Search

This paper contains new results about the well-posedness and the asymptotic dynamics of solutions for a general abstract coupled system that arises in connection with thermoelastic Balakrishnan–Taylor beam models with fractional operators. [ABSTRACT FROM AUTHOR]

Disease heterogeneity has been a critical challenge for precision diagnosis and treatment, especially in neurologic and neuropsychiatric diseases. Many diseases can display multiple distinct brain phenotypes across individuals, potentially reflecting disease subtypes that can be captured using MRI and machine learning methods. However, biological interpretability and treatment relevance are limited if the derived subtypes are not associated with genetic drivers or susceptibility factors. Herein, we describe Gene-SGAN – a multi-view, weakly-supervised deep clustering method – which dissects disease heterogeneity by jointly considering phenotypic and genetic data, thereby conferring genetic correlations to the disease subtypes and associated endophenotypic signatures. We first validate the generalizability, interpretability, and robustness of Gene-SGAN in semi-synthetic experiments. We then demonstrate its application to real multi-site datasets from 28,858 individuals, deriving subtypes of Alzheimer's disease and brain endophenotypes associated with hypertension, from MRI and single nucleotide polymorphism data. Derived brain phenotypes displayed significant differences in neuroanatomical patterns, genetic determinants, biological and clinical biomarkers, indicating potentially distinct underlying neuropathologic processes, genetic drivers, and susceptibility factors. Overall, Gene-SGAN is broadly applicable to disease subtyping and endophenotype discovery, and is herein tested on disease-related, genetically-associated neuroimaging phenotypes. Many diseases can display distinct brain imaging phenotypes across individuals, potentially reflecting disease subtypes. However, biological interpretability is limited if the derived subtypes are not associated with genetic drivers or susceptibility factors. Here, the authors describe a deep-learning method that links imaging phenotypes with genetic factors, thereby conferring genetic correlations to the disease subtypes. [ABSTRACT FROM AUTHOR]

Introduction: Femur head necrosis (FHN) is a challenging clinical disease with unclear underlying mechanism, which pathologically is associated with disordered metabolism. However, the disordered metabolism in cancellous bone of FHN was never analyzed by gas chromatography-mass spectrometry (GC-MS). Objectives: To elucidate altered metabolism pathways in FHN and identify putative biomarkers for the detection of FHN. Methods: We recruited 26 patients with femur head necrosis and 22 patients with femur neck fracture in this study. Cancellous bone tissues from the femoral heads were collected after the surgery and were analyzed by GC-MS based untargeted metabolomics approach. The resulting data were analyzed via uni- and multivariate statistical approaches. The changed metabolites were used for the pathway analysis and potential biomarker identification. Results: Thirty-seven metabolites distinctly changed in FHN group were identified. Among them, 32 metabolites were upregulated and 5 were downregulated in FHN. The pathway analysis showed that linoleic acid metabolism were the most relevant to FHN pathology. On the basis of metabolites network, L-lysine, L-glutamine and L-serine were deemed as the junctions of the whole metabolites. Finally, 9,12-octadecadienoic acid, inosine, L-proline and octadecanoic acid were considered as the potential biomarkers of FHN. Conclusion: This study provides a new insight into the pathogenesis of FHN and confirms linoleic acid metabolism as the core. [ABSTRACT FROM AUTHOR]

The paper is concerned with the exponential attractors for the viscoelastic wave model in Ω ⊂ R 3 : u tt - h t (0) Δ u - ∫ 0 ∞ ∂ s h t (s) Δ u (t - s) d s + f (u) = g , with time-dependent memory kernel h t (·) which is used to model aging phenomena of the material. Conti et al. (Am J Math 140(2):349–389, 2018a; Am J Math 140(6):1687–1729, 2018b) recently provided the correct mathematical setting for the model and a well-posedness result within the novel theory of dynamical systems acting on time-dependent spaces, recently established by Conti et al. (J Differ Equ 255:1254–1277, 2013), and proved the existence and the regularity of the time-dependent global attractor. In this work, we further study the existence of the time-dependent exponential attractors as well as their regularity. We establish an abstract existence criterion via quasi-stability method introduced originally by Chueshov and Lasiecka (J Dyn Differ Equ 16:469–512, 2004), and on the basis of the theory and technique developed in Conti et al. (2018a, b) we further provide a new method to overcome the difficulty of the lack of further regularity to show the existence of the time-dependent exponential attractor. And these techniques can be used to tackle other hyperbolic models. [ABSTRACT FROM AUTHOR]

The paper investigates the well-posedness and the complete regularity of the weak solutions, and the existence of strong global attractor for the strongly damped wave equation with critical nonlinearities on R 3 : u tt - Δ u - Δ u t + h (x , u t) + g (x , u) = f (x) . We show that when both nonlinearities h (x , u t) and g(x, u) are of at most critical growth, (1) the model is well-posed and its weak solution is of higher complete regularity as t > 0 , which ensures that the weak solution is exactly the strong one; (2) the related dynamical system (S (t) , H) possesses a strong (H , H 2) -global attractor of optimal topological property, which is also the standard global attractor of optimal regularity of S(t) in H . The method developed here allows breaking through the long-standing restriction for this model on R 3 : the partial regularity of the weak solutions and almost linearity of h (x , u t) , and helps obtaining the optimal complete regularity of the weak solutions and the existence of strong global attractor. [ABSTRACT FROM AUTHOR]

Previous earthquake damage investigations in Japan have shown that prestressed high-strength concrete (PHC) piles experience shear failure in the event of an earthquake. To investigate the shear behavior of PHC piles, tests were conducted by varying the shear span-effective depth ratio and deformed bars. By verifying the correctness of an ABAQUS model, a finite element model of a pile was established and the effects of the shear span-effective depth ratio, axial load, concrete strength, and deformed bars on the shear capacity were studied. The results indicate that reducing the shear span-effective depth ratio and increasing the prestressing bar ratio and concrete strength can improve the shear capacity of PHC piles. Compared to a common PHC pile, a prestressed high-strength concrete pile reinforced with deformed bars (PRC piles) has higher shear capacity. As the shear span-effective depth ratio increases from 1.0 to 2.0 in steps of 0.25, the shear capacity decreases by 31.73%, 18.45%, 18.73%, and 16.09% in order. When the diameter of the prestressing bar increases from 7.1 to 9.0, 10.7, and 12.6 mm, the shear capacity increases by 19.25%, 9.32%, and 7.35% in order. When the diameter of the deformed bar increases from 12 to 18 mm in steps of 2 mm, the shear capacity increases by 7.2%, 7.4%, and 7.5% in order. As the axial compression ratio increases from 0 to 0.45 in steps of 0.15, the shear capacity of the PHC pile increases by 27.01%, 17.75%, and 12.27% in order, whereas the shear capacity of the PRC pile increases by 17.93%, 13.43%, and 9.77% in order. As the concrete strength increases from 60 to 80 and 100 MPa, its shear capacity increases by 6.30% and 5.87%, respectively. [ABSTRACT FROM AUTHOR]

The paper investigates the well-posedness and the regularity of the solutions, the existence and the continuity of the strong attractors for the structurally damped Kirchhoff wave models with subcritical-critical nonlinearities: u tt - (1 + ϵ ‖ ∇ u ‖ 2 ) Δ u + (- Δ) α u t + h (u t) + g (u) = f (x) , where ϵ ∈ [ 0 , 1 ] is a perturbed extensibility parameter, α ∈ [ 1 / 2 , 1) is a dissipative index. We show that when the nonlinearity g(u) is of either critical growth as α ∈ (1 / 2 , 1) or subcritical growth as α = 1 / 2 , while h (u t) is of critical growth depending on α , the model is well-posed and its weak solution is exactly the strong one; the related solution semigroup S ϵ (t) has a strong (X, Y)-global attractor and a strong (X, Y)-exponential attractor, which are also the standard global and exponential attractor of optimal regularity of S ϵ (t) in X, respectively, where X is the energy space and Y is the strong solution space; these global attractors are upper semicontinuous and these exponential attractors are Hölder continuous with respect to perturbed parameter ϵ in the sense of Y-topology, respectively. [ABSTRACT FROM AUTHOR]

In the abrasive belt grinding process, actual material removal is an important parameter that affects its accuracy. At present, for obtaining the actual material removal, offline measurements are required to establish the mathematical prediction model. To improve the accuracy and efficiency of abrasive belt machine grinding, this paper proposes a novel method for monitoring material removal using multiple sensors and a two-dimensional (2D) convolutional neural network (2D-CNN) learning algorithm. In this method, features of multiple types (color, texture, and shape) are extracted from vision signals, and that of multiple domains (time, frequency, and time–frequency domain) are extracted from sound and tactile signals. These features are constructed into a 2D feature matrix as the input model, and the 2D-CNN prediction model is established between the multisensor features and the material removal rate of the abrasive belt grinding process. An experimental dataset is used to train and verify the established model. The results show that the proposed method can identify that sensor signals are sensitive to the material removal rate. After optimizing and tuning the model parameters, the coefficient of determination of the prediction results is as high as 94.5% and the root mean square error is 0.017. Therefore, the proposed method can be employed for the prediction of material removal rate for different belt specifications and different grinding parameters. Compared to traditional machine learning methods, this method can yield better training results without feature selection and optimization. [ABSTRACT FROM AUTHOR]

Heterogeneity of brain diseases is a challenge for precision diagnosis/prognosis. We describe and validate Smile-GAN (SeMI-supervised cLustEring-Generative Adversarial Network), a semi-supervised deep-clustering method, which examines neuroanatomical heterogeneity contrasted against normal brain structure, to identify disease subtypes through neuroimaging signatures. When applied to regional volumes derived from T1-weighted MRI (two studies; 2,832 participants; 8,146 scans) including cognitively normal individuals and those with cognitive impairment and dementia, Smile-GAN identified four patterns or axes of neurodegeneration. Applying this framework to longitudinal data revealed two distinct progression pathways. Measures of expression of these patterns predicted the pathway and rate of future neurodegeneration. Pattern expression offered complementary performance to amyloid/tau in predicting clinical progression. These deep-learning derived biomarkers offer potential for precision diagnostics and targeted clinical trial recruitment. Alzheimer's disease is heterogeneous in its neuroimaging and clinical phenotypes. Here the authors present a semi-supervised deep learning method, Smile-GAN, to show four neurodegenerative patterns and two progression pathways providing prognostic and clinical information. [ABSTRACT FROM AUTHOR]

The paper investigates the robustness of pullback attractors and pullback exponential attractors of the non-autonomous Kirchhoff wave models with strong nonlinear damping: u tt - (1 + ϵ ‖ ∇ u ‖ 2 ) Δ u - σ (‖ ∇ u ‖ 2) Δ u t + f (u) = g (x , t) , where ϵ ∈ [ 0 , 1 ] is an extensibility parameter. It shows that when the growth exponent p of the nonlinearity f(u) is up to the supercritical range: 1 ≤ p < p ∗ ∗ ≡ N + 4 (N - 4) + , (i) the related process has a pullback attractor A ϵ in natural energy space H = (H 0 1 ∩ L p + 1) × L 2 for each ϵ , and it is upper semicontinuous on the perturbation ϵ ; (ii) the related process has a partially strong pullback exponential attractor M ϵ for each ϵ , and it is Hölder continuous on ϵ ∈ [ 0 , 1 ] . These results deepen and extend those in recent literatures (Chueshov in J Diff Equ 252:1229–1262, 2012; Ding et al. in Appl Math Lett 76:40–45, 2018; Wang and Zhong in Discrete Contin Dyn Syst 7:3189–3209, 2013). The main novelty of this paper is that it provides a new method to investigate the upper semicontinuity of pullback attractors and the stability of pullback exponential attractors in supercritical nonlinearity case. [ABSTRACT FROM AUTHOR]

Quantifying the overall magnitude of every single locus' genetic effect on the widely measured human phenome is of great challenge. We introduce a unified modelling technique that can consistently provide a total genetic contribution assessment (TGCA) of a gene or genetic variant without thresholding genetic association signals. Genome-wide TGCA in five UK Biobank phenotype domains highlights loci such as the HLA locus for medical conditions, the bone mineral density locus WNT16 for physical measures, and the skin tanning locus MC1R and smoking behaviour locus CHRNA3 for lifestyle. Tissue-specificity investigation reveals several tissues associated with total genetic contributions, including the brain tissues for mental health. Such associations are driven by tissue-specific gene expressions, which share genetic basis with the total genetic contributions. TGCA can provide a genome-wide atlas for the overall genetic contributions in each particular domain of human complex traits. Quantifying the effects of individual loci on the human phenome is a challenging task. Here, the authors introduce a modelling technique, TGCA, that assesses total genetic contribution per locus and apply this to UK Biobank phenotype domains, revealing top loci and links to tissue-specific gene expression. [ABSTRACT FROM AUTHOR]

TATB (1,3,5-triamino-2,4,6-trinitrobenzene) is a widely used insensitive high-energy explosive. It is significant to study its structural evolution in order to get a credible understand of its properties and performances. Direct mechanical tests such as hardness tests are useful approaches to get information about its mechanical properties and shed light upon the microstructures. However, due to the poor solubility of TATB to most solvents, it is hard to produce large crystals for such tests. Fortunately, microcosmic approaches such as powder diffraction can reinforce it and has low requirement on samples. In this study, series of in-situ neutron diffraction experiments under different pressures are performed to investigate the structural change and mechanical properties of TATB. The recently reported phase transition at 4 GPa is studied. The microstrains in normal TATB (12–17 µm) are analysed to reveal the information of slip system and transitional process. The lattice parameters and bulk moduli of TATB under different conditions are given. These neutron diffraction results are significant supplement to correlative studies and will help to understand the performances of TATB, such as deformation and phase transition. [ABSTRACT FROM AUTHOR]

The Fusarium wilt disease caused by Fusarium oxysporum f. sp. batatas (Fob) is one of the devastating diseases of sweetpotato. However, the molecular mechanisms of sweetpotato response to Fob is poorly understood. In the present study, comparative quantitative proteomic analysis was conducted to investigate the defense mechanisms involved. Two sweetpotato cultivars with differential Fob infection responses were inoculated with Fob spore suspensions and quantitatively analyzed by Tandem Mass Tags (TMT). 2267 proteins were identified and 1897 of them were quantified. There were 817 proteins with quantitative ratios of 1.2-fold change between Fob-inoculated and mock-treated samples. Further, nine differentially expressed proteins were validated by Parallel Reaction Monitoring (PRM). According to Gene Ontology (GO) annotation information, the proteins functioned in molecular metabolism, cellular component formation, and biological processes. Interestingly, the results showed that sweetpotato resistant response to Fob infection included many proteins associated with signaling transduction, plant resistance, chitinase and subtilisin-like protease. The functions and possible roles of those proteins were discussed. The results provides first insight into molecular mechanisms involved in sweetpotato defense responses to Fob. [ABSTRACT FROM AUTHOR]

Weak interfacial interaction and poor surface wettability always restrict and weaken the performances of energetic composites. Conventional surface modifications can hardly achieve a desired result, due to the inadequacy for solving the interfacial incompatibility. We here demonstrated bioinspired hierarchical-structured 2,6-diamino-3,5-dinitropyrazine-1-oxide particles through in situ "grafting from" polymerization of hyperbranched polyurethane (HBPU) on polydopamine surface. Benefiting from the enhanced interfacial interaction and surface wettability which facilitated mechanical performance, the final results revealed that a remarkable mechanical enhancement was successfully achieved through this way. Meanwhile, improved safety performance was gained, and the impact sensitivity was reduced to a large extent which was ascribed to the cushioning and protective effects of HBPU shells with soft segments. We believe this approach of constructing bioinspired hierarchical interface aiming at solving low surface wettability and weak interface will shed light on the design and preparation of high-performance composites through a novel and effective way. [ABSTRACT FROM AUTHOR]

Objectives: Rapid and accurate diagnosis of coronavirus disease 2019 (COVID-19) is critical during the epidemic. We aim to identify differences in CT imaging and clinical manifestations between pneumonia patients with and without COVID-19, and to develop and validate a diagnostic model for COVID-19 based on radiological semantic and clinical features alone. Methods: A consecutive cohort of 70 COVID-19 and 66 non-COVID-19 pneumonia patients were retrospectively recruited from five institutions. Patients were divided into primary (n = 98) and validation (n = 38) cohorts. The chi-square test, Student's t test, and Kruskal-Wallis H test were performed, comparing 1745 lesions and 67 features in the two groups. Three models were constructed using radiological semantic and clinical features through multivariate logistic regression. Diagnostic efficacies of developed models were quantified by receiver operating characteristic curve. Clinical usage was evaluated by decision curve analysis and nomogram. Results: Eighteen radiological semantic features and seventeen clinical features were identified to be significantly different. Besides ground-glass opacities (p = 0.032) and consolidation (p = 0.001) in the lung periphery, the lesion size (1–3 cm) is also significant for the diagnosis of COVID-19 (p = 0.027). Lung score presents no significant difference (p = 0.417). Three diagnostic models achieved an area under the curve value as high as 0.986 (95% CI 0.966~1.000). The clinical and radiological semantic models provided a better diagnostic performance and more considerable net benefits. Conclusions: Based on CT imaging and clinical manifestations alone, the pneumonia patients with and without COVID-19 can be distinguished. A model composed of radiological semantic and clinical features has an excellent performance for the diagnosis of COVID-19. Key Points: • Based on CT imaging and clinical manifestations alone, the pneumonia patients with and without COVID-19 can be distinguished. • A diagnostic model for COVID-19 was developed and validated using radiological semantic and clinical features, which had an area under the curve value of 0.986 (95% CI 0.966~1.000) and 0.936 (95% CI 0.866~1.000) in the primary and validation cohorts, respectively. [ABSTRACT FROM AUTHOR]

Adriamycin (ADR)-induced chronic heart injury (CHI) is a serious complication of chemotherapy. The present study was designed to assess the ability of fasudil, a Rho kinase inhibitor, to prevent ADR-induced CHI. Forty male 6-week-old C57BL6 mice were randomly divided into the following four groups: (1) control group, (2) CHI induced by adriamycin (ADR group), (3) CHI plus low dose fasudil (ADR + L group), and (4) CHI plus high dose fasudil (ADR + H group). Animals from groups 2–4 received ADR (2.5 mg/kg, i.p.) once a week for 8 weeks, and the control group received saline. Meanwhile, the animals in groups 3–4 received 2 mg/kg/day or 10 mg/kg/day fasudil, respectively. After measurement of cardiac functions, blood samples were collected for biochemical assays. The hearts were excised for histological, immunohistochemistry and western blot study, respectively. Adriamycin produced evident cardiac damage revealed by cardiac functions changes: decreased left ventricular fractional shortening (FS), left ventricular ejection fraction (EF), increased left ventricular volume, cardiac injury marker changes (increased creatine kinase, lactate dehydrogenase), antioxidant enzymes activity changes (decreased superoxide dismutase), and lipid peroxidation (elevated malondialdehyde) to the control group. Fasudil treatment notably ameliorated ADR-induced cardiac damage, restored heart function, suppressed cell apoptosis and senescence, ameliorated redox imbalance, and DNA damage. Fasudil has a protective effect on ADR-induced chronic heart injury, which partially attributed to its antioxidant, anti-apoptotic effects of inhibiting the RhoA/Rho kinase (ROCK) signaling pathway. [ABSTRACT FROM AUTHOR]

The hydrodynamic problems of water entry of a wedge are investigated by a modified ghost-cell immersed boundary method. The modifications correspond to a newly proposed scheme for dealing with fluid–body interaction, and incorporation of CIP (Constraint Interpolation Profile) method and THINC/SW (Tangent of Hyperbola for Interface Capturing with Slope Weighting) method. The modified ghost-cell immersed boundary method uses a compact interpolation structure and gives the fluid properties to the ghost cell to achieve a more accurate treatment of fluid–body interaction. It can preserve the sharpness of the immersed boundary. To validate the new method, simulations of water entry of symmetric and asymmetric wedges in a single degree of freedom and water entry of an asymmetric wedge in three degrees of freedom are carried out, respectively. The variations of pressure, vertical velocity, vertical acceleration, angular displacement, and angular acceleration against time are focused on. The evolution of the free surface and velocity distributions of fluid is also analyzed. The results of numerical simulations are compared with available experimental results and fairly good agreement is obtained, which indicates that the present model is reliable. [ABSTRACT FROM AUTHOR]

Traditionally heparin is adapted according to total body weight (TBW) to providing anticoagulation during cardiopulmonary bypass (CPB), but it may be inaccurate in some patients. The medical records of 100 adult patients who received CPB in Tongji Hospital of Tongji Medical College Huazhong University of Science and Technology over a 10-month period in 2017 were included in the retrospective study. An unfractionated heparin (UFH) bolus of 300 IU/kg TBW was injected before initiation of CPB followed by additional doses (50 to 100 IU/kg) to maintain a target activated coagulation time (ACT) of at least 480 s. We used TBW, ideal body weight (IBW), lean body weight (LBW), or body mass index (BMI) to establish and evaluate a linear model of ACT and the amount of heparin respectively. The linear fit effect of the model based on BMI on the original data is better than the others. As the instruments to measure heparin concentration is unavailable in most medical institutions in China. The new linear model based on BMI is helpful to estimate a more individualized heparin dosage in the heparinized phase and to provide useful reference to the amount of remaining heparin in the neutralization phase. [ABSTRACT FROM AUTHOR]

We propose an arbitrary-order discontinuous Galerkin method for second-order elliptic problem on general polygonal mesh with only one degree of freedom per element. This is achieved by locally solving a discrete least-squares over a neighboring element patch. Under a geometrical condition on the element patch, we prove an optimal a priori error estimates in the energy norm and in the L 2 norm. The accuracy and the efficiency of the method up to order six on several polygonal meshes are illustrated by a set of benchmark problems. [ABSTRACT FROM AUTHOR]

In this report, we described a large Han-Chinese family which presents with various phenotypes from unaffected to manifested nystagmus in females. Infantile nystagmus (IN) is characterized by bilateral, involuntary, and periodic eyeball oscillation, occurring at birth or within the first 6 months. The most common inheritance pattern of IN is an X-linked form with incomplete penetrance among females, and the FERM domain containing 7 gene (FRMD7) is a main disease-causing gene. A combination of exome sequencing and Sanger sequencing, as well as detailed clinical examinations were performed on the Chinese IN family. An FRMD7 c.47T>C (p.Phe16Ser) variant was proposed as the disease-causing variant. Incomplete penetrance was found in females with the FRMD7 c.47T>C variant, and hemizygous male affected subjects presented more severe manifestations compared to heterozygous female affected subjects. These findings could enhance genetic counseling and antenatal diagnosis of IN. [ABSTRACT FROM AUTHOR]

Four prestressed high strength concrete (PHC) piles under low-cycle loading and two piles under monotonic flexural loading were tested to study the test phenomena, failure modes, hysteretic performance, ductility and bearing capacity. It was indicated that PHC piles failed suddenly and the bearing capacity decreased because of the tensile rupturing of prestressing tendons from the results, and the hysteretic curves pinched. Nonlinear finite element models were established to analyze the mechanical properties of PHC piles using ABAQUS and OpenSees. The results obtained from the numerical analysis compared well with the experimental results. In addition, nonlinear finite element models were used to study influence of the position, pattern, number and diameter of deformed bars to the PHC piles reinforced with deformed bars (PRC piles). The analysis results showed that the deformed bars should be arranged evenly in circle direction, and the bearing capacity of PRC increased with the number and diameter of deformed bars. [ABSTRACT FROM AUTHOR]

The application of aluminum nanoparticle is limited due to its passivation Al2O3 layer even though it owns extreme specific surface and high reaction activity. In this work, the aluminum nanoparticles were modified via in situ grafting onto energetic glycidyl azide polymer (GAP) to improve the stability and energy-releasing performance. The results showed that GAP was grafted on the nano-aluminum surface with chemical bonds of -O-(CO-NH)- formed, and the thickness of shell layer of GAP could be tuned by changing the relative ratio of reactants. Furthermore, modified nanoparticles show hydrophobicity with static water contact angle changing from 20.2° to 142.4°. Significant increasing stability of aluminum nanoparticles is obtained in hot water, which is evidenced by that around 10 wt% of modified aluminum is reacted after 210 min. Based on the core-shell configurations, (Al@GAP)/fluorine composites were prepared. The violent combustion phenomenon and high release rate profiles revealed high energy-releasing performance with the assistance of GAP. This synthetic strategy may provide an effective approach to prepare other metal nanoparticles, and possess potential application value in the fields of metallized explosives and high-energy structure with energy release. [ABSTRACT FROM AUTHOR]

Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder primarily characterized by multiple café-au-lait macules, peripheral neurofibromas, skinfold freckling, and Lisch nodules. The causative genetic factor is the neurofibromin 1 gene (NF1), which encodes a Ras GTPase-activating protein called neurofibromin. NF1 variants may lead to loss of neurofibromin function and activation of downstream cell growth. This study aims to discover the disease-causing variants responsible for NF1 in two Han Chinese families by using exome sequencing combined with Sanger sequencing. A recurrent missense variant c.269T>C (p.Leu90Pro) and a novel nonsense variant c.2993dupA (p.Tyr998*) in the NF1 gene were identified. These variants co-segregated with the disorder in the pedigrees and were absent in the normal controls. The results broaden the NF1 mutation spectrum responsible for NF1. This may be helpful in genetic counseling, clinical management, and gene-targeted therapies for NF1. [ABSTRACT FROM AUTHOR]

Familial amyloid polyneuropathy (FAP) is a dominantly inherited disorder. This study aims to explore the genetic features of a Han Chinese family with FAP, characterized by bloating, alternating diarrhea and constipation, and weakness in his feet. Amyloid presented histologically in the vessel walls of hepatic portal area and nerves of the surgically excised liver specimens from the proband by hematoxylin and eosin staining. Amyloid deposition was further confirmed with Congo red treatment. A c.349G>T transversion (p.Ala117Ser) in TTR gene exon 4 was identified in the proband with typical autonomic neuropathy and peripheral motor neuropathy, as well as in his asymptomatic son. The variant was not detected in 200 normal ethnically matched controls. These findings provide new insights into FAP cause and diagnosis and have implications for genetic counseling. [ABSTRACT FROM AUTHOR]

This paper investigates the flexural behavior of high strength concrete filled square steel beam with inner CFRP (carbon fiber-reinforced polymer) circular tube by the ABAQUS/Standard solver. In addition, eight specimens were fabricated and tested to investigate the pure flexural behavior. The test data was used to verify the Finite Element Analysis (FEA) modeling and good agreement was achieved in general. Furthermore, the influences of steel yielding strength, concrete strength, steel ratio and the thickness of CFRP on the flexural performance of the specimens were analyzed by FEA. According to the analysis of bending moment versus strain curves, the materials of CFRP, steel and concrete worked well together subjected to pure bending before the CFRP tube ruptured. The results presented in this paper show that these composite beams have a very ductile response because the concrete is confined by the CFRP tube and the steel tube. The beams' flexural response, including the flexural stiffness and the ultimate load, can be substantially improved by the inner CFRP tube. The parametric studies provide information for the development of formulae to calculate the moment capacity. A comparison of experimental failure loads with the predicted failure loads in accordance with the formulae showed good agreement. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is the second most common neurodegenerative disorder and has an elusive etiology. It is likely multifactorial, and genetic defects contribute to its pathogenesis. At least 25 genetic loci and 20 monogenic genes have been identified in monogenic PD. Recessive F-box protein 7 gene ( FBXO7) mutations reportedly cause hereditary parkinsonism. To explore the roles of four paralogs ( FBXO2, FBXO6, FBXO12, and FBXO41) in PD development, their variants (rs9614, rs28924120, rs6442117, and rs61733550, respectively) were analyzed in 502 Han Chinese patients with PD and 556 age, gender, and ethnicity-matched normal participants in mainland China. Statistically significant differences in genotypic and allelic frequencies were detected only in the FBXO2 variant rs9614 ( P = 0.001 and 0.023, respectively; odds ratio 0.819, 95% confidence interval 0.690-0.973) between patients and controls. These results suggest that the FBXO2 variant rs9614 C allele may decrease the PD risk in mainland Han Chinese and may be a biomarker for PD. [ABSTRACT FROM AUTHOR]

Purpose: Transplantation of mesenchymal stem cells (MSCs) is a promising therapeutic option for patients with acute myocardial infarction. Methods: We show here that the ectopic overexpression of endothelial nitric oxide synthases (eNOS), an endothelial form of NOS, could enhance the ability of MSCs in treating ischemic heart damage after the occlusion of the coronary artery. Results: Adenoviral delivery of human eNOS gene into mouse bone marrow-derived MSCs (BM-MSCs) conferred resistance to oxygen glucose deprivation (OGD)-induced cell death in vitro, and elevated the bioavailability of nitric oxide when injected into the myocardium in vivo. In a rat model of acute myocardial infarction, the transplantation of eNOS-overexpressing BM-MSCs significantly reduced myocardial infarct size, corrected hemodynamic parameters and increased capillary density. We also found that the synergistic effects were consistently better than either treatment alone. Conclusions: These findings reveal a positive role of elevated eNOS expression in cardiac repair, and suggest the combination of eNOS and MSC transplant therapy as a potential approach for treating myocardial infarction. [ABSTRACT FROM AUTHOR]

Limb-girdle muscular dystrophies (LGMD) are a highly heterogeneous group of genetic myopathies characterized by progressive proximal pelvic and/or shoulder girdle muscle weakness, with the onset ages ranging from early childhood to late adulthood. The identification of these dystrophies through genetic testing will not only inform long-term prognosis but will also assist in directing care more efficiently, including more frequent cardiorespiratory monitoring and prophylactic treatments. The aim of this study was to identify the responsible gene in a five-generation Chinese Han pedigree with autosomal recessive LGMD. Exome sequencing was conducted and a novel mutation c.107788T>C (p.W35930R) in the titin gene ( TTN) was identified. The mutation co-segregated with the disorder in the family and was absent in normal controls. Our discovery broadens the mutation spectrum of the TTN gene associated with LGMD2J. [ABSTRACT FROM AUTHOR]

Six Prestressed High Strength Concrete (PHC) pile-to-pile cap connections were tested to evaluate their damage process and failure modes under low cyclic loading. The hysteretic behaviour, rotation angle, ductility and bearing capacity were observed and analyzed. In addition, the effect of connecting forms and cutting-off piles on seismic performance of pile-cap connections was considered and investigated. The experimental results showed that flexural bending failure occurred in all connections. There were two main failure modes. One was tensile rupturing of prestressed bars and headings, resulting in loss of bearing capacity of the connections. The other type was more severe damage due to anchor bar yield and appearance of plastic hinge. Moreover, bond-slip failure of anchor bars was not observed in the cap, and the length of anchor bars met requirements. The analysis indicated that the bearing capacity and energy dissipation capacity increased along with the rotation capacity of the pile connections. Nonlinear finite element models were established to analyze the mechanical properties of these connections using OpenSees. The load-displacement curves obtained from the numerical analysis agreed with the experimental results. The effects of various parameters on the behaviour of the connections were conducted based on the numerical model. [ABSTRACT FROM AUTHOR]

Febrile seizures (FS), the most frequent type of seizures in children, occur in neurologically normal infants and children between the ages of 3 months and 5 years with genetic predisposition. The aim of this study was to identify the responsible gene in a four-generation Chinese Han pedigree with autosomal dominant FS. Seven family members (three affected and four unaffected) were enrolled in this study. Exome sequencing was conducted and a duplication mutation c.649dupC (p.R217Pfs*8) in the proline-rich transmembrane protein 2 gene ( PRRT2) was identified. The mutation co-segregated with the disorder and was absent in normal controls. To our knowledge, this is the first report of a pedigree with complete penetrance of FS, which is caused by mutation in the PRRT2 gene. FS is a novel phenotype of the c.649dupC (p.R217Pfs*8) mutation. Our discovery broadens the spectrum of genetic causes of FS and the spectrum of phenotypes linked to mutation in the PRRT2 gene. [ABSTRACT FROM AUTHOR]

Myocardial infarction (MI) is a major cause of death worldwide. The treatment of MI has improved during the last decade; however, the loss of myocytes remains a problem because the cells cannot be renewed. Cardiac stem cells were recently discovered and were thought to represent a promising treatment for MI. However, the efficiency of cardiac stem cell differentiation into myocyte is not sufficient. Hepatocyte growth factor (HGF) is related to the differentiation and proliferation of cardiac stem cells. p27 is a potent cell cycle inhibitor in most organs, especially the heart. In this study, we investigated the relationship among p27, HGF and cardiac stem cells in post-MI cardiac repair. We found that p27 haploinsufficient mice exhibited preserved cardiac function and improved cardiomyocyte renewal compared with wild-type mice. In addition, p27 haploinsufficiency may not increase cardiac stem cell proliferation but could improve their differentiation by increasing mammalian target of rapamycin expression. [ABSTRACT FROM AUTHOR]

The genomes of two rice cultivars, Nipponbare and 93-11, have been well studied. However, there is little available genetic information about nutraceutical rice cultivars. To remedy this situation, the present study aimed to provide a basic genetic landscape of nutraceutical rice. The genome of Black-1, a black pericarp rice containing higher levels of anthocyanins, flavonoids, and a more potent antioxidant capacity, was sequenced at ≥30 × coverage using Solexa sequencing technology. The complete sequences of Black-1 genome shared more consensus sequences with indica cultivar 93-11 than with Nipponbare. With reference to the 93-11 genome, Black-1 contained 675,207 single-nucleotide polymorphisms, 43,130 insertions and deletions (1-5 bp), 1,770 copy number variations, and 10,911 presence/absence variations. These variations were observed to reside preferentially in Myb domains, NB-ARC domains and kinase domains, providing clues to the diversity of biological functions or secondary metabolisms in this cultivar. Intriguingly, 496 unique genes were identified by comparing it with the genomes of these two rice varieties; among the genes, 119 genes participate in the biosynthesis of secondary metabolites. Furthermore, several unique genes were predicted to be involved in the anthocyanins synthesis pathway. The genome-wide landscape of Black-1 uncovered by this study represents a valuable resource for further studies and for breeding nutraceutical rice varieties. [ABSTRACT FROM AUTHOR]

The aim of this study was to obtain best estimates of the efficacy and safety of cilostazol-based triple antiplatelet therapy (TAPT: aspirin, clopidogrel and cilostazol) compared with dual antiplatelet therapy (DAPT: aspirin and clopidogrel) in patients undergoing coronary stent implantation. We searched the literature to identify all randomized clinical trials examining efficacy and safety of TAPT versus DAPT in patients undergoing coronary stent implantation. Major efficacy outcomes were death, non-fatal myocardial infarction (MI), ischemic stroke and stent thrombosis (ST) and the safety outcome was bleeding. Data were analyzed using the Review Manager 5.0.0 software. A total of 19 trials involving 7,464 patients were included. TAPT and DAPT were associated with similar rates of death, non-fatal MI, ischemic stroke and ST, but compared with DAPT, TAPT had lower rates of target lesion revascularization (TLR) (RR 0.67, 95 % CI 0.56-0.82, P < 0.0001) and target vessel revascularization (TVR) (RR 0.65, 95 % CI 0.55-0.77, P < 0.00001), as well as less late loss of minimal lumen diameter (mean difference −0.14, 95 % CI −0.17-−0.11, P < 0.00001), and less binary angiographic restenosis (RR 0.54, 95 % CI 0.45-0.65, P < 0.00001). TAPT and DAPT had similar rates of bleeding, but TAPT had significantly higher rates of headache, palpitation, rash and gastrointestinal side-effects. Cilostazol-based TAPT compared with DAPT is associated with improved angiographic outcomes and decreased risk of TLR and TVR but does not reduce major cardiovascular events and is associated with an increase in minor adverse events. [ABSTRACT FROM AUTHOR]

In order to solve the problems of GaN heteroepitaxy on sapphire substrate, some techniques were explored. Freestanding GaN substrates have been made by hydride vapor phase epitaxy (HVPE), laser lift-off (LLO), and chemical mechanical polishing techniques. Wafer bending and cracking in the HVPE growth were partly settled by pulsed flow modulation method. High-crystal quality was established for 1.2 mm thick GaN substrate by X-ray diffraction measurement, in which the full width of half maximum values were 72, 110 arcsec for (102), (002) peaks. A novel micro-size patterned sapphire substrate (PSS) and a nano PSS were also fabricated. High-power vertical structure light emitting diodes (VSLEDs) have been developed by Au-Sn eutectic wafer bonding, homemade micro-area LLO, and light extraction structure preparation. The high-injection-level active region with low temperature GaN sandwiched layers was used for low-efficiency droop. The light output power of VSLED was achieved as 400 mW driven at 350 mA, and the dominant wavelength is about 460 nm. The structures and properties of strain modulated superlattices (SLs) and quantum wells as well as advanced simulation of carriers transport across the electron blocking layer were investigated in laser diodes. The hole concentration was achieved as high as 1.6 × 10 cm in AlGaN/GaN SLs:Mg by inserting an AlN layer. High-quality AlGaN epilayers and structures were grown by MOCVD. Some device structures of UV LEDs and detectors were demonstrated. The emission wavelength of 262 nm UV LED has been successfully fabricated. At last, high-quality InN and InGaN materials for solar cell were grown by boundary-temperature-controlled epitaxy and growth-temperature-controlled epitaxy. Hall-effect measurement showed a recorded electron mobility of 3,280 cm/(V s) and a residual electron concentration of 1.47 × 10 cm at 300 K. [ABSTRACT FROM AUTHOR]

AlN with different thicknesses were grown as interlayers (ILs) between GaN and p-type AlGaN/GaN superlattices (SLs) by metal organic vapor phase epitaxy (MOVPE). It was found that the edge-type threading dislocation density (TDD) increased gradually from the minimum of 2.5×10 cm without AlN IL to the maximum of 1×10 cm at an AlN thickness of 20 nm, while the screw-type TDD remained almost unchanged due to the interface-related TD suppression and regeneration mechanism. We obtained that the edge-type dislocations acted as acceptors in p-type AlGaN/GaN SLs, through the comparison of the edge-type TDD and hole concentration with different thicknesses of AlN IL. The Mg activation energy was significantly decreased from 153 to 70 meV with a 10-nm AlN IL, which was attributed to the strain modulation between AlGaN barrier and GaN well. The large activation efficiency, together with the TDs, led to the enhanced hole concentration. The variation trend of Hall mobility was also observed, which originated from the scattering at TDs. [ABSTRACT FROM AUTHOR]

A novel carbon nanotube-patterned sapphire substrate (CPSS) has been utilized for the growth of GaN material and fabrication of a InGaN/GaN light emitting diode (LED) by metal-organic vapor phase epitaxy. Different lateral strain distributions and stress reductions were observed in a GaN thin film on CPSS compared with those on a conventional sapphire substrate. Nanoheteroepitaxy induced by small size nucleation islands of about 50 nm is ascribed to this significant strain modulation. The crystalline quality of the GaN thin film was also improved, as illustrated by X-ray diffraction. Performances of 1 mm × 1 mm LEDs on CPSS were also enhanced, with an operational power increase of 37.5% and higher saturation current. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Migration and proliferation of bone marrow-derived mesenchymal stem cells (BMSCs) is critical to treatment of ischemic injury. The calcium sensing receptor (CaSR) has an important role in maintaining systemic calcium homeostasis, which is related to cell proliferation, apoptosis and paracrine signaling. We hypothesize that CaSR may enhance BMSC proliferation. Rat BMSCs were incubated with various calcium concentrations for 48 h in vitro to activate CaSR. To investigate potential mechanisms responsible for growth enhancement by calcium, the rat BMSC cell cycle progression was analyzed by fluorescence-activated cell sorting (FACS), and induction of apoptosis confirmed by cytofluorimetric analysis using propidium iodide and Annexin V-FITC double staining. Since the mitogen-activated protein kinase (MAPK) signaling pathway was one of the most significantly affected by CaSR, MAPK activation was measured by western blotting. Calcium exposure significantly enhanced rat BMSCs proliferation, as well as the proportion of the population in S phase, in a dose-dependent manner, effects which were abolished by NPS2390 (a CaSR antagonist) and U0126 (a MEK1/2 inhibitor). These results demonstrate that CaSR is involved in rat BMSC proliferation, as seen by an increased proliferation index, decreased apoptosis, and ERK1/2 activation, and provide important insight into the cellular and molecular mechanisms by which CaSR affects cell proliferation. A CaSR agonist may prove useful to enhance BMSC survival during transplantation. [ABSTRACT FROM AUTHOR]

The orthotopic transplantation model of human tumor has been demonstrated to be more patient-like animal tumor model. However, observations of tumor progression and metastasis are limited by the deep location of the colon or limited deep penetration ability of fluorescence through tissue. The purpose of this study is to establish a superficial orthotopic model to allow easier real-time visualization and more sensitive monitoring of fluorescent orthotopic colon tumor. Human colon cancer HT-29 cells were transduced with a pLPCX expression retroviral vector containing green fluorescent protein and neomycin resistance genes. For superficial orthotopic transplantation model, the cecum was identified and pulled out of the peritoneal cavity, the space between the cecum and peritoneum was sutured, the cecum was pulled to subcutaneous tissue, and incision was made on the cecal serosa followed by the implantation of a 1-mm tumor tissue to the cecum. For comparison, a conventional orthotopic transplantation model was established in a separate group of mice simultaneously. When tumor sizes reached 5 mm in diameter, half the mice in each model received 5-FU treatment. Primary tumor and metastases were monitored by fluorescent imaging or caliber measurement. Tumor fluorescence was observed as early as 3 days (median time of 4.7 ± 1.3 days) post-transplantation in the superficial orthotopic transplantation model, which was much earlier than 21 days (median time of 26.2 ± 9.9 days) in conventional orthotopic transplantation model. Although tumor growth of 5-FU-treated mice in conventional orthotopic model was lower than those of the untreated mice, the difference was not significant. However, in superficial orthotopic model, tumor growth was significantly inhibited in 5-FU-treated mice relative to the untreated mice. Fluorescence imaging showed similar metastasis incidence between the superficial and conventional orthotopic transplantation models. The fluorescent superficial orthotopic transplantation colon model allows easier real-time visualization and more sensitive monitoring of tumor growth as well as convenient repeated sampling. It is a valuable orthotopic implantation model for study of colon cancer and evaluation of new anti-cancer therapy. [ABSTRACT FROM AUTHOR]

We aim to study the amelioration effect of adenovirus5-mediated human hepatocyte growth factor gene transfer on postinfarction heart failure in swine model. Twelve Suzhong young swine were randomly divided into 2 groups of 6 pigs each: Ad5-HGF group and mock-vector Ad5 group. Four weeks after ligation of the left anterior descending coronary artery, Ad5-HGF was intracoronarily transferred into the myocardium. Simultaneously, gate cardiac perfusion imaging was performed to evaluate the heart function. Three weeks later, gate cardiac perfusion imaging was performed again, then the hearts were removed and sectioned for immunohistochemical examination to illustrate the effects of Ad5-HGF on infarcted myocardium. The expression of HGF was examined by ELISA. The results were: (1) compared with the mock-vector Ad5 group, high expression of human HGF was observed in the myocardium of Ad5-HGF group; (2) in the Ad5-HGF group, the number of CD117+ cells co-expressing c-Met per mm2 was significantly larger; (3) the improvement in LVEF was greater in the Ad5-HGF group than in the mock-vector Ad5 group. We concluded that: (1) high expression of human HGF was observed in the myocardium through intracoronary gene transfection; (2) HGF can improve the mobilization of CD117+/c-Met+ stem cells into ischemic myocardium. The amelioration effect of HGF on postinfarction heart failure could not be limited to stimulating angiogenesis, anti-apoptosis, anti-fibrosis, but was also involved in the recruitment of stem cells into myocardium. [ABSTRACT FROM AUTHOR]

Based on important factors that affect soil moisture spatial distribution, such as the slope gradients, land use, vegetation cover, and surface water diffusion characteristics together with field measurements of soil moisture data obtained from the surface soil under different land use structures, a soil moisture spatial distribution model was established. The diffusion degree coefficient of surface water for different vegetations was estimated from soil moisture values obtained from field measurements. The model can be solved using the finite unit method. The soil moisture spatial distribution on the hill slopes in the Loess Plateau were simulated by the model. A comparison of the simulated values with measurement data shows that the model is a good fit. [ABSTRACT FROM AUTHOR]

The continuous administration of compound danshen dripping pills (CDDP) showed good efficacy in relieving myocardial ischemia clinically. To probe the underlying mechanism, metabolic features were evaluated in a rat model of acute myocardial ischemia induced by isoproterenol (ISO) and administrated with CDDP using a metabolomics platform. Our data revealed that the ISO-induced animal model showed obvious myocardial injury, decreased energy production, and a marked change in metabolomic patterns in plasma and heart tissue. CDDP pretreatment increased energy production, ameliorated biochemical indices, modulated the changes and metabolomic pattern induced by ISO, especially in heart tissue. For the first time, we found that ISO induced myocardial ischemia was accomplished with a reduced fatty acids metabolism and an elevated glycolysis for energy supply upon the ischemic stress; while CDDP pretreatment prevented the tendency induced by ISO and enhanced a metabolic shift towards fatty acids metabolism that conventionally dominates energy supply to cardiac muscle cells. These data suggested that the underlying mechanism of CDDP involved regulating the dominant energy production mode and enhancing a metabolic shift toward fatty acids metabolism in ischemic heart. It was further indicated that CDDP had the potential to prevent myocardial ischemia in clinic. [ABSTRACT FROM AUTHOR]