Aptamers, and the selection process known as Systematic Evolution of Ligands by Exponential Enrichment (SELEX) used to generate them, were first described more than twenty years ago. Since then, there have been numerous modifications to the selection procedures. This review discusses the use of modified bases as a means of enhancing serum stability and producing effective therapeutic tools, as well as functionalising these nucleic acids to be used as potential diagnostic agents.
Previous studies have attempted to define the biologic properties of the bone-implant interface using a single specimen harvested from the periprosthetic tissues. The purpose of this study was to examine the heterogeneity in cellular and cytokine profiles of multiple samples taken from the tissues surrounding revised hip prostheses. Clinical and radiographic data for nine patients undergoing surgical revision was gathered prospectively. Three tissue samples were taken systematically from the acetabular and/or femoral bed. Morphologic characteristics of the tissues were assessed using hematoxylin and eosin-stained sections. Immunohistochemical staining was performed using monoclonal antibodies to identify macrophages (EMB11 and CD68); activated macrophages (Leu M3); total T lymphocytes (Leu 4 and T11); T-helper lymphocytes (Leu 3A and CD4); cytotoxic/suppressor T lymphocytes (Leu 2A and CD3); and fibroblasts (5B5). In situ hybridization was used to identify the mRNA for specific proteins: interleukin (IL)1 alpha and -beta, IL-2, IL-6, transforming growth factor beta, tumor necrosis factor alpha (TNF alpha), platelet-derived growth factor alpha (PDGF alpha), and interferon gamma. A quantitative assessment was performed for each section by calculating the percentage of positively staining cells using a light microscope and grid-counting technique. A random effect analysis of variance was calculated to determine both the variance between samples within each patient and the variance between different patients. Standard deviations contributed by sampling variance and patient variance were calculated and an F test was applied. Tissue samples taken from different regions of the bone-prosthesis interface showed marked heterogeneity in cellular and cytokine profiles. Critical F values indicating a statistically significant degree of variance between different tissue samples were exceeded for macrophages, cytotoxic/suppressor T lymphocytes, and T-helper lymphocytes. The cytokine profile was significantly different for IL-2, PDGF alpha, and TNF alpha. This tissue heterogeneity may be due to different mechanical and biologic environments along the bone-prosthesis interface. Thus, caution must be exercised in defining the biologic properties of the tissue surrounding revised prostheses according to a single biopsy.
Significant culling of high-producing cows with low fertility reduces profitability of dairy farms as those cows are replaced with heifers. Induced lactation of nonpregnant cows may be a management alternative to reduce culling and increase profits. The objectives of this study were to evaluate the efficacy of bovine somatotropin (bST) to increase milk production in cows induced into lactation with estrogen plus progesterone, and to determine the profitability of inducing cows into lactation vs. using replacement heifers entering the herd as first-lactation cows. Parity 1 or greater, nonpregnant, healthy Holstein cows (n = 28) were induced into lactation by administration of estradiol-17beta (0.075 mg/kg of body weight [BW] per d) and progesterone (0.25 mg/kg of BW per d) for 7 d. Milking began on d 18. Cows were randomly assigned to control or bST treatment groups on d 37 +/- 20 of milking, and milk production was compared for 70 d. After the 70-d comparison, all cows received bST for the duration of lactation. Cows receiving bST produced more milk (28.4 kg/d) than controls (24.1 kg/d), with variable yields among cows. For the economic analysis, induced cows were compared to first-lactation cows in the same herd using fair market value for costs and multiple component pricing for milk. Net present value for an induced cow (1966 dollars) was significantly greater than that for a first-lactation cow (1446 dollars). Our data suggest that bST use in induced cows is profitable. If a reliable method were developed and approved by the FDA, inducing nonpregnant cows into lactation could be used by dairy producers to increase profitability.
Monoclonal antibodies (mAbs) are biopharmaceuticals produced by mammalian cell lines in bioreactors at a variety of scales. Cell engineering, media optimization, process monitoring, and control strategies for in vitro production have become crucial subjects to meet increasing demand for these high value pharmaceuticals. Raman Spectroscopy has gained great attention in the pharmaceutical industry for process monitoring and control to maintain quality assurance. For the first time, this article demonstrated the possibility of subclass independent quantitative mAb prediction by Raman spectroscopy in real time. The developed model estimated the concentrations of different mAb isotypes with average prediction errors of 0.2 (g/L) over the course of cell culture. In situ Raman spectroscopy combined with chemometric methods showed to be a useful predictive tool for monitoring of real time mAb concentrations in a permeate stream without sample removal. Raman spectroscopy can, therefore, be considered as a reliable process analytical technology tool for process monitor, control, and intensification of downstream continuous manufacturing. The presented results provide useful information for pharmaceutical industries to choose the most appropriate spectroscopic technology for their continuous processes.
Operating agricultural equipment accurately can be difficult, tedious, or even hazardous. Automatic control offers many potential advantages over human control; however, previous efforts to automate agricultural vehicles have been unsuccessful due to sensor limitations. With the recent development of Carrier Phase Differential GPS (CDGPS) technology, a single inexpensive GPS receiver can measure a vehicle's position to within a few centimeters and heading to within 0.1˚. The ability to provide accurate real-time information about multiple vehicle states makes CDGPS ideal for automatic control of vehicles. In this work, a CDGPS-based steering control system was designed, simulated, and tested on a large farm tractor. A highly simplified vehicle model proved sufficient for accurate controller design. After various calibration tests, closed-loop heading control was demonstrated to a one-σ accuracy of better than 1˚, and closed-loop line tracking to a standard deviation of better than 2.5 cm. Future plans for research include the use of a pseudo-satellite to eliminate any position bias and extending the current control system to control a towed implement.
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