CoPIRIDE : new technical expertise relating to the anionic polymerisation of 1,3-Butadiene

Abstract onl

Claisen-Umlagerung im Ruehr- und Durchflussbetrieb : Verstaendnis des Mechanismus und Steuerung der Einflussgroessen : the Claisen rearrangement in flow and batch processing : mechanism exploration and control over influencing factors.

Die Claisen-Umlagerung wurde in über 100 Jahren durch zahlreiche Forscher äußerst eingehend im Rührbetrieb untersucht. Insbesondere der Reaktionsmechanismus wurde in allen Details erforscht. Quantenmechanische Modellierung und moderne Kurzzeit-Spektroskopie haben hier ganz neue Impulse gegeben. Auch wurden schon erste Erfahrungen im Durchflussbetrieb in Mikroreaktoren gesammelt. Wie für viele andere Reaktionen so konnte eine massive Beschleunigung in neuen Prozessfenstern erreicht werden. Dieser Übersichtsartikel zeigt, dass das wahre Potenzial dennoch darauf wartet, für den Mikroreaktorbetrieb entdeckt zu werden. The Claisen rearrangement has been extensively studied over the past 100 years in batch mode. Especially the reaction mechanism has been determined in all details. Quantum-mechanical modelling and ultrashort pulse spectroscopy have recently provided entirely new insight. First experiments were carried out in microreactors using flow chemistry. An enhancement of the yield and selctivity in the new processing windows has been observed. This review shows, that the true and full potential has still not been fully explored for the microreactor processing

Developmental neurotoxicity of environmentally relevant pharmaceuticals and mixtures thereof in a zebrafish embryo behavioural test

Humans are exposed daily to complex mixtures of chemical substances via food intake, inhalation, and dermal contact. Developmental neurotoxicity is an understudied area and entails one of the most complex areas in toxicology. Animal studies for developmental neurotoxicity (DNT) are hardly performed in the context of regular hazard studies, as they are costly and time consuming and provide only limited information as to human relevance. There is a need for a combination of in vitro and in silico tests for the assessment of chemically induced DNT in humans. The zebrafish (Danio rerio) embryo (ZFE) provides a powerful model to study DNT because it shows fast neurodevelopment with a large resemblance to the higher vertebrate, including the human system. One of the suitable readouts for DNT testing in the zebrafish is neurobehaviour (stimulus-provoked locomotion) since this provides integrated information on the functionality and status of the entire nervous system of the embryo. In the current study, environmentally relevant pharmaceuticals and their mixtures were investigated using the zebrafish light-dark transition test. Zebrafish embryos were exposed to three neuroactive compounds of concern, carbamazepine (CBZ), fluoxetine (FLX), and venlafaxine (VNX), as well as their main metabolites, carbamazepine 10,11-epoxide (CBZ 10,11E), norfluoxetine (norFLX), and desvenlafaxine (desVNX). All the studied compounds, except CBZ 10,11E, dose-dependently inhibited zebrafish locomotor activity, providing a distinct behavioural phenotype. Mixture experiments with these pharmaceuticals identified that dose addition was confirmed for all the studied binary mixtures (CBZ-FLX, CBZ-VNX, and VNX-FLX), thereby supporting the zebrafish embryo as a model for studying the cumulative effect of chemical mixtures in DNT. This study shows that pharmaceuticals and a mixture thereof affect locomotor activity in zebrafish. The test is directly applicable in environmental risk assessment; however, further studies are required to assess the relevance of these findings for developmental neurotoxicity in humans

Levantamento de insetos-praga associados aos capins tanner-grass, tangola e estrela-africana no Acre.

O presente estudo teve o objetivo de realizar um levantamento de insetos-praga em pastagens formadas com os capins tanner-grass (Brachiaria arrecta), tangola (B. arrecta x B. mutica) e estrelaafricana (Cynodon nlemfuensis) nas condições do estado do Acre, avaliando as injúrias causadas a essas espécies forrageiras. A metodologia de amostragem para avaliação populacional e de injúrias foi diferenciada conforme a espécie e o hábito de cada inseto-praga. As populações adultas das cigarrinhas-das-pastagens foram amostradas quinzenalmente com uso de rede entomológica de 30 cm de diâmetro, em dez pontos de amostragem por hectare em cada pastagem selecionada. A contagem de ninfas foi feita utilizando-se um quadrado de 25 cm de lado, lançado ao acaso por dez vezes na área de 1 ha. Concomitantemente, foram atribuídas notas de danos variando de 1 a 5 a cada pastagem, baseadas no seu aspecto. Cochonilhas e ácaros foram amostrados no ato do levantamento das ninfas de cigarrinhas-das-pastagens, contando-se as colônias presentes, utilizando-se uma lupa de bolso para a contagem dos indivíduos. As lagartas desfolhadoras foram contadas no interior de quadrados de 100 cm x 100 cm, lançados 20 vezes aleatoriamente sobre o pasto, atribuindo-se notas de 0 (zero) a 10 (dez) para o nível de injúria encontrado. Em áreas atacadas pelo percevejo-das-gramíneas, foram retiradas dez amostras de 0,25 m2 da biomassa do pasto, incluindo a liteira, que foram acondicionadas em sacos plásticos e transportadas ao laboratório para a contagem de ninfas e adultos. Os resultados mostraram que o consórcio de capim-tangola com capim-tanzânia (P. maximum cv. Tanzânia) pode favorecer ao incremento populacional de Mahanarva tristis. Pastagens de capim-tangola em monocultura favorecem o incremento populacional de Notozulia entreriana. Por outro lado, altas populações de Blissus antillus (percevejo-das-gramíneas) foram encontradas em áreas de baixada plantadas com o capim tanner-grass durante o início da estação chuvosa (setembro-outubro). Os capins tangola e estrela-africana são suscetíveis ao ataque de Spodoptera frugiperda, principalmente após períodos de estiagem prolongada

Testing real-time systems using TINA

The paper presents a technique for model-based black-box conformance testing of real-time systems using the Time Petri Net Analyzer TINA. Such test suites are derived from a prioritized time Petri net composed of two concurrent sub-nets specifying respectively the expected behaviour of the system under test and its environment.We describe how the toolbox TINA has been extended to support automatic generation of time-optimal test suites. The result is optimal in the sense that the set of test cases in the test suite have the shortest possible accumulated time to be executed. Input/output conformance serves as the notion of implementation correctness, essentially timed trace inclusion taking environment assumptions into account. Test cases selection is based either on using manually formulated test purposes or automatically from various coverage criteria specifying structural criteria of the model to be fulfilled by the test suite. We discuss how test purposes and coverage criterion are specified in the linear temporal logic SE-LTL, derive test sequences, and assign verdicts

Dissociation by steroids of eosinophilic inflammation from airway hyperresponsiveness in murine airways

BACKGROUND: The link between eosinophils and the development of airway hyperresponsiveness (AHR) in asthma is still controversial. This question was assessed in a murine model of asthma in which we performed a dose ranging study to establish whether the dose of steroid needed to inhibit the eosinophil infiltration correlated with that needed to block AHR. METHODS: The sensitised BALB/c mice were dosed with vehicle or dexamethasone (0.01–3 mg/kg) 2 hours before and 6 hours after each challenge (once daily for 6 days) and 2 hours before AHR determination by whole-body plethysmography. At 30 minutes after the AHR to aerosolised methacholine the mice were lavaged and differential white cell counts were determined. Challenging with antigen caused a significant increase in eosinophils in the bronchoalveolar lavage (BAL) fluid and lung tissue, and increased AHR. RESULTS: Dexamethasone reduced BAL and lung tissue eosinophilia (ED(50 )values of 0.06 and 0.08 mg/kg, respectively), whereas a higher dose was needed to block AHR (ED(50 )of 0.32 mg/kg at 3 mg/ml methacholine. Dissociation was observed between the dose of steroid needed to affect AHR in comparison with eosinophilia and suggests that AHR is not a direct consequence of eosinophilia. CONCLUSION: This novel pharmacological approach has revealed a clear dissociation between eosinophilia and AHR by using steroids that are the mainstay of asthma therapy. These data suggest that eosinophilia is not associated with AHR and questions the rationale that many pharmaceutical companies are adopting in developing low-molecular-mass compounds that target eosinophil activation/recruitment for the treatment of asthma

Divergent age-related humoral correlates of protection against respiratory syncytial virus infection in older and young adults: a pilot, controlled, human infection challenge model

Background Respiratory viral infections are typically more severe in older adults. Older adults are more vulnerable to infection and do not respond effectively to vaccines due to a combination of immunosenescence, so-called inflamm-ageing, and accumulation of comorbidities. Although age-related changes in immune responses have been described, the causes of this enhanced respiratory disease in older adults remain poorly understood. We therefore performed volunteer challenge with respiratory syncytial virus (RSV) in groups of younger and older adult volunteers. The aim of this study was to establish the safety and tolerability of this model and define age-related clinical, virological, and immunological outcomes. Methods In this human infection challenge pilot study, adults aged 18–55 years and 60–75 years were assessed for enrolment using protocol-defined inclusion and exclusion criteria. Symptoms were documented by self-completed diaries and viral load determined by quantitative PCR of nasal lavage. Peripheral blood B cell frequencies were measured by enzyme-linked immunospot and antibodies against pre-fusion and post-fusion, NP, and G proteins in the blood and upper respiratory tract were measured. The study was registered with ClinicalTrials.gov, NCT03728413. Findings 381 adults aged 60–75 years (older cohort) and 19 adults aged 18–55 years (young cohort) were assessed for enrolment using protocol-defined inclusion and exclusion criteria between Nov 12, 2018, and Feb 26, 2020. 12 healthy volunteers aged 60–75 years and 21 aged 18–55 years were inoculated intranasally with RSV Memphis-37. Nine (67%) of the 12 older volunteers became infected, developing mild-to-moderate upper respiratory tract symptoms that resolved without serious adverse events or sequelae. Viral load peaked on day 6 post-inoculation and symptoms peaked between days 6 and 8. Increases in circulating IgG-positive and IgA-positive antigen-specific plasmablasts, serum neutralising antibodies, and pre-F specific IgG were similar younger and older adults. However, in contrast to young participants, secretory IgA titres in older volunteers failed to increase during infection and, unlike serum IgG, did not correlate with protection. Interpretation Better understanding of age-related differences in clinical outcomes and immune correlates of protection can overcome reduction in vaccine efficacy with advancing age. We identify correlates of protection in older adults, revealing previously unrecognised factors which might have implications for targeted vaccine discovery and drug development in this vulnerable group. Funding Medical Research Council and GlaxoSmithKline EMINENT Consortium

Search for dark matter-nucleon interactions via Migdal effect with DarkSide-50

Dark matter elastic scattering off nuclei can result in the excitation and ionization of the recoiling atom through the so-called Migdal effect. The energy deposition from the ionization electron adds to the energy deposited by the recoiling nuclear system and allows for the detection of interactions of sub-GeV/c$^2$ mass dark matter. We present new constraints for sub-GeV/c$^2$ dark matter using the dual-phase liquid argon time projection chamber of the DarkSide-50 experiment with an exposure of (12306 $\pm$ 184) kg d. The analysis is based on the ionization signal alone and significantly enhances the sensitivity of DarkSide-50, enabling sensitivity to dark matter with masses down to 40 MeV/c$^2$. Furthermore, it sets the most stringent upper limit on the spin independent dark matter nucleon cross section for masses below $3.6$ GeV/c$^2$.Comment: 7 pages, 3 figure

Search for dark matter particle interactions with electron final states with DarkSide-50

We present a search for dark matter particles with sub-GeV/$c^2$ masses whose interactions have final state electrons using the DarkSide-50 experiment's (12306 $\pm$ 184) kg d low-radioactivity liquid argon exposure. By analyzing the ionization signals, we exclude new parameter space for the dark matter-electron cross section $\bar{\sigma}_e$, the axioelectric coupling constant $g_{Ae}$, and the dark photon kinetic mixing parameter $\kappa$. We also set the first dark matter direct-detection constraints on the mixing angle $\left|U_{e4}\right|^2$ for keV sterile neutrinos.Comment: 6 pages, 2 figure