Discovery of a Potent,CNS‐Penetrant Orexin Receptor Antagonist Based on an N,N‐Disubstituted‐1,4‐diazepane Scaffold that Promotes Sleep in Rats

Silent Night : Antagonism of the orexin (or hypocretin) system has recently been identified as a novel mechanism for the treatment of insomnia. Herein, we describe discovery of a dual (OX₁R/OX₂R) orexin receptor antagonist featuring a 1,4‐diazepane central constraint that blocks orexin signaling in vivo. In telemetry‐implanted rats, oral administration of this antagonist produced a decrease in wakefulness, while increasing REM and non‐REM sleep.

     

Tribological Performance of Some Pennzane®-Based Greases for Vacuum Applications

Commercial greases for space applications usually fulfill the requirements imposed by the severe conditions of use (load, ultrahigh vacuum, speed, etc.). The main requirement is their ability to create an elastohydrodynamic lubrication film, boundary film, or both, for the speed, load, and temperature conditions under which the mechanisms will operate. Three greases, all based on a multiply alkylated cyclopentane (Pennzane®) base oil, were studied. The thickeners were an n-octadecylterephthalamate soap, a lithium soap, and a urea derivative. A four-ball tribometer and a spiral-orbit tribometer were employed to evaluate the greases under ultrahigh vacuum. The results indicated that all three greases yielded very low wear rates and extended lifetimes. In addition, routine physical property data are reported for each grease.     

Preference-based topology optimization for vehicle concept design with concurrent static and crash load cases

In the simulation-based design process of automotive structures, an increasing amount of multi-disciplinary requirements have to be considered. Methods of topology optimization can be used to devise structural concepts early in the design process to obtain the best possible structural layout as starting point for further development steps. Especially relevant for the vehicle design process is the concurrent consideration of static load requirements representing normal operating conditions and energy absorption requirements targeting passive safety in crash events. When the disciplines are considered separately, the heuristic Hybrid Cellular Automaton topology optimization is a suitable method. However, in practical applications, both disciplines are usually addressed sequentially. This complicates the overall process and may reduce the quality of the final optimization result, since optimization objectives may be conflicting. We propose a preference-based Scaled Energy Weighting approach to address the topology optimization of both disciplines concurrently. The main idea is to decouple the user preference from the scaling of the different magnitudes of energies. This enables a multi-objective optimization and ultimately the selection of the desired trade-off solution. We first validate the capability of the method to provide structures optimized for stiffness and energy absorption objectives on beam examples. Finally, the method is applied to optimize a concept structure of an industrial vehicle body, demonstrating its practical feasibility.     

Sugar and cocoa: sweet synergy or bitter antagonisms. Formulating cocoa and chocolate products for health: a narrative review

The potential health effects of cocoa flavanols are well described. Ranging from reducing risk of developing type 2 diabetes and cardiovascular disease at population levels, moderating disease risk factors including endothelial function and lipid metabolism in clinical trials and mechanistic studies in laboratory studies highlighting target tissues and pathways. However, translating these benefits into public health messages is problematic, due to the high energy and sugar content of many cocoa products, including chocolate. This review considered the role of sugar in cocoa products, what are its physiological effects on bioavailability and bioactivity? Considering, then how cocoa products can be reformulated to reduce sugar intake, and the likely effects on beneficial effects of cocoa flavanols and consumer preferences. Ultimately, although interesting physiological effects are seen with cocoa flavanols, their use as a disease‐modifying commodities may be limited the effect such products may have within an individual's and populations overall dietary patterns.     

Thermal stability of SiC Schottky diode anode and cathode metalisations after 1000 h at 350 °C

The thermal stability of two commercially available silicon carbide Schottky diode types has been evaluated following a 1000 h non-biased storage test under vacuum at 350 °C. The Ti-based Schottky (Anode) contact shows excellent stability over the duration of the test with less than 5% change in either extracted Schottky barrier height or ideality values. The Al die attach metalisation on the anode also shows no evidence of degradation after the test. However, a considerable change in series resistance was observed for both diode types, with up to a factor of 100 measured for one of the diodes. The primary early failure mode is related to degradation of the NiAg Ohmic (cathode) die attach metalisation. Demixing of the NiAg alloy, leading to Ag agglomeration is proposed to be the underlying degradation mechanism involved resulting in delamination of the die attach metalisation and the corresponding series resistance increase.     

Flame–vortex interaction driven combustion dynamics in a backward-facing step combustor

The combustion dynamics of propane–hydrogen mixtures are investigated in an atmospheric pressure, lean, premixed backward-facing step combustor. We systematically vary the equivalence ratio, inlet temperature and fuel composition to determine the stability map of the combustor. Simultaneous pressure, velocity, heat release rate and equivalence ratio measurements and high-speed video from the experiments are used to identify and characterize several distinct operating modes. When fuel is injected far upstream from the step, the equivalence ratio entering the flame is temporally and spatially uniform, and the combustion dynamics are governed only by flame–vortex interactions. Four distinct dynamic regimes are observed depending on the operating parameters. At high but lean equivalence ratios, the flame is unstable and oscillates strongly as it is wrapped around the large unsteady wake vortex. At intermediate equivalence ratios, weakly oscillating quasi-stable flames are observed. Near the lean blowout limit, long stable flames extending from the corner of the step are formed. At atmospheric inlet temperature, the unstable mode resonates at the 1/4 wavemode of the combustor. As the inlet temperature is increased, the 5/4 wavemode of the combustor is excited at high but lean equivalence ratios, forming the high-frequency unstable flames. Higher hydrogen concentration in the fuel and higher inlet temperatures reduce the equivalence ratios at which the transitions between regimes are observed. We plot combustion dynamics maps or the response curves, that is the overall sound pressure level as a function of the equivalence ratio, for different operating conditions. We demonstrate that numerical results of strained premixed flames can be used to collapse the response curves describing the transitions among the dynamic modes onto a function of the heat release rate parameter alone, rather than a function dependent on the equivalence ratio, inlet temperature and fuel composition separately. We formulate a theory for predicting the critical values of the heat release parameter at which quasi-stable to unstable and unstable to high-frequency unstable modes take place.     

Does statistical language constitute a "significant" roadblock to readers' interpretations of research results?

Critics of statistical hypothesis testing mention how such tests mislead unsuspecting readers into believing that a statistically significant outcome is important and that a nonsignificant outcome is unimportant. Specifically, they mention how the term significant is misleading. In 3 experiments, the authors investigated whether statistical language influences readers' interpretations of research results. For "statistically na?ve" college students reading brief research abstracts, the term significant contributed somewhat to an overinterpretation of the results' importance. But for reading lengthier abstracts and articles, language per se was associated with no negative outcomes. Although the authors argue that "significant" language changes should not be mandated for quantitative research studies in scientific journals, if such changes are mandated, then use of the term statistical is recommended as a straightforward solution to the problem. (PsycINFO Database Record (c) 2010 APA, all rights reserved)