511 research outputs found

    Free subgroups of one-relator relative presentations

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    Suppose that G is a nontrivial torsion-free group and w is a word over the alphabet G\cup\{x_1^{\pm1},...,x_n^{\pm1}\}. It is proved that for n\ge2 the group \~G= always contains a nonabelian free subgroup. For n=1 the question about the existence of nonabelian free subgroups in \~G is answered completely in the unimodular case (i.e., when the exponent sum of x_1 in w is one). Some generalisations of these results are discussed.Comment: V3: A small correction in the last phrase of the proof of Theorem 1. 4 page

    MicroRNA-34a is a potent tumor suppressor molecule in vivo in neuroblastoma

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    <p>ABSTRACT</p> <p>Background</p> <p>Neuroblastoma is a paediatric cancer which originates from precursor cells of the sympathetic nervous system and accounts for 15% of childhood cancer mortalities. With regards to the role of miRNAs in neuroblastoma, miR-34a, mapping to a chromosome 1p36 region that is commonly deleted, has been found to act as a tumor suppressor through targeting of numerous genes associated with cell proliferation and apoptosis.</p> <p>Methods</p> <p>A synthetic miR-34a (or negative control) precursor molecule was transfected into NB1691<sup>luc </sup>and SK-N-AS<sup>luc </sup>neuroblastoma cells. Quantitative PCR was used to verify increased miR-34a levels in NB1691<sup>luc </sup>and SK-N-AS<sup>luc </sup>cell lines prior to <it>in vitro </it>and <it>in vivo </it>analysis. <it>In vitro </it>analysis of the effects of miR-34a over expression on cell growth, cell cycle and phosphoprotein activation in signal transduction pathways was performed. Neuroblastoma cells over expressing miR-34a were injected retroperitoneally into immunocompromised CB17-SCID mice and tumor burden was assessed over a 21 day period by measuring bioluminescence (photons/sec/cm<sup>2</sup>).</p> <p>Results</p> <p>Over expression of miR-34a in both NB1691<sup>luc </sup>and SK-N-AS<sup>luc </sup>neuroblastoma cell lines led to a significant decrease in cell number relative to premiR-negative control treated cells over a 72 hour period. Flow cytometry results indicated that miR-34a induced cell cycle arrest and subsequent apoptosis activation. Phosphoprotein analysis highlighted key elements involved in signal transduction, whose activation was dysregulated as a result of miR-34a introduction into cells. As a potential mechanism of miR-34a action on phosphoprotein levels, we demonstrate that miR-34a over-expression results in a significant reduction of <it>MAP3K9 </it>mRNA and protein levels. Although <it>MAP3K9 </it>is a predicted target of miR-34a, direct targeting could not be validated with luciferase reporter assays. Despite this fact, any functional effects of reduced MAP3K9 expression as a result of miR-34a would be expected to be similar regardless of the mechanism involved. Most notably, <it>in vivo </it>studies showed that tumor growth was significantly repressed after exogenous miR-34a administration in retroperitoneal neuroblastoma tumors.</p> <p>Conclusion</p> <p>We demonstrate for the first time that miR-34a significantly reduces tumor growth in an <it>in vivo </it>orthotopic murine model of neuroblastoma and identified novel effects that miR-34a has on phospho-activation of key proteins involved with apoptosis.</p

    Geodesic rewriting systems and pregroups

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    In this paper we study rewriting systems for groups and monoids, focusing on situations where finite convergent systems may be difficult to find or do not exist. We consider systems which have no length increasing rules and are confluent and then systems in which the length reducing rules lead to geodesics. Combining these properties we arrive at our main object of study which we call geodesically perfect rewriting systems. We show that these are well-behaved and convenient to use, and give several examples of classes of groups for which they can be constructed from natural presentations. We describe a Knuth-Bendix completion process to construct such systems, show how they may be found with the help of Stallings' pregroups and conversely may be used to construct such pregroups.Comment: 44 pages, to appear in "Combinatorial and Geometric Group Theory, Dortmund and Carleton Conferences". Series: Trends in Mathematics. Bogopolski, O.; Bumagin, I.; Kharlampovich, O.; Ventura, E. (Eds.) 2009, Approx. 350 p., Hardcover. ISBN: 978-3-7643-9910-8 Birkhause

    SARS-CoV-2 positivity in offspring and timing of mother-to-child transmission: living systematic review and meta-analysis

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    OBJECTIVES: To assess the rates of SARS-CoV-2 positivity in babies born to mothers with SARS-CoV-2 infection, the timing of mother-to-child transmission and perinatal outcomes, and factors associated with SARS-CoV-2 status in offspring. DESIGN: Living systematic review and meta-analysis. DATA SOURCES: Major databases between 1 December 2019 and 3 August 2021. STUDY SELECTION: Cohort studies of pregnant and recently pregnant women (including after abortion or miscarriage) who sought hospital care for any reason and had a diagnosis of SARS-CoV-2 infection, and also provided data on offspring SARS-CoV-2 status and risk factors for positivity. Case series and case reports were also included to assess the timing and likelihood of mother-to-child transmission in SARS-CoV-2 positive babies. DATA EXTRACTION: Two reviewers independently extracted data and assessed study quality. A random effects model was used to synthesise data for rates, with associations reported using odds ratios and 95% confidence intervals. Narrative syntheses were performed when meta-analysis was inappropriate. The World Health Organization classification was used to categorise the timing of mother-to-child transmission (in utero, intrapartum, early postnatal). RESULTS: 472 studies (206 cohort studies, 266 case series and case reports; 28 952 mothers, 18 237 babies) were included. Overall, 1.8% (95% confidence interval 1.2% to 2.5%; 140 studies) of the 14 271 babies born to mothers with SARS-CoV-2 infection tested positive for the virus with reverse transcriptase polymerase chain reaction (RT-PCR). Of the 592 SARS-CoV-2 positive babies with data on the timing of exposure and type and timing of tests, 14 had confirmed mother-to-child transmission: seven in utero (448 assessed), two intrapartum (18 assessed), and five during the early postnatal period (70 assessed). Of the 800 SARS-CoV-2 positive babies with outcome data, 20 were stillbirths, 23 were neonatal deaths, and eight were early pregnancy losses; 749 babies were alive at the end of follow-up. Severe maternal covid-19 (odds ratio 2.4, 95% confidence interval 1.3 to 4.4), maternal death (14.1, 4.1 to 48.0), maternal admission to an intensive care unit (3.5, 1.7 to 6.9), and maternal postnatal infection (5.0, 1.2 to 20.1) were associated with SARS-CoV-2 positivity in offspring. Positivity rates using RT-PCR varied between regions, ranging from 0.1% (95% confidence interval 0.0% to 0.3%) in studies from North America to 5.7% (3.2% to 8.7%) in studies from Latin America and the Caribbean. CONCLUSION: SARS-CoV-2 positivity rates were found to be low in babies born to mothers with SARS-CoV-2 infection. Evidence suggests confirmed vertical transmission of SARS-CoV-2, although this is likely to be rare. Severity of maternal covid-19 appears to be associated with SARS-CoV-2 positivity in offspring. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020178076. READERS' NOTE: This article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication

    Analysis of visitors’ mobility patterns through random walk in the Louvre Museum

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    This paper proposes a random walk model to analyze visitors' mobility patterns in a large museum. Visitors' available time makes their visiting styles different, resulting in dissimilarity in the order and number of visited places and in path sequence length. We analyze all this by comparing a simulation model and observed data, which provide us the strength of the visitors' mobility patterns. The obtained results indicate that shorter stay-type visitors exhibit stronger patterns than those with the longer stay-type, confirming that the former are more selective than the latter in terms of their visitation type.Comment: 16 pages, 5 figures, 4 table

    Inhibition of Neuroblastoma Tumor Growth by Targeted Delivery of MicroRNA-34a Using Anti-Disialoganglioside GD2 Coated Nanoparticles

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    Neuroblastoma is one of the most challenging malignancies of childhood, being associated with the highest death rate in paediatric oncology, underlining the need for novel therapeutic approaches. Typically, patients with high risk disease undergo an initial remission in response to treatment, followed by disease recurrence that has become refractory to further treatment. Here, we demonstrate the first silica nanoparticle-based targeted delivery of a tumor suppressive, pro-apoptotic microRNA, miR-34a, to neuroblastoma tumors in a murine orthotopic xenograft model. These tumors express high levels of the cell surface antigen disialoganglioside GD2 (GD(2)), providing a target for tumor-specific delivery.Nanoparticles encapsulating miR-34a and conjugated to a GD(2) antibody facilitated tumor-specific delivery following systemic administration into tumor bearing mice, resulted in significantly decreased tumor growth, increased apoptosis and a reduction in vascularisation. We further demonstrate a novel, multi-step molecular mechanism by which miR-34a leads to increased levels of the tissue inhibitor metallopeptidase 2 precursor (TIMP2) protein, accounting for the highly reduced vascularisation noted in miR-34a-treated tumors.These novel findings highlight the potential of anti-GD(2)-nanoparticle-mediated targeted delivery of miR-34a for both the treatment of GD(2)-expressing tumors, and as a basic discovery tool for elucidating biological effects of novel miRNAs on tumor growth

    Making a Step Forward Towards Urban Resilience. The Contribution of Digital Innovation

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    Starting from 'wicked problem' theory as the landmark for framing disaster events in terms of policy issue for city governments, this paper highlights the contribution provided by Big Data analytics and digital innovation in dealing with disaster risks. The research aims at answering the following question: what is the role that 'smart technologies' play in strengthening urban resilience to disaster risks

    The initial education of high school teachers : a critical review of major issues and trends

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    This paper draws on major research findings in international literature in order to provide a critical review of a number of key issues and trends in the initial education of high school teachers. Firstly, this paper contextualizes the prevalent discourse surrounding the field of initial teacher education (ITE) and explores the effect that this discourse has on the conceptualization of teachers’ work. Secondly, this paper focuses on the debates regarding the most propitious site for the teacher education enterprise, the programme structure for ITE, the field placement or practicum, the relationship between subject study and pedagogy, and the overall effectiveness of teacher education. The paper concludes by considering the new challenges that the field of initial teacher education must confront and the implications of such challenges for the ITE curriculum.peer-reviewe

    Population growth of Mexican free-tailed bats (Tadarida brasiliensis mexicana) predates human agricultural activity

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    Background Human activities, such as agriculture, hunting, and habitat modification, exert a significant effect on native species. Although many species have suffered population declines, increased population fragmentation, or even extinction in connection with these human impacts, others seem to have benefitted from human modification of their habitat. Here we examine whether population growth in an insectivorous bat (Tadarida brasiliensis mexicana) can be attributed to the widespread expansion of agriculture in North America following European settlement. Colonies of T. b. mexicana are extremely large (~106 individuals) and, in the modern era, major agricultural insect pests form an important component of their food resource. It is thus hypothesized that the growth of these insectivorous bat populations was coupled to the expansion of agricultural land use in North America over the last few centuries. Results We sequenced one haploid and one autosomal locus to determine the rate and time of onset of population growth in T. b. mexicana. Using an approximate Maximum Likelihood method, we have determined that T. b. mexicana populations began to grow ~220 kya from a relatively small ancestral effective population size before reaching the large effective population size observed today. Conclusions Our analyses reject the hypothesis that T. b. mexicana populations grew in connection with the expansion of human agriculture in North America, and instead suggest that this growth commenced long before the arrival of humans. As T. brasiliensis is a subtropical species, we hypothesize that the observed signals of population growth may instead reflect range expansions of ancestral bat populations from southern glacial refugia during the tail end of the Pleistocene
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