Chaotic behavior in a simple DC drive

Remarkably complex behavior, namely chaotic behavior, in a simple dc chopper-fed dc motor drive system has been investigated. An iterative map that describes the nonlinear dynamics of the system operating in the continuous conduction mode is derived. It shows that different bifurcation diagrams can be obtained by varying different system parameters, and the system exhibits not only a typical period-doubling route to chaos but also the period-3 window. Analytical modeling of period-1 and hence period-p orbits as well as their stability analysis using the characteristic multipliers are presented. Thus, those stable ranges of various system parameters can be formulated, and hence the chaotic ranges can be determined. The theoretical results are verified by using both PSpice simulation and experimental measurement.published_or_final_versio

Transcriptional regulation of FoxO3 gene by glucocorticoids in murine myotubes.

Glucocorticoids and FoxO3 exert similar metabolic effects in skeletal muscle. FoxO3 gene expression was increased by dexamethasone (Dex), a synthetic glucocorticoid, both in vitro and in vivo. In C2C12 myotubes the increased expression is due to, at least in part, the elevated rate of FoxO3 gene transcription. In the mouse FoxO3 gene, we identified three glucocorticoid receptor (GR) binding regions (GBRs): one being upstream of the transcription start site, -17kbGBR; and two in introns, +45kbGBR and +71kbGBR. Together, these three GBRs contain four 15-bp glucocorticoid response elements (GREs). Micrococcal nuclease (MNase) assay revealed that Dex treatment increased the sensitivity to MNase in the GRE of +45kbGBR and +71kbGBR upon 30- and 60-min Dex treatment, respectively. Conversely, Dex treatment did not affect the chromatin structure near the -17kbGBR, in which the GRE is located in the linker region. Dex treatment also increased histone H3 and/or H4 acetylation in genomic regions near all three GBRs. Moreover, using chromatin conformation capture (3C) assay, we showed that Dex treatment increased the interaction between the -17kbGBR and two genomic regions: one located around +500 bp and the other around +73 kb. Finally, the transcriptional coregulator p300 was recruited to all three GBRs upon Dex treatment. The reduction of p300 expression decreased FoxO3 gene expression and Dex-stimulated interaction between distinct genomic regions of FoxO3 gene identified by 3C. Overall, our results demonstrate that glucocorticoids activated FoxO3 gene transcription through multiple GREs by chromatin structural change and DNA looping

Optimización de la aceptabilidad general mediante pruebas afectivas y metodología de superficie de respuesta de una bebida a base de una mezcla seca de polvo de cacao

This research work had as main objective optimizing the general acceptability though affective tests and response surface methodology of a dry cacao powder mixture based beverage. We obtained formulations of mixtures of cacao powder with different concentrations of 15%, 17.5% and 20%, as well as lecithin concentrations of 0.1%; 0.3%; and 0.5% maintaining a constant content of sugar (25 %), Vanillin (1%) that included cacao powder with different pH values: natural (pH 5) and alkalinized (pH 6.5 and pH 8) and water by difference to 100%, generating a total of fifteen treatments to be evaluated, according to the Box-Behnen design for three factors. The treatments underwent satisfaction level tests to establish the general acceptability. The treatment that included cacao powder with a concentration of 17.5 %, pH 6.5 and lecithin concentration of 0.3 % obtained the best levels of acceptability. The software Statgraphics Plus 5.1 was used to obtain the treatment with maximum acceptability that corresponded to cacao powder with pH 6.81, with a concentration of 18.24 % and soy lecithin in 0.28% with a tendency to what was obtained in the satisfaction levels tests. Finally we characterized in a physical-chemistry and microbiological way the optimum formulation as well as evaluated sensitively obtaining an acceptability of 6.17.El presente trabajo de investigación tuvo como objetivo principal optimizar la aceptabilidad general mediante pruebas afectivas y metodología de superficie de respuesta de una bebida a base de una mezcla seca de polvo de cacao. Se obtuvieron formulaciones de mezclas de polvo de cacao con diferentes concentraciones del 15%, 17,5% y 20%, así mismo con concentraciones de lecitina de 0,1%; 0,3%; y 0,5% manteniendo constante el contenido de azúcar (25%), vainillina (1%) que incluyeron al polvo de cacao con diferente valor de pH: natural (pH 5) y alcalinizado (pH 6,5 y pH 8) y agua por diferencia al 100%, generándose un total de quince tratamientos a evaluar, según el diseño Box-Behnken para tres factores. Los tratamientos fueron sometidos a pruebas de grado de satisfacción para establecer la aceptabilidad en general. El tratamiento que incluía polvo de cacao al 17,5% de concentración, pH 6,5 y una concentración de lecitina de 0,3% obtuvo los mejores niveles de aceptabilidad. Se utilizó el programa Statgraphics Plus 5.1 para obtener el tratamiento con máxima aceptabilidad que correspondió a polvo de cacao a pH 6,81, con una concentración de 18,24% y lecitina de soya en un 0,28% con tendencia a lo obtenido en las pruebas de grado de satisfacción. Finalmente se caracterizó fisicoquímicamente y microbiológicamente a la formulación óptima así mismo se le evaluó sensorialmente obteniendo una aceptabilidad de 6,17

Lack of a significant legacy effect of baseline blood pressure 'treatment naivety' on all-cause and cardiovascular mortality in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial

Objectives: To investigate legacy effects at 14-year follow-up of all-cause and cardiovascular disease (CVD) mortality in 'treatment-naive' or 'previous treatment' groups based on blood pressure (BP)-lowering treatment status at baseline. Methods: A post-hoc observational study of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial. We excluded participants with a previous history of CVD events. Cox proportional hazard model and 95% confidence interval were used to estimate the effects of treatment naive on mortality outcomes. Moreover, a subgroup analysis by estimated 10-year Framingham risk score was performed. Results: In multivariable models adjusting for baseline and in-trial characteristics (BP values and number of BP medications as time-dependent variables), there was no statistically significant difference in 5 and 14-year all-cause mortality with a hazard ratio of 0.93 (95% confidence interval 0.80-1.09) and hazard ratio 0.95 (0.88-1.03) and in 5 and 14-year CVD mortality hazard ratio 0.94 (0.72-1.23) and hazard ratio 0.93 (0.80-1.08). In subgroup by absolute CVD risk, no heterogeneity of the association between treatment naive and short-term or long-term all-cause or CVD mortality were found. All comparisons are between the treatment-naive and previous treatment groups. Conclusion: Physicians are concerned about 'legacy effects' of not treating individuals with a BP of 140 mmHg or over and low absolute risk. When treatment intensification was taken into consideration in the primary prevention population in this study, no adverse legacy effect as a result of baseline BP 'treatment naivety' was evident in 14 years of follow-up. The nonsignificant associations were consistent across the CVD risk subgroups. However, the results may be biased due to unobserved residual confounding and therefore should be interpreted with caution

A Dual Function for Prickle in Regulating Frizzled Stability during Feedback-Dependent Amplification of Planar Polarity

The core planar polarity pathway coordinates epithelial cell polarity during animal development, and loss of its activity gives rise to a range of defects, from aberrant morphogenetic cell movements to failure to correctly orient structures, such as hairs and cilia. The core pathway functions via a mechanism involving segregation of its protein components to opposite cells ends, where they form asymmetric intracellular complexes that couple cell-cell polarity. This segregation is a self-organizing process driven by feedback interactions between the core proteins themselves. Despite intense efforts, the molecular pathways underlying feedback have proven difficult to elucidate using conventional genetic approaches. Here we investigate core protein function during planar polarization of the Drosophila wing by combining quantitative measurements of protein dynamics with loss-of-function genetics, mosaic analysis, and temporal control of gene expression. Focusing on the key core protein Frizzled, we show that its stable junctional localization is promoted by the core proteins Strabismus, Dishevelled, Prickle, and Diego. In particular, we show that the stabilizing function of Prickle on Frizzled requires Prickle activity in neighboring cells. Conversely, Prickle in the same cell has a destabilizing effect on Frizzled. This destabilizing activity is dependent on the presence of Dishevelled and blocked in the absence of Dynamin and Rab5 activity, suggesting an endocytic mechanism. Overall, our approach reveals for the first time essential in vivo stabilizing and destabilizing interactions of the core proteins required for self-organization of planar polarity

Identifying allosteric fluctuation transitions between different protein conformational states as applied to Cyclin Dependent Kinase 2

BACKGROUND: The mechanisms underlying protein function and associated conformational change are dominated by a series of local entropy fluctuations affecting the global structure yet are mediated by only a few key residues. Transitional Dynamic Analysis (TDA) is a new method to detect these changes in local protein flexibility between different conformations arising from, for example, ligand binding. Additionally, Positional Impact Vertex for Entropy Transfer (PIVET) uses TDA to identify important residue contact changes that have a large impact on global fluctuation. We demonstrate the utility of these methods for Cyclin-dependent kinase 2 (CDK2), a system with crystal structures of this protein in multiple functionally relevant conformations and experimental data revealing the importance of local fluctuation changes for protein function. RESULTS: TDA and PIVET successfully identified select residues that are responsible for conformation specific regional fluctuation in the activation cycle of Cyclin Dependent Kinase 2 (CDK2). The detected local changes in protein flexibility have been experimentally confirmed to be essential for the regulation and function of the kinase. The methodologies also highlighted possible errors in previous molecular dynamic simulations that need to be resolved in order to understand this key player in cell cycle regulation. Finally, the use of entropy compensation as a possible allosteric mechanism for protein function is reported for CDK2. CONCLUSION: The methodologies embodied in TDA and PIVET provide a quick approach to identify local fluctuation change important for protein function and residue contacts that contributes to these changes. Further, these approaches can be used to check for possible errors in protein dynamic simulations and have the potential to facilitate a better understanding of the contribution of entropy to protein allostery and function