Keeping an Eye on the Periphery:How Eccentricity affects Visual Selection

After reading the work of this thesis I hope you are convinced that eccentricity is a major factor that cannot be ignored when it comes to understanding visual selection. More specifically, in Chapter 2 we showed that while the proportion of selecting targets and salient items does not change with eccentricity, the dynamics of saliency- and relevance-driven selection do change. That is, the effect of saliency was protracted at a further eccentricity, while the effect of relevance was delayed. This discrepancy between overall selection and performance over time can be explained by the difference in saccade latencies between conditions. That is, as the saccade latency distribution shifted in time with increasing eccentricity, so did the effects of saliency and relevance. In Chapter 3, consistent with earlier work, we challenged existing models of visual selection, showing that the time at which a saccade is initiated greatly influences whether it will be saliency- or relevance-driven. That is, short latency eye movements are more likely to be saliency driven while later eye movements are more likely to be relevance driven. Importantly, we showed for the first time that this separation in time leads to a brief period in between saliency-driven and relevance-driven selection in which the eyes appear to be in ‘limbo’. That is, selection appears to operate randomly, irrespective of saliency and relevance. By fitting different models on the data, we showed that the dynamics of saliency- and relevance-based selection are best described as two independent processes that do not influence each other. We propose an alternative view on the classic priority map model, in which saliency effects are actually a byproduct of a difference in processing speed between different items. That is, on the priority map, salient items are available for selection earlier than non-salient items as they are processed more quickly and elicit therefore more activation at an earlier point in time. After a while, this difference in activation disappears because then non-salient items are processed as well, resulting in a period of non-selectivity. After this, the influence of behavioral relevance takes effect, and activity for the relevant item increases. In Chapter 4 we showed that subjects are more likely to select items that are presented close to fixation than items presented further away. This central selection bias was larger than would be expected based on low-level sensory differences between eccentricities suggesting an important role for attentional competition. In Chapter 5 we were able to determine, for the first time, the time course that the effect of eccentricity follows. Here we showed that eccentricity mainly influences those saccades that are initiated early. That is, eccentricity operates in a similar time window as saliency. As a consequence, the effects of saliency were diminished as the eccentricity difference between the two items grew, but those of relevance were unaffected. In Chapter 6 we showed that attentional capture by salient distractors is modulated by the bias that is described in Chapter 4. That is, even though we saw no effect of eccentricity on attentional capture in overall manual RTs, using eye movement data we showed that participants are more likely to select an item closer to fixation than an item presented further away. Crucially, on those trials in which an eye movement was made towards the distractor reaction times increased with distractor eccentricity while the likelihood of making an eye movement to the distractor in the first place decreases with increasing distractor eccentricity. As these effects go in opposite directions, overall RT showed no effect of distractor eccentricity when all trials were combined together

The representation of occluded image regions in area V1 of monkeys and humans

Neuronal activity in the primary visual cortex (V1) is driven by feedforward input from within the neurons’ receptive fields (RFs) and modulated by contextual information in regions surrounding the RF. The effect of contextual information on spiking activity occurs rapidly and is therefore challenging to dissociate from feedforward input. To address this challenge, we recorded the spiking activity of V1 neurons in monkeys viewing either natural scenes or scenes where the information in the RF was occluded, effectively removing the feedforward input. We found that V1 neurons responded rapidly and selectively to occluded scenes. V1 responses elicited by occluded stimuli could be used to decode individual scenes and could be predicted from those elicited by non-occluded images, indicating that there is an overlap between visually driven and contextual responses. We used representational similarity analysis to show that the structure of V1 representations of occluded scenes measured with electrophysiology in monkeys correlates strongly with the representations of the same scenes in humans measured with functional magnetic resonance imaging (fMRI). Our results reveal that contextual influences rapidly alter V1 spiking activity in monkeys over distances of several degrees in the visual field, carry information about individual scenes, and resemble those in human V1.</p

In vitro immunity:an overview of immunocompetent organ-on-chip models

Impressive advances have been made to replicate human physiology in vitro over the last few years due to the growth of the organ-on-chip (OoC) field in both industrial and academic settings. OoCs are a type of microphysiological system (MPS) that imitates functional and dynamic aspects of native human organ biology on a microfluidic device. Organoids and organotypic models, ranging in their complexity from simple single-cell to complex multi-cell type constructs, are being incorporated into OoC microfluidic devices to better mimic human physiology. OoC technology has now progressed to the stage at which it has received official recognition by the Food and Drug Administration (FDA) for use as an alternative to standard procedures in drug development, such as animal studies and traditional in vitro assays. However, an area that is still lagging behind is the incorporation of the immune system, which is a critical element required to investigate human health and disease. In this review, we summarise the progress made to integrate human immunology into various OoC systems, specifically focusing on models related to organ barriers and lymphoid organs. These models utilise microfluidic devices that are either commercially available or custom-made. This review explores the difference between the use of innate and adaptive immune cells and their role for modelling organ-specific diseases in OoCs. Immunocompetent multi-OoC models are also highlighted and the extent to which they recapitulate systemic physiology is discussed. Together, the aim of this review is to describe the current state of immune-OoCs, the limitations and the future perspectives needed to improve the field.</p

Between law and science:Psychology of the law

Het strafrecht gaat over mensen en misdrijven; van de getuige die een misdrijf ziet, tot de rechter die uiteindelijk moet beslissen over schuld en straf, en alles daartussenin. De rechtspsychologie gaat over het gedrag van al die mensen; gedrag dat onder invloed staat van de rechtsregels en bepalend is voor de uitkomsten van strafrechtelijke procedures. De rechtspsychologie is een wetenschap die inzicht geeft in alle stadia van het strafproces. De professionals die het recht toepassen, maar ook de rechtspsychologen die zaken onderzoeken en daarover adviseren, bevinden zich vaak tussen wet en wetenschap.Tussen Wet en Wetenschap is het Nederlandstalige handboek van de rechtspsychologie. Het is de opvolger van het succesvolle Routes van het Recht. De hoofdstukken zetten op een begrijpelijke manier uiteen wat de wetenschap ons leert over politieonderzoeken, verhoren, herkenningen, leugendetectie, rechterlijke beslissingen en nog veel meer. Het boek is uitstekend geschikt als naslagwerk en cursusmateriaal voor studenten en voor professionals in het recht

Mapping livestock grazing in semi-natural areas in the European Union and United Kingdom

Context: Livestock grazing throughout Europe has resulted in high diversity of semi-natural areas in past centuries. Currently, most low intensity grazing relying on semi-natural vegetation is found primarily in marginal lands. These areas still host a high-level of biodiversity but are subject to abandonment and agricultural intensification. Objectives: Spatial information on areas where semi-natural vegetation is still grazed, and how contextual geographic conditions encourage or limit grazing is missing, hindering their protection. We present an interdisciplinary approach to map the spatial distribution of grazing in semi-natural areas of the European Union (EU) and the United Kingdom (UK). Methods: We first interviewed grazing experts from European countries, who provided us with estimates on grazing across selected land cover classes per environmental zone and Member State. Subsequently, we analysed the spatial distribution of grazing through maximum entropy modeling using pan-European in-situ data on grazing observations (using LUCAS, an EU wide land use survey) and a set of geographic characteristics representing the local socio-economic, terrain, soil and climatic context. Results: The expert-derived estimates on grazing suggest that 20.6% (or 134 thousand km2) of semi-natural areas in the EU + UK are grazed, although with low livestock densities. In addition, we find that there is great variety across the region in the factors that explain the occurrence of grazing: while in some regions, farmers’ age and distance to markets are most important, in others terrain or climate are influencing the location of grazing. Finally, we were able to map both the grazing probability as well as actual spatial distribution of grazing on semi-natural areas for the whole of EU and UK. Conclusions: These data can assist in prioritizing future conservation efforts in these unique land systems.</p

Innovate to Eradicate:Refining Tuberculosis Drug Discovery through Zebrafish

Tuberculosis (TB) remains one of the oldest and most persistent infectious diseases, posing a significant global health challenge with over 10 million new infections annually. Despite the availability of treatments, the rise of drug-resistant strains underscores the urgent need for innovative therapeutics and refined drug discovery strategies. This thesis addresses these challenges by presenting new methodologies to enhance early-stage TB drug development. Chapter 1 provides a comprehensive overview of TB, its causative agents, and current drug discovery efforts. A significant challenge in this field is the difficulty of identifying in vitro active compounds that demonstrate efficacy in vivo. To bridge this translational gap, Chapter 2 reviews an in vivo zebrafish embryo infection model designed for the rapid evaluation of compound activity, discussing its advantages and limitations in antimicrobial drug screening. Chapter 3 illustrates the practical application of the zebrafish model in TB drug discovery through medium-throughput screening of 240 in vitro active compounds, of which only 14 exhibited activity in the zebrafish model, highlighting the importance of early in vivo assessment. Further characterization of one promising compound revealed its action on aspartyl tRNA synthetase (AspS) in mycobacteria, suggesting its potential as a novel protein synthesis inhibitor. In TB research, model organisms are often used for initial experiments due to biosafety concerns. Chapter 4 investigates the differential activity of two clinically used TB pro-drugs, ethionamide and isoniazid, in M. tuberculosis and its model organism, M. marinum. By engineering an M. marinum strain to enhance drug-activating enzyme expression, we adapted the susceptibility of M. marinum to be similar to that of M. tuberculosis. This engineered strain was further used for drug screening to identify several pro-drugs that would have been overlooked in traditional screenings with M. marinum. Chapter 5 focuses on identifying novel gyrase inhibitors that are selective for mycobacteria. Through a medicinal chemistry approach and the derivatization of known gyrase B inhibitors, we identified structural features that increase specificity for mycobacteria. Finally, Chapter 6 addresses the challenge of mycobacterial membrane permeability, which often presents a bottleneck for compounds to reach intracellular targets. We identified a compound that increases membrane permeability by targeting a novel drug target, Rv0164 (MMAR_0407). This chapter also emphasizes the significance of combination therapy, demonstrating that our new compounds can synergistically enhance the efficacy of existing antibiotics, thereby improving TB treatment strategies. In conclusion, this thesis presents optimized drug discovery strategies for the early phases of drug development, leading to the identification and validation of several new active compounds with potential for future therapeutic applications. The results are contextualized within existing literature in Chapter 7, illustrating the importance of ongoing research efforts for the global eradication of tuberculosis, as outlined by the WHO