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991.
Dr. Peter I. Dosa Dr. Tim Ward Dr. Rui E. Castro Prof. Dr. Cecília M. P. Rodrigues Prof. Dr. Clifford J. Steer 《ChemMedChem》2013,8(6):1002-1011
Ursodeoxycholic acid (UDCA) is a bile acid with demonstrated anti‐apoptotic activity in both in vitro and in vivo models. However, its utility is hampered by limited aqueous solubility. As such, water‐soluble prodrugs of UDCA could have an advantage over the parent bile acid in indications where intravenous administration might be preferable, such as decreasing damage from stroke or acute kidney injury. Five phosphate prodrugs were synthesized, including one incorporating a novel phosphoryloxymethyl carboxylate (POMC) moiety. These prodrugs were highly water‐soluble, but showed significant differences in chemical stability, with oxymethylphosphate prodrugs being the most unstable. In a series of NMR experiments, the POMC prodrug was bioactivated to UDCA by alkaline phosphatase (AP) faster than a prodrug containing a phosphate directly attached to the alcohol at the 3‐position of UDCA. Both of these prodrugs showed significant anti‐apoptotic activity in a series of in vitro assays, although the POMC prodrug required the addition of AP for activity, while the other compound was active without exogenous AP. 相似文献
992.
993.
The main objective of this paper was to study the effect of precipitation on the geological development of badlands in arid
regions. Field observations and laboratory investigations were carried out to characterize the surface soils of the Avonlea
badlands in southern Saskatchewan, Canada, which is currently experiencing a rapid development in infrastructure. Three distinct
surface sediments were identified: an upper slope of cemented sandstone, a mid-slope on weathered mudrock and a relatively
flat basal pediment. Each of these soils reacts differently to rainfall events. Precipitation results in grain size reduction
which, together with the consistency limits, explains the water sensitivity of the soils; the fines increased by 16% in the
cemented sandstone, 78% in the weathered mudrock and 33% in the basal pediment. Erosion susceptibility was highest in the
basal pediment (2% clays) followed by cemented sandstone (cementation by 6% active clays) and then by weathered mudrock (cohesion
due to the 40% clay). 相似文献
994.
Poorya Hosseini Sudarshan Martins Tristan Martin Peter Radziszewski Francois-Raymond Boyer 《Minerals Engineering》2011,24(13):1440-1447
Knowledge of the internal variables of a mill is of importance in design and performance optimization of the mill, notwithstanding the difficulty in measuring these variables within the harsh mill environment. To overcome this problem, the research has focused on measuring the internal parameters through non-invasive measurement methods such as the use of the vibration/acoustic signal obtained from the mill. Alternatively, virtual instruments, such as discrete element methods (DEM), are employed. Here, a methodology is developed to simulate on-the-shell acoustic signal emitted from tumbling mills using the information extracted from a DEM simulator. The transfer function which links the forces exerted on the internal surface of the mill and the acoustic signal measured on the outer surface is measured experimentally. Given this transfer function and the force distribution obtained from the DEM simulation, and assuming a linear time-invariant response, the on-the-shell acoustic of a laboratory scale ball mill has been simulated. Comparison of this simulated signal with the signal measured experimentally can be used as a criterion to judge the validity of the DEM simulations, and as a tool for enhancing our understanding of both DEM simulations and the use of acoustics within the context of mineral processing. The results derived from preliminary experiments on a laboratory scale mill shows satisfactory agreement between the actual measurement and the simulated acoustic signal. 相似文献
995.
Karen Hovsepian Peter Anselmo Subhasish Mazumdar 《Knowledge and Information Systems》2011,26(2):195-223
We present a classification algorithm built on our adaptation of the Generalized Lotka–Volterra model, well-known in mathematical
ecology. The training algorithm itself consists only of computing several scalars, per each training vector, using a single
global user parameter and then solving a linear system of equations. Construction of the system matrix is driven by our model
and based on kernel functions. The model allows an interesting point of view of kernels’ role in the inductive learning process.
We describe the model through axiomatic postulates. Finally, we present the results of the preliminary validation experiments. 相似文献
996.
997.
998.
Molenaar Peter C. M.; Sinclair Katerina O.; Rovine Michael J.; Ram Nilam; Corneal Sherry E. 《Canadian Metallurgical Quarterly》2009,45(1):260
Individuals change over time, often in complex ways. Generally, studies of change over time have combined individuals into groups for analysis, which is inappropriate in most, if not all, studies of development. The authors explain how to identify appropriate levels of analysis (individual vs. group) and demonstrate how to estimate changes in developmental processes over time using a multivariate nonstationary time series model. They apply this model to describe the changing relationships between a biological son and father and a stepson and stepfather at the individual level. The authors also explain how to use an extended Kalman filter with iteration and smoothing estimator to capture how dynamics change over time. Finally, they suggest further applications of the multivariate nonstationary time series model and detail the next steps in the development of statistical models used to analyze individual-level data. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献
1000.
Lorena Perrone Dr. Emmanuelle Mothes Maeva Vignes Anaïs Mockel Cindy Figueroa Marie‐Christine Miquel Dr. Marie‐Lise Maddelein Dr. Peter Faller Prof. Dr. 《Chembiochem : a European journal of chemical biology》2010,11(1):110-118
Amyloid‐β peptides (Aβ) and the protein human serum albumin (HSA) interact in vivo. They are both localised in the blood plasma and in the cerebrospinal fluid. Among other functions, HSA is involved in the transport of the essential metal copper. Complexes between Aβ and copper ions have been proposed to be an aberrant interaction implicated in the development of Alzheimer's disease, where Cu is involved in Aβ aggregation and production of reactive oxygen species (ROS). In the present work, we studied copper‐exchange reaction between Aβ and HSA or the tetrapeptide DAHK (N‐terminal Cu‐binding domain of HSA) and the consequence of this exchange on Aβ‐induced ROS production and cell toxicity. The following results were obtained: 1) HSA and DAHK removed CuII from Aβ rapidly and stoichiometrically, 2) HSA and DAHK were able to decrease Cu‐induced aggregation of Aβ, 3) HSA and DAHK suppressed the catalytic HO. production in vitro and ROS production in neuroblastoma cells generated by Cu–Aβ and ascorbate, 4) HSA and DAHK were able to rescue these cells from the toxicity of Cu–Aβ with ascorbate, 5) DAHK was more potent in ROS suppression and restoration of neuroblastoma cell viability than HSA, in correlation with an easier reduction of CuII–HSA than Cu–DAHK by ascorbate, in vitro. Our data suggest that HSA is able to decrease aberrant CuII–Aβ interaction. The repercussion of the competition between HSA and Aβ to bind Cu in the blood and brain and its relation to Alzheimer's disease are discussed. 相似文献