Shape evolution of electrodeposited copper bumps with high peclet numbers

We report the shape evolution of initial copper bumps at Peclet numbers higher than a hundred. The role of vortices and of penetration flow within the cavity was discussed with numerical fluid dynamics computation to obtain a bump with a single hump at the center. The current distributions, or flux profiles, were calculated at the diffusion controlled overpotential and were compared with the electrodeposited bump shapes. For the 100 mu m cavity width, the vortices increase at the upstream corners with Peclet numbers 1410 and 7311. The vortices are the local resistance of mass transfer to the cathode. These vortices cause the hollows in flux profiles at the upstream corner with these Peclet numbers. The penetration flow collides with the photoresist sidewall and the vortices decrease at downstream corners. These decreased vortices cause the increase in flux profile at downstream corners. For a 30 pm cavity width a single large vortex forms for the higher Peclet number 44,500 and a single hump in flux is achieved.</p

Microsatellite Capture Sequencing

Microsatellites (simple sequence repeats, SSRs) that consist of repetitive sequences of one to six bases are ubiquitous in most eukaryotic genomes. The use of molecular markers for this region is efficacious in molecular-assisted breeding, molecular phylogenetics, and population genetics. Recently, the detection of a number of SSRs using a high-throughput DNA sequencing assay has become possible. Particularly, microsatellite capture sequencing using our developed protocol can detect SSRs more effectively by enriching the DNA library using an SSR probe. Our protocol used in this study demonstrates the possibility of using low-input DNA (≥1 ng), and while the use of restriction enzymes was more suitable for identifying the heterozygous genotype than sonication was, sonication facilitated the detection of various SSR flanking regions with both species-specific and common characteristics more than restriction enzyme digestion did. Moreover, a simulation analysis using various scale reads estimated that a few thousand SSRs could be detected from 50 K reads per sample. Furthermore, we described an in silico polymorphic detection and phylogenetic analysis method based on microsatellite capture sequencing data

Phase transitions of a tethered surface model with a deficit angle term

Nambu-Goto model is investigated by using the canonical Monte Carlo simulations on fixed connectivity surfaces of spherical topology. Three distinct phases are found: crumpled, tubular, and smooth. The crumpled and the tubular phases are smoothly connected, and the tubular and the smooth phases are connected by a discontinuous transition. The surface in the tubular phase forms an oblong and one-dimensional object similar to a one-dimensional linear subspace in the Euclidean three-dimensional space R^3. This indicates that the rotational symmetry inherent in the model is spontaneously broken in the tubular phase, and it is restored in the smooth and the crumpled phases.Comment: 6 pages with 6 figure

Discordant Immune Marker Expression Between Preoperatively Biopsied and Matched Surgically Resected Specimens in Patients With Oral Squamous Cell Carcinoma

Programmed cell death ligand 1 (PD-L1) expression and tumor-associated immune cell (TAIC) density can be the biomarkers of survival outcome and for predicting the efficacy of immune checkpoint inhibitors in oral squamous cell carcinoma (OSCC), but whether single biopsy accurately reflects the values of these parameters in resected specimens is unclear. To clarify this, we evaluated the concordance of immune marker expression (PD-L1, PD-1, CD3, CD4, CD8, and CD68) between 39 paired biopsied and surgically resected specimens obtained from patients with OSCC at Kobe City Medical Center General Hospital between July 2011 and January 2016. Immune marker expression was assessed using immunohistochemistry. PD-L1 expression was consistent between the biopsied and surgically resected specimens in only 76.9% of cases. TAIC density was significantly lower in biopsied than in surgically resected specimens. There was considerable discordance in immune marker expression between biopsied and surgically resected specimens. We should take into consideration that PD-L1 positivity and TAIC density would be underestimated by single small biopsies compared to the estimations by surgically resected specimens

Dysphagia Screening Questionnaire : Swallow-10

The Seirei dysphagia screening questionnaire (namely, Seirei dsq) has been used to screen for oropharyngeal dysphagia (OD). Some of the questions in the questionnaire are difficult for people with cognitive decline to answer. We selected 10 items from the Seirei dsq that could be assessed by others, such as care workers (named Swallow-10). This study aims to verify the validity of the scoring method used in Swallow-10. The dataset used in this study was the one used in the development of Seirei dsq : 50 patients with cerebrovascular disease who were diagnosed with OD, 145 patients with cerebrovascular disease who did not have OD, and 170 healthy subjects. Among the answer choices, “A” for severe symptom, “B” for mild symptom and “C” for no symptom were scored with 4, 1 and 0 points respectively. Factor analysis extracted two factors : one related to pharyngeal function and another related to oral function. In addition, the Cronbach’s alpha coefficient was 0.84. ROC analysis indicated that optimal cutoff value was 5 points, with a sensitivity of 90.0% and a specificity of 88.5%. These results suggest that Swallow-10 may be useful as an OD screening tool for subjects with cognitive decline

高齢者における睡眠の質と夜間頻尿関連 : 在宅脳波データを用いた地域密着研究

PURPOSE: We objectively investigated the relationship between sleep quality/efficiency and factors associated with micturition using at-home electroencephalogram assessment. MATERIALS AND METHODS: Participants were recruited from among those enrolled in the Fujiwara-kyo Study, a community based longitudinal evaluation that began in Nara Prefecture, Japan, in 2007. Included participants were men at least 65 years old who woke up in the middle of the night/early morning at least 3 times per week with the urge to void. We evaluated lower urinary tract symptoms using the I-PSS and subjective sleep quality using the Pittsburgh Sleep Quality Index. Uroflowmetry and 3-day frequency volume charting measurements were also obtained. Electroencephalogram recordings were obtained during sleep to evaluate objective sleep quality. RESULTS: Final analysis included data from 47 participants. I-PSS-quality of life score and slow wave sleep time were independent predictors of good subjective sleep quality as determined by Pittsburgh Sleep Quality Index scores. Nocturnal urinary volume was an independent predictor of greater sleep efficiency. Maximum flow rate was an independent predictor of longer slow wave sleep time. CONCLUSIONS: In elderly men with nocturia, sleep quality is associated with lower urinary tract function. Higher subjective sleep quality is associated with longer slow wave sleep time and less severe lower urinary tract symptoms. Higher objective sleep quality is further associated with a higher urinary flow rate and lower nocturnal urinary volume.博士（医学）・甲第669号・平成29年3月15日Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved

Deficiency of mDia, an Actin Nucleator, Disrupts Integrity of Neuroepithelium and Causes Periventricular Dysplasia

During development of the central nervous system, the apical-basal polarity of neuroepithelial cells is critical for homeostasis of proliferation and differentiation of neural stem cells. While adherens junctions at the apical surface of neuroepithelial cells are important for maintaining the polarity, the molecular mechanism regulating integrity of these adherens junctions remains largely unknown. Given the importance of actin cytoskeleton in adherens junctions, we have analyzed the role of mDia, an actin nucleator and a Rho effector, in the integrity of the apical adherens junction. Here we show that mDia1 and mDia3 are expressed in the developing brain, and that mDia3 is concentrated in the apical surface of neuroepithelium. Mice deficient in both mDia1 and mDia3 develop periventricular dysplastic mass widespread throughout the developing brain, where neuroepithelial cell polarity is impaired with attenuated apical actin belts and loss of apical adherens junctions. In addition, electron microscopic analysis revealed abnormal shrinkage and apical membrane bulging of neuroepithelial cells in the remaining areas. Furthermore, perturbation of Rho, but not that of ROCK, causes loss of the apical actin belt and adherens junctions similarly to mDia-deficient mice. These results suggest that actin cytoskeleton regulated by Rho-mDia pathway is critical for the integrity of the adherens junctions and the polarity of neuroepithelial cells, and that loss of this signaling induces aberrant, ectopic proliferation and differentiation of neural stem cells

Use of modified U1 small nuclear RNA for rescue from exon 7 skipping caused by 5′-splice site mutation of human cathepsin A gene

Cathepsin A (CTSA) is a multifunctional lysosomal enzyme, and its hereditary defect causes an autosomal recessive disorder called galactosialidosis. In a certain number of galactosialidosis patients, a base substitution from adenine to guanine is observed at the +3 position of the 7th intron (IVS7 +3a>g) of the CTSA gene. With this mutation, a splicing error occurs; and consequently mRNA lacking the 7th exon is produced. This skipping of exon 7 causes a frame shift of the transcripts, resulting in a non-functional CTSA protein and hence galactosialidosis. This mutation seems to make the interaction between the 5’-splice site of intron 7 of pre-mRNA and U1 small nuclear RNA (U1 snRNA) much weaker. In the present study, to produce properly spliced mRNA from the CTSA gene harboring this IVS7 +3a>g mutation, we examined the possible usefulness of modified U1 snRNA that could interact with the mutated 5’-splice site. Toward this goal, we first prepared a model system using a mutant CTSA mini gene plasmid for delivery into HeLa cells. Then, we examined the effectiveness of modified U1 snRNA on the formation of properly spliced mRNA from this mutant CTSA mini gene. As a result, we succeeded in obtaining improved formation of properly spliced CTSA mRNA. Our results suggest the usefulness of modified U1 snRNA for rescue from exon 7 skipping caused by the IVS7 +3a>g mutation of the CTSA gene

A role for mDia, a Rho-regulated actin nucleator, in tangential migration of interneuron precursors.

神経細胞の配置メカニズムを解明－抑制性神経前駆細胞に特有の移動の機構が明らかに. 京都大学プレスリリース. 2012-1-16.In brain development, distinct types of migration, radial migration and tangential migration, are shown by excitatory and inhibitory neurons, respectively. Whether these two types of migration operate by similar cellular mechanisms remains unclear. We examined neuronal migration in mice deficient in mDia1 (also known as Diap1) and mDia3 (also known as Diap2), which encode the Rho-regulated actin nucleators mammalian diaphanous homolog 1 (mDia1) and mDia3. mDia deficiency impaired tangential migration of cortical and olfactory inhibitory interneurons, whereas radial migration and consequent layer formation of cortical excitatory neurons were unaffected. mDia-deficient neuroblasts exhibited reduced separation of the centrosome from the nucleus and retarded nuclear translocation. Concomitantly, anterograde F-actin movement and F-actin condensation at the rear, which occur during centrosomal and nuclear movement of wild-type cells, respectively, were impaired in mDia-deficient neuroblasts. Blockade of Rho-associated protein kinase (ROCK), which regulates myosin II, also impaired nuclear translocation. These results suggest that Rho signaling via mDia and ROCK critically regulates nuclear translocation through F-actin dynamics in tangential migration, whereas this mechanism is dispensable in radial migration

pH-resistant Inhibitor of Mitochondrial ADP/ATP Carrier

Bongkrekic acid (BKA), isolated from Burkholderia cocovenenans, is known to specifically inhibit the mitochondrial ADP/ATP carrier. However, the manner of its interaction with the carrier remains elusive. In the present study, we tested the inhibitory effects of 17 bongkrekic acid analogues, derived from the intermediates obtained during its total synthesis, on the mitochondrial ATP/ATP carrier. Rough screening of these chemicals, done by measuring their inhibitory effects on the mitochondrial ATP synthesis, revealed that 4 of them, KH-1, 7, 16, and 17, had moderate inhibitory effects. Further characterization of the actions of these 4 analogues on mitochondrial function showed that KH-16 had moderate; KH-1 and KH-17, weak; and KH-7, negligible side effects of both permeabilization of the mitochondrial inner membrane and inhibition of the electron transport, indicating that only KH-7 had a specific inhibitory effect on the mitochondrial ADP/ATP carrier. Although the parental bongkrekic acid showed a strong pH dependency of its action, the inhibitory effect of KH-7 was almost insensitive to the pH of the reaction medium, indicating the importance of the 3 carboxyl groups of BKA for its pH- dependent action. A direct inhibitory effect of KH-7 on the mitochondrial ADP/ATP carrier was also clearly demonstrated