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The cytoskeleton and cell signaling: component localization and mechanical coupling.

The three-dimensional intracellular network formed by the filamentous polymers comprising the cytoskeletal affects the way cells sense their extracellular environment and respond to stimuli. Because the cytoskeleton is viscoelastic, it provides a continuous mechanical coupling throughout the cell that changes as the cytoskeleton remodels. Such mechanical effects, based on network formation, can influence ion channel activity at the plasma membrane of cells and may conduct mechanical stresses from the cell membrane to internal organelles. As a result, both rapid responses such as changes in intracellular Ca2+ and slower responses such as gene transcription or the onset of apoptosis can be elicited or modulated by mechanical perturbations. In addition to mechanical features, the cytoskeleton also provides a large negatively charged surface on which many signaling molecules including protein and lipid kinases, phospholipases, and GTPases localize in response to activation of specific transmembrane receptors. The resulting spatial localization and concomitant change in enzymatic activity can alter the magnitude and limit the range of intracellular signaling events.

Cytoskeleton↗

Exploiting application locality to design low-complexity, highly performing, and power-aware embedded classifiers.

Temporal and spatial locality of the inputs, i.e., the property allowing a classifier to receive the same samples over time--or samples belonging to a neighborhood--with high probability, can be translated into the design of embedded classifiers. The outcome is a computational complexity and power aware design particularly suitable for implementation. A classifier based on the gated-parallel family has been found particularly suitable for exploiting locality properties: Subclassifiers are generally small, independent each other, and controlled by a master-enabling module granting that only a subclassifier is active at a time, the others being switched off. By exploiting locality properties we obtain classifiers with accuracy comparable with the ones designed without integrating locality but gaining a significant reduction in computational complexity and power consumption.

Algorithms↗

Scene content selected by active vision.

The primate visual system actively selects visual information from the environment for detailed processing through mechanisms of visual attention and saccadic eye movements. This study examines the statistical properties of the scene content selected by active vision. Eye movements were recorded while participants free-viewed digitized images of natural and artificial scenes. Fixation locations were determined for each image and image patches were extracted around the observed fixation locations. Measures of local contrast, local spatial correlation and spatial frequency content were calculated on the extracted image patches. Replicating previous results, local contrast was found to be greater at the points of fixation when compared to either the contrast for image patches extracted at random locations or at the observed fixation locations using an image-shuffled database. Contrary to some results and in agreement with other results in the literature, a significant decorrelation of image intensity is observed between the locations of fixation and other neighboring locations. A discussion and analysis of methodological techniques is given that provides an explanation for the discrepancy in results. The results of our analyses indicate that both the local contrast and correlation at the points of fixation are a function of image type and, furthermore, that the magnitude of these effects depend on the levels of contrast and correlation present overall in the images. Finally, the largest effect sizes in local contrast and correlation are found at distances of approximately 1 deg of visual angle, which agrees well with measures of optimal spatial scale selectivity in the visual periphery where visual information for potential saccade targets is processed.

Attention↗

A Monte Carlo investigation of dual-planar circular-orbit cone-beam SPECT.

We use Monte Carlo simulations to study the imaging properties of a design for a dual-planar cone-beam (DPCB) single-photon emission computed tomography (SPECT) system. A dual-planar system uses a dual-camera SPECT system and two cone-beam collimators with foci in different axial planes to increase the effective axial field of view (FOV). We simulated nearly noise-free projection data from a computerized brain phantom and a phantom consisting of a series of points. Four configurations were simulated: parallel-beam low-energy high-resolution (LEHR) as a standard for comparison and DPCB at three radii of rotation (ROR) corresponding to the smallest, average and largest ROR required to clear patients' shoulders based on ergonomic data. We compared global measures of average resolution and total acquired counts for the four configurations. We also estimated local spatial frequency response for reconstructions of point sources. Finally, we estimated a local noise power spectrum by simulating 1000 noise realizations of the brain phantom and estimating a local noise covariance at selected points. The noise power spectra were used to estimate spectral signal to noise ratio (SNR) for each configuration. The resolution in the reconstructed image space ranges from 7.2 mm full-width at half-maximum (FWHM) at the minimum ROR to 9.4 mm FWHM at the maximum ROR. The efficiency is inversely related, ranging from 1.5 times that of parallel LEHR at minimum ROR to 2.5 times that of LEHR at maximum ROR. Estimates of system frequency response roughly correspond to the global resolution estimates, but the cone-beam techniques exhibit an unusual secondary peak in the axial-direction response. Estimates of spectral SNR show that the cone-beam configurations almost always result in higher SNR at all spatial frequencies regardless of ROR. The very largest ROR may be an exception. A larger ROR results in significantly higher SNR for low spatial frequencies with small reductions in SNR for mid-range frequencies. We conclude that the DPCB design allows significant improvements in both resolution and noise as compared to conventional parallel designs and that optimizing the ROR for the cone-beam system may improve the performance of certain imaging tasks.

Brain↗

The response of the strongly coupled AB system of citrate to typical 1H MRS localization sequences.

The response of the strongly coupled AB system of citrate to the STEAM and PRESS spatial localization sequences is developed analytically and then verified experimentally at 2.35 T. At this field strength, the response predicted by the complete strong-coupling calculation is shown to differ greatly from that of the simpler weak-coupling approximation. It is shown that the strong-coupling effects induce a significant field-strength dependence in the time-dependent modulations of the response to either sequence. These effects are illustrated for the STEAM and PRESS responses at field strengths of 1.5, 2.35, and 4.7 T. Independent of the chosen sequence, the increase in the signal-to-noise (S/N) of the frequency response with increasing field strength is shown to be significantly less for the citrate system than for uncoupled spins. The factors which weaken the S/N dependence of the citrate AB signal with increasing field strength are quantified and discussed.

Citrates↗

Localization of implanted radioactive wires and computation of the dose distribution.

A method is described for the spatial localization of implanted curved radioactive wires. The input data are obtained from two orthogonal radiographs taken on a simulator. A specially constructed double light-box is used for the determination of corresponding points on the projections of the wire in the AP and lateral radiographs. The wires are localized as a series of straight segments and formulae are derived for the computation of the segment activity in order to calculate the dose distribution for uniformly and non-uniformly activated wires. All calculations can be included as additional subprograms in a dose computation program for straight linear sources.

Radiotherapy↗

Autonomy in robots and other agents.

The word "autonomous" has become widely used in artificial intelligence, robotics, and, more recently, artificial life and is typically used to qualify types of systems, agents, or robots: we see terms like "autonomous systems," "autonomous agents," and "autonomous robots." Its use in these fields is, however, both weak, with no distinctions being made that are not better and more precisely made with other existing terms, and varied, with no single underlying concept being involved. This ill-disciplined usage contrasts strongly with the use of the same term in other fields such as biology, philosophy, ethics, law, and human rights, for example. In all these quite different areas the concept of autonomy is essentially the same, though the language used and the aspects and issues of concern, of course, differ. In all these cases the underlying notion is one of self-law making and the closely related concept of self-identity. In this paper I argue that the loose and varied use of the term autonomous in artificial intelligence, robotics, and artificial life has effectively robbed these fields of an important concept. A concept essentially the same as we find it in biology, philosophy, ethics, and law, and one that is needed to distinguish a particular kind of agent or robot from those developed and built so far. I suggest that robots and other agents will have to be autonomous, i.e., self-law making, not just self-regulating, if they are to be able effectively to deal with the kinds of environments in which we live and work: environments which have significant large scale spatial and temporal invariant structure, but which also have large amounts of local spatial and temporal dynamic variation and unpredictability, and which lead to the frequent occurrence of previously unexperienced situations for the agents that interact with them.

Animals↗

Scaling laws in NMR scattering via dipolar fields.

Breaking translational symmetry in magnetostatics imparts a scale dependence that is commonly investigated in physics (W. Warren et al., 1993, Science 262, 2005-2008). An interesting and important example arises in nuclear magnetic resonance studies involving the dipolar mean field of adjacent nuclear spins where the scattering (transfer of spatial spin gratings) via intermolecular macroscopic fields carries a signature of the local spatial distribution of the spin density. For arbitrary geometry, the inverse problem of extracting this spin distribution from experiments is intractable. Here we point out a simple, universal crossover in the scaling behavior at the sample's characteristic length scale, xi, of the species fluctuations in the sample along the measurement direction. This behavior is observed experimentally in an oil-water emulsion, an important representation of complex, heterogeneous, soft matter.

Emulsions↗

Three-dimensional spectral-spatial EPR imaging of free radicals in the heart: a technique for imaging tissue metabolism and oxygenation.

It has been hypothesized that free radical metabolism and oxygenation in living organs and tissues such as the heart may vary over the spatially defined tissue structure. In an effort to study these spatially defined differences, we have developed electron paramagnetic resonance imaging instrumentation enabling the performance of three-dimensional spectral-spatial images of free radicals infused into the heart and large vessels. Using this instrumentation, high-quality three-dimensional spectral-spatial images of isolated perfused rat hearts and rabbit aortas are obtained. In the isolated aorta, it is shown that spatially and spectrally accurate images of the vessel lumen and wall could be obtained in this living vascular tissue. In the isolated rat heart, imaging experiments were performed to determine the kinetics of radical clearance at different spatial locations within the heart during myocardial ischemia. The kinetic data show the existence of regional and transmural differences in myocardial free radical clearance. It is further demonstrated that EPR imaging can be used to noninvasively measure spatially localized oxygen concentrations in the heart. Thus, the technique of spectral-spatial EPR imaging is shown to be a powerful tool in providing spatial information regarding the free radical distribution, metabolism, and tissue oxygenation in living biological organs and tissues.

Animals↗

Comparison of relative and absolute sound localization ability in humans.

Sound localization ability has traditionally been studied using either a relative localization task, where thresholds to determine a difference in sound source location is approximately 1-10 degrees, or an absolute localization task, where the range of estimates of the source of a sound are 4-30 degrees. In order to directly relate these two psychophysical methods, we compared the psychometric functions from a relative localization task in a human subject to the same subject's performance on an absolute localization task using three different acoustic stimuli: Gaussian noise, 1-kHz tones, and 4-kHz tones. The results showed that the relative localization threshold was a poor indicator of the range of estimates of the same stimulus in absolute space, however, the width of the relative localization psychometric functions was well correlated with the width of the distribution of estimates made in the absolute localization task. It is concluded that the relative localization psychometric functions, but not threshold, provides a reliable estimate of absolute spatial localization ability in human subjects, and suggested that the same neuronal mechanisms can underlie the psychophysical data using both methods.

Adult↗

Synchrony, waves, and spatial hierarchies in the spread of influenza.

Quantifying long-range dissemination of infectious diseases is a key issue in their dynamics and control. Here, we use influenza-related mortality data to analyze the between-state progression of interpandemic influenza in the United States over the past 30 years. Outbreaks show hierarchical spatial spread evidenced by higher pairwise synchrony between more populous states. Seasons with higher influenza mortality are associated with higher disease transmission and more rapid spread than are mild ones. The regional spread of infection correlates more closely with rates of movement of people to and from their workplaces (workflows) than with geographical distance. Workflows are described in turn by a gravity model, with a rapid decay of commuting up to around 100 km and a long tail of rare longer range flow. A simple epidemiological model, based on the gravity formulation, captures the observed increase of influenza spatial synchrony with transmissibility; high transmission allows influenza to spread rapidly beyond local spatial constraints.

Adult↗

Serrate signals through Notch to establish a Wingless-dependent organizer at the dorsal/ventral compartment boundary of the Drosophila wing.

Growth and patterning of the Drosophila wing is controlled by organizing centers located at the anterior-posterior and dorsal-ventral compartment boundaries. Interaction between cells in adjacent compartments establish the organizer. We report here that Serrate and Notch mediate the interaction between dorsal and ventral cells to direct localized expression of Wingless at the D/V boundary. Serrate serves as a spatially localized ligand which directs Wg expression through activation of Notch. Ligand independent activation of Notch is sufficient to direct Wg expression, which in turn mediates the organizing activity of the D/V boundary.

Animals↗

Spatial-frequency-tuned mechanisms of the red-green channel estimated by oblique masking.

The sustained spatial-frequency-tuned (SF-tuned) mechanisms of nonoriented units were examined by means of orthogonal masking for the Red-Green (R-G) color channel, and those of oriented units by oblique masking for the achromatic channel but not for the color channels. An oblique-masking technique minimizes the artifacts that are due to spatial phase effects, local cues, spatial beats, spatial probability summation, and changing criteria. Therefore the spatial characteristics of the R-G color channel are now investigated by an oblique-masking technique and linked with my paper on orthogonal masking [J. Opt. Soc. Am. A 15, 1 (1998)]. The R-G channel was defined by the minimum-flicker and hue-cancellation techniques. A color monitor system was used to generate spatially localized (D6) vertical color test patterns [0.063-8 cycles per degree (cpd)] and sinusoidal oblique color masks (0.031-16 cpd, 1.2-60% contrasts). Color contrast sensitivity functions (CSFs), threshold elevation (TE) versus mask SF (TvSF) curves, and TE versus mask contrast (TvC) curves were measured by the method of constant stimuli with a two-interval forced-choice technique by using Powell's achromatizing lens under sustained (Gaussian, 2-s-duration) conditions. Results show the following: (1) The color CSF is a low-pass function of SF with average half-height SF of 0.7 cpd and cutoff SF of 14 cpd with the use of a color-detection criterion. (2) TvSF curves are broadly bandpass and fall into five groups, peaking at approximately 0.13, 0.5, 2, 4, and 8 cpd. The root-mean-square cone-color CSF is 3.8-5.4 times the stimulus-color CSF. (3) A "crowding effect" similar to that of the TvSF curves of the achromatic channel was also found, but the TvSF curves of the R-G channel are not sharply peaked, similar to the result for orthogonal masking. Data analysis led to the following conclusions: (1) A simple multiple-mechanism model yields one low-pass color mechanism (with average half-height SF of 0.54 cpd) and five bandpass SF-tuned color mechanisms; these six mechanisms are necessary to explain the CSF, TvSF, and TvC data simultaneously. (2) The bandpass mechanisms peaked at approximately 0.13, 0.5, 2, 4, and 8 cpd with average full bandwidths at half-heights of 3.6, 3.2, 2.1, 1.2, and 1.3 octaves, respectively. (3) Since oblique-masking color mechanisms (unlike achromatic oriented mechanisms) have broad orientation tuning under sustained conditions and there is a significant orthogonal masking, the oblique-masking color mechanisms may have contributions from both oriented and nonoriented units. (4) The high degree of similarity between the SF-tuned filters of mechanisms derived from oblique- and orthogonal-masking data suggests that most of the chromatic SF tuning is already accomplished by nonoriented units. (5) The quality of the fit to oblique- and orthogonal-masking data combined dropped enough to reject the hypothesis that the former taps the performance of only the same nonoriented mechanisms as those by the latter. Adding gain parameters that reduce the TEs for orthogonal masking gave a better fit, suggesting that orientation gains are one of the factors involved in the transformation of information from nonoriented to oriented mechanisms. However, the fit was still worse than that for oblique-(6) Since masking-alone or orthogonal-masking-alone data, suggesting that more factors may be involved. primate parvo lateral geniculate nucleus (pLGN) units behave in a fairly linear manner, the color contrast nonlinearity (which follows the linear filter) of a mechanism may be post-pLGN.

Color Perception↗

Local calcium signaling in neurons.

Transient rises in the cytoplasmic concentration of calcium ions serve as second messenger signals that control many neuronal functions. Selective triggering of these functions is achieved through spatial localization of calcium signals. Several qualitatively different forms of local calcium signaling can be distinguished by the location of open calcium channels as well as by the distance between these channels and the calcium binding proteins that serve as the molecular targets of calcium action. Local calcium signaling is especially prominent at presynaptic active zones and postsynaptic densities, structures that are distinguished by highly organized macromolecular arrays that yield precise spatial arrangements of calcium signaling proteins. Similar forms of local calcium signaling may be employed throughout the nervous system, though much remains to be learned about the molecular underpinnings of these events.

Animals↗

Evidence for spatial modules mediated by temporal synchronization of carbachol-induced gamma rhythm in medial entorhinal cortex.

Fast (gamma) oscillations in the cortex underlie the rapid temporal coordination of large-scale neuronal assemblies in the processing of sensory stimuli. Cortical gamma rhythm is modulated in vivo by cholinergic innervation from the basal forebrain and can be generated in vitro after exogenous cholinergic stimulation. Using the isolated guinea pig brain, an in vitro preparation that allows for the study of an intact cerebrum, we studied the spatial features of gamma activity evoked by the cholinomimetic carbachol (CCh) in the medial entorhinal cortex (mEC). gamma activity induced by either arterial perfusion or intraparenchymal application of CCh showed a phase reversal across mEC layer II and was reduced or abolished in a spatially localized region by focal infusions of atropine, bicuculline, and CNQX. In addition, a spatially restricted zone of gamma activity could be induced by passive diffusion of CCh from a recording pipette. Finally, gamma oscillations recorded at multiple sites across the surface of the mEC using array electrodes during arterial perfusion of CCh demonstrated a decline in synchronization (coherence) as the interelectrode distance increased. This effect was independent of the signal amplitude and was specific for gamma as opposed to theta-like activity induced by CCh in the same experiments. These results suggest that CCh-induced gamma oscillations in the mEC are mediated through direct muscarinic excitation of a highly localized reciprocal inhibitory-excitatory network located in superficial layers. We propose that functional cortical modules of highly synchronous gamma oscillations may organize incoming (cortical) and outgoing (hippocampal) information in the mEC.

Animals↗

Differential localization of collagen type IX isoform messenger RNAs during early ocular development.

PURPOSE: To determine the temporal and spatial localization of the messenger RNAs (mRNAs) for the two collagen alpha 1(IX) isoforms during early development of the embryonic chicken eye. METHODS: The reverse transcription-polymerase chain reaction method was used to amplify mRNAs for the two collagen alpha 1(IX) isoforms. mRNA was extracted from optic vesicles of chicken embryos at stages 14 to 19 and from microdissected ocular tissues of older embryonic eyes. After synthesis of complementary DNA, the polymerase chain reaction was performed for 20, 25, or 30 cycles. This ensured a reliable estimate of the relative abundance of the two mRNAs at different stages and in different ocular tissues. Data from the polymerase chain reaction were confirmed by Northern blot analysis. RESULTS: mRNA for the shorter alpha 1(IX) chain was present in the optic vesicle as early as stage 14, whereas mRNA for the longer alpha 1(IX) chain was not detectable until after the optic vesicle and lens started to invaginate (stage 15; day 2.5). In later stages of development, mRNAs for both alpha 1(IX) chains were present predominantly in the presumptive ciliary epithelium. They were just detectable in the neural retina at stages 20 and 23 (days 3 to 3.5). By E6 no mRNA for the shorter alpha 1(IX) isoform was detected in the retina, although a trace of the longer alpha 1(IX) isoform was still present. In the lens, mRNA for neither isoform was detectable at any stage. CONCLUSIONS: The two isoforms of alpha 1(IX) collagen mRNA are expressed differentially in space and time during early development of the embryonic chicken eye. These molecules may serve as markers for the early specialization of ciliary epithelium as a distinct region of the optic cup.

Animals↗

Neural recruitment explains "Weber's law" of spatial position.

We ask whether the well known Weber's law between spatial localization and element separation for high contrast, spectrally broad-band stimuli is a consequence of the organization of the early visual filters, or a fundamental constraint on the computation of spatial position by more central mechanisms. We address this question by identifying the individual contributions of mechanisms tuned to different ranges of spatial frequencies and contrast. We measure spatial-alignment and bisection error as a function of element separation at each of a number of spatial scales, using spectrally narrow-band stimuli of fixed supra-threshold contrast. We show that stimuli which minimize the extent of neural recruitment across different spatial channels before the site of extraction of the local contrast energy (and to a lesser extent across different contrast channels) do not exhibit Weber's law for either alignment or bisection. We present evidence that Weber's law for localization with increasing separation, found for stimuli of high contrast and broad-band spatial frequency content, is a consequence of the successive disengagement of unitary neural mechanisms, each of which has different spatial and contrast properties, and none of which individually exhibits Weber's law for spatial position.

Contrast Sensitivity↗

ACE: a single-shot method for water-suppressed localization and editing of spectra, images, and spectroscopic images.

A versatile method for localized (1H) NMR spectroscopy is presented. The method intrinsically combines B0-based spatial localization with the possibility of water suppression and spectral editing. With this sequence it is feasible to localize not only single spectra but also phase-encoded images and spectroscopic images. The technique essentially integrates the "Hahn spin-echo" with the "stimulated echo" sequence and is therefore called ACE (acquiring combined echoes). It realizes water-suppressed three-dimensional localization in a single shot and can be used for localized shimming. Studies in which the new method is applied to phantoms with metabolites diluted at low concentrations are presented. Discrimination between lactate and alanine, employing an adapted spectral editing method with complete inversion, combined with simultaneous water suppression and localization of a 0.06-cc volume is shown. The suppression of signals from outside the selected volume is greater than or equal to 24,000. Also, the method is demonstrated by in vivo experiments at 6.3 T. Localized water-suppressed 1H spectra are obtained completely noninvasively, leaving scalp and fur intact, from well-defined volumes of 0.15 cc in the brain of a living rat. Water-suppressed spectroscopic imaging over a localized volume with "body" coil excitation and noninvasive surface coil detection yielded spectra from voxels as small as 25 microliters in the in vivo rat brain.

Animals↗