Genetically Encoded Voltage Indicators in Circulation Research

Membrane potentials display the cellular status of non-excitable cells and mediate communication between excitable cells via action potentials. The use of genetically encoded biosensors employing fluorescent proteins allows a non-invasive biocompatible way to read out the membrane potential in cardiac myocytes and other cells of the circulation system. Although the approaches to design such biosensors date back to the time when the first fluorescent-protein based Förster Resonance Energy Transfer (FRET) sensors were constructed, it took 15 years before reliable sensors became readily available. Here, we review different developments of genetically encoded membrane potential sensors. Furthermore, it is shown how such sensors can be used in pharmacological screening applications as well as in circulation related basic biomedical research. Potentials and limitations will be discussed and perspectives of possible future developments will be provided.     

Characterization of biaxial strain of poly(l‐lactide) tubes

Poly(l ‐lactide) in its l ‐form has promising mechanical properties. Being a semicrystalline polymer, it can be subjected to strain‐induced crystallization at temperatures above T_g and can thereby become oriented. Following a simultaneous (SIM) biaxial strain process or a sequential (SEQ) biaxial strain process, the mechanical properties of biaxially strained tubes can be further improved. This study investigated these properties in relation to their morphology and crystal orientation. Both processes yield the same mechanical strength and modulus, yet exhibit different crystal orientation. Through further wide angle X‐ray scattering analysis it was found that the SEQ biaxial strain yields larger interplanar spacing and distorted crystals and looser packing of chains. However, this does not influence the mechanical properties negatively. A loss of orientation in SEQ biaxially strained samples at high degrees of strain was detected, but was not seen for SIM biaxial strain and did not correlate with mechanical performance in either case. However, post‐annealing reduced the orientation to the same level in both cases, and the modulus and strength decreased for both SIM and SEQ biaxial strain. It is therefore concluded that mechanical properties after biaxial strain are related to strain‐induced amorphous orientation and the packing of crystals, rather than strain‐induced crystallinity. © 2015 Society of Chemical Industry     

Aneurysm miRNA Signature Differs,Depending on Disease Localization and Morphology

Limited comprehension of aneurysm pathology has led to inconclusive results from clinical trials. miRNAs are key regulators of post-translational gene modification and are useful tools in elucidating key features of aneurysm pathogenesis in distinct entities of abdominal and popliteal aneurysms. Here, surgically harvested specimens from 19 abdominal aortic aneurysm (AAA) and 8 popliteal artery aneurysm (PAA) patients were analyzed for miRNA expression and histologically classified regarding extracellular matrix (ECM) remodeling and inflammation. DIANA-based computational target prediction and pathway enrichment analysis verified our results, as well as previous ones. miRNA-362, -19b-1, -194, -769, -21 and -550 were significantly down-regulated in AAA samples depending on degree of inflammation. Similar or inverse regulation was found for miR-769, 19b-1 and miR-550, -21, whereas miR-194 and -362 were unaltered in PAA. In situ hybridization verified higher expression of miR-550 and -21 in PAA compared to AAA and computational analysis for target genes and pathway enrichment affirmed signal transduction, cell-cell-interaction and cell degradation pathways, in line with previous results. Despite the vague role of miRNAs for potential diagnostic and treatment purposes, the number of candidates from tissue signature studies is increasing. Tissue morphology influences subsequent research, yet comparison of distinct entities of aneurysm disease can unravel core pathways.     

Modeling and control of a SOFC-GT-based autonomous power system

In this article, a dynamic, lumped model of a solid oxide fuel cell (SOFC) is described, as a step towards developing control relevant models for a SOFC combined with a gas turbine (GT) in an autonomous power system. The model is evaluated against a distributed dynamic tubular SOFC model. The simulation results confirm that the simple model is able to capture the important dynamics of the SOFC and hence it is concluded that the simple model can be used for control and operability studies of the hybrid system. Several such lumped models can be aggregated to approximate the distributed nature of important variables of the SOFC. Further, models of all other components of a SOFC-GT-based autonomous power system are developed and a control structure for the total system is developed. The controller provides satisfactory performance for load changes at the cost of efficiency.     

THE INFLUENCE OF METAL-CONTAINING COMPOUNDS ON ENHANCEMENT AND INHIBITION OF ASPHALT OXIDATION

Addition of lime to paving asphalts is known to inhibit oxidative aging of pavements. The mechanism of the action of lime in retarding oxidation is not known. In this work, an asphalt was mixed with a vanadium chelate that is known to strongly promote oxidation in asphalts. This enhancement of oxidation was largely neutralized when the mixtures were combined with hydrated lime. It is possible that lime acts by suppressing the catalytic activity of naturally occurring vanadium compounds that occur in almost all asphalts, although other mechanisms for the action of lime are also possible. The use of vanadium compounds in asphalt aging tests also is discussed.     

Terminal decline and cognitive performance in very old age: Does cause of death matter?

Cross-sectional differences and longitudinal changes in cognitive functioning in relation to mortality across a 7-year follow-up period, with 3 times of measurement, were examined in a population-based sample of very old adults. The authors also sought to determine whether cause of death (cerebro/cardiovascular disease [CVD]; non-CVD) modified the magnitude of mortality-related cognitive deficits. Cognitive performance was indexed by tests of general cognitive ability, episodic memory, primary memory, verbal fluency, and visuospatial ability. Results indicated cross-sectional differences on all domains of functioning, with persons who would die within 3 years after baseline testing performing more poorly. Longitudinally, greater decrements were observed on all domains for persons who would die after the first follow-up period, as compared with survivors. Cause of death failed to modify the magnitude of the cross-sectional and longitudinal deficits. The pattern of results point to the general nature of this phenomenon. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Dynamic behavior of an activated sludge plant

The purpose of this paper is to study how and to what extent effluent BOD₅ is related to influent BOD₅ and flow in an activated sludge process. The analysis is based on data collected hourly over a 2-week period at a Wisconsin sewage treatment plant. The methodology applied to establish a dynamic model for the system is that of Box & Jenkins (1970). With this approach, stochastic and transfer function components can be combined to form a model. The relative importance of these two components can be quantitatively assessed. A simple first-order model is able to explain the data very well. In this empirical model, which does not need flow as a predictor variable, the stochastic component is much more important than the transfer function component. Frequent return sludge control is not needed for the plant studied because it possesses remarkable inherent stability.     

An experimental and theoretical study of cementite dissolution in an Fe-Cr-C alloy

The dissolution of cementite at 910 °C in an Fe-2.06Cr-3.91C (at. pct) alloy is investigated experimentally. The Cr concentration profiles in austenite and cementite are measured by means of the scanning transmission electron microscopy/energy dispersive spectrometry (STEM/EDS) technique at different dissolution times. The measurements show the Cr enrichment in the cementite during the dissolution process. The measurements suggest that the main part of the reaction for this alloy is controlled by Cr diffusion in the cementite or in the austenite matrix. This observation is in agreement with predictions of the local equilibrium hypothesis. The carbide fraction and average particle diameter are evaluated as functions of dissolution time. The Cr enrichment of the cementite results in a supersaturation and a possible decomposition of the cementite. Microstructural evidence for such a decomposition is found by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). A new program package called DICTRA,_[11] which is suitable for the simulation of diffusional reactions in multicomponent alloys, has been applied to the present case. The simulation is compared with the experimental data, and a good agreement between the two is found.     

The source of dietary fatty acids alters the activity of secretory sphingomyelinase in the rat

Secretory sphingomyelinase (sSMase) has been suggested to be involved in the development of cardiovascular diseases as well as other human pathologies. To deduce whether dietary fatty acid composition affects the circulating activity of this enzyme, we have compared its activity in serum from rats that had been given a diet containing either butter or a highly n‐6 polyunsaturated [grapeseed oil (GSO)] fat source for 14 wk. The results show that intake of GSO increases the activity of this ceramide‐producing enzyme by about 45%, when compared with intake of butter (387 ± 16 pmol/mL·h vs. 266 ± 15 pmol/mL·h; p <0.001). Furthermore, there was a strong negative correlation between sSMase activity and n‐3 PUFA concentration in serum (p <0.001). Despite the substantial increase in activity, there was no difference in either the circulating substrate (sphingomyelin) or product (ceramide) in the serum. However, since the sSMase activity in the endothelial wall has been implicated to be involved in both atherogenesis and thrombosis, these findings are of interest in the interpretation of dietary fatty acid effects on cardiovascular health.     

Hydrolysis of cationic polyacrylamides

The alkaline hydrolysis of two acrylamide-based polyelectrolytes has been investigated. The experiments were carried out in buffered aqueous solutions in the pH range of 3.5–8.5 and in the temperature range of 22–50°C. ¹³C-NMR analysis of the hydrolysis product showed that choline chloride was the substance released upon hydrolysis. The decrease in charge density of the copolymer due to the hydrolysis was studied by polyelectrolyte titration and nitrogen analysis. The results show that the rate of hydrolysis increased with increasing pH or increasing temperature. In the hydrolysis of C-PAM 1 at 22°C and pH 6, the half-life of the cationic groups was 10 days. At pH 7 the half-life was shorter, 24 h, and at pH 8.5 the reaction was very fast with a half-life of about 0.25 h. The charged groups on C-PAM 2, the polymer with the higher charge density of the two polymers studied, have somewhat longer half lives than those on C-PAM 1. This can be explained by the structure of the polymers.