The role of disulfide bonds in the structure and function of murine epidermal growth factor (mEGF)

A systematic study using solid phase peptide synthesis has been undertaken to examine the role of the disulfide bonds in the structure and function of mEGF. A combination of one, two and three native disulfide pair analogues of an active truncated (4-48) form of mEGF have been synthesised by replacing specific cysteine residues with isosteric alpha-amino-n-butyric acid (Abu). Oxidation of the peptides was performed using either conventional aerobic oxidation at basic pH, in DMSO under acidic conditions or via selective disulfide formation using orthogonal protection of the cysteine pairs. The contribution of individual, or pairs of, disulfide bonds to EGF structure was evaluated by CD and H-1-NMR spectroscopy. The mitogenic activity of each analogue was determined using Balb/c 3T3 mouse fibroblasts. As we have reported previously (Barnham et al. 1998), the disulfide bond between residues 6 and 20 can be removed with significant retention of biological activity (EC50 20-50 nM). The overall structure of this analogue was similar to that of native mEGF, indicating that the loss of the 6-20 disulfide bridge did not affect the global fold of the molecule. We now show that removal of any other disulfide bond, either singly or in pairs, results in a major disruption of the tertiary structure, and a large loss of activity (EC50>900 nM). Remarkably, the linear analogue appears to have greater activity (EC50 580 nM) than most one and two disulfide bond analogues although it does not have a definable tertiary structure.

A cationic vaccine adjuvant based on a saturated quaternary ammonium lipid have different in vivo distribution kinetics and display a distinct CD4 T cell-inducing capacity compared to its unsaturated analog

Adjuvants are often composed of different constituents that can be divided into two groups based on their primary activity: the delivery system which carries and presents the vaccine antigen to antigen-presenting cells, and the immunostimulator that activates and modulates the ensuing immune response. Herein, we have investigated the importance of the delivery system and in particular its physical characteristics by comparing the delivery properties of two lipids which differ only in the degree of saturation of the acyl chains, rendering the liposomes either rigid (DDA, dimethyldioctadecylammonium) or highly fluid (DODA, dimethyldioleoylammonium) at physiological temperature. We show that these delivery systems are remarkably different in their ability to prime a Th1-directed immune response with the rigid DDA-based liposomes inducing a response more than 100 times higher compared to that obtained with the fluid DODA-based liposomes. Upon injection with a vaccine antigen, DDA-based liposomes form a vaccine depot that results in a continuous attraction of antigen-presenting cells that engulf a high amount of adjuvant and are subsequently efficiently activated as measured by an elevated expression of the co-stimulatory molecules CD40 and CD86. In contrast, the fluid DODA-based liposomes are more rapidly removed from the site of injection resulting in a lower up-regulation of co-stimulatory CD40 and CD86 molecules on adjuvant-positive antigen-presenting cells. Additionally, the vaccine antigen is readily dissociated from the DODA-based liposomes leading to a population of antigen-presenting cells that are antigen-positive but adjuvant-negative and consequently are not activated. These studies demonstrate the importance of studying in vivo characteristics of the vaccine components and furthermore show that physicochemical properties of the delivery system have a major impact on the vaccine-induced immune response. © 2012 Elsevier B.V. All rights reserved.

Estimating time-varying risk premia in UK long-term government bonds

Simple models of time-varying risk premia are used to measure the risk premia in long-term UK government bonds. The parameters of the models can be estimated using nonlinear seemingly unrelated regression (NL-SUR), which permits efficient use of information across the entire yield curve and facilitates the testing of various cross-sectional restrictions. The estimated time-varying premia are found to be substantially different to those estimated using models that assume constant risk premia. © 2004 Taylor and Francis Ltd.

Unified model for performance analysis of IEEE 802.11 ad hoc networks in unsaturated conditions

IEEE 802.11 standard has achieved huge success in the past decade and is still under development to provide higher physical data rate and better quality of service (QoS). An important problem for the development and optimization of IEEE 802.11 networks is the modeling of the MAC layer channel access protocol. Although there are already many theoretic analysis for the 802.11 MAC protocol in the literature, most of the models focus on the saturated traffic and assume infinite buffer at the MAC layer. In this paper we develop a unified analytical model for IEEE 802.11 MAC protocol in ad hoc networks. The impacts of channel access parameters, traffic rate and buffer size at the MAC layer are modeled with the assistance of a generalized Markov chain and an M/G/1/K queue model. The performance of throughput, packet delivery delay and dropping probability can be achieved. Extensive simulations show the analytical model is highly accurate. From the analytical model it is shown that for practical buffer configuration (e.g. buffer size larger than one), we can maximize the total throughput and reduce the packet blocking probability (due to limited buffer size) and the average queuing delay to zero by effectively controlling the offered load. The average MAC layer service delay as well as its standard deviation, is also much lower than that in saturated conditions and has an upper bound. It is also observed that the optimal load is very close to the maximum achievable throughput regardless of the number of stations or buffer size. Moreover, the model is scalable for performance analysis of 802.11e in unsaturated conditions and 802.11 ad hoc networks with heterogenous traffic flows. © 2012 KSI.

Chemical reactions of double bonds in activated carbon:microwave and bromination methods

The reaction of localised C=C bonds on the surface of activated carbons has been shown to be an effective method of chemical modification especially using microwave-assisted reactions.

The rise and fall of diasporic bonds in Japanese-Peruvian “Return” migration

Two decades after Japanese-Peruvians and other South Americans of Japanese descent began to migrate back to Japan, the return-migration phenomenon has ended. Induced by the Japanese government in the name of shared ethnicity, Japanese policymakers now largely regard return migration as a failed policy. It failed because return-migrants did not, in the view of policy- makers, assimilate, integrate, or “make it” in Japan as expected. Thus, once-imagined ethnic bonds ceased to exist in Japan. However, ethnic bonds sustained themselves well outside Japan. The Japanese-Peruvian community in Peru has thrived and maintained continuous ties with Japan. What explains the rise and fall of diasporic ethnic bonds? Drawing on my ethnographic research in Japanese-Peruvian communities in Peru and Japan, I found that diasporic ethnic bonds are cultivated or weakened depending upon where diasporic populations are located in relation to their ancestral homeland, and how such ties are utilized, for what, and by whom.

Nondestructive measurement of water content and moisture migration of unsaturated red clays in South China

To reveal the moisture migration mechanism of the unsaturated red clays, which are sensitive to water content change and widely distributed in South China, and then rationally use them as a filling material for highway embankments, a method to measure the water content of red clay cylinders using X-ray computed tomography (CT) was proposed and verified. Then, studies on the moisture migrations in the red clays under the rainfall and ground water level were performed at different degrees of compaction. The results show that the relationship between dry density, water content, and CT value determined from X-ray CT tests can be used to nondestructively measure the water content of red clay cylinders at different migration time, which avoids the error reduced by the sample-to-sample variation. The rainfall, ground water level, and degree of compaction are factors that can significantly affect the moisture migration distance and migration rate. Some techniques, such as lowering groundwater table and increasing degree of compaction of the red clays, can be used to prevent or delay the moisture migration in highway embankments filled with red clays.

An investigation of support effects on the Pt-catalysed selective transformation of α,β-unsaturated substrates

Pt catalyst series were prepared on mesoporous SBA-15, SBA-16, KIT-6, true liquidcrystal-templated meso-macroporous SBA-15 and a commercial, low surface area silicasupport. Support structure can be easily fabricated using surfactant templating as a mode ofstringent control on porosity, surface area and internal structure. The impact of varying Pt-support physicochemical properties was systematically studied for the selective transformation of allylic substrates under chemoselective oxidation and hydrogenation regimes, a class of reactions highly applicable to industry. Pt-based heterogeneous catalysts are well-known for their utilisation in the hydrogenation of α,β-unsaturated aldehydes,although the mode of action and lack of systematic studies in the literature fuels continuing debate into the role of Pt nanoparticles and support choice for this area. This project attempts to shed some light on several frequently asked questions in this field. Successful support synthesis and stability after Pt impregnation is confirmed through HRTEM, XRD and N2 porosimetry. Decreasing metal loading promoted dispersion values,regardless of support choice, with surface PtO2 content also showing visible enhancement.Increasing support surface area and mesoporosity exhibited the following trend on Pt dispersion augmentation; low surface area commercial silica < true liquid crystal-templated SBA-15 < SBA-15 < SBA-16 ~ KIT-6. For the selective oxidation of cinnamyl alcohol,increasing PtO2 surface population confers substantial rate enhancements, with turnover frequencies evidencing PtO2 to be the active species .In the Pt-catalysed hydrogenation of cinnamaldehyde, strong support insensitivity was observed towards catalytic activity; as turnover frequencies normalised to Pt metal reveal constant values. However, structure sensitivity to the desired unsaturated alcohol arose,evidencing the requirement of flat, extended Pt (111) facets for C=O hydrogenation. Pt/SBA-15 proved the most selective, reflecting suppressed cinnamyl alcohol hydrogenation, with DRIFTS and in-situ ATR-IR evidencing the key role of support polarity in re-orientation of cinnamaldehyde to favour di-σCO adsorption and C=O versus C=C hydrogenation. High pressures increased activity, whilst a dramatic shift in selectivity from dominant C=C (1 bar)to C=O hydrogenation (10 bar) was also observed, attributed to surface crowding and suppression of di-σCC and η4 di-σCO+πC=C cinnamaldehyde binding modes.

Ab initio quantum chemical studies on neutral-radical reactions of ethynyl (C2H) and cyano (CN) with unsaturated hydrocarbons

An Ab Initio/RRKM study of the reaction mechanism and product branching ratios of neutral-radical ethynyl (C2H) and cyano (CN) radical species with unsaturated hydrocarbons is performed. The reactions studied apply to cold conditions such as planetary atmospheres including Titan, the Interstellar Medium (ISM), icy bodies and molecular clouds. The reactions of C2H and CN additions to gaseous unsaturated hydrocarbons are an active area of study. NASA's Cassini/Huygens mission found a high concentration of C2H and CN from photolysis of ethyne (C2H2) and hydrogen cyanide (HCN), respectively, in the organic haze layers of the atmosphere of Titan. The reactions involved in the atmospheric chemistry of Titan lead to a vast array of larger, more complex intermediates and products and may also serve as a chemical model of Earth's primordial atmospheric conditions. The C2H and CN additions are rapid and exothermic, and often occur barrierlessly to various carbon sites of unsaturated hydrocarbons. The reaction mechanism is proposed on the basis of the resulting potential energy surface (PES) that includes all the possible intermediates and transition states that can occur, and all the products that lie on the surface. The B3LYP/6-311g(d,p) level of theory is employed to determine optimized electronic structures, moments of inertia, vibrational frequencies, and zero-point energy. They are followed by single point higher-level CCSD(T)/cc-vtz calculations, including extrapolations to complete basis sets (CBS) of the reactants and products. A microcanonical RRKM study predicts single-collision (zero-pressure limit) rate constants of all reaction paths on the potential energy surface, which is then used to compute the branching ratios of the products that result. These theoretical calculations are conducted either jointly or in parallel to experimental work to elucidate the chemical composition of Titan's atmosphere, the ISM, and cold celestial bodies.<.