A Lifshitz Black Hole in Four Dimensional R^2 Gravity

We consider a higher derivative gravity theory in four dimensions with a negative cosmological constant and show that vacuum solutions of both Lifshitz type and Schr\"{o}dinger type with arbitrary dynamical exponent z exist in this system. Then we find an analytic black hole solution which asymptotes to the vacuum Lifshitz solution with z=3/2 at a specific value of the coupling constant. We analyze the thermodynamic behavior of this black hole and find that the black hole has zero entropy while non-zero temperature, which is very similar to the case of BTZ black holes in new massive gravity at a specific coupling. In addition, we find that the three dimensional Lifshitz black hole recently found by E. Ayon-Beato et al. has a negative entropy and mass when the Newton constant is taken to be positive.Comment: 11 pages, no figure; v2, a minor error correcte

A patient-derived xenograft pre-clinical trial reveals treatment responses and a resistance mechanism to karonudib in metastatic melanoma

Karonudib (TH1579) is a novel compound that exerts anti-tumor activities and has recently entered phase I clinical testing. The aim of this study was to conduct a pre-clinical trial in patient-derived xenografts to identify the possible biomarkers of response or resistance that could guide inclusion of patients suffering from metastatic melanoma in phase II clinical trials. Patient-derived xenografts from 31 melanoma patients with metastatic disease were treated with karonudib or a vehicle for 18 days. Treatment responses were followed by measuring tumor sizes, and the models were categorized in the response groups. Tumors were harvested and processed for RNA sequencing and protein analysis. To investigate the effect of karonudib on T-cell-mediated anti-tumor activities, tumor-infiltrating T cells were injected in mice carrying autologous tumors and the mice treated with karonudib. We show that karonudib has heterogeneous anti-tumor effect on metastatic melanoma. Thus, based on the treatment responses, we could divide the 31 patient-derived xenografts in three treatment groups: progression group (32%), suppression group (42%), and regression group (26%). Furthermore, we show that karonudib has anti-tumor effect, irrespective of major melanoma driver mutations. Also, we identify high expression of ABCB1, which codes for p-gp pumps as a resistance biomarker. Finally, we show that karonudib treatment does not hamper T-cell-mediated anti-tumor responses. These findings can be used to guide future use of karonudib in clinical use with a potential approach as precision medicine

Determinants of the level of knwoledge application: a knowledge-based and information-processing perspective

Knowledge application is of key importance in the development of successful new products. Knowledge application refers to an organization's timely response to technological change by utilizing the knowledge and technology generated into new products and processes. This study uses the knowledge-based theory of the firm and considers its roots in the information-processing approach to organization theory to identify and structure potential antecedents of knowledge application. This study develops four hypotheses concerning antecedents of knowledge application. The hypotheses are tested using data collected from 277 high-technology firms. Empirical results indicate that a long-term orientation supported by a research and development (R&D) budget, formal rewards, and information technology directly increases the level of knowledge application, while R&D co-location indirectly increases the level of knowledge application. It is surprising to find that an increase in the level of organizational redundancy reduces the level of knowledge application. The findings also suggest that information technologies, lead-user, and supplier networks do not appear to significantly influence organizational redundancy