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Brookings, SD, United States

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. Source

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.

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. Source

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.

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. Source

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