The Temperature Dependant Efficiency of Photovoltaic Modules - a Long Term Evaluation of Experimental Measurements

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Novel CHK1 inhibitor MU380 exhibits significant single-agent activity in TP53-mutated chronic lymphocytic leukemia cells

Introduction of small-molecule inhibitors of B-cell receptor signaling and BCL2 protein significantly improves therapeutic options in chronic lymphocytic leukemia. However, some patients suffer from adverse effects mandating treatment discontinuation, and cases with TP53 defects more frequently experience early progression of the disease. Development of alternative therapeutic approaches is, therefore, of critical importance. Here we report details of the anti-chronic lymphocytic leukemia single-agent activity of MU380, our recently identified potent, selective, and metabolically robust inhibitor of checkpoint kinase 1. We also describe a newly developed enantioselective synthesis of MU380, which allows preparation of gram quantities of the substance. Checkpoint kinase 1 is a master regulator of replication operating primarily in intra-S and G2/M cell cycle checkpoints. Initially tested in leukemia and lymphoma cell lines, MU380 significantly potentiated efficacy of gemcitabine, a clinically used inducer of replication stress. Moreover, MU380 manifested substantial single-agent activity in both TP53-wild type and TP53-mutated leukemia and lymphoma cell lines. In chronic lymphocytic leukemia-derived cell lines MEC-1, MEC-2 (both TP53-mut), and OSU-CLL (TP53-wt) the inhibitor impaired cell cycle progression and induced apoptosis. In primary clinical samples, MU380 used as a single-agent noticeably reduced the viability of unstimulated chronic lymphocytic leukemia cells as well as those induced to proliferate by anti-CD40/IL-4 stimuli. In both cases, effects were comparable in samples harboring p53 pathway dysfunction (TP53 mutations or ATM mutations) and TP53-wt/ATM-wt cells. Lastly, MU380 also exhibited significant in vivo activity in a xenotransplant mouse model (immunodeficient strain NOD-scid IL2Rγnull) where it efficiently suppressed growth of subcutaneous tumors generated from MEC-1 cells

Power Flow in Traction System and SFC Based Feeder Load Control: Sensitivity Analyses

The paper presents an analysis of active and reactive power control in AC 25 kV 50 Hz railway traction system consisting of both static frequency converter feeder and conventional single-phase transformer feeder. Limits of power sharing between the traction system feeders by means of the converter output voltage is analyzed and, additionally, control strategies aiming to increase the availability of the static frequency converters for services in distribution system is proposed

Implementation of 3GPP LTE Cat-M1 Technology in NS-3 : System Simulation and Performance

As the type of transmitted data over communication networks started to shift from the human-generated to massive Machine-Type Communications (mMTCs), entirely new applications within the Internet of Things (IoT) market emerged. Recently introduced Cellular IoT (CIoT) communication technologies operating in the licensed frequency spectrum (i.e., Narrowband IoT (NB-IoT) and LTE-M) complemented the already implemented and field-tested technologies (e.g., LoRa(WAN) and Sigfox) transmitting data in license-exempt frequency bands. Owing to the licensed spectrum as well as to the standardization efforts put by the Third Generation Partnership Project (3GPP) and International Telecommunication Union (ITU), the CIoT technologies are supposed to handle the massive number of data transmissions by introducing new categories of communication devices. In this regard, this paper elaborates on the critical parameters of the LTE Cat-M introduced by 3GPP. Along with the highlights of the technology in question, the implementation of LTE Cat-M1 in Network Simulator 3 (NS-3) is presented. Out of the obtained simulation data, the focus is primarily given to the network capacity for mMTC scenarios while utilizing the LTE Cat-M technology. What is even more, the side-by-side evaluation with legacy LTE/LTE-A systems is provided.acceptedVersionPeer reviewe