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Validated Model (validated + model)
Selected AbstractsContinuous local intrahippocampal delivery of adenosine reduces seizure frequency in rats with spontaneous seizuresEPILEPSIA, Issue 9 2010Annelies Van Dycke Summary Purpose:, Despite different treatment options for patients with refractory epilepsy such as epilepsy surgery and neurostimulation, many patients still have seizures and/or drug-related cerebral and systemic side effects. Local intracerebral delivery of antiepileptic compounds may represent a novel strategy with specific advantages such as the option of higher local doses and reduced side effects. In this study we evaluate the antiepileptic effect of local delivery of adenosine in the kainic acid rat model, a validated model for temporal lobe epilepsy. Methods:, Fifteen rats, in which intraperitoneal kainic acid injection had induced spontaneous seizures, were implanted with a combination of depth electrodes and a cannula in both hippocampi. Cannulas were connected to osmotic minipumps to allow continuous hippocampal delivery. Rats were freely moving and permanently monitored by video-EEG (electroencephalography). Seizures were scored during 2 weeks of local hippocampal delivery of saline (baseline), followed by 2 weeks of local adenosine (6 mg/ml) (n = 10) or saline (n = 5) delivery (0.23 ,l/h) (treatment). In 7 of 10 adenosine-treated rats, saline was also delivered during a washout period. Results:, During the treatment period a mean daily seizure frequency reduction of 33% compared to the baseline rate was found in adenosine-treated rats (p < 0.01). Four rats had a seizure frequency reduction of at least 50%. Both nonconvulsive and convulsive seizures significantly decreased during the treatment period. In the saline-control group, mean daily seizure frequency increased with 35% during the treatment period. Conclusions:, This study demonstrates the antiseizure effect of continuous adenosine delivery in the hippocampi in rats with spontaneous seizures. [source] Principles of Proper Validation: use and abuse of re-sampling for validationJOURNAL OF CHEMOMETRICS, Issue 3-4 2010Kim H. Esbensen Abstract Validation in chemometrics is presented using the exemplar context of multivariate calibration/prediction. A phenomenological analysis of common validation practices in data analysis and chemometrics leads to formulation of a set of generic Principles of Proper Validation (PPV), which is based on a set of characterizing distinctions: (i) Validation cannot be understood by focusing on the methods of validation only; validation must be based on full knowledge of the underlying definitions, objectives, methods, effects and consequences,which are all outlined and discussed here. (ii) Analysis of proper validation objectives implies that there is one valid paradigm only: test set validation. (iii) Contrary to much contemporary chemometric practices (and validation myths), cross-validation is shown to be unjustified in the form of monolithic application of a one-for-all procedure (segmented cross-validation) on all data sets. Within its own design and scope, cross-validation is in reality a sub-optimal simulation of test set validation, crippled by a critical sampling variance omission, as it manifestly is based on one data set only (training data set). Other re-sampling validation methods are shown to suffer from the same deficiencies. The PPV are universal and can be applied to all situations in which the assessment of performance is desired: prediction-, classification-, time series forecasting-, modeling validation. The key element of PPV is the Theory of Sampling (TOS), which allow insight into all variance generating factors, especially the so-called incorrect sampling errors, which, if not properly eliminated, are responsible for a fatal inconstant sampling bias, for which no statistical correction is possible. In the light of TOS it is shown how a second data set (test set, validation set) is critically necessary for the inclusion of the sampling errors incurred in all ,future' situations in which the validated model must perform. Logically, therefore, all one data set re-sampling approaches for validation, especially cross-validation and leverage-corrected validation, should be terminated, or at the very least used only with full scientific understanding and disclosure of their detrimental variance omissions and consequences. Regarding PLS-regression, an emphatic call is made for stringent commitment to test set validation based on graphical inspection of pertinent t,u plots for optimal understanding of the X,Y interrelationships and for validation guidance. QSAR/QSAP forms a partial exemption from the present test set imperative with no generalization potential. Copyright © 2010 John Wiley & Sons, Ltd. [source] Radiation model of a TiO2 -coated, quartz wool, packed-bed photocatalytic reactorAICHE JOURNAL, Issue 4 2010G. E. Imoberdorf Abstract The radiation field of a packed-bed photocatalytic reactor filled with quartz wool coated with titanium dioxide was modeled using the Monte Carlo technique and the following information: the radiation flux emitted by the lamps, the diameter size distribution of the quartz fiber cloth, the mass of quartz fibers and of TiO2 that was immobilized on the fiber surface as well as the refractive index, and the spectral absorption coefficient of the materials of the system. Modeling predictions were validated with radiometer measurements of the transmitted radiation through the reactor, the root mean square error being <9.7%. Finally, by means of a parametric study, the validated model was used to analyze the effect of the design variables, such as the radii of the quartz fibers, thickness of the TiO2 coatings, and amount of TiO2 -coated quartz wool, on the distribution and nonuniformity of the radiative energy distribution inside the reactor. © 2009 American Institute of Chemical Engineers AIChE J, 2010 [source] Mitochondrial respiration and respiration-associated proteins in cell lines created through Parkinson's subject mitochondrial transferJOURNAL OF NEUROCHEMISTRY, Issue 3 2010A. Raquel Esteves J. Neurochem. (2010) 113, 674,682. Abstract Parkinson's disease (PD) is associated with perturbed mitochondrial function. Studies of cytoplasmic hybrid (cybrid) cell lines containing mitochondria from PD subjects suggest complex I dysfunction in particular is a relatively upstream biochemical defect. To evaluate potential downstream consequences of PD mitochondrial dysfunction, we used a cybrid approach to model PD mitochondrial dysfunction; our cybrid cell lines were generated via transfer of PD or control subject platelet mitochondria to mtDNA-depleted NT2 cells. To confirm our PD cybrid mitochondria did indeed differ from control cybrid mitochondria we measured complex I Vmax activities. Consistent with other PD cybrid reports, relative to control cybrid cell lines the PD cybrid cell line mean complex I Vmax activity was reduced. In this validated model, we used an oxygen electrode to characterize PD cybrid mitochondrial respiration. Although whole cell basal oxygen consumption was comparable between the PD and control cybrid groups, the proton leak was increased and maximum respiratory capacity was decreased in the PD cybrids. PD cybrids also had reduced SIRT1 phosphorylation, reduced peroxisome proliferator-activated receptor-, coactivator-1, levels, and increased NF-kB activation. We conclude mitochondrial respiration and pathways influenced by aerobic metabolism are altered in NT2 cybrid cell lines generated through transfer of PD subject platelet mitochondria. [source] | ||||||||||