Liquid matrix deposition on conductive hydrophobic surfaces for tuning and quantitation in UV-MALDI mass spectrometry

With its highly fluctuating ion production matrix-assisted laser desorption/ionization (MALDI) poses many practical challenges for its application in mass spectrometry. Instrument tuning and quantitative ion abundance measurements using ion signal alone depend on a stable ion beam. Liquid MALDI matrices have been shown to be a promising alternative to the commonly used solid matrices. Their application in areas where a stable ion current is essential has been discussed but only limited data have been provided to demonstrate their practical use and advantages in the formation of stable MALDI ion beams. In this article we present experimental data showing high MALDI ion beam stability over more than two orders of magnitude at high analytical sensitivity (low femtomole amount prepared) for quantitative peptide abundance measurements and instrument tuning in a MALDI Q-TOF mass spectrometer. Samples were deposited on an inexpensive conductive hydrophobic surface and shrunk to droplets <10 nL in size. By using a sample droplet <10 nL it was possible to acquire data from a single irradiated spot for roughly 10,000 shots with little variation in ion signal intensity at a laser repetition rate of 5-20 Hz.

Rate-limiting steps in the development of atherosclerosis: the response-to-influx theory

A large number of processes are involved in the pathogenesis of atherosclerosis but it is unclear which of them play a rate-limiting role. One way of resolving this problem is to investigate the highly non-uniform distribution of disease within the arterial system; critical steps in lesion development should be revealed by identifying arterial properties that differ between susceptible and protected sites. Although the localisation of atherosclerotic lesions has been investigated intensively over much of the 20th century, this review argues that the factor determining the distribution of human disease has only recently been identified. Recognition that the distribution changes with age has, for the first time, allowed it to be explained by variation in transport properties of the arterial wall; hitherto, this view could only be applied to experimental atherosclerosis in animals. The newly discovered transport variations which appear to play a critical role in the development of adult disease have underlying mechanisms that differ from those elucidated for the transport variations relevant to experimental atherosclerosis: they depend on endogenous NO synthesis and on blood flow. Manipulation of transport properties might have therapeutic potential. Copyright (C) 2004 S. Karger AG, Basel.

NeMo: a platform for neural modelling of spiking neurons using GPUs

Simulating spiking neural networks is of great interest to scientists wanting to model the functioning of the brain. However, large-scale models are expensive to simulate due to the number and interconnectedness of neurons in the brain. Furthermore, where such simulations are used in an embodied setting, the simulation must be real-time in order to be useful. In this paper we present NeMo, a platform for such simulations which achieves high performance through the use of highly parallel commodity hardware in the form of graphics processing units (GPUs). NeMo makes use of the Izhikevich neuron model which provides a range of realistic spiking dynamics while being computationally efficient. Our GPU kernel can deliver up to 400 million spikes per second. This corresponds to a real-time simulation of around 40 000 neurons under biologically plausible conditions with 1000 synapses per neuron and a mean firing rate of 10 Hz.

The maximum rate of mammal evolution

How fast can a mammal evolve from the size of a mouse to the size of an elephant? Achieving such a large transformation calls for major biological reorganization. Thus, the speed at which this occurs has important implications for extensive faunal changes, including adaptive radiations and recovery from mass extinctions. To quantify the pace of large-scale evolution we developed a metric, clade maximum rate, which represents the maximum evolutionary rate of a trait within a clade. We applied this metric to body mass evolution in mammals over the last 70 million years, during which multiple large evolutionary transitions occurred in oceans and on continents and islands. Our computations suggest that it took a minimum of 1.6, 5.1, and 10 million generations for terrestrial mammal mass to increase 100-, and 1,000-, and 5,000- fold, respectively. Values for whales were down to half the length (i.e., 1.1, 3, and 5 million generations), perhaps due to the reduced mechanical constraints of living in an aquatic environment. When differences in generation time are considered, we find an exponential increase in maximum mammal body mass during the 35 million years following the Cretaceous–Paleogene (K–Pg) extinction event. Our results also indicate a basic asymmetry in macroevolution: very large decreases (such as extreme insular dwarfism) can happen at more than 10 times the rate of increases. Our findings allow more rigorous comparisons of microevolutionary and macroevolutionary patterns and processes. Keywords: haldanes, biological time, scaling, pedomorphosis

Identification of stimulatory and inhibitory inputs to the hypothalamic-pituitary-adrenal axis during hypoglycaemia or transport in ewes

This study used the novel approach of statistical modelling to investigate the control of hypothalamic-pituitary-adrenal (HPA) axis and quantify temporal relationships between hormones. Two experimental paradigms were chosen, insulin-induced hypoglycaemia and 2 h transport, to assess differences in control between noncognitive and cognitive stimuli. Vasopressin and corticotropin-releasing hormone (CRH) were measured in hypophysial portal plasma, and adrenocorticotropin hormone (ACTH) and cortisol in jugular plasma of conscious sheep, and deconvolution analysis was used to calculate secretory rates, before modelling. During hypoglycaemia, the relationship between plasma glucose and vasopressin or CRH was best described by log(10) transforming variables (i.e. a positive power-curve relationship). A negative-feedback relationship with log(10) cortisol concentration 2 h previously was detected. Analysis of the 'transport' stimulus suggested that the strength of the perceived stimulus decreased over time after accounting for cortisol facilitation and negative-feedback. The time course of vasopressin and CRH responses to each stimulus were different However, at the pituitary level, the data suggested that log(10) ACTH secretion rate was related to log(10) vasopressin and CRH concentrations with very similar regression coefficients and an identical ratio of actions (2.3 : 1) for both stimuli. Similar magnitude negative-feedback effects of log(10) cortisol at -110 min (hypoglycaemia) or -40 min (transport) were detected, and both models contained a stimulatory relationship with cortisol at 0 min (facilitation). At adrenal gland level, cortisol secretory rates were related to simultaneously measured untransformed ACTH concentration but the regression coefficient for the hypoglycaemia model was 2.5-fold greater than for transport. No individual sustained maximum cortisol secretion for longer than 20 min during hypoglycaemia and 40 min during transport. These unique models demonstrate that corticosteroid negative-feedback is a significant control mechanism at both the pituitary and hypothalamus. The amplitude of HPA response may be related to stimulus intensity and corticosteroid negative-feedback, while duration depended on feedback alone.

Effect of heat on rheology of gluten fractions from flours with different bread-making quality

Flours from wheat varieties of differing bread-making quality were fractionated using a sequential salt precipitation technique. The gluten fractions in the different varieties varied in the proportion of HMW, LMW glutenins and gliadins. Their rheological behaviour was examined using constant strain (2%) small deformation oscillation tests over frequencies ranging from 0.005 to 10 Hz, before and after heating at 90 degrees C. The fractions containing a higher proportion of HMW glutenins were associated with a predominantly elastic character, whereas fractions containing mostly gliadins exhibited a viscous-like behaviour. The frequency dependent rheological behaviour of fractions containing HMW proteins was less susceptible to heat, and their elastic character was maintained after heating, whereas the rheology of intermediate fractions and fractions containing mostly gliadins was more susceptible to heating, indicating a rapid change from viscous to elastic behaviour after heating. (c) 2006 Elsevier Ltd. All rights reserved.

Does high-frequency repetitive transcranial magnetic stimulation produce residual and/or cumulative effects within an experimental session?

A common procedure for studying the effects on cognition of repetitive transcranial magnetic stimulation (rTMS) is to deliver rTMS concurrent with task performance, and to compare task performance on these trials versus on trials without rTMS. Recent evidence that TMS can have effects on neural activity that persist longer than the experimental session itself, however, raise questions about the assumption of the transient nature of rTMS that underlies many concurrent (or "online") rTMS designs. To our knowledge, there have been no studies in the cognitive domain examining whether the application of brief trains of rTMS during specific epochs of a complex task may have effects that spill over into subsequent task epochs, and perhaps into subsequent trials. We looked for possible immediate spill-over and longer-term cumulative effects of rTMS in data from two studies of visual short-term delayed recognition. In 54 subjects, 10-Hz rTMS trains were applied to five different brain regions during the 3-s delay period of a spatial task, and in a second group of 15 subjects, electroencephalography (EEG) was recorded while 10-Hz rTMS was applied to two brain areas during the 3-s delay period of both spatial and object tasks. No evidence for immediate effects was found in the comparison of the memory probe-evoked response on trials that were vs. were not preceded by delay-period rTMS. No evidence for cumulative effects was found in analyses of behavioral performance, and of EEG signal, as a function of task block. The implications of these findings, and their relation to the broader literature on acute vs. long-lasting effects of rTMS, are considered.

CO2 emission estimation in the urban environment: measurement of the CO2 storage term

Eddy covariance has been used in urban areas to evaluate the net exchange of CO2 between the surface and the atmosphere. Typically, only the vertical flux is measured at a height 2–3 times that of the local roughness elements; however, under conditions of relatively low instability, CO2 may accumulate in the airspace below the measurement height. This can result in inaccurate emissions estimates if the accumulated CO2 drains away or is flushed upwards during thermal expansion of the boundary layer. Some studies apply a single height storage correction; however, this requires the assumption that the response of the CO2 concentration profile to forcing is constant with height. Here a full seasonal cycle (7th June 2012 to 3rd June 2013) of single height CO2 storage data calculated from concentrations measured at 10 Hz by open path gas analyser are compared to a data set calculated from a concurrent switched vertical profile measured (2 Hz, closed path gas analyser) at 10 heights within and above a street canyon in central London. The assumption required for the former storage determination is shown to be invalid. For approximately regular street canyons at least one other measurement is required. Continuous measurements at fewer locations are shown to be preferable to a spatially dense, switched profile, as temporal interpolation is ineffective. The majority of the spectral energy of the CO2 storage time series was found to be between 0.001 and 0.2 Hz (500 and 5 s respectively); however, sampling frequencies of 2 Hz and below still result in significantly lower CO2 storage values. An empirical method of correcting CO2 storage values from under-sampled time series is proposed.