Robot-assisted adaptive training: custom force fields for teaching movement patterns

Based on recent studies of neuro-adaptive control, we tested a new iterative algorithm to generate custom training forces to "trick" subjects into altering their target-directed reaching movements to a prechosen movement as an after-effect of adaptation. The prechosen movement goal, a sinusoidal-shaped path from start to end point, was never explicitly conveyed to the subject. We hypothesized that the adaptation would cause an alteration in the feedforward command that would result in the prechosen movement. Our results showed that when forces were suddenly removed after a training period of 330 movements, trajectories were significantly shifted toward the prechosen movement. However, de-adaptation occurred (i.e., the after-effect "washed out") in the 50-75 movements that followed the removal of the training forces. A second experiment suppressed vision of hand location and found a detectable reduction in the washout of after-effects, suggesting that visual feedback of error critically influences learning. A final experiment demonstrated that after-effects were also present in the neighborhood of training--44% of original directional shift was seen in adjacent, unpracticed movement directions to targets that were 60 degrees different from the targets used for training. These results demonstrate the potential for these methods for teaching motor skills and for neuro-rehabilitation of brain-injured patients. This is a form of "implicit learning," because unlike explicit training methods, subjects learn movements with minimal instructions, no knowledge of, and little attention to the trajectory.     

Systems biology and the molecular circuits of cancer

Proliferative disorders are a major challenge for human health. The understanding of the organization of cell-cycle events is of the utmost importance to devise effective therapeutic strategies for cancer. The awareness that cells and organisms are complex, modular, hierarchical systems and the availability of genome-wide gene expression and protein analyses, should make it feasible to elucidate human diseases in terms of dysfunctions of molecular systems. Here we review evidence in support of a systems model of the cell cycle, in which two sequential growth-sensitive thresholds control entry into S-phase. The putative molecular determinants that set the threshold for entry into S-phase are consistently altered in cancer cells. Such a framework could be useful in guiding both experimental investigation and data analysis by allowing wiring to other relevant cell modules thereby highlighting the differential responses, or lack of response of cancer cells to intra- and extracellular factors. Pharmacological approaches that take advantage of transformation-induced fragility to glucose shortage are discussed. Extension of this hierarchical, modular approach to tumors as a whole holds promise for the development of effective drug discovery approaches and more efficient therapeutic protocols.     

Reproducibility of BOLD localization of interictal activity in patients with focal epilepsy: intrasession and intersession comparisons

Object  

Simultaneous EEG-fMRI recordings allow the identification of haemodynamic changes induced by neuronal activity during ictal or interictal epileptiform events (IEDs). We evaluated the reproducibility of continuous EEG-fMRI (cEEG-fMRI) in patients with focal epilepsy.     

On the robustness and efficiency of integration algorithms for a 3D finite strain phenomenological SMA constitutive model

Most devices based on shape memory alloys experience large rotations and moderate or finite strains. This motivates the development of finite‐strain constitutive models together with the appropriate computational counterparts. To this end, in the present paper a three‐dimensional finite‐strain phenomenological constitutive model is investigated and a robust and efficient integration algorithm is proposed. Properly defining the variables, extensively used regularization schemes are avoided and a nucleation–completion criterion is defined. Moreover, introducing a logarithmic mapping, a new form of time‐discrete equations is proposed. The solution algorithm as well as a suitable initial guess for the resultant nonlinear equations are also deeply discussed. Extensive numerical tests are performed to show robustness as well as efficiency of the proposed integration algorithm. Implementation of the integration algorithm within a user‐defined subroutine UMAT in the commercial nonlinear finite element software ABAQUS/Standard makes also possible the solution of a variety of boundary value problems. The obtained results show the efficiency and robustness of the proposed approach and confirm the improved efficiency (in terms of solution CPU time) when a nucleation–completion criterion is used instead of regularization schemes, as well as when a logarithmic mapping is used for the time‐discrete evolution equation instead of an exponential mapping. Copyright © 2010 John Wiley & Sons, Ltd.     

Design,Synthesis and Evaluation of Novel Molecular Hybrids between Antiglaucoma Drugs and H2S Donors

Glaucoma is a group of eye diseases consisting of optic nerve damage with corresponding loss of field vision and blindness. Hydrogen sulfide (H₂S) is a gaseous neurotransmitter implicated in various pathophysiological processes. It is involved in the pathological mechanism of glaucomatous neuropathy and exerts promising effects in the treatment of this disease. In this work, we designed and synthetized new molecular hybrids between antiglaucoma drugs and H₂S donors to combine the pharmacological effect of both moieties, providing a heightened therapy. Brinzolamide, betaxolol and brimonidine were linked to different H₂S donors. The H₂S-releasing properties of the new compounds were evaluated in a phosphate buffer solution by the amperometric approach, and evaluated in human primary corneal epithelial cells (HCEs) by spectrofluorometric measurements. Experimental data showed that compounds 1c, 1d and 3d were the hybrids with the best properties, characterized by a significant and long-lasting production of the gasotransmitter both in the aqueous solution (in the presence of L-cysteine) and in the intracellular environment. Because, to date, the donation of H₂S by antiglaucoma H₂S donor hybrids using non-immortalized corneal cells has never been reported, these results pave the way to further investigation of the potential efficacy of the newly synthesized compounds.     

Current Knowledge on the Pathophysiology of Lean/Normal-Weight Type 2 Diabetes

Since early times, being overweight and obesity have been associated with impaired glucose metabolism and type 2 diabetes (T2D). Similarly, a less frequent adult-onset diabetes in low body mass index (BMI) people has been known for many decades. This form is mainly found in developing countries, whereby the largest increase in diabetes incidence is expected in coming years. The number of non-obese patients with T2D is also on the rise among non-white ethnic minorities living in high-income Western countries due to growing migratory flows. A great deal of energy has been spent on understanding the mechanisms that bind obesity to T2D. Conversely, the pathophysiologic features and factors driving the risk of T2D development in non-obese people are still much debated. To reduce the global burden of diabetes, we need to understand why not all obese people develop T2D and not all those with T2D are obese. Moreover, through both an effective prevention and the implementation of an individualized clinical management in all people with diabetes, it is hoped that this will help to reduce this global burden. The purpose of this review is to take stock of current knowledge about the pathophysiology of diabetes not associated to obesity and to highlight which aspects are worthy of future studies.     

Micro- and Nanoplastics’ Effects on Protein Folding and Amyloidosis

A significant portion of the world’s plastic is not properly disposed of and, through various processes, is degraded into microscopic particles termed micro- and nanoplastics. Marine and terrestrial faunae, including humans, inevitably get in contact and may inhale and ingest these microscopic plastics which can deposit throughout the body, potentially altering cellular and molecular functions in the nervous and other systems. For instance, at the cellular level, studies in animal models have shown that plastic particles can cross the blood–brain barrier and interact with neurons, and thus affect cognition. At the molecular level, plastics may specifically influence the folding of proteins, induce the formation of aberrant amyloid proteins, and therefore potentially trigger the development of systemic and local amyloidosis. In this review, we discuss the general issue of plastic micro- and nanoparticle generation, with a focus on their effects on protein folding, misfolding, and their possible clinical implications.     

Cross-Batch Contamination in a Continuous Horizontal Decanter Centrifuge during Virgin Olive Oil Production

Cross-batch contamination in a decanter centrifuge during virgin olive oil production cannot be avoided using current technology. The extent of this contamination is investigated using industrial-scale tests, by measuring the volatile profile and color on three consecutive oil batches, collected at the decanter outlet at different extraction times. The extent of contamination varied, pointing out qualitative consequences, as defective molecules are found. The latter are often active at low concentrations, and the measured cross-batch contamination can lead both to the downgrading of large batches of virgin olive oils and to the adulteration of monovarietal and certified productions. An innovative method, based on the direct determination of the color (L and a* coordinates) of oil at the outlet of the decanter is able to identify the same compositional change point indicated by gas chromatography, and could be successfully used to mitigate the effects of cross-batch contamination. Practical applications: An in-line colorimetric system can be implemented at the decanter outlet to detect the point of change between different olive batches. Otherwise, the virgin olive oil exiting from the decanter at the beginning of one batch can be collected separately in order to avoid the contamination due to the previous batch.     

Formation and Etching of the Insulating Sr-Rich V5+ Phase at the Metallic SrVO3 Surface Revealed by Operando XAS Spectroscopy Characterizations

In the search of low cost and more efficient electronic devices, here the properties of SrVO₃ transparent conductor oxide (TCO) thin film are investigated, both visible-range optically transparent and highly conductive, it stands as a promising candidate to substitute the standard indium-tin-oxide (ITO) in applications. Its surface stability under water (both liquid and vapor) and other gaseous atmospheres is especially addressed. Through the use of spectroscopy characterizations, X-ray photoemission and operando X-ray absorption measurements, the formation of a thin Sr-rich V⁵⁺ layer located at the surface of the polycrystalline SrVO₃ film with aging is observed, and for the first time how it can be removed from the surface by solvating in water atmosphere. The surface recovery is associated to an etching process, here spectroscopically characterized in operando conditions, allowing to follow the stoichiometric modification under reaction. Once exposed in oxygen atmosphere, the Sr-rich V⁵⁺ layer forms again. The findings improve the understanding of aging effects in perovskite oxides, allowing for the development of functionalized films in which it is possible to control or to avoid an insulating surface layer. This constitutes an important step towards the large-scale use of V-based TCOs, with possible implementations in oxide-based electronics.