Parameter estimation of the kinetic α-Pinene isomerization model using the MCSfilter algorithm

This paper aims to illustrate the application of a derivative-free multistart algorithm with coordinate search filter, designated as the MCSFilter algorithm. The problem used in this study is the parameter estimation problem of the kinetic α -pinene isomerization model. This is a well known nonlinear optimization problem (NLP) that has been investigated as a case study for performance testing of most derivative based methods proposed in the literature. Since the MCSFilter algorithm features a stochastic component, it was run ten times to solve the NLP problem. The optimization problem was successfully solved in all the runs and the optimal solution demonstrates that the MCSFilter provides a good quality solution.(undefined)info:eu-repo/semantics/publishedVersio

Modulation of Mrp1 (ABCc1) and Pgp (ABCb1) by Bilirubin at the Blood-CSF and Blood-Brain Barriers in the Gunn Rat

Accumulation of unconjugated bilirubin (UCB) in the brain causes bilirubin encephalopathy. Pgp (ABCb1) and Mrp1 (ABCc1), highly expressed in the blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier (BCSFB) respectively, may modulate the accumulation of UCB in brain. We examined the effect of prolonged exposure to elevated concentrations of UCB on expression of the two transporters in homozygous, jaundiced (jj) Gunn rats compared to heterozygous, not jaundiced (Jj) littermates at different developmental stages (2, 9, 17 and 60 days after birth). BBB Pgp protein expression was low in both jj and Jj pups at 9 days (about 16–27% of adult values), despite the up-regulation in jj animals (2 and 1.3 fold higher than age matched Jj animals at P9 and P17–P60, respectively); Mrp1 protein expression was barely detectable. Conversely, at the BCSFB Mrp1 protein expression was rather high (60–70% of the adult values) in both jj and Jj at P2, but was markedly (50%) down-regulated in jj pups starting at P9, particularly in the 4th ventricle choroid plexuses: Pgp was almost undetectable. The Mrp1 protein down regulation was accompanied by a modest up-regulation of mRNA, suggesting a translational rather than a transcriptional inhibition. In vitro exposure of choroid plexus epithelial cells obtained from normal rats to UCB, also resulted in a down-regulation of Mrp1 protein. These data suggest that down-regulation of Mrp1 protein at the BSCFB, resulting from a direct effect of UCB on epithelial cells, may impact the Mrp1-mediated neuroprotective functions of the blood-cerebrospinal fluid barrier and actually potentiate UCB neurotoxicity

Positive nasal culture of methicillin-resistant Staphylococcus aureus (MRSA) is a risk factor for surgical site infection in orthopedics

Background Although nasal carriage of MRSA has been identified as one of the risk factors for surgical site infection (SSI) with MRSA, there have been no reports of this in the orthopedics field

Data-driven reverse engineering of signaling pathways using ensembles of dynamic models

Signaling pathways play a key role in complex diseases such as cancer, for which the development of novel therapies is a difficult, expensive and laborious task. Computational models that can predict the effect of a new combination of drugs without having to test it experimentally can help in accelerating this process. In particular, network-based dynamic models of these pathways hold promise to both understand and predict the effect of therapeutics. However, their use is currently hampered by limitations in our knowledge of the underlying biochemistry, as well as in the experimental and computational technologies used for calibrating the models. Thus, the results from such models need to be carefully interpreted and used in order to avoid biased predictions. Here we present a procedure that deals with this uncertainty by using experimental data to build an ensemble of dynamic models. The method incorporates steps to reduce overfitting and maximize predictive capability. We find that by combining the outputs of individual models in an ensemble it is possible to obtain a more robust prediction. We report results obtained with this method, which we call SELDOM (enSEmbLe of Dynamic lOgic-based Models), showing that it improves the predictions previously reported for several challenging problems.JRB and DH acknowledge funding from the EU FP7 project NICHE (ITN Grant number 289384). JRB acknowledges funding from the Spanish MINECO project SYNBIOFACTORY (grant number DPI2014-55276-C5-2-R). AFV acknowledges funding from the Galician government (Xunta de Galiza) through the I2C postdoctoral fellowship ED481B2014/133-0. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.info:eu-repo/semantics/publishedVersio

Comparison between two methods of working length determination and its effect on radiographic extent of root canal filling: a clinical study [ISRCTN71486641]

BACKGROUND: Obtaining a correct working length is critical to the success of endodontic therapy. Different methods have been used to identify this crucial measurement. The Aim of this clinical study was to compare the effect of working length determination using apex locator alone or in combination with working length radiograph on the apical extent of root canal filling. METHODS: A total number of 66 patients, 151 canals were randomized into two groups, In group (I) working length was determined by apex locator alone, while in group (II) working length was determined by apex locator confirmed by working length radiograph, length of obturation was assessed, and the total number of radiographs was recorded. The data were analyzed using SAS system and T. tests were carried out. Statistical significance was considered to be P ≤ 0.05. RESULTS: Sixty seven canals in group I were treated with a mean distance from the tip of root canal filling to radiographic apex -0.5 mm ± 0.5 and a mean of a total number of radiographs of 2.0, while in group II eighty four canals were treated with a mean distance from the tip of root canal filling to radiographic apex -0.4 mm ± 0.5 and a mean of a total number of radiographs of 3.2. There was no statistically significant difference in the mean distance from the tip of root filling to radiographic apex between group I and group II (P > 0.05). CONCLUSION: The practice of using electronic apex locator in the determination of working length is useful and reliable with no statistical difference of the radiographic extent of root canal filling when using apex locator alone or in combination with working length radiograph. Under the clinical conditions of this study, it is suggested that the correct use of an apex locator alone could prevent the need for further diagnostic radiographs for determination of working length. This method can be useful in patients who need not to be exposed to repeated radiation because of mental, medical or oral conditions

A cloud-based enhanced differential evolution algorithm for parameter estimation problems in computational systems biology

This is a post-peer-review, pre-copyedit version of an article published in Cluster Computing. The final authenticated version is available online at: https://doi.org/10.1007/s10586-017-0860-1[Abstract] Metaheuristics are gaining increasing recognition in many research areas, computational systems biology among them. Recent advances in metaheuristics can be helpful in locating the vicinity of the global solution in reasonable computation times, with Differential Evolution (DE) being one of the most popular methods. However, for most realistic applications, DE still requires excessive computation times. With the advent of Cloud Computing effortless access to large number of distributed resources has become more feasible, and new distributed frameworks, like Spark, have been developed to deal with large scale computations on commodity clusters and cloud resources. In this paper we propose a parallel implementation of an enhanced DE using Spark. The proposal drastically reduces the execution time, by means of including a selected local search and exploiting the available distributed resources. The performance of the proposal has been thoroughly assessed using challenging parameter estimation problems from the domain of computational systems biology. Two different platforms have been used for the evaluation, a local cluster and the Microsoft Azure public cloud. Additionally, it has been also compared with other parallel approaches, another cloud-based solution (a MapReduce implementation) and a traditional HPC solution (a MPI implementation)Ministerio de Economía y Competitividad; DPI2014-55276-C5-2-RMinisterio de Economía y Competitividad; TIN2013-42148-PMinisterio de Economía y Competitividad; TIN2016-75845-PXunta de Galicia ; R2016/045Xunta de Galicia; GRC2013/05

Quality changes and shelf-life prediction of a fresh fruit and vegetables purple smoothie

The sensory, microbial and bioactive quality changes of untreated (CTRL) and mild heat−treated (HT; 90 ºC/45 s) smoothies were studied and modelled throughout storage (5, 15 and 25 ºC). The overall acceptability was better preserved in HT samples being highly correlated (hierarchical clustering) with the flavour. The sensory quality data estimated smoothie shelf−life (CTRL/HT) of 18/55 (at 5 ºC), 4.5/12 (at 15 ºC), 2.4/5.8 (at 25 ºC) days. The yeast and moulds growth rate was lower in HT compared to CTRL while a lag phase for mesophiles/psychrophiles was observed in HT−5/15 ºC. HT and 5 ºC−storage stabilized the phenolics content. FRAP reported the best correlation (R2=0.94) with the studied bioactive compounds, followed by ABTS (R2=0.81) while DPPH was the total antioxidant capacity method with the lowest adjustment (R2=0.49). Conclusively, modelling was used to estimate the shelf−life of a smoothie based on quality retention after a short time−high temperature heat treatment that better preserved microbial and nutritional quality during storage.The financial support of this research was provided by the Ministerio Español de Economía y Competitividad MINECO (Projects AGL2013−48830−C2−1−R and AGL2013−48993−C2−1−R) and by FEDER funds. G.A. González−Tejedor thanks to Panamá Government for the scholarship to carry out his PhD Thesis. A. Garre (BES−2014−070946) is grateful to the MINECO for awarding him a pre−doctoral grant. We are also grateful to E. Esposito and N. Castillejo for their skilful technical assistance