Novel Positive Allosteric Modulators of µ Opioid Receptor—Insight from In Silico and In Vivo Studies

Opioids are the drugs of choice in severe pain management. Unfortunately, their use involves serious, potentially lethal side effects. Therefore, efforts in opioid drug design turn toward safer and more effective mechanisms, including allosteric modulation. In this study, molecular dynamics simulations in silico and ‘writhing’ tests in vivo were used to characterize potential allosteric mechanism of two previously reported compounds. The results suggest that investigated compounds bind to μ opioid receptor in an allosteric site, augmenting action of morphine at subeffective doses, and exerting antinociceptive effect alone at higher doses. Detailed analysis of in silico calculations suggests that first of the compounds behaves more like allosteric agonist, while the second compound acts mainly as a positive allosteric modulator.     

Physicochemical properties of ready‐to‐eat extruded nixtamalized maize‐based snacks enriched with grasshopper

The aim of this research was to prepare an extruded snack based on nixtamalized maize flour (Zea mays L.) (NMF) enriched with grasshopper meal (Sphenarium purpurascens Ch.) (GM) using a single screw extruder with a compression screw ratio of 3:1. A central experimental design comprising three independent variables, namely, extrusion temperature (T = 120–180 °C), feed moisture content (FMC = 18–22 g/100 g) and the grasshopper meal proportion (GMP = 0–40 g/100 g), was used. Increasing T decreased (P < 0.05) the expansion index (EI), bulk density (BD) and hardness (H). Increasing the FMC increased (P < 0.05) the EI. Increasing the GMP decreased (P < 0.05) the EI, H and water absorption index (WAI) and increased (P < 0.05) the BD and total colour difference (ΔE). The treatments that resulted in better general acceptability were those that contained a lower GMP. An extruded snack acceptable to the consumer can be obtained from a blend of NMF and GM, and up to 8.11 g/100 g of GM can be incorporated without affecting the physicochemical properties and acceptance of the snack.     

Using hydroacoustics to relate fluctuations in fish abundance to river restoration efforts and environmental conditions in the Penobscot River,Maine

Quantifying change after large habitat restoration efforts is critical to assessing the effort's success. After river restoration activities, fish abundance is expected to increase and also fluctuates naturally by season and with environmental conditions. A side‐looking hydroacoustic system was used to estimate fish abundance in the Penobscot River, ME, from 2010 to 2016 during predam (2010–2013) and postdam (2014–2016) removal years during nonice periods. Automated data processing enabled continuous abundance estimates from fish tracks. A threefold increase in mean fish abundance was recorded after dam removal. A fourfold increase in median fish abundance occurred in the fall relative to spring and summer of the same year, regardless of dam presence. Interannual fish abundance in every season monitored increased at least twofold after dam removal. We related variability in fish abundance to tide, discharge, temperature, diurnal cycle, daylength, moon phase, and restoration activities (focusing on dam presence). Daylength corresponding to the fall and summer was the most important indicator for higher fish abundance. Fish abundance was generally greatest in the fall during outgoing tides at night, with lesser peaks occurring during the month of June at night. Before dam removal, fish abundance peaked when water temperature was less than 9.25°C, at night, during outgoing tides. After dam removal, fish abundance peaked when daylength was less than 11.3 hr, at night, during outgoing tides, when water temperature was above 4.56°C and no full moon was present. Peak fish abundance occurred during only 0.02–2.3% of the total time sampled. The threefold increase in fish abundance recorded after dam removal was observed despite yearly stocking efforts of adult alewife increasing 24% in postdam removal years. Finally, parallel studies of fish presence in the Penobscot River were used to compare the utility of this method as an indicator of fish abundance in response to dam removal.     

Using shear force,sarcomere length,particle size,collagen content,and protein solubility metrics to predict consumer acceptance of aged beef tenderness

In this study, the relationship between sensory evaluation and several objective metrics of beef tenderness was tested. Objective metrics included shear force, sarcomere length, collagen content, myofibrillar, and sarcoplasmic protein solubility and particle size analysis. These results were compared to consumer panel scores of tenderness for the same aged beef striploin (longissimus lumborum muscle) samples. There was found to be a significant relationship between sarcomere length, shear force, and particle size with tenderness scores. Collagen content and protein solubilities were not associated to tenderness scores (p > 0.05). Sarcomere length contributions for explaining tenderness variation were overlapped by the contributions of shear force (collinearity). Independent models demonstrated that the lower 95% confidence interval of the fitted regression line exceeded 50% acceptance of tenderness when shear force values <42.6 N and when particle size values <198 μm. We can recommend these as thresholds for consumer acceptance of beef tenderness, although considerations of sample type, analytical methodology, and consumer demographics should be made prior to their adoption. This provision was based on the variation in tenderness scores evident between individual panelists and experimental striploins.     

Assessment of contaminant diffusivities in building materials from porosimetry tests

Recent studies have shown that surface and gaseous contaminant interactions may play an important role in indoor air quality. Modeling is an important tool to improve our knowledge about the phenomena involved and define appropriate ventilation strategies. However, data for sorption isotherms and diffusion in building materials remain woefully lacking. This paper deals with the latter point. It aims at investigating a methodology based on an analysis of the material porosity first and then the application of Carniglia's mathematical model to determine the effective diffusivity of gaseous species in building materials. This methodology, whose main principles are presented in the first part of the paper, was applied to seven commonly found materials. Mercury intrusion porosimetry (MIP) tests, and the calculations using Carniglia's model, reveal typical total porosities and tortuosity factors for these materials. The analysis of pore size distributions (PSDs) also draws one's attention to the possible differences in the pore structures that may exist between two samples of the same type of material and the differences in the effective diffusivities of contaminants that may result from them. The computed effective diffusivities were subsequently compared to data from experiments carried out in the frame of the EC project MATHIS. An agreement was obtained, thus validating Carniglia's methodology - a methodology that offers many practical advantages compared to diffusion-cell methods.     

A practical study of white‐clawed crayfish (Austropotamobius pallipes) mitigation during in‐channel construction works,North‐East England

The article provides a unique opportunity to study a large white‐clawed crayfish mitigation exercise on the River Wansbeck, Northumberland in North East England. The translation was necessary to allow the construction of a dam on the river to reduce flood risk to the town of Morpeth. The study provides an assessment of the methodology used for the capture and translocation activities, and provides an insight into the speed of colonisation and population establishment in a 300‐m diversion channel and the structure of translocated populations. Over 3500 + white‐clawed crayfish were caught when the natural channel was dewatered, with 5400 animals removed the following year when the diversion channel was closed. Average density based on the number of white‐clawed crayfish caught was estimated as in excess of 5 per 1 m². The study demonstrates the importance of the River Wansbeck for white‐clawed crayfish.     

Design and optimization of small hydropower systems in water distribution networks under consideration of rehabilitation measures

Small hydro power systems (SHPSs) are increasingly installed in water distribution systems (WDSs). With only minor adaptations in a WDS, pressure surplus can be utilised. In such systems, a water surplus is also often available. In this work, water consumption data of a real Alpine WDS over one year are used as an input for an Epanet2 long-term simulation model to assess such a SHPS. In addition, the combinations of pressure and water surplus devices in a WDS are investigated. For such a specific investigated case, the yearly profit of 1750 € for a single SHPS could be increased to 3550 € when combining two interacting devices. Further, necessary and upcoming rehabilitation measures are investigated concerning their positive impact on the energy production potential and how additional costs (e.g., higher diameters (200 mm instead of 125 mm)) can be compensated by additional profits from energy production (maximum 5250 € per year).     

Functional Chromatography Reveals Three Natural Products that Target the Same Protein with Distinct Mechanisms of Action

Access to lead compounds with defined molecular targets continues to be a barrier to the translation of natural product resources. As a solution, we developed a system that uses discrete, recombinant proteins as the vehicles for natural product isolation. Here, we describe the use of this functional chromatographic method to identify natural products that bind to the AAA+ chaperone, p97, a promising cancer target. Application of this method to a panel of fungal and plant extracts identified rheoemodin, 1‐hydroxydehydroherbarin, and phomapyrrolidone A as distinct p97 modulators. Excitingly, each of these molecules displayed a unique mechanism of p97 modulation. This discovery provides strong support for the application of functional chromatography to the discovery of protein modulators that would likely escape traditional high‐throughput or phenotypic screening platforms.     

马尼托瓦克移动式起重机专用KZ~(TM)100型缆绳

正在CONEXPO-CON/AGG 2014上,马尼托瓦克展示了配备KZT~(TM)100型缆绳的Grove RT770E型起重机。KZ~(TM)100型缆绳是首次专为移动式起重机设计的合成纤维卷扬缆绳,这项创新成果由马尼托瓦克携手合成纤维缆绳制造商Samson公司共同研制,由马尼托瓦克独家销售,从2014年下半年开始作为Grove系列越野起重机的选购件供应给客户。KZ~(TM)100型卷扬缆绳具有许多优点:质量比钢丝绳轻80%:采用转矩中性平衡结构,可消除负荷旋转和缆绳缠绕     

Analysis of electromigration phenomenon in thick-film and LTCC structures at elevated temperature

Studies on electromigration phenomenon in thick-film structures on alumina and LTCC substrates are presented in this paper. The effects of storage of Au and Ag electrode patterns in temperature range up to 300 °C under voltage bias were examined. The leakage characteristics of electrodes with 100 μm spacing at 50 V dc bias as a function of time and temperature are presented and analyzed. Scanning electron microscope (SEM) equipped with the energy-dispersive X-ray spectroscopy (EDX) detector was applied for determination of metal ions transport. Test structures with Au-based conductive material are much more resistant to electromigration than Ag-based layers.