Implementation of High-Speed Pseudo-Random-Number Generator with Chaotic and Random Neural Networks

Chaotic and random time series generated from improved chaotic and random neural network (CRNN) afford statistically appropriate pseudo-random number series for information security. Randomness of outputs of CRNN is empirically validated in detail, and control methods of an appropriate ratio of chaotic character and randomness in the time series for PRNG is reported. The rate of random number generation has reached 2.8530×10^12 b/s. In future, the generator may play an important role on implementing applications for protecting personal information on the Internet

フレキシブルコイルによる人工心臓用経皮エネルギー伝送に関する研究

学位の種別: 課程博士審査委員会委員 : （主査）東京大学教授 小野 稔, 東京大学特任准教授 林 直人, 東京大学教授 東 隆, 東京大学講師 森 墾, 東京大学講師 野澤 宏彰University of Tokyo(東京大学

The Q223R polymorphism in the leptin receptor associates with objectively measured light physical activity in free-living Japanese

AbstractPhysical activity (PA) is associated with reductions in the risk of all-cause mortality and in the prevalence of cardiovascular disease and stroke. Nevertheless, a large proportion of the general population may not be sufficiently active. PA level has been reported to be influenced by genetic factors, and we investigated whether Q223R polymorphism in the leptin receptor (LEPR) gene was associated with PA level. A total of 556 Japanese adults aged 24–65years old participated in this cross-sectional study. The duration and intensity of PA were objectively evaluated by triaxial accelerometry. Q223R polymorphism was determined by the TaqMan method. The distribution of Q223R polymorphism was: QQ 0.7%, QR 22.6%, and RR 76.6%. The relation between the LEPR genotype and PA level was analyzed by ANCOVA with age and sex as covariates in the Q dominant genetic model. There were significant differences between LEPR genotypes and the time spent in light PA or inactive time. The subjects with RR genotype showed significantly shorter time spent in light PA (RR genotype: 559.4±102.9min/day, QQ/QR genotype: 579.9±103.1min/day) and longer inactive time (RR genotype: 815.5±107.5min/day, QQ/QR genotype: 792.3±107.7min/day) than the subjects with QQ/QR genotype (P<0.05). There were no such differences in the time spent in moderate or vigorous PA. These results suggest that the variety of PA level, especially spontaneous PA in humans, is partly caused by diversity in the LEPR gene

Synthetic and biochemical studies on the effect of persulfidation on disulfide dimer models of amyloid β42 at position 35 in Alzheimer's etiology

Protein persulfidation plays a role in redox signaling as an anti-oxidant. Dimers of amyloid β42 (Aβ42), which induces oxidative stress-associated neurotoxicity as a causative agent of Alzheimer's disease (AD), are minimum units of oligomers in AD pathology. Met35 can be susceptible to persulfidation through its substitution to homoCys residue under the condition of oxidative stress. In order to verify whether persulfidation has an effect in AD, herein we report a chemical approach by synthesizing disulfide dimers of Aβ42 and their evaluation of biochemical properties. A homoCys-disulfide dimer model at position 35 of Aβ42 formed a partial β-sheet structure, but its neurotoxicity was much weaker than that of the corresponding monomer. In contrast, the congener with an alkyl linker generated β-sheet-rich 8–16-mer oligomers with potent neurotoxicity. The length of protofibrils generated from the homoCys-disulfide dimer model was shorter than that of its congener with an alkyl linker. Therefore, the current data do not support the involvement of Aβ42 persulfidation in Alzheimer's disease

An RNA aptamer with potent affinity for a toxic dimer of amyloid β42 has potential utility for histochemical studies of Alzheimer's disease

Oligomers of β-amyloid 42 (Aβ42), rather than fibrils, drive the pathogenesis of Alzheimer's disease (AD). In particular, toxic oligomeric species called protofibrils (PFs) have attracted significant attention. Herein, we report RNA aptamers with higher affinity toward PFs derived from a toxic Aβ42 dimer than toward fibrils produced from WT Aβ42 or from a toxic, conformationally constrained Aβ42 variant, E22P–Aβ42. We obtained these RNA aptamers by using the preincubated dimer model of E22P–Aβ42, which dimerized via a linker located at Val-40, as the target of in vitro selection. This dimer formed PFs during incubation. Several physicochemical characteristics of an identified aptamer, E22P–AbD43, suggested that preferential affinity of this aptamer toward PFs is due to its higher affinity for the toxic dimer unit (KD = 20 ± 6.0 nm) of Aβ42 than for less-toxic Aβ40 aggregates. Comparison of CD data from the full-length and random regions of E22P–AbD43 suggested that the preferential binding of E22P–AbD43 toward the dimer might be related to the formation of a G-quadruplex structure. E22P–AbD43 significantly inhibited the nucleation phase of the dimer and its associated neurotoxicity in SH-SY5Y human neuroblastoma cells. Of note, E22P–AbD43 also significantly protected against the neurotoxicity of WT Aβ42 and E22P–Aβ42. Furthermore, in an AD mouse model, E22P–AbD43 preferentially recognized diffuse aggregates, which likely originated from PFs or higher-order oligomers with curvilinear structures, compared with senile plaques formed from fibrils. We conclude that the E22P–AbD43 aptamer is a promising research and diagnostic tool for further studies of AD etiology

Simultaneous Validation of Seven Physical Activity Questionnaires Used in Japanese Cohorts for Estimating Energy Expenditure: A Doubly Labeled Water Study

Background: Physical activity questionnaires (PAQs) used in large-scale Japanese cohorts have rarely been simultaneously validated against the gold standard doubly labeled water (DLW) method. This study examined the validity of seven PAQs used in Japan for estimating energy expenditure against the DLW method.Methods: Twenty healthy Japanese adults (9 men; mean age, 32.4 [standard deviation {SD}, 9.4] years, mainly researchers and students) participated in this study. Fifteen-day daily total energy expenditure (TEE) and basal metabolic rate (BMR) were measured using the DLW method and a metabolic chamber, respectively. Activity energy expenditure (AEE) was calculated as TEE − BMR − 0.1 × TEE. Seven PAQs were self-administered to estimate TEE and AEE.Results: The mean measured values of TEE and AEE were 2,294 (SD, 318) kcal/day and 721 (SD, 161) kcal/day, respectively. All of the PAQs indicated moderate-to-strong correlations with the DLW method in TEE (rho = 0.57–0.84). Two PAQs (Japan Public Health Center Study [JPHC]-PAQ Short and JPHC-PAQ Long) showed significant equivalence in TEE and moderate intra-class correlation coefficients (ICC). None of the PAQs showed significantly equivalent AEE estimates, with differences ranging from −547 to 77 kcal/day. Correlations and ICCs in AEE were mostly weak or fair (rho = 0.02–0.54, and ICC = 0.00–0.44). Only JPHC-PAQ Short provided significant and fair agreement with the DLW method.Conclusions: TEE estimated by the PAQs showed moderate or strong correlations with the results of DLW. Two PAQs showed equivalent TEE and moderate agreement. None of the PAQs showed equivalent AEE estimation to the gold standard, with weak-to-fair correlations and agreements. Further studies with larger sample sizes are needed to confirm these findings

Accuracy of 12 Wearable Devices for Estimating Physical Activity Energy Expenditure Using a Metabolic Chamber and the Doubly Labeled Water Method: Validation Study

Background: Self-monitoring using certain types of pedometers and accelerometers has been reported to be effective for promoting and maintaining physical activity (PA). However, the validity of estimating the level of PA or PA energy expenditure (PAEE) for general consumers using wearable devices has not been sufficiently established.Objective: We examined the validity of 12 wearable devices for determining PAEE during 1 standardized day in a metabolic chamber and 15 free-living days using the doubly labeled water (DLW) method.Methods: A total of 19 healthy adults aged 21 to 50 years (9 men and 10 women) participated in this study. They followed a standardized PA protocol in a metabolic chamber for an entire day while simultaneously wearing 12 wearable devices: 5 devices on the waist, 5 on the wrist, and 2 placed in the pocket. In addition, they spent their daily lives wearing 12 wearable devices under free-living conditions while being subjected to the DLW method for 15 days. The PAEE criterion was calculated by subtracting the basal metabolic rate measured by the metabolic chamber and 0.1×total energy expenditure (TEE) from TEE. The TEE was obtained by the metabolic chamber and DLW methods. The PAEE values of wearable devices were also extracted or calculated from each mobile phone app or website. The Dunnett test and Pearson and Spearman correlation coefficients were used to examine the variables estimated by wearable devices.Results: On the standardized day, the PAEE estimated using the metabolic chamber (PAEEcha) was 528.8±149.4 kcal/day. The PAEEs of all devices except the TANITA AM-160 (513.8±135.0 kcal/day; P>.05), SUZUKEN Lifecorder EX (519.3±89.3 kcal/day; P>.05), and Panasonic Actimarker (545.9±141.7 kcal/day; P>.05) were significantly different from the PAEEcha. None of the devices was correlated with PAEEcha according to both Pearson (r=−.13 to .37) and Spearman (ρ=−.25 to .46) correlation tests. During the 15 free-living days, the PAEE estimated by DLW (PAEEdlw) was 728.0±162.7 kcal/day. PAEE values of all devices except the Omron Active style Pro (716.2±159.0 kcal/day; P>.05) and Omron CaloriScan (707.5±172.7 kcal/day; P>.05) were significantly underestimated. Only 2 devices, the Omron Active style Pro (r=.46; P=.045) and Panasonic Actimarker (r=.48; P=.04), had significant positive correlations with PAEEdlw according to Pearson tests. In addition, 3 devices, the TANITA AM-160 (ρ=.50; P=.03), Omron CaloriScan (ρ=.48; P=.04), and Omron Active style Pro (ρ=.48; P=.04), could be ranked in PAEEdlw.Conclusions: Most wearable devices do not provide comparable PAEE estimates when using gold standard methods during 1 standardized day or 15 free-living days. Continuous development and evaluations of these wearable devices are needed for better estimations of PAEE

Super-responder to pirfenidone therapy in IPF

Background : Pirfenidone (PFD), an anti-fibrosis drug for idiopathic pulmonary fibrosis (IPF), suppresses disease progression and delays decline of forced vital capacity. However, this drug rarely makes marked improvement of pulmonary function, chest high-resolution computed tomography (HRCT) findings and hypoxia. Case presentation : A 59 year-old-man, who was a former smoker and had a history of alcoholic liver cirrhosis, developed exertional dyspnea and was referred to our hospital. HRCT showed honeycomb changes with surrounding ground-glass opacity (GGO) in a predominantly basal and subpleural distribution. He was diagnosed with IPF and the treatment with PFD was started. At 16 months after the start of treatment, the predicted forced vital capacity value markedly improved from 82.9% to 98.6%. His resting-state partial pressure of arterial oxygen while breathing room air increased from a minimum of 54.7 mmHg (at 2 months treatment) to 72.5 mmHg. The GGO observed at diagnosis disappeared in HRCT. But after 32 months of treatment, his general condition got worse gradually, and he died from chronic progression of IPF after 48 months of treatment. Conclusion : Our case suggests that a complication of chronic liver disease and the existence of GGO may be characteristics of super-responder to PFD treatment for IPF patients