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Results for “reduced representation sequencing”

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PubMed1999

Crossover accelerates evolution in GAs with a Babel-like fitness landscape: mathematical analyses.

The effectiveness of crossover in accelerating evolution in genetic algorithms (GAs) is studied with a haploid finite population of bit sequences. A Babel-like fitness landscape is assumed. There is a single bit sequence (schema) that is significantly more advantageous than all the others. We study the time until domination of the advantageous schema (Τ&subd;). Evolution proceeds with appearance, spread, and domination of the advantageous schema. The most important process determining Τ&subd; is the appearance (creation) of the advantageous schema. Crossover helps this creation process and enhances the rate of evolution. To study this effect, we first establish an analytical method to estimate Τ&subd; with or without crossover. Then, we conduct a numerical analysis using the frequency vector representation of the population with the recurrence relations formulated after GA operations. Finally, we carry out direct computer simulations with simple GAs operating on a population of binary strings directly prepared in the computer memory to examine the performance of the two analytical methods. It is shown that Τ&subd; is reduced greatly by crossover with a mildly high rate when the mutation rate is adjusted to a moderate value and that an advantageous schema has a fairly larger order (the number of bits). From these observations, we can determine implementation criteria for GAs, which are useful when we are applying GAs to engineering problems having a conspicuously discontinuous fitness landscape.

Algorithms↗

PubMed2003

Mental extrapolation of target position is strongest with weak motion signals and motor responses.

Some accounts hold that the position of moving objects is extrapolated either in visual perception or visual short-term memory ("representational momentum"). However, some studies did not find forward displacement of the final position when smooth motion was used, whereas reliable displacement was observed with implied motion. To resolve this conflict, the frequency of position changes was varied to sample motion types between the extreme cases of implied and smooth motion. A continuous function relating frequency of target change and displacement was found: Displacement increased when the frequency of position changes was reduced. Further, the response mode was varied. Probe judgments produced less forward displacement than motor judgments such as mouse or natural pointing movements. Also, localization judgments were susceptible to motion context, but not to variations of probe shape or expectancy about trajectory length. It is suggested that forward displacement results from the extrapolation of the next step in the observed motion sequence.

Analysis of Variance↗

PubMed1976

Reversal of the physiological effects of monocular deprivation in the kitten's visual cortex.

1. Twenty-three kittens were monocularly deprived of vision until the age of 4, 5, 6 or 7 weeks. Their deprived eyes were then opened, and their experienced eyes shut for a further 3-63 days. After this time physiological recordings were made in the visual cortex, area 17. Three control kittens, monocularly deprived for various periods, showed that at the time of reverse-suturing, few neurones could be influenced at all from the deprived eye. 2. Following reverse-suturing, the initially deprived eye regained control of cortical neurones. This switch of cortical ocular dominance was most rapid following reverse-suturing at the age of 4 weeks. Delaying the age of reverse-suturing reduced the rate and then the extent of the cortical ocular dominance changes. 3. The cortex of reverse-sutured kittens is divided into regions of cells dominated by one eye or the other. The relative sizes of these ocular dominance columns changed during reversed deprivation. The columns devoted to the initially deprived eye were very small in animals reverse-sutured for brief periods, but in animals that underwent longer periods of reversed deprivation, the columns driven by that eye were larger, while those devoted to the initially open eye were smaller. 4. Clear progressions of orientation columns across the cortex were apparent in many of the kittens, but, in contrast to the situation in normal or strabismic kittens, these sequences were disrupted at the borders of eye dominance columns: the cortical representations of orientation and ocular dominance were not independent. 5. Binocular units in these kittens were rather rare, but those that could be found often had dissimilar receptive field properties in the two eyes. Commonly, a cell would have a normal orientation selective receptive field in one eye, and an immature, unselective receptive field in the other. Cells that had orientation selective receptive fields in both eyes often had greatly differing orientation preferences in the two eyes, occasionally by nearly 90 degrees. 6. During the reversal of deprivation effects, the proportion of receptive fields exhibiting mature properties declined in the initially experienced eye, while the proportion increased in the initially deprived eye. Similarly, the average band width of orientation tuning of receptive fields in the initially deprived eye decreased, while that of receptive fields in the initially experienced eye increased. 7. One kitten was reverse-sutured twice, to demonstrate that cortical ocular dominance may be reversed a second time, even after one reversal of ocular dominance. 8. It is suggested that the sensitive period for cortical binocular development consists of two phases. In the first phase, all cortical neurones may be modified by experience, but the rate at which they may be modified decreases with age. In the second phase, an increasing number of cortical neurones becomes fixed in their properties, while those that remain modifiable are as modifiable as they were at the end of the first phase. 9...

Age Factors↗

PubMed1998

Interactive modeling of supramolecular assemblies.

The modeling of supramolecular structure presents two major challenges: (1) managing the large amount of sequence, structural and biochemical data, and (2) presenting the data to the user in a flexible and comprehensible manner that addresses these problems. We describe a visualization environment for the creation and analysis of supramolecular models. A set of modular symmetry tools, collectively called SymGen, has been created, providing a flexible platform for the creation of complex assemblies, with interactive control of all symmetry elements and their parameters. A second tool, SymSearch, allows a range of parameters defined within SymGen to be sampled and the resulting conformations to be evaluated. The environment avoids information overload, caused by the large number of atoms in supramolecular complexes, by using a multiresolution spherical harmonic representation that allows the user to display only essential features. Spherical harmonics also enables control of the triangulation level, allowing the user to reduce the complexity of the geometric description to retain interactive speed. The visual fidelity of the surface data is retained by using texture maps that are independent of the resolution of the underlying triangulation. We describe the design and implementation of this environment, and three illustrative examples of its utility.

Capsid↗

PubMedDate not supplied

[Biomedical research: the debate on the reduction and emergence concepts].

The theoretical bases of medical knowledge exert a strong influence on both clinical practice and representations of living and health. In this perspective, reduction and emergence notions play a major role. Microreduction is the predominant analytical strategy used today in biology, as it is usually considered that essential life mechanisms can be reduced to molecular processes. Likewise, macroreduction proposes that parts can be defined in terms of their belonging to wholes, as it is usually assumed, for instance, in genetic epidemiology. With regard to emergence, this notion, which focuses on properties of a whole that cannot be deduced from properties of its parts, is consistent with both nature of living and evolution theory. The apparent success of reduction like analytical modality has generated in scientific community and public opinion an ideological reductionism, which corresponds, ontologically, to both physicalism (things can be entirely understood in terms of their parts), and atomism (things go their own way, independently of other things). Genetic reductionism has generated new cosmological representations of living, where past, present and future of living beings could potentially be deduced from fallacious, simple views of genome sequences. These views may lead to quantitative or qualitative definitions of standard patterns and hierarchies. In practical terms, research activity should integrate limits, strains as well as reductionism advantages. Biologists should also consider risks associated with an ideological, unrestricted reductionism, applied to any existence aspect, a notion with questionable legitimacy and with potential ethical, philosophical, and political involvements that go beyond the simple selection of a research strategy.

Biomedical Research↗

PubMed2004

Normal mode analysis of proteins: a comparison of rigid cluster modes with C(alpha) coarse graining.

The ability to infer dynamic motions from an equilibrium (static) conformation of a protein can be essential in establishing structure-function relationships. In particular, the low-frequency motions are of functional interest because statistical mechanics predicts these motions will have the largest amplitudes. In this paper, we address the computational cost of normal mode analysis (NMA) applied to a C(alpha)-based elastic network model (C(alpha)-NMA) and present a new coarse-grained rigid-body-based analysis (cluster-NMA). This new method represents a protein as a collection of rigid bodies interconnected with harmonic potentials. This representation produces reduced degree-of-freedom (DOF) equations of motion (EOMs) which, even in the case of large structures (10(3+) residues), enables the computation of normal modes to be done on a desktop PC. We present the complete theory and analysis of cluster-NMA and also include its application to a variety of structures. The results of the new method are compared with C(alpha)-NMA and it is shown that cluster-NMA produces very good approximations to the lowest modes at a fraction of the computational cost.

Algorithms↗

PubMed2004

The human and mouse orthologous LIM-only proteins respectively encoded in chromosome 6 and 17 show a different expression pattern.

Thymocytes interact with various subpopulations of thymic epithelial cells (TECs) at different stages of their development. To identify new molecules specifically expressed in TECs and/or thymic nurse cells (TNCs), we used representational difference analysis. We identified a LIM protein located on mouse chromosome 17 (m17TLP) and belonging to the family of the LIM-only proteins (LIMo). We found a new splice variant in addition to the two described A and B isoforms. The three alternative species of m17TLP are found strictly in the thymic stroma. This protein is expressed on a subpopulation of TECs and TNCs. Strikingly, we found that the human ortholog of m17TLP, located on chromosome 6 (h6LIMo), is expressed in most tissues, but not in skeletal muscle. We have identified four human splice variants of h6LIMo which differ in their carboxy-terminal regions. The sequence comprising the genomic structure suggests that CRP2 is the closest known relative of m17TLP. Although the human and mouse nucleotide sequences are 88-97% homologous, this homology is reduced to 47% in the promoter regions, which strongly suggests that their differential expression is related to their promoter regulatory activity.

Alternative Splicing↗

PubMed2005

Ant navigation en route to the goal: signature routes facilitate way-finding of Gigantiops destructor.

We investigated in laboratory conditions how foragers of the tropical ant Gigantiops destructor develop individually distinctive landmark routes. Way-finding along a familiar route involved the recognition of at least two locations, nest and feeding site, and the representation of spatial relations between these places. Familiar visual landmarks were important both at the beginning and at the end of the foraging journey. A motor routine guided the ants at the start of their foraging path towards the first landmarks, which they learnt to pass consistently on the same side, before taking the next direction. At the last stage of the route, landmark recognition allowed them to pinpoint their preferred feeding site without using distant cues or odometric information. By contrast, ants en route to the goal were not systematically guided by a stereotyped sequence of snapshots recalled at each corresponding stage of the route. Each ant slalomed in an idiosyncratic distinctive way around different midway landmarks from a foraging excursion to the next, which induced a variability of the path shapes in their intermediate parts. By reducing the number of landmark recognition-triggered responses, this economical visuomotor strategy may be helpful in the Amazonian forest where many prominent landmarks are alike.

Animals↗

PubMed2006

Unified analysis and mathematical representation of film-thickness behavior of film-substrate systems.

The ellipsometric function p of a film-substrate system is studied as the film thickness d is kept constant and the angle of incidence phi is changed. The generated constant-thickness contours (CTCs) are characterized by an introduced mathematical behavior indicator that represents a group of CTCs. The behavior of each group is developed and studied in the four planes phi-d, X, Z, and p, where X is the film-thickness exponential function and Z is a previously introduced intermediate plane. In the phi-d plane the film-thickness domain is identified and divided into a sequence of disconnected thickness subdomains (DTSs), depending on only N0 and N1, and their number depending on the range in which N0/N1 lies. The behavior of the CTCs in the successive planes X, Z, and p is then studied in each DTS, and the CTC's space is divided into disconnected subfamilies according to the behavior indicator. Equivalence classes that reduce the infinite number of subfamilies into a finite number are then introduced. The transformation from each plane to the next is studied with the origin of the Z plane mapped onto the point at infinity of the p plane, forming a singularity. A multiple-film-thickness inequality is derived to determine the unique solution of the film thickness. The type of reflection being internal or external at both ambient-film and film-substrate interfaces affects the analysis and is also considered. To conclude we introduce the design of polarization-preserving devices and a novel oscillating single-element ellipsometer to fully characterize zero film-substrate systems as examples of applying the knowledge developed here.

Journal Article↗

PubMed2002

Accurate representation of B-DNA double helical structure with implicit solvent and counterions.

High-resolution nuclear magnetic resonance (NMR) and crystallographic data have been taken to refine the force field used in the torsion angle space nucleic acids molecular mechanics program DUPLEX. The population balance deduced from NMR studies of two carcinogen-modified DNA conformers in equilibrium was used to fine tune a sigmoidal, distance-dependent dielectric function so that reasonable relative energies could be obtained. In addition, the base-pair and backbone geometry from high-resolution crystal structures of the Dickerson-Drew dodecamer was used to re-evaluate the deoxyribose pseudorotation profile and the Lennard-Jones nonbonded energy terms. With a modified dielectric function that assumes a very steep distance-dependent form, a deoxyribose pseudorotation profile with reduced energy barriers between C2'- and C3'-endo minima, and a shift of the Lennard-Jones potential energy minimum to a distance approximately 0.4 A greater than the sum of the van der Waals' radii, the sequence-dependent conformational features of the Dickerson-Drew dodecamer in both the solid state and the aqueous liquid crystalline phase are well reproduced. The robust performance of the revised force field, in conjunction with its efficiency through implicit treatment of solvent and counterions, provides a valuable tool for elucidating conformations and structure-function relationships of DNA, including those of molecules modified by carcinogens and other ligands.

Biophysical Phenomena↗

PubMed2005

Sleep-dependent motor memory plasticity in the human brain.

Growing evidence indicates a role for sleep in off-line memory processing, specifically in post-training consolidation. In humans, sleep has been shown to trigger overnight learning on a motor-sequence memory task, while equivalent waking periods produce no such improvement. But while the behavioral characteristics of sleep-dependent motor learning become increasingly well characterized, the underlying neural basis remains unknown. Here we present functional magnetic resonance imaging data demonstrating a change in the representation of a motor memory after a night of sleep. Subjects trained on a motor-skill memory and 12 hours later, after either sleep or wake, were retested during functional magnetic resonance imaging. Following sleep relative to wake, regions of increased activation were expressed in the right primary motor cortex, medial prefrontal lobe, hippocampus and left cerebellum; changes that can support faster motor output and more precise mapping of key-press movements. In contrast, signal decreases were identified in parietal cortices, the left insular cortex, temporal pole and fronto-polar region, reflecting a reduced need for conscious spatial monitoring and a decreased emotional task burden. This evidence of an overnight, systems-level change in the representation of a motor memory holds important implications for acquiring real-life skills and in clinical rehabilitation following brain trauma, such as stroke.

Adult↗

PubMed2025

scMGCL: accurate and efficient integration representation of single-cell multi-omics data.

MOTIVATION: Single-cell multi-omics data integration is essential for understanding cellular states and disease mechanisms, yet integrating heterogeneous data modalities remains a challenge. We present scMGCL, a graph contrastive learning framework for robust integration of single-cell ATAC-seq and RNA-seq data. Our approach leverages self-supervised learning on cell-cell similarity graphs, in which each modality's graph structure serves as an augmentation for the other. This cross-modality contrastive paradigm enables the learning of biologically meaningful, shared representations while preserving modality-specific features. RESULTS: Benchmarking against state-of-the-art methods demonstrates that scMGCL outperforms others in cell-type clustering, label transfer accuracy, and preservation of marker-gene correlations. Additionally, scMGCL significantly improves computational efficiency, reducing runtime and memory usage. The method's effectiveness is further validated through extensive analyses of cell-type similarity and functional consistency, providing a powerful tool for multi-omics data exploration. AVAILABILITY AND IMPLEMENTATION: Code and datasets are released at https://github.com/zlCreator/scMGCL.

Single-Cell Analysis↗

PubMed2004

Tomographic image reconstruction based on a content-adaptive mesh model.

In this paper, we explore the use of a content-adaptive mesh model (CAMM) for tomographic image reconstruction. In the proposed framework, the image to be reconstructed is first represented by a mesh model, an efficient image description based on nonuniform sampling. In the CAMM, image samples (represented as mesh nodes) are placed most densely in image regions having fine detail. Tomographic image reconstruction in the mesh domain is performed by maximum-likelihood (ML) or maximum a posteriori (MAP) estimation of the nodal values from the measured data. A CAMM greatly reduces the number of unknown parameters to be determined, leading to improved image quality and reduced computation time. We demonstrated the method in our experiments using simulated gated single photon emission computed tomography (SPECT) cardiac-perfusion images. A channelized Hotelling observer (CHO) was used to evaluate the detectability of perfusion defects in the reconstructed images, a task-based measure of image quality. A minimum description length (MDL) criterion was also used to evaluate the effect of the representation size. In our application, both MDL and CHO suggested that the optimal number of mesh nodes is roughly five to seven times smaller than the number of projection bins. When compared to several commonly used methods for image reconstruction, the proposed approach achieved the best performance, in terms of defect detection and computation time. The research described in this paper establishes a foundation for future development of a (four-dimensional) space-time reconstruction framework for image sequences in which a built-in deformable mesh model is used to track the image motion.

Algorithms↗

PubMed1998

Clinical application of functional magnetic resonance imaging in presurgical identification of the central sulcus.

OBJECT: The authors sought to evaluate the advantages and limitations of functional magnetic resonance (fMR) imaging when it was used regularly in the clinical context to identify the central sulcus. METHODS: A 1.5-tesla MR system comprising a spoiled gradient recalled acquisition in the steady-state functional sequence and a cross-hand cancellation analysis method were used to evaluate 50 surgical candidates with centrally located space-occupying lesions in the brain. Three-dimensional (3-D) models of the patient's head and brain showing the relative position of the tumor and the eloquent cortex were obtained in each case. A selective and reproducible focal activation was found, indicating the probable central sulcus position in 41 patients (82%). Direct cortical stimulation confirmed the fMR findings in 100% of 22 intraoperatively assessed patients. Failure to identify the central sulcus occurred in 18% of cases and was mainly a consequence of intrinsic damage in the primary sensorimotor region that resulted in severe hand paresis. CONCLUSIONS: Although specific factors were identified that contributed to reduced sensitivity of fMR imaging in the clinical context, the present study supports functional assessment and 3-D representation of specific surgical situations as generally feasible in common practice.

Adolescent↗

PubMed2026

Dissecting spatial patterning and signaling with directional diffusion in spatial multi-omics.

Spatial multi-omics sequencing enables the simultaneous profiling of transcriptomics, proteomics, and epigenomics at a spatial resolution, offering insights into complex tissue organization and molecular regulation. However, the effective integration of multiple omics modalities in a spatial context remains a major challenge. Here, we present SpaDDM, a spatial multi-omics integration framework based on directional diffusion models (DDMs), which supports spatial pattern identification, cross-omics alignment, and inter-and intracellular signaling flow analysis. SpaDDM employs DDM-based graph networks to learn omics-specific representations by jointly incorporating spatial coordinates and molecular measurements within each modality, followed by an attention mechanism to align features across modalities. We benchmarked SpaDDM on diverse spatial multi-omics datasets, including transcriptomics-epigenomics and transcriptomics-proteomics combinations across multiple tissues and species. SpaDDM consistently outperformed existing methods by more accurately deciphering spatial tissue patterns and effectively reducing the boundary noise between spatial regions. Moreover, the learned low-dimensional coembedded representations of individual cells serve as integral mediators for inferring the signaling flows that underlie spatial patterning. Finally, we demonstrated that SpaDDM alignment of complementary information across multi-omics layers facilitates cross-omics translation and significantly improves the prediction of cell state alignments.

Multiomics↗

PubMed2000

Constructing a 3-D mesh model for electrical cardiac activity simulation.

The 3-D ventricle model in this study was reconstructed from a series of MRI torso cross-section data. We used a 3-D voxel array to represent the ventricle. As in cardiac simulations proposed by previous studies, the activation sequence and body surface ECG were simulated in this model. But to reduce the amount of elements in the model, so that the amount of parameters in the model can be handled numerically, we propose another approach to simulate cardiac activity. A mesh model was constructed on the closed surface formed by epicardiac and endocardiac surfaces of the ventricle. We propose a method to simulate the activation sequence on the epicardiac and endocardiac surfaces of the mesh model. As with the uniform double layer theorem, body surface ECG can be estimated in terms of epicardiac and endocardiac surface current source. Consequently, we can also generate ECG waveforms corresponding to this mesh simulation. Both the depolarization sequence and ECG simulated by the mesh model resemble those generated by the 3-D voxel model. However, the mesh model greatly simplified the process of ECG simulation. Both the simulation of depolarization and ECG estimation were expressed in terms of clear and simple mathematical representations. Consequently, we can analytically investigate the effects of the mesh model's parameters on the cardiac activation sequence and ECG. It could be a useful tool to numerically study the relation of ECG waveforms and electrical activity of the heart.

Computer Simulation↗

PubMed2005

[Differential display technique and its progress].

Differential display technique is an important method to isolate differentially expressed gene. Comparing to other methods like representational difference analysis, suppression subtractive hybridization and serial analysis of gene expression, differential display technique is used in higher frequency. Since it was established in 1992, it has overcome many disadvantages and widened its practical fields through improvements and enhancements by global researchers. In this paper the principle and the main advantages and disadvantages of differential display technique were briefly introduced. Meanwhile, the four progressed aspects in designing primer, reducing false positives, identifying differentially expressed gene and techniques derived from DD were introduced in detail.

Blotting, Northern↗

PubMed1995

The pattern of T lymphocyte differentiation is altered during thymic involution.

Thymic involution is likely to be a significant factor in the alteration of peripheral T lymphocyte function with age. The process of thymic involution involves the progressive loss of normal organ architecture and cellular composition, and a significant reduction in the output of mature T lymphocytes. The present study assesses the impact of thymic involution on the T cell differentiation process by quantitating the number and percent representation of various phenotypically distinguishable T cell developmental intermediates in C57BL/6 mice of various ages. The results suggest that several distinct sites in the developmental sequence are impacted by aging. By middle-age (14-17 months), significant perturbations in the frequencies of several CD4-CD8- (DN) subpopulations have occurred. These include a shift towards an increased percentage of Pgp-1+ IL-2R- DN cells, the earliest thymic progenitors, and a decreased percentage and total number of Pgp-1- IL-2R+ DN cells. Furthermore there is a threefold increase in the percentage of DN cells which express CD3 (from 16.6% to 45.5%) which occurs between 4 and 14 months of age. By 24-27 months of age, the percentage of the total DN population increases two- to threefold over that of young (2-3 months) animals, while the fraction of CD4+CD8+ (DP) is significantly reduced. These alterations are consistent with the possibility that thymic involution results in one or more 'developmental' blocks which limit key differentiative transitions within the DN population, and furthermore, the marked increase in the frequency of DN cells displaying CD3 argues that an alternative T cell differentiation pathway plays an increasingly significant role with advancing age.

Aging↗