Addressing Selective Polypharmacology of Antipsychotic Drugs Targeting the Bioaminergic Receptors through the Receptor Dynamic Conformational Ensembles

Selective polypharmacology, where a drug acts on multiple rather than single molecular targets involved in a disease, emerges to develop a structure-based system biology approach to design drugs selectively targeting a disease-active protein network. We focus on the bioaminergic receptors that belong to the group of integral membrane signalling proteins coupled to the G protein and represent targets for therapeutic agents against schizophrenia and depression. Among them, it has been shown that the serotonin (5-HT2A and 5-HT6), dopamine (D2 and D3) receptors induce a cognition-enhancing effect (group 1), while the histamine (H1) and serotonin (5-HT2C) receptors lead to metabolic side effects and the 5-HT2B serotonin receptor causes pulmonary hypertension (group 2). Thus, the problem arises to develop an approach that allows identifying drugs targeting only the disease-active receptors, i.e. group 1. The recent release of several crystal structures of the bioaminergic receptors, involving the D3 and H1 receptors provides the possibility to model the structures of all receptors and initiate a study of the structural and dynamic context of selective polypharmacology. In this work, we use molecular dynamics simulations to generate a conformational space of the receptors and subsequently characterize its binding properties applying molecular probe mapping. All-against-all comparison of the generated probe maps of the selected diverse conformations of all receptors with the Tanimoto similarity coefficient (Tc) enable to separate the receptors of group 1 from group 2. The pharmacophore built based on the Tc-selected receptor conformations, using the multiple probe maps discovers structural features that can be used to design molecules selective towards the receptors of group 1. The importance of several predicted residues to ligand selectivity is supported by the available mutagenesis and ligand structure-activity relationships studies. In addition, the Tc-selected conformations of the receptors for group 1 show good performance in isolation of known ligands from a random decoy. Our computational structure-based protocol to tackle selective polypharmacology of antipsychotic drugs could be applied for other diseases involving multiple drug targets, such as oncologic and infectious disorders.

Face Recognition in the Scrambled Domain via Salience-Aware Ensembles of Many Kernels

With the rapid development of internet-of-things (IoT), face scrambling has been proposed for privacy protection during IoT-targeted image/video distribution. Consequently in these IoT applications, biometric verification needs to be carried out in the scrambled domain, presenting significant challenges in face recognition. Since face models become chaotic signals after scrambling/encryption, a typical solution is to utilize traditional data-driven face recognition algorithms. While chaotic pattern recognition is still a challenging task, in this paper we propose a new ensemble approach – Many-Kernel Random Discriminant Analysis (MK-RDA) to discover discriminative patterns from chaotic signals. We also incorporate a salience-aware strategy into the proposed ensemble method to handle chaotic facial patterns in the scrambled domain, where random selections of features are made on semantic components via salience modelling. In our experiments, the proposed MK-RDA was tested rigorously on three human face datasets: the ORL face dataset, the PIE face dataset and the PUBFIG wild face dataset. The experimental results successfully demonstrate that the proposed scheme can effectively handle chaotic signals and significantly improve the recognition accuracy, making our method a promising candidate for secure biometric verification in emerging IoT applications.

Pulsed evaporative cooling of ion cloud in an electron beam ion trap

A technique for producing cold ensembles of trapped highly charged ions is described. The ions, trapped in an electron beam ion trap, can undergo a drastic contraction during the pulsed mode of evaporative cooling, if a truncated Boltzmann distribution is assumed. The underlying theory and the experimental results are presented.

Bandas de sopro – um diálogo transcultural

Brass bands are among the most widespread instrumental ensembles in the world, yet there has been little academic interest in them. This is because they stand in a space between art and authenticity, as their repertoires are thought to lack artistic merit while their military legacies have disconnected them from the ‘authentic’ music of ‘the people’. This paper aims to show how it is precisely this intermediary position which has attracted the attention of some (ethno)musicologists, and a growing number of studies demonstrate the analytic potential of this musical universe in a wide range of contexts across the globe.

Effect of temporal separation on synchronization in rhythmic performance

A variety of short time delays inserted between pairs of subjects were found to affect their ability to synchronize a musical task. The subjects performed a clapping rhythm together from separate sound-isolated rooms via headphones and without visual contact. One-way time delays between pairs were manipulated electronically in the range of 3 to 78 ms. We are interested in quantifying the envelope of time delay within which two individuals produce synchronous per- formances. The results indicate that there are distinct regimes of mutually coupled behavior, and that `natural time delay'o¨delay within the narrow range associated with travel times across spatial arrangements of groups and ensembleso¨supports the most stable performance. Conditions outside of this envelope, with time delays both below and above it, create characteristic interaction dynamics in the mutually coupled actions of the duo. Trials at extremely short delays (corresponding to unnaturally close proximity) had a tendency to accelerate from anticipation. Synchronization lagged at longer delays (larger than usual physical distances) and produced an increasingly severe deceleration and then deterioration of performed rhythms. The study has implications for music collaboration over the Internet and suggests that stable rhythmic performance can be achieved by `wired ensembles' across distances of thousands of kilometers.

Nonlinear excitations in strongly-coupled plasma lattices: envelope solitons, kinks and intrinsic localized modes

Ensembles of charged particles (plasmas) are a highly complex form of matter, most often modeled as a many-body system characterized by weak inter-particle interactions (electrostatic coupling). However, strongly-coupled plasma configurations have recently been produced in laboratory, either by creating ultra-cold plasmas confined in a trap or by manipulating dusty plasmas in discharge experiments. In this paper, the nonlinear aspects involved in the motion of charged dust grains in a one-dimensional plasma monolayer (crystal) are discussed. Different types of collective excitations are reviewed, and characteristics and conditions for their occurrence in dusty plasma crystals are discussed, in a quasi-continuum approximation. Dust crystals are shown to support nonlinear kink-shaped supersonic solitary longitudinal excitations, as well as modulated envelope localized modes associated with longitudinal and transverse vibrations. Furthermore, the possibility for intrinsic localized modes (ILMs) — Discrete Breathers (DBs) — to occur is investigated, from first principles. The effect of mode-coupling is also briefly considered. The relation to previous results on atomic chains, and also to experimental results on strongly-coupled dust layers in gas discharge plasmas, is briefly discussed.

Selective hydrogenation of acetylene in ethylene rich feed streams at high pressure over ligand modified Pd/TiO2

The selective hydrogenation of acetylene from ethylene rich streams was conducted at high pressure and in the presence of CO over two 1 wt% loaded Pd/TiO2 catalysts with differing dispersions. Although, the more poorly dispersed sample did not result in high acetylene conversion only a small proportion of the total available ethylene was hydrogenated to ethane. The more highly dispersed sample was able to remove acetylene to a level below the detection limit but this was at the expense of significant proportion (ca. 30%) of the available ethylene. Modification of the catalysts by exposure to triphenyl phosphine or diphenyl sulfide and subsequent reduction at 393 K led to improved performance with increased conversion of acetylene and decreased propensity to hydrogenate ethylene resulting in an overall net gain in ethylene. The higher dispersed sample which had been ligand modified provided the best results overall and in particular for the diphenyl sulfide treated sample which was able to completely eliminate acetylene and still obtain a net gain in ethylene. The differences observed are thought to be due to the creation of appropriate active ensembles of Pd atoms which are able to accommodate acetylene but have limited ability to adsorb ethylene. Sub-surface hydrogen formation was suppressed, but not eliminated, by exposure to modifier.

Portfolio of Compositions investigating ensemble improvisation, distributed and real-time scoring, and multi-nodal input and output

This output is a collection of compositions which explore issues of ensemble improvisation, ensemble management and orchestration, real-time and distributed scoring, multi-nodal inputs and outputs, and animated and graphic notation. Compositions include: Activities I; tutti, duet, trio, solo, quartet; Lewitt Notations I; Webwork I; and Sometimes I feel the space between people (voices) in terms of tempos. These compositions are presented in computer animated scores which are synchronized through the network and subject to real-time modification and control. They can be performed by ensembles distributed over large physical spaces connected by the network. The scores for these compositions include software which displays the animations to the performers, software to structure and disseminate score events, and triggering software that allows the control of a performance to be distributed. Scores can also include live electronics which are coordinated with graphic events.

Dissipative Optomechanics in a Michelson--Sagnac Interferometer

Dissipative optomechanics studies the coupling of the motion of an optical element to the decay rate of a cavity. We propose and theoretically explore a realization of this system in the optical domain, using a combined Michelson-Sagnac interferometer, which enables a strong and tunable dissipative coupling. Quantum interference in such a setup results in the suppression of the lower motional sideband, leading to strongly enhanced cooling in the non-sideband-resolved regime. With state-of-the-art parameters, ground-state cooling and low-power quantum-limited position transduction are both possible. The possibility of a strong, tunable dissipative coupling opens up a new route towards observation of such fundamental optomechanical effects as nonlinear dynamics. Beyond optomechanics, the suggested method can be readily transferred to other setups involving nonlinear media, atomic ensembles, or single atoms.

Ensemble effects in the coupling of acetylene to benzene on a bimetallic surface: A study with Pd{111}/Au

Acetylene coupling to benzene on the Pd(lll) surface is greatly enhanced by the presence of catalytically inert Au atoms. LEED and Auger spectroscopy show that progressive annealing of Au overlayers on Pd(lll) leads to the formation of a series of random surface alloys with continuously varying composition. Cyclization activity is a strong function of surface composition-the most efficient catalyst corresponds to a surface of composition similar to 85% Pd. CO TPD and HREELS data show that acetylene cyclization activity is not correlated with the availability of singleton Pd atoms, nor just with the presence of 3-fold pure Pd sites-the preferred chemisorption site for C2H2 on Pd{111}. The data can be quantitatively rationalized in terms of a simple model in which catalytic activity is dominated by Pd6Au and Pd-7 surface ensembles, allowance being made for the known degree to which pure Pd{111} decomposes the reactant and product molecules.

Coherently Opening a High-Q Cavity

We propose a general framework to effectively `open' a high-Q resonator, that is, to release the quantum state initially prepared in it in the form of a traveling electromagnetic wave. This is achieved by employing a mediating mode that scatters coherently the radiation from the resonator into a one-dimensional continuum of modes such as a waveguide. The same mechanism may be used to `feed' a desired quantum field to an initially empty cavity. Switching between an `open' and `closed' resonator may then be obtained by controlling either the detuning of the scatterer or the amount of time it spends in the resonator. First, we introduce the model in its general form, identifying (i) the traveling mode that optimally retains the full quantum information of the resonator field and (ii) a suitable figure of merit that we study analytically in terms of the system parameters. Then, we discuss two feasible implementations based on ensembles of two-level atoms interacting with cavity fields. In addition, we discuss how to integrate traditional cavity QED in our proposal using three-level atoms.

Dynamics of interacting Dicke model in a coupled-cavity array

We consider the dynamics of an array of mutually interacting cavities, each containing an ensemble of N two-level atoms. By exploring the possibilities offered by ensembles of various dimensions and a range of atom-light and photon-hopping values, we investigate the generation of multisite entanglement, as well as the performance of excitation transfer across the array, resulting from the competition between on-site nonlinearities of the matter-light interaction and intersite photon hopping. In particular, for a three-cavity interacting system it is observed that the initial excitation in the first cavity completely transfers to the ensemble in the third cavity through the hopping of photons between the adjacent cavities. Probabilities of the transfer of excitation of the cavity modes and ensembles exhibit characteristics of fast and slow oscillations governed by coupling and hopping parameters, respectively. In the large-hopping case, by seeding an initial excitation in the cavity at the center of the array, a tripartite W state, as well as a bipartite maximally entangled state, is obtained, depending on the interaction time. Population of the ensemble in a cavity has a positive impact on the rate of excitation transfer between the ensembles and their local cavity modes. In particular, for ensembles of five to seven atoms, tripartite W states can be produced even when the hopping rate is comparable to the cavity-atom coupling rate. A similar behavior of the transfer of excitation is observed for a four-coupled-cavity system with two initial excitations.