E96V Mutation in the Kdelr3 Gene Is Associated with Type 2 Diabetes Susceptibility in Obese NZO Mice

Type 2 diabetes (T2D) represents a multifactorial metabolic disease with a strong genetic predisposition. Despite elaborate efforts in identifying the genetic variants determining individual susceptibility towards T2D, the majority of genetic factors driving disease development remain poorly understood. With the aim to identify novel T2D risk genes we previously generated an N2 outcross population using the two inbred mouse strains New Zealand obese (NZO) and C3HeB/FeJ (C3H). A linkage study performed in this population led to the identification of the novel T2D-associated quantitative trait locus (QTL) Nbg15 (NZO blood glucose on chromosome 15, Logarithm of odds (LOD) 6.6). In this study we used a combined approach of positional cloning, gene expression analyses and in silico predictions of DNA polymorphism on gene/protein function to dissect the genetic variants linking Nbg15 to the development of T2D. Moreover, we have generated congenic strains that associated the distal sublocus of Nbg15 to mechanisms altering pancreatic beta cell function. In this sublocus, Cbx6, Fam135b and Kdelr3 were nominated as potential causative genes associated with the Nbg15 driven effects. Moreover, a putative mutation in the Kdelr3 gene from NZO was identified, negatively influencing adaptive responses associated with pancreatic beta cell death and induction of endoplasmic reticulum stress. Importantly, knockdown of Kdelr3 in cultured Min6 beta cells altered insulin granules maturation and pro-insulin levels, pointing towards a crucial role of this gene in islets function and T2D susceptibility.     

Kinetics and thermodynamics of hydrogenation-dehydrogenation for Mg-25%TM (TM = Ti,Nb or V) composites synthesized by reactive ball milling in hydrogen

0.75Mg?0.25TM?H (TM = Ti, Nb or V) samples were mechano-chemically synthesized by reactive ball milling. The detailed reaction mechanism during hydrogen release and uptake was investigated by in-situ synchrotron radiation powder X-ray diffraction (SR-PXD) experiments. The thermodynamic and kinetic properties have been studied by Sievert's method. On the base of calculated values of the Gibbs free energy for reaction of hydrogen absorption (ΔG < 0) it reveals that hydrogenation reaction could thermodynamically proceed at room temperature, which is experimentally confirmed for all of the studied composites. It is clearly shown that β-MgH₂ forms at RT under conditions of experiment. Comparative analysis of the MgTi, MgV and MgNb systems makes it possible to establish that the most effective additive facilitating hydrogen uptake, particularly at RT, is vanadium. It provides the degree of conversion into hydride phase α = 0.86 for the first minute of hydrogenation. In contrast, additives of Nb and Ti provide only α = 0.62 and 0.36, respectively, following the 30 min of exposure. However, this study reveals that for the dehydrogenation process, titanium is the best among the examined additives, which is evidenced by lowest value of activation energy E_a = 53.6 kJ/mol of the hydrogen desorption.     

Converting XML DTDs to UML diagrams for conceptual data integration

Extensible Markup Language (XML) is fast becoming the new standard for data representation and exchange on the World Wide Web, e.g., in B2B e-commerce. Modern enterprises need to combine data from many sources in order to answer important business questions, creating a need for integration of web-based XML data. Previous web-based data integration efforts have focused almost exclusively on the logical level of data models, creating a need for techniques that focus on the conceptual level in order to communicate the structure and properties of the available data to users at a higher level of abstraction. The most widely used conceptual model at the moment is the Unified Modeling Language (UML).

This paper presents algorithms for automatically constructing UML diagrams from XML DTDs, enabling fast and easy graphical browsing of XML data sources on the web. The algorithms capture important semantic properties of the XML data such as precise cardinalities and aggregation (containment) relationships between the data elements. As a motivating application, it is shown how the generated diagrams can be used for the conceptual design of data warehouses based on web data, and an integration architecture is presented. The choice of data warehouses and On-Line Analytical Processing as the motivating application is another distinguishing feature of the presented approach.     

Nanoconfinement degradation in NaAlH4/CMK-1

An ordered mesoporous carbon scaffold (CMK-1) has been synthesized and infiltrated with NaAlH₄ nanoparticles by solvent- and melt-infiltration techniques. Small angle X-ray scattering (SAXS), powder X-ray diffraction (XRD), scanning electron microscopy (SEM), Transmission Electron Microscopy (TEM) and energy dispersive spectroscopy (EDS) are used to characterize the structure, composition and morphology before and after thermal treatment. This study illuminates some of the problems that can be associated with nanoconfinement of hydrogen storage materials including scaffold contamination, residual solvent contamination, sample morphology changes after heating, and other factors that can be detrimental to the application of these systems. Of particular interest is the expulsion of NaAlH₄ decomposition products from the scaffold after heating beyond its melting point under vacuum. This results in the surface of mesoporous carbon particles having arrays of multi-micron-long Al filaments that are >100 nm in diameter.     

Chemometric analysis of mass spectra of cis and trans fatty acid picolinyl esters

Capillary GC of fatty acid methyl esters with MS detection only yields information about the molecular weight of the compound. However, if picolinyl esters of fatty acids are analysed in this way it is possible to obtain more information about their structure, perhaps even the cis or trans configuration. Picolinyl esters of fatty acids are prepared by adding carbonyl-diimidazole, 3-hydroxymethylpyridine and 4-pyrrolidin-o-pyridine to a solution of free fatty acids in dichloromethane. The picolinyl esters dissolved in heptane are then separated by capillary GC on a CP Sil 88 column equipped with a quadropole MS-detector. The mass spectra clearly show the molecular weight and the position of double bonds in the fatty acids, but whether the configuration is cis or trans is impossible to discern visually. However, with the use of principal component analysis, it is possible to distinguish between cis and trans fatty acids of C16:1, C18:1,n-9, C18:1,n-12, C18:2 and C22:1 in two- and three-dimensional score plots. With Soft Independent Modelling of Class Analogy (SIMCA), it is possible to calculate models that can predict from the mass spectra of unknown fatty acids whether they are of the cis or trans configuration, which is demonstrated for C18:1 trans from hardened margarine and butter.     

Enhanced hydrogen reversibility of nanoconfined LiBH4–Mg(BH4)2

This study shows the hydrogen desorption kinetics and reversible hydrogen storage properties of 0.55LiBH₄–0.45Mg(BH₄)₂ melt-infiltrated in different nanoporous carbon aerogels with different BET surface areas of 689 or 2660 m²/g and pore volumes of 1.21 or 3.13 mL/g. These investigations clearly show a significantly improved hydrogen storage capacity after four cycles of hydrogen release and uptake for bulk 0.55LiBH₄–0.45Mg(BH₄)₂ and infiltrated in carbon aerogel and the high surface area scaffold, where 22, 36 and 58% of the initial hydrogen content remain after four cycles of hydrogen release and uptake, respectively. Nanoconfinement in high surface area carbon aerogel appears to facilitate hydrogen release illustrated by release of 13.3 wt% H₂ (93%) and only 8.4 wt% H₂ (58%) from bulk hydride in the first cycle using the same physical condition. Notably, nanoconfinement also appear to have a beneficial effect on hydrogen uptake, since 8.3 wt% H₂ (58%) is released from the high surface area scaffold and only 3.1 wt% H₂ (22%) from the bulk sample during the fourth hydrogen release.     

Detection of the voltage distribution in photovoltaic modules by electroluminescence imaging

We introduce an approach to determine the operating voltage of individual solar cells in photovoltaic (PV) modules by electroluminescence (EL) imaging. The highest EL signal of each solar cell is proportional to its operating voltage. Moreover the sum of all operating voltages equals the externally applied module voltage. Thus the operating voltage of individual solar cells is determined from the measured EL signal. The reliability of this relation is verified by measurements on specially prepared PV modules allowing us to measure the individual operating cell voltage. The experimentally measured cell voltages are deduced with an uncertainty of ±1% from an EL image. Moreover, the operating cell voltages determined from the EL image are used to calculate the module series resistance. Comparing experimentally determined values from the operating cell voltage and the total current flowing supplied to the module with calculated module series resistances using tabulated material and typical solar cell parameters, a very good correspondence is found. Copyright © 2010 John Wiley & Sons, Ltd.