Mean structure of the supercritical turbulent spiral in Taylor-Couette flow.

The large-scale laminar/turbulent spiral patterns that appear in the linearly unstable regime of counter-rotating Taylor-Couette flow are investigated from a statistical perspective by means of direct numerical simulation. Unlike the vast majority of previous numerical studies, we analyse the flow in periodic parallelogram-annular domains, following a coordinate change that aligns one of the parallelogram sides with the spiral pattern. The domain size, shape and spatial resolution have been varied and the results compared with those in a sufficiently large computational orthogonal domain with natural axial and azimuthal periodicity. We find that a minimal parallelogram of the right tilt significantly reduces the computational cost without notably compromising the statistical properties of the supercritical turbulent spiral. Its mean structure, obtained from extremely long time integrations in a co-rotating reference frame using the method of slices, bears remarkable similarity with the turbulent stripes observed in plane Couette flow, the centrifugal instability playing only a secondary role. This article is part of the theme issue 'Taylor-Couette and related flows on the centennial of Taylor's seminal Philosophical transactions paper (Part 2)'.

Cognitive and affective functions in Alzheimer's disease patients with metabolic syndrome.

BACKGROUND AND PURPOSE: The influence of metabolic syndrome (MetS) on cognitive and affective functions in patients with Alzheimer's disease (AD) was examined. METHODS: A total of 570 AD patients were divided into two subgroups depending on waist circumference (WC) (normal versus achieving Japanese diagnostic criteria of MetS). Afterwards, the AD control subgroup was defined as those normal WC patients with no vascular risk factors (VRFs). The AD with MetS (AD-MetS) subgroup was defined as the MetS WC group who had two or more VRFs to qualify as having MetS. Cognitive and affective functions, insulin resistance, vascular endothelial function and white matter changes between AD-MetS and AD controls were compared. RESULTS: Scores on the Mini-Mental State Examination, Hasegawa Dementia Score-Revised, Frontal Assessment Battery and Montreal Cognitive Assessment were worse in the AD-MetS group than in AD controls, but the difference was not significant. Some analyses were conducted twice, once including all patients and once including only late-elderly patients. Scores on the Geriatric Depression Scale were found to be significantly higher for AD-MetS than for AD controls (all ages, late-elderly), as were those for apathy (late-elderly). Furthermore, both the homeostasis model assessment of insulin resistance and reactive hyperemia index scores were significantly worse in AD-MetS than in AD controls, whilst white matter changes showed a tendency to be worse. CONCLUSIONS: Greater cognitive and affective decline occurs in patients with AD-MetS than in those without. Further, insulin resistance and vascular endothelial dysfunction are strongly correlated with AD-MetS before pathological white matter changes can be observed.

'PrP systemic deposition disease': clinical and pathological characteristics of novel familial prion disease with 2-bp deletion in codon 178.

BACKGROUND AND PURPOSE: A novel TYPE of prion disease associated mainly with autonomic-sensory polyneuropathy was reported by us previously. METHODS: Here the autopsy pathology for patient 1 (the sister) and the clinical characteristics of her younger brother (patient 2) are newly reported. Polymerase chain reaction based restriction fragment length polymorphism analysis of the prion protein gene (PRNP) was performed on both patients and their father (normal control). RESULTS: Polymerase chain reaction based restriction fragment length polymorphism analysis revealed a 2-bp deletion (CT) in codon 178 that causes an additional variable 25 amino acids at the C terminal, from the mutation site to the premature stop codon at codon 203, in both patients 1 and 2 but not in their father. The autopsy of patient 1 showed remarkable prion protein (PrP) deposits in the sympathetic ganglion and peripheral nerves, correlated to her severe autonomic sensory failure. PrP deposits were also found in the central nervous system and peripheral organs such as the heart, lung, stomach, jejunum, ileum, colon, urinary bladder and adrenal gland. The symptoms and biopsy findings of patient 2 were nearly the same as those reported previously for patient 1. His cognitive function was well preserved, but autonomic functions were severely impaired. His biopsied samples showed PrP deposits in the sural nerve and nerve plexuses of the stomach and colon. CONCLUSION: The present unique 2-bp deletion (CT) in codon 178 induced a 'PrP systemic deposition disease' such as pan-autonomic failure, sensory neuropathy and mild cognitive impairment with a specific pathology.

Cognitive and affective functions in diabetic patients associated with diabetes-related factors, white matter abnormality and aging.

BACKGROUND AND PURPOSE: Diabetes mellitus (DM) is associated with a decline in cognitive and affective functions. METHODS: In all, 182 outpatients with DM were investigated for associations of cognitive and affective functions with diabetes-related factors and cerebral white matter abnormalities. In addition, the difference in cognitive decline of age-matched late elderly normal subjects and DM patients was investigated. RESULTS: The present study revealed that cognitive and affective functions declined in some DM patients. Furthermore, the decline in these functions was unrelated to fasting blood sugar level but was related to glycosylated hemoglobin (HbA1c) and insulin resistance. Poor HbA1c control was associated with a significant decline in the 'calculation' subscale and insulin resistance for 'naming', 'read list of letters' and 'delayed recall' Montreal Cognitive Assessment (MoCA) subscale scores. Magnetic resonance imaging scans showed that both periventricular hyperintensity (PVH) and deep white matter hyperintensity were associated with Mini Mental State Examination (MMSE) and MoCA scores, but only PVH was related to homeostasis model assessment of insulin resistance scores. Compared with age-matched late elderly normal subjects, 'orientation to time' and 'registration' MMSE subscales declined in late elderly DM patients. CONCLUSIONS: These results suggest that cognitive and affective decline in DM patients was mostly related to glucose control and insulin resistance, whilst amongst late elderly subjects the impairment of 'attention' and 'orientation' were characteristic features of DM patients.

Characteristic RNA foci of the abnormal hexanucleotide GGCCUG repeat expansion in spinocerebellar ataxia type 36 (Asidan).

BACKGROUND AND PURPOSE: Spinocerebellar ataxia type 36 (SCA36), also called Asidan, is an autosomal-dominant neurodegenerative disorder identified as a hexanucleotide GGCCTG repeat expansion in the first intron 1 of the NOP56 gene. In the present study, for the first time an autopsy sample from an Asidan patient was examined and cytoplasmic inclusions and (GGCCUG)n repeat RNA foci were detected. METHODS: Hematoxylin and eosin staining, immunohistochemical staining, as well as fluorescence in situ hybridization were used to investigate the cytoplasmic inclusions of ubiquitin and p62 and the (GGCCUG)n repeat RNA foci. RESULTS: The present study showed both ubiquitin- and p62-positive inclusions in the cytoplasm of the inferior olivary nucleus of the Asidan patient, (GGCCUG)n RNA foci in neuronal nuclei of the cerebrum, cerebellum, inferior olive, spinal cord and temporal muscle, and three types of RNA foci, i.e. single small, multiple small and giant. Of interest is that the giant RNA foci, nearly 10 µm in diameter, that were detected in Purkinje cells, spinal motor neurons and most frequently in the inferior olivary nucleus, may be responsible for pivotal clinical symptoms of Asidan. CONCLUSIONS: The present study is the first report to show neuronal cytoplasmic inclusion bodies and giant RNA foci in an Asidan patient. The relationships between the giant RNA foci and neurodegeneration have yet to be studied.

Pressure-dependent magnetization and magnetoresistivity studies on tetragonal FeS (mackinawite): revealing its intrinsic metallic character.

The transport and magnetic properties of the tetragonal Fe[Formula: see text]S were investigated using magnetoresistivity and magnetization within [Formula: see text] K, [Formula: see text] 70 kOe and [Formula: see text] 3.0 GPa. In addition, room-temperature x-ray diffraction and photoelectron spectroscopy were also applied. In contrast to previously reported nonmetallic character, Fe[Formula: see text]S is intrinsically metallic but due to a presence of a weak localization such metallic character is not exhibited below room temperature. An applied pressure reduces strongly this additional resistive contribution and as such enhances the temperature range of the metallic character which, for ∼3 GPa, is evident down to 75 K. The absence of superconductivity as well as the mechanism behind the weak localization will be discussed.

Superconductivity induced by longitudinal ferromagnetic fluctuations in UCoGe.

From detailed angle-resolved NMR and Meissner measurements on a ferromagnetic (FM) superconductor UCoGe (T(Curie)∼2.5 K and T(SC)∼0.6 K), we show that superconductivity in UCoGe is tightly coupled with longitudinal FM spin fluctuations along the c axis. We found that magnetic fields along the c axis (H∥c) strongly suppress the FM fluctuations and that the superconductivity is observed in the limited magnetic-field region where the longitudinal FM spin fluctuations are active. These results, combined with model calculations, strongly suggest that the longitudinal FM spin fluctuations tuned by H∥c induce the unique spin-triplet superconductivity in UCoGe. This is the first clear example that FM fluctuations are intimately related with superconductivity.

Prediction of CCND1 amplification using plasma DNA as a prognostic marker in oesophageal squamous cell carcinoma.

BACKGROUND: We aimed to develop a new biomarker to predict cyclin D1 (CCND1) status using plasma DNA in oesophageal squamous cell carcinoma (ESCC) patients. METHODS: We evaluated the ratio of the CCND1 (11q13) dosage to the dopamine receptor D2 (DRD2; 11q22-23) dosage (C/D ratio) as CCND1 copy number. This study was divided into three steps: (1) Determination of a cutoff value for the C/D ratio in test scale; (2) Comparison of the C/D ratio in between plasma samples and cancer tissues in ESCC patients showing high plasma C/D ratio; (3) Validation study of the clinical application of the plasma C/D ratio as a diagnostic and prognostic marker, by comparing with clinicopathologic factors in 96 ESCC patients. RESULTS: The plasma C/D ratio was significantly higher in the ESCC group than the controls (P=0.0134). A high plasma C/D ratio reflected the tumour C/D ratio, and significantly correlated with a poorer prognosis (P=0.0186). Moreover, the high C/D ratio was found to be an independent prognostic factor on multivariate analysis (P=0.0266; hazard ratio 5.988). CONCLUSION: Prediction of CCND1 amplification using plasma DNA is thought to be a promising prognostic biomarker in ESCC patients.

Circulating microRNAs in plasma of patients with gastric cancers.

BACKGROUND: We examined plasma microRNA (miRNA) concentrations from patients with gastric cancers (GCs) to assess their clinical application for diagnosing and monitoring diseases. METHODS: We initially investigated the appropriateness of plasma miRNA assay, and then compared plasma miRNA results with the expressions in cancer tissues from eight GC patients, and also compared plasma miRNAs between pre- and post-operative paired samples from 10 GC patients. Then, plasma miRNAs (miR-17-5p, miR-21, miR-106a, miR-106b and let-7a) were analysed in 69 GC patients and 30 healthy volunteers in total. RESULTS: The initial analysis showed that miRNAs were stable and detectable in all plasma samples, and the plasma miRNA levels reflected the tumour miRNAs in most cases. The levels of these miRNAs were significantly reduced in post-operative samples. In large-scale analysis, the plasma concentrations of miRNAs (miR-17-5p, miR-21, miR-106a, miR-106b) were significantly higher in GC patients than controls (P=0.05, 0.006, 0.008 and <0.001 respectively), whereas let-7a was lower in GC patients (P=0.002). The values of the area under the receiver-operating characteristic curve were 0.721 for the miR-106b assay and 0.879 for the miR-106a/let-7a ratio assay. CONCLUSION: Detection of circulating miRNAs might provide new complementary tumour markers for GC.

Anisotropic magnetic fluctuations in the ferromagnetic superconductor UCoGe studied by direction-dependent 59Co NMR measurements.

We have carried out direction-dependent 59Co NMR experiments on a single crystal sample of the ferromagnetic superconductor UCoGe in order to study the magnetic properties in the normal state. The Knight-shift and nuclear spin-lattice relaxation rate measurements provide microscopic evidence that both static and dynamic susceptibilities are ferromagnetic with strong Ising anisotropy. We discuss that superconductivity induced by these magnetic fluctuations prefers spin-triplet pairing state.

Schimke immuno-osseous dysplasia: SMARCAL1 loss-of-function and phenotypic correlation.

BACKGROUND: Schimke immuno-osseous dysplasia (SIOD) is an autosomal recessive pleiotropic disorder caused by mutations in SMARCAL1. SMARCAL1 encodes an enzyme with homology to the SNF2 chromatin remodelling proteins. METHODS: To assess the affect of SMARCAL1 mutations associated with SIOD on SMARCAL1 expression and function, we characterised the effects of various mutations on mRNA and protein expression in patient tissues and cell lines, and the ATPase activity, subcellular localisation, and chromatin binding of SMARCAL1 missense mutants. RESULTS: The SIOD associated SMARCAL1 mutations affected SMARCAL1 protein expression, stability, subcellular localisation, chromatin binding, and enzymatic activity. Further, expressing SMARCAL1 missense mutants in Drosophila melanogaster showed that disease severity was inversely proportionate to overall SMARCAL1 activity. CONCLUSION: Our results show for the first time that SMARCAL1 binds chromatin in vivo and that SIOD arises from impairment of diverse SMARCAL1 functions.

Discovery of superconductivity in quasicrystal.

Superconductivity is ubiquitous as evidenced by the observation in many crystals including carrier-doped oxides and diamond. Amorphous solids are no exception. However, it remains to be discovered in quasicrystals, in which atoms are ordered over long distances but not in a periodically repeating arrangement. Here we report electrical resistivity, magnetization, and specific-heat measurements of Al-Zn-Mg quasicrystal, presenting convincing evidence for the emergence of bulk superconductivity at a very low transition temperature of [Formula: see text] K. We also find superconductivity in its approximant crystals, structures that are periodic, but that are very similar to quasicrystals. These observations demonstrate that the effective interaction between electrons remains attractive under variation of the atomic arrangement from periodic to quasiperiodic one. The discovery of the superconducting quasicrystal, in which the fractal geometry interplays with superconductivity, opens the door to a new type of superconductivity, fractal superconductivity.

Induction of platelet derived-endothelial cell growth factor in the brain after ischemia.

OBJECTIVES: Platelet derived-endothelial cell growth factor (PD-ECGF) is a highly potent angiogenic factor. Although angiogenesis plays an active role in pathophysiology of stroke, the expression pattern of this molecule in ischemic brain has not been investigated. In the present study, therefore, we investigated the change of PD-ECGF expression in the brain after ischemia. METHODS: Using male Wistar rats, the right middle cerebral artery was occluded by a nylon thread for 90 minutes. The animals were decapitated 3 hours, 1, 4 and 10 days after the reperfusion, and frozen sections were prepared. We then performed immunohistochemistry for PD-ECGF and identified the cell phenotype which strongly expressed it by fluorescent double staining. RESULTS: In the sham-operated brain, only small numbers of cells slightly expressed PD-ECGF. The number of positively stained cells increased at the peri-ischemic area from hour 3 of reperfusion. Not only small-sized cells but also large-sized cells became stained. The number of stained cells further increased, and peaked at day 4 for large-sized cells and at day 10 as to small-sized cells. Fluorescent double staining revealed that both large-sized and small-sized cells were neurons, indicating that neurons are the main source of PD-ECGF production in the ischemic brain. DISCUSSION: PD-ECGF has a strong angiogenic property without vascular permeability increasing effect. This molecule may have a therapeutic potential for ischemic stroke treatment.

The relationship between free-stream coherent structures and near-wall streaks at high Reynolds numbers.

The present work is based on our recent discovery of a new class of exact coherent structures generated near the edge of quite general boundary layer flows. The structures are referred to as free-stream coherent structures and were found using a large Reynolds number asymptotic approach to describe equilibrium solutions of the Navier-Stokes equations. In this paper, first we present results for a new family of free-stream coherent structures existing at relatively large wavenumbers. The new results are consistent with our earlier theoretical result that such structures can generate larger amplitude wall streaks if and only if the local spanwise wavenumber is sufficiently small. In a Blasius boundary layer, the local wavenumber increases in the streamwise direction so the wall streaks can typically exist only over a finite interval. However, here it is shown that they can interact with wall curvature to produce exponentially growing Görtler vortices through the receptivity process by a novel nonparallel mechanism. The theoretical predictions found are confirmed by a hybrid numerical approach. In contrast with previous receptivity investigations, it is shown that the amplitude of the induced vortex is larger than the structures in the free-stream which generate it.This article is part of the themed issue 'Toward the development of high-fidelity models of wall turbulence at large Reynolds number'.

Liver Failure From Ultra-Short Bowel Syndrome on the Intestinal Transplant Waiting List: A Retrospective Study.

BACKGROUND: Patients with intestinal failure (IF) are candidates for intestinal transplantation (ITx). In Japan, these patients have few opportunities to undergo cadaveric ITx because of low rates of organ donation. The donor criteria and recipient priority for ITx are still unknown. We reviewed our cases of IF to investigate which patients should be prioritized for ITx. METHODS: Patients with IF who were registered as candidates for cadaveric ITx between January 2010 and November 2015 in our institute were included in this retrospective study. Their data were gathered from their charts and analyzed. RESULTS: Five patients were included. Their primary diseases included total colon aganglionosis (n = 1), chronic idiopathic intestinal pseudo-obstruction syndrome (n = 2), superior mesenteric vein embolization (n = 1), and graft loss after ITx (n = 1). Two patients died of liver failure (LF) during the waiting period. The remaining three are now alive and waiting for transplantation. The lengths of the remaining intestine were more than 20 cm in living cases but less than 20 cm in fatal cases. In the fatal cases, they had several episodes of catheter-related blood stream infection, which caused LF and acute renal failure. CONCLUSIONS: We identified two patients with less than 20 cm residual small bowel who died after acute deterioration of liver function. Patients with ultra-short bowel could have a higher risk of LF. Therefore, they should be referred as soon as possible to a specialized hospital where ITx is a choice of treatment for IF.

Expression of the catalytic and regulatory subunits of protein phosphatase type 2A may be differentially modulated during retinoic acid-induced granulocytic differentiation of HL-60 cells.

To elucidate the regulation of protein phosphatases types 1 (PP1) and 2A (PP2A) during all-trans retinoic acid (ATRA)-induced granulocytic differentiation of HL-60 cells, the phosphatase activity, proteins, and gene expressions of PP1 and PP2A were examined. Treatment with 1 microM ATRA caused an 85% decrease in the PP2A activity in extracts from HL-60 cells, while the PP1 activity was constant. This reduction in PP2A activity appeared to parallel phenotypic and functional changes of HL-60 cells induced by ATRA. Western blot analysis showed that the level of PP2A catalytic subunit (PP2A-C) decreased during the course of ATRA-induced differentiation, whereas expressions of A and B (M(r) 55,000) regulatory subunits of PP2A were relatively unaltered. Expressions of PP1 catalytic subunit isozymes (PP1 alpha, PP1 gamma, and PP1 delta) were not significantly affected by ATRA treatment. Northern blot analysis revealed that mRNA levels of PP2A-C beta and A alpha regulatory subunits were decreased following treatment with ATRA, while levels of PP2A-C alpha and B (M(r) 55,000) alpha regulatory subunit transcripts were relatively constant. Selective down regulation of PP2A-C beta preceded the granulocytic maturation induced by ATRA. Expressions of PP2A-C isoforms and A and B regulatory subunits may be differentially modulated during ATRA-induced granulocytic differentiation of HL-60 cells.

Studies of Pig Complement: Measurement of Pig CH50, ACH50, and Components.

BACKGROUND: On the basis of a comparison of the hemolytic complement titer in pigs with that in humans, the complement system of pigs was investigated. The response of innate immunity, such as the natural antibodies, against humans was also examined. METHODS: Hemolytic complement activity of pig serum was measured with the use of a microtitration technique. CH50 was determined according to the method of Mayer. ACH50 was assayed according to the methods of Platts-Milles and Ishizaka. Hemolytic activities of C1, C4, C2, C3, C5, C8, and C9 were estimated through the use of intermediate cells and reagents, as described previously. In addition, the pig natural anti-human antibody was studied with the use of human peripheral blood mononuclear cells (PBMCs). Human PBMCs were stained with 5% pig serum, followed by staining with fluorescein isothiocyanate-labeled goat anti-pig IgG and IgM. The resulting stained cells were quantified by use of a FACScalibur system. The alternative pathway of pig complement was also measured with the use of human erythrocytes and normal pooled pig serum with or without Mg(++)EGTA. RESULTS: Both the CH50 and ACH50 titers were lower than those of humans. Concerning the components, except for C3, each component, that is, C1, C4, C2, C5, C8, and C9, was also lower than that of humans, based on measured values for human complement components. Pig serum clearly contains natural antibodies, IgG and IgM, to human PBMCs. The alternative pathway of pig complement reacted with human erythrocytes. CONCLUSIONS: As a whole, pig innate immunity, the complement system and natural antibody, recognizes the surfaces of human cells.

Disseminated Metastatic Tissue Calcification After Orthotopic Liver Transplantation: A Case Report.

BACKGROUND: Hypercalcemia has been observed in patients after liver transplantation. However, it is rare that the hypercalcemia induced disseminated tissue calcification and heart failure. CASE REPORT: We report a rare case of heart failure caused by disseminated metastatic tissue calcification that involved extensive progressive myocardial calcification after liver transplantation. A 20-year-old man with end-stage liver disease due to biliary atresia underwent ABO-incompatible living donor liver transplantation. After successful transplantation, he suffered from antibody-mediated rejection. Subsequently, ABO-matched cadaveric liver retransplantation was successfully performed. Hypercalcemia developed gradually following the second transplantation. His serum calcium level increased to 18.3 mg/dL with sudden onset of ventricular tachycardia. Although he was resuscitated with a cardiopulmonary support device, he died of heart and liver failure. Histopathologic examination revealed systemic disseminated metastatic tissue calcification, including massive myocardial calcification. CONCLUSION: Progressive worsening of hypercalcemia resulted in disseminated metastatic tissue calcification and massive metastatic myocardial calcification, which led to heart failure after liver transplantation. Because hypercalcemia after liver transplantation can cause fatal tissue calcification, early intervention for hypercalcemia should be considered.