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1.
Freddy A. Bernal Dr. Marcel Kaiser Prof. Dr. Bernhard Wünsch Prof. Dr. Thomas J. Schmidt 《ChemMedChem》2020,15(1):68-78
Protozoal infections are still a global health problem, threatening the lives of millions of people around the world, mainly in impoverished tropical and sub-tropical regions. Thus, in view of the lack of efficient therapies and increasing resistances against existing drugs, this study describes the antiprotozoal potential of synthetic cinnamate ester analogues and their structure-activity relationships. In general, Leishmania donovani and Trypanosoma brucei were quite susceptible to the compounds in a structure-dependent manner. Detailed analysis revealed a key role of the substitution pattern on the aromatic ring and a marked effect of the side chain on the activity against these two parasites. The high antileishmanial potency and remarkable selectivity of the nitro-aromatic derivatives suggested them as promising candidates for further studies. On the other hand, the high in vitro potency of catechol-type compounds against T. brucei could not be extrapolated to an in vivo mouse model. 相似文献
2.
AG Niessen JG Bollemeijer RJ de Keizer PH de Meijer 《Canadian Metallurgical Quarterly》1994,138(15):770-775
OBJECTIVE: To assess how often the aetiology is established in patients with uveitis, what systemic disease are found and what is the contribution of the internist to the diagnostic process. DESIGN: Retrospective study. SETTING: University Hospital Leiden, the Netherlands. METHOD: From January 1987 to April 1992, 342 patients presented with uveitis. All patients underwent a standard ophthalmological examination. Referral to an internist and individualised laboratory screening followed in patients with recurrent, chronic, bilateral or panuveitis. Recorded were: ophthalmological data, results of laboratory screening, results of analysis by the internist, final diagnosis and presence of systemic disease. RESULTS: 149 (44%) patients were examined by the internist, 18 (5.2%) were seen by another specialist. In 169 (49%) patients a specific diagnosis was made. 74 (22%) had a systemic disease, 74 a primary ocular disease. In 28 (8%) a systemic disease was presumed (5% were HLA-B27 positive, 3% had abnormal laboratory results); 5 (1%) patients had endophthalmitis as a complication of a septic process. CONCLUSION: In approximately 1/3 of the patients with uveitis a systemic disease was found. Examination by the internist tailored to the individual patient is essential in the evaluation of uveitis patients. 相似文献
3.
Bernhard Steffen
Jens Knoop
《Theoretical computer science》1991,80(2):303-318Constant propagation, the replacement of program terms which represent a unique value at run time by their values, is a classical program optimization method. In spite of being treated for years, constant propagation still has been in the unsatisfactory phase of heuristics. We enhance the known constant propagation techniques to obtain an algorithm which is optimal for programs without loops. Fundamental is the introduction of a new decidable set of constants, the finite constants. This set has two different characterizations: a denotational one, which directly specifies our iterative algorithm and an operational one, which delivers the completeness or optimality of this algorithm for programs without loops. The algorithm is implemented in a commercial compiler project. 相似文献
4.
Zusammenfassung Komplexit?t, Anforderungsmanagement und Variantenvielfalt sind zentrale Herausforderungen bei der Entwicklung und Evolution
heutiger softwaregesteuerter Systeme. Diesen wird zunehmend durch den Einsatz modellbasierter Entwicklungsmethoden begegnet.
Dadurch wird das Modell zum zentralen Artefakt und die Erstellung und Nutzung von Modellen zu einer zentralen T?tigkeit in
der Softwareentwicklung. Mit der Bedeutung der Modelle steigen auch die Ansprüche an ihre Qualit?t. Dieser Beitrag untersucht
die Implikationen, die daraus entstehen, insbesondere werden sinnvolle Qualit?tsmerkmale für softwarebeschreibende Modelle
identifiziert und diskutiert. 相似文献
5.
Colzato Lorenza S.; Raffone Antonino; Hommel Bernhard 《Canadian Metallurgical Quarterly》2006,32(3):705
Four experiments were conducted to investigate the relationship between the binding of visual features (as measured by their aftereffects on subsequent binding) and the learning of feature-conjunction probabilities. Both binding and learning effects were obtained, but they did not interact. Interestingly, (shape-color) binding effects disappeared with increasing practice, presumably because of the fact that only 1 of the features involved was relevant to the task. However, this instability was only observed for arbitrary, not highly overlearned combinations of simple geometric features and not for real objects (colored pictures of a banana and strawberry), where binding effects were strong and resistant to practice. These findings suggest that learning has no direct impact on the strength or resistance of bindings or on speed with which features are bound; however, learning does affect the amount of attention particular feature dimensions attract, which again can influence which features are considered in binding. (PsycINFO Database Record (c) 2011 APA, all rights reserved) 相似文献
6.
MD Goldberg JR Canvin P Freestone C Andersen D Laoudj PH Williams IB Holland V Norris 《Canadian Metallurgical Quarterly》1997,79(6):315-322
In the bacterium Escherichia coli, H-NS-(H1, H1a) is a heat-stable protein with a molecular mass of 15.5 kDa involved in nucleoid organisation and gene regulation linked to certain signal transduction pathways. We have shown that, following addition of preparations of everted inner membrane vesicles, heat-stable cleavage products of approximately 10 kDa of H-NS are formed in vitro from newly synthesised, radio-labelled H-NS and from purified H-NS. The 15.5 kDa protein and its cleavage products were also recovered from a minicell system. These results raised the possibility that cleavage of H-NS is physiologically significant. However, the cleavage of H-NS observed appears to occur during cell breakage and to depend on the method of protein extraction and the presence of the outer membrane protease, OmpT. Nevertheless, the results indicate that H-NS may contain at least two separate domains with cleavage occurring between these domains at a preferred OmpT site. Failure to take account of H-NS cleavage in sample preparation and analysis can lead to serious underestimation of H-NS levels. 相似文献
7.
Acute and chronic antidepressant drug treatments respectively decrease and increase the aggressive behaviour of resident rats during encounters with unfamiliar conspecifics. We have now examined the effect of the 5-hydroxytryptamine1A receptor antagonist, WAY-100635, on fluoxetine-, paroxetine- or venlafaxine-induced changes in aggression. WAY-100635 (0.1 mg/kg), which did not modify behaviour when given alone, potentiated the venlafaxine (5.54 mg/kg)-induced reduction in aggression after acute treatment and, during chronic treatment, accelerated the fluoxetine (0.34 mg/kg/day)-induced increase in aggression, from day 5 to day 2. A similar change in time course was seen with paroxetine (0.33 mg/kg/day), although the increase in aggression was smaller. Venlafaxine (5.54 mg/kg/day, alone or co-administered with WAY-100635) increased aggression by day 2. During chronic treatment, therefore, venlafaxine, at the dose used, had a more rapid onset of action than either fluoxetine or paroxetine, whereas the fluoxetine- and paroxetine-, but not the venlafaxine-, induced increase in aggression was accelerated by WAY-100635. These studies further support the hypothesis that selective blockade of the 5-hydroxytryptamine1A receptor augments the effects of antidepressant drugs in an animal model predictive of antidepressant activity, presumably by concomitant blockade of the somatodendritic 5-hydroxytryptamine1A autoreceptor-mediated negative feedback system of serotonergic neurones. 相似文献
8.
9.
Wilhelm Conrad Roentgen's discovery of the X-ray one century ago has been ranked in importance with the discovery and development of anesthesia and the discovery of microorganisms and their role in disease. Roentgen's scientific devotion and the persistence of C. Edmund Kells, who took Roentgen's discovery and applied it to dentistry, had a great impact on how dentists practice today. 相似文献
10.
PB Imrey LA Jackson PH Ludwinski AC England GA Fella BC Fox LB Isdale MW Reeves JD Wenger 《Canadian Metallurgical Quarterly》1996,143(6):624-630
Between February 1991 and April 1992, eight undergraduates at a US residential university and one at a nearby 2-year college contracted serogroup C meningococcal disease. A case-control investigation with 20 controls per case, oropharyngeal carriage surveys, and multilocus enzyme electrophoresis (MEE) of serogroup C isolates were used to identify factors contributing to the outbreak. All eight sterile-site isolates from cases were closely related by MEE and were similar (though not identical) to the strain associated with the 1991-1992 epidemic of meningococcal disease in eastern Canada. Disease was associated with cigarette smoking (p = 0.012), recent patronage of campus-area bars (p = 0.034), estimated amount of time spent in campus-area bars (p = 0.0003), and, especially, recent patronage of one specific bar, bar A (p = 0.0006; odds ratio = 23.1, 95% confidence interval 3.0-571.5). In carriage surveys, 1,528 throat cultures taken from (primarily student) noncases yielded only five (0.3%) strains that were identical by MEE to those from cases. Two of these were found among 22 cultures obtained from bar A employees in spring 1992. Some cases in this outbreak may have followed transmission of the epidemic strain in bar A. Campus bar environments may facilitate the spread of meningococcal disease among teenagers and young adults. 相似文献