J Holsapple - Academia.edu (original) (raw)

Papers by J Holsapple

Direct flow visualization at a hole closest to the valve, using fluorescent particle tracking by ... more Direct flow visualization at a hole closest to the valve, using fluorescent particle tracking by high-speed microscopy. An actual catheter (Codman EDS 3 Clear Ventricular CSF Catheter, Codman & Shurtleff ) was used. The refractive index of the working fluid was matched to that of the catheter material so that optical distortion that can originate from the curvature of the catheter-fluid interface was eliminated. The left and right videos generate the pathlines in Figure 11b and 11c of the main article, respectively. Note that the flow at the hole entrance, shown in the left video, is not the uniform flow that is typically assumed in the classical entrance length estimation. Using this visualization technique, we measured 3D velocity profiles inside the catheter as described in Figure 12 of the main article. Here, the Reynolds number, defined by equation (1) in the article, is 0.5. The videos play 0.2x.

Effects of high fluid shear stress (30 mPa) to astrocytes cultured under the static (0 mPa) or fl... more Effects of high fluid shear stress (30 mPa) to astrocytes cultured under the static (0 mPa) or flow condition (3 mPa). The detachment upon the high shear stress only occurs to astrocytes cultured under the flow condition, in contrast to astrocytes statically cultured, which appear more robustly attached and instead only show weak retraction of their bodies in response to the suddenly imposed high shear stress. Both cultures were at T = 72 h, and the videos show the responses during t = 0 — 1 min; note that t is the duration for which cells are under the high shear stress. The video plays 3x

The treatment of hydrocephalus often involves the placement of a shunt catheter into the cerebros... more The treatment of hydrocephalus often involves the placement of a shunt catheter into the cerebrospinal ventricular space, though such ventricular catheters often fail by tissue obstruction. While diverse cell types contribute to the obstruction, astrocytes are believed to contribute to late catheter failure that can occur months after shunt insertion. Using <i>in vitro</i> microfluidic cultures of astrocytes, we show that applied fluid shear stress leads to a decrease of cell confluency and the loss of their typical stellate cell morphology. Furthermore, we show that astrocytes exposed to moderate shear stress for an extended period of time are detached more easily upon suddenly imposed high fluid shear stress. In the light of these findings and examining the range of values of wall shear stress in a typical ventricular catheter through computational fluid dynamics (CFD) simulation, we find that the typical geometry of ventricular catheters has low wall shear stress zone...

The treatment of hydrocephalus often involves the placement of a shunt catheter into the cerebros... more The treatment of hydrocephalus often involves the placement of a shunt catheter into the cerebrospinal ventricular space, though such ventricular catheters often fail by tissue obstruction. While diverse cell types contribute to the obstruction, astrocytes are believed to contribute to late catheter failure that can occur months after shunt insertion. Using <i>in vitro</i> microfluidic cultures of astrocytes, we show that applied fluid shear stress leads to a decrease of cell confluency and the loss of their typical stellate cell morphology. Furthermore, we show that astrocytes exposed to moderate shear stress for an extended period of time are detached more easily upon suddenly imposed high fluid shear stress. In the light of these findings and examining the range of values of wall shear stress in a typical ventricular catheter through computational fluid dynamics (CFD) simulation, we find that the typical geometry of ventricular catheters has low wall shear stress zone...

Method to measure a 2D velocity profile at a z-slice. The subsequent fluorescent images were bina... more Method to measure a 2D velocity profile at a z-slice. The subsequent fluorescent images were binarized by a contrast-thresholding technique to extract particles that are in focus. The binarized images were processed by our in-house particle tracking code to estimate the velocity field at a given z-slice. By assembling 2D velocity profiles at different z-levels, we constructed 3D velocity profiles, as shown in Figure 12 of the main article. Here, λ is 60 μm, which is 7% of the hole depth, d is 1.18 mm, and the diameter of the fluorescent particles is 5 μm. The video plays 0.01x.

Journal of The Royal Society Interface, 2020

The treatment of hydrocephalus often involves the placement of a shunt catheter into the cerebros... more The treatment of hydrocephalus often involves the placement of a shunt catheter into the cerebrospinal ventricular space, though such ventricular catheters often fail by tissue obstruction. While diverse cell types contribute to the obstruction, astrocytes are believed to contribute to late catheter failure that can occur months after shunt insertion. Using in vitro microfluidic cultures of astrocytes, we show that applied fluid shear stress leads to a decrease of cell confluency and the loss of their typical stellate cell morphology. Furthermore, we show that astrocytes exposed to moderate shear stress for an extended period of time are detached more easily upon suddenly imposed high fluid shear stress. In light of these findings and examining the range of values of wall shear stress in a typical ventricular catheter through computational fluid dynamics (CFD) simulation, we find that the typical geometry of ventricular catheters has low wall shear stress zones that can favour the g...

American Journal of Physiology-Renal Physiology, 1987

Models of cell shape in the rabbit S2 proximal renal tubule were derived from transmission electr... more Models of cell shape in the rabbit S2 proximal renal tubule were derived from transmission electron micrographs and compared with scanning micrographs. Standard morphometric procedures were used to measure basolateral cell membrane surface density (SVt) relative to total epithelial volume in numerous zones of cell height. In the basal 20% region we also measured the volume fraction (F) of intercellular spaces and calculated new surface densities in reference only to the intercellular volume, SVi = SVt/F, or to the cellular volume, SVc = SVt/(1-F). Combined use of these surface densities then enabled us to calculate the diameter, length, and separation of effectively cylindrical microvilli at the cell base. Assuming that lateral cell membranes are radially oriented in the apical region but disposed on microvillus like structures of arbitrary orientation at the cell base, an improved cell model was developed that agreed with the scanning picture throughout the entire cell height. Basa...

Solid Mechanics and its Applications, 1999

This device was developed as a teaching tool to introduce the concepts of chaos to biology and ph... more This device was developed as a teaching tool to introduce the concepts of chaos to biology and physiology students. Our purpose was to make a simple mechanical teaching device to generate data in the lecture hall, classroom and laboratory settings in order to demonstrate the characteristics of random, chaotic and periodic behavior. We knew of the “dripping water faucet” developed by Shaw (1984) and we have used it as a model system for transmitter release (Kriebel, et al, 1990). Moon (1992) has developed vibrating devices that project a laser beam onto a wall which dramatically show transitions from periodic to chaotic motions and he describes other chaotic teaching devices appropriate for advanced students. Lorenz (1993) discusses a water wheel which he had proposed earlier which resembles a Ferris Wheel with leaky buckets filled from an overhead stream of water which changes its dynamics as a function of flow rate and generates continuous data. We modified this concept to make a wheel which produces sets of discrete data as sequences of stop angles. One wheel of our device is used as a power wheel and a paddle wheel is used to dissipate energy such that the turning motion is controlled by the single parameter of water depth on the paddle wheel. We developed this water wheel so that students would develop an understanding of chaos theory for an appreciation of a nonlinear dynamic relevant to biological and physiological systems. Even though Sir D’Arcy Thompson wrote On Growth and Form over 80 years ago showing that form and structure of organisms resulted from dynamical processes governed by simple rules, there has been little infusion of nonlinear dynamics or chaos theory into the general biological curricula. As a result there are no introductory texts or experimental devices available for our students. Nevertheless, the importance of nonlinear dynamics to biology was reintroduced by May (1976) who used the logistic equation to explain population dynamics. Chaos theory has also been applied to describe heart beat dynamics (Glass and Mackey, 1988) and brain function (Mpitsos, et al, 1988; Freeman, 1991). Concepts such as “sensitivity to initial conditions” and transitions from periodic to aperiodic motions are not taught, but are essential in understanding the complexities and dynamical interactions found in biological and physiological systems.

Radiology, 1985

Exencephaly is a rare precursor of anencephaly in which a large amount of brain tissue is present... more Exencephaly is a rare precursor of anencephaly in which a large amount of brain tissue is present despite the absence of the calvaria. It was discovered together with hydramnios in a near-term fetus. Sonographic, angiographic, and pathologic findings are discussed.

Neurotoxicology, 1987

The effect of systemically administered diisopropylfluorophosphate (DFP) on the spontaneous firin... more The effect of systemically administered diisopropylfluorophosphate (DFP) on the spontaneous firing rate and light-evoked responses of rat superior colliculus neurons was determined from average histograms of single unit and multiunit activity. DFP produced a dose-dependent increase in superior colliculus spontaneous activity, and a decrease in light evoked activity. In many experiments, light evoked responses were completely abolished. The changes in spontaneous activity were reversible over a period of about 5 hours following DFP injection. These results establish the retino-tectal pathway as a major target of DFP toxicity.

Vision Research, 2000

An analysis of target detection as a function of target eccentricity was made on eye movement dat... more An analysis of target detection as a function of target eccentricity was made on eye movement data collected from three monkey subjects during active visual search. Target detection probability was invariant across array set size and eccentricity conditions when the cortical density of rele6ant stimuli surrounding the target was held constant. When target color was used to guide search, the effective cortical density was the density of stimuli that shared the target's color. Thus the passive constraint of cortical magnification in combination with an active selection for a stimulus attribute, in this case color, sets the spatial framework for detection of the target.

Vision Research, 2007

Target detection during active visual search was examined. The chance corrected spatial distribut... more Target detection during active visual search was examined. The chance corrected spatial distribution of target detection was found to be symmetrically distributed around the point of fixation and, unexpectedly, was independent of the proximity of fixations to the display boundaries. Memory was found to play a very limited role in target detection, but a significant role in the guidance of eye movements. A model of covert shifts was used to estimate the number and spatial distribution of shifts required to explain observed performance. An increase from one to five shifts per fixation across increasing array set size as estimated by two different methods was inconsistent with unchanging fixation durations, suggesting that multiple covert shifts are not occurring during the fixations in active search.

The Neuroscientist, 2000

ABSTRACT We believe that there is sufficient experimental evidence to support the premise that tr... more ABSTRACT We believe that there is sufficient experimental evidence to support the premise that transmitter is secreted by the simultaneous activation of arrays of fusion pores at docked vesicles. This process is initiated by the action potential that activates calcium channels to increase the number of cytoplasmic calcium ions. Calcium ions trigger fusion pores to flicker open causing transmitter to diffuse from vesicular stores. We define the term porocytosis to identify this process and use the term synaptomere to indicate the anatomical and physiological functional unit of the synapse or junction. Our model shows that the simultaneous flicker of fusion pores in an array can generate unitary-end plate potentials (u-EPPs) and miniature end plate potentials (MEPPs) and that activation of all fusion pores produces EPPs. U-EPPs and EPPs generated with the model show mean values and coefficients of variation similar to experimental observations. The model is robust in that the number of docked vesicles can vary and these can be full to empty depending on nerve frequencies and vesicular traffic. The model shows that the overall process of excitation-secretion coupling is highly deterministic. At the neuromuscular junction, secretion from arrays of fusion pores ensures that a muscle fiber action potential is always produced over a range of frequencies because all transmitter release sites are activated. Our model shows that transmission at the synaptomere guarantees fidelity of information transfer at different frequencies. This characteristic shows a dynamic relationship of the secretory process to memory and learning.

Journal of Neuroscience Research, 1992

"Microphysiologie comparee des elements excitables" 67:245-258, 1957) and stored in large numbers... more "Microphysiologie comparee des elements excitables" 67:245-258, 1957) and stored in large numbers in the motor nerve terminal. Statistical analyses of intervals between ME-PPs and numbers of quanta composing small endplate potentials indicated that quantal release was a random process and that release sites functioned independently of each other. With the discovery of synaptic vesicles it was proposed that each contained one quantum of transmitter. The quantal-vesicular hypothesis (Del Castillo and Katz, as cited above) fails, however, to explain amplitude distributions of MEPPs that are skewed and/or that show multiple peaks (Kriebel et al., Brain Res Review 15167-178, 1990). The drop formation process (Shaw, "The Dripping Faucet as a Model Chaotic System," Santa Cruz, CA: Aerial Press, Inc., 1984) was shown to generate amplitude classes of drops that were similar to classes of MEPPs which suggested that rapid changes in quantal size and ratios of skew-to bell-MEPPs could be explained with a simple dynamic process which determines quantal size at the moment of release (Kriebel et al., as cited above, 1990). Further similarities between miniature endplate currents (MEPCs) and the formation of drops are reported here. We found that rapid changes in MEPC amplitudes and time courses, which accompany an increase in frequency, mimic changes in drop sizes that accompany increases in flow rate. MEPC intervals have a minimum and their distributions are comparable to those of drop intervals. During an increased rate of transmitter release, MEPP amplitudes and intervals were positively correlated. The results suggest that spontaneously released transmitter "packets" are formed at the moment of release and that transmitter supply to the process that forms packets is continuous.

International Journal of Radiation Oncology*Biology*Physics, 2011

Clinical Imaging, 1997

Fifteen patients who sustained spinal cord trauma were evaluated byMR within 72 hours of injury. ... more Fifteen patients who sustained spinal cord trauma were evaluated byMR within 72 hours of injury. Nine patients had hemorrhagic and six had nonhemorrhagic traumatic spinal cord lesions. Three patients with hemorrhagic and all six patients with nonhemorrhagic lesions showed some degree of neurological improvement on follow-up examinations. In two of the three patients with hemorrhagic lesions who improved, the hemorrhage was extensive. This supports the observation that hemorrhagic lesions are not always associated with a poor clinical outcome.

Clinical Imaging, 1995

Three patients with cerebml venous thrombosis (CVT) were imaged with magnetic resonance angiogmph... more Three patients with cerebml venous thrombosis (CVT) were imaged with magnetic resonance angiogmphy (MRA). Initial spin-echo magnetic resonance (MR) demonstrated acute or subacute thrombosis in all patients. The presence of thrombosis was confirmed with MRA. Repeat MRA in the three patients revealed partial recanalization in one and almost complete recanalization in two patients. The etiology of CVT is reviewed, and the advantages ofMRA are compared with conventional Ml? imaging and computed tomography in the evaluation of CVT.

Brain Research, 1982

Action potentials of single motor cortex cells were recorded extracellularly in awake monkeys tra... more Action potentials of single motor cortex cells were recorded extracellularly in awake monkeys trained to make alternating wrist movements between flexion and extension position zones. Spike-triggered averaging of rectified EMG activity was used to test each cell's output effect on both the coactivated (agonist) forearm muscles and their antagonists. Five of 18 adequately tested motor cortex cells, whose activity covaried strongly with alternating wrist movement, not only produced postspike facilitation of agonist muscles but also postspike suppression of antagonist muscles. Five additional cells only facilitated the agonist muscles and had no effect on the recorded antagonists; 8 cells had no effect on either agonist or antagonist muscles. We conclude that the synaptic terminations of some motor cortex cells with flexor and extensor spinal motoneurons are reciprocally organized.

Direct flow visualization at a hole closest to the valve, using fluorescent particle tracking by ... more Direct flow visualization at a hole closest to the valve, using fluorescent particle tracking by high-speed microscopy. An actual catheter (Codman EDS 3 Clear Ventricular CSF Catheter, Codman & Shurtleff ) was used. The refractive index of the working fluid was matched to that of the catheter material so that optical distortion that can originate from the curvature of the catheter-fluid interface was eliminated. The left and right videos generate the pathlines in Figure 11b and 11c of the main article, respectively. Note that the flow at the hole entrance, shown in the left video, is not the uniform flow that is typically assumed in the classical entrance length estimation. Using this visualization technique, we measured 3D velocity profiles inside the catheter as described in Figure 12 of the main article. Here, the Reynolds number, defined by equation (1) in the article, is 0.5. The videos play 0.2x.

Effects of high fluid shear stress (30 mPa) to astrocytes cultured under the static (0 mPa) or fl... more Effects of high fluid shear stress (30 mPa) to astrocytes cultured under the static (0 mPa) or flow condition (3 mPa). The detachment upon the high shear stress only occurs to astrocytes cultured under the flow condition, in contrast to astrocytes statically cultured, which appear more robustly attached and instead only show weak retraction of their bodies in response to the suddenly imposed high shear stress. Both cultures were at T = 72 h, and the videos show the responses during t = 0 — 1 min; note that t is the duration for which cells are under the high shear stress. The video plays 3x

The treatment of hydrocephalus often involves the placement of a shunt catheter into the cerebros... more The treatment of hydrocephalus often involves the placement of a shunt catheter into the cerebrospinal ventricular space, though such ventricular catheters often fail by tissue obstruction. While diverse cell types contribute to the obstruction, astrocytes are believed to contribute to late catheter failure that can occur months after shunt insertion. Using <i>in vitro</i> microfluidic cultures of astrocytes, we show that applied fluid shear stress leads to a decrease of cell confluency and the loss of their typical stellate cell morphology. Furthermore, we show that astrocytes exposed to moderate shear stress for an extended period of time are detached more easily upon suddenly imposed high fluid shear stress. In the light of these findings and examining the range of values of wall shear stress in a typical ventricular catheter through computational fluid dynamics (CFD) simulation, we find that the typical geometry of ventricular catheters has low wall shear stress zone...

The treatment of hydrocephalus often involves the placement of a shunt catheter into the cerebros... more The treatment of hydrocephalus often involves the placement of a shunt catheter into the cerebrospinal ventricular space, though such ventricular catheters often fail by tissue obstruction. While diverse cell types contribute to the obstruction, astrocytes are believed to contribute to late catheter failure that can occur months after shunt insertion. Using <i>in vitro</i> microfluidic cultures of astrocytes, we show that applied fluid shear stress leads to a decrease of cell confluency and the loss of their typical stellate cell morphology. Furthermore, we show that astrocytes exposed to moderate shear stress for an extended period of time are detached more easily upon suddenly imposed high fluid shear stress. In the light of these findings and examining the range of values of wall shear stress in a typical ventricular catheter through computational fluid dynamics (CFD) simulation, we find that the typical geometry of ventricular catheters has low wall shear stress zone...

Method to measure a 2D velocity profile at a z-slice. The subsequent fluorescent images were bina... more Method to measure a 2D velocity profile at a z-slice. The subsequent fluorescent images were binarized by a contrast-thresholding technique to extract particles that are in focus. The binarized images were processed by our in-house particle tracking code to estimate the velocity field at a given z-slice. By assembling 2D velocity profiles at different z-levels, we constructed 3D velocity profiles, as shown in Figure 12 of the main article. Here, λ is 60 μm, which is 7% of the hole depth, d is 1.18 mm, and the diameter of the fluorescent particles is 5 μm. The video plays 0.01x.

Journal of The Royal Society Interface, 2020

The treatment of hydrocephalus often involves the placement of a shunt catheter into the cerebros... more The treatment of hydrocephalus often involves the placement of a shunt catheter into the cerebrospinal ventricular space, though such ventricular catheters often fail by tissue obstruction. While diverse cell types contribute to the obstruction, astrocytes are believed to contribute to late catheter failure that can occur months after shunt insertion. Using in vitro microfluidic cultures of astrocytes, we show that applied fluid shear stress leads to a decrease of cell confluency and the loss of their typical stellate cell morphology. Furthermore, we show that astrocytes exposed to moderate shear stress for an extended period of time are detached more easily upon suddenly imposed high fluid shear stress. In light of these findings and examining the range of values of wall shear stress in a typical ventricular catheter through computational fluid dynamics (CFD) simulation, we find that the typical geometry of ventricular catheters has low wall shear stress zones that can favour the g...

American Journal of Physiology-Renal Physiology, 1987

Models of cell shape in the rabbit S2 proximal renal tubule were derived from transmission electr... more Models of cell shape in the rabbit S2 proximal renal tubule were derived from transmission electron micrographs and compared with scanning micrographs. Standard morphometric procedures were used to measure basolateral cell membrane surface density (SVt) relative to total epithelial volume in numerous zones of cell height. In the basal 20% region we also measured the volume fraction (F) of intercellular spaces and calculated new surface densities in reference only to the intercellular volume, SVi = SVt/F, or to the cellular volume, SVc = SVt/(1-F). Combined use of these surface densities then enabled us to calculate the diameter, length, and separation of effectively cylindrical microvilli at the cell base. Assuming that lateral cell membranes are radially oriented in the apical region but disposed on microvillus like structures of arbitrary orientation at the cell base, an improved cell model was developed that agreed with the scanning picture throughout the entire cell height. Basa...

Solid Mechanics and its Applications, 1999

This device was developed as a teaching tool to introduce the concepts of chaos to biology and ph... more This device was developed as a teaching tool to introduce the concepts of chaos to biology and physiology students. Our purpose was to make a simple mechanical teaching device to generate data in the lecture hall, classroom and laboratory settings in order to demonstrate the characteristics of random, chaotic and periodic behavior. We knew of the “dripping water faucet” developed by Shaw (1984) and we have used it as a model system for transmitter release (Kriebel, et al, 1990). Moon (1992) has developed vibrating devices that project a laser beam onto a wall which dramatically show transitions from periodic to chaotic motions and he describes other chaotic teaching devices appropriate for advanced students. Lorenz (1993) discusses a water wheel which he had proposed earlier which resembles a Ferris Wheel with leaky buckets filled from an overhead stream of water which changes its dynamics as a function of flow rate and generates continuous data. We modified this concept to make a wheel which produces sets of discrete data as sequences of stop angles. One wheel of our device is used as a power wheel and a paddle wheel is used to dissipate energy such that the turning motion is controlled by the single parameter of water depth on the paddle wheel. We developed this water wheel so that students would develop an understanding of chaos theory for an appreciation of a nonlinear dynamic relevant to biological and physiological systems. Even though Sir D’Arcy Thompson wrote On Growth and Form over 80 years ago showing that form and structure of organisms resulted from dynamical processes governed by simple rules, there has been little infusion of nonlinear dynamics or chaos theory into the general biological curricula. As a result there are no introductory texts or experimental devices available for our students. Nevertheless, the importance of nonlinear dynamics to biology was reintroduced by May (1976) who used the logistic equation to explain population dynamics. Chaos theory has also been applied to describe heart beat dynamics (Glass and Mackey, 1988) and brain function (Mpitsos, et al, 1988; Freeman, 1991). Concepts such as “sensitivity to initial conditions” and transitions from periodic to aperiodic motions are not taught, but are essential in understanding the complexities and dynamical interactions found in biological and physiological systems.

Radiology, 1985

Exencephaly is a rare precursor of anencephaly in which a large amount of brain tissue is present... more Exencephaly is a rare precursor of anencephaly in which a large amount of brain tissue is present despite the absence of the calvaria. It was discovered together with hydramnios in a near-term fetus. Sonographic, angiographic, and pathologic findings are discussed.

Neurotoxicology, 1987

The effect of systemically administered diisopropylfluorophosphate (DFP) on the spontaneous firin... more The effect of systemically administered diisopropylfluorophosphate (DFP) on the spontaneous firing rate and light-evoked responses of rat superior colliculus neurons was determined from average histograms of single unit and multiunit activity. DFP produced a dose-dependent increase in superior colliculus spontaneous activity, and a decrease in light evoked activity. In many experiments, light evoked responses were completely abolished. The changes in spontaneous activity were reversible over a period of about 5 hours following DFP injection. These results establish the retino-tectal pathway as a major target of DFP toxicity.

Vision Research, 2000

An analysis of target detection as a function of target eccentricity was made on eye movement dat... more An analysis of target detection as a function of target eccentricity was made on eye movement data collected from three monkey subjects during active visual search. Target detection probability was invariant across array set size and eccentricity conditions when the cortical density of rele6ant stimuli surrounding the target was held constant. When target color was used to guide search, the effective cortical density was the density of stimuli that shared the target's color. Thus the passive constraint of cortical magnification in combination with an active selection for a stimulus attribute, in this case color, sets the spatial framework for detection of the target.

Vision Research, 2007

Target detection during active visual search was examined. The chance corrected spatial distribut... more Target detection during active visual search was examined. The chance corrected spatial distribution of target detection was found to be symmetrically distributed around the point of fixation and, unexpectedly, was independent of the proximity of fixations to the display boundaries. Memory was found to play a very limited role in target detection, but a significant role in the guidance of eye movements. A model of covert shifts was used to estimate the number and spatial distribution of shifts required to explain observed performance. An increase from one to five shifts per fixation across increasing array set size as estimated by two different methods was inconsistent with unchanging fixation durations, suggesting that multiple covert shifts are not occurring during the fixations in active search.

The Neuroscientist, 2000

ABSTRACT We believe that there is sufficient experimental evidence to support the premise that tr... more ABSTRACT We believe that there is sufficient experimental evidence to support the premise that transmitter is secreted by the simultaneous activation of arrays of fusion pores at docked vesicles. This process is initiated by the action potential that activates calcium channels to increase the number of cytoplasmic calcium ions. Calcium ions trigger fusion pores to flicker open causing transmitter to diffuse from vesicular stores. We define the term porocytosis to identify this process and use the term synaptomere to indicate the anatomical and physiological functional unit of the synapse or junction. Our model shows that the simultaneous flicker of fusion pores in an array can generate unitary-end plate potentials (u-EPPs) and miniature end plate potentials (MEPPs) and that activation of all fusion pores produces EPPs. U-EPPs and EPPs generated with the model show mean values and coefficients of variation similar to experimental observations. The model is robust in that the number of docked vesicles can vary and these can be full to empty depending on nerve frequencies and vesicular traffic. The model shows that the overall process of excitation-secretion coupling is highly deterministic. At the neuromuscular junction, secretion from arrays of fusion pores ensures that a muscle fiber action potential is always produced over a range of frequencies because all transmitter release sites are activated. Our model shows that transmission at the synaptomere guarantees fidelity of information transfer at different frequencies. This characteristic shows a dynamic relationship of the secretory process to memory and learning.

Journal of Neuroscience Research, 1992

"Microphysiologie comparee des elements excitables" 67:245-258, 1957) and stored in large numbers... more "Microphysiologie comparee des elements excitables" 67:245-258, 1957) and stored in large numbers in the motor nerve terminal. Statistical analyses of intervals between ME-PPs and numbers of quanta composing small endplate potentials indicated that quantal release was a random process and that release sites functioned independently of each other. With the discovery of synaptic vesicles it was proposed that each contained one quantum of transmitter. The quantal-vesicular hypothesis (Del Castillo and Katz, as cited above) fails, however, to explain amplitude distributions of MEPPs that are skewed and/or that show multiple peaks (Kriebel et al., Brain Res Review 15167-178, 1990). The drop formation process (Shaw, "The Dripping Faucet as a Model Chaotic System," Santa Cruz, CA: Aerial Press, Inc., 1984) was shown to generate amplitude classes of drops that were similar to classes of MEPPs which suggested that rapid changes in quantal size and ratios of skew-to bell-MEPPs could be explained with a simple dynamic process which determines quantal size at the moment of release (Kriebel et al., as cited above, 1990). Further similarities between miniature endplate currents (MEPCs) and the formation of drops are reported here. We found that rapid changes in MEPC amplitudes and time courses, which accompany an increase in frequency, mimic changes in drop sizes that accompany increases in flow rate. MEPC intervals have a minimum and their distributions are comparable to those of drop intervals. During an increased rate of transmitter release, MEPP amplitudes and intervals were positively correlated. The results suggest that spontaneously released transmitter "packets" are formed at the moment of release and that transmitter supply to the process that forms packets is continuous.

International Journal of Radiation Oncology*Biology*Physics, 2011

Clinical Imaging, 1997

Fifteen patients who sustained spinal cord trauma were evaluated byMR within 72 hours of injury. ... more Fifteen patients who sustained spinal cord trauma were evaluated byMR within 72 hours of injury. Nine patients had hemorrhagic and six had nonhemorrhagic traumatic spinal cord lesions. Three patients with hemorrhagic and all six patients with nonhemorrhagic lesions showed some degree of neurological improvement on follow-up examinations. In two of the three patients with hemorrhagic lesions who improved, the hemorrhage was extensive. This supports the observation that hemorrhagic lesions are not always associated with a poor clinical outcome.

Clinical Imaging, 1995

Three patients with cerebml venous thrombosis (CVT) were imaged with magnetic resonance angiogmph... more Three patients with cerebml venous thrombosis (CVT) were imaged with magnetic resonance angiogmphy (MRA). Initial spin-echo magnetic resonance (MR) demonstrated acute or subacute thrombosis in all patients. The presence of thrombosis was confirmed with MRA. Repeat MRA in the three patients revealed partial recanalization in one and almost complete recanalization in two patients. The etiology of CVT is reviewed, and the advantages ofMRA are compared with conventional Ml? imaging and computed tomography in the evaluation of CVT.

Brain Research, 1982

Action potentials of single motor cortex cells were recorded extracellularly in awake monkeys tra... more Action potentials of single motor cortex cells were recorded extracellularly in awake monkeys trained to make alternating wrist movements between flexion and extension position zones. Spike-triggered averaging of rectified EMG activity was used to test each cell's output effect on both the coactivated (agonist) forearm muscles and their antagonists. Five of 18 adequately tested motor cortex cells, whose activity covaried strongly with alternating wrist movement, not only produced postspike facilitation of agonist muscles but also postspike suppression of antagonist muscles. Five additional cells only facilitated the agonist muscles and had no effect on the recorded antagonists; 8 cells had no effect on either agonist or antagonist muscles. We conclude that the synaptic terminations of some motor cortex cells with flexor and extensor spinal motoneurons are reciprocally organized.