Design of Trehalose-Based Amide/Sulfonamide C-type Lectin Receptor Signaling Compounds

Mincle agonists have been shown to induce inflammatory cytokine production, such as tumor necrosis factor-alpha (TNF) and promote the development of a Th1/Th17 immune response that might be crucial to development of effective vaccination against pathogens such as Mycobacterium tuberculosis. As an expansion of our previous work, a library of 6,6′-amide and sulfonamide α,α-d -trehalose compounds with various substituents on the aromatic ring was synthesized efficiently in good to excellent yields. These compounds were evaluated for their ability to activate the human C-type lectin receptor Mincle by the induction of cytokines from human peripheral blood mononuclear cells. A preliminary structure–activity relationship (SAR) of these novel trehalose diamides and sulfonamides revealed that aryl amide-linked trehalose compounds demonstrated improved activity and relatively high potency cytokine production compared to the Mincle ligand trehalose dibehenate adjuvant (TDB) and the natural ligand trehalose dimycolate (TDM) inducing dose-dependent and human-Mincle-specific stimulation in a HEK reporter cell line.     

Supplementing with L-Tryptophan Increases Medium Protein and Alters Expression of Genes and Proteins Involved in Milk Protein Synthesis and Energy Metabolism in Bovine Mammary Cells

The objective of this study was to investigate the effects of supplementing with L-tryptophan (L-Trp) on milk protein synthesis using an immortalized bovine mammary epithelial (MAC-T) cell line. Cells were treated with 0, 0.3, 0.6, 0.9, 1.2, and 1.5 mM of supplemental L-Trp, and the most efficient time for protein synthesis was determined by measuring cell, medium, and total protein at 0, 24, 48, 72, and 96 h. Time and dose tests showed that the 48 h incubation time and a 0.9 mM dose of L-Trp were the optimal values. The mechanism of milk protein synthesis was elucidated through proteomic analysis to identify the metabolic pathway involved. When L-Trp was supplemented, extracellular protein (medium protein) reached its peak at 48 h, whereas intracellular cell protein reached its peak at 96 h with all L-Trp doses. β-casein mRNA gene expression and genes related to milk protein synthesis, such as mammalian target of rapamycin (mTOR) and ribosomal protein 6 (RPS6) genes, were also stimulated (p < 0.05). Overall, there were 51 upregulated and 59 downregulated proteins, many of which are involved in protein synthesis. The results of protein pathway analysis showed that L-Trp stimulated glycolysis, the pentose phosphate pathway, and ATP synthesis, which are pathways involved in energy metabolism. Together, these results demonstrate that L-Trp supplementation, particularly at 0.9 mM, is an effective stimulus in β-casein synthesis by stimulating genes, proteins, and pathways related to protein and energy metabolism.     

Effect of iron alloying in evolution of nanostructure and microstructural stability in nickel

Nanocrystalline materials show many interesting properties such as high strength and hardness due to nanosized grains and high density of interfaces. In this context, the present work reports the effect of Fe (iron) addition in Ni (nickel) on nanostructure retention during the annealing of Ni-Fe alloy (with 0, 18.5, 28.5 and 43 wt% Fe) at 450 °C for 16 h. Furthermore, effect of annealing on the deformation mechanism was investigated. The integral breadth method revealed the decrease in grain size with increase in wt% Fe in Ni. The strain rate sensitivity exponent which is a signature of operating deformation mechanism showed a higher value (0.10803) in case of Ni-18.5 wt% Fe during nanoindentation. However, Ni-0 wt% Fe, Ni-28.5 wt% Fe and Ni-43 wt% Fe were characterized by a relatively low strain rate sensitivity exponent (between 0.02069 and 0.10803). Results indicated the presence of Hall-Petch relationship up to 18.5 wt% Fe and inverse Hall-Petch relationship above 18.5 wt% Fe.     

Absolute Concentration Measurements of Chemically-Important Flame Radicals

A fundamental understanding of flame chemistry is a necessary part of designing and optimizing combustors to meet environmental regulations while maintaining system efficiency. We have performed quantitative, absolute concentration measurements for several free radicals to test various aspects of the predictive capabilities of the natural gas combustion chemistry mechanism, GRI-Mech 2.11, the chemical mechanism for methane combustion. The CH, NO, OH, and HCO radicals were studied in a series of low-pressure methane/O₂/N₂ flames using the technique of laser-induced fluorescence. The results show that GRI-Mech 2.11 predicts well the hydrocarbon oxidation chemistry in lean and near stoichiometric flames, but appears to possess some inadequacies for rich flames. Of special importance is the finding that the rate coefficient for the important CH + N₂ reaction in the current version of GRI-Mech appears to be too low. Also, reburn of NO is correctly predicted in a lean flame but not a rich one.     

Evaluating the potential efficacy of mercury total maximum daily loads on aqueous methylmercury levels in four coastal watersheds

Of the approximately 780 U.S. EPA approved mercury total maximum daily loads (TMDLs), most specify a reduction in total mercury (Hg(T)) loads to reduce methylmercury levels in fish tissue, assuming a 1:1 correspondence. However, mercury methylation is more complex, and therefore, proposed load reductions may not be adequate. Using multiple regression with microlevel and macrolevel variables, the potential efficacy of mercury TMDLs on decreasing aqueous methylmercury levels was investigated in four coastal watersheds: Mugu Lagoon (CA), San Francisco Bay Estuary, Long Island Sound, and south Florida. Hg(T) and methylmercury levels were positively correlated in all watersheds except in Long Island Sound, where spatial differences explained over 40% of the variability in methylmercury levels. A mercury TMDL would be least effective in Long Island Sound due to spatial heterogeneity but most effective in south Florida, where the ratio between aqueous Hg(T) and methylmercury levels was close to 1 and the 95% confidence interval was narrow, indicating a probable reduction in aqueous methylmercury levels if Hg(T) loads were reduced.     

Regulating the geological sequestration of CO2

Governments worldwide should provide incentives for initial large-scale GS projects to help build the knowledge base for a mature, internationally harmonized GS regulatory framework. Health, safety, and environmental risks of these early projects can be managed through modifications of existing regulations in the EU, Australia, Canada, and the U.S. An institutional mechanism, such as the proposed Federal Carbon Sequestration Commission in the U.S., should gather data from these early projects and combine them with factors such as GS industrial organization and climate regime requirements to create an efficient and adaptive regulatory framework suited to large-scale deployment. Mechanisms to structure long-term liability and fund long-term postclosure care must be developed, most likely at the national level, to equitably balance the risks and benefits of this important climate change mitigation technology. We need to do this right. During the initial field experiences, a single major accident, resulting from inadequate regulatory oversight, anywhere in the world, could seriously endanger the future viability of GS. That, in turn, could make it next to impossible to achieve the needed dramatic global reductions in CO2 emissions over the next several decades. We also need to do it quickly. Emissions are going up, the climate is changing, and impacts are growing. The need for safe and effective CO2 capture with deep GS is urgent.     

The spectrum of power from wind turbines

The power spectral density of the output of wind turbines provides information on the character of fluctuations in turbine output. Here both 1-second and 1-hour samples are used to estimate the power spectrum of several wind farms. The measured output power is found to follow a Kolmogorov spectrum over more than four orders of magnitude, from 30 s to 2.6 days. This result is in sharp contrast to the only previous study covering long time periods, published 50 years ago. The spectrum defines the character of fill-in power that must be provided to compensate for wind's fluctuations when wind is deployed at large scale. Installing enough linear ramp rate generation (such as a gas generator) to fill in fast fluctuations with amplitudes of 1% of the maximum fluctuation would oversize the fill-in generation capacity by a factor of two for slower fluctuations, greatly increasing capital costs. A wind system that incorporates batteries, fuel cells, supercapacitors, or other fast-ramp-rate energy storage systems would match fluctuations much better, and can provide an economic route for deployment of energy storage systems when renewable portfolio standards require large amounts of intermittent renewable generating sources.     

Medical care utilization in a regional prepaid medical system

Aggregate dollar medical care utilization is estimated by applying a fee structure to 1967–70 medical care utilization of 3,418 members of the Kaiser Foundation Health Plan of Portland, Oregon. The data indicated a very stable pattern of medical care utilization by the cohort during the period. The average yearly increase in medical care dollar utilization per person (prices constant) was only 1.5 percent. There was some tendency for resource utilizaton to become more concentrated among the highest users. Inpatient services accounted for about 40 percent of the dollar utilization with no tendency to decline or rise over the fouryear period. While age and death were the only factors significantly associated with the likelihood of being a high user in a given year ($2,500 threshold), family size, education, and sex joined these factors in being associated with medical care dollar utilization by an individual. Family size was negatively related while education and being female were related directly to dollar utilization. A limited comparison is made with experience in the U.S.This research was supported by Grant No. 5 RO1 HS-01653, awarded by the National Center of Health Services Research, HRA. Technical support was given by the Health Services Research Center, Kaiser Foundation Hospitals, Portland, Oregon.     

壳牌公司的天然气、炼厂气和液体的处理技术

一般认为,气体及液体处理技术已经很成熟,但多来源且更复杂组成的进料气体及更严格的环保要求和产品规格又不断推动着技术的进步。本文介绍了壳牌所开发使用的处理技术及近两年内的一些最新发展。含硫化氢气体处理技术包括传统的液相吸收、固定床吸收、气相的催化转换反应以及生物处理技术。壳牌公司可根据进料气体的情况和最终产品的要求,对整个工艺整合,并给出最优化的解决方案,以达到更环保,可靠性更高且更节省投资的目的。