181 research outputs found

    Projection Solutions of Frobenius-Perron Operator Equations

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    We construct in this paper the first order and second order piecewise polynomial finite approximation schemes for the computation of invariant measures of a class of nonsingular measurable transformations on the unit interval of the real axis. These schemes are based on the Galerkin’s projection method for L1-spaces and are proved to be convergent for the class of Frobenius-Perron operators

    Further Study On U(1) Gauge Invariance Restoration

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    To further investigate the applicability of the projection scheme for eliminating the unphysical divergence s/me2s/m_e^2 due to U(1) gauge invariance violation, we study the process eβˆ’+W+β†’eβˆ’+tΛ‰+be^-+W^+\to e^-+\bar t+b which possesses advantages of simplicity and clearness. Our study indicates that the projection scheme can indeed eliminate the unphysical divergence s/me2s/m_e^2 caused by the U(1) gauge invariance violation and the scheme can apply to very high energy region.Comment: Latex, 13 pages, 4 EPS fiure

    Rotational Symmetry of Classical Orbits, Arbitrary Quantization of Angular Momentum and the Role of Gauge Field in Two-Dimensional Space

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    We study the quantum-classical correspondence in terms of coherent wave functions of a charged particle in two-dimensional central-scalar-potentials as well as the gauge field of a magnetic flux in the sense that the probability clouds of wave functions are well localized on classical orbits. For both closed and open classical orbits, the non-integer angular-momentum quantization with the level-space of angular momentum being greater or less than ℏ\hbar is determined uniquely by the same rotational symmetry of classical orbits and probability clouds of coherent wave functions, which is not necessarily 2Ο€2\pi-periodic. The gauge potential of a magnetic flux impenetrable to the particle cannot change the quantization rule but is able to shift the spectrum of canonical angular momentum by a flux-dependent value, which results in a common topological phase for all wave functions in the given model. The quantum mechanical model of anyon proposed by Wilczek (Phys. Rev. Lette. 48, 1144) becomes a special case of the arbitrary-quantization.Comment: 6 pages, 5 figure

    Histopathologic and proteogenomic heterogeneity reveals features of clear cell renal cell carcinoma aggressiveness

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    Clear cell renal cell carcinomas (ccRCCs) represent ∼75% of RCC cases and account for most RCC-associated deaths. Inter- and intratumoral heterogeneity (ITH) results in varying prognosis and treatment outcomes. To obtain the most comprehensive profile of ccRCC, we perform integrative histopathologic, proteogenomic, and metabolomic analyses on 305 ccRCC tumor segments and 166 paired adjacent normal tissues from 213 cases. Combining histologic and molecular profiles reveals ITH in 90% of ccRCCs, with 50% demonstrating immune signature heterogeneity. High tumor grade, along with BAP1 mutation, genome instability, increased hypermethylation, and a specific protein glycosylation signature define a high-risk disease subset, where UCHL1 expression displays prognostic value. Single-nuclei RNA sequencing of the adverse sarcomatoid and rhabdoid phenotypes uncover gene signatures and potential insights into tumor evolution. In vitro cell line studies confirm the potential of inhibiting identified phosphoproteome targets. This study molecularly stratifies aggressive histopathologic subtypes that may inform more effective treatment strategies

    Next-Generation Sequencing Analysis Reveals Novel Pathogenic Variants in Four Chinese Siblings With Late-Infantile Neuronal Ceroid Lipofuscinosis

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    Neuronal Ceroid Lipofuscinoses (NCLs) are progressive degenerative diseases mainly affect brain and retina. They are characterized by accumulation of autofluorescent storage material, mitochondrial ATPase subunit C, or sphingolipid activator proteins A and D in lysosomes of most cells. Heterogenous storage material in NCLs is not completely disease-specific. Most of CLN proteins and their natural substrates are not well-characterized. Studies have suggested variants of Late-Infantile NCLs (LINCLs) include the major type CLN2 and minor types CLN5, CLN6, CLN7, and CLN8. Therefore, combination of clinical and molecular analysis has become a more effective diagnosis method. We studied 4 late-infantile NCL siblings characterized by seizures, ataxia as early symptoms, followed by progressive regression in intelligence and behavior, but mutations are located in different genes. Symptoms and progression of 4 types of LINCLs are compared. Pathology of LINCLs is also discussed. We performed Nest-Generation Sequencing on these phenotypically similar families. Three novel variants c.1551+1insTGAT in TPP1, c.244G>T in CLN6, c.554-5A>G in MFSD8 were identified. Potential outcome of the mutations in structure and function of proteins are studied. In addition, we observed some common and unique clinical features of Chinese LINCL patient as compared with those of Western patients, which greatly improved our understanding of the LINCLs

    Deciphering neo-sex and B chromosome evolution by the draft genome of Drosophila albomicans

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    <p>Abstract</p> <p>Background</p> <p><it>Drosophila albomicans </it>is a unique model organism for studying both sex chromosome and B chromosome evolution. A pair of its autosomes comprising roughly 40% of the whole genome has fused to the ancient X and Y chromosomes only about 0.12 million years ago, thereby creating the youngest and most gene-rich neo-sex system reported to date. This species also possesses recently derived B chromosomes that show non-Mendelian inheritance and significantly influence fertility.</p> <p>Methods</p> <p>We sequenced male flies with B chromosomes at 124.5-fold genome coverage using next-generation sequencing. To characterize neo-Y specific changes and B chromosome sequences, we also sequenced inbred female flies derived from the same strain but without B's at 28.5-fold.</p> <p>Results</p> <p>We assembled a female genome and placed 53% of the sequence and 85% of the annotated proteins into specific chromosomes, by comparison with the 12 <it>Drosophila genomes</it>. Despite its very recent origin, the non-recombining neo-Y chromosome shows various signs of degeneration, including a significant enrichment of non-functional genes compared to the neo-X, and an excess of tandem duplications relative to other chromosomes. We also characterized a B-chromosome linked scaffold that contains an actively transcribed unit and shows sequence similarity to the subcentromeric regions of both the ancient X and the neo-X chromosome.</p> <p>Conclusions</p> <p>Our results provide novel insights into the very early stages of sex chromosome evolution and B chromosome origination, and suggest an unprecedented connection between the births of these two systems in <it>D. albomicans</it>.</p

    Synthesis and applications of porous non-silica metal oxide submicrospheres

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    Β© 2016 Royal Society of Chemistry. Nowadays the development of submicroscale products of specific size and morphology that feature a high surface area to volume ratio, well-developed and accessible porosity for adsorbates and reactants, and are non-toxic, biocompatible, thermally stable and suitable as synergetic supports for precious metal catalysts is of great importance for many advanced applications. Complex porous non-silica metal oxide submicrospheres constitute an important class of materials that fulfill all these qualities and in addition, they are relatively easy to synthesize. This review presents a comprehensive appraisal of the methods used for the synthesis of a wide range of porous non-silica metal oxide particles of spherical morphology such as porous solid spheres, core-shell and yolk-shell particles as well as single-shell and multi-shell particles. In particular, hydrothermal and low temperature solution precipitation methods, which both include various structure developing strategies such as hard templating, soft templating, hydrolysis, or those taking advantage of Ostwald ripening and the Kirkendall effect, are reviewed. In addition, a critical assessment of the effects of different experimental parameters such as reaction time, reaction temperature, calcination, pH and the type of reactants and solvents on the structure of the final products is presented. Finally, the practical usefulness of complex porous non-silica metal oxide submicrospheres in sensing, catalysis, biomedical, environmental and energy-related applications is presented

    SVIP Induces Localization of p97/VCP to the Plasma and Lysosomal Membranes and Regulates Autophagy

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    The small p97/VCP-interacting protein (SVIP) functions as an inhibitor of the endoplasmic reticulum (ER)-associated degradation (ERAD) pathway. Here we show that overexpression of SVIP in HeLa cells leads to localization of p97/VCP at the plasma membrane, intracellular foci and juxtanuclear vacuoles. The p97/VCP-positive vacuolar structures colocalized or associated with LC3 and lamp1, suggesting that SVIP may regulate autophagy. In support of this possibility, knockdown of SVIP diminished, whereas overexpression of SVIP enhanced LC3 lipidation. Surprisingly, knockdown of SVIP reduced the levels of p62 protein at least partially through downregulation of its mRNA, which was accompanied by a decrease in starvation-induced formation of p62 bodies. Overexpression of SVIP, on the other hand, increased the levels of p62 protein and enhanced starvation-activated autophagy as well as promoted sequestration of polyubiquitinated proteins and p62 in autophagosomes. These results suggest that SVIP plays a regulatory role in p97 subcellular localization and is a novel regulator of autophagy

    Structural and Functional Diversity of Acidic Scorpion Potassium Channel Toxins

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    Background: Although the basic scorpion K + channel toxins (KTxs) are well-known pharmacological tools and potential drug candidates, characterization the acidic KTxs still has the great significance for their potential selectivity towards different K + channel subtypes. Unfortunately, research on the acidic KTxs has been ignored for several years and progressed slowly. Principal Findings: Here, we describe the identification of nine new acidic KTxs by cDNA cloning and bioinformatic analyses. Seven of these toxins belong to three new a-KTx subfamilies (a-KTx28, a-KTx29, and a-KTx30), and two are new members of the known k-KTx2 subfamily. ImKTx104 containing three disulfide bridges, the first member of the a-KTx28 subfamily, has a low sequence homology with other known KTxs, and its NMR structure suggests ImKTx104 adopts a modified cystine-stabilized a-helix-loop-b-sheet (CS-a/b) fold motif that has no apparent a-helixs and b-sheets, but still stabilized by three disulfide bridges. These newly described acidic KTxs exhibit differential pharmacological effects on potassium channels. Acidic scorpion toxin ImKTx104 was the first peptide inhibitor found to affect KCNQ1 channel, which is insensitive to the basic KTxs and is strongly associated with human cardiac abnormalities. ImKTx104 selectively inhibited KCNQ1 channel with a Kd of 11.69 mM, but was less effective against the basic KTxs-sensitive potassium channels. In addition to the ImKTx104 toxin, HeTx204 peptide, containing a cystine-stabilized a-helix-loop-helix (CS-a/a) fold scaffold motif
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