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

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

Trans-complemented hepatitis C virus particles as a versatile tool for study of virus assembly and infection

AbstractIn this study, we compared the entry processes of trans-complemented hepatitis C virus particles (HCVtcp), cell culture-produced HCV (HCVcc) and HCV pseudoparticles (HCVpp). Anti-CD81 antibody reduced the entry of HCVtcp and HCVcc to almost background levels, and that of HCVpp by approximately 50%. Apolipoprotein E-dependent infection was observed with HCVtcp and HCVcc, but not with HCVpp, suggesting that the HCVtcp system is more relevant as a model of HCV infection than HCVpp. We improved the productivity of HCVtcp by introducing adapted mutations and by deleting sequences not required for replication from the subgenomic replicon construct. Furthermore, blind passage of the HCVtcp in packaging cells resulted in a novel mutation in the NS3 region, N1586D, which contributed to assembly of infectious virus. These results demonstrate that our plasmid-based system for efficient production of HCVtcp is beneficial for studying HCV life cycles, particularly in viral assembly and infection

Hemisphere asymmetry of response to pharmacologic treatment in an Alzheimer’s disease mouse model

The aim of this study was to examine hemisphere asymmetry of response to pharmacologic treatment in an Alzheimer’s disease mouse model using cilostazol as a chemical stimulus. Eight-month-old mice were assigned to vehicle or cilostazol treatment for three months and hemispheres were analyzed using quantitative proteomics. Bioinformatics interpretation showed that following treatment, aggregation of blood platelets significantly decreased in the right hemisphere whereas neurodegeneration significantly decreased and synaptic transmission increased in the left hemisphere only. Our study provides novel evidence on cerebral laterality of pharmacologic activity, with important implications in deciphering regional pharmacodynamic effects of existing drugs thus uncovering novel hemisphere-specific therapeutic targets