321 research outputs found

    Real presence under digital conditions?

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    During the Covid-19 pandemic, Christians were prevented from receiving the Eucharist for the first time in history due to the suspension of public church services. Various digital liturgical offers such as live-stream services were developed and improved to compensate for this loss. Discussing the pastoral chances and theological limits of digitalization in religious contexts, the authors conclude that physical participation in the Eucharistic liturgy cannot be substituted by virtual offers. Regarding the often-distorted perception of time during the pandemic, they highlight the therapeutic dimension of the Eucharist, in which the past, present, and future are interwoven (signum rememorativum, signum demonstrativum, and signum prognosticum). To realize the gift of the Eucharist and to gain a new awareness of the salutary and transforming presence of Christ, the authors point to the practice of Eucharistic adoration, which nevertheless remains oriented towards the communal celebration of the Eucharist and the real encounter with Christ in Communion

    Glutathione reductase-catalyzed cascade of redox reactions to bioactivate potent antimalarial 1,4-naphthoquinones--a new strategy to combat malarial parasites.

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    Our work on targeting redox equilibria of malarial parasites propagating in red blood cells has led to the selection of six 1,4-naphthoquinones, which are active at nanomolar concentrations against the human pathogen Plasmodium falciparum in culture and against Plasmodium berghei in infected mice. With respect to safety, the compounds do not trigger hemolysis or other signs of toxicity in mice. Concerning the antimalarial mode of action, we propose that the lead benzyl naphthoquinones are initially oxidized at the benzylic chain to benzoyl naphthoquinones in a heme-catalyzed reaction within the digestive acidic vesicles of the parasite. The major putative benzoyl metabolites were then found to function as redox cyclers: (i) in their oxidized form, the benzoyl metabolites are reduced by NADPH in glutathione reductase-catalyzed reactions within the cytosols of infected red blood cells; (ii) in their reduced forms, these benzoyl metabolites can convert methemoglobin, the major nutrient of the parasite, to indigestible hemoglobin. Studies on a fluorinated suicide-substrate indicate as well that the glutathione reductase-catalyzed bioactivation of naphthoquinones is essential for the observed antimalarial activity. In conclusion, the antimalarial naphthoquinones are suggested to perturb the major redox equilibria of the targeted infected red blood cells, which might be removed by macrophages. This results in development arrest and death of the malaria parasite at the trophozoite stage

    A RISC-V MCU with adaptive reverse body bias and ultra-low-power retention mode in 22 nm FD-SOI

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    We present a low-power, energy efficient 32-bit RISC-V microprocessor unit (MCU) in 22 nm FD-SOI. It achieves ultra-low leakage,even at high temperatures, by using an adaptive reverse body biasing aware sign-off approach, a low-power optimized physical implementation, and custom SRAM macros with retention mode. We demonstrate the robustness of the chip with measurements over the full industrial temperature range, from -40 {\deg}C to 125 {\deg}C. Our results match the state of the art (SOTA) with 4.8 uW / MHz at 50 MHz in active mode and surpass the SOTA in ultra-low-power retention mode.Comment: accepted at ISOCC 202

    Thiosemicarbazones of 2-acetylpyridine, 2-acetylquinoline, 1-acetylisoquinoline, and related compounds as inhibitors of herpes simplex virus in vitro and in a cutaneous herpes guinea pig model

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    A series of 111 thiosemicarbazones of 2-acetylpyridine, 2-acetylquinoline, 1-acetylisoquinoline, and related compounds were evaluated as inhibitors of herpes simplex virus in vitro and in a cutaneous herpes guinea pig model. All derivatives tested were potent inhibitors of virus replication with mean 50% inhibitory concentrations of 1.1 [mu]g/ml for both type 1 and 2 herpes simplex virus. Inhibitory concentrations for cellular protein and DNA synthesis were considerably higher for many compounds resulting in in vitro therapeutic indices ranging from >100 (highly selective) to All compounds were tested for dermal toxicity following topical administration of saturated solutions in 1,3-butanediol to the shaved, depilated skin of guinea pigs. Approximately 50% of the compounds produced slight to no dermal toxicity whereas the remaining compounds produced moderate to severe dermal toxicity.28 compounds were evaluated in the cutaneous herpes guinea pig model against herpes simplex virus type 1. A number of N4-monosubstituted 2-acetylpyridine thiosemicarbazones produced highly significant reductions in days to healing and lesion score without producing untoward dermal toxicity.Structure-activity relationships revealed that a reduction of the azomethine bond in the molecule (i.e., conversion of a thiosemicarbazone to a thiosemicarbazide) greatly diminished dermal toxicity apparently without producing a proportional decrease in antiviral activity.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26115/1/0000191.pd

    A 16-Channel Fully Configurable Neural SoC With 1.52 μW/Ch Signal Acquisition, 2.79 μW/Ch Real-Time Spike Classifier, and 1.79 TOPS/W Deep Neural Network Accelerator in 22 nm FDSOI

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    With the advent of high-density micro-electrodes arrays, developing neural probes satisfying the real-time and stringent power-efficiency requirements becomes more challenging. A smart neural probe is an essential device in future neuroscientific research and medical applications. To realize such devices, we present a 22 nm FDSOI SoC with complex on-chip real-time data processing and training for neural signal analysis. It consists of a digitally-assisted 16-channel analog front-end with 1.52 μ W/Ch, dedicated bio-processing accelerators for spike detection and classification with 2.79 μ W/Ch, and a 125 MHz RISC-V CPU, utilizing adaptive body biasing at 0.5 V with a supporting 1.79 TOPS/W MAC array. The proposed SoC shows a proof-of-concept of how to realize a high-level integration of various on-chip accelerators to satisfy the neural probe requirements for modern applications

    Gene identification and analysis of transcripts differentially regulated in fracture healing by EST sequencing in the domestic sheep

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    BACKGROUND: The sheep is an important model animal for testing novel fracture treatments and other medical applications. Despite these medical uses and the well known economic and cultural importance of the sheep, relatively little research has been performed into sheep genetics, and DNA sequences are available for only a small number of sheep genes. RESULTS: In this work we have sequenced over 47 thousand expressed sequence tags (ESTs) from libraries developed from healing bone in a sheep model of fracture healing. These ESTs were clustered with the previously available 10 thousand sheep ESTs to a total of 19087 contigs with an average length of 603 nucleotides. We used the newly identified sequences to develop RT-PCR assays for 78 sheep genes and measured differential expression during the course of fracture healing between days 7 and 42 postfracture. All genes showed significant shifts at one or more time points. 23 of the genes were differentially expressed between postfracture days 7 and 10, which could reflect an important role for these genes for the initiation of osteogenesis. CONCLUSION: The sequences we have identified in this work are a valuable resource for future studies on musculoskeletal healing and regeneration using sheep and represent an important head-start for genomic sequencing projects for Ovis aries, with partial or complete sequences being made available for over 5,800 previously unsequenced sheep genes

    Characterization of bacterial operons consisting of two tubulins and a kinesin-like gene by the novel Two-Step Gene Walking method

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    Tubulins are still considered as typical proteins of Eukaryotes. However, more recently they have been found in the unusual bacteria Prosthecobacter (btubAB). In this study, the genomic organization of the btub-genes and their genomic environment were characterized by using the newly developed Two-Step Gene Walking method. In all investigated Prosthecobacters, btubAB are organized in a typical bacterial operon. Strikingly, all btub-operons comprise a third gene with similarities to kinesin light chain sequences. The genomic environments of the characterized btub-operons are always different. This supports the hypothesis that this group of genes represents an independent functional unit, which was acquired by Prosthecobacter via horizontal gene transfer. The newly developed Two-Step Gene Walking method is based on randomly primed polymerase chain reaction (PCR). It presents a simple workflow, which comprises only two major steps—a Walking-PCR with a single specific outward pointing primer (step 1) and the direct sequencing of its product using a nested specific primer (step 2). Two-Step Gene Walking proved to be highly efficient and was successfully used to characterize over 20 kb of sequence not only in pure culture but even in complex non-pure culture samples

    Measurement of nuclear modification factors of gamma(1S)), gamma(2S), and gamma(3S) mesons in PbPb collisions at root s(NN)=5.02 TeV

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    The cross sections for ϒ(1S), ϒ(2S), and ϒ(3S) production in lead-lead (PbPb) and proton-proton (pp) collisions at √sNN = 5.02 TeV have been measured using the CMS detector at the LHC. The nuclear modification factors, RAA, derived from the PbPb-to-pp ratio of yields for each state, are studied as functions of meson rapidity and transverse momentum, as well as PbPb collision centrality. The yields of all three states are found to be significantly suppressed, and compatible with a sequential ordering of the suppression, RAA(ϒ(1S)) > RAA(ϒ(2S)) > RAA(ϒ(3S)). The suppression of ϒ(1S) is larger than that seen at √sNN = 2.76 TeV, although the two are compatible within uncertainties. The upper limit on the RAA of ϒ(3S) integrated over pT, rapidity and centrality is 0.096 at 95% confidence level, which is the strongest suppression observed for a quarkonium state in heavy ion collisions to date. © 2019 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Funded by SCOAP3.Peer reviewe
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