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Flowering time plays an important role in crop regional adaptation, yield and reproductive success. ABRE BINDING FACTORs (ABFs) are bZIP transcription factors that participate in various plant biological processes. However, only a few ABFs have been reported to function in controlling flowering time. Here, we identified and characterized the function of the Brachypodium bZIP transcription factor BdABF in controlling flowering time. The results showed that Bdabf mutation in the promoter region promoted early flowering time in Bdabf T-DNA mutants compared with wild-type (WT) plants. Transcriptomic analysis showed that, compared with WT plants, 447 differentially expressed genes (DEGs) (266 upregulated and 181 downregulated) were identified in circadian rhythm, ABA signaling, IAA signaling, and flavonoid biosynthesis pathways in Bdabf mutants. Quantitative reverse transcription–polymerase chain reaction (qRT–PCR) results showed that the expression profiles of these genes in various pathways were consistent with the RNA-seq-based transcriptome dataset. The TF binding element analysis of these genes involved in different pathways in the promoter region showed that bHLH, bZIP, NF-Y, TIFY, and WRKY transcription factors were enriched. Taken together, our results showed that BdABF was involved in controlling flowering time by activating various metabolic pathways and provided new insights into ABFs controlling flowering time in Brachypodium. [ABSTRACT FROM AUTHOR]

An effective numerical analysis process was carried out to simulate an impact event based on the Hashin failure criterion and the Camanho degradation rule. The middle and shoulder of a cylinder were impacted by the edge of square-shaped impactors, and the remaining burst pressure was predicted. The accuracy of the numerical analysis was verified by results of two experiments that proved that the numerical analysis was reliable. The impact damage at different impact energies (20-200 J) was evaluated. According to the analysis carried out, the impact damage of gas cylinders intensified with increasing impact energy, and there existed a critical value of this energy. The damaged area of gas cylinders under the same impact energy first decreases and then increases from the inner to outer layer, and the maximum increase in the residual bursting pressure could reach 9.6%. [ABSTRACT FROM AUTHOR]

In this study, three typical limestones, including Tavel limestone, Indiana limestone, and Lixhe chalk, were selected from a large number of porous limestones. These limestones with different porosities have been largely studied in previous experimental investigations because of the complexity of mechanical behavior. According to previous experimental studies, porous limestones present two basic plastic mechanisms: plastic shear as a response at low confining pressures and plastic pore collapse at high confining pressures. In related to the plastic mechanisms, two types of plastic volumetric deformation are revealed: plastic compaction induced by pore collapse, and plastic dilatancy by plastic shearing. In this paper, a micromechanics-based plastic model is extended to describe the elastoplastic behavior of porous limestones. The plastic criterion of porous rock is explicitly dependent on the porosity in addition to being directly based on the relevant mechanical properties of solid matrix at the microscopic scale. An additional plastic hardening law for the solid matrix is proposed, in which two plastic deformation mechanisms are considered in hardening law of the solid matrix, including hardening effect caused by the local equivalent plastic deformation and weakening effect caused by the increase in porosity. Three typical porous limestones with different porosity are selected to validate the proposed model on both hydrostatic and triaxial compression tests. By comparing numerical predictions and experimental data, it is shown that the presented model can correctly describe the mechanical behavior of porous rocks. Highlights: Limestones with different porosities have been largely studied in previous experimental investigations because of the complexity of mechanical behavior. In related to the plastic mechanisms, two types of plastic volumetric deformation are revealed: plastic compaction induced by pore collapse, and plastic dilatancy by plastic shearing. A micromechanics-based plastic model is extended to describe the elastoplastic behavior of porous limestones. The plastic criterion of porous rock is explicitly dependent on the porosity in addition to being directly based on the relevant mechanical properties of solid matrix at the microscopic scale. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is a complex and refractory malignant tumor, ranking the third cause of cancer-related deaths worldwide. Lenvatinib is currently employed to treat advanced, unresectable HCC as a first-line drug. The purpose of this study was to explore the pharmacological mechanisms of lenvatinib acting on HCC through the analysis of differential expressed genes based on network pharmacology. The target genes of lenvatinib were collected from PubChem, SwissTargetPrediction, PharmMapper, and BATMAN-TCM online public databases. In addition, related gene targets for HCC were obtained using NCBI Gene Expression Omnibus (NCBI-GEO) database. Afterward, the protein-protein interaction (PPI) network was established to visualize and understand the interaction relationships of overlapping gene targets from both lenvatinib and HCC. Furthermore, according to the data obtained, Gene Ontology (GO) analysis indicated that these intersectant genes were mainly enriched in response to xenobiotic stimulus, gland development, ion channel complex, membrane raft, and steroid binding. Besides, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis suggested that the therapeutic effects of lenvatinib on HCC probably involved bile secretion, MAPK signaling pathway, cGMP-PKG signaling pathway, PI3K-Akt signaling pathway, and Ras signaling pathway. Moreover, a total of six key differential genes, namely, ALB, CCND1, ESR1, AR, CCNA2, and AURKA, were identified as most significant targets associated with lenvatinib treating HCC and further verified by molecular docking, which demonstrated that lenvatinib had a strong binding efficiency with these six key gene-encoded proteins. Taken together, this study systematically provided new insights for researchers to determine the intervention mechanisms of lenvatinib in HCC therapy. [ABSTRACT FROM AUTHOR]

Leishmaniasis is an infectious disease caused by protozoan parasites belonging to the genus Leishmania for which there are no approved human vaccines. Infections localise to different tissues in a species-specific manner with the visceral form of the disease caused by Leishmania donovani and L. infantum being the most deadly in humans. Although Leishmania spp. parasites are predominantly intracellular, the visceral disease can be prevented in dogs by vaccinating with a complex mixture of secreted products from cultures of L. infantum promastigotes. With the logic that extracellular parasite proteins make good subunit vaccine candidates because they are directly accessible to vaccine-elicited host antibodies, here we attempt to discover proteins that are essential for in vitro growth and host infection with the goal of identifying subunit vaccine candidates. Using an in silico analysis of the Leishmania donovani genome, we identified 92 genes encoding proteins that are predicted to be secreted or externally anchored to the parasite membrane by a single transmembrane region or a GPI anchor. By selecting a transgenic L. donovani parasite that expresses both luciferase and the Cas9 nuclease, we systematically attempted to target all 92 genes by CRISPR genome editing and identified four that were required for in vitro growth. For fifty-five genes, we infected cohorts of mice with each mutant parasite and by longitudinally quantifying parasitaemia with bioluminescent imaging, showed that nine genes had evidence of an attenuated infection although all ultimately established an infection. Finally, we expressed two genes as full-length soluble recombinant proteins and tested them as subunit vaccine candidates in a murine preclinical infection model. Both proteins elicited significant levels of protection against the uncontrolled development of a splenic infection warranting further investigation as subunit vaccine candidates against this deadly infectious tropical disease. Author summary: Leishmaniasis is a parasitic infectious disease that is responsible for many tens of thousands of human deaths per year, primarily in impoverished parts of the world. Although there are drugs to treat this parasite infection, resistance is emerging and there are no approved human vaccines. Extracellular parasite proteins can make good vaccine targets because they are directly accessible to host antibodies; however, not all parasite surface proteins can elicit protective immune responses. With the goal of identifying new vaccine targets, we selected over 90 genes that encode parasite cell surface and secreted proteins and used the latest CRISPR gene editing technology to individually target them. Using these mutant parasites, we identified four genes required for parasite growth in the laboratory. We expressed two of the proteins as subunit vaccines and a preclinical infection model was used to determine if they could elicit protective immune responses. We found that two of our candidates were able to confer significant levels of protection in a murine model of visceral leishmaniasis. Our study will contribute to the search for a highly effective vaccine against visceral leishmaniasis to improve the lives of people living in some of the poorest regions on the planet. [ABSTRACT FROM AUTHOR]

This study explored the mechanisms underlying the release and transformation of potassium from potassium‐rich minerals in paddy soils derived from purple soils. While potassium is abundant in these minerals, it is typically insoluble and inaccessible to plants. The agricultural practices employed in paddy soils may activate insoluble mineral potassium, potentially reducing potassium fertilizer applications. The activation of mineral potassium not only helps alleviate the dependence on soluble potassium fertilizers in rice cultivation, but also contributes to enhancing food security and sustainable agricultural development. Despite these potential benefits, the transformation pathways of mineral potassium in paddy soils remain unclear, posing an important science question that requires further investigation. This study collected data from a long‐term fertilizer experiment of paddy soils derived from purple soils with abundant potassium‐rich minerals (1982–2019, rice‐wheat rotation). The results revealed that paddy management could drive the transformation of potassium in illite minerals in paddy soils and meet the long‐term growth needs of crops. Submergence reduction significantly increased the concentration of positive ions such as Fe2+ and Ca2+ and provided a pathway for the free movement of ions, promoting the substitution of these ions with interlayer potassium of minerals. This substitution and alternating reduction and oxidation conditions played an important role in the transformation of potassium in illite minerals. The study indicates the promising potential for using crushed illite rocks in rice paddies as a substitute for traditional potassium fertilizers. [ABSTRACT FROM AUTHOR]

Given the severe waste of cold work moulds in the small batch production stage, a low cost 45 steel surface laser cladding Fe901 coating was proposed to replace cold work mould steel in this stage. Combining with the performance requirements of moulds, the laser cladding process parameters were optimized with the coating surface hardness as the goal. The optimized process parameters were laser power, powder feeding rate and scanning speed. 20 runs of cladding tests were carried out based on the central composite design method. Using Design-Expert software, the hardness-process parameter objective function model was obtained, and the reliability of the model was verified. The cladding process parameters were optimized based on the response surface method. It was found that the optimal ranges of laser power were 1600 to 2100 W, scanning speed were 9.5 to 13.0 mm/s and powder feeding rate were 24.0 to 34.0 g/min. This conclusion showed that the coating could reach the hardness index of cold work die steel. [ABSTRACT FROM AUTHOR]

Cosmetics have a long history in China, but their origins remain unclear. Cosmetic industry potentially originated in the Spring and Autumn Period (770–476 bce), but little is known about the early manufacture and use of cosmetics. The Liujiawa site, located on the southern edge of the Loess Plateau in northern China, was the late capital of the ancient Rui state in the early to mid‐Spring and Autumn Period. During the excavation, a sealed small and exquisite container with suspected cosmetic use was unearthed from tomb M49 belonging to a male associated with the aristocratic class. We report in this paper the multidisciplinary application of ATR‐FTIR, XRD, SEM, stable isotope analysis, GC‐MS and GC‐C‐IRMS analysis of the residue inside the container, demonstrating that the residue, which was made of ruminant adipose fat mixed with monohydrocalcite from cave moonmilk, was likely used as cosmetic face cream by the nobleman of the Rui state. This study provides an early example of cosmetic production in China, and, together with the prevalence of similar cosmetic containers during this period, it suggests the rise of an incipient cosmetics industry. Furthermore, the exploitation of moonmilk, a special stalactite in some limestone caves, reflects the link between early Taoist School and cosmetic production encouraged by the aristocratic class. [ABSTRACT FROM AUTHOR]

Two types of Fe-based coatings (Specimen 1 and Specimen 2) were fabricated on a 45 steel by laser cladding with a high power diode laser (HPDL). The microstructure, phase composition and microhardness of the different coatings were investigated and the wear resistance was analysed. The results showed that the bottom, middle and upper parts of the clad layers exhibited different microstructures: the dominant phases of both specimens were α-Fe martensite and Cr23C6 hard phase. The two Fe-based coatings were also compared to a Cr12MoV die steel. the microhardness of Specimen 1 was significantly higher than that of the Cr12MoV die steel. The presence of the Cr23C6 hard phase in the clad layers of Specimen 1 and Specimen 2 reduced the wear weight loss and the width and depth of the wear scars compared with the Cr12MoV die steel. [ABSTRACT FROM AUTHOR]

Flexible job shop Scheduling problem (FJSP) is a classic problem in combinatorial optimization and a very common form of organization in a real production environment. Traditional approaches for FJSP are ill-suited to deal with complex and changeable production environments. Based on 3D disjunctive graph dispatching, this work proposes an end-to-end deep reinforcement learning (DRL) framework. In this framework, a modified pointer network, which consists of an encoder and a decoder, is adopted to encode the operations to be scheduled according to the selected scheduling features. Then with the attention mechanism, an input is pointed as an action in each decoding step, and a recurrent neural network (RNN) is used to model the decoder network. To train the network to minimize the makespan, a policy gradient algorithm is applied to optimize its parameters. The trained model generates the scheduling solution as a sequence of consecutive actions in real-time without retraining for every new problem instance. Experimental results show that this method can obtain better performance than the classic heuristic rules when only one model is trained on all the test instances. [ABSTRACT FROM AUTHOR]

This study investigates the thermal performance of cryogenic micro-pin fin coolers for high-power laser diode (LD) bars. An open-loop liquid nitrogen cooling system, used to operate LD bars at cryogenic temperatures, is developed and characterized. The comparison study demonstrates that the total thermal resistance value of the micro-pin fin cooler, ranging from 0.03 to 0.04 °C/W, is only 1/3 of that of the micro-gap cooler and, thus, contributes significantly to reducing the LD operating temperature and enhancing its efficiency. In this study, the peak optical power of 68.8 W was observed at an LD bar package base temperature of − 100 °C, providing a 20% increase relative to the optical power of 57.3 W for a nominal operating condition with an LD bar package base temperature of 41 °C. This result clearly illustrates the enhancement in optical performance made possible by cryogenic cooling with a pin fin microcooler. [ABSTRACT FROM AUTHOR]

Vacuole membrane proteins play a critical role in the regulation of plant physiological processes including normal growth and development, and responses to stresses. The killing me slowly 1 (KMS1) gene that encodes a soluble N-ethylmaleimide-sensitive fusion attachment receptor (SNARE) domain-containing vacuole membrane protein was first reported in Arabidopsis. Currently, the function of KMS1 in other plants under stress is poorly understood. In this study, we report cloning, expression, and characterization of a novel KMS1 gene in alfalfa (Medicago sativa L.), designated MsKMS1 (GenBank accession No. JX467688). The full-length cDNA of MsKMS1 was 1 396 bp and contained a complete open reading frame of 1 257 bp, which encoded a putative protein of 418 amino acids. The BLASTp analysis showed that MsKMS1 shared high amino acid sequence similarities with KMS1 from other plants such as Medicago truncatula (99 %), Cicer arietinum (89 %), Glycine max (77 %), Prunus mume (76 %), Ricinus communis (72 %), Populus euphratica (72 %), Theobroma cacao (72 %), and Arabidopsis thaliana (67 %). Transient transformation of onion (Allium cepa) bulb scale epidermal cells by biolistic bombardment showed that MsKMS1 was localized to the plasma membrane. Quantitative real-time PCR revealed that MsKMS1 expression was upregulated under different abiotic stresses (200 mM NaCl, 20 % (m/v) polyethylene glycol 6000] and 10 mg dm-3 abscisic acid. Transgenic tobacco plants were obtained via Agrobacterium-mediated transformation and treated with 200 mM NaCl. Reverse-transcription PCR data showed that MsKMS1 was successfully transcribed and expressed in the leaves of transgenic plants. The MsKMS1-overexpressors showed a lower malondialdehyde content and maintained a higher relative water content and proline content compared with non-transgenic controls under salt stress. These results indicate that the introduction of the MsKMS1 gene could improve salt stress resistance in tobacco plants. This study reveals the role of MsKMS1 in the regulation of plant responses to abiotic stress and provides evidence for further functional studies of the KMS1 family in alfalfa. [ABSTRACT FROM AUTHOR]

In this article, a pair of wavelets for Hermite cubic spline bases are presented. These wavelets are in C 1 and supported on [ − 1 , 1 ]. These spline wavelets are then adapted to the interval [ 0 , 1 ] and we prove that they form a Riesz wavelet in L 2 ([ 0 , 1 ]). The wavelet bases are used to solve the linear optimal control problems. The operational matrices of integration and product are then utilised to reduce the given optimisation problems to the system of algebraic equations. Because of the sparsity nature of these matrices, this method is computationally very attractive and reduces CPU time and computer memory. In order to save the memory requirement and computation time, a threshold procedure is applied to obtain algebraic equations. Illustrative examples are included to demonstrate the validity and applicability of the technique. [ABSTRACT FROM AUTHOR]

The U.S. Spallation Neutron Source (SNS) is a state-of-the-art neutron scattering facility delivering the world's most intense pulsed neutron beams to a wide array of instruments, which are used to conduct investigations in many fields of engineering, physics, chemistry, material science, and biology. Neutrons are produced by spallation of liquid Hg by the bombardment of short (∼1 µs), intense (∼35 A) pulses of protons delivered at 60 Hz by an accumulator ring which is fed by a high-intensity, 1 GeV, H− LINAC (linear accelerator). This facility has operated nearly continuously since 2006 but has recently undergone a 4-month maintenance period, which featured a complete replacement of the 2.5 MeV injector feeding the LINAC. The new injector was developed at ORNL in an off-line beam test facility and consists of an ion source, low energy beam transport, and a Radio Frequency Quadrupole (RFQ). This report first describes the installed configuration of the new injector detailing the ion source system. The first beam current, RFQ transmission, emittance, and energy measurements from the injector installed on the SNS are reported. These data not only show a significant performance improvement for our existing facility but will also make accessible the higher beam current requirements for future SNS upgrade projects: the proton power upgrade and second target station. [ABSTRACT FROM AUTHOR]

A novel E-shaped symmetric configuration is proposed and implemented to document deformation evolutions of single-grain solder joints with different orientations. The configuration is fabricated from two metals with different coefficient of thermal expansions to produce precisely-controlled shear-dominant loading to solder joints when subjected to a thermal excursion. Cooling rates during solder solidification are controlled to produce joints with a large single grain of Sn-based Pb-free solder. Moiré interferometry is employed to measure the detailed in-situ deformations of single grain solder joints during a thermal cycle of −40 °C to 125 °C. The results are analyzed to provide the history of grain orientation-dependent inelastic strain evolutions. The results are aimed at calibrating and verifying the anisotropic constitutive models developed for Sn-based Pb-free solder alloys. [ABSTRACT FROM AUTHOR]

Nanoscale composition fluctuations in InGaN alloy epitaxial layers have been investigated by optical transmission spectroscopy and near-field scanning optical microscopy. A spatial variation of the optical transmission at 488 nm is observed, which is attributed to an inhomogeneous indium distribution. Both the characteristic wavelength and the normalized root mean square magnitude of the compositional fluctuations increase with increasing In concentration. The fluctuations are well described in terms of a spinodal decomposition model. [ABSTRACT FROM AUTHOR]

Composition fluctuations in GaN:Mg have been investigated by optical transmission spectroscopy, near-field scanning optical microscopy (NSOM), and scanning Kelvin probe microscopy (SKPM). An Urbach tail is observed in the optical transmission spectrum of heavily Mg-doped GaN, with the magnitude of Urbach energy increasing with increasing compositional/potential fluctuations. From the relationship between the Urbach energy and the potential fluctuation magnitude, the spatial size of the compositional fluctuations in GaN:Mg (with the average Mg concentration of ∼4×1019 cm-3) is calculated to be 220 nm. The nanoscale compositional fluctuations are determined by NSOM and SKPM. A spatial variation of the transmission mode NSOM intensity is observed with a characteristic wavelength of ∼300 nm, which is attributed to the inhomogeneous distribution of Mg. The normalized root-mean-square (rms) fluctuation of the transmission mode NSOM intensity for heavily Mg-doped GaN is a factor of 5 greater than that for undoped GaN. Similar microstructure patterns are observed in the NSOM and surface potential images of GaN:Mg as probed by SKPM. The variation of local surface potential (on the order of 100 mV) is attributed to the same compositional fluctuations of Mg, which changes the local surface work function. The local Mg concentrations are calculated from the SKPM image. For GaN:Mg with the Mg concentration of 4×1019 cm-3, a rms value of 5.4×1019 cm-3 of the compositional fluctuations has been observed. [ABSTRACT FROM AUTHOR]

Anthocyanins are important secondary metabolites in wheat. Although some genes involved in anthocyanin biosynthesis had been reported, a more depth understanding of molecular mechanisms underlying wheat anthocyanin biosynthesis is needed. In this study, we found that the anthocyanin content of Ziyou-5 was significantly higher than that of Liangxing-66. Further the transcriptome analysis between the wheat varieties Liangxing-66 (yellow wheat) and Ziyou-5 (purple wheat) were performed and the results showed that 9906 (3772 downregulated, 6134 upregulated) differentially expressed genes (DEGs) were detected and mainly enriched in the flavonoid biosynthesis, plant hormone, phenolamides and antioxidant pathways. The qRT–PCR results showed that the transcription profiles of these DEGs were consistent with transcriptomic data. Co-expression analysis revealed that the transcription factors, such as ERF, bHLH, and MYB were involved in the regulation of these genes in different pathways. Thus, our study will provide new insights on molecular mechanisms underlying wheat anthocyanin biosynthesis and provide some candidate genes for wheat breeding. [ABSTRACT FROM AUTHOR]

Qaidam Cashmere goat is one of the few animals that can survive in the harsh environment of the Qinghai-Tibet Plateau and the adjacent alpine areas. It has a strong adaptability, thus shaping the genetic diversity of goat phenotype, morphology, physiology and other aspects. However, the molecular basis behind these genetic mechanisms remains unclear. Here, we conducted genome-wide studies of genetic variation in two different morphologies and geographical coordinates in indigenous Chinese goats to identify selective signaling in genomic regions. In the present study, we resequenced 10 high-altitude Chinese indigenous goat breeds and compared them with low-altitude goats. By combining p and Fst values, we identified 1277 overlapping selection regions that may contribute to the wool fiber traits, reproductive performance, and high-altitude adaptation of goats. Candidate genes enriched in selected regions are associated with the phenotypes in cashmere fiber traits (IGFBP3, TNF, ROCK1, WNT10B, KITLG), reproduction traits (CAMK2D, IL-18, ESR1, ANAPC13), body size (POMC), hypoxic adaptation (TH, ACER1, GNB1, HIF1A) and disease (IL-10). This study provided valuable genetic information for the basis of biological characteristics and genetic improvement of breeds. [ABSTRACT FROM AUTHOR]

Monolayer MoNx and nano-multilayer CrN/Mo 2 N coatings were prepared by arc ion plating and characterized by X-ray diffractometry (XRD), transmission electron microscopy (TEM), friction tester and hardness tester. The results from TEM and XRD analysis showed that the crystal structure of MoNx and CrN/Mo 2 N coatings has a cubic lattice structure. The microhardness of MoNx coatings deposited at lower N 2 pressure is about 2100 HV which is higher than 1950 HV of the coatings deposited at higher N 2 pressure. The variation of friction coefficient of MoNx coatings influenced by N 2 pressure is obvious at higher N 2 pressure. The modulation period of CrN/Mo 2 N coatings is from 58.5 nm to 11.17 nm with increasing substrate rotation speed (Srs) in the range of 1–5 rpm. The maximum hardness of CrN/Mo 2 N nanomultilayer coatings, when the Srs is 7 rpm, is approximately 2950 HV. The value is 1.5 times higher than those of the MoNx monolayer coating (2000 HV). These enhancement effects in superlattice films could be attributed to the resistance to dislocation glide across interface between the MoN and CrN layers. The value of average friction coefficient of CrN/Mo 2 N nanomultilayer coatings is about 0.33 which is higher than 0.3 of MoNx coatings and lower than 0.6 of CrN. The wear rate of CrN/Mo 2 N nanomultilayer coatings is about 7 × 10−7 mm3/N·m which is obviously lower than 3.3 × 10−6 mm3/N·m of CrN coatings and higher than 1.2 × 10−7 mm3/N·m of MoNx coatings. • Monolayer MoNx and nanomultilayer CrN/Mo 2 N coatings were prepared by arc ion plating system. • The N 2 pressure exhibits great effects on the structure and properties of MoNx coatings. • The substrate rotation speed exhibits great effects on the hardness of CrN/Mo 2 N nanomultilayer coatings. [ABSTRACT FROM AUTHOR]

Tungsten oxide sol, containing highly crystalline nanoparticles of orthorhombic WO3 and having good sedimentation stability, was synthesized using a facile, ultrasonic-assisted technique. An additional steric stabilizer, dextran, was proposed to enhance the stability of WO3 nanoparticles in biological media and to reduce their in vivo toxicity. The cytotoxicity of dextran-stabilized and nonstabilized WO3 sols was studied in vitro using dental pulp stem (DPS) cell lines and breast cancer (MCF-7) cell lines. Both tungsten oxide sols demonstrated low cytotoxicity and low genotoxicity for both stem cells and malignant cells and only slightly reduced their metabolic activity in the concentration range studied (from 0.2 to 200 μg/ml). The data obtained support possible theranostic applications of tungsten oxide colloidal solutions. [ABSTRACT FROM AUTHOR]

This study is devoted to experimental investigation of effects of pore pressure on plastic deformation and failure of a water-saturated limestone. The experimental study is composed of three different groups of laboratory tests. The basic mechanical behavior of the rock is first characterized by drained triaxial compression tests on water-saturated samples without pore pressure. The results are compared with those obtained in a previous study from triaxial compression tests on saturated samples with a constant pore pressure. In the second group, water injection tests under a confining pressure of 20 MPa and different values of deviatoric stress are realized to study the effect of pore pressure increase. Finally, undrained triaxial compression tests are carried out for investigating the coupling effect of plastic deformation and pore pressure variation. Based on experimental data, the validity of effective stress concept for plastic yielding and failure strength is discussed. [ABSTRACT FROM AUTHOR]

Summary: Previously, we identified by RNA sequencing that DDIT3, RPL23A, SESN2 and NR4A1 genes were significantly differentially expressed between the mammary glands of lactating Holstein cows with extremely high and low milk protein and fat percentages; thus, these four genes are considered as promising candidates potentially affecting milk yield and composition traits in dairy cattle. In the present study, we further verified whether these genes have genetic effects on milk traits in a Chinese Holstein population. By re‐sequencing part of the non‐coding and the entire coding regions of the DDIT3, RPL23A, SESN2 and NR4A1 genes, a total of 35 SNPs and three insertions/deletions were identified, of which three were found in DDIT3, 12 in RPL23A, 16 in SESN2 and seven in NR4A1. Moreover, two of the insertions/deletions—g.125714860_125714872del and g.125714806delinsCCCC in SESN2—were novel and have not been reported previously. Subsequent single SNP analyses revealed multiple significant association with all 35 SNPs and three indels regressed against the dairy production traits (P‐value = <0.0001–0.0493). In addition, with a linkage disequilibrium analysis, we found one, one, three, and one haplotype blocks in the DDIT3, RPL23A, SESN2 and NR4A1 genes respectively. Haplotype‐based association analyses revealed that some haplotypes were also significantly associated with milk production traits (P‐value = <0.0001–0.0461). We also found that 12 SNPs and two indels (two in DDIT3, two in RPL23A, nine in SESN2 and one in NR4A1) altered the specific transcription factor binding sites in the promoter, thereby regulating promoter activity, suggesting that they might be promising potential functional variants for milk traits. In summary, our findings first determined the genetic associations of DDIT3, RPL23A, SESN2 and NR4A1 with milk yield and composition traits in dairy cattle and also suggested potentially causal variants, which require in‐depth validation. [ABSTRACT FROM AUTHOR]

When vertebrates face acute stressors, their bodies rapidly undergo a repertoire of physiological and behavioral adaptations, which is termed the stress response. Rapid changes in heart rate and blood glucose levels occur via the interaction of glucocorticoids and their cognate receptors following hypothalamic‐pituitary‐adrenal axis activation. These physiological changes are observed within minutes of encountering a stressor and the rapid time domain rules out genomic responses that require gene expression changes. Although behavioral changes corresponding to physiological changes are commonly observed, it is not clearly understood to what extent hypothalamic‐pituitary‐adrenal axis activation dictates adaptive behavior. We hypothesized that rapid locomotor response to acute stressors in zebrafish requires hypothalamic‐pituitary‐interrenal (HPI) axis activation. In teleost fish, interrenal cells are functionally homologous to the adrenocortical layer. We derived eight frameshift mutants in genes involved in HPI axis function: two mutants in exon 2 of mc2r (adrenocorticotropic hormone receptor), five in exon 2 or 5 of nr3c1 (glucocorticoid receptor [GR]) and two in exon 2 of nr3c2 (mineralocorticoid receptor [MR]). Exposing larval zebrafish to mild environmental stressors, acute changes in salinity or light illumination, results in a rapid locomotor response. We show that this locomotor response requires a functioning HPI axis via the action of mc2r and the canonical GR encoded by nr3c1 gene, but not MR (nr3c2). Our rapid behavioral assay paradigm based on HPI axis biology can be used to screen for genetic and environmental modifiers of the hypothalamic‐pituitary‐adrenal axis and to investigate the effects of corticosteroids and their cognate receptor interactions on behavior. Hypothalamic‐pituitary‐adrenocortical axis and glucocorticoid receptor (nr3c1) are required for rapid locomotor response to acute environmental stressors. [ABSTRACT FROM AUTHOR]

Aluminum foam was limited when applied as load carrying structures for its lower strength. Therefore, an effective enhancement method of aluminum foam was reported in the present study by filling of 304 stainless steel tube into a pre-perforated hole and fixed by epoxy glue. The experimental results indicate that the novel tube enhanced foam (with equivalent density of foam) can doubled the specific compressive strength and energy absorption of that of aluminum foam, and even larger than that of the sum of tube and foam which were tested separately. The coupling strengthening mechanisms are suggested to be the instability limitation of steel tube due to the lateral supports (external and internal) supplied by aluminum foam. [ABSTRACT FROM AUTHOR]

The feasibility of laser perforation on two typical rocks (high strength granite and low strength sandstone) was investigated to develop an alternative drilling technique to overcome the ubiquitous problems in the present mechanical drilling technology. The results showed that for granite and sandstone samples, both laser perforation depth and specific energy increase with prolonging laser irradiating duration. As for granite, the laser perforation induced fracture mechanism was attributed to cleavage, with secondary cracks and numerous regular small platforms on the fracture surfaces. For sandstone samples, clean laser perforated holes consisting of a grey glaze layer and a brown heat affected zone (HAZ) were found, with secondary cracks existing in the inner walls. Meanwhile, obvious cavity and large voids could be easily found in the HAZ, which might be helpful for breaking the cementations and mineral grains. Of significance, laser perforation could lead to reduced mechanical performance of both granite and sandstone; for example, after laser perforation with nine holes, granite and sandstone exhibited compressive strengths of 51.48 and 8.92 MPa, respectively. This is approximately only a quarter of their original values, indicating the feasibility of rock fragment by laser technology. [ABSTRACT FROM AUTHOR]

Summary: Background: Chronic viral hepatitis is linked to fibrotic liver injury that can progress to liver cirrhosis with its associated complications. Recent evidence suggests a role of senescence in liver fibrosis, although the senescence regulators contributing to fibrosis progression remain unclear. Aim: To investigate the role of senescence and different senescence markers for fibrosis progression in patients with chronic hepatitis C virus (HCV) infection. Methods: The expression of the cell cycle inhibitors p21, p27 and p16 as well as the senescence markers p‐HP1γ and γ‐H2AX was analysed in liver tissue with different fibrosis stages. Senescence‐associated chitotriosidase activity was measured in sera of HCV patients (n = 61) and age‐matched healthy individuals (n = 22). Results: We found a remarkable up‐regulation of the cell cycle inhibitors and senescence markers in chronic HCV infection compared to healthy liver tissue. Liver tissue with relevant fibrosis stages (F2‐3) or cirrhosis (F4) revealed a significant increase in senescent cells compared to livers with no or minimal fibrosis (F0‐1). In cirrhotic livers, a significantly higher number of p‐HP1γ, p21 and p27 positive cells was detected compared to liver tissue with F2‐3 fibrosis. Importantly, we identified T‐cells as the dominant cell type contributing to increased senescence during fibrosis progression. Compared to healthy individuals, serum chitotriosidase was significantly elevated and correlated with histological fibrosis stages and liver stiffness as assessed by transient elastography. Conclusions: Senescence of hepatic T‐cells is enhanced in chronic viral hepatitis and increases with fibrosis progression. Serological detection of senescence‐associated chitotriosidase might allow for the non‐invasive detection of relevant fibrosis stages. [ABSTRACT FROM AUTHOR]

The strong light-matter interaction in transition metal dichalcogenide (TMD) monolayers (MLs) is governed by robust excitons. Important progress has been made to control the dielectric environment surrounding the MLs, especially through hexagonal boron nitride (hBN) encapsulation which drastically reduces the inhomogeneous contribution to the exciton linewidth. Most studies use exfoliated hBN from high quality flakes grown under high pressure. In this work, we show that hBN grown by molecular beam epitaxy (MBE) over a large surface area substrate has a similarly positive impact on the optical emission from TMD MLs. We deposit MoS2 and MoSe2 MLs on ultrathin hBN films (few MLs thick) grown on Ni/MgO(111) by MBE. Then, we cover them with exfoliated hBN to finally obtain an encapsulated sample: exfoliated hBN/TMD ML/MBE hBN. We observe improved optical quality of our samples compared to TMD MLs exfoliated directly on SiO2 substrates. Our results suggest that hBN grown by MBE could be used as a flat and charge-free substrate for fabricating TMD-based heterostructures on a larger scale. [ABSTRACT FROM AUTHOR]

Previous metabolic studies have demonstrated that leishmania parasites are able to synthesise proline from glutamic acid and threonine from aspartic acid. The first committed step in both biosynthetic pathways involves an amino acid kinase, either a glutamate 5‐kinase (G5K; EC2.7.2.11) or an aspartokinase ( EC2.7.2.4). Bioinformatic analysis of multiple leishmania genomes identifies a single amino acid‐kinase gene (LdBPK 262740.1) variously annotated as either a putative glutamate or aspartate kinase. To establish the catalytic function of this Leishmania donovani gene product, we have determined the physical and kinetic properties of the recombinant enzyme purified from Escherichia coli. The findings indicate that the enzyme is a bona fide G5K with no activity as an aspartokinase. Tetrameric G5K displays kinetic behaviour similar to its bacterial orthologues and is allosterically regulated by proline, the end product of the pathway. The structure‐activity relationships of proline analogues as inhibitors are broadly similar to the bacterial enzyme. However, unlike G5K from E. coli, leishmania G5K lacks a C‐terminal PUA (pseudouridine synthase and archaeosine transglycosylase) domain and does not undergo higher oligomerisation in the presence of proline. Gene replacement studies are suggestive, but not conclusive that G5K is essential. Enzymes: Glutamate 5‐kinase ( EC2.7.2.11); aspartokinase ( EC2.7.2.4). [ABSTRACT FROM AUTHOR]

Owing to the repeatedly observed strong vertical ground motions and compressional damage of engineering structures in recent earthquakes, the multi-directional site response analysis is increasingly critical for the seismic design of important structures, such as nuclear power plants and high earth dams. However, the site response to the vertical component of the ground motion has not been the subject of detailed investigation in the literature. Therefore, in this paper, the vertical site response due to vertical ground motion is investigated by employing both analytical and numerical methods. First, a one-dimensional frequency domain analytical solution, which can be employed for vertical site response analysis in practice, is studied and compared against time domain finite-element (FE) analyses for the two extreme soil state conditions (i.e. undrained and drained conditions). The vertical site response is further investigated with hydro-mechanically (HM) coupled FE analysis, considering solid-fluid interaction. The parametric studies undertaken show that the predicted vertical site response is strongly affected by the parameters characterising the hydraulic phase, namely, soil permeability and soil state conditions, both in terms of frequency content and amplification. The subsequent corresponding quantitative investigation, of the frequency content and amplification function of the vertical site response, shows that depending on the soil permeability the response is dominated by the two types of compressional waves (fast and slow waves). Notably, the parametric studies identify a range of permeability that significantly affects dynamic soil properties in terms of P-wave velocities, damping ratios and vertical site response, and this range is relevant for geotechnical earthquake engineering applications. It is therefore recommended that coupled consolidation analysis is necessary to simulate this effect accurately at such permeability-dependent intermediate transient states between fully undrained and drained conditions. Finally, this work suggests a simple modification of standard total-stress site response analysis to account for vertical ground motion and solid-pore fluid interaction. In order to simulate the attenuation of the response due to solid-pore fluid interaction effects, it is suggested to employ additional HM viscous damping in total-stress analysis, further to the one used to account for hysteretic material damping. This additional viscous damping can be quantified based on the empirical curves proposed in the paper. [ABSTRACT FROM AUTHOR]

Summary: Previously, we re‐sequenced the whole genomes of eight Holstein bulls with high or low milk protein and fat percentage, and we detected two indels in the ACACB (acetyl‐CoA carboxylase beta) gene that were polymorphic between the two groups. Thus, we considered ACACB as a promising candidate gene potentially affecting milk composition traits. Herein, we verified the genetic effects of ACACB on five milk traits in a Chinese Holstein population. We identified six SNPs in the 5′‐promoter region, five in the 5′‐ untranslated region (UTR), 11 in exons, four in the 3′‐UTR and three in the 3′‐flanking region by re‐sequencing the entire coding and regulatory regions of ACACB. One of these SNPs (ss1987461005) is reported here for the first time, and three of the SNPs (rs109482081, rs110819816 and rs109281947) were predicted to result in amino acid replacements. Genotype–phenotype association analyses showed that all the identified SNPs, except for ss1987461005, rs208919019 and rs134447911, were significantly associated with milk yield, fat yield, fat percentage, protein yield or protein percentage (P < 0.0001 to 0.0484). Linkage disequilibrium analyses were conducted among the identified SNPs to confirm the genetic associations. Two SNPs—rs135874354 (g.66218726T>C) and rs210928430 (g.66218117G>A)—were predicted to alter transcription factor binding sites in the 5′‐promoter region of ACACB. A luciferase activity assay showed that the promoter activity of haplotype TG was significantly higher than that of CG (P = 0.0002) and that the promoter activity of haplotype TA was remarkably higher than that of CA (P = 7.4285E−09), showing that the T allele of rs135874354 increased promoter activity. Thus, rs135874354 was considered to be a potentially functional mutation. Our findings have, for the first time, profiled the genetic effect of ACACB on milk production traits in dairy cattle and revealed a potentially causal mutation that requires further the in‐depth validation. [ABSTRACT FROM AUTHOR]

Agricultural soils are strong sources of the potent greenhouse gas N 2 O but soil N 2 O emissions and its microbial mechanism in greenhouse field, especially ammonia-oxidizing microorganisms are unclear. We characterized a potential response in soil N 2 O production and its influencing factors, such as soil temperature, moisture, pH, and inorganic nitrogen to different irrigation methods named drip irrigation (DI), subsurface irrigation (SI) and furrow irrigation (FI) in a long-term irrigation field in greenhouse. The abundance and metabolic activity of ammonia oxidizing archaea (AOA) and bacteria (AOB) in greenhouse soils were also investigated using amoA gene as a molecular biomarker by quantitative PCR and 13 CO 2 -DNA-stable isotope probing (SIP) methods. Results showed that N 2 O flux peaks would obviously occur within 1–8 days after each irrigation. The soil N 2 O flux in FI treatment was significantly higher than that in DI and SI treatments ( P <  0.05). Correlation analysis between soil N 2 O flux and its influencing factors indicated that soil moisture and nitrate nitrogen were substantially affecting soil N 2 O emissions compared with soil temperature, pH and ammonium nitrogen. The copy numbers of AOA amoA gene in FI treatment were significantly higher than those in DI and SI treatments ( P <  0.05), while there is no significant difference of AOB amoA gene among the three treatments. Also, the copy numbers of AOA amoA gene were significantly higher than those of AOB amoA gene. The 13 CO 2 -DNA-SIP and phylogenetic tree results indicated only AOB dominantly involved in Nitrosospira genera was active during the nitrification process in the three irrigation methods. Our findings provided direct evidence that drip irrigation and subsurface irrigation could effectively reduce soil N 2 O emissions in greenhouse. AOA was dominant in abundance, while AOB played a key role in microbial community under the conditions of this experiment. Future characterization of the mechanisms for ammonia oxidation requires deeper studies in the greenhouse field. [ABSTRACT FROM AUTHOR]

Summary: HCV genotype 4 (GT4) has often been overlooked in drug development, even though it infects ~20 million people worldwide. Ledipasvir/sofosbuvir and sofosbuvir/velpatasvir were highly efficacious in GT4 HCV‐infected patients from GS‐US‐337‐1119 and GS‐US‐342‐1138. Here, we characterize the resistance profile of ledipasvir (LDV) and velpatasvir (VEL) in patients with GT4 HCV infection. NS5A deep‐sequencing was performed for 454 patients infected with HCV GT4 at baseline, including 44 patients enrolled in GS‐US‐337‐1119 and 116 patients enrolled in GS‐US‐342‐1138, and at relapse for patients with virologic failure. LDV and VEL susceptibilities of 56 patient isolates were determined. In GS‐US‐337‐1119, SVR12 rates were 100% for all subtypes except 4b and 4r. Phenotypic assessment of 56 HCV NS5A patient isolates from various GT4 subtypes indicated that LDV had high potency for the common subtypes 4a/d, and subtypes 4c/f/k/l/m/n/o/p/r/t despite the presence of resistance‐associated substitutions (RASs). For the rare GT4b, LDV median EC50 was higher, but with a broad range of individual values. Importantly, all GT4b isolates tested had 2‐4 NS5A RASs, some including Y93H. Similarly, the 2 GT4r infected patients who had virologic relapse had rare triple RASs. Reversion of these substitutions to the consensus residue significantly increased LDV susceptibility. In GS‐US‐342‐1138, all patients achieved SVR12, regardless of their subtype or presence of RASs. In vitro data confirmed that VEL is potent against all GT4 isolates tested. LDV and VEL are potent antiviral drugs, estimated to be effective against >95% and >99%, respectively, of GT4 HCV isolates. [ABSTRACT FROM AUTHOR]

Hydrogen (H) plays an important role in determining the reliability and performance of HfO2- and Al2O3-based high-k dielectric electronic devices. In order to understand H behavior, deuterium (D), an isotope of H, was introduced into the poly-Si cap of Al2O3/HfxSi1-xO2/SiO2 high-k stacks by ion implantation. Atom probe tomography was used to image the D distribution in samples annealed under different conditions. The results clearly demonstrated that the D atoms were trapped at the interface of poly-Si and Al2O3 after annealing at 900 K for 10 min. Thus, it is possible that Al2O3 blocks the H atoms at the surface, preventing them from diffusing into the high-k dielectrics during the H2 annealing process in current fabrication technology. The current work also exhibits an example of investigating H behavior in semiconductors by atom probe tomography. [ABSTRACT FROM AUTHOR]

The ability to orchestrate appropriate physiological and behavioral responses to stress is important for survival, and is often dysfunctional in neuropsychiatric disorders that account for leading causes of global disability burden. Numerous studies have shown that the endocannabinoid neurotransmitter system is able to regulate stress responses and could serve as a therapeutic target for the management of these disorders. We used quantitative reverse transcriptase-polymerase chain reactions to show that genes encoding enzymes that synthesize (abhd4, gde1, napepld), enzymes that degrade (faah, faah2a, faah2b), and receptors that bind (cnr1, cnr2, gpr55-like) endocannabinoids are expressed in zebrafish (Danio rerio). These genes are conserved in many other vertebrates, including humans, but fatty acid amide hydrolase 2 has been lost in mice and rats. We engineered transcription activator-like effector nucleases to create zebrafish with mutations in cnr1 and faah2a to test the role of these genes in modulating stress-associated behavior. We showed that disruption of cnr1 potentiated locomotor responses to hyperosmotic stress. The increased response to stress was consistent with rodent literature and served to validate the use of zebrafish in this field. Moreover, we showed for the first time that disruption of faah2a attenuated the locomotor responses to hyperosmotic stress. This later finding suggests that FAAH2 may be an important mediator of stress responses in non-rodent vertebrates. Accordingly, FAAH and FAAH2 modulators could provide distinct therapeutic options for stress-aggravated disorders. [ABSTRACT FROM AUTHOR]

Effect of grain size on magnetoresistance (MR) and electrical and magnetic properties of double perovskite Ba[sub 2]FeMoO[sub 6] (BFMO) have been investigated. BFMO samples with different grain size have been prepared by the conventional solid state reaction followed by sintering in a stream of 5% H[sub 2]/Ar at 1100 °C with various sintering times. The size of grain increases with increasing of sintering time. Temperature dependent magnetization is the same for samples with different grain size. However, electrical resistivity ρ(T) and MR are affected by the grain size; the ρ(T) and the MR value decrease with an increase in grain size. In spite of the different grain size, the ρ(T) shows a metallic behavior below the ferromagnetic transition temperature. Low magnetic field applied to the sample considerably reduces the resistivity over the whole temperature. The magnitude of MR for the sample sintered for 5 h is as large as 31% and 7% with the magnetic ! field of 0.7 T at 12 and 300 K, respectively. © 2001 American Institute of Physics. [ABSTRACT FROM AUTHOR]

Ecosystem scientists will increasingly be called on to inform forecasts and define uncertainty about how changing planet conditions affect human well-being. We should be prepared to leverage the best tools available, including big data. Use of the term 'big data' implies an approach that includes capacity to aggregate, search, cross-reference, and mine large volumes of data to generate new understanding that can inform decision-making about emergent properties of complex systems. Although big-data approaches are not a panacea, there are large-scale environmental questions for which big data are well suited, even necessary. Ecosystems are complex biophysical systems that are not easily defined by any one data type, location, or time. Understanding complex ecosystem properties is data intensive along axes of volume (size of data), velocity (frequency of data), and variety (diversity of data types). Ecosystem scientists have employed impressive technology for generating high-frequency, large-volume data streams. Yet important challenges remain in both theoretical and infrastructural development to support visualization and analysis of large and diverse data. The way forward includes greater support for network science approaches, and for development of big-data infrastructure that includes capacity for visualization and analysis of integrated data products. Likewise, a new paradigm of cross-disciplinary training and professional evaluation is needed to increase the human capital to fully exploit big-data analytics in a way that is sustainable and adaptable to emerging disciplinary needs. [ABSTRACT FROM AUTHOR]

The effects of massive laser shock peening (LSP) treatment with different coverage layers on residual stress, pitting morphologies in a standard corrosive solution and electrochemical corrosion resistance of AISI 4145 steel were investigated by pitting corrosion test, potentiodynamic polarisation test, and SEM observations. Results showed massive LSP treatment can effectively cause an obvious improvement of pitting corrosion resistance of AISI 4145 steel, and increased coverage layer can also gradually improve its corrosion resistance. Massive LSP treatment with multiple layers was shown to influence pitting corrosion behaviour in a standard corrosive solution. [ABSTRACT FROM AUTHOR]

CrN/Mo 2 N films were deposited by multi-cathodic arc ion plating on Si (100), 304 stainless steel and cemented carbide substrates with various bilayer periods (10–105 nm). X-ray diffraction analysis revealed a face-centered-cubic structure of CrN and Mo 2 N sublayers. Rutherford backscattering spectrometry (RBS) was used to probe the elemental composition and their depth profiling. The multilayer structures exhibited characteristic oscillating RBS spectra. The nanohardness slightly increased at larger bilayer periods and the highest value of 29 GPa was obtained at the bilayer period of 105 nm. A correlation was realized among compressive residual stress, critical load, and nanohardness. The highest critical load L c2 of 65–70 N was found for the coatings on cemented carbide substrates with the minimal bilayer period of 12 nm. The coefficients of friction and wear rates of the coatings were in the range of 0.29–0.35 and (6–8) × 10 − 7 mm 3 /N·m, respectively. [ABSTRACT FROM AUTHOR]

We investigate an optimal fourth-order staggered-grid finite-difference scheme for 3D frequency-domain viscoelastic wave modeling. An anti-lumped mass strategy is incorporated to minimize the numerical dispersion. The optimal finite-difference coefficients and the mass weighting coefficients are obtained by minimizing the misfit between the normalized phase velocities and the unity. An iterative damped least-squares method, the Levenberg–Marquardt algorithm, is utilized for the optimization. Dispersion analysis shows that the optimal fourth-order scheme presents less grid dispersion and anisotropy than the conventional fourth-order scheme with respect to different Poisson's ratios. Moreover, only 3.7 grid-points per minimum shear wavelength are required to keep the error of the group velocities below 1%. The memory cost is then greatly reduced due to a coarser sampling. A parallel iterative method named CARP-CG is used to solve the large ill-conditioned linear system for the frequency-domain modeling. Validations are conducted with respect to both the analytic viscoacoustic and viscoelastic solutions. Compared with the conventional fourth-order scheme, the optimal scheme generates wavefields having smaller error under the same discretization setups. Profiles of the wavefields are presented to confirm better agreement between the optimal results and the analytic solutions. [ABSTRACT FROM AUTHOR]

Auditory neuropathy spectrum disorder ( ANSD) is one of the most common diseases leading to hearing and speech communication barriers in infants and young children. The OTOF gene is the first gene identified for autosomal recessive non-syndromic ANSD, and patients with OTOF mutations have shown marked improvement of auditory functions from the cochlear implantation, but the true involvement of OTOF mutations in Chinese ANSD patients is still unknown which precludes the effective management of this disease. Here, we investigated the contribution of OTOF mutations to congenital ANSD patients in China. In all, 37 infants and young Children with ANSD were screened for all the exons of OTOF gene, of them 34 patients had no neonatal risk factors who were considered as congenital ANSD. The clinical manifestation and audiometric features were also investigated and compared in patients with and without OTOF mutations. In all, 14 of these subjects were shown to carry two or three mutant alleles of OTOF with the high frequency of 41.2% in congenital ANSD patients. In total, 15 novel pathogenic mutations and 10 reported mutations were identified. Our results confirmed that mutations in OTOF gene were a major cause of congenital ANSD in China. Identification of OTOF mutations can facilitate diagnosis, clinical intervention and counseling for congenital ANSD. [ABSTRACT FROM AUTHOR]

This paper presents an experimental investigation on the mechanical behavior and permeability evolution of a typical porous limestone, the Anstrude limestone. Hydrostatic and triaxial compression tests are first performed under drained condition to study the basic mechanical behavior of the porous rock. Permeability measurement under both hydrostatic and triaxial compression is carried out for investigating effects of stress state on the permeability evolution along the axial direction of sample. The obtained results allow to identifying two basic plastic deformation mechanisms, the plastic shearing and pore collapse, and their effects on the permeability evolution. Under low confining pressures, the permeability diminution in the elastic phase is controlled by deviatoric stress. After the onset of plastic shearing, the deviatoric stress induces a plastic volumetric dilatation and a permeability increase. When the deviatoric stress reaches the peak strength or after the onset of shear bands, the permeability slightly decreases. Under high confining pressures, the deviatoric stress also induces a permeability diminution before the onset of plastic pore collapse. After the onset of pore collapse, the deviatoric stress leads to a plastic volumetric compaction and permeability decrease. When the deviatoric stress reaches the onset of plastic shearing, the two plastic mechanisms are in competition, the permeability continuously decreases but with a reduced rate. Finally, after the compaction-dilatation transition, the plastic shearing dominates the deformation process while the pore collapse still controls the permeability evolution. [ABSTRACT FROM AUTHOR]