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PubMed1988

Structure of antibody hypervariable loops reproduced by a conformational search algorithm.

The antigen-combining site of antibody molecules consists of six separate loops supported by a conserved beta-sheet framework; antibody specificity arises from length and sequence variation of these 'hypervariable' loops and can be manipulated by transferring sets of loops between different frameworks. Irregular loops are the most difficult parts of protein structure to understand and to model correctly. Here, we describe two computer experiments where all the hypervariable loops were deleted from X-ray structures of mouse immunoglobulins and reconstructed using the conformational search program CONGEN. A protocol was developed for reconstruction of the hypervariable loops in McPC 603 antibody. Calculated loop conformations were generated and a model of the combining site was built from selected low-energy conformations. We then modelled hypervariable loops in another antibody molecule, HyHEL-5. Both models agreed well with the known crystal structures. Our results hold out promise for the success of future modelling studies of complete antigen-combining sites from amino acid sequences.

Algorithms↗
PubMed2003

Fit of implant frameworks: an in vitro comparison between two fabrication techniques.

STATEMENT OF PROBLEM: It has been suggested that a precise fit between the implant and the framework cylinder is necessary to ensure a satisfactory long-term clinical outcome. PURPOSE: The purpose of this study was to compare the precision of fit between implant abutments and framework cylinders in frameworks fabricated by the Procera system and those fabricated from cast gold-alloy. MATERIAL AND METHODS: A total of 19 frameworks, 14 made with the Procera system (type 1) and 5 made of a cast gold-alloy (type 2), were fabricated. A total of 95 implants, 70 type 1 and 25 type 2 frameworks, were evaluated. Three replicas of the space between the implant abutments and the framework cylinders of the master cast were made for each test specimen. The replicas were cut with a scalpel in 2 axial directions: buccal-lingual and right-left. For the purpose of measurement, a microscope with a precision of +/- 0.5 microm was used at original magnification x30. The Student t test was used to determine whether there were significant differences between the framework designs. RESULTS: The buccal-lingual measurements for the type 1 and type 2 frameworks showed mean values of 28.1 microm (SD 9.8) and 42.0 microm (SD 1.8) on the buccal side, respectively, and 25.6 microm (SD 11.2) and 51.6 microm (SD 10.9) on the lingual side, respectively. For the right-left view, the mean measurements were 26.6 microm (SD 8.4) and 49.2 microm (SD 11.4) on the right side, respectively, and 27.4 microm (SD 8.5) and 44.4 microm (SD 6.5) on the left side, respectively. The total mean value for type 1 frameworks was 26.9 microm (SD 9.3); that for type 2 frameworks was 46.8 microm (SD 8.8). CONCLUSION: Within the limitations of this experiment, it was demonstrated that the fit of frameworks made with the Procera system was significantly better than that of the frameworks made with cast gold-alloy (P<.01).

Computer-Aided Design↗
PubMedDate not supplied

Levels of processing: a view from functional brain imaging.

This paper briefly reviews two central assumptions of the levels-of-processing framework in the light of findings from recent PET and fMRI studies: First, to address the suggestion that memory traces can be seen as records of analyses carried out for the purposes of perception and comprehension, studies on encoding-retrieval overlap in brain activation patterns are considered. Second, to address the suggestion that deeper, more semantic, processing results in more durable traces, studies of how encoding activity relates to processing depth and subsequent memory performance are examined. The results show that some of the sensory regions that are activated during initial perception are subsequently reactivated during retrieval, and activity in frontal and medial-temporal brain regions is related to depth of processing and level of memory performance. Collectively, these results provide support for central components of the levels framework.

Brain↗
PubMed2002

Vector entropy imaging theory with application to computerized tomography.

Medical imaging theory for x-ray CT and PET is based on image reconstruction from projections. In this paper a novel vector entropy imaging theory under the framework of multiple criteria decision making is presented. We also study the most frequently used image reconstruction methods, namely, least square, maximum entropy, and filtered back-projection methods under the framework, of the single performance criterion optimization. Finally, we introduce some of the results obtained by various reconstruction algorithms using computer-generated noisy projection data from the Hoffman phantom and real CT scanner data. Comparison of the reconstructed images indicates that the vector entropy method gives the best in error (difference between the original phantom data and reconstruction), smoothness (suppression of noise), grey value resolution and is free of ghost images.

Algorithms↗
PubMed2003

A new approach to elastography using mutual information and finite elements.

Historically, increased mechanical stiffness during tissue palpation exams has been associated with assessing organ health as well as with detecting the growth of a potentially life-threatening cell mass. As such, techniques to image elasticity parameters (i.e., elastography) have recently become of great interest to scientists. In this work, a new method of elastography will be introduced within the context of mammographic imaging. The elastography method proposed represents a non-rigid iterative image registration algorithm that varies material properties within a finite element model to improve registration. More specifically, regional measures of image similarity are used within an objective function minimization framework to reconstruct elasticity images of tissue stiffness. Numerical simulations illustrate: (1) the encoding of stiffness information within the context of a regional image similarity criterion, (2) the methodology for an iterative elastographic imaging framework and (3) elasticity reconstruction simulations. The real strength in this approach is that images from any modality (e.g., magnetic resonance, computed tomography, ultrasound. etc) that have sufficient anatomically-based intensity heterogeneity and remain consistent from a pre- to a post-deformed state could be used in this paradigm.

Adipose Tissue↗
PubMed2006

A difference-matrix metaheuristic for intensity map segmentation in step-and-shoot IMRT delivery.

At an intermediate stage of radiation treatment planning for IMRT, most commercial treatment planning systems for IMRT generate intensity maps that describe the grid of beamlet intensities for each beam angle. Intensity map segmentation of the matrix of individual beamlet intensities into a set of MLC apertures and corresponding intensities is then required in order to produce an actual radiation delivery plan for clinical use. Mathematically, this is a very difficult combinatorial optimization problem, especially when mechanical limitations of the MLC lead to many constraints on aperture shape, and setup times for apertures make the number of apertures an important factor in overall treatment time. We have developed, implemented and tested on clinical cases a metaheuristic (that is, a method that provides a framework to guide the repeated application of another heuristic) that efficiently generates very high-quality (low aperture number) segmentations. Our computational results demonstrate that the number of beam apertures and monitor units in the treatment plans resulting from our approach is significantly smaller than the corresponding values for treatment plans generated by the heuristics embedded in a widely use commercial system. We also contrast the excellent results of our fast and robust metaheuristic with results from an 'exact' method, branch-and-cut, which attempts to construct optimal solutions, but, within clinically acceptable time limits, generally fails to produce good solutions, especially for intensity maps with more than five intensity levels. Finally, we show that in no instance is there a clinically significant change of quality associated with our more efficient plans.

Algorithms↗
PubMed2001

Knowledge management of the neuroscientific literature: the data model and underlying strategy of the NeuroScholar system.

This paper describes the underlying strategy and system's design of a knowledge management system for the neuroscientific literature called 'NeuroScholar'. The problem that the system is designed to address is to delineate fully the neural circuitry involved in a specific behaviour. The use of this system provides experimental neuroscientists with a new method of building computational models ('knowledge models') of the contents of the published literature. These models may provide input for analysis (conceptual or computational), or be used as constraint sets for conventional neural modelling work. The underlying problems inherent in this approach, the general framework for the proposed solution, the practical issues concerning usage of the system and a detailed, technical account of the system are described. The author uses a widely used software specification language (the Universal Modelling Language) to describe the design of the system and present examples from published work concerned with classical eyeblink conditioning in the rabbit.

Animals↗
PubMed2026

CircExor enables interpretable prediction of circRNA localization into extracellular vesicles.

Certain circular RNAs (circRNAs) are selectively enriched in extracellular vesicles (EVs), in which they contribute to intercellular communication and represent promising biomarkers, yet the sequence determinants of their sorting remain unclear. Existing computational predictors are optimized mainly for linear RNAs and rarely address circRNA localization into EVs. Here we introduce circExor, the first framework specifically designed for circRNA EV localization. We curate a dedicated benchmark data set of 2102 circRNAs and implement a variable-length end-to-end concatenation strategy together with k-mer frequency encoding to accommodate circular topology, long sequence length, and length heterogeneity. Using a tree-based classifier, circExor achieves superior performance compared with RNAlocate-v3 and ExoGRU, reaching an AUROC of 0.743 on the internal test set and an average AUROC of 0.680 on the held-out test set. SHAP-based analysis, sequence perturbation analysis, motif mapping, and cell-based experimental validation support the predicted EV tendency and identify YBX1, HNRNPK, HNRNPL, and NOVA2 as candidate RBPs potentially associated with circRNA sorting. CircExor therefore provides a predictive and interpretable framework that links in silico modeling to mechanistic hypotheses, and supports biomarker discovery and candidate prioritization for downstream studies of EV-associated circRNAs.

Journal Article↗
PubMed1995

The Mycobacterium leprae genome: systematic sequence analysis identifies key catabolic enzymes, ATP-dependent transport systems and a novel polA locus associated with genomic variability.

In the framework of the mycobacterial genome sequencing project, a continuous 37,049 bp sequence from the Mycobacterium leprae chromosome has been determined. Computer analysis revealed 10 complete open reading frames, and nine of their products show similarity to known proteins. Seven of these were identified as the enzyme isocitrate lyase, two P-type ATPase cation transporters, two AMP-binding proteins, the ribosomal protein S1, and DNA polymerase I. Interestingly, the polA gene, encoding DNA polymerase, is flanked by two inverted copies of a new class of the M. leprae specific repetitive sequence, RLEP, and this structure resembles a transposable element. A second copy of this element was found at another locus in the genome, but the two copies were not present in equal amounts and could not be found in all isolates of M. leprae. This is the first evidence for genomic variability in the leprosy bacillus and might ultimately be useful for developing a molecular test capable of distinguishing between strains of M. leprae.

Adenosine Triphosphatases↗
PubMed2006

Toward objective and quantitative evaluation of imaging systems using images of phantoms.

The use of imaging phantoms is a common method of evaluating image quality in the clinical setting. These evaluations rely on a subjective decision by a human observer with respect to the faintest detectable signal(s) in the image. Because of the variable and subjective nature of the human-observer scores, the evaluations manifest a lack of precision and a potential for bias. The advent of digital imaging systems with their inherent digital data provides the opportunity to use techniques that do not rely on human-observer decisions and thresholds. Using the digital data, signal-detection theory (SDT) provides the basis for more objective and quantitative evaluations which are independent of a human-observer decision threshold. In a SDT framework, the evaluation of imaging phantoms represents a "signal-known-exactly/background-known-exactly" ("SKE/ BKE") detection task. In this study, we compute the performance of prewhitening and nonprewhitening model observers in terms of the observer signal-to-noise ratio (SNR) for these "SK E/BKE" tasks. We apply the evaluation methods to a number of imaging systems. For example, we use data from a laboratory implementation of digital radiography and from a full-field digital mammography system in a clinical setting. In addition, we make a comparison of our methods to human-observer scoring of a set of digital images of the CDMAM phantom available from the internet (EUREF-European Reference Organization). In the latter case, we show a significant increase in the precision of the quantitative methods versus the variability in the scores from human observers on the same set of images. As regards bias, the performance of a model observer estimated from a finite data set is known to be biased. In this study, we minimize the bias and estimate the variance of the observer SNR using statistical resampling techniques, namely, "bootstrapping" and "shuffling" of the data sets. Our methods provide objective and quantitative evaluation of imaging systems with increased precision and reduced bias.

Algorithms↗
PubMed2004

Geovisualization to support the exploration of large health and demographic survey data.

BACKGROUND: Survey data are increasingly abundant from many international projects and national statistics. They are generally comprehensive and cover local, regional as well as national levels census in many domains including health, demography, human development, and economy. These surveys result in several hundred indicators. Geographical analysis of such large amount of data is often a difficult task and searching for patterns is particularly a difficult challenge. Geovisualization research is increasingly dealing with the exploration of patterns and relationships in such large datasets for understanding underlying geographical processes. One of the attempts has been to use Artificial Neural Networks as a technology especially useful in situations where the numbers are vast and the relationships are often unclear or even hidden. RESULTS: We investigate ways to integrate computational analysis based on a Self-Organizing Map neural network, with visual representations of derived structures and patterns in a framework for exploratory visualization to support visual data mining and knowledge discovery. The framework suggests ways to explore the general structure of the dataset in its multidimensional space in order to provide clues for further exploration of correlations and relationships. CONCLUSION: In this paper, the proposed framework is used to explore a demographic and health survey data. Several graphical representations (information spaces) are used to depict the general structure and clustering of the data and get insight about the relationships among the different variables. Detail exploration of correlations and relationships among the attributes is provided. Results of the analysis are also presented in maps and other graphics.

Journal Article↗
PubMed2003

Prosodic and melodic processing in adults and children. Behavioral and electrophysiologic approaches.

The results of a series of experiments aimed at directly comparing the prosodic level of processing in language with the melodic level of processing in music are reported. The first series of experiments was conducted on adults, musicians and nonmusicians, and the second one on 7- to 9-year-old musician and nonmusician children. However, as this last study is still in progress, only preliminary results will be presented. The theoretic framework within which these experiments are taking place is described. The first problem concerns the specificity of the perceptive and cognitive computations necessary to perceive and understand language. We argue that comparing language with music can provide interesting insights into this complex issue. The second problem is linked to the relationship between different types of learning. Does early musical training influence the way in which musicians process some aspects of language as prosody? These two problems are considered and the results of the experiments are described.

Adult↗
PubMed2026

Longitudinal Clinical, Physiological, and Molecular Profiling of Female Patients With Metastatic Cancer: Protocol and Feasibility of a Multicenter High-Definition Oncology Study.

PURPOSE: A substantial proportion of patients receiving genomically matched therapies do not achieve clinical benefit, underscoring the influence of nongenetic factors on cancer outcomes. High-Definition Oncology (HDO) proposes integrating longitudinal, multimodal patient data-spanning clinical, molecular, physiological, and behavioral domains-to enable truly individualized cancer care. This manuscript describes the HDO study design, framework, and feasibility results in women with metastatic cancer. METHODS: We initiated a prospective, multicenter observational study (HDO study; ClinicalTrials.gov identifier: NCT06590506) enrolling 300 female patients with newly diagnosed metastatic breast, lung, or colorectal cancer. Here, we report the study design, standardized workflows, prespecified feasibility criteria, and early internal pilot results. Eleven data modalities are collected longitudinally, including tumor and germline genomics, germline epigenomics, gut microbiome, blood and stool metabolomics and proteomics, exposome characterization, wearable-derived physiological monitoring, digital footprint assessment, medical imaging, and patient-reported outcomes. Standardized workflows govern clinical procedures, data acquisition, biospecimen processing, and quality control across all participating sites. RESULTS: Feasibility was evaluated in the first 30 participants (10% of planned accrual). Patients completed 100% of scheduled clinical visits, 97.4% of planned plasma collections, 80.7% of stool samples, and all tumor biopsies. Wearable devices captured activity, heart rate, sleep, and blood oxygen saturation data during 95.0%, 84.2%, 90.6%, and 70.7% of total patient-days, respectively. Biospecimens met predefined quality control metrics across all molecular modalities. Engagement with mobile applications for pain and emotion reporting exceeded 80%. CONCLUSION: The HDO study demonstrates the feasibility of comprehensive, longitudinal, multimodal data collection in women with metastatic cancer. This internal pilot establishes an integrated framework for future analyses aimed at characterizing disease trajectories, defining molecular and physiological determinants of outcomes, and developing patient-specific computational models.

Humans↗
PubMed2004

From snakes to region-based active contours defined by region-dependent parameters.

Image and sequence segmentation of a the segmentation task are discussed from the point of view of optimizing the segmentation criterion. Such a segmentation criterion involves so-called (boundary and region) descriptors, which, in general, may depend on their respective boundaries or regions. This dependency must be taken into account when one is computing the criterion derivative with respect to the unknown object domain (defined by its boundary). If this dependency not considered, some correctional terms may be omitted. Computing the derivative of the segmentation criterion with a dynamic scheme is described. The scheme is general enough to provide a framework for a wide variety of applications in segmentation. It also provides a theoretical meaning to the philosophy of active contours.

Journal Article↗
PubMed2001

Optimum receivers for pattern recognition in the presence of Gaussian noise with unknown statistics.

We develop algorithms to detect a known pattern or a reference signal in the presence of additive, disjoint background, and multiplicative white Gaussian noise with unknown statistics. The presence of three different types of noise processes with unknown statistics presents difficulties in estimating the unknown parameters. The standard methods such as expected-maximization-type algorithms are iterative, and in the framework of hypothesis testing they are time-consuming, because corresponding to each hypothesis one must estimate a set of parameters. Other standard methods such as setting the gradient of the likelihood function with respect to the unknown parameters will lead to a nonlinear system of equations that do not have a closed-form solution and require iterative methods. We develop an approach to overcome these handicaps and derive algorithms to detect a known object. We present new methods to estimate unknown parameters within the framework of hypothesis testing. The methods that we present are direct and provide closed-form estimates of the unknown parameters. Computer simulations are used to show that for the images tested, the receivers that we have designed perform better than existing receivers.

Journal Article↗
PubMed1996

Clinical research in a hospital--from the lone rider to teamwork.

Clinical research of high international standard is very demanding and requires clinical data of high quality, software, hardware and competence in research design and statistical treatment of data. Most busy clinicians have little time allocated for clinical research and this increases the need for a potent infrastructure. This paper describes how the Norwegian Radium Hospital, a specialized cancer hospital, has reorganized the clinical research process. This includes a new department, the Clinical Research Office, which serves the formal framework, a central Diagnosis Registry, clinical databases and multicentre studies. The department assists about 120 users, mainly clinicians. Installation of a network software package with over 10 programs has strongly provided an internal standardization, reduced the costs and saved clinicians a great deal of time. The hospital is building up about 40 diagnosis-specific clinical databases with up to 200 variables registered. These databases are shared by the treatment group and seem to be important tools for quality assurance. We conclude that the clinical research process benefits from a firm infrastructure facilitating teamwork through extensive use of modern information technology. We are now ready for the next phase, which is to work for a better external technical framework for cooperation with other institutions throughout the world.

Cancer Care Facilities↗
PubMed2004

The performance of information technology in a cardiovascular system.

Our paper presents the results of a research study concerning the accuracy of the diagnosis and/or therapy for a cardiovascular patient. From the electronic patient records we have built a special database. The structure of this database offers possibilities for performing research studies on: cardiovascular pathology, risk factors action, medical treatment action, efficiency programs for primary and secondary prevention of diseases. The patient's data can be introduced from all intranet workstations of the cardiology department. The database structure is established to permit: optimal allocation of disk space, robust statistical analyses. The coding scheme can be explained as follows: if the information can have two or more values which exclude each other, the information is represented by a character; if the information can have more values which don't exclude each other, the field contains many characters representing possible values. Our paper shows that this database structure makes it possible to analyze every data piece that is stored. This system makes it possible to obtain a comprehensive summary of the cardiovascular population in real time by using standard reports and graphics, drill-down and roll-up on hierarchical dimensions, and analysis of temporal indicators. The database now contains information on 4000 patients undergoing effort tests as well as 2500 patients in the recovery program, and the system is being tested for all registered patients. We hope that field tests can begin in the near future, in the framework of a national cardiovascular infrastructure program.

Cardiovascular Diseases↗
PubMedDate not supplied

Fabrication of an implant-supported reconstruction utilizing CAD/CAM technology.

Recent scientific and technological developments have allowed the dental team to execute revolutionary restorative treatments that would have once been considered unfeasible. This article describes a restorative alternative for fixed implant-supported reconstructions, consisting of a CAD/CAM-generated framework and CAD/CAM-generated all-ceramic cement-retained restorations. Distinct advantages of this type of restoration include the passive fit of the framework, the ability of the ceramist to fabricate individual restorations independent from the framework, and the delivery of optimal aesthetics.

Computer-Aided Design↗