Development of a colon delivery capsule and the pharmacological activity of recombinant human granulocyte colony-stimulating factor (rhG-CSF) in beagle dogs

A peroral dosage form was examined to deliver recombinant human granulocyte colony-stimulating factor (rhG-CSF) to the colon in beagle dogs. A new gelatin capsule with its inside surface coated with ethylcellulose was prepared for this purpose. RhG-CSF was dissolved with propylene glycol and was filled in the capsule. Several kinds of ethylcellulose-gelatin capsules with an ethylcellulose layer of thickness 46 to 221 mm were used. The capsule was filled with propylene glycol solution containing fluorescein as an absorption marker, castor oil derivative and citric acid. The hardness of the capsule was tested after the gelatin layer was dissolved using a hardness tester and was dependent on the thickness of the ethylcellulose layer of the capsule. The time, Tmax, at which plasma fluorescein level reaches its maximum following oral administration of ethylcellulose capsules was used as a parameter for the in-vivo disintegration time of the ethylcellulose capsule into the colon. Capsules of thickness 84 mm with a Tmax of 4-6 h were filled with rhG-CSF solution containing fluorescein and were administered to dogs. After administration, blood samples were collected for 96 h and the blood total leucocyte (BTL) counts were measured as a pharmacological index of rhG-CSF. The maximum BTL count appeared at 10 h then gradually decreased and returned to its normal level at 48 h. These results suggest the usefulness of ethylcellulose capsules for the delivery of rhG-CSF to the colon and the possibility of a new oral rhG-CSF dosage form has been elucidated.     

Managing networks of communities of practice for organizational knowledge creation A Knowledge Management imperative in the era of globalization

This article explores some imperatives of Knowledge Management for organizational knowledge creation in the era of globalization. As the transformation of Knowledge Management practices of Japanese firms in 1990s shows, Nonaka and TakeuchVs original model of organizational knowledge creation needs to be expanded by incorporating the concept of “community of practice” as the “engine” of knowledge creation. As an attempt for such expansion, it proposes a model of knowledge-creating organization as a self-organizing network of interactive, overlapping, and self-managing communities of practice. This article also explores some organizational conditions and managerial implications to prevent “malfunction” of communities of practice in the threats of globalization and to facilitate their dynamic evolution. Knowledge-creating organizations and their managers need to give due recognition to and support for “differences” that exist not only among diverse communities of practices but also within each communities. At a micro level approach, they need to “empower” community members by encouraging “ story-telling” or “narrative” of members’ lives in the communities and by assuring “transparency” of activities and resources to the members. As a macro level approach, they need to develop a “communitarian” organizational structure that fits to organizational knowledge creation in “multiculturalization” of societies.     

Molecular Mechanisms for the Regulation of Insulin-Stimulated Glucose Uptake by Small Guanosine Triphosphatases in Skeletal Muscle and Adipocytes

Insulin is a hormone that regulates the blood glucose level by stimulating various physiological responses in its target tissues. In skeletal muscle and adipose tissue, insulin promotes membrane trafficking of the glucose transporter GLUT4 from GLUT4 storage vesicles to the plasma membrane, thereby facilitating the uptake of glucose from the circulation. Detailed mechanisms underlying insulin-dependent intracellular signal transduction for glucose uptake remain largely unknown. In this article, I give an overview on the recently identified signaling network involving Rab, Ras, and Rho family small guanosine triphosphatases (GTPases) that regulates glucose uptake in insulin-responsive tissues. In particular, the regulatory mechanisms for these small GTPases and the cross-talk between protein kinase and small GTPase cascades are highlighted.     

Macrophage Activation Markers Predict Liver-Related Complications in Primary Biliary Cholangitis

Primary biliary cholangitis (PBC) has a wide variation in clinical presentation and course. There is no significant correlation between these symptoms and the disease stage, although patients with more advanced stages generally have more symptoms. It is important to develop biomarkers in order to identify patients with an increased risk of complications and end-stage liver disease. This study investigated surrogate markers for risk estimation of PBC-related complications, including a study population of 77 patients with PBC who underwent liver biopsy and were measured for serum levels of macrophage activation markers, soluble CD163 (sCD163), soluble mannose receptor (sMR), and zonulin. Patients with PBC were divided into symptomatic (Group S, n = 20) and asymptomatic (Group A, n = 57) groups. The correlations of histological stages based on both Scheuer and Nakanuma classifications with the three serum markers were investigated. The Nakanuma classification involves grading for liver fibrosis and bile duct loss. The three biomarkers were assessed for their diagnostic ability to identify patients with PBC having high risk of developing complications. The predictive factors of these complications were examined as well. Group S had significantly higher serum sMR (p = 0.011) and sCD163 (p = 0.048) levels versus Group A. A composite index of sMR and sCD163 measurements had significantly better prediction performance than sCD163 alone (p = 0.012), although not when compared to sMR alone (p = 0.129). Serum sMR was an independent factor for developing complications on both univariate (Odds ratio (OR) = 30.20, 95% confidence interval (95% CI): 3.410–267.0, p = 0.00220), and multivariate (OR = 33.70, 95% CI: 3.6600–311.0, p = 0.0019) analyses. Patients with PBC having sMR of ≥56.6 had a higher incidence of clinical complications versus those with a sMR of <56.6. Serum sMR predicts the development of complications in patients with PBC. sMR plus sCD163 showed better predictive power than either marker alone, although the addition of sCD163 did not improve the predictive power of sMR. Future prospective studies are required in order to validate the findings of the present study.     

Design and performance of high-precision MT-type connector for1.55-μm zero-dispersion-shifted fiber-ribbon cables

We have found that, for dispersion-shifted fiber (DSF) ribbons, the accuracy with which the fiberhole is positioned in the connector ferrule must be less than 0.6 μm to realize a low average insertion loss of about 0.1 dB. By using the high-precision ferrules, we realized MT-type connectors that achieved a very low average insertion loss of 0.11 dB with a maximum of 0.37 dB. These connectors also satisfied mechanical and environmental stability requirements. We have confirmed that our high-precision MT-type connectors can be used for joining DSF ribbon     

A modified power control scheme for remedying the effects of traffic nonuniformity in LEO satellite communications systems

It has been shown in our previous studies that the geographical traffic nonuniformity considerably affects the performance of the low earth orbit satellite communications systems. In this paper, a new scheme for improving the throughput characteristics of these systems at nonuniform traffic distribution is proposed. In this method, some parts of the users under the satellite which is flying over the area with high traffic load are assigned to its neighbor satellites with lower transmitting power levels. It is shown that the method equalizes the traffic loads of the satellites to some degree and, hence, can improve the throughput characteristics of the system.     

Design of enhanced MT-RJ type connector for physical contact

An enhanced MT-RJ type connector was constructed employing a compact two-fiber ferrule in a newly designed housing for high-density optical duplex connection. The ferrule and the connector housing is designed to achieve physical contact (PC). As a result, the connectors we fabricated perform very well and provide ease of operation by means of direct core endface contact between the plugs. This connector is highly effective for use in the duplex connection of advanced optical networks.     

Heterochrony and evolvability in neural network development

Recent studies in evolutionary computation have focused on using developmental processes together with genetic algorithms in order to achieve more complex designs. Although several models have been proposed, their growth dynamics, and their interactions with evolutionary algorithms are still poorly understood. One particularly neglected concept in artificial developmental systems is heterochrony: how evolution affects development by changing the timing and rate of developmental events. In this article we attempt to address this issue by analyzing heterochronic changes in a well-known artificial developmental model, the cellular encoding model, by using a previously developed heterochrony framework. We have conducted experiments by evolving networks to solve a Boolean problem, and analyzed heterochronic changes in both successful and unsuccessful runs. Our findings show that owing to its properties, the cellular encoding model strongly affects the developmental dynamics and the heterochronic changes that occur during evolution. Our experiments also show that hypermorphic changes (a kind of heterochronic occurrence) lead to greater evolvability in successful runs.     

Endothelin-induced activation of mitogen-activated protein kinases in glomerular mesangial cells from normotensive and stroke-prone spontaneously hypertensive rats

1. Kinase assay in myelin basic protein (MBP) containing polyacrylamide gels revealed that endothelin-1 (ET-1) and ET-3 increased MBP kinase activities in glomerular mesangial cells (MC) from Wistar-Kyoto (WKY) rats and spontaneously hypertensive rat (SHRSP). ET-1 stimulated MBP kinase activities more potently than ET-3. 2. Immunoprecipitation with anti-41-kDa MAPK antiserum showed that the MBP kinases activated by ET-1 correspond to 43- and 41-kDa MAPK. 3. Since Phorbol 12-myristate 13-acetate, a direct activator of protein kinase C, also activated MAPK, protein kinase C was suggested to mediate ET-induced activation of MAPK. 4. These results suggest that MAPK may mediate the ET actions in glomerular mesangial cells from normotensive rats as well as spontaneously hypertensive rats. Since ET is produced by vascular endothelial cells of the kidney and glomerular mesangial cells, the ET signalling pathway may have some physiological and pathophysiological significance in vivo glomerulus.