Radiation therapy is a staple approach for cancer treatment, whereas radioresistance of cancer cells remains a substantial clinical problem. In response to ionizing radiation (IR) induced DNA damage, ...cancer cells can sustain/activate pro-survival signaling pathways, leading to apoptotic resistance and induction of cell cycle checkpoint/DNA repair. Previous studies show that Rac1 GTPase is overexpressed/hyperactivated in breast cancer cells and is associated with poor prognosis. Studies from our laboratory reveal that Rac1 activity is necessary for G2/M checkpoint activation and cell survival in response to IR exposure of breast and pancreatic cancer cells. In this study, we investigated the effect of Rac1 on the survival of breast cancer cells treated with hyper-fractionated radiation (HFR), which is used clinically for cancer treatment. Results in this report indicate that Rac1 protein expression is increased in the breast cancer cells that survived HFR compared with parental cells. Furthermore, this increase of Rac1 is associated with enhanced activities of extracellular signal-regulated kinases 1 and 2 (ERK1/2) and nuclear factor-κB (NF-κB) signaling pathways and increased levels of anti-apoptotic protein Bcl-xL and Mcl-1, which are downstream targets of ERK1/2 and NF-κB signaling pathways. Using Rac1-specific inhibitor and dominant-negative mutant N17Rac1, here we demonstrate that Rac1 inhibition decreases the phosphorylation of ERK1/2 and inhibitory κBα (IκBα), as well as the levels of Bcl-xL and Mcl-1 protein in the HFR-selected breast cancer cells. Moreover, inhibition of Rac1 using either small molecule inhibitor or dominant-negative N17Rac1 abrogates clonogenic survival of HFR-selected breast cancer cells and decreases the level of intact poly(ADP-ribose) polymerase, which is indicative of apoptosis induction. Collectively, results in this report suggest that Rac1 signaling is essential for the survival of breast cancer cells subjected to HFR and implicate Rac1 in radioresistance of breast cancer cells. These studies also provide the basis to explore Rac1 as a therapeutic target for radioresistant breast cancer cells.
The present work aimed at the development of lightweight EMI shielding epoxy-based composites with high mechanical strength for aircraft application. In this regard, we prepared CuO-activated carbon ...nanoparticles by the simple co-precipitation method. The different weight ratios (5, 10 and 15 wt%) of the CuO-activated carbon/epoxy composites are prepared, and their mechanical and EMI shielding properties have been studied. To achieve high mechanical and EMI shielding efficiency, the optimum composition of CuO-activated carbon/epoxy composite matrix is reinforced with the carbon fiber. The carbon fiber-reinforced CuO-activated carbon/epoxy hybrid composite exhibits high thermal and mechanical properties. The synergistic effect of carbon fiber and the 10 wt% CuO-activated carbon/epoxy composite matrix with excellent dielectric and ohmic losses delivered the highest electromagnetic interference shielding effectiveness value of 52.02 dB at 11.48 GHz. Hence, the composite with superior thermal and mechanical properties can be used as a prominent electromagnetic shielding material in aircraft application.
The present work aimed at the simultaneous improvement in the mechanical and electromagnetic shielding properties of Fe3O4‐carbonaceous/epoxy composites by the reinforcement of two plies of carbon ...fiber into the epoxy‐filler matrix. In this study, Fe3O4‐activated carbon and Fe3O4‐activated charcoal composites were synthesized by co‐precipitation method and were introduced into the epoxy matrix with different weight percentage (5, 10, and 15 wt%). The BET surface area analysis revealed the high porosity in the Fe3O4‐activated charcoal composite than that of activated carbon composite. The Fe3O4‐activated carbon/epoxy composite showed better mechanical properties than the later. Both the composites showed nearly same EMI SE value. 10 wt% of the filler‐1/epoxy composite showed the highest shielding effectiveness (SE) value of −22.5 dB at 10 GHz whereas 15 wt% Fe3O4@charcoal/epoxy composite showed better SE value of −27.15 dB at 8.8 GHz. The obtained results were supported by the dielectric and magnetic loss tangent studies. The incorporation of carbon fiber enhanced the mechanical property by three times and the EMI SE value by ~15 dB. Thus, the carbon fiber reinforced Fe3O4/carbonaceous epoxy composites may be the potential electromagnetic shielding material for electronics and aircraft industries.
Nearly 2 decades since its discovery as one of the genes responsible for the Wolf-Hirschhorn Syndrome (WHS), the primary function of the leucine-zipper EF-hand containing transmembrane 1 (LETM1) ...protein in the inner mitochondrial membrane (IMM) or the mechanism by which it regulates mitochondrial Ca
handling is unresolved. Meanwhile, LETM1 has been associated with the regulation of fundamental cellular processes, such as development, cellular respiration and metabolism, and apoptosis. This mini-review summarizes the diversity of cellular functions impacted by LETM1 and highlights the multiple roles of LETM1 in health and disease.
In the present study, inorganic bulk and nano nutrients of zinc oxide, titanium oxide, and silver nanoparticles were synthesized using the chemical reduction method and invigourated with chilli seeds ...cv. PKM 1 each at 750, 1000 and 1250 mg kg−1 by using template-free aqueous solution. After nanoparticles invigouration, the seeds were analyzed for various parameters such as germination (%), shoot length, root length, and seedling vigour. Other important parameters, such as electrical conductivity and antioxidant enzyme activity (catalase and lipid peroxidase), were also analyzed, which in turn reflected the enhancement of seed quality of chilli seeds when they were invigourated with ZnO, TiO2 and silver nanoparticles. The results indicated that the chilli seeds invigourated with ZnO nanoparticles at 1000 mg kg−1 enhanced the germination and seedling vigour in aged seeds.
•Studies on invigouration treatment of bulk (metal ions) for quality of aged chilli seeds.•Invigouration treatment of nanomaterials for improving the quality of aged chilli seeds.•Improved seed germination, seedling vigour and seed health of nanomaterials treated aged chilli seeds.
Neurovascular flow diverters are flexible, braided stent-meshes for intracranial aneurysm treatment. We applied the dynamic push-pull technique to manipulate the flow-diverter mesh density at the ...aneurysm orifice to maximize flow diversion. This study investigated the hemodynamic impact of the dynamic push-pull technique on patient-specific aneurysms by using the developed high-fidelity virtual-stenting computational modeling technique combined with computational fluid dynamics.
We deployed 2 Pipeline Embolization Devices into 2 identical sidewall anterior cerebral artery aneurysm phantoms by using the dynamic push-pull technique with different delivery-wire advancements. We then numerically simulated these deployment processes and validated the simulated mesh geometry. Computational fluid dynamics analysis was performed to evaluate detailed hemodynamic changes by deployed flow diverters in the sidewall aneurysm and a fusiform basilar trunk aneurysm (deployments implemented previously). Images of manipulated flow diverter mesh from sample clinical cases were also evaluated.
The flow diverters deployed in silico accurately replicated in vitro geometries. Increased delivery wire advancement (21 versus 11 mm) by using a dynamic push-pull technique produced a higher mesh compaction at the aneurysm orifice (50% metal coverage versus 36%), which led to more effective aneurysmal inflow reduction (62% versus 50% in the sidewall aneurysm; 57% versus 36% in the fusiform aneurysm). The dynamic push-pull technique also caused relatively lower metal coverage along the parent vessel due to elongation of the flow diverter. High and low mesh compactions were also achieved for 2 real patients by using the dynamic push-pull technique.
The described dynamic push-pull technique increases metal coverage of pure braided flow diverters over the aneurysm orifice, thereby enhancing the intended flow diversion, while reducing metal coverage along the parent vessel to prevent flow reduction in nearby perforators.
Microstructural changes and softening due to static recrystallization have a critical influence on thermo-mechanical behavior of high strength steels during industrial multi-pass hot rolling. ...Numerical simulation using finite element analysis (FEA) can be used to accurately predict the softening behavior during the hot rolling process. Therefore, the implementation of an experimentally defined static recrystallization model into FEA is necessary to get realistic simulation prediction. In this study, the extent of softening during static recrystallization in Si and Mn alloyed high strength steel was measured using double hit tests. A Gleeble™ thermo-mechanical simulator was used to perform the double hit tests with variations in temperature, strain rate, and interpass time. The kinetics of static recrystallization was developed based on the experimental results and implemented into a finite element model of a multi-pass plate hot rolling process using explicit subroutines. Three different modeling approaches were implemented in Abaqus to predict the fraction of static recrystallization and softening during multi-pass hot rolling. Simulation results showed that the fraction of recrystallization significantly depends on the extent of thickness reduction during rolling at a typical industrial multi-pass schedule. Additionally, an increase in temperature greatly increased the fraction of recrystallization and static softening. The suggested approach could be used for the optimization of the hot rolling process for Si and Mn alloyed high strength steels.
Graphic Abstract
•A novel load-controlled iteration scheme is proposed within the XFEM framework for semipermeable piezoelectric material.•Interaction integral approach is used to evaluate the electric displacement ...intensity factor (EDIF).•Effect of polarization angle, crack length, loading parameter is investigated on the electric displacement intensity factor.•EDIF results show an excellent agreement with the results obtained from the iterative capacitor analogy (ICA).
In the present work, a novel load-controlled iteration scheme within the framework of extended finite element method (XFEM) is proposed to model the semipermeable crack in a piezoelectric material. To capture the stress and electric displacement singularity at the crack tip, the electromechanical 6-fold enrichment functions are used. The domain form of electromechanical interaction integral is employed to determine the generalized intensity factor. The accuracy of a proposed scheme based on XFEM is validated against the reference solutions derived from the iterative capacitor analogy (ICA) method. The effect of several crack configurations, polarization angle, far-field mechanical and electrical traction on electric displacement intensity factor (EDIF) are analyzed for cracked semipermeable piezoelectric material.
Bilateral basal ganglia hemorrhage is exceedingly rare. To our knowledge, our patient is the first reported case of a confirmed coronavirus disease 2019 (COVID-19) patient who had bilateral basal ...ganglia hemorrhage. In the absence of other risk factors for bilateral deep cerebral involvement, we suspect that COVID-19 may be contributing to these rare pathologies. Most published data represent a correlation between COVID-19 and neurologic complications, and more research is still needed to prove causation.
A naturally occurring water‐soluble cobalt‐complex cyanocobalamin (Vitamin B12) has been identified as a new and efficient electrocatalyst for the CO2‐to‐CO reduction reaction in aqueous solution. ...Heterogeneous B12‐electrocatalysts prepared by a simple electrochemical immobilization technique on graphene‐oxide (GO)‐modified glassy carbon and carbon paper (CP) electrodes, without any non‐degradable polymer‐binders, showed a highly stable and well‐defined surface‐confined redox peak at E’=−0.138 V vs. RHE with a surface‐excess value, ΓB12=4.28 nmol cm−2. This new electrocatalyst exhibits 93 % Faradaic efficiency for CO2‐to‐CO conversion at an electrolysis potential, −0.882 V vs. RHE (an optimal condition) with a high current density, 29.4 mA cm−2 and turn‐over‐frequency value, 5.2 s−1, without any surface‐fouling problem, in 0.5 m KHCO3. In further, it follows an eco‐friendly, sustainable and water‐based approach with the involvement of biodegradable and non‐toxic chemicals/materials like B12, GO and CP.
Nature‐for‐nature: A naturally occurring and eco‐friendly cobalt complex, cyanocobalamin (vitamin B12)‐modified graphene oxide has been identified for the first time as an efficient electrocatalyst for CO2‐to‐CO conversion in aqueous solution.
PDF
