Biomedical subjects

Z L Lu

Publications and source records attributed to Z L Lu.

At least 19 recordsLinked to original sources

PubMed2006

Large low-field magnetoresistance in nanocrystalline magnetite prepared by sol-gel method.

Nanocrystalline magnetite Fe3O4 samples with a grain size of about 40 nm have been synthesized by an optimized sol-gel method. The single phase of spinel magnetite was confirmed by both X-ray diffraction and transmission electron microscopy. It has been found that the magnetoresistance of the samples at low field (LFMR) is relatively large, and with the decrease of temperature its value at a field of 0.5 T changes dramatically from -2.5% at 300 K to -17.0% at 55 K. With the further decrease of temperature a sharp drop occurs for the magnitude of the magnetoresistance (MR), regarded as a spin (cluster) glass transition in the surface region of the grains that can be confirmed by the zero-field-cooled and field-cooled magnetization and ac susceptibility measurement. The mechanism of the magnetic and transport properties was discussed.

Journal Article↗

PubMed2003

Structure and activation of muscarinic acetylcholine receptors.

A homology model of the M(1) muscarinic acetylcholine receptor, based on the X-ray structure of bovine rhodopsin, has been used to interpret the results of scanning and point mutagenesis studies on the receptor's transmembrane (TM) domain. Potential intramolecular interactions that are important for the stability of the protein fold have been identified. The residues contributing to the binding site for the antagonist, N -methyl scopolamine, and the agonist, acetylcholine, have been mapped. The positively charged headgroups of these ligands probably bind in a charge-stabilized aromatic cage formed by amino acid side chains in TM helices TM3, TM6 and TM7, while residues in TM4 may participate as part of a peripheral docking site. Closure of the cage around the headgroup of acetylcholine may be part of the mechanism for transducing binding energy into receptor activation, probably by disrupting a set of Van der Waals interactions between residues lying beneath the binding site that help to constrain the receptor to the inactive state, in the absence of agonist. This may trigger the reorganization of a hydrogen-bonding network between highly conserved residues in the core of the receptor, whose integrity is crucial for achievement of the activated state.

Acetylcholine↗

PubMed2003

Scanning mutagenesis studies of the M1 muscarinic acetylcholine receptor.

Following the solution of the structure of bovine rhodopsin by X-ray crystallography, it has been possible to build an improved homology model of the M(1) muscarinic acetylcholine receptor. This has been used to interpret the outcome of an extensive series of scanning and point mutagenesis studies on the transmembrane domain of the receptor. Potential intramolecular interactions enhancing the stability of the protein fold have been identified. The residues contributing to the binding site for the antagonist, N-methylscopolamine, and the agonist, acetylcholine have been mapped. The positively charged headgroups of these ligands appear to bind in a charge-stabilized aromatic cage formed by amino acid side chains in transmembrane (TM) helices 3, 6, and 7, while residues in TM 4 may participate in a peripheral docking site. Closure of the cage around the headgroup of acetylcholine may help to transduce binding energy into receptor activation, possibly disrupting a set of Van der Waals interactions between a set of residues underlying the binding site which help to constrain the receptor to the inactive state, in the absence of agonist. This may trigger the reorganization of a hydrogen bonding network between highly conserved residues in the core of the receptor, whose integrity is crucial for activation.

Acetylcholine↗

PubMed2001

Transmembrane domains 4 and 7 of the M(1) muscarinic acetylcholine receptor are critical for ligand binding and the receptor activation switch.

Activation of the muscarinic acetylcholine receptors requires agonist binding followed by a conformational change, but the ligand binding and conformation-switching residues have not been completely identified. Systematic alanine-scanning mutagenesis has been used to assess residues 142-164 in transmembrane helix 4 and 402-421 in transmembrane helix 7 of the M(1) muscarinic acetylcholine receptor. Several inward-facing amino acid side chains in the exofacial parts of transmembrane helices 4 and 7 contribute to acetylcholine binding. Alanine substitution of the aromatic residues in this group reduced signaling efficacy, suggesting that they may form part of a charge-stabilized aromatic cage, which triggers rotation and movement of the transmembrane helices. The mutation of adjacent residues modulated receptor activation, either reducing signaling or causing constitutive activation. In the buried endofacial section of transmembrane helix 7, alanine substitution mutants of the conserved NSXXNPXXY motif displayed strongly reduced signaling efficacy, despite having increased or unchanged acetylcholine affinity. These residues may have dual functions, forming intramolecular contacts that stabilize the receptor in the inactive ground state, but that are broken, allowing them to form new intramolecular bonds in the activated state. This conformational rearrangement is critical to produce a G protein binding site and may represent a key mechanism of receptor activation.

Acetylcholine↗

PubMed2001

The conformational switch in muscarinic acetylcholine receptors.

The recently-determined structure of rhodopsin has provided a suitable basis for modeling the three-dimensional structure of the M1 muscarinic acetylcholine receptor. Using this as a framework for interpreting mutagenesis studies, we have been able to suggest most of the contacts which the receptor makes with acetylcholine and many of the intramolecular contacts which are important for the ground-state structure of the receptor. It is possible to outline a mechanism of G-protein interaction.

Animals↗

PubMed2001

Sensitive calibration and measurement procedures based on the amplification principle in motion perception.

We compare two types of sampled motion stimuli: ordinary periodic displays with modulation amplitude m(o=e) that translate 90 degrees between successive frames and amplifier sandwich displays. In sandwich displays, even-numbered frames are of one type, odd-numbered frames are of the same or different type, and (1) both types have the same period, (2) translate in a consistent direction 90 degrees between frames, and (3) even frames have modulation amplitude m(e), odd frames have modulation amplitude m(o). In both first-order motion (van Santen, J.P.H. & Sperling, G. (1984). Temporal covariance model of human motion perception. Journal of the Optical Society of America A, 1, 451-73) and second-order motion (Werkhoven, P., Sperling, G., & Chubb, C. (1993). Motion perception between dissimilar gratings: a single channel theory. Vision Research, 33, 463-85) the motion strength of amplifier sandwich displays is proportional to the product m(o)m(e) for a wide range of m(e). By setting m(e) to a large value, an amplifier sandwich stimulus with a very small value of m(o) can still produce visible motion. The amplification factor is the ratio of two threshold modulation amplitudes: ordinary circumflexm(o=e) over amplified circumflexm(o), circumflexm(o=e)/circumflexm(o). We find amplification factors of up to about 8x. Light adaptation and contrast gain control in early visual processing distort the representations of visual stimuli so that inputs to subsequent perceptual processes contain undesired distortion products or 'impurities'. Motion amplification is used to measure and thence to reduce these unwanted components in a stimulus to a small fraction of their threshold. Such stimuli are certifiably pure in the sense that the residual impurity is less than a specified value. Six applications are considered: (1) removing (first-order) luminance contamination from moving (second-order) texture gratings; (2) removing luminance contamination from moving chromatic gratings to produce pure isoluminant gratings; (3) removing distortion products in luminance-modulated (first-order) gratings - by iterative application, all significant distortion products can be removed; (4) removing second-order texture contamination from third-order motion displays; (5) removing feature bias from third-order motion displays; (6) and the same general principles are applied to texture-slant discrimination in which x,y spatial coordinates replace the x,t motion coordinates. In all applicable domains, the amplification principle provides a powerful assay method for the precise measurement of very weak stimuli, and thereby a means of producing visual displays of certifiable purity.

Adaptation, Ocular↗

PubMed2001

Characterizing the spatial-frequency sensitivity of perceptual templates.

Filtered external noise has been an important tool in characterizing the spatial-frequency sensitivity of perceptual templates. Typically, low-pass- and/or high-pass-filtered external noise is added to the signal stimulus. Thresholds, the signal energy necessary to maintain given criterion performance levels, are measured as functions of the spatial-frequency passband of the external noise. An observer model is postulated to segregate the impact of the external noise and the internal noise. The spatial-frequency sensitivity of the perceptual template is determined by the relative impact exerted by external noise in each frequency band. The perceptual template model (PTM) is a general observer model that provides an excellent account of human performance in white external noise [Vision Res. 38, 1183 (1998); J. Opt. Soc. Am. A 16, 764 (1999)]. We further develop the PTM for filtered external noise and apply it to derive the spatial-frequency sensitivity of perceptual templates.

Humans↗

PubMed2001

Three-systems theory of human visual motion perception: review and update.

Lu and Sperling [Vision Res. 35, 2697 (1995)] proposed that human visual motion perception is served by three separate motion systems: a first-order system that responds to moving luminance patterns, a second-order system that responds to moving modulations of feature types-stimuli in which the expected luminance is the same everywhere but an area of higher contrast or of flicker moves, and a third-order system that computes the motion of marked locations in a "salience map," that is, a neural representation of visual space in which the locations of important visual features ("figure") are marked and "ground" is unmarked. Subsequently, there have been some strongly confirmatory reports: different gain-control mechanisms for first- and second-order motion, selective impairment of first- versus second- and/or third-order motion by different brain injuries, and the classification of new third-order motions, e.g., isoluminant chromatic motion. Various procedures have successfully discriminated between second- and third-order motion (when first-order motion is excluded): dual tasks, second-order reversed phi, motion competition, and selective adaptation. Meanwhile, eight apparent contradictions to the three-systems theory have been proposed. A review and reanalysis here of the new evidence, pro and con, resolves the challenges and yields a more clearly defined and significantly strengthened theory.

Contrast Sensitivity↗

PubMed2000

A network of conserved intramolecular contacts defines the off-state of the transmembrane switch mechanism in a seven-transmembrane receptor.

Activation of the rhodopsin-like 7-transmembrane (7-TM) receptors requires switching interhelical constraints that stabilize the inactive state to a new set of contacts in the activated state, which binds the cognate G-protein. The free energy to drive this is provided by agonist binding, which has higher affinity to the active than to the inactive conformation. We have sought specific interhelical constraint contacts, using the M(1) muscarinic acetylcholine receptor as a model. Histidine substitutions of particular groups of amino acids, in transmembrane domains 3, 6, and 7, created high-affinity Zn(2+) binding sites, demonstrating the close proximity of their side chains in the inactive state. Alanine point substitutions have shown the effect of weakening the individual intramolecular contacts. In each case, the acetylcholine affinity was increased, implying promotion of the activated state. These amino acids are highly conserved throughout the 7-TM receptor superfamily. We propose that they form an important part of a network of conserved interhelical contacts that defines the off-state of a general transmembrane switch mechanism.

Acetylcholine↗

PubMed2000

Mechanisms of perceptual attention in precuing of location.

What are the mechanisms of spatial attention underlying precue validity effects? We answer this question within the framework of a perceptual template model (PTM) [Lu & Dosher (1998). External noise distinguishes attention mechanisms. Vision Research, 38, 1183-1198; Dosher & Lu (1999). Mechanisms of perceptual learning. Vision Research, 39, 3197-3221] and an external noise plus attention paradigm for orientation judgments in two- to eight-location displays. Attentional mechanisms correspond to behavioral signatures: External noise exclusion produces cuing effects in high external noise and stimulus enhancement produces cuing effects in noiseless displays. We found that external noise exclusion was the primary mechanism of cue validity effects, with large effects in high-noise displays. Stimulus enhancement coexisted as a secondary mechanism in noiseless displays for a subset of observers and display conditions. Contrast threshold ratio tests ruled out attentionally mediated changes in gain control. The ratio rules were also shown to hold for a stochastic PTM model. Effects were equivalent for four-alternative (Experiment 1) and two-alternative (Experiment 2) orientation identification. Precues allow observers to reduce noise and focus on the target in the precued location. External noise exclusion was more important in larger displays. Previous results are reclassified and understood within the PTM framework.

Attention↗

PubMed2000

Attention mechanisms for multi-location first- and second-order motion perception.

We applied the external noise plus attention paradigm to study attention mechanisms involved in concurrent first-order and second-order motion perception at two spatial locations. Cued to attend to one of the locations, the observer was instructed to independently judge direction of motion of either first-order (Experiment 1) or second-order (Experiment 2) motion stimuli at both locations in every trial. Across trials, systematically controlled amounts of external noise were added to the motion displays. We measured motion threshold at three performance criteria in every attention x external noise condition. We find that observers could, without any loss, simultaneously compute first-order motion direction at two widely separated spatial locations across a broad range of external noise conditions. However, considerable loss occurred at the unattended location in processing second-order motion direction at two separated spatial locations. We conclude that, under the conditions investigated in the current study, (1) in first-order motion perception, the visual system could simultaneously process motion direction at two widely separated locations without any capacity limitation; (2) in second-order motion perception, attending to a spatial location enhances stimulus contrast at that location by a factor of about 1.37 (or equivalently, reduces the internal additive noise by a factor of about 0.73).

Attention↗

PubMed2000

Spatial attention: different mechanisms for central and peripheral temporal precues?

The external noise paradigm (Z.-L. Lu & B. A. Dosher, 1998) was applied to investigate mechanisms of spatial attention in location precuing. Observers were precued or simultaneously cued to identify 1 of 4 pseudocharacters embedded in various amounts of external noise. The cues were either central or peripheral. Both central and peripheral precuing significantly reduced threshold in the presence of high external noise (16% and 17.5%). Only peripheral precuing significantly reduced threshold in the presence of low, or no, external noise (11%). A perceptual template model identified different mechanisms of attention for central and peripheral precuing, external noise exclusion for central precuing, and a combination of external noise exclusion and stimulus enhancement (or equivalently, internal additive noise reduction) for peripheral cuing.

Attention↗

PubMed2000

4,5-Diazafluoren-9-one benzoylhydrazone monohydrate.

The title compound, C(18)H(12)N(4)O.H(2)O, adopts the keto tautomeric form and the azomethine C=N double bond is in the E configuration. The dihedral angle between the planes of the diazafluorene moiety and the phenyl ring is 11.3 (1) degrees. In the solid state, the molecules form infinite chain-like structures via O-H.N hydrogen bonds involving the water molecules and diazafluorene moieties.

Crystallography, X-Ray↗

PubMed2000

Noise exclusion in spatial attention.

Precue validity affects the performance of perceptual tasks. These spatial attention effects have been variously attributed to facilitation of processing, capacity allocation, or noise reduction. We used a new attention-plus-external (stimulus)-noise paradigm and model to identify the mechanisms of attention in cue-validity paradigms. A new phenomenon is reported: a large effect of location cue validity in an orientation identification task that specifically occurs when the stimulus is embedded in external (environmental or stimulus) noise. This result identifies the mechanism of the effect as external-noise exclusion, distinguished from stimulus enhancement that manifests itself only in noiseless stimulus environments.

Attention↗

PubMed1999

Perceptual motion standstill in rapidly moving chromatic displays.

In motion standstill, a quickly moving object appears to stand still, and its details are clearly visible. It is proposed that motion standstill can occur when the spatiotemporal resolution of the shape and color systems exceeds that of the motion systems. For moving red-green gratings, the first- and second-order motion systems fail when the grating is isoluminant. The third-order motion system fails when the green/red saturation ratio produces isosalience (equal distinctiveness of red and green). When a variety of high-contrast red-green gratings, with different spatial frequencies and speeds, were made isoluminant and isosalient, the perception of motion standstill was so complete that motion direction judgments were at chance levels. Speed ratings also indicated that, within a narrow range of luminance contrasts and green/red saturation ratios, moving stimuli were perceived as absolutely motionless. The results provide further evidence that isoluminant color motion is perceived only by the third-order motion system, and they have profound implications for the nature of shape and color perception.

Color Perception↗

PubMed1999

Invariance of brain-wave representations of simple visual images and their names.

In two experiments, electric brain waves of 14 subjects were recorded under several different conditions to study the invariance of brain-wave representations of simple patches of colors and simple visual shapes and their names, the words blue, circle, etc. As in our earlier work, the analysis consisted of averaging over trials to create prototypes and test samples, to both of which Fourier transforms were applied, followed by filtering and an inverse transformation to the time domain. A least-squares criterion of fit between prototypes and test samples was used for classification. The most significant results were these. By averaging over different subjects, as well as trials, we created prototypes from brain waves evoked by simple visual images and test samples from brain waves evoked by auditory or visual words naming the visual images. We correctly recognized from 60% to 75% of the test-sample brain waves. The general conclusion is that simple shapes such as circles and single-color displays generate brain waves surprisingly similar to those generated by their verbal names. These results, taken together with extensive psychological studies of auditory and visual memory, strongly support the solution proposed for visual shapes, by Bishop Berkeley and David Hume in the 18th century, to the long-standing problem of how the mind represents simple abstract ideas.

Adult↗

PubMed1999

Invariance between subjects of brain wave representations of language.

In three experiments, electric brain waves of 19 subjects were recorded under several different experimental conditions for two purposes. One was to test how well we could recognize which sentence, from a set of 24 or 48 sentences, was being processed in the cortex. The other was to study the invariance of brain waves between subjects. As in our earlier work, the analysis consisted of averaging over trials to create prototypes and test samples, to both of which Fourier transforms were applied, followed by filtering and an inverse transformation to the time domain. A least-squares criterion of fit between prototypes and test samples was used for classification. In all three experiments, averaging over subjects improved the recognition rates. The most significant finding was the following. When brain waves were averaged separately for two nonoverlapping groups of subjects, one for prototypes and the other for test samples, we were able to recognize correctly 90% of the brain waves generated by 48 different sentences about European geography.

Brain↗

PubMed1999

Measuring the amplification of attention.

An ambiguous motion paradigm, in which the direction of apparent motion is determined by salience (i.e., the extent to which an area is perceived as figure versus ground), is used to assay the amplification of color by attention to color. In the red-green colored gratings used in these experiments, without attention instructions, salience depends on the chromaticity difference between colored stripes embedded in the motion sequence and the yellow background. Selective attention to red (or to green) alters the perceived direction of motion and is found to be equivalent to increasing the physical redness (or greenness) by 25-117%, depending on the observer and color. Whereas attention to a color drastically alters the salience of that color, it leaves color appearance unchanged. A computational model, which embodies separate, parallel pathways for object perception and for salience, accounts for 99% of the variance of the experimental data.

Attention↗