Henrik Pedersen - US grants

Introduction: The transient structure and property changes that occur in glassy polymers during chemical and physical aging and/or annealing below the glass-transition temperature Tg are of great current research interest. This time-dependent behavior, also referred to as volume or enthalpy relaxation (or recovery), originates from the nonequilibrium nature of the glassy state. From an application point of view, it is apparent that this phenomenon is the controlling factor in predicting the "initial" behavior as well as the practical performance of glassy or partially glassy polymeric materials during their useful lifetimes. Research Summary: In this research, the PIs probe the effects of controlled (and accelerated) chemical and physical aging and/or rejuvenation on achievable barrier property levels in a carefully selected glassy polymer of major commercial significance (polyethylene terephthalate). This will be accomplished by conditioning the polymer over a range of temperatures below Tg with small molecule penetrants (at high chemical potentials) which are interactive with small segment regions. Most importantly, the microstructural changes which specifically control the behavior of transport parameters in sorption and diffusion will be directly measured and identified for the first time, via monitoring of the kinetics of the isomerization reaction which governs the distribution of polymer segmental conformers. The research will be accomplished through combined experiments utilizing gas transmission and Fourier Transform I.R. Spectroscopy, together with enthalpy relaxation studies. Significance: The results of this work will contribute strongly to the development of a comprehensive molecular theory which may lead to the design of a variety of new and/or improved processes for the production of glassy polymers with superior properties in packaging applications, as protective coatings, and for use as permselective membranes in energy-efficient separations of gaseous mixtures, to cite only a few examples. Also, knowledge of both transport and mechanical property variations (which can be interrelated through free volume and its distribution) will be acquired in this research. It is anticipated that novel polymer microstructural states with significantly enhanced property levels and application lifetimes will be discovered.

This research project is focused on the study of recombinant cell kinetics and protein production in both free and immobilized cell bioreactor systems. Building on previous work on lac gene expression, a Bacillus subtilis strain has been chosen with a plasmid for constitutive expression of a- amylase. The plasmid, pBD214, contains both the structural gene and the promoter and signal sequences for enzyme secretion. Experimental design and data gathering procedures are integrated with mathematical modeling aspects to uncover a unified picture of gene expression in recombinant cells in prototypical bioreactors. Development of products from the new biotechnology will require efficient bioreactors and an understanding of the kinetics in these reactors. The kinetics of cell growth, plasmid replication and shedding and gene expression are complex and highly coupled processes. Given the state-of- the-art, it is necessary to examine recombinant cell kinetics in different bioreactor systems to decide optimization of cell growth and product formation in a given process. Accurate, unified models would guide and accelerate process development in numerous cases but such models are currently lacking in the field. This work addresses such limitations.

The equipment requested will be used for several projects, including: Structure and Dynamics of Antigen-Antibody Complexes; Applications of Antibody Engineering; Protein Engineering of Allosteric Antibodies; Protein Separations Utilizing Temperature Sensitive Microemulsions; Engineering Protein Crystallization Processes; Mechanisms of Neurite Outgrowth and Guidance; Development of Hepatocyte Long Term Culture and Storage Techniques; Cellular and Developmental Biology in Plant Cell Cultures; and Immobilized Recombinant Cells. The wide dynamic range offered by the combination of the two instruments, and the simultaneous use of the instruments in certain projects, will allow for an enhanced understanding of underlying biochemical and biophysical phenomena.

GER-9553387 Pedersen This project is a joint effort of the Department of Chemical and Biochemical Engineering and the School of Pharmacy at Rutgers University to establish an environmentally Friendly Pharmaceutical Manufacturing Training Program. Such a training program will have a huge impact on promoting the use of environmentally friendly technology in pharmaceutical manufacturing. Such a program is needed because pharmaceutical processes generate large amounts of avoidable pollution. Better designed and controlled processes would decrease the impact on the environment of pharmaceutical processes, and would also result in reduced cost of drugs; more reliably produced drugs and a more competitive US pharmaceutical industry. The objective of the program proposed here is to train professional capable of designing and implementing successful pollution prevention strategies in pharmaceutical operation. These professionals will require solid knowledge of chemical engineering fundamental; optimization techniques; Current Good Manufacturing Practice (CGMP) guidelines; risk assessment techniques, end-of-pipe treatment strategies, FDA and EPA regulations, and unit operations employed in pharmaceutical processes. Training in these areas will be imparted through a number of activities, including: * an extended menu of courses from several academic units, * a new curriculum component consisting of a year-round seminar/discussion session highlighting successful pollution prevention scenarios * a PhD dissertation * another new curriculum component consisting of a supervised teaching experience * a summer internship in industry In addition to training students, the program proposed here will lead to the establishment of a cohesive and self-sustaining research program on environmentally friendly pharmaceutical manufacturing. Such a research program will generate new technologies for preventing pollution in manufacturing processes, and ensure t he viability of the proposed training program beyond the period of NSF funding allocated by the GRT program. Dissertation topics will address four problems that are of direct interest to industry and that offer high potential for pollution prevention: a) process failures in solid dosage manufacturing due to inadequate handling of solid blending and compaction operations. b) failure of large scale bioreactive processes (due to starvation, shear damage, or poor mixing ) c) lack of schedule optimization in batch processes, generating a large amount of emissions from processing steps such as loading, unloading, venting, cleaning, etc. d) inadequate abatement techniques capable of preventing emission of organic solvents in reactive and purification processes. An aggressive plan for minority recruitment has been formulated. Minority recruitment activities include, among others, expansion of an already established minority undergraduate internship program, which serves as an in situ source of minority and female graduate students, an extensive advertisement campaign in college newspapers with large populations of minority students, and a mailing campaign directed to every Chemical Engineering department in the US. As proof of Rutgers' commitment to this project, the University will provide three five-year fellowships to match NSF's contribution (one of these fellowships will be earmarked for a minority student). Additional matching resources will be obtained from the Department of Chemical and Biochemical Engineering and form ongoing projects funded by other federal agencies and by industry. It is anticipated that these matching resources will allow us to significantly expand the number of students supported by the proposed training program.

The National Science Foundation (NSF) Graduate Research Fellowship Program (GRFP) is a highly competitive, federal fellowship program. GRFP helps ensure the vitality and diversity of the scientific and engineering workforce of the United States. The program recognizes and supports outstanding graduate students who are pursuing research-based master's and doctoral degrees in science, technology, engineering, and mathematics (STEM) and in STEM education. The GRFP provides three years of financial support for the graduate education of individuals who have demonstrated their potential for significant research achievements in STEM and STEM education. This award supports the NSF Graduate Fellows pursuing graduate education at this GRFP institution.<br/><br/>This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.