461 research outputs found

    Investigating situated cultural practices through cross-sectoral digital collaborations: policies, processes, insights

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    The (Belfast) Good Friday Agreement represents a major milestone in Northern Ireland's recent political history, with complex conditions allowing for formation of a ‘cross-community’ system of government enabling power sharing between parties representing Protestant/loyalist and Catholic/nationalist constituencies. This article examines the apparent flourishing of community-focused digital practices over the subsequent ‘post-conflict’ decade, galvanised by Northern Irish and EU policy initiatives armed with consolidating the peace process. Numerous digital heritage and storytelling projects have been catalysed within programmes aiming to foster social processes, community cohesion and cross-community exchange. The article outlines two projects—‘digital memory boxes’ and ‘interactive galleon’—developed during 2007–2008 within practice-led PhD enquiry conducted in collaboration with the Nerve Centre, a third-sector media education organisation. The article goes on to critically examine the processes involved in practically realising, and creatively and theoretically reconciling, community-engaged digital production in a particular socio-political context of academic-community collaboration

    Inorganic Polyphosphates Are Important for Cell Survival and Motility of Human Skin Keratinocytes and Play a Role in Wound Healing

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    Inorganic polyphosphate (polyP) is a simple ancient polymer of linear chains of orthophosphate residues linked by high energy phospho-anhydride bonds ubiquitously found in all organisms. Despite its structural simplicity, it plays diverse functional roles. polyP is involved in myriad of processes including serving as microbial phosphagens, buffer against alkalis, Ca2+ storage, metal-chelating agents, pathogen virulence, cell viability and proliferation, structural component and chemical chaperones, and in the microbial stress response. In mammalian cells, polyP has been implicated in blood coagulation, inflammation, bone differentiation, cell bioenergetics, signal transduction, Ca2+-signaling, neuronal excitability, as a protein-stabilizing scaffold, and in wound healing, among others. This chapter will discuss (1) polyP metabolism and roles of polyP in prokaryotic and eukaryotic cells, (2) the contribution of polyP to survival, cell proliferation, and motility involved in wound healing in human skin keratinocytes, (3) the use of polyP-containing platelet-rich plasma (PRP) to promote wound healing in acute and chronic wounds, including burns, and (4) the use of polyP-containing PRP in excisional wound models to promote faster healing. While polyP shows promise as a therapeutic agent to accelerate healing for acute and chronic wounds, the molecular mechanisms as a potent modulator of the wound healing process remain to be elucidated

    Preliminary Jitter Stability Results for the Large UV/Optical/Infrared (LUVOIR) Surveyor Concept Using a Non-Contact Vibration Isolation and Precision Pointing System

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    The need for high payload dynamic stability and ultra-stable mechanical systems is an overarching technology need for large space telescopes such as the Large Ultraviolet / Optical / Infrared (LUVOIR) Surveyor concept. The LUVOIR concept includes a 15-meter-diameter segmented-aperture telescope with a suite of serviceable instruments operating over a range of wavelengths between 100nm to 2.5 um. Wavefront error (WFE) stability of less than 10 picometers RMS of uncorrected system WFE per wavefront control step represents a drastic performance improvement over current space-based telescopes being fielded. Through the utilization of an isolation architecture that involves no mechanical contact between the telescope and the host spacecraft structure, a system design is realized that maximizes the telescope dynamic stability performance without driving stringent technology requirements on spacecraft structure, sensors or actuators. Through analysis of the LUVOIR finite element model and linear optical model, the wavefront error and Line-Of-Sight (LOS) jitter performance is discussed in this paper when using the Vibration Isolation and Precision Pointing System (VIPPS) being developed cooperatively with Lockheed Martin in addition to a multi-loop control architecture. The multi-loop control architecture consists of the spacecraft Attitude Control System (ACS), VIPPS, and a Fast Steering Mirror on the instrument. While the baseline attitude control device for LUVOIR is a set of Control Moment Gyroscopes (CMGs), Reaction Wheel Assembly (RWA) disturbance contribution to wavefront error stability and LOS stability are presented to give preliminary results in this paper. CMG disturbance will be explored in further work to be completed

    The Maternal Personhood of Cattle and Plants at a Hindu Center in the United States

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    Religious experiences with sacred nonhuman natural beings considered to be “persons” remain only vaguely understood. This essay provides a measure of clarification by engendering a dialogue between psychoanalytic self psychology on one side and, on the other, religious experiences of cattle and Tulsi plants as holy mothers at a Hindu cattle sanctuary in the United States. Ethnographic data from the Hindu center uncover experiences of sacred maternal natural beings that are tensive, liminal, and colored with affective themes of nurturance, respect, and intimacy, much like psychoanalytic maternal selfobjects. Devotees protect cattle and ritually venerate plants because these actions facilitate a limited experiential grounding of religiosity on what is perhaps the most fundamental of all relationships, the relationship with the mother, within a theological worldview that somewhat embraces nonhuman natural beings in both doctrine and practice

    The potential of antisense oligonucleotide therapies for inherited childhood lung diseases.

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    Antisense oligonucleotides are an emerging therapeutic option to treat diseases with known genetic origin. In the age of personalised medicines, antisense oligonucleotides can sometimes be designed to target and bypass or overcome a patient's genetic mutation, in particular those lesions that compromise normal pre-mRNA processing. Antisense oligonucleotides can alter gene expression through a variety of mechanisms as determined by the chemistry and antisense oligomer design. Through targeting the pre-mRNA, antisense oligonucleotides can alter splicing and induce a specific spliceoform or disrupt the reading frame, target an RNA transcript for degradation through RNaseH activation, block ribosome initiation of protein translation or disrupt miRNA function. The recent accelerated approval of eteplirsen (renamed Exondys 51™) by the Food and Drug Administration, for the treatment of Duchenne muscular dystrophy, and nusinersen, for the treatment of spinal muscular atrophy, herald a new and exciting era in splice-switching antisense oligonucleotide applications to treat inherited diseases. This review considers the potential of antisense oligonucleotides to treat inherited lung diseases of childhood with a focus on cystic fibrosis and disorders of surfactant protein metabolism

    Stem cell-derived porcine macrophages as a new platform for studying host-pathogen interactions

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    BACKGROUND: Infectious diseases of farmed and wild animals pose a recurrent threat to food security and human health. The macrophage, a key component of the innate immune system, is the first line of defence against many infectious agents and plays a major role in shaping the adaptive immune response. However, this phagocyte is a target and host for many pathogens. Understanding the molecular basis of interactions between macrophages and pathogens is therefore crucial for the development of effective strategies to combat important infectious diseases. RESULTS: We explored how porcine pluripotent stem cells (PSCs) can provide a limitless in vitro supply of genetically and experimentally tractable macrophages. Porcine PSC-derived macrophages (PSCdMs) exhibited molecular and functional characteristics of ex vivo primary macrophages and were productively infected by pig pathogens, including porcine reproductive and respiratory syndrome virus (PRRSV) and African swine fever virus (ASFV), two of the most economically important and devastating viruses in pig farming. Moreover, porcine PSCdMs were readily amenable to genetic modification by CRISPR/Cas9 gene editing applied either in parental stem cells or directly in the macrophages by lentiviral vector transduction. CONCLUSIONS: We show that porcine PSCdMs exhibit key macrophage characteristics, including infection by a range of commercially relevant pig pathogens. In addition, genetic engineering of PSCs and PSCdMs affords new opportunities for functional analysis of macrophage biology in an important livestock species. PSCs and differentiated derivatives should therefore represent a useful and ethical experimental platform to investigate the genetic and molecular basis of host-pathogen interactions in pigs, and also have wider applications in livestock. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12915-021-01217-8

    Pathology of the human pituitary adenomas

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    This article describes pertinent aspects of histochemical and molecular changes of the human pituitary adenomas. The article outlines individual tumor groups with general, specific and molecular findings. The discussion further extends to the unusual adenomas or carcinomas. The description in this article are pertinent not only for the practicing pathologists who are in the position of making proper diagnosis, but also for the pituitary research scientists who engage in solving basic problems in pituitary neoplasms by histochemistry and molecular biology

    Layer-by-Layer Assembled Antisense DNA Microsponge Particles for Efficient Delivery of Cancer Therapeutics

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    Antisense oligonucleotides can be employed as a potential approach to effectively treat cancer. However, the inherent instability and inefficient systemic delivery methods for antisense therapeutics remain major challenges to their clinical application. Here, we present a polymerized oligonucleotides (ODNs) that self-assemble during their formation through an enzymatic elongation method (rolling circle replication) to generate a composite nucleic acid/magnesium pyrophosphate sponge-like microstructure, or DNA microsponge, yielding high molecular weight nucleic acid product. In addition, this densely packed ODN microsponge structure can be further condensed to generate polyelectrolyte complexes with a favorable size for cellular uptake by displacing magnesium pyrophosphate crystals from the microsponge structure. Additional layers are applied to generate a blood-stable and multifunctional nanoparticle via the layer-by-layer (LbL) assembly technique. By taking advantage of DNA nanotechnology and LbL assembly, functionalized DNA nanostructures were utilized to provide extremely high numbers of repeated ODN copies for efficient antisense therapy. Moreover, we show that this formulation significantly improves nucleic acid drug/carrier stability during in vivo biodistribution. These polymeric ODN systems can be designed to serve as a potent means of delivering stable and large quantities of ODN therapeutics systemically for cancer treatment to tumor cells at significantly lower toxicity than traditional synthetic vectors, thus enabling a therapeutic window suitable for clinical translation.United States. Dept. of Defense. Ovarian Cancer Research Program (Teal Innovator Award Grant OC120504)Natural Sciences and Engineering Research Council of Canada (Postdoctoral Fellowship)National Institutes of Health (U.S.) (Ruth L. Kirschstein National Research Service Award 1F32EB017614-01)National Science Foundation (U.S.). Graduate Research Fellowshi
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