Brookings, SD, United States
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Bayly P.V.,Brookings Drive | Taber L.A.,Brookings Biomedical | Kroenke C.D.,Oregon Health And Science University
Journal of the Mechanical Behavior of Biomedical Materials | Year: 2014

Folding of the cerebral cortical surface is a critical process in human brain development, yet despite decades of indirect study and speculation the mechanics of the process remain incompletely understood. Leading hypotheses have focused on the roles of circumferential expansion of the cortex, radial growth, and internal tension in neuronal fibers (axons). In this article, we review advances in the mathematical modeling of growth and morphogenesis and new experimental data, which together promise to clarify the mechanical basis of cortical folding. Recent experimental studies have illuminated not only the fundamental cellular and molecular processes underlying cortical development, but also the stress state and mechanical behavior of the developing brain. The combination of mathematical modeling and biomechanical data provides a means to evaluate hypothesized mechanisms objectively and quantitatively, and to ensure that they are consistent with physical law, given plausible assumptions and reasonable parameter values. © 2013 Elsevier Ltd.


Zaydman M.A.,Brookings Biomedical | Zaydman M.A.,Washington University | Silva J.R.,Brookings Biomedical | Silva J.R.,Washington University | And 2 more authors.
Chemical Reviews | Year: 2012

A number of researchers conducted a study to present an overview of molecular mechanisms in ion channel associated diseases. The study aimed at showing the bases of channelopathies by demonstrating with didactic examples how the molecular properties of a population of ion channels contributed to the generation of a macroscopic ionic current and how mutations changed these molecular properties to generate abnormal currents and caused channelopathies. It was demonstrated that the ionic currents that flowed passively through ion channels generated dynamic electrical signals, transferred ions across compartments, and coupled to intracellular biochemical pathways. Two fundamental properties of ion channels, such as selectivity and gating, allowed for organized ionic permeation while maintaining the barrier property of the membrane.


Suzuki Y.,Brookings Biomedical | Tay J.W.,Brookings Biomedical | Yang Q.,Brookings Biomedical | Wang L.V.,Brookings Biomedical
Optics Letters | Year: 2014

Time-reversed ultrasonically encoded (TRUE) optical focusing in turbid media was previously implemented using both analog and digital phase conjugation. The digital approach, in addition to its large energy gain, can improve the focal intensity and resolution by iterative focusing. However, performing iterative focusing at each focal position can be time-consuming. Here, we show that by gradually moving the focal position, the TRUE focal intensity is improved, as in iterative focusing at a fixed position, and can be continuously scanned to image fluorescent targets in a shorter time. In addition, our setup is, to the best of our knowledge, the first demonstration of TRUE focusing using a digital phase conjugate mirror in a reflection mode, which is more suitable for practical applications. © 2014 Optical Society of America.


Guo Z.,Brookings Biomedical | Hu S.,Brookings Biomedical | Wang L.V.,Brookings Biomedical
Optics Letters | Year: 2010

Optical absorption is closely associated with many physiological important parameters, such as the concentration and oxygen saturation of hemoglobin, and it can be used to quantify the concentrations of nonfluorescent molecules. We propose a method to use acoustic spectra of photoacoustic signals to quantify the absolute optical absorption. This method is self-calibrating and thus insensitive to variations in the optical fluence. Factors such as system bandwidth and acoustic attenuation can affect the quantification but can be canceled by dividing the acoustic spectra measured at two optical wavelengths. Using optical-resolution photoacoustic microscopy, we quantified the absolute optical absorption of black ink samples with various concentrations. We also quantified both the concentration and oxygen saturation of hemoglobin in a live mouse in absolute units. © 2010 Optical Society of America.


Background: In subclinical or silent long QT syndrome, the QT interval is normal under basal conditions. The hypothesis that insults to the repolarization reserve may cause arrhythmias in silent mutation carriers but not in noncarriers has been proposed as a general principle, yet crucial aspects remain descriptive, lacking quantification. Objective: To utilize accurate mathematical models of the human action potential and β-adrenergic stimulation to quantitatively investigate arrhythmia-formation mechanisms peculiar to silent long QT syndrome, using mutation Q357R in KCNQ1 (α subunit of slow-delayed rectifier IKs) as a paradigm. Methods: Markov models were formulated to account for altered IKs kinetics in Q357R compared with wild type and introduced into a detailed model of the human ventricular myocyte action potential. Results: Dominant negative loss of I Ks available reserve accurately represents Q357R. Action potential prolongation with mutant IKs was minimal, reproducing the silent phenotype. Partial block of rapid delayed rectifier current (IKr) was needed in addition to fast pacing and isoproterenol application to cause early afterdepolarizations (EADs) in epicardial cells with mutant IKs, but this did not produce EADs in wild type. Reduced channel expression at the membrane, not IKs kinetic differences, caused EADs in the silent mutant. With mutant IKs, isoproterenol plus partial IKr block resulted in dramatic QT prolongation in the pseudo-electrocardiogram and EADs formed without IKr block in mid-myocardial cells during simulated exercise onset. Conclusion: Multiple severe insults are needed to evince an arrhythmic phenotype in silent mutation Q357R. Reduced membrane I Ks expression, not kinetic changes, underlies the arrhythmic phenotype. © 2012 Heart Rhythm Society.


Guo Z.,Brookings Biomedical | Favazza C.,Brookings Biomedical | Garcia-Uribe A.,Brookings Biomedical | Wang L.V.,Brookings Biomedical
Journal of Biomedical Optics | Year: 2012

Photoacoustic (PA) microscopy (PAM) can image optical absorption contrast with ultrasonic spatial resolution in the optical diffusive regime. Conventionally, accurate quantification in PAM requires knowledge of the optical fluence attenuation, acoustic pressure attenuation, and detection bandwidth. We circumvent this requirement by quantifying the optical absorption coefficients from the acoustic spectra of PA signals acquired at multiple optical wavelengths. With the acoustic spectral method, the absorption coefficients of an oxygenated bovine blood phantom at 560, 565, 570, and 575 nm were quantified with errors of <3%. We also quantified the total hemoglobin concentration and hemoglobin oxygen saturation in a live mouse. Compared with the conventional amplitude method, the acoustic spectral method provides greater quantification accuracy in the optical diffusive regime. The limitations of the acoustic spectral method was also discussed. © 2012 Society of Photo- Optical Instrumentation Engineers (SPIE).


Wang L.,Brookings Biomedical | Xia J.,Brookings Biomedical | Yao J.,Brookings Biomedical | Maslov K.I.,Brookings Biomedical | Wang L.V.,Brookings Biomedical
Physical Review Letters | Year: 2013

Blood flow speed is an important functional parameter. Doppler ultrasound flowmetry lacks sufficient sensitivity to slow blood flow (several to tens of millimeters per second) in deep tissue. To address this challenge, we developed ultrasonically encoded photoacoustic flowgraphy combining ultrasonic thermal tagging with photoacoustic imaging. Focused ultrasound generates a confined heat source in acoustically absorptive fluid. Thermal waves propagate with the flow and are directly visualized in pseudo color using photoacoustic computed tomography. The Doppler shift is employed to calculate the flow speed. This method requires only acoustic and optical absorption, and thus is applicable to continuous fluid. A blood flow speed as low as 0.24 mm·s-1 was successfully measured. Deep blood flow imaging was experimentally demonstrated under 5-mm-thick chicken breast tissue. © 2013 American Physical Society.


Suzuki Y.,Brookings Biomedical | Lai P.,Brookings Biomedical | Xu X.,Brookings Biomedical | Wang L.,Brookings Biomedical
Optics Letters | Year: 2013

By detecting ultrasonically tagged diffuse light, ultrasound-modulated optical tomography images optical contrast with ultrasonic resolution deep in turbid media, such as biological tissue. However, small detection etendues and weak tagged light submerged in strong untagged background light limit the signal detection sensitivity. In this Letter, we report the use of a large-area (∼5 cm × 5cm) photorefractive polymer film that yields more than 10 times detection etendue over previous detection schemes. Our polymer-based system enabled us to resolve absorbing objects embedded inside diffused media thicker than 80 transport mean free paths, by using moderate light power and short ultrasound pulses. © 2013 Optical Society of America.


Grant
Agency: Department of Agriculture | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 90.00K | Year: 2010

We have established that E. coli heat labile enterotoxin (LT) is an excellent mucosal adjuvant (immune enhancer) for stimulating immunity in young pigs and does not cause diarrhea or other adverse reactions when administered by intranasal inoculation, even at a relatively high dosage. Co-administration of LT and the K88 fimbriae from porcine enterotoxigenic E. coli (ETEC; pig scours) strains results in the production of both a intestinal and a systemic immune response and provides solid protection against subsequent challenge with an ETEC strain. Our long-term goal is to construct a multi-pathogen vaccine based on intestinal immune stimulation driven by LT as an adjuvant. The overall objective of the current proposal is to determine whether efficacious immunization against Swine Influenza (SI) can be coupled with ETEC immunization. We will produce non-infectious SI virus-like-particles and administer them along with LT and K88 in a vaccine and subsequently test for protection against the same subtype of SI virus and against ETEC. In future studies, immunization protocols will be optimized, and an assessment will be made of influenza virus strain cross protection. The currently proposed project will show whether LT adjuvant administration can serve as platform technology with which a number of vaccine products can be developed and delivered.


Grant
Agency: Department of Agriculture | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 100.00K | Year: 2011

Enterotoxigenic Escherictia coli causes diarrhea (E. coli scours) in young weaned pigs. There currently are no licensed killed vaccines for the disease, and the available living vaccines do not express toxins which should be a major target of a vaccine. This lack of toxin antigens may affect how well the vaccines protect pigs. We have recently developed an experimental killed vaccine for pig strains of E. coli that completely protects the animals from K88+ E. coli. However, the product would be too cumbersome to mass manufacture and to expensive to use in commercial swine production. The purpose of this current project is to utilize the knowledge gained from developing the experimental vaccine to create a simpler and less expensive product that would have commercial value, and to test that product for safety, potency and effectiveness in protecting weaned pigs from experimental challenge with highly virulent K88+ enterotoxigenic E. coli.

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