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‘Landing on Earth:’ an educational project for the present. A response to Vanessa Andreotti
No full textThis paper responds to Vanessa Andreotti’s keynote address.
In it, I draw out some educational implications of facing the
everyday denials of the climate emergency. In particular,
I mobilise Bruno Latour’s phrase ‘landing on Earth’ to indicate that the very terms through which we understand education, particularly as it relates to the future, require a profound shift
On the Topological Aspects of UAV-Assisted Post-Disaster Wireless Communication Networks
No full textIn the context of sixth-generation (6G) networks, emergency management systems based on wireless communications have recently gained increasing interest. Hereby, fundamentals and open problems of post-disaster communications
are discussed, especially focusing on their topological aspects. The motivation behind this choice is that whenever a natural or man-made disaster occurs, there is a high chance that the terrestrial communication infrastructure is compromised, and therefore alternative networks need to be
deployed efficiently in order to enable the majority of the civilians and first responders to communicate. In this article, we first provide a brief review of existing aerial ad hoc networks for post-disaster communications. Next, we shed light on some new aspects of this problem, which are
related to the topology of the network supporting
the impacted area. Finally, with the aid of selected
simulation results, we show how the cellular infrastructure requirements for a disaster-struck region.
significantly depend on its location and extension
Four Mindsets of Designer-Entrepreneurs
No full textABSTRACT Literature from the business and design
disciplines describes two important subprocesses of
the entrepreneurial journey: new venture creation and
new product development. This study uses evidence
from qualitative research with Designer-entrepreneurs
(D-entrepreneurs) to describe a third important sub-process, which we refer to as the Designer’s Mindset Transition (DMT), which can either hinder or propel the other subprocesses. Thirty-seven participants, including eleven D-entrepreneurs in product-based start-ups, participated in the study. Four designer-entrepreneurs’ mindsets were identified within the DMT subprocess: The Artisan, the Configurator, the The Design Journal DOI: 10.1080/14606925.2021.1958601 705
THE DESIGN JOURNAL VOLUME 24, ISSUE 5
PP 705–726
REPRINTS AVAILABLE DIRECTLY FROM THE PUBLISHERS PHOTOCOPYING
PERMITTED BY LICENSE ONLY © 2021 INFORMA UK LIMITED, TRADING AS TAYLOR & FRANCIS GROUP PRINTED IN THE UK Opportunity Seeker, and the Design Leader. They followed a
progression that moves the Designer-entrepreneur from the
effectual logic (means-oriented) towards a causal logic (goal-oriented). Evidence from the study demonstrates that
designers starting from the Artisan mindset were not always
driven by their purported user-centric approach. Instead, key drivers were their priorities, interests, and beliefs, established at the outset of the venture
S100 Calcium Binding Protein Family Members Associate With Poor Patient Outcome and Response to Proteasome Inhibition in Multiple Myeloma
No full textDespite several new therapeutic options, multiple myeloma (MM) patients experience multiple relapses and inevitably become refractory to treatment. Insights into drug
resistance mechanisms may lead to the development of novel treatment strategies. The S100 family is comprised of 21 calcium binding protein members with 17 S100 genes located in the 1q21 region, which is commonly amplified in MM. Dysregulated expression of S100 family members is associated with tumor initiation, progression and inflammation. However, the relationship between the S100 family and MM pathogenesis and drug response is unknown. In this study, the roles of S100 members were systematically studied at the copy number, transcriptional and protein level with patients’ survival and drug response. Copy number analysis revealed a predominant pattern of gains occurring in S100 genes clustering in the 1q21 locus. In general, gains of
genes encoding S100 family members associated with worse patient survival. However, S100 gene copy number and S100 gene expression did not necessarily correlate,
and high expression of S100A4 associated with poor patient survival. Furthermore, integrated analysis of S100 gene expression and ex vivo drug sensitivity data showed
significant negative correlation between expression of S100 family members (S100A8,S100A9, and S100A12) and sensitivity to some drugs used in current MM treatment,
including proteasome inhibitors (bortezomib, carfilzomib, and ixazomib) and histone deacetylase inhibitor panobinostat. Combined proteomic and pharmacological data
exhibited significant negative association of S100 members (S100A4, S100A8, and S100A9) with proteasome inhibitors and panobinostat. Clinically, the higher expression of S100A4 and S100A10 were significantly linked to shorter progression free survival in patients receiving carfilzomib-based therapy. The results indicate an association and
highlight the potential functional importance of S100 members on chromosome 1q21 in the development of MM and resistance to established myeloma drugs, including
proteasome inhibitor
uniForest: an unsupervised machine learning technique to detect outliers and restrict variance in microbiome studies
No full textIsolation Forests is an unsupervised machine learning technique for detecting outliers in continuous datasets that does not require an underlying equivariant or Gaussian distribution and is suitable for use on small datasets. While this procedure is widely used across quantitative
fields, to our knowledge, this is the first attempt to solely assess its use for microbiome datasets.
Here we present uniForest, an interactive Python notebook (which can be run from any desktop computer using the Google Colaboratory web service) for the processing of microbiome
outliers. We used uniForest to apply Isolation Forests to the Healthy Human Microbiome project dataset and imputed outliers with the mean of the remaining inliers to maintain sample size and assessed its prowess in variance reduction in both community structure and derived ecological statistics (-diversity). We also assessed its functionality in anatomical site made available under aCC-BY 4.0 International license. (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is
bioRxiv preprint doi: https://doi.org/10.1101/2021.05.17.444491; this version posted May 17, 2021. The copyright holder for this preprint
2 differentiation (pre- and postprocessing) using principal component analysis, dissimilarity matrices, and ANOSIM. We observed a minimum variance reduction of 81.17% across the
entire dataset and in alpha diversity at the Phylum level. Application of Isolation Forests also separated the dataset to an extremely high specificity, reducing variance within taxa samples by a minimum of 81.33%. It is evident that Isolation Forests are a potent tool in restricting the effect of variance in microbiome analysis and has potential for broad application in studies where high levels of
microbiome variance is expected. This software allows for clean analyses of otherwise noisy datasets
A novel non-viral delivery method that enables efficient engineering of primary human T cells for ex vivo cell therapy applications
No full textBackground aims: Next-generation immune cell therapy products will require complex modifications using
engineering technologies that can maintain high levels of cell functionality. Non-viral engineering methods
have the potential to address limitations associated with viral vectors. However, while electroporation is the
most widely used non-viral modality, concerns about its effects on cell functionality have led to the exploration of alternative approaches. Here the authors have examined the suitability of the Solupore non-viral
delivery system for engineering primary human T cells for cell therapy applications.
Methods: The Solupore system was used to deliver messenger RNA (mRNA) and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) guide RNA ribonucleoprotein
(RNP) cargos to T cells, and efficiency was measured by flow cytometry. Cell perturbation was assessed by
immune gene expression profiling, including an electroporation comparator. In vitro and in vivo cytotoxicity
of chimeric antigen receptor (CAR) T cells generated using the Solupore system was evaluated using a real-time cellular impedance assay and a Raji-luciferase mouse tumor model, respectively.
Results: Efficient transfection was demonstrated through delivery of mRNA and CRISPR CAS9 RNP cargos
individually, simultaneously and sequentially using the Solupore system while consistently maintaining high
levels of cell viability. Gene expression profiling revealed minimal alteration in immune gene expression,
demonstrating the low level of perturbation experienced by the cells during this transfection process. By contrast, electroporation resulted in substantial changes in immune gene expression in T cells. CAR T cells generated using the Solupore system exhibited efficient cytotoxicity against target cancer cells in vitro and in vivo.
Conclusions: The Solupore system is a non-viral means of simply, rapidly and efficiently delivering cargos to
primary human immune cells with retention of high cell viability and functionality
At the metal–metabolite interface in Aspergillus fumigatus: towards untangling the intersecting roles of zinc and gliotoxin
No full textCryptic links between apparently unrelated metabolic systems represent potential new drug targets in fungi. Evidence of such a link between zinc and gliotoxin (GT) biosynthesis in Aspergillus fumigatus is emerging. Expression of some genes of the GT biosynthetic gene cluster gli is influenced by the zinc-dependent transcription activator ZafA, zinc may relieve GT-mediated fungal growth inhibition and, surprisingly, GT biosynthesis is influenced by zinc availability. In A. fumigatus, dithiol gliotoxin (DTG), which has zinc-chelating properties, is converted to either GT or bis-dethiobis(methylthio)gliotoxin (BmGT) by oxidoreductase GliT and methyltransferase GtmA, respectively. A double deletion mutant lacking both GliT and GtmA was previously observed to be hypersensitive to exogenous GT exposure. Here we show that compared to wild-type exposure, exogenous GT and the zinc chelator N,N,N′,N′-tetrakis(2-pyridinylmethyl)−1,2-ethanediamine (TPEN) inhibit A. fumigatus ΔgliTΔgtmA growth, specifically under zinc-limiting conditions, which can be reversed by zinc addition. While GT biosynthesis is evident in zinc-depleted medium, addition of zinc (1µM) suppressed GT and activated BmGT production. In addition, secretion of the unferrated siderophore, triacetylfusarinine C (TAFC), was evident by A. fumigatus wild-type (at >5µM zinc) and ΔgtmA (at >1µM zinc) in a low-iron medium. TAFC secretion suggests that differential zinc-sensing between both strains may influence fungal Fe3+ requirement. Label-free quantitative proteomic analysis of both strains under equivalent differential zinc conditions revealed protein abundance alterations in accordance with altered metabolomic observations, in addition to increased GliT abundance in ΔgtmA at 5µM zinc, compared to wild-type, supporting a zinc-sensing deficiency in the mutant strain. The relative abundance of a range of oxidoreductase- and secondary metabolism-related enzymes was also evident in a zinc- and strain-dependent manner. Overall, we elaborate new linkages between zinc availability, natural product biosynthesis and oxidative stress homeostasis in A. fumigatu
Electrochemical investigations into enzymatic polymerisation of 1,10-phenanthroline-5,6-dione as a redox mediator for lactate sensing
No full textLactate biosensor fabrication using a chitosan and cross linker configuration realised solution mediation(K3Fe (CN)6) with lactate linear range9.9 × 10−4 to 5.66×10−3 M, sensitivity 1.44×10−3C cm−2 mM−1 and LOD of 0.54 mM. Further development involved use of the heterocyclic quinoid species 1,10-phenanthroline-5,6-dione which acted as a proton and electron acceptor in relation to FADH2 cofactor regeneration. Graphite ink was formulated and utilis ed as an underlying conductive layer for LOx enzyme immobilisation and enzymatic polymerisation of 1,10-phenanthroline-5,6-dioneata GC electrode, resulting in a linear range of 0.74 -2.44×10−3 M, sensitivity of4.11×10−4C cm−2 mM−1 and LODof0.06mM.Scanning electron and electrochemical scanning
microscopy realised surface characterisation of the enzyme layers
Approaches to Analysis of Qualitative Research Data: A Reflection on the Manual and Technological Approaches
No full textThis paper addresses a gap in the literature by providing reflective and critical insights into the experiences during two PhD qualitative studies which adopted different approaches to data analysis. We first consider how the two PhD studies unfolded before discussing the motivations, challenges and benefits of choosing either a technological (NVivo) or manual approach to qualitative data analysis. The paper contributes to the limited literature which has explored the comparative experiences of those undertaking qualitative data analysis using different approaches. It provides insights into how researchers conduct qualitative data analysis using different approaches and the lessons learnt
Evolutionary conservations, changes of circadian rhythms and their effect on circadian disturbances and therapeutic approaches
No full textThe circadian rhythm is essential for the interaction of all living organisms with their environments. Several processes, such as thermoregulation, metabolism, cognition and memory, are regulated by the internal clock. Disturbances in the circadian rhythm have been shown to lead to the development of neuropsychiatric disorders, including attention-deficit hyperactivity disorder (ADHD). Interestingly, the mechanism of the circadian rhythms has been conserved in many different species, and misalignment between circadian rhythms and the environment results in evolutionary regression and lifespan reduction.
This review summarises the conserved mechanism of the internal clock and its major interspecies differences. In addition, it focuses on effects the circadian rhythm disturbances, especially in cases of ADHD, and describes the possibility of recombinant proteins generated by eukaryotic expression systems as therapeutic agents as well as CRISPR/Cas9 technology as a potential tool for research and therapy. The aim is to give an overview about the evolutionary conserved mechanism as well as the changes of the circadian clock. Furthermore, current knowledge about circadian rhythm disturbances and therapeutic approaches is discussed