Application of Rho Kinase Inhibitors for the Treatment of Corneal Endothelial Diseases

ROCK (Rho kinase) signaling regulates a wide spectrum of fundamental cellular events and is involved in a variety of pathological conditions. It has therefore attracted research interest as a potential therapeutic target for combating various diseases. We showed that inhibition of ROCK enhances cell proliferation, promotes cell adhesion onto a substrate, and suppresses apoptosis of corneal endothelial cells (CECs). In addition, we reported that a ROCK inhibitor enhances wound healing in the corneal endothelium in animal models and in pilot clinical research. We also demonstrated the usefulness of a ROCK inhibitor as an adjunct drug in tissue engineering therapy as it enhances the engraftment of CECs onto recipient corneas. In 2013, we initiated a clinical trial to test the effectiveness of injection of cultured human CECs into the anterior chamber of patients with corneal endothelial decompensation. This paper reviews the accumulating evidence supporting the potency of ROCK inhibitors in clinical use, both as eye drops and as adjunct drugs in cell-based therapies, for the treatment of corneal endothelial decompensation

Über die Viruskonzentration ünd die Menge des Virulizidins in den einzelnen Organen bei Leichen der an Encephalitis epidemica japonica gestorbenen Kranken und uber den Zusammenhang zwischen diesen beiden Dingen. I. Über die Viruskonzentration

Über die Verteilung des Encephalitisvirus in versuchsweise infiziertem tierischem Organismus liegen allerdings recht viele Mitteilungen vor, beim menschlichen Körperaber wurde sie bislang noch sehr wenig studiert. Der Verf. hat nun daher im Sommer 1939 bei 5 Leichen der an Encephalitis gestorbenen Kranken (am 4. bis 11. Krankheitstage) und in beliebigen Zeiträumen des Jahres 1940 und 1941 bei 11 Leichen der an nicht encephalitischen Krankheiten gestorbenen Kranken Emulsionen einzelner Organe des ganzen Körpers hergestellt. Diese Emulsionen hat er dann je in der Menge von 0,03cc 7 bis 10 gesunden weissen Mausen intrazerebral injiziert, um aus den Erkrankungsverhältnissen das Virus in den betr. Organismen nachzuweisen. Daraus kam er zu folgenden Ergebnissen. 1. Die Menge des in den einzelnen Organen enthaltenen Virus lässt sich neben der Morbidität der Mäuse von erster Generation folgendermassen anführen: Im Herzblut wurde das Virus in 3 von 5 Fällen im Mittel 7,3% enthalten. 2. In der Grosshirnrinde wurde das Virus in 2 von 5 Fällen 9,8%, im Hirnstamm in 3 von 5 Fällen 14,6%, im Rückenmark in 2 von 5 Fällen 29,3% nachgewiesen. Beim Zentralnervensystem ergab sich, dass das Virus in der 1. Krankheitswoche in grosser Menge vorhanden war, in der 2. aber nahm das Virus aufFällend stark ab. In einem Fall (am 11. Krankheitstage) wurde das Virus in den peripheren Nerven 20% beobachtet. 3. Was das Virus in den Organen der Eingeweide anbetrifft, so zeigte es sich bei der speicheldruse und der Lunge in den samtlichen Fällen als negativ, wahrend es in der Leber in 4 von 5 Fällen 14,6%, in der Milz in 3 von 5 Fällen 7,3%, in der Niere in einem von 5 Fällen 4,9%, in der Nebenniere in 2 von 4 Fällen 8,8% enthalten war. 4. Im Gegensatz dazu war das Virus bei Leichen der an nicht encephalitischen Krankheiten gestorbenen Kranken in den einzelnen Organen in keinem Falle nachweisbar

Optimization of Enzyme-Mediated Calcite Precipitation as a Soil-Improvement Technique : The Effect of Aragonite and Gypsum on the Mechanical Properties of Treated Sand

The effectiveness of magnesium as a substitute material in enzyme-mediated calcite precipitation was evaluated. Magnesium sulfate was added to the injecting solution composed of urea, urease, and calcium chloride. The effect of the substitution on the amount of precipitated materials was evaluated through precipitation tests. X-ray powder diffraction and scanning electron microscopy analyses were conducted to examine the mineralogical morphology of the precipitated minerals and to determine the effect of magnesium on the composition of the precipitated materials. In addition to calcite, aragonite and gypsum were formed as the precipitated materials. The effect of the presence of aragonite and gypsum, in addition to calcite, as a soil-improvement technique was evaluated through unconfined compressive strength tests. Soil specimens were prepared in polyvinyl chloride cylinders and treated with concentration-controlled solutions, which produced calcite, aragonite, and gypsum. The mineralogical analysis revealed that the low and high concentrations of magnesium sulfate effectively promoted the formation of aragonite and gypsum, respectively. The injecting solutions which produced aragonite and calcite brought about a significant improvement in soil strength. The presence of the precipitated materials, comprising 10% of the soil mass within a treated sand, generated a strength of 0.6 MPa

Distribution of grout material within 1-m sand column in insitu calcite precipitation technique

AbstractThis study evaluates the potential of improving an insitu calcite grouting technique. The grout is composed of an equimolar solution of urea–CaCl2 and an enzyme named urease. We examine the distribution of the grout materials and precipitated calcite within sand columns with a diameter of 5cm and a height of 100cm. In the first series of experiments, the concentration distributions of the individual grout materials (i.e., urea, CaCl2 and urease) within the sand specimen are evaluated. In the second series of experiments, an enzyme-reagent mixed solution (i.e., grout) is injected into the sand columns to evaluate the distribution of calcite. Sand samples are collected from various vertical locations within the treated columns and the amount of precipitated calcite is evaluated. Furthermore, attempts are made to achieve the uniform distribution of the injected grout and hence uniform calcite distribution throughout the specimen. The results show that a uniform distribution of the grout materials up to a distance of 1m from the inlet is achievable. It is also observed that a relatively uniform distribution of calcite is achievable as long as the rate of calcite precipitation is well controlled

A Personal Navigation System for Sightseeing across Multiple days

ICMU2006 : The Third International Conference on Mobile Computing and Ubiquitous Networking , Oct 11-13, 2006 , London, U.K.Recently, various personal navigation systems are available on the market. In this paper, we propose a new scheduling function to compose sightseeing tours across multiple days. Scheduling for multiple days is challenging since the number of possible sequences to travel destinations becomes huge and accommodation places have to be carefully chosen considering the schedules before and after each stay. So, some techniques are required to calculate the sightseeing schedule across multiple days at practically short time. In our method, we divide the target area into several sub-areas, and we restrict each day trip to be in a limited number of areas with infrequent passing of area boundary, in order to decrease the number of sequences. We have designed and implemented a genetic algorithm to solve this scheduling problem at a practical time. In this algorithm, accommodation places are represented in chromosome as exclusive alleles, to make schedules which contain only one accommodation place for each day. In order to evaluate our method, we made various sightseeing schedules across multiple days using the digital map of the Tohoku area (Japan Geographical Survey Institute numeric map 25000), and confirmed that the proposed algorithm could compute the near best 6 days schedule in several tens of seconds

Chromosomal Manipulation by Site-Specific Recombinases and Fluorescent Protein-Based Vectors

Feasibility of chromosomal manipulation in mammalian cells was first reported 15 years ago. Although this technique is useful for precise understanding of gene regulation in the chromosomal context, a limited number of laboratories have used it in actual practice because of associated technical difficulties. To overcome the practical hurdles, we developed a Cre-mediated chromosomal recombination system using fluorescent proteins and various site-specific recombinases. These techniques enabled quick construction of targeting vectors, easy identification of chromosome-rearranged cells, and rearrangement leaving minimum artificial elements at junctions. Applying this system to a human cell line, we successfully recapitulated two types of pathogenic chromosomal translocations in human diseases: MYC/IgH and BCR/ABL1. By inducing recombination between two loxP sites targeted into the same chromosome, we could mark cells harboring deletion or duplication of the inter-loxP segments with different colors of fluorescence. In addition, we demonstrated that the intrachromosomal recombination frequency is inversely proportional to the distance between two recombination sites, implicating a future application of this frequency as a proximity sensor. Our method of chromosomal manipulation can be employed for particular cell types in which gene targeting is possible (e.g. embryonic stem cells). Experimental use of this system would open up new horizons in genome biology, including the establishment of cellular and animal models of diseases caused by translocations and copy-number variations

Multi-physics numerical analyses for predicting the alterations in permeability and reactive transport behavior within single rock fractures depending on temperature, stress, and fluid pH conditions

The aim of the current study was to establish a validated numerical model for addressing the changes in permeability and reactive transport behavior within rock fractures based on the fluid pH under coupled thermal-hydraulic-mechanical-chemical (THMC) conditions. Firstly, a multi-physics reactive transport model was proposed, considering the geochemical reactions that depend on the temperature, stress, and fluid chemistry conditions (e.g., fluid pH and solute concentrations), as well as the changes in permeability in the rock fractures driven by these reactions, after which the correctness of the model implementation was verified by solving the 1D reactive transport problem as a fundamental benchmark. Secondly, the validity of the model against actual rock fractures was investigated by utilizing the model to replicate the measurements of the evolving permeability and the effluent element concentrations in single granite fractures obtained by means of two flow-through experiments using deionized water (pH ∼ 6) and a NaOH aqueous solution (pH ∼ 11) as permeants under stressed, temperature-elevated conditions. The model predictions efficiently followed the changes in fracture permeability over time measured by both experiments. Additionally, the observed difference in the changing rates, which may contribute to the difference in the fluid pH between the two experiments, was also captured exactly by the predictions. Moreover, in terms of the effluent element concentrations, among all the elements targeted for measurement, the concentrations of most elements were replicated by the model within one order of discrepancy. Overall, it can be concluded that the developed model should be valid for estimating the changes in permeability and reactive transport behavior within rock fractures induced by geochemical reactions which depend on the fluid pH under coupled THMC conditions

熱環境における岩石の力学・水理学特性および岩盤空洞の挙動

学位の種別: 論文博士審査委員会委員 : (主査)東京大学教授 福井 勝則, 東京大学教授 山冨 二郎, 東京大学教授 徳永 朋祥, 東京大学准教授 増田 昌敬, 京都大学准教授 村田 澄彦University of Tokyo(東京大学