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1.
Dr. Maria L. Di Paolo Dr. Michael S. Christodoulou Dr. Alessandra M. Calogero Dr. Luca Pinzi Prof. Giulio Rastelli Prof. Daniele Passarella Prof. Graziella Cappelletti Prof. Lisa Dalla Via 《ChemMedChem》2019,14(18):1641-1652
A series of 2-phenyloxazoles bearing an amide group at position 4 were designed and synthesized for evaluation as potential inhibitors of human recombinant monoamine oxidases (hrMAOs). Results of kinetics experiments demonstrated that all compounds behave as competitive MAO inhibitors, with good selectivity toward the MAO-B isoform. The most potent and selective derivatives are characterized by inhibition constant (Ki) values in the sub-micromolar range and a good selectivity index (Ki MAO-A/Ki MAO-B>50). Some derivatives were also found to be able to inhibit MAO activity in nerve growth factor (NGF)-differentiated PC12 cells, taken as a model of neuronal cells. In particular, 2-(2-hydroxyphenyl)-N-phenyloxazole-4-carboxamide (compound 4 a ) may be a promising new scaffold, exerting the highest selectivity and inhibitory effect toward MAOs in NGF-differentiated PC12 cell lysates, without compromising cell viability. Molecular docking analysis allowed a rationalization of the experimentally observed binding affinity and selectivity. 相似文献
2.
The authors report the design of a new current-mode A/D converter, based on a modified successive-approximations model, in 1.2 μm CMOS technology. The proposed circuit is characterised by good accuracy and fast dynamic performance, low power consumption and small occupation area. SPICE simulations allow the design approach to be validated and the electrical performance of the ADC to be predicted 相似文献
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Least squares is perhaps the most widely used technique for model fitting. In this article, we illustrate the poor performance of least squares when there are spurious values, or outliers, in a sequence of measurements. A brief overview of three well-known classes of robust alternatives to the least-squares mean is presented. For robust regression, a recent proposal called least median squares (LMS) is decribed. LMS regression is compared to least-squares regression in an example involving the estimation of optical fiber geometry. References are provided for software that is available for robust estimation techniques surveyed in this article. 相似文献
4.
Within the framework of the distinction between episodic and semantic memory, it has been argued that these two memory systems are organised in a hierarchical way. The hierarchical hypothesis assumes that episodic memory is a specific subsystem of semantic memory and therefore implies that episodic memory cannot exist without semantic memory. If this hypothesis is correct, it should be expected that patients with impaired semantic memory also have impaired episodic memory. In the present study, two experiments investigated the influence of semantic encoding on recognition memory performance in a population of 20 patients with Alzheimer's disease and 18 normal controls. Both experiments assessed recognition memory for semantically-related items. In Experiment 2, but not in Experiment 1, subjects were explicitly instructed to make a semantic association between the items. Alzheimer's disease patients were impaired, compared to the normal controls, on the recognition memory performance of both experiments. The ability to make a semantic association between two items was significantly and positively correlated with the subjects' performance on the recognition tasks. A further analysis showed that patients who were impaired on the semantic association task did significantly worse on the recognition task of Experiment 2 than normal controls and patients who were unimpaired on the semantic association task. These findings are discussed in the context of memory deficits in Alzheimer's disease, and are interpreted as supporting the view that episodic memory for an item is affected by the level of semantic awareness of that same item. 相似文献
5.
Early patterning of prelimbic cortical axons to the striatal patch compartment in the neonatal mouse
LK Nisenbaum SM Webster SL Chang KD McQueeney JJ LoTurco 《Canadian Metallurgical Quarterly》1998,20(2-3):113-124
The striatum receives excitatory input from virtually the entire cerebral cortex. In the adult, this input is segregated into two functionally distinct compartments of the striatum, the patch (striosome) and matrix regions. This study determined whether the patterning of corticostriatal afferents from the prelimbic cortex to the striatal patch compartment develops during the early period of collateral formation or instead at the time of peak synaptogenesis. Initial formation of corticostriatal axon collaterals was observed by embryonic day (E) 19. Quantification of corticostriatal collaterals revealed a significant increase in the number and complexity of collateral branches at postnatal day 6 as compared to E19. Concomitant with the increase in collateral branching, a heterogeneous pattern of collateralization consisting of parallel rows of corticostriatal collaterals was observed in the medial striatum. In addition to the rows, clusters of corticostriatal axons occurred more laterally. These clusters colocalized with patches of dense tyrosine hydroxylase-positive fibers, a marker for the striatal patch compartment in the neonatal mouse. Together, these data indicate that corticostriatal patterning occurs during the period of early axon collateralization resulting in a segregation of corticostriatal axon collaterals from the prelimbic cortex to the striatal patch compartment. 相似文献
6.
The precautionary principle (PP), according to one of its definitions, says that lack of certainty, given the current scientific and technological knowledge, shall not delay effective and proportionate actions to prevent hazards, taking into account cost-benefit considerations. Rather than being a single principle, a variety of statements of the PP are found in international treaties and other documents. Apart from any specific legal force of the documents, countries (e.g., France) have used these statements as a starting point for their own guidance documents and regulations for addressing specific environmental and health issues, for example regulation of genetically modified organisms. Thus, any discussion of the precautionary principle must address a complex legal and regulatory situation. We briefly review different statements of the PP and important commentary, largely from the European Union. We provide references to the original source documents (many of which are found in English on the World Wide Web). 相似文献
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A Notghi R Hutchinson D Kumar NB Smith LK Harding 《Canadian Metallurgical Quarterly》1994,35(7):976-981
Segmental colonic transit has been measured in 101 patients. Two MBq of 111Indium absorbed on resin pellets and encapsulated in an enteric coated capsule was given at 7 00 am. Hourly images during the first day, and three images during each subsequent day were acquired for up to three days. Using all scan and patient data the scans were categorised in one of the five patterns of colonic transit: normal, rapid, right delay, left delay, or generalised delay. The geometric centres and per cent activity at each time point was compared between the five groups of colonic transit patients to find the best time for imaging and so to distinguish the five groups. During the first day, early images did not help in diagnosis of patterns of transit, however, in the later images (six hours onwards after the ingestion of the activity) the rapid transit groups could be identified. Images at 27 and 51 hours were both required to distinguish all five groups of patients from each other. Only in the 'normal' transit patients was there some excretion of the activity during the course of the second day, otherwise there was no difference in the images taken in the course of a day (second or third day). A simplified protocol requires a minimum of three images to distinguish all five patterns of colonic transit. The activity should be ingested in the morning (7 00 am) and the first image taken at the end of the working day (8-10 hours after ingestion), the second image on the morning of the second day, and the third image during the course of the third day. This simple protocol would provide all the clinically relevant information necessary for correct classification of the colonic transit. 相似文献
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