Reducible disulfide-based non-viral gene delivery systems

The design and synthesis of safe efficient non-viral vectors for gene delivery has attracted significant attention in recent years due primarily to the severe side-effect profile reported with the use of their viral counterparts. Previous experiments have revealed that the strong interaction between the carriers and nucleic acid may well hinder the release of the gene from the complex in the cytosol adversely affecting transfection efficiency. However, incorporating reducible disulfide bonds within the delivery systems themselves which are then cleaved in the glutathione-rich intracellular environment may help in solving this puzzle. This review focuses on recent development of these reducible carriers. The biological rationale and approaches to the synthesis of reducible vectors are discussed in detail. The in vitro and in vivo evaluations of reducible carriers are also summarized and it is evident that they offer a promising approach in non-viral gene delivery system design.

Studies of the shellside performance of shell-and-tube heat exchangers

Accurate prediction of shellside pressure drop in a baffled shell-and-tube heat exchanger is very difficult because of the complicated shellside geometry. Ideally, all the shellside fluid should be alternately deflected across the tube bundle as it traverses from inlet to outlet. In practice, up to 60% of the shellside fluid may bypass the tube bundle or leak through the baffles. This short-circuiting of the main flow reduces the efficiency of the exchanger. Of the various shellside methods, it is shown that only the multi-stream methods, which attempt to obtain the shellside flow distribution, predict the pressure drop with any degree of accuracy, the various predictions ranging from -30% to +70%, generally overpredicting. It is shown that the inaccuracies are mainly due to the manner in which baffle leakage is modelled. The present multi-stream methods do not allow for interactions of the various flowstreams, and yet it is shown that three main effects are identified, a) there is a strong interaction between the main cross flow and the baffle leakage streams, enhancing the crossflow pressure drop, b) there is a further short-circuit not considered previously i.e. leakage in the window, and c) the crossflow does not penetrate as far, on average, as previously supposed. Models are developed for each of these three effects, along with a new windowflow pressure drop model, and it is shown that the effect of baffle leakage in the window is the most significant. These models developed to allow for various interactions, lead to an improved multi-stream method, named the "STREAM-INTERACTION" method. The overall method is shown to be consistently more accurate than previous methods, with virtually all the available shellside data being predicted to within ±30% and over 60% being within ±20%. The method is, thus, strongly recommended for use as a design method.

Disentangle contextual and permanent individual motivations:an application to shopping behavior

Past studies resulted in conflicting definitions of consumer motivation. On the one hand, motivations are seen as the consumer’s characteristics that shape her general behavior (motivational trait). On the other hand, they are seen as contextual variables representing the reason why the individual is behaving specific to today’s context (motivational state). The objective of this research is to stress the difference between these two concepts and to understand the impact of each on consumer behavior. We applied our empirical study to shopping motivations; our results show a strong interaction between motivational trait and motivational state. Problem and Hypothesis On the one hand, Westbrook and Black (1985) consider shopping motivations as individual permanent characteristics. This concept is shared by other researchers (Rohm and Swaminathan 2004), which show that some shoppers are functional (they shop for convenience, information seeking, and time saving) while some others are hedonic (they shop for social interaction, bargain hunting and browsing). On the other hand, Kaltcheva and Weitz (2006) define motivations as a contextual orientation changing over time, depending on the situation, and show that contextual shopping motivations have a strong impact on shopping behavior. From our knowledge, no research specifically examined the respective impact of both these shopping motivation types. To deal with this issue, we used the notions of “traits” and “states” that have been largely used in marketing research to designate respectively a permanent characteristic of the individual and a temporary orientation of the consumer (Mowen 2000). The reversal theory (Apter 2001) suggests that two opposite states exist: the telic and the paratelic states. In the telic state, individuals set goals for themselves, must be disciplined to reach these goals, and do not behave in accordance with their personal trait. In the paratelic state, individuals are seeking arousal and enjoyment, do not set rules, and one could postulate that they act in accordance with their natural tendencies. Based on these considerations, we hypothesize the following process: in situations involving paratelic states, hedonic as well as functional individuals should behave according to their natural traits, whereas in situations involving telic states, hedonic people should inhibit their natural propensity to enjoy shopping and behave similarly to functional people. Hence, we postulate the following: Hypothesis: Compared to shoppers with functional motivational trait, shoppers with hedonic motivational trait will a) significantly display more hedonic shopping behavior intentions in a condition of paratelic motivational state, and b) not display more hedonic shopping behavior intentions in a condition a telic motivational state Empirical Research First, 108 participants were asked to fill a multi-items scale about their shopping habits, which actually measured their shopping motivational traits. This questionnaire allowed us to highlight four different dimensions in shopping motivational traits: social interaction, novelty/utility seeking, bargain hunting, and browsing. According to their scores on different items, participants were classified as functional or as hedonic on each of these four dimensions (a single individual may be hedonic on some dimensions and functional on others). Then, participants were then induced to adopt either a telic or a paratelic shopping motivational state while reading an appropriate scenario. Finally, participants were asked for their shopping behavior intentions in response to the shopping context. Four items were developed, corresponding to the four shopping motivational trait dimensions we found with our factor analysis. Results As we found four dimensions in shopping motivational trait, we set up four quasi-experimental designs to capture the entire phenomenon: for each dimension, a 2 (motivational trait) x 2 (motivational state) design was built, where the dependant variable was the shopping behavior element corresponding to the studied dimension. Four 2 x 2 Anovas were performed to assess the interaction between motivational trait and motivational state. Concerning the three dimensions - browsing, novelty/utility seeking, and bargain hunting- , in the paratelic state scenario participants with hedonic motivational trait displayed significantly more hedonic shopping behavior intentions than participants with a functional motivational trait (resp. F = 9.701, p = .003; F = 4.979, p = .03; F = 5.757, p = .02); and in the telic state scenario, there was no significant difference in behavior intentions between participants with hedonic or functional motivation trait. Each time, the interaction effect between motivational state and motivational trait was significant (resp. F = 4.859, p = .03; F = 3.314, p = .07; F = 2.98, p = .08). Concerning the fourth dimension, social interaction, shopping behavior intentions of participants with hedonic and with functional motivational traits were significantly different in the paratelic state scenario (F = 29.898, p <.000) as well as in the telic state scenario (F = 9.559, p = .003). However, the interaction effect showed that this behavioral difference was significantly stronger in the paratelic scenario. All these results support our research hypothesis. Discussion and Implications Our study provides consistent support for our hypotheses saying that there is an interaction effect between shopping motivational states and shopping motivational traits. The generalization of the results is strengthened by the study of four different shopping traits: social interaction, novelty/utility seeking, bargain hunting and browsing. As we proposed, when shopping in a goal-oriented state (telic state), behaviors of hedonic and functional shoppers do not differ significantly. Conversely, when shopping for a recreational reason (paratelic state), hedonic and functional shoppers behave significantly different. These results could explain why some previous studies concluded that shopping motivational traits had no impact on shopping behavior: they did not take into consideration the interaction between motivational trait and motivational state. Moreover, our study shows that marketing surveys performed by store managers to draw the personal profile of their customers must be crossed with contextual motivations in order to accurately forecast shopper behavior. Future Developments Our results can be explained by the self-control process, which pushes hedonic-trait shoppers to behave in a rather functional way in utilitarian situations. However, to be certain that this is the very process that occurs, we plan to add self-control perception scales to our existing measures. This is obviously the next step of this research.

Disentangle contextual and permanent individual motivations:an application to shopping behavior

Past studies resulted in conflicting definitions of consumer motivation. Motivations are seen either as the consumer? s characteristics that shape her general behavior (motivational trait), or as contextual variables representing the reason why the individual is behaving specific to today?s context (motivational state). The objective of this research is to understand the impact of each on consumer behavior. Applied to shopping motivations, our study shows a strong interaction between motivational trait and state: motivational traits influence behavior only when associated with a recreational motivational state. In a functional motivational state, individuals prevent their personal characteristics from being fully expressed.

Atomistic simulation of zeolite surfaces

The aim of this paper is to describe the current state of atomistic simulation of zeolite surfaces by describing what has been achieved and to show how the surface structures are modelled. This is illustrated by using atomistic simulation techniques to model the {100} surface of zeolite LTA. The pure siliceous and aluminated CaNa-A and Na-A with Si/Al = 1 structures were considered. The surface showed three stable terminations but the relative stability varied with composition. The resulting surface structures and geometries show extensive framework distortions, especially in the aluminated forms where the cations formed strong interaction with the zeolite framework thereby increasing their adsorption energies and stabilising their cation position. © 2001 Published by Elsevier Science Ltd.

New insights in the deactivation of sulfonic modified SBA-15 catalysts for biodiesel production from low-grade oleaginous feedstock

Arenesulfonic-acid functionalized SBA-15 materials have been used in the production of biodiesel from low grade oleaginous feedstock. These materials display an outstanding catalytic activity, being able to promote the transformation of crude palm oil with methanol into fatty acid methyl esters with high yield (85%) under mild reaction conditions. However, high sensitivity of the catalyst against poisoning by different substances has also been detected. Thus, alkaline metal cations, such as sodium or potassium exert a negative influence on the catalytic activity of these materials, being necessary amounts around 500 ppm of sodium in the reaction media to decrease the catalytic activity of these materials to a half of its initial value in just two reaction runs. The deactivation of arenesulfonic acid functionalized SBA-15 materials seems to occur in this case by ion exchange of the acid protons at the sulfonic groups. Organic unsaponifiable compounds like lecithin or retinol also induce a negative influence in the catalytic activity of these sulfonic acid-based materials, though not so intense as in the case of alkaline metals. The deactivating mechanism associated to the influence of the organic compounds seems to be linked to the adsorption of such substances onto the catalytic acid sites as well as on the silica surface. The accumulation of lecithin in the surface of catalyst, observed by means of thermogravimetric analysis, suggest the creation of a strong interaction, probably by ion pair, between this compound and the sulfonic acid group.

Evidence that interaction between conserved residues in transmembrane helices 2, 3, and 7 are crucial for human VPAC1 receptor activation

The VPAC(1) receptor belongs to family B of G protein-coupled receptors (GPCR-B) and is activated upon binding of the vasoactive intestinal peptide (VIP). Despite the recent determination of the structure of the N terminus of several members of this receptor family, little is known about the structure of the transmembrane (TM) region and about the molecular mechanisms leading to activation. In the present study, we designed a new structural model of the TM domain and combined it with experimental mutagenesis experiments to investigate the interaction network that governs ligand binding and receptor activation. Our results suggest that this network involves the cluster of residues Arg(188) in TM2, Gln(380) in TM7, and Asn(229) in TM3. This cluster is expected to be altered upon VIP binding, because Arg(188) has been shown previously to interact with Asp(3) of VIP. Several point mutations at positions 188, 229, and 380 were experimentally characterized and were shown to severely affect VIP binding and/or VIP-mediated cAMP production. Double mutants built from reciprocal residue exchanges exhibit strong cooperative or anticooperative effects, thereby indicating the spatial proximity of residues Arg(188), Gln(380), and Asn(229). Because these residues are highly conserved in the GPCR-B family, they can moreover be expected to have a general role in mediating function.

Interaction dynamics in small networks of nonlinear elements

We study a small circuit of coupled nonlinear elements to investigate general features of signal transmission through networks. The small circuit itself is perceived as building block for larger networks. Individual dynamics and coupling are motivated by neuronal systems: We consider two types of dynamical modes for an individual element, regular spiking and chattering and each individual element can receive excitatory and/or inhibitory inputs and is subjected to different feedback types (excitatory and inhibitory; forward and recurrent). Both, deterministic and stochastic simulations are carried out to study the input-output relationships of these networks. Major results for regular spiking elements include frequency locking, spike rate amplification for strong synaptic coupling, and inhibition-induced spike rate control which can be interpreted as a output frequency rectification. For chattering elements, spike rate amplification for low frequencies and silencing for large frequencies is characteristic