Biomedical subjects

Ian W Hunter

Publications and source records attributed to Ian W Hunter.

6 recordsLinked to original sources

PubMed2005

Real-time PCR measurement by fluorescence anisotropy.

We have developed an instrument for monitoring real-time PCR using fluorescence anisotropy, enabling an assay chemistry in which the fluorescence from a labeled primer elucidates amplification. The instrument holds the sample temperature constant to within +/-0.03 degrees C during measurement in the extension phase of each PCR cycle and achieves 0.116 mP FA resolution. Primer conjugation with Alexa-Fluor 488, when compared with other fluorophores, is shown to provide the greatest FA range between primer and product. Comparable reproducibility and linearity of the crossing point for a range of target copy numbers is observed between the FA-based assay run in our instrument and the SYBR green assay run in commercial instrumentation. Reproducibility is also consistent with Poisson-distributed experimental error in aliquoting starting copies, a theoretical limit to instrument/assay performance.

Fluorescence Polarization↗

PubMed2004

Microelectrode array fabrication by electrical discharge machining and chemical etching.

Wire electrical discharge machining (EDM), with a complementary chemical etching process, is explored and assessed as a method for developing microelectrode array assemblies for intracortically recording brain activity. Assembly processes based on these methods are highlighted, and results showing neural activity successfully recorded from the brain of a mouse using an EDM-based device are presented. Several structures relevant to the fabrication of microelectrode arrays are also offered in order to demonstrate the capabilities of EDM.

Action Potentials↗

PubMed2004

System identification of the human vestibulo-ocular reflex during head-free tracking.

A method was developed to identify the linear, system level dynamics of the horizontal, angular vestibulo-ocular reflex (VOR) as it stabilized vision during head-free tracking of a visual target. Small amplitude, broad spectrum, stochastic torque perturbations were applied to the head while the subject tracked an unpredictable, moving target with active head and eye motions. Stochastic system identification techniques were used to design the torque and target inputs and to conduct the analysis such that the linear dynamics of the VOR, independently of the visual system's influence on eye motions, were determined. The linear analysis was limited to evaluating VOR dynamics from approximately 0.5 to 4.5 Hz. Nonlinearities in the head-neck system affected the low frequency response of the head to the torque perturbations, and the eye velocity sequence was affected by nonlinearities and degraded by noise at high frequencies. The VOR's gain was near 1.0 between about 0.5 and 2.5 Hz, and then decreased steadily to 0.85 as the frequency increased towards 4.0 Hz. The VOR phase angle was also frequency dependent and corresponded to VOR eye motions lagging the head's disturbance motion by less than 10 ms at frequencies greater than 1.0 Hz.

Adult↗

PubMed2003

Laser Raman spectroscopic analysis of polymorphic forms in microliter fluid volumes.

Knowledge and control of the polymorphic phase of chemical compounds are important aspects of drug development in the pharmaceutical industry. We report herein in situ and real-time Raman spectroscopic polymorphic analysis of optically trapped microcrystals in a microliter volume format. The system studied in particular was the recrystallization of carbamazepine (CBZ) in methanol. Raman spectrometry enabled noninvasive measurement of the amount of dissolved CBZ in a sample as well as polymorphic characterization, whereas exclusive recrystallization of either CBZ form I or CBZ form III from saturated solutions was achieved by specific selection of sample cell cooling profiles. Additionally, using a microcell versus a macroscopic volume gives the advantage of reaching equilibrium much faster while using little compound quantity. We demonstrate that laser Raman spectral polymorphic analysis in a microliter cell is a potentially viable screening platform for polymorphic analysis and could lead to a new high throughput method for polymorph screening.

Crystallization↗

PubMed2003

Recognition of adenosine triphosphate binding sites using parallel cascade system identification.

Parallel cascade identification (PCI) is a method for approximating the behavior of a nonlinear system, from input/output training data, by constructing a parallel array of cascaded dynamic linear and static nonlinear elements. PCI has previously been shown to provide an effective means for classifying protein sequences into structure/function families. In the present study, PCI is used to distinguish proteins that are binding to adenosine triphosphate or guanine triphosphate molecules from those that are nonbinding. Classification accuracy of 87.1% using the hydrophobicity scale of Rose et al. (Hydrophobicity of amino acid residues in globular proteins. Science 229:834-838, 1985), and 88.8% using Korenberg's SARAH1 scale, are obtained, as measured by tenfold cross-validation testing. Nearest-neighbor and K-nearest-neighbor (KNN) classifiers are constructed, and the resulting accuracy is, respectively, 88.0% and 90.8% on the SARAH1-encoded test data set, as measured by the above testing protocol. Significantly improved classification accuracy is achieved by combining PCI and KNN classifiers using quadratic discriminant analysis: accuracy rises from 87.9% (PCI) and 87.4% (KNN) to 96.5% for the combination, as measured by twofold cross-validation testing on the SARAH1-encoded test data set.

Adenosine Triphosphate↗

PubMed2003

Dynamics of the human head-neck system in the horizontal plane: joint properties with respect to a static torque.

The vestibular system has often been studied by perturbing the position of the head. This study was conducted to identify the dynamic properties of the head-neck system in response to horizontal plane perturbations. A quasilinear approach was used to quantify the dynamics of the head-neck system at different levels of static torque. An operating point was established by applying a static torque to the head with a helmet-based perturber. The head-neck dynamics were then probed with a rich spectrum, stochastic, torque perturbation. Impulse response functions (IRFs) were estimated from correlation measures, and parametric models were fit to the IRFs. The results indicated that when the mean torque was held constant, the head-neck system behaved like a second-order, underdamped, passive system between 0.5 and 10.0 Hz. The system was not strictly linear, however. The properties of the system were sensitive to the static component of the torque. As the mean torque increased, the effective stiffness and damping progressively increased, and did so such that the system's damping ratio remained essentially constant. The findings of the study will assist in designing stimuli that are well tolerated by subjects and can induce head motions that span the performance capabilities of the vestibular system.

Atlanto-Axial Joint↗