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Aims There is a scarcity of studies comparing percutaneous coronary intervention (PCI) using new-generation drug-eluting stents (DES) with coronary artery bypass grafting (CABG) in patients with multi-vessel coronary artery disease. Methods and results The CREDO-Kyoto PCI/CABG registry Cohort-3 enrolled 14927 consecutive patients who underwent first coronary revascularization with PCI or isolated CABG between January 2011 and December 2013. The current study population consisted of 2464 patients who underwent multi-vessel coronary revascularization including revascularization of left anterior descending coronary artery (LAD) either with PCI using new-generation DES (N = 1565), or with CABG (N = 899). Patients in the PCI group were older and more often had severe frailty, but had less complex coronary anatomy, and less complete revascularization than those in the CABG group. Cumulative 5-year incidence of a composite of all-cause death, myocardial infarction or stroke was not significantly different between the 2 groups (25.0% versus 21.5%, P = 0.15). However, after adjusting confounders, the excess risk of PCI relative to CABG turned to be significant for the composite endpoint (HR 1.27, 95%CI 1.04–1.55, P = 0.02). PCI as compared with CABG was associated with comparable adjusted risk for all-cause death (HR 1.22, 95%CI 0.96–1.55, P = 0.11), and stroke (HR 1.17, 95%CI 0.79–1.73, P = 0.44), but with excess adjusted risk for myocardial infarction (HR 1.58, 95%CI 1.05–2.39, P = 0.03), and any coronary revascularization (HR 2.66, 95%CI 2.06–3.43, P Conclusions In this observational study, PCI with new-generation DES as compared with CABG was associated with excess long-term risk for major cardiovascular events in patients who underwent multi-vessel coronary revascularization including LAD.

Background:It has been shown that serum lipoprotein(a) [Lp(a)] is elevated in familial hypercholesterolemia (FH) with mutation(s) of the LDL receptor (LDLR) gene. However, few data exist regarding Lp(a) levels in FH with gain-of-function mutations of the PCSK9 gene.Methods and Results:We evaluated 42 mutation-determined heterozygous FH patients with aPCSK9gain-of-function mutation (FH-PCSK9, mean age 52, mean LDL-C 235 mg/dl), 198 mutation-determined heterozygous FH patients with aLDLRmutation (FH-LDLR, mean age 44, mean LDL-C 217 mg/dl), and 4,015 controls (CONTROL, mean age 56, mean LDL-C 109 mg/dl). We assessed their Lp(a), total cholesterol, triglycerides, HDL-C, LDL-C, use of statins, presence of hypertension, diabetes, chronic kidney disease, smoking, body mass index (BMI) and coronary artery disease (CAD). Multiple regression analysis showed that HDL-C, use of statins, presence of hypertension, smoking, BMI, and Lp(a) were independently associated with the presence of CAD. Under these conditions, the serum levels of Lp(a) in patients with FH were significantly higher than those of the CONTROL group regardless of their causative genes, among the groups propensity score-matched (median Lp(a) 12.6 mg/dl [IQR:9.4–33.9], 21.1 mg/dl [IQR:11.7–34.9], and 5.0 mg/dl [IQR:2.7–8.1] in the FH-LDLR, FH-PCSK9, and CONTROL groups, respectively, P=0.002 for FH-LDLR vs. CONTROL, P=0.002 for FH-PCSK9 vs. CONTROL).Conclusions:These data demonstrate that serum Lp(a) is elevated in patients with FH caused by PCSK9 gain-of-function mutations to the same level as that in FH caused by LDLR mutations. (Circ J 2016; 80: 512–518), 出版者照会後に全文公開

It is unknown how much different are the clinical outcomes between asymptomatic and symptomatic patients with severe aortic stenosis (AS). In the CURRENT AS registry enrolling 3, 815 consecutive patients with severe AS, we compared the long-term outcomes between 1808 asymptomatic and 1215 symptomatic patients (exertional dyspnea: N = 813, syncope: N = 136, and angina: N = 266) without heart failure (HF) hospitalization. Symptomatic patients had greater AS severity, and more depressed left ventricular function than asymptomatic patients without much difference in other baseline characteristics. During a median follow-up of 3.2 years, aortic valve replacement (AVR) was performed in 62% of symptomatic patients, and 38% of asymptomatic patients. The cumulative 5-year incidences for the primary outcome measure (a composite of aortic valve-related death or HF hospitalization) was higher in symptomatic patients than in asymptomatic patients (32.3% versus 27.6%, P

Equivalent Transformation (ET) rules can be used to construct correct se- quential and parallel programs, as they are inherently correct. One important method for making ET rules uses logical formulas. Among logical formulas, unsatis able con- junctions of nite atoms, each of which is represented by an atom set in this paper, are especially useful for making many ET rules that are used for constructing efficient pro- grams. This paper proposes a method of proving unsatis ability of an atom set based on computation by ET rules. The proposed method is recursive, in the sense that, during proving the given atom set, it may nd a new atom set based on subset relation or in- ductive structure. Since our proposed method incorporates search based on subset and inductive relations, it can be used to prove unsatis ability of various atom sets that can- not be proven by conventional methods.

To propose methods for making Equivalent Transformation (ET) rules is important for generating correct and sufficiently efficient programs from a specification which is a set of logical formulas. An ET rule is a procedure for replacing a clause set with another one while preserving declarative meaning. This paper proposes a new method for making ET rules via a Logical Equivalence (LE) from a specification. An LE describes an equivalence relationship between two logical formulas under some specified preconditions. We newly formulate an LE and define the correctness of LEs with respect to a specification. It is guaranteed by the method of this paper that an ET rule can be made from a correct LE. The method is useful for the generation of various programs. Many ET rules included in programs which solve constraint satisfaction problems, can be made by the method.

Associations between the changes in LPL/EL mass and those in lipids. (PPTX 2501Â kb)

金沢大学医学系研究科, Aim: Familial hypercholesterolemia (FH) is caused by mutations of FH genes, i.e. LDL-receptor (LDLR), PCSK9 and apolipoprotein B (ApoB) gene. We evaluated the usefulness of DNA analysis for the diagnosis of homozygous FH (homo-FH), and studied the frequency of FH in the Hokuriku district of Japan. Methods: Twenty-five homo-FH patients were recruited. LDLR mutations were identified using the Invader assay method. Mutations in PCSK9 were detected by PCR-SSCP followed by direct sequence analysis. Results: We confirmed 15 true homozygotes and 10 compound heterozygotes for LDLR mutations. Three types of double heterozygotes for LDLR and PCSK9 were found. No FH patients due to ApoB mutations were found. The incidences of homo-FH and hetero-FH in the Hokuriku district were 1/171,167 and 1/208, respectively. Conclusions: Our observations underlined the value of FH gene analysis in diagnosing homo-FH and confirmed extraordinarily high frequency of FH in the Hokuriku district of Japan. © 2010 Elsevier Ireland Ltd. All rights reserved.

金沢大学大学院医学系研究科, A 38-year-old Japanese woman was admitted to hospital for further examination of systemic xanthomas. She had a past history of genital bleeding during her third delivery at the age of 21 years. She was diagnosed with Sheehan's syndrome. Her serum total cholesterol and triglyceride concentrations were 500 and 898 mg/dl, respectively. She was also diagnosed as having type III hyperlipoproteinemia on the basis of the presence of a broad-β-band on agarose gel electrophoresis and extremely high concentrations of very-low-density lipoprotein cholesterol (310 mg/dl). The diagnosis was later confirmed by her apolipoprotein E isoforms (E2/E2) and genotypes (epsilon2/epsilon2). Thyroid and corticosteroid hormone replacement therapy cured the xanthomas, but also elevated her blood pressure. The serum concentration of intermediate-density lipoprotein cholesterol was consistently high, whereas that of low-density lipoprotein cholesterol was relatively low during the follow-up. Coronary atherosclerosis had already developed by the age of 38 years, and progressed significantly over the following 28 years. Severe stenotic lesions were observed in the bilateral renal arteries and carotid arteries, and in the abdominal aorta when she was 66 years old. These findings suggest that the continuous elevation of intermediate-density lipoprotein cholesterol for a long period contributed to the development of the atherosclerotic lesions.

金沢大学大学院医学系研究科, Left ventricular (LV) systolic function in hypertrophic cardiomyopathy (HCM) is usually normal. Late in the disease, however, LV systolic dysfunction and dilatation are recognized. Although abnormalities in cardiac sympathetic nerve activity in patients with HCM have been demonstrated using 123I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy, the changes of cardiac sympathetic nerve activity throughout the clinical course from typical to end-stage HCM are unclear. The objective of this study was to evaluate the relationship between abnormalities on 123I-MIBG myocardial scintigraphy and pathophysiologic changes in patients with HCM. Methods: We performed 123I-MIBG scintigraphy on 46 patients with HCM and 18 age-matched control subjects. The patients were categorized into 3 groups: 28 patients with normal LV systolic function (group A), 9 patients with LV systolic dysfunction (group B), and 9 patients with LV systolic dysfunction and dilatation (group C). With planar 123I-MIBG imaging, the heart-to-mediastinum ratio for early and delayed acquisitions and the washout rate were calculated. With SPECT, polar maps of the LV myocardium were divided into 20 segments. The regional uptake and washout rate were calculated from semiquantitative 20-segment bull's-eye analysis. Results: The early uptake was significantly lower in group C than in the control group (P < 0.01). The washout rate was progressively higher in group A, group B, and group C (P < 0.01). Reduced regional early uptake was found in 2.9 ± 3.4 (group A), 4.1 ± 4.7 (group B), and 7.4 ± 4.3 (group C) segments, respectively. In group C, regional early uptake was significantly reduced, predominantly in the interventricular septal wall, and regional washout rate was increased in the apex and lateral wall. Conclusion: These results suggest that cardiac sympathetic nerve abnormalities in patients with HCM may advance with development of LV systolic dysfunction and dilatation and that 123I-MIBG myocardial scintigraphy may be a useful tool for the evaluation of pathophysiologic changes in HCM.

金沢大学大学院医学系研究科, Congenital long QT syndrome (LQTS) is caused by mutations in various cardiac potassium or sodium channel genes, with 6 different genotypes thus far identified. However, it is unknown whether these genotypes can be differentiated by QT variables. The electrocardiograms obtained from 16 patients with a mutation in KCNQ1 (LQT1), 7 patients with a mutation in HERG (LQT2) and 20 control subjects were analyzed. The corrected QT interval (QTc), Q-T peak interval (QTpc) and dispersion of QTc or QTpc were measured in 6 precordial leads. The corrected interval from T peak to T end (Tpec) was measured in lead V5. The maximum QTc, QTc dispersion, and Tpec were significantly increased in the LQT1 and LQT2 patients than in the controls. However, there were no significant differences in these indices between the LQT1 and LQT2 patients. In contrast, QTpc dispersion was significantly increased in the LQT2 patients (78±25 ms) compared with the LQT1 patients (29±15 ms) and controls (26±19 ms). These results suggest that increased lag of the peak of the T wave in each precordial lead (QTpc dispersion) may be a possible index to differentiate LQTS patients with HERG mutation from those with KCNQ1 mutation.

金沢大学大学院医学系研究科, The Japan Lipid Intervention Trial (J-LIT) study, a nationwide cohort study utilizing the clinical practice of general physicians, was designed to clarify the relationship between the incidence of coronary heart disease and serum lipid concentrations during simvastatin therapy, as well as the safety of the therapy, in a large number of Japanese hypercholesterolemic patients. All the enrolled patients were treated with simvastatin. The current study analyzed the lipid lowering effect and safety of the low-dose simvastatin therapy used in the J-LIT study. Open-labeled simvastatin was given to 51,321 patients at an initial dose of mostly 5 mg/day. After 6 months of the treatment, the average serum total cholesterol (TC) and low density lipoprotein-cholesterol concentrations in all the patients followed up were reduced by 18.3% and 26.0%, respectively, and that of high density lipoprotein-cholesterol increased 2.3% on average. These concentrations were well maintained throughout the 6-year treatment period. A minority of patients (1.4%) unexpectedly had a remarkable reduction in TC concentration by more than 40%. Hyper-responders, even to low-dose statin, were found for the first time in this large-scale and long-term investigation. Overall adverse drug reactions occurred in 3.3% of subjects during the 6-year treatment, the major events being hepatic and musculoskeletal disorders, of which the incidence was less than 1%. Low-dose simvastatin therapy of 5 mg/day effectively controlled the serum TC concentration by reducing it by approximately 20% on average in hypercholesterolemic Japanese patients, a reduction that corresponds to the effect of simvastatin 20 mg/day in Western studies. In addition, the low incidence of drug-related adverse events in this study may. be also related to the low dosage of simvastatin.

金沢大学大学院医学系研究科, Cardiac sympathetic nerve activity is changed in patients with hypertrophic cardiomyopathy (HCM). However, the relationship between heterogeneity of this activity and systolic left ventricular dysfunction in patients with HCM is not well established. This study was performed to evaluate the sympathetic nerve activity in various cardiac regions and to investigate the relationship between cardiac dysfunction and heterogeneity of the cardiac sympathetic nerve activity in patients with HCM. Methods: Cardiac sympathetic nerve activity was evaluated in 25 patients with HCM and 10 control subjects using planar imaging and SPECT by 123l-metaiodobenzylguanidine (MIBG) myocardial scintigraphy. With planar 123I-MIBG imaging, the heart-to-mediastinum activity ratios (H/M), at early (20 min) and delayed (3 h) acquisition, and the washout rate were calculated. Polar maps of the left ventricular myocardium were divided into 20 segments, and the dispersion (maximal to minimal values) and SD of uptake and the washout rate in 20 segments were calculated. Results: The early H/M did not differ between the 2 groups. The delayed H/M was significantly lower and the washout rate of the whole heart was significantly higher in the HCM group than those in the control group. In patients with HCM, the delayed H/M, early uptake dispersion, and SD of early uptake showed good correlation with the left ventricular end-diastolic and end-systolic dimensions and the percentage of fractional shortening. A stepwise regression analysis revealed that the SD of early uptake was a powerful determinant for the percentage of fractional shortening in patients with HCM. Conclusion: These results suggest that the heterogeneity of regional cardiac sympathetic nerve activity may be correlated with cardiac dysfunction in patients with HCM.

金沢大学大学院医学系研究科

金沢大学大学院医学系研究科

金沢大学大学院医学系研究科, A 53-year-old man visited Mt. Arashima-dake in Fukui Prefecture, and was infested by a tick-like organism. He visited a local clinic on July 12, 2004, complaining of high fever, general fatigue and rash. After several days without definite diagnosis, he was admitted to the Fukui Prefectural Hospital, where he was treated with minocycline hydrochloride for 10 days until recovery. His clinical symptoms on admission were high fever (39.6°C), erythematous eruption, eschar on the right upper arm, and regional lymphoadenopathy. The epidemiological status and some clinical findings strongly suggested spotted fever (SF), and SF was confirmed based on the finding that his sera were reactive only to antigens of the SF group rickettsiae in the indirect immunoperoxidase analysis. This case is the first official report of SF rickettsiosis in Fukui Prefecture, the northern part of central Japan.

Initial values of reference vectors have significant influence on recognition accuracy in LVQ. There are several existing techniques, such as SOM and k-means, for setting initial values of reference vectors, each of which has provided some positive results. However, those results are not sufficient for the improvement of recognition accuracy. This study proposes an ACO-used method for initializing reference vectors with an aim to achieve recognition accuracy higher than those obtained through conventional methods. Moreover, we will demonstrate the effectiveness of the proposed method by applying it to the wine data and English vowel data and comparing its results with those of conventional methods., {"references":["Abhishek Bansal and G. N. Pillai, \"High Impedance Fault Detection using\nLVQ Neural Networks\", International Journal of Computer, Information,\nand Systems Science, and Engineering 1;3 www.waset.org Summer 2007.","Yuji Mizuno, Hiroshi Mabuchi, Goutam Chakraborty, Masafumi Matsuhara,\n\"Clustering of EEG Data using Maximum Entropy Method\nand LVQ\" INTERNATIONAL JOURNAL OF COMPUTERS, Issue 4,\nVolume 4, pp.193-200, 2010.","T. Kohonen, \"Self-Organizing Maps\", pringer Verlag, 1995.","Atsushi SATO, Keiji YAMADA, \"A Formulation of Learning Vector\nQuantization Using a New Misclassification Measure\", 14th International\nConference on Pattern Recognition (ICPR-98) - Volume 1, pp.322-pp325,\n1998.","T. Kohonen, \"The Self-Organizing Map\", PROCEEDINGS OF THE\nIEEE, VOL.78, NO.9, pp1464-1480, SEPTEMBER 1990.","John S Baras and Anthony La Vigna, \"Convergence of Kohonen-s\nLearning Vector Quantization\", IJCNN, Vol.3, pp.17-20, 1990.","Kitajima N, \"A new method for initializing reference vectors in LVQ\",\nProceedings of IEEE International Conference on Neural Networks, Vol.5,\npp.2775-2779, 1995.","Marco Dorigo, Luca Maria Gambardella, \"Ant Colony System: A Cooperative\nLearning Approach to the Traveling Salesman Problem\", IEEE\nTRANSACTIONS ON EVOLUTIONARY COMPUTATION, VOL. 1,\nNO. 1, pp.53-66, 1997.","B. Bullnheimer, R. F. Hartl and C. Strauss, \"An improved Ant System\nalgorithm for the vehicle routing problem\", Technical Report POM10/97,\nVienna, Austria: University of Vienna, Institute of Management Science.\nTo appear in Dawid, Feichtinger, & Hartl (Eds.), Annals of Operations\nResearch: Nonlinear Economic Dynamics and Control, 1997.\n[10] B. Bullnheimer, R. F. Hartl and C. Strauss, \"A new rank-based version\nof the ant system\", a computational study, Technical Report POM10/97,\nInstiture of Management Science, University of Vienna, 1997.\n[11] Thomas St¨utzle, Holger H. Hoos, \"MAX-MIN Ant System\", Future\nGeneration Computer Systems, Vol.16, No.8, pp.899-914, 2000.\n[12] M. Dorigo and G. D. Caro, \"Ant Algorithms for Discrete Optimization\",\nArtificial Life, vol.5, No.2, pp. 137-172, MIT Press(1999).\n[13] Marco Dorigo, Vittorio Maniezzo, Alberto Colorni, \"The Ant System:\nOptimization by a colony of cooperating agents\", IIEEE Transactions on\nSystems, Man, and Cybernetics.Part B, Vol.26, No.1, pp.1-13, 1996.\n[14] V.Maniezzo, \"Exact and approximate nondeterministic tree-search procedures\nfor the quadratic assignment problem\" Technical Report CSR\n98-1, C. L. In scenze dell-Informazione, Universita di Bologna, sede di\nCesena,1998.\n[15] E.-G. Talbi, O. Roux, C. Fonlupt, D. Robillard, \"Parallel Ant Colonies\nfor the quadratic assignment problem\", Future Generation Computer\nSystems 17 pp.441-449, 2001.\n[16] Shigeyoshi Tsutsui, \"Cunning Ant System for Quadratic Assignment\nProblem with Local Search and Parallelization\", Proceedings of the\nSecond International Conference on Pattern Recognition and Machine\nIntelligence, pp. 269-278, Springer-Velag , December 18-22, 2007, Indian\nStatistical Institute, Kolkata, 2007.12. Springer LNCS 4815, ISBN: 978-\n3-540-77045-9.\n[17] Payam Refaeilzadeh, Lei Tang, Huan Liu, \"Cross Validation\", In Encyclopedia\nof Database Systems, Editors: M. Tamer ¨Ozsu and Ling Liu.\nSpringer, 2009.\n[18] C. L. Blake, C. J. Merz,UCI Repositoy Machine Learning Databases,\nIrvine, University of California, http://archive.ics.uci.edu/ml/, 2010/12."]}

Since Zilversmit first proposed postprandial lipemia as the most common risk of cardiovascular disease, chylomicrons (CM) and CM remnants have been thought to be the major lipoproteins which are increased in the postprandial hyperlipidemia. However, it has been shown over the last two decades that the major increase in the postprandial lipoproteins after food intake occurs in the very low density lipoprotein (VLDL) remnants (apoB-100 particles), not CM or CM remnants (apoB-48 particles). This finding was obtained using the following three analytical methods; isolation of remnant-like lipoprotein particles (RLP) with specific antibodies, separation and detection of lipoprotein subclasses by gel permeation HPLC and determination of apoB-48 in fractionated lipoproteins by a specific ELISA. The amount of the apoB-48 particles in the postprandial RLP is significantly less than the apoB-100 particles, and the particle sizes of apoB-48 and apoB-100 in RLP are very similar when analyzed by HPLC. Moreover, CM or CM remnants having a large amount of TG were not found in the postprandial RLP. Therefore, the major portion of the TG which is increased in the postprandial state is composed of VLDL remnants, which have been recognized as a significant risk for cardiovascular disease.

金沢大学医薬保健研究域医学系

The purpose of this paper is to propose a framework for constructing correct parallel processing programs based on Equivalent Transformation Framework (ETF). ETF regards computation as In the framework, a problem-s domain knowledge and a query are described in definite clauses, and computation is regarded as transformation of the definite clauses. Its meaning is defined by a model of the set of definite clauses, and the transformation rules generated must preserve meaning. We have proposed a parallel processing method based on “specialization", a part of operation in the transformations, which resembles substitution in logic programming. The method requires “Memo-tree", a history of specialization to maintain correctness. In this paper we proposes the new method for the specialization-base parallel processing without Memo-tree., {"references":["K. Akama, E. Nantajeewarawat, and H. Ogasawara, \"Generation of\ncorrect parallel programs based on specializer generation transformations,\"\nin Proceedings of the 7th international conference on intelligent\ntechnologies, 2006.","H. Ogasawara, K. Akama, and H. Mabuchi, \"Parallel processing framework\nbased on distributed computation of specialization,\" International\nJournal of Innovative Computing, Information and Control, vol. 6, no. 5,\npp. 2371-2381, 2010.","K. Akama and E. Nantajeewarawat, \"Formalization of the equivalent\ntransformation computation models,\" Journal of Advanced Computational\nIntelligence and Intelligent Informatics, vol. 10, no. 3, pp. 245-259, 2006.","Conceptis-Limited. (2005) Pic-a-pix help. [Online]. Available:\nhttp://www.conceptispuzzles.com/online/pap/help.htm","Nikoli. (2010) Sudoku outline. [Online]. Available:\nhttp://www.nikoli.co.jp/en/puzzles/sudoku/index text.htm","W.-J. van Hoeve and I. Katriel, \"Global constraints,\" in Handbook of\nConstraint Programming, F. Rossi, P. van Beek, and T. Walsh, Eds.\nELSEVIER, 2006, ch. 6, pp. 169-208.","J. C. de Kergommeaux, \"Parallel logic programming systems,\" ACM\nComputing Surveys, vol. 26, no. 3, 1994.","G. Gupta, E. Pontelli, K. A. M. Ali, M. Carlsson, and M. V.\nHermenegildo, \"Parallel execution of prolog programs: a survey,\" Programming\nLanguages and Systems, vol. 23, no. 4, pp. 472-602, 2001.","B. Ramkumar and L. V. Kal'e, \"Machine independent and and or parallel\nexecution of logic programs: Part i-the binding environment,\" IEEE Trans.\nParallel Distrib. Syst., vol. 5, no. 2, pp. 170-180, 1994."]}

E-Learning systems are used by many learners and teachers. The developer is developing the e-Learning system. However, the developer cannot do system construction to satisfy all of users- demands. We discuss a method of constructing e-Learning systems where learners and teachers can design, try to use, and share extending system functions that they want to use; which may be nally added to the system by system managers., {"references":["Dougiamas, M. and Taylor, P.C., Moodle: Using Learning Communities\nto Create an Open Source Course Management System. Proceedings of\nthe EDMEDIA 2003 Conference,pp.171-178, Honolulu, Hawaii, 2003.","D. Robinson, K. Coar, The Common Gateway Interface (CGI) Version\n1.1, Network Working Group, RFC3875, Category: Informational, 2004.","Hopkins,J., Component primer, Communications of the ACM, vol.43,\nno.10, pp.27-30, 2000.","IBM San Francisce, Concepts and facilities, IBM Corporation, 1977\nProject, Software Development, vol.6, no.2, 1998.","K.Akama, H.Koike and H.Mabuchi, A Theoretical Foundation of Program\nSynthesis by Equivalent Transformation, Perspectives of System\nInformatics, Lecture Notes in Computer Science ,Vol.2244, pp.131-139,\nSpringer Verlag, Heidelberg, 2001.","Koike,H., K.Akama and E.Boyd, Program synthesis by generating equivalent\ntransformation rules, Proc. of the 2nd International Conference on\nIntelligent Technologies, Bangkok, Thailand, pp.250-259, 2001.","Szyperski,C., Component software: Beyond object-oriented programming,\nAddison-Wesley, 1999.","Mabuchi,H., K.Akama and T.Wakatsuki, Equivalent transformation rules\nas components of programs, International Journal of Innovative Computing,\nInformation & Control, vol.3, no.3, pp.685-696, 2007."]}

In the Equivalent Transformation (ET) computation model, a program is constructed by the successive accumulation of ET rules. A method by meta-computation by which a correct ET rule is generated has been proposed. Although the method covers a broad range in the generation of ET rules, all important ET rules are not necessarily generated. Generation of more ET rules can be achieved by supplementing generation methods which are specialized for important ET rules. A Specialization-by-Equation (Speq) rule is one of those important rules. A Speq rule describes a procedure in which two variables included in an atom conjunction are equalized due to predicate constraints. In this paper, we propose an algorithm that systematically and recursively generate Speq rules and discuss its effectiveness in the synthesis of ET programs. A Speq rule is generated based on proof of a logical formula consisting of given atom set and dis-equality. The proof is carried out by utilizing some ET rules and the ultimately obtained rules in generating Speq rules., {"references":["Akama,K. , Y.Shigeta and E.Miyamoto, Solving logical\nproblems by equivalent transformation - a theoretical foundation,\nJournal of the Japanese Society for Artificial Intelligence (in\nJapanese), vol.13, pp.928-935, 1998.","Akama, K., E.Nantajeewarawat and H.Koike, Program generation\nin the equivalent transformation computation model using the squeeze\nmethod, Proc. of PSI2006, LNCS4378, Springer-Verlag Berlin Heidelberg,\npp.41-54, 2007.","Harada,M., T.Mizuno and S.Hamada, Executable C++ Program\nGeneration form the Structured Object-oriented Design Diagrams,\nTransactions of Information Processing Society of Japan (in\nJapanese), vol.40, no.7, pp.2988-3000, 1999.","Higashino,T, M.Mori, T.Sugiyama, K.Taniguchi and T.Kasami, An\nalgebraic specification of HDLC procedures and its verification, The\nIEICE Transactions on Information and Systems (in Japanese), vol.SE-\n10, no.6, pp.825-836, 1984.","Hopkins,J., Component primer, Communications of the\nACM, vol.43, no.10 pp.27-30, 2000.","IBM San Francisce, Concepts and facilities, IBM Corporation, 1977\nProject, Software Development, vol.6, no.2, 1998.","Ikeda,M., T.Nakamura, Y.Takata and H.Seki, Algebraic Specification of\nUser Interface and Its Automatic Implementation, The Special Interest\nGroup Notes of IPSJ (in Japanese), vol.2001, no.114, pp.9-16, 2001.","Jaffar,J. and M.Maher, Constraint logic programming, A survey, Journal\nof Logic Programming, vol.19/20, pp.503-581, 1994.","Koike,H. , K.Akama and E.Boyd, Program synthesis by generating\nequivalent transformation rules, Proc. of the 2nd International Conference\non Intelligent Technologies, Bangkok, Thailand, pp.250-259, 2001.\n[10] Lloyd,J.W., Foundations of Logic Programming, 2nd Edition, Springer-\nVerlag, 1987.\n[11] Lu,Yiguang, H.Awaya, H.Seki, M.Fujii and K.Ninomiya, On a Translation\nfrom Algebraic Specifications of Abstract Sequential Machines\ninto Programs, The IEICE Transactions on Information and Systems\n(in Japanese), vol.J73-D-I, no.2, pp.201-213, 1990.\n[12] Mabuchi,H. , K.Akama and T.Wakatsuki, Equivalent transformation\nrules as components of programs, International Journal of Innovative\nComputing, Information & Control, vol.3, no.3, pp.685-696, 2007.\n[13] Miura,K. , K.Akama and H.Mabuchi, Creation of ET Rules\nfrom Logical Formulas Representing Equivalent Relations, International\nJournal of Innovative Computing, Information & Control,\nvol.5, (no.4 or no.5), 2009 (to appear).\n[14] Nishida,Y. , K.Akama and H.Koike, An experimental programgeneration\nsystem based on meta-computation, Technical report of\nthe Institute of Electronics, Information and Communication Engineers\n(in Japanese), Matsue, Japan, pp.31-36, 2007.\n[15] Sterling,L. and E.shapiro, The Art of Prolog: Advanced Programming\nTechniques, MIT Press, second edition,\n[16] Szyperski,C., Component software: Beyond object-oriented programming,\nAddison-Wesley, 1999.\n[17] van Hentenryck,P., Constraint logic programming, The Knowledge\nEngineering Review, vol.6, no.3, pp.151-194, 1991.\n[18] Wakatsuki,T., K.Akama and H.Mabuchi, A Framework for Synthesizing\nlow-level Imperative Programs From Deterministic Abstract\nPrograms, Technical report of the Institute of Electronics, Information\nand Communication Engineers (in Japanese), vol.107, no.392, pp.37-\n42, 2007."]}

金沢大学大学院医学系研究科病態検査学, Genetic determinants of HDL cholesterol (HDL-C) levels in the general population are poorly understood. We previously described plasma cholesteryl ester transfer protein (CETP) deficiency due to an intron 14 G(+1)-to-A mutation(Int14 A) in several families with very high HDL-C levels in Japan. Subjects with HDL-C ≥ 100 mg/dl (n = 130) were screened by PCR single strand conformational polymorphism analysis of the CETP gene. Two other mutations were identified by DNA sequencing or primer-mediated restriction map modification of PCR products: a novel intron 14 splice donor site mutation caused by a T insertion at position +3 from the exon14/intron14 boundary (Int14 T) and a missense mutation (Asp442 to Gly) within exon 15 (D442G). The Int14 T mutation was only found in one family. However, the D442G and Int14 A mutations were highly prevalent in subjects with HDL-C ≥ 60 mg/dl, with combined allele frequencies of 9%, 12%, 21%, and 43% for HDL-C 60-79, 80-99, 100-119, and ≥ 120 mg/dl, respectively. Furthermore, prevalences of the D442G and Int14 A mutations were extremely high in a general sample of Japanese men (n = 236), with heterozygote frequencies of 7% and 2%, respectively. These two mutations accounted for about 10% of the total variance of HDL-C in this population. The phenotype in a genetic compound heterozygote (Int14 T and Int14 A) was similar to that of Int14 A homozygotes (no detectable CETP and markedly increased HDL-C), indicating that the Int14 T produces a null allele. In four D442G homozygotes, mean HDL-C levels (86±26 mg/dl) were lower than in Int14 A homozygotes (158±35 mg/dl), reflecting residual CETP activity in plasma. In 47 D442G heterozygotes, mean HDL-C levels were 91±23 mg/dl, similar to the level in D442G homozygotes, and significantly greater than mean HDL-C levels in Int14 A heterozygotes (69±15 mg/dl). Thus, the D442G mutation acts differently to the null mutations with weaker effects on HDL in the homozygous state and stronger effects in the heterozygotes, suggesting dominant expression of a partially defective allele. CETP deficiency, reflecting two prevalent mutations (D442G and Int14 A), is the first example of a genetic deficiency state which is sufficiently common to explain a significant fraction of the variation in HDL-C in the general population.

金沢大学大学院医学系研究科病態検査学