Inflamed site-specific gene delivery using bone marrow-derived CD11b+CD18+ vehicle cells in mice

We report a novel technique that may allow site-specific gene delivery into inflamed tissues. Bone marrow cells from DBA/2 mice were incubated for 7 days in L-929 cell-conditioned medium containing elements that favor the development of mononuclear cells, such as colony-stimulating factors. Flow cytometric analysis revealed that 99.1 +/- 0.9% of the subcloned cells were positive for CD11b and CD18, both of which are ligands of the intercellular adhesion molecule 1 (ICAM-1). These vehicle cells were labeled with a fluorescent lipophilic probe and returned intravenously to the DBA/2 mice. The mice then received, for 1 week, intraperitoneal injections of either lipopolysaccharide (LPS) to enhance ICAM-1 expression in the glomerulus, or saline as a control. In the LPS-treated mice, labeled vehicle cells were detected within the glomerulus cross-section (gcs) 24 hr after the first injection (0.73 +/- 0.10/gcs). The number of labeled vehicle cells within the glomerulus gradually increased for 1 week (1.47 +/- 0.19/gcs) and decreased after discontinuation of the LPS injections. However, in the saline-treated control group, only a negligible number of vehicle cells could be detected in the glomerulus (0.05 +/- 0.03/gcs). A second administration of LPS 4 weeks after injection of the vehicle cells was also able to promote accumulation in the glomerulus. Furthermore, immunohistochemical analysis revealed that the kinetics of the vehicle cell recruitment into the glomerulus corresponded to the level of ICAM-1 expression. On the assumption that the LPS-induced ICAM-1 expression may regulate the site and timing of the delivery of vehicle cells into the glomerulus, vehicle cells were transduced with human glucocerebrosidase (GC) gene, using an adenovirus vector, and reintroduced into the mice. The basal expression of GC gene in the isolated glomeruli of vehicle cell-treated mice rose by 1.7-fold compared with endogenous activity, whereas the GC activity was enhanced 3.2-fold by LPS treatment. Polymerase chain reaction designed to detect human GC-specific sequence revealed that isolated glomeruli of vehicle cell-treated mice contained exclusively the vehicle cell-oriented GC. This indicates that vehicle cells can be used to carry a certain gene to a specific inflamed site. Injection of vehicle cells, with or without LPS, had small effect on urinary protein excretion or serum creatinine levels. These findings suggest that our novel method allows site-specific gene delivery into inflamed glomeruli through interaction of adhesion molecules.     

Performance evaluation of SOFC systems using electrochemical partial oxidation of methane

We simulated the performance of systems using a solid oxide fuel cell (SOFC) stack which generates electricity by electrochemical partial oxidation of methane and a conventional steam‐reforming‐type SOFC (SRSOFC) stack. The net thermal efficiency in an atmospheric partial‐oxidation‐type SOFC (POSOFC)‐SRSOFC system was 8% higher than that in an atmospheric SRSOFC system at system outputs of 35 kW or more. The net thermal efficiency of a pressurized POSOFC‐SRSOFC‐gas turbine (GT) system was slightly higher than that of a pressurized SRSOFC‐GT system. © 2004 Wiley Periodicals, Inc. Electr Eng Jpn, 147(4): 11–19, 2004; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/eej.10314     

Diagnostic system to measure spatial and temporal profiles of shock front using compact two-stage light-gas gun and line reflection method

A diagnostic system has been developed to obtain spatial and temporal profiles of shock front. A two-stage light-gas gun is used to accelerate impactors in velocity range with 4-9 km/s. The system consists of the Faraday-type electromagnetic sensors to measure impactor velocity, optical system with high-speed streak camera to measure shock-wave velocities, and the delay trigger system with self-adjustable pre-event pulse generator. We describe the specifications and performance of this system and data-analysis technique on the tilt and distortion of the shock front. Finally, we obtained the Hugoniot data of copper for system demonstration.     

Solving satisfiability problems using reconfigurable computing

This paper reports on an innovative approach for solving satisfiability problems for propositional formulas in conjunctive normal form (SAT) by creating a logic circuit that is specialized to solve each problem instance on field programmable gate arrays (FPGAs). This approach has become feasible due to recent advances in reconfigurable computing and has opened up an exciting new research field in algorithm design. SAT is an important subclass of constraint satisfaction problems, which can formalize a wide range of application problems. We have developed a series of algorithms that are suitable for a logic circuit implementation, including an algorithm whose performance is equivalent to the Davis-Putnam procedure with powerful dynamic variable ordering. Simulation results show that this method can solve a hard random 3-SAT problem with 400 variables within 1.6 min at a clock rate of 10 MHz. Faster speeds can be obtained by increasing the clock rate. Furthermore, we have actually implemented a 128-variable 256-clause problem instance on FPGAs     

Hypoalbuminemia is an important risk factor of hypotension during hemodialysis

Hypotension during hemodialysis (HD) is an important problem in patients on HD. To investigate the risk factors that contribute to the hypotension during HD, we compared background factors of hypotensive (HP) patients during HD. Among 58 patients undergoing HD in Tamura Memorial Hospital, 12 patients could not continue full HD because of hypotension. We compared the data of ultrafiltration volume, cardiothoracic ratio (CTR), total protein (TP), serum albumin, blood urea nitrogen (BUN), serum creatinine, total cholesterol (TC), hemoglobin (Hb), blood glucose (BS), brain natriuretic peptide (BNP), and cardiac function between HP patients (HP group; n=12) and sex- and age-matched control patients (NP group; n=12). There were no significant differences of age, sex, and duration of HD between the 2 groups. Cardiothoracic ratio is bigger and BNP is higher in the HP group compared with the NP group (CTR: HP 55.8+/-2.9% vs. NP 47.7+/-1.1%, p=0.0165; BNP: HP 602+/-171 vs. NP 147+/-38, p=0.0167). Serum albumin in the HP group is significantly lower compared with the NP group (HP 3.2+/-0.1 g/dL vs. NP 3.5+/-0.1 g/dL, p=0.0130). However, there were no significant differences of ultrafiltration rate (UFR), BS, TC, Hb, and cardiac function between the 2 groups. There is a significant negative correlation between changes of systolic blood pressure (delta systolic blood pressure) and serum albumin in these patients (r=-0.598, p=0.0016). From these data, we conclude that hypoalbuminemia is a major risk factor of hypotension during HD.     

Fabrication of Liquid Helium-Free Superconducting Magnet for Millimeter Wave Gyrotron

A liquid helium free superconducting magnet was designed and fabricated and for an application to a millimeter wave gyrotron and a peniotron. The magnet generates a magnetic field of 5T in a 100mm room temperature bore and has been continuously working for more than 5,400 hours without troubles. The magnet system was applied to the millimeter wave gyrotron experiments to confirm the stability of the magnet. In the experiments, stable operations of the gyrotron were achieved in the frequency range of 30 - 133GHz.     

Algorithms for Distributed Constraint Satisfaction: A Review

When multiple agents are in a shared environment, there usually exist constraints among the possible actions of these agents. A distributed constraint satisfaction problem (distributed CSP) is a problem to find a consistent combination of actions that satisfies these inter-agent constraints. Various application problems in multi-agent systems can be formalized as distributed CSPs. This paper gives an overview of the existing research on distributed CSPs. First, we briefly describe the problem formalization and algorithms of normal, centralized CSPs. Then, we show the problem formalization and several MAS application problems of distributed CSPs. Furthermore, we describe a series of algorithms for solving distributed CSPs, i.e., the asynchronous backtracking, the asynchronous weak-commitment search, the distributed breakout, and distributed consistency algorithms. Finally, we show two extensions of the basic problem formalization of distributed CSPs, i.e., handling multiple local variables, and dealing with over-constrained problems.     

p57Kip2 regulates actin dynamics by binding and translocating LIM-kinase 1 to the nucleus

p57Kip2 is the only cyclin-dependent kinase (Cdk) inhibitor shown to be essential for mouse embryogenesis. The fact suggests that p57 has a specific role that cannot be compensated by other Cdk inhibitors. LIM-kinase 1 (LIMK-1) is a downstream effector of the Rho family of GTPases that phosphorylates and inactivates an actin depolymerization factor, cofilin, to induce the formation of actin fiber. Here we demonstrate that p57 regulates actin dynamics by binding and translocating LIMK-1 from the cytoplasm into the nucleus, which in turn results in a reorganization of actin fiber. The central region of p57, a unique feature among the Cdk inhibitors, and the N-terminal region of LIMK-1, which contains the LIM domains were essential for the interaction. Expression of p57, but not p27Kip1 or a p57 mutant, with a deletion in the central region was shown to induce marked reorganization of actin filament and a translocation of LIMK-1. Our findings indicate p57 may act as a key regulator in embryogenesis by bearing two distinct functions, the regulation of cell cycle through binding to Cdks and the regulation of actin dynamics through binding to LIMK-1, both of which should be important in developmental procedure.     

The incremental perturbation method for large displacement analysis of elastic-plastic structures

A procedure of applying the perturbation method is presented for the incremental numerical analysis of materially and combined non-linear problems of discrete and discretized structral systems. Small but finite strain and stress increments are strictly distinguished from the strain rates and stress rates, respectively. It is shown that, by applying the perturbation procedure not only to the non-linear strain-displacement relations and equilibrium equations, but also to the constitutive equations in terms of rate quantities, all the governing equations can be satisfied to any desired accuracy at every instantaneous configuration in between the starting and terminal points of an incremental step. The proposed method provides also means of finding, to a desired accuracy, every point on an equilibrium path of a discrete system at which a new element will start yielding or unloading and possible critical points on the path. The significance of the proposed method is expected to be appreciated particularly in numerical investigations of critical behaviours and post-buckling behaviours.