234 research outputs found
Lusin-type approximation of Sobolev by Lipschitz functions, in Gaussian and spaces
We establish new approximation results, in the sense of Lusin, of Sobolev
functions by Lipschitz ones, in some classes of non-doubling metric measure
structures. Our proof technique relies upon estimates for heat semigroups and
applies to Gaussian and spaces. As a consequence, we obtain
quantitative stability for regular Lagrangian flows in Gaussian settings
Synergy between Proteasome Inhibitors and Imatinib Mesylate in Chronic Myeloid Leukemia
Resistance developed by leukemic cells, unsatisfactory efficacy on patients with chronic myeloid leukemia (CML) at accelerated and blastic phases, and potential cardiotoxity, have been limitations for imatinib mesylate (IM) in treating CML. Whether low dose IM in combination with agents of distinct but related mechanisms could be one of the strategies to overcome these concerns warrants careful investigation.We tested the therapeutic efficacies as well as adverse effects of low dose IM in combination with proteasome inhibitor, Bortezomib (BOR) or proteasome inhibitor I (PSI), in two CML murine models, and investigated possible mechanisms of action on CML cells. Our results demonstrated that low dose IM in combination with BOR exerted satisfactory efficacy in prolongation of life span and inhibition of tumor growth in mice, and did not cause cardiotoxicity or body weight loss. Consistently, BOR and PSI enhanced IM-induced inhibition of long-term clonogenic activity and short-term cell growth of CML stem/progenitor cells, and potentiated IM-caused inhibition of proliferation and induction of apoptosis of BCR-ABL+ cells. IM/BOR and IM/PSI inhibited Bcl-2, increased cytoplasmic cytochrome C, and activated caspases. While exerting suppressive effects on BCR-ABL, E2F1, and β-catenin, IM/BOR and IM/PSI inhibited proteasomal degradation of protein phosphatase 2A (PP2A), leading to a re-activation of this important negative regulator of BCR-ABL. In addition, both combination therapties inhibited Bruton's tyrosine kinase via suppression of NFκB.These data suggest that combined use of tyrosine kinase inhibitor and proteasome inhibitor might be helpful for optimizing CML treatment
A proposed disease classification system for duck viral hepatitis
The nomenclature of duck viral hepatitis (DVH) was historically not a problem. However, 14 hepatotropic viruses among 10 different genera are associated with the same disease name, DVH. Therefore, the disease name increasingly lacks clarity and may no longer fit the scientific description of the disease. Because one disease should not be attributed to 10 genera of viruses, this almost certainly causes misunderstanding regarding the disease-virus relationship. Herein, we revisited the problem and proposed an update to DVH disease classification. This classification is based on the nomenclature of human viral hepatitis and the key principle of Koch's postulates (“one microbe and one disease”). In total, 10 types of disease names have been proposed. These names were literately matched with hepatitis-related viruses. We envision that this intuitive nomenclature system will facilitate scientific communication and consistent interpretation in this field, especially in the Asian veterinary community, where these diseases are most commonly reported
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Inhibition of PIP4Kγ ameliorates the pathological effects of mutant huntingtin protein.
The discovery of the causative gene for Huntington's disease (HD) has promoted numerous efforts to uncover cellular pathways that lower levels of mutant huntingtin protein (mHtt) and potentially forestall the appearance of HD-related neurological defects. Using a cell-based model of pathogenic huntingtin expression, we identified a class of compounds that protect cells through selective inhibition of a lipid kinase, PIP4Kγ. Pharmacological inhibition or knock-down of PIP4Kγ modulates the equilibrium between phosphatidylinositide (PI) species within the cell and increases basal autophagy, reducing the total amount of mHtt protein in human patient fibroblasts and aggregates in neurons. In two Drosophila models of Huntington's disease, genetic knockdown of PIP4K ameliorated neuronal dysfunction and degeneration as assessed using motor performance and retinal degeneration assays respectively. Together, these results suggest that PIP4Kγ is a druggable target whose inhibition enhances productive autophagy and mHtt proteolysis, revealing a useful pharmacological point of intervention for the treatment of Huntington's disease, and potentially for other neurodegenerative disorders
Calcium-sensing receptor regulates stomatal closure through hydrogen peroxide and nitric oxide in response to extracellular calcium in Arabidopsis
The Arabidopsis calcium-sensing receptor CAS is a crucial regulator of extracellular calcium-induced stomatal closure. Free cytosolic Ca2+ (Ca2+i) increases in response to a high extracellular calcium (Ca2+o) level through a CAS signalling pathway and finally leads to stomatal closure. Multidisciplinary approaches including histochemical, pharmacological, fluorescent, electrochemical, and molecular biological methods were used to discuss the relationship of hydrogen peroxide (H2O2) and nitric oxide (NO) signalling in the CAS signalling pathway in guard cells in response to Ca2+o. Here it is shown that Ca2+o could induce H2O2 and NO production from guard cells but only H2O2 from chloroplasts, leading to stomatal closure. In addition, the CASas mutant, the atrbohD/F double mutant, and the Atnoa1 mutant were all insensitive to Ca2+o-stimulated stomatal closure, as well as H2O2 and NO elevation in the case of CASas. Furthermore, it was found that the antioxidant system might function as a mediator in Ca2+o and H2O2 signalling in guard cells. The results suggest a hypothetical model whereby Ca2+o induces H2O2 and NO accumulation in guard cells through the CAS signalling pathway, which further triggers Ca2+i transients and finally stomatal closure. The possible cross-talk of Ca2+o and abscisic acid signalling as well as the antioxidant system are discussed
Insight-HXMT observations of Swift J0243.6+6124 during its 2017-2018 outburst
The recently discovered neutron star transient Swift J0243.6+6124 has been
monitored by {\it the Hard X-ray Modulation Telescope} ({\it Insight-\rm HXMT).
Based on the obtained data, we investigate the broadband spectrum of the source
throughout the outburst. We estimate the broadband flux of the source and
search for possible cyclotron line in the broadband spectrum. No evidence of
line-like features is, however, found up to . In the absence of
any cyclotron line in its energy spectrum, we estimate the magnetic field of
the source based on the observed spin evolution of the neutron star by applying
two accretion torque models. In both cases, we get consistent results with
, and peak luminosity of which makes the source the first Galactic ultraluminous
X-ray source hosting a neutron star.Comment: publishe
Overview to the Hard X-ray Modulation Telescope (Insight-HXMT) Satellite
As China's first X-ray astronomical satellite, the Hard X-ray Modulation
Telescope (HXMT), which was dubbed as Insight-HXMT after the launch on June 15,
2017, is a wide-band (1-250 keV) slat-collimator-based X-ray astronomy
satellite with the capability of all-sky monitoring in 0.2-3 MeV. It was
designed to perform pointing, scanning and gamma-ray burst (GRB) observations
and, based on the Direct Demodulation Method (DDM), the image of the scanned
sky region can be reconstructed. Here we give an overview of the mission and
its progresses, including payload, core sciences, ground calibration/facility,
ground segment, data archive, software, in-orbit performance, calibration,
background model, observations and some preliminary results.Comment: 29 pages, 40 figures, 6 tables, to appear in Sci. China-Phys. Mech.
Astron. arXiv admin note: text overlap with arXiv:1910.0443
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