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Background Blood pressure (BP) variability has reportedly been a risk factor for various clinical events. To clarify the influence of BP visit‐to‐visit variability on adverse events in patients with nonvalvular atrial fibrillation, a post hoc analysis of the J‐RHYTHM Registry was performed. Methods and Results Of 7406 outpatients with nonvalvular atrial fibrillation from 158 institutions, 7226 (age, 69.7±9.9 years; men, 70.7%), in whom BP was measured 4 times or more (14.6±5.0 times) during the 2‐year follow‐up period or until occurrence of an event, constituted the study group. SD and coefficient of variation of BP values were calculated as BP variability. Thromboembolism, major hemorrhage, and all‐cause death occurred in 110 (1.5%), 121 (1.7%), and 168 (2.3%) patients, respectively. When patients were divided into quartiles of systolic BP‐SD (P =0.015 for thromboembolism; HR, 2.60, 95% CI, 1.36–4.97, P =0.004 for major hemorrhage; and HR, 1.85, 95% CI, 1.11–3.07, P =0.018 for all‐cause death) after adjusting for components of the CHA 2 DS 2 ‐VASc score, warfarin and antiplatelet use, atrial fibrillation type, BP measurement times, and others. These findings were consistent when BP‐coefficient of variation was used instead of BP‐SD. Conclusions Systolic BP visit‐to‐visit variability was significantly associated with all adverse events in patients with nonvalvular atrial fibrillation. Further studies are needed to clarify the causality between BP variability and adverse outcomes in patients with nonvalvular atrial fibrillation. Registration URL: https://www.umin.ac.jp/ctr/ ; Unique Identifier: UMIN000001569.

The sense of strangeness (or discomfort) perceived in certain virtual characters, discussed in Uncanny Valey (UV) theory, can be a key factor in our perceptual and cognitive discrimination. Understanding how this strangeness happens is essential to avoid it in the process of modeling virtual humans. In this paper, we investigate the relationship between images features and the discomfort that human beings can perceive. We extract image features based on Hu Moments (Hum) and Histogram Oriented Gradient (Hog). The saliency detection is also extracted in the specific parts of the virtual face. Finally, a model using Support Vector Machine (SVM) to provide binary classification is suggested. The results indicate accuracy of around 80% in the image estimation process comparing with subjective classification. As a contribution, some areas may benefit from this study for avoiding the creation of characters that may cause strangeness, such as the games, conversational agents and cinema industry.

Biochemical systems in living cells have their optimum concentration ratio among each constituent element to maintain their functionality. However, in the case of the biochemical system with complex interactions and feedbacks among elements, their activity as a system greatly changes by the concentration shift of the entire system irrespective of the concentration ratio among elements. In this study, by using a transcription-translation (TX-TL) system as the subject, we illustrate the principle of the nonlinear relationship between the system concentration and the activity of the system. Our experiment and simulation showed that shifts of the system concentration of TX-TL by dilution and concentration works as a switch of activity and demonstrated its ability to emerge a biochemical system to confer the permeability of small molecules to liposomes. These results contribute to the creation of artificial cells using the switch and provide an insight into the birth of the origin of life.

Here, we report on the design and function of a membrane nanopore through a DNA origami square tube with a cross-section of 100 nm2 . When the nanopore is added onto the giant vesicle membrane, the permeation of hydrophilic fluorescent molecules was observed. It can be sealed by the existence of the four specific single strand DNAs. A controllable artificial nanopore should help to communicate the vesicle components with their environment

We demonstrate a method of pattern formation based on an artificial reaction diffusion system in hydrogel medium. By designing both the reaction term and the diffusion term of the system, we have succeeded in generating a sustainable DNA pattern in the gel. A DNA logic gate anchored in the gel detected the diffused molecules from distant source points to mark the equidistant region from the source points, which produced a Voronoi pattern in the gel. Combined with a diffusion modulation method for DNA molecules, the Voronoi pattern was modified as a weighted Voronoi pattern with different morphologies. The proposed framework will be useful in designing a structured gel system responsive to molecular signals.

An isothermal amplification circuit for specific DNA molecules was implemented in giant unilamellar vesicles. Using this circuit, over 5000-fold amplification of output DNAs was achieved, and the amplification behaviour depended on the concentration of input signal DNAs in a cell-sized compartment. Moreover, initiation of the amplification by photo-stimulation was demonstrated.

The most common way to fabricate DNA nanostructures is to mix individually synthesized DNA oligomers in one pot. However, if DNA nanostructures could be produced through enzymatic reactions, they could be applied in various environments, including in vivo. Herein, an enzymatic method developed to construct a DNA nanostructure from a simple motif called a T-motif is reported. A long, repeated structure was replicated from a circular template by rolling circle amplification and then cleaved into T-motif segments by restriction enzymes. These motifs have been successfully assembled into a ladder-like nanostructure without purification or controlled annealing. This approach is widely applicable to constructing a variety of DNA nanostructures through enzymatic reactions.

In vitro transcription–translation systems (TX–TL) can synthesize most of individual genes encoded in genomes by using strong promoters and translation initiation sequences. This fact raises a possibility that TX–TL using genome as a template can reconstitute the profile of RNA and proteins in living cells. By using cell extracts and genome prepared from different organisms, here we developed a system for in vitro genome transcription–translation (iGeTT) using bacterial genome and cell extracts, and surveyed de novo synthesis of RNA and proteins. Two-dimensional electrophoresis and nano LC–MS/MS showed that proteins were actually expressed by iGeTT. Quantitation of transcription levels of 50 genes for intracellular homeostasis revealed that the levels of RNA synthesis by iGeTT are highly correlated with those in growth phase cells. Furthermore, activity of iGeTT was influenced by transcription derived from genome structure and gene location in genome. These results suggest that intracellular profiles and characters of genome can be emulated by TX–TL using genome as a template.

Cell-sized liposomes and droplets coated with lipid layers have been used as platforms for understanding live cells, constructing artificial cells, and implementing functional biomedical tools such as biosensing platforms and drug delivery systems. However, these systems are very fragile, which results from the absence of cytoskeletons in these systems. Here, we construct an artificial cytoskeleton using DNA nanostructures. The designed DNA oligomers form a Y-shaped nanostructure and connect to each other with their complementary sticky ends to form networks. To undercoat lipid membranes with this DNA network, we used cationic lipids that attract negatively charged DNA. By encapsulating the DNA into the droplets, we successfully created a DNA shell underneath the membrane. The DNA shells increased interfacial tension, elastic modulus, and shear modulus of the droplet surface, consequently stabilizing the lipid droplets. Such drastic changes in stability were detected only when the DNA shell was in the gel phase. Furthermore, we demonstrate that liposomes with the DNA gel shell are substantially tolerant against outer osmotic shock. These results clearly show the DNA gel shell is a stabilizer of the lipid membrane akin to the cytoskeleton in live cells.

Investigations into the refolding of DNA origami leads to the creation of reconstructable nanostructures and deepens our understanding of the sustainability of life. Here, we report the refolding of the DNA origami structure inside a micron-sized compartment. In our experiments, conventional DNA origami and truss-type DNA origami were annealed and purified to remove the excess staples in a test tube. The DNA origami was then encapsulated inside of a micron-sized compartment of water-in-oil droplets, composed of neutral surfactants. The re-annealing process was then performed to initiate refolding in the compartment. The resulting 100-nm-sized DNA nanostructures were observed using atomic force microscopy (AFM), and the qualities of their structures were evaluated based on their shape. We found that the refolding of the DNA origami structure was favored inside the droplets compared with refolding in bulk solution. The refolded structures were able to fold even under &ldquo, quick&rdquo, one-minute annealing conditions. In addition, the smaller droplets (average diameter: 1.2 &micro, m) appeared to be more advantageous for the refolding of the origamis than larger droplets. These results are expected to contribute to understanding the principles of life phenomena based on multimolecular polymer self-assembly in a micron-sized compartment, and for the production and maintenance of artificially designed molecules.

Flexible macroporous silicone gels were prepared using methyltrimethoxysilane and dimethyldimethoxysilane as coprecursors via a two-step reaction catalyzed by acetic acid and ammonia solution. A sheet-shaped material was integrated with the gel by immersing the mesh in the sol during the reaction. The mesh reinforced sheet having a thickness of several millimeters was resistant to bending and pulling and easy to handle, though the physical properties such as hydrophobicity and oleophilicity possessed by the bulk surface were not lost. The composite sheets are used for various applications such as water–oil separation, manipulation of water droplets by adsorption on hydrophobic surfaces, and preparation of giant vesicle dispersions by taking advantage of surface properties and porosity.

A novel grinding technique is proposed with the goal of improving the grindability of the titanium alloy Ti–6Al–4V. This technique is a combination of ultrasonic-assisted grinding and plasma-electrolytic oxidation. To determine its performance in the grinding of Ti–6Al–4V, experiments were conducted to investigate the effect of ultrasonic vibration on grinding forces and work-surface roughness under the presence of plasma oxidation. The results showed that the technique drastically reduced the normal and tangential grinding forces by 60% and 70%, respectively, and decreased the work-surface roughness by 46% compared to conventional grinding, which uses neither ultrasonic assisted grinding nor plasma-electrolytic oxidation.

Background A new electro-mechanical device for measuring the lateral stiffness of the skin is now available. It basically allows to recording the forces that the skin opposes to a lateral displacement (1–2 mm) of a pinching type movement. Preliminary assays of this device to various skin sites and an artificial substrate aimed at defining its major characteristics (sensitivity, reproducibility, variations according to skin site). Methods The calibration of the device (Khelometer®) and assessment of its reproducibility were carried out through the use of elastometer substrates of various stiffness's. The device was then used, in vivo, at different skin sites (scalp, inner and outer forearms, cheeks) of 213 healthy Japanese women of various ages. The short-time effect of a hydrating regimen (7% glycerol) was recorded on the outer forearm. Results This new device offers an appreciable reproducibility in vitro and in vivo (coefficient of variation of 2–4% and 5–14%, respectively). Unlike other biophysical methods, the Khelometer® can be easily applied onto the human scalp that shows a higher stiffness than the two other skin sites, increasing with age and presence of alopecia. In all the three studied skin sites, the impact of age leads to significantly higher lateral skin stiffness (LSS, expressed as N/mm) values. The latter were found significantly different between the two sides of the forearms where the outer (sun-exposed) side showed statistically slightly higher LSS, than the unexposed inner side. LSS values found on cheeks (≈0.5 N/mm) were about four times lower than those of the scalp (≈2 N/mm) and about half those of forearms (≈1 N/mm). The effect of a 7% glycerol based formula was recorded 20 min post application onto the forearm, leading to a slight drop in LSS (approx. 15%) as compared to a vehicle-applied skin site. Conclusion These preliminary studies clearly indicate that this new device, applicable to any skin site, offers appreciable assets such as sensitivity and reproducibility. Accordingly, it appears as a new approach in the non-invasive biophysical measurements of the skin surface, in both advanced and applied research investigations.

An analytical method for quantifying zearalenone (ZEA) in pet foods using a liquid chromatograph-atmospheric pressure chemical ionization-mass spectrometer (LC-APCI-MS) was developed, and an inter-laboratory study was conducted. ZEA was extracted from pet food samples with aqueous acetonitrile. The extract was purified using a multifunctional column, MultiSep 226 Aflazon+, and analysed with LC-APCI-MS. The limit of quantification of ZEA by this method was estimated to be 0.2 mg/kg for dry and semi-dry pet foods, and 0.1 mg/kg for wet pet food. The calibration curve of ZEA for this method showed linearity in the range of 0.1-10 ng of ZEA (0.01-1.0 µg/ml, 0.04-4.0 mg/kg matrix). The mean recoveries, repeatabilities, reproducibilities, and the HorRats for ZEA from the inter-laboratory validation study were 99.0-102%, 2.2-3.0%, 5.6-6.6%, and 0.33-0.36, respectively.

Additional file 1. Questionnaire on competencies required for working activities in prevention and control of non-communicable diseases (NCDs) (Additional file 1).

Background The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 comparative risk assessment (CRA) is a comprehensive approach to risk factor quantification that offers a useful tool for synthesising evidence on risks and risk–outcome associations. With each annual GBD study, we update the GBD CRA to incorporate improved methods, new risks and risk–outcome pairs, and new data on risk exposure levels and risk–outcome associations. Methods We used the CRA framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or groups of risks from 1990 to 2017. This study included 476 risk–outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk and exposure estimates from 46 749 randomised controlled trials, cohort studies, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. We explored the relationship between development and risk exposure by modelling the relationship between the Socio-demographic Index (SDI) and risk-weighted exposure prevalence and estimated expected levels of exposure and risk-attributable burden by SDI. Finally, we explored temporal changes in risk-attributable DALYs by decomposing those changes into six main component drivers of change as follows: (1) population growth; (2) changes in population age structures; (3) changes in exposure to environmental and occupational risks; (4) changes in exposure to behavioural risks; (5) changes in exposure to metabolic risks; and (6) changes due to all other factors, approximated as the risk-deleted death and DALY rates, where the risk-deleted rate is the rate that would be observed had we reduced the exposure levels to the TMREL for all risk factors included in GBD 2017. Findings In 2017, 34·1 million (95% uncertainty interval [UI] 33·3–35·0) deaths and 1·21 billion (1·14–1·28) DALYs were attributable to GBD risk factors. Globally, 61·0% (59·6–62·4) of deaths and 48·3% (46·3–50·2) of DALYs were attributed to the GBD 2017 risk factors. When ranked by risk-attributable DALYs, high systolic blood pressure (SBP) was the leading risk factor, accounting for 10·4 million (9·39–11·5) deaths and 218 million (198–237) DALYs, followed by smoking (7·10 million [6·83–7·37] deaths and 182 million [173–193] DALYs), high fasting plasma glucose (6·53 million [5·23–8·23] deaths and 171 million [144–201] DALYs), high body-mass index (BMI; 4·72 million [2·99–6·70] deaths and 148 million [98·6–202] DALYs), and short gestation for birthweight (1·43 million [1·36–1·51] deaths and 139 million [131–147] DALYs). In total, risk-attributable DALYs declined by 4·9% (3·3–6·5) between 2007 and 2017. In the absence of demographic changes (ie, population growth and ageing), changes in risk exposure and risk-deleted DALYs would have led to a 23·5% decline in DALYs during that period. Conversely, in the absence of changes in risk exposure and risk-deleted DALYs, demographic changes would have led to an 18·6% increase in DALYs during that period. The ratios of observed risk exposure levels to exposure levels expected based on SDI (O/E ratios) increased globally for unsafe drinking water and household air pollution between 1990 and 2017. This result suggests that development is occurring more rapidly than are changes in the underlying risk structure in a population. Conversely, nearly universal declines in O/E ratios for smoking and alcohol use indicate that, for a given SDI, exposure to these risks is declining. In 2017, the leading Level 4 risk factor for age-standardised DALY rates was high SBP in four super-regions: central Europe, eastern Europe, and central Asia; north Africa and Middle East; south Asia; and southeast Asia, east Asia, and Oceania. The leading risk factor in the high-income super-region was smoking, in Latin America and Caribbean was high BMI, and in sub-Saharan Africa was unsafe sex. O/E ratios for unsafe sex in sub-Saharan Africa were notably high, and those for alcohol use in north Africa and the Middle East were notably low. Interpretation By quantifying levels and trends in exposures to risk factors and the resulting disease burden, this assessment offers insight into where past policy and programme efforts might have been successful and highlights current priorities for public health action. Decreases in behavioural, environmental, and occupational risks have largely offset the effects of population growth and ageing, in relation to trends in absolute burden. Conversely, the combination of increasing metabolic risks and population ageing will probably continue to drive the increasing trends in non-communicable diseases at the global level, which presents both a public health challenge and opportunity. We see considerable spatiotemporal heterogeneity in levels of risk exposure and risk-attributable burden. Although levels of development underlie some of this heterogeneity, O/E ratios show risks for which countries are overperforming or underperforming relative to their level of development. As such, these ratios provide a benchmarking tool to help to focus local decision making. Our findings reinforce the importance of both risk exposure monitoring and epidemiological research to assess causal connections between risks and health outcomes, and they highlight the usefulness of the GBD study in synthesising data to draw comprehensive and robust conclusions that help to inform good policy and strategic health planning. Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.

This installation will exhibit dynamic projection mapping on a pancake with an edible retroreflector as an optical marker. Visitors will be able to see a projected character welcoming and attracting them depends on the position of the pancake that they are holding.

This paper evaluates the semiconductor on hexagonal-BN (h-BN) structure for power-supply on chip applications based on numerical simulations. Hexagonal-BN is used as an insulator of semiconductor -on-insulator (SOI) structure. Hexagonal-BN based SOI structure with through-silicon-via(TSV) shows higher heat dissipation performance without degrading electrical characteristics compared with the conventional SOI structure., 2018 International Conference on Solid State Devices and Materials(SSDM2018), September9-13, 2018, Hongo Campus, The University of Tokyo, Tokyo, Japan

Giant vesicles were efficiently produced by squeezing a lipid (l-α-phosphatidylcholine from egg yolk)-coated marshmallow-like flexible macroporous silicone monolith in a buffer. The mean diameter of the obtained vesicles was 2 μm, showing a wide distribution, up to tens of micrometers, which was similar to that of vesicles formed by a natural swelling method. It was possible to prepare vesicle dispersions on a scale from several microliters to several hundred milliliters. A protein synthesis system (PURE system) contained in vesicles prepared using this method functioned effectively. Our absorbing-squeezing method is expected to help in studies that use giant vesicles such as artificial cells and drug delivery systems.

An empirical formula for the stress concentration factor is developed for an unequal-sized cavity pair in an arbitrary orientation. Three-dimensional finite element linear elastic analyses are performed to evaluate the stress concentration factors for different sizes, orientations, and separations of cavities. A suitable mathematical function is chosen to fit the numerical results of the finite element analyses. An application is given for evaluating the maximum stress concentration factor, which governs fatigue crack initiation in aluminum die cast test pieces from an engine block. From the X-ray CT image, the location and geometry of the gas pores are evaluated so as to develop the proposed empirical formula for this actual multi-pore system simplified to a dual spherical pore system. A proof of the formula is shown by comparison with voxel finite element analysis. The proposed empirical formula can be satisfactorily used as a scientific guideline for selecting a casting method for car engine blocks from a fatigue crack initiation perspective.

We propose a method to control the diffusion speed of DNA molecules with a target sequence in a polymer solution. The interaction between solute DNA and diffusion-suppressing DNA that has been anchored to a polymer matrix is modulated by the concentration of the third DNA molecule called the competitor by a mechanism called toehold exchange. Experimental results show that the sequence-specific modulation of the diffusion coefficient is successfully achieved. The diffusion coefficient can be modulated up to sixfold by changing the concentration of the competitor. The specificity of the modulation is also verified under the coexistence of a set of DNA with noninteracting base sequences. With this mechanism, we are able to control the diffusion coefficient of individual DNA species by the concentration of another DNA species. This methodology introduces a programmability to a DNA-based reaction-diffusion system.

Automobile bumper is a most important part in the aspect of safety, which protects the passengers from front and rear collision. Initially, metals were used as bumper to avoid the collision. In this modern era, the development of polymer and its composite plays an effective role in reducing the weight without sacrificing the functionality. However, the awareness of the available light weight polymer materials was not explored successfully by the industries. Hence, an attempt was made to carry out the systematic review on automobile bumper and its materials. Polypropylene (PP) is one of the widely used polymers in developing various automobile parts including automobile bumpers. The required mechanical properties of bumpers were not achieved successfully with the PP. Hence, the different concentration of various micro and nano fillers such as Multi walled carbon nanotubes (MWCNT), Single walled carbon nanotubes (SWNT), carbon black, glass fiber, carbon fiber, nanoclay, etc., were reinforced with PP to achieve the sufficient mechanical properties. One of our study shows that the reinforcement of 1.5 wt% of MWCNT enhanced the mechanical properties significantly, where the tensile strength, flexural strength, flexural modulus, and Young׳s modulus was found to be enhanced by 42.8, 33.7, 17.4, and 16%, respectively compared to pure PP. It was observed that various fillers were used with PP matrix to achieve the required mechanical properties, however the optimum filler concentration is still a concern. It is concluded that more research should be carried out to avoid the muddle in choosing filler and reinforcement concentration before practical usage.

An analytical method to determine fumonisin B1 (FB1), B2 (FB2) and B3 (FB3) in pet foods using a liquid chromatography-electrospray ionization-mass spectrometer (LC-ESI-MS) was developed, and an inter-laboratory study was conducted in eleven laboratories. FB1, FB2 and FB3 were extracted with aqueous acetonitrile. The extract was purified by a multifunctional column, MultiSep 211 Fum, and analysed by LC-ESI-MS. The limit of quantification of fumonisins was estimated to be 0.2 mg/kg for dry and semi-dry pet foods, and 0.1 mg/kg for wet pet food. The calibration curve showed linearity in the range of 0.1-5 ng of fumonisins (0.02-1.0 μg/ml). The values of the mean recovery for FB1 at 0.1-1.0 mg/kg were 93.3-107% and of the relative standard deviation less than 7.9%. These values were 87.3-102 and 8.6% for FB2 and 90.8-102 and 8.6% for FB3, respectively. The mean recovery, repeatability, reproducibility and the Horwitz ratio for FB1 from the inter-laboratory validation study were 92.9-98.9%, 2.6-4.6%, 6.8-10% and 0.41-0.54, respectively. The values for FB2 were 91.5-94.7%, 2.7-5.9%, 6.8-8.9% and 0.33-0.55, respectively, and the values for FB3 were 90.1-94.3%, 3.3-5.9%, 7.3-9.5% and 0.44-0.57, respectively.

A simple method of preparation giant vesicles by squeezing out with a buffer from flexible porous monoliths impregnated with lipids was reported.

Realization of a feedback controller on artificial molecular circuits is one of the important tasks in the field of molecular robotics. In particular, a regulator that keeps the operation of a biological actuator constant is needed in a variety of practical applications. Importantly, such a regulator must be designed using biochemical reaction networks to function normally in a reaction field. In this paper, we propose an integral controller for a molecular robot. Our controller is inspired by an integral control system existing in an intracellular signal transduction pathway, and is realized on DNA strand displacement reactions.