6,409 research outputs found

    On a Subposet of the Tamari Lattice

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    We explore some of the properties of a subposet of the Tamari lattice introduced by Pallo, which we call the comb poset. We show that three binary functions that are not well-behaved in the Tamari lattice are remarkably well-behaved within an interval of the comb poset: rotation distance, meets and joins, and the common parse words function for a pair of trees. We relate this poset to a partial order on the symmetric group studied by Edelman.Comment: 21 page

    Survivin as a therapeutic target in Sonic hedgehog-driven medulloblastoma.

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    Medulloblastoma (MB) is a highly malignant brain tumor that occurs primarily in children. Although surgery, radiation and high-dose chemotherapy have led to increased survival, many MB patients still die from their disease, and patients who survive suffer severe long-term side effects as a consequence of treatment. Thus, more effective and less toxic therapies for MB are critically important. Development of such therapies depends in part on identification of genes that are necessary for growth and survival of tumor cells. Survivin is an inhibitor of apoptosis protein that regulates cell cycle progression and resistance to apoptosis, is frequently expressed in human MB and when expressed at high levels predicts poor clinical outcome. Therefore, we hypothesized that Survivin may have a critical role in growth and survival of MB cells and that targeting it may enhance MB therapy. Here we show that Survivin is overexpressed in tumors from patched (Ptch) mutant mice, a model of Sonic hedgehog (SHH)-driven MB. Genetic deletion of survivin in Ptch mutant tumor cells significantly inhibits proliferation and causes cell cycle arrest. Treatment with small-molecule antagonists of Survivin impairs proliferation and survival of both murine and human MB cells. Finally, Survivin antagonists impede growth of MB cells in vivo. These studies highlight the importance of Survivin in SHH-driven MB, and suggest that it may represent a novel therapeutic target in patients with this disease

    Unique walnut-shaped porous MnO<inf>2</inf>/C nanospheres with enhanced reaction kinetics for lithium storage with high capacity and superior rate capability

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    Unique walnut-shaped porous MnO2/carbon nanospheres via in situ carbonization of amorphous MnO2 nanospheres demonstrate enhanced reaction kinetics for lithium storage.This work is realized in the frame of a program for Changjiang Scholars and Innovative Research Team (IRT_15R52) of Chinese Ministry of Education. B. L. Su acknowledges the Chinese Central Government for an “Expert of the State” position in the Program of the “Thousand Talents” and a Life Membership at the Clare Hall, Cambridge and the financial support of the Department of Chemistry, University of Cambridge. Y. Li acknowledges Hubei Provincial Department of Education for the “Chutian Scholar” program. T. Hasan acknowledges funding from the Royal Academy of Engineering (Graphlex) and an Impact Acceleration Award (GRASS). This work is also financially supported by the National Science Foundation for Young Scholars of China (No. 21301133 and 51302204), International Science & Technology Cooperation Program of China (2015DFE52870) and and Self-determined and Innovative Research Funds of the SKLWUT (2015‐ZD‐7). The authors also would like to thank Dr. Bin-Jie Wang from Shanghai Nanoport (FEI, Shanghai) for TEM analysis, and thank Hang Ping from Wuhan University of Technology for the TGA/DSC tests.This is the author accepted manuscript. The final version is available from the Royal Society of Chemistry via http://dx.doi.org/10.1039/C6TA00594

    Sequential establishment of stripe patterns in an expanding cell population

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    Periodic stripe patterns are ubiquitous in living organisms, yet the underlying developmental processes are complex and difficult to disentangle. We describe a synthetic genetic circuit that couples cell density and motility. This system enabled programmed Escherichia coli cells to form periodic stripes of high and low cell densities sequentially and autonomously. Theoretical and experimental analyses reveal that the spatial structure arises from a recurrent aggregation process at the front of the continuously expanding cell population. The number of stripes formed could be tuned by modulating the basal expression of a single gene. The results establish motility control as a simple route to establishing recurrent structures without requiring an extrinsic pacemaker.published_or_final_versio

    Macroscopic invisibility cloaking of visible light

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    Invisibility cloaks, which used to be confined to the realm of fiction, have now been turned into a scientific reality thanks to the enabling theoretical tools of transformation optics and conformal mapping. Inspired by those theoretical works, the experimental realization of electromagnetic invisibility cloaks has been reported at various electromagnetic frequencies. All the invisibility cloaks demonstrated thus far, however, have relied on nano- or micro-fabricated artificial composite materials with spatially varying electromagnetic properties, which limit the size of the cloaked region to a few wavelengths. Here, we report the first realization of a macroscopic volumetric invisibility cloak constructed from natural birefringent crystals. The cloak operates at visible frequencies and is capable of hiding, for a specific light polarization, three-dimensional objects of the scale of centimetres and millimetres. Our work opens avenues for future applications with macroscopic cloaking devices

    Integrated multiple mediation analysis: A robustness–specificity trade-off in causal structure

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    Recent methodological developments in causal mediation analysis have addressed several issues regarding multiple mediators. However, these developed methods differ in their definitions of causal parameters, assumptions for identification, and interpretations of causal effects, making it unclear which method ought to be selected when investigating a given causal effect. Thus, in this study, we construct an integrated framework, which unifies all existing methodologies, as a standard for mediation analysis with multiple mediators. To clarify the relationship between existing methods, we propose four strategies for effect decomposition: two-way, partially forward, partially backward, and complete decompositions. This study reveals how the direct and indirect effects of each strategy are explicitly and correctly interpreted as path-specific effects under different causal mediation structures. In the integrated framework, we further verify the utility of the interventional analogues of direct and indirect effects, especially when natural direct and indirect effects cannot be identified or when cross-world exchangeability is invalid. Consequently, this study yields a robustness–specificity trade-off in the choice of strategies. Inverse probability weighting is considered for estimation. The four strategies are further applied to a simulation study for performance evaluation and for analyzing the Risk Evaluation of Viral Load Elevation and Associated Liver Disease/Cancer data set from Taiwan to investigate the causal effect of hepatitis C virus infection on mortality

    How consistent are the transcriptome changes associated with cold acclimation in two species of the Drosophila virilis group?

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    This work was financially support by a Marie Curie Initial Training Network grant, “Understanding the evolutionary origin of biological diversity” (ITN-2008–213780 SPECIATION), grants from the Academy of Finland to A.H. (project 132619) and M.K. (projects 268214 and 272927), a grant from NERC, UK to M.G.R. (grant NE/J020818/1), and NERC, UK PhD studentship to D.J.P. (NE/I528634/1).For many organisms the ability to cold acclimate with the onset of seasonal cold has major implications for their fitness. In insects, where this ability is widespread, the physiological changes associated with increased cold tolerance have been well studied. Despite this, little work has been done to trace changes in gene expression during cold acclimation that lead to an increase in cold tolerance. We used an RNA-Seq approach to investigate this in two species of the Drosophila virilis group. We found that the majority of genes that are differentially expressed during cold acclimation differ between the two species. Despite this, the biological processes associated with the differentially expressed genes were broadly similar in the two species. These included: metabolism, cell membrane composition, and circadian rhythms, which are largely consistent with previous work on cold acclimation/cold tolerance. In addition, we also found evidence of the involvement of the rhodopsin pathway in cold acclimation, a pathway that has been recently linked to thermotaxis. Interestingly, we found no evidence of differential expression of stress genes implying that long-term cold acclimation and short-term stress response may have a different physiological basis.PostprintPeer reviewe

    Candida albicans repetitive elements display epigenetic diversity and plasticity

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    Transcriptionally silent heterochromatin is associated with repetitive DNA. It is poorly understood whether and how heterochromatin differs between different organisms and whether its structure can be remodelled in response to environmental signals. Here, we address this question by analysing the chromatin state associated with DNA repeats in the human fungal pathogen Candida albicans. Our analyses indicate that, contrary to model systems, each type of repetitive element is assembled into a distinct chromatin state. Classical Sir2-dependent hypoacetylated and hypomethylated chromatin is associated with the rDNA locus while telomeric regions are assembled into a weak heterochromatin that is only mildly hypoacetylated and hypomethylated. Major Repeat Sequences, a class of tandem repeats, are assembled into an intermediate chromatin state bearing features of both euchromatin and heterochromatin. Marker gene silencing assays and genome-wide RNA sequencing reveals that C. albicans heterochromatin represses expression of repeat-associated coding and non-coding RNAs. We find that telomeric heterochromatin is dynamic and remodelled upon an environmental change. Weak heterochromatin is associated with telomeres at 30?°C, while robust heterochromatin is assembled over these regions at 39?°C, a temperature mimicking moderate fever in the host. Thus in C. albicans, differential chromatin states controls gene expression and epigenetic plasticity is linked to adaptation

    Etiological Profile and Treatment Outcome of Epistaxis at a Tertiary Care Hospital in Northwestern Tanzania: A Prospective Review of 104 Cases.

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    Epistaxis is the commonest otolaryngological emergency affecting up to 60% of the population in their lifetime, with 6% requiring medical attention. There is paucity of published data regarding the management of epistaxis in Tanzania, especially the study area. This study was conducted to describe the etiological profile and treatment outcome of epistaxis at Bugando Medical Centre, a tertiary care hospital in Northwestern Tanzania. This was a prospective descriptive study of the cases of epistaxis managed at Bugando Medical Centre from January 2008 to December 2010. Data collected were analyzed using SPSS computer software version 15. A total of 104 patients with epistaxis were studied. Males were affected twice more than the females (2.7:1). Their mean age was 32.24 ± 12.54 years (range 4 to 82 years). The modal age group was 31-40 years. The commonest cause of epistaxis was trauma (30.8%) followed by idiopathic (26.9%) and hypertension (17.3%). Anterior nasal bleeding was noted in majority of the patients (88.7%). Non surgical measures such as observation alone (40.4%) and anterior nasal packing (38.5%) were the main intervention methods in 98.1% of cases. Surgical measures mainly intranasal tumor resection was carried out in 1.9% of cases. Arterial ligation and endovascular embolization were not performed. Complication rate was 3.8%. The overall mean of hospital stay was 7.2 ± 1.6 days (range 1 to 24 days). Five patients died giving a mortality rate of 4.8%. Trauma resulting from road traffic crush (RTC) remains the most common etiological factor for epistaxis in our setting. Most cases were successfully managed with conservative (non-surgical) treatment alone and surgical intervention with its potential complications may not be necessary in most cases and should be the last resort. Reducing the incidence of trauma from RTC will reduce the incidence of emergency epistaxis in our centre
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