Fracture Simulation of Concrete Beams to assess softening behavior by varying different fractions of Aggregates

Simulating the concrete fracture unlike other elastic and brittle materials quite different due to its quasibrittleness. The present research focussed on assess softening behavior by varying different fractions of aggregates  and cement matrix in micro details. Extended Finite Element Method (XFEM) for crack modeling implemented for simulating and visualizing crack propagation through Cement matrix, Interfacial Transition Zone (ITZ) and Aggregates . This approach permits the initializing crack by from enrichment zone and propagation of crack through element by traction separation law .The crack formation initiates when the maximum principal tensile stress reaches the tensile strength. The work involves creating python script for iterative process of random distribution of aggregates with in the matrix using Monte Carlo method and creating Cohesive zone element for zero thickness ITZ. introduces a finite element modeling technique for investigating multiscale fracture characteristics. This approach encompasses multiple levels of analysis, including the generation of aggregate particles using a Monte Carlo method implemented via a Python script. Additionally, we replicate the Interfacial Transition Zone (ITZ) between aggregate and mortar in the model. The load-deflection curves can be used to assess the softening behavior of concrete and suggest the realistic fraction of coarse aggregate in mix proportion to impart more ductility to beams

Genotoxic agents promote the nuclear accumulation of annexin A2: role of annexin A2 in mitigating DNA damage

Annexin A2 is an abundant cellular protein that is mainly localized in the cytoplasm and plasma membrane, however a small population has been found in the nucleus, suggesting a nuclear function for the protein. Annexin A2 possesses a nuclear export sequence (NES) and inhibition of the NES is sufficient to cause nuclear accumulation. Here we show that annexin A2 accumulates in the nucleus in response to genotoxic agents including gamma-radiation, UV radiation, etoposide and chromium VI and that this event is mediated by the nuclear export sequence of annexin A2. Nuclear accumulation of annexin A2 is blocked by the antioxidant agent N-acetyl cysteine (NAC) and stimulated by hydrogen peroxide (H2O2), suggesting that this is a reactive oxygen species dependent event. In response to genotoxic agents, cells depleted of annexin A2 show enhanced phospho-histone H2AX and p53 levels, increased numbers of p53-binding protein 1 nuclear foci and increased levels of nuclear 8-oxo-2'-deoxyguanine, suggesting that annexin A2 plays a role in protecting DNA from damage. This is the first report showing the nuclear translocation of annexin A2 in response to genotoxic agents and its role in mitigating DNA damage.Natural Sciences and Engineering Research Council of Canada (NSERC); European Union [PCOFUND-GA-2009-246542]; Foundation for Science and Technology of Portugal; Beatrice Hunter Cancer Research Institute; Terry Fox Foundationinfo:eu-repo/semantics/publishedVersio

Casodex treatment induces hypoxia-related gene expression in the LNCaP prostate cancer progression model

BACKGROUND: The changes in gene expression profile as prostate cancer progresses from an androgen-dependent disease to an androgen-independent disease are still largely unknown. METHODS: We examined the gene expression profile in the LNCaP prostate cancer progression model during chronic treatment with Casodex using cDNA microarrays consisting of 2305 randomly chosen genes. RESULTS: Our studies revealed a representative collection of genes whose expression was differentially regulated in LNCaP cells upon treatment with Casodex. A set of 15 genes were shown to be highly expressed in Casodex-treated LNCaP cells compared to the reference sample. This set of highly expressed genes represents a signature collection unique to prostate cancer since their expression was significantly greater than that of the collective pool of ten cancer cell lines of the reference sample. The highly expressed signature collection included the hypoxia-related genes membrane metallo-endopeptidase (MME), cyclin G2, and Bcl2/adenovirus E1B 19 kDa (BNIP3). Given the roles of these genes in angiogenesis, cell cycle regulation, and apoptosis, we further analyzed their expression and concluded that these genes may be involved in the molecular changes that lead to androgen-independence in prostate cancer. CONCLUSION: Our data indicate that one of the mechanisms of Casodex action in prostate cancer cells is induction of hypoxic gene expression

Current concepts in bone metastasis, contemporary therapeutic strategies and ongoing clinical trials

Abstract Background Elucidation of mechanisms regulating bone metastasis has progressed significantly in recent years and this has translated to many new therapeutic options for patients with bone metastatic cancers. However, the rapid rate of progress in both the basic science literature and therapies undergoing clinical trials makes staying abreast with current developments challenging. This review seeks to provide an update on the current state of the science in bone metastasis research and give a snap shot of therapies in clinical trials for bone metastatic cancer. Main body Bone metastasis represents a difficult to treat clinical scenario due to pain, increased fracture risk, decreased quality of life and diminished overall survival outcomes. Multiple types of cancer have the specific ability to home to the bone microenvironment and cause metastatic lesions. This osteotropism was first described by Stephen Paget nearly 100 years ago as the ‘seed and soil’ hypothesis. Once cancer cells arrive at the bone they encounter a variety of cells native to the bone microenvironment which contribute to the establishment of bone metastatic lesions. In the first part of this review, the ‘seed and soil’ hypothesis is revisited while emphasizing recent developments in understanding the impact of native bone microenvironment cells on the metastatic process. Next, approved therapies for treating bone metastasis at the systemic level as well as those that target the bone microenvironment are discussed and current National Comprehensive Cancer Network (NCCN) guidelines relating to treatment of bone metastases are summarized. Finally, all open interventional clinical trials for therapies relating to treatment of bone metastasis have been complied and categorized. Conclusion Understanding the recent advancements in bone metastasis research is important for continued development of novel bone targeted therapies. The plethora of ongoing clinical trials will hopefully translate into improved treatments options for patients suffering from bone metastatic cancers

Sub chronic toxicity studies of lactulose in rats

441-446<span style="font-size: 14.0pt;mso-bidi-font-size:9.0pt;font-family:" times="" new="" roman","serif""="">Lactulose has profound health benefits by way of increasing bifidobacterial flora in the intestine of infants thereby protecting them against enteric infection, constipation and systemic encephalopathy. In the present study to assess the sub chronic toxicity of lactulose syrup, the rats were fed on a basal feed supplemented with lactulose syrup at <span style="font-size:13.5pt; mso-bidi-font-size:8.5pt;font-family:" times="" new="" roman","serif""="">0.5, 1.0, 2.0 and 5.0 % for a period of <span style="font-size:13.5pt;mso-bidi-font-size:8.5pt; font-family:" times="" new="" roman","serif""="">21 <span style="font-size:14.0pt; mso-bidi-font-size:9.0pt;font-family:" times="" new="" roman","serif""="">weeks. Monitoring of food consumption, gain in body weight and physical observations did not reveal any treatment-related toxicity in any of the group of rats. Terminal autopsy also did not reveal any signs of toxicity. Further, no significant alterations in relative organ weight, serum biochemistry and urinalysis were observed up to 1% lactulose supplementation level. The results suggest that supplementation of lactulose in the diet does not produce any toxicity at the doses tested. </span