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In this study, we perform a stability analysis on three-dimensional (3D) geosynthetic-reinforced soil structures (GRSSs), focusing on their response to varying rainfall conditions. The magnitude and distribution of pore water pressure in unsaturated backfills throughout the infiltration event is calculated to determine the time-dependent matric suction and apparent cohesion in backfills. An analytical expression representing the necessary strength for geosynthetic reinforcement in 3D GRSS is derived from the energy balance equation, utilizing the kinematic limit analysis approach. The validities of both the necessary reinforcement strength and the pore water pressure distribution are confirmed in this study. Further exploration is conducted into the effects of the 3D geometric features of the GRSSs, the effective cohesion and friction angle of backfills, alongside factors related to rainfall intensity, duration and patterns. These considerations influence both the required reinforcement strength and the failure pattern of the GRSSs. The findings indicate that the necessary reinforcement strength and critical failure pattern of a GRSS are dictated not only by its 3D geometric properties but also by the unsaturated soil mechanics and the nature of the rainfall it encounters. An identical accumulated rainfall will result in approximately a same required reinforcement strength solution of GRSS after rainfall. This study provides guidance on preliminary design of GRSSs under rainfall conditions. [ABSTRACT FROM AUTHOR]

Roof stability of shallow-buried cylindrical tunnels in rock strata following the generalized Hoek-Brown criterion (GHB) is analyzed in this work. Based on the limit analysis method, a three-dimensional (3D) shallow-buried collapse mechanism for tunnel roofs is developed to derive various stability measures. Optimization codes are programmed to capture the optimal stability measure solutions. The effects of the 3D geometric characteristics, the rock mass strength parameters, and the buried depth on tunnel roof stability are investigated by a parametric analysis. The critical buried depth ratios corresponding to the transition between the shallow-buried and deep-buried tunnel roof collapse mechanisms are also presented. Thereafter a series of stability charts of the required supporting pressure and the factor of safety (FoS) is proposed for design purposes. This study provides a theoretical basis for design and engineering of tunnels with limited buried depth. [ABSTRACT FROM AUTHOR]

Stability analysis for three-dimensional (3D) earth retaining structures (ERSs) is a pivotal problem in geotechnical engineering, particularly for seismically active areas. In this work, the 3D ERSs in soil are assessed for seismic stability following a nonlinear strength criterion. The power-law strength criterion and seismic forces are introduced into the 3D ERS stability analysis via a multi-cone failure mechanism. The coefficient of active soil pressure K a is derived by exploiting the energy balance equation. The upper bound solutions, that is the maximum results of the K a are captured with the help of a genetic algorithm. The validity of the current study is verified by a comparative analysis, and the effects of soil strength nonlinearity, the seismic forces, the soil-wall friction angle, the height, the inclined angle and the 3D geometric traits of ERSs on the K a solutions and the stability of ERSs are investigated. It is indicated that the height and the 3D geometric characteristics of the ERSs will not only determine the K a solutions directly, but also influence the impact of soil strength nonlinearity on the stability of ERSs. Strength criteria should be chosen combining the geometric characteristics of ERSs to derive more critical estimates on the stability of 3D ERSs. Additionally, a range of seismic and static stability charts used for preliminary design are put forward as well. [ABSTRACT FROM AUTHOR]

Abstract Earthquakes act as a dominant trigger for failure of slopes in seismic active regions. In this study, a seismic stability analysis of a three-dimensional (3D) rock slope in Hoek–Brown media is conducted based on the limit analysis method. The energy balance equation is derived by equating the external work rate by rock mass weight and seismic forces to the internal energy dissipation rate, and an optimization code is then programmed to capture the optimized factor of safety (FoS) of a 3D rock slope based on the strength reduction technique. The validity of the equivalent Mohr–Coulomb parameters method and generalized tangent technique in conjunction with the limit analysis method to estimate FoS of a 3D rock slope is investigated. Subsequently, a quasi-static method is used to explore the effect of seismic forces on stability of a 3D rock slope. The results of the parametric analysis indicate that the seismic force exhibits significant negative effects on the stability of a 3D slope and that a significant difference exists between a 3D FoS solution and a solution obtained under two-dimensional (2D) plane strain. A stability chart analysis is performed to produce a set of seismic stability charts for preliminary design purposes. Finally, a case study is performed to apply stability charts in practical situations. [ABSTRACT FROM AUTHOR]

Nitrogen is an essential macronutrient for plants and the common limiting factor for crop productivity worldwide. An effective approach to combat N deficiency and overuse is to understand the mechanism of low-nitrogen tolerance in plants and develop low-nitrogen-tolerant crop cultivars. Wild soybean has a high tolerance to poor environmental conditions, but, until now, no study has illustrated the mechanism of low-nitrogen tolerance at a metabolomic level. In this study, the photosynthetic characteristics and metabolomics of wild and cultivated soybean seedlings were analyzed, and the mechanism of wild soybean’s low-nitrogen tolerance was explained using a sand culture experiment. Wild soybean was less affected by low-nitrogen stress than cultivated soybean as assessed by plant growth parameters and photosynthesis. The root length of wild soybean increased, and a high root-shoot ratio was maintained under low-nitrogen stress. Carotenoids accumulated, which contributed to its higher low-nitrogen tolerance. A total of 48 and 60 differentially accumulated metabolites were identified in leaves and roots, respectively, between the low-nitrogen stress and control groups. The ability of wild soybean to tolerate low nitrogen also resulted from its capability to enhance the TCA cycle, synthesize key amino acids, accumulate metabolites, such as soluble sugars and organic acids, and synthesize favorable secondary metabolites under low-nitrogen stress. The current results reveal the mechanism underlying wild soybean’s high low-nitrogen tolerance and provide the methodology and theoretical basis for utilizing wild soybean, improving cultivated soybean, and studying the low-nitrogen tolerance of other plants. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is an age-related neurodegenerative disorder that displays pathological characteristics including senile plaques and neurofibrillary tangles. Metabolic defects are also present in AD-brain: for example, signs of deficient cerebral glucose uptake may occur decades before onset of cognitive dysfunction and tissue damage. There have been few systematic studies of the metabolite content of AD human brain, possibly due to scarcity of high-quality brain tissue and/or lack of reliable experimental methodologies. Here we sought to: 1) elucidate the molecular basis of metabolic defects in human AD-brain; and 2) identify endogenous metabolites that might guide new approaches for therapeutic intervention, diagnosis or monitoring of AD. Brains were obtained from nine cases with confirmed clinical/neuropathological AD and nine controls matched for age, sex and post-mortem delay. Metabolite levels were measured in post-mortem tissue from seven regions: three that undergo severe neuronal damage (hippocampus, entorhinal cortex and middle-temporal gyrus); three less severely affected (cingulate gyrus, sensory cortex and motor cortex); and one (cerebellum) that is relatively spared. We report a total of 55 metabolites that were altered in at least one AD-brain region, with different regions showing alterations in between 16 and 33 metabolites. Overall, we detected prominent global alterations in metabolites from several pathways involved in glucose clearance/utilization, the urea cycle, and amino-acid metabolism. The finding that potentially toxigenic molecular perturbations are widespread throughout all brain regions including the cerebellum is consistent with a global brain disease process rather than a localized effect of AD on regional brain metabolism. [ABSTRACT FROM AUTHOR]

The cholesterol-fed rabbit is commonly used as a model to study the vascular effects of hypercholesterolemia and resulting atherosclerotic lesions. Here we undertook a proteomic case-control investigation of ascending aortas from male New Zealand White rabbits after 10 weeks on a high-cholesterol (2% w/w) diet (HCD, n = 5) or control diet (n = 5), in order to determine the changes in response to the HCD. Histology confirmed intimal thickening in the HCD group consistent with atherosclerosis, and LC-MS/MS analysis of individually-obtained ascending aortic extracts labelled with isobaric (iTRAQ) tags enabled the identification and quantitation of 453 unique proteins above the 1% false discovery rate threshold. Of 67 proteins showing significant differences in relative abundance (p < 0.05), 62 were elevated and five decreased in ascending aortas from HCD-fed rabbits compared to controls. Six proteins were selected for validation using Multiple Reaction Monitoring, which confirmed the iTRAQ results. Many of the observed protein changes are consistent with known molecular perturbations in the ascending aorta that occur in response to hypercholesterolemia, e.g. elevation of tissue levels of apolipoproteins, extracellular matrix adhesion proteins, glycolytic enzymes, heat shock proteins and proteins involved in immune defense. We also made a number of novel observations, including a 15-fold elevation of glycoprotein (trans-membrane) nmb-like (Gpnmb) in response to HCD. Gpnmb has previously been linked to angiogenesis but not to atherosclerosis. This and additional novel observations merit further investigation as these perturbations may play important and as yet undiscovered roles in the pathogenesis of atherosclerosis in rabbits as well as humans. [ABSTRACT FROM AUTHOR]

Rainfall infiltration is one of the main triggers of slope failure. Based on the upper bound theorem of limit analysis, this work presents an analytical stability analysis of a 3D vertical cut slope subjected to rainfall infiltration. An analytical model that can directly provide pore water pressure change at any depth and time is adopted to calculate the time-dependent matric suction and shear strength of unsaturated soil during the rainfall infiltration process. Thereafter, based on a 3D rotational failure mechanism of a slope, the energy balance equation is built, and the factor of safety (FoS) of the slope is consequently determined in conjunction with the strength reduction technique. The influences of the 3D characteristics of the slope and rainfall patterns on both FoS and failure pattern of the slope are investigated. It is found that the 3D characteristic of slope is a key factor which determines the FoS of slope. Different rainfall infiltration patterns lead to diverse variation rules of both the FoS solutions and the critical failure patterns of slope. However, these rainfall patterns with a same accumulated rainfall result in the same FoS solution of slope at the end of rainfall infiltration. The present work may provide guidance on the stability analysis and preliminary design of slopes subjected to rainfall infiltration. [ABSTRACT FROM AUTHOR]

Soils are assumed to be homogeneous in most designs of geosynthetic-reinforced earth structures (GRESs), thus ignoring the influences of the possible cohesion and cohesion nonhomogeneity of backfills. However, the actual stability of GRESs is directly influenced by the presence of cohesion and cohesion nonhomogeneity of backfills along with the three-dimensional (3D) character of GRESs. In the present study, a chart-based stability analysis of a 3D GRES composed of nonhomogeneous cohesive backfills subjected to the seismic excitation/pore water pressure is conducted by means of the limit analysis method. Work rates by seismic forces and pore water pressure are calculated based on the pseudo-static method and the pore water pressure coefficient, respectively; thereafter the energy balance equation is derived by equating the external work rates of the soil weight and seismic forces/pore water pressure to the sum of the work rate of the geosynthetics and internal energy dissipation caused by soil cohesion. The analytical expression of the required unfactored reinforcement strength is derived and the optimized solutions are consequently captured. A comparison is drawn to verify the present study and a parametric analysis is conducted thereafter to investigate the effects of the 3D character, cohesion nonhomogeneity, seismic excitation and pore water pressure on the stability of GRESs. Finally, a set of stability charts considering the 3D effects, cohesion nonhomogeneity, seismic force and pore water pressure on long-term stability is proposed for preliminary design purposes. • An advanced 3D failure mechanism is adopted to investigate the stability of GRESs in nonhomogeneous cohesive backfills. • Three different categories of reinforcement patterns are considered. • Analytical expressions of the required unfactored reinforcement strength of 3D GRESs are derived. • The effects of factors such as cohesion nonhomogeneity on stability of GRESs are investigated. • A set of stability charts is proposed for preliminary design purposes. [ABSTRACT FROM AUTHOR]

Identity testing is a critical part in the development of a therapeutic synthetic oligonucleotide. Tandem Mass Spectrometry (MS/MS) is commonly used for the analysis of oligonucleotides to obtain structural and sequence information, however there are challenges resulting from chemical modifications introduced to improve their pharmacokinetics and stability. For these structurally complex oligonucleotides, Nuclear Magnetic Resonance (NMR) Spectroscopy has found limited use for characterisation and identity testing, as only partial NMR resonance assignment for oligonucleotides is achieved without isotopic labelling methodologies. Regardless of the choice of method used for oligonucleotide analysis, the specificity is of critical importance. In this work, in-source dissociation mass spectrometry and proton (1H) and carbon (13C) NMR at high temperature were used to analyse danvatirsen, a 16 nucleotide phosphorothioate antisense oligonucleotide, and its closely related switch sequences. Both approaches have shown specificity to distinguish danvatirsen from these similar sequences. [ABSTRACT FROM AUTHOR]

Huntington's disease (HD) is a genetically-mediated neurodegenerative disorder wherein the aetiological defect is a mutation in the Huntington's gene (HTT), which alters the structure of the huntingtin protein (Htt) through lengthening of its polyglutamine tract, thus initiating a cascade that ultimately leads to premature death. However, neurodegeneration typically manifests in HD only in middle age, and mechanisms linking the causative mutation to brain disease are poorly understood. Brain metabolism is severely perturbed in HD, and some studies have indicated a potential role for mutant Htt as a driver of these metabolic aberrations. Here, our objective was to determine the effects of HD on brain metabolism by measuring levels of polar metabolites in regions known to undergo varying degrees of damage. We performed gas-chromatography/mass spectrometry-based metabolomic analyses in a case-control study of eleven brain regions in short post - mortem -delay human tissue from nine well-characterized HD patients and nine matched controls. In each patient, we measured metabolite content in representative tissue-samples from eleven brain regions that display varying degrees of damage in HD, thus identifying the presence and abundance of 63 different metabolites from several molecular classes, including carbohydrates, amino acids, nucleosides, and neurotransmitters. Robust alterations in regional brain-metabolite abundances were observed in HD patients: these included changes in levels of small molecules that play important roles as intermediates in the tricarboxylic-acid and urea cycles, and amino-acid metabolism. Our findings point to widespread disruption of brain metabolism and indicate a complex phenotype beyond the gradient of neuropathologic damage observed in HD brain. [ABSTRACT FROM AUTHOR]

Several recent studies have uncovered the presence of widespread urea elevations in multiple neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease dementia (PDD), vascular dementia (VaD), and Huntington's disease (HD). However, it is currently unknown whether dementia with Lewy bodies also shows these alterations in urea. This study aimed to investigate if and where urea is perturbed in the DLB brain. Tissues from ten brain regions were obtained from 20 diagnosed cases of DLB and 19 controls. Urea concentrations were measured using ultra-high performance liquid chromatography–tandem mass spectrometry (UHPLC–MS/MS). Case–control differences were assessed by nonparametric Mann-Whitney U tests, and s-values, E-values, effect sizes, and risk ratios were determined for each brain region. The results were compared to those previously obtained for AD, PDD, VaD, and HD. As with other previously investigated dementia diseases, DLB shows widespread urea elevations, affecting all ten regions investigated in the current study; the degree of these elevations is lower than that seen in AD or PDD, similar to that seen in HD, and higher than that observed in VaD. The highest urea fold-change was observed in the pons and the lowest in the primary visual cortex. Urea elevations appear to be a shared alterations across at least five neurodegenerative diseases, despite their many differences in clinical and neuropathological presentation. The cause and effects of this perturbation should be the focus of future studies, for its possible contributions to the pathology of these conditions. • Substantial increases were found in ten of ten investigated regions of the DLB brain. • Alzheimer's, Huntington's, Parkinson's disease, and vascular dementia also show elevated urea. • The urea levels observed are similar to those seen in chronic kidney disease. • It is currently unknown where how these high concentrations of urea originate from. • Urea may present a common pathogenic alteration across different dementias. [ABSTRACT FROM AUTHOR]

The uncertain mechanical parameters of clay layer under torrential rain are the key to the dynamic evolution process and stability assessment of landslide geological hazards. Due to the complex environment, engineering geology and physical chemistry process, the mechanical parameters of clay layer show significant spatial variability and correlation. In addition, due to technical and economic conditions constraints, the actual investigation and test data of soft cohesive soil are very limited, which seriously restricts the stability evaluation of clay slope and the prevention of instability disaster. To characterize anisotropic spatial variations of uncertain mechanical parameters for clay layer using incomplete probability data, the elastic modulus, Poisson ratio and shear strength under saturated conditions were measured, and statistical data and variation properties of uncertain mechanical parameters were analyzed. A modeling approach was proposed for characterizing incomplete probability data of clay layer. The accuracy of the proposed approach is verified by comparison of the statistical characteristic for measured data and simulated data. A novel linear fitting method was proposed for assessing scale of fluctuation and autocorrelation distances. The variability and correlation of uncertain mechanical properties for soft cohesive soil layer are discussed. The results show that the mechanical properties of the clay layer are uncertain in spatial position. Both the original observation data and the simulated data of three mechanical parameters have symmetrical correlation structure. The clay layer display the horizontal layered structure on the soil profile, and the vertical autocorrelation distances are shorter than the horizontal distances. This paper clearly illustrates the anisotropic spatial variations of uncertain mechanical parameters for clay layer using incomplete probability data and it can provide scientific data for the uncertainty analysis and risk assessment of clay slope under torrential rain conditions. • A modeling approach was proposed for characterizing incomplete probability data of clay layer. • Statistical data and variation properties of uncertain mechanical parameters were analyzed. • A novel linear fitting method was proposed for assessing scale of fluctuation of spatial variations. • Variability and correlation of uncertain mechanical properties for clay layer were discussed. [ABSTRACT FROM AUTHOR]

Abstract This study aimed at investigating the molecular level organization and photoluminescence in the interlayer space of magadiite (mag) synthesized by the process of solid-state intercalation. Host-guest composites were prepared by an easy grinding process without other operation. Detailed structural investigations were performed by powder X-ray diffraction (XRD), inductively coupled plasma atomic emission spectroscopy (ICP-AES), energy-dispersive X-ray spectrometer (EDS), X-ray photoelectron spectroscopy (XPS), Fourier-transform infrared spectroscopy (FTIR), Thermo-gravimetric analysis and differential thermal analysis (TGA/DTA), field emission scanning electron microscopy (FE-SEM), Ultraviolet-visible spectroscopy (UV–Vis), photoluminescence (PL) and inverted fluorescence microscope. Results confirmed that 8-hydroxyquinoline (8Hq) was intercalated in the interlayer space of mag in the presence of various metal ions (Ca2+, Zn2+ and Mn2+) inside. Basal spacings between silicate layers were controlled by exchanged metal ions and decorated 8Hq. Solid-state intercalation resulted in the lower proportion of intercalated 8Hq, but good luminescence was observed by PL. The complexes in the interlayer space showed special fluorescence properties. A speculative mechanism was proposed for reaction by solid-solid intercalation. This study provided a message for understanding the functional properties of composites 8Hq/Ca, Zn, Mn-mags, such as loading capacity and photoluminescence properties. Graphical abstract Unlabelled Image Highlights • The intercalation of 8Hq into Ca-, Zn-, Mn-magadiite were prepared. • A speculate mechanism is proposed by the combination of solid-solid intercalation. • The addition of the mag influence the fluorescence of the metal-chelates in the confined spaces. [ABSTRACT FROM AUTHOR]

The seismic soil response and soil-buried infrastructure interaction are of immense importance for the resilience of urban centres. Shake table testing offers an efficient tool for modeling the seismic soil-structure interaction. This paper presents the design and commissioning of a suspended continuum soil box supported on an array of shake tables to enable simulating homogeneity and inhomogeneity of soil and non-uniform seismic excitation of extended buried structures such as pipelines and tunnels. The large-scale shaking table model involves a steel box 7.3 m × 1.4 m × 1.2 m supported by 3 shake tables. It comprises 3 active rigid boxes (2 end boxes and one middle box) supported on 3 shaking tables and 2 passive (suspended) soft joint boxes to provide continuous soil medium. The continuous box design is modular and allows its expansion to be supported by the available 9 shaking tables for even much longer soil continuum model. The developed test setup was used to investigate the seismic response of free-field soil to verify the performance of the soil continuum box. The sand test model was instrumented with arrays of accelerometers embedded along its height within both rigid and suspended boxes to evaluate the effect of the test setup on the ground motion characteristics in both segments. Dynamic performance of the continuum box is examined by comparing the results of shaking table tests on the box empty and box containing a sand model. The results demonstrat that the soil box did not experience resonance with the sand model, hence it did not affect its response to the shaking. A quantitative analysis is conducted to evaluate the box boundary effects on the soil seismic response in terms of the L2-norm, μ , the acceleration time history waveform and Fourier spectrum characteristics at soil surface and 0.7m below surface. The consistency of surface peak acceleration under different seismic excitations and intensity levels are compared in terms of standard deviation, β. The results demonstrat that the developed suspended continuum model box performed well and can simulate the continuity and boundary conditions of free-field. • A suspended continuum modeling box for multi-array shaking table test for long underground structures is developed. • A shaking table test for long-line underground structures under multi-point non-uniform seismic excitation is performed. • Dynamic performance of the modeling box is examined. • A quantitative analysis is conducted to evaluate the box boundary effects of the modeling box based on the L2-norm, μ. • The consistency of surface peak acceleration is compared in terms of standard deviation, β. [ABSTRACT FROM AUTHOR]