Clone Detection Method Selection Based on Bandit Algorithm: a Preliminary Analysis

Various clone detection methods have been proposed in the past, with results varying depending on the combination of the methods and parameters setting used (i.e., configurations). To help with the selection of a suitable clone detection configuration, we propose Bandit Algorithm (BA) approach that can help in evaluating the configuration used dynamically while using detection methods. Our preliminary analysis showed that our approach is able to identify the best configurations from four used code clone detection methods

Collaborative study of thresholds for mutagens: proposal of a typical protocol for detection of hormetic responses in cytotoxicity tests

Abstract Background According to the linear no-threshold model (LNT), even the smallest amount of radiation is hazardous. Although the LNT is not based on solid data, this hypothesis has been applied to mutagens and carcinogens. As a result, it has been postulated that there are no thresholds for these chemicals. To demonstrate negativity by experiments is practically impossible, because negative data may leave behind the possibility that additional data might make the resolution power high enough to change negativity to positivity. Furthermore, additional data collection may be endless and we may be trapped in agnosticism. When hormesis is established, in which biological responses are higher at low-doses and lower at high-doses than the control, thresholds could be established between the low- and high-doses. Before examination of thresholds in chemical mutagenesis, hormetic responses in cytotoxicity were tested using cultured mammalian cells. Method Human cells (HeLa S3 and TK6) or Chinese hamster cells (CHL/IU) were cultured in 96-well plates and treated with mitomycin C (MMC) or ethyl methanesulfonate (EMS) at various dose levels and optical density was measured after addition of a reagent to detect cellular activity. In hormetic responses, data might fluctuate to and fro; therefore, experimental conditions were examined from various aspects to eliminate confounding factors including cell numbers, detection time, the edge effect of 96-well plates, and measurement time after addition of the reagent for detection. Results The dose response relationship was never linear. Cellular activities after treatment with MMC or EMS were generally higher at lower doses levels and lower at higher doses than the control, showing hormesis and allowing the establishment of thresholds. Dose response curves sometimes showed two or three peaks, probably reflecting different cellular responses. Conclusion Hormetic responses in cytotoxicity tests were observed and thresholds could be established. Based on the results of this investigation, we put forward a tentative protocol to detect chemical hormesis in cytotoxicity tests, i.e., inoculate 2000 cells per well, add various doses of a test chemical 48 h after inoculation, add a detection dye 10 h after treatment, and measure optical density 2 h after addition of the reagent for detection

Veno‐venous extracorporeal membrane oxygenation for severe pneumonia: COVID‐19 case in Japan

BACKGROUND: Veno‐venous extracorporeal membrane oxygenation (VV‐ECMO) is one of the ultimate treatments for acute respiratory failure. However, the effectiveness of ECMO in patients with novel coronavirus disease (COVID‐19) is unknown. CASE PRESENTATION: A 72‐year‐old woman who was a passenger of a cruise ship tested positive for the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) while in quarantine on board using throat swab. Three days after admission, her condition deteriorated, and she was subsequently intubated. On day 6, VV‐ECMO was introduced. Lopinavir/ritonavir was given; continuous renal replacement therapy was also introduced. On day 10, her chest radiography and lung compliance improved. She was weaned off ECMO on day 12. CONCLUSION: Treatment of severe pneumonia in COVID‐19 by ECMO should recognize lung plasticity considering time to ECMO introduction and interstitial biomarkers. In Japan, centralization of ECMO patients has not been sufficient. Thus, we suggest nationwide centralization and further research to respond to the crisis caused by COVID‐19

Combination of Triple Bond and Adamantane Ring on the Vitamin D Side Chain Produced Partial Agonists for Vitamin D Receptor

Vitamin D receptor (VDR) ligands are therapeutic agents that are used for the treatment of psoriasis, osteoporosis, and secondary hyperparathyroidism and have immense potential as therapeutic agents for autoimmune diseases, cancers, and cardiovascular diseases. However, the major side effect of VDR ligands, the development of hypercalcemia, limits their expanded use. To develop tissue-selective VDR modulators, we have designed vitamin D analogues with an adamantane ring at the side chain terminal, which would interfere with helix 12, the activation function 2, and modulate the VDR potency. Here we report 25- or 26-adamantyl-23,23,24,24-tetradehydro-19-norvitamin D derivatives (ADTK1–4, <b>4b</b>,<b>a</b> and <b>5a</b>,<b>b</b>). These compounds showed high VDR affinities (90% at maximum), partial agonistic activities (EC₅₀ 10^–9–10^–8 M with 40–80% efficacy) in transactivation, and tissue-selective activity in target gene expressions. We investigate the structure–activity relationships of these compounds on the basis of their X-ray crystal structures

Combination of Triple Bond and Adamantane Ring on the Vitamin D Side Chain Produced Partial Agonists for Vitamin D Receptor

Vitamin D receptor (VDR) ligands are therapeutic agents that are used for the treatment of psoriasis, osteoporosis, and secondary hyperparathyroidism and have immense potential as therapeutic agents for autoimmune diseases, cancers, and cardiovascular diseases. However, the major side effect of VDR ligands, the development of hypercalcemia, limits their expanded use. To develop tissue-selective VDR modulators, we have designed vitamin D analogues with an adamantane ring at the side chain terminal, which would interfere with helix 12, the activation function 2, and modulate the VDR potency. Here we report 25- or 26-adamantyl-23,23,24,24-tetradehydro-19-norvitamin D derivatives (ADTK1–4, <b>4b</b>,<b>a</b> and <b>5a</b>,<b>b</b>). These compounds showed high VDR affinities (90% at maximum), partial agonistic activities (EC₅₀ 10^–9–10^–8 M with 40–80% efficacy) in transactivation, and tissue-selective activity in target gene expressions. We investigate the structure–activity relationships of these compounds on the basis of their X-ray crystal structures