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A cell delivery strategy was investigated that was hypothesized to enable magnetic targeting of endothelial cells to the steel surfaces of intraarterial stents because of the following mechanisms: (i) preloading cells with biodegradable polymeric superparamagnetic nanoparticles (MNPs), thereby rendering the cells magnetically responsive; and (ii) the induction of both magnetic field gradients around the wires of a steel stent and magnetic moments within MNPs because of a uniform external magnetic field, thereby targeting MNP-laden cells to the stent wires. In vitro studies demonstrated that MNP-loaded bovine aortic endothelial cells (BAECs) could be magnetically targeted to steel stent wires. In vivo MNP-loaded BAECs transduced with adenoviruses expressing luciferase (Luc) were targeted to stents deployed in rat carotid arteries in the presence of a uniform magnetic field with significantly greater Luc expression, detected by in vivo optical imaging, than nonmagnetic controls.

Non-thermal atmospheric pressure plasma has attracted great interest due to its multiple potential biomedical applications with cancer treatment being among the most urgent. To realize the clinical potential of non-thermal plasma, the exact cellular and molecular mechanisms of plasma effects must be understood. This work aimed at studying the prostate cancer specific mechanisms of non-thermal plasma effects on energy metabolism as a central regulator of cell homeostasis and proliferation. It was found that cancer cells with higher metabolic rate initially are more resistant to plasma treated phosphate-buffered saline (PBS) since the respiratory and calcium sensitive signaling systems were not responsive to plasma exposure. However, dramatic decline of cancer oxidative phosphorylation developed over time resulted in significant progression of cell lethality. The normal prostate cells with low metabolic activity immediately responded to plasma treated PBS by suppression of respiratory functions and sustained elevation of cytosolic calcium. However, over time the normal cells start recovering their mitochondria functions, proliferate and restore the cell population. We found that the non-thermal plasma induced increase in intracellular ROS is of primarily non-mitochondrial origin. The discriminate non-thermal plasma effects hold a promise for clinical cancer intervention.

We study the gradient method under the assumption that an additively inexact gradient is available for, generally speaking, non-convex problems. The non-convexity of the objective function, as well as the use of an inexactness specified gradient at iterations, can lead to various problems. For example, the trajectory of the gradient method may be far enough away from the starting point. On the other hand, the unbounded removal of the trajectory of the gradient method in the presence of noise can lead to the removal of the trajectory of the method from the desired global solution. The results of investigating the behavior of the trajectory of the gradient method are obtained under the assumption of the inexactness of the gradient and the condition of gradient dominance. It is well known that such a condition is valid for many important non-convex problems. Moreover, it leads to good complexity guarantees for the gradient method. A rule of early stopping of the gradient method is proposed. Firstly, it guarantees achieving an acceptable quality of the exit point of the method in terms of the function. Secondly, the stopping rule ensures a fairly moderate distance of this point from the chosen initial position. In addition to the gradient method with a constant step, its variant with adaptive step size is also investigated in detail, which makes it possible to apply the developed technique in the case of an unknown Lipschitz constant for the gradient. Some computational experiments have been carried out which demonstrate effectiveness of the proposed stopping rule for the investigated gradient methods.

Magnetic-based systems utilizing superparamagnetic nanoparticles and a magnetic field gradient to exert a force on these particles have been used in a wide range of biomedical applications. This review is focused on drug targeting applications that require penetration of a cellular barrier as well as strategies to improve the efficacy of targeting in these biomedical applications. Another focus of this review is regenerative applications utilizing tissue engineered scaffolds prepared with the aid of magnetic particles, the use of remote actuation for release of bioactive molecules and magneto-mechanical cell stimulation, cell seeding and cell patterning.

The main reason for this remarkable change in nanomaterial behavior is its enormous surface-to-volume ratio, which provides a very large interfacial surface area as driving force for enhanced interaction of nanomaterial with surrounding it molecules. [...]upon intravenous administration, nanoparticles inevitably form layers of adsorbed biomolecules (mainly proteins) known as a ‘protein corona’ (1,2). The biological identity of nanoparticles, which could be significantly different from their original synthetic identity, determines the physiological behavior of nanoparticles influencing their colloidal stability, targeting capability, kinetics of circulation, transport, cellular uptake and organ accumulation, degradation, drug release, signaling and toxicity (4). Because the relative quantities of the adsorbed proteins on the surface of nanoparticles do not necessarily correlate with their abundance in blood plasma, the composition of protein corona for each particular type of nanomaterial is unique and influenced by multiple factors. [...]particle analysis technologies that work more effectively in complex fluids like blood and serum under little dilution. Using the quantitative structure-activity relationships that will link the information obtained by the most advanced colloidal surface analysis techniques with the protein corona composition data (originated from ideal in vivo conditions) and corresponding biological outcomes, the researchers will be able to make more accurate predictions of nanoparticles association with various relevant cells types, such as circulating immune cells, endothelial cells (lining the lumen of the blood vessels) and organ-related hepatocytes and splenocytes. Because the nanoparticle-cell interactions influence multiple downstream cellular responses, the predictions could be extended to characterize signaling pathways, cytokine secretion, gene expression and toxicity.

We address randomized methods for control and optimization based on generating points uniformly distributed in a set. For control systems this sets are either stability domain in the space of feedback controllers, or quadratic stability domain, or robust stability domain, or level set for a performance specification. By generating random points in the prescribed set one can optimize some additional performance index. To implement such approach we exploit two modern Monte Carlo schemes for generating points which are approximately uniformly distributed in a given convex set. Both methods use boundary oracle to find an intersection of a ray and the set. The first method is Hit-and-Run, the second is sometimes called Shake-and-Bake. We estimate the rate of convergence for such methods and demonstrate the link with the center of gravity method. Numerical simulation results look very promising.

We focus on finding sparse and least-ℓ1-norm solutions for unconstrained nonlinear optimal control problems. Such optimization problems are non-convex and non-smooth, nevertheless recent versions of Newton method for under-determined equations can be applied successively for such problems.

To successfully translate magnetically mediated cell targeting from bench to bedside, there is a need to systematically assess the potential adverse effects of magnetic nanoparticles (MNPs) interacting with 'therapeutic' cells. Here, we examined in detail the effects of internalized polymeric MNPs on primary rat endothelial cells' structural intactness, metabolic integrity and proliferation potential. The intactness of cytoskeleton and organelles was studied by fluorescent confocal microscopy, flow cytometry and high-resolution respirometry. MNP-loaded primary endothelial cells preserve intact cytoskeleton and organelles, maintain normal rate of proliferation, calcium signaling and mitochondria energy metabolism. This study provides supportive evidence that MNPs at doses necessary for targeting did not induce significant adverse effects on structural integrity and functionality of primary endothelial cells - potential cell therapy vectors.

The Caucasian orogenic wedge formed as a consequence of the closure of the Tethyan Ocean, and numerous fields of active mud volcanoes pepper the area adjacent to the Black and Caspian Seas. Stable isotope ratios of boron, helium, and carbon have been measured for gas, fluid and sediment samples from active mud volcanoes of Taman Peninsula and Georgia to estimate the sources and mobilization depths of the fluid phase and mud. Boron concentrations in mud volcano fluids were found to be 5-35× higher than seawater. Fluid isotope ratios vary between δ^sup 11^B=22 and 39[per thousand], while isotope ratios of the smectite- and illite-rich extruded mud are considerably depleted in heavy ^sup 11^B (δ^sup 11^B=-8 to +7[per thousand]). B contents of these muds are ~8× higher than modern marine sediments. This suggests that liquefaction prior to mud volcanism was accompanied by both B enrichment and isotope fractionation, most likely at an intermediate depth mud reservoir at 2-4 km. The hydrocarbon-generating source beds to the mud volcanoes are located at 7 to >10 km depth in the folded Maikop Formation and are of proposed Oligocene-Miocene age. The most likely mechanism is re-hydration of these shales by both hydrocarbons and a geochemically mature fluid from greater depth within the orogenic wedge. Such a deep fluid source is supported by our results from gas analyses, which imply an admixture of minor amounts (less than 1%vol) of ^sup 3^He (Georgia), thermogenic ^sup 13^C in methane as well as \"ultraheavy\" ^sup 13^C in CO^sub 2^ (both Taman and Georgia). The overall results attest active local flow of geochemically different fluids along deep-seated faults penetrating the two study areas in the Caucasian orogenic wedge, with the waters as well as the gases coming from below the Maikop Formation.[PUBLICATION ABSTRACT]