Aminopeptidase N (APN), also known as CD13 antigen or membrane alanyl aminopeptidase, belongs to the M1 family of the MA clan of zinc metallopeptidases. In cancer cells, the inhibition of aminopeptidases including APN causes the phenomenon termed the amino acid deprivation response (AADR), a stress response characterized by the upregulation of amino acid transporters and synthetic enzymes and activation of stress-related pathways such as nuclear factor kB (NFkB) and other pro-apoptotic regulators, which leads to cancer cell death by apoptosis. Recently, APN inhibition has been shown to augment DR4-induced tumor cell death and thus overcome resistance to cancer treatment with DR4-ligand TRAIL, which is available as a recombinant soluble form dulanermin. This implies that APN inhibitors could serve as potential weapons for overcoming cancer treatment resistance. In this study, a series of basically substituted acetamidophenones and the semicarbazones and thiosemicarbazones derived from them were prepared, for which APN inhibitory activity was determined. In addition, a selective anti-proliferative activity against cancer cells expressing APN was demonstrated. Our semicarbazones and thiosemicarbazones are the first compounds of these structural types of Schiff bases that were reported to inhibit not only a zinc-dependent aminopeptidase of the M1 family but also a metalloenzyme. 相似文献
System identification is an inherently iterative process. Yet, limited attempts have been made so far to implement the whole identification loop in a single device. This paper discusses the difficulties of the task and presents a solution based on a Matlab toolbox and a set of virtual instruments. During the identification session, the obtained models may call for refinement or validation by new experiments. Using this integrated software-hardware tool, these subsequent experiments can be accomplished online with the identification procedure. As a demonstration, the modeling of a hairdryer is described. The universal applicability of this solution is believed to be guaranteed by the modular architecture of virtual instrumentation and the general definition of the software interface developed. The interface allows combining Matlab-based identification packages with virtual instruments or pure hardware interfaced to Matlab 相似文献
An approach for automatically testing GUIs in the MATLAB environment has been proposed. We developed a software tool that tests GUIs by simulating the user through an action recorder. We proposed a heuristic test procedure: providing random input to GUI, but guiding the randomness with predefined weights assigned to the user controls. The weights change during the testing process, as the controls are activated. The errors are collected for later investigation. 相似文献
Controllers of industrial furnaces operate differently in different temperature ranges. The controller has different parameter sets for each of these ranges. The operation of controllers is switched according to the temperature. It is desirable to change the parameters continuously following the temperature. The continuous change of parameters instead of mode switching may decrease the switching transients and lead to more accurate temperature control. A furnace identification scheme is investigated in this paper. Measurement problems and possible corrections that result in more accurate models after processing the collected data are shown. A possible "interpolation" technique of frequency-domain models is also shown here. 相似文献
This paper investigates the imperfect fulfilment of the validity conditions of the noise model quantization. The general expressions of the deviations of the moments from Sheppard's corrections are derived. Approximate upper and lower bounds of the bias are given for the measurement of first- and second-order moments of sinusoidal, uniformly distributed, and Gaussian signals. It is shown that because of the uncontrollable mean value at the input of the ADC (offset, drift), the worst-case values have to be investigated; it is illustrated how a simple-form envelope function of the errors can be used as an upper bound. Since the worst-case relative positions of the signal and the quantization characteristics are taken into account, the results are valid for both midtread and midrise quantizers, while in the literature results are given for a selected quantizer type only 相似文献
Very often, university students deliberately form self-organized study groups, e.g. to study collaboratively for an upcoming exam. Yet, very little is known about what regulation problems such self-organized study groups encounter during their learning process and how they try to cope with these problems. Therefore, this study investigates how completely self-organized groups (i.e., non-guided groups outside the classroom that form without external impulse) regulate their collaborative learning process when faced with different kinds of regulation problems. More specifically, we tested the hypotheses that members of self-organized study groups are more satisfied with their group learning experience (a) the more homogeneous their problem perceptions are within their group, (b) the more they apply immediate (rather than non-immediate) strategies to remedy their regulation problems, and (c) the more frequently they apply regulation strategies. In a longitudinal study, N?=?122 students, voluntarily studying for their exams in N?=?52 groups, were asked to indicate the types of problems they experienced, the types of strategies they used to tackle those problems, and their satisfaction with their group learning experience after each of their self-organized study meetings. Hierarchical linear modeling confirmed all hypotheses. Qualitative analysis of two selected groups’ self-reported situational data provided additional insights about the mechanisms that may have contributed to the results. Our study provides important directions for future research, including the recommendation to identify the processes by which groups (a) can reach homogeneity of problem perceptions and (b) coordinate the choice of appropriate strategies within the group.