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The establishment of new therapeutic strategies for metabolic syndrome is urgently needed because metabolic syndrome, which is characterized by several disorders, such as hypertension, increases the risk of lifestyle-related diseases. One approach is to focus on the pre-disease state, a state with high susceptibility before the disease onset, which is considered as the best period for preventive treatment. In order to detect the pre-disease state, we recently proposed mathematical theory called the dynamical network biomarker (DNB) theory based on the critical transition paradigm. Here, we investigated time-course gene expression profiles of a mouse model of metabolic syndrome using 64 whole-genome microarrays based on the DNB theory, and showed the detection of a pre-disease state before metabolic syndrome defined by characteristic behavior of 147 DNB genes. The results of our study demonstrating the existence of a notable pre-disease state before metabolic syndrome may help to design novel and effective therapeutic strategies for preventing metabolic syndrome, enabling just-in-time preemptive interventions.

Introduction Stress-related disorders, such as depression, psychosomatic disorders and anxiety neurosis, are common and increasing in the workplace. Aromas have ataractic and sedation effects on the parasympathetic nerves. They also affect the feelings of fatigue from stress by stimulating the central nervous system. The purpose of this study is to examine the effect of an olfactory stimulus on changes in a physiological index. Using aromas during the loading of stress, we measured beat-to-beat interval (R-R interval) times from electrocardio-gram (ECG) recordings. Methods The subjects in our study were 3 male medical university students (subjects’ codes were A, B and C). After assuming a relaxed seated position for 10 min, the subjects performed a mental arithmetic task for 60 min followed by relaxation for 30 min, and then a rest for 10 min. The mental arithmetic task is a method of adding numbers without using tools. Every subject performed both the control-load and aroma-load tests under the same protocol, while the ECG was measured. They smelled lavandula angustifolia during the aroma-load. Result We analysed the power spectrum of high and low frequencies. The P1 (low frequen-cy)/P2 (high frequency) was defined as the ratio of P1 to P2. There was no change in the P1/P2 of 2 out of 3 subjects by using the aroma. Subjects A and B could avoid mental stress by using the aroma during the mental arithmetic operation. Discussion In an analysis of the power spectrum in the R-R interval times, the high and low frequencies in the physiological index of stress loading suggest that the aromas have an effect on the autonomic nervous system. As the strain on sympathetic nerve was relaxed, we conclude that the aroma affected the sympathetic nerves. Thus, we conclude that the aroma affected a sympathetic nerve, relaxing the strain on it.

The induction of lymphangiogenesis is an important process to promote cancer growth and cancer metastasis via the lymphatic system. Identifying the compounds that can prevent lymphangiogenesis for cancer therapy is urgently required. Chrysin, 5,7-dihydroxyflavone, a natural flavone extracted from Thai propolis, was used to investigate the effect on the lymphangiogenesis process of TR-LE, rat lymphatic endothelial cells. In this study, maximal nontoxic doses of chrysin on TR-LE cells were selected by performing a proliferation assay. The process of lymphangiogenesis in vitro was determined by cord formation assay, adhesion assay and migration assay. Chrysin at a nontoxic dose (25 μM) significantly inhibited cord formation, cell adhesion and migration of TR-LE cells when compared with the control group. We also found that chrysin significantly induced vascular endothelial growth factor C (VEGF-C) mRNA expression and nitric oxide (NO) production in TR-LE cells which was involved in decreasing the cord formation of TR-LE cells. In conclusion, we report for the first time that chrysin inhibited the process of lymphangiogenesis in an in vitro model. This finding may prove to be a natural compound for anti-lymphangiogenesis that could be developed for use in cancer therapy.

Japanese traditional herbal medicine (Kampo) have been used to improve the general physical condition after surgery and to mitigate the side effects of radiation and chemotherapy in tumor patients. Juzentaihoto (JTT) consists of ten medical herbs, and is also called Shi-Quan-Da-Bu-Tang in Chinese herbal medicine. Among Kampo medicines, JTT has especially gained attention as a biological response modifier. Currently, clinical trials of various tumor vaccine therapies are being performed world-wide. However, tumor antigens that are inoculated as vaccines do not have high immunogenicity; thus, it is difficult to obtain an effective therapeutic effect. Thus, it is necessary to develop a tumor vaccine adjuvant that is more potent and very safe. In the present study, we examined the efficacy of JTT as an oral adjuvant when given together with tumor vaccines. As a result, JTT enhanced the phagocytic ability of OVA antigen and the presentation ability of OVA antigen in dendritic cells in vitro. Furthermore, tumor growth was markedly decreased, and the survival period was significantly prolonged in mice inoculated with mouse lymphoma, which is expressed with tumor model antigen. In conclusion, these findings suggest that JTT can be used with tumor vaccines as an immune adjuvant.

Aim Vaccines have made great contributions to human welfare, and can be used even more effectively with adjuvants. The immune-inducible effects of adjuvants are classified into four categories: T-helper (Th)1, Th2, antibody, and cytotoxic T-lymphocyte (CTL) responses. Exogenous antigens are mainly presented to major histocompatibility complex (MHC) class II molecules, but are also presented to MHC class I molecules via the antigen cross-presentation process in dendritic cells. The enhancement of cross-presentation of an injected vaccine antigen by an adjuvant leads to Th1 and CTL responses, resulting in successful intracellular infection and tumor vaccine therapy. Methods It is widely known that herbal medicines have strong immune response effects. With this in mind, we developed a novel vaccine adjuvant from natural compounds used in herbal medicine, through an in vitro model vaccine antigen (ovalbumin, OVA) cross-presentation assay. Results Among 89 natural compounds, 1,2,3,4,6-penta-O-galloyl-β-d-glucose (PGG) most enhanced cross-presentation in dendritic cells. While the expression of MHC class II molecules was suppressed, PGG enhanced the expression of MHC class I molecules, restricted to OVA-derived peptides. Conclusion Restricted MHC class I expression resulting from the use of PGG enhanced cross-presentation by dendritic cells.

Breast cancer is the most common malignancy in women. Apoptosis is important for tumor suppression and may delay cancer progression. It was found that shikonin induced apoptosis in 4T1 murine mammary cancer cells and MDA‑MB‑231 human breast cancer cells in vitro. Total p38 and c‑Jun N‑terminal kinase (JNK) levels were maintained in 4T1 cells, and p38 phosphorylation, but not JNK phosphorylation, was significantly increased. Caspase‑3/7 activity was detected, which suggested that the p38 pathway, but not the JNK signaling pathway, induced apoptosis in 4T1 cells. The anti‑tumor effects of shikonin on orthotopic mouse models were also examined. On day 7 after inoculation of 4T1 cells into mice, tumor volumes in the shikonin‑treated and the control groups began to differ. On day 13, tumors were weighed, and shikonin was revealed to suppress tumor growth in the orthotopic 4T1 model in vivo. In conclusion, shikonin is a potential anti‑tumor drug for breast cancer.

Aspiration pneumonia (AP) has been recognized as one of the most common postoperative complications after hip surgery in elderly. The objective of the present study was to evaluate risk for postoperative complications of AP in elderly patients with femoral neck fractures. We recruited 426 patients (age 84.9 ± 7.4 years) with a history of hip surgery carried out at Toyama Municipal Hospital. AP occurred in 18 out of 426 cases (4.23%). Statistical test has found significant differences in age, gender, serum albumin level, and cognitive impairment, between AP and non-AP groups. Subsequently multiple logistic regression analysis was conducted to investigate the risk factors for AP, including age, gender, serum albumin, cognitive impairment, and activities of daily living (ADL). Adjusted odds ratio showed significant differences in age, gender, and serum albumin, whereas no significant differences were found in cognitive impairment and ADL. This study suggested that serum albumin seemed to be a risk factor for AP but were necessary to assess under adjustment of confounding factors, including age and gender. Monitoring serum albumin level seemed to be important for the postoperative management of AP, especially in elderly patients receiving surgery of femoral neck and trochanteric fractures.

Urinary retention (UR) has been recognized as one of the most common postoperative complications after hip surgery in elderly. The objective of the present study was to evaluate risk for postoperative complications of UR in elderly female patients with femoral neck fractures.We recruited 221 female patients (age 85.3 ± 7.0 years) with a history of hip surgery carried out at Toyama Municipal Hospital. UR occurred in 34 out of 221 cases (15.4%). Multiple logistic regression analysis was conducted to investigate the risk factors for UR, including age, body mass index (BMI), serum albumin, cognitive impairment, and activities of daily living (ADL).The results showed significant association of UR with cognitive impairment (P = .005, odds ratio [OR] 4.11, 95% confidence interval [CI] 1.53-11.03), and ADL (P = .029, OR 2.61, 95% CI 1.11-6.18), under adjustment with age and BMI.This study demonstrated that cognitive function and ADL were the important risk factors for UR, suggested that the postoperative management of UR is important with taking account of neurofunctional assistance and nursing care in daily living, especially in elderly female patients receiving surgery of femoral neck and trochanteric fractures.

The objectives of this study were to determine the effects of deoxyshikonin on lymphangiogenesis. Deoxyshikonin enhanced the ability of human dermal lymphatic microvascular endothelial cells (HMVEC-dLy) to undergo time-dependentin vitrocord formation. Interestingly, an opposite result was observed in cells treated with shikonin. The increased cord formation ability following deoxyshikonin treatment correlated with increased VEGF-C mRNA expression to higher levels than seen for VEGF-A and VEGF-D mRNA expression. We also found that deoxyshikonin regulated cord formation of HMVEC-dLy by increasing the HIF-1αmRNA level, HIF-1αprotein level, and the accumulation of HIF-1αin the nucleus. Knockdown of the HIF-1αgene by transfection with siHIF-1αdecreased VEGF-C mRNA expression and cord formation ability in HMVEC-dLy. Deoxyshikonin treatment could not recover VEGF-C mRNA expression and cord formation ability in HIF-1αknockdown cells. This indicated that deoxyshikonin induction of VEGF-C mRNA expression and cord formation in HMVEC-dLy on Matrigel occurred mainly via HIF-1αregulation. We also found that deoxyshikonin promoted wound healingin vitroby the induction of HMVEC-dLy migration into the wound gap. This study describes a new effect of deoxyshikonin, namely, the promotion of cord formation by human endothelial cells via the regulation of HIF-1α. The findings suggest that deoxyshikonin may be a new drug candidate for wound healing and treatment of lymphatic diseases.

The induction of lymphangiogenesis is an important process to promote cancer growth and cancer metastasis via the lymphatic system. Identifying the compounds that can prevent lymphangiogenesis for cancer therapy is urgently required. Chrysin, 5,7-dihydroxyflavone, a natural flavone extracted from Thai propolis, was used to investigate the effect on the lymphangiogenesis process of TR-LE, rat lymphatic endothelial cells. In this study, maximal nontoxic doses of chrysin on TR-LE cells were selected by performing a proliferation assay. The process of lymphangiogenesis in vitro was determined by cord formation assay, adhesion assay and migration assay. Chrysin at a nontoxic dose (25 μM) significantly inhibited cord formation, cell adhesion and migration of TR-LE cells when compared with the control group. We also found that chrysin significantly induced vascular endothelial growth factor C (VEGF-C) mRNA expression and nitric oxide (NO) production in TR-LE cells which was involved in decreasing the cord formation of TR-LE cells. In conclusion, we report for the first time that chrysin inhibited the process of lymphangiogenesis in an in vitro model. This finding may prove to be a natural compound for anti-lymphangiogenesis that could be developed for use in cancer therapy.

Insulation tests for the stator coil, which decides the motor life, are carried out once several years in power and industrial plant. In the case of high voltage (HV) motors, insulation failure may adversely affect plant operation. Hence, maintenance activities, including insulation tests, research on insulation deterioration, and online Partial Discharge (PD) monitoring, are actively pursued for HV motors.On the other hand, the maintenance of low voltage (LV) motors is restricted to breakdown maintenance (BDM) because (1) a large number of LV motors are in operation in plants and (2) maintenance activities are relatively more expensive than those for HV motors. In this paper, the results of a study on insulation deterioration detection for LV motors are presented. For the deterioration detection, the deference in Zero-Sequence current waveforms between normal conditions and fault conditions is analyzed. This method helps in decreasing the maintenance cost and in online insulation diagnosis for LV motors.

We propose a multielectrode circular position-sensitive device that does not have any discontinuity in the detection region and has multiple electrodes for current output. We have also manufactured a prototype device. The device has a circular detection region that consists of photodiodes radially aligned with regular pitch and a resistance line connecting the outer edges of the photodiodes. All of the photocurrent excited in the photodiodes flows into the resistance line and is extracted from the electrodes connected to the resistance line at even intervals. There is no insensitive region for current output in this device since the detection region and the resistance line are separated; thus, detection with high resolution is possible at every angular position. We conducted a simulation of the detection characteristics and will propose a computational method for the position that uses four-electrode outputs in this paper. We confirmed that it is effective in minimizing the error from both the simulation and the experiment. We will also propose a measurement system of absolute angle using this method, confirming an error of less than 0.1° in the computation results.

When the rectangular slit of an optical encoder projects an image, the containment of higher-order components in the projected image depends on the gap distance. Therefore, we performed the Fourier series expansion of the function describing Fresnel diffraction pattern to obtain a simple relational expression that can show the relation between the gap distance and the containment of each order component and then carried out an experiment to verify the obtained expression. Using this expression, we found that certain orders of the wave components disappear depending on the slit opening ratio and also that the use of a slit with an opening ratio smaller than 0.5 results in lesser distortion of the waveform over a wide range of gap values. Reduction of waveform distortion over such a wide range can prevent increment of errors caused by shaft displacement in the axial direction and assembly errors. Thus, robust performance of the encoder can be achieved. The results of this study are expected to be useful in the design of robust optical encoders.

We have developed a novel evaluation technique of the deterioration degree of insulators for breakers using a chemical analysis and the Mahalanobis–Taguchi (MT) method. It is possible to evaluate the deterioration degree with great accuracy and nondestructively on-site by this technique without the effect of humidity and external noise such as electromagnetic waves. The mechanism of the insulator's surface resistivity reduction was clarified, and it was found that the deterioration degree of insulators could be evaluated by this technique because a linear relationship existed between the results judged by the MT method and the actual measurement results for the surface resistivity. In comparison to electrical methods, such as partial electric discharge and megohmmeters, the evaluation accuracy has been improved by three digits and the range of the deterioration degree that could be evaluated was expanded by seven digits. © 2009 Wiley Periodicals, Inc. Electr Eng Jpn, 168(1): 11–20, 2009; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.20849

The authors have developed a remaining service life diagnostic technology for insulators, which are important parts involved in determining the service life of power distribution equipment. Application of chemical evaluation and the Mahalanobis–Taguchi (MT) method enabled them to diagnose the insulators' degree of deterioration with great accuracy and nondestructively onsite. The theory derives the threshold value of surface resistivity for electric discharge initiation calculated based on the diagnostic results from the MT method and the year in which the master curve of service life and the threshold value intersect. It was clarified that a remaining service life could be predicted by this technology, because there was a good relationship between the check examination results of electric discharge initiation in the laboratory and the results the authors found. © 2009 Wiley Periodicals, Inc. Electr Eng Jpn, 167(2): 1–9, 2009; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.20854

A new type of circular semiconductor position sensitive detector (PSD) called multi electrode circular PSD (ME-CPSD), which consists of a photosensitive region, a resister line, and 16 electrodes, is presented. The photosensitive region is in the shape of a ring, which is formed by the radial arrangement of long and narrow photodiodes. The outer ends of the photodiodes are connected to the continuous resistor line. Photoexcited carriers generated in the photodiode flow to the resistor line and are extracted by the multi electrode, which divides the resistor into 16 equal parts. The angular position of the light spot is calculated from the output current of the selected electrodes. Compared to conventional circular PSDs, the reliability of angular measurement is better, this is because the ME-CPSD does not have an undetectable region caused by unavoidable discontinuities in the structure of conventional circular PSDs. This device can not only measure the absolute angular position but also carry out a more precise angular measurement by selecting narrower electrode intervals. This device has the capability of realizing a high-precision noncontact angular measurement system with a simple construction.

We developed remaining service life diagnostic technology of phenol insulators for circuit breakers. Phenol insulators were analyzed by chemical evaluation such as ion concentration and coloration, and the results were diagnosed by the Mahalanobis-Taguchi system (MTS), which is a pattern information technology. Particularly effective items for diagnosis included ions of nitric acid, sulfuric acid, chloride, and calcium. Since there was a good relationship between the results diagnosed by MTS and the actual measurement results of surface resistivity, we found that applying MTS to the chemical evaluation results allowed deterioration diagnosis of phenol insulators instead of surface resistivity, which couldn't be measured on-site. Time was defined as the end of the service life when electrical discharge was initiated and remaining service life was predicted. The linear relationship (master curve of service life) was clarified between the real number value of elapsed time and the logarithmic value of surface resistivity at 50% RH, and remaining service life was predicted from the diagnosis results by MTS and the year in which the master curve and the threshold value intersect. Surface resistivity (threshold value) for electrical discharge initiation was derived from creepage distance, permittivity of phenol insulators, frequency, etc. We substantiated that the remaining service life of the phenol insulators could be predicted by this technology because a good relationship existed between the check examination results of the electric discharge initiation in the laboratory and the prediction results.

We developed deterioration diagnosis technique for bus Joint in Switchboards. Increase of contact resistance by deterioration of a bus joint causes a temperature rise. However, it is difficult to really measure a temperature rise by a minute change of contact resistance. That is a method to detect a change of contact resistance of a bus joint as a temperature fluctuation. We expect that a serious accident such as a short circuit is prevented beforehand by this technique.

In this paper, by using the Android mobile terminal, we make a application of performing autonomous driving control small electric car as the target. Small EV car (COMS) is treated as experimental subjects. This application will help the Elderly, driving poor people, fast, accurate to park the car and call the car coming for users easily. Moreover, it is also considered that it becomes possible to inform the vehicle information for users. For this study, it introduce that how making the communication system with the car. Also using Map management tool “Mapinfo” for design the path for a small electric vehicle, for example the path to/from parking place. On top of that, we seek a control method to safely autonomous driving on the basis of the data around the vehicle. Also for other cars and pedestrians traveling the parking lot, we aim to correspond to the safety and smooth.

Most switchboards are used for a long term of about 30 years. As for the switchboard, the situation of the use and maintenance is individually and greatly different. So the life-expectancy presumption technique of the switchboards has not been established. We executed the deterioration diagnosis for the switchboards that had been used for 30 years. We paid attention to the surface deterioration of the insulation materials that is the main element that decides the life-expectancy of the switchboards. We evaluated the life-expectancy presumtion technique of aged switchboards based on MTS (Mahalanobis Taguchi system) method. This technique attracts attention in recent years. And we confirmed the presumption result was corresponding to the result of the verification with temperature controlled bath actually.

We present here a case report of a 69-year-old female patient with T granular lymphocyte proliferative disorder (T-GLPD) expressing the gamma/delta T-cell receptor. The patient had been treated for rheumatoid arthritis for 25 years, and presented with mild anaemia. Cell-surface marker analysis was carried out using flow cytometry and natural killer function was determined using a chromium release assay. The case report is followed by a summary of the 21 other gamma/delta T-GLPD cases reported in the literature and a comparison of their clinical characteristics with those of T-GLPD cases expressing the alpha/beta T-cell receptor. The clinical symptoms and the frequency of association with rheumatoid arthritis are similar in gamma/delta and alpha/beta T-GLPD, but a prevalence of the CD8- cell-surface marker and enhanced natural killer function appear to be characteristics of gamma/delta T-GLPD.

Information technology is increasingly important in recent years for the development of our society. IT has brought many changes to everything in our society with incredible speed. Hence, when we investigate R & D themes or plan business strategies in IT, we must understand overall situation around the target technology area besides technology itself. Especially it is crucial to understand overall situation as time series to know what will happen in the near future in the target area. For this purpose, we developed a method to generate Multiple-phased trend maps automatically based on the Internet content. Furthermore, we introduced quantitative indicators to analyze near future possible changes. According to the evaluation of this method we got successful and interesting results.

Strawberries are often replanted in the same field as a single crop or in short rotation cycles causing a progressive deterioration of the soil. The present study was conducted to clarify the growth response of strawberry roots to increasing amounts of strawberry residues. Observation boxes were built using glass windows and filled with commercial compost. In order to simulate the soil accumulation of strawberry plant residues a 3-cm layer with a residue concentration ranging from 0 to 100% was prepared 15 cm from the soil surface. The roots were observed for three weeks starting five days after planting. The root growth was reduced by the presence of the residues. After the first week, the lowest growth was found with the 30% residue treatment. After the primary roots entered the layer containing residue the growth was further reduced in the 100% residue treatment, but the primary roots showed only a slight or no dimorphism when they encountered the layer. The lowest residue treatment did not re...

Background Inhibition of metastasis through upregulation of immune surveillance is a major purpose of chemokine gene therapy. In this study, we focused on a membrane-bound chemokine CXCL16, which has shown a correlation with a good prognosis for colorectal cancer (CRC) patients. Methods We generated a CXCL16-expressing metastatic CRC cell line and identified changes in TNF and apoptosis-related factors. To investigate the effect of CXCL16 on colorectal liver metastasis, we injected SL4-Cont and SL4-CXCL16 cells into intraportal vein in C57BL/6 mice and evaluated the metastasis. Moreover, we analyzed metastatic liver tissues using flow cytometry whether CXCL16 expression regulates the infiltration of M1 macrophages. Results CXCL16 expression enhanced TNF-α-induced apoptosis through activation of PARP and the caspase-3-mediated apoptotic pathway and through inactivation of the NF-κB-mediated survival pathway. Several genes were changed by CXCL16 expression, but we focused on IRF8, which is a regulator of apoptosis and the metastatic phenotype. We confirmed CXCL16 expression in SL4-CXCL16 cells and the correlation between CXCL16 and IRF8. Silencing of IRF8 significantly decreased TNF-α-induced apoptosis. Liver metastasis of SL4-CXCL16 cells was also inhibited by TNF-α-induced apoptosis through the induction of M1 macrophages, which released TNF-α. Our findings suggest that the accumulation of M1 macrophages and the enhancement of apoptosis by CXCL16 might be an effective dual approach against CRC liver metastasis. Conclusions Collectively, this study revealed that CXCL16 regulates immune surveillance and cell signaling. Therefore, we provide the first evidence of CXCL16 serving as an intracellular signaling molecule. Electronic supplementary material The online version of this article (doi:10.1186/1471-2407-14-949) contains supplementary material, which is available to authorized users.

A stacked CdZnTe semiconductor detector, which is able to detect the 6.13 MeV γ-rays from 16N, was prototyped and the response calculation was carried out by a Monte-Carlo simulation. The detector response was simulated by using the electron and photon transport code, EGS4 and taking into account the carrier trapping phenomena. The results of the response calculation agreed with the experimental data from the checking source of 137Cs and 60Co. The prototype's response and sensitivity to 16N were calculated by simulating an incident energy of 6.13 MeV . The source spectra were unfolded with the detector's response function obtained by simulation, and it indicated that the incident γ-ray energy and its intensity ratio was identified. We have acquired the potential to measure the γ-ray energy in the high energy region about 6 MeV with the stacked CdZnTe detector.

The prototype model of the stacked CdZnTe semiconductor detector, which is able to measure the 6.13MeV γ-ray from 16N, was fabricated. The prototype's response calculation was carried out by Monte-Carlo method. The result of the response calculation agreed with the experiment data of check sources of 137Cs and 60Co, and 16N which was measured at vicinity of the primary cooling water pipe of the nuclear reactor. The source spectra were unfolded with detector's response function obtained by simulation, and it is indicated that the incident γ-ray energy and its intensity ratio was identified and that the energy of 6MeV γ-ray could be measured by the prototype of the stacked detector.

The study of a Multi-Agent System using multiple autonomous robots has recently attracted much attention. With the problem of target a tracking as a typical case study, multiple autonomous robots decide their own actions to achieve the whole task which is tracking target. Each autonomous robot’s action influences each other. So, an action decision in coordination with other robots and the environment is needed to achieve the whole task effectively. The game theory is a major mathematical tool for realizing a coordinated action decision. The game theory mathematically deals with a multiagent environment influencing each other as a game situation. The conventional methods model one of the target tracking as a n-person general-sum game, and the use of the non-cooperative Nash equilibrium theory in non-cooperative games and the semi-cooperative Stackelberg equilibrium. The semicooperative Stackelberg equilibrium may obtain better control performance than the non-cooperative Nash equilibrium, but requires the communication among robots. In this study, we propose switching of methods in the equilibrium derivation both from the non-cooperative Nash equilibrium and the semicooperative Stackelberg equilibrium in a coordination algorithm for the target tracking. In the simulation, our proposed method achieves coordination with less connections than the method using the semicooperative Stackelberg equilibrium at all times. Furthermore, the proposed method shows better control performance than the non-cooperative Nash equilibrium.

The objectives of this study were to determine the effects of deoxyshikonin on lymphangiogenesis. Deoxyshikonin enhanced the ability of human dermal lymphatic microvascular endothelial cells (HMVEC-dLy) to undergo time-dependent in vitro cord formation. Interestingly, an opposite result was observed in cells treated with shikonin. The increased cord formation ability following deoxyshikonin treatment correlated with increased VEGF-C mRNA expression to higher levels than seen for VEGF-A and VEGF-D mRNA expression. We also found that deoxyshikonin regulated cord formation of HMVEC-dLy by increasing the HIF-1 α mRNA level, HIF-1 α protein level, and the accumulation of HIF-1 α in the nucleus. Knockdown of the HIF-1 α gene by transfection with siHIF-1 α decreased VEGF-C mRNA expression and cord formation ability in HMVEC-dLy. Deoxyshikonin treatment could not recover VEGF-C mRNA expression and cord formation ability in HIF-1 α knockdown cells. This indicated that deoxyshikonin induction of VEGF-C mRNA expression and cord formation in HMVEC-dLy on Matrigel occurred mainly via HIF-1 α regulation. We also found that deoxyshikonin promoted wound healing in vitro by the induction of HMVEC-dLy migration into the wound gap. This study describes a new effect of deoxyshikonin, namely, the promotion of cord formation by human endothelial cells via the regulation of HIF-1 α . The findings suggest that deoxyshikonin may be a new drug candidate for wound healing and treatment of lymphatic diseases.

We have performed a broad-ranging analysis of the adjuvant effect of a Kampo medicine, juzentaihoto (JTT), on influenza vaccination in a multicenter randomized controlled trial. In this study, the enhancing effect of JTT on antibody titer after influenza vaccination was studied for 28 weeks in elderly people who were in the high-risk group for influenza infection. In total, 91 subjects over 65 years old were recruited from four long-term-care facilities located in Chiba, Gunma, and Toyama prefectures in Japan. Participants were randomly assigned to the JTT and the control groups. Blood samples were taken at 4 weeks before vaccination, at the time of vaccination, and then at 4, 8, 12, and 24 weeks after vaccination. The hemagglutination inhibition (HI) titers against A/California/7/2009 (H1N1), A/Victoria/210/2009 (H3N2), and B/Brisbane/60/2008 were then manually measured. A significant increase in HI titer against H3N2 was observed at week 8 after vaccination in the JTT group compared with the control group (P=0.0229), and the HI titer of the JTT group significantly increased from 4 to 24 weeks (P=0.0468), compared with the control group. In conclusion, our results indicated that JTT increased and prolonged antibody production against A/Victoria/210/2009 (H3N2), in particular, after influenza vaccination.