Kinetic limitations of cooperativity-based drug delivery systems

We study theoretically a novel drug delivery system that utilizes the overexpression of certain proteins in cancerous cells for cell-specific chemotherapy. The system consists of dendrimers conjugated with "keys" (ex: folic acid) which "key-lock" bind to particular cell-membrane proteins (ex: folate receptor). The increased concentration of "locks" on the surface leads to a longer residence time for the dendrimer and greater incorporation into the cell. Cooperative binding of the nanocomplexes leads to an enhancement of cell specificity. However, both our theory and detailed analysis of in vitro experiments indicate that the degree of cooperativity is kinetically limited. We demonstrate that cooperativity and hence the specificity to particular cell type can be increased by making the strength of individual bonds weaker, and suggest a particular implementation of this idea.     

Nitric oxide reduction by CO ON Rh(111): Temperature programmed reaction

The reaction of NO with CO on Rh(111) has been studied with temperature programmed reaction (TPR). Comparisons are made with the reaction of O₂ with CO and the reaction of NO with H₂. The rate-determining step for both CO oxidation reactions is CO(a) + O(a) → CO₂(g). Repulsive interactions between adsorbed CO and adsorbed nitrogen atoms lead to desorption of CO in a peak at 415 K which is in the temperature range where the reaction between CO(a) and O(a) produces CO₂(g). Thus the extent of reaction of CO(a) with NO(a) is less than that between CO(a) and O(a) due to the lower coverage of CO caused by adsorbed N atoms and NO. A similar repulsive interaction between NO(a) and H(a) suppresses the NO + H₂ reaction. CO + NO reaction behavior on Rh(111) is compared to that observed on Pt(111).     

Capacitive micromachined ultrasonic transducers using commercial multi-user MUMPs process: Capability and limitations

The objective of this work is to construct capacitive micromachined ultrasound transducers (cMUTs) using multi-user microelectromechanical systems (MEMS) processess (MUMPs) and to analyze the capability of this process relative to the customized processes commonly in use. The MUMPs process has the advantages of low cost and accessibility to general users since it is not necessary to have access to customized fabrication capability such as wafer-bonding and sacrificial release processes. While other researchers have reported fabricating cMUTs using the MUMPs process none has reported the limitations in the process that arise due to the use of standard design rules that place limitations on the material thicknesses, gap thicknesses, and materials that may be used. In this paper we explain these limitations, and analyze the capabilities using 1D modeling, Finite Element Analysis, and experimental devices. We show that one of the limitations is that collapse voltage and center frequency can not be controlled independently. However, center frequencies up to 9 MHz can be achieved with collapse voltages of less than 200 V making such devices suitable for medical and non-destructive evaluation imaging applications. Since the membrane and base electrodes are made of polysilicon, there is a larger series resistance than that resulting from processes that use metal electrodes. We show that the series resistance is not a significant problem. The conductive polysilicon can also destroy the cMUT if the top membrane is pulled in the bottom. As a solution we propose the application of an additional dielectric layer. Finally we demonstrate a device built with a novel beam construction that produces transmitted pressure pulse into air with 6% bandwidth and agrees reasonably well with the 1D model. We conclude that cMUTs made with MUMPs process have some limitations that are not present in customized processes. However, these limitations may be overcome with the proper design considerations that we have presented putting a low cost, highly accessible means of making cMUT devices into the hands of academic and industrial researchers.     

Synthesis of manganese oxide nanocrystal by ultrasonic bath: effect of external magnetic field

A novel technique was used for the synthesis of manganese oxide nanocrystal by applying an external magnetic field (EMF) on the precursor solution before sonication with ultrasonic bath. The results were compared in the presence and absence of EMF. Manganese acetate solution as precursor was circulated by a pump at constant speed (7 rpm, equal to flow rate of 51.5 mL/min) in an EMF with intensity of 0.38 T in two exposure times (t_MF, 2 h and 24 h). Then, the magnetized solution was irradiated indirectly by ultrasonic bath in basic and neutral media. One experiment was designed for the effect of oxygen atmosphere in the case of magnetic treated solution in neutral medium. The as prepared samples were characterized with X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, transmission electron microscopy (HRTEM, TEM), energy-dispersive spectrum (EDS), and superconducting quantum interference device (SQUID) analysis. In neutral medium, the sonication of magnetized solution (t_MF, 24 h) led mainly to a mixture of Mn₃O₄ (hausmannite) and γ-MnOOH (manganite) and sonication of unmagnetized solution led to a pure Mn₃O₄. In point of particle size, the larger and smaller size of nanoparticles was obtained with and without magnetic treatment, respectively. In addition, the EMF was retarded the nucleation process, accelerated the growth of the crystal, and increased the amount of rod-like structure especially in oxygen atmosphere. In basic medium, a difference was observed on the composition of the products between magnetic treated and untreated solution. For these samples, the magnetic measurements as a function of temperature were exhibited a reduction in ferrimagnetic temperature to T_c = 39 K, and 40 K with and without magnetic treatment, respectively. The ferrimagnetic temperature was reported for the bulk at T_c = 43 K. A superparamagnetic behavior was observed at room temperature without any saturation magnetization and hysteresis in the measured field strength. The effect of EMF on the sample prepared in the basic medium was negligible but, in the case of neutral medium, the EMF affected the slope of the magnetization curves. The magnetization at room temperature was higher for the samples obtained in neutral medium without magnetic treatment. In addition, a horizontal shift loop was observed in neutral medium at low temperature.     

Nitric oxide flow tagging in unseeded air

A scheme for molecular tagging velocimetry is presented that can be used in air flows without any kind of seeding. The method is based on the local and instantaneous creation of nitric oxide (NO) molecules from N(2) and O(2) in the waist region of a focused ArF excimer laser beam. This NO distribution is advected by the flow and can be visualized any time later by laser-induced fluorescence in the gamma bands. The creation of NO is confirmed by use of an excitation spectrum. Two examples of the application of the new scheme for air-flow velocimetry are given in which single laser pulses are used for creation and visualization of NO.     

Nitric oxide heme interactions in nitrophorin 7 investigated by nuclear inelastic scattering

Nitrophorins (NPs) occur in the blood-sucking insect Rhodnius prolixus. These proteins use ferric heme to store nitric oxide (NO) in the salivary glands of the insects and transport it to the victim’s tissues, resulting in vasodilation and reduced blood coagulation. In this work we present a nuclear inelastic scattering (NIS) study in order to characterize the iron-NO interaction in the isoform nitrophorin 7 (NP7). The NIS data obtained for NP7 complexed with NO show a strong band at ～589 cm^?1 which is due to modes with significant Fe-NO stretching and bending character. Another conspicuous feature is a significant peak at ～280 cm^?1 in the region where the heme modes occur. Based on a hybrid calculation method, which uses density functional theory and molecular mechanics, the band at ～280 cm^?1 is assigned to heme modes with substantial doming character.     

Folding and cracking of graphene oxide sheets upon deposition

Graphene Oxide (GO) sheets, suspended in an aqueous solution, were deposited on freshly cleaved highly oriented pyrolytic graphite (HOPG) and studied using Raman spectroscopy, atomic force microscopy (AFM) and scanning tunneling microscopy (STM). AFM phase imaging shows a distinct contrast between GO and the underlying HOPG substrate. Raman spectroscopy clearly showed the presence of GO sheets on the top of HOPG substrate. The AFM and STM images also reveal wrinkling, folding, and tearing of individual GO sheets after depositing onto an HOPG substrate. We have also observed a distinct cracking of a GO sheet after folding. We attribute this new cracking phenomenon to a weakening of C–C bonds during the oxidation of a graphene sheet.     

Overcoming the limitations of gallium oxide through heterogeneous integration

Power electronics,processing over 50%of world's electric energy,enables very efficient electric energy conversion for a wide range of applications such as electric vehicles,data centers,autonomous driving,robotics and smart grids.The availability of low-cost,efficient,and reliable power semiconductor devices that can conduct high current,block high voltage,and switch at high frequencies are key to improving the performance of power electronics systems.     

On some nonlinear effects in ultrasonic fields

Nonlinear effects associated with intense sound fields in fluids are considered theoretically. Special attention is directed to the study of higher effects that cannot be described within the standard propagation models of nonlinear acoustics (the KZK and Burgers equations). The analysis is based on the fundamental equations of motion for a thermoviscous fluid, for which thermal equations of state exist. Model equations are derived and used to analyze nonlinear sources for generation of flow and heat, and other changes in the ambient state of the fluid. Fluctuations in the coefficients of viscosity and thermal conductivity caused by the sound field, are accounted for. Also considered are nonlinear effects induced in the fluid by flexural vibrations. The intensity and absorption of finite amplitude sound waves are calculated, and related to the sources for generation of higher order effects.     

Nitric acid-stabilized superparamagnetic iron oxide nanoparticles studied with X-rays

Using density functional theory, we systematically investigate the adsorption geometries and electrical properties of (3,3) carbon nanotube (CNT) integrated on hydrogen-terminated Si(001):1?×?1 surface. Prior to adsorption of the CNT, the surface is patterned in two different ways by desorbing selective hydrogen atoms from the surface. The (3,3) CNT which is metallic in nature becomes semiconducting with a band gap around the fermi level when it is supported on patterned hydrogen-terminated Si(001):1?×?1 surface. However, the band gap is reduced when a transverse electric field is applied, allowing the (3,3) CNT on the patterned hydrogen-terminated Si(001):1?×?1 to become metallic at a critical field strength. The tuning of electrical properties of the (3,3) CNT integrated with Si surface may have potential technological applications.     

Rectangular cymbal arrays for improved ultrasonic transdermal insulin delivery

Circular cymbal ultrasound arrays have been shown to be effective in delivering therapeutic levels of insulin in rats, rabbits, and pigs. To improve delivery efficiency, a rectangular cymbal design was desired in order to achieve a broader spatial intensity field without increasing the size of the device or the spatial-peak temporal-peak intensity (I(SPTP)). With a similar intensity (50 mWcm(2)), the goal was to determine if the 3x1 rectangular cymbal array could perform significantly better than the 3x3 circular array for glucose reduction in hyperglycemic rabbits. Rabbit experiments were performed using three groups: nonsonicated control (n=3), ultrasound exposure using a circular cymbal array (n=3), and ultrasound exposure using a rectangular cymbal array (n=3). Rabbits were anesthetized and a water tight reservoir that held the insulin was fastened on the rabbit's thigh. At the beginning of the experiment and every 15 min for 90 min, the blood glucose level was determined. For comparison between individual rabbits, the absolute level is normalized by subtracting out the baseline in order to arrive at the change in glucose level. For the control group, the normalized glucose level increased (more hyperglycemic) to +80.0+/-28.8 mgdl (mean+/-SEM). Using the circular array, the glucose level decreased to -146.7+/-17.8 mgdl at 90 min. However, using the rectangular cymbal array, the glucose decreased faster and to a level of -200.8+/-5.9 mgdl after 90 min. These results indicated the feasibility of the rectangular cymbal array as an improved device for drug delivery.     

Superparamagnetic nanoparticles for biomedical applications: Possibilities and limitations of a new drug delivery system

Nanoparticles can be used in biomedical applications, where they facilitate laboratory diagnostics, or in medical drug targeting. They are used for in vivo applications such as contrast agent for magnetic resonance imaging (MRI), for tumor therapy or cardiovascular disease. Very promising nanoparticles for these applications are superparamagnetic nanoparticles based on a core consisting of iron oxides (SPION) that can be targeted through external magnets. SPION are coated with biocompatible materials and can be functionalized with drugs, proteins or plasmids. In this review, the characteristics and applications of SPION in the biomedical sector are introduced and discussed.     

Ultrasound-induced cracking and pyrolysis of some aromatic and naphthenic hydrocarbons

The action of intense ultrasound on solutions of decahydronaphthalene (decalin) or tetrahydronaphthalene (tetralin) causes, in both cases, a dehydrogenation reaction at room temperature. According to thermodynamic calculations, temperatures as high as 500 degrees C are necessary to achieve the same results. The use of Pd and Se as dehydrogenation catalysts has confirmed the dehydrogenation reactions. Benzene and toluene sonication at room temperature causes aromatic ring breakdown with formation of acetylene and other products. The analogy with radiolysis was noticed. A thermodynamic analysis was conducted on the possible reaction products formed from benzene ring cleavage including polymerization products. It was concluded that acetylene formation from benzene is possible for instance at 650 degrees C only if it is accompanied by coke formation. Otherwise temperatures as high as 1700 degrees C are needed. The nature of the 'coke' formed during sonication is discussed, it was revealed by FT-IR spectroscopy to be a crosslinked polystyrene and hence it is a sonopolymer derived from benzene or toluene ring breakdown products reacted with phenyl and polyphenyl radicals. Again the striking analogy between the IR spectrum of irradiated polystyrene and benzene sonopolymer was noticed. The formation of poly-p-phenylene was excluded by the FT-IR pattern which did not match that of an authentic sample.     

Nitric oxide detection inside the cylinder of an SI engine by direct UV absorption spectroscopy

The present work is a first step for the implementation and the development of a rapid and quantitative measurement technique using the UV broadband-lamp absorption spectroscopy. This technique is applied to detect nitric oxide molecules inside the combustion chamber of a methane-fueled spark-ignition engine. The ability of this technique to detect NO in very harsh thermodynamic conditions is proved under certain engine operating conditions. In spite of the broadband absorption, mainly due to the hot CO₂ and H₂O, clear NO absorption γ-bands are observed when the engine is skip-fired or when NO is added at the intake port. It was however, not possible to detect any nitric oxide absorption during the combustion time when each cycle was ignited and no nitric oxide was added. Finally, using the skip-ignition mode, the acquired NO absorption spectra allowed to conclude that evacuation of the in-cylinder residual gases can be complete at the end of the sixth cycle.     

Some physical properties of In doped copper oxide films produced by ultrasonic spray pyrolysis

In this work, we have reported the effect of In doping on structural, optical and surface properties of copper oxide films obtained by a low-cost ultrasonic spray pyrolysis technique. Thicknesses, refractive indices and extinction coefficients of the films have been determined by Spectroscopic ellipsometry technique using Cauchy-Urbach model for fitting. A very good agreement was found between experimental and theoretical parameters with low MSE values. Transmission and reflectance spectra have been taken by UV Spectrophotometer, and band gap values have been determined by optical method. Structural properties of the films were investigated with X-ray diffraction patterns. In doping caused the films to growth through some certain directions. Atomic force microscope images have been taken to see the effect of In doping on surface topography and roughness of copper oxide films. Surface properties of undoped films have been improved by In doping. Lowest roughness values have been obtained for In doping at 1%. As a result, we have concluded that properties of copper oxide films which are commonly used in solar cells may have improved by In doping (especially In doped at 1%).     

Possibilities and limitations of ultrasonic diagnosis of space occupying lesions in internal medicine.

Possibilities and limitations of ultrasonic tumour diagnosis in internal medicine (thyroid gland, liver, pancreas, kidney, malignant lymphomas) are discussed on the basis of a five years experience with about 4,000 examinations a year. A real time and gray-scale technique is used. The accuracy of the presented ultrasonic findings is proven by comparative studies. Besides the well known advantages of ultrasonography the independence from contrast medias must be stressed in comparison to diagnostic radiology. The main limitations of ultrasonography are the impossibility of diagnosing tumours smaller than 1.5-2 cm and the absence of an ultrasonic pattern typical of malignancy. To establish a morphobiological diagnosis, ultrasonically guided fine needle biopsy has proved to be a reliable method.     

Double-layer indium doped zinc oxide for silicon thin-film solar cell prepared by ultrasonic spray pyrolysis

Indium doped zinc oxide(ZnO:In) thin films were prepared by ultrasonic spray pyrolysis on corning eagle 2000 glass substrate.1 and 2 at.% indium doped single-layer ZnO:In thin films with different amounts of acetic acid added in the initial solution were fabricated.The 1 at.% indium doped single-layers have triangle grains.The 2 at.% indium doped single-layer with 0.18 acetic acid adding has the resistivity of 6.82×10-3Ω·cm and particle grains.The doublelayers structure is designed to fabricate the ZnO:In thin film with low resistivity(2.58×10-3Ω·cm) and good surface morphology.It is found that the surface morphology of the double-layer ZnO:In film strongly depends on the substratelayer,and the second-layer plays a large part in the resistivity of the double-layer ZnO:In thin film.Both total and direct transmittances of the double-layer ZnO:In film are above 80% in the visible light region.Single junction a-Si:H solar cell based on the double-layer ZnO:In as front electrode is also investigated.     

Electric field-induced rearrangement of charged species in metal oxide devices with resistive change: thermodynamic limitations

Hypotheses used to interpret results of electrical measurements on metal oxides which are employed for gas sensors and resistive switching memristors are often based on consideration of drift migration of species (such as oxygen vacancies, chemisorbed ions) under electric field. We offer simple conceptual arguments restricting this approach from the view points of potential minimum principle, ambipolar diffusion and non-equilibrium thermodynamics (Glansdorff-Prigogine criterion).     

Barrier-breaking effects of ultrasonic cavitation for drug delivery and biomarker release

Recently, emerging evidence has demonstrated that cavitation actually creates important bidirectional channels on biological barriers for both intratumoral drug delivery and extratumoral biomarker release. To promote the barrier-breaking effects of cavitation for both therapy and diagnosis, we first reviewed recent technical advances of ultrasound and its contrast agents (microbubbles, nanodroplets, and gas-stabilizing nanoparticles) and then reported the newly-revealed cavitation physical details. In particular, we summarized five types of cellular responses of cavitation in breaking the plasma membrane (membrane retraction, sonoporation, endocytosis/exocytosis, blebbing and apoptosis) and compared the vascular cavitation effects of three different types of ultrasound contrast agents in breaking the blood-tumor barrier and tumor microenvironment. Moreover, we highlighted the current achievements of the barrier-breaking effects of cavitation in mediating drug delivery and biomarker release. We emphasized that the precise induction of a specific cavitation effect for barrier-breaking was still challenged by the complex combination of multiple acoustic and non-acoustic cavitation parameters. Therefore, we provided the cutting-edge in-situ cavitation imaging and feedback control methods and suggested the development of an international cavitation quantification standard for the clinical guidance of cavitation-mediated barrier-breaking effects.