On the hierarchical classification of G protein-coupled receptors

MOTIVATION: G protein-coupled receptors (GPCRs) play an important role in many physiological systems by transducing an extracellular signal into an intracellular response. Over 50% of all marketed drugs are targeted towards a GPCR. There is considerable interest in developing an algorithm that could effectively predict the function of a GPCR from its primary sequence. Such an algorithm is useful not only in identifying novel GPCR sequences but in characterizing the interrelationships between known GPCRs. RESULTS: An alignment-free approach to GPCR classification has been developed using techniques drawn from data mining and proteochemometrics. A dataset of over 8000 sequences was constructed to train the algorithm. This represents one of the largest GPCR datasets currently available. A predictive algorithm was developed based upon the simplest reasonable numerical representation of the protein's physicochemical properties. A selective top-down approach was developed, which used a hierarchical classifier to assign sequences to subdivisions within the GPCR hierarchy. The predictive performance of the algorithm was assessed against several standard data mining classifiers and further validated against Support Vector Machine-based GPCR prediction servers. The selective top-down approach achieves significantly higher accuracy than standard data mining methods in almost all cases.

Responsive brushes and gels as components of soft nanotechnology

Progress in the development of generic molecular devices based on responsive polymers is discussed. Characterisation of specially synthesised polyelectrolyte gels, "grafted from" brushes and triblock copolymers is reported. A Landolt pH-oscillator, based on bromate/ sulfite/ferrocyanide, with a room temperature period of 20 min and a range of 3.1

Phase noise influence in coherent optical DnPSK systems with DSP based dispersion compensation

We present a comparative study of the influence of dispersion induced phase noise for n-level PSK systems. From the analysis, we conclude that the phase noise influence for classical homodyne/heterodyne PSK systems is entirely determined by the modulation complexity (expressed in terms of constellation diagram) and the analogue demodulation format. On the other hand, the use of digital signal processing (DSP) in homodyne/intradyne systems renders a fiber length dependence originating from the generation of equalization enhanced phase noise. For future high capacity systems, high constellations must be used in order to lower the symbol rate to practically manageable speeds, and this fact puts severe requirements to the signal and local oscillator (LO) linewidths. Our results for the bit-error-rate (BER) floor caused by the phase noise influence in the case of QPSK, 16PSK and 64PSK systems outline tolerance limitations for the LO performance: 5 MHz linewidth (at 3-dB level) for 100 Gbit/s QPSK; 1 MHz for 400 Gbit/s QPSK; 0.1 MHz for 400 Gbit/s 16PSK and 1 Tbit/s 64PSK systems. This defines design constrains for the phase noise impact in distributed-feed-back (DFB) or distributed-Bragg-reflector (DBR) semiconductor lasers, that would allow moving the system capacity from 100 Gbit/s system capacity to 400 Gbit/s in 3 years (1 Tbit/s in 5 years). It is imperative at the same time to increase the analogue to digital conversion (ADC) speed such that the single quadrature symbol rate goes from today's 25 GS/s to 100 GS/s (using two samples per symbol). © 2014 by Walter de Gruyter Berlin/Boston.

Analytical model for active metamaterials with quantum ingredients

We present an analytical model for describing complex dynamics of a hybrid system consisting of resonantly coupled classical resonator and quantum structures. Classical resonators in our model correspond to plasmonic metamaterials of various geometries, as well as other types of nano- and microstructure, the optical responses of which can be described classically. Quantum resonators are represented by atoms or molecules, or their aggregates (for example, quantum dots, carbon nanotubes, dye molecules, polymer or bio-molecules etc), which can be accurately modelled only with the use of the quantum mechanical approach. Our model is based on the set of equations that combines well established density matrix formalism appropriate for quantum systems, coupled with harmonic-oscillator equations ideal for modelling sub-wavelength plasmonic and optical resonators. As a particular example of application of our model, we show that the saturation nonlinearity of carbon nanotubes increases multifold in the resonantly enhanced near field of a metamaterial. In the framework of our model, we discuss the effect of inhomogeneity of the carbon-nanotube layer (bandgap value distribution) on the nonlinearity enhancement. © 2012 IOP Publishing Ltd.

Structural basis for receptor activity-modifying protein-dependent selective peptide recognition by a G protein-coupled receptor

Association of receptor activity-modifying proteins (RAMP1-3) with the G protein-coupled receptor (GPCR) calcitonin receptor-like receptor (CLR) enables selective recognition of the peptides calcitonin gene-related peptide (CGRP) and adrenomedullin (AM) that have diverse functions in the cardiovascular and lymphatic systems. How peptides selectively bind GPCR:RAMP complexes is unknown. We report crystal structures of CGRP analog-bound CLR:RAMP1 and AM-bound CLR:RAMP2 extracellular domain heterodimers at 2.5 and 1.8 Å resolutions, respectively. The peptides similarly occupy a shared binding site on CLR with conformations characterized by a β-turn structure near their C termini rather than the α-helical structure common to peptides that bind related GPCRs. The RAMPs augment the binding site with distinct contacts to the variable C-terminal peptide residues and elicit subtly different CLR conformations. The structures and accompanying pharmacology data reveal how a class of accessory membrane proteins modulate ligand binding of a GPCR and may inform drug development targeting CLR:RAMP complexes.

Existence Theorems for Non-Cooperative Elliptic Systems

2010 Mathematics Subject Classification: 35J65, 35K60, 35B05, 35R05.

Impact of inter-modal four-wave mixing on the performance of mode- and wavelength-division-multiplexing systems

In this paper, we investigate the impact of inter-modal four-wave mixing on mode- and wavelength-division-multiplexing systems. A set of coupled nonlinear Schrödinger equations, including linear mode coupling, is derived allowing to isolate the inter-modal four-wave mixing terms. The efficiency of inter-modal four-wave mixing between degenerate LP modes is found to be significantly higher than the intra-modal four-wave mixing efficiency. However, it is shown that the inter-modal four-wave mixing efficiency between degenerate modes is significantly reduced by the linear mode coupling.

High frequency inverter topologies integrated with the coupled inductor bridge arm

A new topology of the high frequency alternating current (HFAC) inverter bridge arm is proposed which comprises a coupled inductor, a switching device and an active clamp circuit. Based on it, new single-phase and threephase inverters are proposed and their operating states are analysed along with the traditional H-bridge inverter. Multiphase and multi-level isolated inverters are also developed using the HFAC bridge arm. Furthermore, based on the proposed HFAC, a front-end DC-DC converter is also developed for photovoltaic systems to demonstrate the application of the proposed HFAC converter. Simulation and experimental results from prototype converters are carried out to validate the proposed topologies which can be utilised widely in high frequency power conversion applications such as induction heating and wireless power transfer.

Institutional complexity in Thai state-owned enterprises:the implementation of performance measurement systems

This study explores institutional complexity in Thai State-Owned Enterprises (SOEs). In doing so, a qualitative approach has been employed in this study in order to identify institutional logics in the field of Thai SOEs and to understand organisational and individual perceptions of institutional complexity in the implementation of performance measurement systems (PMS) and how they respond to the complexity. To achieve this goal, two Thai SOEs were studied, both of which faced challenges in the implementation of Economic Value Management (EVM) and Balance Scorecard (BSC) as well as difficulties in linking their individual BSC and incentive systems. The qualitative data were collected from semi-structured interviews and document reviews. The empirical aspects of this study reveal that the institutional logics in the field of Thai SOEs are the logic of bureaucracy, commercial operations, social activities, seniority and unity. Regarding the multiple institutional logics embedded, SOEs experienced the institutional complexity in the implementation of PMS. The results suggest that the organisations have decoupled the EVM and loosely coupled the BSC from organisational practices to cope with institutional complexity and conflict institutional demands. Also, the evidence shows that the institutional logics influence SOEs’ actions towards resisting changes incentive systems and the relationship between individual BSC and incentives.

A multimedia indexing and retrieval framework for multimedia database systems

The main challenges of multimedia data retrieval lie in the effective mapping between low-level features and high-level concepts, and in the individual users' subjective perceptions of multimedia content. ^ The objectives of this dissertation are to develop an integrated multimedia indexing and retrieval framework with the aim to bridge the gap between semantic concepts and low-level features. To achieve this goal, a set of core techniques have been developed, including image segmentation, content-based image retrieval, object tracking, video indexing, and video event detection. These core techniques are integrated in a systematic way to enable the semantic search for images/videos, and can be tailored to solve the problems in other multimedia related domains. In image retrieval, two new methods of bridging the semantic gap are proposed: (1) for general content-based image retrieval, a stochastic mechanism is utilized to enable the long-term learning of high-level concepts from a set of training data, such as user access frequencies and access patterns of images. (2) In addition to whole-image retrieval, a novel multiple instance learning framework is proposed for object-based image retrieval, by which a user is allowed to more effectively search for images that contain multiple objects of interest. An enhanced image segmentation algorithm is developed to extract the object information from images. This segmentation algorithm is further used in video indexing and retrieval, by which a robust video shot/scene segmentation method is developed based on low-level visual feature comparison, object tracking, and audio analysis. Based on shot boundaries, a novel data mining framework is further proposed to detect events in soccer videos, while fully utilizing the multi-modality features and object information obtained through video shot/scene detection. ^ Another contribution of this dissertation is the potential of the above techniques to be tailored and applied to other multimedia applications. This is demonstrated by their utilization in traffic video surveillance applications. The enhanced image segmentation algorithm, coupled with an adaptive background learning algorithm, improves the performance of vehicle identification. A sophisticated object tracking algorithm is proposed to track individual vehicles, while the spatial and temporal relationships of vehicle objects are modeled by an abstract semantic model. ^

Design and fabrication of two switched superconductivity microstrip hairpin filters using series micro-electro-mechanical systems (MEMS) switches

Series Micro-Electro-Mechanical System (MEMS) switches based on superconductor are utilized to switch between two bandpass hairpin filters with bandwidths of 365 MHz and nominal center frequencies of 2.1 GHz and 2.6 GHz. This was accomplished with 4 switches actuated in pairs, one pair at a time. When one pair was actuated the first bandpass filter was coupled to the input and output ports. When the other pair was actuated the second bandpass filter was coupled to the input and output ports. The device is made of a YBa2Cu 3O7 thin film deposited on a 20 mm x 20 mm LaAlO3 substrate by pulsed laser deposition. BaTiO3 deposited by RF magnetron sputtering in utilized as the insulation layer at the switching points of contact. These results obtained assured great performance showing a switchable device at 68 V with temperature of 40 K for the 2.1 GHz filter and 75 V with temperature of 30 K for the 2.6 GHz hairpin filter. ^

Next generation high density three-dimensional magnetic recording systems

This work is the first work using patterned soft underlayers in multilevel three-dimensional vertical magnetic data storage systems. The motivation stems from an exponentially growing information stockpile, and a corresponding need for more efficient storage devices with higher density. The world information stockpile currently exceeds 150EB (ExaByte=1x1018Bytes); most of which is in analog form. Among the storage technologies (semiconductor, optical and magnetic), magnetic hard disk drives are posed to occupy a big role in personal, network as well as corporate storage. However; this mode suffers from a limit known as the Superparamagnetic limit; which limits achievable areal density due to fundamental quantum mechanical stability requirements. There are many viable techniques considered to defer superparamagnetism into the 100's of Gbit/in2 such as: patterned media, Heat-Assisted Magnetic Recording (HAMR), Self Organized Magnetic Arrays (SOMA), antiferromagnetically coupled structures (AFC), and perpendicular magnetic recording. Nonetheless, these techniques utilize a single magnetic layer; and can thusly be viewed as two-dimensional in nature. In this work a novel three-dimensional vertical magnetic recording approach is proposed. This approach utilizes the entire thickness of a magnetic multilayer structure to store information; with potential areal density well into the Tbit/in2 regime. ^ There are several possible implementations for 3D magnetic recording; each presenting its own set of requirements, merits and challenges. The issues and considerations pertaining to the development of such systems will be examined, and analyzed using empirical and numerical analysis techniques. Two novel key approaches are proposed and developed: (1) Patterned soft underlayer (SUL) which allows for enhanced recording of thicker media, (2) A combinatorial approach for 3D media development that facilitates concurrent investigation of various film parameters on a predefined performance metric. A case study is presented using combinatorial overcoats of Tantalum and Zirconium Oxides for corrosion protection in magnetic media. ^ Feasibility of 3D recording is demonstrated, and an emphasis on 3D media development is emphasized as a key prerequisite. Patterned SUL shows significant enhancement over conventional "un-patterned" SUL, and shows that geometry can be used as a design tool to achieve favorable field distribution where magnetic storage and magnetic phenomena are involved. ^

Fluorescence-enhanced optical imaging on three-dimensional phantoms using a hand-held probe based frequency-domain intensified charge coupled device (ICCD) optical imager

Fluorescence-enhanced optical imaging is an emerging non-invasive and non-ionizing modality towards breast cancer diagnosis. Various optical imaging systems are currently available, although most of them are limited by bulky instrumentation, or their inability to flexibly image different tissue volumes and shapes. Hand-held based optical imaging systems are a recent development for its improved portability, but are currently limited only to surface mapping. Herein, a novel optical imager, consisting primarily of a hand-held probe and a gain-modulated intensified charge coupled device (ICCD) detector, is developed towards both surface and tomographic breast imaging. The unique features of this hand-held probe based optical imager are its ability to; (i) image large tissue areas (5×10 sq. cm) in a single scan, (ii) reduce overall imaging time using a unique measurement geometry, and (iii) perform tomographic imaging for tumor three-dimensional (3-D) localization. Frequency-domain based experimental phantom studies have been performed on slab geometries (650 ml) under different target depths (1-2.5 cm), target volumes (0.45, 0.23 and 0.10 cc), fluorescence absorption contrast ratios (1:0, 1000:1 to 5:1), and number of targets (up to 3), using Indocyanine Green (ICG) as fluorescence contrast agents. An approximate extended Kalman filter based inverse algorithm has been adapted towards 3-D tomographic reconstructions. Single fluorescence target(s) was reconstructed when located: (i) up to 2.5 cm deep (at 1:0 contrast ratio) and 1.5 cm deep (up to 10:1 contrast ratio) for 0.45 cc-target; and (ii) 1.5 cm deep for target as small as 0.10 cc at 1:0 contrast ratio. In the case of multiple targets, two targets as close as 0.7 cm were tomographically resolved when located 1.5 cm deep. It was observed that performing multi-projection (here dual) based tomographic imaging using a priori target information from surface images, improved the target depth recovery over using single projection based imaging. From a total of 98 experimental phantom studies, the sensitivity and specificity of the imager was estimated as 81-86% and 43-50%, respectively. With 3-D tomographic imaging successfully demonstrated for the first time using a hand-held based optical imager, the clinical translation of this technology is promising upon further experimental validation from in-vitro and in-vivo studies.

Elemental analysis of glass and ink by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) and laser induced breakdown spectroscopy (LIBS)

The necessity of elemental analysis techniques to solve forensic problems continues to expand as the samples collected from crime scenes grow in complexity. Laser ablation ICP-MS (LA-ICP-MS) has been shown to provide a high degree of discrimination between samples that originate from different sources. In the first part of this research, two laser ablation ICP-MS systems were compared, one using a nanosecond laser and another a femtosecond laser source for the forensic analysis of glass. The results showed that femtosecond LA-ICP-MS did not provide significant improvements in terms of accuracy, precision and discrimination, however femtosecond LA-ICP-MS did provide lower detection limits. In addition, it was determined that even for femtosecond LA-ICP-MS an internal standard should be utilized to obtain accurate analytical results for glass analyses. In the second part, a method using laser induced breakdown spectroscopy (LIBS) for the forensic analysis of glass was shown to provide excellent discrimination for a glass set consisting of 41 automotive fragments. The discrimination power was compared to two of the leading elemental analysis techniques, μXRF and LA-ICP-MS, and the results were similar; all methods generated >99% discrimination and the pairs found indistinguishable were similar. An extensive data analysis approach for LIBS glass analyses was developed to minimize Type I and II errors en route to a recommendation of 10 ratios to be used for glass comparisons. Finally, a LA-ICP-MS method for the qualitative analysis and discrimination of gel ink sources was developed and tested for a set of ink samples. In the first discrimination study, qualitative analysis was used to obtain 95.6% discrimination for a blind study consisting of 45 black gel ink samples provided by the United States Secret Service. A 0.4% false exclusion (Type I) error rate and a 3.9% false inclusion (Type II) error rate was obtained for this discrimination study. In the second discrimination study, 99% discrimination power was achieved for a black gel ink pen set consisting of 24 self collected samples. The two pairs found to be indistinguishable came from the same source of origin (the same manufacturer and type of pen purchased in different locations). It was also found that gel ink from the same pen, regardless of the age, was indistinguishable as were gel ink pens (four pens) originating from the same pack.

The development of optimized high performance liquid chromatography systems for the analysis of improvised explosives

Existing instrumental techniques must be adaptable to the analysis of novel explosives if science is to keep up with the practices of terrorists and criminals. The focus of this work has been the development of analytical techniques for the analysis of two types of novel explosives: ascorbic acid-based propellants, and improvised mixtures of concentrated hydrogen peroxide/fuel. In recent years, the use of these explosives in improvised explosive devices (IEDs) has increased. It is therefore important to develop methods which permit the identification of the nature of the original explosive from post-blast residues. Ascorbic acid-based propellants are low explosives which employ an ascorbic acid fuel source with a nitrate/perchlorate oxidizer. A method which utilized ion chromatography with indirect photometric detection was optimized for the analysis of intact propellants. Post-burn and post-blast residues if these propellants were analyzed. It was determined that the ascorbic acid fuel and nitrate oxidizer could be detected in intact propellants, as well as in the post-burn and post-blast residues. Degradation products of the nitrate and perchlorate oxidizers were also detected. With a quadrupole time-of-flight mass spectrometer (QToFMS), exact mass measurements are possible. When an HPLC instrument is coupled to a QToFMS, the combination of retention time with accurate mass measurements, mass spectral fragmentation information, and isotopic abundance patterns allows for the unequivocal identification of a target analyte. An optimized HPLC-ESI-QToFMS method was applied to the analysis of ascorbic acid-based propellants. Exact mass measurements were collected for the fuel and oxidizer anions, and their degradation products. Ascorbic acid was detected in the intact samples and half of the propellants subjected to open burning; the intact fuel molecule was not detected in any of the post-blast residue. Two methods were optimized for the analysis of trace levels of hydrogen peroxide: HPLC with fluorescence detection (HPLC-FD), and HPLC with electrochemical detection (HPLC-ED). Both techniques were extremely selective for hydrogen peroxide. Both methods were applied to the analysis of post-blast debris from improvised mixtures of concentrated hydrogen peroxide/fuel; hydrogen peroxide was detected on variety of substrates. Hydrogen peroxide was detected in the post-blast residues of the improvised explosives TATP and HMTD.