2,235 research outputs found

    A Gray Code for the Shelling Types of the Boundary of a Hypercube

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    We consider two shellings of the boundary of the hypercube equivalent if one can be transformed into the other by an isometry of the cube. We observe that a class of indecomposable permutations, bijectively equivalent to standard double occurrence words, may be used to encode one representative from each equivalence class of the shellings of the boundary of the hypercube. These permutations thus encode the shelling types of the boundary of the hypercube. We construct an adjacent transposition Gray code for this class of permutations. Our result is a signed variant of King's result showing that there is a transposition Gray code for indecomposable permutations

    Heterochromatin Protein 1a (HP1a) partner specificity is determined by critical amino acids in the chromo shadow domain and C-terminal extension

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    Drosophila melanogaster Heterochromatin Protein 1a (HP1a) is an essential protein critical for heterochromatin assembly and regulation. Its chromo shadow domain (CSD) homodimerizes, a requirement for binding protein partners that contain a PXVXL motif. How does HP1a select among its many different PXVXL-containing partners? HP1a binds tightly to Heterochromatin Protein 2 (HP2), but weakly to PIWI. We investigated differences in homodimerization and the impact of the C-terminal extension (CTE) by contrasting HP1a to its paralogue, HP1b. HP1a and HP1b differ in the dimerization interface, with HP1a having an Arg at position 188 rather than Glu. We find that while this substitution reduces the dimerization constant, it does not impact the binding surface as demonstrated by unchanged partner binding affinities. However, the CTE (only 4 residues in HP1a as compared with 87 residues in HP1b) is critical; the charged residues in HP1a are necessary for tight peptide binding. Examining a panel of amino acid substitutions in the HP1a CSD, we find that Leu-165 in HP1a interacts with HP2 but not PIWI, supporting the conclusion that different sites in the binding surface provide discrimination for partner selection. Partner sequence is also critical for affinity, as the remaining difference in binding between HP2 and PIWI polypeptides is eliminated by swapping the PXVXL motifs between the two. Taken together, these studies indicate that the binding surface of the HP1a CSD plus its short CTE provide the needed discrimination among HP1a\u27s partners, and that the CTE is important for differentiating the interactions of the Drosophila HP1 paralogs. Keywords: Amino Acid; Fluorescence Polarization; HP1; Heterochromatin; Mutagenesis in vitro; PIWI; Peptides; Protein-Protein Interactions

    Financial hardship and Australian midwifery students : A scoping review and thematic analysis

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    Problem: Despite the pressing need to grow the Australian midwifery workforce, the rising cost of living is making midwifery education programs unaffordable for many. Understanding of the financial hardships faced by Australian midwifery students is currently limited. Background: Attrition from midwifery programs is high and rising. In Australia, this is further compounded by the financial pressures brought about by the cost-of-living crisis. Attending compulsory unremunerated clinical placements and being ‘on call’ for continuity of care experiences contributes to the financial challenges of midwifery students. Aim: To identify and synthesise available literature addressing financial hardship faced by Australian midwifery students during their studies. Methods: Arksey and O’Malley’s framework guided this scoping review. Six databases were searched between January 2020 and April 2024. The key findings of eight included papers were thematically analysed. Findings: Four themes were identified; “Attending placements and supporting COCE’s as key contributors to financial hardship”, “Impacts of financial hardship on midwifery students and their wider family”, “Impacts upon the future growth and diversity of the profession” and “The need for universal financial support”. Discussion: The findings highlight the nature of financial challenges, causational factors and the consequences of financial hardship associated with completing midwifery programs in Australia. Appropriate universal financial support is urgently needed if we are to grow and sustain the midwifery workforce. Conclusion: With no primary studies specifically exploring financial hardship faced by Australian midwifery students, further research is required to understand the challenges they face and evaluate the efficacy of funding initiatives

    Hypothermic Oxygenated Perfusion Improves Vascular and Contractile Function by Preserving Endothelial Nitric Oxide Production in Cardiac Grafts Obtained With Donation After Circulatory Death.

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    BACKGROUND Cardiac donation after circulatory death is a promising option to increase graft availability. Graft preservation with 30 minutes of hypothermic oxygenated perfusion (HOPE) before normothermic machine perfusion may improve cardiac recovery as compared with cold static storage, the current clinical standard. We investigated the role of preserved nitric oxide synthase activity during HOPE on its beneficial effects. METHODS AND RESULTS Using a rat model of donation after circulatory death, hearts underwent in situ ischemia (21 minutes), were explanted for a cold storage period (30 minutes), and then reperfused under normothermic conditions (60 minutes) with left ventricular loading. Three cold storage conditions were compared: cold static storage, HOPE, and HOPE with Nω-nitro-L-arginine methyl ester (nitric oxide synthase inhibitor). To evaluate potential confounding effects of high coronary flow during early reperfusion in HOPE hearts, bradykinin was administered to normalize coronary flow to HOPE levels in 2 additional groups (cold static storage and HOPE with Nω-nitro-L-arginine methyl ester). Cardiac recovery was significantly improved in HOPE versus cold static storage hearts, as determined by cardiac output, left ventricular work, contraction and relaxation rates, and coronary flow (P<0.05). Furthermore, HOPE attenuated postreperfusion calcium overload. Strikingly, the addition of Nω-nitro-L-arginine methyl ester during HOPE largely abolished its beneficial effects, even when early reperfusion coronary flow was normalized to HOPE levels. CONCLUSIONS HOPE provides superior preservation of ventricular and vascular function compared with the current clinical standard. Importantly, HOPE's beneficial effects require preservation of nitric oxide synthase activity during the cold storage. Therefore, the application of HOPE before normothermic machine perfusion is a promising approach to optimize graft recovery in donation after circulatory death cardiac grafts

    Fullerenes in circumstellar and interstellar environments

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    We recently identified several emission bands in the Spitzer-IRS spectrum of the unusual planetary nebula Tc 1 with the infrared active vibrational modes of the neutral fullerene species C60 and C70. Since then, the fullerene bands have been detected in a variety of sources representing circumstellar and interstellar environments. Abundance estimates suggest that C60 represents ~0.1%-1.5% of the available carbon in those sources. The observed relative band intensities in various sources are not fully compatible with single-photon heating and fluorescent cooling, and are better reproduced by a thermal distribution at least in some sources. The observational data suggests that fullerenes form in the circumstellar environments of evolved stars, and survive in the interstellar medium. Precisely how they form is still a matter of debate.Comment: 12 pages, 5 figures. To appear in the proceedings of IAU symposium 280 "The Molecular Universe

    False Reports from Patients with Frontotemporal Dementia: Delusions or Confabulations?

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    Patients with behavioral variant frontotemporal dementia (bvFTD) can make false statements consistent with delusions or confabulations. It is unclear whether bvFTD is primarily associated with either delusions or with confabulations and whether they can be explained by the pathophysiology of this disease. In order to clarify this, we retrospectively surveyed the records of 48 patients with bvFTD for the presence of any false reports and identified four patients. Their false reports included continued interaction with a favorite but dead relation, fictitious marriages with movie stars, and two who claimed that their partner was having an affair. When confronted with the falsity of their statements, the patients conveyed a lack of certainty regarding their external or internal source but persisted in the constancy of their reports. On functional neuroimaging, the patients had predominant frontal involvement. This report found that patients with bvFTD can have both fantastic, wish fulfilling confabulations and typical content-specific delusions. We propose that both phenomena result from known disturbances of ventromedial prefrontal cortex in bvFTD, including deficits in source monitoring and in activating an automatic “doubt tag” for false reports

    Critical review of the Appropriate Use Criteria for amyloid imaging: Effect on diagnosis and patient care

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    INTRODUCTION: The utility of the Appropriate Use Criteria (AUC) for amyloid imaging is not established. METHODS: Fifty-three cognitively impaired patients with clinical F18-florbetapir imaging were classified as early and late onset, as well as AUC-consistent or AUC-inconsistent. Chi-square statistics and t test were used to compare demographic characteristics and clinical outcomes as appropriate. RESULTS: Early-onset patients were more likely to be amyloid positive. Change in diagnosis was more frequent in late-onset cases. Change in therapy was more common in early-onset cases. AUC-consistent and AUC-inconsistent cases had comparable rates of amyloid positivity. We saw no difference in the rate of treatment changes in the AUC-consistent group as opposed to the AUC-inconsistent group. DISCUSSION: The primary role of amyloid imaging in the early-onset group was to confirm the clinically suspected etiology, and in the late-onset group in detecting amyloid-negative cases. The rate of therapeutic changes was significantly greater in the early-onset cases
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