Fixed-Point Results on Complete G-Metric Spaces for Mappings Satisfying an Implicit relation of New Type

We prove general fixed-point theorems (generalizing some recent results) in a complete G-metric space.Доведено загальні теореми про нерухому точку у повних G-метричних просторах, що узагальнюють дєякі результати, отримані нещодавно

Impacts of selected stimulation patterns on the perception threshold in electrocutaneous stimulation

<p>Abstract</p> <p>Background</p> <p>Consistency is one of the most important concerns to convey stable artificially induced sensory feedback. However, the constancy of perceived sensations cannot be guaranteed, as the artificially evoked sensation is a function of the interaction of stimulation parameters. The hypothesis of this study is that the selected stimulation parameters in multi-electrode cutaneous stimulation have significant impacts on the perception threshold.</p> <p>Methods</p> <p>The investigated parameters included the stimulated location, the number of active electrodes, the number of pulses, and the interleaved time between a pair of electrodes. Biphasic, rectangular pulses were applied via five surface electrodes placed on the forearm of 12 healthy subjects.</p> <p>Results</p> <p>Our main findings were: 1) the perception thresholds at the five stimulated locations were significantly different (p < 0.0001), 2) dual-channel simultaneous stimulation lowered the perception thresholds and led to smaller variance in perception thresholds compared to single-channel stimulation, 3) the perception threshold was inversely related to the number of pulses, and 4) the perception threshold increased with increasing interleaved time when the interleaved time between two electrodes was below 500 μs.</p> <p>Conclusions</p> <p>To maintain a consistent perception threshold, our findings indicate that dual-channel simultaneous stimulation with at least five pulses should be used, and that the interleaved time between two electrodes should be longer than 500 μs. We believe that these findings have implications for design of reliable sensory feedback codes.</p

GYNOCARE Update: Modern Strategies to Improve Diagnosis and Treatment of Rare Gynecologic Tumors—Current Challenges and Future Directions

More than 50% of all gynecologic tumors can be classified as rare (defined as an incidence of ≤6 per 100, 000 women) and usually have a poor prognosis owing to delayed diagnosis and treatment. In contrast to almost all other common solid tumors, the treatment of rare gynecologic tumors (RGT) is often based on retrospective studies, expert opinion, or extrapolation from other tumor sites with similar histology, leading to difficulty in developing guidelines for clinical practice. Currently, gynecologic cancer research, due to distinct scientific and technological challenges, is lagging behind. Moreover, the overall efforts for addressing these challenges are fragmented across different European countries and indeed, worldwide. The GYNOCARE, COST Action CA18117 (European Network for Gynecological Rare Cancer Research) programme aims to address these challenges by creating a unique network between key stakeholders covering distinct domains from concept to cure: basic research on RGT, biobanking, bridging with industry, and setting up the legal and regulatory requirements for international innovative clinical trials. On this basis, members of this COST Action, (Working Group 1, “Basic and Translational Research on Rare Gynecological Cancer”) have decided to focus their future efforts on the development of new approaches to improve the diagnosis and treatment of RGT. Here, we provide a brief overview of the current state of-the-art and describe the goals of this COST Action and its future challenges with the aim to stimulate discussion and promote synergy across scientists engaged in the fight against this rare cancer worldwide

Selective AKR1C3 inhibitors do not recapitulate the anti-leukaemic activities of the pan-AKR1C inhibitor medroxyprogesterone acetate

Background: We and others have identified the aldo-keto reductase AKR1C3 as a potential drug target in prostate cancer, breast cancer and leukaemia. As a consequence, significant effort is being invested in the development of AKR1C3-selective inhibitors. Methods: We report the screening of an in-house drug library to identify known drugs that selectively inhibit AKR1C3 over the closely related isoforms AKR1C1, 1C2 and 1C4. This screen initially identified tetracycline as a potential AKR1C3-selective inhibitor. However, mass spectrometry and nuclear magnetic resonance studies identified that the active agent was a novel breakdown product (4-methyl(de-dimethylamine)-tetracycline (4-MDDT)). Results: We demonstrate that, although 4-MDDT enters AML cells and inhibits their AKR1C3 activity, it does not recapitulate the anti-leukaemic actions of the pan-AKR1C inhibitor medroxyprogesterone acetate (MPA). Screens of the NCI diversity set and an independently curated small-molecule library identified several additional AKR1C3-selective inhibitors, none of which had the expected anti-leukaemic activity. However, a pan AKR1C, also identified in the NCI diversity set faithfully recapitulated the actions of MPA. Conclusions: In summary, we have identified a novel tetracycline-derived product that provides an excellent lead structure with proven drug-like qualities for the development of AKR1C3 inhibitors. However, our findings suggest that, at least in leukaemia, selective inhibition of AKR1C3 is insufficient to elicit an anticancer effect and that multiple AKR1C inhibition may be required