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.     

Full quantum treatment of surface roughness effects in Silicon nanowire and double gate FETs

We review recent results on the effect of surface roughness on the transport properties of ultra-short devices like Silicon nanowire and double-gate FETs. We use a full quantum treatment within the non equilibrium Green’s function (NEGF) formalism which allows us to take into account quantum confinement, quantum phase interference, out-of-equilibrium, and quasi-ballistic transport and focus on transfer characteristics and low-field mobility.     

Modulation of Viscoelasticity and HIV Transport as a Function of pH in a Reversibly Crosslinked Hydrogel

Materials that respond to physiological stimuli are important in developing advanced biomaterials for modern therapies. The reversibility of covalent crosslinks formed by phenylboronate (PBA) and salicylhydroxamate (SHA) has been exploited to provide a pH‐responsive gel for application to the vaginal tract. Dynamic rheology reveals that the gel frequency‐dependent viscoelastic properties are modulated by pH. At pH 4.8 the viscous component dominates throughout most of the frequency range. As the pH increases, the characteristic relaxation time continues to increase while the G′_Plateau levels off above pH 6. At pH 7.5, the elastic component dominates throughout the frequency sweep and is predominately independent of frequency. Particle tracking assesses the transport of both fluorescently labeled HIV‐1 and 100‐nm latex particles in the PBA–SHA crosslinked gel as a function of pH. At pH 4.8 the ensemble‐averaged mean squared displacement at lag times greater than three seconds reveals that transport of the HIV‐1 and 100‐nm particles becomes significantly impeded by the matrix, exhibiting diffusion coefficients less than 0.0002 µm² s^?1. This pH‐responsive gel thus displays properties that have the potential to significantly reduce the transport of HIV‐1 to susceptible tissues and thus prevent the first stage of male‐to‐female transmission of HIV‐1.     

An investigation of the mechanisms for strength gain or loss of geopolymer mortar after exposure to elevated temperature

When fly ash-based geopolymer mortars were exposed to a temperature of 800 °C, it was found that the strength after the exposure sometimes decreased, but at other times increased. This paper shows that ductility of the mortars has a major correlation to this strength gain/loss behaviour. Specimens prepared with two different fly ashes, with strengths ranging from 5 to 60 MPa, were investigated. Results indicate that the strength losses decrease with increasing ductility, with even strength gains at high levels of ductility. This correlation is attributed to the fact that mortars with high ductility have high capacity to accommodate thermal incompatibilities. It is believed that the two opposing processes occur in mortars: (1) further geopolymerisation and/or sintering at elevated temperatures leading to strength gain; (2) the damage to the mortar because of thermal incompatibility arising from non-uniform temperature distribution. The strength gain or loss occurs depending on the dominant process.     

HPLC/ESI-quadrupole ion trap mass spectrometry for characterization and direct quantification of amphoteric and nonionic surfactants in aqueous samples

An amphoteric (cocamidopropylbetaine, CAPB) and a nonionic (alcohol polyethoxylate, AE) surfactant were characterized by electrospray ionization quadrupole ion trap mass spectrometry (ESI-MS) as to their homologue distribution and ionization/fragmentation chemistry. Quantitative methods involving reversed-phase gradient HPLC and (+)ESI-MSn were developed to directly determine these surfactants in hydroponic plant growth medium that received simulated graywater. The predominant homologues, 12 C alkyl CAPB and 9 EO AE, were monitored to represent the total amount of the respective surfactants. The methods demonstrated dynamic linear ranges of 0.5-250 ng (r2 > 0.996) for CAPB and 8-560 ng (r2 > 0.998) for AE homologue mixture, corresponding to minimum quantification limits of 25 ppb CAPB and 0.4 ppm AE with 20-microL injections. This translated into an even lower limit for individual components due to the polydispersive nature of the surfactants. The procedure was successfully employed for the assessment of CAPB and AE biodegradation in a hydroponic plant growth system used as a graywater bioreactor.