Search

RADA16 is a synthetic peptide that exists as a viscous solution in an acidic formulation. In an acidic aqueous environment, the peptides spontaneously self-assemble into β-sheet nanofibers. Upon exposure and buffering of RADA16 solution to the physiological pH of biological fluids such as blood, interstitial fluid and lymph, the nanofibers begin physically crosslinking within seconds into a stable interwoven transparent hydrogel 3-D matrix. The RADA16 nanofiber hydrogel structure closely resembles the 3-dimensional architecture of native extracellular matrices. These properties make RADA16 formulations ideal topical hemostatic agents for controlling bleeding during surgery and to prevent post-operative rebleeding. A commercial RADA16 formulation is currently used for hemostasis in cardiovascular, gastrointestinal, and otorhinolaryngological surgical procedures, and studies are underway to investigate its use in wound healing and adhesion reduction. Straightforward application of viscous RADA16 into areas that are not easily accessible circumvents technical challenges in difficult-to-reach bleeding sites. The transparent hydrogel allows clear visualization of the surgical field and facilitates suture line assessment and revision. The shear-thinning and thixotropic properties of RADA16 allow its easy application through a narrow nozzle such as an endoscopic catheter. RADA16 hydrogels can fill tissue voids and do not swell so can be safely used in close proximity to pressure-sensitive tissues and in enclosed non-expandable regions. By definition, the synthetic peptide avoids potential microbiological contamination and immune responses that may occur with animal-, plant-, or mineral-derived topical hemostats. In vitro experiments, animal studies, and recent clinical experiences suggest that RADA16 nanofibrous hydrogels can act as surrogate extracellular matrices that support cellular behavior and interactions essential for wound healing and for tissue regenerative applications. In the future, the unique nature of RADA16 may also allow us to use it as a depot for precisely regulated drug and biopharmaceutical delivery.

Cellular senescence acts as a natural barrier against tumor progression Our previous study showed that selective induction of senescence using miR-22, one of senescence-associated microRNAs (SA-miRNAs), suppressed tumor progression (JCB 2011) In this study, we developed functional screening system using miRNA library to identify a potent SA-miRNA that suppress malignant tumor such as anti-cancer drug resistant and cancer stem cells. We focused on microRNA inducing the senescent phenotype in normal human fibroblast cell After transfection of 2028 miRNA mimics library in normal human fibroblast TIG-3, we evaluate the senescence phenotypes such as cell growth arrest and size enlargement using high content analyzer, and found that 349 miRNAs induced cellular senescence More importantly, we identified miR-3140-3p as potent SA-miRNA that significantly suppressed tumor cell proliferation in several types of cancer cells including cancer stem cells and anti-cancer drug resistant cells. We focused on malignant pleural mesothelioma (MPM) which is an aggressive tumor developed from the mesothelial lining cells of the pleura MPM is caused by direct asbestos exposure and is an incurable tumor type for the lack of effective treatment In addition, as Japan is one of the world's highest importers and users of asbestos, the cases of mesothelioma are expected to increase in the near future Therefore, we investigated the possibility of whether SA-miRNAs showed tumor suppressive effects against MPM cell lines Moreover, we tried to develop a new treatment or medicine for the MPM patients using SA-miRNA In vitro and in vivo analysis revealed that several SA-miRNAs drastically suppressed the tumor cell proliferation Based on these findings, the modulation of SA-miRNA is a promising approach to improve the treatment of MPM patients In addition, we performed and completed pre-clinical trials and design first-in-human study in Japan. Citation Format: Yuki Yamamoto, Ayaka Nishiura, Kimiyoshi Yano, Noriaki Matsuda, Ryou-u Takahashi, Yasuhiro Tsutani, Morihito Okada, Hidetoshi Tahara. Preclinical evaluation of a novel senescence-associated miRNA miR-3140-3p for malignant pleural mesothelioma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1402.

This paper discusses an evaluation method of creep-fatigue lives of YH61 single crystal superalloy under multiaxial loading at high temperature. Three types of creep-fatigue tests were performed using three types of the single crystalsuperalloy specimens at 1173K. They were push-pull tests using solid bar specimens, tension-torsion tests using hollow cylinder specimens and biaxial tension-compression tests using cruciform specimens. Anisotropic strain and Mises stress in combination with frequency modified fatigue equation were applied for evaluating the creep-fatigue lives in the three types of tests. The former parameter gave a relatively large scatter but the latter parameter a small scatter in the correlation.

This paper proposes a method of inelastic structural analysis for YH61 nickel base single crystal superalloy. Hill's anisotropic constitutive equation was applied to describe the elastic-plastic deformation of the superalloy. The equation well described the static tensile curves of the solid bar specimen with and axes at 1173K. The equation also well expressed the torsion curves of hollow cylinder specimens with axis at 1173K. The Hill's equation was applied to simulate the creep deformation of the superalloy. The equation gave satisfactory results for predicting the creep deformation of solid bars having and axes. The Hill's equation was used to predict the creep-fatigue deformation of a cruciform specimen in biaxial loading, resulting in a good agreement with the experimental deformation.

Cell sheet technology enables novel approaches to tissue engineering without the use of biodegradable scaffolds. Cell sheet technology consists of a temperature-responsive culture dish, which enables reversible cell adhesion to and detachment from the dish surface by controllable hydrophobicity of the surface. This allows for a non-invasive harvest of cultured cells as an intact monolayer cell sheet including deposited extra cellular matrices. The monolayer cell sheet can be transplanted to host tissues without using biodegradable scaffolds and sutures. Thick tissue constructs and patterned cell sheets using two or more kinds of cell source are also developed by means of layered cell sheets in vitro. This Progress Report summarizes temperature-controlled cell adhesion-detachment behavior and applications of the cell sheet technology to regeneration of cornea, periodontal ligament, bladder epithelia, oesophageal epithelia, myocardium, and liver.

This paper studies crack growth behaviors in thermal fatigue tests for Rene80 conventional cast and YH61 single crystal nickel base superalloys. A cylindrical specimen with 19.5mm outer diameter and 2mm thickness was used in the thermal fatigue tests. A rapid temperature gradient in cylinder thickness was realized by induction heating of the outer surface and water cooling of the inner surface. Thermal fatigue tests were conducted by changing the outer surface temperature from 303 to 1173K and temperature holdings of 10 and 60minits were inserted at 1173K. Temperature gradient in thickness was 650K. Crack growth behaviors were inspected with interrupting tests. Crack initiation sites coincided with the ‹100› direction on the outer surface whereas ‹110› direction on the inner surface. It was confirmed that crack initiation sites coincide with stress distribution obtained from a structural analysis considering the anisotropy of the single crystal. Cracks were arrested at the depth of approximately 1.0mm due to stress gradients in the specimen.

Development of an artificial gill, for the uptake of oxygen from water to air, requires an increase in oxygen transfer rate. In the present study, oxygen transfer rate was enhanced using a washed red blood cell suspension as a thermo-responsive oxygen carrier solution, which changes oxygen affinity with temperature. Oxygen dissolved in water first combined with the oxygen carrier solution at a low temperature using a membrane module. The oxygen carrier solution was then heated to release oxygen into the air using a second membrane module. The water flow rate required to sustain a human being at rest was greatly reduced by heating the oxygen carrier solution due to increase in the limit of the oxygen partial pressure of water of which can be transferred, compared with when oxygen was transferred directly from water. The required membrane surface area is 225 m 2 , sufficient for the development of a compact artificial gill.

Effects of hollow fiber packing fraction on gas transfer rate, blood pressure drop and blood flow characteristics of an intravascular oxygenator (IVOX) were evaluated by in vitro experiments. An IVOX module was prepared by packing hollow fiber membranes, of which packing fraction ranged from 0.056 to 0.338, in a pipe corresponding to vena cava. Overall mass transfer coefficients for oxygen and carbon dioxide were evaluated using water, and gas transfer rates through blood were estimated. Blood flow in the IVOX was evaluated by both pulse response method and electrode method. Blood flow was not uniform and depended on the hollow fiber packing fraction. Easy-flow channels between vascular wall and bundle of the hollow fibers were produced and stagnation of blood flow occurred in the bundle of the hollow fibers at the blood inlet. More uniform blood flow was obtained by optimizing the hollow fiber packing fraction. With respect to gas transfer rate, blood pressure drop and uniformity of the blood flow, the optimum hollow fiber packing fraction was approximately 0.28 when the outside diameter of the hollow fiber was 300 μm. Effect of inner diameter of the hollow fibers was also evaluated, demonstrating that reduction in the inner diameter was an effective way to increase oxygen transfer rate.

We evaluated effects of the number of tied hollow fibers of an outside blood flow membrane oxygenator with cross-wound hollow fibers on the blood flow pattern and oxygen transfer rate. The number of tied hollow fibers in a bundle was varied from one to six, and the blood flow pattern was observed by X-ray computed tomography. The oxygen transfer rate and blood pressure drop were measured by in vitro experiments using bovine blood. Uniform blood flow patterns were obtained for each number of tied hollow fibers. A decrease in the number of tied hollow fibers caused more effective contact of blood with the tied hollow fibers and oxygen transfer rate was enhanced, demonstrating that single hollow fiber was the most effective. Empirical equations were obtained based on these results and optimum structure parameters of the membrane oxygenator were determined by simulation analysis. Optimum membrane surface area and axial jacket length of the oxygenator were 3.0 m 2 and 320 mm, respectively, at a hollow fiber outside diameter of 250 μm.

An outside blood flow membrane oxygenator with an optimum blood flow pattern is developed by a trial and error method where large cost and long time are spent. We modeled the blood flow in the membrane oxygenator as the flow of low Reynolds number in a porous media and evaluated blood pressure drop and oxygen transfer rate using Darcy’s law. Governing equations are solved by the finite element method. Theoretical blood flow patterns agree well with visualized flow patterns obtained by X-ray computed tomography. Calculated values for blood pressure drop and oxygen transfer rate also agree with experimental data. Optimum structure parameters of the membrane oxygenator can hence be determined by simulation analysis.

In order to develop a thermal fatigue life assessment method for high temperature components, out-of-phase thermal fatigue tests were carried out using cylindrical specimens of cobalt-based superalloy HA188 under various temperature ranges. The experiments were conducted in the temperature ranges peaking at 1000°C while starting at 350°C, 760°C and 900°C. A unique testing method was used in which thermal gradients were generated by induction heating for one edge of the specimen and water cooling for the inner and outer surfaces. The results of thermal fatigue test correspond well with the plastic strain range-life data of standard isothermal tests conducted at the peak temperature.

This paper presents multiaxial low cycle fatigue lives of YH61 Ni-base single crystal superalloy at elevated temperature. Tension-torsion low cycle fatigue tests were performed using hollow cylinder specimens with aligning the specimen axis to [100] direction at 1173 K. Biaxial tension-compression low cycle fatigue tests were also performed using cruciform specimens whose x and y axes were aligned to \(\langle 110\rangle \) directions. The effect of strain multiaxiality on the multiaxial low cycle fatigue lives was discussed. Couples of multiaxial stress and strain parameters were applied to the experimental data for correlating the multiaxial low cycle fatigue lives of both types of the specimens. The strain parameters yielded a large scatter in the correlation and Mises equivalent stress was only the parameter to give a satisfactory correlation of multiaxial low cycle fatigue lives of the superalloy.

This paper deals with the effects of two types of corrosion resistance coatings, CoNiCrAIY and Al chemical vapour deposition (CVD) coating, on the fatigue-creep interaction life of a cast Ni base superalloy Rene80. Under a fatigue condition, CoNiCrAIY coating improved the resistance to surface crack initiation, while AICVD coatings reduced the number of cycles to surface crack initiation. However, the surface crack propagation rates of both the coated and non-coated specimens were about the same value. It was found that the fatigue life of the coated specimens was affected by the oxidation of the specimen surface and the properties of the coating material. The life under fatigue creep interaction was affected by the failure mechanism (intergranular cracking) of the base metal Rene80 rather than the oxidation and properties of the coating material.

A new life prediction method is proposed for a cast Ni base superalloy, Rene80, under fatigue -creep interaction (FCI) conditions based on its surface crack propagation behavior.In the previous paper, we proposed that the frequency modified total strain energy parameter was useful for evaluating the failure life (Nf) and crack initiation life (Nc) of a high strength superalloy under FCI conditions. The tensile strain energy parameter was obtained from the total tensile strain energy (ΔWTT) and the loading time (τTT) under tensile stress.In this paper, not only the failure and crack initiation lives but also surface crack propagation behavior are found to be evaluated by this parameter under FCI conditions. The surface crack propagation rate (da/dN) is a function of the parameter and surface crack half length (a); da/dN=B'(ΔWTTτnTT)l·awhere B', l, n are material constants.A new life prediction method taking account of surface crack propagation behavior and initiation life can be defined; N2a=A(ΔWTTτnTT)m+B(ΔWTTτnTT)-l(log(2a)-log(2a0))If the grain size (2a0) and the number of cycles [Nc2a0=A(ΔWTTτnTT)m] needed for the surface crack length to grow to 2a0 are known, the number of cycles (N2a) in a certain crack length (2a) can be determined from the above equation.

It is significant to study the difference between thermal fatigue behavior and high temperature low cycle fatigue, in order to understand the fracture mechanism of metals.In this study, thermal fatigue tests (the upper temperature 800°C, the lower temperature 400°C) and low cycle fatigue tests at 800°C were carried out for super alloy IN738LC, and the initiation of a short crack and its propagation behavior were observed.The results of these fatigue tests showed that the difference in fatigue life between them were caused by the differences in crack initiation life and crack propagation rate during the time of the short crack (2a≤2.0mm).On the other hand, it was observed that the fatigue crack propagation behavior was affected largely by the fracture resistance of grain boundary and cell boundary in crystal grains at high temperatures.

CdSb films with various composition were prepared by the two-source vacuum deposition method. Crystallization of the films was investigated for the various evaporating conditions, and electrical properties such as conductivity, Hall mobility and Seebeck coefficient were measured using as-deposited and annealed films with various Cd contents. The films with 10–25% Cd content (weight %) were amorphous of a low conductivity and large Seebeck coefficient. Crystalline state of CdSb appeared at the Cd content of above 30%. Annealing of amorphous films had a remarkable effect on those properties, while crystalline films had little effect.

The correlation between tensile strength and low cycle fatigue life at elevated temperatures was discussed on a cast Ni base supper alloy (16Cr-3Al-3Ti-9Co-Ni) and a Co base super alloy (11Ni-29Cr-7W-Co). Also, an equation for predicting low cycle fatigue life was developed.In the low cycle fatigue tests, the Co base super alloy showed similar fracture behavior in a wide range of temperature. However, the Ni base super alloy showed brittle fracture behavior at low temperatures (ex. 500°C) because of poor ductility, but showed ductile fracture behavior at high temperatures (ex. 900°C) because of high ductility. In the Ni base super alloy, the failure life was defined as the number of cycles when the nominal stress value of a specimen began to decrease from a steady state stress. Tensile and low cycle fatigue data obtained at 500-900°C for the Ni base super alloy and 600-900°C for the Co base super alloy were analyzed by the stepwise multiple regression procedure, and the effect of tensile strength characteristics on the low cycle fatigue strength was discussed. The results of this analysis showed that the relationship between the plastic strain range (Δep) and cycles to failure (Nf) was expressed by a function of ef, while the relationships between the elastic strain range (Δee) and cycles to failure was given by a function of (σ0.2/E) for both super alloys in a wide range of high temperatures, unlike the results of the Universal Slope method. The life prediction equation obtained was as follows:Δe=Δee+Δep=A(σ0.2/E)lNkf+BenfNmfwhere A, B, k, l, m and n are material constants that are independent of temperature.

A new life prediction method was proposed for high strength materials under fatigue-creep interaction (FCI) based on their tensile total strain energy behavior.The net tensile hysteresis energy is now being used to evaluate FCI life in the frequency modified damage function rule developed by W.J. Ostergren. For high strength materials, however, this damage rule seems to require some modification to give good life assesment, because the elastic strain range is much larger than the inelastic strain range in the FCI behavior of these materials.In this paper, strain controlled tensile or compressive strain hold tests with F-F, F-S and S-F wave forms were performed for Cast Rene 80. The total strain energy including a large elastic strain energy was defined, and FCI life was obtained against this strain energy. Multiple regression analysis was carried out to assess the relationship between strain energy and cycles to failure and was expressed numerically to improve life estimation accuracy.Finally, a frequency modified total strain energy parameter was defined to evaluate the failure lives (Nf) of high strength materials such as Rene 80 under the FCI condition. The total tensile strain energy (ΔWTT) and the time (τTT) under tensile stress loading were used to define this tensile strain energy parameter. Thus, ΔWTT·τnTT·Nmf=Cwhere, n, m and C are constants. A similar relation was also obtained between total strain energy (ΔWTT) and crack initiation life (Nc).

Several isothiocyanates were synthesized and their inhibitory effects upon soil nitrification were examined.Some aryl isothiocyanates, such as 2,4- and 2,5-dichlorophenyl isothiocyanates, showed high activities.

An architecture of the solid phase of chitin gel was examined by scanning electron microscopy. The ultrastructure of the xerogel was microporous with parallel channels surrounded with membranous walls. The pore shapes at cross section were polyhedral with three walls at the junctions. The pore was 30–50 μm in diameter and 80–300 μm in length, and the thickness of the walls was less than 1.5 μm. The gel is considered to be a polyphasic gel, consisting of small droplets of water held up in these pores.