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排序方式: 共有1318条查询结果,搜索用时 15 毫秒
71.
Structure–Activity Relationships of 2‐Sufonylpyrimidines as Quorum‐Sensing Inhibitors to Tackle Biofilm Formation and eDNA Release of Pseudomonas aeruginosa 下载免费PDF全文
Andreas Thomann Christian Brengel Dr. Carsten Börger Dr. Dagmar Kail Dr. Anke Steinbach Dr. Martin Empting Prof. Dr. Rolf W. Hartmann 《ChemMedChem》2016,11(22):2522-2533
Drug‐resistant Pseudomonas aeruginosa (PA) strains are on the rise, making treatment with current antibiotics ineffective. Hence, circumventing resistance or restoring the activity of antibiotics by novel approaches is of high demand. Targeting the Pseudomonas quinolone signal quorum sensing (PQS‐QS) system is an intriguing strategy to abolish PA pathogenicity without affecting the viability of the pathogen. Herein we report the structure–activity relationships of 2‐sulfonylpyrimidines, which were previously identified as dual‐target inhibitors of the PQS receptor PqsR and the PQS synthase PqsD. The SAR elucidation was guided by a combined approach using ligand efficiency and ligand lipophilicity efficiency to select the most promising compounds. In addition, the most effective inhibitors were rationally modified by the guidance of QSAR using Hansch analyses. Finally, these inhibitors showed the capacity to decrease biofilm mass and extracellular DNA, which are important determinants for antibiotic resistance. 相似文献
72.
Non-heme Fe(IV)-oxo intermediates 总被引:1,自引:0,他引:1
High-valent non-heme iron-oxo intermediates have been proposed for decades as the key intermediates in numerous biological oxidation reactions. In the past three years, the first direct characterization of such intermediates has been provided by studies of several alphaKG-dependent oxygenases that catalyze either hydroxylation or halogenation of their substrates. In each case, the Fe(IV)-oxo intermediate is implicated in cleavage of the aliphatic C-H bond to initiate hydroxylation or halogenation. The observation of non-heme Fe(IV)-oxo intermediates and Fe(II)-containing product(s) complexes with almost identical spectroscopic parameters in the reactions of two distantly related alphaKG-dependent hydroxylases suggests that members of this subfamily follow a conserved mechanism for substrate hydroxylation. In contrast, for the alphaKG-dependent non-heme iron halogenase, CytC3, two distinct Fe(IV) complexes form and decay together, suggesting that they are in rapid equilibrium. The existence of two distinct conformers of the Fe site may be the key factor accounting for the divergence of the halogenase reaction from the more usual hydroxylation pathway after C-H bond cleavage. Distinct transformations catalyzed by other mononuclear non-heme enzymes are likely also to involve initial C-H bond cleavage by Fe(IV)-oxo complexes, followed by diverging reactivities of the resulting Fe(III)-hydroxo/substrate radical intermediates. 相似文献
73.
Mark-Alexander Schwarzbich Hao Dai Lambros Kordelas Dietrich W. Beelen Aleksandar Radujkovic Carsten Müller-Tidow Peter Dreger Thomas Luft 《International journal of molecular sciences》2022,23(4)
Weight loss and metabolic activity influence outcome after allogeneic stem cell transplantation (alloSCT). This study evaluates pre-conditioning Leptin, a peptide hormone involved in metabolism and immune homeostasis, as a prognostic factor for survival, relapse and non-relapse mortality (NRM) following alloSCT. Leptin serum levels prior to conditioning were determined in a cohort of patients transplanted for various hematologic malignancies (n = 524) and correlated retrospectively with clinical outcome. Findings related to patients with acute leukemia (AL) from this sample were validated in an independent cohort. Low pre-conditioning serum Leptin was an independent prognostic marker for increased risk of relapse (but not of NRM and overall mortality) following alloSCT for AL of intermediate and advanced stage (beyond first complete remission). Multivariate analysis revealed a hazard ratio (HR) for relapse of 0.75 per log2 increase (0.59–0.96, p = 0.020). This effect was similar in an independent validation cohort. Pre-conditioning serum Leptin was validated as a prognostic marker for early relapse by fitting the multivariate Cox model to the validation data. Pre-conditioning serum Leptin levels may serve as an independent prognostic marker for relapse following alloSCT in intermediate and advanced stage AL patients. Prospective studies are required to prove whether serum Leptin could be used for guiding nutritional intervention in patients with AL undergoing alloSCT. 相似文献
74.
Stefan Weinschenk Carsten Weiss Justus Benrath Volker von Baehr Thomas Strowitzki Manuel Feißt 《International journal of molecular sciences》2022,23(6)
Background. Local anesthetics (LAs) have potent anti-inflammatory properties. Inflammatory down-regulation is crucial in diseases with overactive immune reactions, such as acute respiratory distress syndrome (ARDS) and chronic inflammation. We investigated the influence of four LAs, procaine, lidocaine, mepivacaine, and bupivacaine, on the reduction of tumor necrosis factor-alpha (TNF-α) secretion in lipopolysaccharide (LPS)-activated human leucocytes. Methods. Blood samples of 28 individuals were stimulated with LPS. The reduction of TNF-α production by each of the four LAs added (0.5 mg/mL) was measured and correlated with biometric variables. A response was defined as reduction to <85% of initial levels. Results. All four LAs down-regulated the TNF-α secretion in 44–61%: Bupivacaine (44.4%), lidocaine (61.5%), mepivacaine (44.4%), and procaine (50% of the individuals, “responders”). The TNF-α secretion was reduced to 67.4, 68.0, 63.6, and 67.1% of the initial values in responders. The effects in both patients and healthy persons were the same. Interindividual responses to LAs were not correlated with the duration or type of complaints, basal TNF-α serum level, sex, BMI, or age of responders. Conclusions. Four clinically relevant LAs (amid-LA and ester-LA) attenuate the inflammatory response provoked by LPS. They are potential candidates for drug repositioning in treating overactive immune reactions and chronic inflammation. 相似文献
75.
Energy efficiency in vacuum technology Vacuum is used to produce a huge variety of products of our everyday life. To provide the vacuum environment, a lot of energy is usually used and therefore the vacuum pumps should run as efficient as possible. Actually, many various improvements can be made to gain energy savings on vacuum pumps. With those considered in this paper it's possible to save 928 GWh/a of energy in the EU and thereof 629 GWh/a or 64 % are economically realizable. Only specific improvements concerning the vacuum system are taken into account, basic technology options, like motors, controls, etc., are excluded. To show and discuss the results a conserved energy supply curve is used. 相似文献
76.
77.
This paper shows the application of neural networks in a multiscale analysis of a reinforced concrete beam. A mesoscale model is presented, which simulates the pullout test of a reinforcement bar in concrete. By applying a homogenization procedure, a macroscopic stress vs. crack opening response is obtained from the mesoscale simulations. The neural network is used to approximate this relation in a macroscale simulation and replaces the material formulation of the interface layer between concrete and reinforcement, thus avoiding the computationally expensive parallel simulation on different scales. 相似文献
78.
79.
Kiesel Andrea; Kunde Wilfried; Pohl Carsten; Berner Michael P.; Hoffmann Joachim 《Canadian Metallurgical Quarterly》2009,35(1):292
Expertise in a certain stimulus domain enhances perceptual capabilities. In the present article, the authors investigate whether expertise improves perceptual processing to an extent that allows complex visual stimuli to bias behavior unconsciously. Expert chess players judged whether a target chess configuration entailed a checking configuration. These displays were preceded by masked prime configurations that either represented a checking or a nonchecking configuration. Chess experts, but not novice chess players, revealed a subliminal response priming effect, that is, faster responding when prime and target displays were congruent (both checking or both nonchecking) rather than incongruent. Priming generalized to displays that were not used as targets, ruling out simple repetition priming effects. Thus, chess experts were able to judge unconsciously presented chess configurations as checking or nonchecking. A 2nd experiment demonstrated that experts' priming does not occur for simpler but uncommon chess configurations. The authors conclude that long-term practice prompts the acquisition of visual memories of chess configurations with integrated form-location conjunctions. These perceptual chunks enable complex visual processing outside of conscious awareness. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献
80.
This paper deals with terrestrial worm-like locomotion systems living in a straight line. They are modeled as chains of mass points having ground interaction via spikes which make the velocities unidirectional. A method is presented to construct gaits with any desired time pattern of resting mass points (which are acted on by the propulsive forces). Taking the dynamics into consideration, conclusions about the choice and shift of gaits in connection with actuator data are given. 相似文献