bluuebunny/crossref_metadata_2025_split huggingface dataset:
Baculovirus Kinetics, Insect Cell Culture
Authors: Chan Leslie , Reid Steve , Keld Nielsen Lars 
Published: April 2010

AbstractViral‐based processes continue to represent an important class of cell culture processes. Indeed, the number of viral‐based cell culture processes is increasing with (a) viral vaccine production moving from primary cells to continuous cell lines, (b) increased use of viral biopesticides, (c) increased use of viral expression systems, and (d) the use of viral gene therapy vectors. The inherent complexity combined with the problems of working with human or animal pathogens has meant that the academic treatment of viral production kinetics has lagged behind that of other cell culture systems. The emergence of the baculovirus (an innocuous insect virus) for protein expression changed this situation and the baculovirus is used throughout this article to illustrate how to handle complex viral kinetics. Emphasis is placed on the development of mathematical models, which are essential tools when studying viral production kinetics.
Water and Wastewater Treatment, Automation
Authors: Olsson Gustaf 
Published: April 2010

AbstractAdvanced control is increasingly in demand in water and wastewater treatment systems. Various case studies have shown significant savings in operating costs, including energy costs, and remarkably short pay back times. It has been demonstrated that instrumentation, control, and automation (ICA) may increase the capacity of biological nutrient removing wastewater treatment plants by 10–30%. With further understanding and exploitation of the mechanisms involved in biological nutrient removal, the improvements due to ICA may reach another 20–50% of the total system investments within the next 10–20 years.
Carbonyl Reductase
Authors: Hiroaki Yamamoto 
Published: April 2010

AbstractOptically active alcohols are very useful as building blocks and intermediates for the syntheses of fragrances, agricultural chemicals and, especially, pharmaceuticals. The synthesis of chiral alcohols by enzymatic asymmetric reduction is a powerful and versatile method. Chiral Alcohols are catalyzed by enantioselective alcohol dehydrogenases, carbonyl reductases, and microorganisms containing responsible enzymes. In this review, a variety of the enzymes, their applications, and regeneration methods of coenzymes, NAD(P)H, are summarized.
Enzymatic Synthesis of Chiral Drug Intermediates
Authors: Patel Ramesh N. 
Published: April 2010

AbstractChirality is a key factor for the safety and efficacy of many drug products, and thus the production of single enantiomers of drug intermediates has become increasingly important in the pharmaceutical industry. There has been an enormous potential of microorganisms and enzymes derived therefrom for the transformation of synthetic chemicals with high chemo‐, regio‐, and enatioselectivities. In this article, chemoenzymatic processes, are described, for the synthesis of chiral intermediates for development of pharmaceuticals.
Fluorescence Techniques for Bioprocess Monitoring
Authors: Anton Fabienne , Lindemann Carsten , Hitzmann Bernd , Reardon Kenneth F. , Scheper Thomas 
Published: April 2010

AbstractModern bioprocess control requires instantaneous data acquisition and in‐time evaluation of bioprocess variables. Optical sensor systems are of increasing interest in bioprocess monitoring because they are very sensitive and offer the possibility of on‐line,in situ, and noninvasive process monitoring. In this regard, on‐line fluorescence spectroscopy is a useful tool in the development of methods for bioprocess monitoring because many cellular substances and media components are biogenic fluorophors. This technique and the application of chemometric methods offer a deeper insight into biological processes and thus process monitoring, optimization, and control is accessible. In this review, an overview of the developments and applications of on‐line fluorescence techniques for bioprocess monitoring over the last 25 years is given with emphasis on 2D fluorescence spectroscopy.
Impeller Selection for Animal Cell Culture
Authors: Nienow Alvin W. 
Published: April 2010

Abstract

Impellers in animal (mammalian and insect) cell culture bioreactors essentially have to meet the same tasks as impellers in other bioreactors. However, there are special features of both free suspension and microcarrier cell culture that lead to particular agitation conditions compared to the others. Even at

, the oxygen transfer requirements are very modest and hence so are the specific power input and aeration rate. Because they lack a cell wall, the cells are also perceived to be easily damaged by agitation, which also encourages low levels of these parameters and the selection of “low shear” impellers. Here, it is shown that the concept of “low shear” impellers is misleading and that in free suspension, animal cells are quite robust. Thus, almost any impeller can be chosen. However, if all the tasks, especially homogenization, that impeller(s) have to achieve are considered, certain impeller/vessel characteristics emerge, namely, dual axial flow impellers in a baffled vessel of aspect ratio between about 1 and 1.3, with subsurface feeding. In addition, an open pipe or ring sparger plus variable speed, and moderately overpowered motor are recommended. For microcarriers, the sparse literature suggests that mechanical damage to the cells is significant and related literature on abrasion involving similar particles supports this conclusion. A suitable impeller/vessel configuration to ensure efficient microcarrier suspension is recommended but at this agitation intensity, inhomogeneity, mass transfer, other mixing issues are likely to arise. It is suggested that more work is required on such systems.
Bioreactors, Cell Culture, Commercial Production
Authors: Zhou Tan‐Che , Zhou Wen‐Wen , Hu Weiwei , Zhong Jian‐Jiang 
Published: April 2010

AbstractVarious recombinant proteins expressed by animal cells and secondary metabolites produced by plant cells have significantly increased the demand for high‐value‐added (mainly biopharmaceutical) products in recent years. Without doubt, large‐scale efficient production of these compounds is very important to meet market requirements. As animal cells and plant cells are more sensitive to culture conditions than microorganisms, their bioreactor culture technique is critical to reduce the production cost. In order to favor the desired functions of the cells and achieve cost‐effective large‐scale manufacture, it is necessary to optimize and control the bioreactor environment via operating variables. In this article, the characteristics of various types of cell culture bioreactors including stirred‐tank bioreactors, pneumatically agitated bioreactors, membrane bioreactors, packed and fluidized‐bed bioreactors, and wave bioreactors are discussed. Details of basic bioreactor design principles such as shear force, oxygen supply, and mixing are introduced. The effects of process variables including oxygen and mass transfer, fluid mixing, temperature, pH, and light irradiation on cell cultures are described. Bioreactor operation strategies for cell cultures are compared. For commercial production scale‐up, different criteria are considered and industrial large‐scale examples are also illustrated.
Expanded Bed Chromatography, Surface Energetics of Biomass Deposition
Authors: Fernández Lahore Marcelo , Aguilar Oscar , Reddy Vennapusa Rami , Aasim Muhammad 
Published: April 2010

AbstractThe introduction of Expanded Bed Adsorption (EBA) system has made biochemical engineers face the challenge of operating a “chromatography” in the presence of biomass and other particulate components which are normally present in a crude, unclarified, feedstock. This situation can lead to detrimental consequences in terms of increased adsorbent fouling, decreased adsorbent binding capacity, and poor bed hydrodynamics. Biomass and other suspended biological material can be very sticky, depending on the type of adsorbent employed and the solution chemistry involved and thus, can create severe limitations during processing.A better local understanding of biomass deposition, including the two separate cell‐to‐bead (“interaction”) and cell‐to‐cell (“aggregation”) phenomena has been developed to allow for safer EBA operations. To this end, we propose a surface energetics‐based approach. As per the XDLVO theory, free interfacial energy versus distance profiles were calculated for a large combination of model biomass and adsorbent bead types. The energy minima values (absolute value/U) obtained for each of the analyzed cases were correlated with the corresponding deposition coefficient values (α). A positive correlation was obtained. It was concluded that total interaction energyU ≤ − 25 to − 50 kT and biomass deposition parameter α ≤ 0.15 would be a safe region for EBA operation; for example, biomass interference can be neglected. Deviation in the correlation was found in such cases where moderate or high cell‐to‐cell aggregation occurs, for example, in hydrophobic interaction systems. In the later cases, laser diffraction studies were necessary to fully characterize the system.These novel tools will help in alleviating the current EBA technical constraints and will guide the design of more efficient adsorbent types.
Plasmid Purification, Therapeutic Applications
Authors: Barbosa Hélder S. C. , Marcos João Carlos 
Published: April 2010

AbstractThe present high demand for pure pDNA to be used in non‐viral vectors is expected to increase in the forthcoming years with the approval of products that are already in phase III clinical trials. To supply this demand adequate methods for manufacturing pDNA at large scale are being developed. Purification is a fundamental step on the overall pDNA manufacturing and could account for up to 80% of the total operational costs.This article describes the several methods that are available for the purification of pharmaceutical grade pDNA. Starting from cell lysis, the several options of chromatographic and non‐chromatographic methods are described and the advantages and disadvantages of each one highlighted. The different types of chromatography, anion exchange, size exclusion, hydrophobic interaction and affinity, are compared and the specificity of each one described. A special focus is given to non‐chromatographic methods like, precipitation, membrane processes and liquid extraction that are becoming more important on the design of cost‐effective processes. The role of new materials like monoliths to increase the capacity of chromatography, and specific ligands to increase the selectivity of several separation methods is also referred. The integration of different methods to design industrial processes is described and four different cGMP processes are analyzed.
Biocatalytic Synthesis of β‐lactam Antibiotics
Authors: Deaguero Andria L. , Blum Janna K. , Bommarius Andreas S. 
Published: April 2010

AbstractThe penicillins, cephalosporins, carbapenems, and monobactams, make up the β‐lactam family of antibiotics. There are currently more than 25 antibiotics in this family that are approved by the United States Food and Drug Administration and over 50 companies that manufacture them. Their four‐membered β‐lactam ring, which is the part of the antibiotic that is responsible for their bactericidal capabilities, is sensitive to acids, bases, and heat. Therefore, the original chemical synthesis processes utilized to make these compounds required subzero temperatures, hazardous chemicals for protecting groups, and large volumes of organic solvents, rendering them both environmentally harmful and economically taxing. The original syntheses are increasingly being replaced with biocatalytic syntheses which are carried out at ambient temperatures, in aqueous medium, and without the use of auxiliary chemicals, rendering them environmentally benign and economically advantageous processes. The most important enzymes utilized for these processes are penicillin G acylases, penicillin V acylases, cephalosporin acylases, and expandases.
Bioseparation, Magnetic Particle Adsorbents
Authors: Peuker Urs Alexander , Thomas Owen , Hobley Timothy John , Franzreb Matthias , Berensmeier Sonja , SchÄFer Maria , Hickstein Birgit 
Published: April 2010

Abstract
Downstream processing using magnetic adsorbent particles, so called magnetic beads, is a promising technology for future bioseparation challenges for high‐value as well as for mid‐priced products. Magnetic adsorbent based separation currently applies the same ligand technologies as chromatographic separation. After binding, magnetic forces are used for the separation of protein loaded beads from crude bio suspensions. The concept has been proven in many proof of principle examples but few pilot scale processes, due to two main hurdles: Improved, cheaper magnetic adsorbents are required, as are improved magnetic separators. This review examines where magnetic bead based separations can fit into a downstream process before studying several state of the art synthesis processes for magnetic beads and their magnetic and sorptive properties. An overview of magnetic separator technology is given with special focus on bioprocessing. Examples of the separation and purification of proteins applying magnetic beads to a biosuspension is shown.
Smart Biomaterials and Biosensors: Intelligent Properties of Biomolecules and Cells in Hybrid Devices
Authors: Marx Kenneth A. 
Published: April 2010

AbstractIntelligent properties represent discipline‐independent definitions for complex behaviors of natural (biomacromolecules, cells, organisms), artificial, (algorithms, devices) and hybrid (biosensors) systems. Intelligent properties can be thought of as subproperties of complex adaptive systems that possess: (i) self‐maintenance, (ii) adaptivity, (iii) information preservation, and (iv) spontaneous increase in complexity. The intelligent subproperties includeself‐assembly, self‐organization, self‐repair, self‐replication, self‐maintenance, redundancy, self‐diagnosis, recognition, learning, adaptivity, information storage, signaling, and evolution, to name a few. The properties of biomacromolecules, their complexes, cells, signaling networks, and organism subsystems are discussed within the context of their intelligent properties. Specific biomacromolecules' intelligent properties (e.g. DNA, bacteriorhodopsin) offer a range of application and hybrid device opportunities in creating nanostructures, nanocomputing, microelectronics, optical memory designs, and biosensors. Important biosensor nucleic acid and protein class examples are presented that have basic research and clinical applications. Sophisticated levels of intelligent properties exist within evolved control networks in cells. Therefore, cells have added value integrated into smart biosensors. Cellular networks evolved to control important cellular functions and specific examples of gene regulatory control elements are described. Some naturally occurring smart biomaterials have evolved intelligent properties that play critical roles in maintaining the homeostasis and integrity of an organism. An example is the fibrin gel, critical for blood clotting and wound repair. Our aim has been to better integrate molecular and cellular biochemistry with other scientific disciplines within the context of their applications, interfaces, and shared properties by providing a more universal property language —the intelligent properties—to enrich our understanding of biomolecular systems.
Large‐Scale Protein Purification, Self‐Cleaving Aggregation Tags
Authors: Ghazi Iraj , Wood David W. 
Published: April 2010

AbstractIn the mid‐1980s, the incorporation of affinity tags into recombinant proteins by means of genetic engineering created a highly efficient tool for protein purification. A recent advance in this area has been the addition of self‐cleaving protein domains to conventional affinity tags, which allows the tags to self‐cleave and thus eliminates the requirement for proteolytic removal of the tag. In practice, the native target is released from the affinity tag after purification by a simple temperature, chemical, and/or pH change. Although this is a significant advance for affinity‐tag methods, some limitations still arise from the equipment and consumable resin costs associated with these procedures. In this contribution, we describe solutions to these limitations through the development of a new generation of self‐associating and aggregating tags. One of these tags uses the association of phasin proteins to polyhydroxybutyrate granules coexpressed in the host cell, producing a system where the host cell also produces the affinity matrix. The other is based on reversibly precipitating elastin‐like polypeptide tags that can be separated from cellular contaminants by simple heating and centrifugation. Both these tags allow protein purification to take place using simple mechanical methods, thus eliminating the need for conventional affinity apparatus or reagents. Self‐cleaving aggregation‐tag technologies may dramatically reduce recombinant protein purification costs.
Freezing, Biopharmaceutical Products
Authors: Lam Philippe , Moore Jamie 
Published: April 2010

Abstract
During the manufacturing process of biopharmaceutical products, freeze/thaw of protein solutions are routine operations, allowing product shelf‐life to be extended and providing flexibility in the scheduling of the final fill and finish steps. This article discusses the physics of freezing and thawing, the multiple stresses that can affect protein stability during these operations and the strategies that can be used to mediate these problems.
Flexibility in the use of requesting gestures in squirrel monkeys (Saimiri sciureus)
Authors: Anderson James R. , Kuroshima Hika , Hattori Yuko , Fujita Kazuo 
Published: April 2010

AbstractThree squirrel monkeys, trained to make a requesting gesture, were tested in the presence of a human assistant whose visual attention varied across trials. When food was available in one dish and an empty dish was nearby, the monkeys pointed overwhelmingly toward the former, regardless of where the assistant was looking. Looking at the assistant while pointing (“monitoring”) peaked when she looked at them and when she attempted to engage them in joint attention. When only one dish was present, the monkeys refrained from gesturing if it was empty and if no assistant was present. They gestured more when the assistant made eye contact with them. Furthermore, when the assistant's focus of attention switched from the dish or the ceiling to the monkeys, the latter resumed pointing and increased their monitoring of the assistant. This is the first demonstration of such flexible use of an intentionally communicative requesting gesture in New World monkeys. Am. J. Primatol. 72:707–714, 2010. © 2010 Wiley‐Liss, Inc.
Prolonged effects of short‐term anti‐CD20 B cell depletion therapy in murine systemic lupus erythematosus
Authors: Bekar Kai W. , Owen Teresa , Dunn Robert , Ichikawa Travis , Wang Wensheng , Wang Roger , Barnard Jennifer , Brady Sean , Nevarez Sarah , Goldman Bruce I. , Kehry Marilyn , Anolik Jennifer H. 
Published: April 2010

AbstractObjectiveAlthough B cells are implicated in the pathogenesis of systemic lupus erythematosus, the role of B cell depletion (BCD) as a treatment is controversial, given the variable benefit in human disease. This study was undertaken to test the effects of BCD therapy in a murine lupus model to better understand the mechanisms, heterogeneity, and effects on disease outcomes.Methods(NZB × NZW)F1 female mice with varying degrees of disease severity were treated with an anti‐mouse CD20 (anti‐mCD20) antibody (IgG2a), BR3‐Fc fusion protein (for BAFF blockade), or control anti‐human CD20 monoclonal antibody (∼10 mg/kg each). Tissue samples were harvested and analyzed by flow cytometry. The development and extent of nephritis were assessed by monitoring proteinuria (using a urine dipstick) and by immunohistochemical analysis of the kidneys. Serum immunoglobulin levels were measured by enzyme‐linked immunosorbent assay.ResultsAfter a single injection of anti‐mCD20, BCD was more efficient in the peripheral blood, lymph nodes, and spleen compared with the bone marrow and peritoneum of normal mice as well as younger mice with lupus. Since depletion of the marginal zone and peritoneal B cells was incomplete and variable, particularly in older mice with established nephritis, a strategy of sequential weekly dosing was subsequently used, which improved the extent of depletion. BAFF blockade further enhanced depletion in the spleen and lymph nodes. Early BCD therapy delayed disease onset, whereas BCD therapy in mice with advanced disease reduced the progression of nephritis. These effects were long‐lasting, even after B cell reconstitution occurred, and were associated with a reduction in T cell activation but no significant change in autoantibody production.ConclusionThe lasting benefit of a short course of BCD therapy in lupus‐prone mice with an intact immune system and established disease highlights the validity of this treatment approach.
SIGIRR/TIR‐8 is an inhibitor of toll‐like receptor signaling in primary human cells and regulates inflammation in models of rheumatoid arthritis
Authors: Drexler Stefan K. , Kong Philip , Inglis Julia , Williams Richard O. , Garlanda Cecilia , Mantovani Alberto , Yazdi Amir S. , Brennan Fionula , Feldmann Marc , Foxwell Brian M. J. 
Published: April 2010

AbstractObjectiveSingle‐immunoglobulin interleukin‐1 receptor–related (SIGIRR), which is also known as Toll/interleukin‐1 receptor 8 (TIR‐8), is a member of the TIR domain–containing family of receptors and was first characterized as an inhibitor of interleukin‐1 receptor (IL‐1R) and Toll‐like receptor (TLR) signaling. In the Dextran sulfate sodium–induced colitis model, SIGIRR−/− mice were shown to have increased inflammation and to be more susceptible to endotoxin challenge. Increasing evidence implicates TLR and IL‐1R signaling in the pathology of rheumatoid arthritis (RA). Therefore, the purpose of this study was to investigate the involvement of SIGIRR in regulating inflammation in disease‐relevant models.MethodsPrimary human monocyte‐derived macrophages and dendritic cells (DCs) were used to overexpress SIGIRR as well as to knock down endogenously expressed SIGIRR using small interfering RNAs. SIGIRR was also overexpressed in synovial cells derived from RA patients. To investigate the role of SIGIRR in vivo, zymosan‐induced arthritis (ZIA) and collagen antibody–induced arthritis (CAIA) were induced in SIGIRR‐knockout mice.ResultsSIGIRR overexpression inhibited TLR‐induced cytokine production in macrophages and DCs, while SIGIRR knockdown resulted in increased cytokine production following TLR stimulation. Moreover, SIGIRR overexpression inhibited the spontaneous release of cytokines by human RA synovial cells. The role of SIGIRR as an inhibitor of inflammation was confirmed in vivo, since SIGIRR−/− mice developed a more severe disease in both the ZIA and CAIA models.ConclusionOur study is the first to show the expression pattern and function of SIGIRR in primary human cells. Furthermore, this investigation defines the role of SIGIRR in disease‐relevant cell types and demonstrates that SIGIRR is a potential therapeutic target for RA.