3,806 research outputs found

    Converging organoids and extracellular matrix::New insights into liver cancer biology

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    The Entrenched Political Limitations of Australian Refugee Policy: A Case Study of the Australian Labor Party (2007-2013)

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    This thesis deconstructs Australia’s asylum and refugee policy trajectory under the Labor government between 2007 and 2013. For a short time after the 2007 election, in accordance with its promise to abolish the LNP’s Pacific Solution, Labor began to unwind certain policy structures of externalisation and deterrence that had been in place since the introduction of mandatory detention in 1992. By 2013 however, the ALP had declared that asylum seekers arriving by boat had no prospect of resettlement in Australia. This thesis analyses the political strategy of the ALP in rhetoric, policy choices and policy justifications to derive lessons from Labor’s mitigated challenge to the deterrence/externalisation paradigm. Critical Discourse Analysis is used to examine the political strategies of lead actors, particularly the ALP and the LNP, and to reconcile these strategies with policy outcomes such as irregular arrivals, detention figures, deaths at sea and compliance with obligations under international law. A central argument of this thesis is that Labor’s attempt to sustainably depart from the dominant externalisation paradigm was impaired, not by a lack of commitment to its stated program of reform, but rather by entrenched political limitations of the Australian context. These limitations include the LNP’s rigid partisanship and lack of policy compromise, the deep-rooted nature of mandatory detention, and the Australian public’s historical and continued support for controlled migration. A precise and detailed analysis of the impact of these limitations on Labor’s proposed reform fills a gap in academic knowledge about the political influences on policy action in Australian asylum and refugee policy. I contend that these limitations must be effectively engaged with in any attempt to reform the Australian asylum and refugee policy space

    Operational Modal Analysis of Near-Infrared Spectroscopy Measure of 2-Month Exercise Intervention Effects in Sedentary Older Adults with Diabetes and Cognitive Impairment

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    The Global Burden of Disease Study (GBD 2019 Diseases and Injuries Collaborators) found that diabetes significantly increases the overall burden of disease, leading to a 24.4% increase in disability-adjusted life years. Persistently high glucose levels in diabetes can cause structural and functional changes in proteins throughout the body, and the accumulation of protein aggregates in the brain that can be associated with the progression of Alzheimer’s Disease (AD). To address this burden in type 2 diabetes mellitus (T2DM), a combined aerobic and resistance exercise program was developed based on the recommendations of the American College of Sports Medicine. The prospectively registered clinical trials (NCT04626453, NCT04812288) involved two groups: an Intervention group of older sedentary adults with T2DM and a Control group of healthy older adults who could be either active or sedentary. The completion rate for the 2-month exercise program was high, with participants completing on an average of 89.14% of the exercise sessions. This indicated that the program was practical, feasible, and well tolerated, even during the COVID-19 pandemic. It was also safe, requiring minimal equipment and no supervision. Our paper presents portable near-infrared spectroscopy (NIRS) based measures that showed muscle oxygen saturation (SmO2), i.e., the balance between oxygen delivery and oxygen consumption in muscle, drop during bilateral heel rise task (BHR) and the 6 min walk task (6MWT) significantly (p < 0.05) changed at the post-intervention follow-up from the pre-intervention baseline in the T2DM Intervention group participants. Moreover, post-intervention changes from pre-intervention baseline for the prefrontal activation (both oxyhemoglobin and deoxyhemoglobin) showed statistically significant (p < 0.05, q < 0.05) effect at the right superior frontal gyrus, dorsolateral, during the Mini-Cog task. Here, operational modal analysis provided further insights into the 2-month exercise intervention effects on the very-low-frequency oscillations (<0.05 Hz) during the Mini-Cog task that improved post-intervention in the sedentary T2DM Intervention group from their pre-intervention baseline when compared to active healthy Control group. Then, the 6MWT distance significantly (p < 0.01) improved in the T2DM Intervention group at post-intervention follow-up from pre-intervention baseline that showed improved aerobic capacity and endurance. Our portable NIRS based measures have practical implications at the point of care for the therapists as they can monitor muscle and brain oxygenation changes during physical and cognitive tests to prescribe personalized physical exercise doses without triggering individual stress response, thereby, enhancing vascular health in T2DM

    Novel isoforms of the giant protein Titin in the regulation of lymphocyte trafficking

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    Titin (TTN) is the largest protein in the human genome and is mainly known as the third component of the sarcomere together with actin and myosin. In this context, TTN is responsible for maintaining muscle passive stiffness providing structural, scaffolding, and mechano-signaling properties. Here, we describe unexpected role of TTN in the regulation of human lymphocyte physiology. Human T lymphocytes express three novel TTN isoforms exhibiting cell-specific expression and different distribution to subcellular compartments. By performing fluorescence microscopy 3D imaging, we found that the LTTN1 and the LTTN2 isoforms span cytosolic as well as nuclear compartments, whereas the smallest LTTN3 isoform seems to be restricted to the cytosol. Recent data from our laboratory showed that LTTN1 covers a pivotal role in immune system physiology. Indeed, LTTN1 controls microvilli stricture and, thus, selectin-mediated tethering and rolling, chemokinetriggered integrin activation, chemotaxis, and in vitro cell deformability underflow. The new in vivo data confirmed LTTN1 putative role in T lymphocytes resilience to mechanical stress induced by passive deformation in the microcirculation. This makes LTTN1 a crucial player not only in multiple steps of T lymphocyte trafficking but, and importantly, in T lymphocyte survival. Besides LTTN1, we demonstrated that also LTTN3 is involved in the inside-out pathway of chemokinetriggered integrin activation. LTTN3 facilitates chemotaxis and controls chemokine-triggered integrin-mediated adhesion. Accordingly, it mediates RhoA and Rac1 small GTPases activation. Thus, while LTTN1 is a critical housekeeping regulator of T lymphocyte physiology, our results also suggest a possible involvement of LTTN3 as a central modulator of chemokine-induced signal transduction in T lymphocytes

    Developing active biomaterials for implantable devices: platforms to investigate capacitive charge based control of biofouling

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    Implantable devices, in particular biosensors, have clear utility within medicine, but face a hurdle to long-term function due to adsorption of biomolecules (biofouling) and subsequent immune re- sponse to implants, the foreign body response (FBR). Strategies to control this immune reaction have included material selection, drug release and, more recently, engineered surface properties. The increasing use of embedded electronics within many classes of implanted devices presents an opportunity to exploit electromagnetic phenomena at the device surface to mitigate biofouling and FBR. Such active biomaterials would allow dynamic modification of the apparent material properties of an implanted device. A hypothesis was developed that biological interaction with a biomaterial surface can be altered by capacitive charging. A platform was constructed to test this and related hypotheses around cell and protein surface interactions in vitro and adapted into a second platform for initial characterisa- tion work on an early in vivo model using chick eggs. These platforms were designed to be easy to fabricate and to provide multiple electrical connections into a substrate in contact with biological solutions or tissue. Electrodes were fabricated from fluoropolymer coated tantalum pentoxide, a high-κ dielectric, and compared against adjacent, identically coated, silicon dioxide regions. Cells from the MDA- MB-231 cancer cell line were cultured on these regions under electrical stimulation. A voltage de- pendent reduction of cell attachment and spreading was detected on capacitively charged surfaces compared to uncharged controls. The tentative results, suggest capacitively charged surfaces hold promise as active biomaterials. A second cell type MCF-7 did not reproduce the effect, implying a more coherent understanding is required of the mechanisms behind cell surface interactions on these surfaces. Multiple independent bioelectrochemical cell-surface interactions were observed using the plat- form and several quantification techniques were successfully employed. It is therefore argued that the platform may have wide applicability as a future research tool

    The Palaces of Comfort, Consolation and Distraction - The Pie and Mash shop as a performative space of a contested London working class memory

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    This thesis seeks to interrogate and clarify the history and culture of London’s traditional but fading and largely forgotten eel, pie and mash shops. In doing so the work examines their cultural conduit, the adjacent and evolving identity of the cockney whose contested memoryscapes have, I suggest, great contemporary political and cultural relevance in an age of populism and Brexit. The work excavates a tracing around the shops’ absences in historical literature. It situates their establishment within the dying breath of an older, popular street culture and the birth of a new London working class, centred around unofficial street markets and in a synchronous dance with the ideological accession of the bourgeoisie. The thesis employs the biological notion of a taxon to illustrate the shops’ evolution largely defined by the class-demotion of their clientele that mirrored the changing cartography of the city. By the late nineteenth century, this work argues, the eel and pie shops had become a pillar of a respectable London working class culture whose hyper-local solidarities revolved around micro-class divisions of work and negotiated bourgeois codes of propriety as part of a ‘culture of consolation’ that has remained largely impenetrable to outsiders. The study explores this concomitant cockney identity which became, partly through bourgeois theatrical ventriloquising, a figure of imperial incorporation. This eventually came to represent a particular type of ‘ordinariness’, subsequently reconfigured around the gains of a Welfare State and a national economy that continues to be periodically valorised according its usefulness to capital at times of political stress. Utilising sensory ethnography and memory studies the work explores the landscape and territoriality of the contemporary eel, pie and mash shop. It interrogates the rituals and complex, often competing and polyphonic memory inscriptions which memorialise a largely post-colonial nostalgic melancholia around the loss of fantasy of a British omnipotence. The thesis argues that the shops and their simulacra-like reincarnations amongst the cockney diaspora in the Essex new towns offer an insight into the changing notions of taste and class within the convivialities of a unique but broadly closed heritage of proletarian culture as a zone of resistance in the neoliberal city

    Investigation of the molecular pathogenesis of the multi-host bacterial pathogen Staphylococcus aureus

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    Staphylococcus aureus is a major human and animal bacterial pathogen that causes an array of diseases. The main aim of this thesis is to investigate the key host-pathogen interactions that underpin S. aureus infection. S. aureus abundantly secretes two isoforms of the enzyme lipase into the extracellular milieu, where they scavenge upon polymeric triglycerides. It has previously been suggested that these lipases may interfere with the function of innate immune cells, such as macrophages and neutrophils, but the impact of lipases on phagocytic killing mechanisms remains unknown. We showed that there were no differences in the survival of S. aureus USA300 LAC wild type and its lipase-deficient isogenic mutant after incubation with human whole blood or neutrophils. Furthermore, there was no detectable lipase-dependent effect on phagocytosis, intracellular survival, or escape from both human primary and immortalised cell line macrophages, even upon supplementation with exogenous recombinant lipases. Therefore, we showed that S. aureus lipases do not inhibit bacterial killing mechanisms of human macrophages, neutrophils, or whole blood. Furthermore, the capacity of S. aureus to adapt to distinct host-species ecologies is a major public health and economic concern. Approximately 60 years ago, a human-to-poultry host jump and adaptation of S. aureus belonging to the widespread CC5 clade, led to the avian-adaptation and global expansion of S. aureus in broiler poultry. Our research aims to combine transposon (Tn) mutagenesis of S. aureus with experimental models of infections to identify the immune cell repertoire and bacterial genes involved in avian host-adaptation. To determine the avian immune cell tropism for S. aureus, mCherry-integrated clones from common avian (CC385, CC5) and human (CC8) S. aureus clonal lineages were screened in blood extracted from the transgenic chicken line Runx1-eGFP. We demonstrate that monocytes and heterophils generate the first-line response to S. aureus infection, with avian strains exhibiting differential uptake by heterophils compared to a human strain. Furthermore, our analysis demonstrated that avian S. aureus strains may have adapted to the avian host through the inhibition of degranulation of heterophils as a novel survival mechanism. TraDIS analysis of genes involved in the fitness of S. aureus during infection of peripheral blood leukocytes demonstrated that regulators of the Type VII secretion system and Spl-proteases were required for survival of S. aureus in the face of the innate immune response of PBLs. Taken together, these studies provide new insights into the evolution of S. aureus and the key host-pathogen interactions underpinning S. aureus infections

    The Adirondack Chronology

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    The Adirondack Chronology is intended to be a useful resource for researchers and others interested in the Adirondacks and Adirondack history.https://digitalworks.union.edu/arlpublications/1000/thumbnail.jp
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