Discovery of early-stage biomarkers for diabetic kidney disease using ms-based metabolomics (FinnDiane study)

Diabetic kidney disease (DKD) is a devastating complication that affects an estimated third of patients with type 1 diabetes mellitus (DM). There is no cure once the disease is diagnosed, but early treatment at a sub-clinical stage can prevent or at least halt the progression. DKD is clinically diagnosed as abnormally high urinary albumin excretion rate (AER). We hypothesize that subtle changes in the urine metabolome precede the clinically significant rise in AER. To test this, 52 type 1 diabetic patients were recruited by the FinnDiane study that had normal AER (normoalbuminuric). After an average of 5.5 years of follow-up half of the subjects (26) progressed from normal AER to microalbuminuria or DKD (macroalbuminuria), the other half remained normoalbuminuric. The objective of this study is to discover urinary biomarkers that differentiate the progressive form of albuminuria from non-progressive form of albuminuria in humans. Metabolite profiles of baseline 24 h urine samples were obtained by gas chromatography–mass spectrometry (GC–MS) and liquid chromatography–mass spectrometry (LC–MS) to detect potential early indicators of pathological changes. Multivariate logistic regression modeling of the metabolomics data resulted in a profile of metabolites that separated those patients that progressed from normoalbuminuric AER to microalbuminuric AER from those patients that maintained normoalbuminuric AER with an accuracy of 75% and a precision of 73%. As this data and samples are from an actual patient population and as such, gathered within a less controlled environment it is striking to see that within this profile a number of metabolites (identified as early indicators) have been associated with DKD already in literature, but also that new candidate biomarkers were found. The discriminating metabolites included acyl-carnitines, acyl-glycines and metabolites related to tryptophan metabolism. We found candidate biomarkers that were univariately significant different. This study demonstrates the potential of multivariate data analysis and metabolomics in the field of diabetic complications, and suggests several metabolic pathways relevant for further biological studies

Hybrid materials for molecular sieves

Hybrid microporous organosilica membranes for molecular separations made by acid-catalyzed solgel synthesis from bridged silsesquioxane precursors have demonstrated good performance in terms of flux and selectivity and remarkable hydrothermal stability in various pervaporation and gas separation processes. The availability of wide range of α,ω-bis(trialkoxysilyl)alkane and 1,4-bis (triethoxysilyl)benzene precursors allows tuning of membrane properties such as pore size and chemistry. This chapter presents an overview of the synthesis and application of hybrid organosilica microporous membranes in liquid and gas separation processes. After a concise discussion of the history of solgel-derived microporous ceramic membranes for molecular separations, the solgel chemistry of bridged silsesquioxanes and all relevant processing steps needed to obtain a supported microporous films suitable for molecular separations are discussed. The performance of these membranes is correlated with the membrane compositional properties, such as nature, stiffness and length of the bridging group, and details of the solgel process

El libro de los deberes

Reseña de: ESTÉVEZ ARAUJO, José Antonio (ed.). (2013). El libro de los deberes. Las debilidades e insuficiencias de la estrategia de los derechos. Madrid: Trotta. 264 pp

Stabilization and destabilization of zirconium propoxide precursors by acetylacetone

The stabilizing and destabilizing mechanism in the action of acetylacetone on zirconium propoxide precursors is revealed; the nature of heteroleptic intermediates provides an explanatio

Molecular design approach to a stable heterometallic zirconium-titanium alkoxide - potential precursor of mixed-oxide ceramics

New heterometallic interesting trinuclear, Zr{η3, μ2-NH(C2H4O)2}3[Ti(OiPr)3]2 encountering a nona-coordinated central zirconium atom crystallizes at −30 °C from a solution of zirconium and titanium isopropoxides and diethanolamine (Zr:Ti:L=1:2:3) in hydrocarbons. Due to its solution stability, this structurally characterized compound is an attractive potential precursor in sol–gel technique for the preparation of mixed metal oxide materials

A modified thermo-mechanical modeling approach for shape memory alloy behaviour13;

The Brinson-Lammering constitutive model is modified to account for the nonlinear shape memory alloy behaviour. The model is divided into three modules by keeping each of the three parameters of stress, strain and temperature constant. Experiments were conducted with a NiTiCu material to obtain the model constants. The constants were then incorporated in the model and the behaviour predicted. A good correlation is obtained between the theory and experiments.13

Nona-coordinated MO6N3 centers M = Zr, Hf as a stable building block for the construction of heterometallic alkoxide precursors

The modification of zirconium or hafnium alkoxides with diethanolamine, H2dea, leads to the formation of unique nona-coordinated M{μ-η3-NH(C2H4O)2}3 cores. The mechanism is used to develop a self-assembly approach to the first thermodynamically stable zirconium–titanium and hafnium–titanium precursors, Zr{μ-η3-NH(C2H4O)2}3[Ti(OiPr)3]2 (1) and Hf{μ-η3-NH(C2H4O)2}3[Ti(OiPr)3]2 (2). Mass spectrometric characterization of these compounds demonstrates their volatility. In addition to the solution stability of these compounds the volatility makes them attractive single source precursors for MOCVD and ALD applications. These precursors are also interesting candidates for application in sol–gel synthesis of microporous materials as the stability of the core prevents self-assembly of ligands on the outer surface of the primary particles formed during the hydrolysis. A n-propoxide analog of 1 can be prepared from zirconium n-propoxide but does not yield any crystalline material. It is demonstrated that 1 can be prepared from [Zr(OnPr)(OiPr)3(iPrOH)]2, however, with a lower yield compared to the use of zirconium isopropoxide. The single crystals obtained from systems containing zirconium isopropoxide, titanium isopropoxide and triethanolamine H3tea turned out to be Ti2(OiPr)2({μ-η4-NH(C2H4O)3}2)2 (4). Theoretical calculations indicate that the octacoordinate M{μ-η4-N(C2H4O)3}2 core, anticipated in reaction with H3tea, will have metal–nitrogen bonds that are too long for its stabilization. This explains why the formation of 4 is thermodynamically favored over the formation of heterometallic species