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The contribution of altered post-transcriptional gene silencing to the development of insulin resistance and type 2 diabetes mellitus so far remains elusive. Here, we demonstrate that expression of microRNA (miR)-143 and 145 is upregulated in the liver of genetic and dietary mouse models of obesity. Induced transgenic overexpression of miR-143, but not miR-145, impairs insulin-stimulated AKT activation and glucose homeostasis. Conversely, mice deficient for the miR-143–145 cluster are protected from the development of obesity-associated insulin resistance. Quantitative-mass-spectrometry-based analysis of hepatic protein expression in miR-143-overexpressing mice revealed miR-143-dependent downregulation of oxysterol-binding-protein-related protein (ORP) 8. Reduced ORP8 expression in cultured liver cells impairs the ability of insulin to induce AKT activation, revealing an ORP8-dependent mechanism of AKT regulation. Our experiments provide direct evidence that dysregulated post-transcriptional gene silencing contributes to the development of obesity-induced insulin resistance, and characterize the miR-143–ORP8 pathway as a potential target for the treatment of obesity-associated diabetes.
The powerful avalanche simulation toolbox RAMMS (Rapid Mass Movements) is based on a depth-averaged
hydrodynamic system of equations with a Voellmy-Salm friction relation. The two empirical friction parameters
μ and correspond to a dry Coulomb friction and a viscous resistance, respectively. Although μ and lack a
proper physical explanation, 60 years of acquired avalanche data in the Swiss Alps made a systematic calibration
possible. RAMMS can therefore successfully model avalanche flow depth, velocities, impact pressure and run
out distances. Pudasaini and Hutter (2003) have proposed extended, rigorously derived model equations that
account for local curvature and twist. A coordinate transformation into a reference system, applied to the actual
mountain topography of the natural avalanche path, is performed. The local curvature and the twist of the
avalanche path induce an additional term in the overburden pressure. This leads to a modification of the Coulomb
friction, the free-surface pressure gradient, the pressure induced by the channel, and the gravity components
along and normal to the curved and twisted reference surface. This eventually guides the flow dynamics and
deposits of avalanches. In the present study, we investigate the influence of curvature on avalanche flow in
real mountain terrain. Simulations of real avalanche paths are performed and compared for the different models
approaches. An algorithm to calculate curvature in real terrain is introduced in RAMMS. This leads to a curvature
dependent friction relation in an extended version of the Voellmy-Salm model equations. Our analysis provides
yet another step in interpreting the physical meaning and significance of the friction parameters used in the
RAMMS computational environment.
Capacitive field-effect electrolyte-insulator-semiconductor sensors consisting of an Al-p-Si-SiO2 structure have been used for the electrical detection of unlabelled single- and double-stranded DNA (dsDNA) molecules by their intrinsic charge. A simple functionalization protocol based on the layer-by-layer (LbL) technique was used to prepare a weak polyelectrolyte/probe-DNA bilayer, followed by the hybridization with complementary target DNA molecules. Due to the flat orientation of the LbL-adsorbed DNA molecules, a high sensor signal has been achieved. In addition, direct label-free detection of in-solution hybridized dsDNA molecules has been studied.
Label-free Electrostatic Detection of DNA Amplification by PCR Using Capacitive Field-effect Devices
(2016)
A capacitive field-effect EIS (electrolyte-insulator-semiconductor) sensor modified with a positively charged weak polyelectrolyte of poly(allylamine hydrochloride) (PAH)/single-stranded probe DNA (ssDNA) bilayer has been used for a label-free electrostatic detection of pathogen-specific DNA amplification via polymerase chain reaction (PCR). The sensor is able to distinguish between positive and negative PCR solutions, to detect the existence of target DNA amplicons in PCR samples and thus, can be used as tool for a quick verification of DNA amplification and the successful PCR process.
The continuously growing amount of renewable sources starts compromising the stability of electrical grids. Contradictory to fossil fuel power plants, energy production of wind and photovoltaic (PV) energy is fluctuating. Although predictions have significantly improved, an outage of multi-MW offshore wind farms poses a challenging problem. One solution could be the integration of storage systems in the grid. After a short overview, this paper focuses on two exemplary battery storage systems, including the required power electronics. The grid integration, as well as the optimal usage of volatile energy reserves, is presented for a 5- kW PV system for home application, as well as for a 100- MW medium-voltage system, intended for wind farm usage. The efficiency and cost of topologies are investigated as a key parameter for large-scale integration of renewable power at medium- and low-voltage.
The Saturnian moon Enceladus with its extensive water bodies underneath a thick ice sheet cover is a potential candidate for extraterrestrial life. Direct exploration of such extraterrestrial aquatic ecosystems requires advanced access and sampling technologies with a high level of autonomy. A new technological approach has been developed as part of the collaborative research project Enceladus Explorer (EnEx). The concept is based upon a minimally invasive melting probe called the IceMole. The force-regulated, heater-controlled IceMole is able to travel along a curved trajectory as well as upwards. Hence, it allows maneuvers which may be necessary for obstacle avoidance or target selection. Maneuverability, however, necessitates a sophisticated on-board navigation system capable of autonomous operations. The development of such a navigational system has been the focal part of the EnEx project. The original IceMole has been further developed to include relative positioning based on in-ice attitude determination, acoustic positioning, ultrasonic obstacle and target detection integrated through a high-level sensor fusion. This paper describes the EnEx technology and discusses implications for an actual extraterrestrial mission concept.