Influence fields: a quantitative framework for representation and analysis of active dendrites

Rathour RK, Narayanan R. Influence fields: a quantitative framework for representation and analysis of active dendrites. J Neurophysiol 107: 2313-2334, 2012. First published January 18, 2012; doi:10.1152/jn.00846.2011.-Neuronal dendrites express numerous voltage-gated ion channels (VGICs), typically with spatial gradients in their densities and properties. Dendritic VGICs, their gradients, and their plasticity endow neurons with information processing capabilities that are higher than those of neurons with passive dendrites. Despite this, frameworks that incorporate dendritic VGICs and their plasticity into neurophysiological and learning theory models have been far and few. Here, we develop a generalized quantitative framework to analyze the extent of influence of a spatially localized VGIC conductance on different physiological properties along the entire stretch of a neuron. Employing this framework, we show that the extent of influence of a VGIC conductance is largely independent of the conductance magnitude but is heavily dependent on the specific physiological property and background conductances. Morphologically, our analyses demonstrate that the influences of different VGIC conductances located on an oblique dendrite are confined within that oblique dendrite, thus providing further credence to the postulate that dendritic branches act as independent computational units. Furthermore, distinguishing between active and passive propagation of signals within a neuron, we demonstrate that the influence of a VGIC conductance is spatially confined only when propagation is active. Finally, we reconstruct functional gradients from VGIC conductance gradients using influence fields and demonstrate that the cumulative contribution of VGIC conductances in adjacent compartments plays a critical role in determining physiological properties at a given location. We suggest that our framework provides a quantitative basis for unraveling the roles of dendritic VGICs and their plasticity in neural coding, learning, and homeostasis.

Wrinkled and slack membranes: nonlinear 3D elasticity solutions via smooth DMS-FEM and experiment

The smooth DMS-FEM, recently proposed by the authors, is extended and applied to the geometrically nonlinear and ill-posed problem of a deformed and wrinkled/slack membrane. A key feature of this work is that three-dimensional nonlinear elasticity equations corresponding to linear momentum balance, without any dimensional reduction and the associated approximations, directly serve as the membrane governing equations. Domain discretization is performed with triangular prism elements and the higher order (C1 or more) interelement continuity of the shape functions ensures that the errors arising from possible jumps in the first derivatives of the conventional C0 shape functions do not propagate because the ill-conditioned tangent stiffness matrices are iteratively inverted. The present scheme employs no regularization and exhibits little sensitivity to h-refinement. Although the numerically computed deformed membrane profiles do show some sensitivity to initial imperfections (nonplanarity) in the membrane profile needed to initiate transverse deformations, the overall patterns of the wrinkles and the deformed shapes appear to be less so. Finally, the deformed profiles, computed through the DMS FEM-based weak formulation, are compared with those obtained through an experiment on an ultrathin Kapton membrane, wherein wrinkles form because of the applied boundary displacement conditions. Comparisons with a reported experiment on a rectangular membrane are also provided. These exercises lend credence to the feasibility of the DMS FEM-based numerical route to computing post-wrinkled membrane shapes. Copyright (c) 2012 John Wiley & Sons, Ltd.

A drop of active matter

We study theoretically the hydrodynamics of a fluid drop containing oriented filaments endowed with active contractile or extensile stresses and placed on a solid surface. The active stresses alter qualitatively the wetting properties of the drop, leading to new spreading laws and novel static drop shapes. Candidate systems for testing our predictions include cytoskeletal extracts with motors and ATP, suspensions of bacteria or pulsatile cells, or fluids laden with artificial self-propelled colloids.

A Single-Stage Water-Gas Shift Reaction over Highly Active and Stable Si- and Al-Substituted Pt/CeO2 Catalysts

Ce0.88Si0.1Pt0.02O2-d and Ce0.88Al0.1Pt0.02O2-d catalysts were synthesized by using a low-temperature sonochemical method and characterized by using XRD, TEM, XPS, FTIR, and BET surface analyzer. The catalytic activities of these compounds were investigated for the watergas shift reaction in the temperature range of 140-440 degrees C. The substitution of Si in Ce0.98Pt0.02O2-d increased the releasing capacity of lattice oxygen, whereas the substitution of Al decreased the reducibility of Ce0.98Pt0.02O2-d, as evidenced by hydrogen temperature-programmed reduction studies. However, both the catalysts showed a considerable improvement in terms of activity and stability compared to Ce0.98Pt0.02O2-d. The combined activity measurement and characterization results suggest that the increase in the oxygen vacancy, which acts as a dissociation center for water, is the primary reason for the improvement in the activity of modified Ce0.98Pt0.02O2-d. Both the catalysts are 100?% selective toward H2 production, and approximately 99?% conversion of CO to CO2 was observed at 260 and 270 degrees C for Ce0.88Si0.1Pt0.02O2-d and Ce0.88Al0.1Pt0.02O2-d, respectively. These catalysts do not deactivate during the daily startup/shutdown operations and are sustainable even after prolonged reaction. Notably, these catalysts do not require any pretreatment or activation during startup/shutdown operations.

Active Sequential Hypothesis Testing with Application to a Visual Search Problem

We consider a visual search problem studied by Sripati and Olson where the objective is to identify an oddball image embedded among multiple distractor images as quickly as possible. We model this visual search task as an active sequential hypothesis testing problem (ASHT problem). Chernoff in 1959 proposed a policy in which the expected delay to decision is asymptotically optimal. The asymptotics is under vanishing error probabilities. We first prove a stronger property on the moments of the delay until a decision, under the same asymptotics. Applying the result to the visual search problem, we then propose a ``neuronal metric'' on the measured neuronal responses that captures the discriminability between images. From empirical study we obtain a remarkable correlation (r = 0.90) between the proposed neuronal metric and speed of discrimination between the images. Although this correlation is lower than with the L-1 metric used by Sripati and Olson, this metric has the advantage of being firmly grounded in formal decision theory.

Identification of Active Sources in Single-Channel Convolutive Mixtures Using Known Source Models

We address the problem of identifying the constituent sources in a single-sensor mixture signal consisting of contributions from multiple simultaneously active sources. We propose a generic framework for mixture signal analysis based on a latent variable approach. The basic idea of the approach is to detect known sources represented as stochastic models, in a single-channel mixture signal without performing signal separation. A given mixture signal is modeled as a convex combination of known source models and the weights of the models are estimated using the mixture signal. We show experimentally that these weights indicate the presence/absence of the respective sources. The performance of the proposed approach is illustrated through mixture speech data in a reverberant enclosure. For the task of identifying the constituent speakers using data from a single microphone, the proposed approach is able to identify the dominant source with up to 8 simultaneously active background sources in a room with RT60 = 250 ms, using models obtained from clean speech data for a Source to Interference Ratio (SIR) greater than 2 dB.

Selective excitation and detection of maximum quantum coherence of a group of scalar coupled protons in chiral molecules: an NMR experiment for enantiodiscrimination

The H-1 NMR spectroscopic discrimination of enantiomers in the solution state and the measurement of enantiomeric composition is most often hindered due to either very small chemical shift differences between the discriminated peaks or severe overlap of transitions from other chemically non-equivalent protons. In addition the use of chiral auxiliaries such as, crown ether and chiral lanthanide shift reagent may often cause enormous line broadening or give little degree of discrimination beyond the crown ether substrate ratio, hampering the discrimination. In circumventing such problems we are proposing the utilization of the difference in the additive values of all the chemical shifts of a scalar coupled spin system. The excitation and detection of appropriate highest quantum coherence yields the measurable difference in the frequencies between two transitions, one pertaining to each enantiomer in the maximum quantum dimension permitting their discrimination and the F-2 cross section at each of these frequencies yields an enantiopure spectrum. The advantage of the utility of the proposed method is demonstrated on several chiral compounds where the conventional one dimensional H-1 NMR spectra fail to differentiate the enantiomers.

Active-contour-based automated image quantitation techniques for Western Blot analysis

Western Blot analysis is an analytical technique used in Molecular Biology, Biochemistry, Immunogenetics and other Molecular Biology studies to separate proteins by electrophoresis. The procedure results in images containing nearly rectangular-shaped blots. In this paper, we address the problem of quantitation of the blots using automated image processing techniques. We formulate a special active contour (or snake) called Oblong, which locks on to rectangular shaped objects. Oblongs depend on five free parameters, which is also the minimum number of parameters required for a unique characterization. Unlike many snake formulations, Oblongs do not require explicit gradient computations and therefore the optimization is carried out fast. The performance of Oblongs is assessed on synthesized data and Western Blot Analysis images.

An experiment that shaped the physics of the century

In this article it is pointed out how the different layers of substructure of matter were revealed to us by experiments which were essentially very similar to the famous α-particle scattering experiment performed by Rutherford. This experiment, which revealed the nuclear structure of an atom, paved the way towards our current understanding of the fundamental constituents of matter and shaped the course of physics for the 20th century.

Metabolites of PPI-2458, a selective, irreversible inhibitor of methionine aminopeptidase-2: structure determination and In vivo activity

The natural product fumagillin exhibits potent antiproliferative and antiangiogenic properties. The semisynthetic analog PPI-2458, (3R,4S,5S,6R)-5-methoxy-4-(2R,3R)-2-methyl-3-(3-methylbut-2-enyl) oxiran-2-yl]-1-oxaspiro2.5]octan-6-yl] N-(2R)-1-amino-3-methyl-1-oxobutan-2-yl]carbamate, demonstrates rapid inactivation of its molecular target, methionine aminopeptidase-2 (MetAP2), and good efficacy in several rodent models of cancer and inflammation with oral dosing despite low apparent oral bioavailability. To probe the basis of its in vivo efficacy, the metabolism of PPI-2458 was studied in detail. Reaction phenotyping identified CYP3A4/5 as the major source of metabolism in humans. Six metabolites were isolated from liver microsomes and characterized by mass spectrometry and nuclear resonance spectroscopy, and their structures were confirmed by chemical synthesis. The synthetic metabolites showed correlated inhibition of MetAP2 enzymatic activity and vascular endothelial cell growth. In an ex vivo experiment, MetAP2 inhibition in white blood cells, thymus, and lymph nodes in rats after single dosing with PPI-2458 and the isolated metabolites was found to correlate with the in vitro activity of the individual species. In a phase 1 clinical study, PPI-2458 was administered to patients with non-Hodgkin lymphoma. At 15 mg administered orally every other day, MetAP2 in whole blood was 80% inactivated for up to 48 hours, although the exposure of the parent compound was only similar to 10% that of the summed cytochrome P450 metabolites. Taken together, the data confirm the participation of active metabolites in the in vivo efficacy of PPI-2458. The structures define a metabolic pathway for PPI-2458 that is distinct from that of TNP-470 ((3R, 4S, 5S, 6R)-5-methoxy-4-(2R, 3R)-2-methyl-3-(3-methylbut-2-enyl)oxiran-2-yl]-1-oxaspiro2.5]octan-6 -yl] N-(2-chloroacetyl)carbamate). The high level of MetAP2 inhibition achieved in vivo supports the value of fumagillin-derived therapeutics for angiogenic diseases.

Damage identification of beam-like structures with contiguous and distributed damage

Structural health monitoring of existing infrastructure is currently an active field of research, where elaborate experimental programs and advanced analytical methods are used in identifying the current state of health of critical structures. Change of static deflection as the indicator of damage is the simplest tool in a structural health monitoring scenario of bridges that is least exploited in damage identification strategies. In this paper, some simple and elegant equations based on loss of symmetry due to damage are derived and presented for identification of damage in a bridge girder modeled as a simply supported beam using changes in static deflections and dynamic parameters. A single contiguous and distributed damage, typical of reinforced or prestressed concrete structures, is assumed for the structure. The methodology is extended for a base-line-free as well as base-line-inclusive measurement. Measurement strategy involves application of loads only at two symmetric points one at a time and deflection measurements at those symmetric points as well as at the midspan of the beam. A laboratory-based experiment is used to validate the approach. Copyright (c) 2012 John Wiley & Sons, Ltd.

Live Soap: Stability, Order, and Fluctuations in Apolar Active Smectics

We construct a hydrodynamic theory of noisy, apolar active smectics in bulk suspension or on a substrate. Unlike purely orientationally ordered active fluids, active apolar smectics can be dynamically stable in Stokesian bulk suspensions. Smectic order in these systems is quasilong ranged in dimension d = 2 and long ranged in d = 3. We predict reentrant Kosterlitz-Thouless melting to an active nematic in our simplest model in d = 2, a nonzero second-sound speed parallel to the layers in bulk suspensions, and that there are no giant number fluctuations in either case. We also briefly discuss possible instabilities in these systems. DOI: 10.1103/PhysRevLett.110.118102

Isotropic heating of galaxy cluster cores via rapidly reorienting active galactic nucleus jets

Active galactic nucleus (AGN) jets carry more than sufficient energy to stave off catastrophic cooling of the intracluster medium (ICM) in the cores of cool-core clusters. However, in order to prevent catastrophic cooling, the ICM must be heated in a near-isotropic fashion and narrow bipolar jets with P-jet = 10(44-45) erg s(-1), typical of radio AGNs at cluster centers, are inefficient in heating the gas in the transverse direction to the jets. We argue that due to existent conditions in cluster cores, the supermassive black holes (SMBHs) will, in addition to accreting gas via radiatively inefficient flows, experience short stochastic episodes of enhanced accretion via thin disks. In general, the orientation of these accretion disks will be misaligned with the spin axis of the black holes (BHs) and the ensuing torques will cause the BH's spin axis (and therefore the jet axis) to slew and rapidly change direction. This model not only explains recent observations showing successive generations of jet-lobes-bubbles in individual cool-core clusters that are offset from each other in the angular direction with respect to the cluster center, but also shows that AGN jets can heat the cluster core nearly isotropically on the gas cooling timescale. Our model does require that the SMBHs at the centers of cool-core clusters be spinning relatively slowly. Torques from individual misaligned disks are ineffective at tilting rapidly spinning BHs by more than a few degrees. Additionally, since SMBHs that host thin accretion disks will manifest as quasars, we predict that roughly 1-2 rich clusters within z < 0.5 should have quasars at their centers.

Spontaneous formation of branched nanochains from room temperature molten amides: visible and near-IR active, SERS substrates for non-fluorescent and fluorescent analytes

Highly stable, branched gold nanoworms are formed spontaneously in an acetamide-based room temperature molten solvent without any additional external stabilizing or aggregating agent. The nanoworms can be anchored onto solid substrates such as indium tin oxide (ITO) without any change in morphology. The anchored nanoworms are explored as substrates for surface enhanced Raman scattering (SERS) studies using non-fluorescent 4-mercaptobenzoic acid (4-MBA) and fluorescent rhodamine 6G (R6G) as probe molecules. The anchored nanostructured particles respond to near IR (1064 nm) as well as visible (785, 632.8 and 514 nm) excitation lasers and yield good surface enhancement in Raman signals. Enhancement factors of the order 10(6)-10(7) are determined for the analytes using a 1064 nm excitation source. Minimum detection limits based on adsorption from ethanolic solutions of 1028 M 4-MBA and aqueous solutions of 1027 M R6G are achieved. Experimental Raman frequencies and frequencies estimated by DFT calculations are in fairly good agreement. SERS imaging of the nanostructures suggests that the substrates comprising of three dimensional, highly interlinked particles are more suited than particles fused in one dimension. The high SERS activity of the branched nanoworms may be attributed to both electromagnetic and charge transfer effects.