New task-new results? How the gaze cone is influenced by the method of measurement.

Perceiving direct gaze - the perception of being looked at - is important in everyday life. The gaze cone is a concept to define the area in which observers perceive gaze as direct. The most frequently used methods to measure direct gaze threshold fall into two broad groups: First, a variant of the method of constant stimuli, firstly introduced by Gibson and Pick (The American Journal of Psychology, 76, 386-394, 1963). Second, a variant of the method of adjustment, firstly introduced by Gamer and Hecht (Journal of Experimental Psychology: Human Perception and Performance, 33, 705-715, 2007). Previous studies found a considerable range of thresholds, and although some influences on thresholds are already known (uncertainty, clinical groups), thresholds often vary for no apparent reason. Another important method is a triadic gaze-perception task, which usually finds triadic gaze direction judgments to be overestimated. In two experiments, we compare the method of adjustment with the method of constant stimuli. Experiment 1 additionally examines the influence of the overestimation effect found in the triadic task. Results indicate that thresholds are larger when measured by the method of adjustment than by constant stimuli. Furthermore, Experiment 1 finds a nonlinear overestimation factor, indicating that gaze directions near 0° are less overestimated than larger eccentricities. Correcting the thresholds with individually obtained overestimation factors widens the gaze cone but does not eliminate the average difference between the methods of adjustments and constant stimuli.

Differences in the perception of direct gaze between the externally and internally rotated eye.

The perception of direct gaze provides multiple benefits for the observer. Previous studies have investigated how the information from both eyes is used to estimate gaze direction, showing that the perception of gaze direction differs when only the externally rotated eye versus only the internally rotated eye is visible. We examined the width and center of the area of direct gaze by presenting the observers with either the externally or internally rotated eye, or both eyes with the task to judge whether a computer avatar is looking at them. Two experiments yield evidence for a wider area of direct gaze for the externally rotated eye (around 6°) than for the internally rotated eye (around 4°). The area of direct gaze for both eyes was found to be the same as for the internally rotated eye, but smaller than for the externally rotated eye. When both eyes were present, our results indicate that the perception of direct gaze is more likely to follow the internally rotated eye. The discussion substantiates a new generalization that observers base their judgments on the more rotated eye, which can differ due to angle kappa and vergence, in our study it is the internally rotated eye.

Are the directions of both eyes integrated before or after the perception of direct gaze? Evidence from simulated mild strabismus.

The cone of gaze is a looker's range of gaze directions that is accepted as direct by an observer. The present research asks how the condition of mild strabismus, that is, when the two eyes point in slightly different directions, influences the cone of gaze. Normally, both eyes are rotated in a coordinated manner such that both eyes are directed to the same fixation point. With strabismus, there are two fixation points, and, therefore, two directions into which the two eyes point. This raises the question of the direction and the shape (i.e., width) of the gaze cone. Two experiments are conducted with simulated mild strabismus. Three conditions are tested, the two strabismic conditions of esotropia, and exotropia and one orthotropic (nonstrabismic) condition. Results show that the direction of the gaze cone is roughly the average of the directions of the two eyes. Furthermore, the width of the gaze cone is not affected by simulated strabismus and is thus the same for the strabismic and the orthotropic conditions. The results imply a model where at first the direction of gaze based on both eyes is perceived, and where the gaze cone is implied on the basis of the combined gaze direction.

How vergence influences the perception of being looked at.

Perceiving other people's direct gaze is important for many areas of everyday activity. For horizontal and vertical eye movements, the area of being looked at, known as the cone of gaze, has been well explored. Previous research has shown a range of eye rotations (up to eccentricities of 4°-9°) that people accept as direct gaze. Vergence is an important cue for perceiving the depth of fixation. This study examines the range of vergence angles that support the perception of being looked at. In two experiments, observers adjusted the degree of vergence of the lookers' eyes until they felt just (not) looked at. The first experiment also asked to adjust the point of being exactly looked at, which was 0° (parallel eyes). The thresholds of being just (not) looked at were around 4.5° of convergence and 2.5° divergence, which results in a depth of 7° of vergence. This depth was replicated in Experiment 2, while the thresholds of convergence (3.5°) and divergence (3.5°) slightly differ from Experiment 1. The results indicate a consistent area of vergences being accepted as direct gaze, yielding first-time evidence for a third dimension-the depth dimension-of direct gaze.

Perception of direct gaze in a video-conference setting: the effects of position and size.

A common problem in video conferences is gaze direction. In face-to-face communication, it is common that speaker and listener intermittently look at each other. In a video-conference setting, where multiple participants are on the screen, things are complicated and not necessarily optimal. If the listener feels looked at when the speaker looks into the camera, how tolerant is the listener for slight deviations? And does this depend on the position of the speaker's tile on the screen, or the size of the tile? In a first experiment, participants from a student population judged whether they are looked at, while vertical gaze direction of the looker was varied. Furthermore, the position of the tile on the screen varied. The results showed that a slightly upward directed gaze was optimal for the direct gaze judgment, with a width of ± 4 degrees. Optimal gaze direction was somewhat higher for tiles at the bottom of the screen. A second experiment tested the effect of size on the perception of horizontal gaze directions. Size was found to increase the gaze cone. The paper concludes with some recommendations for a setup of video conference systems, optimized for perceived gaze contact.

Examining Gaze Cone Shape and Size.

Another person's looking behavior is used by observers to judge gaze direction and fixation points. An important task in this context is the judgement of direct gaze, that is, the perception of being looked at. The cone of gaze can be defined as the range of fixation points that support direct gaze. The cone concept implies that this range lawfully increases with distance, but that the cone angle is constant. The present experiment tested the concept with a larger number and a more extended range of distances than previously done, and took care of possible directional errors. The gaze cone was found to be roughly linear, and stable between 1.6 m and 7.9 m - an almost perfect cone. The mean cone size subtended 5.2° in diameter when averaged over ascending and descending series. Measures differed, however, in ascending and descending series, consistent with a conservative bias. Also, the variability of judgements increased slightly with distance. Results are discussed considering whether cone size is actually smaller than often reported in the literature.

The tolerogenic function of annexins on apoptotic cells is mediated by the annexin core domain.

Immunological tolerance is constantly being maintained in the periphery by dendritic cells processing material from apoptotic cells (ACs) in the steady-state. Although research has focused on the uptake of ACs by phagocytes, tolerogenic signals exposed by the ACs are much less well defined. In this article, we show that the annexin (Anx) family members AnxA5 and AnxA13 translocate to the surface of ACs to function as redundant tolerogenic signals in vitro and in vivo. Exposure of bone marrow-derived dendritic cells to AnxA5 or AnxA13 in vitro resulted in the inhibition of both proinflammatory cytokine secretion and the upregulation of costimulatory molecules upon TLR stimulation. The highly conserved Anx core domain was sufficient to mediate these effects, whereas recognition by N-formyl peptide receptor family members was dispensable. In vivo, coinjection of OVA-expressing and Anx-expressing ACs prevented induction of Ag-specific CD8(+) T cells. Moreover, mice immunized with Anx-expressing ACs became refractory to an antigenic challenge. These results suggest that several Anxs contribute to AC-induced suppression of dendritic cell activation. Therefore, manipulating Anx-mediated immunosuppression may prove beneficial for patients with cancer or autoimmune diseases and chronic inflammatory disorders.

Enhancer hijacking activates GFI1 family oncogenes in medulloblastoma.

Medulloblastoma is a highly malignant paediatric brain tumour currently treated with a combination of surgery, radiation and chemotherapy, posing a considerable burden of toxicity to the developing child. Genomics has illuminated the extensive intertumoral heterogeneity of medulloblastoma, identifying four distinct molecular subgroups. Group 3 and group 4 subgroup medulloblastomas account for most paediatric cases; yet, oncogenic drivers for these subtypes remain largely unidentified. Here we describe a series of prevalent, highly disparate genomic structural variants, restricted to groups 3 and 4, resulting in specific and mutually exclusive activation of the growth factor independent 1 family proto-oncogenes, GFI1 and GFI1B. Somatic structural variants juxtapose GFI1 or GFI1B coding sequences proximal to active enhancer elements, including super-enhancers, instigating oncogenic activity. Our results, supported by evidence from mouse models, identify GFI1 and GFI1B as prominent medulloblastoma oncogenes and implicate 'enhancer hijacking' as an efficient mechanism driving oncogene activation in a childhood cancer.

Genome sequencing of SHH medulloblastoma predicts genotype-related response to smoothened inhibition.

Smoothened (SMO) inhibitors recently entered clinical trials for sonic-hedgehog-driven medulloblastoma (SHH-MB). Clinical response is highly variable. To understand the mechanism(s) of primary resistance and identify pathways cooperating with aberrant SHH signaling, we sequenced and profiled a large cohort of SHH-MBs (n = 133). SHH pathway mutations involved PTCH1 (across all age groups), SUFU (infants, including germline), and SMO (adults). Children >3 years old harbored an excess of downstream MYCN and GLI2 amplifications and frequent TP53 mutations, often in the germline, all of which were rare in infants and adults. Functional assays in different SHH-MB xenograft models demonstrated that SHH-MBs harboring a PTCH1 mutation were responsive to SMO inhibition, whereas tumors harboring an SUFU mutation or MYCN amplification were primarily resistant.