Effect of Tirapazamine and Mild Temperature Hyperthermia on the Recovery from Radiation-Induced Damage in Pimonidazole-Unlabeled Quiescent Tumor Cell Population

The aim in this study is to examine the effect of tirapazamine (TPZ) and mild temperature hyperthermia (MTH) on the repair of radiation-induced damage in pimonidazole-unlabeled quiescent (Q) tumor cells. Labeling of proliferating (P) cells in C57BL/6J mice bearing EL4 tumors was achieved by continuous administration of 5-bromo-2-deoxyuridine (BrdU). Tumors were irradiated with γ-rays at 1 h after the administration of pimonidazole followed by TPZ treatment or MTH. Twenty-four hours later, assessment of the responses of Q and total (= P + Q) cells were based on the frequencies of micronucleation and apoptosis using immunofluorescence staining for BrdU. The response of the pimonidazole-unlabeled tumor cell fractions was assessed by means of apoptosis frequency using immunofluorescence staining for pimonidazole. With γ-rays only, the pimonidazole-unlabeled cell fraction showed significantly enhanced radio-sensitivity compared with the whole cell fraction more remarkably in Q cells than total cells. However, a significantly greater decrease in radio-sensitivity in the pimonidazole-unlabeled than the whole cell fraction, evaluated using a delayed assay, was more clearly observed in Q cells than total cells. Post-irradiation MTH more remarkably repressed the decrease in radio-sensitivity in the Q cell than the total cells. Post-irradiation TPZ administration produced a large radio-sensitizing effect on both total and Q cells, especially on Q cells. On the other hand, in pimonidazole-unlabeled cell fractions in both total and Q cells, TPZ suppressed the reduction in sensitivity due to delayed assay much more efficiently than MTH, whereas no radio-sensitizing effect was produced. Not only through suppressing the recovery from radiation-induced damage but also through radio-sensitizing effect, post-irradiation TPZ administration is very useful for repressing the increase in the difference in radio-sensitivity due to the delayed assay not only between total and Q tumor cells but also between the pimonidazole-unlabeled and the whole cell fractions within the total and Q tumor cells.

Damage evolution of rock-encased-backfill structure under stepwise cyclic triaxial loading

Rock-encased-backfill(RB)structures are common in underground mining,for example in the cut-andfill and stoping methods.To understand the effects of cyclic excavation and blasting activities on the damage of these RB structures,a series of triaxial stepwise-increasing-amplitude cyclic loading experiments was conducted with cylindrical RB specimens(rock on outside,backfill on inside)with different volume fractions of rock(VF=0.48,0.61,0.73,and 0.84),confining pressures(0,6,9,and 12 MPa),and cyclic loading rates(200,300,400,and 500 N/s).The damage evolution and meso-crack formation during the cyclic tests were analyzed with results from stress-strain hysteresis loops,acoustic emission events,and post-failure X-ray 3D fracture morphology.The results showed significant differences between cyclic and monotonic loadings of RB specimens,particularly with regard to the generation of shear microcracks,the development of stress memory and strain hardening,and the contact forces and associated friction that develops along the rock-backfill interface.One important finding is that as a function of the number of cycles,the elastic strain increases linearly and the dissipated energy increases exponentially.Also,compared with monotonic loading,the cyclic strain hardening characteristics are more sensitive to rising confining pressures during the initial compaction stage.Another finding is that compared with monotonic loading,more shear microcracks are generated during every reloading stage,but these microcracks tend to be dispersed and lessen the likelihood of large shear fracture formation.The transition from elastic to plastic behavior varies depending on the parameters of each test(confinement,volume fraction,and cyclic rate),and an interesting finding was that the transformation to plastic behavior is significantly lower under the conditions of 0.73 rock volume fraction,400 N/s cyclic loading rate,and 9 MPa confinement.All the findings have important practical implications on the ability of backfill to support underground excavations.

Stress-corrosion coupled damage localization induced by secondary phases in bio-degradable Mg alloys:phase-field modeling

In this study,a phase-field scheme that rigorously obeys conservation laws and irreversible thermodynamics is developed for modeling stress-corrosion coupled damage(SCCD).The coupling constitutive relationships of the deformation,phase-field damage,mass transfer,and electrostatic field are derived from the entropy inequality.The SCCD localization induced by secondary phases in Mg is numerically simulated using the implicit iterative algorithm of the self-defined finite elements.The quantitative evaluation of the SCCD of a C-ring is in good agreement with the experimental results.To capture the damage localization,a micro-galvanic corrosion domain is defined,and the buffering effect on charge migration is explored.Three cases are investigated to reveal the effect of localization on corrosion acceleration and provide guidance for the design for resistance to SCCD at the crystal scale.

Does HSP27 injection induce glaucoma damage in mice?

In a further aging society,excellent eyesight is an integral part of overall well-being and quality of life.Preserving good vision is crucial to maintaining mobility,independence,and mental health.There can be several reasons for visual impairment in elderly people,these include age-related macular degeneration,the leading cause of vision loss among older adults,cataract,glaucoma,diabetic retinopathy,retinal detachment,and others.

Modulation of p75 neurotrophin receptor mitigates brain damage following ischemic stroke in mice

Stroke is a significant leading cause of death and disability in the United States(Tsao et al.,2022).Approximately 87% of strokes fall into the ischemic category,mainly caused by arterial blockage(Jayaraj et al.,2019).Although the only FDA-approved effective medication is tissue plasminogen activator(tPA),it should be administrated within 4.5 hours of ischemic stroke.Furthermore,tPA has been an integral part of managing acute ischemic stro ke.

Parameter calibration of the tensile-shear interactive damage constitutive model for sandstone failure

The tensile-shear interactive damage(TSID)model is a novel and powerful constitutive model for rock-like materials.This study proposes a methodology to calibrate the TSID model parameters to simulate sandstone.The basic parameters of sandstone are determined through a series of static and dynamic tests,including uniaxial compression,Brazilian disc,triaxial compression under varying confining pressures,hydrostatic compression,and dynamic compression and tensile tests with a split Hopkinson pressure bar.Based on the sandstone test results from this study and previous research,a step-by-step procedure for parameter calibration is outlined,which accounts for the categories of the strength surface,equation of state(EOS),strain rate effect,and damage.The calibrated parameters are verified through numerical tests that correspond to the experimental loading conditions.Consistency between numerical results and experimental data indicates the precision and reliability of the calibrated parameters.The methodology presented in this study is scientifically sound,straightforward,and essential for improving the TSID model.Furthermore,it has the potential to contribute to other rock constitutive models,particularly new user-defined models.

An extended micromechanical-based plastic damage model for understanding water effects on quasi-brittle rocks

Water effects on the mechanical properties of rocks have been extensively investigated through experiments and numerical models.However,few studies have established a comprehensive link between the microscopic mechanisms of water-related micro-crack and the constitutive behaviors of rocks.In this work,we shall propose an extended micromechanical-based plastic damage model for understanding weakening effect induced by the presence of water between micro-crack’s surfaces on quasi-brittle rocks,based on the Mori-Tanaka homogenization and irreversible thermodynamics framework.Regarding the physical mechanism,water strengthens micro-crack propagation,which induces damage evolution during the pre-and post-stage,and weakens the elastic effective properties of rock matrix.After proposing a special calibration procedure for the determination of model parameters based on the laboratory compression tests,the proposed micromechanical-based model is verified by comparing the model predictions to the experimental results.The model effectively captures the mechanical behaviors of quasibrittle rocks subjected to the weakening effects of water.

Magnetic resonance imaging findings of radiation-induced breast angiosarcoma:A case report

BACKGROUND Breast conservation surgery(BCS)with adjuvant radiotherapy has become a gold standard in the treatment of early-stage breast cancer,significantly reducing the risk of tumor recurrence.However,this treatment is associated with adverse effects,including the rare but aggressive radiation-induced angiosarcoma(RIAS).Despite its rarity and nonspecific initial presentation,RIAS presents a challenging diagnosis,emphasizing the importance of imaging techniques for early detection and accurate diagnosis.CASE SUMMARY We present a case of a 48-year-old post-menopausal woman who developed skin ecchymosis on the right breast seven years after receiving BCS and adjuvant radiotherapy for breast cancer.Initial mammography and ultrasound were inconclusive,showing post-treatment changes but failing to identify the underlying angiosarcoma.Contrast-enhanced breast magnetic resonance imaging(MRI)revealed diffuse skin thickening and nodularity with distinctive enhan-cement kinetics,leading to the diagnosis of RIAS.This case highlights the crucial role of MRI in diagnosing and determining the extent of RIAS,facilitating timely and appropriate surgical intervention.CONCLUSION Breast MRI is crucial for detecting RIAS,especially when mammography and ultrasound are inconclusive.

Identification of earthquake induced structural damage based on synchroextracting transform

Several popular time-frequency techniques,including the Wigner-Ville distribution,smoothed pseudo-Wigner-Ville distribution,wavelet transform,synchrosqueezing transform,Hilbert-Huang transform,and Gabor-Wigner transform,are investigated to determine how well they can identify damage to structures.In this work,a synchroextracting transform(SET)based on the short-time Fourier transform is proposed for estimating post-earthquake structural damage.The performance of SET for artificially generated signals and actual earthquake signals is examined with existing methods.Amongst other tested techniques,SET improves frequency resolution to a great extent by lowering the influence of smearing along the time-frequency plane.Hence,interpretation and readability with the proposed method are improved,and small changes in the time-varying frequency characteristics of the damaged buildings are easily detected through the SET method.

Numerical study on the blocking effect of skin on Flash-Ball Impact and damage assessment

To explore the response law of non-lethal large-size kinetic energy projectiles to blunt attack on skin tissue,and to evaluate the skin injury characteristics of the attacked personnel and the use safety of kinetic energy projectiles.Based on the LS-DYNA simulation software,a three-layer skin simulation model and a Flash-Ball rubber bullet model are established,and the force-time and deformation-time biomechanical corridors of the Flash-Ball rubber bullet impacting human skin tissue are obtained.The corridor curve and the energy transfer and diffusion are analyzed and compared.The safety evaluation of the damage caused by the rubber bullet shooting a human body at different distances is carried out using the empirical formula of the penetration limit.Finally,the safe shooting distance is obtained.The results show that the model used in the simulation has a good correlation with the experimental data,its biomechanical corridor characteristics are different from those of conventional vehicle impact and smallsize projectile response characteristics.The energy transfer and action time of medium and low-speed impact may cause greater damage.The fat layer is the largest energy absorption unit.The minimum safe shooting distance to ensure skin tissue from penetrating damage is 15.8 m,and the limit specific kinetic energy of skin damage is 7.88 J/cm^(2).This study can be extended to the study of biomechanical response law and safety evaluation under the impact of the same type of large kinetic energy projectile,which provides an important theoretical reference for the police to use large kinetic energy projectiles to conduct safe shooting in peacekeeping operations.

Finite element model updating for structural damage detection using transmissibility data

This paper presents a new finite element model updating method for estimating structural parameters and detecting structural damage location and severity based on the structural responses(output-only data).The method uses the sensitivity relation of transmissibility data through a least-squares algorithm and appropriate normalization of the extracted equations.The proposed transmissibility-based sensitivity equation produces a more significant number of equations than the sensitivity equations based on the frequency response function(FRF),which can estimate the structural parameters with higher accuracy.The abilities of the proposed method are assessed by using numerical data of a two-story two-bay frame model and a plate structure model.In evaluating different damage cases,the number,location,and stiffness reduction of the damaged elements and the severity of the simulated damage have been accurately identified.The reliability and stability of the presented method against measurement and modeling errors are examined using error-contaminated data.The parameter estimation results prove the method’s capabilities as an accurate model updating algorithm.

Shear behavior and off-fault damage of saw-cut smooth and tension-induced rough joints in granite

The damage of rock joints or fractures upon shear includes the surface damage occurring at the contact asperities and the damage beneath the shear surface within the host rock.The latter is commonly known as off-fault damage and has been much less investigated than the surface damage.The main contribution of this study is to compare the results of direct shear tests conducted on saw-cut planar joints and tension-induced rough granite joints under normal stresses ranging from 1 MPa to 50 MPa.The shear-induced off-fault damages are quantified and compared with the optical microscope observation.Our results clearly show that the planar joints slip stably under all the normal stresses except under 50 MPa,where some local fractures and regular stick-slip occur towards the end of the test.Both post-peak stress drop and stick-slip occur for all the rough joints.The residual shear strength envelopes for the rough joints and the peak shear strength envelope for the planar joints almost overlap.The root mean square(RMS)of asperity height for the rough joints decreases while it increases for the planar joint after shear,and a larger normal stress usually leads to a more significant decrease or increase in RMS.Besides,the extent of off-fault damage(or damage zone)increases with normal stress for both planar and rough joints,and it is restricted to a very thin layer with limited micro-cracks beneath the planar joint surface.In comparison,the thickness of the damage zone for the rough joints is about an order of magnitude larger than that of the planar joints,and the coalesced micro-cracks are generally inclined to the shear direction with acute angles.The findings obtained in this study contribute to a better understanding on the frictional behavior and damage characteristics of rock joints or fractures with different roughness.

Cholesterol and Sericin as First Aid for Damaged Cells

Cells are surrounded by a double-layered phospholipid cell membrane responsible for the isolation of intracellular contents, active regulation of uptake from the extracellular environment, and intercellular connection and communication. These cell membranes must be intact and functionally active for cell survival and biological functioning. Compromised damage repair mechanisms usually result in impaired cellular homeostasis, leading to early or late problems. Chronic myopathies, certain myocardial diseases, aging, and acute or chronic neurodegenerative diseases (like Parkinson and Alzheimer) are directly related to cell membrane damage. This study examined the effect of a cholesterol-loaded nanoparticle (methyl-beta cyclodextrin) or the silk protein sericin on cell membrane and DNA integrity and cell viability in an in vitro cell damage model (frozen-thawed rabbit sperm cells). The cells were stored in liquid nitrogen (-196°C), thawed in small batches, and treated with cholesterol-loaded cyclodextrin or sericin before incubation at 35°C for 4 hours. Cell membrane integrity, DNA damage, and viability rates were assessed immediately after thawing and after the incubation period. The administration of sericin and cholesterol in a cell damage model increased cell survival and reduced DNA damage over a 4-hour post-thaw incubation period, suggesting their potential use as a “first aid” intervention at the cellular level.

Residual stress modeling of mitigated fused silica damage sites with CO_(2)laser annealing

A numerical model based on measured fictive temperature distributions is explored to evaluate the residual stress fields of CO_(2)laser-annealed mitigated fused silica damage sites.The proposed model extracts the residual strain from the differences in thermoelastic contraction of fused silica with different fictive temperatures from the initial frozen-in temperatures to ambient temperature.The residual stress fields of mitigated damage sites for the CO_(2)laser-annealed case are obtained by a finite element analysis of equilibrium equations and constitutive equations.The simulated results indicate that the proposed model can accurately evaluate the residual stress fields of laser-annealed mitigated damage sites with a complex thermal history.The calculated maximum hoop stress is in good agreement with the reported experimental result.The estimated optical retardance profiles from the calculated radial and hoop stress fields are consistent with the photoelastic measurements.These results provide sufficient evidence to demonstrate the suitability of the proposed model for describing the residual stresses of mitigated fused silica damage sites after CO_(2)laser annealing.

Experimental study of the damage characteristics of rocks containing non-penetrating cracks under cyclic loading

The damage evolution process of non-penetrating cracks often causes some unexpected engineering disasters.Gypsum specimens containing non-penetrating crack(s)are used to study the damage evolution and characteristics under cyclic loading.The results show that under cyclic loading,the relationship between the number of non-penetrating crack(s)and the characteristic parameters(cyclic number,peak stress,peak strain,failure stress,and failure strain)of the pre-cracked specimens can be represented by a decreasing linear function.The damage evolution equation is fitted by calibrating the accumulative plastic strain for each cycle,and the damage constitutive equation is proposed by the concept of effective stress.Additionally,non-penetrating cracks are more likely to cause uneven stress distribution,damage accumulation,and local failure of specimen.The local failure can change the stress distribution and relieve the inhibition of non-penetrating crack extension and eventually cause a dramatic destruction of the specimen.Therefore,the evolution process caused by non-penetrating cracks can be regarded as one of the important reasons for inducing rockburst.These results are expected to improve the understanding of the process of spalling formation and rockburst and can be used to analyze the stability of rocks or rock structures.

Effects of the initiation position on the damage and fracture characteristics of linear-charge blasting in rock

To study the effects of the initiation position on the damage and fracture characteristics of linear-charge blasting, blasting model experiments were conducted in this study using computed tomography scanning and three-dimensional reconstruction methods. The fractal damage theory was used to quantify the crack distribution and damage degree of sandstone specimens after blasting. The results showed that regardless of an inverse or top initiation, due to compression deformation and sliding frictional resistance, the plugging medium of the borehole is effective. The energy of the explosive gas near the top of the borehole is consumed. This affects the effective crushing of rocks near the top of the borehole, where the extent of damage to Sections Ⅰ and Ⅱ is less than that of Sections Ⅲ and Ⅳ. In addition, the analysis revealed that under conditions of top initiation, the reflected tensile damage of the rock at the free face of the top of the borehole and the compression deformation of the plug and friction consume more blasting energy, resulting in lower blasting energy efficiency for top initiation. As a result, the overall damage degree of the specimens in the top-initiation group was significantly smaller than that in the inverse-initiation group. Under conditions of inverse initiation, the blasting energy efficiency is greater, causing the specimen to experience greater damage. Therefore, in the engineering practice of rock tunnel cut blasting, to utilize blasting energy effectively and enhance the effects of rock fragmentation, using the inverse-initiation method is recommended. In addition, in three-dimensional(3D) rock blasting, the bottom of the borehole has obvious end effects under the conditions of inverse initiation, and the crack distribution at the bottom of the borehole is trumpet-shaped. The occurrence of an end effect in the 3D linear-charge blasting model experiment is related to the initiation position and the blocking condition.

Electronic effects on radiation damage inα-iron:A molecular dynamics study

Iron(Fe)-based alloys,which have been widely used as structural materials in nuclear reactors,can significantly change their microstructure properties and macroscopic properties under high flux neutron irradiation during operation,thus,the problems associated with the safe operation of nuclear reactors have been put forward naturally.In this work,a molecular dynamics simulation approach combined with electronic effects is developed for investigating the primary radiation damage process inα-Fe.Specifically,the influence of electronic effects on the collision cascade in Fe is systematically evaluated based on two commonly used interatomic potentials for Fe.The simulation results reveal that both electronic stopping(ES)and electron-phonon coupling(EPC)can contribute to the decrease of the number of defects in the thermal spike phase.The application of ES reduces the number of residual defects after the cascade evolution,whereas EPC has a reverse effect.The introduction of electronic effects promotes the formation of the dispersive subcascade:ES significantly changes the geometry of the damaged region in the thermal spike phase,whereas EPC mainly reduces the extent of the damaged region.Furthermore,the incorporation of electronic effects effectively mitigates discrepancies in simulation outcomes when using different interatomic potentials.

Temperature dependence of mechanical properties and damage evolution of hot dry rocks under rapid cooling

Understanding the differences in mechanical properties and damage characteristics of granitoid under high temperatures is crucial for exploring deep geothermal resources.This study analyzes the evolution of the acoustic emission(AE)characteristics and mechanical parameters of granodiorite and granite after heating and water cooling by uniaxial compression and variable-angle shear tests under different temperature gradients.We identify their changes in mesostructure and mineral composition with electron probe microanalysis and scanning electron microscopy.Results show that these two hot dry rocks have similar diagenetic minerals and microstructure,but show significantly different mechanical and acoustic characteristics,and even opposing evolution trends in a certain temperature range.At the temperatures ranging from 100℃to 500℃,the compressive and shear mechanical properties of granodiorite switch repeatedly between weakening and strengthening,and those of granite show a continuous weakening trend.At 600℃,both rocks exhibit a deterioration of mechanical properties.The damage mode of granite is characterized by initiating at low stress,exponential evolutionary activity,and intensified energy release.In contrast,granodiorite exhibits the characteristics of initiating at high stress,volatile evolutionary activity,and intermittent energy release,due to its more stable microstructure and fewer thermal defects compared to granite.As the temperature increases,the initiation and propagation of secondary cracks in granodiorite are suppressed to a certain extent,and the seismicity and brittleness are enhanced.The subtle differences in grain size,microscopic heterogeneity,and mineral composition of the two hot dry rocks determine the different acoustic-mechanical characteristics under heating and cooling,and the evolution trends with temperature.These findings are of great significance for the scientific and efficient construction of rock mass engineering by rationally utilizing different rock strata properties.

Damage Evolution of Ballastless Track Concrete Exposed to Flexural Fatigue Loads:The Application of Ultrasonic Pulse Velocity,Impact-echo and Surface Electrical Resistance Method

In order to clarify the fatigue damage evolution of concrete exposed to flexural fatigue loads,ultrasonic pulse velocity(UPV),impact-echo technology and surface electrical resistance(SR) method were used.Damage variable based on the change of velocity of ultrasonic pulse(Du) and impact elastic wave(Di)were defined according to the classical damage theory.The influences of stress level,loading frequency and concrete strength on damage variable were measured.The experimental results show that Du and Di both present a three-stages trend for concrete exposed to fatigue loads.Since impact elastic wave is more sensitive to the microstructure damage in stage Ⅲ,the critical damage variable,i e,the damage variable before the final fracture of concrete of Di is slightly higher than that of Du.Meanwhile,the evolution of SR of concrete exposed to fatigue loads were analyzed and the relationship between SR and Du,SR and Di of concrete exposed to fatigue loads were established.It is found that the SR of concrete was decreased with the increasing fatigue cycles,indicating that surface electrical resistance method can also be applied to describe the damage of ballastless track concrete exposed to fatigue loads.

A creep model for ultra-deep salt rock considering thermal-mechanical damage under triaxial stress conditions

To investigate the specific creep behavior of ultra-deep buried salt during oil and gas exploitation,a set of triaxial creep experiments was conducted at elevated temperatures with constant axial pressure and unloading confining pressure conditions.Experimental results show that the salt sample deforms more significantly with the increase of applied temperature and deviatoric loading.The accelerated creep phase is not occurring until the applied temperature reaches 130℃,and higher temperature is beneficial to the occurrence of accelerated creep.To describe the specific creep behavior,a novel three-dimensional(3D)creep constitutive model is developed that incorporates the thermal and mechanical variables into mechanical elements.Subsequently,the standard particle swarm optimization(SPSO)method is adopted to fit the experimental data,and the sensibility of key model parameters is analyzed to further illustrate the model function.As a result,the model can accurately predict the creep behavior of salt under the coupled thermo-mechanical effect in deep-buried condition.Based on the research results,the creep mechanical behavior of wellbore shrinkage is predicted in deep drilling projects crossing salt layer,which has practical implications for deep rock mechanics problems.