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Critical Goal (critical + goal)

Distribution by Scientific Domains

Medical Sciences	50%
Life Sciences	50%

Selected Abstracts

Development of a Purification Process for Adenovirus: Controlling Virus Aggregation to Improve the Clearance of Host Cell DNA

BIOTECHNOLOGY PROGRESS, Issue 2 2005
John O. Konz
The clearance of host cell DNA is a critical goal for purification process development for recombinant Ad5 (rAd5) based vaccines and gene therapy products. We have evaluated the clearance of DNA by a rAd5 purification process utilizing nuclease digestion, ultrafiltration, and anion exchange (AEX) chromatography and found residual host cell DNA to consistently reach a limiting value of about 100 pg/1011 rAd5 particles. Characterization of the purified rAd5 product using serial AEX chromatography, hydroxyapatite chromatography, or nuclease treatment with and without particle disruption showed that the residual DNA was associated with virus particles. Using a variety of additional physical characterization methods, a population of rAd5 virus in an aggregated state was detected. Aggregation was eliminated using nonionic detergents to attenuate hydrophobic interactions and sodium chloride to attenuate electrostatic interactions. After implementation of these modifications, the process was able to consistently reduce host cell DNA to levels at or below 5 pg/1011 rAd5 particles, suggesting that molecular interactions between cellular DNA and rAd5 are important determinants of process DNA clearance capability and that the co-purifying DNA was not encapsidated. [source]

Translational Potential of Systems-Based Models of Inflammation

CLINICAL AND TRANSLATIONAL SCIENCE, Issue 1 2009
P.T. Foteinou
Abstract A critical goal of translational research is to convert basic science to clinically relevant actions related to disease prevention, diagnosis, and eventually enable physicians to identify and evaluate treatment strategies. Integrated initiatives are identified as valuable in uncovering the mechanism underpinning the progression of human diseases. Tremendous opportunities have emerged in the context of systems biology that aims at the deconvolution of complex phenomena to their constituent elements and the quantification of the dynamic nteractions between these components through the development of appropriate computational and mathematical models. In this review, we discuss the potential role systems-based translation research can have in the quest to better understand and modulate the nflammatory response. [source]

Covalently linked immunomagnetic separation/adenosine triphosphate technique (Cov-IMS/ATP) enables rapid, in-field detection and quantification of Escherichia coli and Enterococcus spp. in freshwater and marine environments

JOURNAL OF APPLIED MICROBIOLOGY, Issue 1 2010
C.M. Lee
Abstract Aims:, Developing a rapid method for detection of faecal pollution is among the critical goals set forth by the Environmental Protection Agency in its revision of water quality criteria. The purpose of this study is to devise and test covalently linked antibody,bead complexes for faecal indicator bacteria (FIB), specifically Escherichia coli or Enterococcus spp., in measuring water quality in freshwater and marine systems. Methods and Results:, Covalently linked complexes were 58,89% more robust than antibody,bead complexes used in previous studies. Freshwater and marine water samples analysed using covalently linked immunomagnetic separation/adenosine triphosphate quantification technique (Cov-IMS/ATP) and culture-based methods yielded good correlations for E. coli (R = 0·87) and Enterococcus spp. (R = 0·94), with method detection limits below EPA recreational water quality health standards for single standard exceedances (E. coli, 38 cells per 100 ml; Enterococcus spp. , 25 cells per 100 ml). Cov-IMS/ATP correctly classified 87% of E. coli and 94% of Enterococcus spp. samples based on these water quality standards. Cov-IMS/ATP was also used as a field method to rapidly distinguish differential loading of E. coli between two stream channels to their confluence. Conclusions:, Cov-IMS/ATP is a robust, in-field detection method for determining water quality of both fresh and marine water systems as well as differential loading of FIB from two converging channels. Significance and Impact of the Study:, To our knowledge, this is the first work to present a viable rapid, in-field assay for measuring FIB concentrations in marine water environments. Cov-IMS/ATP is a potential alternative detection method, particularly in areas with limited laboratory support and resources, because of its increased economy and portability. [source]

The pathogenesis of cell death in Parkinson's disease , 2007

MOVEMENT DISORDERS, Issue S17 2007
C. Warren Olanow MD
Abstract A number of factors have been implicated in the pathogenesis of cell death in Parkinson's disease (PD). These include oxidative stress, mitochondrial dysfunction, inflammation, excitotoxicity, and apoptosis. While the precise pathogenic mechanism leading to neurodegeneration in PD is not known, there is considerable evidence suggesting that cell death occurs by way of a signal-mediated apoptotic process. PD is also characterized by intracellular proteinaceous inclusions or Lewy bodies. Proteolytic stress arises as a consequence of the excessive production of misfolded proteins, which exceed the capacity of the ubiquitin-proteasome system to degrade them. Recent genetic and laboratory studies support the possible relevance of proteolytic stress to both familial and sporadic forms of PD. Postmortem studies have shown that in the SNc of sporadic PD patients there are reduced levels of the alpha subunit of the 20S proteasome and reduced proteolytic enzyme activities. A determination as to the precise cause of cell death in PD, and the identification of specific targets for the development of drugs that might modify disease progression is one of the most critical goals in PD research. It is anticipated that over the next few years there will be a flurry of scientific activity examining the mechanism of cell death and putative neuroprotective interventions. © 2007 Movement Disorder Society [source]