937 resultados para Drug Evaluation
Resumo:
Maximum-likelihood estimates of the parameters of stochastic differential equations are consistent and asymptotically efficient, but unfortunately difficult to obtain if a closed-form expression for the transitional probability density function of the process is not available. As a result, a large number of competing estimation procedures have been proposed. This article provides a critical evaluation of the various estimation techniques. Special attention is given to the ease of implementation and comparative performance of the procedures when estimating the parameters of the Cox–Ingersoll–Ross and Ornstein–Uhlenbeck equations respectively.
Resumo:
Background: The aim of this study is to seek an association between markers of metastatic potential, drug resistance-related protein and monocarboxylate transporters in prostate cancer (CaP). Methods: We evaluated the expression of invasive markers (CD147, CD44v3-10), drug-resistance protein (MDR1) and monocarboxylate transporters (MCT1 and MCT4) in CaP metastatic cell lines and CaP tissue microarrays (n=140) by immunostaining. The co-expression of CD147 and CD44v3-10 with that of MDR1, MCT1 and MCT4 in CaP cell lines was evaluated using confocal microscopy. The relationship between the expression of CD147 and CD44v3-10 and the sensitivity (IC50) to docetaxel in CaP cell lines was assessed using MTT assay. The relationship between expression of CD44v3-10, MDR1 and MCT4 and various clinicopathological CaP progression parameters was examined. Results: CD147 and CD44v3-10 were co-expressed with MDR1, MCT1 and MCT4 in primary and metastatic CaP cells. Both CD147 and CD44v3-10 expression levels were inversely related to docetaxel sensitivity (IC50) in metastatic CaP cell lines. Overexpression of CD44v3-10, MDR1 and MCT4 was found in most primary CaP tissues, and was significantly associated with CaP progression. Conclusions: Our results suggest that the overexpression of CD147, CD44v3-10, MDR1 and MCT4 is associated with CaP progression. Expression of both CD147 and CD44v3-10 is correlated with drug resistance during CaP metastasis and could be a useful potential therapeutic target in advanced disease.
Resumo:
Isoindoline nitroxides are potentially useful probes for viable biological systems, exhibiting low cytotoxicity, moderate rates of biological reduction and favorable Electron Paramagnetic Resonance (EPR) characteristics. We have evaluated the anionic (5-carboxy-1,1,3,3-tetramethylisoindolin-2-yloxyl; CTMIO), cationic (5-(N,N,N-trimethylammonio)-1,1,3,3-tetramethylisoindolin-2-yloxyl iodide, QATMIO) and neutral (1,1,3,3-tetramethylisoindolin-2-yloxyl; TMIO) nitroxides and their isotopically labeled analogs ((2)H(12)- and/or (2)H(12)-(15)N-labeled) as potential EPR oximetry probes. An active ester analogue of CTMIO, designed to localize intracellularly, and the azaphenalene nitroxide 1,1,3,3-tetramethyl-2,3-dihydro-2-azaphenalen-2-yloxyl (TMAO) were also studied. While the EPR spectra of the unlabeled nitroxides exhibit high sensitivity to O(2) concentration, deuteration resulted in a loss of superhyperfine features and a subsequent reduction in O(2) sensitivity. Labeling the nitroxides with (15)N increased the signal intensity and this may be useful in decreasing the detection limits for in vivo measurements. The active ester nitroxide showed approximately 6% intracellular localization and low cytotoxicity. The EPR spectra of TMAO nitroxide indicated an increased rigidity in the nitroxide ring, due to dibenzo-annulation.
Resumo:
Operation in urban environments creates unique challenges for research in autonomous ground vehicles. Due to the presence of tall trees and buildings in close proximity to traversable areas, GPS outage is likely to be frequent and physical hazards pose real threats to autonomous systems. In this paper, we describe a novel autonomous platform developed by the Sydney-Berkeley Driving Team for entry into the 2007 DARPA Urban Challenge competition. We report empirical results analyzing the performance of the vehicle while navigating a 560-meter test loop multiple times in an actual urban setting with severe GPS outage. We show that our system is robust against failure of global position estimates and can reliably traverse standard two-lane road networks using vision for localization. Finally, we discuss ongoing efforts in fusing vision data with other sensing modalities.
Resumo:
A model for drug diffusion from a spherical polymeric drug delivery device is considered. The model contains two key features. The first is that solvent diffuses into the polymer, which then transitions from a glassy to a rubbery state. The interface between the two states of polymer is modelled as a moving boundary, whose speed is governed by a kinetic law; the same moving boundary problem arises in the one-phase limit of a Stefan problem with kinetic undercooling. The second feature is that drug diffuses only through the rubbery region, with a nonlinear diffusion coefficient that depends on the concentration of solvent. We analyse the model using both formal asymptotics and numerical computation, the latter by applying a front-fixing scheme with a finite volume method. Previous results are extended and comparisons are made with linear models that work well under certain parameter regimes. Finally, a model for a multi-layered drug delivery device is suggested, which allows for more flexible control of drug release.
Resumo:
Facial expression recognition (FER) algorithms mainly focus on classification into a small discrete set of emotions or representation of emotions using facial action units (AUs). Dimensional representation of emotions as continuous values in an arousal-valence space is relatively less investigated. It is not fully known whether fusion of geometric and texture features will result in better dimensional representation of spontaneous emotions. Moreover, the performance of many previously proposed approaches to dimensional representation has not been evaluated thoroughly on publicly available databases. To address these limitations, this paper presents an evaluation framework for dimensional representation of spontaneous facial expressions using texture and geometric features. SIFT, Gabor and LBP features are extracted around facial fiducial points and fused with FAP distance features. The CFS algorithm is adopted for discriminative texture feature selection. Experimental results evaluated on the publicly accessible NVIE database demonstrate that fusion of texture and geometry does not lead to a much better performance than using texture alone, but does result in a significant performance improvement over geometry alone. LBP features perform the best when fused with geometric features. Distributions of arousal and valence for different emotions obtained via the feature extraction process are compared with those obtained from subjective ground truth values assigned by viewers. Predicted valence is found to have a more similar distribution to ground truth than arousal in terms of covariance or Bhattacharya distance, but it shows a greater distance between the means.