Evaluation of different techniques in estimating orientation of crack initiation planes and fatigue lifetime under complex multiaxial loading paths

In the present investigation, the accuracy of two methods, i.e., the Shear Strain-Maximum Variance Method (γ-MVM) and the Maximum Damage Method (MDM), in predicting the orientation of the crack initiation planes was checked by considering several results taken from the literature and generated by testing five different metallic materials under complex multiaxial loading. The γ-MVM postulates that the critical plane is that material plane containing the direction experiencing the maximum variance of the resolved shear strain. In contrast, the MDM defines the critical plane as that material plane on which the accumulated damage reaches its maximum value. In the present investigation, the MDM was applied in conjunction with Fatemi-Socie's (FS) multiaxial fatigue criterion, Bannantine-Socie's (BS) cycle counting method, and Miner's linear rule. The validation exercise being performed demonstrated that both the γ-MVM and the MDM were capable of accurately predicting the orientation of the crack initiation planes in the selected metals. Subsequently, the reliability of three different design methodologies suitable for estimating fatigue lifetime of metals subjected to variable amplitude multiaxial loading was assessed quantitatively by using a number of experimental results taken from the literature. In more detail, Methodology A was based on the MDM applied along with the FS criterion, the BS cycle counting method, and Miner's rule. Methodology B made use of the γ-MVM, the FS criterion, the BS cycle counting method, and Miner's linear rule. Finally, Methodology C involved the γ-MVM, the Modified Manson Coffin Curve Method (MMCCM), the classical Rain-Flow cycle counting method, and Miner's linear rule. According to this systematic validation exercise, the usage of these three design procedures was seen to result in satisfactory predictions, with the estimates falling within an error band of three

Dual Thermographic Monitoring of Ti-6Al-4V Cylinders During Direct Laser Deposition

Understanding the thermal phenomena associated with Direct Laser Deposition (DLD) is necessary to begin manipulating fabricated part properties. In this study, a thermally monitored Laser Engineered Net Shaping (LENS) system is used with time-invariant (uncontrolled) build parameters to construct Ti-6Al-4V cylinders with two different build paths. Both paths utilize a circular contour with serpentine hatch fill; however, successive layer patterns are varied and the effects compared between 90° and 120° angular pattern shifts. During fabrication, the part’s thermal history and melt pool temperature are recorded via an in-chamber infrared (IR) camera and a dual-wavelength (DW) pyrometer, respectively. These tools are used for non-destructive thermographic inspection (NTI) of the part to ensure target quality and/or microstructure. A unique calibration method for the IR camera utilizing the DW pyrometer data is presented and a calibration correction factor was utilized for high temperature ranges. The melt pool was found to be 40-50% superheated reaching temperatures up to 2500 ºC at times. Temperature characteristics of two different layers were compared for different hatching patters, and the results show that for a given point in time, maximum temperatures can vary based on laser raster. Temperature gradients varied and peaked at about 1000 ºC/mm along the diameter of the small rods. This can lead to anisotropy in microstructural and mechanical properties allowing for unique property growth per build path. Cooling rates within the melt pool appear to increase as maximum melt pool temperature increases, for instance, from 16,000 ºC/s – 41,000 ºC/s.Mechanical Engineerin

Protection of hippocampal CA1 neurons against ischemia/Reperfusion injury by exercise preconditioning via modulation of Bax/Bcl-2 ratio and prevention of Caspase-3 Activation

Introduction: Ischemia leads to loss of neurons by apoptosis in specific brain regions, especially in the hippocampus. The purpose of this study was investigating the effects of exercise preconditioning on expression of Bax, Bcl-2, and caspase-3 proteins in hippocampal CA1 neurons after induction of cerebral ischemia. Methods: Male rats weighing 260-300 g were randomly allocated into three groups (sham, exercise, and ischemia). The rats in exercise group were trained to run on atreadmill 5 days a week for 4 weeks. Ischemia was induced by the occlusion of both common carotid arteries (CCAs) for 20 min. Levels of expression of Bax, Bcl-2, and caspase-3 proteins in CA1 area of hippocampus were determined by immunohistochemical staining . Results: The number of active caspase-3-positive neurons in CA1 area were significantly increased in ischemia group, compared to sham-operated group (P<0.001), and exercise preconditioning significantly reduced the ischemia/reperfusion-induced caspase-3 activation, compared to the ischemia group (P<0.05). Also, results indicated a significant increase in Bax/Bcl-2 ratio in ischemia group, compared to sham-operated group (P<0.001). Discussion: This study indicated that exercise has a neuroprotective effects against cerebral ischemia when used as preconditioning stimuli

UNIAXIAL FATIGUE BEHAVIOR AND LIFE PREDICTION OF ADDITIVELY MANUFACTURED INCONEL 718 WITH DIFFERENT GRAIN MORPHOLOGY

Understanding the fatigue behavior and failure mechanisms is essential for qualifying and standardizing additively manufactured metallic components. This study investigates the uniaxial fatigue behavior and failure mechanisms of laser powder bed fused (L-PBF) Inconel 718 (IN718) specimens with different grain sizes obtained by altering the process parameters and heat treatment. Uniaxial, fully-reversed strain-controlled fatigue tests were conducted on specimens with machined and polished surface conditions. Microstructural analysis and fractography using a scanning electron microscope were performed to measure the sizes of grains and facets. Fatigue cracks were initiated at the persistent slip bands near or at the surfaces rather than process-induced volumetric defects in all cases. The fatigue behavior of L-PBF IN718 specimens was correlated with the sizes of grains and facets. Fatigue life estimation incorporating the NASGRO equation and √ of the grain sizes was performed and shown to predict fatigue life within scatter bands of five.Mechanical Engineerin

Dual EZH2 and EHMT2 histone methyltransferase inhibition increases biological efficacy in breast cancer cells

Background: Many cancers show aberrant silencing of gene expression and overexpression of histone methyltransferases. The histone methyltransferases (HKMT) EZH2 and EHMT2 maintain the repressive chromatin histone methylation marks H3K27me and H3K9me, respectively, which are associated with transcriptional silencing. Although selective HKMT inhibitors reduce levels of individual repressive marks, removal of H3K27me3 by specific EZH2 inhibitors, for instance, may not be sufficient for inducing the expression of genes with multiple repressive marks. Results: We report that gene expression and inhibition of triple negative breast cancer cell growth (MDA-MB-231) are markedly increased when targeting both EZH2 and EHMT2, either by siRNA knockdown or pharmacological inhibition, rather than either enzyme independently. Indeed, expression of certain genes is only induced upon dual inhibition. We sought to identify compounds which showed evidence of dual EZH2 and EHMT2 inhibition. Using a cell-based assay, based on the substrate competitive EHMT2 inhibitor BIX01294, we have identified proof-of-concept compounds that induce re-expression of a subset of genes consistent with dual HKMT inhibition. Chromatin immunoprecipitation verified a decrease in silencing marks and an increase in permissive marks at the promoter and transcription start site of re-expressed genes, while Western analysis showed reduction in global levels of H3K27me3 and H3K9me3. The compounds inhibit growth in a panel of breast cancer and lymphoma cell lines with low to sub-micromolar IC50s. Biochemically, the compounds are substrate competitive inhibitors against both EZH2 and EHMT1/2. Conclusions: We have demonstrated that dual inhibition of EZH2 and EHMT2 is more effective at eliciting biological responses of gene transcription and cancer cell growth inhibition compared to inhibition of single HKMTs, and we report the first dual EZH2-EHMT1/2 substrate competitive inhibitors that are functional in cells

Barriers to Family Caregivers’ Coping With Patients With Severe Mental Illness in Iran

The broad spectrum of problems caused by caring for a patient with mental illness imposes a high burden on family caregivers. This can affect how they cope with their mentally ill family members. Identifying caregivers’ experiences of barriers to coping is necessary to develop a program to help them overcome these challenges. This qualitative content analysis study explored barriers impeding family caregivers’ ability to cope with their relatives diagnosed with severe mental illness (defined here as schizophrenia, schizoaffective disorders, and bipolar affective disorders). Sixteen family caregivers were recruited using purposive sampling and interviewed using a semi-structured in-depth interview method. Data were analyzed by a conventional content analytic approach. Findings consisted of four major categories: the patient’s isolation from everyday life, incomplete recovery, lack of support by the mental health care system, and stigmatization. Findings highlight the necessity of providing support for caregivers by the mental health care delivery service system.The study was supported by Grant TBZMED·REC.5825 from the deputy of research in Tabriz University of Medical Sciences

Effect of hardness on multiaxial fatigue behaviour and some simple approximations for steels

Constant-amplitude in-phase and 90° out-of-phase axial-torsional fatigue tests were conducted on tubular specimens made from a medium-carbon steel with three hardness levels obtained from normalizing, quenching and tempering and induction hardening to find the effect of hardness on multiaxial fatigue behaviour. In addition, the same loadings were applied on the normalized solid specimens to investigate the effect of specimen geometry on multiaxial fatigue life. Similar fatigue life variation as a function of hardness was found for in-phase and out-of-phase loadings, with higher ductility beneficial in low-cycle fatigue (LCF) and higher strength beneficial in high-cycle fatigue (HCF). Multiaxial fatigue data were satisfactorily correlated for all hardness levels with the Fatemi-Socie parameter. Furthermore, in order to predict multiaxial fatigue life of steels in the absence of any fatigue data, the Roessle-Fatemi hardness method was used. Multiaxial fatigue lives were predicted fairly accurately using the Fatemi-Socie multiaxial model based on only the hardness level of the material. The applicability of the prediction method based on hardness was also examined for Inconel 718 and a stainless steel under a wide range of loading conditions. The great majority of the observed fatigue lives were found to be in good agreement with predicted lives. © 2009 The Authors. Journal compilation © 2009 Blackwell Publishing Ltd

Exercise preconditioning exhibits neuroprotective effects on hippocampal CA1 neuronal damage after cerebral ischemia

Recent evidence has suggested the neuroprotective effects of physical exercise on cerebral ischemic injury. However, the role of physical exercise in cerebral ischemia-induced hippocampal damage remains controversial. The aim of the present study was to evaluate the effects of pre-ischemia treadmill training on hippocampal CA1 neuronal damage after cerebral ischemia. Male adult rats were randomly divided into control, ischemia and exercise + ischemia groups. In the exercise + ischemia group, rats were subjected to running on a treadmill in a designated time schedule (5 days per week for 4 weeks). Then rats underwent cerebral ischemia induction th rough occlusion of common carotids followed by reperfusion. At 4 days after cerebral ischemia, rat learning and memory abilities were evaluated using passive avoidance memory test and rat hippocampal neuronal damage was detected using Nissl and TUNEL staining. Pre-ischemic exercise significantly reduced the number of TUNEL-positive cells and necrotic cell death in the hippocampal CA1 region as compared to the ischemia group. Moreover, pre-ischemic exercise significantly prevented ischemia-induced memory dysfunction. Pre-ischemic exercise mighct prevent memory deficits after cerebral ischemia through rescuing hippocampal CA1 neurons from ischemia-induced degeneration. © 2015, Editorial Board of Neural Regeneration Research. All rights reserved

Fatigue failure mechanisms for AlSi10Mg manufactured by L-PBF under axial and torsional loads: The role of defects and residual stresses

Additive Manufacturing (AM) is with no doubt the most revolutionary manufacturing process developed in the last two decades. Despite the indisputable advantages of this technology, the poor surface quality of net-shape components, the presence of internal defects and the development of process induced residual stresses still represent the main problems for the fatigue strength of critical stressed components. In previous works investigating the same alloy, the uniaxial fatigue strength of both machined and net-shape specimens was correlated with the defect size through a Kitagawa diagram, allowing to describe the problem from the threshold perspective. The aim of this work is to extend this approach by investigating the failure mechanisms under torsion in presence of manufacturing defects, both volumetric and superficial anomalies. Specimens manufactured with laser powder bed fusion (L-PBF) technique out of AlSi10Mg, featuring both machined and net-shape surface state, were tested and analysed. The two experimental campaigns allow to investigate the competition between internal defects and superficial features and their effect on the fatigue performances. Tests wereperformedundertwoloadingconditions,namelyfullyreversetorsion( =−1)andpositivetorqueratio ( = 0.1). It was found that for the net-shape specimens manufacturing residual stresses have a key role in influencing fatigue strength of this material, making the fatigue limit in torsion of the two considered loading conditions comparable. All the tested specimens failed onto a maximum principal stress plane, which is in line with multiaxial tests performed on a cast A356-T6 aluminium alloy. In some relatively high shear stresses there is a competition between Mode I and Mode II crack propagation, whose threshold condition is controlled by th,I

An Experimental-Numerical Investigation of Heat Transfer During Selective Laser Melting

The heat transfer in and around a part being fabricated via Selective Laser Melting (SLM) is numerically simulated while considering the surrounding powder bed modeled to have an effective thermal conductivity. By accurately simulating the powder bed heat transfer during SLM, mechanical properties of parts can be better predicted. Heat transfer to previously-deposited layers and the build plate are also simulated. In order to validate the presented model, a thermocouple was embedded into a substrate used and a SLM system was utilized for performing two experiments. In the first set, various laser power and scan speed combinations were employed while passing the laser over the thermocouple-embedded substrate. This procedure calibrated the numerical model and demonstrated that the heat transfer due to convection and radiation during deposition of a single layer is approximately 10-15% of initial laser power input. The final experiment consisted of building a thin wall of SLM of 17-4 PH stainless steel (SS). The effects of scan pattern and part size on the temperature response of and around the part are demonstrated as significant. Distinct heating and cooling rates are also provided for these various cases; indicating the dependency of final microstructure on part size and the utilized scan pattern.Mechanical Engineerin