597 research outputs found
A model of human skin under large amplitude oscillatory shear
No full textSkin mechanics is of importance in various fields of research when accurate predictions of the mechanical response of skin is essential. This study aims to develop a new constitutive model for human skin that is capable of describing the heterogeneous, nonlinear viscoelastic mechanical response of human skin under shear deformation. This complex mechanical response was determined by performing large amplitude oscillatory shear (LAOS) experiments on ex vivo human skin samples. It was combined with digital image correlation (DIC) on the cross-sectional area to assess heterogeneity. The skin is modeled as a one-dimensional layered structure, with every sublayer behaving as a nonlinear viscoelastic material. Heterogeneity is implemented by varying the stiffness with skin depth. Using an iterative parameter estimation method all model parameters were optimized simultaneously. The model accurately captures strain stiffening, shear thinning, softening effect and nonlinear viscous dissipation, as experimentally observed in the mechanical response to LAOS. The heterogeneous properties described by the model were in good agreement with the experimental DIC results. The presented mathematical description forms the basis for a future constitutive model definition that, by implementation in a finite element method, has the capability of describing the full 3D mechanical behavior of human skin
TRP channels in brown and white adipogenesis from human progenitors: new therapeutic targets and the caveats associated with the common antibiotic, streptomycin
No full textTransient receptor potential (TRP) channels are polymodal cell sensors responding to diverse stimuli and widely implicated in the developmental programs of numerous tissues. The evidence for an involvement of TRP family members in adipogenesis, however, is scant. We present the first comprehensive expression profile of all known 27 human TRP genes in mesenchymal progenitors cells during white or brown adipogenesis. Using positive trilineage differentiation as an exclusion criterion, TRP polycystic (P)3, and TPR melastatin (M)8 were found to be uniquely adipospecific. Knockdown of TRPP3 repressed the expression of the brown fat signature genes uncoupling protein (UCP)-1 and peroxisome proliferator-activated receptor γ coactivator (PGC)-1α as well as attenuated forskolin-stimulated uncoupled respiration. However, indices of generalized adipogenesis, such as lipid droplet morphology and fatty acid binding protein (FAPB)-4 expression, were not affected, indicating a principal mitochondrial role of TRPP3. Conversely, activating TRPM8 with menthol up-regulated UCP-1 expression and augmented uncoupled respiration predominantly in white adipocytes (browning), whereas streptomycin antagonized TRPM8-mediated calcium entry, downregulated UCP-1 expression, and mitigated uncoupled respiration; menthol was less capable of augmenting uncoupled respiration (thermogenesis) in brown adipocytes. TRPP3 and TRPM8 hence appear to be involved in the priming of mitochondria to perform uncoupled respiration downstream of adenylate cyclase. Our results also underscore the developmental caveats of using antibiotics in adipogenic studies.-Goralczyk, A., van Vijven, M., Koch, M., Badowski, C., Yassin, M. S., Toh, S.-A., Shabbir, A., Franco-Obregón, A., Raghunath, M. TRP channels in brown and white adipogenesis from human progenitors: new therapeutic targets and the caveats associated with the common antibiotic, streptomycin
Weil pairing and the Drinfeld modular curve
No full textIn 1974 verscheen er van de hand van de Oekraïnse wiskundige Vladimir Gershonovich Drinfeld een baanbrekend artikel getiteld 'Elliptic modules'. Met deze elliptische modulen, die tegenwoordig Drinfeld modulen worden genoemd, voegde de toen 19-jarige Drinfeld een nieuwe en belangwekkend onderwerp toe aan de arithmetische theorie van functielichamen. Eén van de mooiste resultaten binnen deze theorie is voor een groot deel verkregen dankzij Drinfelds werk. Samen met de resultaten verkregen in zijn artikel uit 1974 weet hij in 1977 een bewijs te geven van een speciaal geval van het zogenaamde Langlands' vermoeden. ...
Zie: Samenvatting
Expressing inflection tonally
No full textThe difference between neuter and feminine agreement on adjectives is expressed by a difference in lexical tone. This paper argues that this distinction is due to a difference in underlying representations en not to a paradigmatic antifaithfulness effect. In particular, it argues for a specific version of REALIZE-MORPHEME, the constraint demanding every underlying morpheme to be present in phonological surface representations. The key argument is that a schwa suffix turns up whenever the tonal change from neuter to feminine is not possible.The definitive version of this paper was published in Catalan Journal of Linguistics (2005) and is available at http://www.raco.cat/index.php/CatalanJournal/article/view/39478/39352Oostendorp, M. van, ‘Expressing Inflection Tonally.’ Catalan Journal of Linguistics 4 (1), 107-127, 2005.Peer reviewe
Skin mechanics
No full textThe skin is the largest organ of the human body. With its layered structure, it is mechanically a very complicated tissue. From the outer surface down, the main layers are the stratum corneum (10-15. μm), the viable epidermis (100-150. μm), dermis (subdivided into the papillary and reticular dermis, μ2 mm), and hypodermis. Although the stratum corneum is part of the epidermis, it is often considered to be a separate layer because of its specific barrier properties. It consists of nonviable cells and is very firm, but pliable and wrinkled. The epidermis is mainly composed of cells migrating to the skin surface. When the cells are closer to the stratum corneum, they become more keratinized. The viable epidermis has an undulated geometry. This undulation becomes less with age. The dermis is largely composed of a very dense network of collagen and elastin fibers, dominating the mechanical behavior of the total skin. The deepest skin layer, the hypodermis or subcutaneous adipose tissue, is composed of loose fatty connective tissue. The dermis contains microstructures such as blood vessels, lymph vessels, nerve endings, sweat glands, hair follicles, and different cell types. The influence of the different layers on the mechanical properties has often been ignored, because authors are mainly interested in the bulk mechanical behavior, dominated by the main components of the skin layer
Betere OV prognoses met anonieme OV-Chipkaartdata
No full textDoor de introductie van de OV-Chipkaart komen er grote hoeveelheden data over reizigersstromen in het OV beschikbaar. Naast data over de voertuigprestaties (via GOVI bijv.) hebben de inzichten uit deze reizigersdata een enorm potentieel voor de optimalisatie van het OV-product. Dit artikel verkent de mogelijkheden om, de privacy van reizigers respecterend, deze data in te zetten voor de voorspelling van nieuwe reispatronen bij aanpassingen in het netwerk en/of de dienstregeling. Het doel is om een relatief eenvoudige “What-if”-methodiek te ontwerpen, die snel en voldoende nauwkeurig reizigersprognoses kan maken. Hiermee ontstaat een nieuwe generatie verkeersmodellen. De aanpak combineert de eenvoud en snelheid van de “sigarenkist” en de visualisatie- en rekenkracht van een verkeersmodel. We hebben de methodiek ingebed in bestaande OmniTRANS-verkeersmodelsoftware. De anonieme OV-chipkaartdata wordt toegedeeld aan het OV netwerk in het model, waardoor huidige stromen gevisualiseerd kunnen worden. Door gebruik te maken van elasticiteiten over de relatie tussen OV-kwaliteit en OV-gebruik (zowel uit de literatuur als op basis van gangbare vuistregels) kunnen eenvoudige prognoses gemaakt worden. Die dienen bijvoorbeeld om inzicht te krijgen in inkomstenderving door omleidingen of om effecten te schatten van budgettaire maatregelen. We hebben de gepresenteerde methodiek succesvol toegepast op het tramnetwerk van HTM in Den Haag, waarmee sneller en nauwkeurige dan voorheen prognoses gemaakt kunnen worden. Voor het afwegen van scenario’s in de ontwikkeling van het railnetwerk en bij het afwegen van tijdelijke omleidingsscenario’s gebruikt HTM de aanpak inmiddels om reizigerseffecten te prognosticeren. Deze analyses helpen in het maken van betere keuzes en in het besluitvormingsproces met de OV-autoriteit Haaglanden. Hoewel waardevol, zijn er ook een aantal beperkingen aan deze methode. De aanpak is unimodaal en door het gebruik van elasticiteiten slechts toepasbaar voor kleine veranderingen op relatief korte termijn. Nu met de OV-Chipkaartdata meer inzichten kunnen worden verkregen, raden wij aan de gehanteerde elasticiteiten te actualiseren. Gedrag van reizigers bij kleine veranderingen kan relatief eenvoudig bepaald worden nu deze data voorhanden is. De volgende stap in ons onderzoek is het koppelen van de reizigersdata aan de voertuigdata, waardoor gedetailleerdere analyses gemaakt kunnen worden van bijvoorbeeld reizigerspunctualiteit.Transport and PlanningCivil Engineering and Geoscience
The highly dynamic heterochromatin protein Swi6 mediates degradation of heterochromatic transcripts
No full textThe aim of my thesis was to investigate the mechanism of heterochromatin repression mediated by heterochromatin protein Swi6 in S. pombe.
Research over the years challenged the view of heterochromatin as a static and transcriptionally inert structure. Especially in fission yeast it has become clear that heterochromatin silencing requires not only the action of chromatin modifying factors, but also transcriptional activity and RNA degradation processes. Moreover, heterochromatin protein Swi6 was shown to be highly dynamic, unlike what was expected for a protein that is perceived as a major structural component of heterochromatin. Yet, the prevailing model of heterochromatin establishment and spreading is thought to occur by iterative HP1 binding to methylated H3K9 and recruitment of histone methylation activity.
Driven by recent findings in our lab that described a new role for Swi6 in repression and provided a possible explanation for its dynamic behavior, I set out to investigate the mechanism in vivo by studying Swi6 dynamics. Therefore, a major focus of my PhD was to establish a suitable, robust microscopy-based method that allowed me to follow rapid dynamics and produce reliable data. The work I have done challenged the role of Swi6 in heterochromatin maintenance and spreading, but coincides with a clear involvement in sustaining tight repression. While H3K9me levels remained high in the absence of Swi6 and even spread into neighboring regions, heterochromatic transcript levels increased. These observations revealed unanticipated functions for Swi6 and made us reconsider the mechanism of Swi6-mediated silencing. As previously proposed, Swi6 could function as a co-transcriptional checkpoint that mediates RNA degradation (Keller et al., 2012). In this model RNA binds to Swi6 and gets primed for destruction as it is handed over to the RNA decay machinery, involving Cid14 and the exosome or the RNAi machinery. The target specificity depends on the epigenetic make-up of the locus, meaning the recognition of H3K9me by the CD of Swi6, while RNA binding occurs in a sequence independent manner (Keller et al., 2012). Therefore, additional processes that confer specificity, like siRNAs, are needed to ensure correct targeting of H3K9me marks to trigger Swi6-mediated turnover of unwanted RNA transcripts and not of any other random region in the genome
DIPOT een Europees project – een 360 gradenbeeld van collecties in depot
No full textHeritage & Value
∗ Corresponding author.
No full textA novel method is introduced for optimal estimation of rigid camera motion from instantaneous velocity measurements. The error surface associated with this prob-lem is highly complex and existing algorithms suffer heavily from local minima. Repeated minimization with different random initializations and selection of the minimum-cost solution are a common (albeit ad hoc) procedure to increase the like-lihood of finding the global minimum. We instead show that the optimal estimation problem can be transformed into one of arbitrary complexity, which allows for a gradual regularization of the error function. A simple reweighting scheme is pre-sented that smoothly increases the problem complexity at each iteration. We show that the resulting method retains all the desirable properties of optimal algorithms, such as unbiasedness and minimal variance of the parameter estimates, but is sub-stantially more robust to local minima. This robustness comes at the expense of a slightly increased computational complexity
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