Mechanical suppression of breast cancer cell invasion and paracrine signaling to osteoclasts requires nucleo-cytoskeletal connectivity

Exercise benefits the musculoskeletal system and reduces the effects of cancer.The effects of exercise are multifactorial,where metabolic changes and tissue adaptation influence outcomes.Mechanical signals,a principal component of exercise,are anabolic to the musculoskeletal system and restrict cancer progression.We examined the mechanisms through which cancer cells sense and respond to low-magnitude mechanical signals introduced in the form of vibration.Low-magnitude,high-frequency vibration was applied to human breast cancer cells in the form of low-intensity vibration(LIV).LIV decreased matrix invasion and impaired secretion of osteolytic factors PTHLH,IL-11,and RANKL.Furthermore,paracrine signals from mechanically stimulated cancer cells,reduced osteoclast differentiation and resorptive capacity.Disconnecting the nucleus by knockdown of SUN1 and SUN2 impaired LIV-mediated suppression of invasion and osteolytic factor secretion.LIV increased cell stiffness;an effect dependent on the LINC complex.These data show that mechanical vibration reduces the metastatic potential of human breast cancer cells,where the nucleus serves as a mechanosensory apparatus to alter cell structure and intercellular signaling.

MRI-Based Patient-Specific Left Ventricular Model to Determine the Effects of Trabeculae Carneae on the Diastolic and Systolic Functions

Introduction Trabeculae carneae are irregular structures that cover the endocardial surfaces of both ventricles of human heart and account for a significant portion of the ventricular mass.However,the role of trabeculae carneae in left ventricular(LV)function is not well understood.Previous reports suggested that trabeculae help squeeze blood from the apical region during systole[1].Our recent study suggests that trabeculae carneae hypertrophy and fibrosis contribute to increased LV stiffness in patients with diastolic heart failure,and severing free-running trabeculae carneae may improve diastolic compliance of the LV[2].Objective To understand the role of trabeculae carneae in the left ventricular diastolic and systolic functions using anatomically detailed patient-specific finite element models of the human LV.Methods(1)Image acquisition An explanted human heart was collected from a 63 year old female donor with a history of stroke and congestive heart failure within 24 hours postmortem from South Texas Blood and Tissue Center(San Antonio,TX).The heart was de-identified in accordance with Institutional Review Board(IRB)requirements and informed consent for research was obtained from the donor’s family.Three-dimensional MRI scanning was conducted on a 3T(128 MHz)MRI system(TIM Trio,Siemens Medical Solutions),comprised of a superconducting magnet with a 60 cm diameter accessible bore,when the heart was submerged in a saline filled plastic container.(2)Finite element analysis Three distinct LV models were derived from the MR images.The first model was the intact trabeculated model(TM)which contained all trabeculae carneae and papillary muscles.This high-resolution anatomically detailed 3D model of the LV was segmented from 2D MR images in DICOM format using Mimics(Materialise NV,Leuven,Belgium).The second model was the papillary model(PM),in which the papillary muscles remain intact but most of the trabeculae carneae were excluded in the smoothing process.The third model was the smooth model(SM)in which the trabeculae carneae and papillary muscles were excluded during image segmentation.Finite element(FE)models of the TM,PM and SM were created by meshing 3D reconstructions of the acquired MR images using tetrahedral elements(ICEM,Ansys Inc.,Canonsburg,PA).The mesh size was selected after a pilot study on mesh sensitivity.The passive cardiac muscle was characterized as a hyperelastic,incompressible,transversely isotropic material with a Fung exponential strain energy function.The material constants were determined by matching the end-diastolic pressure-volume relationship with the empirical Klotz relation[3].A rule-based myocardial fiber algorithm was adopted to generate the myofiber directions [4].The active contraction(i.e.,systolic contraction)was modeled by the time varying'Elastance'active contraction model.The contractile parameter Tmax was determined and calibrated so that the FE predicted ejection fraction(EF)of TM matched the EF of a normal human heart at the specified end-systolic pressure[3].The analysis of the TM,PM,and SM models were implemented using the open-source finite element package FEBio(www.febio.org).In all models,the rigid body motion was suppressed by constraining the base from moving in all directions.The end-diastolic and end-systolic pressure-volume relationships(EDPVR and ESPVR)were obtained and characterized by an exponential function and the slope,respectively.Results Our simulation results showed that independent of the material model,the EDPVR curve shifts to the right in PM and SM compared to TM.However,the ESPVR curve may shift to the right or left in PM compared to TM,while shifting tothe right in SM for all material models.EDPVR was steeper in TM compared to PM and SM;however,ESPVR was found to be steeper in PM than in TM and SM.The predicted parameters of EDPVR and ESPVR showed lower average exponential term in PM and SM compared to TM,indicating a significant improvement in the compliance and global diastolic function of less trabeculated LV models(P<0.01).Similarly,the higher average elastance EEs and lower volume intersect in PM compared to TM,suggests that mild cutting of trabeculae carneae slightly improves the global systolic function of the LV(P=0.89).However,cutting all trabeculae carneae and papillary muscles in SM had a significant adverse effect on the global systolic function(P<0.01).Discussion and conclusions Most patient-specific LV studies in the literature have used smoothed ventricular geometries.We used high resolution MRI to capture the endocardial details of the LV.Though reproducing very fine trabeculae carneae was restricted by the MRI resolution,our results demonstrated the importance of considering endocardial structures,i.e.papillary muscles and trabeculae carneae,in the assessment of LV global function in patient-specific computational LV models.The present work is consistent with the observation that diastolic performance improved after severing trabeculae carneae due to a reduction in LV stiffness[2].Furthermore,our results also suggest that severing trabeculae carneae(without affecting papillary muscle)may improve LV systolic function.Our model results are consistent with experimental measurements using ex vivo rabbit heart perfusion [5].This improvement would be greater in hypertrophic hearts because trabeculae carneae are also hypertrophic and more fibrotic.Left ventricular hypertrophy is often associated with heart failure with preserved ejection fraction(HFpEF).There is no effective treatment for HFpEF,which is characterized by impaired diastolic relaxation due to increased LV stiffness.Our results indicate that trabecular cutting could be an effective treatment for HFpEF.

Mechanical instability of veins under internal pressure

Introduction Tortuous veins are often seen in the retina,cerebrum,and human legs. Venous tortuosity may affect blood flow and the wall remodeling process,both of which are associated with venous diseases. It has been shown that tortuous or vari-

Effect of Laryngopharyngeal Anatomy on Expiratory Airflow and Submicrometer Particle Deposition in Human Extrathoracic Airways

The objective of this study is to systematically assess the influences of the larynopharyneal anatomical details on airflow and particle behaviors during exhalation by means of image-based modeling. A physiologically realistic nose-throat airway was developed with medical images. Individual airway anatomy such as uvula, pharynx, and larynx were then isolated for examination by progressively simplifying this image-based model geometry. Low Reynolds number (LRN) k-w model and Langrangian tracking model were used to simulate the dynamics of airflow and particle transport for a wide range of exhalation conditions (4-45 L/min) and particle sizes (1 nm-1 μm). Results showed that pharyngeal anatomical details exerted a significant impact on breathing resistance and particle profiles. Abrupt pressure drop resulting from the uvula-related airway obstruction was observed. Even though the total deposition rate in the nasal airway is largely unaffected by the upstream effect, the local deposition patterns vary notably. Results of this study also indicate that the pressure drop appears to be an appropriate parameter to characterize the geometric variations for diffusive depositions. Inclusion of pressure drop (D0.5Q-0.62dp0.07) gives an improved correlation than using the conventional diffusion factor (D0.5Q﹣0.28).

Strength Characteristics of Inoculated and Nodularised Thin Wall Ductile Iron Castings

Carbide precipitates in Thin Wall Ductile Iron (TWDI) used for automotive applications needs to be eliminated or reduced for improved strength, ductility, crack propagation resistance and good machinability. Ductile iron thin section profiles (≤3 mm) present danger of massive carbide precipitations in the as-cast sample. Precipitated carbide phase is brittle and negatively affects the mechanical properties of the iron matrix. The suppression of carbide formation is associated with the nucleating properties of the nodularizer and innoculant alloys. This treatment is vital in ensuring that carbide precipitation, flake graphite structure and non-nodular graphite phases are reduced or completely eliminated in the TWDI castings. Therefore, the temperature and technique of treatment would influence the yield of the process, and ultimately the mechanical properties. In this study, the effect of nodularization and inoculation treatment temperature on the microstructure and mechanical properties of TWDI castings is examined. The results indicate that good nodularity and nodule count with better percent elongations are achieved using low treatment temperatures in descending order of 1490°C, 1470°C and 1450°C, but have negative effect at lower treatment temperature of 1430°C. However, TWDI castings have superior properties in terms of nodule counts and nodularity at 1450°C. Treatment temperature does not produce significant influence on ultimate tensile strength (UTS) and hardness of TWDI castings. TWDI castings show poor nodularity, nodule count and ductility at higher inoculation treatment temperatures of 1550°C, 1530°C and 1510°C.

Laser-Assisted Reduction of Highly Conductive Circuits Based on Copper Nitrate for Flexible Printed Sensors

Stretchable electronic sensing devices are defining the path toward wearable electronics. High-performance flexible strain sensors attached on clothing or human skin are required for potential applications in the entertainment,health monitoring, and medical care sectors. In this work,conducting copper electrodes were fabricated onpolydimethylsiloxane as sensitive stretchable microsensors by integrating laser direct writing and transfer printing approaches. The copper electrode was reduced from copper salt using laser writing rather than the general approach of printing with pre-synthesized copper or copper oxide nanoparticles. An electrical resistivity of 96 l X cm was achieved on 40-lm-thick Cu electrodes on flexible substrates. The motion sensing functionality successfully demonstrated a high sensitivity and mechanical robustness.This in situ fabrication method leads to a path toward electronic devices on flexible substrates.

Mechanisms of rectangular groove-induced multiple-microdroplet coalescences

The mechanism of microdroplet coalescence is a fundamental issue for droplet-based microfluidics. We developed an asymmetric expansion (a rectangular groove) along one side of a microchannel to achieve multiple-microdroplet trapping, collision, and coalescence. Compared with reported symmetric expansions, this asymmetric groove could easily trap microdroplets and control two or three microdroplet coalescences precisely without a requirement for temporal and spatial synchronization. To reveal the mechanisms of multiple-droplet coalescences in a groove, we observed five different coalescence patterns under different flow conditions. Moreover, we characterized the flow behavior quantitatively by simulating the velocity vector fields in both the microdroplets and continuous phase, finding good agreement with experiments. Finally, a map of coalescence forms with different capillary numbers () and flow ratios () was obtained. The results could provide a useful guidance for the design and application of droplet-based microfluidic devices.

Protective effects of organic extracts of Alpinia oxyphylla against hydrogen peroxide-induced cvtotoxicitv in PC12 cells

Alpinia oxyphylla,a traditional herb,is widely used for its neuroprotective,antioxidant and memory-improving effects.However,the neuroprotective mechanisms of action of its active ingredients are unclear.In this study,we investigated the neuroprotective effects of various organic extracts of Alpinia oxyphylla on PC12 cells exposed to hydrogen peroxide-induced oxidative injury in vitro.Alpinia oxyphylla was extracted three times with 95%ethanol(representing extracts 1–3).The third 95%ethanol extract was dried and resuspended in water,and then extracted successively with petroleum ether,ethyl acetate and n-butanol(representing extracts 4–6).The cell counting kit-8 assay and microscopy were used to evaluate cell viability and observe the morphology of PC12 cells.The protective effect of the three ethanol extracts(at tested concentrations of 50,100 and 200μg/mL)against cytotoxicity to PC12 cells increased in a concentration-dependent manner.The ethyl acetate,petroleum ether and n-butanol extracts(each tested at 100,150 and 200μg/mL)had neuroprotective effects as well.The optimum effective concentration ranged from 50–200μg/mL,and the protective effect of the ethyl acetate extract was comparatively robust.These results demonstrate that organic extracts of Alpinia oxyphylla protect PC12 cells against apoptosis induced by hydrogen peroxide.Our findings should help identify the bioactive neuroprotective components in Alpinia oxyphylla.

Generation of minimally persistent circle formation for a multi-agent system

In this paper, two methods of generating minimally persistent circle formation are presented. The proposed methods adopt a leader-follower strategy and all followers are firstly motivated to move into the leader＇s interaction range. Based on the information about relative angle and relative distance, two numbering schemes are proposed to generate minimally persistent circle formation. Distributed control laws are also designed to maintain the desired relative distance between agents. The distinctive features of the proposed methods are as follows. First, only 2n - 3 unilateral communication links for n agents are needed during the circle formation process and thus the communication complexity can be reduced. In addition, the formation topology is kept fixed for the whole motion and achieves a self-stability property. Finally, each follower keeps a regualr interval with its neighbors and the formation converges to a uniform circle formation. Simulation results are also provided to demonstrate the effectiveness of the proposed methods.

Secondary relaxation and dynamic heterogeneity in metallic glasses：A brief review

Understanding mechanical relaxation, such as primary（α） and secondary（β） relaxation, is key to unravel the intertwined relation between the atomic dynamics and non-equilibrium thermodynamics in metallic glasses. At a fundamental level, relaxation, plastic deformation, glass transition, and crystallization of metallic glasses are intimately linked to each other, which can be related to atomic packing, inter-atomic diffusion, and cooperative atom movement. Conceptually, βrelaxation is usually associated with structural heterogeneities intrinsic to metallic glasses. However, the details of such structural heterogeneities, being masked by the meta-stable disordered long-range structure, are yet to be understood. In this paper, we briefly review the recent experimental and simulation results that were attempted to elucidate structural heterogeneities in metallic glasses within the framework of β relaxation. In particular, we will discuss the correlation amongβ relaxation, structural heterogeneity, and mechanical properties of metallic glasses.

A universal method to calculate the surface energy density of spherical surfaces in crystals

Surface energy plays an important role in the mechanical performance of nanomaterials; however, determining the surface energy density of curved surfaces remains a challenge. In this paper, we conduct atomic simulations to calculate the surface energy density of spherical surfaces in various crystalline metals. It is found that the average surface energy density of spherical surfaces remains almost constant once its radius exceeds 5 nm. Then, using a geometrical analysis and the scaling law, we develop an analytical approach to estimate the surface energy density of spherical surfaces through that of planar surfaces. The theoretical prediction agrees well with the direct atomic simulations, and thus provides a simple and general method to calculate the surface energy density in crystals.

A primitive approach to Ou MC decrescendo phenomenon with a hands-on therapy—The relation between human bilateral symmetry and disease

The Ou MC decrescendo phenomenon (OuDP) involves the placing of the contralateral hand of the examiner on the acute abdomen of female patients (Ou MC manipulation), which results in an alleviation of pain [1]. Two front-end observations showed that placement of the contralateral hand on the acute abdomen of women alleviated pain (78 of 81 women or 96.3%), while placement of the ipsilateral hand did not (0 of 39 women or 0%). This method named as Ou MC handing remedy (HR) was used to observe the immediate and cumulative effects of OuDP on 38 cases, of which 27 were self-administered and 11 were administered by the therapist. The mean age of the patients was 55.8 years (standard deviation, 22.9 years). Five minutes after initial self-administered HR, there was pain alleviation in 14 cases and symptoms or signs beyond pain improved for another 6 cases while 7 cases unevaluated. Final results showed 9 cured, 5 with partial remission and the remaining 13 with complete remission. Five minutes after initial therapist-administered HR, pain alleviation was found with 10 cases while 1 case unevaluated. The final results showed 7 cases cured, 2 with partial remission, and 2 with complete remission. The resolution of non-infectious conditions (23/ 38) with OuDP is consistent with the restoration of normal tissue function, which seems to contribute to pain alleviation and defense against infections and tumors. Interestingly, the OuDP is capable of being invoked by either the patient or the therapist. These findings warrant further investigation.

Broadband asymmetric transmission for linearly and circularly polarization based on sand-clock structured metamaterial

We proposed a sandwich structure to realize broadband asymmetric transmission(AT) for both linearly and circularly polarized waves in the near infrared spectral region. The structure composes of a silica substrate and two sand-clock-like gold layers on the opposite sides of the substrate. Due to the surface plasmons of gold, the structure shows that the AT parameters of linearly and circularly polarized waves can reach 0.436 and 0.403, respectively. Meanwhile, a broadband property is presented for the AT parameter is over 0.3 between 320 THz and 340 THz. The structure realizes a diode-like AT for linearly wave in forward and circularly wave in backward, respectively. The magnetic dipoles excited by current in the two gold layers contribute to the broadband AT. The current density in top and bottom metallic layers illustrates the mechanism of the polarization conversion for broadband AT in detail.

Nanoindentation of soft solids by a fla punch

Measuring the surface tension and elastic mod- ulus of soft materials and biological tissues under different physiological and pathological conditions is of significance for understanding various phenomena associated with defor- mation. In this paper, the nanoindentation of a circular fiat punch on a soft solid is analyzed with the influence of surface tension. By solving the corresponding singular integral equa- tion, the relation between load and indent depth is obtained. When the radius of the flat punch shrinks to the same order as the ratio of surface tension to elastic modulus, surface ten- sion significantly affects the indentation load-depth relation, which provides a facile method to measure surface tension in soft solids and biological tissues.

Image Interpolation via Gaussian-Sinc Interpolators with Partition of Unity

In this paper,we propose a novel image interpolation method by using Gaussian-Sinc automatic interpolators with partition of unity property.A comprehensive comparison is made with classical image interpolation methods,such as the bicubic interpolation,Lanczos interpolation,cubic Schaum interpolation,cubic B-spline interpolation and cubic Moms interpolation.The experimental results show the effectiveness of the improved image interpolation method via some image quality metrics such as PSNR and SSIM.

A Finite Element Model of Locked Plating in Femoral Shaft Fractures

Introduction: The Locking Compression Plate (LCP) system is a versatile technology that can be used either through conventional compression plating techniques or as an internal fixator with locking head screws. There have been only a few biomechanical studies examining the role of locked screw configuration on construct stability with most recommendations based upon empirical evidence or data from compression plating. This study will attempt to determine how different locked screw configurations, fracture gaps (distance between bone fragments), and interface gaps (distance between plate and bone) will affect the peak stress(von Mises stress) experienced by the plate-screw construct and, thereby, look at ways to minimize the risk of hardware failure. Materials Methods: A finite element model (FEM) was developed of a transverse mid shaft femoral fracture bridged by an eight-hole titanium LCP. Seven different screw configurations were investigated. Three different fracture gaps and three different interface gaps were studied as well. Results: The 1368 configuration was found to experience the least peak stress of 2.10 GPa while the 2367, 2457, and all filled configurations were found to have the highest peak stress (25.29 GPa, 22.78 GPa, and 23.54 GPa, respectively). Peak stress increased when the interface gap increased. Peak stress also increased as the fracture gap increased, with the largest jump between the 1 mm and 2 mm gaps. Conclusions: Every fracture is unique, and has a vast amount of parameters that must be considered when the surgeon is developing a treatment plan. For transverse femoral shaft fractures, the results of this study suggest that a working length of 2 screw holes on either side of the fracture may also lead to lower peak stress. In addition, our results demonstrate that minimizing the fracture gap and interface gap will lead to decreased stress in the plate-screw construct.

Pulse-Impact on Microstructure of Liquid-Phase-Pulse-Impact Diffusion Welded Joints of Particle Reinforcement Aluminum Matrix Composites at Various Temperatures

Investigation was to study the influence of pulse-impact on microstructure of Liquid-Phase-Pulse-Impact Diffusion Welding (LPPIDW) welded joints of aluminum matrix composite SiCp/A356, SiCp/6061Al, Al2O3p/6061Al. Results showed that under the effect of pulse-impact: 1) the interface state between reinforcement particle (SiC, Al2O3) and matrix was prominently;2) the initial pernicious contact-state of reinforcement particles was changed from reinforcement (SiC, Al2O3)/reinforcement (SiC, Al2O3) to reinforcement (SiC, Al2O3)/matrix/ reinforcement (SiC, Al2O3);3) the density of dislocation in the matrix neighboring to and away from the interface in the matrix was higher than its parent composite;and 4) the intensively mutual entwisting of dislocation was occurred. Studies illustrated that: 1) deformation was mainly occurred in the matrix grain;and 2) under the effect of pulse-impact, the matrices around reinforcement (SiC, Al2O3) particles engendered intensive aberration offered a high density nucleus area for matrix crystal, which was in favor of forming nano-grains and improved the properties of the successfully welded composite joints.

Achieving high strength and high ductility in nanostructured metals: Experiment and modelling

Department of Mechanical and Biomedical Engineering, City University of Hong Kong, Kowloon, Hong Kong, Chinagrains to a^1-martensite nanograins with bimodal grain size distribution for lower strain rates to nanotwins in the ultrafine/coarse grained austenite phase for higher strain rates. Meanwhile, we will further address the mechanism-based plastic models to describe the yield strength, strain hardening and ductility in nanostructured metals with bimodal grain size distribution and nanotwinned polycrystalline metals. The proposed theoretical models can comprehensively describe the plastic deformation in these two kinds of nanostructured metals and excellent agreement is achieved between the numerical and experimental results. These models can be utilized to optimize the strength and ductility in nanostructured metals by controlling the size and distribution of nanostructures.

The combined effects of grain and sample sizes on the mechanical properties and fracture modes of gold microwires

Hall-Petch relation was widely applied to evaluate the grain size effect on mechanical properties of metallic material. However, the sample size effect on the Hall-Petch relation was always ignored. In the present study, the mechanical test and microstructure observation were performed to investigate the combined effects of grain and sample sizes on the deformation behaviors of gold microwires. The polycrystalline gold microwires with diameter of 16 ?m were annealed at temperatures from 100°C to 600°C, leading to different ratios(t/d) of wire diameter(t) to grain size(d) from 0.9 to 16.7. When the t/d was lower than 10, the yield stress dropped fast and deviated from the Hall-Petch relation. The free-surface grains played key role in the yield stress softening, and the volume fraction of free-surface grains increased with the t/d decreasing. Furthermore, the effects of t/d on work-hardening behaviors and fracture modes were also studied. With t/d value decreasing from 17 to 3.4, the samples exhibited necking fracture and the dislocation pile-ups induced work-hardening stage was gradually activated.With the t/d value further decreasing(t/d < 3.4), the fracture mode turned into shear failure, and the work-hardening capability lost. As the gold microwire for wire bonding is commonly applied in the packaging of integrated circuit chips, and the fabrication of microwire suffers multi-pass cold-drawing and annealing treatments to control the grain size. The present study could provide instructive suggestion for gold microwire fabrication and bonding processes.