Biomedical subjects

C A Grimes

Publications and source records attributed to C A Grimes.

At least 19 recordsLinked to original sources

PubMed2001

Characterization of nano-dimensional thin-film elastic moduli using magnetoelastic sensors.

Application of magnetoelastic thick-film sensors to the measurement of thin-film elastic moduli is described in this study. An analytical model is derived, that relates the resonant frequency of a magnetoelastic sensor to the elasticity and density of an applied thin-film. Limits of the model are analyzed, and related to experimental measurements using thin-films of silver and aluminum. For 500 nm thick-films, the measured Young's modulus of elasticity for Al and Ag is found to be within 1.6% of standard data. Using commercially available magnetoelastic sensors, the elasticity of coatings, approximately 30 nm thick, can readily be measured.

Aluminum↗

PubMed2001

A wireless, remote query ammonia sensor.

This paper presents a wireless, remote query ammonia sensor comprised of a free-standing magnetoelastic thick-film coated with a polymer, poly(acrylic acid-co-isooctylacrylate), that changes mass in response to atmospheric ammonia concentration. The mass of the polymer layer modulates the resonant frequency the ferromagnetic magnetoelastic substrate, hence by monitoring the frequency response of the sensor, atmospheric NH3 concentration can be determined remotely, without the need for physical connections to the sensor or specific alignment requirements. The effect of copolymer composition, polymer film thickness, and relative humidity level (RH) on the sensitivity of the sensor were investigated. The sensor linearly tracks ammonia concentration below 0.8 vol.%, and tracks higher concentrations logarithmically; within the linear calibration range, a 0.02 vol.% change in NH3 concentration can be detected.

Acrylates↗

PubMed2001

The multifaceted roles of glycogen synthase kinase 3beta in cellular signaling.

Glycogen synthase kinase-3beta (GSK3beta) is a fascinating enzyme with an astoundingly diverse number of actions in intracellular signaling systems. GSK3beta activity is regulated by serine (inhibitory) and tyrosine (stimulatory) phosphorylation, by protein complex formation, and by its intracellular localization. GSK3beta phosphorylates and thereby regulates the functions of many metabolic, signaling, and structural proteins. Notable among the signaling proteins regulated by GSK3beta are the many transcription factors, including activator protein-1, cyclic AMP response element binding protein, heat shock factor-1, nuclear factor of activated T cells, Myc, beta-catenin, CCAAT/enhancer binding protein, and NFkappaB. Lithium, the primary therapeutic agent for bipolar mood disorder, is a selective inhibitor of GSK3beta. This raises the possibility that dysregulation of GSK3beta and its inhibition by lithium may contribute to the disorder and its treatment, respectively. GSK3beta has been linked to all of the primary abnormalities associated with Alzheimer's disease. These include interactions between GSK3beta and components of the plaque-producing amyloid system, the participation of GSK3beta in phosphorylating the microtubule-binding protein tau that may contribute to the formation of neurofibrillary tangles, and interactions of GSK3beta with presenilin and other Alzheimer's disease-associated proteins. GSK3beta also regulates cell survival, as it facilitates a variety of apoptotic mechanisms, and lithium provides protection from many insults. Thus, GSK3beta has a central role regulating neuronal plasticity, gene expression, and cell survival, and may be a key component of certain psychiatric and neurodegenerative diseases.

Alzheimer Disease↗

PubMed2001

Monitoring of bacteria growth using a wireless, remote query resonant-circuit sensor: application to environmental sensing.

A new technique is presented for in-vivo remote query measurement of the complex permittivity spectra of a biological culture solution. A sensor comprised of a printed inductor-capacitor resonant-circuit is placed within the culture solution of interest, with the impedance spectrum of the sensor measured using a remotely located loop antenna; the complex permittivity spectra of the culture is calculated from the measured impedance spectrum. The remote query nature of the sensor platform enables, for example, the in-vivo real-time monitoring of bacteria or yeast growth from within sealed opaque containers. The wireless monitoring technique does not require a specific alignment between sensor and antenna. Results are presented for studies conducted on laboratory strains of Bacillus subtilis, Escherichia coli JM109, Pseudomonas putida and Saccharomyces cerevisiae.

Bacteria↗

PubMed2001

CREB DNA binding activity is inhibited by glycogen synthase kinase-3 beta and facilitated by lithium.

The regulatory influences of glycogen synthase kinase-3 beta (GSK3 beta) and lithium on the activity of cyclic AMP response element binding protein (CREB) were examined in human neuroblastoma SH-SY5Y cells. Activation of Akt (protein kinase B) with serum-increased phospho-serine-9-GSK3 beta (the inactive form of the enzyme), inhibited GSK3 beta activity, and increased CREB DNA binding activity. Inhibition of GSK3 beta by another paradigm, treatment with the selective inhibitor lithium, also increased CREB DNA binding activity. The inhibitory regulation of CREB DNA binding activity by GSK3 beta also was evident in differentiated SH-SY5Y cells, indicating that this regulatory interaction is maintained in non-proliferating cells. These results demonstrate that inhibition of GSK3 beta by serine-9 phosphorylation or directly by lithium increases CREB activation. Conversely, overexpression of active GSK3 beta to 3.5-fold the normal levels completely blocked increases in CREB DNA binding activity induced by epidermal growth factor, insulin-like growth factor-1, forskolin, and cyclic AMP. The inhibitory effects due to overexpressed GSK3 beta were reversed by treatment with lithium and with another GSK 3beta inhibitor, sodium valproate. Overall, these results demonstrate that GSK3 beta inhibits, and lithium enhances, CREB activation.

Calcium-Calmodulin-Dependent Protein Kinases↗

PubMed2000

A remote query magnetoelastic pH sensor.

A remote query magnetoelastic pH sensor comprised of a magnetoelastic thick-film coated with a mass-changing pH-responsive polymer is described. In response to a magnetic query field the magnetoelastic sensor mechanically vibrates at a characteristic frequency that is inversely dependent upon the mass of the attached polymer layer. As the magnetoelastic sensor is magnetostrictive the mechanical vibrations of the sensor launch magnetic flux that can be detected remotely from the sensor using a pickup coil. The pH responsive copolymer is synthesized from 20 mol% of acrylic acid and 80 mol% of iso-octyl acrylate and then deposited onto a magnetoelastic film by dip-coating. For a 1 micrometer polymer coating upon a 30 micrometer thick Metglas [The Metglas alloys are a registered trademark of Honeywell Corporation. For product information see: http://www.electronicmaterials.com:80/businesses/sem/amorph/page5_1_2.htm.] alloy 2826MB magnetoelastic film between pH 5 and 9 the change in resonant frequency is linear, approximately 285 Hz/pH or 0.6%/pH. The addition of 10 mmol/l of KCl to the test solution decreases the sensitivity of the polymer approximately 4%.

Acrylates↗

PubMed2000

Remote query measurement of pressure, fluid-flow velocity, and humidity using magnetoelastic thick-film sensors.

Free-standing magnetoelastic thick-film sensors have a characteristic resonant frequency that can be determined by monitoring the magnetic flux emitted from the sensor in response to a time varying magnetic field. This property allows the sensors to be monitored remotely without the use of direct physical connections, such as wires, enabling measurement of environmental parameters from within sealed, opaque containers. In this work, we report on application of magnetoelastic sensors to measurement of atmospheric pressure, fluid-flow velocity, temperature, and mass load. Mass loading effects are demonstrated by fabrication of a remote query humidity sensor, made by coating the magnetoelastic thick film with a thin layer of solgel deposited Al2O3 that reversibly changes mass in response to humidity.

Atmospheric Pressure↗

PubMed2000

High frequency, small signal MH loops of ferromagnetic thin films.

A method is presented for transforming the high frequency bias susceptibility measurements of ferromagnetic thin films into the form of a MH loop with, depending upon the measurement geometry, the y-axis zero crossing giving a measure of the coercive force or anisotropy field. The loops provide a measure of the quantitative and qualitative high frequency switching properties of ferromagnetic thin films.

Anisotropy↗

PubMed2000

Control of the permeability loss-peak frequency of Ni81Fe19 thin films through laser ablation of triangular and square cluster geometries.

Laser ablation arrays of triangular and square shaped clusters, comprised of 23 micrometers diam circular holes, are defined upon 100 nm thick Ni81Fe19 films used to control the rf permeability spectra. Cluster-to-cluster spacing is varied from 200 to 600 micrometers. For each geometry it is found that the loss peak frequency and permeability magnitude shift lower, in a step-wise fashion, at a cluster-to-cluster spacing between 275 and 300 micrometers. The nonlinear shift in the behavior of the permeability spectra correlates with a dramatic increase in domain wall density.

Environmental Monitoring↗

PubMed2000

Magnetoelastic sensors in combination with nanometer-scale honeycombed thin film ceramic TiO2 for remote query measurement of humidity.

Ribbonlike magnetoelastic sensors can be considered the magnetic analog of an acoustic bell; in response to an externally applied magnetic field impulse the sensors emit magnetic flux with a characteristic resonant frequency. The magnetic flux can be detected external to the test area using a pick-up coil, enabling query remote monitoring of the sensor. The characteristic resonant frequency of a magnetoelastic sensor changes in response to mass loads. [L.D. Landau and E. M. Lifshitz, Theory of Elasticity, 3rd ed. (Pergamon, New York, 1986). p. 100].Therefore, remote query chemical sensors can be fabricated by combining the magnetoelastic sensors with a mass changing, chemically responsive layer. In this work magnetoelastic sensors are coated with humidity-sensitive thin films of ceramic, nanodimensionally porous TiO2 to make remote query humidity sensors.

Biosensing Techniques↗

PubMed2000

Laser pyrolysis fabrication of ferromagnetic gamma'-Fe4N and FeC nanoparticles.

Using the laser pyrolysis method, single phase gamma'-Fe4N nanoparticles were prepared by a two step method involving preparation of nanoscale iron oxide and a subsequent gas-solid nitridation reaction. Single phase Fe3C and Fe7C3 could be prepared by laser pyrolysis from Fe(CO)5 and 3C2H4 directly. Characterization techniques such as XRD, TEM and vibrating sample magnetometer were used to measure phase structure, particle size and magnetic properties of these nanoscale nitride and carbide particles.

Carbon Compounds, Inorganic↗

PubMed2000

A remote query magnetostrictive viscosity sensor.

Magnetically soft, magnetostrictive metallic glass ribbons are used as in-situ remote query viscosity sensors. When immersed in a liquid, changes in the resonant frequency of the ribbon-like sensors are shown to correlate with the square root of the liquid viscosity and density product. An elastic wave model is presented that describes the sensor response as a function of the frictional forces acting upon the sensor surface.

Electricity↗

PubMed2000

A wireless, remote query magnetoelastic CO2 sensor.

This paper presents a wireless, passive, remote query CO2 sensor comprising a ribbon-like magnetoelastic thick-film coated with a mass-changing CO2 responsive polymer synthesized from acrylamide and isooctylacrylate. In response to a magnetic field impulse, the magnetostrictive magnetoelastic sensor vibrates at a characteristic resonant frequency that is inversely dependent upon the mass of the attached CO2 responsive polymer. The mechanical vibrations of the magnetostrictive sensor launch magnetic flux, which can be detected remotely using a pickup coil. By monitoring the resonant frequency of the passive sensor, the atmospheric CO2 concentration can be determined without the need for physical connections to the sensor or specific alignment requirements. The effect of humidity and the CO2 responsive copolymer composition on the measurement sensitivity are reported. Greatest sensitivity is achieved with a polymer comprising a 1:1 mole ratio of acrylamide to isooctyl acrylate. A 0.7% change in atmospheric CO2 concentration can be detected for a 20 microns thick polymer coated sensor.

Acrylamide↗

PubMed1999

Oxidative stress oppositely modulates protein tyrosine phosphorylation stimulated by muscarinic G protein-coupled and epidermal growth factor receptors.

This study's goals were to more fully define the activation of protein tyrosine phosphorylation stimulated by muscarinic receptors, to test if this signaling process is affected by oxidative stress induced by H2O2, and to compare the effects of H2O2 on protein tyrosine phosphorylation activated by epidermal growth factor (EGF) receptors. Experiments used human neuroblastoma SH-SY5Y cells which express endogenous M3 muscarinic and EGF receptors. Carbachol induced time-dependent increases in phosphotyrosine immunoreactivity of several protein bands, which were quantitated, and immunoprecipitation was used to identify the adhesion-related proteins focal adhesion kinase, p130Cas/HEF1, and paxillin, and three shc adapter proteins. Carbachol-induced tyrosine phosphorylation of the adhesion-related proteins was mediated by muscarinic receptors, and was inhibited by a src family kinase inhibitor, PP1. That carbachol can activate src family kinases was indicated further by the finding that carbachol induced an increase in tyrosine phosphorylation of p120-src substrate, which was inhibited by PP1. Oxidative stress induced by H2O2 concentration dependently inhibited carbachol-induced tyrosine phosphorylation of each of the adhesion-related proteins. EGF increased the phosphotyrosine immunoreactivity of 180- and 116-kDa proteins, identified as the EGF receptor and Cbl, respectively. In contrast to the results with carbachol, H2O2 potentiated EGF-induced tyrosine phosphorylation. These results demonstrate that muscarinic receptor activation induces previously unrecognized increases in tyrosine phosphorylation, and that this signaling process is impaired by H2O2, whereas protein tyrosine phosphorylation stimulated by EGF is increased by H2O2. Thus, oxidative stress can oppositely modulate protein tyrosine phosphorylation induced by activation of G protein-coupled and growth factor receptors in the same cells.

Carbachol↗

PubMed1999

Cholinergic stimulation of early growth response-1 DNA binding activity requires protein kinase C and mitogen-activated protein kinase kinase activation and is inhibited by sodium valproate in SH-SY5Y cells.

Activation of muscarinic receptors in human neuroblastoma SH-SY5Y cells with carbachol stimulated a rapid and large increase in early growth response-1 (Egr-1, also called zif268 and NGF1-A) protein levels and DNA binding activity. Egr-1 DNA binding activity was stimulated within 15 min of treatment with carbachol and maintained a maximum 20-fold increase over basal between 1 and 2 h after treatment, and the EC50 was approximately 1 microM carbachol. Carbachol-stimulated Egr-1 DNA binding activity was dependent on protein kinase C, as it was potently inhibited by GF109203X (IC50 approximately 0.1 microM) and was reduced by 85 +/- 5% by down-regulation of protein kinase C. Inhibitors of increases in intracellular calcium levels reduced carbachol-induced Egr-1 DNA binding activity by 25-35%. Carbachol-stimulated activation of Egr-1 was reduced 35% by genistein, a tyrosine kinase inhibitor, and 60% by PD098059, an inhibitor of mitogen-activated protein kinase kinases 1/2 (MEK1/2) that activates extracellular-regulated kinases 1/2 (ERK1/2). A novel inhibitory action was caused by chronic (7-day) administration of sodium valproate but not by two other bipolar disorder therapeutic agents, lithium and carbamazepine. Valproate treatment reduced carbachol-stimulated Egr-1 DNA binding activity by 60% but did not alter carbachol-induced activation of ERK1/2 or p38 or increases in Egr-1 protein levels. These results reveal that muscarinic receptors activate Egr-1 through a signaling cascade primarily encompassing protein kinase C, MEK1/2, and ERK1/2 and that valproate substantially inhibits Egr-1 DNA binding activity stimulated by carbachol or protein kinase C.

Calcium-Calmodulin-Dependent Protein Kinases↗

PubMed1999

A magnetostatic-coupling based remote query sensor for environmental monitoring.

A new type of in situ, remotely monitored magnetism-based sensor is presented that is comprised of an array of magnetically soft, magnetostatically-coupled ferromagnetic thin-film elements or particles combined with a chemically responsive material that swells or shrinks in response to the analyte of interest. As the chemically responsive material changes size the distance between the ferromagnetic elements changes, altering the inter-element magnetostatic coupling. This in turn changes the coercive force of the sensor, the amplitude of the voltage spikes detected in nearby pick-up coils upon magnetization reversal and the number of higher-order harmonics generated by the flux reversal. Since the sensor is monitored through changes in magnetic flux, no physical connections such as wires or cables are needed to obtain sensor information, nor is line of sight alignment required as with laser telemetry; the sensors can be detected from within sealed, opaque or thin metallic enclosures.

Biosensing Techniques↗

PubMed1998

Selective increases in phosphoinositide signaling activity and G protein levels in postmortem brain from subjects with schizophrenia or alcohol dependence.

Comparisons of the activity of the G protein-mediated phosphoinositide signal transduction system and of G protein levels were made in two regions of frontal cortex from eight schizophrenic, alcohol-dependent, and control subjects. G protein-mediated phosphoinositide hydrolysis was measured by stimulating cortical membranes incubated with [3H]phosphatidylinositol with 0.3-10 microM guanosine 5'-O-(3-thio)triphosphate (GTPgammaS). In frontal cortex areas 8/9, GTPgammaS-induced phosphoinositide hydrolysis was 50% greater in schizophrenic than control or alcohol-dependent subjects, whereas there were no differences among these groups of subjects in the response to GTPgammaS in frontal cortex area 10. Agonists for dopaminergic, cholinergic, purinergic, serotonergic, histaminergic, and glutamatergic receptors coupled to the phosphoinositide signaling system increased [3H]phosphatidylinositol hydrolysis in a GTPgammaS-dependent manner. Responses to most agonists were similar in all three subject groups in both cortical regions, with the largest difference being a 40% greater response to dopaminergic receptor stimulation in frontal cortex 8/9 from schizophrenic subjects. Measurements of the levels of phospholipase C-beta, and of alpha-subunits of Gq, Go, Gi1, Gi2, and Gs, made by immunoblot analyses revealed no differences among the groups of subjects except for increased G alpha(o) in schizophrenic subjects and increased G alpha(o) and G alpha(i1) in alcohol-dependent subjects. These results demonstrate that schizophrenia is associated with increased activity of the phosphoinositide signal transduction system and increased levels of G alpha(o), whereas the phosphoinositide system was unaltered in alcohol dependence, but G alpha(o) and G alpha(i1) were increased.

Adult↗

PubMed1998

A remotely interrogatable sensor for chemical monitoring.

A new type of continuously operating, in-situ, remotely monitored sensor is presented. The sensor is comprised of a thin film array of magnetostatically coupled, magnetically soft ferromagnetic thin film structures, adhered to or encased within a thin polymer layer. The polymer is made so that it swells or shrinks in response to the chemical analyte of interest, which in this case is pH. As the polymer swells or shrinks, the magnetostatic coupling between the magnetic elements changes, resulting in changes in the magnetic switching characteristics of the sensor. Placed within a sinusoidal magnetic field the magnetization vector of the coupled sensor elements periodically reverses directions, generating magnetic flux that can be remotely detected as a series of voltage spikes in appropriately placed pickup coils. one preliminary sensor design consists of four triangles, initially spaced approximately 50 micrometers apart, arranged to form a 12 mm x 12 mm square with the triangle tips centered at a common origin. Our preliminary work has focused on monitoring of pH using a lightly crosslinked pH sensitive polymer layer of hydroxyethylmethacrylate and 2-(dimethylamino) ethylmethacrylate. As the polymer swells or shrinks the magnetostatic coupling between the triangles changes, resulting in measurable changes in the amplitude of the detected voltage spirits.

Biosensing Techniques↗