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PubMed2001

Diagnostics and a qualitative model.

First generation expert systems were using shallow knowledge based on heuristic information to solve a diagnostic problem. This approach has many disadvantages, which can be avoided by using deep knowledge. Diagnostic reasoning based on deep knowledge is called model-based diagnostics. Recently, the use of qualitative modeling in relation to deep knowledge in expert systems has become increasingly important. The main purpose of our contribution is to present the model-based diagnostic approach at a formal level. The originality of the presented formalization is the concept of the diagnostic space, the characterization of the minimal diagnoses, and the measurement. The formalization serves as the theoretical background to prove our view to the design of qualitative system models and to establish the diagnostic architecture called DISY. The qualitative system model in our diagnostic approach needs not to be specially adopted for use in the diagnostic domain. The only requirement is that it must simulate the system behavior expressed by normal or abnormal functioning of its components. Proposed DISY architecture is not complex and simply takes into an account the previous diagnostic result to obtain a new one from the additional observation-measurement (medical tests or examinations) of the system.

Decision Support Techniques↗
PubMed2002

Modeling rabbit temporomandibular joint torques during a power stroke.

Little information exists regarding the effects of changes in mandibular form as a result of orthognathic surgery on torques produced about the temporomandibular joint (TMJ). In this study, we have modeled torques produced about the working side TMJ by selected compartments of the rabbit masseter muscle based on published electromyographic activity. The masseter muscle is composed of multiple subregions or compartments that have unique mechanical actions. In a previous study, forces were elicited by electrical stimulation of each compartment and were recorded by a multiaxis force transducer attached to the anterior mandible. Torques were calculated using mandibular lever arms measured from the center of the TMJ. We have extended this modeling to include variations in mandibular width, length, or height to determine the torques that would be generated with variations in mandibular form. Three superficial masseter compartments on the working side and one posterior deep compartment from the balancing side masseter were examined using data collected from a companion study. It was found that the working and balancing side compartments were synergists for pitch torque components but were antagonists for roll and yaw. In modeling an increase of each mandibular dimension by 20%, nonuniform changes in compartment-generated torques were found. The largest increase was found for the posterior superficial masseter yaw torque component. The effects of changing mandibular form on torques produced about the TMJ may be greater than predicted by previous models that assumed a single line of force produced by each jaw muscle.

Analysis of Variance↗
PubMed2007

The influence of squat depth on maximal vertical jump performance.

An increase in the period over which a muscle generates force can lead to the generation of greater force and, therefore, for example in jumping, to greater jump height. The aim of this study was to examine the effect of squat depth on maximum vertical jump performance. We hypothesized that jump height would increase with increasing depth of squat due to the greater time available for the generation of muscular force. Ten participants performed jumps from preferred and deep squat positions. A computer model simulated jumps from the different starting postures. The participants showed no difference in jump height in jumps from deep and preferred positions. Simulated jumps produced similar kinematics to the participants' jumps. The optimal squat depth for the simulated jumps was the lowest position the model was able to jump from. Because jumping from a deep squat is rarely practised, it is unlikely that these jumps were optimally coordinated by the participants. Differences in experimental vertical ground reaction force patterns also suggest that jumps from a deep squat are not optimally coordinated. These results suggest there is the potential for athletes to increase jump performance by exploiting a greater range of motion.

Adult↗
PubMed2026

Mutational signatures in blood-brain barrier: mechanisms, computational insights, and clinical applications in precision oncology.

The blood - brain barrier (BBB) plays a central role in maintaining central nervous system (CNS) homeostasis, and its disruption is a defining feature of malignant brain tumors such as glioblastoma. Emerging evidence indicates that BBB dysfunction not only alters the tumor microenvironment but also shapes the mutational processes that drive genomic instability in CNS malignancies. This review synthesizes current understanding of the biological mechanisms linking BBB breakdown with distinct mutational signatures, including those arising from oxidative stress, hypoxia-induced replication stress, lipid peroxidation, inflammation, and metabolic reprogramming. Advances in next-generation sequencing, coupled with computational tools such as non-negative matrix factorization, Bayesian modeling, and deep learning, have enabled precise extraction of these signatures and their integration with multi-omics data. Clinically, BBB-associated mutational signatures offer significant promise for therapeutic stratification, prediction of treatment response, and noninvasive monitoring through cerebrospinal fluid - derived circulating tumor DNA. Despite these advances, challenges persist due to limited tissue accessibility, low-yield CSF samples, incomplete mechanistic models, and the lack of CNS-specific analytical frameworks. A deeper understanding of BBB-driven mutational processes, supported by improved computational approaches and integrative datasets, holds potential to advance precision oncology in neuro-oncology.

Humans↗
PubMed1995

Multiple identities and the integration of personality.

Life-history interviews show narrators to shift among multiple, often contradictory self-representations. This article outlines a model that accounts for how a relatively small set of self-symbols and metaphors can form a grammar-like system that simultaneously defines and integrates multiple identities. Drawing on generative theories from linguistics, anthropology, and music, the model proposes that this system provides a unitary deep structure that can be configured in various arrangements to yield multiple surface structures. Each "surface" identity constructs an individual's emotions and social relations--and what he or she accepts as "Me" and rejects as "not-Me"--into a distinct pattern, with identity per se appearing as a dialogic or fugue-like structure of opposed voices. Study-of-lives interviews conducted by the author in urban America and rural Morocco are used to present the model and to demonstrate the pivotal role played by multistable or "structurally ambiguous" symbols in anchoring reversible self-representations which integrate personality as a system of organized contraction. The musical analogy is emphasized in order to build a bridge toward current research in cognitive science and toward efforts to formulate a "state integration" theory of personality development.

Adult↗
PubMed2006

Region-specific reduction in entorhinal gamma oscillations and parvalbumin-immunoreactive neurons in animal models of psychiatric illness.

Psychiatric illnesses, particularly schizophrenia, are associated with disrupted markers for interneuronal function and interneuron-mediated brain rhythms such as gamma frequency oscillations. Here we investigate a possible link between these two observations in the entorhinal cortex and hippocampus by using a genetic and an acute model of psychiatric illness. Lysophosphatidic acid 1 receptor-deficient (LPA1-deficient) mice show psychomotor-gating deficits and neurochemical changes resembling those seen in postmortem schizophrenia studies. Similar deficits are seen acutely with antagonism of the NMDA subtype of glutamate receptor. Neither model induced any change in power or frequency of gamma rhythms generated by kainate in hippocampal slices. In contrast, a dramatic decrease in the power of gamma oscillations was seen in superficial, but not deep, medial entorhinal cortex layers in both models. Immunolabeling for GABA, parvalbumin, and calretinin in medial entorhinal cortex from LPA1-deficient mice showed an approximately 40% reduction in total GABA- and parvalbumin-containing neurons, but no change in the number of calretinin-positive neurons. This deficit was specific for layer II (LII). No change in the number of neurons positive for these markers was seen in the hippocampus. Acute NMDA receptor blockade, which selectively reduces synaptic drive to LII entorhinal interneurons, also disrupted gamma rhythms in a similar manner in superficial entorhinal cortex, but not in hippocampus. These data demonstrate an area-specific deficit in gamma rhythmogenesis in animal models of psychiatric illness and suggest that loss, or reduction in function, of interneurons having a large NMDA receptor expression may underlie the network dysfunction that is seen.

Animals↗
PubMed1992

Physiological interaction processes and radio-frequency energy absorption.

Because exposure to microwave fields at the resonant frequency may generate heat deep in the body, hyperthermia may result. This problem has been examined in an animal model to determine both the thresholds for response change and the steady-state thermoregulatory compensation for body heating during exposure at resonant (450 MHz) and supra-resonant (2,450 MHz) frequencies. Adult male squirrel monkeys, held in the far field of an antenna within an anechoic chamber, were exposed (10 min or 90 min) to either 450-MHz or 2,450-MHz CW fields (E polarization) in cool environments. Whole-body SARs ranged from 0-6 W/kg (450 MHz) and 0-9 W/kg (2,450 MHz). Colonic and several skin temperatures, metabolic heat production, and evaporative heat loss were monitored continuously. During brief RF exposures in the cold, the reduction of metabolic heat production was directly proportional to the SAR, but 2,450-MHz energy was a more efficient stimulus than was the resonant frequency. In the steady state, a regulated increase in deep body temperature accompanied exposure at resonance, not unlike that which occurs during exercise. Detailed analyses of the data indicate that temperature changes in the skin are the primary source of the neural signal for a change in physiological interaction processes during RF exposure in the cold.

Animals↗
PubMed2006

Carborne gamma-ray spectrometry. Calibration and applications.

Calibration of carborne gamma-ray spectrometry systems for (137)Cs is carried out with a source successively placed at 791 positions within an area of 34 m x 62 m. A computer model supplements the measurements. Hereby a sensitivity map for a surface contamination is generated as well as line and area sensitivities. Another model converts surface sensitivity to sensitivity for a deep contamination. Use of the sensitivity map for a non-homogeneous distribution of (137)Cs is demonstrated. Applications of line sensitivities for special tasks are discussed.

Automobiles↗
PubMed2025

HIV-phyloTSI: subtype-independent estimation of time since HIV-1 infection for cross-sectional measures of population incidence using deep sequence data.

BACKGROUND: Estimating the time since HIV infection (TSI) at population level is essential for tracking changes in the global HIV epidemic. Most methods for determining TSI give a binary classification of infections as recent or non-recent within a window of several months, and cannot assess the cumulative impact of an intervention. RESULTS: We developed a Random Forest Regression model, HIV-phyloTSI, which combines measures of within-host diversity and divergence to generate continuous TSI estimates directly from viral deep-sequencing data, with no need for additional variables. HIV-phyloTSI provides a continuous measure of TSI up to 9 years, with a mean absolute error of less than 12 months overall and less than 5 months for infections with a TSI of up to a year. It performs equally well for all major HIV subtypes based on data from African and European cohorts. CONCLUSIONS: We demonstrate how HIV-phyloTSI can be used for incidence estimates on a population level.

HIV Infections↗
PubMed2002

Explaining the latitudinal distribution of sunspots with deep meridional flow.

Sunspots, dark magnetic regions occurring at low latitudes on the Sun's surface, are tracers of the magnetic field generated by the dynamo mechanism. Recent solar dynamo models, which use the helioseismically determined solar rotation, indicate that sunspots should form at high latitudes, contrary to observations. We present a dynamo model with the correct latitudinal distribution of sunspots and demonstrate that this requires a meridional flow of material that penetrates deeper than hitherto believed, into the stable layers below the convection zone. Such a deep material flow may have important implications for turbulent convection and elemental abundance in the Sun and similar stars.

Journal Article↗
PubMed1998

High-frequency (600 Hz) SEP activities originating in the subcortical and cortical human somatosensory system.

Digitally high-pass filtered median nerve SEP show an oscillatory burst of low-amplitude high-frequency (600 Hz) wavelets superimposed on the N20 component which itself is generated by excitatory postsynaptic potentials of area 3b pyramidal cells. Prior studies using magnetoencephalography (MEG) localized one wavelet generator close to the primary somatosensory hand cortex. Since MEG recordings are biased towards tangentially oriented and superficial generators, a dipole source analysis of 32-channel electric SEP recordings was employed here to test for the possibility of deep and/or radially oriented burst generators: in 10 normal subjects low noise (16,000 averages) median nerve SEP were evaluated using dipole source analysis before and after applying a digital 475 Hz high-pass filter. Two main oscillatory 600 Hz burst sources were modeled; (i) a deep burst source close to the thalamus, most active in a time window between the brain-stem P14 and the cortical N20 sources, detectable in 7 of 10 subjects; most probably, this activity originates from deep axon segments of thalamocortical fibers; and (ii) a subsequent burst source timed around the N20 and located in the vicinity of the primary somatosensory hand cortex in all subjects, which was already known from MEG data. This superficial oscillatory source may be dominated by repetitive activity conducted in the terminal segments of the thalamocortical projection fibers initiated by the thalamic burst generator.

Brain Stem↗
PubMed2002

Modulation of mutagenic activity in meat samples after deep-frying in vegetable oils.

Previous studies have been carried out on the influence of frying fats on the formation of food mutagens, but most of them have been performed on model systems or under cooking conditions that are more frequent in northern countries. The objective of this work was to study the overall mutagenic activity generated in hamburgers and frankfurters deep-fried under cooking conditions that are normal practice in Spain and other Mediterranean countries, in order to determine if there was any modulation of the mutagenic activity with respect to other cooking conditions previously studied. Hamburgers were prepared from beef purchased in a butcher's shop. Frankfurters as well as the oils [olive, marc olive ('orujo'), sunflower and soya bean oil] and butter were purchased in a local supermarket. The samples were fried in a teflon-coated frying pan at 170-180 degrees C for 10, 20 or 30 min. The mutagens were extracted and the mutagenic activity evaluated using the Salmonella mammalian microsome assay with strain TA98. Two independent assays were carried out for each experimental condition. All the hamburgers showed a mutagenic activity that was more than four times higher than that of the controls. Frankfurters showed a lower mutagenic activity than hamburgers (fried under the same conditions) because they have a lower protein content and a higher fat content. Hamburgers fried in olive oil for 10 min showed a significant increase in the number of revertants with respect to the other oils, probably due to the fact that the temperature reached was approximately 10 degrees C higher. Longer frying times significantly increased the number of revertants in samples fried in oils, except in olive oil, probably due to its lower content of polyunsaturated fatty acids.

Animals↗
PubMed2006

Do intramural virtual electrodes facilitate successful defibrillation? Model-based analysis of experimental evidence.

INTRODUCTION: Recent computer model and experimental studies have suggested that microscopic intramural collagenous planes may facilitate successful defibrillation through the generation of shock-induced virtual electrodes deep within the ventricular wall. Evidence supporting the existence of intramural virtual electrodes has been drawn from several recent studies, which map shock-induced membrane potential (Vm) over the cut transmural surface of dissected segments of porcine left ventricle (LV). The artificially created transmural boundary in these experiments is impermeable to intracellular current. It is not known how this constraint limits the interpretation of these experiments in terms of the shock response of the intact ventricle. METHODS AND RESULTS: This study uses a realistic 3D computer model of LV myocardium to aid experimental interpretation. The model incorporates a microstructural description of intramural cleavage plane discontinuities measured by confocal microscopy of rat LV. Electrical shocks are applied across the model tissue, with and without introduced transmural boundaries. Shocks of varying strength (4-40 V/cm) are also applied to the model and the response analyzed. Results show that shock-induced Vm changes (deltaVm) on a transmural tissue boundary are significantly different to deltaVm of the intact ventricle, and the extent of difference depends on boundary orientation. However, the presence and qualitative behavior of intramural virtual electrodes is preserved irrespective of boundary placement. The model also confirms experimental observations that most rapid transmural activation occurs for shocks of strength 5-10 V/cm. Two distinct mechanisms suppress virtual electrode propagation, and hence slow tissue activation, outside of this optimal shock strength range. CONCLUSIONS: This study supports the hypothesis that distributed microscopic intramural virtual electrodes contribute to rapid activation of the ventricular wall during defibrillation.

Animals↗
PubMed2000

Time window control: a model for cerebellar function based on synchronization, reverberation, and time slicing.

We present a new hypothesis of cerebellar function that is based on synchronization, delayed reverberation, and time windows for triggering spikes. Our model suggests that granule cells admit mossy fiber activity to the parallel fibers only if the Golgi cells are firing synchronously and if the mossy-fiber spikes arrive within short and well-defined time windows. The concept of time window control organizes neuronal activity in discrete 'time slices' that can be used to discern meaningful information from background noise. In particular, Purkinje cell activity can trigger rebound spikes in deep cerebellar nuclei cells, which project via brain stem nuclei and mossy fibers back to the cerebellar cortex. Using a detailed model of deep cerebellar nuclei cells, we demonstrate that the delayed firing of rebound spikes is a robust mechanism so as to ensure that the reverberated activity re-arrives in the mossy fibers just during the granule-cell time window. Large network simulations reveal that synaptic plasticity (LTD and LTP) at the parallel fiber/Purkinje cell synapses that relies on the timing of the parallel fiber and climbing fiber activities allows the system to learn, store, and recall spatiotemporal patterns of spike activity. Climbing fiber spikes function both as teacher and as synchronization signals. The temporal characteristics of the climbing fiber activity are due to intrinsic oscillatory properties of inferior olivary neurons and to reverberating projections between deep cerebellar nuclei, the mesodiencephalic junction, and the inferior olive. Thus, the reverberating loops of the mossy fiber system and climbing fiber system may interact directly with the time windows provided by the circuitry of the cerebellar cortex so as to generate the appropriate spatio-temporal firing patterns in the deep cerebellar nuclei neurons that control premotor systems. In future studies the model will be extended in that high frequency simple spike activities will be included and that their relevance for motor control will be addressed.

Animals↗
PubMed1990

The influence of model parameter values on the prediction of skin surface temperature: I. Resting and surface insulation.

A model is presented of heat transfer and temperature distributions in the skin and superficial tissues. It is based on a finite difference numerical solution of the one-dimensional multilayer coupled bioheat equation. In this paper, the model is used to investigate the influence of the values of parameters chosen to represent the physiological and heat transfer processes on the temperature of the skin under resting conditions and after insulation of the skin surface. Equilibrium resting temperatures were strongly influenced by deep body temperature especially at lower heat transfer coefficients on the skin surface, but slightly affected by the values chosen for skin blood flow and metabolic heat generation; both the heat transfer coefficients and environmental temperature strongly influenced the surface temperature. After surface insulation the temperature elevation was strongly influenced by the thermal conductivities of tissues, skin blood flow and deep boundary temperature; metabolic heat generation was only significantly at unphysiologically high values.

Humans↗
PubMed2026

A multi-scale fusion model based on multi-phase contrast-enhanced CT for predicting pancreatic cancer resectability.

Purpose.Develop a multi-scale fusion model (MSFM) based on multi-phase contrast-enhanced computed tomography (CECT) to predict pancreatic cancer (PC) resectability, thereby assisting expert decision-making.Methods.This retrospective study enrolled 280 patients with PC from four institutions, which were randomly divided into a training cohort (202 patients) and an independent test cohort (78 patients). Three-phase CECT images (arterial, venous, and delayed phases) were used for modeling. The MSFM comprises two sub-networks: (1) a multi-phase fusion network for extracting cross-phase shared fusion features, (2) a phase-specific branch network for capturing phase-specific features; and a post-fusion strategy to generate the final predictive score by integrating the shared fusion features and three groups of phase-specific features. Additionally, a human-machine fusion deep learning model (HMfDL) was constructed by fusing the predictive score of the MSFM with expert assessments.Results.In the independent test, the MSFM achieved an AUC (area under the receiver operating characteristic curve) of 0.8385 (95% CI: 0.7521-0.9249), accuracy of 84.62%, sensitivity of 72.00%, and specificity of 90.57%. This performance outperformed single-phase models (AUC range: 0.7638-0.7781), two-phase models (AUC range: 0.7826-0.7864), and ten states-of-the-art classifiers (AUC range: 0.7404-0.7796). The HMfDL further improved the performance, reaching an AUC of 0.8626 (95% CI: 0.7853-0.9400), accuracy of 91.03%, sensitivity of 80.00%, and specificity of 96.23%. Notably, the HMfDL corrected 58.82% of misdiagnosis made by experts.Conclusions. The MSFM effectively fuses multi-phase CECT to enable highly accurate predictions of PC resectability, and provides valuable support for expert decision-making through HMfDL.

Humans↗
PubMed2025

SHICEDO: single-cell Hi-C data enhancement with reduced over-smoothing.

MOTIVATION: Single-cell Hi-C (scHi-C) technologies have significantly advanced our understanding of the 3D genome organization. However, scHi-C data are often sparse and noisy, leading to substantial computational challenges in downstream analyses. RESULTS: In this study, we introduce SHICEDO, a novel deep-learning model specifically designed to enhance scHi-C contact matrices by imputing missing or sparsely captured chromatin contacts through a generative adversarial framework. SHICEDO leverages the unique structural characteristics of scHi-C matrices to derive customized features that enable effective data enhancement. Additionally, the model incorporates a channel-wise attention mechanism to mitigate the over-smoothing issue commonly associated with scHi-C enhancement methods. Through simulations and real-data applications, we demonstrate that SHICEDO outperforms the state-of-the-art methods, achieving superior quantitative and qualitative results. Moreover, SHICEDO enhances key structural features in scHi-C data, thus enabling more precise delineation of chromatin structures such as A/B compartments, TAD-like domains, and chromatin loops. AVAILABILITY AND IMPLEMENTATION: SHICEDO is publicly available at https://github.com/wmalab/SHICEDO.

Single-Cell Analysis↗
PubMed2002

Bioengineering methods employed in the study of wound healing of sulphur mustard burns.

BACKGROUND/PURPOSE: Sulphur mustard (SM) is a potent incapacitating chemical warfare agent that remains a threat to war fighters and civilians worldwide. SM lesions may require weeks or months to heal, depending upon their severity. This study was undertaken to find a treatment regimen that promotes speedier healing of deep cutaneous SM burns in a weanling pig model. The principal objective of the study was to compare four treatment regimens and establish which achieved the shortest healing time. METHODS: Twelve Yorkshire Cross weanling pigs were exposed to SM liquid for 2h, generating six large deep dermal/full thickness burns on the ventrum of each animal. Three additional animals served as sham-exposed controls. Surgical intervention occurred at 48 h postexposure. Treatments included: (i) full-thickness debridement of the burns with a computer controlled, raster scanned continuous wave CO2 laser followed by autologous split-thickness skin grafting; (ii) full-thickness sharp surgical tangential excision followed by skin grafting, the 'Gold Standard' used in human deep dermal/full-thickness thermal burns management; (iii) partial-thickness laser ablation with no grafting; and (iv) partial-thickness sharp surgical excision with no grafting. Several non-invasive bioengineering methods were used to monitor the progress of wound healing throughout a 36-day healing period: reflectance colourimetry, evaporimetry, laser Doppler perfusion imaging and ballistometry. RESULTS: Bioengineering methods indicated that laser debridement followed by autologous split-thickness skin grafting was as efficacious in improving the wound healing of deep SM burns in weanling swine as the 'Gold Standard.' Regardless of the method of debridement, barrier function, skin colour and mechanical properties returned to near-normal levels within 15 days of treatment in the grafted sites. Regardless of surgical approach, blood flux levels remained approximately 50-60% of normal tissue throughout the 36-day postsurgical observation period. Mid-dermal debridement by sharp surgical tangential excision or laser ablation without the use of skin grafts did not produce as good a result as those attained through the use of grafts, but was better than no surgical treatment of the wounds. CONCLUSION: Bioengineering methods were useful in evaluating multiple characteristics during wound healing: (i) reflectance colourimetry for skin colour, (ii) evaporimetry to measure transepidermal water loss as an indicator of barrier function, (iii) laser Doppler perfusion imaging to assess cutaneous blood flow, and (iv) ballistometry to measure the mechanical properties of skin hardness and elasticity. Perhaps the most useful method was evaporimetry, as a restored barrier function was the best indicator of healed wounds. The use of reflectance colourimetry and ballistometry will continue in future wound healing studies for their contributions in judging cosmetic and functional outcomes. While useful, laser Doppler perfusion imaging was found to be rather time consuming. This methodology will be limited in the future to burn depth estimation prior to treatment, and for evaluation of pharmaceuticals specifically designed to improve or sustain blood flow into damaged areas.

Animals↗