Transition metal-catalyzed alkoxylation and amination reactions involving propargyl or allyl derivatives.

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Engineering mono- and multi-valent inhibitors on a modular repeat-protein scaffold to target oncogenic Tankyrase

Tandem-repeat proteins are a class of proteins ubiquitous in nature and exploited in recent years in biotechnological and pharmaceutical applications due to their favourable biophysical properties. One such repeat motif, the tetratricopeptide repeat (TPR), has already been exploited for biotechnological applications and here the consensus-designed TPR (CTPR) sequence was used as a scaffold to create novel arrays of binding molecules. The platform allows us to display single and multiple functions with diverse geometrical arrangements by grafting short binding sequences onto the loops between adjacent repeats or at the terminal alpha-helices. As proof of concept, proteins were designed to bind to and inhibit the human tankyrase (TNKS), a key regulatory protein involved in Wnt signalling and overexpressed in cancer and other disorders. For this purpose, a tankyrase-binding peptide (TBP) was grafted between two adjacent repeats to create a solvent-exposed loop. A series of mono- and multi- valent TNKS binders, named TBP-CTPR, was assembled by repeating the TNKS-binding unit in tandem in both a monomeric format and also in a trimeric arrangement. The folding and thermodynamic stability of these TBP-CTPR proteins were characterised and the interaction with TNKS was measured using a range of biophysical approaches. Both the engineered TBP- CTPR proteins and TNKS are multivalent, and the effects of multivalency were explored both in the test tube and in the cell. The results show that the proteins interact to form large assemblies. Moreover, the TBP-CTPR proteins were found to have exceptional activity in inhibiting the Wnt signaling pathway upon delivery by encapsulation in fusogenic liposomes. Lastly, hetero-bifunctional constructs were generated by grafting two different binding sequences onto the CTPR scaffold, and a preliminary analysis of their activities was performed. In conclusion, these results point to the tremendous potential of the CTPR scaffold as a platform to build synthetic protein binders, with a particular focus on multivalent interactions

The octopus mind: Implications for cognitive science

Mather consolidates the case for octopus mind and how it may be structured, shifting the starting point of inquiry from “If octopuses had minds, what would they be like?” to “What is the mind of an octopus like?”

Inequality in the rhetoric of Buddhist-kami relations

Title from PDF of title page (University of Missouri--Columbia, viewed on November 5, 2012).The entire thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file; a non-technical public abstract appears in the public.pdf file.Thesis advisor: Professor Edward DrottIncludes bibliographical references.M.A. University of Missouri--Columbia 2012."July 2012"Buddhism has long been praised and viewed as religion that embraces other faiths without compromising itself or the other religion. In history, Buddhism has been thought to meld with the indigenous traditions it encountered harmoniously and with little tension. However, though Buddhist rhetoric seeks to give this impression, under the surface a colonialist attitude can be found. In Japan, this takes form in the lowering and subsequent elevation of indigenous gods (kami). As Buddhism gained power in Japan, Buddhist deities and methods came to be seen as ways to control and subjugate the unruly indigenous gods. From the Nara to the Kamakura period indigenous gods had to regain their status by working their way up the Buddhist eschatological ladder to eventually gain the title of suijaku, emanation of a Buddha. Even with this title however, kami were seen as inferior to their Buddhist counterparts, with few exception. This study analyzes ritual and literary texts from the Nara-Kamakura periods to show the tension between the status of kami and Buddhist deities during these periods. These texts show that kami remained subject to the rule of Buddhist deities despite the awarding of impressive sounding titles and the rhetoric of hongaku which expressed equality of essence. These findings suggest that throughout history Buddhism has not been as egalitarian as it seems, and its rhetoric should be reevaluated for its colonialistic tendencies

Urban air quality estimation study, phase 1

Possibilities are explored for applying estimation theory to the analysis, interpretation, and use of air quality measurements in conjunction with simulation models to provide a cost effective method of obtaining reliable air quality estimates for wide urban areas. The physical phenomenology of real atmospheric plumes from elevated localized sources is discussed. A fluctuating plume dispersion model is derived. Individual plume parameter formulations are developed along with associated a priori information. Individual measurement models are developed

Adaptation to aerobic environment of Lactobacillus johnsonii/gasseri strains

Oxygen is considered one of the main factors affecting probiotic bacteria survival due to the induction of oxidative damages caused by the action of reactive oxygen species (ROS). It has been shown that oxidative stress resistance in lactic acid bacteria is strongly dependent on the type of cell metabolism. Shift from fermentative to respiratory metabolism (through the addition of heme and menaquinone and in presence of oxygen) was associated to increase in biomass, long-term survival, and production of antioxidant enzymes. The aim of this work was to investigate the effect of aerobic (presence of oxygen) and respiratory (presence of oxygen, heme, and menaquinone) cultivation on the growth kinetic, catalase production, oxygen uptake, and oxidative stress response of Lactobacillus johnsonii/gasseri strains previously isolated from infant feces. Seven strains showed to consume oxygen under aerobic and respiratory conditions. The strain AL5 showed a catalase activity in both growth conditions, while AL3 showed this activity only in respiratory condition. Respiratory condition improved their tolerance to oxidative compounds (hydrogen peroxide and ROS generators) and further they showed promising probiotic features. The exploration of respiratory competent phenotypes with probiotic features may be extremely useful for the development of competitive starter or probiotic cultures

A par condicio creditorum e o tratamento diferenciado entre credores no plano de recuperação judicial

O presente estudo tem como tema central a análise do tratamento diferenciado entre os credores sujeitos à recuperação judicial, disciplinada pela Lei 11.101/2005. A necessidade de tratar credores de forma igualitária encontra-se prevista no princípio clássico do direito concursal chamado par condicio creditorum. Assim, busca-se analisar a aplicabilidade desse princípio na recuperação judicial, bem como os elementos que permitam uma compreensão do instituto a fim de construir uma base teórica, problematizar a funcionalidade da Lei através do exame da jurisprudência e doutrina e estabelecer critérios. A relevância do tema justifica-se em razão da matéria ser controvertida e de grande aplicação prática pela existência de diferenciação de tratamento entre credores na maioria das recuperações judiciais. Para tanto, no primeiro capítulo, analisa-se os conceitos básicos e origens para estudo da par condicio creditorum e o contexto dos princípios que norteiam o direito concursal. No segundo capítulo é abordada a importância da jurisprudência e dos credores na construção da recuperação judicial, destacando a problemática existente nas classes de credores originalmente previstas na legislação e a natureza jurídica do plano de recuperação judicial. No terceiro capítulo são analisados os principais casos em que ocorre o tratamento diferenciado entre credores na recuperação judicial, como a criação de subclasses, a existência de credor estratégico ou colaborativo que financie a empresa devedora e a consolidação substantiva de grupos societários, objetivando estabelecer critérios. Finalmente, no quarto capítulo discute-se a soberania da assembleia-geral de credores, o papel do juiz na homologação do plano de recuperação judicial e as hipóteses de controle de legalidade pelo judiciário. Ao final, são expostas as conclusões sobre a pesquisa.The present study has as its central theme the analysis of the unfair discrimination among creditors subject to reorganization, disciplined by Law 11.101/2005. The need to treat creditors in an egalitarian manner is provided for in the classic principle of bankruptcy law called par condicio creditorum. Thus, the study seeks to analyze the applicability of this principle in reorganization, as well as the elements that allow an understanding of the institute in order to build a theoretical basis, problematize the functionality of the Law through the examination of jurisprudence and doctrine and establish criteria. The relevance of the topic is justified because the matter is controversial and of great practical application by the existence of different treatment between creditors in most reorganization process. To do so, the first chapter analyzes the basic concepts and origins for the study of par condicio creditorum and the context of the principles that guide bankruptcy law. The second chapter deals with the importance of jurisprudence and creditors in the construction of the reorganization process, highlighting the problems existing in the classes of claims originally foreseen in the legislation and the legal nature of the plan of reorganization. The third chapter analyzes the main cases in which unfair discrimination occurs between creditors in reorganization process, such as the creation of subclasses, the existence of essential venders that finances the debtor company and the substantive consolidation of corporate groups, aiming to establish criteria. Finally, the fourth chapter discusses the sovereignty of the general assembly of creditors, the role of the judge in the confirmation of the reorganization plan and the hypotheses of legality control by the judiciary. At the end, the conclusions about the research are presented

Comparative analysis of aerobic and respiratory metabolism and genomic characterization of Lactobacillus gasseri strains

Generalmente i batteri lattici sono classificati come anaerobi ossigeno tolleranti che traggono la propria energia da un metabolismo di tipo fermentativo. Tuttavia, negli ultimi anni, sempre più studi hanno evidenziato che in presenza di heme e menachinone, molti batteri lattici hanno la capacità di adottare un metabolismo di tipo aerobio-respirativo. Lo shift metabolico dalla fermentazione alla respirazione conferisce molti vantaggi alla fisiologia cellulare, tra cui maggiore produzione di biomassa, maggiore vitalità nel tempo e produzione di enzimi antiossidanti. Tutti aspetti rilevanti dal punto di vista tecnologico-applicativo. Molti studi si sono focalizzati su specie appartenenti al gruppo di Lactobacillus casei e Lactobacillus plantarum, e pochissimi dati sono presenti in letteratura su ceppi appartenenti alle specie di Lb. johnsonii/gasseri. L'attività di ricerca ha esplorato la risposta adattiva al metabolismo aerobio respirativo nelle specie di interesse, ottenendo risultati rilevanti al fine di comprendere i meccanismi alla base dei cambiamenti metabolici. Inoltre, grazie al sequenziamento dei genomi, importanti informazioni sulle basi genetiche si sono acquisite al fine di supportare le evidenze fenotipiche osservate. L'analisi sui genomi non solo ha evidenziato la presenza dei principali geni coinvolti nel metabolismo aerobio-respirativo ma anche di importati geni codificanti per enzimi antiossidanti, mai annotati prima nei genomi presenti in banca dati delle specie di interesse. Allo stato attuale delle conoscenze, per la prima volta gli aspetti legati il metabolismo aerobio-respirativo, nonché la risposta allo stress ossidativo, sono esplorati in ceppi appartenenti alle specie di Lb. johnsonii/gasseri. Questa attività di ricerca, quindi, ha portato alla selezione di due ceppi con fenotipo di tipo aerobio-respirativo, che presentano attività antiossidanti e probiotiche. Caratteristiche di grande rilevanza nell'ottica dello sviluppo di colture starter e/o probiotiche