Design of a Modern Liposome and Bee Venom Formulation for the Traditional VIT-Venom Immunotherapy

Traditional venom immunotherapy uses injections of whole bee venom in buffer or adsorbed in Al (OH)(3) in an expensive, time-consuming way. New strategies to improve the safety and efficacy of this treatment with a reduction of injections would, therefore, be of general interest. It would improve patient compliance and provide socio-economic benefits. Liposomes have a long tradition in drug delivery because they increase the therapeutic index and avoid drug degradation and secondary effects. However, bee venom melittin (Mel) and phospholipase (PLA(2)) destroy the phospholipid membranes. Our central idea was to inhibit the PLA(2) and Mel activities through histidine alkylation and or tryptophan oxidation (with pbb, para-bromo-phenacyl bromide, and/or NBSN-bromosuccinimide, respectively) to make their encapsulations possible within stabilized liposomes. We strongly believe that this formulation will be nontoxic but immunogenic. In this paper, we present the whole bee venom conformation characterization during and after chemical modification and after interaction with liposome by ultraviolet, circular dichroism, and fluorescence spectroscopies. The PLA(2) and Mel activities were, measured indirectly by changes in turbidity at 400(nm), rhodamine leak-out, and hemolysis. The native whole bee venom (BV) presented 78.06% of alpha-helical content. The alkylation (A-BV) and succynilation (S-BV) of BV increased 0.44 and 0.20% of its alpha-helical content. The double-modified venom (S-A-BV) had a 0.74% increase of alpha-helical content. The BV chemical modification induced another change on protein conformations observed by Trp that became buried with respect to the native whole BV. It was demonstrated that the liposomal membranes must contain pbb (SPC:Cho:pbb, 26:7:1) as a component to protect them from aggregation and/or fusion. The membranes containing pbb maintained the same turbidity (100%) after incubation with modified venom, in contrast with pbb-free membranes that showed a 15% size decrease. This size decrease was interpreted as membrane degradation and was corroborated by a 50% rhodamine leak-out. Another fact that confirmed our interpretation was the observed 100% inhibition of the hemolytic activity after venom modification with pbb and NBS (S-A-BV). When S-A-BV interacted with liposomes, other protein conformational changes were observed and characterized by the increase of 1.93% on S-A-BV alpha-helical content and the presence of tryptophan residues in a more hydrophobic environment. In other words, the S-A-BV interacted with liposomal membranes, but this interaction was not effective to cause aggregation, leak-out, or fusion. A stable formulation composed by S-A-BV encapsulated within liposomes composed by SPC:Cho:pbb, at a ratio of 26:7:1, was devised. Large unilamellar vesicles of 202.5 nm with a negative surface charge (-24.29 mV) encapsulated 95% of S-A-BV. This formulation can, now, be assayed on VIT.

Annual CO-emissions of combined pellet and solar heating systems

Emissions are an important aspect of a pellet heating system. High carbon monoxide emissions are often caused by unnecessary cycling of the burner when the burner is operated below the lowest combustion power. Combining pellet heating systems with a solar heating system can significantly reduce cycling of the pellet heater and avoid the inefficient summer operation of the pellet heater. The aim of this paper was to study CO-emissions of the different types of systems and to compare the yearly CO-emissions obtained from simulations with the yearly CO-emissions calculated based on the values that are obtained by the standard test methods. The results showed that the yearly CO-emissions obtained from the simulations are significant higher than the yearly CO-emissions calculated based on the standard test methods. It is also shown that for the studied systems the average emissions under these realistic annual conditions were greater than the limit values of two Eco-labels. Furthermore it could be seen that is possible to almost halve the CO-emission if the pellet heater is combined with a solar heating system.

Perceptions of Sustainability and Functional Aspects on Liquid Carton Board Packaging Materials versus Competing Materials for Juice Applications in Sweden

This research explores the downstream perceptions of liquid carton board versus competing materials in packaging applications for juice. The methodology used is focus groups. The context is sustainability and functional performance, and related potential implications for the beverage industry value chain. The purpose is to get a deeper insight and understanding of functionality in relation to juice beverage packaging. The results confirm that there is no optimal packaging for every juice product, but a multitude, depending on the distribution channel, retail outlet, customer preferences, and context of consumption. There are some general packaging preferences, but the main deciding criteria for purchase seem to be the product characteristics in terms of quality, taste, brand, price and shelf life. For marketing reasons, packaging has to be adopted to the product and its positioning, liquid carton board packaging seem to have some functional advantages in distribution and is considered as sustainable and functional among many consumers. Major drawbacks seem to be shape limitations, lack of transparency, and lack of a “premium look”. To improve packaging performance and avoid sub-optimization, actors in the beverage industry value chain need to be integrated in development processes.

Economic recovery from the Argentine great depression : institutions, expectations, and the change of macroeconomic regime

This work explores how Argentina overcame the Great Depression and asks whether active macroeconomic interventions made any contribution to the recovery. In particular, we study Argentine macroeconomic policy as it deviated from gold-standard orthodoxy after the final suspension of convertibility in 1929. As elsewhere, fiscal policy in Argentina was conservative, and had little power to smooth output. Monetary policy became heterodox after 1929. The first and most important stage of institutional change took place with the switch from a metallic monetary regime to a fiduciary regime in 1931; the Caja de Conversión (Conversion Office, a currency board) began rediscounting as a means to sterilize gold outflows and avoid deflationary pressures, thus breaking from orthodox "mIes of the game." However, the actual injections of liquidity were small' and were not enough to fully offset the incipient monetary contractions: the "Keynes" effect was weak or negative. Rather, recovery derived from changes in beliefs and expectations surrounding the shift in the monetary and exchange-rate regime,and the delinking of gold flows and the money base. Agents perceivod a new regime, as shown by the path of consumption, investment, and estimated ex ante real interest rates: the "Mundell" effect was dominant. Notably, this change of regime predated a later, and supposedly more significant, stage of institutional reform, namely the creation of the central bank in 1935. Still, the extent of intervention was weak, and insufficient to fully offset externaI shocks to prices and money. Argentine macropolicy was heterodox in terms of the change of regime, but still conservative in terms of the tentative scope of the measures taken .

Effectiveness of high-throughput miniaturized sorbent- and solid phase microextraction techniques combined with gas chromatography–mass spectrometry analysis for a rapid screening of volatile and semi-volatile composition of wines: a comparative study

In this study the feasibility of different extraction procedures was evaluated in order to test their potential for the extraction of the volatile (VOCs) and semi-volatile constituents (SVOCs) from wines. In this sense, and before they could be analysed by gas chromatography–quadrupole first stage masss spectrometry (GC–qMS), three different high-throughput miniaturized (ad)sorptive extraction techniques, based on solid phase extraction (SPE), microextraction by packed sorbents (MEPS) and solid phase microextraction (SPME), were studied for the first time together, for the extraction step. To achieve the most complete volatile and semi-volatile signature, distinct SPE (LiChrolut EN, Poropak Q, Styrene-Divinylbenzene and Amberlite XAD-2) and MEPS (C2, C8, C18, Silica and M1 (mixed C8-SCX)) sorbent materials, and different SPME fibre coatings (PA, PDMS, PEG, DVB/CAR/PDMS, PDMS/DVB, and CAR/PDMS), were tested and compared. All the extraction techniques were followed by GC–qMS analysis, which allowed the identification of up to 103 VOCs and SVOCs, distributed by distinct chemical families: higher alcohols, esters, fatty acids, carbonyl compounds and furan compounds. Mass spectra, standard compounds and retention index were used for identification purposes. SPE technique, using LiChrolut EN as sorbent (SPELiChrolut EN), was the most efficient method allowing for the identification of 78 VOCs and SVOCs, 63 and 19 more than MEPS and SPME techniques, respectively. In MEPS technique the best results in terms of number of extractable/identified compounds and total peak areas of volatile and semi-volatile fraction, were obtained by using C8 resin whereas DVB/CAR/PDMS was revealed the most efficient SPME coating to extract VOCs and SVOCs from Bual wine. Diethyl malate (18.8 ± 3.2%) was the main component found in wine SPELiChrolut EN extracts followed by ethyl succinate (13.5 ± 5.3%), 3-methyl-1-butanol (13.2 ± 1.7%), and 2-phenylethanol (11.2 ± 9.9%), while in SPMEDVB/CAR/PDMS technique 3-methyl-1-butanol (43.3 ± 0.6%) followed by diethyl succinate (18.9 ± 1.6%), and 2-furfural (10.4 ± 0.4%), are the major compounds. The major VOCs and SVOCs isolated by MEPSC8 were 3-methyl-1-butanol (26.8 ± 0.6%, from wine total volatile fraction), diethyl succinate (24.9 ± 0.8%), and diethyl malate (16.3 ± 0.9%). Regardless of the extraction technique, the highest extraction efficiency corresponds to esters and higher alcohols and the lowest to fatty acids. Despite some drawbacks associated with the SPE procedure such as the use of organic solvents, the time-consuming and tedious sampling procedure, it was observed that SPELiChrolut EN, revealed to be the most effective technique allowing the extraction of a higher number of compounds (78) rather than the other extraction techniques studied.

Colombeau's theory and shock wave solutions for systems of PDEs

In this article we study the existence of shock wave solutions for systems of partial differential equations of hydrodynamics with viscosity in one space dimension in the context of Colombeau's theory of generalized functions. This study uses the equality in the strict sense and the association of generalized functions (that is the weak equality). The shock wave solutions are given in terms of generalized functions that have the classical Heaviside step function as macroscopic aspect. This means that solutions are sought in the form of sequences of regularizations to the Heaviside function that have to satisfy part of the equations in the strict sense and part of the equations in the sense of association.

Heaviside generalized functions and shock waves for a Burger kind equation

The purpose of the work is to study the existence and nonexistence of shock wave solutions for the Burger equations. The study is developed in the context of Colombeau's theory of generalized functions (GFs). This study uses the equality in the strict sense and the weak equality of GFs. The shock wave solutions are given in terms of GFs that have the Heaviside function, in x and ( x, t) variables, as macroscopic aspect. This means that solutions are sought in the form of sequences of regularizations to the Heaviside function, in R-n and R-n x R, in the distributional limit sense.

Trait-mediated effects on flowers: Artificial spiders deceive pollinators and decrease plant fitness

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

FTY720 in combination with cyclosporine - an analysis of skin allograft survival and renal function

Acute and chronic nephrotoxicity caused by CsA Continuous administration impair kidney allograft survival. Several clinical and experimental protocols have shown benefits to the kidney after decreasing CsA dose, withdrawing the drug or delaying its introduction after transplantation.FTY720 is a new Compound that has immunosuppressive characteristics and increase allograft survival in animal models without causing the side effects of calcineurin inhibitors (CNIs). FTY720 described mechanism of action that consists to alter the lymphocyte migration pattern without impairment of the immune system response against pathogens.In our mice model, FTY720 administered alone or in combination with CsA during 21 days increased skin allograft survival in a fully mismatched strain combination and did not cause significant changes in renal function. Moreover, renal structure was normal in all groups suggesting that at low doses (10 mg/kg/day) CsA can be associated during short-term period to other immunosuppressive drugs, i.e. FTY720 without affecting the kidney.Combination of immunosuppressive compounds with FTY720 and/or delayed introduction of low cyclosporine dose Could prevent graft rejection and avoid nephrotoxicity. (c) 2006 Elsevier B.V. All rights reserved.

Sequence, evolution and ligand binding properties of mammalian Duffy antigen/receptor for chemokines

The Duffy antigen/receptor for chemokine, DARC, acts as a widely expressed promiscuous chemokine receptor and as the erythrocyte receptor for Plasmodium vivax. To gain insight into the evolution and structure/function relations of DARC, we analyzed the binding of anti-human Fy monoclonal antibodies (mAbs) and human chemokines to red blood cells (RBCs) from 11 nonhuman primates and two nonprimate mammals, and we elucidated the structures of the DARC genes from gorilla, gibbon, baboon, marmoset, tamarin, night monkey and cattle. CXCL-8 and CCL-5 chemokine binding analysis indicated that the promiscuous binding profile characteristic of DARC is conserved across species. Among three mAbs that detected the Fy6 epitope by flow cytometric analysis of human and chimpanzee RBCs, only one reacted with night monkey and squirrel monkey. Only chimpanzee RBCs bound a significant amount of the anti-Fy3 mAb. Fy3 was also poorly detected on RBCs from gorilla, baboon and rhesus monkey, but not from new world monkeys. Alignment of DARC homologous sequences allowed us to construct a phylogenetic tree in which all branchings were in accordance with current knowledge of primate phylogeny. Although DARC was expected to be under strong internal and external selection pressure, in order to maintain chemokine binding and avoid Plasmodium vivax binding, respectively, our present study did not provide arguments in favor of a selection pressure on the extracellular domains involved in ligand specificity. The amino acid variability of DARC-like polypeptides was found to be well correlated with the hydrophylicity indexes, with the highest divergence on the amino-terminal extracellular domain. Analysis of the deduced amino acid sequences highlighted the conservation of some amino acid residues, which should prove to be critical for the structural and functional properties of DARC.

Symbolic power, robotting, and surveilling

Symbolic power is discussed with reference to mathematics and formal languages. Two distinctions are crucial for establishing mechanical and formal perspectives: one between appearance and reality, and one between sense and reference. These distinctions include a nomination of what to consider primary and secondary. They establish the grammatical format of a mechanical and a formal world view. Such views become imposed on the domains addressed by means of mathematics and formal languages. Through such impositions symbolic power of mathematics becomes exercised. The idea that mathematics describes as it prioritises is discussed with reference to robotting and surveillance. In general, the symbolic power of mathematics and formal languages is summarised through the observations: that mathematics treats parts and properties as autonomous, that it dismembers what it addresses and destroys the organic unity around things, and that it simplifies things and reduces them to a single feature. But, whatever forms the symbolic power may take, it cannot be evaluated along a single good-bad axis.

Lower-semicontinuity and optimization of convex functionals

The result that we treat in this article allows to the utilization of classic tools of convex analysis in the study of optimality conditions in the optimal control convex process for a Volterra-Stietjes linear integral equation in the Banach space G([a, b],X) of the regulated functions in [a, b], that is, the functions f : [a, 6] → X that have only descontinuity of first kind, in Dushnik (or interior) sense, and with an equality linear restriction. In this work we introduce a convex functional Lβf(x) of Nemytskii type, and we present conditions for its lower-semicontinuity. As consequence, Weierstrass Theorem garantees (under compacity conditions) the existence of solution to the problem min{Lβf(x)}. © 2009 Academic Publications.

Regional integration and the issue of choosing an appropriate exchange-rate regime in Latin America

Includes bibliography

Pension system reforms, the capital market and saving

Includes bibliography

Ethical Care of the Self and the Teacher in the Pedagogical Relationship: Reflections Based on the Latest Foucault

Our conception of education is that it is the responsible action whereby man becomes human, trains and faces the challenges that life and the world present, as man enters a larger, shared cultural tradition and thus joins the world. However such sharing implies that we must not just rely on tradition, but remain open to new ideas. It is essential for schooling to preserve a field where the art of living intersects with the world for which future generations are being prepared. It is in this field of intersection that this essay seeks to discuss Michel Foucault's thought, care of the self and the role played by others in the acquisition of ethical attitudes pertaining to one's conduct in life. Through reconstructing Foucault's ideas, we elaborate on the hypothesis that, before morally shaping students, teaching them values, or aiding in their skill acquisition in the sense prevailing in schooling today, it is important to understand the notion of care of the self (and how the notion implies interaction with others for effective care of the self). Care of the self is vital for thoroughly understanding the relationships between ethics and education in school. We particularly examine how Foucault's ideas and his analysis of the teacher's role in shaping the student's life conduct can help educators rethink pedagogical action in an ethical sense and find within it a certain openness to the formation of attitudes in educators and students