6-{5-Amino-3-tert-butyl-4-[(E)-(3-methyl-1,2,4-thiadiazol-5-yl)diazen­yl]-1H-pyrazol-1-yl}-1,3,5-triazine-2,4(1H,3H)-dione–1-methyl­pyrrolidin-2-one–water (1/1/1)

In the title compound, C13H16N10O2S·C5H9NO·H2O, the entire 1-methylpyrrolidin-2-one (NMP) mol­ecule is disordered over two sites with occupancies of 0.488 (5) and 0.512 (5). The six-membered triazine ring and the two five-membered pyrazole and thiadia­zole rings, together with the diazene (–N=N–) linkage are almost coplanar (r.m.s. deviation for the non-H atoms = 0.0256 Å) with methyl groups from the tert-butyl substituent on the pyrazole ring located above and below the plane. Three intra­molecular N—H⋯N hydrogen bonds contribute to the planarity of the system. The O atom of the NMP mol­ecule is hydrogen bonded to an O—H group of water. In turn, the water mol­ecule is hydrogen bonded to the mono-azo skeleton through inter­molecular N—H⋯O and O—H⋯N hydrogen bonds. At both ends of the long mol­ecular axis of the main mol­ecule there are inter­molecular N—H⋯N hydrogen bonds, arranged in a head-to-tail fashion, between the N—H group of the triazine ring of one mol­ecule and the N atom of the thia­diazole ring of a neighboring mol­ecule. These form a polymeric chain along [110] or [10]. The main mol­ecules are stacked alternately along the b axis, which effectively cancels their dipole moments. In addition, pairs of alternate molecules are dimerized via inter­molecular hydrogen bonds involving the solvent mol­ecules

Venomics Study of <em>Protobothrops flavoviridis</em> Snake: How Venom Proteins Have Evolved and Diversified?

Venomics projects have been conducted to disclose the divergent profiles and evolution of various venomous animals. Here, we describe the venomics project including genome and transcriptome of habu snake, leading to drug discovery. Venomics project including the decoding of their whole genomes revealed partly a producing mechanism of various venom proteins including accelerated evolution and alternative splicing and how the toxic organisms have evolved from the nontoxic ones. In addition, the venomics analysis of transcriptomes and proteomes beyond species reveals the relationship between the geographical distribution and evolution of toxic organisms. The abundance of different gene products within a gene family caused by accelerated evolution and alternative splicing may contribute to expand the repertoire of effective weapons to prey capture accompanied with neofunctionalization

Jet collimation in the ejecta of double neutron star merger: new canonical picture of short gamma-ray bursts

The observations of jet breaks in the afterglows of short gamma-ray bursts (SGRBs) indicate that the jet has a small opening angle of < 10{\deg}. The collimation mechanism of the jet is a longstanding theoretical problem. We numerically analyze the jet propagation in the material ejected by double neutron star merger, and demonstrate that if the ejecta mass is > 10^{-2} M_{sun}, the jet is well confined by the cocoon and emerges from the ejecta with the required collimation angle. Our results also suggest that there are some populations of choked (failed) SGRBs or low-luminous new types of event. By constructing a model for SGRB 130603B, which is associated with the first kilonova/macronova can- didate, we infer that the equation-of-state of neutron stars would be soft enough to provide sufficient ejecta to collimate the jet, if this event was associated with a double neutron star merger.Comment: 6 pages, 3 figures, accepted for publication in the Astrophysical Journal Letter

Ultimate low system dark count rate for superconducting nanowire single-photon detector

The dark count rate (DCR) is a key parameter of single-photon detectors. By introducing a bulk optical band-pass filter mounted on a fiber-to-fiber optical bench cooled at 3 K and blocking down to 5 micrometer, we suppressed the DCR of a superconducting nanowire single-photon detector by more than three orders of magnitude. The DCR is limited by the blackbody radiation through a signal passband of 20 nm bandwidth. The figure of merit, system detection efficiency, and DCR were 2.7 x 10^11, 2.3 %, and 0.001 Hz, respectively. Narrowing the bandwidth to 100 GHz suppresses the DCR to 0.0001 Hz and the figure of merit increases to 1.8 x 10^12.Comment: to appear in Optics Letter

Artificial Intelligence-based Detection of Epileptic Discharges from Pediatric Scalp Electroencephalograms: A Pilot Study

We developed an artificial intelligence (AI) technique to identify epileptic discharges (spikes) in pediatric scalp electroencephalograms (EEGs). We built a convolutional neural network (CNN) model to automatically classify steep potential images into spikes and background activity. For the CNN model’ training and validation, we examined 100 children with spikes in EEGs and another 100 without spikes. A different group of 20 children with spikes and 20 without spikes were the actual test subjects. All subjects were ≥ 3 to 0.97 when referential and combination EEG montages were used, and 0.99, indicating high performance of the classification method. EEG patterns that interfered with correct classification included vertex sharp transients, sleep spindles, alpha rhythm, and low-amplitude ill-formed spikes in a run. Our results demonstrate that AI is a promising tool for automatically interpreting pediatric EEGs. Some avenues for improving the technique were also indicated by our findings

エネルギー関数の形状に着目した焼きなまし法の適用に関する研究

本論文ではエネルギー関数の形状に着目した焼きなまし法の適用方法について提案し，Boltzmann Machineにおける事後分布推定，観光経路推薦問題を対象としてその有効性を示す．Boltzmann Machine や焼きなまし法等，現在利用されている機械学習や最適化問題の解法は統計物理学に基づくものが多い．これらはいずれも物質を構成する分子の微視的状態を記述するBoltzmann分布をもとに定式化され，Boltzmann Machineでは与えられた分布に適したエネルギー関数を学習により決定する．学習結果から得られる分布は有用な潜在的表現を有することからNeural Networksに対する事前学習法としてよく利用される．また，Boltzmann分布に従う系では，エネルギー関数の値が低い状態が高い出現確率を持ち，温度が低いほどその傾向が強くなる．焼きなまし法はこの性質を利用し，最適化問題における目的関数をエネルギー関数とした手法である．焼きなまし法を用いれば局所最適化法で問題となる局所最適解への収束性を緩和することができ，Traveling Salesman Problem (TSP)等さまざまな問題に対して適用されている．焼きなまし法は，計算量の多さと，温度変化過程の与え方が自明でないことが短所として指摘されている．さらに，本論文では，Deep Boltzmann Machineの事後分布推定に対して効果的でないこと，TSPに対しても問題の規模が大きくなるにつれ，Markov Chain Monte Carlo (MCMC)法における棄却率が高まり，効率が低下するといった問題点があることも明らかにする．これらの問題に対し，本論文ではエネルギー関数の形状に着目することで，焼きなまし法における上記問題の解決を目的とする．従来手法がMCMC法の探索方法を決定する提案分布に対し局所最適化法をそのまま用い，エネルギー関数には最適化問題として一般的に定義されていた目的関数をそのまま用いているのに対し，提案手法では，問題ごとに適切なエネルギー関数と，棄却率の低い提案分布の構築を行う．具体的な例として，Boltzmann Machineと観光経路推薦問題に提案手法を適用し，有効性を示す．Boltzmann Machine は階層構造を持たせたDeep Boltzmann Machineとして広く用いられ，事前学習やマルチモーダルデータに対するモデルとして近年注目を集めている．しかし，現在一般に用いられているGibbs Sampling法を適用しただけでは，層数の増加に伴い事後分布の推定が難しくなる．また，本論文で示す通り，焼きなまし法を適用しても精度を改善することはできない．提案手法では，階層構造を反映したエネルギー関数の構築と温度の制御を行うことで事後分布の推定精度を改善する．観光経路推薦問題への適用においては，TSPに対してMCMC法における提案分布に適切なものを選ぶことで探索効率を改善できることを示す．また，観光経路推薦問題を対象として，訪問スポットの選択も含むようにTSPを拡張した選択的TSPに対しては，従来節点と辺を用いて定式化されていたのに対し，辺のみを用い，さらに，自己ループ辺を導入することで次元数を固定とする定式化を提案し，確率場として問題を定義可能とする．また，経路長に対する制約を連続な関数で表現することで焼きなまし法を適用可能とする．これらの工夫により高速に解を探索可能となり，従来手法では固定とされていたスポット間の移動経路をユーザの嗜好に応じて決定する等の柔軟な経路推薦が可能となる．本論文は5章からなり，1章で序論，2章では本論文の基礎となる関連研究について述べ，3章でBoltzmann Machineに対する焼きなまし法の適用法，4章で観光経路推薦問題に対する焼きなまし法の適用法を提案する．5章では本論文で論じたことをまとめる．3章では，はじめにBoltzmann Machineにより評価値行列から抽出される潜在因子の性質を調査した結果に基づき，事後分布推定におけるBoltzmann Machineの特性について考察する．その後，Deep Boltzmann Machineのエネルギー関数を層ごとに分割し，各層に対応した関数ごとに温度を割り当てることで温度分布を表現可能とする手法を提案する．これにより，種結晶から金属の単結晶を得る手法であるFloating Zone法を導入し，入力側から温度を低下させることで事後分布を高精度に近似できることを示す.4章では，観光経路推薦問題の概要，および既存研究における定式化を紹介した後，本論文で提案する定式化について説明する．提案する定式化を用いて，エネルギー関数により経路長に対する制約を表現する方法，棄却率の低い提案分布を用いてMCMC法を構築する方法を述べる．人工および観光客の位置情報から作成されたデータセットを用いて，提案手法の有効性を示す.本論文で得られた成果は，焼きなまし法を適用するにあたりエネルギー関数の形状を考慮することの重要性を示したものであり，対象としたBoltzmann Machineや，観光経路推薦問題だけでなく，より多様な用途における焼きなまし法の適用可能性の拡大へ貢献するものである．首都大学東京, 2019-03-25, 博士（工学）首都大学東

Exclusion of the Possibility of "False Ripples" From Ripple Band High-Frequency Oscillations Recorded From Scalp Electroencephalogram in Children With Epilepsy

Aim Ripple-band epileptic high-frequency oscillations (HFOs) can be recorded by scalp electroencephalography (EEG), and tend to be associated with epileptic spikes. However, there is a concern that the filtration of steep waveforms such as spikes may cause spurious oscillations or "false ripples." We excluded such possibility from at least some ripples by EEG differentiation, which, in theory, enhances high-frequency signals and does not generate spurious oscillations or ringing. Methods The subjects were 50 pediatric patients, and ten consecutive spikes during sleep were selected for each patient. Five hundred spike data segments were initially reviewed by two experienced electroencephalographers using consensus to identify the presence or absence of ripples in the ordinary filtered EEG and an associated spectral blob in time-frequency analysis (Session A). These EEG data were subjected to numerical differentiation (the second derivative was denoted as EEG ''). The EEG '' trace of each spike data segment was shown to two other electroencephalographers who judged independently whether there were clear ripple oscillations or uncertain ripple oscillations or an absence of oscillations (Session B). Results In Session A, ripples were identified in 57 spike data segments (Group A-R), but not in the other 443 data segments (Group A-N). In Session B, both reviewers identified clear ripples (strict criterion) in 11 spike data segments, all of which were in Group A-R (p < 0.0001 by Fisher's exact test). When the extended criterion that included clear and/or uncertain ripples was used in Session B, both reviewers identified 25 spike data segments that fulfilled the criterion: 24 of these were in Group A-R (p < 0.0001). Discussion We have demonstrated that real ripples over scalp spikes exist in a certain proportion of patients. Ripples that were visualized consistently using both ordinary filters and the EEG '' method should be true, but failure to clarify ripples using the EEG '' method does not mean that true ripples are absent. Conclusion The numerical differentiation of EEG data provides convincing evidence that HFOs were detected in terms of the presence of such unusually fast oscillations over the scalp and the importance of this electrophysiological phenomenon