The Language of Social Touch Is Intuitive and Quantifiable.

Touch is a powerful communication tool, but we have a limited understanding of the role played by particular physical features of interpersonal touch communication. In this study, adults living in Sweden performed a task in which messages (attention, love, happiness, calming, sadness, and gratitude) were conveyed by a sender touching the forearm of a receiver, who interpreted the messages. Two experiments (N = 32, N = 20) showed that within close relationships, receivers could identify the intuitive touch expressions of the senders, and we characterized the physical features of the touches associated with successful communication. Facial expressions measured with electromyography varied by message but were uncorrelated with communication performance. We developed standardized touch expressions and quantified the physical features with 3D hand tracking. In two further experiments (N = 20, N = 16), these standardized expressions were conveyed by trained senders and were readily understood by strangers unacquainted with the senders. Thus, the possibility emerges of a standardized, intuitively understood language of social touch.

Distinction of self-produced touch and social touch at cortical and spinal cord levels.

Differentiation between self-produced tactile stimuli and touch by others is necessary for social interactions and for a coherent concept of "self." The mechanisms underlying this distinction are unknown. Here, we investigated the distinction between self- and other-produced light touch in healthy volunteers using three different approaches: fMRI, behavioral testing, and somatosensory-evoked potentials (SEPs) at spinal and cortical levels. Using fMRI, we found self-other differentiation in somatosensory and sociocognitive areas. Other-touch was related to activation in several areas, including somatosensory cortex, insula, superior temporal gyrus, supramarginal gyrus, striatum, amygdala, cerebellum, and prefrontal cortex. During self-touch, we instead found deactivation in insula, anterior cingulate cortex, superior temporal gyrus, amygdala, parahippocampal gyrus, and prefrontal areas. Deactivation extended into brain areas encoding low-level sensory representations, including thalamus and brainstem. These findings were replicated in a second cohort. During self-touch, the sensorimotor cortex was functionally connected to the insula, and the threshold for detection of an additional tactile stimulus was elevated. Differential encoding of self- vs. other-touch during fMRI correlated with the individual self-concept strength. In SEP, cortical amplitudes were reduced during self-touch, while latencies at cortical and spinal levels were faster for other-touch. We thus demonstrated a robust self-other distinction in brain areas related to somatosensory, social cognitive, and interoceptive processing. Signs of this distinction were evident at the spinal cord. Our results provide a framework for future studies in autism, schizophrenia, and emotionally unstable personality disorder, conditions where symptoms include social touch avoidance and poor self-vs.-other discrimination.

Faster Indentation Influences Skin Deformation To Reduce Tactile Discriminability of Compliant Objects.

To discriminate the compliance of soft objects, we rely upon spatiotemporal cues in the mechanical deformation of the skin. However, we have few direct observations of skin deformation over time, in particular how its response differs with indentation velocities and depths, and thereby helps inform our perceptual judgments. To help fill this gap, we develop a 3D stereo imaging method to observe contact of the skin's surface with transparent, compliant stimuli. Experiments with human-subjects, in passive touch, are conducted with stimuli varying in compliance, indentation depth, velocity, and time duration. The results indicate that contact durations greater than 0.4 s are perceptually discriminable. Moreover, compliant pairs delivered at higher velocities are more difficult to discriminate because they induce smaller differences in deformation. In a detailed quantification of the skin's surface deformation, we find that several, independent cues aid perception. In particular, the rate of change of gross contact area best correlates with discriminability, across indentation velocities and compliances. However, cues associated with skin surface curvature and bulk force are also predictive, for stimuli more and less compliant than skin, respectively. These findings and detailed measurements seek to inform the design of haptic interfaces.

Predictive modeling for assessing the long-term thermal stability of a new fully-liquid quadrivalent meningococcal tetanus toxoid conjugated vaccine.

Establishing product stability is critical for pharmaceuticals. We used a modeling approach to predict the thermal stability of a fully-liquid quadrivalent meningococcal (serogroups A, C, W, Y) conjugate vaccine (MenACYW-TT; MenQuadfi®) at potential transportation and storage temperatures. Vaccine degradation was determined by measuring the rate of hydrolysis through an increase of free polysaccharide (de-conjugated or unconjugated polysaccharide) content during six months storage at 25 °C, 45 °C and 56 °C. A procedure combining advanced kinetics and statistics was used to screen and compare kinetic models describing observed free polysaccharide increase as a function of time and temperature for each serogroup. Statistical analyses were used to quantify prediction accuracy. A two-step kinetic model described the increase in free polysaccharide content for serogroup A; whereas, one-step kinetic models were found suitable to describe the other serogroups. The models were used to predict free polysaccharide increases for each serogroup during long-term storage under recommended conditions (2-8 °C), and during temperature excursions to 25 °C or 40 °C. In both cases, serogroup-specific simulations accurately predict the respective observed experimental data. Experimental data collected to 48 months at 5 °C were within 99% predictive bands. The models described here can be used with confidence to establish shelf-life for this fully-liquid quadrivalent meningococcal conjugate vaccine; as well as, monitor in real-time free polysaccharide increase for vaccines experiencing temperature excursions during shipment/storage.

Identifying 3-D spatiotemporal skin deformation cues evoked in interacting with compliant elastic surfaces.

We regularly touch soft, compliant fruits and tissues. To help us discriminate them, we rely upon cues embedded in spatial and temporal deformation of finger pad skin. However, we do not yet understand, in touching objects of various compliance, how such patterns evolve over time, and drive perception. Using a 3-D stereo imaging technique in passive touch, we develop metrics for quantifying skin deformation, across compliance, displacement, and time. The metrics map 2-D estimates of terminal contact area to 3-D metrics that represent spatial and temporal changes in penetration depth, surface curvature, and force. To do this, clouds of thousands of 3-D points are reduced in dimensionality into stacks of ellipses, to be more readily comparable between participants and trials. To evaluate the robustness of the derived 3-D metrics, human subjects experiments are performed with stimulus pairs varying in compliance and discriminability. The results indicate that metrics such as penetration depth and surface curvature can distinguish compliances earlier, at less displacement. Observed also are distinct modes of skin deformation, for contact with stiffer objects, versus softer objects that approach the skin's compliance. These observations of the skin's deformation may guide the design and control of haptic actuation.

Tactile Exploration Strategies With Natural Compliant Objects Elicit Virtual Stiffness Cues.

When interacting with deformable objects, tactile cues at the finger pad help inform our perception of material compliance. Nearly all prior studies have relied on highly homogenous, engineered materials such as silicone-elastomers and foams. In contrast, we employ soft plum fruit varying in ripeness; ecological substances associated with tasks of everyday life. In this article, we investigate volitional exploratory strategies and contact interactions, for comparison to engineered materials. New measurement techniques are introduced, including an ink-based method to capture finger pad to fruit contact interactions, and instrumented force and optical sensors to capture imposed force and displacement. Human-subjects experiments are conducted for both single finger touch and two finger grasp. The results indicate that terminal contact areas between soft and hard plums are indistinguishable, but the newly defined metric of virtual stiffness can differentiate between the fruits' ripeness, amidst their local variations in geometry, stiffness, and viscoelasticity. Moreover, it affords discrimination independent of one's touch force. This metric illustrates the tie between the deployment of active, exploratory strategies and the elicitation of optimal cues for perceptual discrimination. Compared to single finger touch, perceptual discrimination improves further in pinch grasp, which is indeed a more natural gesture for judging ripeness.

Roles of Force Cues and Proprioceptive Joint Angles in Active Exploration of Compliant Objects.

We employ distinct exploratory procedures to improve our perceptual judgments of an object's properties. For instance, with respect to compliance, we exert pressure against a resisting force. The present work investigates ties between strategies for active control of the finger and resultant cues by which compliances may be discriminated. In particular, we employ elastic spheres that co-vary in compliance and radius, as these generate non-differentiable contact areas and are discriminable only in active touch with proprioceptive inputs. During human-subjects psychophysical experiments, we measure touch force, fingertip displacement, and joint kinematics. Two active touch paradigms are used, with and without a force constraint. First, in behaviorally-controlled situations that make force cues non-useful, the results indicate that participants can employ a force-matching strategy between the compliant objects and rely upon displacement-related cues to differentiate them. We show these cues are directly tied to a proprioception mechanism, specifically, the angle of the MCP joint. However, in the fully active paradigm, participants control displacements instead and discriminate via force-related cues. Similar to prior findings in passive touch, we find that force-related cues, likewise, are used in active touch for the optimal and efficient discrimination of compliant objects.

Uncovering Human-to-Human Physical Interactions that Underlie Emotional and Affective Touch Communication.

Couples often communicate their emotions, e.g., love or sadness, through physical expressions of touch. Prior efforts have used visual observation to distinguish emotional touch communications by certain gestures tied to one's hand contact, velocity and position. The work herein describes an automated approach to eliciting the essential features of these gestures. First, a tracking system records the timing and location of contact interactions in 3-D between a toucher's hand and a receiver's forearm. Second, data post-processing algorithms extract dependent measures, derived from prior visual observation, tied to the intensity and velocity of the toucher's hand, as well as areas, durations and parts of the hand in contact. Third, behavioral data were obtained from five couples who sought to convey a variety of emotional word cues. We found that certain combinations of six dependent measures well distinguish the touch communications. For example, a typical sadness expression invokes more contact, evolves more slowly, and impresses less deeply into the forearm than a typical attention expression. Furthermore, cluster analysis indicates 2-5 distinct expression strategies are common per word being communicated. Specifying the essential features of touch communications can guide haptic devices in reproducing naturalistic interactions.

Force-Rate Cues Reduce Object Deformation Necessary to Discriminate Compliances Harder than the Skin.

Grasping and manipulating an object requires us to perceive its material compliance. Compliance is thought to be encoded by relationships of force, displacement, and contact area at the finger pad. Prior work suggests that objects must be sufficiently deformed to become discriminable, but the utility of time-dependent cues has not been fully explored. The studies herein find that the availability of force-rate cues improve compliance discriminability so as to require less deformation of stimulus and finger pad. In particular, we tested the impact of controlling force-rate and displacement-rate cues in passive touch psychophysical experiments. An ink-based method to mark the finger pad was used to measure contact area per stimulus, simultaneously with displacement and force. Compliances spanned a range harder and softer than the finger pad. The results indicated harder compliances were discriminable at lower peak forces when the stimulus control mode was displacement-rate (0.5 N) compared to force-rate (1.3 N). That is, when displacement-rate was controlled to be equal between the two compliances, the resultant force-rate psychophysical cues could be more readily discriminated. In extending prior studies, while some magnitude of finger pad deformation may be sufficient for discriminability, temporal cues tied to force afford more efficient judgments.

Imaging the 3-D Deformation of the Finger Pad When Interacting with Compliant Materials.

We need to understand the physics of how the skin of the finger pad deforms, and their tie to perception, to accurately reproduce a sense of compliance, or 'softness,' in tactile displays. Contact interactions with compliant materials are distinct from those with rigid surfaces where the skin flattens completely. To capture unique patterns in skin deformation over a range of compliances, we developed a stereo imaging technique to visualize the skin through optically clear stimuli. Accompanying algorithms serve to locate and track points marked with ink on the skin, correct for light refraction through stimuli, and estimate aspects of contact between skin and stimulus surfaces. The method achieves a 3-D spatial resolution of 60-120 microns and temporal resolution of 30 frames per second. With human subjects, we measured the skin's deformation over a range of compliances (61-266 kPa), displacements (0-4 mm), and velocities (1- 15 mm/s). The results indicate that the method can differentiate patterns of skin deformation between compliances, as defined by metrics including surface penetration depth, retention of geometric shape, and force per gross contact area. Observations of biomechanical cues of this sort are key to understanding the perceptual encoding of compliance.

In the Tactile Discrimination of Compliance, Perceptual Cues in Addition to Contact Area Are Required.

In our ability to discriminate compliant, or 'soft,' objects, we rely upon information acquired from interactions at the finger pad. We have yet to resolve the most pertinent perceptual cues. However, doing so is vital for building effective, dynamic displays. By introducing psychophysical illusions through spheres of various size and elasticity, we investigate the utility of contact area cues, thought to be key in encoding compliance. For both active and passive touch, we determine finger pad-to-stimulus contact areas, using an ink-based procedure, as well as discrimination thresholds. The findings indicate that in passive touch, participants cannot discriminate certain small compliant versus large stiff spheres, which generate similar contact areas. In active touch, however, participants easily discriminate these spheres, though contact areas remain similar. Supplementary cues based on stimulus rate and/or proprioception seem vital. One cue that does differ for illusion cases is finger displacement given a volitionally applied force.

A Standard Methodology to Characterize the Intrinsic Material Properties of Compliant Test Stimuli.

Understanding how we perceive differences in material compliance, or 'softness,' is a central topic in the field of haptics. The intrinsic elasticity of an object is the primary factor thought to influence our perceptual estimates. Therefore, most studies test and report the elasticity of their stimuli, typically as stiffness or modulus. However, many reported estimates are of very high magnitude for silicone-elastomers, which may be due to artifacts in characterization technique. This makes it very difficult to compare the perceptual results between the studies. The work herein defines a standardized and easy-to-implement way to characterize test stimuli. The procedure involves the unconstrained, uniaxial compression of a plate into cylindrical substrates 10 mm tall by 10 mm diameter. The resultant force-displacement data are straightforwardly converted into stress-strain data, from which a modulus is readily derived. This procedure was used to re-characterize stimuli from prior studies. The revised results from the validated method herein are 200-1,100 percent lower than modulus values either reported and/or approximated from stiffness. This is practically significant when differences of 10-15 percent are perceptually discriminable. The re-characterized estimates are useful in comparing prior studies and designing new studies. Furthermore, this characterization methodology may help more readily bridge studies on perception with those designing technology.

A highly efficient chemoenzymatic approach toward glycoprotein synthesis.

[reaction: see text] A highly efficient endoglycosidase-catalyzed synthesis of homogeneous glycoproteins is described. By using ribonuclease B as a model system, it was demonstrated that Endo-A could efficiently attach a preassembled oligosaccharide to a GlcNAc-containing protein in a regio- and stereospecific manner, when the corresponding sugar oxazoline was used as the donor substrate. The method allows the synthesis of both natural and tailor-made N-linked glycoproteins in excellent yield.

Measuring tactile cues at the fingerpad for object compliances harder and softer than the skin.

Distinguishing an object's compliance, into percepts of "softness" and "hardness," is crucial to our ability to grasp and manipulate it. Biomechanical cues at the skin's surface such as contact area and force rate have been thought to help encode compliance. However, no one has directly measured contact area with compliant materials, and few studies have considered compliances softer than the fingerpad. Herein, we developed a novel method to precisely measure the area in contact between compliant stimuli and the fingerpad, at given levels of force and displacement. To determine the method's robustness, we conducted psychophysical and biomechanical experiments with human subjects. The results indicate that cues including contact area at stimulus peak force of 3 Newtons, force rate over stimulus movement and at peak force, displacement and/or time to reach peak force may help in discriminating compliances while the directional spread of contact area is less important. Between softer and harder compliances, some cues were slightly more evident, though not yet definitively. Based upon the method's utility, the next step is to conduct broader experiments to distill the mixture of cues that encode compliance. The importance of such work lies in building haptic displays, for example, to render virtual tissues.

Glycopeptide synthesis through endo-glycosidase-catalyzed oligosaccharide transfer of sugar oxazolines: probing substrate structural requirement.

An array of sugar oxazolines was synthesized and tested as donor substrates for the Arthrobacter endo-beta-N-acetylglucosaminidase (Endo-A)-catalyzed glycopeptide synthesis. The experiments revealed that the minimum structure of the donor substrate required for Endo-A catalyzed transglycosylation is a Man beta1-->4-GlcNAc oxazoline moiety. Replacement of the beta-D-Man moiety with beta-D-Glc, beta-D-Gal, and beta-D-GlcNAc monosaccharides resulted in the loss of substrate activity for the disaccharide oxazoline. Despite this, the enzyme could tolerate modifications such as attachment of additional sugar residues or a functional group at the 3- and/or 6-positions of the beta-D-Man moiety, thus allowing a successful transfer of selectively modified oligosaccharides to the peptide acceptor. On the other hand, the enzyme has a great flexibility for the acceptor portion and could take both small and large GlcNAc-peptides as the acceptor. The studies implicate a great potential of the endoglycosidase-catalyzed transglycosylation for constructing both natural and selectively modified glycopeptides.

A novel fluorescence-based assay for the transglycosylation activity of endo-beta-N-acetylglucosaminidases.

A fluorescence-based assay for the transglycosylation activity of endo-beta-N-acetylglucosaminidases (ENGases) was developed. The assay was based on the findings that a coupled chitinase can specifically capture and hydrolyze the fluorogenic intermediate that is formed by the ENGase-catalyzed transglycosylation to release a fluorophore, but does not hydrolyze the donor asparagine-linked N-glycan and the acceptor 4-methylumbelliferyl N-acetylglucosaminide. The assay method was verified by detecting the transglycosylation activities of the known ENGases. Its application for assessing the effects of organic solvents on transglycosylation activity was demonstrated. The novel coupled assay provides a highly sensitive, easy, and quantitative method for screening endo-beta-N-acetylglucosaminidases with transglycosylation activities useful for glycoconjugate synthesis.

Highly efficient endoglycosidase-catalyzed synthesis of glycopeptides using oligosaccharide oxazolines as donor substrates.

A highly efficient chemoenzymatic synthesis of N-glycopeptides was achieved. It was found that using synthetic oligosaccharide oxazolines, the mimics of the presumed oxazolinium ion intermediate formed in a retaining mechanism of substrate-assisted catalysis, as the donor substrates and GlcNAc-peptides as the acceptors, the endo-beta-N-acetylglucosaminidase (ENGase)-catalyzed transglycosylation gave a high yield (73-82%) of the corresponding glycopeptides in a regio- and stereospecific manner, regardless of the size of the peptide portions. The use of the oligosaccharide oxazolines as donor substrates not only expanded the substrate availability but also led to a substantial enhancement of the synthetic efficiency, compared to the use of natural N-glycans.