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PubMed2002

Ecosystem management and ecological modeling.

It is the intention of this paper to demonstrate that environmental technology must be supplemented by other tools to be able to solve environmental problems properly. Five cases are used to illustrate the possibilities of ecological engineering, a new engineering field based on ecology, as chemical engineering is based on chemistry. It encompasses restoration of ecosystems, utilization of ecosystems to the benefit of both mankind and nature, construction of ecosystems, and ecologically sound planning of ecosystems from a holistic point of view. Ecological engineering requires a good knowledge of the system properties of ecosystems to be able to fully utilize the possibilities that ecosystem management offers. Models reflecting the ecosystem properties are furthermore needed to be able to quantify the effects of the ecological engineering solutions to the environmental problems. This is clearly demonstrated in two of the five case studies presented in the paper.

Algorithms↗
PubMed2003

Nucleic acid nanotechnology-towards Angstrom-scale engineering.

Nucleic acids and analogues are suitable building blocks for reliable self-assembly of nanometer-sized two- or three-dimensional materials. In order to mimic or approach nature with respect to size and function, Angstrom-scale chemical engineering is emerging as pivotal for future developments. Efforts within nucleic acid nanotechnology will be focussed on generating rigid and stable low nanometer-sized structures carrying functionalities with predictable spatial positioning allowing, by encoded self-assembly, functional nucleic acid architectures to be built towards applications within the biological and material sciences.

Chelating Agents↗
PubMed2004

Development of a physiologically based pharmacokinetic model for volatile fractions of gasoline using chemical lumping analysis.

Physiologically based pharmacokinetic (PBPK) models have often been used to describe the absorption, distribution, metabolism, and excretion of chemicals in animals but have been limited to single chemicals and simple mixtures due to the numerous parameters required in the models. To overcome the barrier to modeling more complex mixtures, we used a chemical lumping approach, used in the past in chemical engineering but not in pharmacokinetic modeling, in a rat PBPK model for gasoline hydrocarbons. Our previous gasoline model consisted of five individual components (benzene, toluene, ethylbenzene, xylene, and hexane) and a lumped chemical that included all remaining components of whole gasoline. Despite being comprised of hundreds of components, the lumped component could be described using a single set of chemical parameters that depended on the blend of gasoline. In the present study, we extend this approach to evaporative fractions of gasoline. The PBPK model described the pharmacokinetics of all of the volatility-weighted fractions of gasoline when differences in partitioning and metabolism between fractions were taken into account. Adjusting the ventilation rate parameter to account for respiratory depression at high exposures also allowed a much improved description of the data. At high exposure levels, gasoline components competitively inhibit each other's metabolism, and the model successfully accounted for binary interactions of this type, including between the lumped component and the five other chemicals. The model serves as a first example of how the engineering concept of chemical lumping can be used in pharmacokinetics.

Adsorption↗
PubMed1992

Phosphorous pentachloride chemical burn--a slowly healing injury.

A 51-year-old chemical engineer sustained phosphorous pentachloride partial skin thickness burns over 20 per cent of his body surface area. Although macroscopically and microscopically the wound seemed to be superficial, the course of clinical healing of this injury was very slow and painful. Retrospectively this burn should have been treated by early excision and grafting.

Accidents, Occupational↗
PubMedDate not supplied

Metabolic engineering: techniques for analysis of targets for genetic manipulations.

Metabolic engineering has been defined as the purposeful modification of intermediary metabolism using recombinant DNA techniques. With this definition metabolic engineering includes: (1) inserting new pathways in microorganisms with the aim of producing novel metabolites, e.g., production of polyketides by Streptomyces; (2) production of heterologous peptides, e.g., production of human insulin, erythropoitin, and tPA; and (3) improvement of both new and existing processes, e.g., production of antibiotics and industrial enzymes. Metabolic engineering is a multidisciplinary approach, which involves input from chemical engineers, molecular biologists, biochemists, physiologists, and analytical chemists. Obviously, molecular biology is central in the production of novel products, as well as in the improvement of existing processes. However, in the latter case, input from other disciplines is pivotal in order to target the genetic modifications; with the rapid developments in molecular biology, progress in the field is likely to be limited by procedures to identify the optimal genetic changes. Identification of the optimal genetic changes often requires a meticulous mapping of the cellular metabolism at different operating conditions, and the application of metabolic engineering to process optimization is, therefore, expected mainly to have an impact on the improvement of processes where yield, productivity, and titer are important design factors, i.e., in the production of metabolites and industrial enzymes. Despite the prospect of obtaining major improvement through metabolic engineering, this approach is, however, not expected to completely replace the classical approach to strain improvement-random mutagenesis followed by screening. Identification of the optimal genetic changes for improvement of a given process requires analysis of the underlying mechanisms, at best, at the molecular level. To reveal these mechanisms a number of different techniques may be applied: (1) detailed physiological studies, (2) metabolic flux analysis (MFA), (3) metabolic control analysis (MCA), (4) thermodynamic analysis of pathways, and (5) kinetic modeling. In this article, these different techniques are discussed and their applications to the analysis of different processes are illustrated.

Animals↗
PubMed2001

Introducing integrated product and process development into the education of science and engineering undergraduates: a lecture course with an accompanying case-study programme at the ETH chemistry department.

Increased quality requirements in the development of chemical products and a growing awareness within society of the activities of chemical companies present a new challenge to the education of young scientists. Nowadays, the teaching of chemists, chemical engineers and environmental scientists at universities has to go beyond the traditional, discipline-orientated knowledge acquisition. The students also have to learn to work and communicate in interdisciplinary teams, to solve application-oriented tasks and to integrate scientific, economical, ecological and social aspects into their work. For this reason, a case-study programme was launched at the chemistry department of the Swiss Federal Institute of Technology. In this paper, we describe the organisational aspects of the programme, its inclusion into academic and industrial environments and summarise some of the scientific methodologies applied. One of the seven case-studies, an assessment of a modern insecticide, is presented in more detail. Finally, we discuss how far the case-study programme is suitable for introducing a new mode of knowledge production to universities.

Agriculture↗
PubMed2002

Design and construction of novel molecular conjugates for signal amplification (II): use of multivalent polystyrene microparticles and lysine peptide chains to generate immunoglobulin-horseradish peroxidase conjugates.

Spherical polystyrene microparticles expressing a large number of highly reactive functional groups were chemically engineered to generate antibody-enzyme conjugates as novel signal amplification systems. Chemically modified goat anti-human IgG and horseradish peroxidase (HRP) were combined in a 1:5 ratio and attached to 0.44 microm streptavidin microparticles or N-succinimidyl-S-acetylthioacetate (SATA)-activated 0.29 microm amino microparticles with highly reactive free sulfhydryl groups on their surface. The numbers of HRP molecules/microparticle were further increased by coupling HRP to primary amines on N-terminal biotinylated or bromoacetylated polypeptides containing 20 lysine residues prior to conjugation with streptavidin or sulfhydryl groups-containing microparticles. The antibody-poly-HRP immunoconjugates contained an estimated number of 10(5)HRP/streptavidin microparticle and 10(6)HRP/amino microparticle, respectively. These microparticle immunoconjugates efficiently bound to plasma anti-HIV-1 antibodies that had been captured by HIV antigens on 5 microm carboxyl magnetic microparticles and, upon reaction with orthophenyldiamine substrate, produced a detection signal with 5-8 times more sensitivity as compared to conventional HRP-conjugated goat anti-human IgG. The signal amplification technique by microparticle immunoconjugates may provide potentially novel tools for the development of highly sensitive diagnostic systems.

HIV Antibodies↗
PubMed1997

Methods for the treatment of collagenous tissues for bioprostheses.

Collagenous tissue as a biomaterial possesses many favourable characteristics and advantages over synthetic materials. The resemblance to human tissue suggests that it has a performance advantage over alternative materials. This advantage has been exploited to produce clinical devices that have been implanted in patients for more than a quarter of a century. The method of treating collagenous tissue for bioprostheses has developed from crude exposure of tissue to chemicals to a sophisticated level of considering the biochemical, chemical, engineering and clinical aspects of the process. This review focuses on the various chemical and physical treatments that have made the bioprostheses possible, highlighting the chemical agents and the cross-linking mechanism involved.

Animals↗
PubMed2001

Advances in directed protein evolution by recursive genetic recombination: applications to therapeutic proteins.

Recent developments in directed evolution technologies combined with innovations in robotics and screening methods have revolutionized protein engineering. These methods are being applied broadly to many fields of biotechnology, including chemical engineering, agriculture and human therapeutics. More specifically, DNA shuffling and other methods of genetic recombination and mutation have resulted in the improvement of proteins of therapeutic interest. Optimizing genetic diversity and fitness through iterative directed evolution will accelerate improvements in engineered protein therapeutics.

Antibodies↗
PubMed2000

[Tissue engineering: possibilities and perspectives].

Successful tissue engineering requires intensive co-oporation between clinicians, biologists (cell culture, gene therapy), chemical engineers (biomaterials) and industrial partners. In case of wound healing tissue engineered constructs have already been applied successfully in burns and chronic wounds. In order to improve carrier and matrix function biomaterials still have to be optimized. The potential of such constructs might even be enhanced by gene therapeutical methods. The complex mammalian organism has to be considered as the gold standard and the model for perfect tissue engineering. The problem of vascularization of complex organs yet has to be solved. In general it seems to be more promising to substitute deficient components in vivo and to rely on modulating influences within the host organism rather than to create complex organs ex vivo.

Animals↗
PubMed2006

Chemical tools for activity-based proteomics.

Several approaches for proteome analysis and the generation of proteome subsets rely on engineered chemical probes that are tailored towards the detection of different protein classes. The concepts are presented in this review covering the literature until mid-2005.

Enzyme Inhibitors↗
PubMed2002

Engineering of molecular and cellular biocatalysts: selected contributions by James E. Bailey.

James (Jay) E. Bailey was a pioneer in biotechnology and biochemical engineering. During his 30 years in academia he made seminal contributions to many fields of chemical engineering science, including catalysis and reaction engineering, bioprocess engineering, mathematical modeling of cellular processes, recombinant DNA technology, enzyme engineering, and metabolic engineering. This article celebrates some of his contributions to the engineering of molecular and cellular biocatalysts, and identifies the influence he had on current and future research in biotechnology.

Biochemistry↗
PubMed2006

American Association of Anatomists meeting on regenerative medicine.

Several years ago, the American Association of Anatomists (AAA) launched an innovative mini-meeting format as part of their annual meeting. The AAA continued this tradition by sponsoring a 2-day mini-symposium as a part of its meeting at FASEB Experimental Biology, 2006 in San Francisco, CA, USA. This year, the mini-symposium was focused on the promising and rapidly developing field of 'regenerative medicine'. The mini-symposium on 'regenerative medicine' included four separate but thematically integrated sessions: stem cells for regenerative medicine; biomimetic matrices for regenerative medicine; endothelial-mesenchymal transformation in cardiovascular regenerative medicine; and tissue engineering technologies for regenerative medicine. The goal of these sessions was to identify progress and highlight new trends and directions in the evolving field of regenerative medicine. It was an exciting 2-day mini-symposium that reviewed the differential potential of embryonic and adult stem cells, their role in tissue turnover and possible applications in tissue regeneration; identified important evolving basic science issues, such as the role of endothelial-mesenchymal transformation and stem cell recruitment in cardiovascular regenerative medicine; and, finally, clearly demonstrated how understanding basic scientific principles can be translated into novel cell therapeutics and tissue engineering modalities. The workshop also demonstrated the multidisciplinary (speakers included stem cell and developmental biologists, chemical engineers, tissue engineers, biophysicists, mathematicians and surgeons) and international (speakers represented US, Japan, Canada, Switzerland and Korea) character of ongoing efforts in the area of regenerative medicine and stem cell biology, impressive progress in this field, and confirmed the strong potential for clinical translation of emerging regenerative medicine technologies.

Anatomy↗
PubMed2006

Latest development in drug discovery on G protein-coupled receptors.

G protein-coupled receptors (GPCRs) represent the family of proteins with the highest impact from social, therapeutic and economic point of view. Today, more than 50% of drug targets are based on GPCRs and the annual worldwide sales exceeds 50 billion dollars. GPCRs are involved in all major disease areas such as cardiovascular, metabolic, neurodegenerative, psychiatric, cancer and infectious diseases. The classical drug discovery process has relied on screening compounds, which interact favorably with the GPCR of interest followed by further chemical engineering as a mean of improving efficacy and selectivity. In this review, methods for sophisticated chemical library screening procedures will be presented. Furthermore, development of cell-based assays for functional coupling of GPCRs to G proteins will be discussed. Finally, the possibility of applying structure-based drug design will be summarized. This includes the application of bioinformatics knowledge and molecular modeling approaches in drug development programs. The major efforts established through large networks of structural genomics on GPCRs, where recombinantly expressed GPCRs are subjected to purification and crystallization attempts with the intention of obtaining high-resolution structures, are presented as a promising future approach for tailor-made drug development.

Animals↗
PubMed2004

Dynamic control and information processing in chemical reaction systems by tuning self-organization behavior.

Specific external control of chemical reaction systems and both dynamic control and signal processing as central functions in biochemical reaction systems are important issues of modern nonlinear science. For example nonlinear input-output behavior and its regulation are crucial for the maintainance of the life process that requires extensive communication between cells and their environment. An important question is how the dynamical behavior of biochemical systems is controlled and how they process information transmitted by incoming signals. But also from a general point of view external forcing of complex chemical reaction processes is important in many application areas ranging from chemical engineering to biomedicine. In order to study such control issues numerically, here, we choose a well characterized chemical system, the CO oxidation on Pt(110), which is interesting per se as an externally forced chemical oscillator model. We show numerically that tuning of temporal self-organization by input signals in this simple nonlinear chemical reaction exhibiting oscillatory behavior can in principle be exploited for both specific external control of dynamical system behavior and processing of complex information.

Biochemistry↗
PubMedDate not supplied

Modeling of oxygen uptake in perfluorocarbon emulsions. Some comparisons with uptake by blood.

The use of perfluorocarbons emulsified in water as blood substitutes (artificial blood), is well known. Although considerable research has been devoted to the study of stability, toxicity, and gas solubility properties of these emulsions, there is no quantitative guide to the oxygen transport behavior in such emulsions, especially with reference to this transport process in actual blood. This paper describes a mathematical model from which the oxygen flux into a straight, cylindrical tube carrying a perfluorocarbon emulsion may be computed. The solutions to the proposed model can be adapted to that for a capillary or for a single tube in a blood oxygenator. The rates of oxygen transfer, so obtained, have been compared with analogous transfer rates that can be achieved in natural blood flowing under identical conditions. Therefore, the minimal solubilization capacity for oxygen required of a perfluorocarbon emulsion can be estimated on a quantitative basis. The modeling approach used in this study is based on the well tested theory of mass transfer in microheterogeneous media reported in the chemical engineering literature.

Blood↗