47 research outputs found

    Derivation of lithofacies from geophysical logs : a review of methods from manual picking to machine learning

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    The aims of this report are to document: 1. A range of methods that are currently used by the BGS stratigraphers to extract lithological information from geophysical logs (includes manual classification, cut-off analysis, mineral composition by linear inversion). 2. Alternative methods which, at present, are not routinely applied but are sufficiently practical and accessible that they could become important, including unsupervised (k-mean clustering) and supervised machine learning approaches. The report does not aim or claim to be a complete inventory of all possible methods to derive lithological information from geophysical logs. The authors welcome correspondence and information on any additional methods that are available or emerging

    Peptide Inhibitors Targeting the \u3cem\u3eNeisseria gonorrhoeae\u3c/em\u3e Pivotal Anaerobic Respiration Factor AniA

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    Neisseria gonorrhoeae causes the sexually transmitted infection gonorrhea, which is highly prevalent worldwide and has a major impact on reproductive and neonatal health. The superbug status of N. gonorrhoeae necessitates the development of drugs with different mechanisms of action. Here, we focused on targeting the nitrite reductase AniA, which is a pivotal component of N. gonorrhoeae anaerobic respiration and biofilm formation. Our studies showed that gonococci expressing AniA containing the altered catalytic residues D137A and H280A failed to grow under anaerobic conditions, demonstrating that the nitrite reductase function is essential. To facilitate the pharmacological targeting of AniA, new crystal structures of AniA were refined to 1.90-Å and 2.35-Å resolutions, and a phage display approach with libraries expressing randomized linear dodecameric peptides or heptameric peptides flanked by a pair of cysteine residues was utilized. Biopanning experiments led to the identification of 29 unique peptides, with 1 of them, C7-3, being identified multiple times. Evaluation of their ability to interact with AniA using enzyme-linked immunosorbent assay and computational docking studies revealed that C7-3 was the most promising inhibitor, binding near the type 2 copper site of the enzyme, which is responsible for interaction with nitrite. Subsequent enzymatic assays and biolayer interferometry with a synthetic C7-3 and its derivatives, C7-3m1 and C7-3m2, demonstrated potent inhibition of AniA. Finally, the MIC50 value of C7-3 and C7-3m2 against anaerobically grown N. gonorrhoeae was 0.6 mM. We present the first peptide inhibitors of AniA, an enzyme that should be further exploited for antigonococcal drug development

    Volume 01

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    Introduction from Dean Dr. Charles Ross Three Decades of Digging: Undergraduate Archeology at Longwood by Jessica Fields and Stephanie Neeley Interactions of Allelopathy and Heat Stress in Plants by Derek W. Hambright and Mary E. Lehman Inertial Electrostatic Confinement D-D Fusion Device: Construction and Simulation by Andrew R. Grzankowski Shackled Nim by Zachary Johnson Development of GC-MS and Chemometric Methods for the Analysis of Accelerants in Arson Cases by Boone M. Prentice A Comparison of Image Analysis Methods in cDNA Microarrays by Ashley M. Swandby Perceived Sexual Activity of Short and Long-Term Relationships by Victoria Morgan and Katie Williamson Elderly Male Communication by Kristine G. Bender Three Poems: “Adam and Eve and an Orange Tree”, “The Name of Everything Before Dying”, and “The ‘Poet Voice’” by Katelyn N. Romaine There\u27s Nothing Like Dancing, After All : Marriage and Gender in the Dance Scenes of Jane Austen\u27s Novels by D. Nicole Swann Two Poems: “Age Nine with Mother” and “The Apple That Crawls Away From the Tree” by Jessica Fox Untitled by Mike McAteer Room 9 by Alex Grabiec Two Photographs: “Gracie” and “Emily” by Laura Nodtvedt Bowling Lanes Night by Nick Costa Two Paintings: “Can and Kettle” and “Scarecrow” by Rachel Wolfe Exploring Henrik Ibsen\u27s “Perr Gynt” by Zack Dalton Creative Writing Scholarship at Longwood University Music Scholarship at Longwood – Senior Recital Arianne K. Burrus Longwood University Theater – Peer Gyn

    Bone marrow fat accumulation accelerated by high fat diet is suppressed by exercise

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    Marrow adipose tissue (MAT), associated with skeletal fragility and hematologic insufficiency, remains poorly understood and difficult to quantify. We tested the response of MAT to high fat diet (HFD) and exercise using a novel volumetric analysis, and compared it to measures of bone quantity. We hypothesized that HFD would increase MAT and diminish bone quantity, while exercise would slow MAT acquisition and promote bone formation. Eight week-old female C57BL/6 mice were fed a regular (RD) or HFD, and exercise groups were provided voluntary access to running wheels (RD-E, HFD-E). Femoral MAT was assessed by μCT (lipid binder osmium) using a semi-automated approach employing rigid co-alignment, regional bone masks and was normalized for total femoral volume (TV) of the bone compartment. MAT was 2.6-fold higher in HFD relative to RD mice. Exercise suppressed MAT in RD-E mice by more than half compared with RD. Running similarly inhibited MAT acquisition in HFD mice. Exercise significantly increased bone quantity in both diet groups. Thus, HFD caused significant accumulation of MAT; importantly running exercise limited MAT acquisition while promoting bone formation during both diets. That MAT is exquisitely responsive to diet and exercise, and its regulation by exercise appears to be inversely proportional to effects on exercise induced bone formation, is relevant for an aging and sedentary population

    Variation in human herpesvirus 6B telomeric integration, excision and transmission between tissues and individuals

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    Human herpesviruses 6A and 6B (HHV-6A/6B) are ubiquitous pathogens that persist lifelong in latent form and can cause severe conditions upon reactivation. They are spread by community-acquired infection of free virus (acqHHV6A/6B) and by germline transmission of inherited chromosomally-integrated HHV-6A/6B (iciHHV-6A/6B) in telomeres. We exploited a hypervariable region of the HHV-6B genome to investigate the relationship between acquired and inherited virus and revealed predominantly maternal transmission of acqHHV-6B in families. Remarkably, we demonstrate that some copies of acqHHV-6B in saliva from healthy adults gained a telomere, indicative of integration and latency, and that the frequency of viral genome excision from telomeres in iciHHV-6B carriers is surprisingly high and varies between tissues. In addition, newly formed short telomeres generated by partial viral genome release are frequently lengthened, particularly in telomerase-expressing pluripotent cells. Consequently, iciHHV-6B carriers are mosaic for different iciHHV-6B structures, including circular extra-chromosomal forms that have the potential to reactivate. Finally, we show transmission of an HHV-6B strain from an iciHHV-6B mother to her non-iciHHV-6B son. Altogether we demonstrate that iciHHV-6B can readily transition between telomere-integrated and free virus forms

    Toward Large-Area Sub-Arcsecond X-Ray Telescopes II

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    In order to advance significantly scientific objectives, future x-ray astronomy missions will likely call for x-ray telescopes with large aperture areas (approx. = 3 sq m) and fine angular resolution (approx. = 1"). Achieving such performance is programmatically and technologically challenging due to the mass and envelope constraints of space-borne telescopes and to the need for densely nested grazing-incidence optics. Such an x-ray telescope will require precision fabrication, alignment, mounting, and assembly of large areas (approx. = 600 sq m) of lightweight (approx. = 2 kg/sq m areal density) high-quality mirrors, at an acceptable cost (approx. = 1 M$/sq m of mirror surface area). This paper reviews relevant programmatic and technological issues, as well as possible approaches for addressing these issues-including direct fabrication of monocrystalline silicon mirrors, active (in-space adjustable) figure correction of replicated mirrors, static post-fabrication correction using ion implantation, differential erosion or deposition, and coating-stress manipulation of thin substrates

    Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure

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    Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies

    Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure

    Get PDF
    Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies

    Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure

    Get PDF
    Abstract: Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies
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