High-throughput discovery of organic cages and catenanes using computational screening fused with robotic synthesis.

Supramolecular synthesis is a powerful strategy for assembling complex molecules, but to do this by targeted design is challenging. This is because multicomponent assembly reactions have the potential to form a wide variety of products. High-throughput screening can explore a broad synthetic space, but this is inefficient and inelegant when applied blindly. Here we fuse computation with robotic synthesis to create a hybrid discovery workflow for discovering new organic cage molecules, and by extension, other supramolecular systems. A total of 78 precursor combinations were investigated by computation and experiment, leading to 33 cages that were formed cleanly in one-pot syntheses. Comparison of calculations with experimental outcomes across this broad library shows that computation has the power to focus experiments, for example by identifying linkers that are less likely to be reliable for cage formation. Screening also led to the unplanned discovery of a new cage topology-doubly bridged, triply interlocked cage catenanes.

Impact of hand sanitizer format (gel/foam/liquid) and dose amount on its sensory properties and acceptability for improving hand hygiene compliance.

BACKGROUND: Effective alcohol-based hand rubs (ABHRs) and healthcare worker compliance with hand hygiene guidelines are important in the prevention of infection transmission in healthcare settings. Compliance to hand hygiene guidelines is affected by many factors including education, ABHR availability, time pressure, skin health, and user acceptance of the sensory properties of ABHRs during and after application. AIM: To examine the effect of ABHR format (gel/foam/liquid) and dose (0.7 mL, 1.5 mL, 3 mL) on its sensory properties and acceptability, and to consider how this might affect healthcare workers' hand hygiene compliance. METHODS: Sensory descriptive analysis established key sensory differences between ten market-leading ABHRs (three gels, four foams, two liquids, one aerosol foam). Focus groups reinforced these differences. FINDINGS: All formats were less desirable at the highest dose as they were more difficult to handle than the lower doses. Foams and gels became stickier, less clean-feeling and slower to dry at higher doses. Liquids gave a cleaner, smoother, more moisturized feel, but the increased difficulty in handling and applying the product negated these benefits. Overall, the gel and foam formats were more desirable than the liquid. The key desirable properties include: fast absorption, soft/moisturized hand feel, not sticky, clean feel, and low smell. CONCLUSION: The 1.5 mL dose yielded the most acceptable properties with no extreme negative consequences. The foam provided the benefits of both the liquid and gel and combined them into a more widely acceptable format that may lead to greater hand hygiene compliance.

Neuropsychological presentation and adaptive skills in high-functioning adolescents with visual impairment: A preliminary investigation.

Studies in infants and young children with congenital visual impairment (VI) have indicated early developmental vulnerabilities, conversely research with older children and adults have highlighted areas of cognitive strength. A minimal amount is known, however, about the possible combination of strengths and weaknesses in adolescence, and this present study therefore aims to explore the neuropsychological presentation and adaptive behavior profile in high-functioning adolescents with congenital VI. Participants completed a battery of commonly used neuropsychological measures assessing memory, executive function, and attention. The measures utilized focused on auditory neuropsychological function, because only subtests that could be completed with auditory administration were suitable for this sample. Parents completed standardized measures of adaptive behavior, executive function, and social communication. Compared to aged-based norms for normal sight, adolescents with VI demonstrated strengths in aspects of working memory and verbal memory. Furthermore, performance across the neuropsychological battery was within or above the average range for the majority of the sample. In contrast, parent-report measures indicated areas of weakness in adaptive functioning, social communication, and behavioral executive functioning. Overall, this study provides preliminary evidence that relative to fully sighted peers, high-functioning adolescents with VI present with an uneven profile of cognitive and adaptive skills, which has important implications for assessment and intervention.

Combining cycloisomerization with trienamine catalysis: a regiochemically flexible enantio- and diastereoselective synthesis of hexahydroindoles.

The synthesis of polysubstituted hexahydroindoles through trienamine-organocatalyzed cycloadditions of pyrrolidinyl dienals, prepared by palladium-catalyzed cycloisomerization, is reported. The cycloadditions of this novel class of dienals proceed with excellent levels of enantio- and diastereoselectivity, with the regioselectivity of cycloaddition with respect to the tethering ring readily tuned through design of the cycloisomerization substrate. This work culminates in the first examples of double-stereodifferentiating trienamine catalysis, where catalyst stereocontrol dominates facial selectivity in the cycloaddition, affording azacyclic products that are specifically functionalized at every position.

Marked selective impairment in autism on an index of magnocellular function.

Atypical high-level vision in autism is sometimes attributed to a core deficit in the function of lateral geniculate nucleus magnocells or their retinal drives. While some physiological measures provide indirect, suggestive evidence for such a deficit, support from behavioural measures is lacking and contradictory. We assessed luminance contrast increment thresholds on pulsed- and steady- pedestals in 17 children with autism spectrum conditions (ASC) compared to 17 typically developing children; these two conditions correspond to widely-used indices of magnocellular and parvocellular function. As a group, children with ASC had strikingly elevated thresholds on the steady pedestal-paradigm, yet performed similarly to controls on the pulsed pedestal paradigm, a finding that would typically be interpreted to reflect impaired magnocellular function. The effect size of the impairment was large and a substantial minority (41.2%) of the ASC group showed significantly impaired performance on an individual basis. This finding is consistent with a selective magnocellular deficit. It directly contradicts previous claims that such deficits are confined to 'complex' visual stimuli and likely does not reflect atypical attention, adaptation or high-level vision. The pattern of results is not clearly predicted by notions of imbalance of excitation versus inhibition, atypical lateral connectivity or enhanced perceptual function that account for a range of other findings associated with perception in autism. It may be amenable to explanation in terms of decreased endogenous neural noise, a novel alternative we outline here.

Light scattering from deformed droplets and droplets with inclusions. I. Experimental results.

We provide experimental results from the scattering of light by deformed liquid droplets and droplets with inclusions. The characterization of droplet deformation could lead to improved measurement of droplet size as measured by commercial aerodynamic particle-sizing instruments. The characterization of droplets with inclusions can be of importance in some industrial, occupational, and military aerosol monitoring situations. The nozzle assembly from a TSI Aerodynamic Particle Sizer was used to provide the accelerating flow conditions in which experimental data were recorded. A helium-neon laser was employed to generate the light-scattering data, and an externally triggered, pulsed copper vapor laser provided illumination for a droplet imaging system arranged orthogonal to the He-Ne scattering axis. The observed droplet deformation correlates well over a limited acceleration range with theoretical predictions derived from an analytical solution of the Navier-Stokes equation.

Light Scattering from Deformed Droplets and Droplets with Inclusions. II. Theoretical Treatment.

We provide theoretical results from the scattering of light by deformed liquid droplets and droplets with inclusions. With improved instrumentation and computer technologies available, researchers are able to employ two-dimensional angular optical scattering as a tool for analyzing such particle systems and which then could be applied in industrial, occupational, and military aerosol measurement. We present numerically calculated spatial light-scattering data from various droplet morphologies. We describe characteristic features of the theoretical data and compare these with the experimental results.

A novel instrument for studying the flow behaviour of erythrocytes through microchannels simulating human blood capillaries.

A novel instrument has been developed to study the microrheology of erythrocytes as they flow through channels of dimensions similar to human blood capillaries. The channels are produced in silicon substrates using microengineering technology. Accurately defined, physiological driving pressures and temperatures are employed whilst precise, real-time image processing allows individual cells to be monitored continuously during their transit. The instrument characterises each cell in a sample of ca. 1000 in terms of its volume and flow velocity profile during its transit through a channel. The unique representation of the data in volume/velocity space provides new insight into the microrheological behaviour of blood. The image processing and subsequent data analysis enable the system to reject anomalous events such as multiple cell transits, thereby ensuring integrity of the resulting data. By employing an array of microfluidic flow channels we can integrate a number of different but precise and highly reproducible channel sizes and geometries within one array, thereby allowing multiple, concurrent isobaric measurements on one sample. As an illustration of the performance of the system, volume/velocity data sets recorded in a microfluidic device incorporating multiple channels of 100 microns length and individual widths ranging between 3.0 and 4.0 microns are presented.

A silicon micromachined device for use in blood cell deformability studies.

An application of silicon micromachining to the analysis of blood cell rheology is described. The system, based upon a micromachined flow cell, provides a specific measurement of each cell in a statistically significant population in terms of both flow velocity profile and an index of cell volume while the cells flow through an array of microchannels. The rationale, design, and fabrication of the silicon micromachined flow cell is discussed. Interrelated considerations determining the design of the associated fluidic, mechanical, imaging, and real-time image analysis subsystems are examined. Sample data comparing normal and iron deficiency anaemic blood are presented to illustrate the potential of this technique.

Sialuria: a second case.

A case of sialuria is described in a girl who presented in the neonatal period with hepatosplenomegaly, and who has moderate developmental delay at the age of 2 years. There was massive urinary excretion of free sialic acid (N-acetylneuraminic acid). The clinical, biochemical and ultramicroscopical features were distinct from those described in Salla disease and in infantile sialic acid storage disorder.