1,032 research outputs found

    Міжнародна наукова конференція «Шляхи розвитку науково-технічного співробітництва Росії, України і Білорусі»

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    7 жовтня 2011 року у Москві, у приміщенні Президії РАН на Ленінському проспекті 32А, відбулася міжнародна наукова конференція «Шляхи розвитку науково-технічного співробітництва Росії, України і Білорусі». Конференція була організована Інститутом проблем розвитку науки РАН (ІПРАН РАН) за підтримки Президії РАН. У ролі партнерської організації1виступив Російський гуманітарний науковий фонд

    Long and repeat-rich intronic sequences favor circular RNA formation under conditions of reduced spliceosome activity

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    Circular RNAs (circRNAs), an important class of regulatory RNAs, have been shown to be the most prevalent in the brain compared with other tissues. However the processes governing their biogenesis in neurons are still elusive. Moreover, little is known about whether and how different biogenesis factors work in synchrony to generate neuronal circRNAs. To address this question, we pharmacologically inhibited the spliceosome and profiled rat neuronal circRNAs using RNA sequencing. We identified over 100 circRNAs that were up-regulated and a few circRNAs that were down-regulated upon spliceosome inhibition. Bioinformatic analysis revealed that up-regulated circRNAs possess significantly longer flanking introns compared with the un-changed circRNA population. Moreover, the flanking introns of up-regulated circRNAs harbor a higher number of distinct repeat sequences and more reverse complementary motifs compared with the unchanged circRNAs. Taken together, our data demonstrate that the biogenesis of circRNAs containing distinct intronic features becomes favored under conditions of limited spliceosome activity

    Quantum-classical transition of the escape rate of uniaxial antiferromagnetic particles in an arbitrarily directed field

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    Quantum-classical escape rate transition has been studied for uniaxial antiferromagnetic particles with an arbitrarily directed magnetic field. In the case that the transverse and longitudinal fileds coexist, we calculate the phase boundary line between first- and second-order transitions, from which phase diagrams can be obtained. It is shown that the effects of the applied longitudinal magnetic field on quantum-classical transition vary greatly for different relative magnitudes of the non-compensation.Comment: to be appeared in Phys. Rev.

    Dynamic Regulation by Polycomb Group Protein Complexes Controls Pattern Formation and the Cell Cycle in Drosophila

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    SummaryPolycomb group (PcG) proteins form conserved regulatory complexes that modify chromatin to repress transcription. Here, we report genome-wide binding profiles of PhoRC, the Drosophila PcG protein complex containing the DNA-binding factor Pho/dYY1 and dSfmbt. PhoRC constitutively occupies short Polycomb response elements (PREs) of a large set of developmental regulator genes in both embryos and larvae. The majority of these PREs are co-occupied by the PcG complexes PRC1 and PRC2. Analysis of PcG mutants shows that the PcG system represses genes required for anteroposterior, dorsoventral, and proximodistal patterning of imaginal discs and that it also represses cell cycle regulator genes. Many of these genes are regulated in a dynamic manner, and our results suggest that the PcG system restricts signaling-mediated activation of target genes to appropriate cells. Analysis of cell cycle regulators indicates that the PcG system also dynamically modulates the expression levels of certain genes, providing a possible explanation for the tumor phenotype of PcG mutants

    Considerations on the quantum double-exchange Hamiltonian

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    Schwinger bosons allow for an advantageous representation of quantum double-exchange. We review this subject, comment on previous results, and address the transition to the semiclassical limit. We derive an effective fermionic Hamiltonian for the spin-dependent hopping of holes interacting with a background of local spins, which is used in a related publication within a two-phase description of colossal magnetoresistant manganites.Comment: 7 pages, 3 figure

    CLRM-14. OPEN-LABEL, MULTINATIONAL, MULTICENTER, PHASE 3B/4 STUDY OF TRASTUZUMAB DERUXTECAN (T-DXD) IN PATIENTS WITH OR WITHOUT BASELINE BRAIN METASTASIS (BM) WITH PREVIOUSLY TREATED ADVANCED/METASTATIC HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR 2–POSITIVE BREAST CANCER (HER2+ BC): DESTINY-BREAST12

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    Abstract BACKGROUND Despite treatment advances, up to 50% of patients with advanced HER2+ BC develop BM (Zimmer. Cancer Rep. 2020). Patients with HER2+ BC with BM have a worse prognosis than patients without BM. In DESTINY-Breast01, T-DXd demonstrated efficacy in the overall population and preliminary efficacy in a subgroup with stable BM, with a confirmed objective response rate (ORR) of 61.4% and an extracranial confirmed ORR by independent central review (ICR) of 58.3%, median progression-free survival (PFS) of 19.4 and 18.1 mo, and median duration of response (DOR) of 20.8 and 16.9 mo (Modi. Cancer Res. 2021; Jerusalem. Ann Oncol. 2020). Here we describe a trial evaluating T-DXd in patients with previously treated advanced/metastatic HER2+ BC ±BM. DESIGN DESTINY-Breast12 (NCT04739761) is an open-label, multicenter, international (86 sites in the US, Europe, Australia, and Japan), phase 3b/4 study assessing T-DXd 5.4 mg/kg q3w efficacy and safety in patients with previously treated advanced/metastatic HER2+ BC ±BM that progressed with ≥1 prior anti-HER2–based regimen and received ≤2 lines of therapy in the metastatic setting (excluding patients with prior tucatinib). Patients (n=250/cohort) will be enrolled in cohort 1 (−BM at baseline) or 2 (+BM at baseline). BM must be untreated and not needing immediate local therapy or previously treated and stable or progressing. Primary endpoints are ORR (cohort 1) and PFS (cohort 2) (both by RECIST version 1.1 per ICR). Secondary endpoints are OS, DOR, time to progression, duration of subsequent therapy, PFS2, safety, and changes in symptoms, functioning, and QOL in both cohorts; incidence of new symptomatic CNS metastasis (CNSM) in cohort 1; and ORR and CNS ORR by RECIST 1.1 per ICR, CNS PFS and DOR, and time to new CNSM in cohort 2. This is an encore; the original presentation will be at The European Society for Medical Oncology 2021

    Isovector and isoscalar superfluid phases in rotating nuclei

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    The subtle interplay between the two nuclear superfluids, isovector T=1 and isoscalar T=0 phases, are investigated in an exactly soluble model. It is shown that T=1 and T=0 pair-modes decouple in the exact calculations with the T=1 pair-energy being independent of the T=0 pair-strength and vice-versa. In the rotating-field, the isoscalar correlations remain constant in contrast to the well known quenching of isovector pairing. An increase of the isoscalar (J=1, T=0) pair-field results in a delay of the bandcrossing frequency. This behaviour is shown to be present only near the N=Z line and its experimental confirmation would imply a strong signature for isoscalar pairing collectivity. The solutions of the exact model are also discussed in the Hartree-Fock-Bogoliubov approximation.Comment: 5 pages, 4 figures, submitted to PR

    Universality, vortices and confinement: modified SO(3) lattice gauge theory at non-zero temperature

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    We investigate the adjoint SU(2) lattice gauge theory in 3+1 dimensions with the Wilson plaquette action modified by a Z(2) monopole suppression term. For the zero-twist sector we report indications for the existence of a finite temperature effect decoupled from the unphysical bulk transitions.Comment: 17 pages, 10 figures. Some figures and text added. To appear on Phys. Rev.

    Mutations of the EPHB6 Receptor Tyrosine Kinase Induce a Pro-Metastatic Phenotype in Non-Small Cell Lung Cancer

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    Alterations of Eph receptor tyrosine kinases are frequent events in human cancers. Genetic variations of EPHB6 have been described but the functional outcome of these alterations is unknown. The current study was conducted to screen for the occurrence and to identify functional consequences of EPHB6 mutations in non-small cell lung cancer. Here, we sequenced the entire coding region of EPHB6 in 80 non-small cell lung cancer patients and 3 tumor cell lines. Three potentially relevant mutations were identified in primary patient samples of NSCLC patients (3.8%). Two point mutations led to instable proteins. An in frame deletion mutation (del915-917) showed enhanced migration and accelerated wound healing in vitro. Furthermore, the del915-917 mutation increased the metastatic capability of NSCLC cells in an in vivo mouse model. Our results suggest that EPHB6 mutations promote metastasis in a subset of patients with non-small cell lung cancer
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