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At least 19 recordsLinked to original sources

Detection and normalization of biases present in spotted cDNA microarray data: a composite method addressing dye, intensity-dependent, spatially-dependent, and print-order biases.

Microarrays are often used to identify target genes that trigger specific diseases, to elucidate the mechanisms of drug effects, and to check SNPs. However, data from microarray experiments are well known to contain biases resulting from the experimental protocols. Therefore, in order to elucidate biological knowledge from the data, systematic biases arising from their protocols must be removed prior to any data analysis. To remove these biases, many normalization methods are used by researchers. However, not all biases are eliminated from the microarray data because not all types of errors from experimental protocols are known. In this paper, we report an effective way of removing various types of biases by treating each microarray dataset independently to detect biases present in the dataset. After the biases contained in each dataset were identified, a combination of normalization methods specifically made for each dataset was applied to remove biases one at a time.

Algorithms↗

Local histogram correction of MRI spatially dependent image pixel intensity nonuniformity.

We describe a computationally straightforward post-hoc statistical method of correcting spatially dependent image pixel intensity nonuniformity based on differences in local tissue intensity distributions. Pixel intensity domains for the various tissues of the composite image are identified and compared to the distributions of local samples. The nonuniformity correction is calculated as the difference of the local sample median from the composite sample median for the tissue class most represented by the sample. The median was chosen to reduce the effecters on determining the sample statistic and to allow a sample size small enough to accurately estimate the spatial variance of the image intensity nonuniformity. The method was designed for application to two-dimensional images. Simulations were used to estimate optimal conditions of local histogram kernel size and to test the accuracy of the method under known spatially dependent nonuniformities. The method was also applied to correct a phantom image and cerebral MRIs from 15 healthy subjects. Results show that the method accurately models simulated spatially dependent image intensity differences. Further analysis of clinical MR data showed that the variance of pixel intensities within the cerebral MRI slices and the variance of slice volumes within individuals were significantly reduced after nonuniformity correction. Improved brain-cerebrospinal fluid segmentation was also obtained. The method significantly reduced the variance of slice volumes within individuals, whether it was applied to the native images or images edited to remove nonbrain tissues. This statistical method was well behaved under the assumptions and the images tested. The general utility of the method was not determined, but conditions for testing the method under a variety of imaging sequences is discussed. We believe that this algorithm can serve as a method for improving MR image segmentation for clinical and research applications.

Adult↗

A gender- and sexual orientation-dependent spatial attentional effect of invisible images.

Human observers are constantly bombarded with a vast amount of information. Selective attention helps us to quickly process what is important while ignoring the irrelevant. In this study, we demonstrate that information that has not entered observers' consciousness, such as interocularly suppressed (invisible) erotic pictures, can direct the distribution of spatial attention. Furthermore, invisible erotic information can either attract or repel observers' spatial attention depending on their gender and sexual orientation. While unaware of the suppressed pictures, heterosexual males' attention was attracted to invisible female nudes, heterosexual females' attention was attracted to invisible male nudes, gay males behaved similarly to heterosexual females, and gay/bisexual females performed in-between heterosexual males and females.

Adult↗

Brightness induction by local contrast and the spatial dependence of assimilation.

Two mechanisms of brightness perception (1) brightness induction by local contrast and (2) assimilation, were examined for a variety of visual stimuli. Local contrast is the primary determinant of brightness perception, making objects appear brighter on a background of lower luminance and darker on a background of greater luminance. Assimilation is the opposite effect, whereby objects on a brighter (but not necessarily more luminant) background appear brighter or on a dark background appear darker. We have compared the relative strength of the two effects using stimuli which permit them to be studied separately. Brightness induction by local contrast is quantitatively stronger in all situations. Further, the strength of assimilation is strongly dependent on spatial parameters in the visual scene. These results are shown to be true both for simple visual stimuli as well as for complicated Mondrian-like patterns. The Retinex theory of brightness perception predicts that the two effects are equal. Our results show a range of relative strengths (assimilation vs brightness induction due to contrast) from 0.59 to 0.63 at 5' down to 0.34 at 43'.

Humans↗

Reversible lesion of the rat's orbitofrontal cortex interferes with hippocampus-dependent spatial memory.

In this study, tetrodotoxin (TTX) inactivation was employed to evaluate the involvement of the rat's orbitofrontal cortex (OFC) in hippocampus-dependent spatial memory using Morris water maze (MWM) and place avoidance learning (PAL) tasks. In Experiment 1, rats trained in MWM task with two blocks of four trials per day for 3 consecutive days received bilateral injections of either TTX or saline into the OFC 60 min before each daily training session. The acquisition of spatial memory was evaluated 24h after the last training day and it was shown an impairment by the TTX. In Experiment 2, bilateral intra-OFC injections of TTX or saline were made immediately after two blocks of four trials. Testing 24h later, it was revealed that TTX also impairs spatial memory consolidation. In Experiments 3 and 4, rats were trained in a single 30-min session to avoid a 60 degrees segment of the stable circular (80-cm diameter) arena, entering which was punished by a mild shock (PAL task) and retention was tested 24h later in a 30-min extinction session. Bilateral injections of TTX or saline were made into the OFC 60 min before training or immediately after training. Again, TTX impaired the place avoidance retention when it was injected into the OFC either before (acquisition phase) or after (consolidation phase) training. These findings indicate that functional integrity of the OFC is necessary for both the acquisition and the consolidation of hippocampus-dependent spatial memory in rats.

Anesthetics, Local↗

Temporal and spatial dependency of the ventriloquism effect.

The perception of the spatial location of an auditory stimulus can be captured by a spatially disparate visual stimulus, a phenomenon known as the ventriloquism effect. This study investigated the temporal and spatial dependency of this illusion. In the temporal domain, only disparities of 50-100 ms were perceived as simultaneous, and disparities where the visual stimulus occurred before the auditory stimulus were more effective in creating the illusion. In the spatial domain, the illusion was elicited most strongly at spatial disparities below spatial discrimination thresholds. There was also a significant interaction between temporal and spatial disparities. These results indicate that both temporal and spatial parameters are critical in the perception of real world objects in extrapersonal space.

Acoustic Stimulation↗

Theoretical description of the spatial dependence of sickle hemoglobin polymerization.

We have generalized the double nucleation mechanism of Ferrone et al. (Ferrone, F. A., J. Hofrichter, H. Sunshine, and W. A. Eaton. 1980. Biophys. J. 32:361-377; Ferrone, F. A., J. Hofrichter, and W. A. Eaton. 1985. J. Mol. Biol. 183:611-631) to describe the spatial dependence of the radial growth of polymer domains of sickle hemoglobin. Although this extended model requires the consideration of effects such as monomer diffusion, which are irrelevant to a spatially uniform description, no new adjustable parameters are required because diffusion constants are known independently. We find that monomer diffusion into the growing domain can keep the net unpolymerized monomer concentration approximately constant, and in that limit we present an analytic solution of the model. The model shows the features reported by Basak, S., F. A. Ferrone, and J. T. Wang (1988. Biophys J. 54:829-843) and provides a new means of determining the rate of polymer growth. When spatially integrated, the model exhibits the exponential growth seen in previous studies, although molecular parameters derived from analysis of the kinetics assuming uniformity must be modified in some cases to account for the spatially nonuniform growth. The model developed here can be easily adapted to any spatially dependent polymerization process.

Hemoglobin, Sickle↗

ARCADIA reveals spatially dependent transcriptional programs through integration of scRNA-seq and spatial proteomics.

MOTIVATION: Cellular states are strongly influenced by spatial context, but single-cell RNA sequencing (scRNA-seq) loses information about local tissue organization, while spatial proteomic assays capture limited marker panels that constrain transcriptomic inference. Integrating these modalities can elucidate how spatial niches shape transcriptional programs, yet existing approaches depend on either feature-level correspondence such as gene-protein linkage or cell-level barcode pairing, which is often unavailable. RESULTS: We present ARCADIA (ARchetype-based Clustering and Alignment with Dual Integrative Autoencoders), a generative framework for cross-modal integration that operates without cell barcode pairing and does not assume direct feature-to-feature correspondence. ARCADIA identifies modality-specific archetypes, that is, convex combinations of cells representing extreme phenotypic states, and aligns these anchors across modalities by minimizing the discrepancy between their cell-type composition profiles. The aligned archetypes define a shared coordinate system that anchors dual variational autoencoders (VAEs) trained with cross-modal geometric regularization, preserving archetype structure and spatial neighborhood information while enabling bidirectional translation between modalities. On semi-synthetic CITE-seq data, ARCADIA outperforms existing weak-linkage methods. Applied to independent human tonsil scRNA-seq and CODEX data, ARCADIA reconstructs known tissue architecture and reveals spatially dependent transcriptional programs linking B-cell maturation and T-cell activation or exhaustion to microenvironmental niches. AVAILABILITY AND IMPLEMENTATION: Source code is accessible at https://github.com/azizilab/ARCADIA_public. Reproducibility scripts and data are available at https://github.com/azizilab/arcadia_reproducibility.

Proteomics↗

The spatial dependence of spin-echo signals.

The signals in NMR spin echoes which are refocused by 90 degrees pulses are spatially modulated. The spatial modulation is not normally observed in images or profiles obtained using Hahn or stimulated echoes, but may cause errors if the sample structure varies on the distance scale of the modulation. Localized spectra measured using stimulated echoes will also show errors under these conditions. Simple Fourier-transform arguments show that conditions which allow the modulation to become visible in an image or profile have the effect of introducing a second echo into the time-domain acquisition window. Phase cycling may be used to remove the spatial dependence of the signals.

Artifacts↗

Spatially dependent deadtime losses in high count rate cardiac PET.

Cardiac PET scans result in nonhomogeneous distributions of activity within the body, which might lead to great variations in singles rates around the detector ring. Conventional deadtime correction algorithms assume that the singles rates are uniform. This paper investigates singles nonuniformities during several typical cardiac scanning protocols (bolus injections of 15O-water and 82Rb, slow infusion of 18F-FDG and static imaging with FDG) and estimates how such nonuniformities might affect quantitative data. Nonuniformity was observed in all studies and was described by an asymmetry index which increased to 58% during bolus water injection, the most inhomogeneous study. These results are valid for any scanner with a ring diameter of approximately 78 cm and are independent of the amount of activity injected. Deadtime losses depend on the amount of activity and on the scanner type. Nonhomogeneities in singles can be shown to produce spatially dependent deadtime correction factors; for our scanner, these were seen to differ by up to 16% from the mean deadtime correction during bolus water injection. To demonstrate the distortions generated by average deadtime correction, the activity distribution during a clinical cardiac study was simulated using a phantom. A simple local deadtime correction and its implementation on our system are described, and the resulting improvements in both absolute and relative quantitation of the phantom study are shown.

Deoxyglucose↗

N-dimensional fractional diffusion equation and Green function approach: spatially dependent diffusion coefficient and external force.

We investigate an N-dimensional fractional diffusion equation with radial symmetry by using the Green function approach. We consider, in our analysis, the spatial dependence on the diffusion coefficient and the presence of an external force. In particular, we employ boundary conditions in a finite interval and after we extend it to a semi-infinite interval. We also show that a rich class of diffusive processes, including normal and anomalous ones, can be obtained from the solutions found here.

Journal Article↗

The spatial dependence of the poststimulus undershoot as revealed by high-resolution BOLD- and CBV-weighted fMRI.

The hemodynamic response to neural activity consists of changes in blood flow, blood volume and oxygen metabolism. Changes in the vascular state after sensory stimulation have different spatial and temporal characteristics in the brain. This has been shown using imaging techniques, such as BOLD functional magnetic resonance imaging (fMRI), which monitor vascular changes once the stimulus is turned on, and the eventual return to baseline levels, once the stimulus is turned off. The BOLD fMRI signal during sensory stimulation has been well characterized and modeled in terms of the spatial and temporal characteristics of the vascular response. However, the return of the signals to baseline levels after sensory stimulation is not as well characterized. During this period, a poststimulus undershoot in the BOLD signal is observed. This poststimulus undershoot has been modeled and investigated to characterize the physiological mechanisms (cerebral blood flow (CBF), cerebral blood volume (CBV), and cerebral oxygen consumption) associated with the response. However, the data in the literature, which lack any spatially dependent information, appear to be contradictory in terms of the mechanisms associated with this poststimulus response. With a high spatial resolution cat model at 9.4 T, we show that CBV changes in the tissue persist once the stimulus is turned off, while CBV changes in the surface vessels quickly return to baseline levels, despite a concurrent undershoot in the BOLD signal in both the tissue and surface vessel areas. In addition, the BOLD data alone indicate that different physiological mechanisms regulate the poststimulus response in the tissue versus the surface vessel regions.

Animals↗

Preserved performance in a hippocampal-dependent spatial task despite complete place cell remapping.

The spatially localized firing of hippocampal place cells is thought to underlie the navigational function of the hippocampus. Performance on a spatial task learned using a particular place cell map should therefore deteriorate if the map is disrupted. To test this prediction, we trained rats on a hippocampal-dependent spatial task in a black box and tested them in a white box. Although the change from black to white induced remapping of most place cells, navigational performance remained essentially intact. Furthermore, place cell activity was also unrelated to specific aspects of the task such as tone onset, response, or goal location. Together, these results imply that the spatial information needed to solve this navigation task is represented outside the hippocampus and suggest that the place cells encode some other aspect, such as the spatial context.

Animals↗

Correction of spatially dependent phase shifts for partial Fourier imaging.

Partial Fourier MR images (PFI) are constructed from data that have fewer phase encoding views than are conventionally acquired using direct Fourier transform spin echo acquisition. The PFI data acquisition is structured to obtain the same spatial resolution as conventional acquisition, trading off signal-to-noise reduction for acquisition time improvement. The "missing" views can be zero filled or, if the data are Hermitian, supplied by symmetry (basic algorithm). The effect of spatially dependent phase shifts (SDPS) on PFI constructed with zero-fill or the basic algorithm is illustrated. The causes and typical magnitudes of such SDPS are discussed. In spin echo data only the low order, slowly varying SDPS, is shown to be significant. Through use of simulated and actual data sets these typical SDPS are shown to produce significant artifacts in PFI, when the amount of missing data is close to one-half. The artifacts are reduced when less data are missing. Good images can be generated with the zero-fill algorithm if less than 25% of the data is missing. Several methods of correcting phase shifts in PFI are developed: the basic Hermitian algorithm with frequency (x) direction correction (BAX), basic Fourier correction algorithm (BFC) and an improved iterative Fourier correction algorithm (IFC). The BFC and IFC can produce good images when as much as 46% of the data is missing. Data with rapidly varying SDPS, for example, gradient refocused data, make the phase correction task more difficult. With less than 25% of the data missing, however, acceptable gradient refocused PFI images can be created.

Fourier Analysis↗

Biomass-diversity responses and spatial dependencies in disturbed tallgrass prairies.

Monotonic, hump-shaped and zero-correlation productivity-diversity relationships have been found to date in many ecosystems. This diversity of responses has puzzled ecologists in their search for general principles on ecosystem functioning. Some state that the scale of observation is crucial in defining this relationship. We have developed a spatial model of tallgrass prairies where biomass and litter dynamics are defined by uncoupled difference equations. In this system, we periodically apply prescribed fire as a disturbance that propagates through neighboring cells. The model shows percolation thresholds at points where small-scale spatial heterogeneity and large-scale, global correlation coexist, resulting in power-law distributions in available areas for non-dominant species. These points maximize the biomass-diversity relationship. Our results suggest that spatial dependencies and the disturbance heterogeneity hypothesis are the cornerstone processes accounting for unimodality in productivity-diversity relationships.

Biomass↗

Spatial dependence of the nonlinear BOLD response at short stimulus duration.

Most functional magnetic resonance imaging studies use linear models to predict the measured response by convolution of an impulse response with the stimulus profile. Using very short visual presentation times (<2 s), deviation from the linear model in the measured BOLD data from the human brain was found for the response integral, amplitude, and width. In this study, high temporal and spatial resolution were used to quantify nonlinear effects and investigate the spatial dependence. Data at 4 Tesla showed at short stimulus duration a nonlinearity, i.e., deviation from a linear model, with an index up to 400%, whereas data at 7 Tesla exhibited a nonlinearity index up to 40%. The effect was more pronounced for response amplitude than for response area. A reduced width and sharpening of responses at shorter stimulus duration was also found. A voxel-based analysis of 7 Tesla data with 1.2 x 1.2 x 2 mm(3) resolution revealed a correlation between response onset and nonlinearity index. This suggests that the nonlinearity effects are a tissue-specific phenomenon and are likely to be more localized to the site of neuronal activity. The observed magnetic field dependence and the demonstrated nonlinearity in the response width support the hypothesis that the source of the nonlinearity at short stimulus duration has a considerable hemodynamic contribution. The nonlinearity was modeled as a "switch"-type initial hemodynamic response onset. Understanding these nonlinearities in the BOLD response is important for design and the analysis of rapid event-related fMRI experiments with brief stimulus presentations.

Brain Mapping↗

Short-scan SPECT imaging with non-uniform attenuation and 3D distance-dependent spatial resolution.

Image quality and quantitative accuracy in single-photon emission computed tomography (SPECT) can be degraded by, e.g., the effects of photon attenuation and finite spatial resolution. It is generally considered that adequate compensation for such effects on SPECT images requires data acquired over 2 pi. Recently, using the existing consistency condition on the data function, Noo and Wagner (2001 Inverse Problems 17 1357-72) have shown analytically that data acquired over only pi can be used to correct completely for the effect of uniform attenuation in SPECT. It remains unknown, however, whether data acquired only over pi in SPECT with non-uniform attenuation and/or 3D distance-dependent spatial resolution (DDSR) contain complete information for accurate image reconstruction. In this work, we develop a heuristic perspective, which is referred to as the potato peeler perspective to show conceptually that data in SPECT with non-uniform attenuation and/or 3D DDSR acquired over 2 pi contain redundant information and that such information can be used to reduce the scanning angle in SPECT. Specifically, we show heuristically that, in SPECT with only non-uniform attenuation, the scanning angle can be reduced from 2 pi to pi and that, in SPECT with both non-uniform attenuation and DDSR with a physically realistic form, the scanning angle can be reduced from 2 pi to pi in a practical sense. We conduct computer simulation studies, and the results from these studies corroborate the observations obtained based upon the heuristic potato peeler perspective.

Algorithms↗

High resolution EEG: a new model-dependent spatial deblurring method using a realistically-shaped MR-constructed subject's head model.

This paper presents a new model-dependent method for the spatial deblurring of scalp-recorded EEG potentials based on boundary-element and cortical imaging techniques. This model-dependent spatial deblurring (MDSD) method used MR images for the reconstruction of the subject's head model, and a layer of 364 radially-oriented equivalent current dipoles as a source model. The validation of the MDSD method was performed on simulated potential distributions generated from equivalent dipoles oriented radially, obliquely, and tangentially to the head surface. Furthermore, this method was used to localize neocortical sources of human movement-related and somatosensory-evoked potentials. It was shown that the new MDSD method improved markedly the spatial resolution of the simulated surface potentials and scalp-recorded event-related potentials. The spatial information content of the scalp-recorded EEG potentials increased progressively by increasing the spatial sampling from 28 to 128 channels. These results indicate that the new method could be satisfactorily used for high resolution EEG studies.

Brain↗