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PubMed1981

[Roentgenologically wasted time in bronchial carcinoma -a review (author's transl)].

The importance of roentgenologically wasted time, its frequency, causes and relation to specific characteristics of bronchial carcinoma are discussed in details along the literature. A short casuistic will show the actuality of the problem. There may be gained some important conclusions from the literature, but the differences in methods and the missing security in some definitions don't allow reliable answers to some detailproblems. The following conclusion could be derived from literature: 1. The roentgenologically protracted rate amounts to more than 30% on average. It decreases with increasing in experience of the readers of fluorographies. But even among them in the part of protracted cases amounts up to 10%. 2. Late protracted roentgenologic roentgenologic diagnosis is caused by -overlooking minimal lesions, -false algorithm in diagnostic procedure, -false diagnosis, -inadequate techniques, -the misinterpretation of developing malign lesion on the basis of existing alterations aetiologically known, -the delay on the patient's part. 3. The most important cause of all protracted x-ray findings is misinterpreted obstructive pneumonitis; it is followed by parenchymal cloudy densities, by striped atelectasis, old tuberculous processes, peripheral coin lesions and hilus alterations. 4. The time roentgenologically wasted is differing in wide range up to some years. 5. With increasing wasted time the portion of central tumors is also rising. 6. Even in patients considered as radically resected there exists still a negative correlation between the roentgenologically wasted time and prognosis. 7. The average of wasted time in x-ray lesions is running parallel to the screening intervals. 8. There seem to exist some differences between the different histological types in view of the roentgenologically wasted time. 9. There are no correlations between the age of the patients and the roentgenologically wasted time.

Adenocarcinoma↗
PubMed2005

Parallel magnetic resonance imaging using the GRAPPA operator formalism.

In this article it is shown that GRAPPA reconstruction can be reformulated as a matrix operator, similar to ladder or propagator operators used in quantum mechanics, that shifts data in k-space. Using this formalism, it is shown that there exists an infinitesimal GRAPPA operator that shifts data in k-space by arbitrarily small amounts. Other desired k-space shifts can then be accomplished through repeated applications of this infinitesimal GRAPPA operator. Implications of these ideas are described.

Algorithms↗
PubMed2005

Computing sensitivity and selectivity in parallel factor analysis and related multiway techniques: the need for further developments in net analyte signal theory.

Sensitivity and selectivity are important figures of merit in multiway analysis, regularly employed for comparison of the analytical performance of methods and for experimental design and planning. They are especially interesting in the second-order advantage scenario, where the latter property allows for the analysis of samples with a complex background, permitting analyte determination even in the presence of unsuspected interferences. Since no general theory exists for estimating the multiway sensitivity, Monte Carlo numerical calculations have been developed for estimating variance inflation factors, as a convenient way of assessing both sensitivity and selectivity parameters for the popular parallel factor (PARAFAC) analysis and also for related multiway techniques. When the second-order advantage is achieved, the existing expressions derived from net analyte signal theory are only able to adequately cover cases where a single analyte is calibrated using second-order instrumental data. However, they fail for certain multianalyte cases, or when third-order data are employed, calling for an extension of net analyte theory. The results have strong implications in the planning of multiway analytical experiments.

Algorithms↗
PubMed2005

Intermolecular packing and alignment in an ordered beta-hairpin antimicrobial peptide aggregate from 2D solid-state NMR.

The aggregation and packing of a membrane-disruptive beta-hairpin antimicrobial peptide, protegrin-1 (PG-1), in the solid state are investigated to understand its oligomerization and hydrogen-bonding propensity. Incubation of PG-1 in phosphate buffer saline produced well-ordered nanometer-scale aggregates, as indicated by 13C and 15N NMR line widths, chemical shifts, and electron microscopy. Two-dimensional 13C and 1H spin diffusion experiments using C-terminus strand and N-terminus strand labeled peptides indicate that the beta-hairpin molecules in these ordered aggregates are oriented parallel to each other with like strands lining the intermolecular interface. In comparison, disordered and lyophilized peptide samples are randomly packed with both parallel and antiparallel alignments. The PG-1 aggregates show significant immobilization of the Phe ring near the beta-turn, further supporting the structural ordering. The intermolecular packing of PG-1 found in the solid state is consistent with its oligomerization in lipid bilayers. This solid-state aggregation approach may be useful for determining the quaternary structure of peptides in general and for gaining insights into the oligomerization of antimicrobial peptides in lipid bilayers in particular.

Algorithms↗
PubMed2004

A simple quantitative method for evaluation of angiogenesis activity.

Angiogenesis plays a major role in many physiological and pathological processes. Pathological development of diseased conditions like growth and metastasis of solid tumors and psoriasis is associated with angiogenesis. Assays developed, thus far, for evaluation of angiogenesis activity are qualitative or semiquantitative. In vivo angiogenesis assays are more physiologically relevant than in vitro models and, however, time-consuming, labor-intensive, and expensive. The ex vivo rat aorta tube formation model has been demonstrated to correlate well to the physiological conditions. The present study established a reproducible and quantitative assay for evaluating angiogenesis with rat aorta ring cultures. Rat thoracic aortas were harvested, cross-sectioned into rings of 1-mm thickness using a set of aligned blades, and cultured in a three-dimensional extracellular matrix. Endothelial cells outgrow consistently from the aorta rings cultured in endothelial cell growth medium. Angiogenic activity was quantified by a colorimetric 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2H-tetrazolium/phenazine methosulfate method. The colorimetric assay was reproducible, and its results were compared in parallel with that of the imaging analysis method. IC(50) values of several known antiangiogenics, SU5416, suramin, paclitaxel, and 2-methoxyestradiol, were determined and were comparable to those obtained using the imaging analysis method. We have established a simple, reproducible, and quantitative assay for evaluation of angiogenesis activity with the cultured rat aorta ring, which can be used to screen for angiogenics and angiostatics.

Algorithms↗
PubMed2003

Simple rules underlying gene expression profiles of more than six subtypes of acute lymphoblastic leukemia (ALL) patients.

MOTIVATIONS AND RESULTS: For classifying gene expression profiles or other types of medical data, simple rules are preferable to non-linear distance or kernel functions. This is because rules may help us understand more about the application in addition to performing an accurate classification. In this paper, we discover novel rules that describe the gene expression profiles of more than six subtypes of acute lymphoblastic leukemia (ALL) patients. We also introduce a new classifier, named PCL, to make effective use of the rules. PCL is accurate and can handle multiple parallel classifications. We evaluate this method by classifying 327 heterogeneous ALL samples. Our test error rate is competitive to that of support vector machines, and it is 71% better than C4.5, 50% better than Naive Bayes, and 43% better than k-nearest neighbour. Experimental results on another independent data sets are also presented to show the strength of our method. AVAILABILITY: Under http://sdmc.lit.org.sg/GEDatasets/, click on Supplementary Information.

Algorithms↗
PubMed2026

Atlas-level single-cell integration and clustering-free differential expression analysis with GEDI 2.0.

MOTIVATION: GEDI is a generative framework for multi-sample, multi-condition single-cell analysis that performs batch correction, latent representation learning, and clustering-free differential expression within a unified model. However, the original implementation suffered from prohibitive memory use and runtime, preventing its application to modern atlas-scale datasets. RESULTS: We present GEDI 2.0, a complete high-performance reimplementation featuring a standalone C++ computational core with pre-allocated workspaces, strict sparse-matrix preservation, optimized BLAS routines, and multi-threaded block-coordinate descent. Across extensive benchmarks spanning up to 500 000 cells and 10 000 features, GEDI 2.0 achieves 40%-63.6% mean reduction in peak memory, 2.98× mean single-threaded speedups, and up to 11.5× acceleration with parallel execution, while maintaining full numerical equivalence to the original method. These improvements enable GEDI 2.0 to analyze million-cell datasets, a scale not achievable with the legacy implementation. GEDI 2.0 provides R and Python interfaces and seamless interoperability with common single-cell workflows. AVAILABILITY AND IMPLEMENTATION: Source code, documentation, reproducible codebase, and tutorials are available at https://github.com/csglab/gedi2.

Single-Cell Analysis↗
PubMed2006

Parallelization of multicategory support vector machines (PMC-SVM) for classifying microarray data.

BACKGROUND: Multicategory Support Vector Machines (MC-SVM) are powerful classification systems with excellent performance in a variety of data classification problems. Since the process of generating models in traditional multicategory support vector machines for large datasets is very computationally intensive, there is a need to improve the performance using high performance computing techniques. RESULTS: In this paper, Parallel Multicategory Support Vector Machines (PMC-SVM) have been developed based on the sequential minimum optimization-type decomposition method for support vector machines (SMO-SVM). It was implemented in parallel using MPI and C++ libraries and executed on both shared memory supercomputer and Linux cluster for multicategory classification of microarray data. PMC-SVM has been analyzed and evaluated using four microarray datasets with multiple diagnostic categories, such as different cancer types and normal tissue types. CONCLUSION: The experiments show that the PMC-SVM can significantly improve the performance of classification of microarray data without loss of accuracy, compared with previous work.

Algorithms↗
PubMed2002

Photon-density waves in macroscopic and microscopic plane-parallel scattering samples.

We investigate the validity of the Boltzmann equation to predict the reflection and transmission coefficients for an intensity modulated laser beam passing through a microscopic medium consisting of discrete scatterers. For a one-dimensional model system we demonstrate that the Boltzmann equation works remarkably well for small modulation frequencies, even to describe a medium comprised of only 10 scatterers. Discrepancies can be found only if the modulation wavelength of the laser intensity is commensurate with the spacing between the scatterers and if the medium is sufficiently ordered.

Algorithms↗
PubMedDate not supplied

Cerebral cartography--a method for visualizing cortical structures.

We present a method for visualizing the human cortex on one planar map. The data are taken from a 3D MRI study. Ray tracing with non-parallel rays is used to project the cortical relief onto a non-planar projection surface, which is in turn mapped onto the plane by cartographical projection. Two modifications of the method are proposed: the spherical mapping uses a sphere as the projection surface; the model-based mapping uses an analytically defined model of the scalp to generate the normal vectors. The cerebral cartography can be used for example for producing anatomical reference maps on which EEG measurement data can be superimposed.

Algorithms↗
PubMedDate not supplied

A parallel coordinates style interface for exploratory volume visualization.

We present a user interface, based on parallel coordinates, that facilitates exploration of volume data. By explicitly representing the visualization parameter space, the interface provides an overview of rendering options and enables users to easily explore different parameters. Rendered images are stored in an integrated history bar that facilitates backtracking to previous visualization options. Initial usability testing showed clear agreement between users and experts of various backgrounds (usability, graphic design, volume visualization, and medical physics) that the proposed user interface is a valuable data exploration tool.

Algorithms↗
PubMed2005

A clinician's approach to clinical ethical reasoning.

We offer a systematic strategy that situates clinical ethical reasoning within the paradigm of clinical reasoning. The trajectory of this strategy parallels clinical reasoning: a plain statement of the initial problem, careful gathering of data, a differential diagnostic assessment, and articulation and confirmation of a justified plan. This approach pays special attention to the goals of medical care, because so much depends on whether or not physician and patient share the same goals. This approach also addresses the heterogeneity of clinical problems that at first appear ethical and acknowledges the ethical pluralism that pervades clinical ethics.

Aged↗
PubMed2003

Pattern recognition in gene expression profiling using DNA array: a comparative study of different statistical methods applied to cancer classification.

Large-scale parallel measurements of the expression of many thousands genes are now available with high-density array made with collections of cDNA fragments, or oligonucleotide corresponding to different transcripts. These technologies have been applied to cancer investigations since the availability of such a large number of markers makes DNA array a powerful diagnostic tool for tumour and patient classification. Over the last two years, a series of computational tools have been developed for the analysis of different aspects of gene profiling. Our work tries to compare a series of supervised statistical techniques on the basis of their ability to correctly classify different types of tumours. A simulation approach was initially used to control the huge source of variation among and between patients, and to evaluate the ability of algorithms to classify tumours in relation to different types of experimental variables. Different techniques for reduction of data dimension were then added to the discriminant analysis and compared according to their ability to capture the main genetic information. The simulation results have been tested by applying the selected classification algorithms to two experimental microarray datasets of human cancers, and by measuring the correspondent rates of misclassification. Our analyses identify in these datasets a series of genes principally involved in tumour characterization. The functional role of these discriminant transcripts is discussed.

Algorithms↗
PubMedDate not supplied

Appraising the instantaneous secretory rates of luteinizing hormone and testosterone in response to selective mu opiate receptor blockade in late pubertal boys.

The pulsatile properties of gonadotropin and testosterone release were examined before and after chronic mu opiate receptor blockade with naltrexone, 50 mg every other day, in four normal boys in late puberty (ages 14 8/12 to 15 1/12 years). The nature of spontaneous secretory events was appraised for immunoactive LH and testosterone in blood withdrawn every 20 minutes for 24 hours, using a novel, discrete deconvolution algorithm to estimate apparent instantaneous secretory rates. The application of this methodology revealed that the frequency of discrete LH instantaneous secretory rates increased after mu opiate receptor blockade (P = 0.011). More strikingly, all parameters of testosterone secretory events responded significantly to mu opiate receptor blockade, including increases in mean estimated secretory rate (+47%, P = 0.02), testosterone pulse frequency (+ 64%, P less than 0.001) and amplitude (+ 20%, P = 0.027). Correspondingly, decreases in testosterone interpulse secretory intervals (-35%, P = 0.001), secretory pulse duration (-19%, P = 0.042) and interpulse valley duration (-35%, P = 0.006) also were noted. There was a prominent diurnal rhythm in testosterone secretion with maximal values in the morning and late evening, and marked reductions in the afternoon, sometimes to prepubertal levels. This variation in the testosterone secretory profile paralleled that of LH. In response to naltrexone, the FSH concentration series showed a significant increase in the mean FSH concentration (+ 18%) P = 0.003) and mean peak amplitude (+ 15%, P = 0.002). These data provide indirect evidence of functional coupling of the opiate system with the hypothalamic GnRH pulse generator.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed2000

Discovering patterns in microarray data.

The human genome is a complex system characterized by gene interactions and nonlinear behaviors. Complex systems cannot be viewed as the aggregate of their isolated pieces but must be studied as an integrated whole. Microarray technologies offer the opportunity to see the entire biological system as it existed at one moment in time. It is tempting to try to analyze the entire microarray at once to immediately discover the pattern being sought, for example, the pattern of a breast cancer. However, such an analysis would be a mistake because microarrays provide massively parallel information, the analysis of which is a nondeterministic polynomial time (NP)-hard problem. Current statistical methods are not sufficiently powerful to solve this NP-hard problem. The best approach to microarray analysis is to begin with a small number of the elements in the microarray known to be a pattern and ask questions of the other elements in the microarray; i.e., perform instantaneous scientific experiments regarding whether each of the other elements in the microarray are related to the known pattern.

Algorithms↗
PubMed2006

Simultaneous sustained release of fludarabine monophosphate and Gd-DTPA from an interstitial liposome depot in rats: potential for indirect monitoring of drug release by magnetic resonance imaging.

INTRODUCTION: Cytostatic depot preparations are interstitially administered for local chemotherapy and prevention of tumor recurrence. It would be of interest to monitor in patients as to when, to what extent, and exactly where, the drug is actually released. Liposomes containing a hydrophilic cytostatic and a hydrophilic contrast agent might be expected to release both agents simultaneously. If so, then drug release could be indirectly followed by monitoring contrast enhancement at the injection site. METHODS: Multivesicular liposomes containing the antimetabolite fludarabine monophosphate and the magnetic resonance imaging (MRI) contrast agent Gd-DTPA were subcutaneously injected in rats and both agents were monitored at the injection site for 6 weeks by 19F nuclear magnetic resonance spectroscopy (MRS) in vivo and contrast-enhanced 1H MRI (T1w 3D FLASH), respectively, in a 1.5-T whole-body tomograph. The MRS and MRI data were analyzed simultaneously by pharmacokinetic modeling using NONMEM. RESULTS: During an initial lag time, the amount of drug at the injection site stayed constant while the contrast-enhanced depot volume expanded beyond the volume injected. Drug amount and depot volume then decreased in parallel. Lag time and elimination half-life were 9 and 6 days, respectively, in three animals, and were about 50% shorter in another animal where the depot split into sub-depots. CONCLUSION: The preliminary data in rats suggest that simultaneous release of a hydrophilic cytostatic and a hydrophilic contrast agent from an interstitial depot can be achieved by encapsulation in liposomes. Thus, there seems to be a potential for indirect drug monitoring through imaging.

Algorithms↗
PubMed1996

Experimental determination of the dose kernel in high-energy x-ray beams.

A semiempirical method to characterize the pencil-beam dose kernel is presented. Results from measurements are described by mathematical models of the applicable physical processes. The measurements were made with 6 and 25 MV x-ray beams from a linear accelerator. Broad-beam notations were used consistently, and the pencil-beam quantities were obtained by differentiation. The results were compared to pencil-beam kernels calculated by Monte Carlo techniques. The analysis of the measured data included a number of approximations. It was assumed that all the constituent pencil beams in the field are parallel, i.e., the divergence is ignored. Furthermore, the lateral variations of the incident photon fluence and the energy spectrum were disregarded. Monte Carlo calculations, on the other hand, are based on an average energy spectrum over the field, and are free from divergence and variations in the incident photon fluence. Measured and Monte Carlo calculated pencil beams nevertheless agreed well, and the approximations mentioned caused at maximum 2.7% discrepancies for the largest field size at 6 MV.

Algorithms↗
PubMed2006

Complete predicted three-dimensional structure of the facilitator transmembrane protein and hepatitis C virus receptor CD81: conserved and variable structural domains in the tetraspanin superfamily.

Tetraspanins are a superfamily of transmembrane proteins implicated in cellular development, motility, and activation through their interactions with a large range of proteins and with specific membrane microdomains. The complete three-dimensional structure of the tetraspanin CD81 has been predicted by molecular modeling and from the crystallographic structure of the EC2 large extracellular domain. Periodicity of sequence conservation, homology modeling, secondary structure prediction, and protein docking were used. The transmembrane domain appears organized as a four-stranded left-handed coiled coil directly connecting to two helices of the EC2. A smaller extracellular loop EC1 contains a small largely hydrophobic beta-strand that packs in a conserved hydrophobic groove of the EC2. The palmitoylable intracellular N-terminal segment forms an amphipathic membrane-parallel helix. Structural variability occurs mainly in an hypervariable subdomain of the EC2 and in intracellular regions. Therefore, the variable interaction selectivity of tetraspanins originates both from sequence variability within structurally conserved domains and from the occurrence of small structurally variable domains. In CD81 and other tetraspanins, the numerous membrane-exposed aromatic residues are asymmetrically clustered and protrude on one side of the transmembrane domain. This may represent a functional specialization of these two sides for interactions with cholesterol, proteins, or membrane microdomains.

Algorithms↗