Association between TCF7L2 gene polymorphisms and susceptibility to Type 2 Diabetes Mellitus: a large Human Genome Epidemiology (HuGE) review and meta-analysis

<p>Abstract</p> <p>Background</p> <p>Transcription factor 7-like 2 (<it>TCF7L2</it>) has been shown to be associated with type 2 diabetes mellitus (T2MD) in multiple ethnic groups in the past two years, but, contradictory results were reported for Chinese and Pima Indian populations. The authors then performed a large meta-analysis of 36 studies examining the association of type 2 diabetes mellitus (T2DM) with polymorphisms in the <it>TCF7L2 </it>gene in various ethnicities, containing rs7903146 C-to-T (IVS3C>T), rs7901695 T-to-C (IVS3T>C), a rs12255372 G-to-T (IVS4G>T), and rs11196205 G-to-C (IVS4G>C) polymorphisms and to evaluate the size of gene effect and the possible genetic mode of action.</p> <p>Methods</p> <p>Literature-based searching was conducted to collect data and three methods, that is, fixed-effects, random-effects and Bayesian multivariate mete-analysis, were performed to pool the odds ratio (<it>OR</it>). Publication bias and study-between heterogeneity were also examined.</p> <p>Results</p> <p>The studies included 35,843 cases of T2DM and 39,123 controls, using mainly primary data. For T2DM and IVS3C>T polymorphism, the Bayesian <it>OR </it>for TT homozygotes and TC heterozygotes versus CC homozygote was 1.968 (95% credible interval (<it>CrI</it>): 1.790, 2.157), 1.406 (95% <it>CrI</it>: 1.341, 1.476), respectively, and the population attributable risk (PAR) for the TT/TC genotypes of this variant is 16.9% for overall. For T2DM and IVS4G>T polymorphism, TT homozygotes and TG heterozygotes versus GG homozygote was 1.885 (95%<it>CrI</it>: 1.698, 2.088), 1.360 (95% <it>CrI</it>: 1.291, 1.433), respectively. Four <it>OR</it>s among these two polymorphisms all yielded significant between-study heterogeneity (P < 0.05) and the main source of heterogeneity was ethnic differences. Data also showed significant associations between T2DM and the other two polymorphisms, but with low heterogeneity (<it>P </it>> 0.10). Pooled <it>OR</it>s fit a codominant, multiplicative genetic model for all the four polymorphisms of <it>TCF7L2 </it>gene, and this model was also confirmed in different ethnic populations when stratification of IVS3C>T and IVS4G>T polymorphisms except for Africans, where a dominant, additive genetic mode is suggested for IVS3C>T polymorphism.</p> <p>Conclusion</p> <p>This meta-analysis demonstrates that four variants of <it>TCF7L2 </it>gene are all associated with T2DM, and indicates a multiplicative genetic model for all the four polymorphisms, as well as suggests the <it>TCF7L2 </it>gene involved in near 1/5 of all T2MD. Potential gene-gene and gene-environmental interactions by which common variants in the <it>TCF7L2 </it>gene influence the risk of T2MD need further exploration.</p

A model for homeopathic remedy effects: low dose nanoparticles, allostatic cross-adaptation, and time-dependent sensitization in a complex adaptive system

BACKGROUND: This paper proposes a novel model for homeopathic remedy action on living systems. Research indicates that homeopathic remedies (a) contain measurable source and silica nanoparticles heterogeneously dispersed in colloidal solution; (b) act by modulating biological function of the allostatic stress response network (c) evoke biphasic actions on living systems via organism-dependent adaptive and endogenously amplified effects; (d) improve systemic resilience. DISCUSSION: The proposed active components of homeopathic remedies are nanoparticles of source substance in water-based colloidal solution, not bulk-form drugs. Nanoparticles have unique biological and physico-chemical properties, including increased catalytic reactivity, protein and DNA adsorption, bioavailability, dose-sparing, electromagnetic, and quantum effects different from bulk-form materials. Trituration and/or liquid succussions during classical remedy preparation create “top-down” nanostructures. Plants can biosynthesize remedy-templated silica nanostructures. Nanoparticles stimulate hormesis, a beneficial low-dose adaptive response. Homeopathic remedies prescribed in low doses spaced intermittently over time act as biological signals that stimulate the organism’s allostatic biological stress response network, evoking nonlinear modulatory, self-organizing change. Potential mechanisms include time-dependent sensitization (TDS), a type of adaptive plasticity/metaplasticity involving progressive amplification of host responses, which reverse direction and oscillate at physiological limits. To mobilize hormesis and TDS, the remedy must be appraised as a salient, but low level, novel threat, stressor, or homeostatic disruption for the whole organism. Silica nanoparticles adsorb remedy source and amplify effects. Properly-timed remedy dosing elicits disease-primed compensatory reversal in direction of maladaptive dynamics of the allostatic network, thus promoting resilience and recovery from disease. SUMMARY: Homeopathic remedies are proposed as source nanoparticles that mobilize hormesis and time-dependent sensitization via non-pharmacological effects on specific biological adaptive and amplification mechanisms. The nanoparticle nature of remedies would distinguish them from conventional bulk drugs in structure, morphology, and functional properties. Outcomes would depend upon the ability of the organism to respond to the remedy as a novel stressor or heterotypic biological threat, initiating reversals of cumulative, cross-adapted biological maladaptations underlying disease in the allostatic stress response network. Systemic resilience would improve. This model provides a foundation for theory-driven research on the role of nanomaterials in living systems, mechanisms of homeopathic remedy actions and translational uses in nanomedicine

Kaelteversorgung von Schienenfahrzeug-Transformatoren mit HT-Supraleitung Schlussbericht

The refrigeration system for the HTS-transformer was designed in cooperation with the transformer manufacturer and the requirements for the refrigerator have been determined. Several active and passive refrigeration systems were investigated, two of them have been elaborated more detailed. All the refrigeration systems are based on the concept of a liquid nitrogen flow rate of 1000 g/s passing through the 6 MVA transformer at a temperature of approx. 66 K and at a pressure of approx. 3 bars. The passive system uses as refrigerant source a tank with liquid nitrogen, weighing approx. 2300 kg and consuming 500 kg liquid nitrogen per day. After evaporating and preheating the nitrogen used exits to atmosphere with a vacuum pump. The active system elaborated more detailed applies a Stirling engine for refrigeration, will weigh 1600 kg and needs an average electric power of 25 kW. The refrigeration system for a transformer of ceramic superconducting material has significant advantages with regard to weight, power consumption and investment costs compared to a transformer of the same size manufactured as metallic superconductors. (orig.)In Zusammenarbeit mit dem Transformatorhersteller wurden die Kaelteversorgung des HTS-Transformators konzipiert und die Anforderungen an die Kaelteanlage festgelegt. Verschiedene sogenannte passive und aktive Systeme fuer die Kaelteversorgung wurden untersucht, zwei davon naeher ausgearbeitet. Die Kuehlkonzepte sehen vor, dass fuer einen Transformator der Leistung 6 MVA ein Strom an fluessigem Stickstoff von 1000 g/s mit einer Temperatur von ca. 66 K und unter einem Druck von rund 3 bar durch den Transformator geleitet wird. Das passive System ist gekennzeichnet durch Einsatz eines Tanks fuer fluessigen Stickstoff als Kaeltequelle, hat ein Gewicht von etwa 2300 kg und einen Verbrauch an fluessigem Stickstoff von 500 kg/Tag. Der Stickstoff wird nach Verdampfung und Anwaermung mit Hilfe einer Vakuumpumpe an die Umgebung abgegeben. Das naeher ausgearbeitete aktive System verwendet eine Stirlingmaschine zur Kaelteerzeugung, hat ein Gewicht von 1600 kg und benoetigt eine elektrische Leistung von im Mittel 25 kW. Die Kaelteversorgung fuer einen Transformator mit keramischen Supraleitern hat hinsichtlich Gewicht, Leistungsbedarf und Investitionskosten deutliche Vorteile gegenueber einem entsprechend grossen Transformator mit metallischen Supraleitern. (orig.)SIGLEAvailable from TIB Hannover: F01B268+a / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekBundesministerium fuer Bildung, Wissenschaft, Forschung und Technologie, Bonn (Germany)DEGerman

Selective plating concept for silicon heterojunction solar cell metallization

We introduce a new plated metallization process for Silicon Heterojunction (SHJ) solar cells by selective plating of copper onto a positively masking seed layer. This process tackles the issues of high silver consumption and low grid conductivity of screen printed contacts on SHJ solar cells. Compared to other metallization approaches of plating into a negative mask, our process does not require expensive process steps or consumables to plate and then remove the mask. The process involves the deposition of a full area PVD layer of a valve metal like Al or Ti onto the ITO surface of a SHJ solar cell. The valve metal layer is self-passivating in nature and provides the ideal mix of conductivity for plating current distribution and selectivity for copper plating. As the next step, the grid is locally defined by printing or laser transferring the seed layer. Now a pulsed Cu plating step is applied to plate on the seed layer selectively while the valve metal layer is partly oxidized and parasitic Cu deposition on the valve metal surface is dissolved during reverse pulses. The valve metal layer is finally etched off in a subsequent etch bath

Novel plating processes for silicon heterojunction solar cell metallization using a structured seed layer

We present metallization approaches for silicon heterojunction solar cells by plating onto a structured seed layer. Our approaches do not require expensive processing steps or consumables. The process starts with a full area deposition of a dielectric or alternatively a blanket metal layer such as Al onto indium tin oxide (ITO). Next, the grid-shaped seed layer is applied via printing or laser-transfer. An efficiency of 22.2% was obtained using a dielectric layer and laser-transfer, outperforming screen-printing by 0.4%. Applying Al instead of a dielectric has the advantage that the plating current spreads more homogeneously on the solar cell surface, which is of particular importance for plating on bifacial solar cells. For using an Al blanket layer on top of ITO and a grid-shaped seed layer, we developed a plating process that selectively plates on the seed layer and not on the Al layer