Orthogonal Cues Research Articles

Combination Chemical and Mechanical Tumor Immunomodulation Using Cavitating Mesoporous Silica Nanoparticles.

Combinatorial methods to repolarize tumor-associated macrophages from anti-inflammatory to pro-inflammatory phenotypes offers a promising route for cancer immunotherapy. However, most studies examine biochemical combinations alone. Therefore, we studied simultaneous chemical and mechanical stimuli as orthogonal cues for enhanced immunomodulation. We engineered the surfaces of hydrophobically functionalized mesoporous silica nanoparticles (F108-hMSNs) to encapsulate the immunomodulator resiquimod and kill cancer cells through high-intensity focused ultrasound (HIFU)-mediated inertial cavitation, releasing damage-associated molecular patterns (DAMPs) for prolonged macrophage stimulation. The HIFU doses alone did not affect cells, but in combination with F108-hMSNs, achieved significantly higher cancer cell death and DAMP generation. Inflammatory markers (CD86, MHC II, iNOS) were upregulated in tumor-associated-like macrophages treated with F108-hMSNs in the presence of HIFU and experienced the greatest inflammatory phenotypic shift of all conditions tested. This work suggests that chemical and mechanical activation facilitated by engineered nanoparticles offer a promising treatment against immunologically cold tumors.

Dissociable effects of attention and expectation on perceptual sensitivity to action-outcomes

Self-generated sensations evoke attenuated neural response - physiological attenuation - and is perceived with less intensity - perceptual attenuation. This phenomenon is referred as sensory attenuation and is proposed to reflect the silencing of predicted sensations. The present study aimed to investigate the independent contribution of expectation and attention on sensory attenuation. The expectation associated with the stimulus feature and the focus of attention was manipulated independently by orthogonal cues. We found pronounced sensory attenuation at the unattended location when the stimulus was self-generated (Experiment 1). When the stimulus was externally-generated (Experiment 2), sensory attenuation was observed at the attended location. Sensory attenuation of expected action-outcome was not observed when the attention cue was uninformative (Experiment 3A). The findings corroborate the claim from Bayesian models that attention mediates sensory attenuation. The results also highlight the paradoxes in Bayesian proposals of perception–action interaction.

Physiologic biomechanics enhance reproducible contractile development in a stem cell derived cardiac muscle platform

Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) allow investigations in a human cardiac model system, but disorganized mechanics and immaturity of hPSC-CMs on standard two-dimensional surfaces have been hurdles. Here, we developed a platform of micron-scale cardiac muscle bundles to control biomechanics in arrays of thousands of purified, independently contracting cardiac muscle strips on two-dimensional elastomer substrates with far greater throughput than single cell methods. By defining geometry and workload in this reductionist platform, we show that myofibrillar alignment and auxotonic contractions at physiologic workload drive maturation of contractile function, calcium handling, and electrophysiology. Using transcriptomics, reporter hPSC-CMs, and quantitative immunofluorescence, these cardiac muscle bundles can be used to parse orthogonal cues in early development, including contractile force, calcium load, and metabolic signals. Additionally, the resultant organized biomechanics facilitates automated extraction of contractile kinetics from brightfield microscopy imaging, increasing the accessibility, reproducibility, and throughput of pharmacologic testing and cardiomyopathy disease modeling.

Action biases perceptual decisions toward expected outcomes.

We predict how our actions will influence the world around us. Prevailing models in the action control literature propose that we use these predictions to suppress or “cancel” perception of expected action outcomes, to highlight more informative surprising events. However, contrasting normative Bayesian models in sensory cognition suggest that we are more, not less, likely to perceive what we expect—given that what we expect is more likely to occur. Here we adjudicated between these models by investigating how expectations influence perceptual decisions about action outcomes in a signal detection paradigm. Across three experiments, participants performed one of two manual actions that were sometimes accompanied by brief presentation of expected or unexpected visual outcomes. Contrary to dominant cancellation models but consistent with Bayesian accounts, we found that observers were biased to report the presence of expected action outcomes. There were no effects of expectation on sensitivity. Computational modeling revealed that the action-induced bias reflected a sensory bias in how evidence was accumulated rather than a baseline shift in decision circuits. Expectation effects remained in Experiments 2 and 3 when orthogonal cues indicated which finger was more likely to be probed (i.e. task-relevant). These biases toward perceiving expected action outcomes are suggestive of a mechanism that would enable generation of largely veridical representations of our actions and their consequences in an inherently uncertain sensory world.

Recent advances on multicue object tracking: a survey

The performance of single cue object tracking algorithms may degrade due to complex nature of visual world and environment challenges. In recent past, multicue object tracking methods using single or multiple sensors such as vision, thermal, infrared, laser, radar, audio, and RFID are explored to a great extent. It was acknowledged that combining multiple orthogonal cues enhance tracking performance over single cue methods. The aim of this paper is to categorize multicue tracking methods into single-modal and multi-modal and to list out new trends in this field via investigation of representative work. The categorized works are also tabulated in order to give detailed overview of latest advancement. The person tracking datasets are analyzed and their statistical parameters are tabulated. The tracking performance measures are also categorized depending upon availability of ground truth data. Our review gauges the gap between reported work and future demands for object tracking.

Feature expectation heightens visual sensitivity during fine orientation discrimination.

Attending to a stimulus enhances the sensitivity of perceptual decisions. However, it remains unclear how perceptual sensitivity varies according to whether a feature is expected or unexpected. Here, observers made fine discrimination judgments about the orientation of visual gratings embedded in low spatial-frequency noise, and psychophysical reverse correlation was used to estimate decision 'kernels' that revealed how visual features influenced choices. Orthogonal cues alerted subjects to which of two spatial locations was likely to be probed (spatial attention cue) and which of two oriented gratings was likely to occur (feature expectation cue). When an expected (relative to unexpected) feature occurred, decision kernels shifted away from the category boundary, allowing observers to capitalize on more informative, "off-channel" stimulus features. By contrast, the spatial attention cue had a multiplicative influence on decision kernels, consistent with an increase in response gain. Feature expectation thus heightens sensitivity to the most informative visual features, independent of selective attention.

ASSESSING THE IMPACT OF CUE REDUNDANCY ON INEXPERIENCED AUDITORS� JUDGMENT ACCURACY

ABSTRACT Auditors may consciously or subconsciously rely on redundant cues to confirm an initial hypothesis or to gain the approval of superiors. Inexperienced auditors required to examine a large numbers of evidential cues are even more susceptible to judgment bias and inefficiency. Reliance on evidential cues with little informational content (redundant) instead of orthogonal cues with substantial informational content can lead to overconfidence and thus could impair judgment. In the current study a lab experiment involving twenty seven graduate and senior accounting students at a large university in the Southeastern United States was conducted to examine the ability of inexperienced auditors to mitigate the negative effects of cue redundancy vis a vis an unstructured audit task: going concern assessment. In the current study, however, an automated bankruptcy prediction model was used to assess judgment bias. Contrary to the findings in cognitive behavior (Shepard 1964; Oskamp 1965; Ryback 1967; and Einhorn, 1979), auditors because of their adherence to the principle of Conservatism highly emphasized in the auditing and accounting pronouncements (US GAAP and IFRS) were able to mitigate the negative effects of cue redundancy. This finding was reflected in their confidence estimates, their judgment accuracy estimates and the dispersion of their accuracy estimates around their group means. Additionally, the length of time it took them to complete the task didn’t increase when the redundant cues were provided. Significant implications to the teaching of auditing practice sets in the classroom and on the job and to other professions where cue redundancy is present and where more emphasis on Conservatism could improve judgment accuracy are addressed. Keywords cue redundancy, auditing, going concern, bankruptcy prediction, accounting, education

Directing epithelial to mesenchymal transition through engineered microenvironments displaying orthogonal adhesive and mechanical cues

Cell interactions with their extracellular matrix (ECM) microenvironments play a major role in directing cellular processes that can drive wound healing and tissue regeneration but, if uncontrolled, lead to pathological progression. One such process, epithelial to mesenchymal transition (EMT), if finely controlled could have significant potential in regenerative medicine approaches. Despite recent findings that highlight the influence of biochemical and mechanical properties of the ECM on EMT, it is still unclear how these two orthogonal cues act synergistically to control epithelial cell phenotype. Here, we cultured lung epithelial cells on combinations of different mutants of fibronectin's cell binding domain that preferentially engage specific integrins and substrates of varying stiffness. Our results suggest that while stiff substrates induce spontaneous EMT, this response can be overcome by with fragments of fibronectin that support α3 and α5 integrin engagement. Furthermore, we found that substrate-induced EMT correlates with transforming growth factor beta activation by resident epithelial cells and is dependent on Rho/ROCK signaling. Suppressing cell-contractility was sufficient to maintain an epithelial phenotype. Our results suggest that integrin-specific engagement of fibronectin adhesive domains and the mechanics of the ECM act synergistically to direct EMT.

When cross-modal spatial attention fails.

There is now convincing evidence that an involuntary shift of spatial attention to a stimulus in one modality can affect the processing of stimuli in other modalities, but inconsistent findings across different paradigms have led to controversy. Such inconsistencies have important implications for theories of cross-modal attention. The authors investigated why orienting attention to a visual event sometimes influences responses to subsequent sounds and why it sometimes fails to do so. They examined visual-cue-on-auditory-target effects in two paradigms--implicit spatial discrimination (ISD) and orthogonal cuing (OC)--that have yielded conflicting findings in the past. Consistent with previous research, visual cues facilitated responses to same-side auditory targets in the ISD paradigm but not in the OC paradigm. Furthermore, in the ISD paradigm, visual cues facilitated responses to auditory targets only when the targets were presented directly at the cued location, not when they appeared above or below the cued location. This pattern of results confirms recent claims that visual cues fail to influence responses to auditory targets in the OC paradigm because the targets fall outside the focus of attention.

The suppression of reflexive visual and auditory orienting when attention is otherwise engaged.

Two experiments were conducted to examine whether abrupt onsets are capable of reflexively capturing attention when they occur outside the current focus of spatial attention, as would be expected if exogenous orienting operates in a truly automatic fashion. The authors established a highly focused attentional state by means of the central presentation of a stream of visual or auditory characters, which participants sometimes had to monitor. No intramodal reflexive cuing effects were observed in either audition or vision when participants performed either an exogenous visual or auditory orthogonal cuing task together with the central focused attention task. These results suggest that reflexive unimodal orienting is not truly automatic. The fact that cuing effects were eliminated under both unimodal and cross-modal conditions is consistent with the view that auditory and visual reflexive spatial orienting are controlled by a common underlying neural substrate.

How automatic are audiovisual links in exogenous spatial attention?

Three experiments on healthy humans investigated the degree of automaticity of crossmodal spatial attention shifts by assessing the intentionality criterion. We used the orthogonal cuing paradigm in which a lateralized cue, either visual or auditory was followed by a unimodal or crossmodal target that occurred at the same or opposite side. In all experiments, the cue was always uninformative as to target location. In Experiment 1, where both side and modality of targets were unpredictable, we found faster discriminations for visual targets following uninformative auditory cues on the same side. This result was replicated in Experiment 2, where target side was blocked and participants could orient attention in advance toward the appropriate side, and in Experiment 3, where they were additionally informed about target modality. Our results suggest that this sort of crossmodal orienting is automatic because it occurred even when participants were provided with detailed information about the target to prevent uninformative auditory cues from orienting attention. This is consistent with the notion that peripheral auditory stimuli are very powerful in capturing visual attention.

A Review and Analysis of the Policy-Capturing Methodology in Organizational Research: Guidelines for Research and Practice

Policy-capturing has been employed extensively in the past to examine how organizational decision makers use the information available to them when making evaluative judgments. The purpose of this article is to provide researchers with guidelines for enhancing the reliability and validity of their studies. More specifically, the authors identify issues researchers may want to consider when designing such studies and offer suggestions for effectively addressing them. They draw on a review of 37 articles from 5 major journals to identify “best practice” and discuss the advantages and disadvantages of alternative approaches to resolving the various issues. The key issues are (a) the realism of the approach and its effect on both internal and external validity, (b) the limits of the full factorial design, (c) the need for orthogonal cues, (d) sample size and statistical power, and (e) the assessment of reliability. The analysis also includes comparisons with conjoint analysis, a similar methodology used in the marketing research literature.

Interactions between coincident and orthogonal cues to texture boundaries.

Arrays with horizontal or vertical texture boundaries formed by element orientation and length cues were displayed, and the texture boundary formed by one cue was specified as the target. The boundaries formed by the two cues were coincident on some trials and orthogonal on others. Observers' accuracy in reporting the orientation of the target boundary was improved by a coincident nontarget boundary and was worsened by an orthogonal one. Conditional mutual information measures are used to show how effects due to contextual modulation can be distinguished from effects due to additive combination of the cues. The results of five experiments are interpreted as evidence that the transmission of information about specific texture boundary cues is modulated by task context but not by a coincident or orthogonal boundary in another cue. We therefore distinguish between the effects of "context," as shown by the effects of any variable not called the target, and "modulatory contextual effects," as shown by the effects of one variable on the transmission of information specifically about another.

Extrinsic Reward Valences and Productivity of Business Faculty: A within-and between-Subjects Decision Modeling Experiment

The valences of six extrinsic rewards that can accrue to business faculty members were investigated. A decision modeling experiment was designed with 16 different hypothetical reward situations to elicit effort decisions from 52 respondents. Using instrumentality theory, valences were represented by within-subject regression coefficients, obtained by regressing effort decisions on a set of orthogonal cues. Exploratory analyses yielded significant effects of reward type for the valences within all rank and tenure categories and for the valences of tenure and recognition across rank and tenure categories. Significant correlations were found between research productivity and the valences of mobility and promotion. Interactions with rank were found for the correlations of research productivity with the valences of money and mobility. The findings were consistent with need theories and support conceptual connections between valences and needs.

Drug discrimination procedures: A method to analyze adaptation level of affective states

AbstractWhen contrasting drugs (i.e., chlordiazepoxide versus pentylenetetrazol) are examined in drug‐drug, drug‐saline, or drug 1‐drug 2‐saline tasks, one can begin to assess whether such drugs represent orthogonal cues or reflect an underlying cue dimension. Both adaptation level theory and opponent‐process theory are applied to the analysis of drug discriminative performance. Three indices that can differentiate between orthogonal and opponent affective states utilizing drug‐drug discrimination tasks are discussed in relation to these two theories, and a model to characterize further the similarity between pharmacologically and environmentally induced anxiety is proposed.

The effect of cue-criterion correlations, cue intercorrelations and the sign of the cue intercorrelation on performance in suppressor variable tasks

The subjects' performance was investigated in a two-cue MCPL-experiment with a 2 (Cue-criterion correlations, r e1 = .60 and .80) × 2 (Total task predictability, R e 2 = 1.00 and .70) × 2 (Sign of r ij ) × 5 (Blocks) factorial design. The difference in R e 2 was due entirely to an increase in the cue intercorrelation, r ij. Effects of R e 2 on performance were therefore interpreted as effects of the cue intercorrelation. Two control conditions, with orthogonal cues and the same values of r ei as in the experimental conditions, were included in the design. Subject consistency was directly related to the cue-criterion correlations, and the cue-judgment beta-weights were directly related to the magnitude of the cue intercorrelation. The sign of r ij determined the level of consistency.

Entangled task dismensions: An impediment to interpersonal learning

The effects of intercorrelated task dimensions on interpersonal learning (IPL) were investigated. Each S was first trained to utilize one of two different judgment policies for a two-cue probability learning task. Ss were then paired so that in each pair S 1 had been trained to depend in a positive, linear fashion upon one cue and to ignore the other, and S 2 had been trained to depend upon the cue S 1 ignored and to ignore the cue upon which S 1 depended. Each pair then worked together on a task in which they were required to reach a mutually agreeable public judgment on 10 trials. For half the pairs (Group I) the task-trial cues were highly intercorrelated (+.90): for the other half (Group II) the cues were orthogonal. An interpersonal-prediction task followed. IPL about the Other, as measured by the correlation of one S's judgments with the other S's predictions of his judgments, was significantly better for Group II ( p < .001). Differences in IPL were not a result of group differences in amount or type of communication during interaction. Group differences in IPL disappeared after Group I also had access to a set of task trials with orthogonal cues. The results demonstrate that IPL is a function of the properties of the task system the Ss encounter, as well as the properties of the cognitive system the Ss bring to the task.