Identification of an unknown b-agonist in feed by liquid chromatography/bioassay/quadrupole time-of-flight tandem mass spectrometry with accurate mass measurement.

A new approach to the search for residues of unknown growth promoting agents such as anabolic steroids and -agonists in feed is presented. Following primary extraction and clean-up, samples are separated using gradient liquid chromatography (LC). The effluent is split towards two identical 96-well fraction collectors and an optional electrospray quadrupole time-of-flight mass spectrometry (QTOFMS) system for accurate mass measurement. One 96-well plate is used for a bioassay (enzyme-immuno assay, receptor assay) and will detect the bioactivity and position of the relevant peak in the chromatogram. The positive well in the second 96-well plate is used for identification by LC/QTOFMS/MS. The value of this LC/bioassay/QTOFMS/MS methodology is highlighted by the finding and structure elucidation of a new -agonist in a feed extract.

Accurate computational methods for two-electron atom-laser interactions

We discuss the application of quantitatively accurate computational methods to the study of laser-driven two-electron atoms in short intense laser pulses. The fundamental importance of such calculations to the subject area is emphasized. Calculations of single- and double-electron ionization rates at 390 nm are presented. (C) 2001 Optical Society of America.

Accurate and efficient non-adiabatic quantum molecular dynamics approach for laser-matter interactions

A non-adiabatic quantum molecular dynamics approach for treating the interaction of matter with intense, short-duration laser pulses is developed. This approach, which is parallelized to run on massively-parallel supercomputers, is shown to be both accurate and efficient. Illustrative results are presented for harmonic generation occurring in diatomic molecules using linearly polarized laser pulses.

A new lead for nonpeptidic active-site-directed inhibitors of the severe acute respiratory syndrome coronavirus main protease discovered by a combination of screening and docking methods.

The coronavirus main protease, Mpro, is considered to be a major target for drugs suitable for combating coronavirus infections including severe acute respiratory syndrome (SARS). An HPLC-based screening of electrophilic compounds that was performed to identify potential Mpro inhibitors revealed etacrynic acid tert-butylamide (6a) as an effective nonpeptidic inhibitor. Docking studies suggested a binding mode in which the phenyl ring acts as a spacer bridging the inhibitor's activated double bond and its hydrophobic tert-butyl moiety. The latter is supposed to fit into the S4 pocket of the target protease. Furthermore, these studies revealed etacrynic acid amide (6b) as a promising lead for nonpeptidic active-site-directed Mpro inhibitors. In a fluorimetric enzyme assay using a novel fluorescence resonance energy transfer (FRET) pair labeled substrate, compound 6b showed a Ki value of 35.3 M. Since the novel lead compound does not target the S1', S1, and S2 subsites of the enzyme's substrate-binding pockets, there is room for improvement that underlines the lead character of compound 6b.

Accurate substrate modelling of RF CMOS

The losses within the substrate of an RF IC can have significant effect on performance in a mixed signal application. in order to model substrate coupling accurately, it is represented by an RC network to account for both resistive and dielectric losses at high frequency (> 1 GHz). A small-signal equivalent circuit model of an RF IC inclusive of substrate parasitic effect is analysed in terms of its y-parameters and an extraction procedure for substrate parameters has been developed. By coupling the extracted substrate parameters along with extrinsic resistances associated with gate, source and drain, a standard BSIM3 model has been extended for RF applications. The new model exhibits a significant improvement in prediction of output reflection coefficient S-22 in the frequency range from 1 to 10 GHz in device mode of operation and for a low noise amplifier (LNA) at 2.4 GHz. Copyright (C) 2006 John Wiley & Sons, Ltd.

Accurate available bandwidth estimation in IEEE 802.11-based ad hoc networks

Quality of Service (QoS) support in IEEE 802.11-based ad hoc networks relies on the networks’ ability to estimate the available bandwidth on a given link. However, no mechanism has been standardized to accurately evaluate this resource. This remains one of the main issues open to research in this field. This paper proposes an available bandwidth estimation approach which achieves more accurate estimation when compared to existing research. The proposed approach differentiates the channel busy caused by transmitting or receiving from that caused by carrier sensing, and thus improves the accuracy of estimating the overlap probability of two adjacent nodes’ idle time. Simulation results testify the improvement of this approach when compared with well known bandwidth estimation methods in the literature.

Simple and accurate analytical model of planar grids and high-impedance surfaces, comprising metal strips or patches

Simple analytical formulas are introduced for the grid impedance of electrically dense arrays of square patches and for the surface impedance of high-impedance surfaces based on the dense arrays of metal strips or square patches over ground planes. Emphasis is on the oblique-incidence excitation. The approach is based on the known analytical models for strip grids combined with the approximate Babinet principle for planar grids located at a dielectric interface. Analytical expressions for the surface impedance and reflection coefficient resulting from our analysis are thoroughly verified by full-wave simulations and compared with available data in open literature for particular cases. The results can be used in the design of various antennas and microwave or millimeter wave devices which use artificial impedance surfaces and artificial magnetic conductors (reflect-array antennas, tunable phase shifters, etc.), as well as for the derivation of accurate higher-order impedance boundary conditions for artificial (high-) impedance surfaces. As an example, the propagation properties of surface waves along the high-impedance surfaces are studied.

Rhodopsin and the Others: A Historical Perspective on Structural Studies of G Protein-Coupled Receptors

The role of rhodopsin as a structural prototype for the study of the whole superfamily of G protein-coupled receptors (GPCRs) is reviewed in an historical perspective. Discovered at the end of the nineteenth century, fully sequenced since the early 1980s, and with direct three-dimensional information available since the 1990s, rhodopsin has served as a platform to gather indirect information on the structure of the other superfamily members. Recent breakthroughs have elicited the solution of the structures of additional receptors, namely the beta 1- and beta 2-adrenergic receptors and the A(2A) adenosine receptor, now providing an opportunity to gauge the accuracy of homology modeling and molecular docking techniques and to perfect the computational protocol. Notably, in coordination with the solution of the structure of the A(2A) adenosine receptor, the first "critical assessment of GPCR structural modeling and docking" has been organized, the results of which highlighted that the construction of accurate models, although challenging, is certainly achievable. The docking of the ligands and the scoring of the poses clearly emerged as the most difficult components. A further goal in the field is certainly to derive the structure of receptors in their signaling state, possibly in complex with agonists. These advances, coupled with the introduction of more sophisticated modeling algorithms and the increase in computer power, raise the expectation for a substantial boost of the robustness and accuracy of computer-aided drug discovery techniques in the coming years.

Towards accurate estimation of the proportion of true null hypotheses in multiple testing

Background

Biomedical researchers are now often faced with situations where it is necessary to test a large number of hypotheses simultaneously, eg, in comparative gene expression studies using high-throughput microarray technology. To properly control false positive errors the FDR (false discovery rate) approach has become widely used in multiple testing. The accurate estimation of FDR requires the proportion of true null hypotheses being accurately estimated. To date many methods for estimating this quantity have been proposed. Typically when a new method is introduced, some simulations are carried out to show the improved accuracy of the new method. However, the simulations are often very limited to covering only a few points in the parameter space.

Results

Here I have carried out extensive in silico experiments to compare some commonly used methods for estimating the proportion of true null hypotheses. The coverage of these simulations is unprecedented thorough over the parameter space compared to typical simulation studies in the literature. Thus this work enables us to draw conclusions globally as to the performance of these different methods. It was found that a very simple method gives the most accurate estimation in a dominantly large area of the parameter space. Given its simplicity and its overall superior accuracy I recommend its use as the first choice for estimating the proportion of true null hypotheses in multiple testing.

A 60 GHz wide tuning range SiGe bipolar VCO for HDMI and wireless docking applications

A wide tuning range voltage controlled oscillator (VCO) with novel architecture is proposed in this work. The entire circuit consists of a VCO core, a summing circuit, a single-ended to differential (STD) converter and a buffer amplifier. The VCO core oscillates at half the desired frequency and the second harmonic of the VCO core is extracted by the summing circuit, which is then converted to a differential pair by the STD. The entire VCO circuit operates from 58.85 to 70.85 GHz with 20% frequency tuning range. The measured VCO gain is less than 1.6 GHz/V. The measured phase noise at 3 MHz offset is less than -78 dBc/Hz across the entire tuning range. The differential phase error of the output signals is measured by down converting the VCO output signals to low gigahertz frequency using an on-chip mixer. The measured differential phase error is less than 8°. The VCO circuit, which is constructed using 0.35 µm SiGe technology, occupies 770 × 550 µm2 die area and consumes 62 mA under 3.5 V supply.