Dextran Sodium Sulphate Colitis Mouse Model: Traps and Tricks

Inflammatory bowel disease (IBD) is a complex multifactorial disease of unknown etiology. Thus, dozens of different animal models of IBD have been developed in past decades. Animal models of IBD are valuable and indispensable tools that provide a wide range of options for investigating involvement of various factors into the pathogenesis of IBD and to evaluate different therapeutic options. However, the dextran sulphate sodium (DSS-) induced colitis model has some advantages when compared to other animal models of colitis. It is well appreciated and widely used model of inflammatory bowel disease because of its simplicity. It has many similarities to human IBD, which are mentioned in the paper. In spite of its simplicity and wide applicability, there are also traps that need to be taken into account when using DSS model. As demonstrated in the present paper, various factors may affect susceptibility to DSS-induced lesions and modify results

Morphological and Molecular Alterations in 1,2 Dimethylhydrazine and Azoxymethane Induced Colon Carcinogenesis in Rats

The dimethyhydrazine (DMH) or azoxymethane (AOM) model is a well-established, well-appreciated, and widely used model of experimental colon carcinogenesis. It has many morphological as well as molecular similarities to human sporadic colorectal cancer (CC), which are summarized and discussed in this paper. In addition, the paper combines present knowledge of morphological and molecular features in the multistep development of CC recognized in the DMH/AOM rat model. This understanding is necessary in order to accurately identify and interpret alterations that occur in the colonic mucosa when evaluating natural or pharmacological compounds in DMH/AOM rat colon carcinogenesis. The DMH/AOM model provides a wide range of options for investigating various initiating and environmental factors, the role of specific dietary and genetic factors, and therapeutic options in CC. The limitations of this model and suggested areas in which more research is required are also discussed

Stability and Performance Analysis of Control Systems Subject to Bursts of Deadline Misses

Control systems are by design robust to various disturbances, ranging from noise to unmodelled dynamics. Recent work on the weakly hard model - applied to controllers - has shown that control tasks can also be inherently robust to deadline misses. However, existing exact analyses are limited to the stability of the closed-loop system. In this paper we show that stability is important but cannot be the only factor to determine whether the behaviour of a system is acceptable also under deadline misses. We focus on systems that experience bursts of deadline misses and on their recovery to normal operation. We apply the resulting comprehensive analysis (that includes both stability and performance) to a Furuta pendulum, comparing simulated data and data obtained with the real plant. We further evaluate our analysis using a benchmark set composed of 133 systems, which is considered representative of industrial control plants. Our results show the handling of the control signal is an extremely important factor in the performance degradation that the controller experiences - a clear indication that only a stability test does not give enough indication about the robustness to deadline misses

DMAC: Deadline-Miss-Aware Control

The real-time implementation of periodic controllers requires solving a co-design problem, in which the choice of the controller sampling period is a crucial element. Classic design techniques limit the period exploration to safe values, that guarantee the correct execution of the controller alongside the remaining real-time load, i.e., ensuring that the controller worst-case response time does not exceed its deadline. This paper presents DMAC: the first formally-grounded controller design strategy that explores shorter periods, thus explicitly taking into account the possibility of missing deadlines. The design leverages information about the probability that specific sub-sequences of deadline misses are experienced. The result is a fixed controller that on average works as the ideal clairvoyant time-varying controller that knows future deadline hits and misses. We obtain a safe estimate of the hit and miss events using the scenario theory, that allows us to provide probabilistic guarantees. The paper analyzes controllers implemented using the Logical Execution Time paradigm and three different strategies to handle deadline miss events: killing the job, letting the job continue but skipping the next activation, and letting the job continue using a limited queue of jobs. Experimental results show that our design proposal - i.e., exploring the space where deadlines can be missed and handled with different strategies - greatly outperforms classical control design techniques

Steroid biotransformations in biphasic systems with Yarrowia lipolytica expressing human liver cytochrome P450 genes

BACKGROUND: Yarrowia lipolytica efficiently metabolizes and assimilates hydrophobic compounds such as n-alkanes and fatty acids. Efficient substrate uptake is enabled by naturally secreted emulsifiers and a modified cell surface hydrophobicity and protrusions formed by this yeast. We were examining the potential of recombinant Y. lipolytica as a biocatalyst for the oxidation of hardly soluble hydrophobic steroids. Furthermore, two-liquid biphasic culture systems were evaluated to increase substrate availability. While cells, together with water soluble nutrients, are maintained in the aqueous phase, substrates and most of the products are contained in a second water-immiscible organic solvent phase. RESULTS: For the first time we have co-expressed the human cytochromes P450 2D6 and 3A4 genes in Y. lipolytica together with human cytochrome P450 reductase (hCPR) or Y. lipolytica cytochrome P450 reductase (YlCPR). These whole-cell biocatalysts were used for the conversion of poorly soluble steroids in biphasic systems. Employing a biphasic system with the organic solvent and Y. lipolytica carbon source ethyl oleate for the whole-cell bioconversion of progesterone, the initial specific hydroxylation rate in a 1.5 L stirred tank bioreactor was further increased 2-fold. Furthermore, the product formation was significantly prolonged as compared to the aqueous system. Co-expression of the human CPR gene led to a 4-10-fold higher specific activity, compared to the co-overexpression of the native Y. lipolytica CPR gene. Multicopy transformants showed a 50-70-fold increase of activity as compared to single copy strains. CONCLUSIONS: Alkane-assimilating yeast Y. lipolytica, coupled with the described expression strategies, demonstrated its high potential for biotransformations of hydrophobic substrates in two-liquid biphasic systems. Especially organic solvents which can be efficiently taken up and/or metabolized by the cell might enable more efficient bioconversion as compared to aqueous systems and even enable simple, continuous or at least high yield long time processes

Efficacy of face-to-face versus self-guided treatments for disordered gambling: A meta-analysis

Background and aims In the light of growing traditional and novel forms of gambling, the treatment of disordered gambling is gaining increasing importance and practical relevance. Most studies have examined face-to-face treatments. Although trials implementing self-guided treatments have recently been conducted, these options have not yet been systematically examined. The primary objective of this meta-analysis, therefore, was to analyze the efficacy of all types of psychological face-to-face and self-guided treatments. Methods A multilevel literature search yielded 27 randomized controlled studies totaling 3,879 participants to provide a comprehensive comparative evaluation of the short- and long-term efficacies of face-to-face and self-guided treatments for disordered gambling. Results As expected, the results revealed significantly higher effect sizes for face-to-face treatments (16 studies with Hedges’s g ranging from 0.67 to 1.15) as compared with self-guided treatments (11 studies with Hedges’s g ranging from 0.12 to 0.30) regarding the reduction of problematic gambling behavior. The intensity of treatment moderated the therapy effect, particularly for self-guided treatments. Discussion and Conclusions The results of this meta-analysis favor face-to-face treatments over self-guided treatments for the reduction of disordered gambling. Although the findings broaden the scope of knowledge about psychological treatment modalities for disordered gambling, further research is needed to identify the reasons for these differences with the goal to optimize the treatment for this disabling condition