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PubMed1999

DNA microarrays of the complex human cytomegalovirus genome: profiling kinetic class with drug sensitivity of viral gene expression.

We describe, for the first time, the generation of a viral DNA chip for simultaneous expression measurements of nearly all known open reading frames (ORFs) in the largest member of the herpesvirus family, human cytomegalovirus (HCMV). In this study, an HCMV chip was fabricated and used to characterize the temporal class of viral gene expression. The viral chip is composed of microarrays of viral DNA prepared by robotic deposition of oligonucleotides on glass for ORFs in the HCMV genome. Viral gene expression was monitored by hybridization to the oligonucleotide microarrays with fluorescently labelled cDNAs prepared from mock-infected or infected human foreskin fibroblast cells. By using cycloheximide and ganciclovir to block de novo viral protein synthesis and viral DNA replication, respectively, the kinetic classes of array elements were classified. The expression profiles of known ORFs and many previously uncharacterized ORFs provided a temporal map of immediate-early (alpha), early (beta), early-late (gamma1), and late (gamma2) genes in the entire genome of HCMV. Sequence compositional analysis of the 5' noncoding DNA sequences of the temporal classes, performed by using algorithms that automatically search for defined and recurring motifs in unaligned sequences, indicated the presence of potential regulatory motifs for beta, gamma1, and gamma2 genes. In summary, these fabricated microarrays of viral DNA allow rapid and parallel analysis of gene expression at the whole viral genome level. The viral chip approach coupled with global biochemical and genetic strategies should greatly speed the functional analysis of established as well as newly discovered large viral genomes.

Base Sequence↗
PubMed2002

Neural activity in monkey dorsal and ventral cingulate motor areas: comparison with the supplementary motor area.

The cingulate motor areas are a recently discovered group of discrete cortical regions located in the cingulate sulcus with direct connections to the primary motor cortex and spinal cord. Although much is known about their anatomical relationship with other motor areas, relatively little is known about their functional neurophysiology. We investigated neural mechanisms of motor processing in the dorsal and ventral cingulate motor areas (CMAd and CMAv) during two-dimensional visually guided arm movements. Single-neuron activity in CMAd and CMAv was recorded during an instructed delay task requiring combined elbow and shoulder movements. Neural activity associated with the onset of a visual cue (signal activity), delay (set activity), and motor response (movement activity) were assessed, and their onset time, duration, magnitude, and parameters of directional specificity were calculated. To determine how CMAd and CMAv compared with other premotor areas, we also analyzed the activity of neurons in the supplementary motor area (SMA) during the same task in the same monkeys. Comparison of CMAd, CMAv, and SMA revealed remarkably similar response properties. All three areas contained signal, set, and movement activity in similar proportions and in all possible combinations within single neurons. The average onset time of signal and set activity and the duration of signal activity were not significantly different across areas. The directional tuning of activities in all three areas were uniformly distributed and highly correlated within the same neuron. There were, however, some notable differences in movement activity between motor areas. Neurons with only movement activity were more numerous in CMAd and CMAv, whereas neurons with both set and movement activity were more prevalent in SMA. Furthermore, movement activity in SMA began earlier and had a shorter duration than movement activity in CMAd and CMAv, although there was substantial overlap in their distributions. These results indicate that CMAd and CMAv participate in the visual guidance of limb movements using similar neurophysiological mechanisms as SMA. The earlier average onset and shorter duration of movement activity in SMA suggest a more prominent role for this area in movement initiation, whereas the later onset and longer duration of movement activity in CMAd and CMAv suggest a more influential role in movement execution. Notwithstanding these differences, however, the remarkable similarities in response types and their combinatorial organization within single neurons across all cortical areas attests to the parallel organization and distributed nature of information processing in these three motor areas.

Algorithms↗
PubMed2005

Superresolution imaging from limited-aperture optical diffracted field data.

The use of an optical waveguide to attain a numerical aperture of unity in computational coherent optical imaging applications is described. It is shown that for the case of a one-dimensional (slitlike) object radiating into an optical waveguide consisting of two plane-parallel mirrors the complex field amplitude across any cross section of the waveguide contains sufficient information to reconstruct the object's transmittance function with a numerical aperture of unity. We include the derivation of an inversion algorithm for performing the object reconstruction as well as computer simulations of the procedure.

Journal Article↗
PubMedDate not supplied

[Hyperprolactinaemia--pitfalls in PRL assessment].

Prolactin (PRL) is one of the most commonly assessed hormones, and hyperprolactinaemia seems to be often endocrine disorder. Hyperprolactinaemia is not a disease, but only a symptom indicating relevant medical conditions to be diagnosed and properly treated. Laboratory findings should be always cautiously interpreted with reference to clinical context. Possible problems could be evoked by errors during sampling and assessment itself. While interpreting laboratory results, one have to pay attention on pulsate secretion profile of PRL (within hours), and shows marked diurnal cycle (with maximum during sleep period). PRL level depends also on emotional status (stress amplifies PRL secretion), and also on dietary habits and stimulants. Lastly, a growing body of evidence proven that in some cases elevated PRL level could be caused by presence of polymeric form of PRL--so called "macroprolactin". This form has diminished receptor-binding specificity and weak, if any, biological effect while immunoreactivity is preserved. In clinical practice, in cases of macroprolactinaemia high level of circulating hormone does not correlate with slight, if even, clinical symptoms. To avoid errors in prolactin assessment blood should be drawn fasting, preferentially in series or during dynamic test after dopaminergic blockade with metoclopramide. Interpretation must parallel include clinical data. It is essential that PRL level is proportional to pituitary lactotroph tumor size. Extremely high PRL concentration could exceed technical capability of laboratory equipment and remain underestimated, or even undiagnosed. Beneath presented algorithm could be useful in planning diagnostic and therapeutic procedures.

Algorithms↗
PubMed2003

A new algorithm for computational image analysis of deformable motion at high spatial and temporal resolution applied to root growth. Roughly uniform elongation in the meristem and also, after an abrupt acceleration, in the elongation zone.

A requirement for understanding morphogenesis is being able to quantify expansion at the cellular scale. Here, we present new software (RootflowRT) for measuring the expansion profile of a growing root at high spatial and temporal resolution. The software implements an image processing algorithm using a novel combination of optical flow methods for deformable motion. The algorithm operates on a stack of nine images with a given time interval between each (usually 10 s) and quantifies velocity confidently at most pixels of the image. The root does not need to be marked. The software calculates components of motion parallel and perpendicular to the local tangent of the root's midline. A variation of the software has been developed that reports the overall root growth rate versus time. Using this software, we find that the growth zone of the root can be divided into two distinct regions, an apical region where the rate of motion, i.e. velocity, rises gradually with position and a subapical region where velocity rises steeply with position. In both zones, velocity increases almost linearly with position, and the transition between zones is abrupt. We observed this pattern for roots of Arabidopsis, tomato (Lycopersicon lycopersicum), lettuce (Lactuca sativa), alyssum (Aurinia saxatilis), and timothy (Phleum pratense). These velocity profiles imply that relative elongation rate is regulated in a step-wise fashion, being low but roughly uniform within the meristem and then becoming high, but again roughly uniform, within the zone of elongation. The executable code for RootflowRT is available from the corresponding author on request.

Algorithms↗
PubMed1993

Algorithm for semi-automatic sorting of objects to specified tissue domains. An aid for co-ordinating morphometric data with identified tissue components.

A personal computer-based technique was developed that reduces the extent of human efforts in obtaining data, like numerical density of profiles on area, describing the distribution of specific features of histological sections, e.g., density of synaptic profiles or of histochemical reaction products in specified tissue compartments. The procedure consists of (i) marking the objects to be counted, (ii) recording the borderlines of (reference) tissue domains of interest, and (iii) allocating the marked objects to the corresponding domains automatically. This automatic sorting of objects into defined tissue domains is achieved by an algorithm operating on two sets of coordinates: (i) coordinates of points that constitute the boundary of tissue domains (perimeter points) and (ii) coordinates of points marking the particular objects to be sorted. The principle of the sorting calculation is to construct 'segments' of the loop by lines parallel to the ordinate which pass through neighbouring perimeter points. The 'items' to be sorted are classified by the sign of marker flags allocated to each point depending on which side of the perimeter segment they are located. Segmentation and classification procedures are sequentially repeated along the entire perimeter of each domain specified by the operator which may result during the procedure in multiple changes of the sign of the flags. The internal or external location of each item finally is represented by the last sign of its flag. Objects, allocated to domains can be counted and processed further for numerical density determination.

Algorithms↗
PubMed2003

Honey characterization and adulteration detection by pattern recognition applied on HPAEC-PAD profiles. 1. Honey floral species characterization.

An improved COFRAC (COmité FRançais d'ACréditation) method for the analysis and evaluation of the quality of honey by high-performance anion-exchange chromatography of sugar profiles is proposed. With this method, both minor and major sugars are simultaneously analyzed and the technique is integrated in a new chemometric approach, which uses the entire chromatographic sugars profile of each analyzed sample to characterize honey floral species. Sixty-eight authentic honey samples (6 varieties) were analyzed by high-performance anion-exchange chromatography-pulsed amperometric detection. A new algorithm was developed to create automatically the corresponding normalized data matrix, ready-to-use in various chemometric procedures. This algorithm transforms the analytical profiles to produce the corresponding calibrated table of the surfaces or intensities according to retention times of peaks. The possibility of taking into account unknown peaks (those for which no standards are available) allows the maximum chemical information provided by the chromatograms to be retained. The parallel application of principal component analysis (PCA)/linear discriminant analysis (LDA) and artificial neural networks (ANN) shows a high capability in the classification of the analyzed samples (LDA, 93%; ANN, 100%) and a very good discrimination of honey groups. This work is the starting point of the elaboration of a new system designed for the automatic pattern recognition of food samples (first application on honey samples) from chromatographic analyses for food characterization and adulteration detection.

Algorithms↗
PubMedDate not supplied

Interactive transparency rendering for large CAD models.

Transparency is an important graphics effect that can be used to significantly increase the realism of the rendered scene or to enable more effective visual inspection in engineering visualization. In this paper, we propose achieving interactive transparency rendering of a static scene by sorting the triangles in back-to-front order on CPU and supplying the sorted triangles to the graphics pipeline for rendering on GPU hardware. Our sorting method sorts the triangles in object space and is built upon the Binary Space Partition (BSP) and depth-sort methods with its behavior readily tunable to exploit the strengths of both methods. We propose novel techniques to optimize the BSP construction process with respect to multiple factors including tree construction time, tree size, and expected sorting cost. We also propose an improved depth-sort algorithm that can produce correct depth order without triangle split when no cyclic occlusion exists. We demonstrate that the proposed system results in a penalty factor of 4-6 for various types of parts, among which the largest one has nearly 1.2 million triangles. In addition, the penalty factor may be further improved if sorting in CPU and rendering in GPU are executed in parallel. Two approximation strategies are also studied to test the practicality of our system against large CAD assemblies. Experimental results on an assembly containing over 16 million triangles distributed in about 10,000 transparent parts show that the proposed system still results in a penalty factor of 4-6 while producing few artifacts.

Algorithms↗
PubMed2004

Fast fragments: the development of a parallel effective fragment potential method.

The Effective Fragment Potential (EFP) method for solvation decreases the cost of a fully quantum mechanical calculation by dividing a chemical system into an ab initio region that contains the solute plus some number of solvent molecules, if desired, and an "effective fragment" region that contains the remaining solvent molecules. Interactions introduced with this fragment region (for example, Coulomb and polarization interactions) are added as one-electron terms to the total system Hamiltonian. As larger systems and dynamics are just starting to be studied with the EFP method, more needs to be done to decrease the calculation time of the method. This article considers parallelization of both the EFP fragment-fragment and mixed quantum mechanics (QM)-EFP interaction energy and gradient computation within the GAMESS suite of programs. The iteratively self-consistent polarization term is treated with a new algorithm that makes use of nonblocking communication to obtain better scalability. Results show that reasonable speedup is achieved with a variety of sizes of water clusters and number of processors.

Journal Article↗
PubMed1991

Simultaneous multinuclear magnetic resonance imaging and spectroscopy.

A technique has been developed to perform simultaneous multinuclear magnetic resonance imaging and spatially localized spectroscopy. It is inherently superior in terms of time efficiency over current approaches which use sequential or interleaved methods. The pulse sequence uses a parallel excitation and acquisition scheme to acquire multislice proton images concurrently with phosphorus-31 spectroscopic images. Because the phosphorus signal is necessarily collected in the presence of a gradient, an essential element of the technique is an algorithm to extract pure chemical-shift information.

Algorithms↗
PubMed2006

Quantum mechanical single molecule partition function from path integral Monte Carlo simulations.

An algorithm for calculating the partition function of a molecule with the path integral Monte Carlo method is presented. Staged thermodynamic perturbation with respect to a reference harmonic potential is utilized to evaluate the ratio of partition functions. Parallel tempering and a new Monte Carlo estimator for the ratio of partition functions are implemented here to achieve well converged simulations that give an accuracy of 0.04 kcal/mol in the reported free energies. The method is applied to various test systems, including a catalytic system composed of 18 atoms. Absolute free energies calculated by this method lead to corrections as large as 2.6 kcal/mol at 300 K for some of the examples presented.

Journal Article↗
PubMed2003

Initial evaluation of commercial optical CT-based 3D gel dosimeter.

We evaluated the OCTOPUS-ONE research laser CT scanner developed and manufactured by MGS Research, Inc. (Madison, CT). The scanner is designed for imaging 3D optical density distributions in BANG gels. The scanner operates in a translate-rotate configuration with a single scanning laser beam. The rotating cylindrical gel phantom is immersed in a refractive index matching solution and positioned at the center of a square tank made of plastic and glass. A stationary polarized He-Ne laser beam (633 nm) is reflected from a mirror moving parallel to the tank wall and scans the gel. Another mirror moves synchronously along the opposite side of the tank and collects the transmitted light and sends it to a single stationary silicon photodetector. A filtered backprojection algorithm is used to reconstruct projection data in a plane. The laser-mirrors-detector assembly is mounted on a horizontal platform that moves vertically for slice selection. We have tested the mechanical and optical setup, projection centering on the axis of rotation, linearity, and spatial resolution. We found the optical detector to respond linearly to transmitted light from control samples. The spatial resolution of the scanner was determined by employing a split field resolution technique. We obtained the horizontal and vertical full widths at half maxima of the laser beam intensity profiles as 0.6 and 0.8 mm, respectively. Dose calibration tests of the gel were performed using a nine-field (2 x 2 cm2 each) dose pattern irradiated at different dose levels. Finally, we compared gel-derived 2D planar dose distribution against radiochromic film measured dose distribution for both the nine-field and a uniform 5 x 5 cm2 field of 6 MV x rays. Very similar dose distributions were observed in gel and radiochromic film except in regions of steep dose gradient and highest dose. A dose normalization of 15.6% was required between the two dosimeters due to differences in overall radiation response. After normalization, analysis using the gamma evaluation showed that the radiochromic film and gel-measured dose distributions differed by a maximum gamma of 1.3 using 5% and 1.5 mm dose difference and distance-to-agreement criteria. The optical CT scanner has great potential as a 3D dosimeter, but a few refinements and further testing are necessary before its routine clinical use.

Algorithms↗
PubMed1998

Beginning insulin treatment of obese patients with evening 70/30 insulin plus glimepiride versus insulin alone. Glimepiride Combination Group.

OBJECTIVE: This study tested a simple algorithm for beginning insulin for obese patients with type 2 diabetes after sulfonylurea failure, comparing suppertime 70/30 insulin plus continued glimepiride with insulin alone. RESEARCH DESIGN AND METHODS: This was a multicenter ambulatory randomized double-masked parallel comparison. There were 208 subjects with secondary failure to sulfonylureas who took glimepiride titrated to 8 mg b.i.d. for 8 weeks; 145 subjects with fasting plasma glucose (FPG) 180-300 mg/dl (10-16.7 mmol/l) on this treatment were randomized to placebo plus insulin (PI) or glimepiride plus insulin (GI) for 24 weeks. A dosage of 70/30 insulin before supper was titrated, seeking fasting capillary blood glucose (FBG) 120 mg/dl (6.7 mmol/l), equivalent to FPG 140 mg/dl (7.8 mmol/l). Outcome measures included FPG, HbA1c, insulin dosage, weight, serum insulin and lipids, and adverse events. RESULTS: FPG and HbA1c were equivalent at baseline: 261 vs. 250 mg/dl (14.5 vs. 13.9 mmol/l), and 9.9 vs. 9.7%. At 24 weeks, the FPG target was achieved in both groups (136 vs. 138 mg/dl, 7.6 vs. 7.6 mmol/l), and HbA1c values were equal (7.7 vs. 7.6%). However, with GI, control improved faster and fewer subjects dropped out (3 vs. 15%, P < 0.01), and less insulin was needed (49 vs. 78 U/d, P < 0.001). The outcomes were alike in other respects. No subject had severe hypoglycemia. CONCLUSIONS: Injection of 70/30 insulin before supper safely restored glycemic control of type 2 diabetes not controlled by glimepiride alone. Control was restored more rapidly and with less injected insulin when glimepiride was continued.

Aged↗
PubMed1995

Transmission maximum-likelihood reconstruction with ordered subsets for cone beam CT.

An iterative algorithm is presented for accelerated reconstruction of cone beam transmission CT data (CBCT). CBCT supplies an attenuation map for SPECT attenuation compensation and anatomical correlation. Iterative algorithms are necessary to reduce truncation artifacts and 3D reconstruction artifacts. An existing transmission maximum-likelihood algorithm (TRML) is accurate but the reconstruction time is too long. The new algorithm is a modified EM algorithm, based on ordered subsets (OSEM). OSEM was evaluated in comparison to TRML using a thorax phantom and a 3D Defrise phantom. A wide range of image measures were evaluated, including spatial resolution, noise, log likelihood, region quantification, truncation artifact removal, and 3D artifact removal. For appropriate subset size, OSEM produced essentially the same image as TRML, but required only one-tenth as many iterations. Thus, adequate images were available in two to four iterations (20-30 min on a SPARC 2 workstation). Further, OSEM still approximately maximizes likelihood: divergence occurs only for very high (and clinically irrelevant) iterations. Ordered subsets are likely to be useful in other geometries (fan and parallel) and for emission CT as well. Therefore, with ordered subsets, high-quality iterative reconstruction is now available in clinically practical reconstructions times.

Algorithms↗
PubMed1991

Mathematical resolution of mixed in vivo voltammetry signals. Models, equipment, assessment by simultaneous microdialysis sampling.

A microcomputer-assisted curve-fitting procedure was developed for the quantitative estimation of the components of the mixed "catechol peak" recorded with differential normal pulse voltammetry (DNPV) at electrochemically pretreated carbon fiber microelectrodes in the living brain. The contribution of each of the relevant electroactive species is fitted by a normal probability function, the parameters of which are previously determined in vitro for each electrode and substance. The voltammogram is thus modeled as a mixture of normal curves corresponding to the individual oxidizable substances plus a low order polynomial approximating the baseline. In a former approach the function was solved by linear least squares techniques. As a further improvement, we now propose a non-linear model of the voltammogram and a Gauss-Newton iterative algorithm with stepwise regression for parameter estimation. This report shows the application of the method for the resolution of the dopamine (DA) and dihydroxyphenylacetic acid (DOPAC) components of the DNPV signal recorded from the striatum of freely moving animals in response to amphetamine and pargyline. The method was validated by the chemical assay of contralateral microdialysates collected simultaneously. The changes detected by both methodologies were closely parallel, with highly significant correlation coefficients (0.87 and 0.99 for DA and DOPAC, respectively, P less than 0.001). This study further illustrates that the in vivo voltammetry methodology can be improved substantially by incorporating a suitable mathematical treatment of the electrochemical signals.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1993

Thermal stability and conformational transitions of scrapie amyloid (prion) protein correlate with infectivity.

The scrapie amyloid (prion) protein (PrP27-30) is the protease-resistant core of a larger precursor (PrPSc) and a component of the infectious scrapie agent; the potential to form amyloid is a result of posttranslational event or conformational abnormality. The conformation, heat stability, and solvent-induced conformational transitions of PrP27-30 were studied in the solid state in films by CD spectroscopy and correlated with the infectivity of rehydrated and equilibrated films. The exposure of PrP27-30 in films to 60 degrees C, 100 degrees C, and 132 degrees C for 30 min did not change the beta-sheet secondary structure; the infectivity slightly diminished at 132 degrees C and correlated with a decreased solubility of PrP27-30 in sodium dodecyl sulfate (SDS), probably due to cross-linking. Exposing PrP27-30 films to formic acid (FA), trifluoroacetic acid (TFA), trifluoroethanol (TFE), hexafluoro-2-propanol (HFIP), and SDS transformed the amide CD band, diminished the mean residue ellipticity of aromatic bands, and inactivated scrapie infectivity. The convex constraint algorithm (CAA) deconvolution of the CD spectra of the solvent-exposed and rehydrated solid state PrP27-30 identified five common spectral components. The loss of infectivity quantitatively correlated with a decreasing proportion of native, beta-pleated sheet-like secondary structure component, an increasing amount of alpha-helical component, and an increasingly disordered tertiary structure. The results demonstrate the unusual thermal stability of the beta-sheet secondary structure of PrP27-30 protein in the solid state. The conformational perturbations of PrP27-30 parallel the changes in infectivity and suggest that the beta-sheet structure plays a key role in the physical stability of scrapie amyloid and in the ability to propagate and replicate scrapie.

Algorithms↗
PubMedDate not supplied

Biomedical simulation of heat transfer in a human heart.

Theory and practical experiences from numerical simulations of heat transfer in the field of medicine are presented in this paper. The cooling of a human heart during surgery was taken as an illustrative example. All phases of the simulation process are described starting with the construction of an irregularly shaped 3-dimensional model. The mathematical model is based on diffusion and Navier-Stokes equations. The system of partial differential equations is solved by finite difference approximation using an explicit time-stepping scheme to obtain the time evolution of the solution for the complete simulated interval, which is typically 1 h. A typical domain is composed of several million voxels; therefore, the program was parallelized to speed up the simulation. A speed-up of 8.2 was obtained on 16 processors in a Linux cluster.

Algorithms↗
PubMed1998

Optimal design of planar-concave collimators for SPECT--an analytical approach.

In this paper we present an analytical tool for the design and optimization of planar-concave collimators for SPECT. We conclude that a single general planar-concave collimator that eliminates the non-isotropic blurring for all SPECT applications does not exist. On the other hand, it is possible to achieve pseudo-optimal collimators for different clinical applications by a careful choice of the design parameters. By classifying the clinical applications into two groups, for instance body and brain studies, the non-isotropic blurring for most SPECT situations may be dramatically reduced by means of planar-concave collimators. The results based on Monte Carlo simulations show that the shape of the point source response function of the reconstructed image obtained from the planar-concave collimator is more isotropic than that obtained from a conventional parallel-hole collimator. Specifically, the ratio of the FWHM of the reconstructed point response function in the radial and tangential direction is increased from 0.5 for the parallel-hole to 0.85 for the planar-concave collimator for sources 200 mm away from the centre of rotation.

Algorithms↗