Challenging futures of biodiversity offsets and banking : Critical issues for robust forms of biodiversity conservation

The underlying project “Innovation in Governance” (Grant No. 01UU0906) from which this publication derives is funded by the Federal Ministry of Education and Research (BMBF), Germany.The interactive and anticipatory assessment exercise on which this report is based was part of a broader research project that focused on the innovation dynamics of governance instruments in the areas of environmental markets, public participation methods and sustainability transition management. By circulating these workshop results, we seek to contribute to a debate on biodiversity offsets and banking design with regard to constituting political reality in biodiversity conservation models.BMBF, 01UU0906, Innovation in Governanc

Challenging futures of citizen panels : critical issues for robust forms of public participation

The underlying project “Innovation in Governance” (Grant No. 01UU0906) from which this publication derives is funded by the Federal Ministry of Education and Research (BMBF), Germany.The interactive and anticipatory assessment exercise on which this report is based was part of a broader research project that focused on the innovation dynamics of governance instruments in the areas of public participation methods, environmental markets and sustainability transition management. By circulating these workshop results, we seek to contribute to a debate on citizen panel design with regard to constituting political reality in public participation models.BMBF, 01UU0906, Innovation in Governanc

Prehabilitation of elderly frail or pre-frail patients prior to elective surgery (PRAEP-GO): study protocol for a randomized, controlled, outcome assessor-blinded trial

Background: Frailty is expressed by a reduction in physical capacity, mobility, muscle strength, and endurance. (Pre-) frailty is present in up to 42% of the older surgical population, with an increased risk for peri- and postoperative complications. Consequently, these patients often suffer from a delayed or limited recovery, loss of autonomy and quality of life, and a decrease in functional and cognitive capacities. Since frailty is modifiable, prehabilitation may improve the physiological reserves of patients and reduce the care dependency 12 months after surgery. Methods: Patients >= 70 years old scheduled for elective surgery or intervention will be recruited in this multicenter, randomized controlled study, with a target of 1400 participants with an allocation ratio of 1:1. The intervention consists of (1) a shared decision-making process with the patient, relatives, and an interdisciplinary and interprofessional team and (2) a 3-week multimodal, individualized prehabilitation program including exercise therapy, nutritional intervention, mobility or balance training, and psychosocial interventions and medical assessment. The frequency of the supervised prehabilitation is 5 times/week for 3 weeks. The primary endpoint is defined as the level of care dependency 12 months after surgery or intervention. Discussion: Prehabilitation has been proven to be effective for different populations, including colorectal, transplant, and cardiac surgery patients. In contrast, evidence for prehabilitation in older, frail patients has not been clearly established. To the best of our knowledge, this is currently the largest prehabilitation study on older people with frailty undergoing general elective surgery

Verfahren zur Herstellung pharmazeutischer Plasmid-DNA

Voß C. Processes for the production of pharmaceutical grade plasmid DNA. Bielefeld (Germany): Bielefeld University; 2008.Plasmid DNA is currently used in gene therapy and genetic vaccination as a vector system for the delivery of therapeutic genes. Clinical trials as well as future therapeutics demand large amounts of high quality plasmid DNA that fulfils the specifications set by regulatory authorities. This thesis describes the development, analysis, and evaluation of pharmaceutical plasmid DNA production processes comprising cultivation, product isolation, and purification as well as stability assessment during storage and application. Cultivations on defined media have been analyzed and compared to state of the art cultivations on semidefined medium. The influence of amino acid supplementation as well as the effect of the physiological conditions of the inoculation culture on growth and product formation have been determined. In this way, batch cultivation processes utilizing glycerol based defined media could be established having yield coefficients Y_x/s and product selectivities S_p/x comparable to or exceeding the values obtained with a semidefined medium. Additional proteome analysis indicated a stringent response that could influence plasmid replication. A semi continuous alkaline lysis was combined with froth flotation for large scale product isolation. The procedure was able to produce a highly clear lysate that could directly be applied to subsequent purification. This process was compared to other modes of operation with respect to product formation, contamination with chromosomal DNA, and plasmid form distribution. For the purification of plasmids, DNA-binding proteins were analyzed as potential affinity ligands. In addition, a recombinant RNase has been produced and its capability for RNA depletion could successfully be demonstrated. The partitioning of nucleic acids in reverse micellar two-phase systems was examined and used to develop an extraction process for plasmid purification which could be integrated into different purification schemes that allowed the complete depletion of all contaminants. Finally, the stability of purified plasmid DNA during long term storage and its implication on the effectivity after gene transfer has been investigated

Neue Verfahren zur Produktion von Plasmid-DNA als Biopharmazeutikum

Voß C. Neue Verfahren zur Produktion von Plasmid-DNA als Biopharmazeutikum. Bielefeld; 2001

Isolation of Plasmid-DNA by inverse micelles two phase system - Optimization of the reverse extraction

Streitner N, Voß C, Flaschel E. Isolation of Plasmid-DNA by inverse micelles two phase system - Optimization of the reverse extraction. CHEMIE INGENIEUR TECHNIK. 2008;80(6):831-837

Reverse micellar extraction systems for the purification of pharmaceutical grade plasmid DNA

Streitner N, Voß C, Flaschel E. Reverse micellar extraction systems for the purification of pharmaceutical grade plasmid DNA. JOURNAL OF BIOTECHNOLOGY. 2007;131(2):188-196.Plasmid DNA as an active pharmaceutical ingredient (API) is gaining more and more importance. For the production of multigram quantities of this substance robust and scalable processes comprising several purification steps have to be designed. One main challenge is the initial separation of plasmid DNA and RNA in such a purification scheme. In this study we investigated the distribution of plasmid DNA and RNA in reverse micellar two-phase systems which is considered to be the basis for the development of an extractive purification step that can easily be integrated into common processes. For this purpose the distribution of the 4.6 kb plasmid pUT649 and Escherichia coli RNA in systems comprising isooctane, ethylhexanol, and the surfactant methyltrioctylammoniumchloride (TOMAC) under the influence of different salts was studied. Anion concentrations at which the partitioning behaviour for nucleic acids inverted (inversion point) were identified. Systems capable of separating RNA from plasmid DNA were further analysed and applied to extract RNA from plasmid DNA out of a preconditioned cleared lysate. The capability of reverse micellar systems for plasmid form separation was also shown by capillary and agarose gel electrophoresis. (C) 2007 Elsevier B.V. All rights reserved

Production of recombinant RNase Ba and its application in downstream processing of plasmid DNA for pharmaceutical use

Voß C, Lindau D, Flaschel E. Production of recombinant RNase Ba and its application in downstream processing of plasmid DNA for pharmaceutical use. BIOTECHNOLOGY PROGRESS. 2006;22(3):737-744.The demand for new strategies in downstream processing of biopharmaceutical plasmid DNA has increased in response to the importance of nucleic acids as active pharmaceutical ingredients (API) in gene therapy and genetic vaccination. Led by the problematic usage of animal-derived proteins for producing reagents of clinical applications, we present an opportunity of removing RNA prior to chromatographic steps by using a recombinant RNase Ba (barnase of Bacillus amyloliquefaciens) as an alternative to bovine RNase A. An expression vector for RNase Ba production was constructed enabling periplasmic localization of the recombinant protein. Cultivation of the RNase-producing clone showed stable activity (3.6 kU mL(-1) during stationary phase) throughout the cultivation process. After purification the RNase activity was tested and compared to that of commercially available RNase A. RNase Ba showed no DNase activity even after prolonged incubation with plasmid DNA. Thus, it is a suitable substitute for bovine RNase A in pharmaceutical purification processes

Computation of nitrate concentrations in coastal waters using an in situ ultraviolet spectrophotometer: Behavior of different computation methods in a case study a steep salinity gradient in the southern North Sea

Absorption spectra of seawater can be used to estimate the concentration of nitrate based on the UV absorption characteristic of nitrate. However the results of that estimation show an increased uncertainty compared to wet chemical methods. This is caused by the close proximity and the magnitude of the bromide peak (as the main component of seawater salt) close to the nitrate signal in the UV. Current data processing methods are optimized to give good results under constant conditions in terms of temperature, salinity, and CDOM concentration. However, in coastal regions all three parameters are highly variable. In this work three methods to determine nitrate concentration from the seawater UV spectrum are compared: (A) via the subtraction of the seawater spectrum and CDOM absorbance from the total absorbance of the sample and then fitting the nitrate absorption to the remaining absorbance, (B) the subtraction of the seawater spectrum and fitting the spectral signature of nitrate and CDOM as suggested by Sakamoto et al. (2009) and (C) the direct determination via the fitting of the spectral signature of all components to the sample spectrum. The results of all three methods correlate (R>0.99) very well with each other as well as to the results of the wet chemical analysis. An extensive dataset of a transect from the Southern North Sea into the Weser estuary (RV HEINCKE transect 345), which covers a broad salinity range as well as a broad range of nitrate concentrations, is used to exemplary show the potential and the limitations of all three methods under these conditions

Plasmid topology - An important factor influencing the performance of DNA drug delivery

Schleef M, Voß C, Schmidt T, Flaschel E. Plasmid topology - An important factor influencing the performance of DNA drug delivery. JOURNAL OF LIPOSOME RESEARCH. 2003;13(1):82-83