Processing time not modality dominates shift costs in the modality-shifting effect

Shifting attention between visual and auditory targets is associated with reaction time costs, known as the modality-shifting effect. The type of modality shifted from e.g., auditory or visual is suggested to have an effect on the degree of cost. Studies report greater costs shifting from visual stimuli, yet notably used visual stimuli that are also identified slower than the auditory. It is not clear whether the cost is specific to modality effects, or with identification speed independent of modality. Here, in order to interpret whether the effects are due to modality or identification time, switch costs are instead compared with auditory stimuli that are identified slower than the visual (inverse of tested previously). A second condition used the same auditory stimuli at a low intensity, allowing comparison of semantically identical stimuli that are even slower to process. The current findings contradicted suggestions of a general difficulty in shifting from visual stimuli (as previously reported), and instead suggest that cost is reduced when targets are preceded by a more rapidly processed stimulus. ‘Modality-Shifting’ as it is often termed induces shifting costs, but the costs are not because of a change of modality per se, but because of a change in identification speed, where the degree of cost is dependent on the processing time of the surrounding stimuli

An activatable NIR fluorescent rosol for selectively imaging nitroreductase activity

Hypoxia (pO2 ≤ ~1.5%) is an important characteristic of tumor microenvironments that directly correlates with resistance against first-line therapies and tumor proliferation/infiltration. The ability to accurately identify hypoxic tumor cells/tissue could afford tailored therapeutic regimens for personalized treatment, development of more-effective therapies, and discerning the mechanisms underlying disease progression. Fluorogenic constructs identifying aforesaid cells/tissue operate by targeting the bioreductive activity of primarily nitroreductases (NTRs), but collectively present photophysical and/or physicochemical shortcomings that could limit effectiveness. To overcome these limitations, we present the rational design, development, and evaluation of the first activatable ultracompact xanthene core-based molecular probe (NO 2 -Rosol) for selectively imaging NTR activity that affords an "OFF-ON" near-infrared (NIR) fluorescence response (> 700 nm) alongside a remarkable Stokes shift (> 150 nm) via NTR activity-facilitated modulation to its energetics whose resultant interplay discontinues an intramolecular d-PET fluorescence-quenching mechanism transpiring between directly-linked electronically-uncoupled π-systems comprising its components. DFT calculations guided selection of a suitable fluorogenic scaffold and nitroaromatic moiety candidate that when adjoined could (i) afford such photophysical response upon bioreduction by upregulated NTR activity in hypoxic tumor cells/tissue and (ii) employ a retention mechanism strategy that capitalizes on an inherent physical property of the NIR fluorogenic scaffold for achieving signal amplification. NO 2 -Rosol demonstrated 705 nm NIR fluorescence emission and 157 nm Stokes shift, selectivity for NTR over relevant bioanalytes, and a 28-/12-fold fluorescence enhancement in solution and between cells cultured under different oxic conditions, respectively. In establishing feasibility for NO 2 -Rosol to provide favorable contrast levels in solutio/vitro, we anticipate NO 2 -Rosol doing so in preclinical studies

Molecular memory with downstream logic processing exemplified by switchable and self-indicating guest capture and release

While many processes in biological cells can be understood in terms of molecular logic gates that process information sequentially and combinationally, the design and construction of such devices in the laboratory are unknown. Here the authors achieve this by the reversibly-controlled capture and release of guest molecules from host containers