A Novel LRRK2 Variant p.G2294R in the WD40 Domain Identified in Familial Parkinson’s Disease Affects LRRK2 Protein Levels

Leucine-rich repeat kinase 2 (LRRK2) is a major causative gene of late-onset familial Parkinson’s disease (PD). The suppression of kinase activity is believed to confer neuroprotection, as most pathogenic variants of LRRK2 associated with PD exhibit increased kinase activity. We herein report a novel LRRK2 variant—p.G2294R—located in the WD40 domain, detected through targeted gene-panel screening in a patient with familial PD. The proband showed late-onset Parkinsonism with dysautonomia and a good response to levodopa, without cognitive decline or psychosis. Cultured cell experiments revealed that p.G2294R is highly destabilized at the protein level. The LRRK2 p.G2294R protein expression was upregulated in the patient’s peripheral blood lymphocytes. However, macrophages differentiated from the same peripheral blood showed decreased LRRK2 protein levels. Moreover, our experiment indicated reduced phagocytic activity in the pathogenic yeasts and α-synuclein fibrils. This PD case presents an example wherein the decrease in LRRK2 activity did not act in a neuroprotective manner. Further investigations are needed in order to elucidate the relationship between LRRK2 expression in the central nervous system and the pathogenesis caused by altered LRRK2 activity.     

Broadband bowtie belt nanoantennas

In this article, we study a linear array of bowtie nanoantennas placed between two metallic strips that can work from 800 to 1420 nm (600 nm linewidth), with an electric field enhancement factor close to 20. We study the dynamical change of the position of the electric field enhancement amongst different elements in the array and, at the same time, the effects of dispersion on the scalability of the array elements. A systematic analysis and methodology to produce an array that can operate over a large bandwidth whilst maintaining the electric field enhancement without significant variation is provided.     

Continuous hydrolysis of olive oil by lipase in microporous hydrophobic membrane bioreactor

Continuous hydrolysis of olive oil byCandida cylindracea’s lipase was studied in a microporous hydrophobic membrane bioreactor. Olive oil and buffer solution, fed continuously through two compartments partitioned by membrane, caused reaction at the interface of lipase-adsorbed membrane and buffer solution. Fatty acid was obtained in a single phase without being mixed with components of other phases. At all mean residence times, countercurrent flow mode was superior to cocurrent one. The lipase was adsorbed onto the membrane, and its adsorption was suggested to be partially specific from the experiments with enzymes having various levels of purity. The percent hydrolysis depended hyperbolically on the interfacial enzyme concentration. The hydrolysis seemed to be limited by diffusion of fat or fatty acid through the micropores of the membrane at higher interfacial enzyme concentrations. The lipase was stabilized significantly by glycerol added to the buffer solution. Satisfactory performance of the membrane bioreactor was obtained in a longterm continuous operation which lasted for 24 days by feeding buffer-glycerol (18.0%) solution over the adsorbed lipase. The operational half-life of the adsorbed enzyme was 15 days at 40 C.     

Preparation of one-dimensional polymer films by modification of a hydroxymethylbenzene self-assembled monolayer on iron with alkyltriethoxysilanes for preventing iron corrosion

A self-assembled monolayer (SAM) of p-hydroxymethylbenzene HOCH₂C₆H₄ - (HOMB) moiety adsorbed on iron by the formation of a covalent bond between carbon and iron atoms was prepared by electrochemical derivatization of an iron electrode with p-hydroxymethylbenzenediazonium tetrafluoroborate HOCH₂C₆H₄N₂BF₄. The electrode covered with the HOMB SAM was modified with alkyltriethoxysilanes C_nH_2n+1Si(OC₂H₅)₃ (C_nTES, n = 8 or 18) to prepare a film of one-dimensional polymer. The protective ability of the polymer film was determined by polarization measurement of the covered electrode in an aerated 0.5 M NaCl solution. The ability was enhanced by modification of the HOMB SAM with C_nTES markedly. The iron surface coated with the one-dimensional polymer film of the HOMB SAM modified with C₈TES was characterized by contact angle measurement and FTIR reflection and X-ray photoelectron spectroscopies. The persistence in the protective ability of the polymer film against iron corrosion in 0.5 M NaCl may be associated with the strong adsorption via the covalent bond, revealed by electron-probe microanalysis.     

Direct digital design of computed torque controllers

Direct digital design of computed torque controllers for a robot manipulator is discussed in this article. A simple discrete-time model of the robot manipulator obtained by Euler's method is used for the design. Taking account of computation delay in the digital processor, we propose predictor-based designs of the PD and PID type controllers. The PID-type controller is designed based on a modified version of the discrete-time integral controller proposed by Mita. For both controllers, the feedback gains can be determined easily by using simple formulas. A simulation example is presented to illustrate the relevance of the proposed designs and the robustness of PID-type controller against physical parameter variations. © 1994 John Wiley & Sons, Inc.     

Separation of di- and tripeptides with solvent extraction and an emulsion liquid membrane

The extraction equilibria of various di- and tripeptides with di-2-ethylhexylphosphoric acid (D2EHPA) were studied at low pH values. The complex extracted to organic phase consisted of one molecule of peptide and two molecules of D2EHPA dimer. The extraction constants of the peptides correlated well with the distribution coefficients of peptides between 1-octanol and water, which is a measure of hydrophobicity. The permeation rates of peptides through an emulsion liquid membrane were examined by using D2EHPA as a carrier, Span 80 as an emulsifier and kerosene as a diluent. The rates varied considerably with peptide type, depending upon the hydrophobicity.     

Protection against adoptive transfer of autoimmune diabetes mediated through very late antigen-4 integrin

The very late antigen-4 (VLA-4) integrin expressed on the surface of lymphocytes and macrophages can regulate their migration to inflammatory sites as well as control cellular activation. The role of VLA-4 in the establishment of autoimmune diabetes is not easily predicted given the multiplicity of adhesion pathways and their differential use by various cell types. The contribution of VLA-4 to insulin-dependent diabetes mellitus was investigated by administration of VLA-4-specific monoclonal antibodies (MoAb) in an adoptive transfer model of disease in NOD mice. This study shows that VLA-4-specific MoAbs profoundly inhibit the development of diabetes with protection sustained by repeated MoAb exposure. Insulitis was completely inhibited during treatment and progressed to a severe degree once MoAb treatment was suspended, yet approximately 40% of treated recipients failed to become diabetic during 1-2 months post-treatment. Although we cannot rule out depletion of a relatively minor subpopulation of cells by prolonged anti-VLA-4 MoAb exposure, this inhibition of diabetes onset by treatment with MoAbs to VLA-4 supports a dependence on VLA-4 for cellular functions leading to diabetes and demonstrates that a significant disease modifying effect can be mediated by targeting the VLA-4 integrin.     

Performance prediction of a hybrid‐excitation synchronous machine with axially arranged excitation poles and permanent‐magnet poles

This paper presents a method of predicting the steady‐state performance of a new hybrid‐excitation synchronous machine (HESM) theoretically. The field pole of this HESM is axially divided into two parts; one is an excitation part and the other a permanent‐magnet (PM) part. A nonlinear equivalent circuit, which can include the saliency of the rotor and the magnetic saturation due to the iron core, is derived. Based on this equivalent circuit, the steady‐state performance of the HESM is calculated, and the results are confirmed through experiments. © 2004 Wiley Periodicals, Inc. Electr Eng Jpn, 150(2): 43–49, 2005; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/eej.20033