Bactericidal effects of high-energy visible light on common otitis media pathogens.

AIMS: This study assessed the use of high-energy, visible light on the survival rates of three bacteria commonly found in middle ear infections (i.e. otitis media; Streptococcus pneumoniae, Moraxella catarrhalis and Haemophilus influenzae). METHOD AND RESULTS: Bacteria were cultured and then subjected to a single, 4-h treatment of 405 nm wavelength light at two different intensities. All three bacteria species were susceptible to the light at clinically significant rates (>99.9% reduction). Bacteria were susceptible to the high-energy visible (HEV) light in a dose-dependent manner (lower survival rates with increased intensity and duration of exposure). CONCLUSIONS: The results suggest that HEV light may provide a non-surgical, non-pharmaceutical approach to the therapeutic treatment of otitis media. SIGNIFICANCE AN IMPACT OF THE STUDY: Given the growing concerns surrounding antibiotic resistance, this study demonstrates a rapid, alternative method for effective inactivation of bacterial pathogens partly responsible for instances of otitis media.

A Flow Sensor-Based Suction-Index Control Strategy for Rotary Left Ventricular Assist Devices.

Rotary left ventricular assist devices (LVAD) have emerged as a long-term treatment option for patients with advanced heart failure. LVADs need to maintain sufficient physiological perfusion while avoiding left ventricular myocardial damage due to suction at the LVAD inlet. To achieve these objectives, a control algorithm that utilizes a calculated suction index from measured pump flow (SIMPF) is proposed. This algorithm maintained a reference, user-defined SIMPF value, and was evaluated using an in silico model of the human circulatory system coupled to an axial or mixed flow LVAD with 5-10% uniformly distributed measurement noise added to flow sensors. Efficacy of the SIMPF algorithm was compared to a constant pump speed control strategy currently used clinically, and control algorithms proposed in the literature including differential pump speed control, left ventricular end-diastolic pressure control, mean aortic pressure control, and differential pressure control during (1) rest and exercise states; (2) rapid, eight-fold augmentation of pulmonary vascular resistance for (1); and (3) rapid change in physiologic states between rest and exercise. Maintaining SIMPF simultaneously provided sufficient physiological perfusion and avoided ventricular suction. Performance of the SIMPF algorithm was superior to the compared control strategies for both types of LVAD, demonstrating pump independence of the SIMPF algorithm.

Electroactive Interface for Enabling Spectroelectrochemical Investigations in Evanescent-Wave Cavity-Ring-Down Spectroscopy.

In this study, we report the development of an electrically active solid-liquid interface for the evanescent-wave cavity-ring-down spectroscopic (EW-CRDS) technique to enable spectroelectrochemical investigations of redox events. Because of a high-quality transparent conductive electrode film of indium tin oxide (ITO) coated on the interface of total internal reflection of the EW-CRDS platform, a cavity ring-down time of about 900 ns was obtained allowing spectroelectrochemical studies at solid-liquid interfaces. As a proof-of-concept on the capabilities of the developed platform, measurements were performed to address the effects of an applied electric potential to the adsorption behavior of the redox protein cytochrome c (Cyt-C) onto different interfaces, namely, bare-ITO, 3-aminopropyl triethoxysilane (APTES), and Cyt-C antibody. For each interface, the adsorption and desorption constants, the surface equilibrium constant, the Gibbs free energy of adsorption, and the surface coverage were optically measured by our electrically active EW-CRDS tool. Optical measurements at a set of constant discrete values of the applied electric potential were acquired for kinetic adsorption analysis. Cyclic voltammetry (CV) scans under synchronous optical readout were performed to study the effects of each molecular interface on the redox process of surface-adsorbed protein species. Overall, the experimental results demonstrate the ability of the electro-active EW-CRDS platform to unambiguously measure electrode-driven redox events of surface-confined molecular species at low submonolayer coverages and at a single diffraction-limited spot. Such capability is expected to open several opportunities for the EW-CRDS technique to investigate a variety of electrochemical phenomena at solid-liquid interfaces.

Discovery of benzofuran propanoic acid GPR120 agonists: From uHTS hit to mechanism-based pharmacodynamic effects.

The transformation of an aryloxybutanoic acid ultra high-throughput screening (uHTS) hit into a potent and selective series of G-protein coupled receptor 120 (GPR120) agonists is reported. uHTS hit 1 demonstrated an excellent rodent pharmacokinetic profile and selectivity over the related fatty acid receptor GPR40, but only modest GPR120 potency. Optimization of the "left-hand" aryl group led to compound 6, which demonstrated a GPR120 mechanism-based pharmacodynamic effect in a mouse oral glucose tolerance test (oGTT). Further optimization gave rise to the benzofuran propanoic acid series (exemplified by compound 37), which demonstrated acute mechanism-based pharmacodynamic effects. The combination of in vivo efficacy and attractive rodent pharmacodynamic profiles suggests compounds generated from this series may afford attractive candidates for the treatment of Type 2 diabetes.

Observation and modeling of conformational molecular structures driving the self-assembly of tri-adamantyl benzene on Ag(111).

The self-organization of tri-adamantyl (TAB) benzene molecules has been investigated using low temperature scanning tunneling microscopy (LT-STM). The molecular structures have also been studied using molecular modeling. In particular, these calculations have been performed on large areas (1000 nm(2)) from the atomic structure of the molecular building block, combining molecular dynamics (MD) and Monte-Carlo (MC) approaches. These investigations show that the structure of the molecule and its flexibility allow for the formation of different networks as a function of surface coverage. The calculations demonstrate that the stability of the largest structures is obtained through the increase of the interfacial energy induced by the rotation of the adamantyl groups, a behavior whose consequences explain the subtle contrasts observed in the experimental STM images.

Electrochemical dissolved oxygen removal from microfluidic streams for LOC sample pretreatment.

Current water quality monitoring for heavy metal contaminants largely results in analytical snapshots at a particular time and place. Therefore, we have been interested in miniaturized and inexpensive sensors suitable for long-term, real-time monitoring of the drinking water distribution grid, industrial wastewater effluents, and even rivers and lakes. Among the biggest challenges for such sensors are the issues of in-field device calibration and sample pretreatment. Previously, we have demonstrated use of coulometric stripping analysis for calibration-free determination of copper and mercury. For more negatively reduced metals, O2 reduction interferes with stripping analysis; hence, most electroanalysis techniques rely on pretreatments to remove dissolved oxygen (DO). Current strategies for portable DO removal offer limited practicality, because of their complexity, and often cause inadvertent sample alterations. Therefore, we have designed an indirect in-line electrochemical DO removal device (EDOR), utilizing a silver cathode to reduce DO in a chamber that is fluidically isolated from the sample stream by an O2-permeable membrane. The resulting concentration gradient supports passive DO diffusion from the sample stream into the deoxygenation chamber. The DO levels in the sample stream were determined by cyclic voltammetry (CV) and amperometry at a custom thin-layer cell (TLC) detector. Results show removal of 98% of the DO in a test sample at flow rates approaching 50 µL/min and power consumption as low as 165 mW h L(-1) at steady state. Besides our specific stripping application, this device is well-suited for LOC applications where miniaturized DO removal and/or regulation are desirable.

Development of a rocking chair for use by children with spinal cord injuries.

PURPOSE: Activity-based locomotor training improves intrinsic trunk control in children with spinal cord injury (SCI). To reinforce these improvements, there is a need to develop community integration activities to allow a patient to apply the retrained nervous system at home. One activity that has been explored is rocking in a rocking chair. This paper describes the design, fabrication, and evaluation of a rocking chair for children with SCI. MATERIALS AND METHODS: The Quality Function Deployment (QFD) design process was used. Fundamental needs and features for the rocking chair were defined in a focus group with experienced therapists, and needs were then rated for importance. A House of Quality (HOQ) matrix was developed to correlate needs with design features, and a prototype design was generated. Virtual motion studies and finite element analysis (FEA) were utilized to assess the design. The chair was fabricated and physical testing was performed, including tipping and static and dynamic load assessments. RESULTS AND CONCLUSIONS: The needs identified through the QFD process were categorized into (1) safety, (2) therapeutic, (3) practical and aesthetic, and (4) data to track chair use. Features selected to meet these needs include safety stops, padding, straps, a stable base, armrests, adjustable footrest, and sensors to capture rocking data. FEA showed a factor of safety (FOS) > 5. Physical testing confirmed physical integrity, load-bearing capacity, and stability of the prototype glider rocking chair. The prototype provides a safe tool for further investigation of rocking for promotion of trunk muscle activation in children with SCI.

Rocking in a rocking chair promotes carryover of gained trunk control capacity, from clinic to home in a population that is non-ambulatory.Rocking provides opportunity for self-practice in population with severely compromised capacity.Rocking is a movement that may be performed when other types of movement cannot be readily performed, e.g., resistance exercise, movement against gravity.Rocking creates opportunity for repetitive, voluntary, self-directed movement that is inherently pleasurable and reinforcing.

Cardiac cell culture model as a left ventricle mimic for cardiac tissue generation.

A major challenge in cardiac tissue engineering is the delivery of hemodynamic mechanical cues that play a critical role in the early development and maturation of cardiomyocytes. Generation of functional cardiac tissue capable of replacing or augmenting cardiac function therefore requires physiologically relevant environments that can deliver complex mechanical cues for cardiomyocyte functional maturation. The goal of this work is the development and validation of a cardiac cell culture model (CCCM) microenvironment that accurately mimics pressure-volume changes seen in the left ventricle and to use this system to achieve cardiac cell maturation under conditions where mechanical loads such as pressure and stretch are gradually increased from the unloaded state to conditions seen in vivo. The CCCM platform, consisting of a cell culture chamber integrated within a flow loop was created to accomplish culture of 10 day chick embryonic ventricular cardiomyocytes subject to 4 days of stimulation (10 mmHg, ∼13% stretch at a frequency of 2 Hz). Results clearly show that CCCM conditioned cardiomyocytes accelerate cardiomyocyte structural and functional maturation in comparison to static unloaded controls as evidenced by increased proliferation, alignment of actin cytoskeleton, bundle-like sarcomeric α-actinin expression, higher pacing beat rate at lower threshold voltages, and increased shortening. These results confirm the CCCM microenvironment can accelerate immature cardiac cell structural and functional maturation for potential cardiac regenerative applications.

Self-assembly of a catechol-based macrocycle at the liquid-solid interface: experiments and molecular dynamics simulations.

This combined experimental (STM, XPS) and molecular dynamics simulation study highlights the complex and subtle interplay of solvent effects and surface interactions on the 2-D self-assembly pattern of a Schiff-base macrocycle containing catechol moieties at the liquid-solid interface. STM imaging reveals a hexagonal ordering of the macrocycles at the n-tetradecane/Au(111) interface, compatible with a desorption of the lateral chains of the macrocycle. Interestingly, all the triangular-shaped macrocycles are oriented in the same direction, avoiding a close-packed structure. XPS experiments indicate the presence of a strong macrocycle-surface interaction. Also, MD simulations reveal substantial solvent effects. In particular, we find that co-adsorption of solvent molecules with the macrocycles induces desorption of lateral chains, and the solvent molecules act as spacers stabilizing the open self-assembly pattern.

Development of Inspired Therapeutics Pediatric VAD: Benchtop Evaluation of Impeller Performance and Torques for MagLev Motor Design.

PURPOSE: Despite the availability of first-generation extracorporeal mechanical circulatory support (MCS) systems that are widely used throughout the world, there is a need for the next generation of smaller, more portable devices (designed without cables and a minimal number of connectors) that can be used in all in-hospital and transport settings to support patients in heart failure. Moreover, a system that can be universally used for all indications for use including cardiopulmonary bypass (CPB), uni- or biventricular support (VAD), extracorporeal membrane oxygenation (ECMO) and respiratory assist that is suitable for use for adult, neonate, and pediatric patients is desirable. Providing a single, well designed, universal technology could reduce the incidence of human errors by limiting the need for training of hospital staff on a single system for a variety of indications throughout the hospital rather than having to train on multiple complex systems. The objective of this manuscript is to describe preliminary research to develop the first prototype pump for use as a ventricular assist device for pediatric patients with the Inspired Universal MCS technology. The Inspired VAD Universal System is an innovative extracorporeal blood pumping system utilizing novel MagLev technology in a single portable integrated motor/controller unit which can power a variety of different disposable pump modules intended for neonate, pediatric, and adult ventricular and respiratory assistance. METHODS: A prototype of the Inspired Pediatric VAD was constructed to determine the hemodynamic requirements for pediatric applications. The magnitude/range of hydraulic torque of the internal impeller was quantified. The hydrodynamic performance of the prototype pump was benchmarked using a static mock flow loop model containing a heated blood analogue solution to test the pump over a range of rotational speeds (500-6000 RPM), flow rates (0-3.5 L/min), and pressures (0 to ~ 420 mmHg). The device was initially powered by a shaft-driven DC motor in lieu of a full MagLev design, which was also used to calculate the fluid torque acting on the impeller. RESULTS: The pediatric VAD produced flows as high as 4.27 L/min against a pressure of 127 mmHg at 6000 RPM and the generated pressure and flow values fell within the desired design specifications. CONCLUSIONS: The empirically determined performance and torque values establish the requirements for the magnetically levitated motor design to be used in the Inspired Universal MagLev System. This next step in our research and development is to fabricate a fully integrated and functional magnetically levitated pump, motor and controller system that meets the product requirement specifications and achieves a state of readiness for acute ovine animal studies to verify safety and performance of the system.

Development of Inspired Therapeutics Pediatric VAD: Computational Analysis and Characterization of VAD V3.

PURPOSE: Pediatric heart failure patients remain in critical need of a dedicated mechanical circulatory support (MCS) solution as development efforts for specific pediatric devices continue to fall behind those for the adult population. The Inspired Pediatric VAD is being developed as a pediatric specific MCS solution to provide up to 30-days of circulatory or respiratory support in a compact modular package that could allow for patient ambulation during treatment. METHODS: Hydrodynamic performance (flows, pressures), impeller/rotor mechanical properties (torques, forces), and flow shear stress and residence time distributions of the latest design version, Inspired Pediatric VAD V3, were numerically predicted and investigated using computational fluid dynamics (CFD) software (SolidWorks Flow Simulator). RESULTS: Hydrodynamic performance was numerically predicted, indicating no change in flow and pressure head compared to the previous device design (V2), while displaying increased impeller/rotor torques and translation forces enabled by improved geometry. Shear stress and flow residence time volumetric distributions are presented over a range of pump rotational speeds and flow rates. At the lowest pump operating point (3000 RPM, 0.50 L/min, 75 mmHg), 79% of the pump volume was in the shear stress range of 0-10 Pa with < 1% of the volume in the critical range of 150-1000 Pa for blood damage. At higher speed and flow (5000 RPM, 3.50 L/min, 176 mmHg), 65% of the volume resided in the 0-10 Pa range compared to 2.3% at 150-1000 Pa. CONCLUSIONS: The initial computational characterization of the Inspired Pediatric VAD V3 is encouraging and future work will include device prototype testing in a mock circulatory loop and acute large animal model.

Endothelial cell culture model for replication of physiological profiles of pressure, flow, stretch, and shear stress in vitro.

The phenotype and function of vascular cells in vivo are influenced by complex mechanical signals generated by pulsatile hemodynamic loading. Physiologically relevant in vitro studies of vascular cells therefore require realistic environments where in vivo mechanical loading conditions can be accurately reproduced. To accomplish a realistic in vivo-like loading environment, we designed and fabricated an Endothelial Cell Culture Model (ECCM) to generate physiological pressure, stretch, and shear stress profiles associated with normal and pathological cardiac flow states. Cells within this system were cultured on a stretchable, thin (∼500 µm) planar membrane within a rectangular flow channel and subject to constant fluid flow. Under pressure, the thin planar membrane assumed a concave shape, representing a segment of the blood vessel wall. Pulsatility was introduced using a programmable pneumatically controlled collapsible chamber. Human aortic endothelial cells (HAECs) were cultured within this system under normal conditions and compared to HAECs cultured under static and "flow only" (13 dyn/cm(2)) control conditions using microscopy. Cells cultured within the ECCM were larger than both controls and assumed an ellipsoidal shape. In contrast to static control control cells, ECCM-cultured cells exhibited alignment of cytoskeletal actin filaments and high and continuous expression levels of ß-catenin indicating an in vivo-like phenotype. In conclusion, design, fabrication, testing, and validation of the ECCM for culture of ECs under realistic pressure, flow, strain, and shear loading seen in normal and pathological conditions was accomplished. The ECCM therefore is an enabling technology that allows for study of ECs under physiologically relevant biomechanical loading conditions in vitro.

Adsorptive behavior of CO2, CH4 and their mixtures in carbon nanospace: a molecular simulation study.

Using molecular simulation, four types of nanoporous carbons are examined as adsorbents for the separation of CO(2)/CH(4) mixtures at ambient temperature and pressures up to 10 MPa. First, the adsorption selectivity of CO(2) is investigated in carbon slit pores and single-walled carbon nanotube bundles in order to find the optimal pore dimensions for CO(2) separation. Then, the adsorptive properties of the optimized slit pore and nanotube bundle are compared with two realistic nanoporous carbon models: a carbon replica of zeolite Y and an amorphous carbon. For the four carbon models, adsorption isotherms and isosteric heats of adsorption are presented for both pure components and mixtures. Special attention is given to the calculation of excess isotherms and isosteric heats, which are necessary to assess the performance of model nanoporous materials in the context of experimental measurements. From these results, we discuss the impact that variables such as pore size, pore morphology, pressure and mixture composition have on the performance of nanoporous carbons for CO(2) separation.

Microporous carbon adsorbents with high CO2 capacities for industrial applications.

In this study we attempt to investigate the potential use of two zeolite template carbon (ZTC), EMT-ZTC and FAU-ZTC, to capture CO(2) at room temperature. We report their high pressure CO(2) adsorption isotherms (273 K) that show for FAU-ZTC the highest carbon capture capacity among published carbonaceous materials and competitive data with the best organic and inorganic adsorbing frameworks ever-known (zeolites and mesoporous silicas, COFs and MOFs). The importance of these results is discussed in light of mitigation of CO(2) emissions. In addition to these new experimental CO(2) adsorption data, we also present new insight into the adsorption process of the two structures by Monte Carlo simulations: we propose that two separate effects are responsible for the apparent similarity of the adsorption behaviour of the two structures: (i) pore blocking occurring on EMT-ZTC, and (ii) the change of the carbon polarizability due to the extreme curvature of FAU-ZTC.

Photobleaching reduction in modulated super-resolution microscopy.

Important breakthroughs in far-field imaging techniques have been made since the first demonstrations of stimulated emission depletion (STED) microscopy. To date, the most straightforward and widespread deployment of STED microscopy has used continuous wave (CW) laser beams for both the excitation and depletion of fluorescence emission. A major drawback of the CW STED imaging technique has been photobleaching effects due to the high optical power needed in the depletion beam to reach sub-diffraction resolution. To overcome this hurdle, we have applied a synchronous detection approach based on modulating the excitation laser beam, while keeping the depletion beam at CW operation, and frequency filtering the collected signal with a lock-in amplifier to record solely the super-resolved fluorescence emission. We demonstrate here that such approach allows an important reduction in the optical power of both laser beams that leads to measurable decreases in photobleaching effects in STED microscopy. We report super-resolution images with relatively low powers for both the excitation and depletion beams. In addition, typical unwanted scattering effects and background signal generated from the depletion beam, which invariably arises from mismatches in refractive index in the material composing the sample, are largely reduced by using the modulated STED approach. The capability of acquiring super-resolution images with relatively low power is quite relevant for studying a variety of samples, but particularly important for biological species as exemplified in this work.

Design and Computational Evaluation of a Pediatric MagLev Rotary Blood Pump.

Pediatric heart failure (HF) patients have been a historically underserved population for mechanical circulatory support (MCS) therapy. To address this clinical need, we are developing a low cost, universal magnetically levitated extracorporeal system with interchangeable pump heads for pediatric support. Two impeller and pump designs (pump V1 and V2) for the pediatric pump were developed using dimensional analysis techniques and classic pump theory based on defined performance criteria (generated flow, pressure, and impeller diameter). The designs were virtually constructed using computer-aided design (CAD) software and 3D flow and pressure features were analyzed using computational fluid dynamics (CFD) analysis. Simulated pump designs (V1, V2) were operated at higher rotational speeds (~5,000 revolutions per minute [RPM]) than initially estimated (4,255 RPM) to achieve the desired operational point (3.5 L/min flow at 150 mm Hg). Pump V2 outperformed V1 by generating approximately 30% higher pressures at all simulated rotational speeds and at 5% lower priming volume. Simulated hydrodynamic performance (achieved flow and pressure, hydraulic efficiency) of our pediatric pump design, featuring reduced impeller size and priming volume, compares favorably to current commercially available MCS devices.

Dual diffusion mechanism of argon confined in single-walled carbon nanotube bundles.

The adsorption and diffusion mechanisms of argon at 120 K were examined in a (25,0) single-walled carbon nanotube (SWCNT) bundle using a combination of Grand Canonical Monte Carlo and microcanonical molecular dynamics simulations. Interstices between the SWCNTs provided the most energetically favorable adsorption sites and filled completely at low relative pressure, followed by adsorption in the SWCNTs. We calculated the self-diffusivities from the average mean squared displacements of argon molecules. In both flexible and rigid bundles, we observed a bimodal diffusion mechanism, with single-file diffusion occurring in the interstitial sites and Fickian diffusion in the SWCNTs. Strong system size effects were observed in our simulations. The largest system sizes showed very little influence of the nanotube flexibility on the diffusion of argon even at the lowest pressures studied.

Transition from single-file to Fickian diffusion for binary mixtures in single-walled carbon nanotubes.

The transition from single-file diffusion to Fickian diffusion in narrow cylindrical pores is investigated for systems of rigid single-walled armchair carbon nanotubes, solvated with binary mixtures of Lennard-Jones fluids (Ar/Ne, Ar/Kr, and Ar/Xe). A range of effects is examined including the mixture concentration, the size ratio of the two components, and the nanotube diameter. The transition from single-file to Fickian diffusion in varying carbon nanotube diameters is analyzed in terms of the Fickian self-diffusivity and the single-file mobility of the mixture components. It is found that the single-file to Fickian carbon nanotube transition diameter is a unique property of the individual molecule's diameter and remains unchanged regardless of the mixture composition. In applications of binary mixtures, each component may crossover from single-file to Fickian diffusion in a different carbon nanotube diameter, giving rise to bimodal diffusion in some nanotubes. This transition allows for one species to diffuse in single-file while the other diffuses by a Fickian mechanism, yielding orders of magnitude difference between the self-diffusional rates of the two molecules. This phenomenon might be further extended to alter the diffusional motion of molecules in nanoporous materials.

Fully integrated three-dimensional electrodes for electrochemical detection in microchips: fabrication, characterization, and applications.

A scalable and rather inexpensive solution to producing microanalytical systems with "on-chip" three-dimensional (3D) microelectrodes is presented in this study, along with applicability to practical electrochemical (EC) detection scenarios such as preconcentration and interferant removal. This technique to create high-aspect-ratio (as much as 4:1) gold microstructures in constrained areas involved the modification of stud bump geometry with microfabricated silicon molds via an optimized combination of temperature, pressure, and time. The microelectrodes that resulted consisted of an array of square pillars approximately 18 microm tall and 20 microm wide on each side, placed at the end of a microfabricated electrophoresis channel. This technique increased the active surface area of the microelectrodes by as much as a factor of 50, while mass transfer and, consequently, preconcentration collection efficiencies were increased to approximately 100%, compared to approximately 30% efficiency for planar nonmodified microelectrodes (samples that were used included the neurotransmitters dopamine and catechol). The 3D microelectrodes were used both in a stand-alone configuration, for direct EC detection of model catecholamine analytes, and, more interestingly, in dual electrode configurations for EC sample processing prior to detection downstream at a second planar electrode. In particular, the 3D electrodes were shown to be capable of performing coulometry or complete (100%) redox conversion of analyte species over a wide range of concentrations, from 4.3 microM to 4.4 mM, in either plug-flow or continuous-flow formats.