Elongation/compaction of giant DNA caused by depletion interaction with a flexible polymer

Structural changes in giant DNA induced by the addition of the flexible polymer Polyethylene Glycol (PEG) were examined by the method of single-DNA observation. In dilute DNA conditions, individual DNA assumes a compact state via a discrete coil-globule transition, whereas in concentrated solution, DNA molecules exhibit an extended conformation via macroscopic phase segregation. The long-axis length of the stretched state in DNA is about 10(3) times larger than that of the compact state. Phase segregation at high DNA concentrations occurs at lower PEG concentrations than the compaction at low DNA concentrations. These opposite changes in the conformation of DNA molecule are interpreted in terms of the free energy, including depletion interaction. (c) 2006 American Institute of Physics

Introduction of accelerated BOIN design and facilitation of its application

Purpose: During discussions at the Data Science Roundtable meeting in Japan, there were instances where the adoption of the BOIN design was declined, attributed to the extension of study duration and increased sample size in comparison to the 3+3 design. We introduce an accelerated BOIN design aimed at completing a clinical phase I trial at a pace comparable to the 3+3 design. Additionally, we introduce how we could have applied the BOIN design within our company, which predominantly utilized the 3+3 design for most of its clinical oncology dose escalation trials. Methods: The accelerated BOIN design is adaptable by using efficiently designated stopping criterion for the existing BOIN framework. Our approach is to terminate the dose escalation study if the number of evaluable patients treated at the current dose reaches 6 and the decision is to stay at the current dose for the next cohort of patients. In addition, for lower dosage levels, considering a cohort size smaller than 3 may be feasible when there are no safety concerns from non-clinical studies. We demonstrate the accelerated BOIN design using a case study and subsequently evaluate the performance of our proposed design through a simulation study. Results: In the simulation study, the average difference in the percentage of correct MTD selection between the accelerated BOIN design and the standard BOIN design was -2.43%, the average study duration and the average sample size of the accelerated BOIN design was reduced by 14.8 months and 9.22 months, respectively, compared with the standard BOIN design. Conclusion: We conclude that our proposed accelerated BOIN design not only provides superior operating characteristics but also enables the study to be completed as fast as the 3+3 design

Comparison of Baseline Covariate Adjustment Methods for Restricted Mean Survival Time

The restricted mean survival time is a clinically easy-to-interpret measure that does not require any assumption of proportional hazards. We focus on two ways to directly model the survival time and adjust the covariates. One is to calculate the pseudo-survival time for each subject using leave-one-out, and then perform a model analysis using all pseudo-values to adjust for covariates. The pseudo-survival time is used to reflect information of censored subjects in the model analysis. The other method adjusts for covariates using subjects for whom the time-to-event was observed while adjusting for the censored subjects using the inverse probability of censoring weighting (IPCW). This paper evaluates the performance of these two methods in terms of the power to detect group differences through a simple example dataset and computer simulations. The simple example illustrates the intuitive behavior of the two methods. With the method using pseudo-survival times, it is difficult to interpret the pseudo-values. We confirm that the pseudo-survival times are different from the actual data obtained in a primary biliary cholangitis clinical trial because of the many censored data. In the simulations, the method using IPCW is found to be more powerful. Even in the case of group differences with respect to the censor incidence rates and covariates, the method using IPCW maintains a nominal significance level for the type-1 error rate. We conclude that the IPCW method should be used to estimate the restricted mean survival time when adjusting the covariates

Computer-aided diagnosis of lung nodule using gradient tree boosting and Bayesian optimization

We aimed to evaluate computer-aided diagnosis (CADx) system for lung nodule classification focusing on (i) usefulness of gradient tree boosting (XGBoost) and (ii) effectiveness of parameter optimization using Bayesian optimization (Tree Parzen Estimator, TPE) and random search. 99 lung nodules (62 lung cancers and 37 benign lung nodules) were included from public databases of CT images. A variant of local binary pattern was used for calculating feature vectors. Support vector machine (SVM) or XGBoost was trained using the feature vectors and their labels. TPE or random search was used for parameter optimization of SVM and XGBoost. Leave-one-out cross-validation was used for optimizing and evaluating the performance of our CADx system. Performance was evaluated using area under the curve (AUC) of receiver operating characteristic analysis. AUC was calculated 10 times, and its average was obtained. The best averaged AUC of SVM and XGBoost were 0.850 and 0.896, respectively; both were obtained using TPE. XGBoost was generally superior to SVM. Optimal parameters for achieving high AUC were obtained with fewer numbers of trials when using TPE, compared with random search. In conclusion, XGBoost was better than SVM for classifying lung nodules. TPE was more efficient than random search for parameter optimization.Comment: 29 pages, 4 figure

Copper-Catalyzed Regio- And Enantioselective Hydroallylation of 1-Trifluoromethylalkenes: Effect of Crown Ether

A Cu-catalyzed regio- and enantioselective hydroallylation of 1-trifluoromethylalkenes with hydrosilanes and allylic chlorides has been developed. Anin situgenerated CuH species undergoes the hydrocupration regio- and enantioselectively to form a chiral α-CF3alkylcopper intermediate, which then leads to the optically active hydroallylated product. The key to success is the use of not only an appropriate chiral bisphosphine ligand but also 18-crown-6 to suppress the otherwise predominant β-F elimination from the α-CF3alkylcopper intermediate. The asymmetric Cu catalysis successfully constructs the nonbenzylic and nonallylic CF3-substituted Csp3chiral center, which is difficult to operate by other means.Kojima Y., Miura M., Hirano K.. Copper-Catalyzed Regio- And Enantioselective Hydroallylation of 1-Trifluoromethylalkenes: Effect of Crown Ether. ACS Catalysis. 11(18), 11663-11670, (2021), 17 September 2021; © 2021 American Chemical Society. https://doi.org/10.1021/acscatal.1c02947

Recent Progress in Electrical Insulation Techniques for HTS Power Apparatus

AbstractThis paper describes the electrical insulation techniques at cryogenic temperatures, i.e. Cryodielectrics, for HTS power apparatus, e.g. HTS power transmission cables, transformers, fault current limiters and SMES. Breakdown and partial discharge characteristics are discussed for different electrical insulation configurations of LN2, sub-cooled LN2, solid, vacuum and their composite insulation systems. Dynamic and static insulation performances with and without taking account of quench in HTS materials are also introduced

Synthesis of gem-difluoroalkenes by copper-catalyzed regioselective hydrodefluorination of 1-trifluoromethylalkenes

A copper-catalyzed regioselective hydrodefluorination of 1-trifluoromethylalkenes with hydrosilanes has been developed. The copper catalysis is compatible with several functional groups, including alkyl chloride, ether, ester, nitrile, and imide moieties, to form the corresponding gem-difluoroalkenes in good yields. Additionally, asymmetric induction is also possible by using the chiral DTBM-SEGPHOS ligand, and gem-difluoroalkene with point chirality at the allylic position is obtained with high enantioselectivity

Morphological and Histopathological Changes in Orofacial Structures of Experimentally Developed Acromegaly-Like Rats: An Overview

Tongue enlargement and mandibular prognathism are clinically recognized in almost all patients with acromegaly. An acromegaly-like rat model recently developed by exogenous administration of insulin-like growth factor I (IGF-I) was used to investigate morphological and histopathological changes in orofacial structures and to clarify whether these changes were reversible. Exogenous administration of IGF-I evoked specific enlargement of the tongue with identifiable histopathological changes (increased muscle bundle width, increased space between muscle bundles, and increased epithelial thickness), elongation of the mandibular alveolar bone and ascending ramus, and lateral expansion of the mandibular dental arch. Regarding histopathological changes in the mandibular condyle, the cartilaginous layer width, bone matrix ratio, and number of osteoblasts were all significantly greater in this rat model. After normalization of the circulating IGF-I level, tongue enlargement and histopathological changes in the tongue and mandibular condyle were reversible, whereas morphological skeletal changes in the mandible remained

Pd-catalysed, Ag-assisted C2-H alkenylation of benzophospholes

A palladium-catalysed, silver-assisted regioselective C2-H alkenylation of benzophospholes with terminal alkenes has been developed. The palladium catalysis accommodates styrenes and electron-deficient alkenes including ester, ketone, nitrile, and phosphonate. Thus, this protocol enables the rapid construction of various benzophosphole-vinylene conjugations from the two simple C-H starting substrates. Optical properties of newly synthesized C2-alkenylated benzophospholes are also investigated.Tokura Y., Xu S., Kojima Y., et al. Pd-catalysed, Ag-assisted C2-H alkenylation of benzophospholes. Chemical Communications 58, 12208 (2022); https://doi.org/10.1039/D2CC04942B