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Blood-Based Immune Profiling Combined with Machine Learning Discriminates Psoriatic Arthritis from Psoriasis Patients

Psoriasis (Pso) is a chronic inflammatory skin disease, and up to 30% of Pso patients develop psoriatic arthritis (PsA), which can lead to irreversible joint damage. Early detection of PsA in Pso patients is crucial for timely treatment but difficult for dermatologists to implement. We, therefore, aimed to find disease-specific immune profiles, discriminating Pso from PsA patients, possibly facilitating the correct identification of Pso patients in need of referral to a rheumatology clinic. The phenotypes of peripheral blood immune cells of consecutive Pso and PsA patients were analyzed, and disease-specific immune profiles were identified via a machine learning approach. This approach resulted in a random forest classification model capable of distinguishing PsA from Pso (mean AUC = 0.95). Key PsA-classifying cell subsets selected included increased proportions ofdifferentiated CD4+CD196+CD183-CD194+ and CD4+CD196-CD183-CD194+ T-cells and reduced proportions of CD196+ and CD197+ monocytes, memory CD4+ and CD8+ T-cell subsets and CD4+ regulatory T-cells. Within PsA, joint scores showed an association with memory CD8+CD45RACD197- effector T-cells and CD197+ monocytes. To conclude, through the integration of in-depth flow cytometry and machine learning, we identified an immune cell profile discriminating PsA from Pso. This immune profile may aid in timely diagnosing PsA in Pso.

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Blood-Based Immune Profiling Combined with Machine Learning Discriminates Psoriatic Arthritis from Psoriasis Patients

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Drug-induced caspase 8 upregulation sensitises cisplatin-resistant ovarian carcinoma cells to rhTRAIL-induced apoptosis

Background: Drug resistance is a major problem in ovarian cancer. Triggering apoptosis using death ligands such as tumour necrosis factor-related apoptosis inducing ligand (TRAIL) might overcome chemoresistance. Methods: We investigated whether acquired cisplatin resistance affects sensitivity to recombinant human (rh) TRAIL alone or in combination with cisplatin in an ovarian cancer cell line model consisting of A2780 and its cisplatin-resistant subline CP70. Results: Combining cisplatin and rhTRAIL strongly enhanced apoptosis in both cell lines. CP70 expressed less caspase 8 protein, whereas mRNA levels were similar compared with A2780. Pre-exposure of particularly CP70 to cisplatin resulted in strongly elevated caspase 8 protein and mRNA levels. Caspase 8 mRNA turnover and protein stability in the presence or absence of cisplatin did not differ between both cell lines. Cisplatin-induced caspase 8 protein levels were essential for the rhTRAIL-sensitising effect as demonstrated using caspase 8 small-interfering RNA (siRNA) and caspase-8 overexpressing constructs. Cellular FLICE-inhibitory protein (c-FLIP) and p53 siRNA experiments showed that neither an altered caspase 8/c-FLIP ratio nor a p53-dependent increase in DR5 membrane expression following cisplatin were involved in rhTRAIL sensitisation. Conclusion: Cisplatin enhances rhTRAIL-induced apoptosis in cisplatin-resistant ovarian cancer cells, and induction of caspase 8 protein expression is the key factor of rhTRAIL sensitisation. © 2011 Cancer Research UK All rights reserved.

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Improved Efficacy of Oral Immunotherapy Using Non-Digestible Oligosaccharides in a Murine Cow's Milk Allergy Model

From teh UU repository: "Background: Oral immunotherapy (OIT) is a promising therapeutic approach to treat food allergic patients. However, there are some concerns regarding its safety and long-term efficacy. The use of non-digestible oligosaccharides might improve OIT efficacy since they are known to directly modulate intestinal epithelial and immune cells in addition to acting as prebiotics. Aim: To investigate whether a diet supplemented with plant-derived fructo-oligosaccharides (FOS) supports the efficacy of OIT in a murine cow's milk allergy model and to elucidate the potential mechanisms involved. Methods: After oral sensitization to the cow's milk protein whey, female C3H/HeOuJ mice were fed either a control diet or a diet supplemented with FOS (1% w/w) and received OIT (10 mg whey) 5 days a week for 3 weeks by gavage. Intradermal (i.d.) and intragastric (i.g.) challenges were performed to measure acute allergic symptoms and mast cell degranulation. Blood and organs were collected to measure antibody levels and T cell and dendritic cell populations. Spleen-derived T cell fractions (whole spleen-and CD25-depleted) were transferred to naive recipient mice to confirm the involvement of regulatory T cells (Tregs) in allergy protection induced by OIT + FOS. Results: OIT + FOS decreased acute allergic symptoms and mast cell degranulation upon challenge and prevented the challenge-induced increase in whey-specific IgE as observed in sensitized mice. Early induction of Tregs in the mesenteric lymph nodes (MLN) of OIT + FOS mice coincided with reduced T cell responsiveness in splenocyte cultures. CD25 depletion in OIT + FOS-derived splenocyte suspensions prior to transfer abolished protection against signs of anaphylaxis in recipients. OIT + FOS increased serum galectin-9 levels. No differences in short-chain fatty acid (SCFA) levels in the cecum were observed between the treatment groups. Concisely, FOS supplementation significantly improved OIT in the acute allergic skin response, %Foxp3+ Tregs and %LAP+ Th3 cells in MLN, and serum galectin-9 levels. Conclusion: FOS supplementation improved the efficacy of OIT in cow's milk allergic mice. Increased levels of Tregs in the MLN and abolished protection against signs of anaphylaxis upon transfer of CD25-depleted cell fractions, suggest a role for Foxp3+ Tregs in the protective effect of OIT + FOS. "

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People 1

person

Igor Mayer

Professor

Projects 34

project

Audiovisual Education and Training Network for European Vocational Excellence

The European creative visual industry is undergoing rapid technological development, demanding solid initiatives to maintain a competitive position in the marketplace. AVENUE, a pan-European network of Centres of Vocational Excellence, addresses this need through a collaboration of five independent significant ecosystems, each with a smart specialisation. AVENUE will conduct qualified industry-relevant research to assess, analyse, and conclude on the immediate need for professional training and educational development. The primary objective of AVENUE is to present opportunities for immediate professional and vocational training, while innovating teaching and learning methods in formal education, to empower students and professionals in content creation, entrepreneurship, and innovation, while supporting sustainability and healthy working environments. AVENUE will result in a systematised upgrade of workforce to address the demand for new skills arising from rapid technological development. Additionally, it will transform the formal education within the five participating VETs, making them able to transition from traditional artistic education to delivering skills, mindsets and technological competencies demanded by a commercial market. AVENUE facilitates mobility, networking and introduces a wide range of training formats that enable effective training within and across the five ecosystems. A significant portion of the online training is Open Access, allowing professionals from across Europe to upgrade their skills in various processes and disciplines. The result of AVENUE will be a deep-rooted partnership between five strong ecosystems, collaborating to elevate the European industry. More than 2000 professionals, employees, students, and young talents will benefit from relevant and immediate upgrading of competencies and skills, ensuring that the five European ecosystems remain at the forefront of innovation and competitiveness in the creative visual industry.

Ongoing

project

Beweegniveau herkend: oog voor excellentie

De belangrijkste opdracht voor leerkrachten bewegings-onderwijs in het primair onderwijs is kinderen leren bewegen. Het HAN Centre of Expertise Sport & Talent krijgt vanuit het werkveld bewegingsonderwijs continu vragen hoe het beweegniveau van kinderen vast te stellen en met welke programma?s excellente bewegers geholpen kunnen worden om zich verder te ontwikkelen. Om alle kinderen goed te leren bewegen moeten leerkrachten bewegingsonderwijs kinderen onderwijs op maat kunnen aanbieden. Onderwijs op maat betekent een programma dat aansluit bij het niveau van een kind. Een valide, betrouwbaar en eenvoudig toepasbaar instrument om het beweegniveau te meten ontbreekt echter. Op basis van de praktijkvragen zijn voor dit project de volgende onderzoeksvragen geformuleerd: Hoe kan de docent bewegingsonderwijs het beweegniveau van elk kind op een valide, betrouwbare en eenvoudige wijze (h)erkennen? En hoe ziet een programma eruit om excellente bewegers verder te helpen ontwikkelen? Opbrengsten: 1. een instrument om het beweegniveau in kaart te brengen en 2. beweegprogramma?s voor excellente bewegers. Om het beweegniveau van kinderen vast te stellen worden drie meetinstrumenten (KTK, ooghandcoördinatietest, Scale for Identification of Sport Potential) gebruikt. Deze meetinstrumenten worden gezien als middelen om het sportief talent van kinderen vast te stellen. In deze studie wordt onderzocht of met de gezamenlijke scores van de drie testen een beweegquotiënt kan worden berekend waarmee het beweegniveau van een kind kan worden uitgedrukt. Met experts uit de vakwereld bewegingsonderwijs zal een programma worden ontwikkeld voor excellente bewegers in de leeftijd van 6 tot 9 jaar. Dit programma zal vervolgens op 10 scholen worden uitgevoerd en geanalyseerd en resultaten worden vergeleken met vergelijkbare controlegroepen. In de laatste fase van het project staat valorisatie centraal. Via een online medium, artikelen, symposium en cursussen zullen leerkrachten bewegingsonderwijs kennismaken met het instrument om beweegniveau te meten en programma?s om excellente bewegers te helpen in hun ontwikkeling.

Finished

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Circulair ontwerp voor lupeol extractie uit reststromen van industriële lupine verwerking vergeleken met concurrerende processen

Lupineschillen (lupine zaadhuid) zijn een reststroom van lupineverwerking. Lupineschillen vormen 25% van de totale biomassa van de lupineboon, terwijl sojaschillen slechts 5% van de totale biomassa van de sojaboon zijn. Er zijn onvoldoende rendabele toepassingen voor lupineschillen waardoor de rentabiliteit van de lupine supply chain achter blijft bij de veel competitievere soja supply chain. Lupineschillen zijn rijk aan de actieve stof lupeol waarvan recent farmaceutische en cosmetische anti-aging werkingen zijn vastgesteld, waaronder anti-tumor werking. Lupeol komt naast lupine ook in hoge concentraties voor in berkenbast. Berkenbast bevat bovendien een chemische voorloper van lupeol namelijk betuline. Recentelijk is er een chemische syntheseroute ontwikkeld voor lupeol op basis van betuline. Als deze syntheseroute kosteneffectief is, dan kan deze route de ontwikkeling van nieuwe toepassingen van lupineschillen blokkeren.Het doel van deze studie is het opstellen van een circulair ontwerp voor lupeol extractie uit twee reststromen met behulp van superkritische CO2 extractie en de kosteneffectiviteit van deze circulaire ontwerpen met elkaar vergelijken voor het selecteren van het meest optimale proces voor lupeol extractie en/of synthese. Bovendien worden mogelijke cosmetische anti-aging effecten van lupeol getest.Met behulp van superkritische CO2 extractie is het mogelijk om lupeol kosteneffectief uit lupineschillen te extraheren. De alternatieve syntheseroute van lupeol uit betuline zoals deze in de wetenschappelijke literatuur was gepubliceerd bleek niet reproduceerbaar te zijn. Patentliteratuur leverde een reproduceerbare syntheseroute. Vergelijking van de twee routes was nog niet mogelijk vanwege de lage omzetting efficiënties van de syntheseroute. Daarnaast zijn er mogelijke intellectuele eigendom issues. De effectiviteit van lupeol is in vitro en in vivo getest. Hieruit bleek dat lupeol in tegenstelling tot de literatuur minimale effecten had op huidcellen. De huidelasticiteit bij proefpersonen nam enigszins toe na gebruik van een cosmetische formulering met lupeol.Uit onze studie is gebleken dat we kosteneffectief lupeol kunnen extraheren met behulp van superkritische CO2, dat de alternatieve routes voor lupeol synthese nog niet mogelijk zijn en dat we enige anti-aging effecten van lupeol hebben kunnen vinden bij toepassing in cosmetische producten.

Finished

project

CO2Cap - CO2 from air capturing via a modified Schauberger system

Climate change is one of the most critical global challenges nowadays. Increasing atmospheric CO2 concentration brought by anthropogenic emissions has been recognized as the primary driver of global warming. Therefore, currently, there is a strong demand within the chemical and chemical technology industry for systems that can covert, capture and reuse/recover CO2. Few examples can be seen in the literature: Hamelers et al (2013) presented systems that can use CO2 aqueous solutions to produce energy using electrochemical cells with porous electrodes; Legrand et al (2018) has proven that CDI can be used to capture CO2 without solvents; Shu et al (2020) have used electrochemical systems to desorb (recover) CO2 from an alkaline absorbent with low energy demand. Even though many efforts have been done, there is still demand for efficient and market-ready systems, especially related to solvent-free CO2 capturing systems. This project intends to assess a relatively efficient technology, with low-energy costs which can change the CO2 capturing market. This technology is called whorlpipe. The whorlpipe, developed by Viktor Schauberger, has shown already promising results in reducing the energy and CO2 emissions for water pumping. Recently, studies conducted by Wetsus and NHL Stenden (under submission), in combination with different companies (also members in this proposal) have shown that vortices like systems, like the Schauberger funnel, and thus “whorlpipe”, can be fluid dynamically represented using Taylor-Couette flows. This means that such systems have a strong tendency to form vortices like fluid-patterns close to their air-water interface. Such flow system drastically increase advection. Combined with their higher area to volume ratio, which increases diffusion, these systems can greatly enhance gas capturing (in liquids), and are, thus, a unique opportunity for CO2 uptake from the air, i.e. competing with systems like conventional scrubbers or bubble-based aeration.

Finished

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CrossReTour

Cross-Re-Tour supports European tourism SME while implementing digital and circular economy innovations. The three year project promotes uptake and replication by tourism SMEs of tools and solutions developed in other sectors, to mainstream green and circular tourism business operations.At the start of the project existing knowledge-gaps of tourism SMEs will be researched through online dialogues. This will be followed by a market scan, an overview of existing state of the art solutions to digital and green constraints in other economic sectors, which may be applied to tourism SME business operations: water, energy, food, plastic, transport and furniture /equipment. The scan identifies best practices from other sectors related to nudging of clients towards sustainable behaviour and nudging of staff on how to best engage with new tourism market segments.The next stage of the project relates to two design processes: an online diagnostic tool that allows for measuring and assessing (160) SME’s potential to adapt existing solutions in digital and green challenges, developed in other economic sectors. Next to this, a knowledge hub, addresses knowledge constraints and proposes solutions, business advisory services, training activities to SMEs participating. The hub acts as a matchmaker, bringing together 160 tourism SMEs searching for solutions, with suppliers of existing solutions developed in other sectors. The next key activity is a cross-domain open innovation programme, that will provide 80 tourism SMEs with financial support (up to EUR 30K). Examples of partnerships could be: a hotel and a supplier of refurbished matrasses for hospitals; a restaurant and a supplier of food rejected by supermarkets, a dance event organiser and a supplier of refurbished water bottles operating in the cruise industry, etc.The 80 cross-domain partnerships will be supported through the knowledge hub and their business innovation advisors. The goal is to develop a variety of innovative partnerships to assure that examples in all operational levels of tourism SMEs.The innovation projects shall be presented during a show-and-share event, combined with an investors’ pitch. The diagnostic tool, market scan, knowledge hub, as well as the show and share offer excellent opportunities to communicate results and possible impact of open innovation processes to a wider international audience of destination stakeholders and non-tourism partners. Societal issueSupporting the implementation of digital and circular economy solutions in tourism SMEs is key for its transition towards sustainable low-impact industry and society. Benefit for societySolutions are already developed in other sectors but the cross-over towards tourism is not happening. The project bridges this gap.

Other

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CureQ Predict, Delay & Cure polyglutamine(Q) caused neurodegeneration

Huntington’s disease (HD) and various spinocerebellar ataxias (SCA) are autosomal dominantly inherited neurodegenerative disorders caused by a CAG repeat expansion in the disease-related gene1. The impact of HD and SCA on families and individuals is enormous and far reaching, as patients typically display first symptoms during midlife. HD is characterized by unwanted choreatic movements, behavioral and psychiatric disturbances and dementia. SCAs are mainly characterized by ataxia but also other symptoms including cognitive deficits, similarly affecting quality of life and leading to disability. These problems worsen as the disease progresses and affected individuals are no longer able to work, drive, or care for themselves. It places an enormous burden on their family and caregivers, and patients will require intensive nursing home care when disease progresses, and lifespan is reduced. Although the clinical and pathological phenotypes are distinct for each CAG repeat expansion disorder, it is thought that similar molecular mechanisms underlie the effect of expanded CAG repeats in different genes. The predicted Age of Onset (AO) for both HD, SCA1 and SCA3 (and 5 other CAG-repeat diseases) is based on the polyQ expansion, but the CAG/polyQ determines the AO only for 50% (see figure below). A large variety on AO is observed, especially for the most common range between 40 and 50 repeats11,12. Large differences in onset, especially in the range 40-50 CAGs not only imply that current individual predictions for AO are imprecise (affecting important life decisions that patients need to make and also hampering assessment of potential onset-delaying intervention) but also do offer optimism that (patient-related) factors exist that can delay the onset of disease.To address both items, we need to generate a better model, based on patient-derived cells that generates parameters that not only mirror the CAG-repeat length dependency of these diseases, but that also better predicts inter-patient variations in disease susceptibility and effectiveness of interventions. Hereto, we will use a staggered project design as explained in 5.1, in which we first will determine which cellular and molecular determinants (referred to as landscapes) in isogenic iPSC models are associated with increased CAG repeat lengths using deep-learning algorithms (DLA) (WP1). Hereto, we will use a well characterized control cell line in which we modify the CAG repeat length in the endogenous ataxin-1, Ataxin-3 and Huntingtin gene from wildtype Q repeats to intermediate to adult onset and juvenile polyQ repeats. We will next expand the model with cells from the 3 (SCA1, SCA3, and HD) existing and new cohorts of early-onset, adult-onset and late-onset/intermediate repeat patients for which, besides accurate AO information, also clinical parameters (MRI scans, liquor markers etc) will be (made) available. This will be used for validation and to fine-tune the molecular landscapes (again using DLA) towards the best prediction of individual patient related clinical markers and AO (WP3). The same models and (most relevant) landscapes will also be used for evaluations of novel mutant protein lowering strategies as will emerge from WP4.This overall development process of landscape prediction is an iterative process that involves (a) data processing (WP5) (b) unsupervised data exploration and dimensionality reduction to find patterns in data and create “labels” for similarity and (c) development of data supervised Deep Learning (DL) models for landscape prediction based on the labels from previous step. Each iteration starts with data that is generated and deployed according to FAIR principles, and the developed deep learning system will be instrumental to connect these WPs. Insights in algorithm sensitivity from the predictive models will form the basis for discussion with field experts on the distinction and phenotypic consequences. While full development of accurate diagnostics might go beyond the timespan of the 5 year project, ideally our final landscapes can be used for new genetic counselling: when somebody is positive for the gene, can we use his/her cells, feed it into the generated cell-based model and better predict the AO and severity? While this will answer questions from clinicians and patient communities, it will also generate new ones, which is why we will study the ethical implications of such improved diagnostics in advance (WP6).

Ongoing

project

Designing Shape-Changing Textiles

In dit project zal ArtEZ onder leiding van onderzoeker Pauline van Dongen samenwerken met het Next Nature Network, UNStudio, AMOLF en het Ecomimicry Instituut aan kennisontwikkeling en -deling m.b.t. het potentieel van shape-changing textiles voor de bevordering van duurzaam gedrag en een duurzame omgeving. Shape-changing textiles zijn stoffen die actief van vorm kunnen veranderen in interactie met de drager of de omgeving. Door hun adaptieve, responsieve en interactieve eigenschappen gaan deze stoffen een andere relatie aan met de gebruiker, wat mogelijkheden biedt voor duurzame gedragsverandering. ArtEZ en de consortiumpartners verbinden hun state-of-the-art kennis vanuit ecologisch-, technisch- en designperspectief om door middel van ontwerpend onderzoek nieuwe kennis te ontwikkelen over hoe deze innovatieve materialen kunnen bijdragen aan verduurzaming van gedrag en omgeving. Aan de basis van dit onderzoek ligt een expliciete praktijkvraag van MKB-ondernemingen, die we op basis van een uitgebreid vraagarticulatieproces als volgt geformuleerd hebben: Hoe kunnen shape-changing textiles, ontwikkeld en ontworpen op basis van ecologische principes en processen, een andere relatie tot de drager/gebruiker en zijn/haar omgeving genereren om duurzaamheid te bevorderen? We willen deze hoofdvraag en een aantal deelvragen beantwoorden door in drie werkpakketten met het consortium te inventariseren welke relevante kennis er op dit moment beschikbaar is. Deze kennis zullen we door middel van ontwerpend onderzoek toetsen en verder ontwikkelen, waarna we de opgedane inzichten vervolgens analyseren en duiden om voor de MKB-partners en ons breder netwerk toepasbare kennis te genereren. Concrete voorbeelden hiervan zijn onder andere prototypes die getest kunnen worden met gebruikers (AMOLF en UN Studio) en de basis kunnen vormen voor een samplebibliotheek van shape-changing textiles. Daarnaast ontwikkelen we met Next Nature Network een speculatief toekomstscenario dat gepubliceerd en gedeeld kan worden met een breder publiek.

Finished

project

Development of ROS1-positive cell lines to improve personalized therapy in lung cancer patients

Every year in the Netherlands around 10.000 people are diagnosed with non-small cell lung cancer, commonly at advanced stages. In 1 to 2% of patients, a chromosomal translocation of the ROS1 gene drives oncogenesis. Since a few years, ROS1+ cancer can be treated effectively by targeted therapy with the tyrosine kinase inhibitor (TKI) crizotinib, which binds to the ROS1 protein, impairs the kinase activity and thereby inhibits tumor growth. Despite the successful treatment with crizotinib, most patients eventually show disease progression due to development of resistance. The available TKI-drugs for ROS1+ lung cancer make it possible to sequentially change medication as the disease progresses, but this is largely a ‘trial and error’ approach. Patients and their doctors ask for better prediction which TKI will work best after resistance occurs. The ROS1 patient foundation ‘Stichting Merels Wereld’ raises awareness and brings researchers together to close the knowledge gap on ROS1-driven oncogenesis and increase the options for treatment. As ROS1+ lung cancer is rare, research into resistance mechanisms and the availability of cell line models are limited. Medical Life Sciences & Diagnostics can help to improve treatment by developing new models which mimic the situation in resistant tumor cells. In the current proposal we will develop novel TKI-resistant cell lines that allow screening for improved personalized treatment with TKIs. Knowledge of specific mutations occurring after resistance will help to predict more accurately what the next step in patient treatment could be. This project is part of a long-term collaboration between the ROS1 patient foundation ‘Stichting Merels Wereld’, the departments of Pulmonary Oncology and Pathology of the UMCG and the Institute for Life Science & Technology of the Hanzehogeschool. The company Vivomicx will join our consortium, adding expertise on drug screening in complex cell systems.

Finished

Editorials 1

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Products 599

Blood-Based Immune Profiling Combined with Machine Learning Discriminates Psoriatic Arthritis from Psoriasis Patients

Drug-induced caspase 8 upregulation sensitises cisplatin-resistant ovarian carcinoma cells to rhTRAIL-induced apoptosis

Improved Efficacy of Oral Immunotherapy Using Non-Digestible Oligosaccharides in a Murine Cow's Milk Allergy Model

(Ronde Tafel) - Webinar Smart Assembly Factory - 2021-05-26

De digitale Kunstkammer. Cultureel erfgoed en crossmedia CELL Cahier # 1

Festival beleving : de waarde van publieksevenementen.

Identification of biomarkers to detect residual pertussis toxin using microarray analysis of dendritic cells

Flexnode Plus Project: results of testing a hydrogen-based reversible fuel cell system

Cell control with agents

People 1

Igor Mayer

Projects 34

Audiovisual Education and Training Network for European Vocational Excellence

Beweegniveau herkend: oog voor excellentie

Circulair ontwerp voor lupeol extractie uit reststromen van industriële lupine verwerking vergeleken met concurrerende processen

Classification of Multiple Sclerosis (MS) and Healthy-Control blood samples using Transfer Learning

CO2Cap - CO2 from air capturing via a modified Schauberger system

CrossReTour

CureQ Predict, Delay & Cure polyglutamine(Q) caused neurodegeneration

Designing Shape-Changing Textiles

Development of ROS1-positive cell lines to improve personalized therapy in lung cancer patients

Editorials 1

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