212 research outputs found

    Full-Scale, On-Campus Events Welcomed Back by Students

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    Delegating Immigration Admission Powers to the States

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    Control over immigration is generally seen as a purely federal power that cannot or should not be exercised by the states. Although some scholars have challenged this assumption, their focus is almost always on the ability of states to regulate (or remove) immigrants who are already within their borders. This Article calls for states to intervene in the immigration process at a much earlier stage. It proposes delegating to the states the power to admit new immigrants into the country by giving states control over the issuance of temporary and permanent visas. States would also be able to buy excess visas from one another, allocating a scarce resource equitably throughout the country. By embracing both federalism and free market incentives, this Article’s proposal would break the democratic dysfunction that currently prevents reform at the federal level, while allowing for innovation that better reflects the desires and needs of local communities

    Effect of functionalized PHEMA micro- and nano-particles on the viscoelastic properties of fibrin-agarose biomaterials

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    Two types of PHEMA-based particles, exhibiting either carboxyl or tertiary ammine functional groups, were incorporated to fibrin-agarose (FA) hydrogels, and the effect of the addition of these synthetic particles on the viscoelastic and microstructural properties of the biomaterials was evaluated. Experimental results indicated that the incorporation of both types of polymeric particles to FA scaffolds was able to improve the biomechanical properties of the biomaterials under steady state and oscillatory shear stresses, resulting in scaffolds characterized by higher values of the storage, loss, and shear moduli. In addition, the microstructural evaluation of the scaffolds showed that the nanoparticles exhibiting carboxyl functional groups were homogeneously distributed across the fibrous network of the hydrogels. The addition of both types of artificial polymeric particles was able to enhance the viscoelastic properties of the FA hydrogels, allowing the biomaterials to reach levels of mechanical consistency under shear stresses in the same range of some human native soft tissues, which could allow these biomaterials to be used as scaffolds for new tissue engineering applications.Peer ReviewedPostprint (author's final draft

    Micromechanical Analysis of the Hyaluronan-Rich Matrix Surrounding the Oocyte Reveals a Uniquely Soft and Elastic Composition

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    The cumulus cell-oocyte complex (COC) matrix is an extended coat that forms around the oocyte a few hours before ovulation and plays vital roles in oocyte biology. Here, we analyzed the micromechanical response of mouse COC matrix by colloidal-probe atomic force microscopy. We found that the COC matrix is elastic insofar as it does not flow and its original shape is restored after force release. At the same time, the COC matrix is extremely soft. Specifically, the most compliant parts of in vivo and in vitro expanded COC matrices yielded Young's modulus values of 0.5 ± 0.1 Pa and 1.6 ± 0.3 Pa, respectively, suggesting both high porosity and a large mesh size (≥100 nm). In addition, the elastic modulus increased progressively with indentation. Furthermore, using optical microscopy to correlate these mechanical properties with ultrastructure, we discovered that the COC is surrounded by a thick matrix shell that is essentially devoid of cumulus cells and is enhanced upon COC expansion in vivo. We propose that the pronounced nonlinear elastic behavior of the COC matrix is a consequence of structural heterogeneity and serves important functions in biological processes such as oocyte transport in the oviduct and sperm penetration

    Gelatin-Hyaluronic Acid Hydrogels with Tuned Stiffness to Counterbalance Cellular Forces and Promote Cell Differentiation

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    [EN] Cells interact mechanically with their environment, exerting mechanical forces that probe the extracellular matrix (ECM). The mechanical properties of the ECM determine cell behavior and control cell differentiation both in 2D and 3D environments. Gelatin (Gel) is a soft hydrogel into which cells can be embedded. This study shows significant 3D Gel shrinking due to the high traction cellular forces exerted by the cells on the matrix, which prevents cell differentiation. To modulate this process, Gel with hyaluronic acid (HA) has been combined in an injectable crosslinked hydrogel with controlled Gel-HA ratio. HA increases matrix stiffness. The addition of small amounts of HA leads to a significant reduction in hydrogel shrinking after cell encapsulation (C2C12 myoblasts). We show that hydrogel stiffness counterbalanced traction forces of cells and this was decisive in promoting cell differentiation and myotube formation of C2C12 encapsulated in the hybrid hydrogels.The authors are grateful for the financial support received from the Spanish Ministry through the MAT2013-46467-C4-1-R project (including the FEDER financial support), the BES-2011-046144, and the EEBB-I-14-08725 grants. CIBER-BBN is an initiative funded by the VI National R&D&I Plan 2008-2011, Iniciativa Ingenio 2010, Consolider Program. CIBER actions are financed by the Instituto de Salud Carlos III with assistance from the European Regional Development Fund. M.S.S. acknowledges ERC through HealInSynergy 306990.Poveda Reyes, S.; Moulisova, V.; Sanmartín Masiá, EDR.; Quintanilla-Sierra, L.; Salmerón Sánchez, M.; Gallego Ferrer, G. (2016). Gelatin-Hyaluronic Acid Hydrogels with Tuned Stiffness to Counterbalance Cellular Forces and Promote Cell Differentiation. Macromolecular Bioscience. 16(9):1311-1324. https://doi.org/10.1002/mabi.201500469S1311132416

    Claudin-1 Is a p63 Target Gene with a Crucial Role in Epithelial Development

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    The epidermis of the skin is a self-renewing, stratified epithelium that functions as the interface between the human body and the outer environment, and acts as a barrier to water loss. Components of intercellular junctions, such as Claudins, are critical to maintain tissue integrity and water retention. p63 is a transcription factor essential for proliferation of stem cells and for stratification in epithelia, mutated in human hereditary syndromes characterized by ectodermal dysplasia. Both p63 and Claudin-1 null mice die within few hours from birth due to dehydration from severe skin abnormalities. These observations suggested the possibility that these two genes might be linked in one regulatory pathway with p63 possibly regulating Claudin-1 expression. Here we show that silencing of ΔNp63 in primary mouse keratinocytes results in a marked down-regulation of Claudin-1 expression (−80%). ΔNp63α binds in vivo to the Claudin-1 promoter and activates both the endogenous Claudin-1 gene and a reporter vector containing a –1.4 Kb promoter fragment of the Claudin-1 gene. Accordingly, Claudin-1 expression was absent in the skin of E15.5 p63 null mice and natural p63 mutant proteins, specifically those found in Ankyloblepharon–Ectodermal dysplasia–Clefting (AEC) patients, were indeed altered in their capacity to regulate Claudin-1 transcription. This correlates with deficient Claudin-1 expression in the epidermis of an AEC patient carrying the I537T p63 mutation. Notably, AEC patients display skin fragility similar to what observed in the epidermis of Claudin-1 and p63 null mice. These findings reinforce the hypothesis that these two genes might be linked in a common regulatory pathway and that Claudin-1 may is an important p63 target gene involved in the pathogenesis of ectodermal dysplasias

    New Investigations in the Environment, History and Archaeology of the Iraqi Hilly Flanks: Shahrizor Survey Project 2009-2011

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    Recent palaeoenvironmental, historical, and archaeological investigations, primarily consisting of site reconnaissance, in the Shahrizor region within the province of Sulaymaniyah in Iraqi Kurdistan are bringing to light new information on the region’s social and socio-ecological development. This paper summarises two seasons of work by researchers from German, British, Dutch, and Iraqi-Kurdish institutions working in the survey region. Palaeoenvironmental data have determined that during the Pleistocene many terraces developed which came to be occupied by a number of the larger tell sites in the Holocene. In the sedimentary record, climatic and anthropogenic patterns are noticeable, and alluviation has affected the recovery of archaeological remains through site burial in places. Historical data show the Shahrizor shifting between periods of independence, either occupied by one regional state or several smaller entities, and periods that saw the plain’s incorporation within large empires, often in a border position. New archaeological investigations have provided insight into the importance of the region as a transit centre between Western Iran and northern and southern Mesopotamia, with clear material culture links recovered. Variations between periods’ settlement patterns and occupations are also beginning to emerge

    Suspended manufacture of biological structures

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    We present a novel method of extrusion-based ALM for the production of cell-laden strucutres from low viscosity polymers. The traditional planar print bed is replaced with a bed of micoparticulate fluid gel. During the extrusion process, the fluid gel is displaced whilst providing a support strucutre for the low viscosity material allowing manufacture of relatively complex geometries. The extruded structure can then be easily removed from this self-healing fluid bed. For this study, a bi-layered cell-seeded construct was produced to model the osteochondral junction. Osteochondral plugs were produced by the addition of chondrocytes and osteoblasts to 1.5%w/v gellan and 1.5%w/v gellan-5% nano-hydroxyapatite respectively. The consecutive extrusion of these two solutions into the fluid bed followed by further ionic crosslinking produced the bi-layered construct that was implant into a femoral condyle defect in vitro. Cell viability following extrusion was confirmed using calcein AM/PI live/dead staining showing excellent viability. Constructs were then sectioned, and qRT-PCR was performed, showing a native collagen phenotype across the construct with evidence of matrix markers in the cartilage-like region which were also identified using fluroescent-IHC. Constructs were also tested for their bulk relaxation properties. Addition of nano-hydroxyapatite in the bone-like region resulted in a faster, more elastic relaxation than gellan alone, something that has previously been reported to favour osteogenic differentiation. We have demonstrated the efficacy of suspended manufacturing to maintain viability and phenotype of two populations of human primary cells in a single construct thus emulating the structure of the osteochondral junction. Please click Additional Files below to see the full abstract
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