Antibody fragments as probe in biosensor development

Today's proteomic analyses are generating increasing numbers of biomarkers, making it essential to possess highly specific probes able to recognize those targets. Antibodies are considered to be the first choice as molecular recognition units due to their target specificity and affinity, which make them excellent probes in biosensor development. However several problems such as difficult directional immobilization, unstable behavior, loss of specificity and steric hindrance, may arise from using these large molecules. Luckily, protein engineering techniques offer designed antibody formats suitable for biomarker analysis. Minimization strategies of antibodies into Fab fragments, scFv or even single-domain antibody fragments like VH, VL or VHHs are reviewed. Not only the size of the probe but also other issues like choice of immobilization tag, type of solid support and probe stability are of critical importance in assay development for biosensing. In this respect, multiple approaches to specifically orient and couple antibody fragments in a generic one-step procedure directly on a biosensor substrate are discussed

Profit-driven planning and analysis of a WEEE recycling facility with a multi-period MILP model

Electronic waste is one of the fastest-growing waste streams in the world. The challenges associated with the recycling of Waste Electrical and Electronic Equipment (WEEE) represent both threats, as the improper disposal of this waste can harm the environment and human health, and opportunities, as this category of waste contains valuable and rare resources that can be recovered and repurposed, contributing to the circular economy. The EU is leading the way in improving the collection and treatment of WEEE, but this has not been sufficient to meet the targets set in its WEEE directive. Therefore, additional efforts must be made to ensure the costeffective and environmentally sound recycling of WEEE, both in the public and private sectors. In this thesis, we propose a multi-period MILP model for the planning of a WEEE recycling facility in Belgium and conduct various analyses to provide insights on what elements are the most crucial to the profitability of such a facility. The originality of our approach lies in the multi-period aspect of the model, and the addition of a limited amount of labour to be allocated to various labour-intensive tasks of WEEE recycling. Our main findings are that labour is the most critical resource, both in cost and utilization, such that the optimal quantity of WEEE to process is the one that results in complete utilization of labour, with little to no overtime. As such, the flexibility of labour, both in possible task allocation and overtime capabilities, is crucial to the proper functioning of the facility, especially when taking into account possible deviations from the optimal plan, caused by the heterogeneity of WEEE and other variations such as the timing of deliveries.nhhma

Mare Geneticum : Balancing Governance of Marine Genetic Resources in International Waters

Peer reviewedPublisher PD

The complementarity of green supply chain management practices and the impact on environmental performance

Although the importance of integrating different Green Supply Chain Management (GSCM) activities has been highlighted in the literature, the potential interdependencies between these practices and their performance impacts have not been investigated. The purpose of this study is to examine the collective impact of internal and external GSCM practices on two aspects of environmental performance: environmental impact and environmental cost savings. GSCM is proposed as a collective competency, combining four distinct, but interrelated, sets of practices: environmental management systems, eco design, source reduction and external environmental practices. Using survey data from 138 Omani manufacturing firms and Structural Equation Modelling, we find strong empirical support for the complementarity of GSCM practices. We find a strong positive relationship between the level of collective GSCM competency and the environmental impact achieved. Our findings support the belief that complementarities between GSCM practices lead to better performance. Managers should therefore focus on implementing bundles of GSCM practices rather than searching for individual best practices. We find an indirect, mediated influence on environmental cost savings, which is consistent with previous results in other emerging market contexts

Managing high-end ex-demonstration product returns

Some manufacturers demonstrate their products so that customers can gain experience before making a purchase. We present a novel application of a closed-loop supply chain where product returns from demonstrations of high-end IT equipment are substantial and the major delay in the system is due to the long demonstration time at the client sites. In addition, the product lifecycle is short and the value erodes rapidly over time, with steep drops in the resale revenue when new product generations are introduced. We present a finite lifecycle model that captures the key trade-offs in this environment, that is, either to reuse a collected ex-demo product for a next demonstration or to salvage its residual value in the secondary market and use a new product to satisfy the next demo request. We derive two cost/revenue signals that enable us to distinguish between fast and slow value erosion. We show that the fast/slow erosion decision is dynamic and depends on the rate of value erosion and the length of the demonstration time. We analyze the optimal demo pool strategies and show that in the case of fast erosion it may be better to postpone reuse activities until later in the lifecycle. We illustrate our model using empirical data from a large IT manufacturer and formulate several guidelines so as to better manage high value ex-demonstration product returns

Best Performance Frontiers for Buy-Online-Pickup-in-Store order fulfilment

With the proliferation of omni-channel retailing, Buy-Online-Pickup-in-Store (BOPS) retail services have gained increasing popularity as they have benefits for both customers and retailers. However, using conventional retail stores to fulfil orders received online whilst also serving walk-in customers is challenging for retailers, particularly when a high customer service level is promised to online customers (e.g., order by a certain time and pick up in store after a specific time later the same day). This paper examines store picking operations for same day BOPS services. Specifically, we derive Best Performance Frontiers (BPFs) for single wave and multi-wave order picking. New relationships, propositions, and results are presented to determine the minimum picking rate needed in stores to guarantee a target service level, the number of picking waves a retailer should launch in an ordering cycle, and the timing of picking waves. We also examine demand surge scenarios with different order arrival rates in an ordering cycle. Insights and implications of the results are discussed for retailers that seek to benchmark their current BOPS performances and understand how to schedule and improve the picking of online orders in conventional retail stores and the picking rates needed to guarantee a desired service level for online customers

Electrochemical detection of Toxocara canis excretory-secretory antigens in children from rural communities in Esmeraldas Province, Ecuador: association between active infection and high eosinophilia.

BACKGROUND: The diagnosis of active Toxocara canis infections in humans is challenging. Larval stages of T. canis do not replicate in human tissues and disease may result from infection with a single T. canis larva. Recently, we developed a nanobody-based electrochemical magnetosensor assay with superior sensitivity to detect T. canis excretory-secretory (TES) antigens. Here, we evaluate the performance of the assay in children from an Ecuadorian birth cohort that followed children to five years of age. METHODS: Samples were selected based on the presence of peripheral blood eosinophilia and relative eosinophil counts. The samples were analyzed by the nanobody-based electrochemical magnetosensor assay, which utilizes a bivalent biotinylated nanobody as capturing agent on the surface of streptavidin pre-coated paramagnetic beads. Detection was performed by a different nanobody chemically labelled with horseradish peroxidase. RESULTS: Of 87 samples tested, 33 (38%) scored positive for TES antigen recognition by the electrochemical magnetosensor assay. The average concentration of TES antigen in serum was 2.1 ng/ml (SD = 1.1). The positive result in the electrochemical assay was associated with eosinophilia > 19% (P = 0.001). Parasitological data were available for 57 samples. There was no significant association between positivity by the electrochemical assay and the presence of other soil-transmitted helminth infections. CONCLUSIONS: Our nanobody-based electrochemical assay provides highly sensitive quantification of TES antigens in serum and has potential as a valuable tool for the diagnosis of active human toxocariasis

Heating as a rapid purification method for recovering correctly-folded thermotolerant VH and VHH domains

BACKGROUND: Recombinant antibodies from Camelidae (VHHs) are potentially useful tools for both basic research and biotechnological applications because of their small size, robustness, easy handling and possibility to refold after chemio-physical denaturation. Their heat tolerance is a particularly interesting feature because it has been recently related to both high yields during recombinant expression and selective purification of folded protein. RESULTS: Purification of recombinant RE3 VHH by heat treatment yielded the same amount of antibody as purification by affinity chromatography and negligible differences were found in stability, secondary structure and functionality. Similar results were obtained using another class of thermotolerant proteins, the single domain VH scaffold, described by Jespers et al. [8]. However, thermosensitive VHs could not withstand the heat treatment and co-precipitated with the bacterial proteins. In both cases, the thermotolerant proteins unfolded during the treatment but promptly refolded when moved back to a compatible temperature. CONCLUSION: Heat treatment can simplify the purification protocol of thermotolerant proteins as well as remove any soluble aggregate. Since the re-folding capability after heat-induced denaturation was previously correlated to higher performance during recombinant expression, a unique heating step can be envisaged to screen constructs that can provide high yields of correctly-folded proteins

<i>Mare Geneticum</i>: balancing governance of marine genetic resources in international waters

A fair and effective regime regulating benefit-sharing of marine genetic resources (MGR) in areas beyond national jurisdiction (ABNJ) must consider the inclusion of developing states, support scientific research and safeguard investments of the private sector. The present innovative proposal ensures a delicate balance through an approach based on open access, albeit with limitations. Access to MGR in ABNJ is facilitated, but conditional on the public release of collected samples and raw data. Adoption of the open access principle guarantees a powerful form of non-monetary benefit-sharing. The balance is maintained by the option for an extended embargo period, allowing samples and data to be kept confidential for a certain period, against payment to a biodiversity contribution fund. Monetary benefit-sharing, as a sector-negotiated percentage on revenue, could be imposed at the point of product commercialisation, and would offer a tangible payment system with a low transaction cost