ABSTRACT Hierarchical State Transition Matrix (HSTM) is a table-based modeling language for devel... more ABSTRACT Hierarchical State Transition Matrix (HSTM) is a table-based modeling language for developing designs of software systems. Although widely used and adopted by (particularly Japanese) software industry, there is still lack of mechanized formal verification supports for conducting rigorous and automatic analysis to improve reliability of HSTM designs. In this paper, we first present a formalization of HSTM designs as state transition systems. Consequentially, based on this formalization, we propose a symbolic encoding approach, through which correctness of a HSTM design with respect to LTL properties could be represented as Bounded Model Checking (BMC) problems that could be determined by Satisfiability Modulo Theories (SMT) solving. We have implemented our encoding approach in a tool called Garakabu2 with the state-of-the-art SMT solver CVC3 as its back-ended solver. Furthermore, in our preliminary experiments, a conceptually simple but steadily effective way of accelerating SMT solving for HSTM designs is investigated and reported.
Gan to Kagaku Ryoho Cancer Chemotherapy, Nov 1, 2012
Patient 1 was a 63-year-old woman whose chief complaint was a mass in the left breast. Physical e... more Patient 1 was a 63-year-old woman whose chief complaint was a mass in the left breast. Physical examination revealed an inverted left nipple, a very large mass on the anterior aspect of the sternum, and erythema. Because the tumor had directly invaded the sternum, T4cN3M0, stage IIIC breast cancer was diagnosed. The patient preoperatively received chemotherapy with 6 courses of FEC100 (5-fluorouracil, epirubicin, and cyclophosphamide) and 5 courses of nanoparticle albumin -bound paclitaxel (260 mg/m2), which enabled a partial response. Patient 2 was an 83-year-old woman whose chief complaint was a mass in the upper internal and external quadrants of the right breast measuring 20×15 cm and erythema. The mass was accompanied by enlarged right axillary lymph nodes(T4bN1M0, stage IIIB breast cancer). Both patients underwent core needle biopsy of the skin and breast masses. They were both diagnosed with invasive, lobular, triple-negative breast cancer (estrogen receptor negative, progesterone receptor negative, human epidermal growth factor receptor 2 negative). The surgical resection line was drawn to include the extensive skin invasion, and mastectomy and axillary dissection were performed. Skin grafting was scheduled but the retromammary space on the healthy side was dissected to the anterior border of the latissimus dorsi muscle, and the skin of the healthy side was used to cover the defect on the affected side. Consequently, the pendulous breast on the healthy side was elevated. This surgical technique provided an excellent aesthetic outcome without any skin problems, because autologous skin was used to fill the defect. Radiotherapy could subsequently be administered as scheduled. This procedure may be useful for elderly patients.
The small GTPase-effector proteins CDC42EP1-5/BORG1-5 interact reciprocally with CDC42 or the sep... more The small GTPase-effector proteins CDC42EP1-5/BORG1-5 interact reciprocally with CDC42 or the septin cytoskeleton. Here we show that, in the cerebellum, CDC42EP4 is exclusively expressed in Bergmann glia and localizes beneath specific membrane domains enwrapping dendritic spines of Purkinje cells. CDC42EP4 forms complexes with septin hetero-oligomers, which interact with a subset of glutamate transporter GLAST/EAAT1. In Cdc42ep4(-/-) mice, GLAST is dissociated from septins and is delocalized away from the parallel fibre-Purkinje cell synapses. The excitatory postsynaptic current exhibits a protracted decay time constant, reduced sensitivity to a competitive inhibitor of the AMPA-type glutamate receptors (γDGG) and excessive baseline inward current in response to a subthreshold dose of a nonselective inhibitor of the glutamate transporters/EAAT1-5 (DL-TBOA). Insufficient glutamate-buffering/clearance capacity in these mice manifests as motor coordination/learning defects, which are aggravated with subthreshold DL-TBOA. We propose that the CDC42EP4/septin-based glial scaffold facilitates perisynaptic localization of GLAST and optimizes the efficiency of glutamate-buffering and clearance.
Effects of atrial natriuretic peptides (ANP) on Type II cells of the rat lung were examined, usin... more Effects of atrial natriuretic peptides (ANP) on Type II cells of the rat lung were examined, using autoradiographic and morphometric techniques. The injection of an excess of ANP, together with [125I]ANP, significantly inhibited the uptake of radioactive ANP in the lung tissue. Following autoradiography, silver grains of [125I]ANP labelled Type II cells, endothelial cells and smooth muscle cells of vessels, bronchi and bronchioles. As for morphometric changes in subcellular structures of Type II cells after the injection of ANP, the volume and surface densities of the rough endoplasmic reticulum increased at 15 minutes, while those of the Golgi complex increased from 5 minutes, peaking at 30 minutes. At 15 minutes the volume and surface densities of mitochondria significantly increased. The volume and surface densities of multivesicular bodies with an electron-dense matrix also increased from 15 minutes after the injection. Lamellar bodies showed decreased volume and surface densities at 15 minutes whereas the densities showed an increase at 30 minutes and were higher at 60 minutes than those in the control. These results suggest that Type II cells provide a binding site for ANP which facilitates the production of lamellar bodies in addition to their secretion.
Gan to Kagaku Ryoho Cancer Chemotherapy, Nov 1, 2010
A 51-year-old postmenopausal woman was diagnosed as having adenocarcinoma (gastric cancer type 4)... more A 51-year-old postmenopausal woman was diagnosed as having adenocarcinoma (gastric cancer type 4) from gastric biopsy by upper endoscopy. Her chief complaint was abdominal dilatation. Meanwhile, a breast CT suggested tumor in her left breast and was diagnosed as an invasive lobular carcinoma based on a core needle biopsy. After gastric biopsy, tissues are stained by ER and PgR in immunohistochemistry. The diagnosis was modified from gastric cancer to T2N1M1, stage IV left breast cancer, accompanied by a treatment. Chemotherapy with EC 6 course consisted of a weekly PTX 4 course (epirubicin, cyclophosphamide-weekly paclitaxel) was performed. After the chemotherapy, breast mass, ascites and tumor marker were dramatically improved. Then hormonal therapy was administered. She passed away 2 and 1/2 years after her first visit to the hospital. Metastatic gastric tumors simulating type 4 advanced gastric cancer (MGTS type 4) and invasive lobular carcinoma are known to have an unfavorable prognosis. There is no doubt, however, that the multidisciplinary treatments have brought a satisfaction to her and family. We should keep in mind a possibility of gastric metastasis of breast cancer, when consulting a female patient with gastric cancer type 4.
A comprehensive search for DNA methylated genes identified candidate tumor suppressor genes that ... more A comprehensive search for DNA methylated genes identified candidate tumor suppressor genes that have been proven to be involved in the apoptotic process of the p53 pathway. In this study, we investigated p53 mutation in relation to such epigenetic alteration in primary gastric cancer. The methylation profiles of the 3 genes: PGP9.5, NMDAR2B, and CCNA1, which are involved in the p53 tumor suppressor pathway in combination with p53 mutation were examined in 163 primary gastric cancers. The effect of epigenetic reversion in combination with chemotherapeutic drugs on apoptosis was also assessed according to the tumor p53 mutation status. p53 gene mutations were found in 44 primary gastric tumors (27%), and super-high methylation of any of the 3 genes was only found in cases with wild type p53. Higher p53 pathway aberration was found in cases with male gender (p = 0.003), intestinal type (p = 0.005), and non-infiltrating type (p = 0.001). The p53 pathway aberration group exhibited less ...
To develop a cell type-specific and temporal regulation system of gene targeting in the cerebellu... more To develop a cell type-specific and temporal regulation system of gene targeting in the cerebellum, we used the NMDA-type glutamate receptor GluRe3 subunit gene and Cre recombinase- progesterone receptor fusion (CrePR) gene in combination. Injection of the CrePR gene placed under the control of the 10 kb 59 region of the GluRe3 gene into C57BL/6 eggs yielded the ECP25 line
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience
Phospholipase C (PLC) beta4, one of the four isoforms of PLCbetas, is the sole isoform expressed ... more Phospholipase C (PLC) beta4, one of the four isoforms of PLCbetas, is the sole isoform expressed in the mouse ventral posterolateral thalamic nucleus (VPL), a key station in pain processing. The mouse thalamus also has been shown to express a high level of metabotropic glutamate receptor type 1 (mGluR1), which stimulates PLCbetas through activation of Galphaq/11 protein. It is therefore expected that the thalamic mGluR1-PLCbeta4 cascade may play a functional role in nociceptive transmission. To test this hypothesis, we first studied behavioral responses to various nociceptive stimuli in PLCbeta4 knock-out mice. We performed the formalin test and found no difference in the pain behavior in the first phase of the formalin test, which is attributed to acute nociception, between PLCbeta4 knock-out and wild-type mice. Consistent with this result, acute pain responses in the hot plate and tail flick tests were also unaffected in the PLCbeta4 knock-out mice. However, the nociceptive behavi...
ABSTRACT Hierarchical State Transition Matrix (HSTM) is a table-based modeling language for devel... more ABSTRACT Hierarchical State Transition Matrix (HSTM) is a table-based modeling language for developing designs of software systems. Although widely used and adopted by (particularly Japanese) software industry, there is still lack of mechanized formal verification supports for conducting rigorous and automatic analysis to improve reliability of HSTM designs. In this paper, we first present a formalization of HSTM designs as state transition systems. Consequentially, based on this formalization, we propose a symbolic encoding approach, through which correctness of a HSTM design with respect to LTL properties could be represented as Bounded Model Checking (BMC) problems that could be determined by Satisfiability Modulo Theories (SMT) solving. We have implemented our encoding approach in a tool called Garakabu2 with the state-of-the-art SMT solver CVC3 as its back-ended solver. Furthermore, in our preliminary experiments, a conceptually simple but steadily effective way of accelerating SMT solving for HSTM designs is investigated and reported.
Gan to Kagaku Ryoho Cancer Chemotherapy, Nov 1, 2012
Patient 1 was a 63-year-old woman whose chief complaint was a mass in the left breast. Physical e... more Patient 1 was a 63-year-old woman whose chief complaint was a mass in the left breast. Physical examination revealed an inverted left nipple, a very large mass on the anterior aspect of the sternum, and erythema. Because the tumor had directly invaded the sternum, T4cN3M0, stage IIIC breast cancer was diagnosed. The patient preoperatively received chemotherapy with 6 courses of FEC100 (5-fluorouracil, epirubicin, and cyclophosphamide) and 5 courses of nanoparticle albumin -bound paclitaxel (260 mg/m2), which enabled a partial response. Patient 2 was an 83-year-old woman whose chief complaint was a mass in the upper internal and external quadrants of the right breast measuring 20×15 cm and erythema. The mass was accompanied by enlarged right axillary lymph nodes(T4bN1M0, stage IIIB breast cancer). Both patients underwent core needle biopsy of the skin and breast masses. They were both diagnosed with invasive, lobular, triple-negative breast cancer (estrogen receptor negative, progesterone receptor negative, human epidermal growth factor receptor 2 negative). The surgical resection line was drawn to include the extensive skin invasion, and mastectomy and axillary dissection were performed. Skin grafting was scheduled but the retromammary space on the healthy side was dissected to the anterior border of the latissimus dorsi muscle, and the skin of the healthy side was used to cover the defect on the affected side. Consequently, the pendulous breast on the healthy side was elevated. This surgical technique provided an excellent aesthetic outcome without any skin problems, because autologous skin was used to fill the defect. Radiotherapy could subsequently be administered as scheduled. This procedure may be useful for elderly patients.
The small GTPase-effector proteins CDC42EP1-5/BORG1-5 interact reciprocally with CDC42 or the sep... more The small GTPase-effector proteins CDC42EP1-5/BORG1-5 interact reciprocally with CDC42 or the septin cytoskeleton. Here we show that, in the cerebellum, CDC42EP4 is exclusively expressed in Bergmann glia and localizes beneath specific membrane domains enwrapping dendritic spines of Purkinje cells. CDC42EP4 forms complexes with septin hetero-oligomers, which interact with a subset of glutamate transporter GLAST/EAAT1. In Cdc42ep4(-/-) mice, GLAST is dissociated from septins and is delocalized away from the parallel fibre-Purkinje cell synapses. The excitatory postsynaptic current exhibits a protracted decay time constant, reduced sensitivity to a competitive inhibitor of the AMPA-type glutamate receptors (γDGG) and excessive baseline inward current in response to a subthreshold dose of a nonselective inhibitor of the glutamate transporters/EAAT1-5 (DL-TBOA). Insufficient glutamate-buffering/clearance capacity in these mice manifests as motor coordination/learning defects, which are aggravated with subthreshold DL-TBOA. We propose that the CDC42EP4/septin-based glial scaffold facilitates perisynaptic localization of GLAST and optimizes the efficiency of glutamate-buffering and clearance.
Effects of atrial natriuretic peptides (ANP) on Type II cells of the rat lung were examined, usin... more Effects of atrial natriuretic peptides (ANP) on Type II cells of the rat lung were examined, using autoradiographic and morphometric techniques. The injection of an excess of ANP, together with [125I]ANP, significantly inhibited the uptake of radioactive ANP in the lung tissue. Following autoradiography, silver grains of [125I]ANP labelled Type II cells, endothelial cells and smooth muscle cells of vessels, bronchi and bronchioles. As for morphometric changes in subcellular structures of Type II cells after the injection of ANP, the volume and surface densities of the rough endoplasmic reticulum increased at 15 minutes, while those of the Golgi complex increased from 5 minutes, peaking at 30 minutes. At 15 minutes the volume and surface densities of mitochondria significantly increased. The volume and surface densities of multivesicular bodies with an electron-dense matrix also increased from 15 minutes after the injection. Lamellar bodies showed decreased volume and surface densities at 15 minutes whereas the densities showed an increase at 30 minutes and were higher at 60 minutes than those in the control. These results suggest that Type II cells provide a binding site for ANP which facilitates the production of lamellar bodies in addition to their secretion.
Gan to Kagaku Ryoho Cancer Chemotherapy, Nov 1, 2010
A 51-year-old postmenopausal woman was diagnosed as having adenocarcinoma (gastric cancer type 4)... more A 51-year-old postmenopausal woman was diagnosed as having adenocarcinoma (gastric cancer type 4) from gastric biopsy by upper endoscopy. Her chief complaint was abdominal dilatation. Meanwhile, a breast CT suggested tumor in her left breast and was diagnosed as an invasive lobular carcinoma based on a core needle biopsy. After gastric biopsy, tissues are stained by ER and PgR in immunohistochemistry. The diagnosis was modified from gastric cancer to T2N1M1, stage IV left breast cancer, accompanied by a treatment. Chemotherapy with EC 6 course consisted of a weekly PTX 4 course (epirubicin, cyclophosphamide-weekly paclitaxel) was performed. After the chemotherapy, breast mass, ascites and tumor marker were dramatically improved. Then hormonal therapy was administered. She passed away 2 and 1/2 years after her first visit to the hospital. Metastatic gastric tumors simulating type 4 advanced gastric cancer (MGTS type 4) and invasive lobular carcinoma are known to have an unfavorable prognosis. There is no doubt, however, that the multidisciplinary treatments have brought a satisfaction to her and family. We should keep in mind a possibility of gastric metastasis of breast cancer, when consulting a female patient with gastric cancer type 4.
A comprehensive search for DNA methylated genes identified candidate tumor suppressor genes that ... more A comprehensive search for DNA methylated genes identified candidate tumor suppressor genes that have been proven to be involved in the apoptotic process of the p53 pathway. In this study, we investigated p53 mutation in relation to such epigenetic alteration in primary gastric cancer. The methylation profiles of the 3 genes: PGP9.5, NMDAR2B, and CCNA1, which are involved in the p53 tumor suppressor pathway in combination with p53 mutation were examined in 163 primary gastric cancers. The effect of epigenetic reversion in combination with chemotherapeutic drugs on apoptosis was also assessed according to the tumor p53 mutation status. p53 gene mutations were found in 44 primary gastric tumors (27%), and super-high methylation of any of the 3 genes was only found in cases with wild type p53. Higher p53 pathway aberration was found in cases with male gender (p = 0.003), intestinal type (p = 0.005), and non-infiltrating type (p = 0.001). The p53 pathway aberration group exhibited less ...
To develop a cell type-specific and temporal regulation system of gene targeting in the cerebellu... more To develop a cell type-specific and temporal regulation system of gene targeting in the cerebellum, we used the NMDA-type glutamate receptor GluRe3 subunit gene and Cre recombinase- progesterone receptor fusion (CrePR) gene in combination. Injection of the CrePR gene placed under the control of the 10 kb 59 region of the GluRe3 gene into C57BL/6 eggs yielded the ECP25 line
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience
Phospholipase C (PLC) beta4, one of the four isoforms of PLCbetas, is the sole isoform expressed ... more Phospholipase C (PLC) beta4, one of the four isoforms of PLCbetas, is the sole isoform expressed in the mouse ventral posterolateral thalamic nucleus (VPL), a key station in pain processing. The mouse thalamus also has been shown to express a high level of metabotropic glutamate receptor type 1 (mGluR1), which stimulates PLCbetas through activation of Galphaq/11 protein. It is therefore expected that the thalamic mGluR1-PLCbeta4 cascade may play a functional role in nociceptive transmission. To test this hypothesis, we first studied behavioral responses to various nociceptive stimuli in PLCbeta4 knock-out mice. We performed the formalin test and found no difference in the pain behavior in the first phase of the formalin test, which is attributed to acute nociception, between PLCbeta4 knock-out and wild-type mice. Consistent with this result, acute pain responses in the hot plate and tail flick tests were also unaffected in the PLCbeta4 knock-out mice. However, the nociceptive behavi...
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Papers by Masahiko Watanabe