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In urban basins, localized torrential rain increases the water level of rivers in an extremely short time, thereby leading to flooding within an hour. Therefore, to achieve early evacuation, the water level should be accurately forecasted. The outflow process in urban areas employs the sewer system to discharge the water back to rivers. However, the data for the sewer system are not freely available, and it requires much work and time to design a physical model based on such data. Thus, a vector autoregressive model to develop a water level forecast system that uses observed rainfall and water level is being used. Additionally, this model was used to ensure information conducive to evacuation approximately 20 min in advance and to assess its forecast accuracy, despite the very limited data—water levels at one point and average rainfall at another—without the need to build a physical model such as that which is used in sewer pipe calculations. Compared to the observed water level, the calculated water level increased faster; and thus, the forecast leaned toward safety in evacuation. Furthermore, the data from past five torrential rainfall events to achieve a stable forecast; this method can be applied to basins with limited observation data. Therefore, these results indicate that this method can be applied as a water level forecast method for basins with an extremely fast flood arrival time.

本稿においては，甲南大学で実施されている授業改善アンケートデータを用いて，複数クラスが開講されている同一科目における，学生の授業評価に関する共通性を統計的に検証する。各設問の選択肢を授業評価として「肯定的」か「非肯定的」かに集約し，クラス横断的に共通する分布形状を読み取ることができるかどうかで共通性の有無を判断する。分析の結果，開講された４クラスのうち３クラスについて各設問に関し８割以上の肯定的評価が観察され，同一科目の複数クラス間で学生の授業評価に共通するパターンを見い出すことができた。

In recent years, climate change intensifies heavy rainfall, resulting in annual flood damage. Population is increasing worldwide, and urbanization is expected to continue expanding. Under these circumstances, once an inundation occurs, the damage is expected to be more extensive than ever before. Therefore, in this study, we are analyzing the effects of DEM resolution and land use data, which are the calculation conditions for inundation calculations in flood forecasting, on inundation characteristics such as inundation magnitude and duration during large-scale inundation. In this paper, the target watershed was the Tone River in Japan, where major floods have occurred in the past, and the analysis was conducted in the plain area. DEM data and land use data are important factors in determining inundation characteristics; The higher the resolution of the DEM data, the better it can represent the microtopography, which in turn affects the inundation flow. Also, land use data determines the roughness coefficient, which affects the velocity of floodwaters, and the infiltration capacity and initial loss into the ground. In this paper, The DEM data were analyzed with resolutions of 5m, 25m, 50, 100m, and 250m. The land use data for the years 1978, 1987, 1997, 2006 and 2016 were used to analyze the inundation characteristics due to increasing urbanization.The results of inundation analysis with different resolutions of DEM data show that the resolution has no significant effect on the inundation rate. However, as for the inundation area, the larger the mesh size, the larger the inundation area, which is expected to be caused by the homogenization of DEM data. It was also found that as urbanization progresses, the inundation area spreads faster. In addition, the urbanization process affects the diminishing period of inundation rather than the expansion process, because it loses the function of infiltration capacity, and the inundation depth is less likely to decrease.

Assessing a compound’s mutagenicity using machine learning is an important activity in the drug discovery and development process. Traditional methods of mutagenicity detection, such as Ames test, are expensive and time and labor intensive. In this context, in silico methods that predict a compound mutagenicity with high accuracy are important. Recently, machine-learning (ML) models are increasingly being proposed to improve the accuracy of mutagenicity prediction. While these models are used in practice, there is further scope to improve the accuracy of these models. We hypothesize that choosing the right features to train the model can further lead to better accuracy. We systematically consider and evaluate a combination of novel structural and molecular features which have the maximal impact on the accuracy of models. We rigorously evaluate these features against multiple classification models (from classical ML models to deep neural network models). The performance of the models was assessed using 5- and 10-fold cross-validation and we show that our approach using the molecule structure, molecular properties, and structural alerts as feature sets successfully outperform the state-of-the-art methods for mutagenicity prediction for the Hansen et al. benchmark dataset with an area under the receiver operating characteristic curve of 0.93. More importantly, our framework shows how combining features could benefit model accuracy improvements.

Background Several rodent models with chemically induced colon cancer have been developed. Among these models, dextran sulfate sodium (DSS), a colitis inducer, combined with azoxymethane as a colon mutagenic carcinogen, is commonly used. We previously reported that although benzo [a] pyrene (BP) is mutagenic but not carcinogenic in the colon, it rapidly develops colon tumors at a high incidence/multiplicity after treatment with DSS. In the present study, we examined whether other colon-mutagenic non-carcinogens (CMNCs) induced colon tumors after treatment with DSS. Results o-Aminoazotoluene, 7,12-dimethylbenz[a]anthracene, and N-ethyl-N-nitrosourea were selected as CMNCs. Male CD2F1 mice were orally administered CMNC for 5 consecutive days. After a 9-day dose-free period, mice were treated with 4% DSS in drinking water for 1 week. Three months after DSS treatment, colon samples were collected for histopathology and β-catenin immunohistochemistry analyses. All CMNCs in combination with DSS induced colonic adenocarcinomas at a high incidence/multiplicity in the distal and middle parts of the colon, coinciding with the location of colitis. Unlike in normal cells where β-catenin is exclusively located on the cell membrane, in adenocarcinoma cells, it was translocated to both the nucleus and cytoplasm or only to cytoplasm. The translocation of β-catenin is closely associated with colon carcinogenesis in rodents and humans. No colonic tumors or dysplastic lesions were found after exposure to either CMNC or DSS alone. Conclusion We provided further evidence clearly showing that CMNCs can rapidly induce colonic tumors in mice with DSS-induced colitis, even if they are not colonic carcinogens.

We create robots to help people, and we believe that our robots can be more helpful if they look and behave as humans do. People usually prefer help from those whom they like. Some people can be li...

"Nutraceuticals" are well-tolerated natural dietary compounds with drug-like properties that make them attractive as Alzheimer's disease (AD) therapeutics. Combination therapy for AD has garnered attention following a recent National Institute on Aging mandate, but this approach has not yet been fully validated. In this report, we combined the two most promising nutraceuticals with complementary anti-amyloidogenic properties: the plant-derived phenolics (-)-epigallocatechin-3-gallate (EGCG, an α-secretase activator) and ferulic acid (FA, a β-secretase modulator). We used transgenic mice expressing mutant human amyloid β-protein precursor and presenilin 1 (APP/PS1) to model cerebral amyloidosis. At 12 months of age, we orally administered EGCG and/or FA (30 mg/kg each) or vehicle once daily for 3 months. At 15 months, combined EGCG-FA treatment reversed cognitive impairment in most tests of learning and memory, including novel object recognition and maze tasks. Moreover, EGCG- and FA-treated APP/PS1 mice exhibited amelioration of brain parenchymal and cerebral vascular β-amyloid deposits and decreased abundance of amyloid β-proteins compared with either EGCG or FA single treatment. Combined treatment elevated nonamyloidogenic soluble APP-α and α-secretase candidate and down-regulated amyloidogenic soluble APP-β, β-C-terminal APP fragment, and β-secretase protein expression, providing evidence for a shift toward nonamyloidogenic APP processing. Additional beneficial co-treatment effects included amelioration of neuroinflammation, oxidative stress, and synaptotoxicity. Our findings offer preclinical evidence that combined treatment with EGCG and FA is a promising AD therapeutic approach.

It is often assumed that genotoxic substances will be detected more easily by using in vitro rather than in vivo genotoxicity tests since higher concentrations, more cytotoxicity and static exposures can be achieved. However, there is a paucity of data demonstrating whether genotoxic substances are detected at lower concentrations in cell culture in vitro than can be reached in the blood of animals treated in vivo. To investigate this issue, we compared the lowest concentration required for induction of chromosomal damage in vitro (lowest observed effective concentration, or LOEC) with the concentration of the test substance in blood at the lowest dose required for biologically relevant induction of micronuclei in vivo (lowest observed effective dose, or LOED). In total, 83 substances were found for which the LOED could be identified or estimated, where concentrations in blood and micronucleus data were available via the same route of administration in the same species, and in vitro chromosomal damage data were available. 39.8 % of substances were positive in vivo at blood concentrations that were lower than the LOEC in vitro, 22.9 % were positive at similar concentrations, and 37.3 % of substances were positive in vivo at higher concentrations. Distribution analysis showed a very wide scatter of > 6 orders of magnitude across these 3 categories. When mode of action was evaluated, the distribution of clastogens and aneugens across the 3 categories was very similar. Thus, the ability to detect induction of micronuclei in bone marrow in vivo regardless of the mechanism for micronucleus induction, is clearly not solely determined by the concentration of test substance which induced chromosomal damage in vitro.

Several plant-derived compounds have demonstrated efficacy in pre-clinical Alzheimer's disease (AD) rodent models. Each of these compounds share a gallic acid (GA) moiety, and initial assays on this isolated molecule indicated that it might be responsible for the therapeutic benefits observed. To test this hypothesis in a more physiologically relevant setting, we investigated the effect of GA in the mutant human amyloid β-protein precursor/presenilin 1 (APP/PS1) transgenic AD mouse model. Beginning at 12 months, we orally administered GA (20 mg/kg) or vehicle once daily for 6 months to APP/PS1 mice that have accelerated Alzheimer-like pathology. At 18 months of age, GA therapy reversed impaired learning and memory as compared with vehicle, and did not alter behavior in nontransgenic littermates. GA-treated APP/PS1 mice had mitigated cerebral amyloidosis, including brain parenchymal and cerebral vascular β-amyloid deposits, and decreased cerebral amyloid β-proteins. Beneficial effects co-occurred with reduced amyloidogenic and elevated nonamyloidogenic APP processing. Furthermore, brain inflammation, gliosis, and oxidative stress were alleviated. We show that GA simultaneously elevates α- and reduces β-secretase activity, inhibits neuroinflammation, and stabilizes brain oxidative stress in a pre-clinical mouse model of AD. We further demonstrate that GA increases abundance of a disintegrin and metalloproteinase domain-containing protein 10 (ADAM10, Adam10) proprotein convertase furin and activates ADAM10, directly inhibits β-site APP cleaving enzyme 1 (BACE1, Bace1) activity but does not alter Adam10 or Bace1 transcription. Thus, our data reveal novel post-translational mechanisms for GA. We suggest further examination of GA supplementation in humans will shed light on the exciting therapeutic potential of this molecule.

All metropolitan cities in Japan are located in low-lying areas that surround ports. Accordingly, significant floods that occur in these cities will trigger the simultaneous occurrence of flooding by river water and inland flooding. However, existing studies have focused on the impact of flooding by river water, inland flooding, and high tide in tidal rivers, and disaster mitigation measures focused on detailed flooding processes in such flooding areas have not been conducted thus far. This study focused on a tidal river, i.e., Katabira River of Yokohama city, one of Japan&rsquo, s metropolitan cities, to construct a simultaneous occurrence model of flooding by river water and inland flooding, including the impact of a high tide. Numerical analysis was conducted using this model, and the results show that the flooded area significantly changed from 0.004 to 0.149 km2 according to the tide level of the estuary. Moreover, by simultaneously solving the calculation of flooding by river water and inland flooding, we found that there was a difference of 50 min between the occurrences of these floods. Therefore, we found that there is a possibility that, if evacuation is not conducted at the time of occurrence of inland flooding, evacuation during subsequent river-water flooding may not be possible. Based on these results, our proposed method was found to be useful for tidal rivers of metropolitan cities.

The aim of this paper is to verify the accuracy of the real-time flood prediction model, using the time-series analysis. Forecast information of water level is important information that encourages residents to evacuate. Generally, flood forecasting is conducted by using runoff analysis. However, in developing countries, there are not enough hydrological data in a basin. Therefore, this study assumes where poor hydrologic data basin and evaluates it through reproducibility and prediction by using time series analysis which statistical model with the water level data and rainfall data. The model is applied to the one catchment of the upper Tone River basin, one of the first grade river in Japan. This method is possible to reproduce hydrograph, if the observation stations exist several points in the basin. And using the estimated parameters from past flood events, we can apply this method to predict the water level until the flood concentration time which the reference point and observation station. And until this time, the peak water level can be predicted with the accuracy of several 10cm. Prediction can be performed using only water level data, but by adding rainfall data, prediction can be performed for a longer time.

This study is to analyze the evacuation behavior of residents living in the mountainous area and predict landslide disasters during heavy rain. 70% of Japan has are mountainous areas, and landslide disasters have occurred due to heavy rains caused by typhoons and heavy rainfall, etc. the annual average amount of damage caused by landslide disasters is 1000 in recent years. Also, landslide disaster warning information and evacuation information are important, it is difficult to predict landslide disasters, however, if we issued the evacuation advisory when the disasters already happened, there will be not enough time for the evacuation. In order to protect residents from such disasters, it is important to clarify "what information is effective for evacuation" and "when should those information be released?" Therefore, we conducted a survey on the residents in the mountainous areas which suffered from the heavy rain disaster in 2017 and analyzed the answers.As a result, some residents evacuated before the evacuation information was issued. Because some landslide disasters occurred even before the first evacuation information was transmitted, and they felt danger. This result shows that the early information based on the prediction of the disasters is important in mountainous areas.Therefore, we suggested a method for predicting landslide disasters, the method uses a rainfall and runoff tank model with high reproducibility and robustness of geological characteristics and uses the cumulative rainfall at the time of disaster occurrence as an index. As a result, this model predicted the occurrence of the landslide disaster 3 hours earlier by using forecasted rainfall. it is an effective method.

Background Acetone is a common alternative solvent used in the Ames test when test chemicals are unstable or poorly soluble in water or dimethyl sulfoxide (DMSO). Yet, there is a very limited number of studies evaluating acetone as a solvent in the modified Ames test with preincubation (preincubation test). Results We evaluated the acetone as a solvent for the preincubation test. Fourteen mutagens dissolved in acetone was added each to the reaction mixture at 2 different volumes (25 or 50 μL) to examine mutagenicity using bacterial test strains recommended in the Organization for Economic Cooperation and Development (OECD) test guideline 471, and compared with DMSO (100 μL). Cytotoxicity of acetone was also examined in these bacterial strains. TA1537 was most sensitive to the cytotoxicity of acetone, the degree of which was moderate and similar to DMSO in TA1537 without S9 mix. In other strains, cytotoxicity was limited to a mild degree with or without S9 mix. Cytotoxicity of acetone did not affect detection of mutagenicity of any mutagens; many of them being comparable or less mutagenic than those with DMSO. Conclusions These findings indicate that acetone is a viable candidate as a solvent for the preincubation test in the 5 bacterial strains.

To date, there is no effective Alzheimer's disease (AD)-modifying therapy. Nonetheless, combination therapy holds promise, and nutraceuticals (natural dietary compounds with therapeutic properties) and their synthetic derivatives are well-tolerated candidates. We tested whether combination therapy with octyl gallate (OG) and ferulic acid (FA) improves cognition and mitigates AD-like pathology in the presenilin-amyloid β-protein precursor (PSAPP) transgenic mouse model of cerebral amyloidosis. One-year-old mice with established β-amyloid plaques received daily doses of OG and FA alone or in combination for 3 months. PSAPP mice receiving combination therapy had statistically significant improved cognitive function versus OG or FA single treatment on some (but not all) measures. We also observed additional statistically significant reductions in brain parenchymal and cerebral vascular β-amyloid deposits as well as brain amyloid β-protein abundance in OG- plus FA-treated versus singly-treated PSAPP mice. These effects coincided with enhanced nonamyloidogenic amyloid β-protein precursor (APP) cleavage, increased α-secretase activity, and β-secretase inhibition. We detected elevated expression of nonamyloidogenic soluble APP-α and the α-secretase candidate, a disintegrin and metalloproteinase domain-containing protein 10. Correspondingly, amyloidogenic β-carboxyl-terminal APP fragment and β-site APP-cleaving enzyme 1 expression levels were reduced. In parallel, the ratio of β- to α-carboxyl-terminal APP fragment was decreased. OG and FA combination therapy strikingly attenuated neuroinflammation, oxidative stress, and synaptotoxicity. Co-treatment afforded additional statistically significant benefits on some, but not all, of these outcome measures. Taken together, these data provide preclinical proof-of-concept for AD combination therapy.

Plasmodium spp. protozoa cause malaria and are known to infect humans and a variety of animal species including macaque monkeys. Here we report both our experience with malaria recrudescence in cynomolgus monkeys (Macaca fascicularis) in a toxicity study and the results of a survey on Plasmodium infection in cynomolgus monkeys imported to Japan for laboratory use. A cynomolgus monkey from the toxicity study presented with severe anemia and Plasmodium protozoa in erythrocytes on a thin blood smear and was subsequently diagnosed with symptomatic malaria. In this animal, congestion and accumulation of hemozoin (malaria pigment) in macrophages were noted in the enlarged and darkly discolored spleen. As a follow-up for the experience, spleen sections from 800 cynomolgus monkeys in toxicity studies conducted between 2003 and 2013 were retrospectively examined for hemozoin deposition as a marker of Plasmodium infection. The origin of the animals included Cambodia, China, Indonesia, and Vietnam. Hemozoin deposition was confirmed in 44% of all examined monkeys. Monkeys from Indonesia showed the highest incidence of hemozoin deposition (approx. 80%). A high prevalence of Plasmodium infection in laboratory monkeys was also confirmed with polymerase chain reaction (PCR) by using Plasmodium genus-specific primers. Although Japan is not a country with endemic malaria, it is important to be aware of the prevalence and potential impact of background infection with Plasmodium spp. and recrudescence of symptomatic malaria in imported laboratory monkeys on pharmaceutical toxicity studies.

Benzo[a]pyrene (BP) is highly mutagenic and yet does not lead to tumor development in the murine colon. We recently reported the generation of colonic tumors one week after treatment with BP followed by dextran sulfate sodium (DSS), a colitis-inducer. In this BP/DSS model, male CD2F1 mice were treated orally with BP at 125 mg/kg/day for 5 days, followed by 4% DSS in drinking water for one week. There has been no report so far on the molecular mechanisms involved in tumor development in this model. In the present study, we performed global gene expression analysis on the colonic mucosae obtained from BP-exposed mice one week after treatment with DSS and those treated with the vehicle, BP, or DSS alone. Global gene expression analysis revealed that there were 563 genes preferentially altered (≥2-fold vs vehicle group) in the colonic mucosae exposed to both BP and DSS. Furthermore, comparative gene expression analysis combined with Ingenuity Pathway Analysis™ identified 2 genes associated with Wnt/β-catenin signaling pathway that were preferentially up-regulated (≥2-fold vs vehicle group) when BP and DSS were treated in combination in the distal part (site of predilection for tumor induction) of the colonic mucosae, especially in colonic tumors: WNT inhibitory factor 1 (Wif1; 14.6-fold increase) and interferon induced membrane protein 3 (Ifitm3; 5.7-fold increase). In colonic tumors, expression of Wif1 and Ifitm3 proteins were both confirmed by western blot analysis. These findings suggest that these genes are associated with rapid induction of colonic tumors in mice after exposure to BP/DSS, providing insights into the mechanisms of the BP/DSS short-term colon carcinogenesis.

The lifespan and age-specific fecundity of female ring-tailed lemurs (Lemur catta) were estimated from a 24-year longitudinal dataset based on individual identification at Berenty Reserve, Madagascar. The mean lifespan of females in 10-year (1989-1998) birth cohorts was 4.9 ± 4.9 years (n = 77), and the longest recorded lifespan in the population was 20 years. The mortality rate of adult females increased to ≥20% at 10-11 years old and reached 33-50% at 12-15 years old. Although the birth rate of old females (12-17 years old) was 72.0%, slightly lower than that of prime adult females (4-11 years old), i.e. 80.2%, no significant difference was found between them. Half of the females who reached the age of 12 years gave birth in the last year of their life. The oldest mother to give birth was 17 years old. These results suggest that most females can maintain reproductive performance in their later life and that there is no evidence for a postreproductive lifespan in this species.

The behavior of a social robot is designed based on either its emotional state or social situation. In this research, we defined these expressions as the affective and social expressions, and proposed a new emotional expression method to integrate these two expressions. It is known that a human has involuntary facial muscles around the eyes, and voluntary facial muscles around the mouth. Thus, it is considered that facial muscles around the eyes express the affective expressions, while facial muscles around the mouth express the social expressions. In an experiment involving a human-robot conversation, using the proposed method, the results showed a sense of human likeness and sociality. Furthermore, the intimacy evaluation results showed that the social expressions work effectively when the intimacy does not require high social bonding such as the desire for friendship. However, the affective expressions are necessary for evaluating intimacy that requires higher social bonding, such as wanting to live with someone.

Amyloid precursor protein (APP) proteolysis is required for production of amyloid-β (Aβ) peptides that comprise β-amyloid plaques in the brains of patients with Alzheimer disease (AD). Here, we tested whether the experimental agent methylene blue (MB), used for treatment of methemoglobinemia, might improve AD-like pathology and behavioral deficits. We orally administered MB to the aged transgenic PSAPP mouse model of cerebral amyloidosis and evaluated cognitive function and cerebral amyloid pathology. Beginning at 15 months of age, animals were gavaged with MB (3 mg/kg) or vehicle once daily for 3 months. MB treatment significantly prevented transgene-associated behavioral impairment, including hyperactivity, decreased object recognition, and defective spatial working and reference memory, but it did not alter nontransgenic mouse behavior. Moreover, brain parenchymal and cerebral vascular β-amyloid deposits as well as levels of various Aβ species, including oligomers, were mitigated in MB-treated PSAPP mice. These effects occurred with inhibition of amyloidogenic APP proteolysis. Specifically, β-carboxyl-terminal APP fragment and β-site APP cleaving enzyme 1 protein expression and activity were attenuated. Additionally, treatment of Chinese hamster ovary cells overexpressing human wild-type APP with MB significantly decreased Aβ production and amyloidogenic APP proteolysis. These results underscore the potential for oral MB treatment against AD-related cerebral amyloidosis by modulating the amyloidogenic pathway.

The recent discovery that the potent carcinogen acrylamide (AA) is present in a variety of fried and baked foods raises health concerns, particularly for children, because AA is relatively high in child-favoured foods such as potato chips and French fries. To compare the susceptibility to AA-induced genotoxicity of young versus adult animals, we treated 3- and 11-week-old male gpt delta transgenic F344 rats with 0, 20, 40 or 80 p.p.m. AA via drinking water for 4 weeks and then examined genotoxicity in the bone marrow, liver and testis. We also analysed the level of N7-(2-carbamoyl-2-hydroxyethyl)-guanine (N7-GA-Gua), the major DNA adduct induced by AA, in the liver, testis and mammary gland. At 40 and 80 p.p.m., both age groups yield similar results in the comet assay in liver; but at 80 p.p.m., the bone marrow micronucleus frequency and the gpt-mutant frequency in testis increased significantly only in the young rats, and N7-GA-Gua adducts in the testis was significantly higher in the young rats. These results imply that young rats are more susceptible than adult rats to AA-induced testicular genotoxicity.