Transdermal Delivery of Ultradeformable Cationic Liposomes Complexed with miR211-5p (UCL-211) Stabilizes BRAFV600E+ Melanocytic Nevi.

Small non-coding RNAs (e.g. siRNA, miRNA) are involved in a variety of melanocyte-associated skin conditions and act as drivers for alterations in gene expression within melanocytes.

Ultrasonic measurement of temperature distributions in extreme environments: Electrical power plants testing in utility-scale steam generators.

Thermal heterogeneities within energy conversion and storage, material processing, nuclear processes, aerospace, and military applications are often inaccessible to characterization by insertion sensors. When sensor deployment is possible, conventional pointwise temperature probes quickly degrade when inserted into harsh environments typical of such processes. We developed spatially-resolved ultrasonic thermometry to noninvasively measure the spatial distributions of thermal properties in such applications, even when sizable thermal gradients are present.

Asymmetric depth-filtration: A versatile and scalable method for high-yield isolation of extracellular vesicles with low contamination.

We developed a novel asymmetric depth filtration (DF) approach to isolate extracellular vesicles (EVs) from biological fluids that outperforms ultracentrifugation and size-exclusion chromatography in purity and yield of isolated EVs. By these metrics, a single-step DF matches or exceeds the performance of multistep protocols with dedicated purification procedures in the isolation of plasma EVs. We demonstrate the selective transit and capture of biological nanoparticles in asymmetric pores by size and elasticity, low surface binding to the filtration medium, and the ability to cleanse EVs held by the filter before their recovery with the reversed flow all contribute to the achieved purity and yield of preparations.

Quantification of Desiccated Extracellular Vesicles by Quartz Crystal Microbalance.

Extracellular vesicle (EV) quantification is a procedure through which the biomedical potential of EVs can be used and their biological function can be understood. The number of EVs isolated from cell culture media depends on the cell status and is especially important in studies on cell-to-cell signaling, disease modeling, drug development, etc. Currently, the methods that can be used to quantify isolated EVs are sparse, and each have limitations.

Dynamic surface tension probe for measuring the concentration of extracellular vesicles.

The concentration of extracellular vesicles (EVs) is an essential attribute of biofluids and EV preparations. EV concentration in body fluids was correlated with health status. The abundance of EV secreted by cultured cells into growth medium is vital in signaling studies, tissue and disease models, and biomanufacturing of acellular therapeutic secretome.

Imaging of Extracellular Vesicles by Atomic Force Microscopy.

Exosomes and other extracellular vesicles (EVs) are molecular complexes consisting of a lipid membrane vesicle, its surface decoration by membrane proteins and other molecules, and diverse luminal content inherited from a parent cell, which includes RNAs, proteins, and DNAs. The characterization of the hydrodynamic sizes of EVs, which depends on the size of the vesicle and its coronal layer formed by surface decorations, has become routine. For exosomes, the smallest of EVs, the relative difference between the hydrodynamic and vesicles sizes is significant.

Membrane proteins significantly restrict exosome mobility.

Exosomes are membrane nanovesicles implicated in cell-to-cell signaling in which they transfer their molecular cargo from the parent to the recipient cells. This role essentially depends on the exosomes' small size, which is the prerequisite for their rapid migration through the crowded extracellular matrix and into and out of circulation. Here we report much lower exosome mobility than expected from the size of their vesicles, implicate membrane proteins in a substantially impeded rate of migration, and suggest an approach to quantifying the impact.

Ultrasound measurements of segmental temperature distribution in solids: Method and its high-temperature validation.

A novel approach that uses noninvasive ultrasound to measure the temperature distribution in solid materials is described and validated in high-temperature laboratory experiments. The approach utilizes an ultrasound propagation path with naturally occurring or purposefully introduced echogenic features that partially redirect the energy of an ultrasound excitation pulse back to the transducer, resulting in a train of echoes. Their time of flight depends on the velocity of ultrasound propagation, which changes with temperature distribution in different segments of the propagation path.

Size and shape characterization of hydrated and desiccated exosomes.

Exosomes are stable nanovesicles secreted by cells into the circulation. Their reported sizes differ substantially, which likely reflects the difference in the isolation techniques used, the cells that secreted them, and the methods used in their characterization. We analyzed the influence of the last factor on the measured sizes and shapes of hydrated and desiccated exosomes isolated from the serum of a pancreatic cancer patient and a healthy control.

Surface tension of water in the presence of perfluorocarbon vapors.

Fluorocarbons are highly hydrophobic, biocompatible compounds with a variety of medical applications. Despite significant interest, the study of interfacial properties of fluorocarbons in aqueous systems has received limited attention. In this study, we investigate the influence of perfluoropentane and perfluorohexane vapors on the surface tension of water at room temperature.

Identification of reduced-order thermal therapy models using thermal MR images: theory and validation.

In this paper, we develop and validate a method to identify computationally efficient site- and patient-specific models of ultrasound thermal therapies from MR thermal images. The models of the specific absorption rate of the transduced energy and the temperature response of the therapy target are identified in the reduced basis of proper orthogonal decomposition of thermal images, acquired in response to a mild thermal test excitation. The method permits dynamic reidentification of the treatment models during the therapy by recursively utilizing newly acquired images.

Identification of controlled-complexity thermal therapy models derived from magnetic resonance thermometry images.

Medical imaging provides information valuable in diagnosis, planning, and control of therapies. In this paper, we develop a method that uses a specific type of imaging--the magnetic resonance thermometry--to identify accurate and computationally efficient site and patient-specific computer models for thermal therapies, such as focused ultrasound surgery, hyperthermia, and thermally triggered targeted drug delivery. The developed method uses a sequence of acquired MR thermometry images to identify a treatment model describing the deposition and dissipation of thermal energy in tissues.

Bidirectional power stroke by ncd kinesin.

Optical trapping experiments reveal details of molecular motor dynamics. In noisy data, temporal structure within the power stroke of motors can be analyzed by ensemble averaging, but this obscures infrequent subcategories of events. We have here developed an analysis method that uses Kalman filtering of measurements, model-based estimation of the power strokes produced by the motor head, and automatic event classification to discriminate between different types of motor events.

Comparison of surfactants used to prepare aqueous perfluoropentane emulsions for pharmaceutical applications.

Perfluoropentane (PFP), a very hydrophobic, nontoxic, noncarcinogenic fluoroalkane, has generated much interest in biomedical applications, including occlusion therapy and controlled drug delivery. For most of these applications, the dispersion within aqueous media of a large quantity of PFP droplets of the proper size is critically important. Surprisingly, the interfacial tension of PFP against water in the presence of surfactants used to stabilize the emulsion has rarely, if ever, been measured.

Method for measuring thickness of dielectric films using microdielectric fringe-effect sensors.

A method for noninvasive thickness measurements of dielectric films using fringe-effect (FE) sensors is developed and experimentally validated. The fringing electrical field, created by electrodes microfabricated at the film substrate, depends on the film thickness and dielectric permittivity of the film under test (FUT). The unknown film thickness is estimated by matching the theoretical prediction of thickness-dependent sensor admittance with the measured value.

Physiological control of blood pumps using intrinsic pump parameters: a computer simulation study.

Implantable flow and pressure sensors, used to control rotary blood pumps, are unreliable in the long term. It is, therefore, desirable to develop a physiological control system that depends only on readily available measurements of the intrinsic pump parameters, such as measurements of the pump current, voltage, and speed (in revolutions per minute). A previously proposed DeltaP control method of ventricular assist devices (VADs) requires the implantation of two pressure sensors to measure the pressure difference between the left ventricle and aorta.

Control of thermal therapies with moving power deposition field.

A thermal therapy feedback control approach to control thermal dose using a moving power deposition field is developed and evaluated using simulations. A normal tissue safety objective is incorporated in the controller design by imposing constraints on temperature elevations at selected normal tissue locations. The proposed control technique consists of two stages.

MR thermometry-based feedback control of efficacy and safety in minimum-time thermal therapies: phantom and in-vivo evaluations.

The experimental validation of a model-based, thermal therapy control system which automatically and simultaneously achieves the specified efficacy and safety objectives of the treatment is reported. MR-thermometry measurements are used in real-time to control the power of a stationary, focused ultrasound transducer in order to achieve the desired treatment outcome in minimum time without violating the imposed safety constraints. Treatment efficacy is quantified in terms of the thermal dose delivered to the target.

Direct thermal dose control of constrained focused ultrasound treatments: phantom and in vivo evaluation.

The first treatment control system that explicitly and automatically balances the efficacy and safety goals of noninvasive thermal therapies is described, and its performance is evaluated in phantoms and in vivo using ultrasound heating with a fixed, focused transducer. The treatment efficacy is quantified in terms of thermal dose delivered to the target. The developed feedback thermal dose controller has a cascade structure with the main nonlinear dose controller continuously generating the reference temperature trajectory for the secondary, constrained, model predictive temperature controller.

Minimum-time thermal dose control of thermal therapies.

The problem of controlling noninvasive thermal therapies is formulated as the problem of directly controlling thermal dose of the target. To limit the damage to the surrounding normal tissue, the constraints on the peak allowable temperatures in the selected spacial locations are imposed. The developed controller has a cascade structure with a linear, constrained, model predictive temperature controller in the secondary loop.

Standard-independent estimation of dielectric permittivity with microdielectric fringe-effect sensors.

Microdielectric spectroscopy with planar fringe-effect (FE) interdigital sensors is a useful method for noninvasive characterization of the interfacial properties of the materials. Unfortunately, obtaining an accurate dielectric spectrum is difficult because of the complexity of the probing electrical field created by the FE sensor and the contribution of the sensor substrate and stray elements to the overall measurements. Previously, quantitative microdielectric spectroscopy required the calibration of the FE sensor with standard materials that are known to be dielectrically similar to an unknown sample of interest.

Physiologic control of rotary blood pumps: an in vitro study.

Rotary blood pumps (RBPs) are currently being used as a bridge to transplantation as well as for myocardial recovery and destination therapy for patients with heart failure. Physiologic control systems for RBPs that can automatically and autonomously adjust the pump flow to match the physiologic requirement of the patient are needed to reduce human intervention and error, while improving the quality of life. Physiologic control systems for RBPs should ensure adequate perfusion while avoiding inflow occlusion via left ventricular (LV) suction for varying clinical and physical activity conditions.

Quantitative measurements of dielectric spectra with microdielectric fringe-effect sensors.

The parallel-plate method is a gold standard for measuring dielectric properties of materials. However, it requires sampling of the material under testing (MUT), which makes it less suitable for real time, dynamic, and in situ measurements. The alternative to the parallel-plate method is to use the microdielectric fringe-effect (FE) sensors, which can be placed inside the process or laboratory equipment to provide rapid, on-line, and noninvasive characterization of the dielectric properties.

Control strategy for maintaining physiological perfusion with rotary blood pumps.

We present arguments and simulation results in favor of a novel strategy for control of rotary blood pumps. We suggest that physiological perfusion is achieved when the blood pump is controlled to maintain an average reference differential pressure. In the case of rotary left ventricular assist devices, our simulations show that maintaining a constant average pressure difference between the left ventricle and aorta results in physiological perfusion over a wide range of physical activities and clinical cardiac conditions.

Nonlinear controller for ventricular assist devices.

This paper presents the design of a gain-scheduled proportional integral (PI) feedback controller for ventricular assist devices to maintain physiologically motivated perfusion. The selected control objective is to maintain an average differential pressure deltaP between the left ventricle and the aorta. Computer simulations for different pathological conditions, ranging from the normal heart to left heart asystole, and a wide range of physiological scenarios, ranging from rest to strenuous exercise, were used to validate the performance of the controller and the effectiveness of the selected control objective in ensuring physiologically adequate perfusion under different clinical and cardiac demand conditions.