One-Dimensional Numerical Study on Ignition of the Helium Envelope in Dynamical Accretion during the Double-Degenerate Merger

In order for a double-detonation model to be viable for normal type Ia supernovae, the adverse impact of helium-burning ash on early-time observables has to be avoided, which requires that the helium envelope mass should be at most 0.02 solar mass. Most of the previous studies introduced detonation by artificial hot spots, and therefore the robustness of the spontaneous helium detonation remains uncertain. In the present work, we conduct a self-consistent hydrodynamic study on the spontaneous ignition of the helium envelope in the context of the double-degenerate channel, by applying an idealized one-dimensional model and a simplified 7 isotope reaction network. We explore a wide range of the progenitor conditions, and demonstrate that the chance of direct initiation of detonation is limited. Especially, the spontaneous detonation requires the primary envelope mass of >~ 0.03 solar mass. Ignition as deflagration is instead far more likely, which is feasible for the lower envelope mass down to ~ 0.01 solar mass, which might lead to subsequent detonation once the deflagration to detonation transition (DDT) would be realized. High-resolution multi-dimensional simulations are required to further investigate the DDT possibility, as well as accurately derive the threshold between the spontaneous detonation and deflagration ignition regimes. Another interesting finding is the effect of the composition; while mixing with the core material enhances detonation as previously suggested, it rather narrows the chance for deflagration due to the slower rate of 12C(alpha,gamma)16O reaction at the lower temperature ~108K, with the caveat that we presently neglect the proton-catalyzed reaction sequence of 12C(p,gamma)13O(alpha,p)16O.Comment: accepted for publication in Ap

Integrity Analysis of Authenticated Encryption Based on Stream Ciphers

We study the security of authenticated encryption based on a stream cipher and a universal hash function. We consider ChaCha20-Poly1305 and generic constructions proposed by Sarkar, where the generic constructions include 14 AEAD (authenticated encryption with associated data) schemes and 3 DAEAD (deterministic AEAD) schemes. In this paper, we analyze the integrity of these schemes both in the standard INT-CTXT notion and in the RUP (releasing unverified plaintext) setting called INT-RUP notion. We present INT-CTXT attacks against 3 out of the 14 AEAD schemes and 1 out of the 3 DAEAD schemes. We then show INT-RUP attacks against 1 out of the 14 AEAD schemes and the 2 remaining DAEAD schemes. We next show that ChaCha20-Poly1305 is provably secure in the INT-RUP notion. Finally, we show that 4 out of the remaining 10 AEAD schemes are provably secure in the INT-RUP notion

濃度勾配を有する予混合気中の斜めデトネーションに関する研究

学位の種別: 課程博士審査委員会委員 : （主査）東京大学教授 津江 光洋, 東京大学教授 鈴木 宏二郎, 東京大学准教授 寺本 進, 東京大学准教授 中谷 辰爾, 東京大学教授 土橋 律University of Tokyo(東京大学

Prediction of Total Drug Clearance in Humans Using Animal Data: Proposal of a Multimodal Learning Method Based on Deep Learning

Research into pharmacokinetics plays an important role in the development process of new drugs. Accurately predicting human pharmacokinetic parameters from preclinical data can increase the success rate of clinical trials. Since clearance (CL) which indicates the capacity of the entire body to process a drug is one of the most important parameters, many methods have been developed. However, there are still rooms to be improved for practical use in drug discovery research; "improving CL prediction accuracy" and "understanding the chemical structure of compounds in terms of pharmacokinetics". To improve those, this research proposes a multimodal learning method based on deep learning that takes not only the chemical structure of a drug but also rat CL as inputs. Good results were obtained compared with the conventional animal scale-up method; the geometric mean fold error was 2.68 and the proportion of compounds with prediction errors of 2-fold or less was 48.5%. Furthermore, it was found to be possible to infer the partial structure useful for CL prediction by a structure contributing factor inference method. The validity of these results of structural interpretation of metabolic stability was confirmed by chemists

Predicting Total Drug Clearance and Volumes of Distribution Using the Machine Learning-Mediated Multimodal Method through the Imputation of Various Nonclinical Data

Pharmacokinetic research plays an important role in the development of new drugs. Accurate predictions of human pharmacokinetic parameters are essential for the success of clinical trials. Clearance (CL) and volume of distribution (Vd) are important factors for evaluating pharmacokinetic properties, and many previous studies have attempted to use computational methods to extrapolate these values from nonclinical laboratory animal models to human subjects. However, it is difficult to obtain sufficient, comprehensive experimental data from these animal models, and many studies are missing critical values. This means that studies using nonclinical data as explanatory variables can only apply a small number of compounds to their model training. In this study, we perform missing-value imputation and feature selection on nonclinical data to increase the number of training compounds and nonclinical datasets available for these kinds of studies. We could obtain novel models for total body clearance (CLtot) and steady-state Vd (Vdss) (CLtot: geometric mean fold error [GMFE], 1.92; percentage within 2-fold error, 66.5%; Vdss: GMFE, 1.64; percentage within 2-fold error, 71.1%). These accuracies were comparable to the conventional animal scale-up models. Then, this method differs from animal scale-up methods because it does not require animal experiments, which continue to become more strictly regulated as time passes

Analysis of electrokinetic response of solid-liquid mixture during expression operation

In the expression process of slurry material using a filter-press of compression type, the process is divided into two periods: the filtration period and the consolidation period. Identification of the exact time of culmination of filtration period is essential for operating the press effectively. This study focused on the electrokinetic phenomena during expression operation of zinc oxide slurry to obtain information on the status of the filter chamber. We have measured the time course of electrical potential difference (EPD) between both ends of expressed material during the expression process using a labolatory piston press. The absolute value of EPD increased with the progress of the filtration period, followed by the decrease during the consolidation period. It was observed that the time at which the absolute value of the EPD began to decline coincided with the time at which the filtration period ended. EPD reached the plateau value at the end of consolidation. In a consolidation of homogeneous semisolid material, the absolute value of EPD increased at the beginning of the operation, followed by the decline to the plateau value. We have extended the theoretical equation of streaming potential for a straight capillary to be applied to a tortuous flow path of the expressed material. The time course of EPD can be qualitatively explained by using the proposed equation for EPD and calculated liquid pressure distributions based on the conventional filtration andconsolidation theories by considering the medium resistance

Optimizing Charge Switching in Membrane Lytic Peptides for Endosomal Release of Biomacromolecules.

Endocytic pathways are practical routes for the intracellular delivery of biomacromolecules. Along with this, effective strategies for endosomal cargo release into the cytosol are desired to achieve successful delivery. Focusing on compositional differences between the cell and endosomal membranes and the pH decrease within endosomes, we designed the lipid-sensitive and pH-responsive endosome-lytic peptide HAad. This peptide contains aminoadipic acid (Aad) residues, which serve as a safety catch for preferential permeabilization of endosomal membranes over cell membranes, and His-to-Ala substitutions enhance the endosomolytic activity. The ability of HAad to destabilize endosomal membranes was supported by model studies using large unilamellar vesicles (LUVs) and by increased intracellular delivery of biomacromolecules (including antibodies) into live cells. Cerebral ventricle injection of Cre recombinase with HAad led to Cre/loxP recombination in a mouse model, thus demonstrating potential applicability of HAad in vivo

最先端手術への教育とクリニカルアナトミーラボ

Recently, endoscopic surgery is the most common procedurein the field of thoracic surgery. The newestthoracic surgeryapproaches are the video-assisted thoracic surgery（VATS）, the one-port video-assisted thoracic surgery, and the robotic surgery. The individual advantages and disadvantages of these procedures have been discussed. VATS covers a field of view of the surgical field from the leg to the head. The basic method in performing VATS is that the surgeon operates on the abdominal area of the patient and the assistant expands the surgical field from the patient’s back. It is currently the standard surgical procedure. The advantage of one-port VATS is the one port itself and its cosmetic advantages and pain reduction. The advantage of robotic surgery is that it has a clear three-dimensional enlarged field of view and can be performed using the delicate moving robotic arm. However, a good surgical training system should be established for the familiarization of these procedures. The clinical anatomy laboratory is the most efficient surgical training in addition to dry and wet lab training. Our institution has fresh-frozen cadavers, which are rare in Japan. The participating thoracic surgeons underwent training for VATS lobectomy, subxiphoid extended thymectomy, and pleurectomy decortication. This training is beneficial for educational and clinical purposes. In the future, we must obtain consistent surgical education before and after graduation using fresh-frozen cadavers. At the same time, a good organ model for training is also necessary. The surgeon has to cooperate with anatomy doctors for the development of a good surgical organ model. For the development of future surgical medicine, surgical training programs should be implemented