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1.
As an advanced approach to identify suitable targeting molecules required for various diagnostic and therapeutic interventions, we developed a procedure to devise peptides with customizable features by an iterative computer-assisted optimization strategy. An evolutionary algorithm was utilized to breed peptides in silico and the “fitness” of peptides was determined in an appropriate laboratory in vitro assay. The influence of different evolutional parameters and mechanisms such as mutation rate, crossover probability, gaussian variation and fitness value scaling on the course of this artificial evolutional process was investigated. As a proof of concept peptidic ligands for a model target molecule, the cell surface glycolipid ganglioside GM1, were identified. Consensus sequences describing local fitness optima were reached from diverse sets of L- and proteolytically stable D lead peptides. Ten rounds of evolutional optimization encompassing a total of just 4400 peptides lead to an increase in affinity of the peptides towards fluorescently labeled ganglioside GM1 by a factor of 100 for L- and 400 for D-peptides. 相似文献
2.
Frankia is the diverse bacterial genus that fixes nitrogen within root nodules of actinorhizal trees and shrubs. Systematic and ecological
studies of Frankia have been hindered by the lack of morphological, biochemical, or other markers to readily distinguish strains. Recently,
nucleotide sequence of 16 S RNA from the small ribosomal subunit has been used to classify and identify a variety of microorganisms.
We report nucleotide sequences from portions of the 16 S ribosomal RNA from Frankia strains AcnI1 isolated from Alnus viridis ssp. crispa (Ait.) Turrill and PtI1 isolated from Purshia tridentata (Pursh) DC. The number of nucleotide base substitutions and gaps we find more than doubles the previously reported sequence
diversity for the same variable regions within other strains of Frankia. 相似文献
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The Effect of Visual Representation Style in Problem-Solving: A Perspective from Cognitive Processes
Using results from a controlled experiment and simulations based on cognitive models, we show that visual presentation style can have a significant impact on performance in a complex problem-solving task. We compared subject performances in two isomorphic, but visually different, tasks based on a card game of SET. Although subjects used the same strategy in both tasks, the difference in presentation style resulted in radically different reaction times and significant deviations in scanpath patterns in the two tasks. Results from our study indicate that low-level subconscious visual processes, such as differential acuity in peripheral vision and low-level iconic memory, can have indirect, but significant effects on decision making during a problem-solving task. We have developed two ACT-R models that employ the same basic strategy but deal with different presentations styles. Our ACT-R models confirm that changes in low-level visual processes triggered by changes in presentation style can propagate to higher-level cognitive processes. Such a domino effect can significantly affect reaction times and eye movements, without affecting the overall strategy of problem solving. 相似文献
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Joost le Feber Stelina Tzafi Pavlidou Niels Erkamp Michel J. A. M. van Putten Jeannette Hofmeijer 《PloS one》2016,11(2)
Improvement of neuronal recovery in the ischemic penumbra around a brain infarct has a large potential to advance clinical recovery of patients with acute ischemic stroke. However, pathophysiological mechanisms leading to either recovery or secondary damage in the penumbra are not completely understood. We studied neuronal dynamics in a model system of the penumbra consisting of networks of cultured cortical neurons exposed to controlled levels and durations of hypoxia. Short periods of hypoxia (pO2≈20mmHg) reduced spontaneous activity, due to impeded synaptic function. After ≈6 hours, activity and connectivity partially recovered, even during continuing hypoxia. If the oxygen supply was restored within 12 hours, changes in network connectivity were completely reversible. For longer periods of hypoxia (12–30 h), activity levels initially increased, but eventually decreased and connectivity changes became partially irreversible. After ≈30 hours, all functional connections disappeared and no activity remained. Since this complete silence seemed unrelated to hypoxic depths, but always followed an extended period of low activity, we speculate that irreversible damage (at least partly) results from insufficient neuronal activation. This opens avenues for therapies to improve recovery by neuronal activation. 相似文献
7.
Niels Nyholm 《Biotechnology and bioengineering》1977,19(4):467-492
The kinetics of phosphate limited growth of two green algae Chorella pyrenoidosa and Selenastrum capricornutum have been studied in chemostats. Several kinetic models which express the specific growth rate as a function of the intracellular phosphours content have been examined, and one of the models was found to be significantly better than the other models. The principles of this model were described in a recent paper by Nyholm. The kinetics of phosphate uptake have been investigated by adding pulses of phosphate to the chemostats. The uptake by phosphours deficient cells could be described by Michaelis–Menten kinetics for phosphate concentrations below approximately 500 μg P/liter. Further, with the assumption of a discontinuous adjustment of the uptake rate at the onset of phosphours deficiency, a complete kinetic model for growth and phosphate removal is proposed. The mean cell size and the contents of chlorophyll and RNA per unit dry weight have been measured for C. pyrenoidosa as a function of the dilution rate. 相似文献
8.
Abstract A diatom biofilm was grown in a chamber developed for culture of biofilms in chemical gradients. The diatoms grew on a polycarbonate membrane filter which separated a sterile reservoir, with added phosphate, from a reservoir without phosphate. Within 3 weeks of inoculation, a thick biofilm developed on the surface of the filter. The biofilms were homogeneous and therefore suitable for calculations of O2 diffusion fluxes from concentration profiles of O2 . Profiles of O2 , pH, and gross photosynthesis at different light intensities and liquid medium concentrations of dissolved inorganic carbon and O2 were measured with microelectrodes. Respiratory activity in a layer of the biofilm was determined as the difference between gross photosynthesis and outflux of O2 from that layer. The photosynthetic activity in a well-developed biofilm grown at 360 μEinst m−2 s−1 and 2.4 mM HCO3 − was limited by the supply of inorganic carbon. Exposure to light above 360 μEinst m−2 s−1 stimulated gross photosynthesis as well as respiratory processes without affecting net outflux of O2 . Higher concentrations of inorganic carbon, on the other hand, enhanced gross photosynthesis without concurrent increase in respiratory rate, resulting in an increased outflux of O2 . High concentrations of O2 in the liquid medium decreased the net outflux of O2 with little effect on the gross photosynthesis. The effects of inorganic carbon and O2 on the metabolic activities of the biofilm were consistent with the presence of photorespiratory activity. 相似文献
9.
Niels Nyholm 《Journal of theoretical biology》1978,70(4):415-425
A simulation model is suggested which describes transient growth of the green alga Chlorella pyrenoidosa after exposure of phosphate limited chemostatic cultures to phosphate shocks. The specific growth rate is related to an internal concentration of functional phosphorus. The model includes a metabolic activity functional as suggested by Powell (1969), and it is assumed that phosphate taken up by the cells passes through an intermediate pool of not functional phosphorus which is thought to inhibit growth. Comparisons are made with a simpler model described previously. 相似文献
10.