101 research outputs found
Towards efficient perfusion recellularization of porcine liver grafts with liver-derived organoids
No full textCurrently, the only effective treatment for end-stage liver diseases is liver transplantation. However, the waiting list with patients who are in need of a new liver is long, because too few good-quality donor livers are available. New techniques in the field of tissue engineering are being investigated to create a reconstructed liver, which might offer a solution for the shortage of transplantable livers. In this study, after decellularization had been performed, the potential of recellularization of porcine liver grafts with liver-derived organoids was researched. In advance of organoid recellularization, the reseeding protocol was optimized by studying different flow rates and different numbers of cell injections in recellularization experiments with HepG2 cells. A flow rate of either 5 ml/min or 11 ml/min was used. The experiments were performed by multi-step perfusion of either 4 or 10 cell injections inside the perfusion system. In addition to optimization experiments and experiments with organoids, reendothelialization of vascular structures inside a porcine liver graft was tested by HUVEC reseeding. The results of these experiments have shown that regarding cellular spreading, cell position and cells viability, the optimal parameters are a flow rate of 5 ml/min and 10 injections. Furthermore, this study has shown that it is possible to culture HepG2 cells, HUVECs as well as organoids inside a porcine liver graft, and that it is possible to keep the cells viable for up to one week. Organoid reseeding was successful and the organoids have shown their organoid-like behaviour. Although more experiments should be done, organoid reseeding has shown to be a promising cell type for recellularization of liver grafts.Biomedical Engineering | Medical Instruments and Medical Safety (MIMS
VERITAS Discovery of Very High Energy Gamma-Ray Emission from S3 1227+25 and Multiwavelength Observations
No full textFunding Information: This study was partly based on observations conducted using the 1.8 m Perkins Telescope Observatory (PTO) in Arizona (USA), which is owned and operated by Boston University. The BU group was supported in part by NASA Fermi Guest Investigator grant 80NSSC22K1571. Funding Information: A.A. and M.S. acknowledge support through NASA grants 80NSSC22K1515, 80NSSC22K0950, 80NSSC20K1587, and 80NSSC20K1494 and NSF grant PHY-1914579. Funding Information: This work has made use of data from the Asteroid Terrestrial-impact Last Alert System (ATLAS) project. The ATLAS project is primarily funded to search for near-Earth asteroids through NASA grants NN12AR55G, 80NSSC18K0284, and 80NSSC18K1575; by-products of the NEO search include images and catalogs from the survey area. This work was partially funded by Kepler/K2 grants J1944/80NSSC19K0112 and HST GO-15889 and STFC grants ST/T000198/1 and ST/S006109/1. The ATLAS science products have been made possible through the contributions of the University of Hawaii Institute for Astronomy, the Queens University Belfast, the Space Telescope Science Institute, the South African Astronomical Observatory, and the Millennium Institute of Astrophysics (MAS), Chile. Funding Information: This research has made use of data from the OVRO 40 m monitoring program (Richards et al. ), supported by private funding from the California Institute of Technology and the Max Planck Institute for Radio Astronomy, and by NASA grants NNX08AW31G, NNX11A043G, and NNX14AQ89G and NSF grants AST-0808050 and AST-1109911. Funding Information: This work has made use of data from the Steward Observatory, supported by NASA Fermi Guest Investigator grant NNX12AO93G. Funding Information: S.K. acknowledges support from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program under grant agreement No. 771282. Funding Information: This research is supported by grants from the U.S. Department of Energy Office of Science, the U.S. National Science Foundation, and the Smithsonian Institution; by NSERC in Canada; and by the Helmholtz Association in Germany. This research used resources provided by the Open Science Grid, which is supported by the National Science Foundation and the U.S. Department of Energy’s Office of Science, and resources of the National Energy Research Scientific Computing Center (NERSC), a U.S. Department of Energy Office of Science User Facility operated under contract No. DE-AC02-05CH11231. We acknowledge the excellent work of the technical support staff at the Fred Lawrence Whipple Observatory and at the collaborating institutions in the construction and operation of the instrument. Publisher Copyright: © 2023. The Author(s). Published by the American Astronomical Society.We report the detection of very high energy gamma-ray emission from the blazar S3 1227+25 (VER J1230+253) with the Very Energetic Radiation Imaging Telescope Array System (VERITAS). VERITAS observations of the source were triggered by the detection of a hard-spectrum GeV flare on 2015 May 15 with the Fermi-Large Area Telescope (LAT). A combined 5 hr VERITAS exposure on May 16 and 18 resulted in a strong 13? detection with a differential photon spectral index, "= 3.8 ± 0.4, and a flux level at 9% of the Crab Nebula above 120 GeV. This also triggered target-of-opportunity observations with Swift, optical photometry, polarimetry, and radio measurements, also presented in this work, in addition to the VERITAS and Fermi-LAT data. A temporal analysis of the gamma-ray flux during this period finds evidence of a shortest variability timescale of ? obs = 6.2 ± 0.9 hr, indicating emission from compact regions within the jet, and the combined gamma-ray spectrum shows no strong evidence of a spectral cutoff. An investigation into correlations between the multiwavelength observations found evidence of optical and gamma-ray correlations, suggesting a single-zone model of emission. Finally, the multiwavelength spectral energy distribution is well described by a simple one-zone leptonic synchrotron self-Compton radiation model.Peer reviewe
Generation of prolactin-inducible protein (Pip) knockout mice by CRISPR/Cas9-mediated gene engineering
No full textProlactin-inducible protein (PIP) is a multifunctional glycoprotein that is highly expressed and found in the secretions of apocrine glands, such as salivary, lacrimal, and sweat glands including the mammary glands. PIP has been implicated in various diseases, including breast cancer, gross cystic disease of the breast, keratoconus of the eye and the autoimmune Sjgren’s syndrome. Here we have generated a Pip knockout (KO) mouse using the CRISPR/Cas9 system. The Cas9 protein and two single guide RNAs targeting specific regions for both exons 1 and 2 of the Pip gene were microinjected into mouse embryos. The deletions and insertions promoted by CRISPR/Cas9 system on the Pip gene successfully disrupted PIP protein coding, as confirmed by PCR genotyping, sequencing and ultimately Western blot analysis. This mouse model was generated in the inbred C57Bl/6J mouse, which exhibits lower genetic variation. This novel CRISPR Pip KO mouse model will be not only be useful for future studies to interrogate the multifunctional role of PIP in physiological processes but will facilitate a broader understanding of the function of PIP in vivo while providing unprecedented insight into its role in a spectrum of diseases attributed to the deregulation of the PIP gene.The presentation of the authors' names and (or) special characters in the title of the pdf file of the accepted manuscript may differ slightly from what is displayed on the item page. The information in the pdf file of the accepted manuscript reflects the original submission by the author
Urbanizing the North-eastern Frontier: the frontier intelligentsia and the making of colonial Queenstown, c.1859-1857
No full textIncludes abstract.Includes bibliographical references.The rich and varied literature on the eastern Cape frontier has not yet reached the north-eastern frontier of the mid-nineteenth century. Urban centres and towns have also been largely ignored. Moreover, the perspective of the Anglophone intellectuals in these towns has rarely been analysed, and has instead been subsumed within a uniform ‘frontier voice’
Memory, language and trauma in the work of Félix Grande
No full textPhDMy thesis explores how memory and trauma permeate the work of the poet Félix Grande
(Mérida, Spain, 1937). It addresses the question of how his particular understanding of
memory is opposed to a rather bleak view of it held by many other Spanish poets of the
time. Grande does not yield to a generalized discrediting of memory. On the contrary,
memory is the driving force behind his writing, and this thesis constitutes an analysis of
its mechanisms. The originality of Grande’s work stems from the ways in which it shares
common ground with contemporary research carried out by disciplines that integrate
Memory and Trauma Studies. His poetic voice struggles to grasp aspects of memory
whose articulation proves traumatic. These elements resist symbolic translation and turn
his poetry into a work of constant rumination without closure. Grande’s work illustrates
that literature is both inextricably linked to memory, and is well equipped to deal with
trauma, as the labour carried out by memory, weaving and un-weaving, especially in its
attempts to mourn, is at the heart of his artistic production. Finally, his work instantiates a
relationship with language and memory which, while recognising the limits of language
to express and of memory to retrieve the past, goes beyond this initial distrust to offer a
positive perspective on these faculties, as the means for establishing modes of survival
and rethinking our connections to the unknown
The world is changing: ethics and genre development in three twentieth-century high fantasies.
No full textThis thesis examines three genre high fantasy texts published between 1954 and 2001: J. R. R. Tolkien’s 'The Lord of the Rings', Ursula K. Le Guin’s 'Earthsea' cycle and Patricia A. McKillip’s 'The Riddle-Master’s Game'. The emphasis is on examining how the three texts use a common set of structures to articulate a developing argument about forms of human engagement with the physical world in the face of environmental crisis.
Using theories of literary ecology and narrative paradigm, I examine the common structure shared by the three high fantasies and the weight of ethical implications it carries. The texts position the transcendent impulse of the mode of tragedy, and the behaviour it generates, as the source of crisis, and posit as a solution to the problem the integrative ethic characteristic of the comedic mode. They argue that a transition between these two ethics is necessary for the continued survival of the Secondary World. This thesis examines each text’s use of narrative paradigm to articulate methods by which this ethical transition may be achieved.
An argumentative trend is documented across the three fantasies through the representation of situation, problem and solution. In each text, as the Secondary World becomes more completely a closed physical system, the source of the solution to the problem caused by the transcendent presence and the achievement of ethical transition are both relocated within the control of human actors. The three fantasies express a gradual movement toward the acceptance of not only human responsibility for, but the necessity for action to remedy, the damaged state of the world.
I argue that the texts’ dominant concern is with the human relationship with and to context. Indeed, I argue that the three fantasies reflect the developing understanding of the human role in not only precipitating, but responding to, environmental crisis, and may function as both a reflection of and an intervention in that crisis.Thesis (Ph.D.) -- University of Adelaide, School of Humanities, 200
Current Income and Private Consumption-Saving Decisions: Testing the Finite Horizon Model
No full textThis paper considers the effects of fiscal policy on private consumption in a framework that encompasses both the conventional (Keynesian) view of fiscal policy and the Ricardian debt neutrality hypothesis. The model is built on Blanchard's stochastic model of intertemporal optimization with finitely lived consumers. As an extension to the basic framework public consumption is explicitly incorporated in the model. The model nests also the excess sensitivity hypothesis whereby the role of current income on consumption can be investigated. Empirical analyses are based on annual data from ten EU countries covering the years 1961–1994 and use the nonlinear instrumental variable GMM estimator both in country-specific and panel estimations. The tests reject clearly the Ricardian debt neutrality for majority of the countries in the sample. Moreover, deviations from Ricardian neutrality seem to arise from excess sensitivity of consumption to current income rather than from a finite planning horizon on the part of consumers. The results also suggest that in the consumers' utility functions, government consumption and private consumption tend to be unrelated or complements rather than substitutes.private consumption; private saving; current income; fiscal policy; planning horizon
Fiscal Policy and Private Consumption – Saving Decisions: Evidence from Finland
No full textThe paper presents a theoretical model of private consumption that emcompasses both the conventional (Keynesian) view of fiscal policy and the Ricardian debt neutrality hypothesis. The effects of fiscal policy on private consumption are analyzed in an extended framework built on Blanchard's stochastic model of intertemporal optimization with finitely lived consumers, in which private consumption depends on expected lifetime wealth. The model also nests various hypotheses concerning the relationship between public spending and private consumption. Empirical analysis is based on the Finnish annual data from 1960–1995 and uses the nonlinear instrumental variable GMM estimator. The tests cannot reject the hypothesis that consumers are Ricardian. Moreover, the results suggest that in the consumers' utility functions, government consumption is a substitute for private consumption.private consumption; private saving; fiscal policy; planning horizon
Grafting luminescent metal-organic species into mesoporous MCM-41 silica from europium(III)tetramethylheptanedionate, Eu(thd)3
No full textMixed systems with Eu(III) β-diketonates as optically active guest species, and mesoporous silicas MCM-41 as a host matrix have been investigated. The grafting of europium(III) onto the inner walls of unmodified MCM-41 has been achieved starting from Eu(thd)3 (thd = 2,2,6,6- tetramethyl-3,5-heptanedionate), using two routes: wet impregnation (WI) at room temperature,and chemical vapour infiltration (CVI) at 185 °C. In received hybrids, denoted Eu(thd)x@MCM- 41, the same maximum yield [Eu]/[Si] = 8.2 at% on average has been achieved with either methods. The molar ratio x = [thd]/[Eu] is 0.6 on average for WI samples, and 1.5 for CVI samples. In the latter, higher contents in thd compensate lower contents in silanols with respect to the former. Rationalizing the possible bonds exchanged at the silica surface leads to a great diversity of possible co-ordination schemes according to the expression Σ[Si(OH)nx (O)xEu(thd)3-x] (where Σ means that surface species are considered). Chromophore neutral ligands phenanthroline (phen) or bipyridine (bipy) have been added to induce efficient Eu3+ luminescence under 270–280 nm excitation, via the antenna effect. For the most favourable case, (phen)yEu(thd)x@MCM-41, the emission intensity at 612 nm under excitation at 270 nm is 2/3 that for the genuine heteroleptic complex Eu(thd)3(phen). Moreover the hybrid material is stable up to 440 °C
Hundreds of variants clustered in genomic loci and biological pathways affect human height
No full textMost common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits(1), but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait(2,3). The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P<0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways
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