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Mavacamten improves left ventricular outflow tract obstruction (LVOT), exercise capacity, symptoms, and health status versus placebo in patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM). As mavacamten is used in clinical practice, generating data in the real-world setting becomes important to understand its safety and effectiveness. DISCOVER-HCM (NCT05489705) is an observational, multicenter, prospective registry study to assess patient characteristics, treatment patterns, and longitudinal outcomes in patients receiving mavacamten and/or other treatments for symptomatic obstructive HCM. Up to 1500 patients from 65 sites in the US and Puerto Rico will be enrolled over approximately 2 years. Inclusion and exclusion criteria are outlined in the Table. The study will include 2 years of retrospective and 5 years of prospective data collection (Figure). The primary objective is to estimate the incidence of new/worsening heart failure due to systolic dysfunction (symptomatic left ventricular ejection fraction <50%). Secondary and exploratory objectives include evaluation of treatment effectiveness (e.g., LVOT gradients), additional safety endpoints (e.g., occurrences of arrhythmias and major adverse cardiovascular events), and quality of life outcomes (e.g., Kansas City Cardiomyopathy Questionnaire 23). A sub-study will assess longitudinal cardiac biomarkers to characterize markers of response over time. DISCOVER-HCM is the first real-world prospective registry study to characterize use, health outcomes, effectiveness, safety and other markers of health in patients with obstructive HCM receiving mavacamten and other therapies. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract Hyperactivated macrophages play a key role in the initiation and perpetuation of mucosal inflammation in Crohn’s disease (CD). Increasing evidence suggests that the basic helix-loop-helix (bHLH) repressor Twist1 can suppress activation of nuclear factor-κB (NF-κB) and the subsequent production of TNF-α, which are both essential elements of macrophage activation. Thus, developing novel therapeutic strategies to enhance Twist1 expression and to inhibit macrophage activation may be beneficial for CD treatment. In the present study, a series of trifluoroethyl thiazolo[3,2-b][1,2,4]triazole derivatives were used to investigate their potential anti-inflammatory activities and the underlying mechanism. In a biological activity screen, compound 7# (Thiazolo[3,2- b ][1,2,4]triazole-5-methanamine, 6-phenyl-α-(trifluoromethyl)-, (α R)-, TT-TFM) suppressed the activation of macrophages. Consistent with the in vitro data, TT-TFM protected against 2,4,6-trinitrobenzene sulfonic acid (TNBS), dextran sulfate sodium (DSS)-induced acute colitis and IL-10 knockout (KO) chronic colitis, as judged by body weight changes and colonic pathological damage. A mechanistic study based on microarray analysis and gene interference experiments indicated that TT-TFM exerted anti-inflammatory effects by enhancing Twist1 expression and subsequently blocking the NF-κB/TNF-α pathway. In addition, pretreatment with lentiviruses encoding shRNA targeting Twist1 could abolish the therapeutic effect of TT-TFM in TNBS colitis. Ultimately, TT-TFM showed anti-colitis activity by reducing NF-κB activation and the TNF-α level by promoting Twist1 expression; thus, TT-TFM may offer a therapeutic strategy for CD patients. [ABSTRACT FROM AUTHOR]

Four relatively rigid assemblies I–IV have been designed to understand the factor governing the photoinduced electron transfer (PET) process in 2-ureido-4[1 H ]-pyrimidinone quadruple hydrogen-bonded systems. Upon excitation, PET from the N,N -dimethylaniline group to the singlet anthracene takes place giving rise to a long-lived charge-separation state up to 56 μs for assembly I and 13 μs for assembly II . Moreover, the introduction of CH 2 group(s) to assemblies I and II can significantly influence, or even switch off the intra-assembly PET process. Spectroscopic and electrochemical studies demonstrate efficient electronic communication responsible for the PET process in 2-ureido-4[1 H ]-pyrimidinone quadruple hydrogen-bonded N , N -dimethylaniline-anthracene assemblies. The fast single-step electron-transfer and slow charge-recombination, as well as the high excitation energy conversion efficiency (78%), enable the assemblies to be advantageous for high light-energy conversion. [ABSTRACT FROM AUTHOR]

Background: This study is aimed to quantify the strength of the association between rs1801133 polymorphism and ischemic stroke risk. Methods: We have searched Medline, Springer, and Embase for studies investigating the association between rs1801133 polymorphism and ischemic stroke risk. We estimated the pooled odds ratio with its 95% confidence intervals to assess this possible association. Results: Forty case-control studies comprising 8809 cases and 9130 controls are eligible for this meta-analysis on the basis of relation of rs1801133 polymorphism to ischemic stroke risk. Hardy-Weinberg equilibrium was used to perform in controls for excluding articles. The overall analysis suggested that rs1801133 polymorphism was associated with increased risk of ischemic stroke (ORT versus C = 1.16, 95% CI 1.10-1.22; ORTT versus TC + CC = 1.32, 95% CI 1.18-1.47; ORTT + TC versus CC = 1.11, 95% CI 1.04-1.18). Subgroup analysis showed that T allele was a significant strength between T allele and stroke risk in Asian, Caucasian, male and young-middle populations (OR = 1.19, 1.11, 1.30, 1.16, respectively). Compared with TC + CC, TT genotype was found to be a risk factor for developing ischemic stroke in Asian, Caucasian and male (OR = 1.41, 1.20, 1.77, respectively). Additionally, TT + TC retained a significant increase for ischemic stroke only in Asian comparable to CC genotype (OR = 1.14). Conclusions: The rs1801133 polymorphism could be capable of increasing ischemic stroke susceptibility in Asian, male and young-middle populations. [ABSTRACT FROM AUTHOR]

Abstract: Saikosaponin D is an agonist of the glucocorticoid receptor (GR), and our preliminary study showed that it possesses neuroprotective effects in corticosterone-treated PC12 cells. However, further proof is required, and the molecular mechanisms of this neuroprotection remain unclear. This study sought to further examine the cytoprotective efficiency and potential mechanisms of action of Saikosaponin D in corticosterone-treated PC12 cells. The cells were treated with 250μM corticosterone in the absence or presence of Saikosaponin D for 24h; cell viability was then determined, and Hoechst 33342/propidium iodide (PI) and annexin/PI double staining, and TUNEL staining were performed. Next, mPTP, MMP, [Ca2+]i, translocation of the GR to the nucleus and Western blot analyses for caspase-3, caspase-9, cytochrome C, GR, GILZ, SGK-1, NF-Κb (P65), IκB-α, Bad, Akt, Hsp90 and HDAC-6 were investigated. The neuroprotective effects of Saikosaponin D were further confirmed by Hoechst 33342/PI, annexin/PI and TUNEL staining assays. These additional data suggested that Saikosaponin D partially reversed the physiological changes induced by corticosterone by inhibiting the translocation of the GR to the mitochondria, restoring mitochondrial function, down-regulating the expression of pro-apoptotic-related signalling events and up-regulating anti-apoptotic-related signalling events. These findings suggest that SSD exhibited its anti-apoptotic effects via differential regulation of mitochondrial and nuclear GR translocation, partial reversal of mitochondrial dysfunction, inhibition of the mitochondrial apoptotic pathway, and selective activation of the GR-dependent survival pathway. [Copyright &y& Elsevier]

Despite the external application of hydrogen sulfide (H2S) conferring plant tolerance against various environmental cues, the physiological significance of l-cysteine desulfhydrase (L-DES)-associated endogenous H2S production involved in salt-stress signaling was poorly understood. To address this gap, the participation of in planta changes of H2S homeostasis involved in alfalfa salt tolerance was investigated. The increasing concentration of NaCl (from 50 to 300mM) progressively caused the induction of total l-DES activity and the increase of endogenous H2S production. NaCl-triggered toxicity symptoms (175mM), including seedling growth inhibition and lipid peroxidation, were alleviated by sodium hydrosulfide (NaHS; 100μM), a H2S donor, whereas aggravated by an inhibitor of l-DES or a H2S scavenger. A weaker or negative response was observed in lower or higher dose of NaHS. Further results showed that endogenous l-DES-related H2S modulated several genes/activities of antioxidant defence enzymes, and also regulated the contents of antioxidant compounds, thus counterbalancing the NaCl-induced lipid peroxidation. Moreover, H2S maintained K+/Na+ homeostasis by preventing the NaCl-triggered K+ efflux, which might be result form the impairment of SKOR expression. Together, our findings indicated that endogenous H2S homeostasis enhance salt tolerance by coupling the reestablishment of redox balance and restraining K+ efflux in alfalfa seedlings. [ABSTRACT FROM AUTHOR]

Abstract: Male hypogonadism is frequently accompanied with type 2 diabetes due to testicular dysfunction, but the origin of the pathogenesis is not known. We measured whether pro-inflammatory factors including endoplasmic reticulum (ER) stress chaperones and inhibitory κBβ (IκBβ) contribute to testis damage in type 2 diabetic rats produced by a high-fat diet (HFD) and low dose streptozotocin (STZ). We determined whether these can be attenuated by the anti-inflammatory activity of argirein a derivative of rhein as compared to valsartan. Reduced testosterone and LH (luteinizing hormone) levels in serum were significant in association with a decrease in the levels of mRNA and steroidogenic acute regulatory protein (StAR), insulin receptor substrate (IRS-1), activated IκBβ and ER stress chaperone C/EBP homologous protein (CHOP) in the diabetic testis and sperm count, motility and sexual behaviors were reduced in vivo. Additionally, Leydig cells cultured with high glucose showed upregulated IκBβ, ER stress sensor PERK (PKR-like ER kinase) and p-Akt/Akt in vitro. These changes may be due to a component of inflammation linked to activated NADPH oxidase and were significantly alleviated by either argirein or valsartan. In conclusion, diabetic testopathy induced by a HFD and low STZ is characterized by an entity of inflammation and is alleviated by argirein and valsartan through normalizing activated IκBβ and ER stress. [Copyright &y& Elsevier]

Abstract: By using a 78-bar space truss, the configuration and properties of a linear active structure are studied experimentally, and the experiment technique for constructing an active structure is practiced in this paper. An active truss is constructed by using piezoelectric stack actuator and adopting linear quadratic optimal control approach for coupling mode space. The modal shapes and modal parameters are measured for active truss and passive truss respectively on dSPACE plate of hardware-in-the-Loop simulation system. In addition, the transfer function of the active truss is measured when it is under a random excitation. It is shown that the damping of an active structure increases as a result of the control means introduced. Meanwhile, difference of the mode is much great between the passive truss and the active one because the mode of the bar is controlled nearby the piezoelectric actuators. [Copyright &y& Elsevier]

Abstract: It has been two decades since the first presentation of “A new model and theory on yield and failure of materials under complex stress state” at ICM-6 held at Kyoto, Japan in 1991. The twin-shear element model and a new strength theory were proposed at ICM-6. However, only the two equations were introduced, the characteristics and its applications of this strength theory have not been studied in details. A great deal of researches on this new strength theory and its applications are developed since then by Yu and other scholars at other Universities and Institutes in some countries. Some behaviour of the unified strength theory are described here. The advances in the unified strength theory and its applications are summarized briefly in the framework of continuum mechanics and engineering application. [Copyright &y& Elsevier]

Abstract: The aim of this study is to quantify patterns of age-related shape change in the human thorax using Procrustes superimposition. Landmarks (n=106) selected from anonymized computed tomography (CT) scans of 63 adult males free of skeletal pathology were used to describe the form of the rib cage. Multivariate linear regression was used to determine a relationship between landmark location and age. Linear and quadratic models were also investigated. A permutation test employing 1×105 random trials was used to assess the model significance for both model formulations. Linear relationships between the centroid size (CS) of a landmark set and the corresponding individual''s height, weight, and BMI were conducted to enable scaling of the dimensionless results from the Procrustes analysis. A significance level of α=0.05 was used for all tests. The average age of the study subjects was 57.0±17.3 years. Complete landmark sets were obtained from most of the scans (44 of 63). The quadratic relationship between the age and landmark location was found to be significant (p=0.037), thereby establishing a relationship between the age and thoracic shape change. The linear relationship was mildly significant as well (p=0.073). Significant relationships between the centroid size of the dataset and subject weight, height and BMI were determined, with the best-correlated value being weight (p=0.002, R 2=0.22). Landmark datasets calculated using the quadratic model exhibited shape change consistent with the clinical observations (increasing kyphosis and rounding of the thoracic cage). Procrustes superimposition represents a potential improvement in the approach used to generate computational models for injury biomechanics studies. The coefficients from the quadratic model are provided and can be used to generate the complete set of model landmark data points at a given age. [Copyright &y& Elsevier]

Abstract: A gas chromatographic detector using direct current micro-plasma discharged a distance of less than 50 μm under helium at atmospheric pressure is described. The micro-plasma device was assembled on glass substrates; the volume of the plasma region was only 0.58 nL. Very low power consumption (15 mW) and only carrier helium flow were needed to maintain micro-plasma stability. Organic compounds with various functional groups were chromatographically separated and fed into the micro-plasma. Fluctuations in plasma current were detected as the sample passed through the micro-plasma. All non-halogen organics showed positive peaks, while simple alkyl halides showed negative peaks. Compounds with both aromatic and halogen groups exhibited hybrid peak shapes, consisting of both positive and negative peaks. The detection limits (3σ) ranged from 24.5 pg for m-xylene to 756 pg for 1,2-dichloroethane, depending on differences in ionization and electron-capture efficiency. [Copyright &y& Elsevier]

Abstract: Most previous studies on shakedown of thick-walled cylinders were based on the assumption that the compressive and tensile strengths of the materials were identical. In this paper the shakedown of an internally pressurized cylinder made of a material with a strength-difference and intermediate principal stress effects is dealt with by using a unified strength criterion which consists of a family of convex piecewise linear strength criteria. Through an elasto-plastic analysis the solutions for the loading stresses, residual stresses, elastic limit, plastic limit and shakedown limit of the cylinder are derived. It is shown that the present solutions include the classical plasticity solutions as special cases and have the ability to account for the strength-difference and intermediate principal stress effects. Finally, the influence of the two effects on the shakedown limit of the cylinder is investigated. The results show that the shakedown limit depends on the two effects and is underestimated if these effects are neglected as in the classical plasticity solution based on the Tresca criterion. [Copyright &y& Elsevier]

The study and design of structures under dynamic loads require a knowledge of the plastic response and deformation behavior under impact loading. The calculations of dynamic plastic response of structures are useful for the design and investigation of colliding vehicle, engine and various impacting structures. The unified solutions of dynamic plastic load-carrying capacities, moment fields and velocity fields of a simply supported circular plate are introduced. The strength is different in tension and compression and the effect on the yield criteria is taken into account by using the unified strength theory. Upper bound and lower bound plastic responses of the plate, under moderate partial uniformly distributed impulsive loading, are obtained. The static and kinematical admissibility of the dynamic plastic solutions are discussed. The unified solutions of the static plastic load-carrying capacities, moment fields and velocity fields of a simply supported circular plate are also obtained according to the dynamic solutions in this paper. The solutions are suitable for many materials with or without different strengths in tension and compression and the effect of intermediate principal stress.The solutions based on the Tresca, the von Mises, the Mohr–Coulomb theory, and the twin-shear strength theory, as well as the unified yield criterion, are all the special cases of the unified solutions. The influences of the coefficient of failure criteria, b, and tension-compression strength ratio, α, on the dynamic and static solutions, are investigated. It is shown that the effects of different strengths in tension and compression and yield criteria on the dynamic load-carrying capacity are greater than in the static plastic limit state. [Copyright &y& Elsevier]

Nonisothermal crystallization kinetics and melting behavior of bimodal-medium-density- polyethylene (BMDPE) and the blends of BMDPE/LDPE were studied using differential scanning calorimetry (DSC) at various scanning rates. The Avrami analysis modified by Jeziorny and a method developed by Mo were employed to describe the nonisothermal crystallization process of BMDPE. The BMDPE DSC data were analyzed by the theory of Ozawa. Kinetic parameters such as the Avrami exponent (n), the kinetic crystallization rate constant (Zc), the peak temperatures (Tp) and the half-time of crystallization (t1/2) etc. were determined at various scanning rates. The appearance of double melting peaks and the double crystallization peaks in the heating and cooling DSC curves of BMDPE/LDPE blends indicated that the BMDPE and LDPE could crystallize respectively. [Copyright &y& Elsevier]

A non-linear Unified Strength criterion for rock material is presented. It is the development of the Unified Strength Theory (in: M. Jono, T. Inoue (Eds.), Mechanical Behaviour of Materials-VI (ICM-6), Pergamon, Oxford, 1991, pp. 841–846) and the modification of the Hoek–Brown strength criterion (Underground Excavations in Rock, The Institution of Mining and Metallurgy, London, 1980). The effect of intermediate principal stress on rock strength is considered in the non-linear Unified Strength criterion. The Hoek–Brown criterion is a single-shear strength criterion that forms the lower bound, and the non-linear twin-shear strength criterion forms the upper bound in the deviatoric plane. All the failure criteria ranging from the Hoek–Brown criterion (lower bound) and the non-linear twin-shear criterion (upper bound) and a series of criteria ranging between these two bounds may be introduced by the non-linear Unified Strength criterion. The theory can also be generalized to rock mass strength. [Copyright &y& Elsevier]

Epoxy composites based on vapor grown carbon fiber (VGCF) were fabricated and analyzed for room temperature thermophysical properties. An unprecedented high thermal conductivity of 695 W/m K for polymer matrix composites was obtained. The densities of all the composites are lower than 1.5 g/cc. In addition the high value of coefficient of thermal expansion (CTE) of the polymer material was largely reduced by the incorporation of VGCF. Also, unlike metal matrix composite (MMC), the epoxy composite has an electrically insulating surface. Based on the composite thermal conductivities, the room temperature thermal conductivity of VGCF, heat-treated at 2600°C, was estimated to be 1260 W/m K. Furthermore, the longitudinal CTE of the heat-treated VGCF was determined, for the first time, to be −1.5 ppm/K. [Copyright &y& Elsevier]

Abstract This study focuses on the Mesozoic–Cenozoic tectono-thermal events in the Central Uplift of the South Yellow Sea Basin (SYSB) based on the CSDP-2 borehole. CSDP-2 is the first borehole to penetrate the integrated Paleozoic–Mesozoic sedimentary strata and recovered approximately 2736 m of core. The drilling results confirm a significant stratigraphic hiatus, i.e., Indosinian unconformity, between the Neogene–Quaternary and the underlying Lower Triassic. The eroded thickness estimated from sonic log and vitrinite reflectance data range from ∼1200 to 1400 m. Multiple paleo-thermometer data from the CSDP-2 cores, including vitrinite reflectance, apatite/zircon fission-track (AFT/ZFT) and fluid inclusions, were used to reconstruct the Mesozoic–Cenozoic thermal history in the study area. There was a continuous heating process during the early Mesozoic. The peak paleo-temperature may have reached up to 160 °C (base Permian) during the Late Jurassic, with the highest paleo-geothermal gradient of approximately 58.8 °C·km−1. The tectono-thermal evolution was dominated by the Mesozoic intracontinental collision between the Yangtze Craton and the Sino-Korean platform. The heating process was mainly caused by rapid burial on the passive continental margin and igneous activities. The paleo-temperature significantly decreased following the Late Jurassic. Two rapid cooling processes ca. 100–65 Ma and ca. 35 Ma are suggested by the AFT modeling results. Cooling history indicates that the tectonic uplift and denudation likely occurred from the Early Cretaceous to the Miocene. The reconstruction results of thermal evolution confirm that the Mesozoic–Paleozoic source rocks are mature or even highly mature, and hydrocarbon generation, migration and charge undoubtedly occurred in the Central Uplift, showing substantial hydrocarbon potential. Moreover, the reconstruction of the tectono-thermal history provides important constraints for regional tectonic studies. Highlights • Mesozoic–Cenozoic tectono-thermal events in the Central Uplift of the South Yellow Sea Basin was discussed. • Tectono-thermal history was reconstructed based on multiple paleo-thermometer data from the CSDP-2 borehole. • Substantial hydrocarbon potential in the marine deposits in the SYSB was confirmed. [ABSTRACT FROM AUTHOR]

Visual perception is the fundamental skill required for a child to recognize words, and to read and write. There was no visual perception assessment tool developed for preschool children based on Chinese characters in Taiwan. The purposes were to develop the computerized visual perception assessment tool for Chinese Characters Structures and to explore the psychometrical characteristic of assessment tool. This study adopted purposive sampling. The study evaluated 551 kindergarten-age children (293 boys, 258 girls) ranging from 46 to 81 months of age. The test instrument used in this study consisted of three subtests and 58 items, including tests of basic strokes, single-component characters, and compound characters. Based on the results of model fit analysis, the higher-order item response theory was used to estimate the performance in visual perception, basic strokes, single-component characters, and compound characters simultaneously. Analyses of variance were used to detect significant difference in age groups and gender groups. The difficulty of identifying items in a visual perception test ranged from -2 to 1. The visual perception ability of 4- to 6-year-old children ranged from -1.66 to 2.19. Gender did not have significant effects on performance. However, there were significant differences among the different age groups. The performance of 6-year-olds was better than that of 5-year-olds, which was better than that of 4-year-olds. This study obtained detailed diagnostic scores by using a higher-order item response theory model to understand the visual perception of basic strokes, single-component characters, and compound characters. Further statistical analysis showed that, for basic strokes and compound characters, girls performed better than did boys; there also were differences within each age group. For single-component characters, there was no difference in performance between boys and girls. However, again the performance of 6-year-olds was better than that of 4-year-olds, but there were no statistical differences between the performance of 5-year-olds and 6-year-olds. Results of tests with basic strokes, single-component characters and compound characters tests had good reliability and validity. Therefore, it can be apply to diagnose the problem of visual perception at preschool. [ABSTRACT FROM AUTHOR]

Highlights: [•] Processes of underwater explosion near boundaries are modeled with a coupled method. [•] Shock wave characteristics of underwater explosion near boundaries are compared. [•] The cavitation near the free surface and structures is described and captured. [•] Boundaries have significant influence on the shock wave propagation characteristics. [Copyright &y& Elsevier]

Abstract: Diabetic cardiomyopathy is associated with high morbidity and mortality of heart failure. Overactivation of the local chymase–Ang II system plays a dominant role in diabetic cardiomyopathy. Astragalus polysaccharide (APS) is used in traditional Chinese medicine to boost immunity. To study the effect of APS on local system of chymase-Ang II in diabetic cardiomyopathy, we investigated APS/normal saline (NS)-administrated streptozotocin-induced diabetic hamsters. After APS/NS administration at a dose of 1 g/kg per day for 10 weeks, hemodynamic parameters, levels of insulin (INS), C-peptide (C-P), glycosylated serum protein (GSP), lipoproteins, myocardial enzymes, and Ang II (plasma and myocardial) were tested; myocardial collagen (type I and III), myocardial ultrastructure, and activities of matrix metalloproteinase (MMPs) were measured; activities and expression of cardiac chymase and ACE were detected by using quantitative real-time RT-PCR and RIA; protein expression of cardiac phosphoric extracellular signal-regulated kinase 1/2 (p-ERK1/2) was measured by Western blot. AP-administrated diabetic hamsters had lower levels of GSP, lipoproteins, myocardial enzymes, myocardial Ang II, expression of collagen I and I/ III, activities of pro-MMP-2 and MMP-2, activities and expression of chymase, and expression of p-ERK1/2 than NS-administrated diabetic hamsters and could better protect the myocardial ultrastructure. There was no difference in hemodynamic parameters between two groups. These results indicate that APS could inhibit diabetic cardiomyopathy in hamsters depending on the suppression of the local cardiac chymase–Ang II system. [Copyright &y& Elsevier]

Transversely isotropic materials are of primary interest in many engineering applications. In this paper, general description of the properties of strain localization is deduced for the elastoplastic materials with transversely isotropic elasticity which follow the non-associated plasticity and are subjected to tri-axial stress states. Then the explicit expressions for the direction of localized band and the corresponding hardening modulus at the onset of strain localization are obtained for plane strain condition. Furthermore, the effect of deviation from isotropic elasticity in the formulation of strain localization is discussed based on those yield criteria such as Tresca criterion and twin-shear criterion. In the end, the influences of yield criteria on the properties of strain localization are elucidated. [Copyright &y& Elsevier]

Anxiety is often comorbid with pain. Delta opioid receptors (DORs) are promising targets for the treatment of pain and mental disorders with little addictive potential. However, their roles in anxiety symptoms at different stages of pain are unclear. In the current study, mice with inflammatory pain at the fourth hour following complete Freund's adjuvant (CFA) injection displayed significant anxiety-like behavior, which disappeared at the seventh day. Combining electrophysiology, optogenetics, and pharmacology, we found that activation of delta opioid receptor 1 (DOR1) in the central nucleus amygdala (CeA) inhibited both the anxiolytic excitatory input from the basolateral amygdala (BLA) and the anxiogenic excitatory input from the parabrachial nucleus (PBN). In contrast, activation of delta opioid receptor 2 (DOR2) did not affect CeA excitatory synaptic transmission in normal and 4-h CFA mice but inhibited the excitatory projection from the PBN rather than the BLA in 7-day CFA mice. Furthermore, the function of both DOR1 and DOR2 was downregulated to the point of not being detectable in the CeA of mice at the 21st day following CFA injection. Taken together, these results suggest that functional switching of DOR1 and DOR2 is associated with anxiety states at different stages of pain via modulating the activity of specific pathways (BLA-CeA and PBN-CeA). [ABSTRACT FROM AUTHOR]

Abstract: (Bi1− x R x )NbO4 (R=Ce,Nd,Dy,Er; x =0.03mol) ceramics with 0.1wt.% CuO+V2O5 as a sintering aid were prepared by conventional solid state reaction process. The microwave dielectric properties of (Bi1− x R x )NbO4 ceramics were investigated as a functional of R ions. The microwave dielectric properties such as dielectric constant, Q value and temperature coefficient of resonant frequency (TCF) are found to correlate with the R ions. When R=Ce, the dielectric constant, Q value and TCF are 44.7, 5000 and −4.9ppm/°C, respectively at about 5GHz. The relation of microwave dielectric properties and the ionic radii, polarizability and bond valence of R (R=Ce, Nd, Dy, Er) was discussed. The Q value decreased with decreasing the bond valence and the size of R ions. The dielectric constant decreased with decreasing polarizability. [Copyright &y& Elsevier]

• Grinding kinetics and efficiency of cemented tungsten carbide (WC) ball were investigated. • WC ball has higher density and lower energy-specific breakage than steel ball. • WC ball has high throughput for coarse feed size and low energy efficiency for fine feed size. • A preliminary criterion was established for grinding ball selection. Cemented tungsten carbide balls (hereafter abbreviated as WC balls) are commonly applied in grinding of wasted tool steel for reuse owing to their extraordinary surface hardness (89.5 HRA) and high density (14.5 –14.9 g/cm3). In this study, grinding tests were conducted with WC balls on quartz ore to estimate comminution kinetics. Compared with steel balls, they provided high breakage rates, lower energy-specific breakage rates, and finer breakage distributions due to their high density. Simulations were conducted using an energy-based population balance model. The simulated results demonstrated that WC balls had higher throughput for coarse particles and lower energy efficiency for fine particles. Subsequently, a preliminary criterion for ball selection was established and indicated that WC balls could be substituted for steel balls to certain particle size ranges. [ABSTRACT FROM AUTHOR]

The generation of transgenic chickens is of both biomedical and agricultural significance, and recently chicken transgenesis technology has been greatly advanced. However, major issues still exist in the efficient production of transgenic chickens. This study was designed to optimize the production of enhanced green fluorescence protein (EGFP)-transgenic broilers, including egg windowing at the blunt end (air cell) of egg, and the direct transfection of circulating primordial germ cells by microinjection of the Tol2 plasmid-liposome complex into the early embryonic dorsal aorta. For egg windowing, we discovered that proper manipulation of the inner shell membrane at the blunt end could improve the rate of producing G0 transgenic roosters. From 27 G0 roosters, we successfully collected semen with EGFP-positive sperms from 16 and 19 roosters after direct fluorescence observation and fluorescence-activated cell sorting analyses (13 detected by both methods), respectively. After artificial insemination using the G0 rooster with the highest number of EGFP fluorescent sperm, one G1 EGFP transgenic broiler (1/81, 1.23%) was generated. Our results indicate that appropriate egg windowing and screening of potentially transgene-positive roosters can improve the production of germline-transmitted transgenic birds. [ABSTRACT FROM AUTHOR]

This paper presents an original investigation of the seismic cracking behavior of Guandi concrete gravity dam, which is located in the highly seismic zone of China. For this purpose, three dimensional nonlinear finite element analyses are carried out for the Guandi dam-reservoir-foundation system, with the effects of contraction joints and cross-stream seismic excitation considered. The Concrete Damaged Plasticity (CDP) model is utilized to model concrete cracking under seismic loading. The opening/closing and sliding behaviors of contraction joints during earthquake events are modeled using two different surface-to-surface contact models (soft and hard pressure-clearance relationships), which aims to quantify the effect of grouting materials between the joint surfaces. The dynamic interaction between the impounded water and the dam-foundation system is explicitly taken into account by modeling the reservoir water with three dimensional fluid finite elements in the Lagrangian formulation. Several case studies are examined and the results reveal the significant influence of contraction joints and cross-stream ground motions on the dynamic response and damage-cracking risk of the Guandi concrete gravity dam. [ABSTRACT FROM AUTHOR]

Morphological awareness is the foundation for the important developmental skills involved with vocabulary, as well as understanding the meaning of words, orthographic knowledge, reading, and writing. Visual perception of space and radicals in two-dimensional positions of Chinese characters' morphology is very important in identifying Chinese characters. The important predictive variables of special and visual perception in Chinese characters identification were investigated in the growth model in this research. The assessment tool is the "Computerized Visual Perception Assessment Tool for Chinese Characters Structures" developed by this study. There are two constructs, basic stroke and character structure. In the basic stroke, there are three subtests of one, two, and more than three strokes. In the character structure, there are three subtests of single-component character, horizontal-compound character, and vertical-compound character. This study used purposive sampling. In the first year, 551 children 4-6 years old participated in the study and were monitored for one year. In the second year, 388 children remained in the study and the successful follow-up rate was 70.4%. This study used a two-wave cross-lagged panel design to validate the growth model of the basic stroke and the character structure. There was significant correlation of the basic stroke and the character structure at different time points. The abilities in the basic stroke and in the character structure steadily developed over time for preschool children. Children's knowledge of the basic stroke effectively predicted their knowledge of the basic stroke and the character structure. [ABSTRACT FROM AUTHOR]

Seismic reflection profiles reveal the structural characteristics beneath the East China Sea shelf margin and the Okinawa Trough, and provide new constraints on the Late Cenozoic evolution of the East China continental margin. The Frontal Shelf Basin between the Taiwan-Sinzi Uplift and the trough axis occupies the western half of the Northern-Middle Okinawa Trough. In this basin, the Middle-Late Miocene sediments are confined to grabens or half-grabens dominated by listric faults, whereas the overlying Pliocene-Quaternary sequence is characterized by a uniform thickness and dense planar-type faults, suggesting that rifting of the Northern-Middle Okinawa Trough initiated during the Middle Miocene but slowed down during the earliest Pliocene. Since that time, the opening of the Okinawa Trough has been dominated by diffuse rifting. The Southern Okinawa Trough is predominately filled by Quaternary sediments, indicating that its back-arc rifting began during the earliest Pleistocene. Contractional structures identified in the pre-Quaternary sequence beneath the continental slope, along with an erosional Pleistocene-pre-Pleistocene unconformity in the Southern Okinawa Trough, demonstrate the existence of pre-rifting compression and uplifting in this region. We use this evidence and previously published results, to propose an evolutionary model of the East China continental margin during the Late Cenozoic. The Northern-Middle Okinawa Trough began rifting during the Middle Miocene on a paleo-uplift. The Luzon Arc initially impinged upon the Eurasian continental margin during the Late Miocene near the southeastern end of the Miyako Fault Belt and activated the proto-Taiwan Orogeny in today's Southern Okinawa Trough and adjacent regions. During the Late Miocene-Pliocene, the orogeny quickly propagated southwestward along with the west-northwest-moving Philippine Sea Plate. Subsequently, the rifting of the Southern Okinawa Trough was initiated during the earliest Pleistocene and propagated southwestward following the post-collisional collapse of the proto-Taiwan Orogen. This geodynamic scenario resembles that of present-day northern Taiwan. [ABSTRACT FROM AUTHOR]

• During the Early Triassic, the study area is dominated by fine-grained mixed rocks that formed in a storm-controlled neritic shelf environment. • Mixed sediments formed via facies mixing and punctuated mixing. • From southeast to northwest, the South Yellow Sea Basin contains four paleogeographic units: coast, carbonate platform, shallow shelf, and deep-water basin. • The Qinglong Formation strata exhibit weak hydrocarbon generation and strong sealing. Drilling results from borehole CSDP-2 show that typical fine-grained mixed rocks occur in the Lower Triassic succession in the Central Uplift of the South Yellow Sea Basin, which reveals the storm event and possible double-provenance supply, and advances the previous understanding. We document the rock types, sedimentary structures and textures, and formation mechanisms of fine-grained mixed rocks on the basis of core and thin-section observations, XRD whole-rock geochemical, major and trace element, and laser particle-size analyses. During the Early Triassic, a storm-controlled neritic shelf and restricted platform were the main sedimentary environments of the Central Uplift, and the deposition was dominated by fine-grained mixed rocks, with some argillaceous siltstone and silt-bearing limestone. Formation of the fine-grained mixed rocks is attributed to facies mixing and punctuated mixing under the comprehensive influence of the paleogeographic background, paleoclimate variations, eustatic sea-level change, sediment supply, and storm events. Facies mixing is apparent in the succession as alternations of restricted platform, evaporated platform, brackish platform, and lagoon deposits. Mixed rocks formed by punctuated mixing exhibit an orderly succession of turbidity current, debris flow, storm current, and weak tractive current sediments. The geological significances of this research are twofold. In the South Yellow Sea Basin, the neritic shelf that formed in the Central Uplift gradually changed to a shallow-water carbonate platform in the Southern Depression and Wunansha Uplift. A deep-water basin formed in the Northern Depression. This palaeogeographic pattern is consistent with that of the Lower Yangtze continental region, revealing that two possible ancient provenances, the Cathaysia Wuyi Terrane and the North China Craton, may exist simultaneously. The Lower Triassic strata are characterized by weak hydrocarbon generation and strong sealing, and could act as caprocks for the underlying Permian hydrocarbon system. [ABSTRACT FROM AUTHOR]

In this paper, it is assumed the rock-like materials contain penny-shaped microcracks. The modes II and III stress intensity factors at tips of the three-dimensional penny-shaped microcracks are determined. The micro-failure orientation angle α is given out to describe the failure of rock-like materials. The formulation between the micro-failure orientation angle α and stress components is obtained from the mixed-mode fracture criterion. Failure characteristic parameters under true triaxial compression condition are defined, which are an invariant and are relative to the intermediate and minimum principal stresses. A three-dimensional nonlinear strength criterion of rock-like materials, in which the effects of the intermediate principal stress on the failure of rock-like materials is taken into account, is developed based on micromechanical methods. The theoretical nonlinear strength criterion is novel, which is not found in the previous references. By comparison with experimental data, it is shown that the present theoretical strength criterion is in good agreement with the experimental results. [ABSTRACT FROM AUTHOR]

Abstract: In this paper, the strength envelope of rock masses is considered to follow a non-linear unified strength criterion that considers the effect of the intermediate principal stress. A unified slip line method for resolving the differential equation system that governs the stress field is established to research the ultimate bearing capacity, which can be adapted for a wide variety of rock masses. Through this new theory, a suitable characteristic method for rock masses of interest can be obtained, and the relationships between different types of characteristic methods are revealed. The characteristic methods are based on different strength criteria, such as the Hoek–Brown criterion, modified Hoek–Brown criterion, or non-linear twin-shear strength criterion; each of these criteria is a special case of the proposed theory. Moreover, a series of new characteristic methods can be easily derived from it. In terms of the proposed theory, the ultimate bearing capacity with the Hoek–Brown criterion forms the lower bound; the ultimate bearing capacity with a non-linear twin-shear strength criterion forms the upper bound; and a series of the ultimate bearing capacities ranging between these two bounds may be derived from a non-linear unified strength criterion. A comparison is made between existing numerical analyses and non-linear finite element analysis solutions with the Drucker–Prager strength criterion. It is shown that the present results are in good agreement with existing numerical analyses and non-linear finite element analysis solutions with the Drucker–Prager strength criterion. [Copyright &y& Elsevier]