Numerical Calculation for Discretization of Continuous Quadratic Performance Index

A new procedure of numerical calculation to discretize a quadratic performance index denned for a linear time-invariant continuous system is proposed. The procedure is based on the Padé approximation with scaling and repeated squaring. Theoretical bounds of truncation errors involved in the resulting discretized weighting matrices are provided in terms of the maximum singular value norm for the proposed procedure. It is also shown that the paper by Van Loan which proposed another procedure of numerical calculation for the same problem contains some errors and a certain modification is required for his procedure. Numerical examples show that the new procedure is superior to the old one (of the modified version) from the viewpoint of accuracy, efficiency, and reliability

Development of a Multicomponent Intervention to Prevent Alzheimer's Disease

Recent advances in vascular risk management have successfully reduced the prevalence of Alzheimer's Disease (AD) in several epidemiologic investigations. It is now widely accepted that cerebrovascular disease is both directly and indirectly involved in AD pathogenesis. Herein, we review the non-pharmacological and pharmacological therapeutic approaches for AD treatment. MIND [Mediterranean and DASH (Dietary Approaches to Stop Hypertension) Intervention for Neurodegenerative Delay] diet is an important dietary treatment for prevention of AD. Multi domain intervention including diet, exercise, cognitive training, and intensive risk managements also prevented cognitive decline in the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) study. To confirm these favorable effects of life-style intervention, replica studies are being planned worldwide. Promotion of β-amyloid (Aβ) clearance has emerged as a promising pharmacological approach because insufficient removal of Aβ is more important than excessive Aβ production in the pathogenesis of the majority of AD patients. Most AD brains exhibit accompanying cerebral amyloid angiopathy, and Aβ distribution in cerebral amyloid angiopathy closely corresponds with the intramural periarterial drainage (IPAD) route, emphasizing the importance of Aβ clearance. In view of these facts, promotion of the major vascular-mediated Aβ elimination systems, including capillary transcytosis, the glymphatic system, and IPAD, have emerged as new treatment strategies in AD. In particular, the beneficial effects of cilostazol were shown in several clinical observation studies, and cilostazol facilitated IPAD in a rodent AD model. The COMCID (Cilostazol for prevention of Conversion from MCI to Dementia) trial, evaluating the efficacy of cilostazol for patients with mild cognitive impairment is currently ongoing in Japan. Such therapeutic approaches involving maintenance of cerebrovascular integrity and promotion of vascular-mediated Aβ clearance have the potential to be mainstream treatments for sporadic AD

Combined Use of a Solid-Phase Hexapeptide Ligand Library with Liquid Chromatography and Two-Dimensional Difference Gel Electrophoresis for Intact Plasma Proteomics

The intact plasma proteome is of great interest in biomarker studies because intact proteins reflect posttranslational protein processing such as phosphorylation that may correspond to disease status. We examined the utility of a solid-phase hexapeptide ligand library in combination with conventional plasma proteomics modalities for comprehensive profiling of intact plasma proteins. Plasma proteins were sequentially fractionated using depletion columns for albumin and immunoglobulin, and separated using an anion-exchange column. Proteins in each fraction were treated with a solid-phase hexapeptide ligand library and compared to those without treatment. Two-dimensional difference gel electrophoresis demonstrated an increased number of protein spots in the treated samples. Mass spectrometric studies of these protein spots with unique intensity in the treated samples resulted in the identification of high- and medium-abundance proteins. Our results demonstrated the possible utility of a solid-phase hexapeptide ligand library to reveal greater number of intact plasma proteins. The characteristics of proteins with unique affinity to the library remain to be clarified by more extensive mass spectrometric protein identification, and optimized protocols should be established for large-scale plasma biomarker studies

Production of viral vectors using recombinase-mediated cassette exchange

DNA viruses are often used as vectors for foreign gene expression, but large DNA region from cloned or authentic viral genomes must usually be handled to generate viral vectors. Here, we present a unique system for generating adenoviral vectors by directly substituting a gene of interest in a small transfected plasmid with a replaced gene in a replicating viral genome in Cre-expressing 293 cells using the recombinase-mediated cassette exchange (RMCE) reaction. In combination with a positive selection of the viral cis-acting packaging signal connected with the gene of interest, the purpose vector was enriched to 97.5 and 99.8% after three and four cycles of infection, respectively. Our results also showed that the mutant loxP V (previously called loxP 2272), a variant target of Cre used in the RMCE reaction, was useful as a non-compatible mutant to wild-type loxP. This method could be useful for generating not only a large number of adenovirus vectors simultaneously, but also other DNA virus vectors including helper-dependent adenovirus vector

Transplantation of genetically marked cardiac muscle cells

AbstractWe examined the possibility that cardiomyocytes could be genetically marked or modified before being grafted to the heart under conditions applicable to the clinical setting. We used a replication-defective recombinant adenovirus carrying the β-galactosidase reporter gene, and delivered it to cultured murine fetal cardiac myocytes. Virtually all fetal cardiomyocytes in a primary culture expressed β-galactosidase 24 hours after recombinant adenovirus infection. These cells were transplanted to the hearts of syngenic adult recipient mice. Expression of the β-galactosidase gene in the grafted cells was demonstrated by staining with 5-bromo-4-chloro-3-indoyl-β-d-galactosidase, resulting in a blue color at the histochemical level and an electron-dense deposit on transmission electron microscopic analysis. Gene expression was recognized from 7 days to 12 weeks after transplantation. Implanted cardiomyocytes aligned themselves along the layers of the host myocardium. Formation of gap junctions was demonstrated by transmission electron microscopy. Neither inflammation nor fibrous scar tissue was detectable by histologic analysis. This study demonstrates that ex vivo gene transfer to the heart by means of the adenoviral vector is possible. (J Thorac Cardiovasc Surg 1997;113:10-8

Superoxide Anion Radical Scavenging Activities of Herbs and Pastures in Northern Japan Determined Using Electron Spin Resonance Spectrometry

Free radicals are not only destructive to the living cells but also reduce the quality of animal products through oxidation. As a result the superoxide anion radical (O2・-), one of the most destructive reactive oxygen species, is a matter of concern for the animal scientists as well as feed manufacturers to ensure the quality of product to reach consumers demand. The superoxide anion radical scavenging activities (SOSA) of water and MeOH extracts of 2 herbs and 9 pasture samples collected from lowland and highland swards were determined against a 5,5-dimethyl-1-pyroline-N-oxide-O2・-spin adduct based on a hypoxanthine-xanthine oxidase reaction using electron spin resonance spectrometry. Both the water and MeOH extracted SOSA differed among the herbs and pastures. Species and altitudinal variations were observed between extraction methods. The herbs were higher in both water and MeOH extracted SOSA than the pastures except for water extracts of one pasture, white clover (Trifolium repens L.). Among the pastures, quackgrass (Agrophyron repens L.) showed higher SOSA in both the MeOH and water extracts, and timothy (Phleum pretense L.) showed higher MeOH extracted SOSA. It is apparent that the kind and amount of antioxidants differ among herbs and pastures. Animal health and quality of animal products could be improved by adequate selection and combining of herbs and pastures having higher SOSA

Clinical training stress and autonomic nervous function in female medical technology students : analysis of heart rate variability and 1/f fluctuation

To evaluate the level of stress induced by clinical training, ambulatory electrocardiograms from 12 healthy female medical technology students were recorded and the spectral components of heart rate variability (HRV) were analyzed as an index of autonomic nervous function. The HF power reflecting parasympathetic tone was significantly decreased at awakening, compared with that before clinical training (p 0.01). The LF/HF ratio reflecting sympathetic activity also significantly increased during, compared with before clinical training (p 0.01). The slope of the spectral density also changed before and during the clinical training from -1.20 0.04 to -1.09 0.03 (p 0.05). The 1/f fluctuation of HRV appeared comfortable, and tension was apparently adequate while undergoing clinical training. None of these HRV indices statistically changed while asleep. Thus, the students perceived the stress as a comfortable level of tension and analyzing spectral components and 1/f fluctuation of HRV might be a useful method for evaluating study stress