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.     

Effects of SO2 on selective catalytic reduction of NO with NH3 over a TiO2 photocatalyst

The effect of SO₂ gas was investigated on the activity of the photo-assisted selective catalytic reduction of nitrogen monoxide (NO) with ammonia (NH₃) over a TiO₂ photocatalyst in the presence of excess oxygen (photo-SCR). The introduction of SO₂ (300 ppm) greatly decreased the activity of the photo-SCR at 373 K. The increment of the reaction temperature enhanced the resistance to SO₂ gas, and at 553 K the conversion of NO was stable for at least 300 min of the reaction. X-ray diffraction, FTIR spectroscopy, thermogravimetry and differential thermal analysis, x-ray photoelectron spectroscopy (XPS), elemental analysis and N₂ adsorption measurement revealed that the ammonium sulfate species were generated after the reaction. There was a strong negative correlation between the deposition amount of the ammonium sulfate species and the specific surface area. Based on the above relationship, we concluded that the deposition of the ammonium sulfate species decreased the specific surface area by plugging the pore structure of the catalyst, and the decrease of the specific surface area resulted in the deactivation of the catalyst.     

Anti‐Sway Crane Control Considering Wind Disturbance and Container Mass

A method for estimating the sway angle using an observer has already been proposed. The state observer estimates the sway angle accurately and must use the detected sway angle value. However, the estimated sway angle has an error owing to rope length error, friction force, and wind. Moreover, the container mass cannot be determined, and therefore the observer parameter is not suitable. We already proposed robust antisway control for overcoming rope length error without adding a new sensor. Further, we designed a friction disturbance observer to cancel out the influence of the friction force. In this paper, we first propose a container mass estimation method when a crane system performs rolling up control. The observer parameter can be selected using the estimated mass value. Second, in crane parallel shift control, we propose a robust antisway control even when there is a wind disturbance. We design a wind disturbance observer and propose a wind disturbance estimator to separate the friction observer output from the wind disturbance observer output. We confirm through experiments that the proposed method can reduce vibration.     

Analysis of Cerebrospinal Fluid Extracellular Vesicles by Proximity Extension Assay: A Comparative Study of Four Isolation Kits

There is a lack of reliable biomarkers for disorders of the central nervous system (CNS), and diagnostics still heavily rely on symptoms that are both subjective and difficult to quantify. The cerebrospinal fluid (CSF) is a promising source of biomarkers due to its close connection to the CNS. Extracellular vesicles are actively secreted by cells, and proteomic analysis of CSF extracellular vesicles (EVs) and their molecular composition likely reflects changes in the CNS to a higher extent compared with total CSF, especially in the case of neuroinflammation, which could increase blood–brain barrier permeability and cause an influx of plasma proteins into the CSF. We used proximity extension assay for proteomic analysis due to its high sensitivity. We believe that this methodology could be useful for de novo biomarker discovery for several CNS diseases. We compared four commercially available kits for EV isolation: MagCapture and ExoIntact (based on magnetic beads), EVSecond L70 (size-exclusion chromatography), and exoEasy (membrane affinity). The isolated EVs were characterized by nanoparticle tracking analysis, ELISA (CD63, CD81 and albumin), and proximity extension assay (PEA) using two different panels, each consisting of 92 markers. The exoEasy samples did not pass the built-in quality controls and were excluded from downstream analysis. The number of detectable proteins in the ExoIntact samples was considerably higher (~150% for the cardiovascular III panel and ~320% for the cell regulation panel) compared with other groups. ExoIntact also showed the highest intersample correlation with an average Pearson’s correlation coefficient of 0.991 compared with 0.985 and 0.927 for MagCapture and EVSecond, respectively. The median coefficient of variation was 5%, 8%, and 22% for ExoIntact, MagCapture, and EVSecond, respectively. Comparing total CSF and ExoIntact samples revealed 70 differentially expressed proteins in the cardiovascular III panel and 17 in the cell regulation panel. To our knowledge, this is the first time that CSF EVs were analyzed by PEA. In conclusion, analysis of CSF EVs by PEA is feasible, and different isolation kits give distinct results, with ExoIntact showing the highest number of identified proteins with the lowest variability.     

A comparative study of DPSK and OOK WDM transmission over transoceanic distances and their performance degradations due to nonlinear phase noise

We have compared experimentally the transmission performance of return-to-zero differential phase-shift keying (RZ-DPSK) with RZ-ON-OFF keying (OOK), nonreturn-to-zero differential phase-shift keying (NRZ-DPSK), and NRZ-OOK for 100/spl times/10-Gb/s transmission with a spectral efficiency of 0.22 b/s/Hz over transoceanic distances. The Q degradation of the RZ-DPSK after transmission over 9180 km was 3 dB greater than that of RZ-OOK. The experimental results clearly showed the major cause of degradation for DPSK is not cross-phase modulation but self-phase modulation. The calculated nonlinear phase noise, i.e., the Gordon-Mollenauer effect, agreed with the experimental results. A distributed-Raman-amplifier assisted erbium-doped-fiber-amplified transmission line acted well in reducing the nonlinear phase noise.     

Solution intercalation of polystyrene and the comparison with poly(ethyl methacrylate)

Polystyrene nanocomposites have been prepared via solution intercalation method. Combination of wide-angle X-ray diffraction and thermogravimetric analysis is used to study the effect of solvents on the morphology of the nanocomposites as a function of the amount of residual solvent. d-Spacing of the polystyrene nanocomposites has a minimum value when the residual solvent concentration is between 2 and 4 wt%. Different interaction level between the solvent molecules and polymer chains is considered to be the reason for this special d-spacing change behavior. By comparing the solution intercalation of polystyrene and poly(ethyl methacrylate) from different solvents, it is concluded that the interactions between polymer-surfactant, solvent-surfactant, and polymer-solvent play important role for the solution intercalation of polymers.     

Suppression control method for torque vibration of three-phase HB-type stepping motor utilizing feedforward control

This paper proposes a method to reduce the vibration of the three-phase HB-type stepping motor with cogging torque by the feedforward compensation control. The compensation signal to suppress the vibration of the motor frame is obtained by the repetitive controller installing an online Fourier transformer and utilizing an acceleration sensor attached to the motor frame or an acoustic sensor such as a microphone placed close to the frame. The sensor is used only for the acquisition of the feedforward compensation data. The feedforward compensation signal at an arbitrary operating point is derived from the amplitude and phase data of the frequency components and the operating point data. Compensation data obtained by the repetitive controller is applied to the operating point changed by reference frequency and load condition in steady state. The compensation signal for the new operating point will be generated from compensation data utilizing polynomial equation approximation and linear interpolation method. The effectiveness of this proposed method is confirmed by the experimental results.     

Digitally tunable optical filters using arrayed-waveguide grating(AWG) multiplexers and optical switches

Two novel configurations for digitally tunable optical filters based on arrayed-waveguide grating (AWG) multiplexers are described in detail with emphasis on the connection of the AWG multiplexer and optical switches. Performance comparisons show that conventional configurations are disadvantaged by the switch size required and loss imbalance among the optical frequency-division-multiplexed (FDM) channels; the proposed configurations require only O(√(N)) switch elements to select one of N FDM channels, and the loss imbalance is lower by up to 75% in decibel     

Tuning-current splitting network for three-section DBR lasers

A simple current-splitting network for DBR-laser frequency tuning is proposed that distributes a single control current among two tuning sections and can adjust the current distribution without yielding impedance mismatching. The nonlinear characteristics of the tuning sections realise the non-proportional current splitting suitable for continuous tuning; 470 GHz (3.8 nm) tuning range is achieved     

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.