Intergenerational Metabolomic Analysis of Mothers with a History of Gestational Diabetes Mellitus and Their Offspring

Shared metabolomic patterns at delivery have been suggested to underlie the mother-to-child transmission of adverse metabolic health. This study aimed to investigate whether mothers with gestational diabetes mellitus (GDM) and their offspring show similar metabolomic patterns several years postpartum. Targeted metabolomics (including 137 metabolites) was performed in plasma samples obtained during an oral glucose tolerance test from 48 mothers with GDM and their offspring at a cross-sectional study visit 8 years after delivery. Partial Pearson’s correlations between the area under the curve (AUC) of maternal and offspring metabolites were calculated, yielding so-called Gaussian graphical models. Spearman’s correlations were applied to investigate correlations of body mass index (BMI), Matsuda insulin sensitivity index (ISI-M), dietary intake, and physical activity between generations, and correlations of metabolite AUCs with lifestyle variables. This study revealed that BMI, ISI-M, and the AUC of six metabolites (carnitine, taurine, proline, SM(-OH) C14:1, creatinine, and PC ae C34:3) were significantly correlated between mothers and offspring several years postpartum. Intergenerational metabolite correlations were independent of shared BMI, ISI-M, age, sex, and all other metabolites. Furthermore, creatinine was correlated with physical activity in mothers. This study suggests that there is long-term metabolic programming in the offspring of mothers with GDM and informs us about targets that could be addressed by future intervention studies.     

Numerical solution for shape optimization of an impactor penetrating into a semi-infinite target

The shape of the impactor with the maximum depth of penetration (DOP) for a given impact velocity is found using a numerical procedure for solving a corresponding non-classical variational problem. It is shown that the optimum shape in a general case is close to a blunt cone. The variation of the optimal shape of the impactor and the dependence of the DOP vs. the initial (impact) velocity and friction coefficient is studied. The analysis is performed also for optimal conical impactors.     

Numerical investigation of the flow inside the combustion chamber of a plant oil stove

Recently a low cost cooking device for developing and emerging countries was developed at KIT in cooperation with the company Bosch und Siemens Hausger te GmbH.After constructing an innovative basic design further development was required.Numerical investigations were conducted in order to investigate the flow inside the combustion chamber of the stove under variation of different geometrical parameters.Beyond the performance improvement a further reason of the investigations was to rate the effects of manufacturing tolerance problems.In this paper the numerical investigation of a plant oil stove by means of RANS simulation will be presented.In order to reduce the computational costs different model reduction steps were necessary.The simulation results of the basic configuration compare very well with experimental measurements and problematic behaviors of the actual stove design could be explained by the investigation.     

Novel Design of Neuropeptide-Based Drugs with β-Sheet Breaking Potential in Amyloid-Beta Cascade: Molecular and Structural Deciphers

Our work discusses the investigation of 75 peptide-based drugs with the potential ability to break the β-sheet structures of amyloid-beta peptides from senile plaques. Hence, this study offers a unique insight into the design of neuropeptide-based drugs with β-sheet breaker potential in the amyloid-beta cascade for Alzheimer’s disease (AD). We started with five peptides (¹⁵QKLVFF²⁰, ¹⁶KLVFF²⁰, ¹⁷LVFF²⁰, ¹⁶KLVF¹⁹ and ¹⁵QKLV¹⁸), to which 14 different organic acids were attached at the N-terminal. It was necessary to evaluate the physiochemical features of these sequences due to the biological correlation with our proposal. Hence, the preliminary analysis of different pharmacological features provided the necessary data to select the peptides with the best biocompatibility for administration purposes. Our approaches demonstrated that the peptides ¹⁷LVFF²⁰, NA-¹⁷LVFF²⁰, ¹⁶KLVF¹⁹ and NA-¹⁶KLVF¹⁹ (NA-nicotinic acid) have the ability to interfere with fibril formation and hence improve the neuro and cognitive functions. Moreover, the peptide conjugate NA-¹⁶KLVF¹⁹ possesses attractive pharmacological properties, demonstrated by in silico and in vitro studies. Tandem mass spectrometry showed no fragmentation for the spectra of ¹⁶KLVF¹⁹. Such important results suggest that under the action of protease, the peptide cleavage does not occur at all. Additionally, circular dichroism confirmed docking simulations and showed that NA-¹⁶KLVF¹⁹ may improve the β-sheet breaker mechanism, and thus the entanglement process of amyloid-beta peptides can be more effective.     

Six-layer lamination of a new dry film negative-tone photoresist for fabricating complex 3D microfluidic devices

We present a new epoxy-based negative-tone dry film photoresist (DFR) for fabricating multilayer microfluidic devices using a lamination process combined with a standard photolithography technology. As proof-of-concept, a complex 3D-hydrodynamic focusing device was produced via a six-layer lamination process of 33 µm-thick DFR layers. The bonding strength of the new DFR was tested on silicon, glass, and titanium substrates, respectively. A maximum bonding strength of 37 MPa was obtained for the dry film photoresist laminated on glass. No leakage was found, and burst tests proved excellent robustness and sealing reliability of the microchannels.     

Diaphragm gauge for measuring explosive impulse

The measurement of shock and stress waves under the action of explosion and impact loading has long been a concern of scientists and engineers. A number of methods have been developed over the years for measuring the physical parameters that are involved in the material dynamics resulting from an explosion. This work describes the development, calibration and validation of a passive copper diaphragm gauge aimed at measuring the impulse acting on it, resulting from an explosion in air. It is found that the diaphragm deformation (central deflection) can be used to measure the impulse, given the calibration curve. Once the gauge is calibrated, it can be used to measure the impulse acting on it in other media (water, soil, etc.). Such gauges are useful in measuring explosion induced impulses acting on structures. This usefulness is the result of the gauge simplicity and reproducibility. It can be used as a passive gauge or, when instrumented with strain gauges, as a passive and active (electronic) gauge.     

A nondimensional analysis of dusty shock waves in steady flows

The governing equations describing the flow field which results when a dust-gas suspension passes through a normal shock wave were nondimensionalized. The nondimensionalization resulted in a set of nondimensional groups of parameters which, if kept constant, lead to a self-similar solution. An investigation of these nondimensional groups of parameters revealed, for example, that the relaxation length depends linearily on the material density of the solid particles. Dependence of the relaxation length on the other parameters of thd dust is discussed.     

The influence of P2O5 on clinker reactions

Synthetic clinkers, similar to high-silica Portland Cement clinkers, were prepared from raw material containing at times more than 50% oil shale from Har-Tuv area (central Israel) to which phosphate rock and laboratory grade CaCO₃ and SiO₂ were added. Although some clinkers contained more than 3% P₂O₅, their mineralogical composition was satisfactory (50 to 60% C₃S). This result was obtained by taking into account in the SM formula the P₂O₅ concentrations. The resultant relatively high silica concentrations raise the melting point of the raw meal, causing a non-equilibrium state which allows the formation of C₃S and its preservation.     

The microstructure and infra-red spectra of hydrated tricalcium silicate containing phosphate

The influence of phosphate, in the concentration range 0.7 to 4.5%, on the hydration reaction of tricalcium silicate was examined with a scanning electron microscope and an infra-red spectrometer. Correlation between the morphology and infra-red vibrations, on the one hand, and the free lime content dependence on the phosphate concentration, on the other, is discussed.This paper is in partial fulfilment of the MSc degree of Y. Rubinsztain, at the Hebrew University.