201 research outputs found

    Castle studies and the 'landscape' agenda

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    Reproduced with permission of the publisher. © The Society for Landscape Studies and the individual authors 2004.The growth in interest in the wider settlement settings and landscape contexts of medieval castles is reviewed. While overtly militaristic approaches to castle study sometimes ensured that sites were frequently examined in isolation from their surroundings, some early scholars were aware of the importance of viewing castles in their wider contexts. From the 1970s onwards, excavation, survey and settlement studies have all made a decisive contribution to our enhanced understanding of the ‘landscape’ dimension of medieval fortification. Changing approaches to the study of Norman castles, in particular, are explored, and recommendations for future study are identified

    Designability of lattice model heteropolymers

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    Protein folds are highly designable, in the sense that many sequences fold to the same conformation. In the present work we derive an expression for the designability in a 20 letter lattice model of proteins which, relying only on the Central Limit Theorem, has a generality which goes beyond the simple model used in its derivation. This expression displays an exponential dependence on the energy of the optimal sequence folding on the given conformation measured with respect to the lowest energy of the conformational dissimilar structures, energy difference which constitutes the only parameter controlling designability. Accordingly, the designability of a native conformation is intimately connected to the stability of the sequences folding to them.Comment: in press on Phys. Rev.

    Glenohumeral Hydrodistension for Postoperative Stiffness After Arthroscopic Primary Rotator Cuff Repair

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    Background: Postoperative stiffness is a known complication after rotator cuff repair (RCR). Glenohumeral hydrodistension (GH) has been a treatment modality for shoulder pathology but has not been used to treat postoperative stiffness after RCR. Purpose/Hypothesis: The purpose of this study was to identify the risk factors for postoperative stiffness after RCR and review outcomes after treatment with GH. Our hypotheses were that stiffness would be associated with diabetes and hyperlipidemia and correlated with the tendons involved and that patients with stiffness who underwent GH would have significant improvement in range of motion (ROM). Study Design: Case series; Level of evidence, 4.Methods:Included were 388 shoulders of patients who underwent primary RCR by a single surgeon between 2015 and 2019. Shoulders with revision RCRs were excluded. Patient characteristics, medical comorbidities, and perioperative details were collected. A total of 40 shoulders with postoperative stiffness (10.3%) received GH injectate of a 21-mL mixture (15 mL of sterile water, 5 mL of 0.5% ropivacaine, and 1 mL of triamcinolone [10 mg/mL]). The primary outcome measure was ROM in forward flexion, internal rotation, external rotation, and abduction. Statistical tests were performed using analysis of variance. Results: Patients with diabetes had significantly decreased internal rotation at final follow-up after RCR as compared with patients without diabetes. GH to treat stiffness was performed most commonly between 1 and 4 months after RCR (60%), and patients who received GH saw statistically significant improvements in forward flexion, external rotation, and abduction after the procedure. Patients with hyperlipidemia had the most benefit after GH. Among those undergoing concomitant procedures, significantly more patients who had open subpectoral biceps tenodesis underwent GH. Patients who underwent subscapularis repair or concomitant subacromial decompression had significant improvement in ROM after GH. Only 1 patient who received GH underwent secondary surgery for resistant postoperative stiffness. Conclusion: Patients with diabetes had increased stiffness. Patients with a history of hyperlipidemia or concomitant open subpectoral biceps tenodesis were more likely to undergo GH for postoperative stiffness. Patients who underwent subscapularis repair demonstrated the most improvement in ROM after GH. After primary RCR, GH can increase ROM and is a useful adjunct for patients with stiffness to limit secondary surgery

    Randomly Charged Polymers, Random Walks, and Their Extremal Properties

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    Motivated by an investigation of ground state properties of randomly charged polymers, we discuss the size distribution of the largest Q-segments (segments with total charge Q) in such N-mers. Upon mapping the charge sequence to one--dimensional random walks (RWs), this corresponds to finding the probability for the largest segment with total displacement Q in an N-step RW to have length L. Using analytical, exact enumeration, and Monte Carlo methods, we reveal the complex structure of the probability distribution in the large N limit. In particular, the size of the longest neutral segment has a distribution with a square-root singularity at l=L/N=1, an essential singularity at l=0, and a discontinuous derivative at l=1/2. The behavior near l=1 is related to a another interesting RW problem which we call the "staircase problem". We also discuss the generalized problem for d-dimensional RWs.Comment: 33 pages, 19 Postscript figures, RevTe

    Analysis of LIGO data for gravitational waves from binary neutron stars

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    We report on a search for gravitational waves from coalescing compact binary systems in the Milky Way and the Magellanic Clouds. The analysis uses data taken by two of the three LIGO interferometers during the first LIGO science run and illustrates a method of setting upper limits on inspiral event rates using interferometer data. The analysis pipeline is described with particular attention to data selection and coincidence between the two interferometers. We establish an observational upper limit of R<\mathcal{R}<1.7 \times 10^{2}peryearperMilkyWayEquivalentGalaxy(MWEG),with90coalescencerateofbinarysystemsinwhicheachcomponenthasamassintherange13 per year per Milky Way Equivalent Galaxy (MWEG), with 90% confidence, on the coalescence rate of binary systems in which each component has a mass in the range 1--3 M_\odot$.Comment: 17 pages, 9 figure

    An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

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    For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

    Applications and efficiencies of the first cat 63K DNA array

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    The development of high throughput SNP genotyping technologies has improved the genetic dissection of simple and complex traits in many species including cats. The properties of feline 62,897 SNPs Illumina Infinium iSelect DNA array are described using a dataset of over 2,000 feline samples, the most extensive to date, representing 41 cat breeds, a random bred population, and four wild felid species. Accuracy and efficiency of the array\u2019s genotypes and its utility in performing population-based analyses were evaluated. Average marker distance across the array was 37,741 Kb, and across the dataset, only 1% (625) of the markers exhibited poor genotyping and only 0.35% (221) showed Mendelian errors. Marker polymorphism varied across cat breeds and the average minor allele frequency (MAF) of all markers across domestic cats was 0.21. Population structure analysis confirmed a Western to Eastern structural continuum of cat breeds. Genome-wide linkage disequilibrium ranged from 50\u20131,500 Kb for domestic cats and 750 Kb for European wildcats (Felis silvestris silvestris). Array use in trait association mapping was investigated under different modes of inheritance, selection and population sizes. The efficient array design and cat genotype dataset continues to advance the understanding of cat breeds and will support monogenic health studies across feline breeds and populations

    Driver Fusions and Their Implications in the Development and Treatment of Human Cancers.

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    Gene fusions represent an important class of somatic alterations in cancer. We systematically investigated fusions in 9,624 tumors across 33 cancer types using multiple fusion calling tools. We identified a total of 25,664 fusions, with a 63% validation rate. Integration of gene expression, copy number, and fusion annotation data revealed that fusions involving oncogenes tend to exhibit increased expression, whereas fusions involving tumor suppressors have the opposite effect. For fusions involving kinases, we found 1,275 with an intact kinase domain, the proportion of which varied significantly across cancer types. Our study suggests that fusions drive the development of 16.5% of cancer cases and function as the sole driver in more than 1% of them. Finally, we identified druggable fusions involving genes such as TMPRSS2, RET, FGFR3, ALK, and ESR1 in 6.0% of cases, and we predicted immunogenic peptides, suggesting that fusions may provide leads for targeted drug and immune therapy

    Search for Tensor, Vector, and Scalar Polarizations in the Stochastic Gravitational-Wave Background

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    The detection of gravitational waves with Advanced LIGO and Advanced Virgo has enabled novel tests of general relativity, including direct study of the polarization of gravitational waves. While general relativity allows for only two tensor gravitational-wave polarizations, general metric theories can additionally predict two vector and two scalar polarizations. The polarization of gravitational waves is encoded in the spectral shape of the stochastic gravitational-wave background, formed by the superposition of cosmological and individually unresolved astrophysical sources. Using data recorded by Advanced LIGO during its first observing run, we search for a stochastic background of generically polarized gravitational waves. We find no evidence for a background of any polarization, and place the first direct bounds on the contributions of vector and scalar polarizations to the stochastic background. Under log-uniform priors for the energy in each polarization, we limit the energy densities of tensor, vector, and scalar modes at 95% credibility to Ω0T<5.58×10-8, Ω0V<6.35×10-8, and Ω0S<1.08×10-7 at a reference frequency f0=25 Hz. © 2018 American Physical Society

    Search for gravitational waves from Scorpius X-1 in the second Advanced LIGO observing run with an improved hidden Markov model

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    We present results from a semicoherent search for continuous gravitational waves from the low-mass x-ray binary Scorpius X-1, using a hidden Markov model (HMM) to track spin wandering. This search improves on previous HMM-based searches of LIGO data by using an improved frequency domain matched filter, the J-statistic, and by analyzing data from Advanced LIGO's second observing run. In the frequency range searched, from 60 to 650 Hz, we find no evidence of gravitational radiation. At 194.6 Hz, the most sensitive search frequency, we report an upper limit on gravitational wave strain (at 95% confidence) of h095%=3.47×10-25 when marginalizing over source inclination angle. This is the most sensitive search for Scorpius X-1, to date, that is specifically designed to be robust in the presence of spin wandering. © 2019 American Physical Society
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