209 research outputs found

    A regularity condition and a limit theorem for Harris ergodic Markov chains

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    Let (Xn)n≥0 be a Harris ergodic Markov chain and f be a real function on its state space. Consider the block sums ζ(i) for f ,i≥1, between consecutive visits to the atom given by the splitting technique of Nummelin. A regularity condition on the invariant probability measure π and a drift property are introduced and proven to characterize the finiteness of the third moment of ζ(i). This is applied to obtain versions of an almost sure invariance principle for the partial sums of (f(Xn)), which is moreover given in the general case, due to Philipp and Stout for the countable state space case and to Csáki and Csörgo when the chain is strongly aperiodic. Conditions on the strong mixing coefficients are considered. A drift property equivalent to the finiteness of the second moment of ζ(i) is also given and applied to the functional central limit theorem.Facultad de Ciencias Exacta

    SERIMI: Class-Based Matching for Instance Matching Across Heterogeneous Datasets

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    State-of-the-art instance matching approaches do not perform well when used for matching instances across heterogeneous datasets. This shortcoming derives from their core operation depending on direct matching, which involves a direct comparison of instances in the source with instances in the target dataset. Direct matching is not suitable when the overlap between the datasets is small. Aiming at resolving this problem, we propose a new paradigm called class-based matching. Given a class of instances from the source dataset, called the class of interest, and a set of candidate matches retrieved from the target, class-based matching refines the candidates by filtering out those that do not belong to the class of interest. For this refinement, only data in the target is used, i.e., no direct comparison between source and target is involved. Based on extensive experiments using public benchmarks, we show our approach greatly improves the quality of state-of-the-art systems; especially on difficult matching tasks

    Getting lost in a story: how narrative engagement emerges from narrative perspective and individual differences in alexithymia

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    The present research examines how narrative engagement, or the extent to which people immerse themselves into the world of a story, varies as a function of narrative perspective and individual differences in alexithymia. The authors hypothesised that narrative engagement would be higher when people assume a first-person (rather than third-person) perspective and for people lower (rather than higher) on alexithymia. In an online study (N = 541) and a lab study (N = 55), participants with varying levels of alexithymia read first- and/or third-person narrated texts and then rated their narrative engagement. As expected, first-person stories evoked more narrative engagement than third-person stories, and global alexithymia was negatively correlated with narrative engagement. Narrative perspective did not interact with cognitive facets of alexithymia (i.e. difficulties identifying, verbalising, and understanding feelings). However, narrative perspective did interact with affective facets of alexithymia (i.e. emotionalising and fantasising): First-person (rather than third-person) stories elicited more narrative engagement at lower levels of affective alexithymia, but not at higher levels of affective alexithymia. The interaction effect was significant in Study 1; the interaction was significant in Study 2 after controlling for trait absorption. Together, these findings suggest that alexithymia is linked to difficulties in mentally simulating narrative worlds.Pathways through Adolescenc

    RIP4 inhibits STAT3 signaling to sustain lung adenocarcinoma differentiation.

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    Loss of epithelial differentiation and extracellular matrix (ECM) remodeling are known to facilitate cancer progression and are associated with poor prognosis in patients with lung cancer. We have identified Receptor-interacting serine/threonine protein kinase 4 (RIP4) as a regulator of tumor differentiation in lung adenocarcinoma (AC). Bioinformatics analyses of human lung AC samples showed that poorly differentiated tumors express low levels of RIP4, whereas high levels are associated with better overall survival. In vitro, lung tumor cells expressing reduced RIP4 levels showed enhanced activation of STAT3 signaling and had a greater ability to invade through collagen. In contrast, overexpression of RIP4 inhibited STAT3 activation, which abrogated interleukin-6-dependent induction of lysyl oxidase, a collagen cross-linking enzyme. In an autochthonous mouse model of lung AC initiated by Kras(G12D) expression with loss of p53, Rip4 knockdown tumors progressed to a poorly differentiated state marked by an increase in Hmga2, reduced Ttf1, and enrichment of genes regulating extracellular remodeling and Jak-Stat signaling. Tail vein injections of cells overexpressing Rip4 showed a reduced potential to invade and form tumors, which was restored by co-expression of Stat3. Altogether, our work has identified that loss of RIP4 enhances STAT3 signaling in lung cancer cells, promoting the expression of ECM remodeling genes and cancer dedifferentiation

    Calcium phosphate formation from sea urchin - (brissus latecarinatus) via modified mechano-chemical (ultrasonic) conversion method

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    This study aims to produce apatite structures, such as hydroxyapatite (HA) and fluorapatite (FA), from precursor calcium phosphates of biological origin, namely from sea urchin, with mechano-chemical stirring and hot-plating conversion method. The produced materials were heat treated at 800 °C for 4 hours. X-ray diffraction and scanning electron microscopy (SEM) studies were conducted. Calcium phosphate phases were developed. The SEM images showed the formation of micro to nano-powders. The experimental results suggest that sea urchin, Brissus latecarinatus skeleton could be an alternative source for the production of various mono or biphasic calcium phosphates with simple and economic mechano-chemical (ultrasonic) conversion method

    Therapeutic vulnerability of multiple myeloma to MIR17PTi, a first-in-class inhibitor of pri-mir-17-92

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    The microRNA cluster miR-17-92 is oncogenic and represents a valuable therapeutic target in c-MYC (MYC)-driven malignancies. Here, we developed novel LNA gapmeR antisense oligonucleotides (ASOs) to induce RNase H-mediated degradation of MIR17HG primary transcripts and, consequently, to prevent biogenesis of miR-17-92 microRNAs (miR-17-92s). The leading LNA-ASO, named MIR17PTi, impaired proliferation of several cancer cell lines (n=48) established from both solid and hematologic tumors by on-target antisense activity, and more effectively as compared to miR-17-92s inhibitors. By focusing on multiple myeloma (MM), we found that MIR17PTi triggers apoptosis via impairment of homeostatic MYC/miR-17-92 feed-forward loops (FFLs) in patient-derived MM cells; and induced MYC-dependent synthetic lethality. We show that alteration of a BIM-centered FFL is instrumental for MIR17PTi to induce cytotoxicity in MM cells. MIR17PTi exerts strong in vivo anti-tumor activity in NOD-SCID mice bearing clinically relevant models of MM, with advantageous safety and pharmacokinetics profiles in non-human primates. Altogether, MIR17PTi is a novel pharmacological tool to be tested in early-phase clinical trials against MM and other MYC-driven malignancies

    Genomic patterns of progression in smoldering multiple myeloma

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    We analyzed whole genomes of unique paired samples from smoldering multiple myeloma (SMM) patients progressing to multiple myeloma (MM). We report that the genomic landscape, including mutational profile and structural rearrangements at the smoldering stage is very similar to MM. Paired sample analysis shows two different patterns of progression: a “static progression model”, where the subclonal architecture is retained as the disease progressed to MM suggesting that progression solely reflects the time needed to accumulate a sufficient disease burden; and a “spontaneous evolution model”, where a change in the subclonal composition is observed. We also observe that activation-induced cytidine deaminase plays a major role in shaping the mutational landscape of early subclinical phases, while progression is driven by APOBEC cytidine deaminases. These results provide a unique insight into myelomagenesis with potential implications for the definition of smoldering disease and timing of treatment initiation
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