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The chaos machine: analogue computing rediscovered (1)
Analogue computers provide actual rather than virtual representations of model systems. They are powerful and engaging computing machines that are cheap and simple to build. This two-part Retronics article helps you build (and understand!) your own analogue computer to simulate the Lorenz butterfly that's become iconic for Chaos theory
Communicative success in spatial dialogue: The impact of functional features and dialogue strategies
This paper addresses the impact of dialogue strategies and functional features of spatial arrangements on communicative success. To examine the sharing of cognition between two minds in order to achieve a joint goal, we collected a corpus of 24 extended German-language dialogues in a referential communication task that involved furnishing a dolls’ house. Results show how successful communication, as evidenced by correct placement of furniture items, is affected by a) functionality of the furniture arrangement, b) previous task experience, and c) dialogue features such as description length and orientation information. To enhance research in this area, our 'Dolldialogue' corpus is now available as a free resource on www.dolldialogue.spac
Program for computing partial pressures from residual gas analyzer data
A computer program for determining the partial pressures of various gases from residual-gas-analyzer data is given. The analysis of the ion currents of 18 m/e spectrometer peaks allows the determination of 12 gases simultaneously. Comparison is made to ion-gage readings along with certain other control information. The output data are presented in both tabular and graphical form
Optimal randomized multilevel algorithms for infinite-dimensional integration on function spaces with ANOVA-type decomposition
In this paper, we consider the infinite-dimensional integration problem on
weighted reproducing kernel Hilbert spaces with norms induced by an underlying
function space decomposition of ANOVA-type. The weights model the relative
importance of different groups of variables. We present new randomized
multilevel algorithms to tackle this integration problem and prove upper bounds
for their randomized error. Furthermore, we provide in this setting the first
non-trivial lower error bounds for general randomized algorithms, which, in
particular, may be adaptive or non-linear. These lower bounds show that our
multilevel algorithms are optimal. Our analysis refines and extends the
analysis provided in [F. J. Hickernell, T. M\"uller-Gronbach, B. Niu, K.
Ritter, J. Complexity 26 (2010), 229-254], and our error bounds improve
substantially on the error bounds presented there. As an illustrative example,
we discuss the unanchored Sobolev space and employ randomized quasi-Monte Carlo
multilevel algorithms based on scrambled polynomial lattice rules.Comment: 31 pages, 0 figure
Accessibility of physical states and non-uniqueness of entanglement measure
Ordering physical states is the key to quantifying some physical property of
the states uniquely. Bipartite pure entangled states are totally ordered under
local operations and classical communication (LOCC) in the asymptotic limit and
uniquely quantified by the well-known entropy of entanglement. However, we show
that mixed entangled states are partially ordered under LOCC even in the
asymptotic limit. Therefore, non-uniqueness of entanglement measure is
understood on the basis of an operational notion of asymptotic convertibility.Comment: 8 pages, 1 figure. v2: main result unchanged but presentation
extensively changed. v3: figure added, minor correction
Fundamental Cycles and Graph Embeddings
In this paper we present a new Good Characterization of maximum genus of a
graph which makes a common generalization of the works of Xuong, Liu, and Fu et
al. Based on this, we find a new polynomially bounded algorithm to find the
maximum genus of a graph
Genomic characterization of Gli-activator targets in sonic hedgehog-mediated neural patterning
Sonic hedgehog (Shh) acts as a morphogen to mediate the specification of distinct cell identities in the ventral neural tube through a Gli-mediated (Gli1-3) transcriptional network. Identifying Gli targets in a systematic fashion is central to the understanding of the action of Shh. We examined this issue in differentiating neural progenitors in mouse. An epitope-tagged Gli-activator protein was used to directly isolate cis-regulatory sequences by chromatin immunoprecipitation (ChIP). ChIP products were then used to screen custom genomic tiling arrays of putative Hedgehog (Hh) targets predicted from transcriptional profiling studies, surveying 50-150 kb of non-transcribed sequence for each candidate. In addition to identifying expected Gli-target sites, the data predicted a number of unreported direct targets of Shh action. Transgenic analysis of binding regions in Nkx2.2, Nkx2.1 (Titf1) and Rab34 established these as direct Hh targets. These data also facilitated the generation of an algorithm that improved in silico predictions of Hh target genes. Together, these approaches provide significant new insights into both tissue-specific and general transcriptional targets in a crucial Shh-mediated patterning process
Anti-oestrogen therapy switches off tumour suppressors and proapoptotic genes in breast cancer and reveals a new therapeutic opportunity
Background
Previous studies in the Tenovus Centre have demonstrated that the development of antioestrogen resistance in vitro is accompanied by unfavourable changes in the breast cancer phenotype leading to increase tumour cell growth rate. Here evidence is presented to suggest that this is in part due to antihormones causing the epigenetic silencing of oestrogen-induced genes involved in the negative regulation of cell growth. Importantly, we show that reversal of this process using the demethylation agent 5-azacytidine (5AZA) allows oestrogen-induced cell kill by a previously unrecognised mechanism.
Methods
The breast cancer cell lines used in this study were MCF7, MCF7-derived tamoxifen-resistant variant (TamR) and TamR sublines that had been withdrawn from tamoxifen (TamRwd) for up to 6 months. Cells were challenged by oestradiol (E2), antihormones and 5AZA. Cell growth responses were assessed by anchorage-dependent growth assays and alterations in expression/activity of oestrogen receptor (ER) and ER-regulated genes were analysed by real-time PCR, western blotting and/or immunocytochemistry.
Results
Compared with the parental MCF7 cells, TamR cells showed a significant upregulated basal rate of growth that was maintained on tamoxifen withdrawal for 6 months. Following the tamoxifen withdrawal, the cells remained ER-positive and showed a slight growth response to E2. In contrast, they showed no growth inhibitory response to tamoxifen. Examination of the methylation status of the promoters of two classically ER-regulated genes switched off in TamR and TamRwd cells, pS2 and progesterone receptor (PR), confirmed their increased methylation and that 5AZA was able to reverse this process, allowing the re-expression of pS2 and PR on E2 treatment. Although pS2 and PR are not thought to play a role in the regulation of cell growth, these data provide proof of principal that gene silencing occurs in TamR cells and that it can be reinstated by 5AZA plus E2. To determine whether tamoxifen was capable of inducing the methylation of ER-regulated genes involved in cell growth, TamRwd cells pretreated with 5AZA were subject to an E2 dose–response challenge. In contrast to TamRwd cells treated with E2, which promoted a growth response, E2 in combination with 5AZA was strongly inhibitory at physiological doses of the steroid (10-9 M), with this action being reversed by tamoxifen. An Affymetrix analysis of the TamR cells has revealed multiple E2-regulated genes that are switched off in the resistant cells whose ontology indicates tumour suppressor/proapoptotic functions.
Conclusion
Our data suggest that antihormone resistance may be associated with the epigenetic silencing of growth inhibitory genes leading to enhanced growth rates. We propose that reinstatement of the expression of such genes using demethylation agents in combination with E2 may provide a previously unrecognised therapeutic opportunity in breast cancer
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