“She’s a waterfall”: motion after-effect and perceptual design in video games involving virtual musicianship

A particularly unpleasant version of motion aftereffect was revealed after extensively playing proprietary video games in which the task is to co-ordinate spatially distributed responses in time with music. During playing, key musical and rhythmic phrases descend as coloured shapes from the top of the screen. After playing, static text is presented that appears to slide upwards, reflecting a neural reaction contrary to the falling shapes. The game both serves as a contemporary example of motion aftereffect and also highlights certain cross-modal associations between space, time, and sound in the design of stimulus-response relations

The Advantage of Ambiguity? Enhanced Neural Responses to Multi-Stable Percepts Correlate with the Degree of Perceived Instability

Artwork can often pique the interest of the viewer or listener as a result of the ambiguity or instability contained within it. Our engagement with uncertain sensory experiences might have its origins in early cortical responses, in that perceptually unstable stimuli might preclude neural habituation and maintain activity in early sensory areas. To assess this idea, participants engaged with an ambiguous visual stimulus wherein two squares alternated with one another, in terms of simultaneously opposing vertical and horizontal locations relative to fixation (i.e., stroboscopic alternating motion; von Schiller, 1933). At each trial, participants were invited to interpret the movement of the squares in one of five ways: traditional vertical or horizontal motion, novel clockwise or counter-clockwise motion, and, a free-view condition in which participants were encouraged to switch the direction of motion as often as possible. Behavioral reports of perceptual stability showed clockwise and counter-clockwise motion to possess an intermediate level of stability compared to relatively stable vertical and horizontal motion, and, relatively unstable motion perceived during free-view conditions. Early visual evoked components recorded at parietal–occipital sites such as C1, P1, and N1 modulated as a function of visual intention. Both at a group and individual level, increased perceptual instability was related to increased negativity in all three of these early visual neural responses. Engagement with increasingly ambiguous input may partly result from the underlying exaggerated neural response to it. The study underscores the utility of combining neuroelectric recording with the presentation of perceptually multi-stable yet physically identical stimuli, in revealing brain activity associated with the purely internal process of interpreting and appreciating the sensory world that surrounds us

Conformational control of anticancer activity: the application of arene-linked dinuclear ruthenium(II) organometallics

Dinuclear metal complexes have emerged as a promising class of biologically active compounds which possess unique anticancer activity. Here, we describe a novel series of arene-linked dinuclear organometallic Ru(II) complexes, where the relative conformation of the ruthenium centres is controlled by the stereochemical configuration of 1,2-diphenylethylenediamine linker moieties, as confirmed by X-ray crystallography. The reactivity and cytotoxicity of these compounds is compared to flexible dinuclear and mononuclear analogues, demonstrating in all cases the complexes can undergo aquation, coordinate to typical biological donor ligands and importantly, in the case of dinuclear analogues, crosslink oligonucleotide and peptide sequences. Differences in the conformation of the isomeric dinuclear compounds lead to significantly different levels of cytotoxicity against A2780, A2780cisR and HEK-293 cell lines; isomers with a closed conformation are significantly more cytotoxic than isomers with a more open conformation and they are also significantly less susceptible to acquired resistance mechanisms operating in the A2780cisR cell line. These rigid dinuclear compounds possess markedly increased cytotoxicity relative to the non-cytotoxic mononuclear analogues that does not appear to be related to differences in complex lipophilicity or cellular uptake, which, in general, remain similar in magnitude across the series. Thus, the molecular conformation of such dinuclear species may be crucial in determining the nature of the adducts formed on coordination to biological targets in a cellular environment, and opens up a novel route toward the development of more active metal-based anticancer agents

Potential of cycloaddition reactions to generate cytotoxic metal drugs in vitro

Severe general toxicity issues blight many chemotherapeutics utilized in the treatment of cancers, resulting in the need for more selective drugs able to exert their biological activity at only the required location(s). Toward this aim, we report the development of an organometallic ruthenium compound, functionalized through a η6-bound arene ligand with a bicyclononyne derivative, able to participate in strain-promoted cycloaddition reactions with tetrazines. We show that combination of the ruthenium compound with a ditetrazine in biological media results in the in situ formation of a dinuclear molecule that is more cytotoxic toward cancer cells than the starting mononuclear ruthenium compound and tetrazine components. Such an approach may be extended to in vivo applications to construct a cytotoxic metallodrug at a tumor site, providing a novel approach toward the turn-on cytotoxicity of metallodrugs in the treatment of cancer

Recent progress in the development of organometallics for the treatment of cancer

From their early successes in medicine, organometallic compounds continue to attract interest as potential chemotherapeutics to treat a range of diseases. Here, we show from recent literature selected largely from the last two years that organometallics offer unique opportunities in medicine and, increasingly, a mechanistic-based approach is applied to their development, which has not always been the case

The contribution of perceptual factors and training on varying audiovisual integration capacity

The suggestion that the capacity of audiovisual integration has an upper limit of 1 was challenged in 4 experiments using perceptual factors and training to enhance the binding of auditory and visual information. Participants were required to note a number of specific visual dot locations that changed in polarity when a critical auditory stimulus was presented, under relatively fast (200-ms stimulus onset asynchrony [SOA]) and slow (700-ms SOA) rates of presentation. In Experiment 1, transient cross-modal congruency between the brightness of polarity change and pitch of the auditory tone was manipulated. In Experiment 2, sustained chunking was enabled on certain trials by connecting varying dot locations with vertices. In Experiment 3, training was employed to determine if capacity would increase through repeated experience with an intermediate presentation rate (450 ms). Estimates of audiovisual integration capacity (K) were larger than 1 during cross-modal congruency at slow presentation rates (Experiment 1), during perceptual chunking at slow and fast presentation rates (Experiment 2), and, during an intermediate presentation rate posttraining (Experiment 3). Finally, Experiment 4 showed a linear increase in K using SOAs ranging from 100 to 600 ms, suggestive of quantitative rather than qualitative changes in the mechanisms in audiovisual integration as a function of presentation rate. The data compromise the suggestion that the capacity of audiovisual integration is limited to 1 and suggest that the ability to bind sounds to sights is contingent on individual and environmental factors

The development of RAPTA compounds for the treatment of tumors

© 2015 Elsevier B.V. Ruthenium(II)-arene RAPTA-type compounds have been extensively explored for their medicinal properties. Herein a comprehensive review of this class of compounds is provided. A discussion of the basic RAPTA structure is given together with the ways it has been modified to elucidate the key role of each part and to afford targeted derivatives. The various mechanistic studies conducted on RAPTA compounds are described and these are linked to the observed macroscopic biological properties. Ultimately, the review shows that certain RAPTA compounds display quite unique properties that point towards a clinical investigation

Local context effects during emotional item directed forgetting in younger and older adults

This paper explored the differential sensitivity young and older adults exhibit to the local context of items entering memory. We examined trial-to-trial performance during an item directed forgetting task for positive, negative, and neutral (or baseline) words each cued as either to-be-remembered (TBR) or to-be-forgotten (TBF). This allowed us to focus on how variations in emotional valence (independent of arousal) and instruction (TBR vs. TBF) of the previous item (trial n-1) impacted memory for the current item (trial n) during encoding. Different from research showing impairing effects of emotional arousal, both age groups showed a memorial boost for stimuli when preceded by items high in positive or negative valence relative to those preceded by neutral items. This advantage was particularly prominent for neutral trial n items that followed emotional items suggesting that, regardless of age, neutral memories may be strengthened by a local context that is high in valence. A trending age difference also emerged with older adults showing greater sensitivity when encoding instructions changed between trial n-1 and n. Results are discussed in light of age-related theories of cognitive and emotional processing, highlighting the need to consider the dynamic, moment-to-moment fluctuations of these systems

Synthesis, Molecular Structure and Cytotoxicity of Molecular Materials Based on Water Soluble Half-Sandwich Rh(III) and Ir(III) Tetranuclear Metalla-Cycles

The neutral dinuclear complexes [(eta(5)-C5Me5)(2)Rh-2(mu-dhnq)Cl-2] (1) and [(eta(5)-C5Me5)(2)Ir-2(mu-dhnq)Cl-2] (2) (dhnqH(2) = 5,8-dihydroxy-1,4-naphthoquinone) were obtained from the reaction of [(eta(5)-C5Me5)M(mu-Cl)Cl](2) (M = Rh, Ir) with dhnqH(2) in the presence of CH3COONa. Treatment of 1 or 2 in methanol with linear ditopic ligands L (L = pyrazine, 4,4'-bipyridine or 1,2-bis(4-pyridyl) ethylene), in the presence of AgCF3SO3, affords the corresponding tetranuclear metalla-rectangles [(eta(5)-C5Me5)(4)M-4(mu-dhnq)(2)(mu-L)(2)](4+) (L = pyrazine, M = Rh, 3; M = Ir, 4; L = 4,4'-bipyridine, M = Rh, 5; M = Ir, 6; L = 1,2-bis(4-pyridyl) ethylene, M = Rh, 7; M = Ir, 8). All complexes were isolated as their triflate salts and were fully characterized by infrared, H-1 and C-13 NMR spectroscopy, and some representative complexes by single-crystal X-ray structure analysis. The X-ray structures of 3, 5 and 6 confirm the formation of the tetranuclear metalla-cycles, and suggest that complexes 5 and 6 possess a cavity of sufficient size to encapsulate small guest molecules. In addition, the antiproliferative activity of the metalla-cycles 3-8 was evaluated against the human ovarian A2780 (cisplatin sensitive) and A2780cisR (cisplatin resistant) cancer cell lines and on non-tumorigenic human embryonic kidney HEK293 cells. All cationic tetranuclear metalla-rectangles were found to be highly cytotoxic, with IC50 values in the low micromolar range

A network modelling approach to assess non-pharmaceutical disease controls in a worker population : an application to SARS-CoV-2

As part of a concerted pandemic response to protect public health, businesses can enact non-pharmaceutical controls to minimise exposure to pathogens in workplaces and premises open to the public. Amendments to working practices can lead to the amount, duration and/or proximity of interactions being changed, ultimately altering the dynamics of disease spread. These modifications could be specific to the type of business being operated. We use a data-driven approach to parameterise an individual-based network model for transmission of SARS-CoV-2 amongst the working population, stratified into work sectors. The network is comprised of layered contacts to consider the risk of spread in multiple encounter settings (workplaces, households, social and other). We analyse several interventions targeted towards working practices: mandating a fraction of the population to work from home; using temporally asynchronous work patterns; and introducing measures to create ‘COVID-secure’ workplaces. We also assess the general role of adherence to (or effectiveness of) isolation and test and trace measures and demonstrate the impact of all these interventions across a variety of relevant metrics. The progress of the epidemic can be significantly hindered by instructing a significant proportion of the workforce to work from home. Furthermore, if required to be present at the workplace, asynchronous work patterns can help to reduce infections when compared with scenarios where all workers work on the same days, particularly for longer working weeks. When assessing COVID-secure workplace measures, we found that smaller work teams and a greater reduction in transmission risk reduced the probability of large, prolonged outbreaks. Finally, following isolation guidance and engaging with contact tracing without other measures is an effective tool to curb transmission, but is highly sensitive to adherence levels. In the absence of sufficient adherence to non-pharmaceutical interventions, our results indicate a high likelihood of SARS-CoV-2 spreading widely throughout a worker population. Given the heterogeneity of demographic attributes across worker roles, in addition to the individual nature of controls such as contact tracing, we demonstrate the utility of a network model approach to investigate workplace-targeted intervention strategies and the role of test, trace and isolation in tackling disease spread