High-throughput proteomics using matrix-assisted laser desorption/ionization mass spectrometry

It has become evident that the mystery of life will not be deciphered just by decoding its blueprint, the genetic code. In the life and biomedical sciences, research efforts are now shifting from pure gene analysis to the analysis of all biomolecules involved in the machinery of life. One area of these postgenomic research fields is proteomics. Although proteomics, which basically encompasses the analysis of proteins, is not a new concept, it is far from being a research field that can rely on routine and large-scale analyses. At the time the term proteomics was coined, a gold-rush mentality was created, promising vast and quick riches (i.e., solutions to the immensely complex questions of life and disease). Predictably, the reality has been quite different. The complexity of proteomes and the wide variations in the abundances and chemical properties of their constituents has rendered the use of systematic analytical approaches only partially successful, and biologically meaningful results have been slow to arrive. However, to learn more about how cells and, hence, life works, it is essential to understand the proteins and their complex interactions in their native environment. This is why proteomics will be an important part of the biomedical sciences for the foreseeable future. Therefore, any advances in providing the tools that make protein analysis a more routine and large-scale business, ideally using automated and rapid analytical procedures, are highly sought after. This review will provide some basics, thoughts and ideas on the exploitation of matrix-assisted laser desorption/ionization in biological mass spectrometry - one of the most commonly used analytical tools in proteomics - for high-throughput analyses.

Formation of high levels of acrylamide during the processing of flour derived from sulfate-deprived wheat

When wheat was grown under conditions of severe sulfate depletion, dramatic increases in the concentration of free asparagine were found in the grain of up to 30 times as compared to samples receiving the normal levels of sulfate fertilizer. The effect was observed both in plants grown in pots, where the levels of nutrients were carefully controlled, and in plants grown in field trials on soil with poor levels of natural nutrients where sulfate fertilizer was applied at levels from 0 to 40 kg sulfur/Ha. Many of the other free amino acids were present at higher levels in the sulfate-deprived wheat, but the levels of free glutamine showed increases similar to those observed for asparagine. In baked cereal products, asparagine is the precursor of the suspect carcinogen acrylamide, and when flours from the sulfate-deprived wheat were heated at 160 degrees C for 20 min, levels of acrylamide between 2600 and 5200 mu g/kg were found as compared to 600-900 mu g/kg in wheat grown with normal levels of sulfate fertilization.

A practical method for testing high-speed networking hardware architectures

This paper deals with the key issues encountered in testing during the development of high-speed networking hardware systems by documenting a practical method for "real-life like" testing. The proposed method is empowered by modern and commonly available Field Programmable Gate Array (FPGA) technology. Innovative application of standard FPGA blocks in combination with reconfigurability are used as a back-bone of the method. A detailed elaboration of the method is given so as to serve as a general reference. The method is fully characterised and compared to alternatives through a case study proving it to be the most efficient and effective one at a reasonable cost.

Classification of instability modes in a model of aluminium reduction cells with a uniform magnetic field

A unified view on the interfacial instability in a model of aluminium reduction cells in the presence of a uniform, vertical, background magnetic field is presented. The classification of instability modes is based on the asymptotic theory for high values of parameter β, which characterises the ratio of the Lorentz force based on the disturbance current, and gravity. It is shown that the spectrum of the travelling waves consists of two parts independent of the horizontal cross-section of the cell: highly unstable wall modes and stable or weakly unstable centre, or Sele’s modes. The wall modes with the disturbance of the interface being localised at the sidewalls of the cell dominate the dynamics of instability. Sele’s modes are characterised by a distributed disturbance over the whole horizontal extent of the cell. As β increases these modes are stabilized by the field.

The advection of high-resolution tracers by low-resolution winds

The usefulness of any simulation of atmospheric tracers using low-resolution winds relies on both the dominance of large spatial scales in the strain and time dependence that results in a cascade in tracer scales. Here, a quantitative study on the accuracy of such tracer studies is made using the contour advection technique. It is shown that, although contour stretching rates are very insensitive to the spatial truncation of the wind field, the displacement errors in filament position are sensitive. A knowledge of displacement characteristics is essential if Lagrangian simulations are to be used for the inference of airmass origin. A quantitative lower estimate is obtained for the tracer scale factor (TSF): the ratio of the smallest resolved scale in the advecting wind field to the smallest “trustworthy” scale in the tracer field. For a baroclinic wave life cycle the TSF = 6.1 ± 0.3 while for the Northern Hemisphere wintertime lower stratosphere the TSF = 5.5 ± 0.5, when using the most stringent definition of the trustworthy scale. The similarity in the TSF for the two flows is striking and an explanation is discussed in terms of the activity of potential vorticity (PV) filaments. Uncertainty in contour initialization is investigated for the stratospheric case. The effect of smoothing initial contours is to introduce a spinup time, after which wind field truncation errors take over from initialization errors (2–3 days). It is also shown that false detail from the proliferation of finescale filaments limits the useful lifetime of such contour advection simulations to 3σ−1 days, where σ is the filament thinning rate, unless filaments narrower than the trustworthy scale are removed by contour surgery. In addition, PV analysis error and diabatic effects are so strong that only PV filaments wider than 50 km are at all believable, even for very high-resolution winds. The minimum wind field resolution required to accurately simulate filaments down to the erosion scale in the stratosphere (given an initial contour) is estimated and the implications for the modeling of atmospheric chemistry are briefly discussed.

Multivariable cluster analysis for high-speed industrial machinery

The overall operation and internal complexity of a particular production machinery can be depicted in terms of clusters of multidimensional points which describe the process states, the value in each point dimension representing a measured variable from the machinery. The paper describes a new cluster analysis technique for use with manufacturing processes, to illustrate how machine behaviour can be categorised and how regions of good and poor machine behaviour can be identified. The cluster algorithm presented is the novel mean-tracking algorithm, capable of locating N-dimensional clusters in a large data space in which a considerable amount of noise is present. Implementation of the algorithm on a real-world high-speed machinery application is described, with clusters being formed from machinery data to indicate machinery error regions and error-free regions. This analysis is seen to provide a promising step ahead in the field of multivariable control of manufacturing systems.

Induced random fields in the LiHoxY1-xF4 quantum ising magnet in a transverse magnetic field

The LiHoxY1-xF4 magnetic material in a transverse magnetic field Bxx̂ perpendicular to the Ising spin direction has long been used to study tunable quantum phase transitions in a random disordered system. We show that the Bx-induced magnetization along the x̂ direction, combined with the local random dilution-induced destruction of crystalline symmetries, generates, via the predominant dipolar interactions between Ho3+ ions, random fields along the Ising ẑ direction. This identifies LiHoxY1-xF4 in Bx as a new random field Ising system. The random fields explain the rapid decrease of the critical temperature in the diluted ferromagnetic regime and the smearing of the nonlinear susceptibility at the spin-glass transition with increasing Bx and render the Bx-induced quantum criticality in LiHoxY1-xF4 likely inaccessible.

Reversible addition of CO to coordinatively unsaturated high-spin iron(II) complexes

Several new coordinatively unsaturated iron(II) complexes of the types [Fe(EN-iPr)X2] (E = P, S, Se; X = Cl, Br) and [Fe(ON-iPr)2X]X containing bidentate EN ligands based on N-(2-pyridinyl)aminophosphines as well as oxo, thio, and seleno derivatives thereof were prepared and characterized by NMR spectroscopy and X-ray crystallography. Mössbauer spectroscopy and magnetization studies confirmed their high-spin nature with magnetic moments very close to 4.9 μB, reflecting the expected four unpaired d-electrons in all these compounds. Stable low-spin carbonyl complexes of the types [Fe(PN-iPr)2(CO)X]X (X = Cl, Br) and cis-CO,cis-Br-[Fe(PN-iPr)(CO)2X2] (X = Br) were obtained by reacting cis-Fe(CO)4X2 with the stronger PN donor ligands, but not with the weaker EN donor ligands (E = O, S, Se). Furthermore, the reactivity of [Fe(PN-iPr)X2] toward CO was investigated by IR spectroscopy. Whereas at room temperature no reaction took place, at −50 °C [Fe(PN-iPr)X2] added readily CO to form, depending on the nature of X, the mono- and dicarbonyl complexes [Fe(PN-iPr)(X)2(CO)] (X = Cl) and [Fe(PN-iPr)(CO)2X2] (X = Cl, Br), respectively. In the case of X = Br, two isomeric dicarbonyl complexes, namely, cis-CO,trans-Br-[Fe(PN-iPr)(CO)2Br2] (major species) and cis-CO,cis-Br-[Fe(PN-iPr)(CO)2Br2] (minor species), are formed. The addition of CO to [Fe(PN-iPr)X2] was investigated in detail by means of DFT/B3LYP calculations. This study strongly supports the experimental findings that at low temperature two isomeric low-spin dicarbonyl complexes are formed. For kinetic reasons cis,trans-[Fe(PN-iPr)(CO)2Br2] releases CO at elevated temperature, re-forming [Fe(PN-iPr)Br2], while the corresponding cis,cis isomer is stable under these conditions.

Upper-ocean heat budget and ocean eddy transport in the south-east Pacific in a high-resolution coupled model

We present an analysis of the oceanic heat advection and its variability in the upper 500 m in the southeastern tropical Pacific (100W–75W, 25S–10S) as simulated by the global coupled model HiGEM, which has one of the highest resolutions currently used in long-term integrations. The simulated climatology represents a temperature advection field arising from transient small-scale (<450 km) features, with structures and transport that appear consistent with estimates based on available observational data for the mooring at 20S, 85W. The transient structures are very persistent (>4 months), and in specific locations they generate an important contribution to the local upper-ocean heat budget, characterised by scales of a few hundred kilometres, and periods of over a year. The contribution from such structures to the local, long-term oceanic heat budget however can be of either sign, or vanishing, depending on the location; and, although there appears some organisation in preferential areas of activity, the average over the entire region is small. While several different mechanisms may be responsible for the temperature advection by transients, we find that a significant, and possibly dominant, component is associated with vortices embedded in the large-scale, climatological salinity gradient associated with the fresh intrusion of mid-latitude intermediate water which penetrates north-westward beneath the tropical thermocline

Numerical-asymptotic boundary integral methods in high-frequency acoustic scattering

In this article we describe recent progress on the design, analysis and implementation of hybrid numerical-asymptotic boundary integral methods for boundary value problems for the Helmholtz equation that model time harmonic acoustic wave scattering in domains exterior to impenetrable obstacles. These hybrid methods combine conventional piecewise polynomial approximations with high-frequency asymptotics to build basis functions suitable for representing the oscillatory solutions. They have the potential to solve scattering problems accurately in a computation time that is (almost) independent of frequency and this has been realized for many model problems. The design and analysis of this class of methods requires new results on the analysis and numerical analysis of highly oscillatory boundary integral operators and on the high-frequency asymptotics of scattering problems. The implementation requires the development of appropriate quadrature rules for highly oscillatory integrals. This article contains a historical account of the development of this currently very active field, a detailed account of recent progress and, in addition, a number of original research results on the design, analysis and implementation of these methods.

Hydrochemical processes in lowland rivers: insights from in situ, high-resolution monitoring

This paper introduces new insights into the hydrochemical functioning of lowland river systems using field-based spectrophotometric and electrode technologies. The streamwater concentrations of nitrogen species and phosphorus fractions were measured at hourly intervals on a continuous basis at two contrasting sites on tributaries of the River Thames – one draining a rural catchment, the River Enborne, and one draining a more urban system, The Cut. The measurements complement those from an existing network of multi-parameter water quality sondes maintained across the Thames catchment and weekly monitoring based on grab samples. The results of the sub-daily monitoring show that streamwater phosphorus concentrations display highly complex dynamics under storm conditions dependent on the antecedent catchment wetness, and that diurnal phosphorus and nitrogen cycles occur under low flow conditions. The diurnal patterns highlight the dominance of sewage inputs in controlling the streamwater phosphorus and nitrogen concentrations at low flows, even at a distance of 7 km from the nearest sewage treatment works in the rural River Enborne. The time of sample collection is important when judging water quality against ecological thresholds or standards. An exhaustion of the supply of phosphorus from diffuse and multiple septic tank sources during storm events was evident and load estimation was not improved by sub-daily monitoring beyond that achieved by daily sampling because of the eventual reduction in the phosphorus mass entering the stream during events. The results highlight the utility of sub-daily water quality measurements and the discussion considers the practicalities and challenges of in situ, sub-daily monitoring.

Absolute high spectral resolution measurements of surface solar radiation for detection of water vapour continuum absorption

Solar-pointing Fourier transform infrared (FTIR) spectroscopy offers the capability to measure both the fine scale and broadband spectral structure of atmospheric transmission simultaneously across wide spectral regions. It is therefore suited to the study of both water vapour monomer and continuum absorption behaviours. However, in order to properly address this issue, it is necessary to radiatively calibrate the FTIR instrument response. A solar-pointing high-resolution FTIR spectrometer was deployed as part of the ‘Continuum Absorption by Visible and Infrared radiation and its Atmospheric Relevance’ (CAVIAR) consortium project. This paper describes the radiative calibration process using an ultra-high-temperature blackbody and the consideration of the related influence factors. The result is a radiatively calibrated measurement of the solar irradiation at the ground across the IR region from 2000 to 10 000 cm−1 with an uncertainty of between 3.3 and 5.9 per cent. This measurement is shown to be in good general agreement with a radiative-transfer model. The results from the CAVIAR field measurements are being used in ongoing studies of atmospheric absorbers, in particular the water vapour continuum.

High leverage interventions: three cases of defensive action and their lessons for OR/MS today.

This paper has two aims. First, to present cases in which scientists developed a defensive system for their homeland: Blackett and the air defense of Britain in WWII, Forrester and the SAGE system for North America in the Cold War, and Archimedes’ work defending Syracuse during the Second Punic War. In each case the historical context and the individual’s other achievements are outlined, and a description of the contribution’s relationship to OR/MS is given. The second aim is to consider some of the features the cases share and examine them in terms of contemporary OR/MS methodology. Particular reference is made to a recent analysis of the field’s strengths and weaknesses. This allows both a critical appraisal of the field and a set of potential responses for strengthening it. Although a mixed set of lessons arise, the overall conclusion is that the cases are examples to build on and that OR/MS retains the ability to do high stakes work.

Interface dynamics in planar neural field models

Neural field models describe the coarse-grained activity of populations of interacting neurons. Because of the laminar structure of real cortical tissue they are often studied in two spatial dimensions, where they are well known to generate rich patterns of spatiotemporal activity. Such patterns have been interpreted in a variety of contexts ranging from the understanding of visual hallucinations to the generation of electroencephalographic signals. Typical patterns include localized solutions in the form of traveling spots, as well as intricate labyrinthine structures. These patterns are naturally defined by the interface between low and high states of neural activity. Here we derive the equations of motion for such interfaces and show, for a Heaviside firing rate, that the normal velocity of an interface is given in terms of a non-local Biot-Savart type interaction over the boundaries of the high activity regions. This exact, but dimensionally reduced, system of equations is solved numerically and shown to be in excellent agreement with the full nonlinear integral equation defining the neural field. We develop a linear stability analysis for the interface dynamics that allows us to understand the mechanisms of pattern formation that arise from instabilities of spots, rings, stripes and fronts. We further show how to analyze neural field models with linear adaptation currents, and determine the conditions for the dynamic instability of spots that can give rise to breathers and traveling waves.