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排序方式: 共有9430条查询结果,搜索用时 15 毫秒
61.
Dr. Armin Welker Dr. Christian Kersten Dr. Christin Müller Dr. Ramakanth Madhugiri Collin Zimmer Patrick Müller Robert Zimmermann Stefan Hammerschmidt Hannah Maus Prof. John Ziebuhr Prof. Christoph Sotriffer Prof. Tanja Schirmeister 《ChemMedChem》2021,16(2):340-354
Inhibition of coronavirus (CoV)-encoded papain-like cysteine proteases (PLpro) represents an attractive strategy to treat infections by these important human pathogens. Herein we report on structure-activity relationships (SAR) of the noncovalent active-site directed inhibitor (R)-5-amino-2-methyl-N-(1-(naphthalen-1-yl)ethyl) benzamide ( 2 b ), which is known to bind into the S3 and S4 pockets of the SARS-CoV PLpro. Moreover, we report the discovery of isoindolines as a new class of potent PLpro inhibitors. The studies also provide a deeper understanding of the binding modes of this inhibitor class. Importantly, the inhibitors were also confirmed to inhibit SARS-CoV-2 replication in cell culture suggesting that, due to the high structural similarities of the target proteases, inhibitors identified against SARS-CoV PLpro are valuable starting points for the development of new pan-coronaviral inhibitors. 相似文献
62.
Silvia Saturio Alicja M. Nogacka Marta Surez Nuria Fernndez Laura Mantecn Leonardo Mancabelli Christian Milani Marco Ventura Clara G. de los Reyes-Gaviln Gonzalo Solís Silvia Arboleya Miguel Gueimonde 《International journal of molecular sciences》2021,22(7)
The establishment of the gut microbiota poses implications for short and long-term health. Bifidobacterium is an important taxon in early life, being one of the most abundant genera in the infant intestinal microbiota and carrying out key functions for maintaining host-homeostasis. Recent metagenomic studies have shown that different factors, such as gestational age, delivery mode, or feeding habits, affect the gut microbiota establishment at high phylogenetic levels. However, their impact on the specific bifidobacterial populations is not yet well understood. Here we studied the impact of these factors on the different Bifidobacterium species and subspecies at both the quantitative and qualitative levels. Fecal samples were taken from 85 neonates at 2, 10, 30, 90 days of life, and the relative proportions of the different bifidobacterial populations were assessed by 16S rRNA–23S rRNA internal transcribed spacer (ITS) region sequencing. Absolute levels of the main species were determined by q-PCR. Our results showed that the bifidobacterial population establishment is affected by gestational age, delivery mode, and infant feeding, as it is evidenced by qualitative and quantitative changes. These data underline the need for understanding the impact of perinatal factors on the gut microbiota also at low taxonomic levels, especially in the case of relevant microbial populations such as Bifidobacterium. The data obtained provide indications for the selection of the species best suited for the development of bifidobacteria-based products for different groups of neonates and will help to develop rational strategies for favoring a healthy early microbiota development when this process is challenged. 相似文献
63.
Clarisse Roblin Steve Chiumento Cdric Jacqueline Eric Pinloche Cendrine Nicoletti Hamza Olleik Elise Courvoisier-Dezord Agns Amouric Christian Basset Louis Dru Marie Ollivier Aurlie Bogey-Lambert Nicolas Vidal Mohamed Atta Marc Maresca Estelle Devillard Victor Duarte Josette Perrier Mickael Lafond 《International journal of molecular sciences》2021,22(6)
The world is on the verge of a major antibiotic crisis as the emergence of resistant bacteria is increasing, and very few novel molecules have been discovered since the 1960s. In this context, scientists have been exploring alternatives to conventional antibiotics, such as ribosomally synthesized and post-translationally modified peptides (RiPPs). Interestingly, the highly potent in vitro antibacterial activity and safety of ruminococcin C1, a recently discovered RiPP belonging to the sactipeptide subclass, has been demonstrated. The present results show that ruminococcin C1 is efficient at curing infection and at protecting challenged mice from Clostridium perfringens with a lower dose than the conventional antibiotic vancomycin. Moreover, antimicrobial peptide (AMP) is also effective against this pathogen in the complex microbial community of the gut environment, with a selective impact on a few bacterial genera, while maintaining a global homeostasis of the microbiome. In addition, ruminococcin C1 exhibits other biological activities that could be beneficial for human health, as well as other fields of applications. Overall, this study, by using an in vivo infection approach, confirms the antimicrobial clinical potential and highlights the multiple functional properties of ruminococcin C1, thus extending its therapeutic interest. 相似文献
64.
Oliver Schmutzler Sebastian Graf Nils Behm Wael Y. Mansour Florian Blumendorf Theresa Staufer Christian Krnig Dina Salah Yanan Kang Jan N. Peters Yang Liu Neus Feliu Wolfgang J. Parak Anja Burkhardt Elisabetta Gargioni Sabrina Gennis Sharah Chandralingam Finn Heg Wolfgang Maison Kai Rothkamm Florian Schulz Florian Grüner 《International journal of molecular sciences》2021,22(7)
Quantitative cellular in vitro nanoparticle uptake measurements are possible with a large number of different techniques, however, all have their respective restrictions. Here, we demonstrate the application of synchrotron-based X-ray fluorescence imaging (XFI) on prostate tumor cells, which have internalized differently functionalized gold nanoparticles. Total nanoparticle uptake on the order of a few hundred picograms could be conveniently observed with microsamples consisting of only a few hundreds of cells. A comparison with mass spectroscopy quantification is provided, experimental results are both supported and sensitivity limits of this XFI approach extrapolated by Monte-Carlo simulations, yielding a minimum detectable nanoparticle mass of just 5 pg. This study demonstrates the high sensitivity level of XFI, allowing non-destructive uptake measurements with very small microsamples within just seconds of irradiation time. 相似文献
65.
New high-temperature copper alloys 总被引:3,自引:0,他引:3
S Constantinescu A Popa J. R. Groza I Bock 《Journal of Materials Engineering and Performance》1996,5(6):695-698
New high-strength, high-temperature Cu-Ni-Si alloys have been developed using additions of Cr, Zr, and/or Ti. These new alloys
remain as precipitation hardenable as the base alloy, but the main strengthening phase may be different than Ni2Si (e.g., Cr2Ti). Substantial increases in mechanical strength were observed at both room and high temperature (773 K) when additions of
Cr+Zr+Ti and Cr+Zr were made. Industrial testing of these alloys indicated a sevenfold increase in the lifetime of lateral
blocks in continuous casting equipment of copper alloys. 相似文献
66.
Carbon Aerogels as Electrode Material in Supercapacitors 总被引:5,自引:0,他引:5
U. Fischer R. Saliger V. Bock R. Petricevic J. Fricke 《Journal of Porous Materials》1997,4(4):281-285
Due to their large specific surface area and their high electrical conductivity carbon aerogels are promising materials for electrodes in electrochemical double-layer capacitors (supercapacitor). The carbon aerogels were made via pyrolysis of resorcinol formaldehyde aerogels. The latter were prepared by supercritical and subcritical drying as well. The important findings of our investigation were, that the highest capacities of 46 F/cm3 were measured for samples with a density of about 800 kg/m3 pyrolyzed at 800°C. Also it was shown that RF-gels with molar resorcinol/catalyst ratios 1000 or higher can be dried subcritically without cracking or significant shrinkage. Carbon aerogels derived from these RF-aerogels have a small mesopore surface area, however an especially large micropore area. They provide electrical capacities which are most suitable for their use in supercapacitors. 相似文献
67.
68.
Computational Problem Solving in Spatial Substrates -- A Cognitive Systems Engineering Approach
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Christian Freksa 《International Journal of Software and Informatics》2015,9(2):279-288
The ability to perform spatial tasks is crucial for everyday life and of great importance to cognitive agents such as humans, animals, and autonomous robots. A common artificial intelligence approach to accomplish spatial tasks is to represent spatial configurations and tasks in form of detailed knowledge about various aspects of space and
time. Suitable algorithms then use the representations to compute solutions to spatial problems. In comparison, natural embodied and situated agents often solve spatial tasks without detailed knowledge about geometric, topological, or mechanical laws; they directly relate actions to effects that are due to spatio-temporal affordances in their bodies and environments. Accordingly, we propose a paradigm that makes the spatio-temporal
substrate an integral part of the engine that drives spatial problem solving. We argue that spatial and temporal structures in body and environment can substantially support (and even replace) reasoning effort in computational processes: physical manipulation and perception in spatial environments substitute formal computation. While the approach is well known – for example, we employ diagrams as spatial substrate for geometric problem solving and maps for wayfinding – the underlying principle has not been systematically investigated or formally analyzed as a paradigm of cognitive processing. Topology, distance, and orientation constraints are all integrated and interdependent in truly 2- or 3-dimensional space. Exploiting this fact may not only help overcome the need for acquiring detailed knowledge about the interrelationships between different aspects of space; it also can point to a way of avoiding exploding computational complexity that occurs when we deal with these aspects of space in complex real-world scenarios. Our approach employs affordance-based object-level problem solving to complement knowledge-level formal approaches. We will assess strengths and weaknesses of the new cognitive systems paradigm. 相似文献
69.
We investigate a metric facility location problem in a distributed setting. In this problem, we assume that each point is a client as well as a potential location for a facility and that the opening costs for the facilities and the demands of the clients are uniform. The goal is to open a subset of the input points as facilities such that the accumulated cost for the whole point set, consisting of the opening costs for the facilities and the connection costs for the clients, is minimized. We present a randomized distributed algorithm that computes in expectation an ${\mathcal {O}}(1)$ -approximate solution to the metric facility location problem described above. Our algorithm works in a synchronous message passing model, where each point is an autonomous computational entity that has its own local memory and that communicates with the other entities by message passing. We assume that each entity knows the distance to all the other entities, but does not know any of the other pairwise distances. Our algorithm uses three rounds of all-to-all communication with message sizes bounded to $\mathcal{O}(\log(n))$ bits, where n is the number of input points. We extend our distributed algorithm to constant powers of metric spaces. For a metric exponent ?≥1, we obtain a randomized ${\mathcal {O}}(1)$ -approximation algorithm that uses three rounds of all-to-all communication with message sizes bounded to $\mathcal{O}(\log(n))$ bits. 相似文献
70.
Guyu Zhang Christian A. Duncan Jinko Kanno Rastko R. Selmic 《Journal of Intelligent and Robotic Systems》2014,74(3-4):869-891
We present a set of algorithms for the navigation of Unmanned Ground Vehicles (UGVs) towards a set of pre-identified target nodes in coordinate-free and localization-free wireless sensor and actuator networks. The UGVs are equipped with a set of wireless listeners that provide sensing information about the potential field generated by the network of actuators. Two main navigation scenarios are considered: single-UGV, single-destination navigation and multi-UGV, multi-destination navigation. For the single-UGV, single-destination case, we present both centralized and distributed navigation algorithms. Both algorithms share a similar two-phase concept. In the first phase, the system assigns level numbers to individual nodes based on their hop distance from the target nodes. In the second phase, the UGV uses the potential field created by the network of actuators to move towards the target nodes, requiring cooperation between triplets of actuator nodes and the UGV. The hop distance to the target nodes is used to control the main moving direction while the potential field, which can be measured by listeners on the UGV, is used to determine the UGV’s movement. For the multi-UGV, multi-destination case, we present a decentralized allocation algorithm such that multiple UGVs avoid converging to the same destination. After each UGV determines its destination, the proposed navigation scheme is applied. The presented algorithms do not attempt to localize UGVs or sensor nodes and are therefore suitable for operating in GPS-free/denied environments. We also present a study of the communication complexity of the algorithms as well as simulation examples that verify the proposed algorithms and compare their performances. 相似文献