Kırık örgü test örnekleri için çatlakdan önce yorulma cycle hesaplaması.

This study is done for predicting fatigue crack initiation life and propagation life of a crack initiated at a notch and grown to a desired length. Both numerical analysis and experimental study was done for single edge notch bend type specimen. Crack initiation life prediction was done using strain-life approach applying different available models. For this purpose 2-D and 3-D finite element model of the specimen was created in Abaqus. By simulating the 2-D and 3-D model under static loading, notch maximum stress was found to calculate the notch elastic stress concentration factor. Applying Neuber’s rule local stresses and strains of notched part was calculated. These values were then compered to values found by elasto-plastic analysis done for 3-D model in Abaqus. Then, fatigue crack initiation life was predicted. For the propagation part, the required number of cycles to grow the initiated crack from 1 mm length to a desired length was calculated by using Walker and Paris equations. At the end the predicted lives were compared to experimental ones. It is found that reasonable agreement could be obtained, and the established procedure could be used in planning the preparation stages of cracked beam specimens.M.S. - Master of Scienc

Rapid cascade synthesis of poly-heterocyclic architectures from indigo

The base-induced propargylation of the dye indigo results in the rapid and unprecedented one-pot synthesis of highly functionalized representatives of the pyrazino[1,2-a:4,3-a′]diindole, pyrido[1,2-a:3,4-b′]diindole and benzo[b]indolo[1,2-h]naphthyridine heterocyclic systems, with the last two reflecting the core skeleton of the anticancer/antiplasmodial marine natural products fascaplysin and homofascaplysins and a ring B-homologue, respectively. The polycyclic compounds 6–8, whose structures were confirmed through single-crystal X-ray crystallographic analysis, arise from sequential inter/intramolecular substitution–addition reactions, and in some cases, ring rearrangement reactions. Preliminary studies on controlling the reaction path selectivity, and the potential reaction mechanisms, are also described. Initial biological activity studies with these new heterocyclic derivatives indicated promising in vitro antiplasmodial activity as well as good anticancer activity. The chemistry described is new for the indigo moiety and cascade reactions from this readily available and cheap starting material should be more broadly applicable in the synthesis of additional new heterocyclic systems difficult to access by other means

Fatigue Precracking Time Estimates for Three-Point Bending Specimens

Specimens containing sharp cracks are needed in certain types of mechanical tests, first and foremost for fracture toughness measurement of materials. Their use, however, is not just limited to this type of test. Another category of experiments deals with characterizing nonlinear vibrations of beams containing breathing cracks. To produce cracked beam specimens, fatigue cracks can be grown ahead of sharp notches under controlled loading. ASTM E399 and ASTM E1820 standards provide guidance on such procedures for preparation of fracture toughness test specimens. However, certain issues which might become important in testing of vibrations of cracked beams, such as the time required for specimen preparation is not addressed in these standards. In this article, both low cycle fatigue methods and linear elastic fracture mechanics methods are used to estimate the number of loading cycles required to have a crack of desired length at the notch tip. Calculation results are compared with experimental ones, and the effects of various factors influencing the required number of loading cycles for a certain crack size are discussed

Comparison of IL-28B favorable genotype frequency between healthy and patients infected with HCV

Introduction: Combination of interferon-alpha (IFN-α) and Ribavirin (RBV) drugs is used for treatment of hepatitis C virus (HCV) chronic infection. Various factors play role in the response rate of HCV infected patients to treatment. HCV genotype along with viral load, age, race, obesity, insulin resistance, fibrosis and interleukin 28B gene (IL-28B) polymorphisms are considered the most important ones. In recent years, it has been claimed that some polymorphisms close to IL-28B gene play a significant role in response to combined therapy among which IL-28B polymorphisms have a more important role in sustained virological response (SVR). In this study, frequency of genotypes of rs8099917 polymorphism of interleukin 28B gene in 2 groups of Iranian healthy individuals and HCV infected patients living in Tehran was compared.   Materials & Methods: Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to compare the frequency of genotypes of rs8099917 polymorphism between 105 healthy individuals and 105 chronic HCV infected patients. The results were analyzed with SPSS version 15 using χ2 test.   Findings: The genotype frequency of this polymorphism in the healthy individuals was demonstrated as GG: 1%, GT: 25.7% and TT: 73.3%, while in HCV infected patients, it was shown as GT: 58.1% and TT: 41.9%.. No GG genotype was detected in the patients infected with HCV.   Discussion & Conclusion: Our investigation came to the conclusion that  a significant difference existed between the 2 groups of Iranian healthy and HCV infected individuals regarding the frequency of rs8099917 genotypes and frequency of favorable TT genotype, because it was higher among the healthy individuals than that of the patients infected with HC

Hyaluronic acid‐decorated liposomal nanoparticles for targeted delivery of 5‐fluorouracil into HT‐29 colorectal cancer cells

The use of liposomes as drug carriers improves the therapeutic efficacy of anti-cancer drugs, while at the same time reducing side effects. Hyaluronic acid (HA) is recognized by the CD44 receptor, which is over-expressed in many cancer cells. In this study, we developed HA-modified liposomes encapsulating 5-fluorouracil (5-FU) and tested them against a CD44 expressing colorectal cell line (HT29) and a non-CD44 expressing hepatoma cell line (HEPG2). The average size of 5-FU-lipo and 5-FU-lipo-HA nanoparticles were 112±28 nm and 144±77 nm respectively. The MTT assay showed selective cancer cell death depending on CD44 expression in a time-dependent manner. Apoptosis assays and cell cycle analysis indicated that G0/G1 arrest occurred. The colony formation study revealed that cells treated with 5-FU-lipo and 5-FU-lipo-HA had reduced colony formation. QRT-PCR study showed that the oncogenic mRNA and miRNA levels were significantly reduced in the 5-FU-lipo-HA treated group, while tumor suppressors were increased in that group. We suggest that optimal targeted delivery and release of 5-FU into colorectal cancer cells, renders them susceptible to apoptosis, cell cycle arrest and decreased colony formation

miR-142-3p as tumor suppressor miRNA in the regulation of tumorigenicity, invasion and migration of human breast cancer by targeting Bach-1 expression

Background: Breast cancer is the most common type of cancer among women, and despite improved treatments, it remains a major challenge. However, improved mechanistic insight may lead to novel therapeutic strategies. miR-142-3p belongs to the miR-142 family and is involved in pathogenesis and metastasis of various types of malignancies by targeting several important messenger RNAs (mRNAs) including Bach-1. This is especially true for breast cancer, where Bach-1 is involved in the metastatic spread by deregulation of metastasis-associated genes. Methods: In this study, we collected 24 breast cancer tissues with 24 adjusted normal tissues to measure the expression levels of miR-142-3p and Bach-1 mRNA using quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and IHC. miR-142-3p targeting of Bach-1 expression in MCF-7 and MDA-MB-468 breast cancer cells was evaluated using bioinformatics, qRT-PCR and western blot analyses. The cellular proliferation, invasion, and migration were assessed by MTT, transwell matrigel and wound healing assay and the EMT-associated proteins C-X-C chemokine receptor type 4 (CXCR-4), matrix metalloproteinase-9 (MMP9), and vascular endothelial growth factor receptor (VEGFR) were analyzed by western blot analysis. Also, the expression levels of tumor suppressors including miR-330, miR-145, and miR-34a were estimated by qRT-PCR. Results: Analysis of paired specimens of primary malignant and normal tissues showed that miR-142-3p was downregulated, while Bach-1 mRNA and protein both were overexpressed in the breast cancer tumors. This inverse relationship was confirmed by cell line experiments demonstrating that miR-142-3p expression reduced Bach-1 mRNA levels. Furthermore, replacement of miR-142-3p could inhibit the proliferation, invasion, and migration in breast cancer potentially by targeting of Bach-1 mRNA and subsequent inhibition of CXCR4, MMP9, and VEGFR protein expressions. In addition, induction of miR-142-3p could upregulate tumor suppressor miRNAs, including miR-330, miR-145, and miR34a. Conclusion: For the first time, our results revealed that miR-142-3p could target Bach-1in breast cancer cells leading to the reduction of EMT-related proteins and reduced cell proliferation, invasion, and migration. The results also demonstrated that miR-142-3p could regulate important tumor suppressor miRNAs in breast cancer cells. In conclusion, our results suggest that miR-142-3p could be a good candidate for the targeted therapy of breast cancer, especially for the invasive type

Hyaluronic acid‐decorated liposomal nanoparticles for targeted delivery of 5‐fluorouracil into HT‐29 colorectal cancer cells

The use of liposomes as drug carriers improves the therapeutic efficacy of anti-cancer drugs, while at the same time reducing side effects. Hyaluronic acid (HA) is recognized by the CD44 receptor, which is over-expressed in many cancer cells. In this study, we developed HA-modified liposomes encapsulating 5-fluorouracil (5-FU) and tested them against a CD44 expressing colorectal cell line (HT29) and a non-CD44 expressing hepatoma cell line (HEPG2). The average size of 5-FU-lipo and 5-FU-lipo-HA nanoparticles were 112±28 nm and 144±77 nm respectively. The MTT assay showed selective cancer cell death depending on CD44 expression in a time-dependent manner. Apoptosis assays and cell cycle analysis indicated that G0/G1 arrest occurred. The colony formation study revealed that cells treated with 5-FU-lipo and 5-FU-lipo-HA had reduced colony formation. QRT-PCR study showed that the oncogenic mRNA and miRNA levels were significantly reduced in the 5-FU-lipo-HA treated group, while tumor suppressors were increased in that group. We suggest that optimal targeted delivery and release of 5-FU into colorectal cancer cells, renders them susceptible to apoptosis, cell cycle arrest and decreased colony formation