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.     

Membrane separation of indigenous noroviruses from sewage sludge and treated wastewater.

In this study, feasibility of membrane separation for the removal of indigenous noroviruses (NVs) is evaluated. The indigenous NV gene was never detected from ultrafiltration (UF) permeates of sewage sludge and treated wastewater. Indigenous NV gene was also not detected from permeates of sewage sludge and treated wastewater by microfiltration (MF) with a pore size of 0.1 microm (MF0.1). Even though the pore size of MF (0.1 microm) was much larger than the diameter of virus particle (approximately 30-40nm), more than 4-log10 reduction value (LRV) at maximum was achieved by membrane separation with MF0.1. NV genes were often detected from permeates of sewage sludge and treated wastewater by MF with a pore size of 0.45 microm (MF0.45), although the maximum log10 reduction values were more than 3.59 for sewage sludge and more than 2.90 for treated wastewater. It is important to verify factors determining the removal efficiency of viruses with MF membranes.     

A case of chronic encephalitis due to double infection with herpes simplex and measles viruses

In a healthy 49-year-old man, a decrease in job efficiency was noticed along with bizarre behavior. On admission, he was euphoric, childish, superficial and had increased libido. Neurological findings were normal. There were no abnormal findings on routine blood tests, hematochemistry or urine analysis. MRI showed no abnormal findings. However, single photon emission CT (SPECT) showed diffuse hypoaccummulation of tracer from the temporal to frontal regions. Lumbar puncture showed clear cerebrospinal fluid (CSF) with pleocytosis and an elevated protein level. Moreover, antibody IgG titers to herpes simplex virus (HSV) and measles virus were elevated, according to EIA [serum HSV -1,202.2x, measles virus 47.1x: CSF HSV-116.1x, measles virus 9.9x]. The ratio of serum to CSF antibody titers of HSV and measles virus were 12.5 and 4.75, respectively. The antibody index values of HSV and measles virus IgG titers were 8.42 and 22.22. The ratio of albumin was 105.7. Chronic, progressive HSV encephalitis is rare, and there have been very few reports of encephalitis due to double infection by HSV and another virus. Our patient was diagnosed as having encephalitis due to double infection with HSV and measles virus, because the ratio of serum to CSF antibody titers was less than 20 and the antibody index values were over 1.91. Moreover, since the IgG index was elevated and the ratio of albumin was not low, it was suggested that the blood-brain-barrier had not been disrupted, and antibodies were being produced chronically in the medullary cavity. Hyperaccummulation of tracer on SPECT studies has been reported in the early stages of HSV encephalitis. In our case, while CT and MRI showed no abnormal findings, SPECT showed diffuse hypoaccummulation. SPECT appears to be a useful tool in the diagnosis of this disorder. In case of chronic, progressive personality change in middle-aged adults, we must be aware of double virus infection of the brain as a possible causal factor.     

Decentralized adaptive coordinated control of multiple robot arms without using a force sensor

This paper presents a distributed adaptive coordinated control method for multiple robot arms grasping a common object. The cases of rigid contact and rolling contact are analyzed. In the proposed controller, the dynamic parameters of both object and robot arms are estimated adaptively. The desired motions of the robot arms are generated by an estimated object reference model. The control method requires only the measurements of the positions and velocities of the object and robot arms, but not the measurements of forces and moments at contact points. The asymptotic convergence of trajectory is proven by the Lyapunov-like Lemma. Experiments involving two robot arms handling a common object are shown.     

Sub-50-nm physical gate length CMOS technology and beyond usingsteep halo

Sub-50-nm CMOS devices are investigated using steep halo and shallow source/drain extensions. By using a high-ramp-rate spike annealing (HRR-SA) process and high-dose halo, 45-nm CMOS devices are fabricated with drive currents of 650 and 300 μA/μm for an off current of less than 10 nA/μm at 1.2 V with T_ox^inv =2.5 nm. For an off current less than 300 nA/μm, 33-nm pMOSFETs have a high drive current of 400 uA/μm. Short-channel effect and reverse short-channel effect are suppressed simultaneously by using the HRR-SA process to activate a source/drain extension (SDE) after forming a deep source/drain (S/D). This process sequence is defined as a reverse-order S/D (R-S/D) formation. By using this formation, 24-nm nMOSFETs are achieved with a high drive current of 800 μA/μm for an off current of less than 300 μA/μm at 1.2 V. This high drive current might be a result of a steep halo structure reducing the spreading resistance of source/drain extensions     

Acute progressive polyneuropathy in a patient with Waldenstr?m macroglobulinemia

A case of Waldenstr?m's macroglobulinemia (WM) (IgM-kappa type) associated with acute-onset demyelinating peripheral neuropathy is reported. A 49-year-old woman was admitted to our hospital because of general fatigue and recurrent syncope attacks. She was treated with vincristine, cyclophosphamide, epirubicin and prednisolone. By 10th hospital day, her clinical condition improved and serum viscosity was reduced. However, on the 21st hospital day, she suffered from rapidly progressive writing and gait disturbance. Neurological examination showed muscular atrophy and weakness in the distal part of four extremities. Deep tendon reflexes were diminished. There was no sensory deficit. Cerebrospinal fluid was normal. Anti-myelin associated glycoprotein activity of her serum was negative. Both motor and sensory nerve conduction velocities were markedly decreased. Biopsy of sural nerve revealed marked demyelination and onion bulb formation. There was IgM deposition on myelin sheath. Minimal axonal changes excluded the possibility of vincristine neuropathy. Plasmapheresis improved her symptoms, but nerve conduction velocities remained unchanged. Polyneuropathy associated with WM is usually gradual onset and sensory dominant. In this case, associated neuropathy was acute onset, progressive and motor dominant. This type of neuropathy in patients with WM is very rare.     

Spontaneous hemorrhage of an adrenal cortical adenoma causing Cushing''s syndrome

A modified surgical splint for Le Fort I osteotomies with transverse expansion is presented. The splint is made of a transpalatal stainless steel bar with acrylic abutment against the palatal surface of the molar and bicuspid tooth. It is rigid and renders excellent retention. It causes minimal patient discomfort, and oral hygiene is hardly compromised.     

Strengthening of nickel -base superalloys for nuclear heat exchanger application

Strengthening mechanisms of nickel-base superalloys have been discussed with the background of the Japanese research and development activities in this field. As candidates for materials of intermediate heat exchangers which will be used for a future programme of nuclear steelmaking systems, two kinds of alloys have successfully been developed in Japan. The designs of these alloys have been reviewed from metallurgical aspects including their composition and creep properties. In addition to the conventional methods to strengthen these alloys, such as solid solution hardening or particle precipitation hardening, a grain-boundary precipitation strengthening due to tungsten-rich ₂ phase in the Ni-Cr-W system, would be expected as a further advanced method.     

Development of an anisotropic conductive adhesive film (ACAF) from epoxy resins

A thermoset type anisotropic conductive adhesive film (ACAF), which electrically connects an ITO glass and a flex circuit both having conducting pattersn of less than 100 μm in pitch, has been developed. In this development, bisphenol A and bisphenol F epoxy resins were tested to formulate an ACAF with easy-to-handle tackiness, flexibility, and strenght. A curing agent that gives fast cure and long shelf-life properties to the epoxy resin was also selected. The tensile stress–strain responses of obtained adhesive films were successfully used for determining the formulation. Good aftercure physical properties (electrical and mechanical) were obtained. Durability against high temperature and high humidity were also tested to confirm long-term stability of the conduction of this ACAF. © 1995 John Wiley & Sons, Inc.     

Study on stiffness visualization and safety control based on will-consensus building for tele-palpation robot system

This paper proposes a method for visualizing the stiffness of a soft object in a palpation-support information system by the teleoperation of a robot hand. It is important that a palpation system display a body’s shape and stiffness. In our method, the stiffness of the contact area between the soft object and the robot finger is estimated by a recursive least-squares method with forgetting factor that uses an impedance dynamics model. With the estimated stiffness and direction of contact force, we calculate the scalar parameter for visualization of stiffness. Moreover, we propose a safety control method for the palpation system, which is part of a tele-control method based on will-consensus building. The system configuration, estimated algorithm, and experimental results are presented.