467 research outputs found
Experimental application of a dynamic observer to capture and predict the dynamics of a flat-plate boundary layer
No full textThe recent approach, proposed by Guzman-Inigo et al. \cite{GuzmanInigo2014}, using System Identification to derive a Reduced Order Model from snapshots of a flow is applied to a transitional boundary layer growing over a flat-plate. It is shown that such an approach can indeed be applied to experimental PIV snapshots. Using a proper learning dataset and a proper local sensor, it is shown that the evolution of boundary layer can be properly estimated from the time evolution of the local probe and with no more than ten POD modes for the Reduced Order Model. The influence of the various parameters on the efficiency of the system identification technique is discussed
Comparison of the heat transfer capabilities of conventional single- and two-phase cooling systems for electric vehicle IGBT power module
No full textThis paper presents a comparison of conventional single-phase water/glycol liquid and innovative two-phase cooling technology for thermal management of high power electronics automotive IGBT modules during full drive cycle. The proposed two-phase cooling system is built using conventional automotive air conditioning components (condenser, expansion valve, compressor, and vapor and liquid lines) and conventional cold plate as used for single-phase cooling, thus the design does not require the development of new technology for its implementation. 3-D numerical simulation in COMSOL and experimental results of two-phase cooling have been obtained on a prototype and compared to conventional water/glycol cooling high power electronics modules, with considerable improvement on working temperature, power transfer capacity and equalization of die temperatures during a full driving cycle. These results suggest that two-phase cooling using the same cold plates as in single-phase cooling can be used to substantially improve the performance and reliability, of EV power converters without major changes
Biology of mesenchymal stromal cells: Chondrogenesis, paracrine signalling and cartilage repair
No full textThe management of articular cartilage lesions is one of the weighty challenges for orthopaedic surgeons. The use of mesenchymal stem/stromal cells (MSCs) has demonstrated as an alternative cell source for cartilage repair due to their multilineage differentiation potential and hypoimmunogenic properties. Despite the advances in cartilage repair techniques, there is no consensus relating to the most suitable cell type for cartilage repair or osteoarthritis treatment. In the paper I, we characterised and compared in vitro chondrogenic capacity of cells harvested from Hoffa’s fat pad (HFPSCs), synovial membrane (SMSCs), umbilical cord (UCSCs) and articular cartilage. We demonstrated poorer in vitro chondrogenesis of MSCs from umbilical cord compared to cells harvested from adult joint tissues. The study of TGF-β receptors revealed low expression of TGF-β receptor type II in umbilical cord stromal cells (UCSCs). This finding may explain the reason for poor chondrogenesis of UCSCs. In the paper II, we investigated the secretomes of HFPSCs, SMSCs, UCSCs and chondrocytes (ACs) to unveil in vitro secretory protein profiles that contribute to paracrine signalling and immunomodulatory characteristics. We found that UCSCs secretes less catabolic factors and less pro-inflammatory factors compared to cells from the adult origin. Considering the anti-inflammatory and pro-anabolic paracrine effects of secreted soluble molecules, UCSCs could be used as an adjuvant therapy for cartilage repair. In the paper III, we investigated if in vitro chondrogenic potential of donor-matched surplus chondrocytes from Autologous Chondrocyte Implantation (ACI)-treated patients could predict clinical outcomes. Counterintuitive, we did not observe any correlation between in vitro chondrogenic capacity of cultured cells and short-term clinical outcomes. Additionally, constitutive expression of previously proposed and novel chondrogenic markers had no value to predict clinical outcomes. Of interest, high-throughput LC-MS/MS protein analysis revealed prolyl 4‑hydroxylase 1, an enzyme involved in collagen biosynthesis, as a novel biomarker linked to superior chondrogenic capacity
Temporal variation in environmental conditions and the structure of fish assemblages around an offshore oil platform in the North Sea
No full textCopyright © 2015 The Author. Published by Elsevier Ltd.. All rights reserved. Acknowledgements The author would like to thank ICES for providing fish and oceanographic data, OSPAR for providing data for offshore structures in the North Sea, and Imants G. Priede, Alan Jamieson, Jim Mair, Inigo Martinez, Michelle Horsfield, Anne Walls and all the crew members of the Miller platform for invaluable advice and support in conducting this fish biology project. This work was coordinated by Oceanlab, University of Aberdeen and supported by the BP Fellowship in Applied Fisheries Programme.Peer reviewe
Isolation, characterization and chondrogenic differentiation of adult stem cell-derived MUSE-cells
No full textArticular cartilage is coating the layers of freely movable joints, enabling a smooth surface
and acts resisting to forces. The tissue is aneural and avascular, and has a poor ability to selfrenew
in cases of tissue damage. Therefore, cartilage lesions often lead to degenerative
disorders such as osteoarthritis (OA). OA is considered the most common form of arthritis
affecting people worldwide, causing pain and physical disability. Approaches in cartilage
regeneration, especially the use of mesenchymal stem cells (MSCs), have been promising, yet
limited. Finding a the most suitable cell type for transplantation strategies is still matter of
debate. The recent discovery of a pluripotent stem cell type that represent a minor fraction of
the stromal cells present in tissues (MUSE-cells) offer an attractive alternative that deserve to
be investigated.
The main objective of this study was to establish protocols for the isolation and
characterization of MUSE-cells from Hoffa’s fat pad (HFP) and umbilical cords (MC), and to
compare the chondrogenic differentiation potential between the MUSE- and non-MUSE-cell
populations. MUSE-cells were isolated from the total pull of mesenchymal stem cells by cell
sorting, using the embryonic marker SSEA-3 as specific cell surface antigen. Scaffold-free 3D
cultures maintained in chondrogenic conditions were used to induce cartilage differentiation.
Single cell cluster formation assays were used for functional characterization of MUSE.
Pluripotent NTERA-2 cells were used as positive control.
Mesenchymal cells displaying phenotypic characteristics of stem cells (MSCs) were
successfully isolated from fresh tissues. Scaffold-free spheroids of HFP-MSCs showed a more
intense Alcian blue (matrix) staining and had better cartilage-like morphology than those
formed from mixed cord MSCs (MC-MSCs). SSEA-3+ MUSE-cells could be identified and
isolated from HFP (8% of total MSCs) but were nearly undetectable in MC (0.8% of total
MSCs). Phenotypic characterization of sorted cells after cell expansion, and functional
characterization by single cell cluster formation abilities confirmed the pluripotent nature of
the cells.
IV
We have demonstrated that the adipose tissue of the infrapatellar pocket (HFP) is a good
source of MSCs, with the ability to produce cartilage-like spheroids, and contain a fraction of
SSEA-3+ cells (MUSE-cells) with the ability to self-renew. This cell subtype was also highly
positive for the pluripotency marker SSEA-4. MC-MSCs on the other hand, did not manage to
produce spheroids with properties similar to those of native cartilage, and had not SSEA-3+
MUSE-cells. The chondrogenic abilities of MUSE- and non-MUSE-cells from HFP is under
investigation at the time of writing this thesis.
Keywords: Articular cartilage, Articular cartilage disorders, Multilineage-differentiating
stress enduring (MUSE) cells, Regenerative medicine, Hoffa’s fat pad, Umbilical cord,
Chondrogenesis, Mesenchymal stem cells, SSEA-3, SSEA-4, Cell sorting
Synergistic effects of Radiotherapy and Immune Checkpoint Inhibitors in Cancer Treatment
No full textBackground: Use of immune checkpoint inhibitors have improved survival in patients suffering from cancer types such as advanced melanoma and NSCLC. Through increased understanding of immunological reactions associated with radiotherapy, a potential for synergy of radiotherapy and immune checkpoint inhibitors has emerged. Preclinical proof-of-concept studies have confirmed synergy of the treatments in mouse models.
Objectives: The primary objective was to identify proof-of-concepts in human data supporting combinations of radiotherapy and immune checkpoint inhibition, and identify characteristics of potential examples. A secondary objective was to assess if larger patient materials supported synergistic effects of such treatment regimens.
Methods: A literature search in PubMed was conducted to identify original data on patients treated with combinations of radiotherapy and immune checkpoint inhibition.
Results and discussion: Six case reports described impressive treatment responses following radiotherapy and immune checkpoint inhibition. A large double blinded RCT, including 799 patients, failed to present evidence for improved median survival in metastatic castration resistant prostate cancer (11,2 months for radiotherapy and Ipilimumab vs. 10,0 months for radiotherapy and placebo). Seven retrospective studies on patients (n=200) with advanced melanoma showed median survival over the expected, while two (n=38) failed to do so. Three of the retrospective studies specifically looked radiographically for abscopal responses outside the irradiated field, noting unusually frequent responses. A single small prospective trial (n=22) on advanced melanoma did not find a median survival over the expected. The studies varied in characteristics of the patient populations, methodologies and in radiotherapy regimens.
Conclusion: Case reports and retrospective studies investigating abscopal responses after radiation presented circumstantial evidence for synergy of radiotherapy and immune checkpoint inhibition. The single identified randomized controlled trial failed to prove increased survival of a relevant combination regimen in metastatic castration resistant prostate cancer, while retrospective studies in advanced melanoma were more encouraging
Kartleggelse av skaderisiko innen kampsporten Mixed Martial Arts
No full textBakgrunn: Mixed martial arts (MMA) er en fullkontakt kampsport i sterk vekst. I MMA trener utøverne flere typer kampgrener for å oppnå den beste kombinasjonen. Til tross for økende oppmerksomhet rundt sporten, er det mangel på studier om skaderisiko og skadeforekomst. Denne oppgaven vil forsøke kartlegge de vanligste skadene og risikofaktorene, og sammenligne med annen idrett.
Materiale og metode: informasjon er hentet fra besøk ved 19 forskjellige kampsportgym i inn- og utland, litteratur, egeninteresse i kampsport og søk i PubMed for artikkler. Data ble samlet inn fra to nettbaserte spørreundersøkelser, en for kampsport og en for annen type idrett.
Resulater: Skaderate var 2,57 per utøver og de hadde i gjennomsnitt skadet 3,43 ledd. Flest skader var forstuelse (27,6 %), kuttskade (22,4%) og hudinfeksjon (15,5%). De hyppigst skadede ledd var fingre/tær (21,6 %), ankler (20,1%) og knær (20,1%). Hjernerystelse forekom hos 8,6 % og 6,4 % hadde skadet hodet. Legehjelp var oppsøkt av 61,1 % av utøverne. Risikofaktorer for skade var konkurransedeltakelse, antall treningstimer ukentlig og hankjønn, mens treningserfaring og konkurranse i annen idrett medførte mindre risiko. MMA hadde lavere skadeforekomst enn annen idrett. Det var også 17 % flere av andre idrettsutøvere som hadde oppsøkt legehjelp. Det var en større risiko for hudinfeksjoner, nakke-, skulder- og albueskader i MMA, men mindre risiko belastningsskader, ankelskader og hodeskader.
Fortolkning: Arbeid for å redusere skader innen MMA burde involvere forhindring og behandling av forstuelser, kuttskader, og hudinfeksjoner. Samt håndtering og forhindring av leddskade, spesielt finger-, tær-, kne- og nakkeskader. Skadeforebyggende tiltak kan også tilpasses eksponering for risikofaktorer. Studien viser at skade innen MMA ikke er forhøyet sammenlignet med annen idrett, men alvorligheten av skadene må undersøkes videre
Biology of signalling receptors in human articular chondrocytes. Implications for chondrogenesis and cartilage repair.
No full textArticular cartilage is the thin avascular tissue covering the ends of adjacent bones that provides frictionless movement to the skeleton. Cartilage injuries are frequent, but due to its avascular nature the cartilage of skeletally matured individuals has a poor healing capacity. Degenerative diseases such as osteoarthritis (OA), is characterised by the gradual destruction of articular cartilage, typically affecting hand-, hip- and knee joints. In the orthopaedic field, there is a growing interest in transitioning from joint-replacement surgery in end-stage disease to biological repair techniques applied at an earlier stage. Short- and mid-term clinical outcomes of these cell-based therapies are promising, but the long-term results are unsatisfactory. The field is so far progressing based on trial-error approaches and there is an urgent need to increase our understanding on the biological principles governing tissue homeostasis and disease development. Hence, the aim of this thesis was to investigate cell-signalling receptors in chondrocytes in the context of chondrogenesis and cartilage repair. We found novel evidence of functional leukotriene B₄ receptors expressed in chondrocytes, but no clear read-outs upon stimulation of the receptors with their cognate ligand. The vitamin D receptor is expressed at very low levels in cartilage, but its expression is enhanced in monolayer cultures and under inflammatory conditions. We were able to demonstrate that the chondrocyte exhibit 1α-hydroxylase activity facilitating active hormone production. In dedifferentiated chondrocytes, vitamin D promoted cell proliferation, but the overall effect on chondrogenesis was unfavourable. In the last study, we have searched for potential biomarkers of chondrogenesis, with focus on cell adhesion molecules and other cell surface receptors. Our data shows that all studied cell-cell and cell-matrix receptors are not good predictors of chondrogenesis. Of note, high throughput proteomic analyses uncovered the potential of prolyl 4-hydroxylase, an enzyme implicated in collagen biosynthesis, as a predictor of intrinsic chondrogenesis
Addressing the challenges of climate change risks and adaptation in coastal areas: A review
No full textClimate change is and will continue altering the world's coasts, which are the most densely populated and economically active areas on earth and home for highly valuable ecosystems. While there is considerable relevant research, in the authors' experience this problem remains challenging for coastal engineering. This paper reviews important challenges in this respect and identifies three key actions to address them: (a) refocusing traditional practice towards more climate-aware approaches; (b) developing more comprehensive risk frameworks that include the multi-dimensionality and non-stationarity of their components and consideration of uncertainty; and (c) building bridges between risk assessment and adaptation theory and practice. We conclude that the way forward includes numerous activities including increased observations; the attribution of coastal impacts to their drivers; enhanced climate projections and their integration into impact models; more impact assessments at the local scale; dynamic projections of spatially-distributed exposure and vulnerability; and the exploration of inherently adaptive options. Given the complexity of the possible solutions, more practical guidance is required.Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Coastal Engineerin
The secretome of cartilage, chondrocytes and chondroprogenitors : Implications for cell transplantation strategies
No full textLeddbrusk har dårlig eller ingen reparasjonsevne, noe som gjør leddslitasje til et alvorlig medisinsk problem hos voksne. Flere metoder har blitt utviklet for å reparere bruskskader ved å bruke kroppens egne celler og vev. Selv om resultatene er lovende, har reparert bruskvev både dårligere kvalitet og mekaniske egenskaper, sammenlignet med friskt bruskvev. For å bedre kvaliteten til reparasjonsvevet, trengs en bedre forståelse av hvordan cellene oppfører seg i laboratoriekulturer. Dette kan gjøres ved å studere proteiner som skilles ut fra cellene, noe som kan gi viktig informasjon om cellenes kommunikasjon og hvordan vevsdannelsen reguleres.
I sitt arbeid har Polacek studert de fysiologiske egenskapene til brusk- og stamceller i laboratoriet. Fra tidligere er det kjent at disse cellene blir mindre spesifikke de-differensieres) og gradvis mister sine egenskaper når de dyrkes. Resultatene hans har vist at de-differensierte bruskceller, dyrket under standard forhold, skiller ut andre proteiner enn bruskcellene i kroppen. De fleste proteiner laget av kroppens bruskceller blir en del av omkringliggende vev, men proteiner fra cellene som dyrkes i laboratoriet viser ikke samme tendens. Selv om dyrkede bruskceller er uspesifikke, har Polacek vist at de fortsatt kan gå tilbake til sin opprinelige form (re-differensiere), hvis dyrket i 3-dimensjonelle- og lav-oksygen-kulturer. Cellene vil da gå fra å vokse og dele seg, til en fase hvor de produserer vev. Kandidaten har også sett på proteiner dannet av stamceller dyrket i laboratoriet, og vist at disse er bedre egnet enn bruskceller til å produsere vev. Dette indikerer at stamcellene kan være velegnet for cellebaserte vevsreparasjoner
- …
