The effects of glare and inhomogeneous visual fields on contrast detection in the context of driving

An experiment was carried out to investigate how contrast threshold for target detection is affected by the presence of glare and by extraneous light sources using the method of ascending limits. The target was located at either a foveal or a peripheral (10° right) location, glare was adjacent to the foveal location, simulating the headlamps of an oncoming vehicle, and extraneous light sources were at either foveal or peripheral (10° right or left) locations. Contrast threshold for a foveal target without glare was affected mainly by the surrounding local luminance distribution. However, in the presence of glare and also for the peripheral target (both with and without glare) the global luminance distribution matters. Glare increased the contrast needed for detection of the foveal target, but this effect was reduced by the presence of extraneous light sources that were peripheral to the target. For peripheral targets, contrast threshold was also reduced by the presence of extraneous light at a non-target location and this effect was increased in the presence of glare. Glare equations tend to be based on tests using uniform, homogenous fields: these data indicate that, in the presence of extraneous light sources, the influence of glare is over-estimated

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

The effect of memory in inducing pleasant emotions with musical and pictorial stimuli

Music is known to evoke emotions through a range of mechanisms, but empirical investigation into the mechanisms underlying different emotions is sparse. This study investigated how affective experiences to music and pictures vary when induced by personal memories or mere stimulus features. Prior to the experiment, participants were asked to select eight types of stimuli according to distinct criteria concerning the emotion induction mechanism and valence. In the experiment, participants (N = 30) evaluated their affective experiences with the self-chosen material. EEG was recorded throughout the session. The results showed certain interaction effects of mechanism (memory vs. stimulus features), emotional valence of the stimulus (pleasant vs. unpleasant), and stimulus modality (music vs. pictures). While effects were mainly similar in music and pictures, the findings suggest that when personal memories are involved, stronger positive emotions were experienced in the context of music, even when the music was experienced as unpleasant. Memory generally enhanced social emotions specifically in pleasant conditions. As for sadness and melancholia, stimulus features did not evoke negative experiences; however, these emotions increased strongly with the involvement of memory, particularly in the condition of unpleasant music. Analysis of EEG-data corroborated the findings by relating frontomedial theta activity to memory-evoking material

Crystal structures of Trichoderma reesei beta-galactosidase reveal conformational changes in the active site.

We have determined the crystal structure of Trichoderma reesei (Hypocrea jecorina) β-galactosidase (Tr-β-gal) at a 1.2Å resolution and its complex structures with galactose, IPTG and PETG at 1.5, 1.75 and 1.4Å resolutions, respectively. Tr-β-gal is a potential enzyme for lactose hydrolysis in the dairy industry and belongs to family 35 of the glycoside hydrolases (GH-35). The high resolution crystal structures of this six-domain enzyme revealed interesting features about the structure of Tr-β-gal. We discovered conformational changes in the two loop regions in the active site, implicating a conformational selection-mechanism for the enzyme. In addition, the Glu200, an acid/base catalyst showed two different conformations which undoubtedly affect the pK(a) value of this residue and the catalytic mechanism. The electron density showed extensive glycosylation, suggesting a structure stabilizing role for glycans. The longest glycan showed an electron density that extends to the eighth monosaccharide unit in the extended chain. The Tr-β-gal structure also showed a well-ordered structure for a unique octaserine motif on the surface loop of the fifth domain

Luminance-corrected 3D point clouds for road and street environments

A novel approach to evaluating night-time road and street environment lighting conditions through 3D point clouds is presented. The combination of luminance imaging and 3D point cloud acquired with a terrestrial laser scanner was used for analyzing 3D luminance on the road surface. A calculation of the luminance (cd/m2) was based on the RGB output values of a Nikon D800E digital still camera. The camera was calibrated with a reference luminance source. The relative orientation between the luminance images and intensity image of the 3D point cloud was solved in order to integrate the data sets into the same coordinate system. As a result, the 3D model of road environment luminance is illustrated and the ability to exploit the method for evaluating the luminance distribution on the road surface is presented. Furthermore, the limitations and future prospects of the methodology are addressed. The method provides promising results for studying road lighting conditions in future lighting optimizations. The paper presents the methodology and its experimental application on a road section which consists of five luminaires installed on one side of a two-lane road in Otaniemi, Espoo, Finland.Peer reviewe

The peroxisomal zebrafish SCP2-thiolase (type-1) is a weak transient dimer as revealed by crystal structures and native mass spectrometry

Abstract The SCP2 (sterol carrier protein 2)-thiolase (type-1) functions in the vertebrate peroxisomal, bile acid synthesis pathway, converting 24-keto-THC-CoA and CoA into choloyl-CoA and propionyl-CoA. This conversion concerns the β-oxidation chain shortening of the steroid fatty acyl-moiety of 24-keto-THC-CoA. This class of dimeric thiolases has previously been poorly characterized. High-resolution crystal structures of the zebrafish SCP2-thiolase (type-1) now reveal an open catalytic site, shaped by residues of both subunits. The structure of its non-dimerized monomeric form has also been captured in the obtained crystals. Four loops at the dimer interface adopt very different conformations in the monomeric form. These loops also shape the active site and their structural changes explain why a competent active site is not present in the monomeric form. Native mass spectrometry studies confirm that the zebrafish SCP2-thiolase (type-1) as well as its human homolog are weak transient dimers in solution. The crystallographic binding studies reveal the mode of binding of CoA and octanoyl-CoA in the active site, highlighting the conserved geometry of the nucleophilic cysteine, the catalytic acid/base cysteine and the two oxyanion holes. The dimer interface of SCP2-thiolase (type-1) is equally extensive as in other thiolase dimers; however, it is more polar than any of the corresponding interfaces, which correlates with the notion that the enzyme forms a weak transient dimer. The structure comparison of the monomeric and dimeric forms suggests functional relevance of this property. These comparisons provide also insights into the structural rearrangements that occur when the folded inactive monomers assemble into the mature dimer