Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Generative models”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 631 records · Page 35Linked to original sources
PubMed1995

Detection of vulnerability loci by association and sib-pair methods.

A haplotype-based haplotype relative risk (HHRR) analysis of simulated data for 200 affected offspring and their parents (Genetic Analysis Workshop 9, Problem 1) detected linkage disequilibrium at 2 of 360 marker loci. An additive model was suggested but not proven by haplotypes of affected vs. unaffected offspring. These findings were consistent with the generating model. Affected sib pair analysis failed to detect additional loci. Discussion among workshop participants suggested that the chi-square test used here (2 [transmitted vs. nontransmitted] x n [alleles] for each locus) was invalid because of the nonindependence of proportions of transmitted alleles. In post-workshop analyses, transmission disequilibrium tests (TDTs) for each allele at each locus detected only the true associations if p values were corrected by one of two methods: Bonferroni correction for 2,035 TDTs, or correcting each test for n (number of tests at the locus) minus 1 and then for the number of loci tested. Screening loci for linkage disequilibrium requires careful attention to correction for multiple comparisons.

Alleles↗
PubMed1998

Assessment of regional left ventricular wall stress after myocardial infarction by echocardiography-based structural analysis.

OBJECTIVES: The objective of this study was to determine the distribution of regional left ventricular (LV) wall stress after myocardial infarction (MI). BACKGROUND: After a large MI, structural changes occur in the heart that ultimately may lead to alterations in LV size and shape, a process generally referred to as ventricular remodeling. Regional variation in myocardial wall stress may be responsible for initiation of physiologic and cellular changes that result in myocardial hypertrophy, dilatation, and remodeling after MI. Simplified geometric analytic methods of estimating global LV wall stress cannot determine regional variation such as that occurring after MI. METHODS AND RESULTS: To assess regional LV wall stress after MI, we applied the finite element method to patient-specific end-systolic LV models generated from echocardiographic imaging. After validation by comparison with analytic solutions of LV wall stress in idealized ventricles, LV models were constructed from rotated orthogonal apical images from 13 normal volunteers, 16 patients with recent (<4 days) anterior MI, and 7 patients with recent infero-posterior MI. The mean Von Mises stress was calculated for the entire LV and for 5 separate regions of the LV. Von Mises LV wall stress was increased globally in patients with anterior MI (211 +/- 46 kdyne/cm2; P < .002) or infero-posterior MI (175 +/- 23 kdyne/cm2; P = .04) compared with normal patients (144 +/- 57 kdyne/cm2). Global wall stress correlated directly with ejection fraction (P < .0001) and inversely with wall motion index (P < .004) in patients with anterior MI. Wall stress in the apical regions was increased by a factor of 2.3 in patients with anterior MI (P < .0001), whereas other regions did not differ from normal patients. There were no individual regions that were significantly different from normal in patients with infero-posterior MI. CONCLUSIONS: Anterior MI is associated with an increase in apical end-systolic wall stress compared with normal and infero-posterior MI. This may be an important stimulus for LV remodeling after anterior MI.

Female↗
PubMed1999

Conjoint recognition.

The process-dissociation model has stimulated important advances in the study of dual-process conceptions of memory. The authors review some limiting properties of that model and consider the degree of support for its parent theory (the recollection-familiarity distinction). A 2nd-generation model (conjoint recognition) is proposed that addresses these limitations and supplies additional capabilities, such as goodness-of-fit tests, the ability to measure dual processes for false-memory responses, and statistical procedures for testing within- and between-conditions hypotheses about its parameters. The conjoint-recognition model also implements an alternative theoretical interpretation (the identity-similarity distinction of fuzzy-trace theory). Worked applications to data are provided.

Adolescent↗
PubMed2004

Computer-aided tissue engineering: overview, scope and challenges.

Advances in computer-aided technology and its application with biology, engineering and information science to tissue engineering have evolved a new field of computer-aided tissue engineering (CATE). This emerging field encompasses computer-aided design (CAD), image processing, manufacturing and solid free-form fabrication (SFF) for modelling, designing, simulation and manufacturing of biological tissue and organ substitutes. The present Review describes some salient advances in this field, particularly in computer-aided tissue modeling, computer-aided tissue informatics and computer-aided tissue scaffold design and fabrication. Methodologies of development of CATE modelling from high-resolution non-invasive imaging and image-based three-dimensional reconstruction, and various reconstructive techniques for CAD-based tissue modelling generation will be described. The latest development in SFF to tissue engineering and a framework of bio-blueprint modelling for three-dimensional cell and organ printing will also be introduced.

Animals↗
PubMed2006

Mimicking the action of GroEL in molecular dynamics simulations: application to the refinement of protein structures.

Bacterial chaperonin, GroEL, together with its co-chaperonin, GroES, facilitates the folding of a variety of polypeptides. Experiments suggest that GroEL stimulates protein folding by multiple cycles of binding and release. Misfolded proteins first bind to an exposed hydrophobic surface on GroEL. GroES then encapsulates the substrate and triggers its release into the central cavity of the GroEL/ES complex for folding. In this work, we investigate the possibility to facilitate protein folding in molecular dynamics simulations by mimicking the effects of GroEL/ES namely, repeated binding and release, together with spatial confinement. During the binding stage, the (metastable) partially folded proteins are allowed to attach spontaneously to a hydrophobic surface within the simulation box. This destabilizes the structures, which are then transferred into a spatially confined cavity for folding. The approach has been tested by attempting to refine protein structural models generated using the ROSETTA procedure for ab initio structure prediction. Dramatic improvements in regard to the deviation of protein models from the corresponding experimental structures were observed. The results suggest that the primary effects of the GroEL/ES system can be mimicked in a simple coarse-grained manner and be used to facilitate protein folding in molecular dynamics simulations. Furthermore, the results support the assumption that the spatial confinement in GroEL/ES assists the folding of encapsulated proteins.

Algorithms↗
PubMed2005

Three-dimensional quantitative structure-activity relationship analysis of cytochromes p450: effect of incorporating higher-affinity ligands and potential new applications.

Recently, two new classes of reversible inhibitors, the benzbromarones (BZBRs) and the N-3 substituted phenobarbitals (PBs), were used to study the active site characteristics of CYP2C9 and 2C19, respectively. Since these ligands are some of the first CYP2C ligands to extend into the low nanomolar K(i) range (K(i) < 100 nM), they were subjected to three-dimensional quantitative structure-activity relationship (3D-QSAR) analysis. Given that BZBRs or the PB ligands bind very tightly, it can be assumed that these structures complement the binding pocket(s) for these enzymes. Thus, the resulting models should output a 3D arrangement of interaction sites predicted to be important for near optimal binding to the CYP2C9 and CYP2C19 enzymes. These predicted interaction regions may then improve the ability to predict drug-drug interactions. The resulting models generated from these new high affinity ligands are discussed, as are novel uses of 3D-QSAR and molecular modeling techniques that may be useful in the study of cytochromes P450 specifically.

Cytochrome P-450 Enzyme System↗
PubMed2006

Beyond logistic regression: structural equations modelling for binary variables and its application to investigating unobserved confounders.

BACKGROUND: Structural equation modelling (SEM) has been increasingly used in medical statistics for solving a system of related regression equations. However, a great obstacle for its wider use has been its difficulty in handling categorical variables within the framework of generalised linear models. METHODS: A large data set with a known structure among two related outcomes and three independent variables was generated to investigate the use of Yule's transformation of odds ratio (OR) into Q-metric by (OR-1)/(OR+1) to approximate Pearson's correlation coefficients between binary variables whose covariance structure can be further analysed by SEM. Percent of correctly classified events and non-events was compared with the classification obtained by logistic regression. The performance of SEM based on Q-metric was also checked on a small (N = 100) random sample of the data generated and on a real data set. RESULTS: SEM successfully recovered the generated model structure. SEM of real data suggested a significant influence of a latent confounding variable which would have not been detectable by standard logistic regression. SEM classification performance was broadly similar to that of the logistic regression. CONCLUSION: The analysis of binary data can be greatly enhanced by Yule's transformation of odds ratios into estimated correlation matrix that can be further analysed by SEM. The interpretation of results is aided by expressing them as odds ratios which are the most frequently used measure of effect in medical statistics.

Cesarean Section↗
PubMed2003

The academic trajectories of immigrant youths: analysis within and across cohorts.

Two nationally representative cohorts--from the National Educational Longitudinal Study (NELS) and High School and Beyond (HSB)--were used to examine the effects of generation and duration of residence on students' performance on standardized tests over a two-year period. In multivariate models, generational status predicts variation in students' performance on baseline (sophomore) tests, with effects stronger for the later age cohort (NELS) than for the earlier age cohort (HSB). With regard to the trajectory of achievement, generational status has a greatly reduced role for both cohorts. The best predictors of the trajectory of achievement are not those that are based on nativity per se, but those that reflect the social environment experienced in the United States (i.e., ethnicity and family's socioeconomic status).

Acculturation↗
PubMed2002

Experimental rodent models of brainstem tumors.

Despite recent advances in surgical technology, resection is not an option for many brainstem tumors. Experimental models have played essential roles in examining new approaches to therapy. The objective of the present study was to generate models by determining coordinates for safe inoculation into the brainstem of mice and rats, and to establish whether the implantation of heterotopic cells would create reproducible survival curves. Morbidity and survival studies were used to map stereotactic coordinates allowing successful inoculation of tumor cells. Survival studies were used to investigate the time course of tumor growth. Tumor location was examined by light microscopy and magnetic resonance imaging. Mice survived injections of 2 microL of saline at interaural, lateral, and depth coordinates of -2.5, 1.0, and 3.5 mm and -1.5, 1.0, and 3.5 mm. Rats survived injections at interaural, lateral, and depth coordinates of -2.0, 2.0, and 7.0 mm and -3.0, 0, and 7.0 mm. Median survival of mice challenged with 5 x 10(5) EMT6 and 10(4) B16 tumor cells was 11 and 10 days, respectively. Median survival for rats challenged with 10(4) 9L and F98 cells was 14 and 13 days, respectively. The present study demonstrates a feasible approach to preparing models of brainstem tumors. Limitations of these models are discussed.

Animals↗
PubMed1997

[A model for handling grievances in nursing services].

A model for management of grievances in a nursing service is described, in terms of the guidelines for model generation, based on a qualitative, exploratory, descriptive and theory generating research strategy and design. Potgieter's (1992) research served as the conceptual framework for the description of a model case. The statements derived from this description was used as basis for the description of the model. The central concepts were identified, defined and classified. The model was implemented in practice and was evaluated by means of a retrospective case study. Guidelines for the implementation of the model were consequently described and the model was positively evaluated by a panel of experts. The testing of hypothesis is recommended to validate the model.

Employee Grievances↗
PubMed1992

Alloplastic cranial implants made from computed tomographic scan-generated casts.

The complexity of cranioplasty increases with increased defect size. It is difficult to produce a symmetric, accurate implant presurgically or at the time of surgery when the defect is greater than 50 cm2. The procedure is also more difficult to perform when the defect is located in the temporal, infratemporal, or frontal areas. A new procedure generates a three-dimensional cast of the skull through computed tomography and computer-aided design reformation. This article describes the process of model generation and the production of a preprocessed cranial implant. To date, six cranial implants have been made with this technique. The whole head models are accurate and help the neurosurgeon-prosthodontist team in the creation of a symmetric, anatomically correct restoration. It is the technique of choice for large implants or where the cranial bones are thin. It is not necessary to augment or alter the implant during surgery. The technique reduces surgical time, and postsurgical complications have been minimal.

Artificial Intelligence↗
PubMedDate not supplied

Optimal synthesis of protein purification processes.

There has been an increasing interest in the development of systematic methods for the synthesis of purification steps for biotechnological products, which are often the most difficult and costly stages in a biochemical process. Chromatographic processes are extensively used in the purification of multicomponent biotechnological systems. One of the main challenges in the synthesis of purification processes is the appropriate selection and sequencing of chromatographic steps that are capable of producing the desired product at an acceptable cost and quality. This paper describes mathematical models and solution strategies based on mixed integer linear programming (MILP) for the synthesis of multistep purification processes. First, an optimization model is proposed that uses physicochemical data on a protein mixture, which contains the desired product, to select a sequence of operations with the minimum number of steps from a set of candidate chromatographic techniques that must achieve a specified purity level. Since several sequences that have the minimum number of steps may satisfy the purity level, it is possible to obtain the one that maximizes final purity. Then, a second model that may use the total number of steps obtained in the first model generates a solution with the maximum purity of the product. Whenever the sequence does not affect the final purity or more generally does not impact the objective function, alternative models that are of smaller size are developed for the optimal selection of steps. The models are tested in several examples, containing up to 13 contaminants and a set of 22 candidate high-resolution steps, generating sequences of six operations, and are compared to the current synthesis approaches.

Biotechnology↗
PubMed1993

Computer model of membrane current and intracellular Ca2+ flux in the isolated guinea pig ventricular myocyte.

This paper presents the equations and responses of a mathematical model that simulates the transmembrane current and intracellular concentrations of Ca2+ ([Ca2+]), Na+ ([Na+]), and K+ ([K+]) of an isolated guinea pig myocyte. The structure of the model is closely related to the formulation of DiFrancesco and Noble (9). Quantitative values are based on a large number of experimental constraints, taken from the literature on isolated myocytes as well as our own experimental studies, that describe the properties of individual channels and integrated responses of whole cells under a variety of conditions. The model was constructed as a homeostatic system. The equilibrium of the model corresponds to the resting potential and intracellular ionic concentrations of unstimulated myocytes. The model generates deviations from equilibrium corresponding to the behavior of cells after stimulation of action potentials at different rates, blockade of Na-K-adenosinetriphosphatase (ATPase), reduction in extracellular [K+], and injection of constant depolarizing current. Simulations from the model suggest that changes in myoplasmic [Ca2+] at different stimulation rates, the generation of restitution and postextrasystolic potentiation, and the development of intracellular [Ca2+] oscillations arise simply from different interactions between uptake of Ca2+ into the sarcoplasmic reticulum via the Ca(2+)-ATPase, Ca(2+)-induced Ca2+ release of Ca2+ into the myoplasm, flux between regions of uptake and release, and leakage between sarcoplasmic reticulum and myoplasm. The model also demonstrates that a wide variety of basic electrophysiological responses of the isolated guinea pig myocyte can be simulated with quantitative precision by a single set of equations based on experimentally measured transmembrane current and intracellular [Ca2+] and [Na+].

Action Potentials↗
PubMed1996

Non-isotopic method for quantitation of platelets and erythrocytes in experimental thrombi.

Experimental animal models of thrombosis have been established in several species to examine factors responsible for thrombotic disorders in man. One technical facet of all thrombosis models is the need to quantitate cell deposition on thrombogenic surfaces, and this is routinely accomplished with radioisotopic labeling of specific components. Data reported here demonstrate that formalin-fixed thrombi can be hydrolyzed with chymotrypsin allowing recovery and quantitation of platelets and erythrocytes incorporated within the clot. Recovery of platelets from in vitro generated, model thrombi averaged 99 +/- 10% (mean +/- 1 SD; n = 7; range 88-116%) of calculated content; recovery of erythrocytes was 94.1 +/- 1.1% (n = 6) as measured by recovery of cellular hemoglobin after chymotrypsin hydrolysis of clots. Chymotrypsin was also shown to release platelets and erythrocytes from string-bound thrombi generated in vivo with an arterio-venous shunt model in beagle dogs. Platelet recovery from these string clots after chymotrypsin hydrolysis was independently verified with a quantitative Western blot assay of platelet antigens. These data demonstrate that experimental thrombi can be hydrolyzed with chymotrypsin, thereby not only eliminating the need for radioisotopes, but also permitting flow cytometric analysis of cells comprising the thrombus.

Animals↗
PubMed1997

The power of iterated generalized least squares (GLS) method to detect direct relationships in the analysis of correlated quantitative traits.

We examined the power of the stepwise iterated generalized least squares (GLS) method by modeling the relationship between quantitative traits and other variables using the simulated data for Problem 2A. The comparison between the generating model provided by the workshop and the results of the stepwise iterated GLS model showed that this method could be used as a first step in identifying the underlying model for genetic data. The estimated covariance matrices also provide useful information about the genetic properties of the traits.

Computer Simulation↗
PubMed2005

Statistical face models for the rediction of soft-tissue deformations after orthognathic osteotomies.

This paper describes a technique to approximately predict the facial morphology after standardized orthognathic ostoetomies. The technique only relies on the outer facial morphology represented as a set of surface points and does not require computed tomography (CT) images as input. Surface points may either be taken from 3D surface scans or from 3D positions palpated on the face using a tracking system. The method is based on a statistical model generated from a set of pre- and postoperative 3D surface scans of patients that underwent the same standardized surgery. The model contains both the variability of preoperative facial morphologies and the corresponding postoperative deformations. After fitting the preoperative part to 3D data from a new patient the preoperative face is approximated by the model and the preiction of the postoperative morphology can be extracted at the same time. We built a model based on a set of 15 patient data sets and tested the predictive power in leave-one-out tests for a set of relevant cephalometric landmarks. The average prediction error was found to be between 0.3 and 1.2 mm at all important facial landmarks in the relevant areas of upper and lower jaw. Thus the technique provides an easy and powerful way of prediction which avoids time, cost and radiation required by other prediction techniques such as those based on CT scans.

Computer Simulation↗
PubMed1980

Intracardiac electrogram parameters, electrode surface area and pacer input impedance: their correlations.

Small surface area electrodes are accused of sensing defects which were related to alterations that they induce in the endocardiac electrograms. Since several factors affect the cardiac signal coming from electrode to sensing circuit, i.e. electrode surface area, electrode-tissue interface, pacemaker input impedance and sensing amplifier pass-band, Authors present their studies performed on 252 implanted electrodes of various type. Study was carried out by connecting in parallel to the recorder a variable resistor in order to simulate different pacer input impedances. The results showed a significant reduction in RS amplitude when recorder was paralleled with resistor values lower than 40 K. Slew rates showed a similar behaviours since RS steep tract did not change his duration with load, while total QRS duration is reduced. High speed analysis has shown that the RS segment is not linear in about 40% of cases: the main tract is used for calculations. The most significant attenuations and distortions of endocardial electrogram were observed with smallest electrodes and lowest resistances parallel connected: in these cases the sensing impedance at the electrode-tissue interface appears to be between 3 to 5 K ohms. The results suggest that the most of the alledged sensing faults experienced in the past were probably due to small tip electrodes connected to low input impedance generators or to impending failure situations. The AA. conclude that the main question does not concerne a true electrode inefficiency but a wrongly chosen pacemaker-electrode combination, i.e. small tip electrode connected with old generator models. To avoid the evaluation error, it would be instrumental that the pacemaker manufacturers would specify input characteristics of their generators. So, the implanting clinician becomes able to exactly evaluate the true signal arriving to the sensing circuit by connecting in parallel with the recorder input a resistor whose value approximates the input resistance of the generator to be implanted.

Cardiac Pacing, Artificial↗
PubMed1996

Testing models of female reproductive migratory behaviour and population structure in the Caribbean hawksbill turtle, Eretmochelys imbricata, with mtDNA sequences.

Information on the reproductive behaviour and population structure of female hawksbill turtles, Eretmochelys imbricata, is necessary to define conservation priorities for this highly endangered species. Two hypotheses to explain female nest site choice, natal homing and social facilitation, were tested by analyzing mtDNA control region sequences of 103 individuals from seven nesting colonies in the Caribbean and western Atlantic. Under the social facilitation model, newly mature females follow older females to a nesting location, and subsequently use this site for future nesting. This model generates an expectation that female lineages will be homogenized among regional nesting colonies. Contrary to expectations of the social facilitation model, mtDNA lineages were highly structured among western Atlantic nesting colonies. These analyses identified at least 6 female breeding stocks in the Caribbean and western Atlantic and support a natal homing model for recruitment of breeding females. Reproductive populations are effectively isolated over ecological time scales, and recovery plans for this species should include protection at the level of individual nesting colonies.

Animals↗