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Evolutionary optimization of radial basis function classifiers for data mining applications.

In many data mining applications that address classification problems, feature and model selection are considered as key tasks. That is, appropriate input features of the classifier must be selected from a given (and often large) set of possible features and structure parameters of the classifier must be adapted with respect to these features and a given data set. This paper describes an evolutionary algorithm (EA) that performs feature and model selection simultaneously for radial basis function (RBF) classifiers. In order to reduce the optimization effort, various techniques are integrated that accelerate and improve the EA significantly: hybrid training of RBF networks, lazy evaluation, consideration of soft constraints by means of penalty terms, and temperature-based adaptive control of the EA. The feasibility and the benefits of the approach are demonstrated by means of four data mining problems: intrusion detection in computer networks, biometric signature verification, customer acquisition with direct marketing methods, and optimization of chemical production processes. It is shown that, compared to earlier EA-based RBF optimization techniques, the runtime is reduced by up to 99% while error rates are lowered by up to 86%, depending on the application. The algorithm is independent of specific applications so that many ideas and solutions can be transferred to other classifier paradigms.

Algorithms↗

Amyloid precursor protein cross-linking stimulates beta amyloid production and pro-inflammatory cytokine release in monocytic lineage cells.

Beta amyloid peptide-containing neuritic plaques are a defining feature of Alzheimer's disease pathology. Beta amyloid are 38-43 residue peptides derived by proteolytic cleavage of amyloid precursor protein. Although much attention has focused on the proteolytic events leading to beta amyloid generation, the function of amyloid precursor protein remains poorly described. Previously, we reported that amyloid precursor protein functions as a pro-inflammatory receptor on monocytic lineage cells and defined a role for amyloid precursor protein in adhesion by demonstrating that beta(1) integrin-mediated pro-inflammatory activation of monocytes is amyloid precursor protein dependent. We demonstrated that antibody-induced cross-linking of amyloid precursor protein in human THP-1 monocytes and primary mouse microglia stimulates a tyrosine kinase-based pro-inflammatory signaling response leading to acquisition of a reactive phenotype. Here, we have identified pro-inflammatory mediators released upon amyloid precursor protein-dependent activation of monocytes and microglia. We show that amyloid precursor protein cross-linking stimulated tyrosine kinase-dependent increases in pro-inflammatory cytokine release and a tyrosine kinase-independent increase in beta amyloid 1-42 generation. These data provide much needed insight into the function of amyloid precursor protein and provide potential therapeutic targets to limit inflammatory changes associated with the progression of Alzheimer's disease.

Amyloid beta-Peptides↗

State-of-the-Art computed tomography of primate skulls--comparison of different scan-protocols.

To evaluate the image quality of different scan-protocols on 3 different CT-scanners for data acquisition of skulls of apes and monkeys with special respect on imaging the paranasal sinuses, we compared CT image quality in 452 skulls on either the Philips "Mx8000" Multi-Slice CT, the "Aura" Spiral CT or the "T omoscanM" CT scanner. Therefore, we used sequential and volume scanning as well as different slice thickness, table feed, voltage and X-ray current intensity. Representative axial scans of the anonymized studies as well as three-dimensional reconstructions were independently analyzed by an experienced radiologist and an anthropologist, using a study protocol covering relevant anatomical findings. Low-Dose protocols at 40 mAs demonstrated an equal diagnostic value with better CT-performance due to lower overheatening of the X-ray tube in all studies. Resolution, especially in small anatomical structures, was best with multi-slice CT. On both single-slice scanners resolution was significantly better with sequential-protocols (slice 2-5 mm; feed 1:1) than with volume-protocols. Volume scans are required for 3D-reconstruction. Best 3D results were achieved with "M x8000" due to its better spatial resolution, followed by the "Aura" scanner. Multi-slice CT (MSCT) was found to be the superior method for the radiographic evaluation of small anatomical structures. However, there is no significant loss of information with thin sequential scans in LD technique on a single-slice spiral CT scanner. Volume-data aquisition is required for 3D reconstruction.

Animals↗

Modified Alderman-Grant resonator with high-power stability for proton electron double resonance imaging.

Proton-electron double resonance imaging (PEDRI) requires a dual EPR/NMR resonator. In order to saturate electron spins, long high-power RF EPR pulses are needed. Dissipated power causes resonator and sample heating, resulting in instability of the resonator frequency and coupling, which in turn causes a reduction in sensitivity. To overcome this problem, we designed, built, and tested a modified Alderman-Grant (MAG) resonator for in vivo and in vitro applications. We improved the temperature stability by using fused quartz in critical structural components of the resonator and employing a design that minimized moving parts. All of the components of the resonator and matching circuit, including coupling capacitors, were rigidly positioned on the surface of the quartz tube. Electrical coupling circuitry between the feeding cable and resonator was employed to provide independent coupling and tuning adjustments, which improved the ease and speed of operation. The equivalent schematic of the matching circuit is presented along with calculations of critical parameters. The resonator exhibits no frequency shift with 20 W of continuous power irradiation, and can handle intermittent power of 60 W for up to 3 min without detuning, enabling stable and reliable data acquisition for PEDRI of biological samples.

Computer-Aided Design↗

Modeling reading, spelling, and past tense learning with artificial neural networks.

The connectionist modeling of reading, spelling, and past tense acquisition is discussed. We show how the same simple pattern association network for all three tasks can achieve perfect performance on training data containing many irregular words, provide near human level generalization performance, and exhibit some realistic developmental and brain damage effects. It is also shown how reaction times (such as naming latencies) can be extracted from these networks along with independent priming and speed-accuracy trade-off effects. We argue that all the remaining problems with these models will be solved by supplementing them with an appropriate connectionist semantic route.

Humans↗

The use of thallium-201 lung/heart ratios.

This survey gives an overview of the methodology of thallium-201 lung/heart uptake ratios often used as an independent factor in the assessment of patients with coronary artery disease undergoing myocardial perfusion scintigraphy. Different techniques have been used in the past. The most sensitive method is one which calculates a lung/heart ratio from scintigraphy obtained immediately after cessation of exercise. If single photon emission tomography (SPET) is routinely performed the anterior projection of the data set obtained during tomographic acquisition should be used in preference to a separate planar anterior static images recorded before or after the SPET procedure. The lung/heart ratio is useful as a prognostic indicator of outcome as it accurately mimics the degree of left ventricular dysfunction. With the increasing popularity of pharmacological stress testing there is evidence that this ratio still offer valid information. Additional work in this field is nevertheless required to further confirm this observation. In routine clinical practice, the lung/heart ratio should help and enable physicians to prioritise patients for urgent intervention.

Coronary Disease↗

Improved assessment of mitral valve stenosis by volumetric real-time three-dimensional echocardiography.

OBJECTIVES: This study was performed to determine the feasibility, accuracy and reproducibility of real-time volumetric three-dimensional echocardiography (3-D echo) for the estimation of mitral valve area in patients with mitral valve stenosis. BACKGROUND: Planimetry of the mitral valve area (MVA) by two-dimensional echocardiography (2-D echo) requires a favorable parasternal acoustic window and depends on operator skill. Transthoracic volumetric 3-D echo allows reconstruction of multiple 2-D planes in any desired orientation and is not limited to parasternal acquisition, and could thus enhance the accuracy and feasibility of calculating MVA. METHODS: In 48 patients with mitral stenosis (40 women; mean age 61 +/- 13 years) MVA was determined by planimetry using volumetric 3-D echo and compared with measurements obtained by 2-D echo and Doppler pressure half-time (PHT). All measurements were performed by two independent observers. Volumetric data were acquired from an apical view. RESULTS: Although 2-D echo allowed planimetry of the mitral valve in 43 of 48 patients (89%), calculation of the MVA was possible in all patients when 3-D echo was used. Mitral valve area by 3-D echo correlated well with MVA by 2-D echo (r = 0.93, mean difference, 0.09 +/- 0.14 cm2) and by PHT (r = 0.87, mean difference, 0.16 +/- 0.19 cm2). Interobserver variability was significantly less for 3-D echo than for 2-D echo (SD 0.08cm2 versus SD 0.23cm2, p < 0.001). Furthermore, it was much easier and faster to define the image plane with the smallest orifice area when 3-D echo was used. CONCLUSIONS: Transthoracic real-time volumetric 3-D echo provides accurate and highly reproducible measurements of mitral valve area and can easily be performed from an apical approach.

Cardiac Volume↗

Proteins of the glycine decarboxylase complex in the hydrogenosome of Trichomonas vaginalis.

Trichomonas vaginalis is a unicellular eukaryote that lacks mitochondria and contains a specialized organelle, the hydrogenosome, involved in carbohydrate metabolism and iron-sulfur cluster assembly. We report the identification of two glycine cleavage H proteins and a dihydrolipoamide dehydrogenase (L protein) of the glycine decarboxylase complex in T. vaginalis with predicted N-terminal hydrogenosomal presequences. Immunofluorescence analyses reveal that both H and L proteins are localized in hydrogenosomes, providing the first evidence for amino acid metabolism in this organelle. All three proteins were expressed in Escherichia coli and purified to homogeneity. The experimental Km of L protein for the two H proteins were 2.6 microM and 3.7 microM, consistent with both H proteins serving as substrates of L protein. Analyses using purified hydrogenosomes showed that endogenous H proteins exist as monomers and endogenous L protein as a homodimer in their native states. Phylogenetic analyses of L proteins revealed that the T. vaginalis homologue shares a common ancestry with dihydrolipoamide dehydrogenases from the firmicute bacteria, indicating its acquisition via a horizontal gene transfer event independent of the origins of mitochondria and hydrogenosomes.

Amino Acid Sequence↗

Is there a synergy between physical exercise and drug therapies for osteoporosis?

Combining physical exercise with drug therapies for osteoporosis has been attempted with the aim to maximize osteogenic stimulus. Potential synergetic effects may prevent post-menopausal bone loss, or maximise gains during peak bone mass acquisition. However, research studies yielded mixed results, impeding the emergence of a consensus on the effects of exercise and drug therapies for osteoporosis on bone tissue. Independent, additive or synergetic effects of exercise and drug therapies have been reported, but while animal studies offer promising results, human studies are less clear. The aim of this work was to critically review existing data on the subject in an attempt to clarify existing knowledge and to encourage further investigations with a 2 x 2 factorial design, as elucidation of these questions will benefit osteoporosis prevention.

Bone Density Conservation Agents↗

[Intra-individual comparison of gastric peristalsis after ingestion of a semiliquid and solid test meal].

AIM: Patients with various disorders of gastric function were studied with radiolabeled test meals of different consistency to elaborate the effect of ingested media on gastric peristalsis and emptying. METHODS: In 12 patients parameters of gastric function were intraindividually compared after ingestion of a semiliquid and a solid test meal. In addition to the standard evaluation derived from time activity curves condensed images were established from two fixed time intervals (early and late period). These images were used to evaluate the amplitude and frequency of gastric contractions using Fourier analysis. RESULTS: As expected gastric emptying was influenced by the consistency of the test meal. Mean emptying rates for the solid meal were significant lower than those for the semiliquid one (p < 0.01). The amplitude and frequency of gastric contractions, however, did not depend on the consistency of the test meal. Within the course of the examination contraction amplitudes significantly increased (p < 0.05) from the early to the late period using both, solid as well as semiliquid test meals. The frequency of gastric contractions remained unchanged. CONCLUSION: As shown by an intraindividual data comparison amplitude and frequency of gastric contractions seem to be independent of the consistency of ingested test meals whereas gastric emptying is significantly influenced by the administered media. Semiliquid meals offer advantages with respect to the shorter examination time and simpler preparation and therefore may be preferred for routine use. Since amplitudes seem to vary within the observation period standardized acquisition protocols are recommended for the evaluation of this parameter.

Adult↗

Evolution of genes, evolution of species: the case of aminoacyl-tRNA synthetases.

All of the aminoacyl-tRNA synthetase (aaRS) sequences currently available in the data banks have been subjected to a systematic analysis aimed at finding gene duplications, genetic recombinations, and horizontal transfers. Evidence is provided for the occurrence (or probable occurrence) of such phenomena within this class of enzymes. In particular, it is suggested that the monomeric PheRS from the yeast mitochondrion is a chimera of the alpha and beta chains of the standard tetrameric protein. In addition, it is proposed that the dimeric and tetrameric forms of GlyRS are the result of a double and independent acquisition of the same specificity within two different subclasses of aaRS. The phylogenetic reconstructions of the evolutionary histories of the genes encoding aaRS are shown to be extremely diverse. While large segments of the population are consistent with the broad grouping into the three Woesian domains, some phylogenetic reconstructions do not place the Archae and the Eucarya as sister groups but, rather, show a gram-negative bacteria/eukaryote clustering. In addition, many individual genes pose difficulties that preclude any simple evolutionary scheme. Thus, aaRS's are clearly a paradigm of F. Jacob's "odd jobs of evolution" but, on the whole, do not call into question the evolutionary scenario originally proposed by Woese and subsequently refined by others.

Amino Acid Sequence↗

Respiratory gating of cardiac PET data in list-mode acquisition.

PURPOSE: Respiratory motion has been identified as a source of artefacts in most medical imaging modalities. This paper reports on respiratory gating as a means to eliminate motion-related inaccuracies in PET imaging. METHODS: Respiratory gating was implemented in list mode with physiological signal recorded every millisecond together with the PET data. Respiration was monitored with an inductive respiration monitor using an elasticised belt around the patient's chest. Simultaneous ECG gating can be maintained independently by encoding ECG trigger signal into the list-mode data. Respiratory gating is performed in an off-line workstation with gating parameters defined retrospectively. The technique was applied on a preliminary set of patient data with C(15)O. RESULTS: Motion was visually observed in the cine displays of the sagittal and coronal views of the reconstructed respiratory gated images. Significant changes in the cranial-caudal position of the heart could be observed. The centroid of the cardiac blood pool showed an excursion of 4.5-16.5 mm (mean 8.5+/-4.8 mm) in the cranial-caudal direction, with more limited excursion of 1.1-7.0 mm (mean 2.5+/-2.2 mm) in the horizontal direction and 1.3-3.7 mm (mean 2.4+/-0.9 mm) in the vertical direction. CONCLUSION: These preliminary data show that the extent of motion involved in respiration is comparable to myocardial wall thickness, and respiratory gating may be considered in order to reduce this effect in the reconstructed images.

Artifacts↗

Adult human mesenchymal stem cell as a target for neoplastic transformation.

The neoplastic process may involve a cancer stem cell. This concept has emerged largely from the careful analysis of tumour biopsy systems from haematological, breast and brain tumours. However, the experimental systems necessary to provide the cellular and molecular evidence to support this important concept have been lacking. We have used adult mesenchymal stem cells (hMSC) transduced with the telomerase hTERT gene to investigate the neoplastic potential of adult stem cells. The hTERT-transduced line, hMSC-TERT20 at population doubling level (PDL) 256 showed loss of contact inhibition, anchorage independence and formed tumours in 10/10 mice. hMSC-TERT4 showed loss of contact inhibition at PDL 95, but did not exhibit anchorage independence and did not form tumours in mice. Both lines had a normal karyotype but showed deletion of the Ink4a/ARF locus. At later passage, hMSC-TERT4 also acquired an activating mutation in KRAS. In hMSC-TERT20, expression of the cell cycle-associated gene, DBCCR1 was lost due to promoter hypermethylation. This epigenetic event correlated with acquisition of tumorigenicity. These data suggest that the adult hMSCs can be targets for neoplastic transformation and have implications for the development of novel anticancer therapeutics and for the use of hMSC in tissue engineering and transplantation protocols.

Adult↗

Testing hypotheses of convergence with multivariate data: morphological and functional convergence among herbivorous lizards.

Despite its importance to evolutionary theory, convergence remains an understudied phenomenon and is usually investigated using qualitative data. This paper advances a new, multidimensional view of convergence. Three patterns indicative of convergence are discussed, and techniques to discover and test convergent patterns in a quantitative framework are developed. These concepts and methods are applied to a dataset of digitized coordinates on 1554 lizard skulls and 1292 lower jaws to test hypotheses of convergence among herbivorous lizards. Encompassing seven independent acquisitions of herbivory, this lizard sample provides an ideal natural experiment for exploring ideas of convergence among different systems (here, morphological and functional). Three related questions are addressed: (1) Do herbivorous lizards show evidence of convergence in skull and lower jaw morphology? (2) What, if any, is the morphospace pattern associated with this convergence? (3) Is it possible to predict the direction of convergence using functional models? Relative warp analysis and permutation tests reveal that the skulls and lower jaws of herbivorous lizards do show evidence of convergence. Herbivore skulls deviate from their carnivorous or omnivorous sister groups toward the same area of morphospace. Without a phylogenetic perspective, this pattern would not be recognizable. Lower jaws of herbivores are not convergent in morphology but are convergent in function: herbivores deviate away from their carnivorous sister groups toward higher values of mechanical advantage. These results illustrate the desirability of quantitative methods, informed by phylogenetic information, in the study of convergence.

Adaptation, Biological↗

Redesign and improved performance of the tropospheric ozone lidar at the Jet Propulsion Laboratory Table Mountain Facility.

Improvements to the tropospheric ozone lidar at the Jet Propulsion Laboratory Table Mountain Facility for measurements of ozone profiles in the troposphere and lower stratosphere, between approximately 5-and 20-km altitude, are described. The changes were primarily related to the receiver optical subsystems and the data-acquisition system. The original 40-cm Cassegrain telescope was replaced with a faster (f/3) 91-cm Newtonian mirror. In the focal plane of this mirror, the lidar signal is divided into two parts by use of two separate optical fibers as field stops corresponding to different but neighboring 0.6-mrad fields of view. We then separate the two received wavelengths by aligning each transmitted beam to one of the fibers. In addition, two 50-mm telescopes are used for the collection of near-range returns. The four optical signals are brought to a chopper wheel for independent signal selection in the time and range domain. For each channel, an interference filter is used for skylight rejection and additional cross-talk prevention. The signals are detected with miniature photomultiplier tubes and input to a fast photon-counting system. The goals of these modifications were to increase the spatial and temporal resolution of the lidar, to extend the altitude range covered, to improve the quality of the raw data, and to enable regular and routine operation of the system for long-term measurements.

Journal Article↗

Cerebral glucose metabolic rates after 30 and 45 minute acquisitions: a comparative study.

This study was undertaken to determine if measurements of absolute regional cerebral metabolic rate for glucose (rCMRglc) and variance of rCMRglc are independent of time between 30 and 45 min following injection of the radiotracer. Sixteen subjects received two sets of 18FDG PET scans commencing 30 and 45 min following intravenous injection of 18FDG. No statistically significant differences were detected in either absolute rCMRglc or rCMRglc variance between the two sets of scans. These data demonstrate that for most FDG PET studies, scanning can commence 30 min after injection of the radiotracer without compromising the metabolic data.

Adult↗

Aerobactin production as a virulence factor: a reevaluation.

Iron starvation is one of the major barriers that virulent bacteria must overcome in order to proliferate in the host. Virtually all microorganisms possess high affinity iron (III) transport systems mediated by low molecular weight iron specific chelators called siderophores, the synthesis of which is activated under iron-limiting conditions. Siderophore aerobactin is frequently produced by enterobacteria which cause various types of infections in humans and animals. The status of aerobactin production as a virulence factor is evaluated both from data derived from experimental infection systems and the actual presence of this siderophore in clinical isolates. Aerobactin appears to be an important contributor to extracellular pathogenesis (mostly, that of Escherichia coli strains causing septicaemia and urinary tract infections) and to the extracellular stages of growth of intracellular pathogens like Shigella. When invasive bacteria actually enter target cells, acquisition of iron seems to occur independently of siderophore production. The feasibility of an antimicrobial therapy aimed at interfering with siderophore functioning is discussed.

Enterobacteriaceae↗

Construction and characterization of Moraxella catarrhalis mutants defective in expression of transferrin receptors.

We have previously reported the construction of an isogenic mutant defective in expression of OmpB1, the TbpB homologue, in Moraxella catarrhalis 7169. In this report, we have extended these studies by constructing and characterizing two new isogenic mutants in this clinical isolate. One mutant is defective in expression of TbpA, and the other mutant is defective in expression of both TbpA and TbpB. These isogenic mutants were confirmed by using PCR analysis, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and sequencing. In vitro growth studies, comparing all three mutants, demonstrated that the tbpA mutant and the tbpAB mutant were severely limited in their ability to grow with human holotransferrin as the sole source of iron. In contrast, the ompB1 (tbpB) mutant was capable of utilizing iron from human transferrin, although not to the extent of the parental strain. While affinity chromatography with human holotransferrin showed that each Tbp was capable of binding independently to transferrin, solid-phase transferrin binding studies using whole cells demonstrated that the tbpA mutant exhibited binding characteristics similar to those seen with the wild-type bacteria. However, the ompB1 (tbpB) mutant exhibited a diminished capacity for binding transferrin, and no binding was detected with the double mutant. These data suggest that the M. catarrhalis TbpA is necessary for the acquisition of iron from transferrin. In contrast, TbpB is not essential but may serve as a facilitory protein that functions to optimize this process. Together these mutants are essential to provide a more thorough understanding of iron acquisition mechanisms utilized by M. catarrhalis.

Bacterial Outer Membrane Proteins↗