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PubMed2002

Genesis: cluster analysis of microarray data.

A versatile, platform independent and easy to use Java suite for large-scale gene expression analysis was developed. Genesis integrates various tools for microarray data analysis such as filters, normalization and visualization tools, distance measures as well as common clustering algorithms including hierarchical clustering, self-organizing maps, k-means, principal component analysis, and support vector machines. The results of the clustering are transparent across all implemented methods and enable the analysis of the outcome of different algorithms and parameters. Additionally, mapping of gene expression data onto chromosomal sequences was implemented to enhance promoter analysis and investigation of transcriptional control mechanisms.

Algorithms↗
PubMed1984

Algorithms for restriction map comparisons.

An algorithm is presented which compares two restriction maps, yielding a measure of distance between the maps and relating the maps by an alignment. This new algorithm finds the minimum weighted sum of genetic events required to convert one map into the other, where the genetic events are the appearance/disappearance of restriction sites and changes in the number of bases between restriction sites. The algorithm is illustrated by comparison of the beta-delta region of the globin gene cluster of four primate species. The results are in excellent agreement with known evolutionary relationships.

Animals↗
PubMed2006

Rapid detection of similarity in protein structure and function through contact metric distances.

The characterization of biological function among newly determined protein structures is a central challenge in structural genomics. One class of computational solutions to this problem is based on the similarity of protein structure. Here, we implement a simple yet efficient measure of protein structure similarity, the contact metric. Even though its computation avoids structural alignments and is therefore nearly instantaneous, we find that small values correlate with geometrical root mean square deviations obtained from structural alignments. To test whether the contact metric detects functional similarity, as defined by Gene Ontology (GO) terms, it was compared in large-scale computational experiments to four other measures of structural similarity, including alignment algorithms as well as alignment independent approaches. The contact metric was the fastest method and its sensitivity, at any given specificity level, was a close second only to Fast Alignment and Search Tool--a structural alignment method that is slower by three orders of magnitude. Critically, nearly 40% of correct functional inferences by the contact metric were not identified by any other approach, which shows that the contact metric is complementary and computationally efficient in detecting functional relationships between proteins. A public 'Contact Metric Internet Server' is provided.

Algorithms↗
PubMed2006

Renal glucose excretion as a function of blood glucose concentration in subjects with type 2 diabetes--results of a hyperglycaemic glucose clamp study.

BACKGROUND: The purpose of this study was to investigate renal glucose excretion as a function of blood glucose concentration and to evaluate the within-subject variability and between-subject variability in subjects with type 2 diabetes. METHODS: Twenty-two subjects with type 2 diabetes [age 58 (12) years, diabetes duration 7 (6) years, endogenous creatinine clearance 117 (38) ml min(-1) 1.73 m(-2); median (inter-quartile range, IQR)] underwent two five-period hyperglycaemic glucose clamp experiments at intervals of 7-21 days. Starting from an initial blood glucose level of 12.2 mmol l(-1), subsequent glucose clamp levels were chosen using an algorithm based on urinary glucose concentrations measured at the end of the preceding glucose clamp period. That is, blood glucose was either stepwise decreased or increased depending on whether urinary glucose concentration was above or below 11.1 mmol l(-1), respectively. RESULTS: As expected, increasing the blood glucose from 7.8 to 13.3 mmol l(-1) during the glucose clamps resulted in a steep increase of urinary glucose excretion from 0.06 to 0.77 mmol min(-1). With decreasing blood glucose, a measurable glucosuria persisted up to a blood glucose level of 7.8 mmol l(-1). When defining the (pseudo)threshold for renal glucose excretion (PRT(G)) as the highest blood glucose level during glucose clamps associated with a concomitant glucose concentration in urine of <2.8 mmol l(-1), median (IQR) PRT(G) was 11.0 (1.1) mmol l(-1). The within-subject variability of PRT(G), i.e. the difference between two assessments, was low, 0.1 (0.0) mmol l(-1) while the between-subject variability of PRT(G) was high, ranging from 7.7 to 12.2 mmol l(-1). CONCLUSION: Renal glucose excretion increases in a proportional manner with increasing blood glucose. When decreasing blood glucose to euglycaemic blood glucose levels, glucosuria persists so that the classical concept of a renal threshold for glucose excretion cannot be upheld in subjects with type 2 diabetes.

Adult↗
PubMed2005

TORT/MCNP coupling method for the calculation of neutron flux around a core of BWR.

For the analysis of BWR neutronics performance, accurate data are required for neutron flux distribution over the In-Reactor Pressure Vessel equipments taking into account the detailed geometrical arrangement. The TORT code can calculate neutron flux around a core of BWR in a three-dimensional geometry model, but has difficulties in fine geometrical modelling and lacks huge computer resource. On the other hand, the MCNP code enables the calculation of the neutron flux with a detailed geometry model, but requires very long sampling time to give enough number of particles. Therefore, a TORT/MCNP coupling method has been developed to eliminate the two problems mentioned above in each code. In this method, the TORT code calculates angular flux distribution on the core surface and the MCNP code calculates neutron spectrum at the points of interest using the flux distribution. The coupling method will be used as the DOT-DOMINO-MORSE code system. This TORT/MCNP coupling method was applied to calculate the neutron flux at points where induced radioactivity data were measured for 54Mn and 60Co and the radioactivity calculations based on the neutron flux obtained from the above method were compared with the measured data.

Algorithms↗
PubMed1995

A real-time electrical impedance tomograph.

Electrical properties of tissues in the human body can be imaged using a technology known as Electrical Impedance Tomography. In this modality, sinusoidal electrical currents are applied to the body using electrodes attached to the skin, and voltages that are developed on the electrodes are measured. Using these data, a reconstruction algorithm computes the conductivity and permittivity distributions within the body. This paper describes the reconstruction algorithm, image display algorithm, and hardware of a real-time Electrical Impedance Tomograph known as the Real-Time Imaging System. The reconstruction algorithm, executed by a commercially available coprocessor board that resides in a 386-based personal computer, is a modification of the Newton's One Step Error Reconstructor (NOSER) that minimizes algorithm execution time by precomputing many quantities. The image display algorithm, also executed by the coprocessor board, maps the output of the reconstruction algorithm into an image which is displayed using a video graphics board. The architecture of the system and execution times of algorithms implemented by the system are discussed. Using the continuous data acquisition mode of the Real-Time Imaging System, data from the thorax of a normal human subject were collected. Admittivity changes in the chest, as a result of respiration and the cardiac cycle, are presented. Data that were collected from the leg of a normal subject are shown which demonstrate capabilities of the triggered data acquisition mode of the system, allowing data acquisition synchronization with an electrocardiogram.

Algorithms↗
PubMed2005

Adaptive estimation of normals and surface area for discrete 3-D objects: application to snow binary data from X-ray tomography.

Estimating the normal vector field on the boundary of discrete three-dimensional objects is essential for rendering and image measurement problems. Most of the existing algorithms do not provide an accurate determination of the normal vector field for shapes that present edges. Here, we propose a new and simple computational method in order to obtain accurate results on all types of shapes, whatever their local convexity degree. The presented method is based on the gradient vector field analysis of the object distance map. This vector field is adaptively filtered around each surface voxel using angle and symmetry criteria so that as many relevant contributions as possible are accounted for. This optimizes the smoothing of digitization effects while preserving relevant details of the processed numerical object. Thanks to the precise normal field obtained, a projection method can be proposed to immediately derive the surface area from a raw discrete object. An empirical justification of the validity of such an algorithm in the continuous limit is also provided. Some results on simulated data and snow images from X-ray tomography are presented, compared to the Marching Cubes and Convex Hull results, and discussed.

Algorithms↗
PubMed2004

Conditional entropy as an indicator of pleomorphism in astrocytic tumors.

The entropies of nuclear arrangements as an indicator of pleomorphism are assessed using a morphometric method. Sixty astrocytic tumors (grades I, II, III and IV; 15 cases each) were reviewed and analyzed. All slides were stained with HE and MIB-1 antibody. The MIB-1 labeling index (LI) was assessed by counting nuclei under a microscope. Images of HE-stained slides were digitized and segmented using the watershed algorithm. Then, six nuclear parameters were measured automatically: (i) the number of total nuclei in the image, (ii) percentage of total nuclear area in the image, (iii) the mean area of the nucleus, (iv) the standard deviation of the area of the nucleus, (v) the entropy of nuclear arrangement (Entropysimple), and (vi) conditional entropy of nuclear arrangement (Entropyconditional). Entropysimple was defined according to the area of the nucleus and Entropyconditional was defined according to both the area of the nucleus and the area of its neighboring nuclei. Image processing and image analysis were performed with public domain software developed in the laboratory. Segmentation of the images resulted in inappropriate segmentation in a few percent of the images. The measurements obtained for each parameter were classified using discriminant analysis. The percentage of correct classification with Entropyconditional was 62%, which was the highest value among all the measurements. Classification based on the combination of all measurements resulted in a rate of correct classification of 88%. Thus, conditional entropy of nuclear arrangement is useful for grading of astrocytic tumors and it is proposed as an indicator of pleomorphism.

Astrocytoma↗
PubMed2006

The comparable size and overlapping nature of upper limb distal and proximal muscle representations in the human motor cortex.

The purpose of this study was to determine the relative size and location of proximal and distal upper limb muscle representations in the human motor cortex. Motor-evoked potentials (MEPs) evoked by transcranial magnetic stimulation were recorded in the proximal muscle anterior deltoid (AD) and in the distal muscles extensor carpi radialis (ECR) and first dorsal interosseus (1DI). The coil was moved in steps of 1 cm along a grid drawn on a tight-fitting polyester cap placed on the subject's head. At each location, four stimuli were delivered at 1.2 times the active motor threshold (AMT), and MEPs averaged in real-time. The peak-to-peak amplitude of each muscle's mean MEP was measured at each stimulation site. The area of a muscle's representation was measured by a pixel-counting algorithm. The optimal point of each muscle's areal representation, which corresponds to the locus near which the largest MEPs are obtained, was determined by fitting a 3D Lorentzian function to the data points. The optimal point of distal muscles tended to be situated more laterally along the motor strip than that of proximal muscles. However, there was no statistically significant difference between the size of the areal representations and they overlapped considerably. Additionally, in another five subjects, using a small 45-mm coil placed in a hyper-focal orientation, maps were obtained at a stimulus intensity of 1.1-1.15 times the AMT of the muscle with the lowest threshold, usually the 1DI. Even in this very stringent condition, the mapped representations of the AD, ECR and 1DI overlapped, notwithstanding that sharp demarcations between borders were also apparent. These observations demonstrate that stimulus spread alone does not explain the overlap of muscle representations. These results show that commonly used proximal and distal upper-limb muscles, taken individually, are controlled by motor cortical territories of approximately equal size that significantly overlap despite differences in the location of their optimal points.

Adult↗
PubMedDate not supplied

Myocardial perfusion as assessed by positron emission tomography during long-term mechanical circulatory support.

Although mechanical circulatory support (MCS) can improve myocardial function in patients with advanced heart failure, its effects on relative myocardial perfusion are unclear. Using positron emission tomographic imaging techniques, the authors assessed relative myocardial perfusion in patients with ischemic or idiopathic cardiomyopathy who were receiving chronic MCS with a left ventricular assist device (pulsatile HeartMate [n = 2] [Thoratec Corporation, Pleasanton, CA] or nonpulsatile Jarvik 2000 [n = 4] [Jarvik Heart, Inc., New York, NY]). Relative myocardial perfusion was compared at lower and higher levels of MCS (50 vs. 100 - 110 ejections/min for the HeartMate and 8000 vs. 12,000 rpm for the Jarvik 2000). The size and severity of perfusion defects at rest and after dipyridamole stress were measured objectively and subjectively by computer algorithms and visual inspection, respectively. Relative myocardial perfusion increased > 5% from baseline in only one of six patients when MCS was increased. No change in relative myocardial perfusion of > 5% was seen in any of the other five patients, even after subsequent dipyridamole stress positron emission tomographic imaging. These pilot study findings suggest that the decreased metabolic requirements induced by ventricular unloading correspondingly decreased blood flow requirements to physiologically inactive myocardium.

Adult↗
PubMed1998

Pacing impedance variability in tined steroid eluting leads.

The aim of the study was to investigate pacing impedance (PI) behavior in ambulatory patients. Eighteen atrial and 18 ventricular tined steroid eluting leads with 1.2-mm2 and 5.6-mm2 electrodes were implanted in 20 patients. At 9-27 months after implantation PI was measured automatically by means of additional algorithms downloaded via telemetry links into implanted Thera pulse generators. PI was determined based on the voltage drop on the output capacitor during the 5 V-1 ms pacing impulse, at the programmable sampling rates from 1 second to 30 minutes. The study examined in particular: (1) PI trends and variations associated with different breathing patterns, body postures, provocative maneuvers, bike exercise, and during 24 hours; (2) impact of pacing rate and AV-delay on PI; (3) correlation between PI variability and pacing threshold, lead configuration, absolute PI value, age, gender, disease, and cardiac chamber. The most important findings were: (1) large PI variations of up to 450 omega were observed in properly functioning leads, (2) PI variability exhibited a weak negative correlation with pacing thresholds as if electrode positional stability was not a major factor underlying PI variations, (3) unipolar and bipolar PI variations were equivalent to each other (correlation factor = 0.93) implying that PI was mostly dependent on the circumstances around the lead tip.

Aged↗
PubMed2003

Near-infrared thermo-optical response of the localized reflectance of intact diabetic and nondiabetic human skin.

We observed a difference in the thermal response of localized reflectance signal of human skin between type 2 diabetics and nondiabetics. We investigated the use of this thermo-optical behavior as the basis for a noninvasive method for the determination of the diabetic status of a subject. We used a two-site temperature differential method, which is predicated upon the measurement of localized reflectance from two areas on the surface of the skin. Each of these areas is subjected to a different thermal perturbation. The response of localized reflectance to temperature perturbation was measured and used in a classification algorithm. We used a discriminant function to classify subjects as diabetic or nondiabetic. In a prediction set of twenty-four noninvasive tests collected from six diabetic and six nondiabetic subjects, the sensitivity ranged between 73 and 100%, and the specificity ranged between 75 and 100%, depending on the thermal conditions and the probe-skin contact time. The difference in the thermo-optical response of the skin of the two groups is explained in terms of a difference in the response of cutaneous microcirculation, which is manifested as a difference in the near-infrared light absorption. Another factor is the difference in the temperature response of the scattering coefficient between the two groups, which may be caused by cutaneous structural differences induced by nonenzymatic glycation of skin protein fibers, and possibly by the difference in blood cell aggregation.

Algorithms↗
PubMed2003

A patch source model for treatment planning of ruthenium ophthalmic applicators.

Beta-ray emitting Ru-106/Rh-106 ophthalmic applicators have been used for close to 4 decades in the treatment of choroidal melanoma. The form factor of these applicators is a spherically concave silver bowl with an inner radius of curvature between 12 and 14 mm, and a total shell thickness of 1 mm. The radioactive nuclide is deposited in a layer 0.1 mm below the concave surface of the applicator. Calculation of dose distributions for clinical treatment planning purposes is complicated by the concave nature of the distributed source, the asymmetric shape of the active region of some applicators, imperfections in the manufacturing process which can result in an inhomogeneous distribution of activity across the active surface, and absorption and scatter in the 0.1 mm layer of silver which seals and protects the radioactive layer. A semi-empirical method of calculating dose distributions for these applicators is described which is fundamentally compatible with treatment planning systems that use the AAPM TG43 brachytherapy formalism. Dose to water is estimated by summing a "patch source" dose function over a discrete number of overlapping patches uniformly distributed over the active surface of the applicator. The patch source dose function differs conceptually from a point source dose function in that it is intended to represent the macroscopic behavior of a small, disk-like region of the applicator. The patch source dose function includes an anisotropy term to account for angular variation in absorption and scatter as particles traverse the 0.1 mm silver window. It geometrically models the nearfield of a patch with properties akin to both a small disk and infinite plane, and models the farfield as if the patch were a point. This allows a manageable number of discrete patches (300 to 1000) to provide accuracy appropriate for clinical treatment planning. This approach has the advantages of using familiar concepts and data structures, it is computationally quick, and it readily adapts to asymmetric applicator shapes and inhomogeneities in the radionuclide distribution. A method for optimizing the patch source dose function parameters is presented, and the dosimetric calculations are compared with published Monte Carlo calculations and measurements.

Algorithms↗
PubMedDate not supplied

Characterization of a p(66)Be(49) neutron therapy beam II: skin-sparing and dose transition effects.

Results of buildup measurements in A-150 tissue equivalent plastic are presented for a p(66)Be(49) neutron beam. These measurements were taken in air and behind various materials to answer questions about skin-sparing, bolussing materials, recovery of skin-sparing, and dosimetry in small radiobiological samples. The depth for Dmax for this beam is 1.6 g cm-2. An algorithm is also presented that reproduces the measured dose buildup curves.

Computers↗
PubMed1999

Analytical considerations of beam hardening in medical accelerator photon spectra.

Beam hardening is a well-known phenomenon for therapeutic accelerator beams passing through matter in narrow beam geometry. This study assesses quantitatively the magnitude of beam hardening of therapeutic beams in water. A formal concept of beam hardening is proposed which is based on the decrease of the mean attenuation coefficient with depth. On the basis of this concept calculations of beam hardening effects are easily performed by means of a commercial spreadsheet program. Published accelerator spectra and the tabulated values of attenuation coefficients serve as input for these calculations. It is shown that the mean attenuation coefficient starts at depth zero with an almost linear decrease and then slowly levels off to a limit value. A similar behavior is found for the beam hardening coefficient. A physically reasonable, semianalytical model is given which fits the data better than previously published functions. The energy dependence of the initial attenuation coefficient is evaluated and shown. It fits well to published experimental data. The initial beam hardening coefficient, however, shows no energy dependence. Its mean value (eta0) approximately 0.006 cm(-1)) is also in close agreement to the measured data.

Algorithms↗
PubMed2003

The effect of superior auditory skills on vocal accuracy.

The relationship between auditory perception and vocal production has been typically investigated by evaluating the effect of either altered or degraded auditory feedback on speech production in either normal hearing or hearing-impaired individuals. Our goal in the present study was to examine this relationship in individuals with superior auditory abilities. Thirteen professional musicians and thirteen nonmusicians, with no vocal or singing training, participated in this study. For vocal production accuracy, subjects were presented with three tones. They were asked to reproduce the pitch using the vowel /a/. This procedure was repeated three times. The fundamental frequency of each production was measured using an autocorrelation pitch detection algorithm designed for this study. The musicians' superior auditory abilities (compared to the nonmusicians) were established in a frequency discrimination task reported elsewhere. Results indicate that (a) musicians had better vocal production accuracy than nonmusicians (production errors of 1/2 a semitone compared to 1.3 semitones, respectively); (b) frequency discrimination thresholds explain 43% of the variance of the production data, and (c) all subjects with superior frequency discrimination thresholds showed accurate vocal production; the reverse relationship, however, does not hold true. In this study we provide empirical evidence to the importance of auditory feedback on vocal production in listeners with superior auditory skills.

Adult↗