Transition in subicular burst firing neurons from epileptiform activity to suppressed state by feedforward inhibition

The subiculum, a para-hippocampal structure positioned between the cornu ammonis 1 subfield and the entorhinal cortex, has been implicated in temporal lobe epilepsy in human patients and in animal models of epilepsy. The structure is characterized by the presence of a significant population of burst firing neurons that has been shown previously to lead epileptiform activity locally. Phase transitions in epileptiform activity in neurons following a prolonged challenge with an epileptogenic stimulus has been shown in other brain structures, but not in the subiculum. Considering the importance of the subicular burst firing neurons in the propagation of epileptiform activity to the entorhinal cortex, we have explored the phenomenon of phase transitions in the burst firing neurons of the subiculum in an in vitro rat brain slice model of epileptogenesis. Whole-cell patch-clamp and extracellular field recordings revealed a distinct phenomenon in the subiculum wherein an early hyperexcitable state was followed by a late suppressed state upon continuous perfusion with epileptogenic 4-aminopyridine and magnesium-free medium. The suppressed state was characterized by inhibitory post-synaptic potentials in pyramidal excitatory neurons and bursting activity in local fast-spiking interneurons at a frequency of 0.1-0.8Hz. The inhibitory post-synaptic potentials were mediated by GABA(A) receptors that coincided with excitatory synaptic inputs to attenuate action potential discharge. These inhibitory post-synaptic potentials ceased following a cut between the cornu ammonis 1 and subiculum. The suppression of epileptiform activity in the subiculum thus represents a homeostatic response towards the induced hyperexcitability. Our results suggest the importance of feedforward inhibition in exerting this homeostatic control.

STUDENT'S-t MIXTURE MODEL BASED MULTI-INSTRUMENT RECOGNITION IN POLYPHONIC MUSIC

We address the problem of multi-instrument recognition in polyphonic music signals. Individual instruments are modeled within a stochastic framework using Student's-t Mixture Models (tMMs). We impose a mixture of these instrument models on the polyphonic signal model. No a priori knowledge is assumed about the number of instruments in the polyphony. The mixture weights are estimated in a latent variable framework from the polyphonic data using an Expectation Maximization (EM) algorithm, derived for the proposed approach. The weights are shown to indicate instrument activity. The output of the algorithm is an Instrument Activity Graph (IAG), using which, it is possible to find out the instruments that are active at a given time. An average F-ratio of 0 : 7 5 is obtained for polyphonies containing 2-5 instruments, on a experimental test set of 8 instruments: clarinet, flute, guitar, harp, mandolin, piano, trombone and violin.

A simple model for spatial disaggregation of evaporative fraction: Comparative study with thermal sharpened land surface temperature data over India

[1] Evaporative fraction (EF) is a measure of the amount of available energy at the earth surface that is partitioned into latent heat flux. The currently operational thermal sensors like the Moderate Resolution Imaging Spectroradiometer (MODIS) on satellite platforms provide data only at 1000 m, which constraints the spatial resolution of EF estimates. A simple model (disaggregation of evaporative fraction (DEFrac)) based on the observed relationship between EF and the normalized difference vegetation index is proposed to spatially disaggregate EF. The DEFrac model was tested with EF estimated from the triangle method using 113 clear sky data sets from the MODIS sensor aboard Terra and Aqua satellites. Validation was done using the data at four micrometeorological tower sites across varied agro-climatic zones possessing different land cover conditions in India using Bowen ratio energy balance method. The root-mean-square error (RMSE) of EF estimated at 1000 m resolution using the triangle method was 0.09 for all the four sites put together. The RMSE of DEFrac disaggregated EF was 0.09 for 250 m resolution. Two models of input disaggregation were also tried with thermal data sharpened using two thermal sharpening models DisTrad and TsHARP. The RMSE of disaggregated EF was 0.14 for both the input disaggregation models for 250 m resolution. Moreover, spatial analysis of disaggregation was performed using Landsat-7 (Enhanced Thematic Mapper) ETM+ data over four grids in India for contrasted seasons. It was observed that the DEFrac model performed better than the input disaggregation models under cropped conditions while they were marginally similar under non-cropped conditions.

Inhibition of Mycobacterium tuberculosis topoisomerase I by m-AMSA, a eukaryotic type II topoisomerase poison

m-AMSA, an established inhibitor of eukaryotic type II topoisomerases, exerts its cidal effect by binding to the enzyme-DNA complex thus inhibiting the DNA religation step. The molecule and its analogues have been successfully used as chemotherapeutic agents against different forms of cancer. After virtual screening using a homology model of the Mycobacterium tuberculosis topoisomerase I, we identified m-AMSA as a high scoring hit. We demonstrate that m-AMSA can inhibit the DNA relaxation activity of topoisomerase I from M. tuberculosis and Mycobacterium smegmatis. In a whole cell assay, m-AMSA inhibited the growth of both the mycobacteria. (C) 2014 Elsevier Inc. All rights reserved.

The impact of latent heating on the location and strength of the tropical easterly jet

The tropical easterly jet (TEJ) is a prominent atmospheric circulation feature observed during the Asian summer monsoon. It is generally assumed that sensible heating over the Tibetan Plateau directly influences the location of the TEJ. However, other studies have suggested the importance of latent heating in determining the jet location. In this paper, the relative importance of latent heating on the maintenance of the TEJ is explored through simulations with a general circulation model. The simulation of the TEJ by the Community Atmosphere Model, version 3.1 is discussed in detail. These simulations showed that the location of the TEJ is well correlated with the location of the precipitation. Significant zonal shifts in the location of the precipitation resulted in similar shifts in the zonal location of the TEJ. These zonal shifts had minimal effect on the large-scale structure of the jet. Further, provided that precipitation patterns were relatively unchanged, orography did not directly impact the location of the TEJ. These changes were robust even with changes in the cumulus parameterization. This suggests the potential important role of latent heating in determining the location and structure of the TEJ. These results were used to explain the significant differences in the zonal location of the TEJ in the years 1988 and 2002. To understand the contribution of the latitudinal location of latent heating on the strength of the TEJ, aqua-planet simulations were carried out. It has been shown that for similar amounts of net latent heating, the jet is stronger when heating is in the higher tropical latitudes. This may partly explain the reason for the jet to be very strong during the JJA monsoon season.

Chemical kinetics and self-ignition in a model supersonic hydrogen-air combustor

Self-ignition tests of a model scramjet combustor were conducted by using parallel sonic injection of gaseous hydrogen from the base of a blade-like strut into a supersonic vitiated airstream. The range of stagnation pressure and temperature studied varied from 1.0 to 4.5 MPa and from 1300 to 2200 K, respectively. Experimental results show that the self-ignition limit, in terms of either global or local quantities of pressure and temperature, exhibits a nonmonotonic behavior resembling the classical homogeneous explosion limit of the hydrogen-oxygen system. Specifically, for a given temperature, increasing pressure from a low value can render a nonignitable mixture to first become ignitable, then nonignitable again, This correspondence shows that, despite the globally supersonic nonpremixed configuration studied herein, ignition is strongly influenced by the intricate chemical reaction mechanism and thereby exhibits the homogeneous explosion character. Consequently, self-ignition criteria based on a global reaction rate approximating the complex chemistry are inadequate. An auxiliary computational study on counterflow ignition was also conducted to systematically investigate the contamination effects of vitiated air. Results indicate that the net contamination effects for the present experimental data are expected to be substantially smaller than contributions from the individual contamination species because of the counterbalancing influences of the H2O-inhibition and NO-promotion reactions in effecting ignition.

A Trabecular Bone Explant Model of Osteocyte–Osteoblast Co-Culture for Bone Mechanobiology

The osteocyte network is recognized as the major mechanical sensor in the bone remodeling process, and osteocyte-osteoblast communication acts as an important mediator in the coordination of bone formation and turnover. In this study, we developed a novel 3D trabecular bone explant co-culture model that allows live osteocytes situated in their native extracellular matrix environment to be interconnected with seeded osteoblasts on the bone surface. Using a low-level medium perfusion system, the viability of in situ osteocytes in bone explants was maintained for up to 4 weeks, and functional gap junction intercellular communication (GJIC) was successfully established between osteocytes and seeded primary osteoblasts. Using this novel co-culture model, the effects of dynamic deformational loading, GJIC, and prostaglandin E-2 (PGE(2)) release on functional bone adaptation were further investigated. The results showed that dynamical deformational loading can significantly increase the PGE(2) release by bone cells, bone formation, and the apparent elastic modulus of bone explants. However, the inhibition of gap junctions or the PGE(2) pathway dramatically attenuated the effects of mechanical loading. This 3D trabecular bone explant co-culture model has great potential to fill in the critical gap in knowledge regarding the role of osteocytes as a mechano-sensor and how osteocytes transmit signals to regulate osteoblasts function and skeletal integrity as reflected in its mechanical properties.

Dendrites Inhibition in Rechargeable Lithium Metal Batteries

The specific high energy and power capacities of rechargeable lithium metal (Li⁰) batteries are ideally suited to portable devices and are valuable as storage units for intermittent renewable energy sources. Lithium, the lightest and most electropositive metal, would be the optimal anode material for rechargeable batteries if it were not for the fact that such devices fail unexpectedly by short-circuiting via the dendrites that grow across electrodes upon recharging. This phenomenon poses a major safety issue because it triggers a series of adverse events that start with overheating, potentially followed by the thermal decomposition and ultimately the ignition of the organic solvents used in such devices.

In this thesis, we developed experimental platform for monitoring and quantifying the dendrite populations grown in a Li battery prototype upon charging under various conditions. We explored the effects of pulse charging in the kHz range and temperature on dendrite growth, and also on loss capacity into detached “dead” lithium particles.

Simultaneously, we developed a computational framework for understanding the dynamics of dendrite propagation. The coarse-grained Monte Carlo model assisted us in the interpretation of pulsing experiments, whereas MD calculations provided insights into the mechanism of dendrites thermal relaxation. We also developed a computational framework for measuring the dead lithium crystals from the experimental images.

Model systems for the study of drug hypersensitivity

I. It was not possible to produce anti-tetracycline antibody in laboratory animals by any of the methods tried. Tetracycline protein conjugates were prepared and characterized. It was shown that previous reports of the detection of anti-tetracycline antibody by in vitro-methods were in error. Tetracycline precipitates non-specifically with serum proteins. The anaphylactic reaction reported was the result of misinterpretation, since the observations were inconsistent with the known mechanism of anaphylaxis and the supposed antibody would not sensitize guinea pig skin. The hemagglutination reaction was not reproducible and was extremely sensitive to minute amounts of microbial contamination. Both free tetracyclines and the conjugates were found to be poor antigens.

II. Anti-aspiryl antibodies were produced in rabbits using 3 protein carriers. The method of inhibition of precipitation was used to determine the specificity of the antibody produced. ε-Aminocaproate was found to be the most effective inhibitor of the haptens tested, indicating that the combining hapten of the protein is ε-aspiryl-lysyl. Free aspirin and salicylates were poor inhibitors and did not combine with the antibody to a significant extent. The ortho group was found to participate in the binding to antibody. The average binding constants were measured.

Normal rabbit serum was acetylated by aspirin under in vitro conditions, which are similar to physiological conditions. The extent of acetylation was determined by immunochemical tests. The acetylated serum proteins were shown to be potent antigens in rabbits. It was also shown that aspiryl proteins were partially acetylated. The relation of these results to human aspirin intolerance is discussed.

III. Aspirin did not induce contact sensitivity in guinea pigs when they were immunized by techniques that induce sensitivity with other reactive compounds. The acetylation mechanism is not relevant to this type of hypersensitivity, since sensitivity is not produced by potent acetylating agents like acetyl chloride and acetic anhydride. Aspiryl chloride, a totally artificial system, is a good sensitizer. Its specificity was examined.

IV. Protein conjugates were prepared with p-aminosalicylic acid and various carriers using azo, carbodiimide and mixed anhydride coupling. These antigens were injected into rabbits and guinea pigs and no anti-hapten IgG or IgM response was obtained. Delayed hypersensitivity was produced in guinea pigs by immunization with the conjugates, and its specificity was determined. Guinea pigs were not sensitized by either injections or topical application of p-amino-salicylic acid or p-aminosalicylate.

Model-based influences on humans' choices and striatal prediction errors.

The mesostriatal dopamine system is prominently implicated in model-free reinforcement learning, with fMRI BOLD signals in ventral striatum notably covarying with model-free prediction errors. However, latent learning and devaluation studies show that behavior also shows hallmarks of model-based planning, and the interaction between model-based and model-free values, prediction errors, and preferences is underexplored. We designed a multistep decision task in which model-based and model-free influences on human choice behavior could be distinguished. By showing that choices reflected both influences we could then test the purity of the ventral striatal BOLD signal as a model-free report. Contrary to expectations, the signal reflected both model-free and model-based predictions in proportions matching those that best explained choice behavior. These results challenge the notion of a separate model-free learner and suggest a more integrated computational architecture for high-level human decision-making.

The Supervised IBP: Neighbourhood Preserving Infinite Latent Feature Models

We propose a probabilistic model to infer supervised latent variables in the Hamming space from observed data. Our model allows simultaneous inference of the number of binary latent variables, and their values. The latent variables preserve neighbourhood structure of the data in a sense that objects in the same semantic concept have similar latent values, and objects in different concepts have dissimilar latent values. We formulate the supervised infinite latent variable problem based on an intuitive principle of pulling objects together if they are of the same type, and pushing them apart if they are not. We then combine this principle with a flexible Indian Buffet Process prior on the latent variables. We show that the inferred supervised latent variables can be directly used to perform a nearest neighbour search for the purpose of retrieval. We introduce a new application of dynamically extending hash codes, and show how to effectively couple the structure of the hash codes with continuously growing structure of the neighbourhood preserving infinite latent feature space.

Primary cultured cells as sensitive in vitro model for assessment of toxicants-comparison to hepatocytes and gill epithelia

In an effort to develop cultured cell models for toxicity screening and environmental biomonitoring, we compared primary cultured gill epithelia and hepatocytes from freshwater tilapia (Oreochromis niloticus) to assess their sensitivity to AhR agonist toxicants. Epithelia were cultured on permeable supports (terephthalate membranes, "filters") and bathed on the apical with waterborne toxicants (pseudo in vivo asymmetrical culture conditions). Hepatocytes were cultured in multi-well plates and exposed to toxicants in culture medium. Cytochrome P4501A (measured as 7-Ethoxyresorufin-O-deethylase, EROD) was selected as a biomarker. For cultured gill epithelia, the integrity of the epithelia remained unchanged on exposure to model toxicants, such as 1,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), benzo(a)pyrene B[a]P, polychlorinated biphenyl (PCB) mixture (Aroclor 1254), and polybrominated diphenyl ether (PBDE) mixture (DE71). A good concentration-dependent response of EROD activity was clearly observed in both cultured gill epithelia and hepatocytes. The time-course response of EROD was measured as early as 3 h, and was maximal after 6 h of exposure to TCDD, B [alp and Aroclor 1254. The estimated 6 h EC50 for TCDD, B [a]P, and Aroclor 1254 was 1.2x10(-9), 5.7x10(-8) and 6.6x10(-6) M. For the cultured hepatocytes, time-course study showed that a significant induction of EROD took place at 18 h, and the maximal induction of EROD was observed at 24 h after exposure. The estimated 24 It EC50 for TCDD, B[a]P, and Aroclor 1254 was 1.4x10(-9), 8.1x10(-8) and 7.3x10(-6) M. There was no induction or inhibition of EROD in DE71 exposure to both gill epithelia and hepatocytes. The results show that cultured gill epithelia more rapidly induce EROD and are slightly more sensitive than cultured hepatocytes, and could be used as a rapid and sensitive tool for screening chemicals and monitoring environmental AhR agonist toxicants. (c) 2006 Elsevier B.V. All rights reserved.

Smoothing LDA Model for Text Categorization

Abstract. Latent Dirichlet Allocation (LDA) is a document level language model. In general, LDA employ the symmetry Dirichlet distribution as prior of the topic-words’ distributions to implement model smoothing. In this paper, we propose a data-driven smoothing strategy in which probability mass is allocated from smoothing-data to latent variables by the intrinsic inference procedure of LDA. In such a way, the arbitrariness of choosing latent variables'priors for the multi-level graphical model is overcome. Following this data-driven strategy,two concrete methods, Laplacian smoothing and Jelinek-Mercer smoothing, are employed to LDA model. Evaluations on different text categorization collections show data-driven smoothing can significantly improve the performance in balanced and unbalanced corpora.