Noise-Induced Coherence and Network Oscillations in a Reduced Bursting Model

The dynamics of the Hindmarsh-Rose (HR) model of bursting thalamic neurons is reduced to a system of two linear differential equations that retains the subthreshold resonance properties of the HR model. Introducing a reset mechanism after a threshold crossing, we turn this system into a resonant integrate-and-fire (RIF) model. Using Monte-Carlo simulations and mathematical analysis, we examine the effects of noise and the subthreshold dynamic properties of the RIF model on the occurrence of coherence resonance (CR). Synchronized burst firing occurs in a network of such model neurons with excitatory pulse-coupling. The coherence level of the network oscillations shows a stochastic resonance-like dependence on the noise level. Stochastic analysis of the equations shows that the slow recovery from the spike-induced inhibition is crucial in determining the frequencies of the CR and the subthreshold resonance in the original HR model. In this particular type of CR, the oscillation frequency strongly depends on the intrinsic time scales but changes little with the noise intensity. We give analytical quantities to describe this CR mechanism and illustrate its influence on the emerging network oscillations. We discuss the profound physiological roles this kind of CR may have in information processing in neurons possessing a subthreshold resonant frequency and in generating synchronized network oscillations with a frequency that is determined by intrinsic properties of the neurons. PACS 05.45.-a, 05.40.Ca, 87.18.Sn, 87.19     

Changes in the free-radical state and the level of free iron during the development of drug resistance in tumor cells

The free-radical state of K562 human erythroleukemia cells changes during the development of resistance to doxorubicin, an antitumor antibiotic with prooxidant action widely used in oncology. It was found that the level of superoxide anion in the resistant cells decreased. The addition of doxorubicin to the culture medium induced a much smaller increase in O ₂ ^? generation in the resistant cells than in the sensitive cells. Again, the semiquinone-type EPR signal with a g-factor of 2.006 considerably decreased in the resistant cells grown without doxorubicin as compared with the sensitive cells under the same conditions. The EPR study has shown that the level of paramagnetic nitrosyl complexes of nonheme iron in the resistant cells decreased, which indicates that the content of free nonheme iron declined in development of drug resistance. In addition, we have found with the use of RT-PCR that the level of mRNA of the transferrin receptor decreased in the resistant cells. The data suggest that the suppression of free-radical processes during the development of resistance of K562 cells to doxorubicin is a coordinated redox-dependent adaptive response.     

Retrospective optimization of time-dependent fermentation control strategies using time-independent historical data

We have previously shown the usefulness of historical data for fermentation process optimization. The methodology developed includes identification of important process inputs, training of an artificial neural network (ANN) process model, and ultimately use of the ANN model with a genetic algorithm to find the optimal values of each critical process input. However, this approach ignores the time-dependent nature of the system, and therefore, does not fully utilize the available information within a database. In this work, we propose a method for incorporating time-dependent optimization into our previously developed three-step optimization routine. This is achieved by an additional step that uses a fermentation model (consisting of coupled ordinary differential equations (ODE)) to interpret important time-course features of the collected data through adjustments in model parameters. Important process variables not explicitly included in the model were then identified for each model parameter using automatic relevance determination (ARD) with Gaussian process (GP) models. The developed GP models were then combined with the fermentation model to form a hybrid neural network model that predicted the time-course activity of the cell and protein concentrations of novel fermentation conditions. A hybrid-genetic algorithm was then used in conjunction with the hybrid model to suggest optimal time-dependent control strategies. The presented method was implemented upon an E. coli fermentation database generated in our laboratory. Optimization of two different criteria (final protein yield and a simplified economic criteria) was attempted. While the overall protein yield was not increased using this methodology, we were successful in increasing a simplified economic criterion by 15% compared to what had been previously observed. These process conditions included using 35% less arabinose (the inducer) and 33% less typtone in the media and reducing the time required to reach the maximum protein concentration by 10% while producing approximately the same level of protein as the previous optimum.     

Murburn posttranslational modifications of proteins: Cellular redox processes and murzyme-mediated metabolo-proteomics

Murburn concept constitutes the thesis that diffusible reactive species or DRS are obligatorily involved in routine metabolic and physiological activities. Murzymes are defined as biomolecules/proteins that generate/modulate/sustain/utilize DRS. Murburn posttranslational modifications (PTMs) result because murburn/murzyme functionalism is integral to cellular existence. Cells must incorporate the inherently stochastic nature of operations mediated by DRS. Due to the earlier/inertial stigmatic perception that DRS are mere agents of chaos, several such outcomes were either understood as deterministic modulations sponsored by house-keeping enzymes or deemed as unregulated nonenzymatic events resulting out of “oxidative stress”. In the current review, I dispel the myths around DRS-functions, and undertake systematic parsing and analyses of murburn modifications of proteins. Although it is impossible to demarcate all PTMs into the classical or murburn modalities, telltale signs of the latter are evident from the relative inaccessibility of the locus, non-specificities and mechanistic details. It is pointed out that while many murburn PTMs may be harmless, some others could have deleterious or beneficial physiological implications. Some details of reversible/irreversible modifications of amino acid residues and cofactors that may be subjected to phosphorylation, halogenation, glycosylation, alkylation/acetylation, hydroxylation/oxidation, etc. are listed, along with citations of select proteins where such modifications have been reported. The contexts of these modifications and their significance in (patho)physiology/aging and therapy are also presented. With more balanced explorations and statistically verified data, a definitive understanding of normal versus pathological contexts of murburn modifications would be obtainable in the future.     

Aeolian process effects on vegetation communities in an arid grassland ecosystem

Many arid grassland communities are changing from grass dominance to shrub dominance, but the mechanisms involved in this conversion process are not completely understood. Aeolian processes likely contribute to this conversion from grassland to shrubland. The purpose of this research is to provide information regarding how vegetation changes occur in an arid grassland as a result of aeolian sediment transport. The experimental design included three treatment blocks, each with a 25 × 50 m area where all grasses, semi-shrubs, and perennial forbs were hand removed, a 25 × 50 m control area with no manipulation of vegetation cover, and two 10 × 25 m plots immediately downwind of the grass-removal and control areas in the prevailing wind direction, 19° north of east, for measuring vegetation cover. Aeolian sediment flux, soil nutrients, and soil seed bank were monitored on each treatment area and downwind plot. Grass and shrub cover were measured on each grass-removal, control, and downwind plot along continuous line transects as well as on 5 × 10 m subplots within each downwind area over four years following grass removal. On grass-removal areas, sediment flux increased significantly, soil nutrients and seed bank were depleted, and Prosopis glandulosa shrub cover increased compared to controls. Additionally, differential changes for grass and shrub cover were observed for plots downwind of vegetation-removal and control areas. Grass cover on plots downwind of vegetation-removal areas decreased over time (2004-2007) despite above average rainfall throughout the period of observation, while grass cover increased downwind of control areas; P. glandulosa cover increased on plots downwind of vegetation-removal areas, while decreasing on plots downwind of control areas. The relationships between vegetation changes and aeolian sediment flux were significant and were best described by a logarithmic function, with decreases in grass cover and increases in shrub cover occurring with small increases in aeolian sediment flux.     

Development of resistance in Cronobacter sakazakii ATCC 29544 to thermal and nonthermal processes after exposure to stressing environmental conditions

Aims: The objective was to study the response of Cronobacter sakazakii ATCC 29544 cells to heat, pulsed electric fields (PEF), ultrasound under pressure (Manosonication, MS) and ultraviolet light (UV‐C) treatments after exposure to different sublethal stresses that may be encountered in food‐processing environments. Methods and Results: Cronobacter sakazakii stationary growth‐phase cells (30°C, 24 h) were exposed to acid (pH 4·5, 1 h), alkaline (pH 9·0, 1 h), osmotic (5% NaCl, 1 h), oxidative (0·5 mmol l^?1 H₂O₂, 1 h), heat (47·5°C, 1 h) and cold (4°C, 4 h) stress conditions and subjected to the subsequent challenges: heat (60°C), PEF (25 kV cm^?1, 35°C), MS (117 μm, 200 kPa, 35°C) and UV‐C light (88·55 mW cm^?2, 25°C) treatments. The inactivation kinetics of C. sakazakii by the different technologies did not change after exposure to any of the stresses. The combinations of sublethal stress and lethal treatment that were protective were: heat shock–heat, heat shock–PEF and acid pH–PEF. Conversely, the alkaline shock sensitized the cells to heat and UV‐C treatments, the osmotic shock to heat treatments and the oxidative shock to UV‐C treatments. The maximum adaptive response was observed when heat‐shocked cells were subjected to a heat treatment, increasing the time to inactivate 99·9% of the population by 1·6 times. Conclusions: Cronobacter sakazakii resistance to thermal and nonthermal preservation technologies can increase or decrease as a consequence of previous exposure to stressing conditions. Significance and Impact of the Study: The results help in understanding the physiology of the resistance of this emerging pathogen to traditional and novel preservation technologies.     

Mathematical Modelling of Mycobacterium tuberculosis VNTR Loci Estimates a Very Slow Mutation Rate for the Repeats

Minisatellites are highly variable tandem repeats used for over 20 years in humans for DNA fingerprinting. In prokaryotes fingerprinting techniques exploiting VNTR (variable number of tandem repeats) polymorphisms have become widely used recently in bacterial typing. However although many investigations into the mechanisms underlying minisatellite variation in humans have been performed, relatively little is known about the processes that mediate bacterial minisatellite polymorphism. An understanding of this is important since it will influence how the results from VNTR experiments are interpreted. The minisatellites of Mycobacterium tuberculosis are well characterized since they are some of the few polymorphic loci in what is otherwise a very homogeneous organism. Using VNTR results from a well-defined and characterized set of M. tuberculosis strains we show that the repeats at a locus are likely to evolve by stepwise contraction or expansion in the number of repeats. A stochastic continuous-time population mathematical model was developed to simulate the evolution of the repeats. This allowed estimation of the tendency of the repeats to increase or decrease and the rate at which they change. The majority of loci tend to lose rather than gain repeats. All of the loci mutate extremely slowly, with an average rate of 2.3 x 10(-8), which is 350 times slower than that of a set of VNTR repeats with similar diversity observed experimentally in Escherichia coli. This suggests that the VNTR profile of a strain of M. tuberculosis will be indicative of its clonal lineage and will be unlikely to vary in epidemiologically-related strains.     

Voles on small islands: effects of food limitation and alien predation

Ecosystems of three trophic levels may be bottom-up (by food-plant availability) and/or top-down (by predators) limited. Top-down control might be of greater consequence when the predation impact comes from an alien predator. We conducted a replicated two-factor experiment with field voles (Microtus agrestis) during 2004-2005 on small islands of the outer archipelago of the Baltic Sea, south-west Finland, manipulating both predation impact by introduced American mink (Mustela vison) and winter food supply. In autumn 2004, we live-trapped voles on five islands from which mink had been consistently removed, and on four islands where mink were present, and provided half of these islands with 1.8 kg oats per vole. Body mass of female voles increased as a response to supplementary food, whereas both food supplementation and mink removal increased the body mass of male voles in subsequent spring. During winter, there was a positive effect of supplementary food, but in the subsequent summer, possible positive long-term impacts of food supplementation on field voles were not detected. Mink removal appeared not to affect density estimates of field voles during the winter and summer immediately after food addition. Trapping data from 2004 to 2005 and 2007 suggested, however, that in two out of three summers densities of voles were significantly higher in the absence than in the presence of mink. We conclude that vole populations on small islands in the archipelago of the Baltic Sea are mainly bottom-up limited during winter (outside the growing season of food plants), when food availability is low, and limited by mink predation during summer which slows population growth during the reproductive season of voles.     

一类受马氏调制的连续型传染病模型

本文借鉴保险上的方法来考虑这样一个传染病模型,即在一个区域中,初始有一定的传染病人,假设一方面病人不断增加,且传染率受当时病人数目的影响;另一方面病人减少（死亡或治愈）的发生频率及数目受一外界环境的影响,而外界环境假定为一有限状态的马氏过程。在这些假设下,我们得出初始状态为i时疾病灭绝的概率以及平稳状态下的疾病灭绝概率。     

生物质热裂解生产生物燃料的研究进展

生物质能源是一种绿色的可以替代化石能源的一种可再生的能源。尽管高温分解生物质处于发展阶段,但在目前水平,高温裂解因其可以在氧存在下热分解将生物材料直接转化为固态,液态和气态能源产品而受到广泛关注。本文介绍了生物质的热裂解,包括慢速热裂解、快速热裂解、闪解、催化热裂解等过程,重点讨论了在各种生物质材料的热裂解过程中各种操作参数如温度和生物粒子大小等对生物燃料收率的影响。