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At least 793 records · Page 44Linked to original sources
PubMed2001

A novel method using edge detection for signal extraction from cDNA microarray image analysis.

Gene expression analyses by probes of hybridization from mRNA to cDNA targets arrayed on membranes or activated glass surfaces have revolutionized the way of profiling mega level gene expression. The main remaining problems however are sensitivity of detection, reproducibility and data processing. During processing of microarray images, especially irregularities of spot position and shape could generate significant errors: small regions of signal spots can be mis-included into background area and vice versa. Here we report a novel method to eliminate such obstacles by sensing their edges. Application of edge detection technology on separating spots from the background decreases the probability of the errors and gives more accurate information about the states of spots such as the pixel number, degree of fragmentation, width and height of spot, and circumference of spot. Such information can be used for the quality control of cDNA microarray experiments and filtering of low quality spots. We analyzed the cDNA microarray image that contains 10,368 genes using edge detection and compared the result with that of conventional method which draws circle around the spot.

DNA, Complementary↗
PubMed1998

Cloning of cell-specific secreted and surface proteins by subtractive antibody screening.

To identify and clone genes that encode cell- or tissue-specific secreted and surface proteins, a polyclonal antiserum was raised against a complex mixture of surface or secreted proteins from the target cell, followed by immunodepletion of antibodies that recognize proteins from a nontarget cell or tissue. The depleted antiserum is used to screen bacteriophage cDNA expression libraries. Because of our interest in how adipocytes communicate with other cells, we have used this method to clone cDNAs encoding secreted and plasma membrane proteins that are induced during adipocyte differentiation. We describe several of these, including a novel plasma membrane-associated protein, S3-12.

3T3 Cells↗
PubMed2004

A structural model for metallic glasses.

Despite the intense interest in metallic glasses for a variety of engineering applications, many details of their structure remain a mystery. Here, we present the first compelling atomic structural model for metallic glasses. This structural model is based on a new sphere-packing scheme-the dense packing of atomic clusters. Random positioning of solvent atoms and medium-range atomic order of solute atoms are combined to reproduce diffraction data successfully over radial distances up to approximately 1 nm. Although metallic glasses can have any number of chemically distinct solute species, this model shows that they contain no more than three topologically distinct solutes and that these solutes have specific and predictable sizes relative to the solvent atoms. Finally, this model includes defects that provide richness to the structural description of metallic glasses. The model accurately predicts the number of solute atoms in the first coordination shell of a typical solvent atom, and provides a remarkable ability to predict metallic-glass compositions accurately for a wide range of simple and complex alloys.

Crystallography↗
PubMed2006

A unique and universal molecular barcode array.

Molecular barcode arrays allow the analysis of thousands of biological samples in parallel through the use of unique 20-base-pair (bp) DNA tags. Here we present a new barcode array, which is unique among microarrays in that it includes at least five replicates of every tag feature. The use of smaller dispersed replicate features dramatically improves performance versus a single larger feature and allows the correction of previously undetectable hybridization defects.

Base Sequence↗
PubMed2006

Dose-dependent cell-based assays in V-shaped microfluidic channels.

The capability of lab-on-a-chip technologies in controlling cell transportation, generating concentration gradients, and monitoring cellular responses offers an opportunity to integrate dose-dependent cell-based bioassays on a chip. In this study, we have developed microfluidic modules featured with channel components and sandbag structures for positioning biological cells within the microchip. We have demonstrated that by geometric modulation of the microchannel architectures, it is possible to immobilize individual cells at desired locations with controllable numbers, to generate defined concentration gradients at various channel lengths, and to improve the efficiency and reproducibility in data acquisition. The microfluidic module was used to exercise a series of cell-based assays, including the measurement of kinetics and dynamics of intracellular enzymatic activities, the analysis of cellular response under the stimulation of two chemicals with defined concentration profiles, and the study of laser irradiation effect on cellular uptake of photosensitizers. The results demonstrated the capabilities of the microfluidic module for simultaneously conducting multiple sets of dose-dependent, cell-based bioassays, and for quantitatively comparing responses of individual cells under various stimulations.

Biological Assay↗
PubMed2006

Sticking coefficient and pressure dependence of desorption rate in the statistical rate theory approach to the kinetics of gas adsorption. Carbon monoxide adsorption/desorption rates on the polycrystalline rhodium surface.

The statistical rate theory (SRT) fundamental kinetic equation for the Langmuir model of adsorption reveals some features which are difficult to understand. These are the infinitely high adsorption rate for zero coverage limit, infinitely high desorption rate at full saturation of the surface and dependence of the desorption rate on the adsorbate pressure. These features do not allow for a correct formulation of such important physical parameters as sticking and initial sticking probabilities. In this work these peculiar features of the fundamental SRT kinetic equation are discussed and explained. It is shown that the non-physical behavior of the SRT kinetic equation follows from neglecting possible changes of adsorbate concentration near the adsorbing surface. A simple model accounting for the changes of adsorbate concentration close to the adsorbing surface is discussed. As a result, it was shown that application of even such a simple model leads to fully physical behavior of the SRT kinetic equation for the Langmuir model of adsorption. The model is used to build up equations describing the kinetics of adsorption/desorption of carbon monoxide on the energetically heterogeneous rhodium surface. The values of the parameters in these equations were determined from the analysis of equilibrium adsorption isotherms and from the description of experimental conditions. One additional parameter (having well defined limiting values) had to be adjusted in order to satisfactorily reproduce kinetic data. The experimental data used in this work were taken from the article by Yamada and Tamaru (T. Yamada and K. Tamaru, Surf. Sci., 1984, 138, L155).

Journal Article↗
PubMed2006

A DFT computational study of spin crossover in iron(III) and iron(II) tripodal imidazole complexes. A comparison of experiment with calculations.

B3LYP* functionals were used to model the sixteen iron(II) (1A, LS and 5T, HS) and iron(III) (2T, LS and 6A, HS) complexes of the 1:3 Schiff base condensate of tris(2-aminoethyl)amine and imidazole-4-carboxaldehyde, H3L1, and its deprotonated forms, [H2L1]1-, [HL1]2-, and [L1]3-. This ligand system is unusual in that [FeH3L1]3+, [FeH3L1]2+ and [FeL1]- all exhibit a spin crossover between 100-300 K. This makes these complexes ideal for a hybrid DFT computational approach and provides an opportunity to refine the value of the exact exchange admixture parameter, c3, and to predict properties of partially protonated complexes that are not experimentally available. The accepted value of 0.20 is larger than the value of approximately 0.13 that was found to best reproduce experimental data in terms of spin state predictions. With iron(III) B3LYP calculations showed that all of the complexes were low spin at 298 K with the exception of [FeH3L1]3+ which is spin crossover in agreement with experimental results. It was also shown for iron(III) that the ligand field increased as the number of protons decreased. In contrast all of the iron(II) complexes were close to the spin crossover region regardless of protonation state. Experimental structures are fairly well modeled by this system in regard to the key structural indicators of spin state, which are the bite and trans angles. The calculated iron to nitrogen atom distances are always larger in the high spin form than the low spin form but all iron to nitrogen bond distances are larger than the experimental values. In general non-bonded interactions are not well modeled by this methodology.

Journal Article↗
PubMed1994

Variability of glutathione S-transferase isoenzyme patterns in matched normal and cancer human breast tissue.

The determination of GST levels in blood has been proposed to a marker of tumour burden in general, whereas level of the P1 isoenzyme has been identified as a prognostic factor for breast-cancer patients receiving no adjuvant chemotherapy. Particular glutathione S-transferase (GST) isoenzymes differ in their substrate specificity, however, and their presence or absence might therefore account for the resistance of tumours to particular chemotherapeutic drugs, as already established for cultured cell lines. Determination of the GST isoenzyme profile of a cancer tissue could have prognostic value in the selection of treatment if the levels of expression/activity show a degree of variation comparable with that exhibited by actual patient responses. Using reversed-phase h.p.l.c. to quantify affinity-isolated GSTs, we have analysed full isoenzyme profiles in the first large sample of matched normal and cancer human tissues (18 breast-cancer patients). In no patients did the tumour tissues express any isoenzymes that were not found in normal breast tissue. In addition to the GSTs, another enzyme, identified as enoyl-CoA isomerase, was regularly found in breast tissue cytosol following elution from a hexyl-glutathione affinity column. In most cases, the average level of GST was substantially elevated in the cancer tissues above the levels in normal breast tissue from the same patient. Furthermore, the relative levels of the isoenzymes were substantially more variable in the cancer samples than in the normal breast tissue, providing a plausible mechanism for the well established variable response to treatment.

Adult↗
PubMed2003

A kinetic model of the branch-point between the methionine and threonine biosynthesis pathways in Arabidopsis thaliana.

This work proposes a model of the metabolic branch-point between the methionine and threonine biosynthesis pathways in Arabidopsis thaliana which involves kinetic competition for phosphohomoserine between the allosteric enzyme threonine synthase and the two-substrate enzyme cystathionine gamma-synthase. Threonine synthase is activated by S-adenosylmethionine and inhibited by AMP. Cystathionine gamma-synthase condenses phosphohomoserine to cysteine via a ping-pong mechanism. Reactions are irreversible and inhibited by inorganic phosphate. The modelling procedure included an examination of the kinetic links, the determination of the operating conditions in chloroplasts and the establishment of a computer model using the enzyme rate equations. To test the model, the branch-point was reconstituted with purified enzymes. The computer model showed a partial agreement with the in vitro results. The model was subsequently improved and was then found consistent with flux partition in vitro and in vivo. Under near physiological conditions, S-adenosylmethionine, but not AMP, modulates the partition of a steady-state flux of phosphohomoserine. The computer model indicates a high sensitivity of cystathionine flux to enzyme and S-adenosylmethionine concentrations. Cystathionine flux is sensitive to modulation of threonine flux whereas the reverse is not true. The cystathionine gamma-synthase kinetic mechanism favours a low sensitivity of the fluxes to cysteine. Though sensitivity to inorganic phosphate is low, its concentration conditions the dynamics of the system. Threonine synthase and cystathionine gamma-synthase display similar kinetic efficiencies in the metabolic context considered and are first-order for the phosphohomoserine substrate. Under these conditions outflows are coordinated.

Adenosine Monophosphate↗
PubMed2002

Why do neuroprotective drugs that are so promising in animals fail in the clinic? An industry perspective.

1. No neuroprotective drug has yet been shown to be effective in treating acute ischaemic stroke in the clinic, despite evidence of efficacy in animal models. 2. An academic/industry round-table group recently published guidelines to be met if a drug was to be progressed to clinical trial. 3. Major points included obtaining full dose-response evaluation and measurement of the therapeutic time window for efficacy, functional behavioural testing in addition to measurement of infarct volume, measurement of physiological parameters, use of appropriate models (transient and permanent focal ischaemia) and reproducibility of data by external laboratories. 4. The present paper examines both failed compounds and disodium 4-[(tert-butylimino) methyl] benzene-1, 3-disulphonate N-oxide (NXY-059), a nitrone radical-trapping agent currently in clinical development. It aims to determine whether these guidelines were met by compounds that have failed and, thus, determine whether following the guidelines, as is being done with NXY-059, will increase the chances of developing efficacious drugs for treating acute ischaemic stroke. 5. It is concluded that we will only achieve the goal of producing a clinically effective neuroprotective agent if the guidelines have been met by the novel compound under investigation.

Animals↗
PubMed2002

P wave signal-averaged electrocardiography to identify risk for atrial fibrillation.

AF is the most common sustained cardiac arrhythmia, and this prevalence is increasing. The impact of AF on morbidity and mortality is substantial, as are the socioeconomic consequences like higher health care costs, chronic disease management, and disabilities. Early recognition of patients at high risk for AF, combined with effective management, may help prevent AF from becoming chronic, helping to minimize potential health risks, costs, and other complications. P wave signal-averaged electrocardiography (SAECG) has been shown to have a potential role in identifying patients at risk of developing paroxysmal AF and those likely to change from paroxysmal AF to chronic AF. The theoretical rationale of P wave SAECG in patients with AF is delay in the intraatrial and interatrial conduction. Intraatrial conduction delays can be seen on the surface electrocardiogram as P wave prolongation, which is more visible with averaging techniques and high resolution recording devices. Averaging followed by amplification after proper filtering of the electrical signal allows more precise measurements of duration and amplitude of the P wave. Data on reproducibility, filter settings, number of beats to be averaged, and definitions of the onset and offset depend on the system used, which can be QRS or, preferably, P wave triggered. A prolonged P wave duration is one of the best predictors of perioperative AF, but the role of P wave SAECG in the paroxysmal form is less well defined. Combining P wave duration with other predictors for AF improves the diagnostic value of P wave SAECG.

Atrial Fibrillation↗
PubMed2003

Phantom validation of multichannel magnetocardiography source localization.

Multichannel magnetocardiography (MMCG) is used clinically for noninvasive localization of the site of origin of cardiac arrhythmias. However, its accuracy in unshielded environments is still unknown. The aim of this study was to test the accuracy of three-dimensional localization of intracardiac sources by means of MMCG in an unshielded catheterization laboratory using a saline-filled phantom, together with a nonmagnetic catheter designed for multiple monophasic action potential recordings in a clinical setting. A nine-channel direct current superconducting quantum interference device (DC-SQUID) system (sensitivity fT/Hz0.5) was used for MMCG from 36 points in a measuring area of 20 x 20 cm. The artificial sources to be localized were dipoles embedded in the distal end of the catheter, placed 12 cm below the sensor's plane. Equivalent current dipoles, effective magnetic dipoles, and distributed currents models were used for the inverse solution. The localization error was estimated as the three-dimensional difference between the physical position of the tip of the catheter and the three-dimensional localization of the dipoles derived by means of the inverse solution calculated from MMCG data. The reproducibility was tested by repeating the MMCG after repositioning the phantom and the measurement system. The average location error of the catheter dipole was 9 +/- 4 mm and was due primarily to imprecise depth estimation. Localization was reproducible within 0.73 mm. The distributed currents model provided an accurate image of current distribution centered over the catheter tip. The authors conclude that MMCG estimation is accurate enough to guarantee proper localization of cardiac dipolar sources even in an unshielded clinical electrophysiological laboratory.

Arrhythmias, Cardiac↗
PubMed2001

Positive outcomes in traumatic brain injury-vegetative state: patients treated with bromocriptine.

OBJECTIVE: To assess the effects of multidisciplinary rehabilitation interventions and use of bromocriptine on outcome in patients with traumatic brain injury-vegetative state (TBI-VS). DESIGN: Retrospective review of clinical cases. SETTING: Free-standing rehabilitation hospital; Acute and extended rehabilitation hospital. PARTICIPANTS: Five consecutive TBI-VS patients, as well as 33 TBI-VS patients and 37 traumatic brain injury-minimally conscious state (TBI-MCS) patients reported in the literature. INTERVENTIONS: Bromocriptine administration, systematic neuropsychologic testing, sensory stimulation, and traditional comprehensive rehabilitation with physical therapy, occupational therapy, and speech therapy. MAIN OUTCOME MEASURES: Disability Rating Scale (DRS) at 1, 3, 6, and 12 months postinjury and FIM instrument scores at 1 month and 12 months postinjury, Coma Recovery Scale, and Barry Rehabilitation Inpatient Screening of Cognition. RESULTS: The 5 TBI-VS patients emerged from a VS into a MCS and regained functional status. Their recovery of physical and cognitive functioning, as rated by the DRS, was greater than previously reported in the literature for patients in a VS or MCS at 3, 6, and 12 months postinjury. CONCLUSION: Bromocriptine administration, systematic neuropsychologic testing, sensory stimulation, a comprehensive rehabilitation program, or a combination of these treatments may enhance functional recovery in this TBI-VS patient group. Further systematic study to quantify the contribution of these variables and to reproduce this data in a larger patient population should be performed.

Activities of Daily Living↗
PubMed2000

Increase in systolic blood pressure and catecholamine level during hyperinsulinemia in a placebo-controlled euglycemic clamp in healthy subjects.

Hyperinsulinemia has been shown to induce vasodilation and activation of the sympathetic nervous system. Whether these effects result in changes in blood pressure (BP) is discussed controversially. We measured BP and catecholamine levels in 50 healthy subjects during a 40-min baseline phase and during a 100-min euglycemic clamp phase. In a double-blind, between-subject comparison, 30 subjects were infused with 1.5mU insulin/kg x min, 20subjects were infused with saline solution. Insulin levels increased during insulin infusion from (mean+/-SE) 23.7 0.6 pmol/l to 406.2+/-3.0 pmol/l, but remained unchanged during placebo infusion. Blood glucose levels were identical during both conditions. Systolic BP increased from 116.6+/-1.5 mmHg to 119.8+/-1.8 mmHg during insulin infusion and decreased from 116.6+/-2.3 mmHg to 114.0+/-2.4 mmHg during placebo infusion (p<0.001, for the difference between the effects of insulin vs. placebo). Heart rate was higher during insulin infusion as compared to placebo infusion (63.8+/-1.9 vs. 60.9+/-2.4 beats/min, p<0.05). Norepinephrine levels increased from 1.25+/-0.09 to 1.58+/-0.12 nmol/l during insulin infusion and remained unchanged during placebo infusion (1.24+/-0.09 vs. 1.29+/-0.11 pmol/l; p<0.001). Epinephrine levels were also higher during insulin as compared to placebo infusion (249.8+/-17.4 vs. 212.8+/-21.1 pmol/l, p<0.001). The changes did not depend on whether the subject experienced his first or second clamp. Data demonstrate reproducable increasing effects of hyperinsulinemia within the normal physiological range on catecholamine release and systolic BP in healthy humans.

Adolescent↗
PubMed2004

A reoptimization of the five-site water potential (TIP5P) for use with Ewald sums.

The five-site transferable interaction potential (TIP5P) for water is most accurate at reproducing experimental data when used with a simple spherical cutoff for the long-ranged electrostatic interactions. When used with other methods for treating long-ranged interactions, the model is considerably less accurate. With small modifications, a new TIP5P-like potential can be made which is very accurate for liquid water when used with Ewald sums, a more physical and increasingly more commonly used method for treating long-ranged electrostatic interactions. The new model demonstrates a density maximum near 4 degrees C, like the TIP5P model, and otherwise is similar to the TIP5P model for thermodynamic, dielectric, and dynamical properties of liquid water over a range of temperatures and densities. An analysis of this and other commonly used water models reveals how the quadrupole moment of a model can influence the dielectric response of liquid water.

Journal Article↗
PubMed2005

Coarse-grained description of polymer blends as interacting soft-colloidal particles.

We present a theoretical approach which maps polymer blends onto mixtures of soft-colloidal particles. The analytical mesoscale pair correlation functions reproduce well data from united atom molecular dynamics simulations of polyolefin mixtures without fitting parameters. The theory exactly recovers the analytical expressions for density and concentration fluctuation structure factors of soft-colloidal mixtures (liquid alloys).

Journal Article↗
PubMed2005

Exciton migration in a polythiophene: probing the spatial and energy domain by line-dipole Forster-type energy transfer.

We study exciton migration in low molecular weight poly[3-(2,5-dioctylphenyl)thiophene] in dilute solution by means of ultrafast spectroscopy and Monte Carlo simulations of resonance energy transfer using the line-dipole Forster approach. The model includes the build-up of polymer chains, site-selective exciton generation, and diffusion through incoherent energy transfer. Time-resolved, ensemble-averaged experimental data are reproduced, namely photoluminescence spectral migration and stimulated emission anisotropy decays measured by streak camera and femtosecond transient absorption spectroscopy under site-selective excitation conditions. Importantly, the relatively simple line-dipole Forster-type approach beyond the point-dipole approximation reproduces both experiments quantitatively. Since explicit chain conformations are used in the model, the simulations yield a descriptive microscopic picture of exciton migration. The effective conjugation length (l(seg)=2.9 nm, 7.4 monomer units) and the disorder of the chains (Omega=0.8) are yielded as the only fitting parameters. We find an extra component that is not covered by our fits in anisotropy decays at early times for high excitation energies. This is interpreted within the context that the effective conjugation is limited by conformational disorder.

Journal Article↗