Electrochemically Grown Ultrathin Platinum Nanosheet Electrodes with Ultralow Loadings for Energy-Saving and Industrial-Level Hydrogen Evolution.

Nanostructured catalyst-integrated electrodes with remarkably reduced catalyst loadings, high catalyst utilization and facile fabrication are urgently needed to enable cost-effective, green hydrogen production via proton exchange membrane electrolyzer cells (PEMECs). Herein, benefitting from a thin seeding layer, bottom-up grown ultrathin Pt nanosheets (Pt-NSs) were first deposited on thin Ti substrates for PEMECs via a fast, template- and surfactant-free electrochemical growth process at room temperature, showing highly uniform Pt surface coverage with ultralow loadings and vertically well-aligned nanosheet morphologies. Combined with an anode-only Nafion 117 catalyst-coated membrane (CCM), the Pt-NS electrode with an ultralow loading of 0.015 mgPt cm-2 demonstrates superior cell performance to the commercial CCM (3.0 mgPt cm-2), achieving 99.5% catalyst savings and more than 237-fold higher catalyst utilization. The remarkable performance with high catalyst utilization is mainly due to the vertically well-aligned ultrathin nanosheets with good surface coverage exposing abundant active sites for the electrochemical reaction. Overall, this study not only paves a new way for optimizing the catalyst uniformity and surface coverage with ultralow loadings but also provides new insights into nanostructured electrode design and facile fabrication for highly efficient and low-cost PEMECs and other energy storage/conversion devices.

Excessive Adventitial and Perivascular Vascularisation Correlates with Vascular Inflammation and Intimal Hyperplasia.

Albeit multiple studies demonstrated that vasa vasorum (VV) have a crucial importance in vascular pathology, the informative markers and metrics of vascular inflammation defining the development of intimal hyperplasia (IH) have been vaguely studied. Here, we employed two rat models (balloon injury of the abdominal aorta and the same intervention optionally complemented with intravenous injections of calciprotein particles) and a clinical scenario (arterial and venous conduits for coronary artery bypass graft (CABG) surgery) to investigate the pathophysiological interconnections among VV, myeloperoxidase-positive (MPO+) clusters, and IH. We found that the amounts of VV and MPO+ clusters were strongly correlated; further, MPO+ clusters density was significantly associated with balloon-induced IH and increased at calciprotein particle-provoked endothelial dysfunction. Likewise, number and density of VV correlated with IH in bypass grafts for CABG surgery at the pre-intervention stage and were higher in venous conduits which more frequently suffered from IH as compared with arterial grafts. Collectively, our results underline the pathophysiological importance of excessive VV upon the vascular injury or at the exposure to cardiovascular risk factors, highlight MPO+ clusters as an informative marker of adventitial and perivascular inflammation, and propose another mechanistic explanation of a higher long-term patency of arterial grafts upon the CABG surgery.

Homology between SARS CoV-2 and human proteins.

An extremely high contagiousness of SARS CoV-2 indicates that the virus developed the ability to deceive the innate immune system. The virus could have included in its outer protein domains some motifs that are structurally similar to those that the potential victim's immune system has learned to ignore. The similarity of the primary structures of the viral and human proteins can provoke an autoimmune process. Using an open-access protein database Uniprot, we have compared the SARS CoV-2 proteome with those of other organisms. In the SARS CoV-2 spike (S) protein molecule, we have localized more than two dozen hepta- and octamers homologous to human proteins. They are scattered along the entire length of the S protein molecule, while some of them fuse into sequences of considerable length. Except for one, all these n-mers project from the virus particle and therefore can be involved in providing mimicry and misleading the immune system. All hepta- and octamers of the envelope (E) protein, homologous to human proteins, are located in the viral transmembrane domain and form a 28-mer protein E14-41 VNSVLLFLAFVVFLLVTLAILTALRLCA. The involvement of the protein E in provoking an autoimmune response (after the destruction of the virus particle) seems to be highly likely. Some SARS CoV-2 nonstructural proteins may also be involved in this process, namely ORF3a, ORF7a, ORF7b, ORF8, and ORF9b. It is possible that ORF7b is involved in the dysfunction of olfactory receptors, and the S protein in the dysfunction of taste perception.

Discovering space - Grounding spatial topology and metric regularity in a naive agent's sensorimotor experience.

In line with the sensorimotor contingency theory, we investigate the problem of the perception of space from a fundamental sensorimotor perspective. Despite its pervasive nature in our perception of the world, the origin of the concept of space remains largely mysterious. For example in the context of artificial perception, this issue is usually circumvented by having engineers pre-define the spatial structure of the problem the agent has to face. We here show that the structure of space can be autonomously discovered by a naive agent in the form of sensorimotor regularities, that correspond to so called compensable sensory experiences: these are experiences that can be generated either by the agent or its environment. By detecting such compensable experiences the agent can infer the topological and metric structure of the external space in which its body is moving. We propose a theoretical description of the nature of these regularities and illustrate the approach on a simulated robotic arm equipped with an eye-like sensor, and which interacts with an object. Finally we show how these regularities can be used to build an internal representation of the sensor's external spatial configuration.

Why Early Tactile Speech Aids May Have Failed: No Perceptual Integration of Tactile and Auditory Signals.

Tactile speech aids, though extensively studied in the 1980's and 1990's, never became a commercial success. A hypothesis to explain this failure might be that it is difficult to obtain true perceptual integration of a tactile signal with information from auditory speech: exploitation of tactile cues from a tactile aid might require cognitive effort and so prevent speech understanding at the high rates typical of everyday speech. To test this hypothesis, we attempted to create true perceptual integration of tactile with auditory information in what might be considered the simplest situation encountered by a hearing-impaired listener. We created an auditory continuum between the syllables /BA/ and /VA/, and trained participants to associate /BA/ to one tactile stimulus and /VA/ to another tactile stimulus. After training, we tested if auditory discrimination along the continuum between the two syllables could be biased by incongruent tactile stimulation. We found that such a bias occurred only when the tactile stimulus was above, but not when it was below its previously measured tactile discrimination threshold. Such a pattern is compatible with the idea that the effect is due to a cognitive or decisional strategy, rather than to truly perceptual integration. We therefore ran a further study (Experiment 2), where we created a tactile version of the McGurk effect. We extensively trained two Subjects over 6 days to associate four recorded auditory syllables with four corresponding apparent motion tactile patterns. In a subsequent test, we presented stimulation that was either congruent or incongruent with the learnt association, and asked Subjects to report the syllable they perceived. We found no analog to the McGurk effect, suggesting that the tactile stimulation was not being perceptually integrated with the auditory syllable. These findings strengthen our hypothesis according to which tactile aids failed because integration of tactile cues with auditory speech occurred at a cognitive or decisional level, rather than truly at a perceptual level.

Optimality and stability of intentional and unintentional actions: I. Origins of drifts in performance.

We address the nature of unintentional changes in performance in two papers. This first paper tested a hypothesis that unintentional changes in performance variables during continuous tasks without visual feedback are due to two processes. First, there is a drift of the referent coordinate for the salient performance variable toward the actual coordinate of the effector. Second, there is a drift toward minimum of a cost function. We tested this hypothesis in four-finger isometric pressing tasks that required the accurate production of a combination of total moment and total force with natural and modified finger involvement. Subjects performed accurate force-moment production tasks under visual feedback, and then visual feedback was removed for some or all of the salient variables. Analytical inverse optimization was used to compute a cost function. Without visual feedback, both force and moment drifted slowly toward lower absolute magnitudes. Over 15 s, the force drop could reach 20% of its initial magnitude while moment drop could reach 30% of its initial magnitude. Individual finger forces could show drifts toward both higher and lower forces. The cost function estimated using the analytical inverse optimization reduced its value as a consequence of the drift. We interpret the results within the framework of hierarchical control with referent spatial coordinates for salient variables at each level of the hierarchy combined with synergic control of salient variables. The force drift is discussed as a natural relaxation process toward states with lower potential energy in the physical (physiological) system involved in the task.

Ultrathin Polymer Membranes with Patterned, Micrometric Pores for Organs-on-Chips.

The basal lamina or basement membrane (BM) is a key physiological system that participates in physicochemical signaling between tissue types. Its formation and function are essential in tissue maintenance, growth, angiogenesis, disease progression, and immunology. In vitro models of the BM (e.g., Boyden and transwell chambers) are common in cell biology and lab-on-a-chip devices where cells require apical and basolateral polarization. Extravasation, intravasation, membrane transport of chemokines, cytokines, chemotaxis of cells, and other key functions are routinely studied in these models. The goal of the present study was to integrate a semipermeable ultrathin polymer membrane with precisely positioned pores of 2 µm diameter in a microfluidic device with apical and basolateral chambers. We selected poly(l-lactic acid) (PLLA), a transparent biocompatible polymer, to prepare the semipermeable ultrathin membranes. The pores were generated by pattern transfer using a three-step method coupling femtosecond laser machining, polymer replication, and spin coating. Each step of the fabrication process was characterized by scanning electron microscopy to investigate reliability of the process and fidelity of pattern transfer. In order to evaluate the compatibility of the fabrication method with organs-on-a-chip technology, porous PLLA membranes were embedded in polydimethylsiloxane (PDMS) microfluidic devices and used to grow human umbilical vein endothelial cells (HUVECS) on top of the membrane with perfusion through the basolateral chamber. Viability of cells, optical transparency of membranes and strong adhesion of PLLA to PDMS were observed, thus confirming the suitability of the prepared membranes for use in organs-on-a-chip devices.

Analytical Inverse Optimization in Two-Hand Prehensile Tasks.

The authors explored application of analytical inverse optimization (ANIO) method to the normal finger forces in unimanual and bimanual prehensile tasks with discrete and continuously changing constraints. The subjects held an instrumented handle vertically with one or two hands. The external torque and grip force changed across trials or within a trial continuously. Principal component analysis showed similar percentages of variance accounted for by the first two principal components across tasks and conditions. Compared to unimanual tasks, bimanual tasks showed significantly more frequent inability to find a cost function leading to a stable solution. In cases of stable solutions, similar second-order polynomials were computed as cost functions across tasks and condition. The bimanual tasks, however, showed significantly worse goodness-of-fit index values. The authors show that ANIO can be used in tasks with slowly changing constraints making it an attractive tool to study optimality of performance in special populations. They also show that ANIO can fail in multifinger tasks, likely due to irreproducible behavior across trials, more likely to happen in bimanual tasks compared to unimanual tasks.

The Change in Fingertip Contact Area as a Novel Proprioceptive Cue.

Humans, many animals, and certain robotic hands have deformable fingertip pads [1, 2]. Deformable pads have the advantage of conforming to the objects that are being touched, ensuring a stable grasp for a large range of forces and shapes. Pad deformations change with finger displacements during touch. Pushing a finger against an external surface typically provokes an increase of the gross contact area [3], potentially providing a relative motion cue, a situation comparable to looming in vision [4]. The rate of increase of the area of contact also depends on the compliance of the object [5]. Because objects normally do not suddenly change compliance, participants may interpret an artificially induced variation in compliance, which coincides with a change in the gross contact area, as a change in finger displacement, and consequently they may misestimate their finger's position relative to the touched object. To test this, we asked participants to compare the perceived displacements of their finger while contacting an object varying pseudo-randomly in compliance from trial to trial. Results indicate a bias in the perception of finger displacement induced by the change in compliance, hence in contact area, indicating that participants interpreted the altered cutaneous input as a cue to proprioception. This situation highlights the capacity of the brain to take advantage of knowledge of the mechanical properties of the body and of the external environment.

Patterned polymer matrix promotes stemness and cell-cell interaction of adult stem cells.

BACKGROUND: The interaction of stem cells with their culture substrates is critical in controlling their fate and function. Declining stemness of adult-derived human mesenchymal stem cells (hMSCs) during in vitro expansion on tissue culture polystyrene (TCPS) severely limits their therapeutic efficacy prior to cell transplantation into damaged tissues. Thus, various formats of natural and synthetic materials have been manipulated in attempts to reproduce in vivo matrix environments in which hMSCs reside. RESULTS: We developed a series of patterned polymer matrices for cell culture by hot-pressing poly(ε-caprolactone) (PCL) films in femtosecond laser-ablated nanopore molds, forming nanofibers on flat PCL substrates. hMSCs cultured on these PCL fiber matrices significantly increased expression of critical self-renewal factors, Nanog and OCT4A, as well as markers of cell-cell interaction PECAM and ITGA2. The results suggest the patterned polymer fiber matrix is a promising model to maintain the stemness of adult hMSCs. CONCLUSION: This approach meets the need for scalable, highly repeatable, and tuneable models that mimic extracellular matrix features that signal for maintenance of hMSC stemness.

The brain uses extrasomatic information to estimate limb displacement.

A fundamental problem faced by the brain is to estimate whether a touched object is rigidly attached to a ground reference or is movable. A simple solution to this problem would be for the brain to test whether pushing on the object with a limb is accompanied by limb displacement. The mere act of pushing excites large populations of mechanoreceptors, generating a sensory response that is only weakly sensitive to limb displacement if the movements are small, and thus can hardly be used to determine the mobility of the object. In the mechanical world, displacement or deformation of objects frequently co-occurs with microscopic fluctuations associated with the frictional sliding of surfaces in contact or with micro-failures inside an object. In this study,we provide compelling evidence that the brain relies on these microscopic mechanical events to estimate the displacement of the limb in contact with an object, and hence the mobility of the touched object. We show that when pressing with a finger on a stiff surface, fluctuations that resemble the mechanical response of granular solids provoke a sensation of limb displacement. Our findings suggest that when acting on an external object, prior knowledge about the sensory consequences of interacting with the object contributes to proprioception.

Segregation of tactile input features in neurons of the cuneate nucleus.

Our tactile perception of external objects depends on skin-object interactions. The mechanics of contact dictates the existence of fundamental spatiotemporal input features-contact initiation and cessation, slip, and rolling contact-that originate from the fact that solid objects do not interpenetrate. However, it is unknown whether these features are represented within the brain. We used a novel haptic interface to deliver such inputs to the glabrous skin of finger/digit pads and recorded from neurons of the cuneate nucleus (the brain's first level of tactile processing) in the cat. Surprisingly, despite having similar receptive fields and response properties, each cuneate neuron responded to a unique combination of these inputs. Hence, distinct haptic input features are encoded already at subcortical processing stages. This organization maps skin-object interactions into rich representations provided to higher cortical levels and may call for a re-evaluation of our current understanding of the brain's somatosensory systems.

Spatio-temporal skin strain distributions evoke low variability spike responses in cuneate neurons.

A common method to explore the somatosensory function of the brain is to relate skin stimuli to neurophysiological recordings. However, interaction with the skin involves complex mechanical effects. Variability in mechanically induced spike responses is likely to be due in part to mechanical variability of the transformation of stimuli into spiking patterns in the primary sensors located in the skin. This source of variability greatly hampers detailed investigations of the response of the brain to different types of mechanical stimuli. A novel stimulation technique designed to minimize the uncertainty in the strain distributions induced in the skin was applied to evoke responses in single neurons in the cat. We show that exposure to specific spatio-temporal stimuli induced highly reproducible spike responses in the cells of the cuneate nucleus, which represents the first stage of integration of peripheral inputs to the brain. Using precisely controlled spatio-temporal stimuli, we also show that cuneate neurons, as a whole, were selectively sensitive to the spatial and to the temporal aspects of the stimuli. We conclude that the present skin stimulation technique based on localized differential tractions greatly reduces response variability that is exogenous to the information processing of the brain and hence paves the way for substantially more detailed investigations of the brain's somatosensory system.

A microfluidic-enabled mechanical microcompressor for the immobilization of live single- and multi-cellular specimens.

A microcompressor is a precision mechanical device that flattens and immobilizes living cells and small organisms for optical microscopy, allowing enhanced visualization of sub-cellular structures and organelles. We have developed an easily fabricated device, which can be equipped with microfluidics, permitting the addition of media or chemicals during observation. This device can be used on both upright and inverted microscopes. The apparatus permits micrometer precision flattening for nondestructive immobilization of specimens as small as a bacterium, while also accommodating larger specimens, such as Caenorhabditis elegans, for long-term observations. The compressor mount is removable and allows easy specimen addition and recovery for later observation. Several customized specimen beds can be incorporated into the base. To demonstrate the capabilities of the device, we have imaged numerous cellular events in several protozoan species, in yeast cells, and in Drosophila melanogaster embryos. We have been able to document previously unreported events, and also perform photobleaching experiments, in conjugating Tetrahymena thermophila.

Optimization and variability of motor behavior in multifinger tasks: what variables does the brain use?

The neural control of movement has been described using different sets of elemental variables. Two possible sets of elemental variables have been suggested for finger pressing tasks: the forces of individual fingers and the finger commands (also called finger modes or central commands). The authors analyzed which of the 2 sets of the elemental variables is more likely used in the optimization of the finger force sharing and which set is used for the stabilization of performance. They used two recently developed techniques-the analytical inverse optimization (ANIO) and the uncontrolled manifold (UCM) analysis-to evaluate each set of elemental variables with respect to both aspects of performance. The results of the UCM analysis favored the finger commands as the elemental variables used for performance stabilization, while ANIO worked equally well on both sets of elemental variables. A simple scheme is suggested as to how the CNS could optimize a cost function dependent on the finger forces, but for the sake of facilitation of the feed forward control it substitutes the original cost function by a cost function, which is convenient to optimize in the space of finger commands.

Comparison of interfinger connection matrix computation techniques.

A hypothesis was proposed that the central nervous system controls force production by the fingers through hypothetical neural commands. The neural commands are scaled between values of 0 to 1, indicating no intentional force production or maximal voluntary contraction (MVC) force production, respectively. A matrix of interfinger connections transforms neural commands into finger forces. Two methods have been proposed to compute the interfinger connection matrix. The first method uses only single finger MVC trials and multiplies the interfinger connection matrix by a gain factor. The second method uses a neural network model based on experimental data. The performance of the two methods was compared on the MVC data and on a data set of submaximal forces, collected over a range of total forces and moments of force. The methods were compared in terms of (1) ability to predict finger forces, (2) accuracy of neural command reconstruction, and (3) preserved planarity of force data for submaximal force production task. Both methods did a reasonable job of predicting the total force in multifinger MVC trials; however, the neural network model performed better in regards to all other criteria. Overall, the results indicate that for modeling multifinger interaction the neural network method is preferable.

On-chip open microfluidic devices for chemotaxis studies.

Microfluidic devices can provide unique control over both the chemoattractant gradient and the migration environment of the cells. Our work incorporates laser-machined micro and nanofluidic channels into bulk fused silica and cover slip-sized silica wafers. We have designed "open" chemotaxis devices that produce passive chemoattractant gradients without an external micropipette system. Since the migration area is unobstructed, cells can be easily loaded and strategically placed into the devices with a standard micropipette. The reusable monolithic glass devices have integral ports that can generate multiple gradients in a single experiment. We also used cover slip microfluidics for chemotaxis assays. Passive gradients elicited from these cover slips could be readily adapted for high throughput chemotaxis assays.We have also demonstrated for the first time that cells can be recruited into cover slip ports eliciting passive chemoattractant gradients. This proves, in principle, that intravital cover slip configurations could deliver controlled amounts of drugs, chemicals, or pathogens as well as recruit cells for proteomic or histological analysis in living animals while under microscopic observation. Intravital cover slip fluidics will create a new paradigm for in vivo observation of biological processes.

Silica coating of polymer nanowires produced via nanoimprint lithography from femtosecond laser machined templates.

In this paper we report on the fabrication of regular arrays of silica nanoneedles by deposition of a thin layer of silica on patterned arrays of polymer nanowires (or polymer nanohair). An array of high-aspect-ratio nanoscale diameter holes of depths greater than 10 µm was produced at the surface of a fused silica wafer by an amplified femtosecond laser system operated in single-pulse mode. Cellulose acetate (CA) film was imprinted into the nanoholes and peeled off to form a patterned array of standing CA nanowires, a negative replica of the laser machined nanoholes. The cellulose acetate replica was then coated with silica in a chemical vapor deposition process using silicon tetrachloride vapor at 65 °C. Field emission scanning electron microscopy, focused ion beam sectioning, energy dispersive x-ray analysis and Fourier-transform infrared spectroscopy were used to characterize the silica nanoneedles. Precisely patterned, functionalized arrays of standing silica nanoneedles are useful for a number of applications.

Reconstruction of the unknown optimization cost functions from experimental recordings during static multi-finger prehension.

The goal of the research is to reconstruct the unknown cost (objective) function(s) presumably used by the neural controller for sharing the total force among individual fingers in multifinger prehension. The cost function was determined from experimental data by applying the recently developed Analytical Inverse Optimization (ANIO) method (Terekhov et al. 2010). The core of the ANIO method is the Theorem of Uniqueness that specifies conditions for unique (with some restrictions) estimation of the objective functions. In the experiment, subjects (n = 8) grasped an instrumented handle and maintained it at rest in the air with various external torques, loads, and target grasping forces applied to the object. The experimental data recorded from 80 trials showed a tendency to lie on a 2-dimensional hyperplane in the 4-dimensional finger-force space. Because the constraints in each trial were different, such a propensity is a manifestation of a neural mechanism (not the task mechanics). In agreement with the Lagrange principle for the inverse optimization, the plane of experimental observations was close to the plane resulting from the direct optimization. The latter plane was determined using the ANIO method. The unknown cost function was reconstructed successfully for each performer, as well as for the group data. The cost functions were found to be quadratic with nonzero linear terms. The cost functions obtained with the ANIO method yielded more accurate results than other optimization methods. The ANIO method has an evident potential for addressing the problem of optimization in motor control.

Minimal adhesion surface area in tangentially loaded digital contacts.

The stick-to-slip transition of a fingertip in contact with a planar surface does not occur instantaneously. As the tangential load increases, portions of the skin adhere while others slip, giving rise to an evolution of the contact state, termed partial slip. We develop a quasi-static model that predicts that if the coefficient of kinetic friction is larger than the coefficient of static friction, then the stuck surface area diminishes as the tangential load increases until reaching a 'minimal adhesion surface area' where it vanishes abruptly. This phenomenon was observed in recently measured finger-slip image data (André et al., 2011) that were processed by an optic flow detection algorithm. We examined the results of 10 trials. Four of them exhibited the minimal adhesion surface area phenomenon, four of them did not, and two were inconclusive.