Histone deacetylase inhibitor vorinostat suppresses the growth of uterine sarcomas in vitro and in vivo

<p>Abstract</p> <p>Background</p> <p>Uterine sarcomas are very rare malignancies with no approved chemotherapy protocols. Histone deacetylase (HDAC) inhibitors belong to the most promising groups of compounds for molecular targeting therapy. Here, we described the antitumor effects of suberoylanilide hydroxamic acid (SAHA; vorinostat) on MES-SA uterine sarcoma cells <it>in vitro </it>and <it>in vivo</it>. We investigated effects of vorinostat on growth and colony forming ability by using uterine sarcoma MES-SA cells. We analyzed the influence of vorinostat on expression of different HDACs, p21^WAF1and activation of apoptosis. Finally, we examined the antitumor effects of vorinostat on uterine sarcoma <it>in vivo</it>.</p> <p>Results</p> <p>Vorinostat efficiently suppressed MES-SA cell growth at a low dosage (3 μM) already after 24 hours treatment. Decrease of cell survival was even more pronounced after prolonged treatment and reached 9% and 2% after 48 and 72 hours of treatment, respectively. Colony forming capability of MES-SA cells treated with 3 μM vorinostat for 24 and 48 hours was significantly diminished and blocked after 72 hours. HDACs class I (HDAC2 and 3) as well as class II (HDAC7) were preferentially affected by this treatment. Vorinostat significantly increased p21^WAF1expression and apoptosis. Nude mice injected with 5 × 10⁶MES-SA cells were treated for 21 days with vorinostat (50 mg/kg/day) and, in comparison to placebo group, a tumor growth reduction of more than 50% was observed. Results obtained by light- and electron-microscopy suggested pronounced activation of apoptosis in tumors isolated from vorinostat-treated mice.</p> <p>Conclusions</p> <p>Our data strongly indicate the high therapeutic potential of vorinostat in uterine sarcomas.</p

Does Empathy Attenuate the Criminogenic Effect of Low Self-Control in Late Life?

The present study investigates whether empathy shapes the criminogenic effect of low self-control in late adulthood. Based on the assumption that the capacity to understand and share the thoughts and emotions of other people moderates the significance of the capability to consider the distant consequences of behaviour on oneself, we posit that poor self-control is less consequential among senior citizens of high empathy. The results of a postal survey of 3,000 randomly selected older adults from Germany indicate that both low trait self-control and weak trait empathy increase offending in advanced age. Furthermore, the findings provide evidence of an interaction according to which the relationship between the risk-taking component of the self-control trait and criminal activity is stronger for older adults characterised by low empathy. Impulsivity, on the other hand, seems to mediate the association of empathy and offending in late life

Does empathy attenuate the criminogenic effect of low self-control in late life?

The present study investigates whether empathy shapes the criminogenic effect of low self-control in late adulthood. Based on the assumption that the capacity to understand and share the thoughts and emotions of other people moderates the significance of the capability to consider the distant consequences of behaviour on oneself, we posit that poor self-control is less consequential among senior citizens of high empathy. The results of a postal survey of 3,000 randomly selected older adults from Germany indicate that both low trait self-control and weak trait empathy increase offending in advanced age. Furthermore, the findings provide evidence of an interaction according to which the relationship between the risk-taking component of the self-control trait and criminal activity is stronger for older adults characterised by low empathy. Impulsivity, on the other hand, seems to mediate the association of empathy and offending in late life.</p

Enabling End-Users in Designing and Executing of Complex, Collaborative Robotic Processes

Over the last years, capabilities of robotic systems have quantitatively and qualitatively improved. But going beyond isolated robotic systems, the integration and interoperability of robotic capabilities in complex work processes remains a major challenge. This lack of tools to integrate robots needs to be addressed on technical, semantic and organizational level. In the ROBxTASK research project, we developed an approach to support cooperation between different types of users in order to enable domain experts, with no robotic know-how, to work with robot-assisted workflows. By engineering robotic skills at a useful and usable level of abstraction for experts in different domains, we aim to increase re-usability of these skills on two different levels, (robotic) device level, and on level of application specific workflows. The researched prototype consists of a web platform, which allows (a) engineers to register (robotic) devices and the implemented skills of the devices, (b) domain experts to use a graphical task design environment to create workflows across multiple robotic devices and lastly (c) robot co-workers to download and execute the workflow code in a local environment with digital twins or real robots. Additionally skills and workflows can be shared across organisations. Initial user studies have shown that the visual programming environment is accessible and the defined skill-set is easy to understand even for domain experts that are inexperienced in the field of robotics