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.     

Synthesis of optical quality ZnO nanowires utilizing ultrasonic spray pyrolysis

ZnO nanowires were grown by an ultrasonic spray pyrolysis technique. The aspect ratio and size of the wire were dependent mainly on the pH value of a precursor solution and the growth temperature. By high-resolution transmission electron microscopic analysis and photoluminescence measurements, it was confirmed that the nanowires are monocrystalline with good optical quality.     

Preliminary spectrum shifter design for intermediate energy nuclear data benchmark experiments with DT neutrons

Integral benchmark experiments with DT neutrons are not always sufficient for nuclear data benchmarking in the MeV region, below 10 MeV. A neutron spectrum shifter, which will be placed between a sample and a DT neutron source, is effective to moderate DT neutrons incident to the sample. In order to estimate effects of the spectrum shifter, the ratio of the contribution of 14 MeV neutrons in the leakage neutron and gamma-ray spectra was calculated with MCNP-4C for an experimental configuration at FNS of JAEA, Japan. The calculations were carried out for a Li₂TiO₃ sample with a Be, D₂O, or ⁷LiD spectrum shifter. It was found out that the Be shifter was superior to others and the Be shifter was effective to decrease the contribution of 14 MeV neutrons especially for secondary gamma-ray spectrum measurements.     

An Efficient Dynamic Formulation for Multibody Systems

The objective of this article is to present an efficient extension ofRosenthal's order-n algorithm to multibody systems containing closedloops. The equations of motion are created by using relative coordinatesand partial velocity theory. Closed topological loops are handled by cutjoint technique. The set of constraint equations of cut joints isadjoined to the system's equation of motion by using Lagrangemultipliers. This results in the equation of motion as adifferential-algebraic equation (DAE) rather than an ordinarydifferential equation. This DAE is then solved by applying the extendedRosenthal's order-n algorithm proposed in this article. While solvingDAE, violation of the kinematic constraint equations of cut joints iscorrected by coordinate projection method. Some numerical simulationsare carried out to demonstrate efficiency of the proposed method.     

Self-flux synthesis and photoluminescent properties of LiAl5O8

Pure-phase LiAl₅O₈ was selected as an oxide ceramic red phosphor material without dopants (color centers) and was synthesized using a self-flux method. The LiAl₅O₈ was formed by heating a powder mixture consisting of γ-Al₂O₃:Li₂SO₄ = 1:2 (molar ratio) at over 1100 °C for 1 h. Photoluminescence (PL) properties for the synthesized LiAl₅O₈ were investigated. The maximum intensity of the excitation spectrum for the photoluminescent emission of LiAl₅O₈ synthesized was at 274 nm. The peak intensity of the emission spectrum was at a wavelength of 667 nm (red color). The intensity of the peak emission spectrum increased with the heating temperature, i.e., the maximum peak intensity of the red emission spectrum was detected for the LiAl₅O₈ synthesized by heating at 1500 °C for 1 h.     

Detection of relative and uniform motion

We measured the lowest velocity (velocity threshold) for discriminating motion direction in relative and uniform motion stimuli, varying the contrast and the spatial frequency of the stimulus gratings. The results showed significant differences in the effects of contrast and spatial frequency on the threshold, as well as on the absolute threshold level between the two motion conditions, except when the contrast was 1% or lower. Little effect of spatial frequency was found for uniform motion, whereas a bandpass property with a peak at approximately 5 cycles per degree was found for relative motion. It was also found that contrast had little effect on uniform motion, whereas the threshold decreased with increases in contrast up to 85% for relative motion. These differences cannot be attributed to possible differences in eye movements between the relative and the uniform motion conditions, because the spatial-frequency characteristics differed in the two conditions even when the presentation duration was short enough to prevent eye movements. The differences also cannot be attributed to detecting positional changes, because the velocity threshold was not determined by the total distance of the stimulus movements. These results suggest that there are two different motion pathways: one that specializes in relative motion and one that specializes in uniform or global motion. A simulation showed that the difference in the response functions of the two possible pathways accounts for the differences in the spatial-frequency and contrast dependency of the velocity threshold.     

A firm as a dialectical being: towards a dynamic theory of a firm

Today, firms are facing many contradictions: efficiency versuscreativity; exploitation versus exploration; speed versus time-consumingresource building. This paper argues that a firm's capabilityto synthesize such contradictions is the key to understandingwhy a firm can be more efficient at producing knowledge thanmarket. A firm can create new knowledge and capability thatgo beyond the balancing point in the existing frontier withits synthesizing capability, which is embedded in its knowledgevision, its ba, its creative routines, its incentive systemsand its distributed leadership.     

Laser Thomson scattering and optical emission studies of striated PDP micro‐discharge plasmas

Abstract— Properties of a plasma‐display‐panel (PDP) like discharge were examined by emission and laser Thomson scattering (LTS) measurements. Emission measurements were performed using an intensified CCD camera. By varying several external parameters such as the amplitude of the input voltage, gas composition, and pressure, the influence of these parameters on the discharge behavior was studied. Results of emission measurements showed that they were in good agreement with similar emission measurements on real PDP cells. LTS measurements were performed for the striated PDP‐like discharge at a pressure of 100 Torr and the results showed clear modulations in both profiles of electron density and electron temperature.     

A sole del(15q) anomaly in post-myelodysplasia acute myeloid leukemia

We report the second case of post-myelodysplasia acute myeloid leukemia (post-MDS AML) with a sole chromosome change del(15q). This anomaly is rarely seen. To our knowledge, only seven cases so far have been reported in human neoplasias, including one case each of acute myeloid leukemia (AML), acute lymphoid leukemia, post myelodysplasia AML, myelodysplastic syndrome, myelofibrosis, macroglobulinemia, Hodgkin's lymphoma and uterine leiomyoma. This case suggests that del(15q) is related to lympho-myeloproliferative disorders. Moreover, we speculate that certain oncogene(s) located on 15q might have some role in the progression of the disease, since the del(15q) anomaly appeared only in the AML phase in this case.