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

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

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

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

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

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

RCRC Issue Briefs: Why Children Should Be the #1 Disaster Priority

The Resilient Children/Resilient Communities Initiative (RCRC) Issue Briefs, in this document, are designed to be used by the RCRC communities and all other communities who are seeking to elevate children’s disaster resilience to the attention of local, state, and federal legislators or other decision-makers. These reports can also be used by legislators and decision–makers at all levels of government as informative briefs to better understand the issues faced by communities in disasters within the context of COVID-19 and other disasters. Readers are encouraged to explore topics and voices that most resonate with their own community. To access an online and interactive version of RCRC Issue Briefs, please visit https://rcrctoolbox.org/rcrc-issue-briefs

Informes Temáticos RCRC: Porqué los Niños Deben Ser la Prioridad #1 en Desastres

Los Informes Temáticos RCRC, en este documento, están diseñados para ser utilizados por las comunidades de la iniciativa RCRC y todas las otras comunidades que buscan elevar la resiliencia de los niños ante desastres a la atención de legisladores locales, estatales y federales u otros responsables de la toma de decisiones. Estos informes también pueden ser utilizados por legisladores y responsables de la toma de decisiones en todos los niveles de gobierno como documentos informativos para comprender mejor los problemas que enfrentan las comunidades en desastres en el contexto de COVID-19 y otros desastres. Se anima a los lectores a explorar los temas y mensajes que más resuenan con su propia comunidad. Para acceder a una versión online e interactiva de los Informes Temáticos RCRC, visite https://rcrctoolbox.org/rcrc-issue-briefs-es/

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

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

miR-23b/SP1/c-myc forms a feed-forward loop supporting multiple myeloma cell growth

Deregulated microRNA (miR)/transcription factor (TF)-based networks represent a hallmark of cancer. We report here a novel c-Myc/miR-23b/Sp1 feed-forward loop with a critical role in multiple myeloma (MM) and Waldenstrom's macroglobulinemia (WM) cell growth and survival. We have found miR-23b to be downregulated in MM and WM cells especially in the presence of components of the tumor bone marrow milieu. Promoter methylation is one mechanism of miR-23b suppression in myeloma. In gain-of-function studies using miR-23b mimics-transfected or in miR-23b-stably expressing MM and WM cell lines, we observed a significant decrease in cell proliferation and survival, along with induction of caspase-3/7 activity over time, thus supporting a tumor suppressor role for miR-23b. At the molecular level, miR-23b targeted Sp1 3'UTR and significantly reduced Sp1-driven nuclear factor-kappa B activity. Finally, c-Myc, an important oncogenic transcription factor known to stimulate MM cell proliferation, transcriptionally repressed miR-23b. Thus MYC-dependent miR-23b repression in myeloma cells may promote activation of oncogenic Sp1-mediated signaling, representing the first feed-forward loop with critical growth and survival role in myeloma

RIP4 inhibits STAT3 signaling to sustain lung adenocarcinoma differentiation.

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