Valence-state mixing and reduced magnetic moment inFe3-δGeTe2single crystals with varying Fe content probed by x-ray spectroscopy.

We present a spectroscopic study of the magnetic properties ofFe3-δGeTe2single crystals with varying Fe content, achieved by tuning the stoichiometry of the crystals. We carried out x-ray absorption spectroscopy and analyzed the x-ray circular magnetic dichroism spectra using the sum rules, to determine the orbital and spin magnetic moments of the materials. We find a clear reduction of the spin and orbital magnetic moment with increasing Fe deficiency. Magnetic susceptibility measurements show that the reduction in magnetization is accompanied by a reduced Curie temperature. Multiplet calculations reveal that the Fe2+state increasingly mixes with a higher valence state when the Fe deficiency is increased. This effect is correlated with the weakening of the magnetic moment. As single crystals are the base material for exfoliation processes, our results are relevant for the assembly of 2D magnetic heterostructures.

Lack of association between angiotensin-converting enzyme genotype and muscle strength in Peruvian older people.

Aging can be associated with decreasing muscle strength, and related factors are comorbidities, sex, physical activity, and possibly genetic factors. Among genetic factors the renin-angiotensin system is of interest, but data on the Peruvian population is lacking. The objective of our study was to evaluate the association of grip strength and angiotensin convertase enzyme (ACE) polymorphism in Peruvian older people. A cross-sectional study in a convenience sample of 104 participants over 60 years in Lima, Perú, with analysis of the ACE polymorphism, was performed. We studied 104 participants, 46 men (44,2%) and 58 women (55,8%), with a mean age and standard deviation (SD) of 73,7 (7,4) years, range between 60-90 years. The frequency of D/D, I/D and I/I genotypes was 12,7; 43,7 and 43,7% respectively. The genotype distribution of ACE polymorphism agreed with the Hardy-Weinberg equilibrium (p=0,746). The mean (SD) of grip strength in the D/D, I/D and I/I polymorphisms were 24,8 (7,2); 22,8 (7,2) and 23,4 (7,6) kg respectively; no significant difference was observed (p=0,41) between genetic groups. In this small convenience sample of older Peruvians, no association was found between grip strength and ACE genotype.

Deep-learning-based, computer-aided classifier developed with a small dataset of clinical images surpasses board-certified dermatologists in skin tumour diagnosis.

BACKGROUND: Application of deep-learning technology to skin cancer classification can potentially improve the sensitivity and specificity of skin cancer screening, but the number of training images required for such a system is thought to be extremely large. OBJECTIVES: To determine whether deep-learning technology could be used to develop an efficient skin cancer classification system with a relatively small dataset of clinical images. METHODS: A deep convolutional neural network (DCNN) was trained using a dataset of 4867 clinical images obtained from 1842 patients diagnosed with skin tumours at the University of Tsukuba Hospital from 2003 to 2016. The images consisted of 14 diagnoses, including both malignant and benign conditions. Its performance was tested against 13 board-certified dermatologists and nine dermatology trainees. RESULTS: The overall classification accuracy of the trained DCNN was 76·5%. The DCNN achieved 96·3% sensitivity (correctly classified malignant as malignant) and 89·5% specificity (correctly classified benign as benign). Although the accuracy of malignant or benign classification by the board-certified dermatologists was statistically higher than that of the dermatology trainees (85·3% ± 3·7% and 74·4% ± 6·8%, P < 0·01), the DCNN achieved even greater accuracy, as high as 92·4% ± 2·1% (P < 0·001). CONCLUSIONS: We have developed an efficient skin tumour classifier using a DCNN trained on a relatively small dataset. The DCNN classified images of skin tumours more accurately than board-certified dermatologists. Collectively, the current system may have capabilities for screening purposes in general medical practice, particularly because it requires only a single clinical image for classification.

Effects of gait intervention using the draw-in maneuver on knee joint function and the thoracic kyphosis angle in knee osteoarthritis.

BACKGROUND: To evaluate whether the knee adduction moment (KAM) could be reduced by a short instruction in the Draw-in (DI) maneuver in healthy adults, and whether knee joint function would improve with a longer DI gait intervention in patients with knee osteoarthritis (OA). METHOD: In Study 1, healthy adults received 10 minutes supervised instruction in DI gait in and then practiced the gait independently for 10 minutes. Three-dimensional motion analysis measurement was performed in each phase. In Study 2, patients with OA performed a 20-minute DI gait intervention daily for 6 weeks. At baseline and after 6 weeks, knee pain, the Knee injury and Osteoarthritis Outcome Score, the MOS 8 item Short-Form Health Survey, thoracic kyphosis angle, knee joint range of motion, knee extension muscle strength, hip abduction muscle strength, and activity level were evaluated. RESULTS: In Study 1, the DI gait to decrease KAM could be learning following only 10 minutes of instruction and 10 minutes of self-practice in healthy adults. In Study 2, knee pain was reduced by 19 % and the thoracic kyphosis angle was reduced by 2.6° after 6 weeks. No significant changes in other parameters were detected, and the implementation rate was 86 ±â€¯14 %. SIGNIFICANCE: In healthy adults, DI gait instruction for 10 minutes of instruction and 10 minutes of self-practice reduced the KAM. In patients with knee OA, 20 minutes of DI gait per day for 6 weeks may reduce knee pain and thoracic kyphosis.

Kimura's disease: effects of age on clinical presentation.

BACKGROUND: Kimura's disease (KD) is known to be dominant among young Asian men, but it can also occur in middle- and advanced-aged people. The clinical characteristics of KD, especially by age, are not well known. AIM: This study was performed to investigate the effects of age on the clinical characteristics of KD. DESIGN: We conducted a case series study. METHODS: All case studies of patients diagnosed with KD were collected via a PubMed search of studies published until August 2018. The data were analyzed by age group. RESULTS: In total, 215 studies were reviewed (238 patients; mean age of 36 years). The male:female ratio was 4:1 overall, 17:1 in patients aged <20 years, 4:1 in patients aged 20-39 years and 2:1 in patients aged ≥40 years (P = 0.01). The percentage of patients with pruritus was 15.4% overall, 3.8% in patients aged <20 years, 15.5% in patients aged 20-39 years and 21.7% in patients aged ≥40 years (P = 0.02). The time to diagnosis was 5.3 years overall, 3.2 years in patients aged <20 years, 4.7 years in patients aged 20-39 years and 7.1 years in patients aged ≥40 years (P < 0.01). CONCLUSIONS: The proportion of female patients affected the incidence of pruritus, and the time to diagnosis increased as the patients' age increased. There were no significant age-related differences in region/race, complications, multiplicity, laterality, anatomical distribution, maximum size, eosinophil count, immunoglobulin E level, initial treatment, recurrence or outcomes. This may be useful information for the diagnosis of KD.

Cr2Te3 Thin Films for Integration in Magnetic Topological Insulator Heterostructures.

Chromium telluride compounds are promising ferromagnets for proximity coupling to magnetic topological insulators (MTIs) of the Cr-doped (Bi,Sb)2(Se,Te)3 class of materials as they share the same elements, thus simplifying thin film growth, as well as due to their compatible crystal structure. Recently, it has been demonstrated that high quality (001)-oriented Cr2Te3 thin films with perpendicular magnetic anisotropy can be grown on c-plane sapphire substrate. Here, we present a magnetic and soft x-ray absorption spectroscopy study of the chemical and magnetic properties of Cr2Te3 thin films. X-ray magnetic circular dichroism (XMCD) measured at the Cr L2,3 edges gives information about the local electronic and magnetic structure of the Cr ions. We further demonstrate the overgrowth of Cr2Te3 (001) thin films by high-quality Cr-doped Sb2Te3 films. The magnetic properties of the layers have been characterized and our results provide a starting point for refining the physical models of the complex magnetic ordering in Cr2Te3 thin films, and their integration into advanced MTI heterostructures for quantum device applications.

Comparison of hemodynamic parameters that can predict an aneurysmal rupture: 20 patient-specific models experiment.

Hemodynamic analysis of cerebral aneurysms is widely performed to understand the mechanism of aneurysmal rupture. Computational fluid dynamics (CFD) studies have suggested that several hemodynamic parameters are associated with such ruptures. However, a number of factors remain to be addressed to correlate these parameters with aneurysmal ruptures, especially under analytical conditions. Specifically, CFD analysis is often performed with rigid wall models due to computational cost limitations. Here, to evaluate the effects of the deformation of the aneurysmal wall, experimental flow measurement with elastic models under pulsating conditions was conducted using three-dimensional particle image velocimetry (3D PIV). By analyzing 20 patient-specific, elastic, silicone aneurysm models, the hemodynamic parameters of ruptured and unruptured aneurysms were statistically compared to identify the variables that can effectively predict an aneurysmal rupture. Our analyses yielded three parameters (average wall shear stress ratio, in-phase deviation ratio, and pressure difference) which could effectively predict an aneurysmal rupture. These results suggested that measurement of wall shear stress (WSS) at both the aneurysm dome and parent artery is important and that pressure difference can also be a potential indicator of aneurysmal rupture.

Plasmin and plasminogen activator inhibitor type 1 promote cellular motility by regulating the interaction between the urokinase receptor and vitronectin.

The urokinase receptor (uPAR) coordinates plasmin-mediated cell-surface proteolysis and promotes cellular adhesion via a binding site for vitronectin on uPAR. Because vitronectin also binds plasminogen activator inhibitor type 1 (PAI-1), and plasmin cleavage of vitronectin reduces PAI-1 binding, we explored the effects of plasmin and PAI-1 on the interaction between uPAR and vitronectin. PAI-1 blocked cellular binding of and adhesion to vitronectin by over 80% (IC50 approximately 5 nM), promoted detachment of uPAR-bearing cells from vitronectin, and increased cellular migration on vitronectin. Limited cleavage of vitronectin by plasmin also abolished cellular binding and adhesion and induced cellular detachment. A series of peptides surrounding a plasmin cleavage site (arginine 361) near the carboxy-terminal end of vitronectin were synthesized. Two peptides spanning res 364-380 blocked binding of uPAR to vitronectin (IC50 approximately 8-25 microM) identifying this region as an important site of uPAR-vitronectin interaction. These data illuminate a complex regulatory scheme for uPAR-dependent cellular adhesion to vitronectin: Active urokinase promotes adhesion and also subsequent detachment through activation of plasmin or complex formation with PAI-1. Excess PAI-1 may also promote migration by blocking cellular adhesion and/or promoting detachment, possibly accounting in part for the strong correlation between PAI-1 expression and tumor cell metastasis.

Protein kinase C-mediated necrosis-apoptosis switch of cortical neurons by conditioned medium factors secreted under the serum-free stress.

Cortical neurons die in necrosis in the low-density (LD) culture, and in apoptosis in the high-density (HD) culture under the serum-free condition without any supplements. The neuronal death in LD culture was delayed by conditioned medium (CM) factors prepared from the HD culture. The CM switched the cell death mode from necrosis to apoptosis, characterized by various cell death markers and transmission electron microscopy. The CM inhibited the rapid decrease in cellular ATP levels and [3H]-2-deoxy glucose ([3H]-2-DG) uptake in the LD culture. Inhibitors of phospholipase C and protein kinase C effectively abolished the CM-induced elevation of survival activity, [3H]-2-DG uptake and ATP levels, and necrosis-apoptosis switch. All these results suggest that CM caused the cell death mode switch from necrosis to apoptosis through phospholipase C- and protein kinase C-mediated mechanisms.

Protein kinase C-mediated cell death mode switch induced by high glucose.

Cortical neurons rapidly die in necrosis due to poor glucose uptake in the low-density (LD) culture under serum-free condition without any supplements. The scanning and transmission electron microscopical analyses characterized the necrosis by membrane disruption, mitochondrial swelling and loss of cytoplasmic electron density. High-glucose treatment delayed the neuronal death by suppressing necrosis, but induced apoptosis through increase in Bax levels, cytochrome c release, caspase-3 activation and DNA ladder formation. Although pyruvate as well as high glucose inhibited necrotic cell death and rapid decrease in cellular ATP levels, possibly related to decreased [(3)H]-2-deoxy glucose uptake under the serum-free condition, it did not induce apoptosis. Protein kinase C inhibitors blocked these changes related to the cell death mode switch. Several neurotrophic factors did not affect the necrosis, but potentiated high-glucose-induced survival activity, while inhibiting cytochrome c release. All these results suggest that high-glucose treatment causes neuronal cell death mode switch by inhibiting necrosis, while inducing apoptosis, which is prevented by neurotrophic factors.

Five novel RPGR mutations in families with X-linked retinitis pigmentosa.

X-linked forms of retinitis pigmentosa (XLRP) are among the most severe because of their early onset, often leading to significant visual impairment before the fourth decade. RP3, genetically localized at Xp21.1, accounts for 70% of XLRP in different populations. The RPGR (Retinitis Pigmentosa GTPase Regulator) gene that was isolated from the RP3 region is mutated in 20% of North American families with XLRP. From mutation analysis of 27 independent XLRP families, we have identified five novel RPGR mutations in 5 of the families (160delA, 789 A>T, IVS8+1 G>C, 1147insT and 1366 G>A). One of these mutations was detected in a family from Chile. Hum Mutat 17:151, 2001.

Molecular characterization of two forms of nontoxic-nonhemagglutinin components of Clostridium botulinum type A progenitor toxins.

The entire sequences of the type A nontoxic-nonhemagglutinin gene and an adjacent open reading frame designated as orf 22-a, which are located between the neurotoxin and the HA-35 genes were determined. SDS-PAGE and N-terminal amino acid sequence analyses of the purified type A progenitor toxins (12S, 16S and 19S) indicate that the nontoxic-nonhemagglutinins of 16S and 19S are single peptides of approximately 120k, but that of 12S has a cleavage at the site between Pro-144 and Phe-145 of this protein.

Disease expression in X-linked retinitis pigmentosa caused by a putative null mutation in the RPGR gene.

PURPOSE: To determine the disease expression in X-linked retinitis pigmentosa (XLRP) caused by a putative null mutation in the RPGR (retinitis pigmentosa GTPase regulator) gene. METHODS: In a family with XLRP, haplotype analysis was performed with polymorphic microsatellite markers from the Xp chromosomal region, and genomic polymerase chain reaction sequencing was used to identify sequence variations in the RPGR gene. Hemizygotes and heterozygotes were evaluated clinically and with visual function tests. Optical coherence tomography (OCT) was performed on heterozygotes. Postmortem donor retinas from a heterozygote were examined by microscopy and immunocytochemistry. RESULTS: X-linked inheritance was confirmed by haplotype analysis using Xp markers. Sequence analysis of the RPGR gene identified a single base pair change, a G-->T transversion, that converts codon 52 GGA (Gly) to TGA (stop codon); the mutation segregates with the disease. A hemizygote in the third decade of life had barely measurable rod function and severely impaired cone function that diminished further over a 7-year interval. Heterozygotes varied in degree of disease expression from mild to severe. Perimetry showed loci with normal rod and cone sensitivity interspersed with loci having either equal rod and cone dysfunction or rod > cone dysfunction. Electroretinographic photoreceptor responses had equal reductions in rod and cone maximal amplitude. OCT cross sectional reflectance images of retinal regions with severe dysfunction showed reduced thickness of the retina and retinal pigment epithelium-choriocapillaris (RPE-CC) complex and increased reflections posteriorly. Regions with mild dysfunction showed similar OCT findings but with preserved retinal thickness. Retinal histopathology in a heterozygote revealed loss of photoreceptors throughout, with retention of only a few islands of cones with tiny or absent outer segments and rods lacking outer segments. CONCLUSIONS: This RPGR gene mutation, in its mildest expression in heterozygotes, causes a relatively equal disturbance of rod and cone photoreceptor function. Detectable structural change by OCT at the level of the RPE-CC can be present in patches of retina with minimal functional disturbance. More advanced disease stages in heterozygotes show greater rod than cone dysfunction, and the end stage in hemizygotes and heterozygotes is that of typical RP, with only barely detectable cone function from residual cones in a thinned retina with abnormal RPE and choriocapillaris.

Phenotype of an X-linked retinitis pigmentosa family with a novel splice defect in the RPGR gene.

PURPOSE: To assess the clinical phenotype in a Swedish family with X-linked retinitis pigmentosa (XLRP) resulting from a novel splice defect in the RPGR gene. METHODS: RPGR mutation analysis was performed in one family with XLRP, and several individuals from the family were examined clinically. RESULTS: The causative mutation in the family was demonstrated to be a single base-pair change at the splice donor site in intron 7 that resulted in skipping of the complete exon 7 in the mature RPGR transcript. The aberrant mRNA is predicted to produce an RPGR protein with an in-frame deletion of 53 amino acids, corresponding to an RCC1-homology repeat. Clinical studies that included ophthalmological examination and full-field electroretinography showed that this splice mutation resulted in a comparatively less severe form of RP. CONCLUSIONS: Correlation of a causative RPGR genotype with clinical findings in hemizygotes and carrier heterozygotes is an important step toward predictive diagnosis and should assist in the development of gene-based therapies in the future.

Inhibition of thrombin-induced platelet aggregation by uteroglobin.

Uteroglobin, a steroid-dependent, small molecular weight (15K) protein in the rabbit, inhibited thrombin-induced aggregation of both rabbit and human gel-filtered platelets (GFP). GFP aggregation by arachidonic acid was not affected by uteroglobin. There were no effects of uteroglobin on thrombin-induced clotting of plasma or purified fibrinogen, or inhibition of thrombin by antithrombin III. Additionally, preliminary results suggest that uteroglobin does not interfere with binding of thrombin to platelets. We suggest that inhibition of platelet aggregation by uteroglobin may function in preventing thrombosis and ensuring free flow of blood through the microvasculature of the uterus and the placenta and may induce some of the antimotility effects of progesterone on the uterus.

Glycosphingolipids of porcine pancreas.

Neutral and acidic glycosphingolipids were purified from porcine pancreas by chromatography on columns of DEAE-Sephadex and Iatrobeads. The chemical structures of the purified glycolipids were determined by carbohydrate analysis, methylation analysis, enzyme treatment, fatty acid analysis, NMR and IR. The major glycolipid of porcine pancreas was Gal(alpha,1-4)Gal(beta,1-)ceramide. Gangliosides GM3 and GD3 were major acidic components and galactosylceramide 3-sulfate was also found.

Morbidity and mortality after thoracoscopic pneumonoplasty.

BACKGROUND: Both video-assisted thoracic surgery and open pneumonoplasty procedures have been used to achieve lung reduction in emphysema patients. METHODS: The surgical and hospital course of 339 patients with a mean forced expiratory volume in 1 second of 750 mL and a mean ratio of forced expiratory volume in 1 second to forced vital capacity of 35% undergoing video-assisted thoracic surgical laser pneumonoplasty was analyzed. RESULTS: The incidence of myocardial infarctions was 0.9% and the hospital mortality rate was 4.1%. CONCLUSIONS: Factors leading to increased morbidity and mortality were advanced age (65 years and greater, especially greater than 75 years), sex (men greater than women), carbon dioxide retention in the resting state (especially an arterial carbon dioxide tension greater than 55 mm Hg), forced expiratory volume in 1 second less than 700 mL for men and 500 mL for women, maximum voluntary ventilation less than 25% predicted, and a ratio of residual volume/total lung capacity greater than 60%.

Blocking effect of serotonin on beta-adrenoceptor activity in follicle-enclosed Xenopus oocytes.

The effects of serotonin (5-HT) on a beta-adrenergic response were studied, using the voltage clamp technique, in Xenopus laevis oocytes surrounded by their follicular cells. noradrenaline induced marked hyperpolarization, with a specific increase in the permeability of the membrane toward K+. Application of 10 microM 5-HT had little effect on the resting membrane, but significantly depressed the response to 0.1 microM noradrenaline. The dose-response curve for noradrenaline showed a parallel shift to the right in the presence of 5-HT, suggesting that 5-HT competes with noradrenaline for common binding sites at the beta-adrenoceptor.