Modeling and Experimental Analysis of Roughness Effect on Ultrasonic Nondestructive Evaluation of Micro-crack

A high-precision evaluation of ultrasonic detection sensitivity for a micro-crack can be restricted by a corroded rough surface when the surface microtopography is of the same order of magnitude as the crack depth.In this study,a back-surface micro-crack is considered as a research target.A roughness-modified ultrasonic testing model for micro-cracks is established based on a multi-Gaussian beam model and the principle of phase-screen approximation.The echo signals of micro-cracks and noises corresponding to different rough front surfaces and rough back surfaces are obtained based on a reference reflector signal acquired from a two-dimensional simulation model.Further compari-son between the analytical and numerical models shows that the responses of micro-cracks under the effects of dif-ferent corroded rough surfaces can be accurately predicted.The numerical and analytical results show that the echo signal amplitude of the micro-crack decreases significantly with an increase in roughness,whereas the noise ampli-tude slightly increases.Moreover,the effect of the rough front surface on the echo signal of the micro-crack is greater than that of the rough back surface.When the root-mean-square(RMS)height of the surface microtopography is less than 15μm,the two rough surfaces have less influence on the echo signals detected by a focused transducer with a frequency of 5 MHz and diameter of 6 mm.A method for predicting and evaluating the detection accuracy of micro-cracks under different rough surfaces is proposed by combining the theoretical model and a finite element simulation.Then,a series of rough surface samples containing different micro-cracks are fabricated to experimentally validate the evaluation method.

STUDYING THE ROLE OF MACROPHAGES IN CIRCULATING PROSTATE CANCER CELLS BY IN VIVO FLOW CYTOMETRY

Metastasis is a very complicated multi-step process and accounts for the low survival rate of the cancerous patients.To metastasize,t he malignant cells must detach from the primary tumor and migrate to secondary sites in the body through either blood or lymph circulation.Macrophages appear to be directly involved in tumor progression and metastasis.However,the role of macrophages in affecting cancer metast asis has not been fully elucidated.Here,we have utilized an emerging technique,namely in vivo flow cytometry(IVFC)to study the depletion kinetics of circulating prostate cancer cells in mice and determine how depletion of macrophages by the liposome encapsulated clodronate affects the depletion kinetics.Our results show diferent depletion kinetics of PC-3 cells between the macrophagedeficient group and the control group.The number of circulating tumor cells(CTCs)in the macrophage-deficient group decreases in a slower manner compared to the control mice group.The differences in depletion kinetics indicate that the absence of macrophages facilitates the stay of prostate cancer cells in circulation.In addition,our imaging data suggest that macrophages might be able to arrest,phagocytose and digest PC-3 cells.Therefore,phagocy tosis may mainly contribute to the de-pletion kinetic diferences.The developed methods elaborated here would be useful to study the relationship between macr ophages and tumor metastasis in small animal cancer models.

Visualization of integrin molecules by fluorescence imaging and techniques

Integrin molecules are transmembraneαβheterodimers involved in cell adhesion,trafficking,and signaling.Upon activation,integrins undergo dynamic conformational changes that regulate their affinity to ligands.The physiological functions and activation mechanisms of integrins have been heavily discussed in previous studies and reviews,but the fluorescence imaging techniques-which are powerful tools for biological studies-have not.Here we review the fluorescence labeling methods,imaging techniques,as well as Förster resonance energy transfer assays used to study integrin expression,localization,activation,and functions.

Toluidine blue O and porphyrin-mediated photodynamic therapy on three main pathogenic bacteria of periodontitis using portable LED phototherapy device

Photodynamic therapy(PDT)has been commonly used in treating many diseases,such as cancer and infectious diseases.We investigated the different effects of PDT on three main pathogenic bacteria of periodontitis-Prevotella melaninogenica(P.m.),Porphyromonas gingitvalis(P.g.)and Aggregatibacter actinomycetercomitans(A.a-).The portable red light-ermitting diode(LED)phototherapy device was used to assess the exogenous PDT effects with different light doses and photosensitizer concentrations(Toluidine blue O,TBO).The portable blue LED phototherapy device was used to assess the endogenous PDT effects with the use of endogenous photosensit izers(porphyrin)under dfferent light doses.We found out that both exogenous and endogenous PDT were able to restrict the growth of all the three bacteria significantly.Moreover,the optimal PDT conditions for these bacteria were obtained through this in vitro screening and could guide the clinical PDT on periodontitis.

ICAM-1 depletion in the center of immunological synapses is important for calcium releasing in T-cells

T-cell activation requires the formation of the immunological sy napse(IS)bet ween a T-cll and anantigen-presenting cell(AP C)to control the development of the adaptive immune response.How-ever,calcium release,an initial signal of T-cell activation,has been found to occur before IS for-mation.The mechanism for triggering the calcium signaling and relationship bet ween calciumrelease and IS format ion remains unclear.Herein,using live-cell imaging,we found that int ercellularadhesion molecule 1(ICAM-1),an essential mdlecule for IS formation,accumulated and then wasdepleted at the center of the synapse before complete IS formation.During the proces of ICAM1depletion,calcium was released.if ICAM-1 failed to be depleted from the center of the synapse,thesustained calcium signaling could not be induced.Moreover,depletion of ICAM-1 in ISs preferen-tially ccurred with the contact of antigen-specific T-cels and dendritic clls(DCs).Blocking thebinding ofICA M-1 and lymphocy te finction-associated antigen 1(LFA-1),ICAM-1 failed to depleteat the center of the synapse,and calcium release in T-clls decreased.In studying the mechanism ofhow the depletion ofiCA M1 could influence calcium release in T-clls,we found that the movementof ICAM-1 was associat ed with the localization of LFA-1 in the IS,which afected the localization ofcalcium microdomains,ORAIl and mitochondria in IS.Therefore,the depletion of ICAM-1 in the center of the synapse is an important factor for an initial sust ained calcium release in T-cells.

2-APQC,a small-molecule activator of Sirtuin-3(SIRT3),alleviates myocardial hypertrophy and fibrosis by regulating mitochondrial homeostasis

Sirtuin 3(SIRT3)is well known as a conserved nicotinamide adenine dinucleotide^(+)(NAD^(+))-dependent deacetylase located in the mitochondria that may regulate oxidative stress,catabolism and ATP production.Accumulating evidence has recently revealed that SIRT3 plays its critical roles in cardiac fibrosis,myocardial fibrosis and even heart failure(HF),through its deacetylation modifications.Accordingly,discovery of SIRT3 activators and elucidating their underlying mechanisms of HF should be urgently needed.Herein,we identified a new small-molecule activator of SIRT3(named 2-APQC)by the structure-based drug designing strategy.2-APQC was shown to alleviate isoproterenol(ISO)-induced cardiac hypertrophy and myocardial fibrosis in vitro and in vivo rat models.Importantly,in SIRT3 knockout mice,2-APQC could not relieve HF,suggesting that 2-APQC is dependent on SIRT3 for its protective role.Mechanically,2-APQC was found to inhibit the mammalian target of rapamycin(mTOR)-p70 ribosomal protein S6 kinase(p70S6K),c-jun N-terminal kinase(JNK)and transforming growth factor-β(TGF-β)/small mother against decapentaplegic 3(Smad3)pathways to improve ISO-induced cardiac hypertrophy and myocardial fibrosis.Based upon RNA-seq analyses,we demonstrated that SIRT3-pyrroline-5-carboxylate reductase 1(PYCR1)axis was closely assoiated with HF.By activating PYCR1,2-APQC was shown to enhance mitochondrial proline metabolism,inhibited reactive oxygen species(ROS)-p38 mitogen activated protein kinase(p38MAPK)pathway and thereby protecting against ISO-induced mitochondrialoxidative damage.Moreover,activation of SIRT3 by 2-APQC could facilitate AMP-activated protein kinase(AMPK)-Parkin axis to inhibit ISO-induced necrosis.Together,our results demonstrate that 2-APQC is a targeted SIRT3 activator that alleviates myocardial hypertrophy and fibrosis by regulating mitochondrial homeostasis,which may provide a new clue on exploiting a promising drug candidate for the future HF therapeutics.

Experimental and numerical studies of impact on filament-wound composite cylinder

This study focused on the impact behavior of carbon-fiber-wrapped composite cylinders subjected to impact from flat-ended, hemispherical-nosed and conical-nosed impactors. Damage morphologies of the cylinders and mechanisms of the damage were analyzed. Change laws of the maximum impact forces, durations of impact processes and energies absorbed by the cylinders after impact with different impactors and impact energies were obtained. A finite element model was developed and the simulation results were in reason- able agreement with the tests. Finally, taking the flat-ended impactor as an example, stress distributions of the cylinders under pressurization and impact were discussed.

Creep-fatigue lives prediction and sensitivity study of 316H at 550 ℃

In Volume 2/3 of R5 ＂An assessment procedure for the high temperature response of structures＂, the strain based ductility exhaustion method is suggested to calculate the creep damage of stress concentration region, which involves description of creep dwell initial stress, stress drop and creep ductility. Considering lots of uncertainty existed in these assessment, some sensitivity analysis is required in R5 procedure to ensure the conservatism of assessment results. In this paper, laboratory creep-fatigue test data of 316H at 550 ℃ with different loading conditions are selected as a special case to investigate whether the basic R5 approach is conservative, and the different material data combinations of cyclic stress-strain, creep deformation and creep ductility are used to identify those significant parameters affecting the assessment results. The analytical results indicate that the creep deformation model and creep ductility data are more significant to the results comparing with cyclic stress-strain data. If the upper bound of creep deformation law and lower bound of creep ductility data are used to predict their creep-fatigue lives, the degree of conservatism can be as large as a factor of -300, but if the modified creep deformation model and cast specific ductility data are used, very well prediction results can be gained within a factor of ±2.0 although there is slight non-conservatism.