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.

Mellan etnologi och modern sociologi : K. Rob. V. Wikman som medlare i Finland och Sverige

Between ethnology and sociology: K. Rob. V. Wikman as a mediator in Finland and Sweden K. Rob. V. Wikman, professor in sociology at the Åbo Akademi University in Turku, Finland, played a central role both within Finnish and Swedish sociology in the 1940s and 1950s. He was a student of Westermarck and thus his own research represented an ethnosociological tradition, which at that time was challenged by modern, American-influenced sociological ideas. The aim of this article is to discuss the adaptation of “modern sociology” and the drawing of boundaries in Nordic sociology after the Second World War by focusing on Wikman’s work in Finnish as well as Swedish sociology, especially the assessor assignments he was given, and by giving emphasis to some of those that served as border poles or border markers in this process. The comparative starting point gives us reason to discuss some nationally characterized similarities and differences that can be observed in the establishment process of modern sociology in Finland and Sweden.

Från traditionellt akademiskt bibliotek till modern lärmiljö : Högskolan Dalarnas bibliotek – förväntningar och resultat

I denna rapport beskrivs idéerna bakom Högskolan Dalarnas prisbelönta bibliotek i Falun. Planerings- och byggprocessen beskrivs och det färdiga resultatet utvärderas, samt de erfarenheter som har gjorts delas.

From a traditional academic library to a modern learning environment : Dalarna University Library - expectations and results

This report describes the ideas and vision behind Dalarna University's award-winning library in Falun. A description of the planning and construction processes and an evaluation of the final outcome are presented together with experiences and observations drawn from the project.

"Vox Populi, Vox Dei" - A Discussion of Dissent Within the Modern Catholic Church

The final question is: what happens in the meantime? Is it effective to dissent while conservatives hold power and clearty are not about to make any major changes? What good does it do to repeatedly bang one's head against the wall when progress is not being made? There is no one simple answer to this question, but rather several applicable ones. The first possible answer is that dissent currently does little good. The conservative hierarchy is still the dominant force within Catholicism. This hierarchy has made a habit, evidenced by the birth control debate, of pressing its conservative agenda despite popular opposition. Many people think, that if this hierarchy has not given in to the mass of opinion against it yet, dissent is futile and useless. Why argue with someone who does not listen to your argument?

Beethoven’s Influence on Modern Musical Thought

Ludwig van Beethoven is undoubtedly one of the most important and influential composers of Western art music. From a young age, he exhibited considerable talent, independence, and willful nonconformity. Over the course of his life, these themes came through both in his compositions, and in his attitude towards social norms regarding music. Composing symphonies, sonatas, string quartets, concertos, and one opera, Beethoven shattered musical boundaries and set the stage for how musicians and listeners would think about music for the next 200 years, up to modern day. This afternoon I will explore various ways in which Beethoven’s conception of music continues to influence our thinking about music, even rock, through analysis of The Beatles’ “A Day in the Life,” off their 1967 album Sgt. Pepper’s Lonely Hearts Club Band.

Musilian Concept of Modern Man

German-Austrian Robert Musil (1880-1942) is considered an artist with an extremely unorthodox conception of art to a basic human problem. In his time, there existed a dissociation of substance from social values. Musil actually started with this foundation in considering the taunting dilemma that the accelerating technology of the century is overstepping each day the ability of the human mind to adjust to it. Musil maintained that social organization, patterns of thought and cherished ideals correspond to a reality that no longer exists

Investor disagreement: the modern approach

Disagreement between economists is a well know fact. However, it took a long time for this concept to be incorporated in economic models. In this survey, we review the consequences and insights provided by recent models. Since disagreement between market agents can be generated through different hypotheses, the main differences between them are highlighted. Finally, this work concludes with a short review of nowcasting using google trends, emphasizing advances connecting both literatures.