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Results for “Model interpretability”

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At least 829 records · Page 46Linked to original sources

PubMed1999

Possibility of breakdown of overdamped and narrowing limits in low-frequency Raman spectra: phenomenological band-shape analysis using the multiple-random-telegraph model.

Depolarized low-frequency Raman spectra of liquid water and heavy water are investigated from 266 K to 356 K. The reduced Raman spectra below 250 cm(-1) are reproduced by a superposition of one relaxation mode and two damped harmonic oscillator modes. The multiple-random-telegraph (MRT) model, which takes into account inertia and memory effects, is applied to analyze the relaxation component. Two damped harmonic oscillators around 50 cm(-1) and 180 cm(-1) are known as a bendinglike mode and a stretchinglike mode, respectively. It is found that the intensity of the bendinglike mode in water (heavy water) gradually decreases with increasing temperature, and finally vanishes above about 296 K (306 K). The relaxation time of the MRT model is interpreted as representing the averaged lifetime of the vibrating unit. At high temperature, the relaxation time becomes short, that is to say, the vibrating unit is quickly destroyed before the 50 cm(-1) mode is oscillating sufficiently. In the present analysis, the strongly disrupted oscillation cannot be distinguished from the relaxation mode which includes the inertia and memory effects. It is found that the low-frequency Raman spectrum of liquid water at high temperature is a good example demonstrating an application of the MRT model.

Journal Article↗

PubMed2006

Robust, bistable patterning of the dorsal surface of the Drosophila embryo.

In many developing systems, the fate of a cell is determined by its position in a time-independent spatial distribution of a morphogen. However, during dorsal-ventral patterning in the Drosophila embryo, an initial low-level signal refines to a narrow, high-intensity band. This refinement suggests that cells respond to the local transient morphogen distribution that results from interactions between bone morphogenetic proteins (BMPs), their receptors, the BMP-binding proteins Sog and Tsg, the metalloprotease Tld, and a putative, positively regulated component that locally enhances surface binding of BMPs within the region of high signaling. We develop a computational model for dorsal surface patterning and show that, when positive feedback of a cell surface BMP-binding protein is incorporated, bistability in the kinetic interactions transduces the transient BMP distribution into a switch-like spatial distribution of the BMP-bound receptor. We also show that the inclusion of positive feedback leads to the observed contraction of signaling, because cells near the dorsal midline outcompete adjacent lateral cells for limited amounts of BMP. In the model, cells interpret the morphogen distribution by differentiating according to the history of their exposure rather than to a threshold concentration in a static spatial gradient of the morphogen.

Animals↗

PubMed1992

Evaluation strategies for some nonstandard conditionals during adolescence.

380 adolescents and young adults between the ages of 11 and 29 years participated in three experiments in which they were asked to evaluate both universally quantified nonstandard and standard conditionals using items of information bearing upon them. Subjects found it much easier to avoid a biconditional interpretation with the nonstandard than with the standard conditionals, which throws doubt on the explanation of desire for symmetry of biconditional conversion. It was argued, from data of other studies, that a modified version of the Piagetian view that biconditional conversion occurs as a result of a desire to avoid the complications of dealing with three factors explains most cases of such conversion in adolescence. Results also confirmed that it is more profitable to analyse performance on tasks of this kind using a two-stage model of interpretation and information use previously developed to explain performance with standard universally quantified conditionals than to view such tasks as providing truth-table values. Such an analysis was extended to the nonstandard conditionals studied in the present paper. The origins of the dramatic differences in information-use strategies adopted by adolescents for standard and nonstandard conditionals remain unclear.

Adolescent↗

PubMed2006

Magnetic resonance angiography of collateral vessel growth in a rabbit femoral artery ligation model.

Collateral vessel growth was visualized in a rabbit femoral artery ligation model by serial contrast-enhanced magnetic resonance angiography (MRA) at 1.5 T in comparison with X-ray angiography (XRA). XRA and MRA were performed directly after femoral artery ligation (day 0+) and after 7 and 21 days. XRA (in-plane resolution, 0.3x0.3 mm) was performed with arterial catheterization for fast injection of iodinated contrast agent just proximal to the aortic bifurcation. MRA (in-plane, 0.6x0.6 mm) was performed at 1.5 T with a five-element phased-array coil and slow injection of gadolinium-based MR contrast agent into an ear vein. Collateral vessel scores on two-dimensional XRA projections and on three-dimensional digitally subtracted rotational MRA maximum intensity projections were obtained by two observers and compared. Collateral vessel counts and minimal detectable vessel diameters for MRA and XRA were combined in a computational flow model to interpret differences in spatial detection limits between imaging modalities in terms of flow. Collateral vessel scores were significantly higher in the ligated limb at day 7 (P < 0.05) and more so at day 21 (P < 0.001), in comparison with day 0+ or in the non-ligated control limb on both XRA and MRA. Significantly more (smaller) vessels were visualized with XRA than with MRA, particularly on day 21 (P < 0.05). Inter-observer agreement was high for both XRA (kappa = 0.82) and MRA (kappa = 0.78). The flow model showed that collateral vessels with diameters > 0.3 mm scored by XRA as well as MRA represent nearly 100% of the total blood flow, whereas smaller (0.1-0.3 mm diameter) vessels that can only be detected with XRA contribute little to the blood flow. Serial contrast-enhanced MRA can non-invasively visualize sub-millimeter collateral vessels that represent nearly 100% of the restored blood flow, in a femoral artery ligation model.

Animals↗

PubMed1994

Small perturbations in nonlinear age-structured population equations.

A non-linear age-structured population dynamic model described by partial integro-differential equations is considered, where the non-linear term reflects the interaction among individuals. This non-linear model is interpreted as a perturbed linear one. An approximation method based on the ideas of averaging, of a slow time transformation and a power series expansion is suggested. The asymptotic properties of the approximate solution are analyzed. It is shown that the approximate solution remains close to the true solution as t-->infinity.

Aging↗

PubMedDate not supplied

Development of neural network QSPR models for Hansch substituent constants. 2. Applications in QSAR studies of HIV-1 reverse transcriptase and dihydrofolate reductase inhibitors.

In this paper, the applications of a Hansch substituent constant predictor(1) to Quantitative Structure-Activity Relationships (QSAR) studies of E. coli dihydrofolate reductase (DHFR) inhibitors 2,4-diamino-5-(substituted-benzyl)pyrimidines as well as HIV-1 reverse transcriptase (RT) inhibitors 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) derivatives are demonstrated. Both data sets contain functional groups for which the substituent constants (pi, MR, F and R) could not be found in standard substituent constant tables. The substituent constant predictor allowed us to derive predicted pi, MR, F and R values for all substituents in both data sets, thus enabling the generation of easily interpretable QSAR models of comparable or better predictivity than previous models.

Folic Acid Antagonists↗

PubMed1998

Interpreting indirect replies.

A model is proposed that explains how people arrive at specific interpretations of indirect replies. The model is based on Grice's (1975) conversational logic, coupled with Goffman's (1967) insights regarding face management. The model assumes that hearers, upon recognizing that a speaker has violated the relevance maxim, will generate an inference in order to make sense of the remark; this inference will then be based on the hearer's belief about why the violation occurred. Face management is assumed to be a major motivation for violating the relevance maxim, and thus it should serve as a frame for interpreting the violation. As a result, the most likely interpretation of an indirect reply is one that would be face-threatening in the situation. The results of three experiments provided support for these propositions. Specifically, relevance violations were generally interpreted as conveying nonliteral meaning. In these situations negative information was most face-threatening, and as a result the replies were usually interpreted as conveying negative information. In addition, when face management as "a reason" for a relevance violation was eliminated or contradicted, relevance violations became much more ambiguous and difficult to comprehend.

Female↗

PubMed2004

The chloroplast Rieske iron-sulfur protein. At the crossroad of electron transport and signal transduction.

We have addressed the functional and structural roles of three domains of the chloroplast Rieske iron-sulfur protein; that is, the flexible hinge that connects the transmembrane helix to the soluble cluster-bearing domain, the N-terminal stromal protruding domain, and the transmembrane helix. To this aim mutants were generated in the green alga Chlamydomonas reinhardtii. Their capacities to assemble the cytochrome b6f complex, perform plastoquinol oxidation, and signal redox-induced activation of the light-harvesting complex II kinase during state transition were tested in vivo. Deletion of one residue and extensions of up to five residues in the flexible hinge had no significant effect on complex accumulation or electron transfer efficiency. Deletion of three residues (Delta3G) dramatically decreased reaction rates by a factor of approximately 10. These data indicate that the chloroplast iron-sulfur protein-linking domain is much more flexible than that of its counterpart in mitochondria. Despite greatly slowed catalysis in the Delta3G mutant, there was no apparent delay in light-harvesting complex II kinase activation or state transitions. This indicates that conformational changes occurring in the Rieske protein did not represent a limiting step for kinase activation within the time scale tested. No phenotype could be associated with mutations in the N-terminal stromal-exposed domain. In contrast, the N17V mutation in the Rieske protein transmembrane helix resulted in a large decrease in the cytochrome f synthesis rate. This reveals that the Rieske protein transmembrane helix plays an active role in assembly-mediated control of cytochrome f synthesis. We propose a structural model to interpret this phenomenon based on the C. reinhardtii cytochrome b6f structure.

Amino Acid Sequence↗

PubMed2026

Decoding TnsC Filament Assembly in CRISPR-Associated Transposons Using Interpretable Deep Learning and Molecular Simulations.

CRISPR-associated transposons (CASTs) enable programmable DNA integration, yet how the TnsC regulator forms processive filaments on DNA to coordinate RNA-guided transposition in type V-K CAST systems remains unknown. Here, we integrate large-scale molecular simulations, interpretable deep learning using graph attention networks (GATs), and causal inference analyses to define the molecular determinants of TnsC filament nucleation and elongation. We show that TnsC nucleates by inducing localized DNA deformation that propagates along extended filaments, with Granger causality revealing that TnsC motions precede and predict DNA deformation. Interpretable GAT models demonstrate that elongation is determined during early recognition between incoming and DNA-bound subunits, followed by structural reorganization that regenerates the recruitment interface and enables processive assembly. These results elucidate the molecular mechanism of processive TnsC filament assembly and explain why isolated TnsC filaments preferentially elongate in the 5' → 3' direction, while accessory transposition factors can reshape the interaction landscape and alter filament growth polarity. Together, these findings advance our understanding of CAST function and inform the engineering of programmable DNA integration platforms. Beyond CAST systems, this work introduces an interpretable GAT approach as a general and transferable deep learning strategy for uncovering molecular mechanisms in biological systems, while demonstrating the power of causal inference for dissecting directional relationships in molecular dynamics.

Deep Learning↗

PubMed1976

Interpretation of osmotic pressure in solutions of one and two nondiffusible components.

Osmotic pressure data from aqueous solutions of nondiffusible serum albumin (BSA), chondroitin sulfate (CHS), and dextran T110 (D110), taken singly and in binary combinations, were interpreted in terms of excluded volume. The principal solvent was phosphate-buffered saline, pH 7.2, at 23 degrees C. Osmotic pressures were measured with a membrane osmometer fitted with Amicon PM-10 membranes. Data from each solution were fit by stepwise regression with a three- or four-term polynomial in integral powers of total nondiffusible solute concentration in accordance with the general solution theory of McMillan and Mayer (1945, J. Chem. Phys. 13:276) as extended by Yamakawa (1971, Modern Theory of Polymer Solutions, Harper & Row, New York). The date display a high internal consistency, and the results correlate well with published molecular weights and exclusion data where available. Number average molecular weights calculated from the "first virial coefficients" are: BSA, 67,000 +/- 11%; D110, 76,000 +/- 11%, CHS, 39,000 +/- 6%. Excluded volumes (in cubic centimeters per molecule) calculated from the "second virial coefficients" are: BSA, 0.97 X 10(-18); D110, 3.04 X 10(-18); CHS, 14.3 X 10(-18); BSA-D110, 6.8 X 10(-18); BSA-CHS, 7.8 X 10(-18). Uncertainty is about 30%. An empirical model for interpretation of calculated excluded volumes is proposed. It appears that CHS has the "largest" exclusion effect of the three molecules.

Animals↗

PubMed1983

Methodology for the differential diagnosis of a complex data set. A case study using data from routine CT scan examinations.

Data from routine CT scan examinations are employed to illustrate the use of the polychotomous logistic regression model as a statistical diagnostic tool. The assumptions of the model, the interpretation of its parameters, and its capabilities are described in detail. In carrying out the analysis on the CT data, a large, relatively sparse data set, many technical difficulties were encountered. Modifications to the methodology that were necessary to permit its implementation are described, and it is demonstrated that an unbiased analysis of T + 1 diagnostic categories can be implemented by separately performing T individual simple logistic analyses. The limitations of the methodology are discussed. It is hoped that this paper may serve as a basis for the practical implementation of the polychotomous logistic model in similar diagnostic settings.

Adult↗

PubMed2000

A three-dimensional, two-way, parabolic equation model for acoustic backscattering in a cylindrical coordinate system

A new PE model for solving three-dimensional, forward and backward sound propagation in a cylindrical coordinate system is presented. The model marches a wave field in the radial direction including the azimuthal diffraction effects, and solves for a backscattered field based on a three-dimensional, single scattering approach. A periodic sidewall boundary condition is applied for computations in a 360-degree sector, while an approximate sidewall boundary condition is used for calculation in a sector less than 360 degrees. These two sidewall boundary conditions are verified by the numerical results. The major drawback of using the cylindrical coordinate system, when the backscattering solution is valid within a limited area, is analyzed using a geometrical-optical interpretation. The model may be useful for studying three-dimensional backscattering phenomena comprising azimuthal diffraction effects.

Journal Article↗

PubMed1983

Physical principles for economies of skilled movements.

This paper presents some elementary principles regarding constraints on movements, which may be useful in modeling and interpreting motor control strategies for skilled movements. Movements which are optimum with respect to various objectives, or "costs", are analyzed and compared. The specific costs considered are related to movement time, distance, peak velocity, energy, peak acceleration, and rate of change of acceleration (jerk). The velocity patterns for the various minimum cost movements are compared with each other and with some skilled movement patterns. The concept of performance trade-offs between competing objectives is used to interpret the distance-time relationships observed in skilled movements. Examples of arm movements during violin bowing and jaw movements during speech are used to show how skilled movements are influenced by considerations of physical economy, or "ease", of movement. Minimum-cost solutions for the various costs, which include the effect of frictional forces, are given in Appendices.

Arm↗

PubMed2006

Nonlinear dependence of hydraulic conductivity on tissue deformation during intratumoral infusion.

Efficiency of intratumoral infusion for drug and gene delivery depends on intrinsic tissue structures as well as infusion-induced changes in these structures. To this end, we investigated effects of infusion pressure (P(inf)) and infusion-induced tissue deformation on infusion rate (Q) in three mouse tumor models (B16.F10, 4T1, and U87) and developed a poroelastic model for interpreting data and understanding mechanisms of fluid transport in tumors. The collagen concentrations in these tumors were 2.9+/-1.2, 12.2+/-0.9, and 18.1+/-3.5 microg/mg wet wt. of tissues, respectively. During the infusion, there existed a threshold infusion pressure (P(t)), below which fluid flow could not be initiated. The values of P(t) for these tumors were 7.36, 36.8, and 29.4 mmHg, respectively. Q was a bell-shaped function of P(inf) in 4T1 tumors but increased monotonically with increasing P(inf) in other tumors. These observations were consistent with results from numerical simulations based on the poroelastic model, suggesting that both the existence of P(t) and the nonlinear relationships between Q and P(inf) could be explained by infusion-induced tissue deformation that anisotropically affected the hydraulic conductivity of tissues. These results may be useful for further investigations of intratumoral infusion of drugs and genes.

Animals↗

PubMed2006

Frequency domain analysis of noise in simple gene circuits.

Recent advances in single cell methods have spurred progress in quantifying and analyzing stochastic fluctuations, or noise, in genetic networks. Many of these studies have focused on identifying the sources of noise and quantifying its magnitude, and at the same time, paying less attention to the frequency content of the noise. We have developed a frequency domain approach to extract the information contained in the frequency content of the noise. In this article we review our work in this area and extend it to explicitly consider sources of extrinsic and intrinsic noise. First we review applications of the frequency domain approach to several simple circuits, including a constitutively expressed gene, a gene regulated by transitions in its operator state, and a negatively autoregulated gene. We then review our recent experimental study, in which time-lapse microscopy was used to measure noise in the expression of green fluorescent protein in individual cells. The results demonstrate how changes in rate constants within the gene circuit are reflected in the spectral content of the noise in a manner consistent with the predictions derived through frequency domain analysis. The experimental results confirm our earlier theoretical prediction that negative autoregulation not only reduces the magnitude of the noise but shifts its content out to higher frequency. Finally, we develop a frequency domain model of gene expression that explicitly accounts for extrinsic noise at the transcriptional and translational levels. We apply the model to interpret a shift in the autocorrelation function of green fluorescent protein induced by perturbations of the translational process as a shift in the frequency spectrum of extrinsic noise and a decrease in its weighting relative to intrinsic noise.

Animals↗

PubMedDate not supplied

New combined log and tracer test interpretation method for identifying transfers in fissured aquifers.

Tracer tests represent the most appropriate approach for assessing hydrodispersive parameters such as transversal and longitudinal dispersivities or kinematic porosity on an aquifer scale. They are generally carried out by injecting a tracer in a borehole and measuring its concentration over time in neighboring boreholes by extracted volume sampling or downhole measurements. Logging is one of the most suitable methods for evaluating fissured reservoirs. But short circuits between fractures with different hydraulic potential through boreholes induce mixing phenomena that cannot be avoided without packers. This mixing can shift the breakthrough curves deduced from the logs for each producing fracture and distort determination of their location. The method proposed in this paper aims at measuring the flow rate and the solute breakthrough for hydraulically active fractures, in open boreholes. It involves estimating a velocity profile along the borehole column by the analysis of two successive logs: a shift function according to depth is thus determined by comparison between log portions on each successive one. The velocity gradients reflect the inward or outward flow rates produced by each fracture. On the basis of these flow rates, it is possible to determine the mixing effects inside the borehole and then to plot unbiased breakthrough curves for each producing fracture. This method was applied at a granitic site in the eastern Pyrenees. In spite of some questionable limitations, the results showed that the method seems adapted to situations with many fractures. The precise hydraulic pattern which is obtained at the borehole scale is discussed in terms of a dual porosity model. Furthermore, interpretation of the breakthrough curves for fractures corrected for mixing effects revealed that Peclet numbers are strongly underestimated if this phenomenon is not considered.

Environmental Monitoring↗

PubMed1995

Synthesis of 2'-fluoro-5-[11C]-methyl-1-beta-D-arabinofuranosyluracil ([11C]-FMAU): a potential nucleoside analog for in vivo study of cellular proliferation with PET.

Rapid in vivo catabolism limits the use of currently available radiotracers used in tumor proliferation studies with PET. This is manifested by the need to develop complex mathematical models to interpret kinetic and metabolite data obtained from imaging studies with agents such as carbon-11 labeled thymidine. A potential carbon-11 labeled radiotracer for cellular proliferation, 2'-fluoro-5-([11C]-methyl)-1-beta-D-arabinofuranosyluracil (FMAU), has been prepared using a previously described method for preparation of [11C]methyl-thymidine where selective alkylation of a pyrimidyl dianion is accomplished with [11C]methyl iodide at the 5-position of the pyrimidine ring. FMAU shares many in vivo characteristics of thymidine, including cellular transport, phosphorylation by mammalian kinase, and incorporation into DNA. Most importantly, in vivo catabolism of FMAU is limited, potentially yielding simplified kinetic models for determination of cellular proliferation with positron emission tomography.

Animals↗

PubMed1991

Effect of aniosmotic media on the volume of the T-lymphocyte nucleus.

Time-resolved measurements of the nuclear volume response of human peripheral T-lymphocytes, under aniosmotic conditions, are presented. In the experiments slit scanning FlowCytometry methods were used. We propose an extension to the standard solid viscoelastic model to interpret the observed dynamical behavior of the nucleus. It is shown that experimental and theoretical evidence indicates a passive nuclear response merely induced by a mechanical link (i.e., the cytoskeleton) between the cell membrane and the nuclear envelope. Implications of this work to the field of cellular mechanics and cytoskeletal rheology are surveyed.

Cell Nucleus↗