Extending the MNREAD sentence corpus: Computer-generated sentences for measuring visual performance in reading.

The MNREAD chart consists of standardized sentences printed at 19 sizes in 0.1 logMAR steps. There are 95 sentences distributed across the five English versions of the chart. However, there is a demand for a much larger number of sentences: for clinical research requiring repeated measures, and for new vision tests that use multiple trials at each print size. This paper describes a new sentence generator that has produced over nine million sentences that fit the MNREAD constraints, and demonstrates that reading performance with these new sentences is comparable to that obtained with the original MNREAD sentences. We measured reading performance with the original MNREAD sentences, two sets of our new sentences, and sentences with shuffled word order. Reading-speed versus print-size curves were obtained for each sentence set from 14 readers with normal vision at two levels of blur (intended to simulate acuity loss in low vision) and with unblurred text. We found no significant differences between the new and original sentences in reading acuity and critical print size across all levels of blur. Maximum reading speed was 7% slower with the new sentences than with the original sentences. Shuffled sentences yielded slower maximum reading speeds and larger reading acuities than the other sentences. Overall, measures of reading performance with the new sentences are similar to those obtained with the original MNREAD sentences. Our sentence generator substantially expands the reading materials for clinical research on reading vision using the MNREAD test, and opens up new possibilities for measuring how text parameters affect reading.

Spatial-frequency and contrast properties of crowding.

Crowding, the difficulty in recognizing a letter flanked by other letters, has been explained as a lateral masking effect. The purpose of this study was to examine the spatial-frequency and contrast dependencies of crowding, and to compare them with the properties of pattern masking. In experiment 1, we measured contrast thresholds for identifying the middle letters in strings of three randomly chosen lower-case letters (trigrams), for a range of letter spacings. Letters were digitally filtered using a set of bandpass filters, with peak object spatial frequencies ranging from 0.63 to 10 c/letter. Bandwidth of the filters was 1 octave. Frequencies of the target and flanking letters were the same, or differed by up to 2 octaves. Contrast of the flanking letters was fixed at the maximum value. Testing was conducted at the fovea and 5 degrees eccentricity. We found that crowding exhibits spatial-tuning functions like masking, but with generally broader bandwidths than those for masking. The spatial extent of crowding was found to be about 0.5 deg at the fovea and 2 deg at 5 degrees eccentricity, independent of target letter frequency. In experiment 2, we measured the contrast thresholds for identifying the middle target letters in trigrams for a range of flanking letter contrasts at 5 degrees eccentricity. At low flanker contrast, crowding does not show a facilitatory region, unlike pattern masking. At high flanker contrast, threshold rises with contrast with an exponent of 0.13-0.3, lower than corresponding exponents for pattern masking. In experiment 3, we varied the contrast ratio between the flanking letters and the target letters, and found that the magnitude of crowding increases monotonically with contrast ratio. This finding contradicts a prediction based on a grouping explanation for crowding. Our results are consistent with the postulation that crowding and masking may share the same first stage linear filtering process, and perhaps a similar second-stage process, with the additional property that the second-stage process in crowding pools information over a spatial extent that varies with eccentricity.

SANE (Structure Assisted NOE Evaluation): an automated model-based approach for NOE assignment.

A reliable automated approach for assignment of NOESY spectra would allow more rapid determination of protein structures by NMR. In this paper we describe a semi-automated procedure for complete NOESY assignment (SANE, Structure Assisted NOE Evaluation), coupled to an iterative procedure for NMR structure determination where the user is directly involved. Our method is similar to ARIA [Nilges et al. (1997) J. Mol. Biol., 269, 408-422], but is compatible with the molecular dynamics suites AMBER and DYANA. The method is ideal for systems where an initial model or crystal structure is available, but has also been used successfully for ab initio structure determination. Use of this semi-automated iterative approach assists in the identification of errors in the NOE assignments to short-cut the path to an NMR solution structure.

Psychophysics of reading. XX. Linking letter recognition to reading speed in central and peripheral vision.

Our goal is to link spatial and temporal properties of letter recognition to reading speed for text viewed centrally or in peripheral vision. We propose that the size of the visual span - the number of letters recognizable in a glance - imposes a fundamental limit on reading speed, and that shrinkage of the visual span in peripheral vision accounts for slower peripheral reading. In Experiment 1, we estimated the size of the visual span in the lower visual field by measuring RSVP (rapid serial visual presentation) reading times as a function of word length. The size of the visual span decreased from at least 10 letters in central vision to 1.7 letters at 15 degrees eccentricity, in good agreement with the corresponding reduction of reading speed measured by Chung and coworkers (Chung, S. T. L., Mansfield, J. S., & Legge, G. E. (1998). Psychophysics of reading. XVIII. The effect of print size on reading speed in normal peripheral vision. Vision Research, 38, 2949-2962). In Exp. 2, we measured letter recognition for trigrams (random strings of three letters) as a function of their position on horizontal lines passing through fixation (central vision) or displaced downward into the lower visual field (5, 10 and 20 degrees ). We also varied trigram presentation time. We used these data to construct visual-span profiles of letter accuracy versus letter position. These profiles were used as input to a parameter-free model whose output was RSVP reading speed. A version of this model containing a simple lexical-matching rule accounted for RSVP reading speed in central vision. Failure of this version of the model in peripheral vision indicated that people rely more on lexical inference to support peripheral reading. We conclude that spatiotemporal characteristics of the visual span limit RSVP reading speed in central vision, and that shrinkage of the visual span results in slower reading in peripheral vision.

Invariant recognition of natural objects in the presence of shadows.

Shadows are frequently present when we recognize natural objects, but it is unclear whether they help or hinder recognition. Shadows could improve recognition by providing information about illumination and 3-D surface shape, or impair recognition by introducing spurious contours that are confused with object boundaries. In three experiments, we explored the effect of shadows on recognition of natural objects. The stimuli were digitized photographs of fruits and vegetables displayed with or without shadows. In experiment 1, we evaluated the effects of shadows, color, and image resolution on naming latency and accuracy. Performance was not affected by the presence of shadows, even for gray-scale, blurry images, where shadows are difficult to identify. In experiment 2, we explored recognition of two-tone images of the same objects. In these images, shadow edges are difficult to distinguish from object and surface edges because all edges are defined by a luminance boundary. Shadows impaired performance, but only in the early trials. In experiment 3, we examined whether shadows have a stronger impact when exposure time is limited, allowing little time for processing shadows; no effect of shadows was found. These studies show that recognition of natural objects is highly invariant to the complex luminance patterns caused by shadows.

Permeability, cytotoxicity, and genotoxicity of Cr(III) complexes and some Cr(V) analogues in V79 Chinese hamster lung cells.

The permeabilities and genotoxicities of the Cr(III) complexes [Cr(en)(3)](3+), mer-[Cr(glygly)(2)](-), cis-[Cr(phen)(2)(OH(2))(2)](3+), and trans-[Cr(salen)(OH(2))(2)](+) and the Cr(V) analogues of cis-[Cr(phen)(2)(OH(2))(2)](3+) and trans-[Cr(salen)(OH(2))(2)](+) [en being 1,2-ethanediamine, glygly being glycylglycine, phen being 1,10-phenanthroline, and salen being N,N'-ethylenebis(salicylideneiminato)] have been studied in V79 Chinese hamster lung cells. Following exposure of approximately 10(6) cells to 0.4 mM Cr(III) for 4 h, the Cr uptake by single cells was less than 10(-)(14) g/cell (as determined by GFAAS analysis and as confirmed by PIXE analysis where the Cr concentration was below the limit of detection). Importantly, the Cr(V) analogue of cis-[Cr(phen)(2)(OH(2))(2)] was significantly more permeable than the Cr(III) complex. The cytotoxicity of the Cr(III) complexes increased in the following order: mer-[Cr(glygly)(2)](-) < [Cr(en)(3)](3+) approximately cis-[Cr(phen)(2)(OH(2))(2)](3+) < trans-[Cr(salen)(OH(2))(2)](+). No genotoxic effects were observed following exposure to mer-[Cr(glygly)(2)](-) or [Cr(en)(3)](3+) at concentrations up to 6 mM. The Cr(III) imine complexes trans-[Cr(salen)(OH(2))(2)](+) and cis-[Cr(phen)(2)(OH(2))(2)](3+), which could be oxidized to Cr(V) complexes, induced MN in vitro at rates of 13.6 and 3.3 MN/1000 BN cells/micromol of Cr, respectively. The comparative permeabilities and genotoxicities of trans-[Cr(salen)(OH(2))(2)](+) and [CrO(salen)](+) were similar due to the instability of the Cr(V) complex at physiological pH values (7.4). There was a substantial increase in the permeability of [Cr(O)(2)(phen)(2)](+), compared to that of the Cr(III) analogue, which was accompanied by a highly genotoxic response. Consequently, any Cr(III) complex that is absorbed by cells and can be oxidized to Cr(V) must be considered as a potential carcinogen. This has potential implications for the increased use of Cr(III) complexes as dietary supplements and highlights the need to consider the genotoxicities of a variety of Cr(III) complexes when determining the carcinogenic potential of Cr(III) particularly when "high" deliberately administered doses are concerned.

Solution structure of the cysteine-rich domain of the Escherichia coli chaperone protein DnaJ.

The solution structure of the cysteine-rich (CR) domain of Escherichia coli DnaJ has been solved by NMR methods. The structure of a 79 residue CR domain construct shows a novel fold with an overall V-shaped extended beta-hairpin topology. The CR domain is characterized by four C-X-X-C-X-G-X-G sequence motifs that bind two zinc ions. Residues in these two zinc modules show strong similarities in the grouping of resonances in the (15)N-(1)H HSQC spectrum and display pseudo-symmetry of the motifs in the calculated structures. The conformation of the cysteine residues coordinated to the zinc ion resembles that of the rubredoxin-knuckle, but there are significant differences in hydrogen bonding patterns in the two motifs. Zinc (15)N-(1)H HSQC titrations indicate that the fold of the isolated DnaJ CR domain is zinc-dependent and that one zinc module folds before the other. The C-X-X-C-X-G-X-G sequence motif is highly conserved in CR domains from a wide variety of species. The three-dimensional structure of the E. coli CR domain indicates that this sequence conservation is likely to result in a conserved structural motif.

The effect of contrast on reading speed in dyslexia.

Contrast coding has been reported to differ between dyslexic and normal readers. Dyslexic readers require higher levels of contrast to detect sinewave gratings for certain spatiotemporal conditions, and dyslexic readers show faster visual search at low contrast. We investigated whether these differences in early contrast coding generalize to reading performance by measuring reading speed as a function of text contrast for dyslexic children and adults and for age-matched controls. Contrast affected reading performance of dyslexic and normal readers similarly. For both groups, reading speed was relatively constant between 100 and 2% contrast, and decreased rapidly below 2% contrast. This pattern of results held true for both children and adults, for text with and without sentence context, across a range of character sizes, and for reading aloud and reading silently. We conclude that earlier findings of group differences in contrast effects on grating detection or visual search tasks do not generalize to reading.

NMR solution structure of the inserted domain of human leukocyte function associated antigen-1.

The interaction between the leukocyte function-associated antigen-1 (LFA-1) and the intercellular adhesion molecule is thought to be mediated primarily via the inserted domain (I-domain) in the alpha-subunit. The activation of LFA-1 is an early step in triggering the adhesion of leukocytes to target cells decorated with intercellular adhesion molecules. There is some disagreement in the literature over the respective roles of conformational changes in the I-domain and of divalent cations (Mg(2+), Mn(2+)) in the activation of LFA-1 for intercellular adhesion molecule binding. X-ray crystallographic structures of the I-domains of LFA-1 and Mac-1 in the presence and absence of cations show structural differences in the C-terminal alpha-helix; this change was proposed to represent the active and inactive conformations of the I-domain. However, more recent X-ray results have called this proposal into question. The solution structure of the Mg(2+) complex of the I-domain of LFA-1 has been determined by NMR methods, using a model-based approach to nuclear Overhauser enhancement spectroscopy peak assignment. The protein adopts the same structure in solution as that of the published I-domain X-ray structures, but the C-terminal region, where the X-ray structures are most different from each other, is different again in the solution structures. The secondary structure of this helix is well formed, but NMR relaxation data indicate that there is considerable flexibility present, probably consisting of breathing or segmental motion of the helix. The conformational diversity seen in the various X-ray structures could be explained as a result of the inherent flexibility of this C-terminal region and as a result of crystal contacts. Our NMR data are consistent with a model where the C-terminal helix has the potential flexibility to take up alternative conformations, for example, in the presence and absence of the intercellular adhesion molecule ligand. The role of divalent cations appears from our results not to be as a direct mediator of a conformational change that alters affinity for the ligand. Rather, the presence of the cation appears to be involved in some other way in ligand binding, perhaps by acting as a bridge to the ligand and by modulation of the charge of the binding surface.

Reading with a head-mounted video magnifier.

PURPOSE: This study compared the effectiveness of a head-mounted video magnifier, low-vision enhancement system (LVES), with closed-circuit TV (CCTV) and large print as a device or means of improving reading performance in people with low vision. METHODS: The reading performance of ten low-vision participants was assessed in two ways: (1) By measuring reading speed as a function of print size with LVES and without LVES, and (2) by comparing reading speed and comprehension of news articles using the LVES vs. a popular non-head-mounted video magnifier, the CCTV. RESULTS: Maximum reading speeds with LVES matched the maximum reading speeds with unaided vision attained by enlarging print. The critical print size (the smallest print size that could be read at maximum reading speed) improved significantly for all participants using LVES compared with unaided vision. When comparing reading performance using LVES and CCTV, we found that reading speed and comprehension for the two conditions were equivalent. The two low-vision participants with lowest acuities (20/640 and 20/960) could not read the 10-point newspaper articles with LVES, even with an 8 D auxiliary reading lens that permitted a very close reading distance. CONCLUSIONS: Head-mounted video magnifiers, such as LVES, can support good low-vision reading performance, but the restricted range of magnification may limit the usefulness of the device as a reading magnifier for people with very low acuity.

Structural basis for LFA-1 inhibition upon lovastatin binding to the CD11a I-domain.

The lymphocyte function-associated antigen (LFA-1) belongs to the family of beta2-integrins and plays an important role in T-cell activation and leukocyte migration to sites of inflammation. We report here that lovastatin, a drug clinically used for lowering cholesterol levels, inhibits the interaction of human LFA-1 with its counter-receptor intercellular adhesion molecule-1. Using nuclear magnetic resonance spectroscopy and X-ray crystallography we show that the inhibitor binds to a highly conserved domain of the LFA-1 alpha-chain called the I-domain. The first three-dimensional structure of an integrin inhibitor bound to its receptor reveals atomic details for a hitherto unknown mode of LFA-1 inhibition. It also sheds light into possible mechanisms of LFA-1 mediated signalling and will support the design of novel anti-adhesive and immunosuppressive drugs.

The structure of a tunicate C-type lectin from Polyandrocarpa misakiensis complexed with D -galactose.

C-type lectins are calcium-dependent carbohydrate-recognising proteins. Isothermal titration calorimetry of the C-type Polyandrocarpa lectin (TC14) from the tunicate Polyandrocarpa misakiensis revealed the presence of a single calcium atom per monomer with a dissociation constant of 2.6 microM, and confirmed the specificity of TC14 for D -galactose and related monosaccharides. We have determined the 2.2 A X-ray crystal structure of Polyandrocarpa lectin complexed with D -galactose. Analytical ultracentrifugation revealed that TC14 behaves as a dimer in solution. This is reflected by the presence of two molecules in the asymmetric unit with the dimeric interface formed by antiparallel pairing of the two N-terminal beta-strands and hydrophobic interactions. TC14 adopts a typical C-type lectin fold with differences in structure from other C-type lectins mainly in the diverse loop regions and in the second alpha-helix, which is involved in the formation of the dimeric interface. The D -galactose is bound through coordination of the 3 and 4-hydroxyl oxygen atoms with a bound calcium atom. Additional hydrogen bonds are formed directly between serine, aspartate and glutamate side-chains of the protein and the sugar 3 and 4-hydroxyl groups. Comparison of the galactose binding by TC14 with the mannose binding by rat mannose-binding protein reveals how monosaccharide specificity is achieved in this lectin. A tryptophan side-chain close to the binding site and the distribution of hydrogen-bond acceptors and donors around the 3 and 4-hydroxyl groups of the sugar are essential determinants of specificity. These elements are, however, arranged in a very different way than in an engineered galactose-specific mutant of MBPA. Possible biological functions can more easily be understood from the fact that TC14 is a dimer under physiological conditions.

What is low vision? A re-evaluation of definitions.

PURPOSE: To re-evaluate definitions of low vision, visual impairment, and disability. METHODS: We review current definitions of legal blindness and low vision and how these definitions are variably based on disability or impairment. We argue for a definite distinction being made between criteria for visual impairment and visual disability, low vision being defined as the presence of a visual impairment that results in a disability. Visual impairment is defined according to population norms and a statistical cut-off is used. Visual disability is defined by consideration of the level of visual measures which result in measurable or reportable disability. We consider the evidence that contrast sensitivity should be a criterion for visual disability in addition to visual acuity and visual field. CONCLUSIONS: According to the current information, we define visual impairment as best monocular or binocular visual acuity <(worse than) 6/7.5, total horizontal visual field <146 degrees (Goldmann III-4e) or <109 degrees (III-3e), and contrast sensitivity <1.5 (PelliRobson); we define visual disability as best monocular or binocular visual acuity <6/12 or contrast sensitivity <1.05.

Analysis of the distribution of Cu, Fe and Zn and other elements in brindled mouse kidney using a scanning proton microprobe.

An analysis of the distribution of trace metals in the kidney cortex in normal and brindled male mice has been carried out with a scanning proton microprobe. Enzyme histochemical staining techniques were used to distinguish between proximal and distal tubules. Average copper levels were increased in brindled kidney tissue sections, with the above-normal Cu accumulation found to occur entirely within the proximal tubules. Therefore, the proximal tubule is now regarded as the location where the defect in Cu transport in brindled mice is manifested the most clearly. The distribution of Fe was found to be non-uniform with some tubule cross-sections exhibiting high concentrations in both genotypes. The distribution of Zn was found to be uniform, and the concentration was similar for each genotype.

Psychophysics of reading. XVIII. The effect of print size on reading speed in normal peripheral vision.

Reading in peripheral vision is slow and requires large print, posing substantial difficulty for patients with central scotomata. The purpose of this study was to evaluate the effect of print size on reading speed at different eccentricities in normal peripheral vision. We hypothesized that reading speeds should remain invariant with eccentricity, as long as the print is appropriately scaled in size--the scaling hypothesis. The scaling hypothesis predicts that log-log plots of reading speed versus print size exhibit the same shape at all eccentricities, but shift along the print-size axis. Six normal observers read aloud single sentences (approximately 11 words in length) presented on a computer monitor, one word at a time, using rapid serial visual presentation (RSVP). We measured reading speeds (based on RSVP exposure durations yielding 80% correct) for eight print sizes at each of six retinal eccentricities, from 0 (foveal) to 20 deg in the inferior visual field. Consistent with the scaling hypothesis, plots of reading speed versus print size had the same shape at different eccentricities: reading speed increased with print size, up to a critical print size and was then constant at a maximum reading speed for larger print sizes. Also consistent with the scaling hypothesis, the plots shifted horizontally such that average values of the critical print size increased from 0.16 deg (fovea) to 2.22 deg (20 deg peripheral). Inconsistent with the scaling hypothesis, the plots also exhibited vertical shifts so that average values of the maximum reading speed decreased from 807 w.p.m. (fovea) to 135 w.p.m. (20 deg peripheral). Because the maximum reading speed is not invariant with eccentricity even when the print size was scaled, we reject the scaling hypothesis and conclude that print size is not the only factor limiting maximum reading speed in normal peripheral vision.

The viewpoint complexity of an object-recognition task.

There is an ongoing debate about the nature of perceptual representation in human object recognition. Resolution of this debate has been hampered by the lack of a metric for assessing the representational requirements of a recognition task. To recognize a member of a given set of 3-D objects, how much detail must the objects' representations contain in order to achieve a specific accuracy criterion? From the performance of an ideal observer, we derived a quantity called the view complexity (VX) to measure the required granularity of representation. VX is an intrinsic property of the object-recognition task, taking into account both the object ensemble and the type of decision required of an observer. It does not depend on the visual representation or processing used by the observer. VX can be interpreted as the number of randomly selected 2-D images needed to represent the decision boundaries in the image space of a 3-D object-recognition task. A low VX means the task is inherently more viewpoint invariant and a high VX means it is inherently more viewpoint dependent. By measuring the VX of recognition tasks with different object sets, we show that the current confusion about the nature of human perceptual representation is partly due to a failure in distinguishing between human visual processing and the properties of a task and its stimuli. We find general correspondence between the VX of a recognition task and the published human data on viewpoint dependence. Exceptions in this relationship motivated us to propose the view-rate hypothesis: human visual performance is limited by the equivalent number of 2-D image views that can be processed per unit time.

Psychophysics of reading. XVII. Low-vision performance with four types of electronically magnified text.

Most people with low vision need magnification to read. Page navigation is the process of moving a magnifier during reading. Modern electronic technology can provide many alternatives for navigating through text. This study compared reading speeds for four methods of displaying text. The four methods varied in their page-navigation demands. The closed-circuit television (CCTV) and MOUSE methods involved manual navigation. The DRIFT method (horizontally drifting text) involved no manual navigation, but did involve both smooth-pursuit and saccadic eye movements. The rapid serial visual presentation (RSVP) method involved no manual navigation, and relatively few eye movements. There were 7 normal subjects and 12 low-vision subjects (7 with central-field loss, CFL group, and 5 with central fields intact, CFI group). The subjects read 70-word passages at speeds that yielded good comprehension. Taking the CCTV reading speed as a benchmark, neither the normal nor low-vision subjects had significantly different speeds with the MOUSE method. As expected from the reduced navigational demands, normal subjects read faster with the DRIFT method (85% faster) and the RSVP method (169%). The CFI group read significantly faster with DRIFT (43%) and RSVP (38%). The CFL group showed no significant differences in reading speed for the four methods.

Permeability, cytotoxicity, and genotoxicity of chromium (V) and chromium (VI) complexes in V79 Chinese hamster lung cells.

The genotoxicity of Cr(V) complexes in mammalian cells (V79 Chinese hamster lung cells) has been studied for the first time using the in vitro micronucleus assay. Two complexes were investigated, [CrO(ehba)2]-, which undergoes ligand-exchange and disproportionation reactions in the cell growth medium, and [CrO(mampa)]-, which is chemically inert in the medium for the duration of the exposure period. Results of in vitro micronucleus assays show that both complexes are genotoxic and exhibit similar potencies to that of [Cr2O7]2-. The permeabilities of the Cr(V) complexes were also investigated for the first time using particle-induced X-ray emission (PIXE) analysis of individual cells. The Cr uptake increased in the order: [Cr(phen)2-(H2O)2]3+ < [CrO(ehba)2]- < [CrO(mampa)]- < [Cr2O7]2-. Clonal assays showed that Cr(VI) exhibits an expectedly higher cytotoxicity than the Cr(V) complexes. While the genotoxicities of the Cr(V) and Cr(VI) complexes increase according to their permeabilities, the genotoxicities of the Cr(V) complexes are equal to, if not greater than, that of Cr(VI) in terms of the amount of Cr entering the cell. This supports other evidence that Cr(V), produced as a metabolic intermediate from the intracellular reduction of Cr(VI), may be important in Cr-induced cancers.