Peripheral vision outside the focus of attention may rely on summary statistics. We used a gaze-contingent paradigm to directly test this assumption by asking whether search performance differed between targets and statistically-matched visualizations of the same targets. Four-object search displays included one statistically-matched object that was replaced by an unaltered version of the object during the first eye movement. Targets were designated by previews, which were never altered. Two types of statistically-matched objects were tested: One that maintained global shape and one that did not. Differences in guidance were found between targets and statistically-matched objects when shape was not preserved, suggesting that they were not informationally equivalent. Responses were also slower after target fixation when shape was not preserved, suggesting an extrafoveal processing of the target that again used shape information. We conclude that summary statistics must include some global shape information to approximate the peripheral information used during search.
Summary statistics; Visual search guidance; Gaze contingent; Eye movements; Extrafoveal processing; Shape
Multiple studies show that reactive oxygen species (ROS) play a major role in prostate cancer (PCa) development and progression. Previously, we reported an induction of Spermidine/Spermine N1-Acetyl Transferase (SSAT) by androgen-activated androgen receptor (AR)-JunD protein complex that leads to over-production of ROS in PCa cells. In our current research, we identify small molecules that specifically block AR-JunD in this ROS-generating metabolic pathway.
A high throughput assay based on Gaussia Luciferase reconstitution was used to identify inhibitors of the AR-JunD interaction. Selected hits were further screened using a fluorescence polarization competitor assay to eliminate those that bind to the AR Ligand Binding Domain (LBD), in order to identify molecules that specifically target events downstream to androgen activation of AR. Eleven molecules were selected for studies on their efficacy against ROS generation and growth of cultured human PCa cells by DCFH dye-oxidation assay and DNA fluorescence assay, respectively. In situ Proximity Ligation Assay (PLA), SSAT promoter-luciferase reporter assay, and western blotting of apoptosis and cell cycle markers were used to study mechanism of action of the lead compound.
Selected lead compound GWARJD10 with EC50 10 μM against ROS production was shown to block AR-JunD interaction in situ as well as block androgen-induced SSAT gene expression at IC50 5 μM. This compound had no effect on apoptosis markers, but reduced cyclin D1 protein level.
Inhibitor of AR-JunD interaction, GWARJD10 shows promise for prevention of progression of PCa at an early stage of the disease by blocking growth and ROS production.
AR-JunD protein-protein interaction; small molecule inhibitors; cellular reactive oxygen species; cyclin D1
The visual-search literature has assumed that the top-down target representation used to guide search resides in visual working memory (VWM). We directly tested this assumption using contralateral delay activity (CDA) to estimate the VWM load imposed by the target representation. In Experiment 1, observers previewed four photorealistic objects and were cued to remember the two objects appearing to the left or right of central fixation; Experiment 2 was identical except that observers previewed two photorealistic objects and were cued to remember one. CDA was measured during a delay following preview offset but before onset of a four-object search array. One of the targets was always present, and observers were asked to make an eye movement to it and press a button. We found lower magnitude CDA on trials when the initial search saccade was directed to the target (strong guidance) compared to when it was not (weak guidance). This difference also tended to be larger shortly before search-display onset and was largely unaffected by VWM item-capacity limits or number of previews. Moreover, the difference between mean strong- and weak-guidance CDA was proportional to the increase in search time between mean strong-and weak-guidance trials (as measured by time-to-target and reaction-time difference scores). Contrary to most search models, our data suggest that trials resulting in the maintenance of more target features results in poor search guidance to a target. We interpret these counterintuitive findings as evidence for strong search guidance using a small set of highly discriminative target features that remain after pruning from a larger set of features, with the load imposed on VWM varying with this feature-consolidation process.
visual search; guidance; target representation; contralateral delay activity (CDA); visual working memory (VWM); visual working memory capacity; event-related potentials (ERPs)
Oculomotor inhibition of return (O-IOR) is an increase in saccade latency prior to an eye movement to a recently fixated location compared to other locations. It has been proposed that this temporal O-IOR may have spatial consequences, facilitating foraging by inhibiting return to previously attended regions. In order to test this possibility, participants viewed arrays of objects and of words while their eye movements were recorded. Temporal O-IOR was observed, with equivalent effects for object and word arrays, indicating that temporal O-IOR is an oculomotor phenomenon independent of array content. There was no evidence for spatial inhibition of return (IOR). Instead, spatial facilitation of return was observed: participants were significantly more likely than chance to make return saccades and to re-fixate just-visited locations. Further, the likelihood of making a return saccade to an object or word was contingent on the amount of time spent viewing that object or word before leaving it. This suggests that, unlike temporal O-IOR, return probability is influenced by cognitive processing. Taken together, these results are inconsistent with the hypothesis that IOR functions as a foraging facilitator. The results also provide strong evidence for a different oculomotor bias that could serve as a foraging facilitator: saccadic momentum, a tendency to repeat the most recently executed saccade program. We suggest that models of visual attention could incorporate saccadic momentum in place of IOR.
inhibition of return; facilitation of return; eye movement control; saccadic momentum; foraging facilitator
Eyetracking during reading has provided a critical source of on-line behavioral data informing basic theory in language processing. Similarly, event-related potentials (ERPs) have provided an important on-line measure of the neural correlates of language processing. Recently there has been strong interest in co-registering eyetracking and ERPs from simultaneous recording to capitalize on the strengths of both techniques, but a challenge has been devising approaches for controlling artifacts produced by eye movements in the EEG waveform. In this paper we describe our approach to correcting for eye movements in EEG and demonstrate its applicability to reading. The method is based on independent components analysis, and uses three criteria for identifying components tied to saccades: (1) component loadings on the surface of the head are consistent with eye movements; (2) source analysis localizes component activity to the eyes, and (3) the temporal activation of the component occurred at the time of the eye movement and differed for right and left eye movements. We demonstrate this method's applicability to reading by comparing ERPs time-locked to fixation onset in two reading conditions. In the text-reading condition, participants read paragraphs of text. In the pseudo-reading control condition, participants moved their eyes through spatially similar pseudo-text that preserved word locations, word shapes, and paragraph spatial structure, but eliminated meaning. The corrected EEG, time-locked to fixation onsets, showed effects of reading condition in early ERP components. The results indicate that co-registration of eyetracking and EEG in connected-text paragraph reading is possible, and has the potential to become an important tool for investigating the cognitive and neural bases of on-line language processing in reading.
eyetracking; event-related potentials (ERPs); reading; eye movements; coregistration; pseudo-reading
Search displays are typically presented immediately after a target cue, but in the real-world, delays often exist between target designation and search. Experiments 1 and 2 asked how search guidance changes with delay. Targets were cued using a picture or text label, each for 3000ms, followed by a delay up to 9000ms before the search display. Search stimuli were realistic objects, and guidance was quantified using multiple eye movement measures. Text-based cues showed a non-significant trend towards greater guidance following any delay relative to a no-delay condition. However, guidance from a pictorial cue increased sharply 300–600 msec after preview offset. Experiment 3 replicated this guidance enhancement using shorter preview durations while equating the time from cue onset to search onset, demonstrating that the guidance benefit is linked to preview offset rather than a more complete encoding of the target. Experiment 4 showed that enhanced guidance persists even with a mask flashed at preview offset, suggesting an explanation other than visual priming. We interpret our findings as evidence for the rapid consolidation of target information into a guiding representation, which attains its maximum effectiveness shortly after preview offset.
visual search guidance; consolidation; eye movements; visual working memory; target representation
The synthesis and reactivity of dibenzyl cationic tantalum imido complexes is described. The trialkyl tantalum imido compounds Bn3Ta=NCMe3 (1) and Np3Ta=NCMe3 (2) were synthesized as starting materials for the study of dialkyl cationic tantalum imido complexes. Compound 1 undergoes insertion reactions with diisopropylcarbodiimide and 2,6-dimethylphenylisocyanide to give (bisamidinate)imido complex 5 and (bisimino-acyl)imido complex 6, respectively. Treatment of compound 1 with B(C6F5)3 gives the zwitterionic tantalum complex [Bn2Ta=NCMe3][BnB(C6F5)3] (7) which is stabilized by η6-coordination of the benzyl triaryl borate anion. Coordination of the aryl anion can be displaced by three equivalents of pyridine to give the Lewis base complex 8. Treatment of compound 1 with [Ph3C][B(C6F5)4] gives the cationic tantalum imido complex [Bn2Ta=NCMe3][B(C6F5)4] (3). This salt forms insoluble aggregates unless trapped by THF coordination or an insertion reaction with an alkyne or an alkene. Cation 3 undergoes migratory insertion reactions with diphenylacetylene, phenylacetylene, norbornene, and cis-cyclooctene to give the corresponding alkenyl or modified alkyl imido complexes. The characterization of these products and the significance of these insertion reactions with respect to Ziegler-Natta polymerizations and hydroamination reactions are described.
To correlate the metabolic changes with size changes for tumor response by concomitant PET-CT evaluation of lung cancers after radiotherapy.
36 patients were studied pre- and post-radiotherapy with18FDG PET-CT scans at a median interval of 71 days. All of the patients were followed clinically and radiographically after a mean period of 342 days for assessment of local control or failure rates. Change in size (sum of maximum orthogonal diameters) was correlated with that of maximum standard uptake value (SUV) of the primary lung cancer before and after conventional radiotherapy.
There was a significant reduction in both SUV and size of the primary cancer after radiotherapy (p < 0.00005). Among the 20 surviving patients, the sensitivity, specificity, and accuracy using PET (SUV) were 94%, 50%, 90% respectively and the corresponding values using and CT (size criteria) were 67%, 50%, and 65% respectively. The metabolic change (SUV) was highly correlated with the change in size by a quadratic function. In addition, the mean percentage metabolic change was significantly larger than that of size change (62.3 ± 32.7% vs 47.1 ± 26.1% respectively, p = 0.03)
Correlating and incorporating metabolic change by PET into size change by concomitant CT is more sensitive in assessing therapeutic response than CT alone.
Bovine anaplasmosis is a vector-borne disease that results in substantial economic losses in other parts of the world but so far not in northern Europe. In August 2002, a fatal disease outbreak was reported in a large dairy herd in the Swiss canton of Grisons. Diseased animals experienced fever, anorexia, agalactia, and depression. Anemia, ectoparasite infestation, and, occasionally, hemoglobinuria were observed. To determine the roles of vector-borne pathogens and to characterize the disease, blood samples were collected from all 286 animals: 50% of the cows were anemic. Upon microscopic examination of red blood cells, Anaplasma marginale inclusion bodies were found in 47% of the cows. The infection was confirmed serologically and by molecular methods. Interestingly, we also found evidence of infections with Anaplasma phagocytophilum, large Babesia and Theileria spp., and Mycoplasma wenyonii. The last two species had not previously been described in Switzerland. Anemia was significantly associated with the presence of the infectious agents detected, with the exception of A. phagocytophilum. Remarkably, concurrent infections with up to five infectious vector-borne agents were detected in 90% of the ill animals tested by PCR. We concluded that A. marginale was the major cause of the hemolytic anemia, while coinfections with other agents exacerbated the disease. This was the first severe disease outbreak associated with concurrent infections with vector-borne pathogens in alpine Switzerland; it was presumably curtailed by culling of the entire herd. It remains to be seen whether similar disease outbreaks will have to be anticipated in northern Europe in the future.