•We analyzed the data management system (DMS) appropriate for international collaboration.•We define the principal requirements for all components of the DMS.•We evaluated application of DMS ...requirements to the JT-60SA experiment.•We evaluated the role network bandwidth and time delay between EU and Japan.
Remote operation and data analysis are becoming key requirements of any fusion devices. In this framework a well-conceived data management system integrated with a suite of analysis and support tools are essential components for an efficient remote exploitation of any fusion device. The following components must be considered: data archiving data model architecture; remote data and computers access; pulse schedule, data analysis software and support tools; remote control room specifications and security issues. The definition of a device-generic data model plays also important role in improving the ability to share solution and reducing learning time. As for the remote control room, the implementation of an Operation Request Gateway has been identified as an answer to security issues meanwhile remotely proving all the required features to effectively operate a device.
Previous requirements have been analyzed for the new JT-60SA tokamak device. Remote exploitation is paramount in the JT-60SA case which is expected to be jointly operated between Japan and Europe. Due to the geographical distance of the two parties an optimal remote operation and remote data-analysis is considered as a key requirement in the development of JT-60SA. It this case the effects of network speed and delay have been also evaluated and tests have confirmed that the performance can vary significantly depending on the technology used.
Abstract 4076
Despite recent advances in the use of newly developed drugs, high-risk multiple myeloma (MM) patients harboring del13q, t(4;14) or del17p revealed significantly shorter survival. To ...overcome the limitation, we have screened forty synthetic anilinoquinazoline (AQ) derivatives, and found a novel compound, Q15, which significantly inhibited the growth of MM cell lines with high-risk chromosomal abnormalities. The purpose of this study is to examine anti-tumor and anti-osteoclastogenic activities of Q15 and to clarify the possibility of development of new drug effective for high-risk MM and bone diseases.
Forty AQ derivatives were synthesized and screened for anti-proliferative effect on KMS34 cells. Q15 strongly inhibited growth of t(4;14)-positive KMS34 cells and induced apoptosis in much lower concentration (IC50=78nM) compared with gefitinib (IC50=2500nM), a representative AQ. Q15 also inhibited growth of other MM cell lines harboring high-risk chromosomal abnormalities. It was also found that Q15 did not inhibit intracellular tyrosine phosphorylation induced by EGF, FGF-2, HGF and IL-6, suggesting that Q15 showed anti-tumor activity in a different mechanism from that of gefitinib. In vivo anti-myeloma activity was evaluated by intraperitoneal injection of Q15 into KMS34-bearing lcr/SCID mice. Twenty mg/kg Q15 significantly delayed the tumor growth in these mice. Histopathological examinations revealed apoptosis of MM cells in Q15-treated mice. Growth of colony-forming cells was not suppressed by much higher concentrations (25μ M) of Q15 than IC50, suggesting low hematopoietic toxicity of Q15. In pharmacokinetic study using high-performance liquid chromatography (HPLC), the plasma concentration of Q15 in mice reached a maximum (Cmax=4.5μ M) at 1.5hr after injection, and its half life (T1/2) was 4.5hr. In addition, anti-osteoclastogenic activity was also examined by adding Q15 to M-CSF/RANK ligand-induced osteoclastogenic culture of bone marrow mononuclear cells from C57BL/6JJcl mice. The number of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated osteoclasts was reduced in the presence of Q15.
Q15, a novel AQ derivative, has anti-MM activity in vivo and is a potentially safe and effective drug for high-risk MM with bone lesions.
No relevant conflicts of interest to declare.
Target exon resequencing using Massively Parallel DNA Sequencing (MPS) is a new powerful strategy to discover causative genes in rare Mendelian disorders such as deafness. We attempted to identify ...genomic variations responsible for deafness by massive sequencing of the exons of 112 target candidate genes. By the analysis of 216randomly selected Japanese deafness patients (120 early-onset and 96 late-detected), who had already been evaluated for common genes/mutations by Invader assay and of which 48 had already been diagnosed, we efficiently identified causative mutations and/or mutation candidates in 57 genes. Approximately 86.6% (187/216) of the patients had at least one mutation. Of the 187 patients, in 69 the etiology of the hearing loss was completely explained. To determine which genes have the greatest impact on deafness etiology, the number of mutations was counted, showing that those in GJB2 were exceptionally higher, followed by mutations in SLC26A4, USH2A, GPR98, MYO15A, COL4A5 and CDH23. The present data suggested that targeted exon sequencing of selected genes using the MPS technology followed by the appropriate filtering algorithm will be able to identify rare responsible genes including new candidate genes for individual patients with deafness, and improve molecular diagnosis. In addition, using a large number of patients, the present study clarified the molecular epidemiology of deafness in Japanese. GJB2 is the most prevalent causative gene, and the major (commonly found) gene mutations cause 30-40% of deafness while the remainder of hearing loss is the result of various rare genes/mutations that have been difficult to diagnose by the conventional one-by-one approach. In conclusion, target exon resequencing using MPS technology is a suitable method to discover common and rare causative genes for a highly heterogeneous monogenic disease like hearing loss.
We have previously reported that antigen coupled with liposomes induced antigen-specific and IgE-selective unresponsiveness in mice. This antigen preparation was investigated for application in a ...novel vaccine protocol to induce minimal IgE synthesis. In this study, ovalbumin (OVA)−liposome conjugates were made using liposomes of four different lipid components, including unsaturated carrier lipid and three different saturated carrier lipids, after which the induction of anti-OVA antibody production was investigated in mice. All of the OVA−liposome conjugates induced IgE-selective unresponsiveness. The membrane fluidity of liposomes, as measured by detecting changes in the fluorescence polarization of a 1,6-diphenyl-1,3,5-hexatriene (DPH) probe located in the bilayers, was significantly higher in liposomes consisting of unsaturated carrier lipids than those of the other liposomes consisting of saturated carrier lipids. The highest titer of anti-OVA IgG was observed in mice immunized with OVA−liposomes made using liposomes consisting of unsaturated carrier lipids. In addition, among these OVA−liposomes, the one possessing the longest carbon chain induced the lowest IgG antibody production. These results suggest that the membrane fluidity of liposomes might affect the adjuvant effect of liposomes but not the induction of IgE-selective unresponsiveness in immunizations with surface-linked liposomal antigens.
Many Japanese women have trouble with cold hands and feet. We examined how the skin temperature of the hands and feet are related to the environmental temperature. The subjects were eight otherwise ...healthy women aged 20-22 years, who complained of cold hands and feet. The dorsal and ventral skin temperatures of the hands and feet of a subject were measured using a thermotracer over two menstrual cycles. As the outside temperature and temperature in the bedroom increased from spring to summer, both the basal body and skin temperature of the hands and feet increased. However, the skin temperature of the hands and feet did not change with the basal body temperature, but were influenced more by the increase in bedroom temperature. Therefore, we compared subjects who woke up in a bedroom warmed to about 22℃ with those who woke in a bedroom at a normal winter temperature of about 9.6℃. During the low phase of body temperate, the basal body temperature and skin temperature of the hands of the subjects were significantly higher in the warmed bedroom. In other words, on warming the bedroom temperature in winter, the thermoregulatory center was under the illusion that it was spring or early summer, which played a dominant role in altering the circulation to the hands and feet.
Many Japanese women have trouble with cold hands and feet. We reported how the skin temperature of the hands and feet are related to the environmental temperature in previous paper. As the outside ...temperature and the temperature in the bedroom increased from spring to summer, both the basal body and skin temperature of the hands and feet increased. However, the skin temperature of the hands and feet did not change with the basal body temperature, but were influenced more by the increase in bedroom temperature. The subjects were two otherwise healthy women aged 21 years, who complained of cold hands and feet. The dorsal and ventral skin temperatures of the hands and feet of a subject were measured using a thermotracer. Therefore, we compared subjects who woke up in a bedroom warmed to about 22-24℃ with those who woke in a bedroom at a normal winter temperature of about 9-17℃. During the low phase of body temperature, the basal body temperature and skin temperature of the hands of the subjects were significantly higher in the warmed bedroom. By contrast, during the high phase of body temperature, the skin temperature was relatively low, although the basal body temperature rose when we warmed the bedroom temperature. It was suggested that on warming the bedroom temperature of about 22℃ during high phase of body temperature in winter, skin temperature decreased because the basal body temperature was too high and her palm were sweating.
Control of IgE Ab production is important for the prevention of IgE-related diseases. However, in contrast to the existing information on the induction of IgE production, little is known about the ...regulation of the production of this isotype, with the exception of the well-documented mechanism involving T cell subsets and their cytokine products. In this study, we demonstrate an alternative approach to interfere with the production of IgE, independent of the activity of T cells, which was discovered during the course of an investigation intended to clarify the mechanism of IgE-selective unresponsiveness induced by surface-coupled liposomal Ags. Immunization of mice with OVA-liposome conjugates induced IgE-selective unresponsiveness without apparent Th1 polarization. Neither IL-12, IL-10, nor CD8(+) T cells participated in the regulation. Furthermore, CD4(+) T cells of mice immunized with OVA-liposome were capable of inducing Ag-specific IgE synthesis in athymic nude mice immunized with alum-adsorbed OVA. In contrast, immunization of the recipient mice with OVA-liposome did not induce anti-OVA IgE production, even when CD4(+) T cells of mice immunized with alum-adsorbed OVA were transferred. In the secondary immune response, OVA-liposome enhanced anti-OVA IgG Ab production, but it did not enhance ongoing IgE production, suggesting that the IgE-selective unresponsiveness induced by the liposomal Ag involved direct effects on IgE, but not IgG switching in vivo. These results suggest the existence of an alternative mechanism not involving T cells in the regulation of IgE synthesis.
We previously reported that liposomes having differential lipid components displayed differential adjuvant effects when antigen was coupled with liposomes via glutaraldehyde. In the present study, ...antigen−liposome conjugates prepared using liposomes having differential lipid components were added to the macrophage culture, and phagocytosis and the antigen digest of liposome-coupled antigen by macrophages were then investigated. Antigen presentation by macrophages to an antigen-specific T-cell clone was further investigated using the same conjugates. Antigen−liposome conjugates which induced higher levels of antibody production in vivo were recognized more often, and the liposome-coupled antigen was digested to a greater degree by macrophages than antigen−liposome conjugates which induced lower levels of antibody production. These results correlated closely with those regarding antigen presentation by macrophages; when antigen was coupled to liposomes showing higher adjuvant effect, macrophages cocultured with antigen−liposome conjugates activated antigen-specific T-cells at a higher degree. The concentration of OVA in the macrophage culture added as antigen−liposome conjugates was approximately 32 μg/mL. However, the extent of T-cell activation was almost equal to that when 800 μg/mL of soluble OVA was added to the culture. The results of the present study demonstrated that the adjuvant activity of liposomes observed primary in vivo correlated closely with the recognition of antigen−liposome conjugates and antigen presentation of liposome-coupled antigen by macrophages, suggesting that the adjuvant effects of liposomes are exerted at the beginning of the immune response, i.e., recognition of antigen by antigen-presenting cells.
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