140 research outputs found

    Finding Flicker: Critical Differences in Temporal Frequency Capture Attention

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    Rapid visual flicker is known to capture attention. Here we show slow flicker can also capture attention under reciprocal temporal conditions. Observers searched for a target line (vertical or horizontal) among tilted distractors. Distractor lines were surrounded by luminance modulating annuli, all flickering sinusoidally at 1.3 or 12.1 Hz, while the target’s annulus flickered at frequencies within this range. Search times improved with increasing target/distractor frequency differences. For target–distractor frequency separations >5 Hz reaction times were minimal with high-frequency targets correctly identified more rapidly than low frequency targets (~400 ms). Critically, however, at these optimal frequency separations search times for low and high-frequency targets were unaffected by set size (slow flicker popped out from high flicker, and vice versa), indicating parallel and symmetric search performance when searching for high or low frequency targets. In a “cost” experiment using 1.3 and 12.1 Hz flicker, the unique flickering annulus sometimes surrounded a distractor and, on other trials, surrounded the target. When centered on a distractor, the unique frequency produced a clear and symmetrical search cost. Together, these symmetric pop-out and search costs demonstrate that temporal frequency is a pre-attentive visual feature capable of capturing attention, and that it is relative rather than absolute frequencies that are critical. The shape of the search functions strongly suggest that early visual temporal frequency filters underlie these effects

    Generating HPV specific T helper cells for the treatment of HPV induced malignancies using TCR gene transfer

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    <p>Abstract</p> <p>Background</p> <p>Infection with high risk Human Papilloma Virus (HPV) is associated with cancer of the cervix, vagina, penis, vulva, anus and some cases of head and neck carcinomas. The HPV derived oncoproteins E6 and E7 are constitutively expressed in tumor cells and therefore potential targets for T cell mediated adoptive immunotherapy. Effective immunotherapy is dependent on the presence of both CD4+ and CD8+ T cells. However, low precursor frequencies of HPV16 specific T cells in patients and healthy donors hampers routine isolation of these cells for adoptive transfer purposes. An alternative to generate HPV specific CD4+ and CD8+ T cells is TCR gene transfer.</p> <p>Methods</p> <p>HPV specific CD4+ T cells were generated using either a MHC class I or MHC class II restricted TCR (from clones A9 and 24.101 respectively) directed against HPV16 antigens. Functional analysis was performed by interferon-γ secretion, proliferation and cytokine production assays.</p> <p>Results</p> <p>Introduction of HPV16 specific TCRs into blood derived CD4+ recipient T cells resulted in recognition of the relevant HPV16 epitope as determined by IFN-γ secretion. Importantly, we also show recognition of the endogenously processed and HLA-DP1 presented HPV16E6 epitope by 24.101 TCR transgenic CD4+ T cells and recognition of the HLA-A2 presented HPV16E7 epitope by A9 TCR transgenic CD4+ T cells.</p> <p>Conclusion</p> <p>Our data indicate that TCR transfer is feasible as an alternative strategy to generate human HPV16 specific CD4+ T helper cells for the treatment of patients suffering from cervical cancer and other HPV16 induced malignancies.</p

    Effects of Multisensory Contexts on Tofu and Soy Sauce Evaluation and Consumption

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    We examined the effects of an informative pitch and multisensory contexts as potential factors influencing individuals’ experience of tofu with soy sauce and the amount consumed outside the lab. Two hundred and sixteen participants watched one of two pitches (promoting either vegetarian diets or exercise) and were guided into one of three multisensory contexts (‘sustainable’, ‘meat’, or ‘neutral’ theme). Participants rated the aroma and appearance of soy sauce and the taste of tofu dipped in it using the intuitive ‘one touch’ EmojiGrid valence and arousal measuring tool. Our results showed that the ‘meat’ context increased arousal ratings for soy sauce and the tendency to consume more tofu relative to the other contexts. Pitch did not influence affective ratings or amounts consumed. We conclude that the multisensory context has the potential to positively affect peoples’ choices and perceptions of plant-based and sustainable food and promote its consumption

    Electrodermal activity as an index of food neophobia outside the lab

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    IntroductionUnderstanding how food neophobia affects food experience may help to shift toward sustainable diets. Previous research suggests that individuals with higher food neophobia are more aroused and attentive when observing food-related stimuli. The present study examined whether electrodermal activity (EDA), as index of arousal, relates to food neophobia outside the lab when exposed to a single piece of food.MethodsThe EDA of 153 participants was analyzed as part of a larger experiment conducted at a festival. Participants completed the 10-item Food Neophobia Scale. Subsequently, they saw three lids covering three foods: a hotdog labeled as “meat”, a hotdog labeled as “100% plant-based”, and tofu labeled as “100% plant-based”. Participants lifted the lids consecutively and the area-under-the-curve (AUC) of the skin conductance response (SCR) was captured between 20 s before and 20 s after each food reveal.ResultsWe found a significant positive correlation between food neophobia and AUC of SCR during presentation of the first and second hotdog and a trend for tofu. These correlations remained significant even when only including the SCR data prior to the food reveal (i.e., an anticipatory response).DiscussionThe association between food neophobia and EDA indicates that food neophobic individuals are more aroused upon the presentation of food. We show for the first time that the anticipation of being presented with food already increased arousal for food neophobic individuals. These findings also indicate that EDA can be meaningfully determined using wearables outside the lab, in a relatively uncontrolled setting for single-trial analysis

    Efficient Visual Search from Synchronized Auditory Signals Requires Transient Audiovisual Events

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    BACKGROUND: A prevailing view is that audiovisual integration requires temporally coincident signals. However, a recent study failed to find any evidence for audiovisual integration in visual search even when using synchronized audiovisual events. An important question is what information is critical to observe audiovisual integration. METHODOLOGY/PRINCIPAL FINDINGS: Here we demonstrate that temporal coincidence (i.e., synchrony) of auditory and visual components can trigger audiovisual interaction in cluttered displays and consequently produce very fast and efficient target identification. In visual search experiments, subjects found a modulating visual target vastly more efficiently when it was paired with a synchronous auditory signal. By manipulating the kind of temporal modulation (sine wave vs. square wave vs. difference wave; harmonic sine-wave synthesis; gradient of onset/offset ramps) we show that abrupt visual events are required for this search efficiency to occur, and that sinusoidal audiovisual modulations do not support efficient search. CONCLUSIONS/SIGNIFICANCE: Thus, audiovisual temporal alignment will only lead to benefits in visual search if the changes in the component signals are both synchronized and transient. We propose that transient signals are necessary in synchrony-driven binding to avoid spurious interactions with unrelated signals when these occur close together in time

    The transverse aortic constriction heart failure animal model: a systematic review and meta-analysis

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    The transverse aortic constriction (TAC) model is frequently used to study adverse cardiac remodeling upon pressure overload. We set out to define the most important characteristics that define the degree of cardiac remodeling in this model. A systematic review and meta-analyses were performed on studies using the TAC mouse/rat model and reporting echocardiographic outcome parameters. We included all animal studies in which a constriction around the transverse aorta and at least one of the predefined echocardiography or MRI outcome parameters were assessed. A total of 502 articles and > 3000 wild-type, untreated animals undergoing TAC were included in this study and referenced to a control group. The duration of aortic constriction correlated to the degree of adverse remodeling. However, the mouse data is strongly biased by the preferential use of male C57Bl/6 mice (66% of studies). Furthermore, mostly ketamine/xylazine anesthetics, 27G needle constriction, and silk sutures are used. Nonetheless, despite the homogeneity in experimental design, the model contained a substantial degree of heterogeneity in the functional outcome measures. When looking at study quality, only 12% reported randomization, 23% mentioned any sort of blinding, 25% adequately addressed the outcomes, and an amazingly low percentage (2%) showed sample size calculation. Meta-analyses did not detect specific study characteristics that explained the heterogeneity in the reported outcome measures, however this might be related to the strong bias towards the use of specific mouse lines, sex as well as age or to poor reporting of characteristics of study quality

    The Phenotypic Spectrum of PNKP-Associated Disease and the Absence of Immunodeficiency and Cancer Predisposition in a Dutch Cohort

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    Background: We aimed to expand the number of currently known pathogenic PNKP mutations, to study the phenotypic spectrum, including radiological characteristics and genotype-phenotype correlations, and to assess whether immunodeficiency and increased cancer risk are part of the DNA repair disorder caused by mutations in the PNKP gene. Methods: We evaluated nine patients with PNKP mutations. A neurological history and examination was obtained. All patients had undergone neuroimaging and genetic testing as part of the prior diagnostic process. Laboratory measurements included potential biomarkers, and, in the context of a DNA repair disorder, we performed a detailed immunologic evaluation, including B cell repertoire analysis. Results: We identified three new mutations in the PNKP gene and confirm the phenotypic spectrum of PNKP-associated disease, ranging from microcephaly, seizures, and developmental delay to ataxia with oculomotor apraxia type 4. Irrespective of the phenotype, alpha-fetoprotein is a biochemical marker and increases with age and progression of the disease. On neuroimaging, (progressive) cerebellar atrophy was a universal feature. No clinical signs of immunodeficiency were present, and immunologic assessment was unremarkable. One patient developed cancer, but this was attributed to a concurrent von HippelLindau mutation. Conclusions: Immunodeficiency and cancer predisposition do not appear to be part of PNKP-associated disease, contrasting many other DNA repair disorders. Furthermore, our study illustrates that the previously described syndromes microcephaly, seizures, and developmental delay, and ataxia with oculomotor apraxia type 4, represent the extremes of an overlapping spectrum of disease. Cerebellar atrophy and elevated serum alpha-fetoprotein levels are early diagnostic findings across the entire phenotypical spectrum

    Statement on Advancing the Assessment of Chemical Mixtures and their Risks for Human Health and the Environment

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    The number of anthropogenic chemicals, manufactured, by-products, metabolites and abiotically formed transformation products, counts to hundreds of thousands, at present. Thus, humans and wildlife are exposed to complex mixtures, never one chemical at a time and rarely with only one dominating effect. Hence there is an urgent need to develop strategies on how exposure to multiple hazardous chemicals and the combination of their effects can be assessed. A workshop, “Advancing the Assessment of Chemical Mixtures and their Risks for Human Health and the Environment” was organized in May 2018 together with Joint Research Center in Ispra, EU-funded research projects and Commission Services and relevant EU agencies. This forum for researchers and policy-makers was created to discuss and identify gaps in risk assessment and governance of chemical mixtures as well as to discuss state of the art science and future research needs. Based on the presentations and discussions at this workshop we want to bring forward the following Key Messages: We are at a turning point: multiple exposures and their combined effects require better management to protect public health and the environment from hazardous chemical mixtures. Regulatory initiatives should be launched to investigate the opportunities for all relevant regulatory frameworks to include prospective mixture risk assessment and consider combined exposures to (real-life) chemical mixtures to humans and wildlife, across sectors. Precautionary approaches and intermediate measures (e.g. Mixture Assessment Factor) can already be applied, although, definitive mixture risk assessments cannot be routinely conducted due to significant knowledge and data gaps. A European strategy needs to be set, through stakeholder engagement, for the governance of combined exposure to multiple chemicals and mixtures. The strategy would include research aimed at scientific advancement in mechanistic understanding and modelling techniques, as well as research to address regulatory and policy needs. Without such a clear strategy, specific objectives and common priorities, research, and policies to address mixtures will likely remain scattered and insufficient

    On the limits of top-down control of visual selection

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    In the present study, observers viewed displays in which two equally salient color singletons were simultaneously present. Before each trial, observers received a word cue (e.g., the word red, or green) or a symbolic cue (a circle colored red or green) telling them which color singleton to select on the upcoming trial. Even though many theories of visual search predict that observers should be able to selectively attend the target color singleton, the results of the present study show that observers could not select the target singleton without interference from the irrelevant color singleton. The results indicate that the irrelevant color singleton captured attention. Only when the color of the target singleton remained the same from one trial to the next was selection perfect—an effect that is thought to be the result of passive automatic intertrial priming. The results of the present study demonstrate the limits of top-down attentional control
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