Predictive glycoengineering of biosimilars using a Markov chain glycosylation model

Biosimilar drugs must closely resemble the pharmacological attributes of innovator products to ensure safety and efficacy to obtain regulatory approval. Glycosylation is one critical quality attribute that must be matched, but it is inherently difficult to control due to the complexity of its biogenesis. This usually implies that costly and time-consuming experimentation is required for clone identification and optimization of biosimilar glycosylation. Here, we describe a computational method that utilizes a Markov model of glycosylation to predict optimal glycoengineering strategies to obtain a specific glycosylation profile with desired properties. The approach uses a genetic algorithm to find the required quantities to perturb glycosylation reaction rates that lead to the best possible match with a given glycosylation profile. Furthermore, the approach can be used to identify cell lines and clones that will require minimal intervention while achieving a glycoprofile that is most similar to the desired profile. Thus, this approach can facilitate biosimilar design by providing computational glycoengineering guidelines that can be generated with a minimal time and cost

Biochemical characterization of human gluconokinase and the proposed metabolic impact of gluconic acid as determined by constraint based metabolic network analysis.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.The metabolism of gluconate is well characterized in prokaryotes where it is known to be degraded following phosphorylation by gluconokinase. Less is known of gluconate metabolism in humans. Human gluconokinase activity was recently identified proposing questions about the metabolic role of gluconate in humans. Here we report the recombinant expression, purification and biochemical characterization of isoform I of human gluconokinase alongside substrate specificity and kinetic assays of the enzyme catalyzed reaction. The enzyme, shown to be a dimer, had ATP dependent phosphorylation activity and strict specificity towards gluconate out of 122 substrates tested. In order to evaluate the metabolic impact of gluconate in humans we modeled gluconate metabolism using steady state metabolic network analysis. The results indicate that significant metabolic flux changes in anabolic pathways linked to the hexose monophosphate shunt (HMS) are induced through a small increase in gluconate concentration. We argue that the enzyme takes part in a context specific carbon flux route into the HMS that, in humans, remains incompletely explored. Apart from the biochemical description of human gluconokinase, the results highlight that little is known of the mechanism of gluconate metabolism in humans despite its widespread use in medicine and consumer products.info:eu-repo/grantAgreement/EC/FP7/23281

Enhancing understanding, Flow and Self-Efficacy in Learners with Developmental and Attention Difficulties through ICT-based Interventions

AbstractThe purpose of this paper is to investigate in which ways technologies may be used to increase inclusion and a feeling of flow and self-efficacy in learning processes when it comes to learners with developmental and attention deficits (focus learners) in a mainstream classroom. The paper is one piece of outcome of a wider study on ICT facilitated inclusion, and this current piece of research addresses the challenges of enhancing focus learners’ comprehension when working with the curriculum. Several technologies have been tried out in a real school context and seven types of interventions are identified as valuable for focus learners’ capability in learning processes. The paper discusses the findings and concludes that conscious use of technology-based interventions makes it possible to provide learning challenges balanced to the learners’ individual skills. But a broader understanding and acceptance by all stakeholders of the specific challenges of this group of learners in mainstream educational systems seems needed to fulfil the potential.</jats:p

Inducing omnipotence or powerlessness in learners with developmental and attention difficulties through structuring technologies

Schoolwork of learners with developmental and attention difficulties is often characterised by low productivity, many errors due to carelessness or inattention and poor organizing ability. Focus learners have difficulties performing at the same level as their peers. This paper addresses these challenges and investigates the potential of technologies for creating and facilitating learning environments, where learners with developmental and attention difficulties are well-supported with respect to overviewing, structuring and planning tasks, evaluating and adjusting participation and management of time. Would it be possible to take advantage of the affordances of Persuasive Technologies and how could Persuasive Technology Tools in the hand of teachers and learners assist, motivate and enable the presence, participation and achievements of learners with developmental and attention difficulties at school? Using this lens, the authors examine, to what extent technology may assist teachers to create more ideal learning environments by reducing the threat for these learners and enable them to participate in learning. Virtual Learning Environments (VLEs), digital templates, timers and calendars are identified as specific valuable tools for enhancing the learners’ ability to become ready to learn, join and maintain within the learning processes. Likewise, visualisations in the classroom, notifications, video instructions, assessment and evaluation tools to seems to help the learner to navigate, remember, become aware and understand their own role in the classroom. This paper suggest technologies for structuring and overviewing as basic assistive tools for equalizing the learning possibilities for learners with developmental and attention difficulties in an inclusive school setting

Strengthening Inclusion of Learners With Attention Difficulties Through Interventions With Digital Technology In Processes of Production

Abstract This paper investigates the potential of digital technologies for strengthening the participation and inclusion of learners with developmental and attention deficits (focus learners) into the mainstream classroom. The paper describes the authors’ approach to the challenge of researching the extent, to which digital technologies may support the learning process of focus learners - in particular in those aspects of the learning process that deal with the construction of learning products and the communication and dissemination of knowledge to peers, teachers or others. On the basis of the actual analysis and a succeeding discussion, the paper concludes that in order to create ownership, pedagogic strategies and interventions with digital technologies (whether viewed from the perspective of teaching or the perspective of learning) should incorporate opportunities for developing digital multimodal reifications. These, in turn, then stimulate learner reflection and awareness. Finally, the authors of the paper emphasize importance of opportunities for reflection, tools and structures for construction and dissemination of learners’ knowledge (to demonstrate “I am able to” and “I know”).</jats:p