A Nationwide Nitrogen Deposition Monitoring Network (NNDMN) containing 43 monitoring sites was established in China to measure gaseous NH3, NO2, and HNO3 and particulate NH4+ and NO3− in air and/or ...precipitation from 2010 to 2014. Wet/bulk deposition fluxes of Nr species were collected by precipitation gauge method and measured by continuous-flow analyzer; dry deposition fluxes were estimated using airborne concentration measurements and inferential models. Our observations reveal large spatial variations of atmospheric Nr concentrations and dry and wet/bulk Nr deposition. On a national basis, the annual average concentrations (1.3–47.0 μg N m−3) and dry plus wet/bulk deposition fluxes (2.9–83.3 kg N ha−1 yr−1) of inorganic Nr species are ranked by land use as urban > rural > background sites and by regions as north China > southeast China > southwest China > northeast China > northwest China > Tibetan Plateau, reflecting the impact of anthropogenic Nr emission. Average dry and wet/bulk N deposition fluxes were 20.6 ± 11.2 (mean ± standard deviation) and 19.3 ± 9.2 kg N ha−1 yr−1 across China, with reduced N deposition dominating both dry and wet/bulk deposition. Our results suggest atmospheric dry N deposition is equally important to wet/bulk N deposition at the national scale. Therefore, both deposition forms should be included when considering the impacts of N deposition on environment and ecosystem health.
The effects of quenching and tempering on the microstructure evolution and bake hardening (BH) behavior of both ferrite and dual phase steels were investigated. The C–Mn steels were heated to the ...soaking temperature, quenched in water and then tempered in the 100–500°C range. After pre-straining, the baking treatment (180°C for 20min) was carried out to measure the BH values. It was found that increased quenching temperature reduced the BH value. Furthermore, the BH value turned to be negative when the quenching temperature exceeded 670°C and 710°C for the steels annealed at 800°C and 900°C, respectively. The ferrite aging and the martensite tempering played key roles in the bake hardening behavior during the tempering process. In the present study, three stages were identified during tempering of the above steels: (1) the relief of residual stresses in the ferrite; (2) the precipitation of carbides in both ferrite and martensite; (3) the dissolution of carbides in the ferrite. The BH values of both ferrite and dual phase steels had a complex variation with the tempering temperature. After an apparent increment, the BH value reduced, and then was slightly enhanced when the tempering temperature increased from 25°C to 500°C.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
•The modified rotating-angle softened-truss model (MRA-STM) is presented.•MRA-STM with the deep-beam analogy is used to analyse RC interior beam–column joints.•Computational scheme and solution ...procedure for the proposed analysis are presented.•The proposed model provides an effective means of solving the problems.
A theoretical model is presented for analysing the shear behaviour and predicting the shear strength of reinforced concrete (RC) interior beam–column joints. The model presented is referred to as the modified rotating-angle softened-truss model (MRA-STM), which is modified from the rotating-angle softened-truss model and the modified compression field theory. In the proposed methodology, the RC interior joint is treated as an RC shear panel that is subjected to vertical and horizontal shear stresses transferred from adjacent columns and beams. Employing the deep beam analogy, the characteristic strut and truss actions typical in beam–column joints are represented by the effective transverse compression stresses and the softened concrete truss in the model. Sixteen RC interior beam–column joints were subsequently analysed with the proposed model. Shear strengths of the RC interior beam–column joints predicted by the proposed model show very good agreement with the experimental results.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Calcineurin inhibitors affect kidney electrolyte handling and blood pressure through an effect on the distal tubule. The second generation calcineurin inhibitor voclosporin causes hypomagnesemia and ...hypercalciuria less often than tacrolimus. This suggests different effects on the distal tubule, but this has not yet been investigated experimentally.
Rats were treated with voclosporin, tacrolimus or vehicle for 28 days. Dosing was based on a pilot experiment to achieve clinically therapeutic concentrations. Drug effects were assessed by electrolyte handling at day 18 and 28, thiazide testing at day 20, telemetric blood pressure recordings, and analysis of mRNA and protein levels of distal tubular transporters at day 28.
Compared to vehicle, tacrolimus but not voclosporin significantly increased the fractional excretions of calcium (>4-fold), magnesium and chloride (both 1.5-fold) and caused hypomagnesemia. Tacrolimus but not voclosporin significantly reduced distal tubular transporters at mRNA and/or protein level, including the sodium-chloride cotransporter, transient receptor melastatin 6, transient receptor potential vanilloid 5, cyclin M2, sodium-calcium exchanger and calbindin-D28K. Tacrolimus but not voclosporin reduced the mRNA level and urinary excretion of epidermal growth factor. The saluretic response to hydrochlorothiazide at day 20 was similar in the voclosporin and vehicle groups, whereas it was lower in the tacrolimus group. The phosphorylated form of the sodium-chloride cotransporter was significantly higher at day 28 in rats treated with voclosporin than in those treated with tacrolimus. Tacrolimus transiently increased blood pressure, whereas voclosporin caused a gradual but persistent increase in blood pressure which was further characterized by high renin, normal aldosterone, and low endothelin-1.
In contrast to tacrolimus, voclosporin does not cause hypercalciuria and hypomagnesemia, but similarly causes hypertension. Our data reveal differences between the distal tubular effects of tacrolimus and voclosporin and provide a pathophysiological basis for the clinically observed differences between the two calcineurin inhibitors.
This paper presents the experimental and analytical studies to investigate the effect of concentrated butt-joints on the flexural properties of laminated bamboo-timber flitch beam (BTFB, or ...bio-flitch beam). The experimental results reveal that the concentrated butt-joints significantly reduce the flexural strength of the BTFB. They also suggest that the failure mechanism of the BTFB with or without concentrated butt-joints are completely different but less evidence shows an obvious effect of the butt-joints on the modulus of elasticity in bending. In addition, laminated bamboo lumber with concentrated butt-joints is found to be unsuitable for structural applications. The analytical predictions are in close agreement with the experimental results that demonstrate the potentials of the proposed analytical model as a forensic investigation instrument to estimate the strength reduction of the structure, if the butt-jointed laminated bamboo was, unfortunately, used in construction.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
The paper presents a new multi-material topology optimization method with a novel adjoint sensitivity analysis that can accommodate not only multiple plasticity but also multiple hardening models for ...individual materials in composite structures. Based on the proposed method, an integrated framework is developed which details the nonlinear finite element analysis, sensitivity analysis and optimization procedure. The proposed method and framework are implemented and illustrated by three numerical examples presented in this paper. An in-depth analysis of the numerical results has revealed the significant impact of the selection of plasticity and hardening model on the results of topology.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Over the last decade, advances in genetic techniques have resulted in the identification of rare hereditary disorders of renal magnesium and salt handling. Nevertheless, approximately 20% of all ...patients with tubulopathy lack a genetic diagnosis.
We performed whole-exome and -genome sequencing of a patient cohort with a novel, inherited, salt-losing tubulopathy; hypomagnesemia; and dilated cardiomyopathy. We also conducted subsequent
functional analyses of identified variants of
, a gene that encodes a small Rag guanosine triphosphatase (GTPase).
In eight children from unrelated families with a tubulopathy characterized by hypomagnesemia, hypokalemia, salt wasting, and nephrocalcinosis, we identified heterozygous missense variants in
that mostly occurred
. Six of these patients also had dilated cardiomyopathy and three underwent heart transplantation. We identified a heterozygous variant in
that segregated with the phenotype in eight members of a large family with similar kidney manifestations. The GTPase RagD, encoded by
, plays a role in mediating amino acid signaling to the mechanistic target of rapamycin complex 1 (mTORC1). RagD expression along the mammalian nephron included the thick ascending limb and the distal convoluted tubule. The identified
variants were shown to induce a constitutive activation of mTOR signaling
.
Our findings establish a novel disease, which we call autosomal dominant kidney hypomagnesemia (ADKH-RRAGD), that combines an electrolyte-losing tubulopathy and dilated cardiomyopathy. The condition is caused by variants in the
gene, which encodes Rag GTPase D; these variants lead to an activation of mTOR signaling, suggesting a critical role of Rag GTPase D for renal electrolyte handling and cardiac function.
Spatially resolved transcriptomic technologies are promising tools to study complex biological processes such as mammalian embryogenesis. However, the imbalance between resolution, gene capture, and ...field of view of current methodologies precludes their systematic application to analyze relatively large and three-dimensional mid- and late-gestation embryos. Here, we combined DNA nanoball (DNB)-patterned arrays and in situ RNA capture to create spatial enhanced resolution omics-sequencing (Stereo-seq). We applied Stereo-seq to generate the mouse organogenesis spatiotemporal transcriptomic atlas (MOSTA), which maps with single-cell resolution and high sensitivity the kinetics and directionality of transcriptional variation during mouse organogenesis. We used this information to gain insight into the molecular basis of spatial cell heterogeneity and cell fate specification in developing tissues such as the dorsal midbrain. Our panoramic atlas will facilitate in-depth investigation of longstanding questions concerning normal and abnormal mammalian development.
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•Stereo-seq enables large field-of-view spatial transcriptomics at cellular resolution•Stereo-seq reveals the spatial cell-type heterogeneity of mouse embryonic tissues•Stereo-seq maps the spatiotemporal transcriptomic dynamics during mouse organogenesis•Stereo-seq defines the spatiotemporal window of developmental disease vulnerability
Stereo-seq combines DNA nanoball-patterned arrays and tissue RNA capture to achieve large field-of-view spatial transcriptomics at cellular resolution, enabling the dissection of spatial cell-type heterogeneity of mouse embryonic tissues.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
2-Hydroxy-ethyl methacrylate (HEMA) is the major component released from resin-modified glass ionomer cements and dental adhesives. Human tissues mainly affected by HEMA are oral epithelium and ...dental pulp. We treated human gingival epithelial S–G cells and pulp fibroblasts (HPF) with various concentrations of HEMA, to evaluate its effects on cell growth, cell cycle progression, intracellular glutathione (GSH) level and reactive oxygen species (ROS) production. HEMA-induced growth inhibition in HPF and S–G cells in a dose-dependent manner, which may be partially explained by induction of cell cycle perturbation. G
2/M phase arrest was noted after exposure of HPF to 5 and 10
m
m of HEMA, concomitant with glutathione depletion and ROS production. S-phase arrest occurred in S–G cells when treated with 2.5 and 5
m
m, while at 10
m
m a sub-G
0/G
1 peak was noted, indicating the potential induction of apoptosis. GSH depletion was marked in S–G cells only at concentrations of 5 and 10
m
m, but excessive ROS production was noted at concentration of 1
m
m and rose with dose increase between 1 and 5
m
m, then lessened at 10
m
m. This suggested that the increase of ROS in S–G cells was not mainly caused by GSH depletion. These results helped to define the mechanism of the cytotoxicity caused by HEMA.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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