Deformation mechanisms of idealised cermets under multi-axial loading

The response of idealised cermets comprising approximately 60% by volume steel spheres in a Sn/Pb solder matrix is investigated under a range of axisymmetric compressive stress states. Digital volume correlation (DVC) analysis of X-ray micro-computed tomography scans (μ-CT), and the measured macroscopic stress-strain curves of the specimens revealed two deformation mechanisms. At low triaxialities the deformation is granular in nature, with dilation occurring within shear bands. Under higher imposed hydrostatic pressures, the deformation mechanism transitions to a more homogeneous incompressible mode. However, DVC analyses revealed that under all triaxialities there are regions with local dilatory and compaction responses, with the magnitude of dilation and the number of zones wherein dilation occurs decreasing with increasing triaxiality. Two numerical models are presented in order to clarify these mechanisms: (i) a periodic unit cell model comprising nearly rigid spherical particles in a porous metal matrix and (ii) a discrete element model comprising a large random aggregate of spheres connected by non-linear normal and tangential “springs”. The periodic unit cell model captured the measured stress-strain response with reasonable accuracy but under-predicted the observed dilation at the lower triaxialities, because the kinematic constraints imposed by the skeleton of rigid particles were not accurately accounted for in this model. By contrast, the discrete element model captured the kinematics and predicted both the overall levels of dilation and the simultaneous presence of both local compaction and dilatory regions with the specimens. However, the levels of dilation in this model are dependent on the assumed contact law between the spheres. Moreover, since the matrix is not explicitly included in the analysis, this model cannot be used to predict the stress-strain responses. These analyses have revealed that the complete constitutive response of cermets depends both on the kinematic constraints imposed by the particle aggregate skeleton, and the constraints imposed by the metal matrix filling the interstitial spaces in that skeleton.The authors are grateful to the Office of Naval Research (ONR) for their financial support through grant number N00014121063

Wrinkling to crinkling transitions and curvature localization in a magnetoelastic film bonded to a non-magnetic substrate

International audienceThis work studies experimentally and numerically the post-bifurcation response of a magnetorheological elastomer (MRE) film bonded to a soft non-magnetic (passive) substrate. The film-substrate system is subjected to a combination of an axial mechanical pre-compression and a transverse magnetic field. The non-trivial interaction of the two fields leads to a decrease of the critical magnetic field with applied pre-compression, while the observed wrinkling patterns evolve into crinkles, a bifurcation mode that is defined by the accompanied curvature localization and strong shearing of the side faces of the wrinkled geometry. Using a magneto-elastic variational formulation in a two-dimensional finite element numerical setting, we find that the crinkling is an intrinsic feature of magnetoelasticity and its presence is directly associated with the repulsive magnetic forces of the neighboring wrinkled-crinkled faces. As a result, the presence of the magnetic field prohibits the formation of creases and folds. In an effort to obtain a good quantitative agreement between the numerical and the experimental results, we also introduce an approximate way to model the friction of the lateral film-substrate faces. This analysis reveals the strong effects of friction upon the magneto-mechanical wrinkling modes

Evaluation of cannabinoid CB1 and CB2 receptors expression in mobile tongue squamous cell carcinoma: associations with clinicopathological parameters and patients’ survival

Cannabinoid receptors (CB1R and CB2R) constitute essential members of the endocannabinoid system (ECS) which participates in many different functions indispensable to homeostatic regulation in several tissues, exerting also antitumorigenic effects. The present study aimed to assess the clinical significance of CB1R and CB2R protein expression in mobile tongue squamous cell carcinoma (SCC). CB1R and CB2R expression was assessed immunohistochemically on 28 mobile tongue SCC tissue samples and was analyzed in relation with clinicopathological characteristics and overall and disease-free patients’ survival. CB1R, CB2R, and concomitant CB1R/CB2R expression was significantly increased in older compared to younger mobile tongue SCC patients (p = 0.0243, p = 0.0079, and p = 0.0366, respectively). Enhanced CB2R and concomitant CB1R/CB2R expression was significantly more frequently observed in female compared to male mobile tongue SCC patients (p = 0.0025 and p = 0.0016, respectively). Elevated CB2R expression was significantly more frequently observed in mobile tongue SCC patients presenting well-defined tumor shape compared to those with diffuse (p = 0.0430). Mobile tongue SCC patients presenting enhanced CB1R, CB2R, or concomitant CB1R/CB2R expression showed significantly longer overall (log-rank test, p = 0.004, p = 0.011, p = 0.018, respectively) and disease-free (log-rank test, p = 0.003, p = 0.007, p = 0.027, respectively) survival times compared to those with low expression. In multivariate analysis, CB1R was identified as an independent prognostic factor for disease-free patients’ survival (Cox-regression analysis, p = 0.032). The present study provides evidence that CB1R and CB2R may play a role in the pathophysiological aspects of the mobile tongue SCC and even each molecule may constitute a potential target for the development of novel anti-cancer drugs for this type of malignancy. © 2015, International Society of Oncology and BioMarkers (ISOBM)

Clinical Significance of Hu-Antigen Receptor (HuR) and Cyclooxygenase-2 (COX-2) Expression in Human Malignant and Benign Thyroid Lesions

Hu-antigen R (HuR) is considered to play a crucial role in tumor formation and growth by binding to mRNAs encoding proteins such as Cyclooxygenase-2 (COX-2) and inducing their expression via mRNA stabilization and/or altered translation. The present study aimed to evaluate the clinical significance of HuR and COX-2 proteins’ expression in human benign and malignant thyroid lesions. HuR and COX-2 proteins’ expression was assessed immunohistochemically on paraffin-embedded thyroid tissues obtained from 98 patients with benign (n = 48) and malignant (n = 50) lesions and was statistically analyzed with clinicopathological parameters, follicular cells’ proliferative capacity and recurrence risk rate. Enhanced HuR and COX-2 expression was significantly more frequently observed in malignant compared to benign thyroid lesions (p = 0.0073 and p = 0.0016, respectively), as well as in papillary carcinomas compared to hyperplastic nodules (p = 0.0039 and p = 0.0009, respectively). Positive associations of both HuR and COX-2 expression with follicular cells’ proliferation rate were also noted (p = 0.0087 and p = 0.0127, respectively). In malignant thyroid lesions, elevated COX-2 expression was significantly associated with female patients’ gender (p = 0.0381) and the presence of lymph node metastases (p = 0.0296). The present data support evidence that both HuR and COX-2 may be involved in the malignant state of thyroid neoplasia and may be utilized in the diagnosis of malignant thyroid tumors. © 2015, Arányi Lajos Foundation

Elevated Hu-antigen Receptor (HuR) expression is associated with tumor aggressiveness and poor prognosis but not with COX-2 expression in invasive breast carcinoma patients

Hu-antigen R (HuR), a RNA-binding protein, is considered to play a crucial role in tumor development and progression by stabilizing or regulating a group of cellular mRNAs of cancer-related genes, such as cyclooxygenase-2 (COX-2). The present study aimed to evaluate the clinical significance of HuR and COX-2 expression in invasive breast carcinoma. HuR and COX-2 protein expression was assessed immunohistochemically on paraffin-embedded breast cancer tissue sections obtained from 121 patients and was statistically analyzed with clinicopathological parameters, estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2), as well as with tumor cells' proliferative capacity and overall and disease-free patients' survival. High HuR expression was positively associated with larger tumor size and advanced disease stage (p = 0.0234 and p = 0.0361, respectively), being more frequently observed in ER negative cases (p = 0.0208). High COX-2 expression was negatively associated with histological (p < 0.0001) and nuclear (p = 0.0033) grade and tumor cells' proliferative rate (p = 0.0015), being more frequently observed in luminal-A compared to other molecular subtypes (p = 0.0221). High HuR expression was associated with poor overall and disease-free patients' survival at both univariate (log-rank test, p = 0.0092 and p = 0.0004, respectively) and multivariate (Cox-regression analysis, p = 0.0223 and p = 0.0004, respectively) level. On the other hand, high COX-2 expression was associated with favorable overall and disease-free patients' survival merely at univariate level (log-rank test, p = 0.0389 and p = 0.0154, respectively). HuR expression was not associated with COX-2 expression (Spearman R = 0.1489, p = 0.1032). The present data support evidence that HuR is associated with tumor aggressiveness and poor prognosis in breast carcinoma, reinforcing its potential as promising therapeutic target in this type of neoplasia

High farnesoid X receptor (FXR) expression is a strong and independent prognosticator in invasive breast carcinoma

Farnesoid X Receptor (FXR), a nuclear receptor superfamily member, is related with bile acids, glucose and lipids metabolism and recently with cancer. In the present study the clinical significance of FXR expression in invasive breast carcinoma was evaluated. FXR protein expression was assessed immunohistochemically on paraffin-embedded breast cancer tissues obtained from 115 breast cancer patients and was statistically analyzed with clinicopathological parameters, estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) expression, as well as with tumor cells’ proliferative capacity and overall and disease-free patients’ survival. FXR positivity was noted in 91 (79.1%) and high FXR expression in 51 (44.3%) out of 115 invasive breast carcinoma cases. High FXR expression was significantly associated with smaller tumor size (p=0.0318) and increased tumor cells’ proliferative rate (p=0.0375). Invasive breast carcinoma patients presenting high FXR expression showed significantly longer overall and disease-free survival times compared to those with low FXR expression (log-rank test, p=0.0052 and p=0.0058). In multivariate analysis, FXR expression was identified as independent prognostic factor of overall and disease-free patients’ survival (Cox-regression analysis, p=0.0023 and p=0.0049, respectively). The present data support evidence that FXR may be implicated at the earlier stage of breast malignant disease progression, being a strong and independent prognosticator of favorable overall and disease-free survival in invasive breast carcinoma. © 2017, Cancer Research Institute Slovak Acad. of Sciences. All rights reserved

Elevated Hu-Antigen Receptor (HuR) Expression is Associated with Tumor Aggressiveness and Poor Prognosis but not with COX-2 Expression in Invasive Breast Carcinoma Patients

Hu-antigen R (HuR), a RNA-binding protein, is considered to play a crucial role in tumor development and progression by stabilizing or regulating a group of cellular mRNAs of cancer-related genes, such as cyclooxygenase-2 (COX-2). The present study aimed to evaluate the clinical significance of HuR and COX-2 expression in invasive breast carcinoma. HuR and COX-2 protein expression was assessed immunohistochemically on paraffin-embedded breast cancer tissue sections obtained from 121 patients and was statistically analyzed with clinicopathological parameters, estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2), as well as with tumor cells’ proliferative capacity and overall and disease-free patients’ survival. High HuR expression was positively associated with larger tumor size and advanced disease stage (p = 0.0234 and p = 0.0361, respectively), being more frequently observed in ER negative cases (p = 0.0208). High COX-2 expression was negatively associated with histological (p &lt; 0.0001) and nuclear (p = 0.0033) grade and tumor cells’ proliferative rate (p = 0.0015), being more frequently observed in luminal-A compared to other molecular subtypes (p = 0.0221). High HuR expression was associated with poor overall and disease-free patients’ survival at both univariate (log-rank test, p = 0.0092 and p = 0.0004, respectively) and multivariate (Cox-regression analysis, p = 0.0223 and p = 0.0004, respectively) level. On the other hand, high COX-2 expression was associated with favorable overall and disease-free patients’ survival merely at univariate level (log-rank test, p = 0.0389 and p = 0.0154, respectively). HuR expression was not associated with COX-2 expression (Spearman R = 0.1489, p = 0.1032). The present data support evidence that HuR is associated with tumor aggressiveness and poor prognosis in breast carcinoma, reinforcing its potential as promising therapeutic target in this type of neoplasia. © 2017, Arányi Lajos Foundation

Expression and clinical significance of concomitant fak/src and p-paxillin in mobile tongue squamous cell carcinoma

Background/Aim: The focal adhesion kinase (FAK)/SRC phosphorylation cascade and its downstream target paxillin have been implicated in malignant transformation, tumor growth and progression, together with metastasis. The present study aimed to evaluate the clinical significance of concomitant FAK/SRC and p-paxillin expression in mobile tongue squamous cell carcinoma (SCC). Materials and Methods: FAK, SRC and phosphopaxillin expression in 48 mobile tongue SCC tissue samples was assessed immunohistochemically and analyzed with respect to clinicopathological characteristics and patient survival. Results: Concomitant high FAK/SRC expression was significantly associated with high grade of tumor differentiation (p=0.048) and longer disease-free patient survival (log-rank test, p=0.019). High p-paxillin expression was significantly associated with greater depth of invasion (p=0.002), lymph node metastasis (p=0.048) and poorer disease-free patient survival (log-rank test, p=0.021; Coxregression analysis, p=0.031). Conclusion: The present study provides evidence that FAK/SRC and paxillin play a role in the pathophysiological aspects of mobile tongue SCC and could constitute therapeutic targets

Impact of deserosalization on small bowel anastomosis healing in swine: A pilot study

Background: Healing is related to gastrointestinal anastomotic leak, which is a severe and common complication. This study aimed to investigate the feasibility and the impact of deserosalization on healing of jejuno-jejunal anastomoses in an animal model. Materials and Methods: Seven swine underwent three types of side-to-side jejuno-jejunal anastomosis twice and survived seven days. Three different types of jejuno-jejunal sideto- side anastomoses were performed twice at 20-cm distance from each other in each animal: no serosa removal, one-sided, and two-sided serosa removal, respectively. Bursting pressure, tissue hydroxyproline concentration, and pathology scores were evaluated. Results: Hydroxyproline tissue concentration was a mean±standard deviation of 0.37±0.09, 0.38±0.08, and 0.30±0.05 nmoI/ml respectively (p&lt;0.05). Bursting pressure was a mean±standard deviation of 59.02±8.60, 73.20±11.09, and 100.01±7.49 mmHg, respectively (p&lt;0.001). The histopathological assessment did not find any statistically significant differences. Conclusion: Deserosalization in jejunojejunal anastomosis was technically feasible and seemed to improve mechanical strength and collagen deposition in this experimental porcine model. Further investigation is warranted. © 2020 International Institute of Anticancer Research. All rights reserved

Histone deacetylase (Hdac)−1, −2, −4, and −6 in uveal melanomas: Associations with clinicopathological parameters and patients’ survival

Background: Uveal melanoma (UM) represents the most common primary intraocular malignancy in adults, exerting high metastatic potential and poor prognosis. Histone deacetylases (HDACs) play a key role in carcinogenesis, and HDAC inhibitors (HDACIs) are currently being explored as anti‐cancer agents in clinical settings. The aim of this study was to evaluate the clinical significance of HDAC−1, −2, −4, and −6 expression in UM. Methods: HDAC−1, −2, −4, and −6 expression was examined immunohistochemically in 75 UM tissue specimens and was correlated with tumors’ clinicopathological characteristics, the presence of tumor‐infiltrating lymphocytes (TILS), as well as with our patients’ overall survival (OS). Results: HDAC−2 was the most frequently ex-pressed isoform (66%), whereas we confirmed in addition to the expected nuclear expression the presence of cytoplasmic expression of class I HDAC isoforms, namely HDAC−1 (33%) and HDAC−2 (9.5%). HDAC−4 and −6 expression was cytoplasmic. HDAC−1 nuclear expression was associated with increased tumor size (p = 0.03), HDAC−6 with higher mitotic index (p = 0.03), and nuclear HDAC−2 with epithelioid cell morphology (p = 0.03) and presence of tumor‐infiltrating lympho-cytes (p = 0.04). The association with the remaining parameters including Monosomy 3 was not significant. Moreover, the presence as well as the nuclear expression pattern of HDAC−2 were correlated with patients’ improved OS and remained significant in multivariate survival analysis. Conclusions: These findings provide evidence for a potential role of HDACs and especially HDAC−2 in the biological mechanisms governing UM evolution and progression. © 2021 by the authors. Licensee MDPI, Basel, Switzerland