Wiecinski P.N.,University of Wisconsin - Madison |
Wiecinski P.N.,Lancaster Laboratories |
Metz K.M.,University of Wisconsin - Madison |
Metz K.M.,Albion College |
And 9 more authors.
Environmental Science and Technology | Year: 2013
Once released into the environment, engineered nanoparticles (eNPs) are subjected to processes that may alter their physical or chemical properties, potentially altering their toxicity vis-à-vis the as-synthesized materials. We examined the toxicity to zebrafish (Danio rerio) embryos of CdSecore/ZnSshell quantum dots (QDs) before and after exposure to an in vitro chemical model designed to simulate oxidative weathering in soil environments based on a reductant-driven Fenton's reaction. Exposure to these oxidative conditions resulted in severe degradation of the QDs: the Zn shell eroded, Cd2+ and selenium were released, and amorphous Se-containing aggregates were formed. Products of QD weathering exhibited higher potency than did as-synthesized QDs. Morphological endpoints of toxicity included pericardial, ocular and yolk sac edema, nondepleted yolk, spinal curvature, tail malformations, and craniofacial malformations. To better understand the selenium-like toxicity observed in QD exposures, we examined the toxicity of selenite, selenate, and amorphous selenium nanoparticles (SeNPs). Selenite exposures resulted in high mortality to embryos/larvae while selenate and SeNPs were nontoxic. Co-exposures to SeNPs + CdCl2 resulted in dramatic increase in mortality and recapitulated the morphological endpoints of toxicity observed with exposure to products of QD weathering. Cadmium body burden was increased in larvae exposed to weathered QDs or SeNP + CdCl 2 suggesting the increased potency of products of QD weathering was due to selenium modulation of cadmium toxicity. Our findings highlight the need to examine the toxicity of eNPs after they have undergone environmental weathering processes. © 2013 American Chemical Society.
Wei W.,University of California at Davis |
Ninonuevo M.R.,University of California at Davis |
Sharma A.,University of California at Davis |
Danan-Leon L.M.,University of California at Davis |
And 2 more authors.
Analytical Chemistry | Year: 2011
The analysis of heparan sulfate glycosaminoglycans (HSGAGs) variations in human serum at the disaccharide level has a great potential for disease diagnosis and prognosis. However, the lack of available analytical methodology for the compositional analysis of HSGAGs in human serum remains to be addressed to delineate the possible role of HSGAGs on the onset and/or progression of a disease. In this study, we have developed a method for the in-depth compositional analysis of the 12 heparin/HS-derived disaccharides from human serum using a combination of technologies-fractionation, exhaustive digestion, solid phase extraction, and LC-MS/MS. The method exhibits high recovery (72-110%) and good reproducibility (standard deviation of less than 5%) with a low limit of detection and quantification. Errors from the method validation were within 1.1%. Nondetectable non- or low-sulfated disaccharides in human serum were also detected using the optimized protocol. Further applying this method, the comprehensive analysis of HSGAGs compositions in human sera from female donors showed considerable variations in disaccharide patterns and compositions. © 2011 American Chemical Society.
Wadhwa M.,UK National Institute for Biological Standards and Control |
Dilger P.,UK National Institute for Biological Standards and Control |
Hamill M.,UK National Institute for Biological Standards and Control |
Bending D.,University College London |
And 14 more authors.
Journal of Immunological Methods | Year: 2012
One candidate preparation of human sequence recombinant transforming growth factor-β3 (TGF-β3) was formulated and lyophilized at NIBSC prior to evaluation in a collaborative study for its suitability to serve as an international standard. The preparation was tested by 8 laboratories using in vitro bioassays and immunoassays. The candidate preparation 09/234 was judged suitable to serve as an international standard based on the data obtained for biological activity and stability. On the basis of the results reported here, the preparation coded 09/234 was established by the WHO Expert Committee on Biological Standardisation (ECBS) as the WHO 1st IS for human TGF-β3 with an assigned value for TGF-β3 activity of 19, 000. IU/ampoule. © 2012 Elsevier B.V.
Schlehuber L.D.,TransForm Pharmaceuticals |
Schlehuber L.D.,Avaxia Biologics, Inc. |
McFadyen I.J.,TransForm Pharmaceuticals |
Shu Y.,TransForm Pharmaceuticals |
And 18 more authors.
Vaccine | Year: 2011
As a result of thermal instability, some live attenuated viral (LAV) vaccines lose substantial potency from the time of manufacture to the point of administration. Developing regions lacking extensive, reliable refrigeration (" cold-chain" ) infrastructure are particularly vulnerable to vaccine failure, which in turn increases the burden of disease. Development of a robust, infectivity-based high throughput screening process for identifying thermostable vaccine formulations offers significant promise for vaccine development across a wide variety of LAV products. Here we describe a system that incorporates thermal stability screening into formulation design using heat labile measles virus as a prototype. The screening of >11,000 unique formulations resulted in the identification of liquid formulations with marked improvement over those used in commercial monovalent measles vaccines, with <1.0. log loss of activity after incubation for 8. h at 40 °C. The approach was shown to be transferable to a second unrelated virus, and therefore offers significant promise towards the optimization of formulation for LAV vaccine products. © 2011 Elsevier Ltd.
Ausin C.,Therapeutic Proteins |
Kauffman J.S.,Lancaster Laboratories |
Duff R.J.,Lancaster Laboratories |
Shivaprasad S.,Lancaster Laboratories |
Beaucage S.L.,Therapeutic Proteins
Tetrahedron | Year: 2010
Heat-sensitive thiophosphate protecting groups derived from the alcohol 4 or 10 have provided insights in the design of DNA oligonucleotide prodrugs. Indeed, functional groups stemming from the alcohol 9, 15, 16 or 22 may be applicable to thiophosphate protection of immunostimulatory CpG DNA motifs, whereas those originating from the alcohol 3, 5, 12, 13, 18, 20 or 22 offer adequate protection of terminal phosphodiester functions against ubiquitous exonucleases that may be found in biological environments. Functional groups derived from the alcohol 9, 15, 16, 19 or 23 are suitable for the protection of phosphodiester functions flanking the CpG motifs of immunomodulatory DNA sequences.