72 research outputs found

    Neue Parameter für die Wirkstofftestung gegen Trypanosoma cruzi

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    Chagas disease is a zoonosis caused by Trypanosoma cruzi and transmitted by triatomine bugs. Autochthonous to Latin America, Chagas disease has spread globally through travel and migration. New drugs are needed urgently, in particular drugs that cure the chronic stage. This is where high-content imaging makes a key contribution: assays with fluorescent parasites in cell culture allow to determine pharmacodynamic parameters and to better assess the antichagasic potential of new molecules

    Direct and indirect effects of the COVID-19 pandemic on mortality in Switzerland

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    The direct and indirect impact of the COVID-19 pandemic on population-level mortality is of concern to public health but challenging to quantify. Using data for 2011–2019, we applied Bayesian models to predict the expected number of deaths in Switzerland and compared them with laboratory-confirmed COVID-19 deaths from February 2020 to April 2022 (study period). We estimated that COVID-19-related mortality was underestimated by a factor of 0.72 (95% credible interval [CrI]: 0.46–0.78). After accounting for COVID-19 deaths, the observed mortality was −4% (95% CrI: −8 to 0) lower than expected. The deficit in mortality was concentrated in age groups 40–59 (−12%, 95%CrI: −19 to −5) and 60–69 (−8%, 95%CrI: −15 to −2). Although COVID-19 control measures may have negative effects, after subtracting COVID-19 deaths, there were fewer deaths in Switzerland during the pandemic than expected, suggesting that any negative effects of control measures were offset by the positive effects. These results have important implications for the ongoing debate about the appropriateness of COVID-19 control measures

    Polarons as Nucleation Droplets in Non-Degenerate Polymers

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    We present a study of the nucleation mechanism that allows the decay of the metastable phase (trans-cisoid) to the stable phase (cis-transoid) in quasi one-dimensional non-degenerate polymers within the continuum electron-phonon model. The electron-phonon configurations that lead to the decay, i.e. the critical droplets (or transition state), are identified as polarons of the metastable phase. We obtain an estimate for the decay rate via thermal activation within a range of parameters consistent with experimental values for the gap of the cis-configuration. It is pointed out that, upon doping, the activation barriers of the excited states are quite smaller and the decay rate is greatly enhanced. Typical activation energies for electron or hole polarons are ≈0.1\approx 0.1 eV and the typical size for a critical droplet (polaron) is about 20A˚20 \AA. Decay via quantum nucleation is also studied and it is found that the crossover temperature between quantum nucleation and thermal activation is of order Tc≤40oKT_c \leq 40 ^oK. Metastable configurations of non-degenerate polymers may provide examples for mesoscopic quantum tunneling.Comment: REVTEX 3.0, 28 PAGES, 3 FIGURES AVAILABLE UPON REQUEST, PITT 94-0

    Combination with tomatidine improves the potency of posaconazole against Trypanosoma cruzi

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    Azoles such as posaconazole (Posa) are highly potent against Trypanosoma cruzi. However, when tested in chronic Chagas disease patients, a high rate of relapse after Posa treatment was observed. It appears that inhibition of T. cruzi cytochrome CYP51, the target of azoles, does not deliver sterile cure in monotherapy. Looking for suitable combination partners of azoles, we have selected a set of inhibitors of sterol and sphingolipid biosynthetic enzymes. A small-scale phenotypic screening was conducted in vitro against the proliferative forms of T. cruzi, extracellular epimastigotes and intracellular amastigotes. Against the intracellular, clinically relevant forms, four out of 15 tested compounds presented higher or equal activity as benznidazole (Bz), with EC50 values </=2.2 muM. Ro48-8071, an inhibitor of lanosterol synthase (ERG7), and the steroidal alkaloid tomatidine (TH), an inhibitor of C-24 sterol methyltransferase (ERG6), exhibited the highest potency and selectivity indices (SI = 12 and 115, respectively). Both were directed to combinatory assays using fixed-ratio protocols with Posa, Bz, and fexinidazole. The combination of TH with Posa displayed a synergistic profile against amastigotes, with a mean SigmaFICI value of 0.2. In vivo assays using an acute mouse model of T. cruzi infection demonstrated lack of antiparasitic activity of TH alone in doses ranging from 0.5 to 5 mg/kg. As observed in vitro, the best combo proportion in vivo was the ratio 3 TH:1 Posa. The combination of Posa at 1.25 mpk plus TH at 3.75 mpk displayed suppression of peak parasitemia of 80% and a survival rate of 60% in the acute infection model, as compared to 20% survival for Posa at 1.25 mpk alone and 40% for Posa at 10 mpk alone. These initial results indicate a potential for the combination of posaconazole with tomatidine against T. cruzi

    Photoinduced absorption and photoluminescence in poly(2,5-dimethoxy-p- phenylene vinylene)

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    We report a study of the photoexcited states in the conjugated polymer poly(2,5-dimethoxy-p-phenylene vinylene). Photoluminescence due to radiative recombination of singlet excitons is observed at energiesjust below the onset of the pi-pi* absorption band at 2.1 eV. Photoinduced absorption at 80 K shows bands peaking at 0.68, 1.35, and 1.80 eV. The features at 0.68 and 1.8 eV are associated with the same excited state which we propose is a doubly charged bipolaron, while the third at 1.35 eV is unrelated. We assign this 1.35-eV absorption to a triplet-triplet transition of a triplet exciton. The bipolarons are long lived with significant numbers surviving in excess of 100 ms at 80 K, and have a weak temperature dependence such that photoinduced absorption is readily detectable even at room temperature. The triplet exciton has a lifetime of order 2.5 ms at 80 K but this falls rapidly at higher temperature and the response is not detected at room temperature. We contrast these results with those obtained previously for the related poly(arylene vinylene) polymers poly(p-phenylene vinylene), and poly(2,5-thienylene vinylene) and for other conjugated polymers, and draw attention to the important role played in the photophysics of these materials by neutral excited states

    Determination Method for Ractopamine in Swine and Cattle Tissues Using LC/MS

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    Assembly of 2D ionic layers by reaction of alkali halides with the organic electrophile 7,7,8,8-tetracyano-p-quinodimethane (TCNQ)

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    Sublimation of alkali halides (NaCl and LiCl) onto a pre-assembled hydrogen-bonded layer of TCNQ on Au(111) resulted in the formation of 2D ionic layers via a direct charge-transfer reaction without involvement of the substrate. The presented approach allows for the fabrication of different ionic layers, decoupled from the substrate and offering new, potentially interesting properties
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