ore pellet induration systems using process models

Mathematical models of straight-grate pellet induration processes have been developed and carefully validated by a number of workers over the past two decades. However, the subsequent exploitation of these models in process optimization is less clear, but obviously requires a sound understanding of how the key factors control the operation. In this article, we show how a thermokinetic model of pellet induration, validated against operating data from one of the Iron Ore Company of Canada (IOCC) lines in Canada, can be exploited in process optimization from the perspective of fuel efficiency, production rate, and product quality. Most existing processes are restricted in the options available for process optimization. Here, we review the role of each of the drying (D), preheating (PH), firing (F), after-firing (AF), and cooling (C) phases of the induration process. We then use the induration process model to evaluate whether the first drying zone is best to use on the up- or down-draft gas-flow stream, and we optimize the on-gas temperature profile in the hood of the PH, F, and AF zones, to reduce the burner fuel by at least 10 pct over the long term. Finally, we consider how efficient and flexible the process could be if some of the structural constraints were removed (i.e., addressed at the design stage). The analysis suggests it should be possible to reduce the burner fuel lead by 35 pct, easily increase production by 5+ pct, and improve pellet quality.

Ergodicity and stability of generalised Markov branching processes with resurrection

This paper concentrates on investigating ergodicity and stability for generalised Markov branching processes with resurrection. Easy checking criteria including several clear-cut corollaries are established for ordinary and strong ergodicity of such processes. The equilibrium distribution is given in an elegant closed form for the ergodic case. The probabilistic interpretation of the results is clear and thus explained.

Heat and mass transfer in two-phase porous materials under intensive microwave heating

Computational results for the intensive microwave heating of porous materials are presented in this work. A multi-phase porous media model has been developed to predict the heating mechanism. Combined finite difference time-domain and finite volume methods were used to solve equations that describe the electromagnetic field and heat and mass transfer in porous media. The coupling between the two schemes is through a change in dielectric properties which were assumed to be dependent both on temperature and moisture content. The model was able to reflect the evolution of both temperature and moisture fields as well as energy penetration as the moisture in the porous medium evaporates. Moisture movement results from internal pressure gradients produced by the internal heating and phase change.

Direct measurement of powder flavour adhesion on to a food surface using a novel adhesion tester

The firm adhesion of flavouring particles onto crisp surfaces during coating processes is a major concern in the snack production industry. Detachment of flavouring powders from products during handling and production stages can lead to substantial financial losses for the industry, in terms of variable flavour performance and extended cleaning down time of fugitive particle build-up on process equipment. Understanding the adhesion strength of applied bulk particulates used for flavouring formulations will help analysts to evaluate the efficiency of coating processes and potentially enable them to assess the adhesion strength of newly formulated flavouring powder prior to commitment to full scale plant trials. A rapid prototype of a novel adhesion tester has been designed and constructed. The apparatus operates according to the principle of impact force acting on particles attached to the surface of the food substrate. The main component is a circular plate to which four sample holders are attached and which is subjected to vertical travel down a guide shaft. Several flavouring powders have been tested extensively. By plotting the detachment versus impact force, the difference obtained between adhesion strength of different flavouring powders (which is a strong function of particle size) has been discussed.

Stability analysis of the amplifier with negative impedance compensation

A novel amplifier design technique based on negative impedance compensation has been proposed in our recent paper. In this paper, we investigate the stability of this amplifier system. The parameter space approach has been used to determine system parameters in the negative impedance circuit such that the stability of the amplifier system can be guaranteed in a certain region represented by those parameters. The simulation results have demonstrated that stable circuit behavior for the amplifier can be achieved

Monitorización de la temperatura del pie como herramienta en la neuropatía diabética

Objteivo: Valorar si existe relación entre el aumento de temperatura en el pie y la neuropatía diabética periférica. Métodos: La muestra fueron 27 pacientes diabéticos a que se le realizó una exploración neurológica y vascular, además, haciendo uso de un termómetro infrarrojo medimos la temperatura en distintos puntos anatómicos de la planta del pie. Resultados: La temperatura es mayor los pacientes con neuropatía con una diferencia de 2,24ºC (p=0,454) en el pie derecho y 0,86ºC (p=0,589) en el pie izquierdo. Conclusión: Los resultados sugieren que la automonitorización de la temperatura del pie por parte del paciente diabético podría ayudar a reducir la alta incidencia de complicaciones en el pie diabético.

Phylogeographic analysis of the red seaweed Palmaria palmata reveals a Pleistocene marine glacial refugium in the English Channel

Phylogeography has provided a new approach to the analysis of the postglacial history of a wide range of taxa but, to date, little is known about the effect of glacial periods on the marine biota of Europe. We have utilized a combination of nuclear, plastid and mitochondrial genetic markers to study the biogeographic history of the red seaweed Palmaria palmata in the North Atlantic. Analysis of the nuclear rDNA operon (ITS1-5.8S-ITS2), the plastid 16S-trnI-trnA-23S-5S, rbcL-rbcS and rpl12-rps31-rpl9 regions and the mitochondrial cox2–3 spacer has revealed the existence of a previously unidentified marine refugium in the English Channel, along with possible secondary refugia off the southwest coast of Ireland and in northeast North America and/or Iceland. Coalescent and mismatch analyses date the expansion of European populations from approximately 128 000 bp and suggest a continued period of exponential growth since then. Consequently, we postulate that the penultimate (Saale) glacial maximum was the main event in shaping the biogeographic history of European P. palmata populations which persisted throughout the last (Weichselian) glacial maximum (c. 20 000 bp) in the Hurd Deep, an enigmatic trench in the English Channel.

High glucose decreases intracellular glutathione concentrations and upregulates inducible nitric oxide synthase gene expression in intestinal epithelial cells

Diabetes is associated with oxidative stress and increased levels of inflammatory cytokines. The aim of the study was to assess the effects of inflammatory cytokines and oxidative stress associated with raised glucose levels on inducible nitric oxide synthase (iNOS) promoter activity in intestinal epithelial cells. High glucose (25 mmol/l) conditions reduced glutathione (GSH) levels in the human intestinal epithelial cell line, DLD-1. Addition of the antioxidant alpha-lipoic acid resulted in the restoration of GSH levels to normal. Upregulation of basal iNOS promoter activity was observed when cells were incubated in high glucose alone. This effect was significantly reduced by the addition of the antioxidant, alpha-lipoic acid and completely blocked with inhibition of NFkappa B activity. Cytokine stimulation [interleukin-1 beta, tumor necrosis factor-alpha, interferon-gamma] induced iNOS promoter activity in all conditions and this was accompanied by an increase in nitric oxide (NO) production. Inhibition of NFkappa-B activity decreased but did not completely inhibit cytokine-induced iNOS promoter activity and subsequent NO production. In conclusion, high glucose-induced iNOS promoter activity is mediated in part through intracellular GSH and NFkappa-B.

Robust fuzzy Gustafson-Kessel clustering for nonlinear system identification

This paper deals with Takagi-Sugeno (TS) fuzzy model identification of nonlinear systems using fuzzy clustering. In particular, an extended fuzzy Gustafson-Kessel (EGK) clustering algorithm, using robust competitive agglomeration (RCA), is developed for automatically constructing a TS fuzzy model from system input-output data. The EGK algorithm can automatically determine the 'optimal' number of clusters from the training data set. It is shown that the EGK approach is relatively insensitive to initialization and is less susceptible to local minima, a benefit derived from its agglomerate property. This issue is often overlooked in the current literature on nonlinear identification using conventional fuzzy clustering. Furthermore, the robust statistical concepts underlying the EGK algorithm help to alleviate the difficulty of cluster identification in the construction of a TS fuzzy model from noisy training data. A new hybrid identification strategy is then formulated, which combines the EGK algorithm with a locally weighted, least-squares method for the estimation of local sub-model parameters. The efficacy of this new approach is demonstrated through function approximation examples and also by application to the identification of an automatic voltage regulation (AVR) loop for a simulated 3 kVA laboratory micro-machine system.

Chemotherapy-Induced CXC-Chemokine/CXC-Chemokine Receptor Signaling in Metastatic Prostate Cancer Cells Confers Resistance to Oxaliplatin through Potentiation of Nuclear Factor-κB Transcription and Evasion of Apoptosis

Constitutive activation of nuclear factor (NF)-kappa B is linked with the intrinsic resistance of androgen-independent prostate cancer (AIPC) to cytotoxic chemotherapy. Interleukin-8 (CXCL8) is a transcriptional target of NF-kappa B whose expression is elevated in AIPC. This study sought to determine the significance of CXCL8 signaling in regulating the response of AIPC cells to oxaliplatin, a drug whose activity is reportedly sensitive to NF-kappa B activity. Administration of oxaliplatin to PC3 and DU145 cells increased NF-kappa B activity, promoting antiapoptotic gene transcription. In addition, oxaliplatin increased the transcription and secretion of CXCL8 and the related CXC-chemokine CXCL1 and increased the transcription and expression of CXC-chemokine receptors, especially CXC-chemokine receptor (CXCR) 2, which transduces the biological effects of CXCL8 and CXCL1. Stimulation of AIPC cells with CXCL8 potentiated NF-kappa B activation in AIPC cells, increasing the transcription and expression of NF-kappa B-regulated antiapoptotic genes of the Bcl-2 and IAP families. Coadministration of a CXCR2-selective antagonist, AZ10397767 (Bioorg Med Chem Lett 18:798-803, 2008), attenuated oxaliplatin-induced NF-kappa B activation, increased oxaliplatin cytotoxicity, and potentiated oxaliplatin-induced apoptosis in AIPC cells. Pharmacological inhibition of NF-kappa B or RNA interference-mediated suppression of Bcl-2 and survivin was also shown to sensitize AIPC cells to oxaliplatin. Our results further support NF-kappa B activity as an important determinant of cancer cell sensitivity to oxaliplatin and identify the induction of autocrine CXCR2 signaling as a novel mode of resistance to this drug.