Showing papers by "Istituto Italiano di Tecnologia published in 2011"

The Physiology, Signaling, and Pharmacology of Dopamine Receptors

Abstract: G protein-coupled dopamine receptors (D1, D2, D3, D4, and D5) mediate all of the physiological functions of the catecholaminergic neurotransmitter dopamine, ranging from voluntary movement and reward to hormonal regulation and hypertension. Pharmacological agents targeting dopaminergic neurotransmission have been clinically used in the management of several neurological and psychiatric disorders, including Parkinson's disease, schizophrenia, bipolar disorder, Huntington's disease, attention deficit hyperactivity disorder (ADHD(1)), and Tourette's syndrome. Numerous advances have occurred in understanding the general structural, biochemical, and functional properties of dopamine receptors that have led to the development of multiple pharmacologically active compounds that directly target dopamine receptors, such as antiparkinson drugs and antipsychotics. Recent progress in understanding the complex biology of dopamine receptor-related signal transduction mechanisms has revealed that, in addition to their primary action on cAMP-mediated signaling, dopamine receptors can act through diverse signaling mechanisms that involve alternative G protein coupling or through G protein-independent mechanisms via interactions with ion channels or proteins that are characteristically implicated in receptor desensitization, such as β-arrestins. One of the future directions in managing dopamine-related pathologic conditions may involve a transition from the approaches that directly affect receptor function to a precise targeting of postreceptor intracellular signaling modalities either directly or through ligand-biased signaling pharmacology. In this comprehensive review, we discuss dopamine receptor classification, their basic structural and genetic organization, their distribution and functions in the brain and the periphery, and their regulation and signal transduction mechanisms. In addition, we discuss the abnormalities of dopamine receptor expression, function, and signaling that are documented in human disorders and the current pharmacology and emerging trends in the development of novel therapeutic agents that act at dopamine receptors and/or on related signaling events.

Direct generation of functional dopaminergic neurons from mouse and human fibroblasts

Abstract: Transplantation of dopaminergic neurons can potentially improve the clinical outcome of Parkinson's disease, a neurological disorder resulting from degeneration of mesencephalic dopaminergic neurons. In particular, transplantation of embryonic-stem-cell-derived dopaminergic neurons has been shown to be efficient in restoring motor symptoms in conditions of dopamine deficiency. However, the use of pluripotent-derived cells might lead to the development of tumours if not properly controlled. Here we identified a minimal set of three transcription factors--Mash1 (also known as Ascl1), Nurr1 (also known as Nr4a2) and Lmx1a--that are able to generate directly functional dopaminergic neurons from mouse and human fibroblasts without reverting to a progenitor cell stage. Induced dopaminergic (iDA) cells release dopamine and show spontaneous electrical activity organized in regular spikes consistent with the pacemaker activity featured by brain dopaminergic neurons. The three factors were able to elicit dopaminergic neuronal conversion in prenatal and adult fibroblasts from healthy donors and Parkinson's disease patients. Direct generation of iDA cells from somatic cells might have significant implications for understanding critical processes for neuronal development, in vitro disease modelling and cell replacement therapies.

Custom Pictorial Structures for Re-identification

Abstract: We propose a novel methodology for re-identification, based on Pictorial Structures (PS). Whenever face or other biometric information is missing, humans recognize an individual by selectively focusing on the body parts, looking for part-to-part correspondences. We want to take inspiration from this strategy in a re-identification context, using PS to achieve this objective. For single image re-identification, we adopt PS to localize the parts, extract and match their descriptors. When multiple images of a single individual are available, we propose a new algorithm to customize the fit of PS on that specific person, leading to what we call a Custom Pictorial Structure (CPS). CPS learns the appearance of an individual, improving the localization of its parts, thus obtaining more reliable visual characteristics for re-identification. It is based on the statistical learning of pixel attributes collected through spatio-temporal reasoning. The use of PS and CPS leads to state-of-the-art results on all the available public benchmarks, and opens a fresh new direction for research on re-identification.

Breaking the diffusion limit with super-hydrophobic delivery of molecules to plasmonic nanofocusing SERS structures

Abstract: Surface-enhanced Raman sensors often rely on random chance for molecules to come near optical hotspots. Here, researchers use super-hydrophobic artificial surfaces and evaporation to direct molecules to plasmonic light-focusing structures. Molecules can be localized and detected even at attomolar concentrations.

Design of HyQ – a hydraulically and electrically actuated quadruped robot:

Abstract: A new versatile hydraulically powered quadruped robot (HyQ) has been developed to serve as a platform to study not only highly dynamic motions, such as running and jumping, but also careful navigat...

Reversible Tunability of the Near-Infrared Valence Band Plasmon Resonance in Cu2–xSe Nanocrystals

Abstract: We demonstrate that colloidal Cu2–xSe nanocrystals exhibit a well-defined infrared absorption band due to the excitation of positive charge carrier oscillations (i.e., a valence band plasmon mode), which can be tuned reversibly in width and position by varying the copper stoichiometry. The value of x could be incrementally varied from 0 (no plasmon absorption, then a broad peak at 1700 nm) to 0.4 (narrow plasmon band at 1100 nm) by oxidizing Cu2Se nanocrystals (upon exposure either to oxygen or to a Ce(IV) complex), and it could be incrementally restored back to zero by the addition of a Cu(I) complex. The experimentally observed plasmonic behavior is in good agreement with calculations based on the electrostatic approximation.

Hierarchical self-assembly of suspended branched colloidal nanocrystals into superlattice structures

Abstract: Self-assembly of molecular units into complex and functional superstructures is ubiquitous in biology. The number of superstructures realized by self-assembly of man-made nanoscale units is also growing. However, assemblies of colloidal inorganic nanocrystals 1‐3 are still at an elementary level, not only because of the simplicity of the shape of the nanocrystal building blocks and their interactions, but also because of the poor control over these parameters in the fabrication of more elaborate nanocrystals. Here, we show how monodisperse colloidal octapod-shaped nanocrystals self-assemble, in a suitable solution environment, on two sequential levels. First, linear chains of interlocked octapods are formed, and subsequently the chains spontaneously self-assemble into threedimensional superstructures. Remarkably, all the instructions for the hierarchical self-assembly are encoded in the octapod shape. The mechanical strength of these superstructures is improvedbyweldingtheconstituentnanocrystalstogether. The organization of colloidal nanocrystals into ordered structures is a necessary step towards the fabrication of artificial solids and new devices. Superstructures can be built either by self-assembly directly in solution, or on a substrate following solvent evaporation or de-wetting 4 6 . A variety of forces can be involved in their formation: van der Waals (vdW) attractions between the particles, steric repulsions between the hydrophobic tails of the surfactants (often coating the nanocrystal surface), capillary forces during solvent evaporation, attractive depletion forces, Coulomb forces between surface charges or electric dipoles, and magnetic forces 1,3,5,7 12 . The assembly of many ordered threedimensional (3D) superstructures, for example, simple, binary, or ternary assemblies of spherical nanoparticles 13 17 , and smectic-like multilayers of hexagonally packed nanorods 18 , as well as liquid crystalline phases, is found to be solely driven by entropy 19 21 . More elaborate assemblies could be achieved from such simple building blocks by encoding information for the self-assembly in the surface pattern of the nanoparticles, for instance by DNA functionalization to modify the strength and directionality of particleparticle

An octopus-bioinspired solution to movement and manipulation for soft robots.

Abstract: Soft robotics is a challenging and promising branch of robotics. It can drive significant improvements across various fields of traditional robotics, and contribute solutions to basic problems such as locomotion and manipulation in unstructured environments. A challenging task for soft robotics is to build and control soft robots able to exert effective forces. In recent years, biology has inspired several solutions to such complex problems. This study aims at investigating the smart solution that the Octopus vulgaris adopts to perform a crawling movement, with the same limbs used for grasping and manipulation. An ad hoc robot was designed and built taking as a reference a biological hypothesis on crawling. A silicone arm with cables embedded to replicate the functionality of the arm muscles of the octopus was built. This novel arm is capable of pushing-based locomotion and object grasping, mimicking the movements that octopuses adopt when crawling. The results support the biological observations and clearly show a suitable way to build a more complex soft robot that, with minimum control, can perform diverse tasks.

Methods and Technologies for the Implementation of Large-Scale Robot Tactile Sensors

Abstract: Even though the sense of touch is crucial for humans, most humanoid robots lack tactile sensing. While a large number of sensing technologies exist, it is not trivial to incorporate them into a robot. We have developed a compliant “skin” for humanoids that integrates a distributed pressure sensor based on capacitive technology. The skin is modular and can be deployed on nonflat surfaces. Each module scans locally a limited number of tactile-sensing elements and sends the data through a serial bus. This is a critical advantage as it reduces the number of wires. The resulting system is compact and has been successfully integrated into three different humanoid robots. We have performed tests that show that the sensor has favorable characteristics and implemented algorithms to compensate the hysteresis and drift of the sensor. Experiments with the humanoid robot iCub prove that the sensors can be used to grasp unmodeled, fragile objects.

Live-cell 3D super-resolution imaging in thick biological samples

Abstract: We demonstrate three-dimensional (3D) super-resolution live-cell imaging through thick specimens (50-150 μm), by coupling far-field individual molecule localization with selective plane illumination microscopy (SPIM). The improved signal-to-noise ratio of selective plane illumination allows nanometric localization of single molecules in thick scattering specimens without activating or exciting molecules outside the focal plane. We report 3D super-resolution imaging of cellular spheroids.

Exploiting oncogene-induced replicative stress for the selective killing of Myc-driven tumors

Abstract: Oncogene-induced replicative stress activates an Atr- and Chk1-dependent response, which has been proposed to be widespread in tumors. We explored whether the presence of replicative stress could be exploited for the selective elimination of cancer cells. To this end, we evaluated the impact of targeting the replicative stress-response on cancer development. In mice (Mus musculus), the reduced levels of Atr found on a mouse model of the Atr-Seckel syndrome completely prevented the development of Myc-induced lymphomas or pancreatic tumors, both of which showed abundant levels of replicative stress. Moreover, Chk1 inhibitors were highly effective in killing Myc-driven lymphomas. By contrast, pancreatic adenocarcinomas initiated by K-Ras G12V

Sequential Cation Exchange in Nanocrystals: Preservation of Crystal Phase and Formation of Metastable Phases

Abstract: We demonstrate that it is possible to convert CdSe nanocrystals of a given size, shape (either spherical or rod shaped), and crystal structure (either hexagonal wurtzite, i.e., hexagonal close packed (hcp), or cubic sphalerite, i.e., face-centered cubic (fcc)), into ZnSe nanocrystals that preserve all these characteristics of the starting particles (i.e., size, shape, and crystal structure), via a sequence of two cation exchange reactions, namely, Cd2+ ⇒Cu+ ⇒Zn2+. When starting from hexagonal wurtzite CdSe nanocrystals, the exchange of Cd2+ with Cu+ yields Cu2Se nanocrystals in a metastable hexagonal phase, of which we could follow the transformation to the more stable fcc phase for a single nanorod, under the electron microscope. Remarkably, these metastable hcp Cu2Se nanocrystals can be converted in solution into ZnSe nanocrystals, which yields ZnSe nanocrystals in a pure hcp phase.

Altered Intrinsic Functional Connectivity of Anterior and Posterior Insula Regions in High-Functioning Participants With Autism Spectrum Disorder

Abstract: Impaired understanding of others' sensations and emotions as well as abnormal experience of their own emotions and sensations is frequently reported in individuals with Autism Spectrum Disorder (ASD). It is hypothesized that these abnormalities are based on altered connectivity within "shared" neural networks involved in emotional awareness of self and others. The insula is considered a central brain region in a network underlying these functions, being located at the transition of information about bodily arousal and the physiological state of the body to subjective feelings. The present study investigated the intrinsic functional connectivity properties of the insula in 14 high-functioning participants with ASD (HF-ASD) and 15 typically developing (TD) participants in the age range between 12 and 20 years by means of "resting state" or "nontask" functional magnetic resonance imaging. Essentially, a distinction was made between anterior and posterior regions of the insular cortex. The results show a reduced functional connectivity in the HF-ASD group, compared with the TD group, between anterior as well as posterior insula and specific brain regions involved in emotional and sensory processing. It is suggested that functional abnormalities in a network involved in emotional and interoceptive awareness might be at the basis of altered emotional experiences and impaired social abilities in ASD, and that these abnormalities are partly based on the intrinsic functional connectivity properties of such a network.

A hybrid bioorganic interface for neuronal photoactivation

Abstract: A key issue in the realization of retinal prosthetic devices is reliable transduction of information carried by light into specific patterns of electrical activity in visual information processing networks. Soft organic materials can be used to couple artificial sensors with neuronal tissues. Here, we interface a network of primary neurons with an organic blend. We show that primary neurons can be successfully grown onto the polymer layer without affecting the optoelectronic properties of the active material or the biological functionality of neuronal network. Moreover, action potentials can be triggered in a temporally reliable and spatially selective manner with short pulses of visible light. Our results may lead to new neuronal communication and photo manipulation techniques, thus paving way to the development of artificial retinas and other neuroprosthetic interfaces based on organic photodetectors.

Imitation Learning of Positional and Force Skills Demonstrated via Kinesthetic Teaching and Haptic Input

Abstract: A method to learn and reproduce robot force interactions in a human–robot interaction setting is proposed. The method allows a robotic manipulator to learn to perform tasks that require exerting forces on external objects by interacting with a human operator in an unstructured environment. This is achieved by learning two aspects of a task: positional and force profiles. The positional profile is obtained from task demonstrations via kinesthetic teaching. The force profile is obtained from additional demonstrations via a haptic device. A human teacher uses the haptic device to input the desired forces that the robot should exert on external objects during the task execution. The two profiles are encoded as a mixture of dynamical systems, which is used to reproduce the task satisfying both the positional and force profiles. An active control strategy based on task-space control with variable stiffness is then proposed to reproduce the skill. The method is demonstrated with two experiments in which the robo...

Synapsin I Is an Oligomannose-Carrying Glycoprotein, Acts As an Oligomannose-Binding Lectin, and Promotes Neurite Outgrowth and Neuronal Survival When Released via Glia-Derived Exosomes

Abstract: Oligomannosidic glycans play important roles in nervous system development and function. By performing a phage display screening with oligomannose-specific antibodies, we identified an oligomannose-mimicking peptide that was functionally active in modulating neurite outgrowth and neuron–astrocyte adhesion. Using the oligomannose-mimicking peptide in crosslinking experiments, synapsin I was identified as a novel oligomannose-binding protein in mouse brain. Further analyses not only verified that synapsin I is an oligomannose-binding lectin, but also indicated that it is a glycoprotein carrying oligomannose and Lewisx. We also found that synapsin I is expressed in glia-enriched cultures and is released from glial cells via exosomes. Incubation of glial-derived exosomes in the presence of high KCl concentrations or subjecting glial cell cultures to either oxygen/glucose deprivation or hydrogen peroxide resulted in release of synapsin I from exosomes. Application of synapsin I promoted neurite outgrowth from hippocampal neurons and increased survival of cortical neurons upon hydrogen peroxide treatment or oxygen/glucose deprivation. Coculture experiments using wild-type hippocampal neurons and wild-type or synapsin-deficient glial cells showed enhanced neurite outgrowth when synapsin was expressed by glial cells. Synapsin-induced neurite outgrowth was dependent on oligomannose on synapsin I and the neural cell adhesion molecule NCAM at the neuronal cell surface. The data indicate that, under conditions of high neuronal activity and/or oxidative stress, synapsin can be released from glial-derived exosomes and promotes neurite outgrowth and neuronal survival by modulating the interactions between glia and neurons.

Absorption Spectra and Excited State Energy Levels of the N719 Dye on TiO2 in Dye-Sensitized Solar Cell Models

Abstract: We have investigated the absorption spectrum and the alignment of ground and excited state energies for the prototypical N719 Ru(II) sensitizer adsorbed on an extended TiO2 model by means of high level DFT/TDDFT calculations. The calculated and experimental absorption spectra for the dye on TiO2 are in excellent agreement over the explored energy range, with an absorption maximum deviation below 0.1 eV, allowing us to assign the underlying electronic transitions. We find the lowest optically active excited state to lie ca. 0.3 eV above the lowest TiO2 state. This state has a sizable contribution from the dye π* orbitals, strongly mixed with unoccupied TiO2 states. A similarly strong coupling is calculated for the higher-lying transitions constituting the visible absorption band centered at ca. 530 nm in the combined system. An ultrafast, almost instantaneous, electron injection component can be predicted on the basis of the strong coupling and of the matching of the visible absorption spectrum and density...

Social interaction discovery by statistical analysis of F-formations.

Abstract: We present a novel approach for detecting social interactions in a crowded scene by employing solely visual cues. The detection of social interactions in unconstrained scenarios is a valuable and important task, especially for surveillance purposes. Our proposal is inspired by the social signaling literature, and in particular it considers the sociological notion of F-formation. An F-formation is a set of possible configurations in space that people may assume while participating in a social interaction. Our system takes as input the positions of the people in a scene and their (head) orientations; then, employing a voting strategy based on the Hough transform, it recognizes F-formations and the individuals associated with them. Experiments on simulations and real data promote our idea.

SYN1 loss-of-function mutations in autism and partial epilepsy cause impaired synaptic function

Abstract: Several genes predisposing to autism spectrum disorders (ASDs) with or without epilepsy have been identified, many of which are implicated in synaptic function. Here we report a Q555X mutation in synapsin 1 (SYN1), an X-linked gene encoding for a neuron-specific phosphoprotein implicated in the regulation of neurotransmitter release and synaptogenesis. This nonsense mutation was found in all affected individuals from a large French-Canadian family segregating epilepsy and ASDs. Additional mutations in SYN1 (A51G, A550T and T567A) were found in 1.0 and 3.5% of French-Canadian individuals with autism and epilepsy, respectively. The majority of these SYN1 mutations were clustered in the proline-rich D-domain which is substrate of multiple protein kinases. When expressed in synapsin I (SynI) knockout (KO) neurons, all the D-domain mutants failed in rescuing the impairment in the size and trafficking of synaptic vesicle pools, whereas the wild-type human SynI fully reverted the KO phenotype. Moreover, the nonsense Q555X mutation had a dramatic impact on phosphorylation by MAPK/Erk and neurite outgrowth, whereas the missense A550T and T567A mutants displayed impaired targeting to nerve terminals. These results demonstrate that SYN1 is a novel predisposing gene to ASDs, in addition to epilepsy, and strengthen the hypothesis that a disturbance of synaptic homeostasis underlies the pathogenesis of both diseases.

AwAS-II: A new Actuator with Adjustable Stiffness based on the novel principle of adaptable pivot point and variable lever ratio

Abstract: The Actuator with Adjustable Stiffness (AwAS) is an actuator which can independently control equilibrium position and stiffness by two motors. The first motor controls the equilibrium position while the second motor regulates the compliance. This paper describes the design and development of AwAS-II which is an improved version of the original realization. AwAS tuned the stiffness by controlling the location of the springs and adjusting its arm, length. Instead AwAS-II regulates the compliance by implementing a force amplifier based on a lever mechanism on which a pivot point can adjust the force amplification ratio from zero to infinitive. As in the first implementation, the actuator which is responsible for adjusting the stiffness in AwAS II is not working against the spring forces. Its displacement is perpendicular to the force generated by springs which makes changing the stiffness energetically efficient. As the force amplification ratio can theoretically change from zero to infinitive consequently the level of stiffness can tune from very soft to completely rigid. Because this range does not depends on the spring's rate and length of the lever, thus soft springs and small lever can be used which result in a lighter and more compact setup. Furthermore as the lever arm is shorter the time required for the stiffness regulation is smaller.

A new variable stiffness actuator (CompAct-VSA): Design and modelling

Abstract: This paper describes the design and modelling of a new variable stiffness actuator (CompAct-VSA). The principle of operation of CompAct-VSA is based on a lever arm mechanism with a continuously regulated pivot point. The proposed concept allows for the development of an actuation unit with a wide range of stiffness and a fast stiffness regulation response. The implementation of the actuator makes use of a cam shaped lever arm with a variable pivot axis actuated by a rack and pinion transmission system. This realization results in a highly integrated and modular assembly. Size and weight are indeed an open issue in the VSAs design, which ultimately limit their implementation in multi-dof robotic systems. The paper introduces the mechanics, the principle of operation and the model of the actuator. Preliminary results are presented to demonstrate the fast stiffness regulation response and the wide range of stiffness achieved by the proposed CompAct-VSA design.

Ultra-thin conductive free-standing PEDOT/PSS nanofilms

Abstract: Free-standing conductive ultra-thin films based on poly(3,4-ethylenedioxythiophene)/poly(styrenesulfonate) (PEDOT/PSS) are realized. A fabrication process based on a modified Supporting Layer technique is proposed that provides for the easy production of conductive nanofilms having a very large surface area with typical thickness of tens of nanometres. The proposed free-standing nanofilms can be manipulated, folded and unfolded in water many times without suffering from cracks, disaggregation or from loss of conductive properties. After collecting them onto rigid or soft substrates, they retain their functionality. Structural and functional properties of the nanofilms are described by means of their thickness, topography, conductivity and Young's modulus. Strong dependences of these properties on residual water, post-deposition treatments and environmental moisture are clearly evidenced. Possible applications are foreseen in the field of sensing and actuation, as well as in the biomedical field, e.g. as smart substrates for cell culturing and stimulation.

Evidence for composite cost functions in arm movement planning: an inverse optimal control approach.

Abstract: An important issue in motor control is understanding the basic principles underlying the accomplishment of natural movements. According to optimal control theory, the problem can be stated in these terms: what cost function do we optimize to coordinate the many more degrees of freedom than necessary to fulfill a specific motor goal? This question has not received a final answer yet, since what is optimized partly depends on the requirements of the task. Many cost functions were proposed in the past, and most of them were found to be in agreement with experimental data. Therefore, the actual principles on which the brain relies to achieve a certain motor behavior are still unclear. Existing results might suggest that movements are not the results of the minimization of single but rather of composite cost functions. In order to better clarify this last point, we consider an innovative experimental paradigm characterized by arm reaching with target redundancy. Within this framework, we make use of an inverse optimal control technique to automatically infer the (combination of) optimality criteria that best fit the experimental data. Results show that the subjects exhibited a consistent behavior during each experimental condition, even though the target point was not prescribed in advance. Inverse and direct optimal control together reveal that the average arm trajectories were best replicated when optimizing the combination of two cost functions, nominally a mix between the absolute work of torques and the integrated squared joint acceleration. Our results thus support the cost combination hypothesis and demonstrate that the recorded movements were closely linked to the combination of two complementary functions related to mechanical energy expenditure and joint-level smoothness.