Magnetic separations in biotechnology—a review

Magnetic separation technology has a broad range of potential applications in both small and large scale biotechnology. This review considers a selection of magnetic techniques and their possible uses.     

Bioprocess applications of model-based estimation techniques

The last decade has seen the development of a number of approaches for estimating those variables which are difficult to measure on-line in industrial process situations. Whilst a range of techniques is available, a common element is the use of process knowledge in the form of a system model. In the case of bioprocess systems, although a large range of models has been presented in the literature, their use in estimation schemes on an industrial scale has been limited. A number of reasons can be identified for their low level of utilisation. Of particular significance is the uncertainty which exists in quantifying system performance and the process-model mismatch which inevitably results. The level of ‘pre-defined model’ uncertainty, together with the knowledge gained during the course of the fermentation, serves to dictate estimator structure. The paper considers a range of estimation strategies and contrasts, through industrial applications, their performance characteristics and utility.     

Self-efficacy and work-related performance: The integral role of individual differences.

The present study estimated the unique contribution of self-efficacy to work-related performance controlling for personality (the Big 5 traits), intelligence or general mental ability, and job or task experience. Results, based on a meta-analysis of the relevant literatures, revealed that overall, across all studies and moderator conditions, the contribution of self-efficacy relative to purportedly more distal variables is relatively small. Within moderator categories, there were several cases in which self-efficacy made unique contributions to work-related performance. For example, self-efficacy predicted performance in jobs or tasks of low complexity but not those of medium or high complexity, and self-efficacy predicted performance for task but not job performance. Overall, results suggest that the predictive validity of self-efficacy is attenuated in the presence of individual differences, though this attenuation does depend on the context. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Preliminary irradiation test results from the Yankee Atomic Electric Company reactor vessel test irradiation program

The Yankee Atomic Electric Company test irradiation program was implemented to characterize the irradiation response of representative Yankee Rowe reactor vessel beltline plate materials and to remove uncertainties in the analysis of existing irradiation data on the Yankee Rowe reactor vessel steel. Plate materials each containing 0·24 w/o copper, but different nickel contents at 0·63 w/o and 0·19 w/o, were heat treated to simulate the Yankee vessel heat treatment (austenitized at 982°C (1800°F)) and to simulate Regulatory Guide 1·99 database materials (austenitized at 871°C (1600°F)). These heat treatments produced different microstructures so the effect of microstructure on irradiation damage sensitivity could be tested. Because the nickel content of the test plates varied and the copper level was constant, the effect of nickel on irradiation embrittlement was also tested. Correlation monitor material, HSST-02, was included in the program to benchmark the Ford Nuclear Reactor (University of Michigan Test Reactor) which had never been used before for this type of irradiation program. Materials taken from plate surface locations (versus 1/4T) were included to test whether or not the improved toughness properties of the plate surface layer, resulting from the rapid quench, are maintained after irradiation. If the improved properties are maintained, pressurized thermal shock calculations could utilize this margin. Finally, for one experiment, irradiations were conducted at two irradiation temperatures (260°C and 288°C) to determine the effect of irradiation temperature on embrittlement. The preliminary results of the irradiation program show an average temperature effect of 38°C for a 28°C difference in irradiation temperature. The results suggest that for nickel bearing steels, the superior toughness of plate surface material is maintained after irradiation and for the copper content tested, nickel has little effect on irradiation response. No apparent microstructure effect on irradiation response was noted and the HSST-02 material's response to irradiation was similar to results from power reactor and other test reactor tests, thus qualifying the Ford Test Reactor for irradiation experiments such as those conducted for the Yankee Atomic program.     

Mortar finite element discretization for the flow in a nonhomogeneous porous medium

Darcy’s equations model the flow of a viscous incompressible fluid in a rigid porous medium. One of the parameters of the system depends on the permeability of the medium and, when this medium is not homogeneous, the variations of the parameter could be very high. To handle this phenomenon, we propose a discretization of the model that relies on the mortar finite element method. Indeed, the idea is to construct a decomposition of the domain such that the permeability is constant on each element of the partition and to use independent meshes on the different subdomains. We perform the a priori and a posteriori analysis of this discretization and present some numerical experiments which are in good coherency with the results of the analysis.     

Connective Ethnography for the Exploration of e-Science

E-science comprises diverse sites, connected in complex and heterogeneous ways. While ethnography is well established as a way of exploring the detail of the knowledge production process, some strategic adaptations are prompted by this spatial complexity of e-science. This article describes a study that focused on the biological discipline of systematics, exploring the ways in which use of a variety of information and communication technologies has become a routine part of disciplinary practice. The ethnography combined observation and interviews within systematics institutions with mailing list participation, exploration of web landscapes, and analysis of expectations around information and communications technologies as portrayed in policy documents. Exploring connections among these different activities offers a means of understanding multiple dimensions of e-science as a focus of practice and policy. It is important when studying e-science to engage critically with claims about the transformative capacity of new technologies and to adopt methodologies that remain agnostic in the face of such claims: A connective approach to ethnography offers considerable promise in this regard.     

Neutrophil Extracellular Traps and Their Implications in Cardiovascular and Inflammatory Disease

Neutrophils are primary effector cells of innate immunity and fight infection by phagocytosis and degranulation. Activated neutrophils also release neutrophil extracellular traps (NETs) in response to a variety of stimuli. These NETs are net-like complexes composed of cell-free DNA, histones and neutrophil granule proteins. Besides the evolutionarily conserved mechanism to capture and eliminate pathogens, NETs are also associated with pathophysiological processes of various diseases. Here, we elucidate the mechanisms of NET formation and their different implications in disease. We focused on autoinflammatory and cardiovascular disorders as the leading cause of death. Neutrophil extracellular traps are not only present in various cardiovascular diseases but play an essential role in atherosclerotic plaque formation, arterial and venous thrombosis, as well as in the development and progression of abdominal aortic aneurysms. Furthermore, NETosis can be considered as a source of autoantigens and maintains an inflammatory milieu promoting autoimmune diseases. Indeed, there is further need for research into the balance between NET induction, inhibition, and degradation in order to pharmacologically target NETs and their compounds without impairing the patient’s immune defense. This review may be of interest to both basic scientists and clinicians to stimulate translational research and innovative clinical approaches.     

Characterization and Reconstitution of Human Lipoyl Synthase (LIAS) Supports ISCA2 and ISCU as Primary Cluster Donors and an Ordered Mechanism of Cluster Assembly

Lipoyl synthase (LIAS) is an iron–sulfur cluster protein and a member of the radical S-adenosylmethionine (SAM) superfamily that catalyzes the final step of lipoic acid biosynthesis. The enzyme contains two [4Fe–4S] centers (reducing and auxiliary clusters) that promote radical formation and sulfur transfer, respectively. Most information concerning LIAS and its mechanism has been determined from prokaryotic enzymes. Herein, we detail the expression, isolation, and characterization of human LIAS, its reactivity, and evaluation of natural iron–sulfur (Fe–S) cluster reconstitution mechanisms. Cluster donation by a number of possible cluster donor proteins and heterodimeric complexes has been evaluated. [2Fe–2S]-cluster-bound forms of human ISCU and ISCA2 were found capable of reconstituting human LIAS, such that complete product turnover was enabled for LIAS, as monitored via a liquid chromatography–mass spectrometry (LC–MS) assay. Electron paramagnetic resonance (EPR) studies of native LIAS and substituted derivatives that lacked the ability to bind one or the other of LIAS’s two [4Fe–4S] clusters revealed a likely order of cluster addition, with the auxiliary cluster preceding the reducing [4Fe–4S] center. These results detail the trafficking of Fe–S clusters in human cells and highlight differences with respect to bacterial LIAS analogs. Likely in vivo Fe–S cluster donors to LIAS are identified, with possible connections to human disease states, and a mechanistic ordering of [4Fe–4S] cluster reconstitution is evident.     

Out-of-Field Hippocampus from Partial-Body Irradiated Mice Displays Changes in Multi-Omics Profile and Defects in Neurogenesis

The brain undergoes ionizing radiation exposure in many clinical situations, particularly during radiotherapy for brain tumors. The critical role of the hippocampus in the pathogenesis of radiation-induced neurocognitive dysfunction is well recognized. The goal of this study is to test the potential contribution of non-targeted effects in the detrimental response of the hippocampus to irradiation and to elucidate the mechanisms involved. C57Bl/6 mice were whole body (WBI) or partial body (PBI) irradiated with 0.1 or 2.0 Gy of X-rays or sham irradiated. PBI consisted of the exposure of the lower third of the mouse body, whilst the upper two thirds were shielded. Hippocampi were collected 15 days or 6 months post-irradiation and a multi-omics approach was adopted to assess the molecular changes in non-coding RNAs, proteins and metabolic levels, as well as histological changes in the rate of hippocampal neurogenesis. Notably, at 2.0 Gy the pattern of early molecular and histopathological changes induced in the hippocampus at 15 days following PBI were similar in quality and quantity to the effects induced by WBI, thus providing a proof of principle of the existence of out-of-target radiation response in the hippocampus of conventional mice. We detected major alterations in DAG/IP3 and TGF-β signaling pathways as well as in the expression of proteins involved in the regulation of long-term neuronal synaptic plasticity and synapse organization, coupled with defects in neural stem cells self-renewal in the hippocampal dentate gyrus. However, compared to the persistence of the WBI effects, most of the PBI effects were only transient and tended to decrease at 6 months post-irradiation, indicating important mechanistic difference. On the contrary, at low dose we identified a progressive accumulation of molecular defects that tended to manifest at later post-irradiation times. These data, indicating that both targeted and non-targeted radiation effects might contribute to the pathogenesis of hippocampal radiation-damage, have general implications for human health.