78 research outputs found

    The Passing of Print

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    This paper argues that ephemera is a key instrument of cultural memory, marking the things intended to be forgotten. This important role means that when ephemera survives, whether accidentally or deliberately, it does so despite itself. These survivals, because they evoke all those other objects that have necessarily been forgotten, can be described as uncanny. The paper is divided into three main sections. The first situates ephemera within an uncanny economy of memory and forgetting. The second focuses on ephemera at a particular historical moment, the industrialization of print in the nineteenth century. This section considers the liminal place of newspapers and periodicals in this period, positioned as both provisional media for information as well as objects of record. The third section introduces a new configuration of technologies – scanners, computers, hard disks, monitors, the various connections between them – and considers the conditions under which born-digital ephemera can linger and return. Through this analysis, the paper concludes by considering digital technologies as an apparatus of memory, setting out what is required if we are not to be doubly haunted by the printed ephemera within the digital archive

    Acute ACAT1/SOAT1 Blockade Increases MAM Cholesterol and Strengthens ER-Mitochondria Connectivity.

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    Cholesterol is a key component of all mammalian cell membranes. Disruptions in cholesterol metabolism have been observed in the context of various diseases, including neurodegenerative disorders such as Alzheimer\u27s disease (AD). The genetic and pharmacological blockade of acyl-CoA:cholesterol acyltransferase 1/sterol O-acyltransferase 1 (ACAT1/SOAT1), a cholesterol storage enzyme found on the endoplasmic reticulum (ER) and enriched at the mitochondria-associated ER membrane (MAM), has been shown to reduce amyloid pathology and rescue cognitive deficits in mouse models of AD. Additionally, blocking ACAT1/SOAT1 activity stimulates autophagy and lysosomal biogenesis; however, the exact molecular connection between the ACAT1/SOAT1 blockade and these observed benefits remain unknown. Here, using biochemical fractionation techniques, we observe cholesterol accumulation at the MAM which leads to ACAT1/SOAT1 enrichment in this domain. MAM proteomics data suggests that ACAT1/SOAT1 inhibition strengthens the ER-mitochondria connection. Confocal and electron microscopy confirms that ACAT1/SOAT1 inhibition increases the number of ER-mitochondria contact sites and strengthens this connection by shortening the distance between these two organelles. This work demonstrates how directly manipulating local cholesterol levels at the MAM can alter inter-organellar contact sites and suggests that cholesterol buildup at the MAM is the impetus behind the therapeutic benefits of ACAT1/SOAT1 inhibition

    Driver Behavior in Traffic

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    DTFH61-09-H-00007Existing traffic analysis and management tools do not model the ability of drivers to recognize their environment and respond to it with behaviors that vary according to the encountered driving situation. The small body of literature on characterizing drivers behavior is typically limited to specific locations (i.e., by collecting data on specific intersections or freeway sections) and is very narrow in scope. This report documented the research performed to model driver behavior in traffic under naturalistic driving data. The research resulted in the development of hybrid car-following model. In addition, a neuro-fuzzy reinforcement learning, an agent-based artificial intelligence machine-learning technique, was used to model driving behavior. The naturalistic driving database was used to train and validate driver agents. The proposed methodology simulated events from different drivers and proved behavior heterogeneities. Robust agent activation techniques were also developed using discriminant analysis. The developed agents were implemented in VISSIM simulation platform and were evaluated by comparing the behavior of vehicles with and without agent activation. The results showed very close resemblance of the behavior of agents and driver data. Prototype agents prototype (spreadsheets and codes) were developed. Future research recommendations include training agents using more data to cover a wider region in the Wiedemann regime space, and sensitivity analysis of agent training parameters

    Christianity as Public Religion::A Justification for using a Christian Sociological Approach for Studying the Social Scientific Aspects of Sport

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    The vast majority of social scientific studies of sport have been secular in nature and/or have tended to ignore the importance of studying the religious aspects of sport. In light of this, Shilling and Mellor (2014) have sought to encourage sociologists of sport not to divorce the ‘religious’ and the ‘sacred’ from their studies. In response to this call, the goal of the current essay is to explore how the conception of Christianity as ‘public religion’ can be utilised to help justify the use of a Christian sociological approach for studying the social scientific aspects of sport. After making a case for Christianity as public religion, we conclude that many of the sociological issues inherent in modern sport are an indirect result of its increasing secularisation and argue that this justifies the need for a Christian sociological approach. We encourage researchers to use the Bible, the tools of Christian theology and sociological concepts together, so to inform analyses of modern sport from a Christian perspective

    Improved systematic tRNA gene annotation allows new insights into the evolution of mitochondrial tRNA structures and into the mechanisms of mitochondrial genome rearrangements

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    Transfer RNAs (tRNAs) are present in all types of cells as well as in organelles. tRNAs of animal mitochondria show a low level of primary sequence conservation and exhibit ‘bizarre’ secondary structures, lacking complete domains of the common cloverleaf. Such sequences are hard to detect and hence frequently missed in computational analyses and mitochondrial genome annotation. Here, we introduce an automatic annotation procedure for mitochondrial tRNA genes in Metazoa based on sequence and structural information in manually curated covariance models. The method, applied to re-annotate 1876 available metazoan mitochondrial RefSeq genomes, allows to distinguish between remaining functional genes and degrading ‘pseudogenes’, even at early stages of divergence. The subsequent analysis of a comprehensive set of mitochondrial tRNA genes gives new insights into the evolution of structures of mitochondrial tRNA sequences as well as into the mechanisms of genome rearrangements. We find frequent losses of tRNA genes concentrated in basal Metazoa, frequent independent losses of individual parts of tRNA genes, particularly in Arthropoda, and wide-spread conserved overlaps of tRNAs in opposite reading direction. Direct evidence for several recent Tandem Duplication-Random Loss events is gained, demonstrating that this mechanism has an impact on the appearance of new mitochondrial gene orders

    AvBD1 nucleotide polymorphisms, peptide antimicrobial activities and microbial colonisation of the broiler chicken gut

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    Abstract Background The importance of poultry as a global source of protein underpins the chicken genome and associated SNP data as key tools in selecting and breeding healthy robust birds with improved disease resistance. SNPs affecting host peptides involved in the innate defences tend to be rare, but three non-synonymous SNPs in the avian ÎČ-defensin (AvBD1) gene encoding the variant peptides NYH, SSY and NYY were identified that segregated specifically to three lines of commercial broiler chickens Line X (LX), Line Y(LY) and Line Z. The impacts of such amino acid changes on peptide antimicrobial properties were analysed in vitro and described in relation to the caecal microbiota and gut health of LX and LY birds. Results Time-kill and radial immune diffusion assays indicated all three peptides to have antimicrobial properties against gram negative and positive bacteria with a hierarchy of NYH > SSY > NYY. Calcein leakage assays supported AvBD1 NYH as the most potent membrane permeabilising agent although no significant differences in secondary structure were identified to explain this. However, distinct claw regions, identified by 3D modelling and proposed to play a key role in microbial membrane attachment, and permeation, were more distinct in the NYH model. In vivo AvBD1 synthesis was detected in the bird gut epithelia. Analyses of the caecal gut microbiota of young day 4 birds suggested trends in Lactobacilli sp. colonisation at days 4 (9% LX vs × 30% LY) and 28 (20% LX vs 12% LY) respectively, but these were not statistically significant (P > 0.05). Conclusion Amino acid changes altering the killing capacity of the AvBD1 peptide were associated with two different bird lines, but such changes did not impact significantly on caecal gut microbiota

    A dual role for SAMHD1 in regulating HBV cccDNA and RT-dependent particle genesis

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    Chronic hepatitis B is one of the world's unconquered diseases with more than 240 million infected subjects at risk of developing liver disease and hepatocellular carcinoma. Hepatitis B virus reverse transcribes pre-genomic RNA to relaxed circular DNA (rcDNA) that comprises the infectious particle. To establish infection of a naĂŻve target cell, the newly imported rcDNA is repaired by host enzymes to generate covalently closed circular DNA (cccDNA), which forms the transcriptional template for viral replication. SAMHD1 is a component of the innate immune system that regulates deoxyribonucleoside triphosphate levels required for host and viral DNA synthesis. Here, we show a positive role for SAMHD1 in regulating cccDNA formation, where KO of SAMHD1 significantly reduces cccDNA levels that was reversed by expressing wild-type but not a mutated SAMHD1 lacking the nuclear localization signal. The limited pool of cccDNA in infected Samhd1 KO cells is transcriptionally active, and we observed a 10-fold increase in newly synthesized rcDNA-containing particles, demonstrating a dual role for SAMHD1 to both facilitate cccDNA genesis and to restrict reverse transcriptase-dependent particle genesis

    The EHA Research Roadmap: Normal Hematopoiesis.

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    International audienceIn 2016, the European Hematology Association (EHA) published the EHA Roadmap for European Hematology Research1 aiming to highlight achievements in the diagnostics and treatment of blood disorders, and to better inform European policy makers and other stakeholders about the urgent clinical and scientific needs and priorities in the field of hematology. Each section was coordinated by 1–2 section editors who were leading international experts in the field. In the 5 years that have followed, advances in the field of hematology have been plentiful. As such, EHA is pleased to present an updated Research Roadmap, now including 11 sections, each of which will be published separately. The updated EHA Research Roadmap identifies the most urgent priorities in hematology research and clinical science, therefore supporting a more informed, focused, and ideally a more funded future for European hematology research. The 11 EHA Research Roadmap sections include Normal Hematopoiesis; Malignant Lymphoid Diseases; Malignant Myeloid Diseases; Anemias and Related Diseases; Platelet Disorders; Blood Coagulation and Hemostatic Disorders; Transfusion Medicine; Infections in Hematology; Hematopoietic Stem Cell Transplantation; CAR-T and Other Cell-based Immune Therapies; and Gene Therapy
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