Mechanism and kinetics of homogeneous catalysis

A model-based approach using a diverse set of data including monomer consumption, evolution of molecular weight, and end-group analysis was employed to determine each of the reaction specific rate constants involved in 1-hexene polymerization process catalyzed by a family of group IV single-site catalysts. The primary set of elementary reaction steps included initiation, normal propagation, misinsertion, recovery from misinsertion, monomer independent and dependent chain transfer. Robust determination of kinetic constants and reaction mechanisms for a series of Group IV amine bis-phenolate complexes led to the development of several structure−activity relationships.^ For some of the catalysts of the bis-phenolate family the primary set of elementary reactions had proven inadequate and further investigation using the analysis developed here revealed the presence of additional key reaction steps. The kinetic study of the Zr[tBu-ONTHFO]Bn2/B(C 6F5)3 system under sub-stoichiometric activator conditions uncovered the formation of the binuclear complex (BNC) consisting of the neutral catalytic species and an active site connected via degenerative transfer of benzyl ligand. The kinetic study of the Zr[tBu-ONNEt2O]Bn2/B(C6F5)3 system showed that a special polymeric site was formed which was capable to incorporate the growing oligomer chains attached to the normal active site to form branched polymer.^ The approach was next applied to studying the kinetics of other catalytic systems, e.g., the zwitterionic ring-opening polymerization using N-heterocyclic carbene, where several new reaction steps were proposed and then experimentally validated, including the attack of active zwitterions on cyclic chains that leads to high molecular weight cyclic poly(caprolactones)

Ottobre-Dicembre 1935: il partito conservatore britannico e i riflessi della guerra Abissina

La crisi etiopica rappresenta, com’è noto, uno dei momenti di svolta decisivi per gli equilibri internazionali negli anni tra le due guerre. Vista dalla prospettiva britannica, e in particolare da quella degli ambienti del partito conservatore, essa può essere vista come uno dei momenti che misero maggiormente in risalto la debolezza ma soprattutto l’ambiguità in politica estera del National Government, egemonizzato proprio dal partito di Baldwin. Incarnazione di questo atteggiamento fu il ministro degli Esteri Samuel Hoare, che nelle convulse settimane che seguirono l’annuncio dell’invasione italiana dell’Etiopia finì nello stesso tempo per essere artefice e vittima di una linea politica giocata costantemente sul filo del rasoio. Ricostruendo dall’ottica delle varie anime del partito conservatore britannico le concitate fasi che vanno dallo scoppio della guerra, all’inizio di ottobre del 1935, fino al dicembre di quello stesso anno, ovvero al fallimento del Piano Hoare-Laval, questo contributo intende delineare i tratti i tratti caratterizzanti di quella svolta che si consumò nei rapporti tra ampi strati del mondo conservatore e il fascismo. I due mesi che seguirono lo scoppio della guerra d’Etiopia e il conseguente naufragio dell’ambiguo progetto di Hoare lasciarono cicatrici profonde. Anche se la rottura definitiva si sarebbe compiuta di fatto solo nel giugno del 1940, essi segnarono in modo indelebile i rapporti tra i due paesi. Pur non eliminando definitivamente il dialogo tra Londra e Roma, infatti, la crisi Abissina tolse ai rapporti tra il fascismo e il partito conservatore quell’alone retorico di benevola, paternalistica amicizia – in taluni casi di entusiastico sostegno – che sin dalla marcia su Roma era stato costruito e rinsaldato con il contributo della stampa, degli osservatori politici, degli ammiratori più o meno occasionali e dei giudizi provenienti dai vari ambienti culturali allo scopo di legittimare una comunanza d’intenti che, all’indomani di quella crisi, si scoprì definitivamente essere contraddistinta unicamente da precisi calcoli politici

Europe and its Fears in the Age of Anxiety: Historiography and Perspectives

It is a common belief that the dimension of fear, increasingly used by media by borrowing expressions such as "Society of fear", "Politics of fear" or "Culture of Fear", has emerged as a collective feeling in contemporary society after the attacks on the Twin Towers of 11 September 2001. In reality, Fear was already present in Western collective sensibility, as already happened in the course of history during phases characterised by profound economic, political or social changes, in close connection with a widespread sense of uncertainty and anxiety. This contribution provides a general view, from a historical perspective, of the theme of fear and more generally of the history of emotions in the West, with particular attention to the European case study, first of all reconstructing the evolution of the historiographical debate, from the first reflections by Lucien Febvre, advanced during the rise of totalitarianism in Europe, to the progressive affirmation of studies on this issue, in particular from the second half of the Seventies, until the wide and differentiated recent literature. After comparing the different methodological approaches, describing the different types of sources used by scholars and posing the question of which social actors to study to better understand the characterizing traits of a collective feeling so important but also so elusive, the essay finally poses the issue of the periodization of collective fears - proposing a subdivision of the latter between short-term fears and long-term fears - and their dynamics during the twentieth century and the beginning of the new millennium

Schema2QA: High-Quality and Low-Cost Q&A Agents for the Structured Web

Building a question-answering agent currently requires large annotated datasets, which are prohibitively expensive. This paper proposes Schema2QA, an open-source toolkit that can generate a Q&A system from a database schema augmented with a few annotations for each field. The key concept is to cover the space of possible compound queries on the database with a large number of in-domain questions synthesized with the help of a corpus of generic query templates. The synthesized data and a small paraphrase set are used to train a novel neural network based on the BERT pretrained model. We use Schema2QA to generate Q&A systems for five Schema.org domains, restaurants, people, movies, books and music, and obtain an overall accuracy between 64% and 75% on crowdsourced questions for these domains. Once annotations and paraphrases are obtained for a Schema.org schema, no additional manual effort is needed to create a Q&A agent for any website that uses the same schema. Furthermore, we demonstrate that learning can be transferred from the restaurant to the hotel domain, obtaining a 64% accuracy on crowdsourced questions with no manual effort. Schema2QA achieves an accuracy of 60% on popular restaurant questions that can be answered using Schema.org. Its performance is comparable to Google Assistant, 7% lower than Siri, and 15% higher than Alexa. It outperforms all these assistants by at least 18% on more complex, long-tail questions

Rapid neuronal signaling cascades initiated by corticosterone

Besides inducing transcription by activating nuclear receptors, corticosterone (CORT) acts rapidly to alter cellular activity through multiple signaling cascades. Pharmacology-based experiments presented here show that nanomolar doses of CORT activate several pathways in primary hippocampal cultures within 20 minutes, a time-frame that excludes genomic mechanisms mediated by classical glucocorticoid (GR) and mineralocorticoid (MR) nuclear receptors. Moreover, none of these effects were subject to inhibition by either a series of structurally-unrelated antagonists of the classical GR and MR or by inhibitors of translation. Accordingly, a major aim of this work was to identify mechanisms proximal to the cell membrane that could potentially mediate these rapid actions of CORT. Initial time-course studies showed that 10 nM CORT rapidly triggers protein tyrosine kinase (PTK) activation that can be blocked by the small molecule inhibitor, PP2. It was also found that Src kinase is rapidly activated by CORT through tyrosine phosphorylation at Y416 and dephosphorylation at Y527. These events were subject to regulation by another key PTK member, Pyk2 (proline-rich tyrosine kinase 2). A series of experiments designed to study the potential mechanisms that regulate Pyk2, revealed that CORT increases the phosphorylation status of at least three tyrosine sites within Pyk2, namely, Y402, Y579/580 and Y881. Further, pharmacological probing uncovered requisite roles for other signaling pathways, such as the classical PLC-PKC pathway and the “novel” PKA and PKB pathways. Interestingly, further investigations revealed that the rapid CORT-induced activation of Pyk2/Src occurs in a G-protein dependent manner. This, together with the observation that membrane-impermeable BSA-conjugated CORT (CORT-BSA) produces similar responses profile to that obtained with CORT, led to pilot experiments to probe whether GPR30, a recently-described G protein-coupled receptor that appears to transduce signals from other steroid ligands, might be the putative receptor for CORT. Support for this view was provided by the finding that the rapid actions of CORT and CORT-BSA on Pyk2/Src activation could be blocked by a novel inhibitor of GPR30. Nevertheless, further studies will be needed to establish the role of GPR30 more firmly. Other studies sought to identify downstream targets of Pyk2/Src. Results show that Pyk2/Src regulates activation of c-Abl (another PTK) and RhoA, both of which are regulators of a number of cellular processes, including actin cytoskeleton remodeling. Furthermore, it was found that CORT triggers phosphorylation of the NR2B subunit of NMDAR, increases surface expression of NMDAR and activates downstream MAP kinases; all of these events depend on Src, one of whose direct substrates is the NR2B subunit. In a summary, the evidence presented in this dissertation suggests that, by acting via a G protein-coupled receptor, rather than through classical nuclear receptor mechanisms, CORT rapidly activates a series of intracellular signaling cascades that lie proximal to the neuronal plasma membrane; Pyk2/Src are early kinases involved and beyond these divergent pathways come into play, ultimately influencing functions ranging from rearrangements of the actin cytoskeleton, spine structure, scaffold protein clustering and function, to synaptic plasticity and transcriptional regulation

HIPERDIA: CUIDE DA SUA SAÚDE DA MANEIRA CORRETA

Pretendeu-se com este trabalho investigar o cotidiano enfrentado pela Estratégia de Saúde da Família Jardim Vista Alegre no Município de Vicentina/MS no cuidado à saúde dos Hipertensos e Diabéticos e criar soluções para que esta população busque cada vez mais participar das reuniões mensais, junto com a equipe de multiprofissional. Foi notado que com o programa do governo “Farmácia Popular” os hipertensos/Diabéticos não se sentiam mais “obrigados” a participar das reuniões mensais e com isso perdendo os seus direitos e benefícios de serem acompanhados de forma correta pela equipe de multiprofissional. A partir desta realidade em junho de 2013 com o apoio da equipe de multiprofissional, coordenação de atenção básica e da secretaria municipal de saúde, vem sendo realizado uma série de atividade de educação em saúde a fim de efetivar plenamente as ações do Hiperdia. Pode-se observar uma mudança satisfatória com a presença de grande parte dos pacientes cadastrados no programa; inclusive com relatos de satisfação por parte dos presentes, o que possibilitou a redução de riscos relacionados a complicações do diabetes e da hipertensão, articulando atividades de promoção e prevenção das doenças, despertando o interesse e participação dos presentes, bem como um maior controle pressórico e da taxa de glicemia, incentivando a mudança de hábitos, como no caso da alimentação correta, redução do sedentarismo, controle do tabagismo, importância da atividade física visando uma melhor qualidade de vida

The Stimulation of Inducible Nitric-oxide Synthase by the Prion Protein Fragment 106–126 in Human Microglia Is Tumor Necrosis Factor-α-dependent and Involves p38 Mitogen-activated Protein Kinase

A synthetic peptide consisting of amino acid residues 106-126 of the human prion protein (PrP-(106--126)) has been previously demonstrated to be neurotoxic and to induce microglial activation. The present study investigated the expression of the inducible form of the nitric-oxide synthase (NOS-II) in human microglial cells treated with PrP-(106--126). Using reverse transcriptase-polymerase chain reaction, we found that PrP-(106--126) induces NOS-II gene expression after 24 h of treatment and that this effect is accompanied by a peak of nuclear factor kappa B (NF-kappa B) binding at 30 min as evaluated by electrophoretic mobility shift assay. Since our previous data demonstrated tumor necrosis factor-alpha (TNF-alpha) to be a potent inducer of NOS-II in these cells, we analyzed the expression of this cytokine in PrP-(106--126)-treated microglia. PrP-(106--126) caused the release of TNF-alpha as detected by enzyme-linked immunosorbent assay, and a blocking antibody, anti-TNF-alpha, abolished NOS-II induction elicited by this peptide. Moreover, PrP-(106-126) activates p38 mitogen-activated protein kinase, and the inhibition of this pathway determines the ablation of NF-kappa B binding induced by this fragment peptide

Prediction of the anti-inflammatory mechanisms of curcumin by module-based protein interaction network analysis

AbstractCurcumin, the medically active component from Curcuma longa (Turmeric), is widely used to treat inflammatory diseases. Protein interaction network (PIN) analysis was used to predict its mechanisms of molecular action. Targets of curcumin were obtained based on ChEMBL and STITCH databases. Protein–protein interactions (PPIs) were extracted from the String database. The PIN of curcumin was constructed by Cytoscape and the function modules identified by gene ontology (GO) enrichment analysis based on molecular complex detection (MCODE). A PIN of curcumin with 482 nodes and 1688 interactions was constructed, which has scale-free, small world and modular properties. Based on analysis of these function modules, the mechanism of curcumin is proposed. Two modules were found to be intimately associated with inflammation. With function modules analysis, the anti-inflammatory effects of curcumin were related to SMAD, ERG and mediation by the TLR family. TLR9 may be a potential target of curcumin to treat inflammation