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To investigate the functions of the p53 tumor suppressor, we created a new knock-in gene replacement mouse model in which the endogenous Trp53 gene is substituted by one encoding p53ER(TAM), a p53 fusion protein whose function is completely dependent on ectopic provision of 4-hydroxytamoxifen. We show here that both tissues in vivo and cells in vitro derived from such mice can be rapidly toggled between wild-type and p53 knockout states. Using this rapid perturbation model, we define the kinetics, dependence, persistence and reversibility of p53-mediated responses to DNA damage in tissues in vivo and to activation of the Ras oncoprotein and stress in vitro. This is the first example to our knowledge of a new class of genetic model that allows the specific, rapid and reversible perturbation of the function of a single endogenous gene in vivo.  相似文献   
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Riassunto Dae polimeri reticolati di nuova sintesi, contenenti gruppi amminici terziari, sono in grado di assorbire selettivamente eparina dal sangue. Essi non sono emolitici e non interferiscono con i fattori della coagulazione.

Acknowledgment. This work was supported by the Programma Speciale Technologie Biomediche of the Italian National Council of Researches.  相似文献   
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Riassunto Viene descritta la presenza, nel succo dei sarcosomi del muscolo di ratto, di 4 componenti proteici separabili mediante elettroforesi su carta. I 4 componenti sono rappresentati nella misura di rispettivamente 26.1, 18.4, 33.2 e 22.3 per 100 delle proteine totali.  相似文献   
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Magnetic iron oxide nanoparticles(IONPs) are heavily explored as diagnostic and therapeutic agents due to their low cost, tunable properties, and biocompatibility. In particular, upon excitation with an alternating current(AC) magnetic field, the NPs generate localized heat that can be exploited for therapeutic hyperthermia treatment of diseased cells or pathogenic microbes. In this review, we focus on how structural changes and inter-particle interactions affect the heating efficiency of iron oxide-based magnetic NPs. Moreover, we present an overview of the different approaches to evaluate the heating performance of IONPs and introduce a new theranostic modality based on magnetic imaging guided–hyperthermia.  相似文献   
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This article responds to Dominelli’s contribution by mapping three lines of discussion. The first relates to the issue of how to understand voluntary work with regard to the realization of citizenship. The authors argue that this understanding depends on the way citizenship is conceived. Whereas a rights-based conception of citizenship focuses on issues of equal access to voluntary work, a duty-oriented notion of citizenship tends to see voluntarism as embedded in an educational strategy, alongside professionalized social work. The authors plead for an alternative understanding of voluntary work and social work as joined partners in practices of ‘learning democracy’. The second line of discussion revolves around the relation between social and political dimensions of citizenship. With Dominelli, the authors point out how the obscuring of the political dimension risks to nurture societal discourses that put pressure on the welfare state. The third point relates to the difficulties in positioning voluntary work with regard to professional social work. One of these difficulties is the tendency to over-romanticize voluntary work as warm, informal, generous, while giving an exclusively technical reading of social work professionalization.  相似文献   
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Some evidence indicates that in anuran amphibians, visual signalling can be important during social interactions such as territorial disputes among males, especially in diurnal species. The correct identification of a signal is not a trivial matter. A visual signal provides a visual cue during a social interaction, and to be effective it must elicit an immediate response in the receiver. We tested the hypothesis that visual displays in an agonistic context constitute aggressive signals, in three nocturnal species of Hylidae. We predicted that the production of visual displays would increase in the presence of a conspecific intruder male. Males of Hypsiboas raniceps, Dendropsophus nanus and Lysapsus limellum were submitted to two treatments: (1) Self Image, a reflection in a mirror, simulating the presence of an intruder; and (2) Control, a black rectangle covering the mirror. We observed three visual displays: vocal-sac display (inflate the vocal sac and maintain it inflated for some time), limb lifting (rapid up-and-down movements of one or more limbs), and toe/finger trembling (rapid up-and-down movements of one or more toes and/or fingers). This last display was observed only in H. raniceps males. Contrary to our hypothesis, the emission rates of all visual displays of the focal animals did not differ between treatments; and the behavioural response did not differ among species. Therefore, we suggest that these behaviours could not be used directly for communication in agonistic contexts, and may represent displacement activities (involuntary responses). Alternatively, an aggressive bimodal stimulus may be necessary to trigger a behavioural response by using visual signals during territory defence in these three species.  相似文献   
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