New modified Square Root and Schoolfield models for predicting bacterial growth rate as a function of temperature

Summary A new modified Square Root model and two new modified Schoolfield models were evaluated for their ability to predict the growth rate ofYersinia enterocolitica as a function of temperature. The new Square Root model fits the data better than both the original Square Root model and the Zwietering Square Root model. Both new Schoolfield models, a six-and a four-parameter equation, fit the data better than the original Schoolfield model. The new four-parameter Schoolfield model was developed by removing the term describing low temperature inactivation from the new six-parameter Schoolfield model. Inclusion of the two extra parameters in the new six-parameter Schoolfield model (F=318) did not significantly improve the fit compared to the new fourparameter Schoolfield model (F=488).     

Experimental design for optimal parameter estimation of an enzyme kinetic process based on the analysis of the Fisher information matrix

The investigation of enzyme kinetics is increasingly important, especially for finding active substances and understanding intracellular behaviors. Therefore, the determination of an enzyme's kinetic parameters is crucial. For this a systematic experimental design procedure is necessary to avoid wasting time and resources. The parameter estimation error of a Michaelis-Menten enzyme kinetic process is analysed analytically to reduce the search area as well as numerically to specify the optimum for parameter estimation. From analytical analysis of the Fisher information matrix the fact is obtained, that an enzyme feed will not improve the estimation process, but substrate feeding is favorable with small volume flow. Unconstrained and constrained process conditions are considered. If substrate fed-batch process design is used instead of pure batch experiments the improvements of the Cramer-Rao lower bound of the variance of parameter estimation error reduces to 82% for mu(max) and to 60% for K(m) of the batch values in average.     

Experimental design of a simple medium for the bioluminescence of Aliivibrio fischeri and mathematical modelling for growth estimation

Increasing numbers of studies are using Aliivibrio fischeri (A. fischeri), a marine bioluminescent bacterium as a model, however the culture medium used for its growth are complex and expensive. The objectives of this study were: (1) to evaluate the effect of yeast extract, tryptone, and NaCl to select a simple and inexpensive culture medium suitable for A. fischeri growth and bioluminescence induction; and (2) to compare the performance of mathematical models to predict the growth of A. fischeri. A fractional factorial design was performed to evaluate the effect of yeast extract, tryptone, and sodium chloride on the luminescence of A. fischeri. The result showed that sodium chloride is the most important factor, congruent with its inducer role in bioluminescence. The best medium for bioluminescence induction was selected through an optimization plot, this medium is inexpensive, and generates the same luminescence as commercial formulations. The estimation of A. fischeri growth at OD₆₀₀ measurement was statistically analyzed. All evaluated models fitted the data adequately (r²  > 0.96). The nonlinear models Gompertz, Richards and logistic provided a lower variation and a better fit of the growth estimation (r² >0.99), showing that these mathematical models can be used for the accurate growth prediction of A. fischeri.     

Optimal control for selected cancer chemotherapy ODE models: a view on the potential of optimal schedules and choice of objective function

In this article, four different mathematical models of chemotherapy from the literature are investigated with respect to optimal control of drug treatment schedules. The various models are based on two different sets of ordinary differential equations and contain either chemotherapy, immunotherapy, anti-angiogenic therapy or combinations of these. Optimal control problem formulations based on these models are proposed, discussed and compared. For different parameter sets, scenarios, and objective functions optimal control problems are solved numerically with Bock’s direct multiple shooting method.In particular, we show that an optimally controlled therapy can be the reason for the difference between a growing and a totally vanishing tumor in comparison to standard treatment schemes and untreated or wrongly treated tumors. Furthermore, we compare different objective functions. Eventually, we propose an optimization-driven indicator for the potential gain of optimal controls. Based on this indicator, we show that there is a high potential for optimization of chemotherapy schedules, although the currently available models are not yet appropriate for transferring the optimal therapies into medical practice due to patient-, cancer-, and therapy-specific components.     

Optimization of the xylan degradation activity of monolithic enzymatic membranes as a function of their composition using design of experiments

The aim of this work was the development and optimization of enzymatic monolithic membranes with high catalytic activity for the degradation of xylan into xylooligosaccharides. The chemometric tool design of experiments has been utilized here for the first time for the optimization of the enzymatic activity of the monolithic membranes based on their constituents. The effect of three process variables, including the amount of various monomer contents and the porogenic solvents ratio, has been studied on the enzymatic activity of the resulted membranes. The experimental design chosen was a central face centred with six central points in order to obtain an orthogonal model, with the precision of the results being independent of the range of values considered for each parameter. The software Modde(c) 6.0 from Umetrics(c) was used to build and analyze the results of the experimental design using partial least squares regression. The optimization of the suggested model provided the best membrane composition to achieve maximum enzymatic activity, which can be related to the amount of enzyme immobilized on the monolithic membrane. The predictive capacity of the model was evaluated performing additional experiments.     

Growth versus molting time of caterpillars as a function of temperature,nutrient concentration and the phenolic rutin

Summary A factorial experiment tested the effects of varying nutrient concentration (normal versus diluted), presence or absence of the phenolic allelochemical rutin and daytime temperature (20, 25 and 30° C) on growth, molting and food utilization efficiencies of tobacco hornworms (Manduca sexta). Two of the utilization efficiencies (approximate digestibility and efficiency of conversion of ingested food) were unaffected by temperature; the third one, efficiency of conversion of digested food, was affected by temperature but there was no consistent effect. Lower temperatures significantly increased the proportion of the stadium spent molting, with larvae at a daytime temperature of 20° C spending 9% more of the stadium in molting than larvae at 30° C. Growth time was not influenced by nutrient concentration. When temperature was low and rutin absent, molt time and the proportion of the stadium spent molting were affected by nutrient concentration. Addition of the phenolic rutin did not have an appreciable effect on growth time or digestive processes. However, it increased molting time by 7 to 14% and thus increased the duration of the stadium and reduced relative growth rate. These results indicate that the effect of food quality on growth rate is a function of the thermal conditions of insect herbivores. At cooler temperatures, a disproportionate increase in time spent molting, rather than altered food utilization efficiencies, contributed to lower growth rates. The consequences for larval growth of fluctuating temperatures due to diurnal cycles and the presence of predators forcing larvae into thermally suboptimal microhabitats are discussed.     

Environmental factors affect the response of microbial extracellular enzyme activity in soils when determined as a function of water availability and temperature

Microorganisms govern soil carbon cycling with critical effects at local and global scales. The activity of microbial extracellular enzymes is generally the limiting step for soil organic matter mineralization. Nevertheless, the influence of soil characteristics and climate parameters on microbial extracellular enzyme activity (EEA) performance at different water availabilities and temperatures remains to be detailed. Different soils from the Iberian Peninsula presenting distinctive climatic scenarios were sampled for these analyses. Results showed that microbial EEA in the mesophilic temperature range presents optimal rates under wet conditions (high water availability) while activity at the thermophilic temperature range (60°C) could present maximum EEA rates under dry conditions if the soil is frequently exposed to high temperatures. Optimum water availability conditions for maximum soil microbial EEA were influenced mainly by soil texture. Soil properties and climatic parameters are major environmental components ruling soil water availability and temperature which were decisive factors regulating soil microbial EEA. This study contributes decisively to the understanding of environmental factors on the microbial EEA in soils, specifically on the decisive influence of water availability and temperature on EEA. Unlike previous belief, optimum EEA in high temperature exposed soil upper layers can occur at low water availability (i.e., dryness) and high temperatures. This study shows the potential for a significant response by soil microbial EEA under conditions of high temperature and dryness due to a progressive environmental warming which will influence organic carbon decomposition at local and global scenarios.     

Suitability of Zostera marina populations for transplantation to the Wadden Sea as determined by a mesocosm shading experiment

As part of eelgrass re-establishment efforts in the Wadden Sea, five northwest European eelgrass (Zostera marina L.) populations were studied in a mesocosm filled with Wadden Sea water over a 2-year period. The original habitats of these populations varied with regard to salinity, tidal regime, latitude, substrate type and water nutrient content. The reproductive strategies ranged from semi-annual to perennial. Experimental parameters studied were: planting density (64 and 121 plants m⁻²) and irradiance corresponding to 75%, 89%, 95% and 98% light reduction at the bottom. Three out of five Z. marina populations were successfully transplanted. Planting density, although initially positively correlated, had no effect on final transplantation success. The populations maintained their original reproductive strategy. The reproductive strategy of the donor population did not show a clear correlation with transplantation success. The maximum light reduction tolerated at the bottom was 75%–89%. The populations did not differ in shading tolerance. Assuming a light attenuation coefficient in the Wadden Sea of k=2.0 m⁻¹, this corresponds to a maximum transplantation depth of between 0.45 m and 0.85 m below mean sea level. The differences in transplantation success, and the conservative reproductive strategy of different Z. marina populations, indicate genetic differences and/or low phenotypic plasticity. Moreover, this implies that the characteristics of a donor population must be carefully considered prior to transplantation.     

Mdm2 inhibitors as a platform for the design of P-glycoprotein inhibitors

Chemoresistance is thought to be the cause of low treatment efficacy and mortality in more than 90% of patients with advanced cancer. The activation of drug efflux by P-glycoprotein is the key mechanism of resistance. All known P-gp inhibitors are used only in the combination therapy. We propose a new approach based on the multitarget rational design of drugs, which possess both the antitumor and efflux pump inhibitory activity. In this work, the principle possibility of combining the ability to inhibit P-gp and p53-Mdm2 protein-protein interaction in one structure is considered. The biological activity of a number of known and newly synthesized compounds was evaluated using cell lines with different p53 status. The possibility of using computer modeling for the search for P-glycoprotein inhibitors among Mdm2 inhibitors was analyzed; P-gp interaction site and binding modes of substrates and inhibitors were identified. The results obtained in cells that have the native balance of drug resistance and sensitivity showed the ability of the cells to both actively throw out xenobiotics and to lose this ability using P-gp inhibitors. The data obtained indicate that Mdm2 inhibitors are a promising platform for the development of multitarget drugs that can overcome tumor resistance by inhibiting the P-glycoprotein activity.     

The potential of mining slag as a substrate for microbial growth and the microbiological analysis of slag and slag seepage

The potential of a Cu/Ni mining slag to act as a substrate for the growth of the bacteria Thiobacillus ferrooxidans, Thiobacillus thiooxidants, and Thiobacillus thioparus was examined. As well, slag and seepage samples were screened for the presence of the Thiobacillus species. For the 28 samples employed in the environmental recovery studies, T. ferrooxidans was recovered in 25 samples, T. thiooxidans in 19 samples, and T. thioparus in 27 samples. For T. ferrooxidans, the development of a colour change in the medium corresponded with the presence of motile bacilli as detected microscopically. For T. thiooxidans and T. thioparus, a decrease in culture pH of greater than 0.2 units usually corresponded with the presence of motile bacilli. The potential for growth on slag was determined by adding slag samples to media (devoid of an electron donor) appropriate for the growth of the three Thiobacillus species. All pulverized slag samples supported the growth of the three species.     

A response surface model based on absorbance data for the growth rates of Salmonella enterica serovar typhimurium as a function of temperature, NaCl, and pH

Response surface model was developed for predicting the growth rates of Salmonella enterica sv. Typhimurium in tryptic soy broth (TSB) medium as a function of combined effects of temperature, pH, and NaCl. The TSB containing six different concentrations of NaCl (0, 2, 4, 6, 8, and 10%) was adjusted to an initial of six different pH levels (pH 4, 5, 6, 7, 8, 9, and 10) and incubated at 10 or 20 degrees C. In all experimental variables, the primary growth curves were well (r2 = 0.900 to 0.996) fitted to a Gompertz equation to obtain growth rates. The secondary response surface model for natural logarithm transformations of growth rates as a function of combined effects of temperature, pH, and NaCl was obtained by SAS's general linear analysis. The predicted growth rates of the S. Typhimurium were generally decreased by basic (9, 10) or acidic (5, 6) pH levels or increase of NaCl concentrations (0-8%). Response surface model was identified as an appropriate secondary model for growth rates on the basis of coefficient determination (r2 = 0.960), mean square error (MSE = 0.022), bias factor (B(f) = 1.023), and accuracy factor (A(f) = 1.164). Therefore, the developed secondary model proved reliable predictions of the combined effect of temperature, NaCl, and pH on growth rates for S. Typhimurium in TSB medium.     

The bioenergetics of the southern catfish (Silurus meridionalis Chen): growth rate as a function of ration level, body weight, and temperature

A feeding-growth experiment was conducted in the laboratory on 114 young southern catfish ( Silurus meridionalis Chen) with initial weights of 8.71–127.9g at 15, 20, 25 and 30°C. The experiment consisted of eight weight-temperature groups, with five ration levels ranging from starvation to satiation in each group. A multiple regression equation fitted to the experimental data was developed to describe the relation between specific growth rate (SGR) and the three factors, ration level (RL), body weight ( W ) and temperature ( T ): SGR = 0.471 + 0.172ln W −0.0443 T +0.0682 T ln(RL + l). This predicts that with increasing temperature the specific growth rate decreases at lower ration levels and increases at higher ration levels. The equation, SGR = a + b ln(RL + l), may be considered as the basic growth model where a is the maintenance metabolism exponent and b is the conversion exponent of the net energy; body weight and temperature influence the two parameters. With this relationship the two antagonistic effects of temperature on growth can be understood, increasing temperature imposes a negative effect on growth due to increment in energy cost for maintenance metabolism, and a positive effect due to higher efficiency of transforming food energy into net energy; the positive effect will increase at higher ration levels. This could also explain why at a restricted ration level relationships between growth and temperature are different in different species.     

Intrauterine growth retarded piglet as a model for humans – Studies on the perinatal development of the gut structure and function

The overall acceptance of pig models for human biomedical studies is steadily growing. Results of rodent studies are usually confirmed in pigs before extrapolating them to humans. This applies particularly to gastrointestinal and metabolism research due to similarities between pig and human physiology. In this context, intrauterine growth retarded (IUGR) pig neonate can be regarded as a good model for the better understanding of the IUGR syndrome in humans. In pigs, the induction of IUGR syndrome may include maternal diet intervention, dexamethasone treatment or temporary reduction of blood supply. However, in pigs, like in humans, circa 8% of neonates develop IUGR syndrome spontaneously. Studies on the pig model have shown changes in gut structure, namely a reduced thickness of mucosa and muscle layers, and delayed kinetic of disappearance of vacuolated enterocytes were found in IUGR individuals in comparison with healthy ones. Functional changes include reduced dynamic of gut mucosa rebuilding, decreased activities of main brush border enzymes, and changes in the expression of proteins important for carbohydrate, amino acids, lipid, mineral and vitamin metabolism. Moreover, profiles of intestinal hormones are different in IUGR and non-IUGR piglets. It is suggested that supplementation of the mothers during the gestation and/or the IUGR offspring after birth can help in restoring the development of the gastrointestinal tract. The pig provides presumably the optimal animal model for humans to study gastrointestinal tract structure and function development in IUGR syndrome.     

Soil calcium content as the driving factor for vegetative structure and soil microbial function diverging across a fire chronosequence of the boreal forests in northeast China

中国东北地区北方森林土壤钙对植被结构和土壤功能随火烧序列恢复趋势分化的驱动作用随着火后恢复时间的延长,各生物物理因子对森林群落结构恢复和重建的重要性也发生着变化。本研究的主要目的是明确我国北方森林在火灾干扰后地上植被和土壤微生物功能的关键恢复时期及其主导性驱动因子。在东北大兴安岭林区,选择不同时期的火烧林地,组成一个50年的火烧演替序列,分析随火烧后恢复时间的增加,乔木、灌木和草本物种的生物量在整个群落中所占比重的动态变化特征。同时,采集不同火烧林地的土壤样品,分析其养分含量、微生物生物量以及酶活性等理化指标,并以这些理化数据为基础,估算土壤微生物的生长效率和碳素利用效率,以反应土壤微生物功能随火烧时间的演变规律。研究结果发现,在选定的火烧序列内,不同功能群物种在森林群落的恢复和重建中的贡献表现出明显的时期变异性。草本物种的比重从最初的75%下降到1.5%,而乔木物种的比重则从火烧 初期的0.04%上升到后期的70%。土壤微生物的生长效率和碳素利用效率平均为0.242和0.236,在火烧恢复的第9、15和31年的取值明显大于火烧后的第2和3 年。火烧后恢复时期也影响了土壤中金属离子的含量,土壤中钙和铁的含量都在火烧序列后期得到明显提高,其中钙的含量与群落中木本物种间呈正相关关系,而与微生物功能间呈负相关关系。在本研究选定的火烧序列内,火烧干扰后的第15和31年是地上群落结构和土壤微生物功能恢复的关键期,地上和地下恢复过程在这两个时期呈现出分异趋势,而土壤中钙含量的变化对这一分异趋势发挥了一定的驱动作用。     

Alterations in the production and concentration of selected alkaloids as a function of rising atmospheric carbon dioxide and air temperature: implications for ethno-pharmacology

The influence of recent and projected changes in atmospheric carbon dioxide concentration [CO₂] with and without concurrent increases in air temperature was determined with respect to growth characteristics and production of secondary compounds (alkaloids) in tobacco (Nicotiana tabacum L.) and jimson weed (Datura stramonium L.) over a ca. 50‐day period. Rising [CO₂] above that present at the beginning of the 20th century resulted in consistent, significant increases in leaf area, and above ground dry weight (both species), but decreased leaf area ratio (LAR) and specific leaf area (SLA) in jimson weed. Increased temperature resulted in earlier development and increased leaf area for both species, but increases in above ground final dry weight were observed only for jimson weed. The secondary compounds evaluated included the alkaloids, nicotine, atropine and scopolamine. These compounds are generally recognized as having impacts with respect to herbivory as well as human physiology. Rising [CO₂] reduced the concentration of nicotine in tobacco; but had no effect on atropine, and increased the concentration of scopolamine in jimson weed. However, because of the stimulatory effect of [CO₂] on growth, the amount of all three secondary compounds increased on a per plant basis in both species. Temperature per se had no effect on nicotine or scopolamine concentration, but significantly increased the concentration and amounts of atropine per plant. Overall, the underlying mechanism of CO₂ induced changes in secondary compounds remains unclear; however, these data suggest that the increase in [CO₂] and temperature associated with global climate change may have significant effects not only with respect to herbivory, but on the production of secondary compounds of pharmacological impact.