Methods for determining agent concentration profiles in agarose gel during convection-enhanced delivery

Convection-enhanced delivery (CED) is a promising technique to deliver large molecular weight drugs to the human brain for treatment of Parkinson's, Alzheimer's, or brain tumors. Researchers have used agarose gels to study mechanisms of agent transport in soft tissues like brain due to its similar mechanical and transport properties. However, inexpensive quantitative techniques to precisely measure achieved agent distribution in agarose gel phantoms during CED are missing. Such precise measurements of concentration distribution are needed to optimize drug delivery. An optical experimental method to accurately quantify agent concentration in agarose is presented. A novel geometry correction algorithm is used to determine real concentrations from observable light intensities captured by a digital camera. We demonstrate the technique in dye infusion experiments that provide cylindrical and spherical distributions when infusing with porous membrane and conventional single-port catheters, respectively. This optical method incorporates important parameters, such as optimum camera exposure, captured camera intensity calibration, and use of collimated light source for maximum precision. We compare experimental results with numerical solutions to the convection diffusion equation. The solutions of convection-diffusion equations in the cylindrical and spherical domains were found to match the experimental data obtained by geometry correction algorithm.     

Regorafenib and Ruthenium Complex Combination Inhibit Cancer Cell Growth by Targeting PI3K/AKT/ERK Signalling in Colorectal Cancer Cells

Cancer is one of the leading cause of lethality worldwide, CRC being the third most common cancer reported worldwide, with 1.85 million cases and 850,000 deaths annually. As in all other cancers, kinases are one of the major enzymes that play an essential role in the incidence and progression of CRC. Thus, using multi-kinase inhibitors is one of the therapeutic strategies used to counter advanced-stage CRC. Regorafenib is an FDA-approved drug in the third-line therapy of refractory metastatic colorectal cancer. Acquired resistance to cancers and higher toxicity of these drugs are disadvantages to the patients. To counter this, combination therapy is used as a strategy where a minimal dose of drugs can be used to get a higher efficacy and reduce drug resistance development. Ruthenium-based compounds are observed to be a potential alternative to platinum-based drugs due to their significant safety and effectiveness. Formerly, our lab reported Ru-1, a ruthenium-based compound, for its anticancer activity against multiple cancer cells, such as HepG2, HCT116, and MCF7. This study evaluates Ru-1′s activity against regorafenib-resistant HCT116 cells and as a combination therapeutic with regorafenib. Meanwhile, the mechanism of the effect of Ru-1 alone and with regorafenib as a combination is still unknown. In this study, we tested a drug combination (Ru-1 and regorafenib) against a panel of HT29, HCT116, and regorafenib-resistant HCT116 cells. The combination showed a synergistic inhibitory activity. Several mechanisms underlying these numerous synergistic activities, such as anti-proliferative efficacy, indicated that the combination exhibited potent cytotoxicity and enhanced apoptosis induction. Disruption of mitochondrial membrane potential increased intracellular ROS levels and decreased migratory cell properties were observed. The combination exhibited its activity by regulating PI3K/Akt and p38 MAP kinase signalling. This indicates that the combination of REG/Ru-1 targets cancer cells by modulating the PI3K/Akt and ERK signalling.     

Upregulation of Heme Oxygenase-1 Combined with Increased Adiponectin Lowers Blood Pressure in Diabetic Spontaneously Hypertensive Rats through a Reduction in Endothelial Cell Dysfunction, Apoptosis and Oxidative Stress

This study was designed to investigate the effect of increased levels of HO-1 on hypertension exacerbated by diabetes. Diabetic spontaneously hypertensive rat (SHR) and WKY (control) animals were treated with streptozotocin (STZ) to induce diabetes and stannous chloride (SnCl₂) to upregulate HO-1. Treatment with SnCl₂ not only attenuated the increase of blood pressure (p<0.01), but also increased HO-1 protein content, HO activity and plasma adiponectin levels, decreased the levels of superoxide and 3-nitrotyrosine (NT), respectively. Reduction in oxidative stress resulted in the increased expression of Bcl-2 and AKT with a concomitant reduction in circulating endothelial cells (CEC) in the peripheral blood (p<0.005) and an improvement of femoral reactivity (response to acetylcholine). Thus induction of HO-1 accompanied with increased plasma adiponectin levels in diabetic hypertensive rats alters the phenotype through a reduction in oxidative stress, thereby permitting endothelial cells to maintain an anti-apoptotic environment and the restoration of endothelial responses thus preventing hypertension.     

Exhaust dyeing of meta-aramid yarn at low temperature and time

Exhaust dyeing of aramid fibre is difficult due to its high crystalline and compact structure. In this study aramid yarn is pre-treated with solvent dimethyl sulphoxide to facilitate the dyeing process and then dyeing is achieved with a cationic dye. Pre-treatment at high temperature leads to the reduction in tensile strength of yarn which is not desirable. Therefore, in this work pre-treatment has been carried out at different temperatures and time to standardise those parameters to enhance the dye uptake with minimum reduction in strength. Further, dyeing temperature and time has been standardised keeping the standard pre-treatment parameters fixed. From the study, pre-treatment temperature of 30°C for 10 min and dyeing temperature of 100°C for 30 min are found suitable for better colour strength without much compromising on strength of yarn. The fastness properties of untreated and treated dyed yarns were comparable.     

A comparative study of the structural,optical, magnetic and magnetocaloric properties of HoCrO3 and HoCr0.85Mn0.15O3 orthochromites

In the present study, the physical properties including structural, optical and magnetic of HoCr_1-xMn_xO₃ (x = 0, 0.15) have been thoroughly investigated and compared. A detailed structural analysis of the compounds provided a way to correlate the optical and magnetic properties with the change in Cr-site ionic radius, tilt angles and distortion in CrO₆ octahedra due to Mn substitution. Further, the shift in the Raman phonon modes was associated with the increased structural distortion owing to Mn substitution in HoCrO₃ compound. The variation in the Urbach energy values, measured from the diffuse reflectance spectroscopy, was found to be closely related to the octahedral distortion. The optical band gap reduced from 3.22 eV to 2.01 eV after Mn substitution. Other optical parameters such as skin depth, refractive index, extinction coefficient and optical conductivity were also perceived to vary noticeably in the substituted compound. The overall structural distortion with Mn substitution resulted in the decrease of antiferromagnetic transition temperature of the pristine compound. The strong magnetic entropy change was observed at low temperatures in pure HoCrO₃ compound and its value was enhanced on Mn substitution. Therefore, the present work provides a convenient method to tune the multifunctional properties of HoCrO₃ compound, which has practical applications such as photocatalyst and low-temperature magnetic refrigerant.     

Correlating the Dipolar Interactions Induced Magneto-Viscoelasticity and Thermal Conductivity Enhancements in Nanomagnetic Fluids

The effective thermal management of electronic system holds the key to maximize their performance. The recent miniaturization trends require a cooling system with high heat flux capacity, localized cooling, and active control. Nanomagnetic fluids (NMFs) based cooling systems have the ability to meet the current demand of the cooling system for the miniaturized electronic system. However, the thermal characteristics of NMFs have a long way to go before the internal mechanisms are well understood. This review mainly focuses on the three aspects to establish a correlation between the thermal and rheological properties of the NMFs. First, the background, stability, and factors affecting the properties of the NMFs are discussed. Second, the ferrohydrodynamic equations are introduced for the NMFs to explain the rheological behavior and relaxation mechanism. Finally, different theoretical and experimental models are summarized that explain the thermal characteristics of the NMFs. Thermal characteristics of the NMFs are significantly affected by the morphology and composition of the magnetic nanoparticles (MNPs) in NMFs as well as the type of carrier liquids and surface functionalization that also influences the rheological properties. Thus, understanding the correlation between the thermal characteristics of the NMFs and rheological properties helps develop cooling systems with improved performance.     

Miniaturized omni-directional ZOR antenna with its co-equal circuit for 5G applications

Microsystem Technologies - This paper presents a hexagonal-shaped omni-directional Zeroth Order Resonator (ZOR) antenna for 5G application. 5G which is 1000 times faster than 4G technology, works...