345 research outputs found
Phenotype variability and allelic heterogeneity in KMT2B-Associated disease
No full textBackground: Mutations in Lysine-Specific Histone Methyltransferase 2B gene (KMT2B) have been reported to be associated with complex early-onset dystonia. Almost all reported KMT2B mutations occurred de novo in the paternal germline or in the early development of the patient. We describe clinico-genetic features on four Japanese patients with novel de novo mutations and demonstrate the phenotypic spectrum of KMT2B mutations. Methods: We performed genetic studies, including trio-based whole exome sequencing (WES), in a cohort of Japanese patients with a seemingly sporadic early-onset generalized combined dystonia. Potential effects by the identified nucleotide variations were evaluated biologically. Genotype-phenotype correlations were also investigated. Results: Four patients had de novo heterozygous mutations in KMT2B, c.309delG, c.1656dupC, c.3325_3326insC, and c.5636delG. Biological analysis of KMT2B mRNA levels showed a reduced expression of mutant transcript frame. All patients presented with motor milestone delay, microcephaly, mild psychomotor impairment, childhood-onset generalized dystonia and superimposed choreoathetosis or myoclonus. One patient cannot stand due to axial hypotonia associated with cerebellar dysfunction. Three patients had bilateral globus pallidal deep brain stimulation (DBS) with excellent or partial response. Conclusions: We further demonstrate the allelic heterogeneity and phenotypic variations of KMT2B-associated disease. Haploinsufficiency is one of molecular pathomechanisms underlying the disease. Cardinal clinical features include combined dystonia accompanying mild psychomotor disability. Cerebellum would be affected in KMT2B-associated disease
Late-onset spastic paraplegia: Aberrant SPG11 transcripts generated by a novel splice site donor mutation
No full textWe identified a novel homozygous mutation in the splice site donor (SSD) of intron 30 (c.5866 + 1G > A) in consanguineous Japanese SPG11 siblings showing late-onset spastic paraplegia using the whole-exome sequencing. Phenotypic variability was observed, including age-at-onset, dysarthria and pes cavus. Coding DNA sequencing revealed that the mutation affected the recognition of the constitutive SSD of intron 30, splicing upstream onto a nearby cryptic SSD in exon 30. The use of constitutive splice sites of intron 29 was confirmed by sequencing. The mutant transcripts are mostly subject to degradation by the nonsense-mediated mRNA decay system. SPG11 transcripts, escaping from the nonsense-mediated mRNA decay pathway, would generate a truncated protein (p.Tyr1900Phefs5X) containing the first 1899 amino acids and followed by 4 aberrant amino acids. This study showed a successful clinical application of whole-exome sequencing in spastic paraplegia and demonstrated a further evidence of allelic heterogeneity in SPG11. The confirmation of aberrant transcript by splice site mutation is a prerequisite for a more precise molecular diagnosis
Was the 1952 Tokachi-oki earthquake (Mw=8.1) a typical underthrust earthquake?: Plate interface reflectivity measurement by an air gun-ocean bottom seismometer experiment in the Kuril Trench
No full textThe Kuril Trench subduction zone is one of the most seismogenic regions, where underthrust earthquakes with M > 8 recur along the trench. The seismic gap between the source areas of the 1973 Nemuro-oki and 2003 Tokachi-oki earthquakes, which are typical underthrust earthquakes faulting with rupture velocities of ～3 km/s, has been ruptured by the 1952 Tokachi-oki earthquake. The seismic gap has also slipped incidental to neighboring asperities. The difference in slip pattern on the plate interface generally appears as a spatial difference in seismic structure on the plate interface, such as a reflectivity of the plate interface. We estimated the crustal velocity structure and analyzed the reflectivity of the plate interface to investigate the physical properties of the plate interface by performing an air gun-ocean bottom seismometer experiment on the along-trench profile across the seismic gap. Strong reflections from the plate interface were observed in the 1952 Tokachi-oki source area including the seismic gap, rather than in the 1973 Nemuro-oki source area. The strong reflectivity of the plate interface in such the seismic gap with an incidental slip suggests that a slip pattern in the corresponding seismic gap would be conditionally stable. The coupling condition in the source areas of the eastern part of the source area of the 1952 earthquake is different from that in source areas of typical underthrust earthquakes, such as the 2003 Tokachi-oki and 1973 Nemuro-oki earthquakes. Our results suggest that the 1952 Tokachi-oki earthquake was a complex earthquake with the characteristic of a tsunami earthquake
From the 'Rescue of the Nation State' to the Emergence of European Spaces. EUIJ-Kansai Workshop on "New Research Horizons of the History of European Integration", May 10, 2008, Toyonaka (Osaka)
No full textThe aim of this paper is to make some contribution to the discussion on the future direction of the historical research on the European integration processes. What I intend to do here is, broadly, to link the contemporary European studies to the Historical studies, and concretely, to emphasise the transnational dimension of European integration. This exercise should be read as presenting my "wish list" to the Integration Historians
Performance Analysis of Thermoelectric Modules Consisting of Square Truncated Pyramid Elements Under Constant Heat Flux
No full textSystem design of a thermoelectric (TE) power generation module is pursued in order to improve the TE performance. Square truncated pyramid shaped P-N pairs of TE elements are connected electronically in series in the open space between two flat insulator boards. The performance of the TE module consisting of 2-paired elements is numerically simulated using commercial software and original TE programs. Assuming that the heat radiating into the hot surface is regulated, i.e., the amount of heat from the hot surface to the cold one is steadily constant, as it happens for solar radiation heating, the performance is significantly improved by changing the shape and the alignment pattern of the elements. When the angle theta between the edge and the base is smaller than 72 degrees, and when the cold surface is kept at a constant temperature, two patterns in particular, amongst the 17 studied, show the largest TE power and efficiency. In comparison to other geometries, the smarter square truncated pyramid shape can provide higher performance using a large cold bath and constant heat transfer by heat radiation
Analysis of the Performance of Thermoelectric Modules Under Concentrated Radiation Heat Flux
No full textThe concentration of solar radiation by either a lens or a mirror is one of the options for practical utilisation of light to obtain higher temperatures. However, it is difficult to maintain high temperatures on the hot side of the module due to solar diurnal motion. This study evaluates the influence of the thermoelectric (TE) output by optical light concentration. Three-dimensional partial differential equations describing heat balance and TE phenomena were simultaneously solved by applying numerical methods, and the temperature distribution in the whole TE module as well as the current density were simulated. It was shown that the three models of light concentration on a single TE module (BiTe-based, four legs having dimensions of 10 mm x 10 mm x 10 mm) generate a similar output in the external load. This happens because the long leg becomes a large thermal resistance, and because the alumina plate (1 mm thick) with a high thermal conductivity covers the top of the TE modules. The homogenised temperature at the hot junctions generates a similar output in all three models when the cold terminals were kept at constant temperature
SimpleBounce: A simple package for the false vacuum decay
No full textWe present SimpleBounce, a C++ package for finding the bounce solution for the false vacuum decay. This package is based on a flow equation which is proposed by the author R. Sato (2020) and solves Coleman–Glaser–Martin’s reduced problem (S. R. Coleman et al. 1978): the minimization problem of the kinetic energy while fixing the potential energy. The bounce configuration is obtained by a scale transformation of the solution of this problem. For models with 1–8 scalar field(s), the bounce action can be calculated with O(0.1) % accuracy in O(0.1) s. This package is available at http://github.com/rsato64/SimpleBounce
APPLICATION OF A MARKOV PROCESS TO A MECHANICAL MODEL OF GRANULAR MATERIALS (2)
No full textIn the previous paper the author proposed a mechanical model of particulate materials as aMarkov process and explained the concepts of the potential barrier and the potential slip planewhich are introduced in the proposed model. Furthermore, the strain of particulate materialswas defined by using the change of contact angles at the contact points of particles and the dis-continuous motion of particles.In this paper the results of shearing tests obtained by the modified triaxial apparatus whichis designed and constructed, and can generate three different principal stresses are presented.The results of numerical experiments which are carried out by using the proposed model arealso presented. From both results it is shown that the proposed model can versatilely follow themechanical behaviours of particulate materials such as sands with complicated stress paths include-ing the stress reverse and repeated loading.In the previous paper the author proposed a mechanical model of particulate materials as aMarkov process and explained the concepts of the potential barrier and the potential slip planewhich are introduced in the proposed model. Furthermore, the strain of particulate materialswas defined by using the change of contact angles at the contact points of particles and the dis-continuous motion of particles.In this paper the results of shearing tests obtained by the modified triaxial apparatus whichis designed and constructed, and can generate three different principal stresses are presented.The results of numerical experiments which are carried out by using the proposed model arealso presented. From both results it is shown that the proposed model can versatilely follow themechanical behaviours of particulate materials such as sands with complicated stress paths include-ing the stress reverse and repeated loading
Rescue of Metabolic Alterations in AR113Q Skeletal Muscle by Peripheral Androgen Receptor Gene Silencing
No full textSummarySpinal and bulbar muscular atrophy (SBMA), a progressive degenerative disorder, is caused by a CAG/glutamine expansion in the androgen receptor (polyQ AR). Recent studies demonstrate that skeletal muscle is an important site of toxicity that contributes to the SBMA phenotype. Here, we sought to identify critical pathways altered in muscle that underlie disease manifestations in AR113Q mice. This led to the unanticipated identification of gene expression changes affecting regulators of carbohydrate metabolism, similar to those triggered by denervation. AR113Q muscle exhibits diminished glycolysis, altered mitochondria, and an impaired response to exercise. Strikingly, the expression of genes regulating muscle energy metabolism is rescued following peripheral polyQ AR gene silencing by antisense oligonucleotides (ASO), a therapeutic strategy that alleviates disease. Our data establish the occurrence of a metabolic imbalance in SBMA muscle triggered by peripheral expression of the polyQ AR and indicate that alterations in energy utilization contribute to non-neuronal disease manifestations
Multiplicative Characters and Gaussian Fluctuation Limits
No full textIt is known that extreme characters of several inductive limits of compact groups exhibit multiplicativity in a certain sense. In the paper, we formulate such multiplicativity for inductive limit quantum groups and provide explicit examples of multiplicative characters in the case of quantum unitary groups. Furthermore, we show a Gaussian fluctuation limit theorem using this concept of multiplicativity.The author gratefully acknowledges comments from Professor Makoto Katori at the early stage of this work. The author is grateful to Professor Yoshimichi Ueda for the useful discussion and his comments on the draft of this paper. Finally, the author gratefully thanks the referees for their kind reading and comments. This work was supported by JSPS Research Fellowship for Young Scientists PD (KAKENHI Grand Number 22J00573)
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