New control strategies for neuroprosthetic systems

The availability of techniques to artificially excite paralyzed muscles opens enormous potential for restoring both upper and lower extremity movements with\ud neuroprostheses. Neuroprostheses must stimulate muscle, and control and regulate the artificial movements produced. Control methods to accomplish these tasks include feedforward (open-loop), feedback, and adaptive control. Feedforward control requires a great deal of information about the biomechanical behavior of the limb. For the upper extremity, an artificial motor program was developed to provide such movement program input to a neuroprosthesis. In lower extremity control, one group achieved their best results by attempting to meet naturally perceived gait objectives rather than to follow an exact joint angle trajectory. Adaptive feedforward control, as implemented in the cycleto-cycle controller, gave good compensation for the gradual decrease in performance observed with open-loop control. A neural network controller was able to control its system to customize stimulation parameters in order to generate a desired output trajectory in a given individual and to maintain tracking performance in the presence of muscle fatigue. The authors believe that practical FNS control systems must\ud exhibit many of these features of neurophysiological systems

What is the Priestley–Taylor wet-surface evaporation parameter? Testing four hypotheses

This study compares four different hypotheses regarding the nature of the Priestley–Taylor parameter α. They are as follows: α is a universal constant. The Bowen ratio (H/LE, where H is the sensible heat flux, and LE is the latent heat flux) for equilibrium (i.e., saturated air column near the surface) evaporation is a constant times the Bowen ratio at minimal advection (Andreas et al., 2013). Minimal advection over a wet surface corresponds to a particular relative humidity value. α is a constant fraction of the difference from the minimum value of 1 to the maximum value of α proposed by Priestley and Taylor (1972). Formulas for α are developed for the last three hypotheses. Weather, radiation, and surface energy flux data from 171 FLUXNET eddy covariance stations were used. The condition LEref=LEp \u3e0.90 was taken as the criterion for nearly saturated conditions (where LEref is the reference, and LEp is the apparent potential evaporation rate from the equation by Penman, 1948). Daily and monthly average data from the sites were obtained. All formulations for α include one model parameter which is optimized such that the root mean square error of the target variable was minimized. For each model, separate optimizations were done for predictions of the target variables α, wet-surface evaporation (α multiplied by equilibrium evaporation rate) and actual evaporation (the latter using a highly successful version of the complementary relationship of evaporation). Overall, the second and fourth hypotheses received the best support from the data

Population Genomics of Early Events in the Ecological Differentiation of Bacteria

Genetic exchange is common among bacteria, but its effect on population diversity during ecological differentiation remains controversial. A fundamental question is whether advantageous mutations lead to selection of clonal genomes or, as in sexual eukaryotes, sweep through populations on their own. Here, we show that in two recently diverged populations of ocean bacteria, ecological differentiation has occurred akin to a sexual mechanism: A few genome regions have swept through subpopulations in a habitat-specific manner, accompanied by gradual separation of gene pools as evidenced by increased habitat specificity of the most recent recombinations. These findings reconcile previous, seemingly contradictory empirical observations of the genetic structure of bacterial populations and point to a more unified process of differentiation in bacteria and sexual eukaryotes than previously thought.National Science Foundation (U.S.) (Grant DEB-0918333)Woods Hole Center for Oceans & Human HealthGordon and Betty Moore FoundationUnited States. Dept. of Energy. Genomes To Lif

The Borrelia afzelii outer membrane protein BAPKO_0422 binds human Factor-H and is predicted to form a membrane-spanning beta-barrel

The deep evolutionary history of the Spirochetes places their branch point early in the evolution of the diderms, before the divergence of the present day Proteobacteria. As a Spirochete, the morphology of the Borrelia cell envelope shares characteristics of both Gram-positive and Gram-negative bacteria. A thin layer of peptidoglycan, tightly associated with the cytoplasmic membrane is surrounded by a more labile outer membrane (OM). This OM is rich in lipoproteins but with few known integral membrane proteins. The OmpA domain is an eight-stranded membrane-spanning β-barrel, highly conserved among the Proteobacteria but so far unknown in the Spirochetes. In the present work we describe the identification of four novel OmpA-like β-barrels from Borrelia afzelii, the most common cause of erythema migrans rash in Europe. Structural characterisation of one these proteins (BAPKO_0422) by small angle X-ray scattering (SAXS) and circular dichroism indicate a compact globular structure rich in β-strand consistent with a monomeric β-barrel. Ab initio molecular envelopes calculated from the scattering profile are consistent with homology models and demonstrate that BAPKO_0422 adopts a peanut shape with dimensions 25 x 45 Å. Deviations from the standard C-terminal signature sequence are apparent; in particular the C-terminal Phe residue commonly found in Proteobacterial OM proteins is replaced by Ile/Leu or Asn. BAPKO_0422 is demonstrated to bind human factor-H and therefore may contribute to immune evasion by inhibition of the complement response. Encoded by chromosomal genes, these proteins are highly conserved between Borrelia subspecies and may be of diagnostic or therapeutic value

The neural basis of perceived intensity in natural and artificial touch

Electrical stimulation of sensory nerves is a powerful tool for studying neural coding because it can activate neural populations in ways that natural stimulation cannot. Electrical stimulation of the nerve has also been used to restore sensation to patients who have suffered the loss of a limb. We have used long-term implanted electrical interfaces to elucidate the neural basis of perceived intensity in the sense of touch. To this end, we assessed the sensory correlates of neural firing rate and neuronal population recruitment independently by varying two parameters of nerve stimulation: pulse frequency and pulse width. Specifically, two amputees, chronically implanted with peripheral nerve electrodes, performed each of three psychophysical tasks-intensity discrimination, magnitude scaling, and intensity matching-in response to electrical stimulation of their somatosensory nerves. We found that stimulation pulse width and pulse frequency had systematic, cooperative effects on perceived tactile intensity and that the artificial tactile sensations could be reliably matched to skin indentations on the intact limb. We identified a quantity we termed the activation charge rate (ACR), derived from stimulation parameters, that predicted the magnitude of artificial tactile percepts across all testing conditions. On the basis of principles of nerve fiber recruitment, the ACR represents the total population spike count in the activated neural population. Our findings support the hypothesis that population spike count drives the magnitude of tactile percepts and indicate that sensory magnitude can be manipulated systematically by varying a single stimulation quantity

Analysis of reflex modulation with a biologically realistic neural network

In this study, a neuromusculoskeletal model was built to give insight into the mechanisms behind the modulation of reflexive feedback strength as experimentally identified in the human shoulder joint. The model is an integration of a biologically realistic neural network consisting of motoneurons and interneurons, modeling 12 populations of spinal neurons, and a one degree-of-freedom musculoskeletal model, including proprioceptors. The model could mimic the findings of human postural experiments, using presynaptic inhibition of the Ia afferents to modulate the feedback gains. In a pathological case, disabling one specific neural connection between the inhibitory interneurons and the motoneurons could mimic the experimental findings in complex regional pain syndrome patients. It is concluded that the model is a valuable tool to gain insight into the spinal contributions to human motor control. Applications lay in the fields of human motor control and neurological disorders, where hypotheses on motor dysfunction can be tested, like spasticity, clonus, and tremor

Relating reflex gain modulation in posture control to underlying neural network properties using a neuromusculoskeletal model

During posture control, reflexive feedback allows humans to efficiently compensate for unpredictable mechanical disturbances. Although reflexes are involuntary, humans can adapt their reflexive settings to the characteristics of the disturbances. Reflex modulation is commonly studied by determining reflex gains: a set of parameters that quantify the contributions of Ia, Ib and II afferents to mechanical joint behavior. Many mechanisms, like presynaptic inhibition and fusimotor drive, can account for reflex gain modulations. The goal of this study was to investigate the effects of underlying neural and sensory mechanisms on mechanical joint behavior. A neuromusculoskeletal model was built, in which a pair of muscles actuated a limb, while being controlled by a model of 2,298 spiking neurons in six pairs of spinal populations. Identical to experiments, the endpoint of the limb was disturbed with force perturbations. System identification was used to quantify the control behavior with reflex gains. A sensitivity analysis was then performed on the neuromusculoskeletal model, determining the influence of the neural, sensory and synaptic parameters on the joint dynamics. The results showed that the lumped reflex gains positively correlate to their most direct neural substrates: the velocity gain with Ia afferent velocity feedback, the positional gain with muscle stretch over II afferents and the force feedback gain with Ib afferent feedback. However, position feedback and force feedback gains show strong interactions with other neural and sensory properties. These results give important insights in the effects of neural properties on joint dynamics and in the identifiability of reflex gains in experiments

Structural and Functional Insights into the Pilotin-Secretin Complex of the Type II Secretion System

Gram-negative bacteria secrete virulence factors and assemble fibre structures on their cell surface using specialized secretion systems. Three of these, T2SS, T3SS and T4PS, are characterized by large outer membrane channels formed by proteins called secretins. Usually, a cognate lipoprotein pilot is essential for the assembly of the secretin in the outer membrane. The structures of the pilotins of the T3SS and T4PS have been described. However in the T2SS, the molecular mechanism of this process is poorly understood and its structural basis is unknown. Here we report the crystal structure of the pilotin of the T2SS that comprises an arrangement of four α-helices profoundly different from previously solved pilotins from the T3SS and T4P and known four α-helix bundles. The architecture can be described as the insertion of one α-helical hairpin into a second open α-helical hairpin with bent final helix. NMR, CD and fluorescence spectroscopy show that the pilotin binds tightly to 18 residues close to the C-terminus of the secretin. These residues, unstructured before binding to the pilotin, become helical on binding. Data collected from crystals of the complex suggests how the secretin peptide binds to the pilotin and further experiments confirm the importance of these C-terminal residues in vivo