The Metabolic Efficacy of a Cannabidiolic Acid (CBDA) Derivative in Treating Diet- and Genetic-Induced Obesity

Obesity is a global medical problem; its common form is known as diet-induced obesity (DIO); however, there are several rare genetic disorders, such as Prader–Willi syndrome (PWS), that are also associated with obesity (genetic-induced obesity, GIO). The currently available therapeutics for treating DIO and GIO are very limited, and they result in only a partial improvement. Cannabidiolic acid (CBDA), a constituent of Cannabis sativa, gradually decarboxylates to cannabidiol (CBD). Whereas the anti-obesity properties of CBD have been reasonably identified, our knowledge of the pharmacology of CBDA is more limited due to its instability. To stabilize CBDA, a new derivative, CBDA-O-methyl ester (HU-580, EPM301), was synthesized. The therapeutic potential of EPM301 in appetite reduction, weight loss, and metabolic improvements in DIO and GIO was tested in vivo. EPM301 (40 mg/kg/d, i.p.) successfully resulted in weight loss, increased ambulation, as well as improved glycemic and lipid profiles in DIO mice. Additionally, EPM301 ameliorated DIO-induced hepatic dysfunction and steatosis. Importantly, EPM301 (20 and 40 mg/kg/d, i.p.) effectively reduced body weight and hyperphagia in a high-fat diet-fed Magel2^null mouse model for PWS. In addition, when given to standard-diet-fed Magel2^null mice as a preventive treatment, EPM301 completely inhibited weight gain and adiposity. Lastly, EPM301 increased the oxidation of different nutrients in each strain. All together, EPM301 ameliorated obesity and its metabolic abnormalities in both DIO and GIO. These results support the idea to further promote this synthetic CBDA derivative toward clinical evaluation in humans.     

Initial Stages of Na<Subscript>2</Subscript>SO<Subscript>4</Subscript>-Induced Degradation of β-Ni–36Al at 700 °C: I-Intrinsic Behavior

The early-stage scaling behavior of a β-Ni–36Al alloy undergoing Na₂SO₄-deposit-induced degradation at 700 °C was systematically studied using SEM and TEM. After 20 h of exposure in an O₂–1000 ppm SO₂ ambient, the deposit-coated alloy formed a dense but thin Al₂O₃ scale on most areas of the surface; however, large nodules formed locally. Nodule formation occurred where the scale had lost its protective character, with rapid internal oxidation ensuing. The presence of sulfur both in the environment and in the salt played a key role in nodule formation. Removal of SO₂/SO₃ from the gas mixture, or of the Na₂SO₄ deposit from the surface, prevented nodule formation, while removing the sulfur source after nodule formation prevented further nodule growth. The degradation could be linked to the dissolution of reaction products in the Na₂SO₄ deposit and the formation of a low-temperature eutectic liquid. Further, when an Na₂SO₄–48% MgSO₄ deposit was used, the nodule density increased.     

Bioenergy plantations or long-term carbon sinks? – A model based analysis

In order to mitigate climate change bio-productive land may be used mainly in two ways: afforestation with long-rotation forests with the primary aim to act as carbon sinks, and short-rotation forests that are used for energy purposes and thereby replace fossil fuels. Under an ambitious climate target, land that may be used for both bioenergy plantations and long-rotation forests, are likely to be scarce, and thereby competition between long-rotation forests and bioenergy plantations can be expected. The goal of the study is to analyze the cost-effectiveness of bioenergy plantations versus long-rotations forests aimed at capturing and storing carbon. The study is performed by solving and analyzing a linear optimization model that links the energy system, an afforestation sector and the pulp and timber market. Many earlier studies tend to suggest that long-rotation forests offer lower costs per ton of CO₂ avoided. Our study, however, shows that long-rotation forests for the purpose of carbon sequestration will not be cost-effective in the long run under a stringent climate policy. Thus, economic efficiency considerations tend to support short-rotation plantations for high carbon prices. The reason for this is that scarcity of land increases the opportunity cost of land, a feature which is generally not captured in static near-term analysis, but it is captured in a dynamic model like ours. For less stringent carbon targets long-rotation forests, that are harvested and sold as timber are cost-effective during a transient phase.     

On the partitioning of dynamic workforce scheduling problems

This problem is based on the British Telecom workforce scheduling problem, in which technicians (with different skills) are assigned to tasks (which require different skills) which arrive (partially) dynamically during the day. In order to manage their workforce, British Telecom divides the different regions into several areas. At the beginning of each day all the technicians in a region are assigned to one of these areas. During the day, each technician is limited to tasks within the assigned area.     

Statistical analysis of the arc behavior in dry hyperbaric GMA welding from 1 to 250 bar

In this paper, mathematical approaches were developed for predicting the hyperbaric GMAW process arc behavior and stability. The variation of stochastic parameters is related to the electrical stability that can be resolved into a number of varying parameters. The results show that most of the arc instability can be traced to the frequency domain of the voltage or current waveform. Uncorrelated current and voltage wave frequencies at higher pressures are found to have a great influence on process stability.     

Rosiglitazone,but Not Epigallocatechin‐3‐Gallate,Attenuates the Decrease in PGC‐1α Protein Levels in Palmitate‐Induced Insulin‐Resistant C2C12 Cells

Alteration of lipid metabolism is an important mechanism for the treatment of insulin resistance. PGC‐1α, a key regulator of mitochondrial biogenesis and function, plays an important role in the improvement of insulin sensitivity by increasing fatty acids β‐oxidation. In the present study, the effects of epigallocatechin‐3‐gallate (EGCG), an anti‐obesity agent and enhancer of lipid catabolism, on PGC‐1α protein expression was examined and compared with anti‐diabetic drug rosiglitazone (RGZ). After differentiation of C2C12 myoblasts to myotubes, insulin resistance was induced by palmitate treatment. Then the expression of the PGC‐1a gene and glucose uptake were evaluated before and after treatment with RGZ and EGCG. Palmitate treatment significantly decreased PGC‐1α protein expression in C2C12 cells (P < 0.05). RGZ could restore the expression of PGC‐1α in palmitate treated cells (P > 0.05), while EGCG had no significant effect on the expression of this gene (P < 0.05). RGZ and EGCG significantly improved glucose uptake (by 2‐ and 1.54‐fold, respectively) in myotubes treated with palmitate. These data suggest that RGZ and EGCG both exert their anti‐diabetic activity by increasing insulin sensitivity, but with different molecular mechanisms. This effect of RGZ, unlike EGCG, is mediated, at least partly, by increasing PGC‐1α protein expression.     

Acrylonitrile–butadiene rubber functionalization for the toughening modification of recycled poly(ethylene terephthalate)

The incorporation of functionalized acrylonitrile–butadiene rubber (NBR) into recycled poly(ethylene terephthalate) (PET) was introduced as an effective route for modifying the properties of PET and as a new method for PET recycling as well. To achieve modified NBR, glycidyl methacrylate (GMA) was grafted onto NBR with optimized reactive mixing, in which the highest grafting degree and lowest gel content were generated. PET/NBR blends with and without GMA functionalization were produced by melt mixing, and the mechanical properties, dynamic mechanical thermal properties, and phase morphologies of the systems were determined and compared. We found that low amounts of peroxide initiator (dicumyl peroxide) and high levels of the GMA monomer in the presence of the styrene comonomer led to the maximum grafting degree and suppressed the competing rubber crosslinking and GMA homopolymerization reactions. The blend compatibility with PET determined from dynamic mechanical thermal analysis spectra and scanning electron microscopy images was greatly improved when the NBR‐grafted GMA was used instead of the neat NBR in the blend recipes. As a result, the rubber phase dispersed in the PET matrix more finely, and the impact strength of the blend advanced very significantly. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40483.     

Effect of Heating Rate on Phase and Microstructural Evolution During Pressureless Sintering of a Nanostructured Transition Alumina

Deagglomeration of a nanocrystalline transition alumina performed using different techniques was first demonstrated to be active in the achievement of a better powder compaction ability under uniaxial pressing and consequently in the development of a highly dense and homogeneous microstructure during pressureless sintering. A major effect, however, was associated to the heating rate chosen during the densification cycle. In fact, the influence of different heating rates (10°C/min or 1°C/min) on phase and microstructural evolution during sintering was investigated in depth on the above best green bodies. A low-rate thermal cycle leads to a significant reduction of the α-Al₂O₃ crystallization temperature and promotes a more effective particle rearrangement during phase transformation. As a consequence, in the low-rate treated material, it was possible to avoid the development of a vermicular structure as usually expected during the densification of a transition alumina and to yield a more homogenously fired microstructure.     

运用蚁群优化法对钢结构进行基于性能的抗震设计

运用蚁群优化法(ACO)对钢结构进行了基于性能的抗震设计。这个离散的数学运算法比其他算法更为有效并精确。采用了非线性分析以得到结构在各种地震性能水平下的结构响应,采用一个简单的计算机程序,对包含一阶弹性和二阶几何刚度的特性进行推覆分析。采用两个实例说明了ACO在轻钢结构中的应用,证明其可满足抗弯钢结构在多种地震性能水平下的要求,同时也与标准遗传算法的结果进行对比,表明ACO更适合解决此类优化问题。     

A rarefaction-tracking method for hyperbolic conservation laws

A numerical method for scalar conservation laws in one space dimension is presented. The solution is approximated by local similarity solutions. While many commonly used approaches are based on shocks, the presented method uses rarefaction and compression waves. The solution is represented by particles that carry function values and move according to the method of characteristics. Between two neighboring particles, an interpolation is defined by an analytical similarity solution of the conservation law. An interaction of particles represents a collision of characteristics. The resulting shock is resolved by merging particles so that the total area under the function is conserved. The method is variation diminishing; nevertheless, it has no numerical dissipation away from shocks. Although shocks are not explicitly tracked, they can be located accurately. Numerical examples are presented, and specific applications and extensions of the approach outlined.