The transport of anions across cellular membranes is an important biological function governed by specialised proteins. In recent years, many small molecules have emerged that mimick the anion transport behaviour of these proteins, but only a few of these synthetic molecules also display the gating/switching behaviour seen in biological systems. A small series of thiosquaramides was synthesised and their pH-dependent chloride binding and anion transport behaviour was investigated using 1H NMR titrations, single crystal X-ray diffraction and a variety of vesicle-based techniques. Spectrophotometric titrations and DFT calculations revealed that the thiosquaramides are significantly more acidic than their oxosquaramide analogues, with pKa values between 4.0 and 9.0. This led to the observation that at pH 7.2 the anion transport ability of the thiosquaramides is fully switched OFF due to deprotonation of the receptor, but is completely switched ON at lower pH.

Abstract-Decades of research have repeatedly shown that people perform poorly at estimating and understanding conditional probabilities that are inherent in Bayesian reasoning problems. Yet in the medical domain, both physicians and patients make daily, life-critical judgments based on conditional probability. Although there have been a number of attempts to develop more effective ways to facilitate Bayesian reasoning, reports of these findings tend to be inconsistent and sometimes even contradictory. For instance, the reported accuracies for individuals being able to correctly estimate conditional probability range from 6% to 62%. In this work, we show that problem representation can significantly affect accuracies. By controlling the amount of information presented to the user, we demonstrate how text and visualization designs can increase overall accuracies to as high as 77%. Additionally, we found that for users with high spatial ability, our designs can further improve their accuracies to as high as 100%. By and large, our findings provide explanations for the inconsistent reports on accuracy in Bayesian reasoning tasks and show a significant improvement over existing methods. We believe that these findings can have immediate impact on risk communication in health-related fields.

A macrocyclic tetralactam host is threaded by a highly fluorescent squaraine dye that is flanked by two polyethyleneglycol (PEG) chains with nanomolar dissociation constants in water. Furthermore, the rates of bimolecular association are very fast with kon ~106–107 M−1s−1. The association is effective under cell culture conditions and produces large changes in dye optical properties including turn-on near-infrared fluorescence that can be imaged using cell microscopy. Association constants in water are ~1000 times higher than in organic solvents and strongly enthalpically favored at 27 °C. The threading rate is hardly affected by the length of the PEG chains that flank the squaraine dye. For example, macrocyle threading by a dye conjugate with two appended PEG2000 chains is only three times slower than threading by a conjugate with triethyleneglycol chains that are twenty times shorter. The results are a promising advance towards synthetic mimics of streptavidin/biotin.

A new squaraine rotaxane molecular shuttle exhibits high chemical stability and acts as a deep-red, fluorescent and colorimetric sensor for Cl À anion with reversible, ratiometric response. The molecular design encapsulates a dihydroxyl substituted squaraine dye inside an anthracene-containing tetralactam macrocycle and a "clicked capping" reaction was used to convert an appropriate pseudorotaxane precursor into a permanently interlocked rotaxane in high yield. Reversible binding of Cl À to the rotaxane in solution, or on the surface of prototype dipsticks, causes lateral displacement of the surrounding macrocycle away from the central squaraine station and a substantial 30-40 nm shift in the squaraine absorption/fluorescence maxima that can be easily detected by the naked eye. The collective attributes of intense absorption/emission and ratiometric response at deep-red wavelengths is a significant advance in optical Cl À sensor performance by an organic molecule.

We show how brain sensing can lend insight to the evaluation of visual interfaces and establish a role for fNIRS in visualization. Research suggests that the evaluation of visual design benefits by going beyond performance measures or questionnaires to measurements of the user's cognitive state. Unfortunately, objectively and unobtrusively monitoring the brain is difficult. While functional near-infrared spectroscopy (fNIRS) has emerged as a practical brain sensing technology in HCI, visual tasks often rely on the brain's quick, massively parallel visual system, which may be inaccessible to this measurement. It is unknown whether fNIRS can distinguish differences in cognitive state that derive from visual design alone. In this paper, we use the classic comparison of bar graphs and pie charts to test the viability of fNIRS for measuring the impact of a visual design on the brain. Our results demonstrate that we can indeed measure this impact, and furthermore measurements indicate that there are not universal differences in bar graphs and pie charts.

Dynamic difficulty adjustments can be used in humancomputer systems in order to improve user engagement and performance. In this paper, we use functional near-infrared spectroscopy (fNIRS) to obtain passive brain sensing data and detect extended periods of boredom or overload. From these physiological signals, we can adapt a simulation in order to optimize workload in real-time, which allows the system to better fit the task to the user from moment to moment. To demonstrate this idea, we ran a laboratory study in which participants performed path planning for multiple unmanned aerial vehicles (UAVs) in a simulation. Based on their state, we varied the difficulty of the task by adding or removing UAVs and found that we were able to decrease errors by 35% over a baseline condition. Our results show that we can use fNIRS brain sensing to detect task difficulty in real-time and construct an interface that improves user performance through dynamic difficulty adjustment.

A macrocyclic tetralactam is threaded by a complementary squaraine dye that is flanked by two polyethylene glycol chains to produce a pseudorotaxane complex with favorable near-infrared fluorescence properties. The association thermodynamics and kinetics were measured for a homologous series of squaraines with different N-alkyl substituents at both ends of the dye. The results show that subtle changes in substituent steric size have profound effects on threading kinetics without greatly altering the very high association constant.

A programmable pre-assembly method is described and shown to produce near-infrared fluorescent molecular probes with tunable multivalent binding properties. The modular assembly process threads one or two copies of a tetralactam macrocycle onto a fluorescent PEGylated squaraine scaffold containing a complementary number of docking stations. Appended to the macrocycle periphery are multiple copies of a ligand that is known to target a biomarker. The structure and high purity of each threaded complex was determined by independent spectrometric methods and also by gel electrophoresis. Especially helpful were diagnostic red-shift and energy transfer features in the absorption and fluorescence spectra. The threaded complexes were found to be effective multivalent molecular probes for fluorescence microscopy and in vivo fluorescence imaging of living subjects. Two multivalent probes were prepared and tested for targeting of bone in mice. A pre-assembled probe with twelve bone-targeting iminodiacetate ligands produced more bone accumulation than an analogous pre-assembled probe with six iminodiacetate ligands. Notably, there was no loss in probe fluorescence at the bone target site after 24 hours in the living animal, indicating that the pre-assembled fluorescent probe maintained very high mechanical and chemical stability on the skeletal surface. The study shows how this versatile pre-assembly method can be used in a parallel combinatorial manner to produce libraries of near-infrared fluorescent multivalent molecular probes for different types of imaging and diagnostic applications, with incremental structural changes in the number of targeting groups, linker lengths, linker flexibility, and degree of PEGylation.