Alternating links, rational balls, and cube tilings

When does the double cover of the three-sphere branched along an alternating link bound a rational homology ball? Heegaard Floer homology generates a necessary condition for it to bound: the link's chessboard lattice must be cubiquitous, implying that its normalized determinant is less than or equal to one. We conjecture that the converse holds and prove it when the normalized determinant equals one. The proof involves flows on planar graphs and the Haj\'os-Minkowski theorem that a lattice tiling of Euclidean space by cubes contains a pair of cubes which touch along an entire facet. We extend our main results to the study of ribbon cobordism and ribbon concordance

The Neural Correlates of Bodily Self-Consciousness in Virtual Worlds

Bodily Self-Consciousness (BSC) is the cumulative integration of multiple sensory modalities that contribute to our sense of self. Sensory modalities, which include proprioception, vestibulation, vision, and touch are updated dynamically to map the specific, local representation of ourselves in space. BSC is closely associated with bottom-up and top-down aspects of consciousness. Recently, virtual- and augmented-reality technology have been used to explore perceptions of BSC. These recent achievements are partly attributed to advances in modern technology, and partly due to the rise of virtual and augmented reality markets. Virtual reality head-mounted displays can alter aspects of perception and consciousness unlike ever before. Consequently, many strides have been made regarding BSC research. Previous research suggests that BSC results from the perceptions of embodiment (i.e., the feeling of ownership towards a real or virtual extremity) and presence (i.e., feeling physically located in a real or virtual space). Though physiological mechanisms serving embodiment and presence in the real world have been proposed by others, how these perceptual experiences interact and whether they can be dissociated is still poorly understood. Additionally, less is known about the physiological mechanisms underlying the perception of presence and embodiment in virtual environments. Therefore, five experiments were conducted to examine the perceptions of embodiment and presence in virtual environments to determine which physiological mechanisms support these perceptions. These studies compared performance between normal or altered embodiment/presence conditions. Results from a novel experimental paradigm using virtual reality (Experiment 4) are consistent with studies in the literature that reported synchronous sensorimotor feedback corresponded with greater strength of the embodiment illusion. In Experiment 4, participants recorded significantly faster reaction times and better accuracy in correlated feedback conditions compared to asynchronous feedback conditions. Reaction times were also significantly faster, and accuracy was higher for conditions where participants experienced the game from a first- versus third-person perspective. Functional magnetic resonance imaging (fMRI) data from Experiment 5 revealed that many frontoparietal networks contribute to the perception of embodiment, which include premotor cortex (PMC) and intraparietal sulcus (IPS). fMRI data revealed that activity in temporoparietal networks, including the temporoparietal junction and right precuneus, corresponded with manipulations thought to affect the perception of presence. Furthermore, data suggest that networks associated with embodiment and presence overlap, and brain areas that support perception may be predicated upon those that support embodiment. The results of these experiments offer further clues into the psychophysiological mechanisms underlying BSC

(Re)creating modern languages: conversations about the curriculum in UK higher education

This toolkit is designed to support colleagues who are planning to review the teaching in their institution. It offers frameworks for thinking through and planning comprehensive curriculum change, drawing on the experience of colleagues from a wide range of UK Modern Languages departments who have recently undertaken these changes or are working through them at the time of writing. It also showcases examples of excellent and innovative practice at module level, providing ideas for (re)thinking how language departments can work with external partners to enhance student experience. The toolkit provides a range of models for thinking about how language degrees are structured

A high-resolution integrated map of copy number polymorphisms within and between breeds of the modern domesticated dog

<p>Abstract</p> <p>Background</p> <p>Structural variation contributes to the rich genetic and phenotypic diversity of the modern domestic dog, <it>Canis lupus familiaris</it>, although compared to other organisms, catalogs of canine copy number variants (CNVs) are poorly defined. To this end, we developed a customized high-density tiling array across the canine genome and used it to discover CNVs in nine genetically diverse dogs and a gray wolf.</p> <p>Results</p> <p>In total, we identified 403 CNVs that overlap 401 genes, which are enriched for defense/immunity, oxidoreductase, protease, receptor, signaling molecule and transporter genes. Furthermore, we performed detailed comparisons between CNVs located within versus outside of segmental duplications (SDs) and find that CNVs in SDs are enriched for gene content and complexity. Finally, we compiled all known dog CNV regions and genotyped them with a custom aCGH chip in 61 dogs from 12 diverse breeds. These data allowed us to perform the first population genetics analysis of canine structural variation and identify CNVs that potentially contribute to breed specific traits.</p> <p>Conclusions</p> <p>Our comprehensive analysis of canine CNVs will be an important resource in genetically dissecting canine phenotypic and behavioral variation.</p

ANSI/NISO Z39.99-2017 ResourceSync Framework Specification

This ResourceSync specification describes a synchronization framework for the web consisting of various capabilities that allow third-party systems to remain synchronized with a server’s evolving resources. The capabilities may be combined in a modular manner to meet local or community requirements. This specification also describes how a server should advertise the synchronization capabilities it supports and how third-party systems may discover this information. The specification repurposes the document formats defined by the Sitemap protocol and introduces extensions for them

Method validation and preliminary qualification of pharmacodynamic biomarkers employed to evaluate the clinical efficacy of an antisense compound (AEG35156) targeted to the X-linked inhibitor of apoptosis protein XIAP

Data are presented on pharmacodynamic (PD) method validation and preliminary clinical qualification of three PD biomarker assays. M65 Elisa, which quantitates different forms of circulating cytokeratin 18 (CK18) as putative surrogate markers of both apoptotic and nonapoptotic tumour cell death, was shown to be highly reproducible: calibration curve linearity r2=0.996, mean accuracy >91% and mean precision <3%, n=27. Employing recombinant (r) CK18 and caspase cleaved CK18 (CK18 Asp396 neo-epitope) as external standards, kit to kit reproducibly was <6% (n=19). rCK18 was stable in plasma for 4 months at −20°C and −80°C, for 4 weeks at 4°C and had a half-life of 2.3 days at 37°C. Cytokeratin 18 Asp396 NE, the M30 Apoptosense Elisa assay antigen, was stable in plasma for 6 months at −20°C and −80°C, for 3 months at 4°C, while its half-life at 37°C was 3.8 days. Within-day variations in endogenous plasma concentrations of the M30 and M65 antigens were assessed in two predose blood samples collected from a cohort of 15 ovarian cancer patients receiving carboplatin chemotherapy and were shown to be no greater than the variability associated with methods themselves. Between-day fluctuations in circulating levels of the M30 and M65 antigens and in XIAP mRNA levels measured in peripheral blood mononuclear cells by quantitative (q) RT–PCR were evaluated in two predose blood samples collected with a 5- to 7-day gap from 23 patients with advanced cancer enrolled in a phase I trial. The mean variation between the two pretreatment values ranged from 13 to 14 to 25%, respectively, for M65, M30 and qRT–PCR. These data suggest that the M30 and M65 Elisa's and qRT–PCR as PD biomarker assays have favourable performance characteristics for further investigation in clinical trials of anticancer agents which induce tumour apoptosis/necrosis or knockdown of the anti-apoptotic protein XIAP

American Gut: an Open Platform for Citizen Science Microbiome Research

McDonald D, Hyde E, Debelius JW, et al. American Gut: an Open Platform for Citizen Science Microbiome Research. mSystems. 2018;3(3):e00031-18

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

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