13,452 research outputs found

    Excitonic quantum confinement modified optical conductivity of monolayer and few-layered MoS2

    Get PDF
    2016-2017 > Academic research: refereed > Publication in refereed journal201804_a bcmaVersion of RecordPublishe

    Evidence for a nuclear compartment of transcription and splicing located at chromosome domain boundaries

    Get PDF
    The nuclear topography of splicing snRNPs, mRNA transcripts and chromosome domains in various mammalian cell types are described. The visualization of splicing snRNPs, defined by the Sm antigen, and coiled bodies, revealed distinctly different distribution patterns in these cell types. Heat shock experiments confirmed that the distribution patterns also depend on physiological parameters. Using a combination of fluorescencein situ hybridization and immunodetection protocols, individual chromosome domains were visualized simultaneously with the Sm antigen or the transcript of an integrated human papilloma virus genome. Three-dimensional analysis of fluorescence-stained target regions was performed by confocal laser scanning microscopy. RNA transcripts and components of the splicing machinery were found to be generally excluded from the interior of the territories occupied by the individual chromosomes. Based on these findings we present a model for the functional compartmentalization of the cell nucleus. According to this model the space between chromosome domains, including the surface areas of these domains, defines a three-dimensional network-like compartment, termed the interchromosome domain (ICD) compartment, in which transcription and splicing of mRNA occurs

    Biological impacts of 'hot-spot' mutations of hepatitis B virus X proteins are genotype B and C differentiated

    Get PDF
    AIM: To investigate the biological impacts of “hot-spot” mutations on genotype B and C HBV X proteins (HBx). METHODS: Five types of “hot-spot” mutations of genotype B or C HBV X genes, which sequentially lead to the amino acid substitutions of HBx as I127T, F132Y, K130M+V131I, I127T+K130M+V131I, or K130M+V131I+F132Y, respectively, were generated by means of site-directed mutagenesis. To evaluate the anti-proliferative effects, HBx or related mutants’ expression vectors were transfected separately to the Chang cells by lipofectamine, and the cells were cultured in hygromycin selective medium for 14 d, drug-resistant colonies were fixed with cold methanol, stained with Giemsa dyes and scored (increase of the colonies indicated the reduction of the anti-proliferation activity, and vice versa). Different types of HBx expression vectors were co-transfected separately with the reporter plasmid pCMVβ to Chang cells, which were lysed 48 h post-transfection and the intra-cellular β-galactosidase activities were monitored (increase of the β-galactosidase activities indicated the reduction of the transactivation activity, and vice versa). All data obtained were calculated by paired-samples t-test. RESULTS: As compared to standard genotype B HBx, mutants of I127T and I127T+K130M+V131I showed higher transactivation and anti-proliferative activities, while the mutants of F132Y, K130M+V131I, and K130M+V131I+F132Y showed lower activities. As compared to standard genotype C HBx, I127T mutant showed higher transactivation activity, while the other four types of mutants showed no differences. With regard to anti-proliferative activity, compared to standard genotype C HBx, F132Y and K130M+V131I mutants showed lower activities, and K130M+V131I +F132Y mutant, on the other hand, showed higher activity, while the mutants of I127T and I127T+K130M+V131I showed no differences. CONCLUSION: “Hot-spot” mutations affect the anti-proliferation and transactivation activities of genotype B and/or C HBx, and the biological impacts of most “hot-spot” mutations on HBx are genotype B and C differentiated.published_or_final_versio

    The incidence of liver injury in Uyghur patients treated for TB in Xinjiang Uyghur autonomous region, China, and its association with hepatic enzyme polymorphisms nat2, cyp2e1, gstm1 and gstt1.

    Get PDF
    BACKGROUND AND OBJECTIVE: Of three first-line anti-tuberculosis (anti-TB) drugs, isoniazid is most commonly associated with hepatotoxicity. Differences in INH-induced toxicity have been attributed to genetic variability at several loci, NAT2, CYP2E1, GSTM1and GSTT1, that code for drug-metabolizing enzymes. This study evaluated whether the polymorphisms in these enzymes were associated with an increased risk of anti-TB drug-induced hepatitis in patients and could potentially be used to identify patients at risk of liver injury. METHODS AND DESIGN: In a cross-sectional study, 2244 tuberculosis patients were assessed two months after the start of treatment. Anti-TB drug-induced liver injury (ATLI) was defined as an ALT, AST or bilirubin value more than twice the upper limit of normal. NAT2, CYP2E1, GSTM1 and GSTT1 genotypes were determined using the PCR/ligase detection reaction assays. RESULTS: 2244 patients were evaluated, there were 89 cases of ATLI, a prevalence of 4% 9 patients (0.4%) had ALT levels more than 5 times the upper limit of normal. The prevalence of ATLI was greater among men than women, and there was a weak association with NAT2*5 genotypes, with ATLI more common among patients with the NAT2*5*CT genotype. The sensitivity of the CT genotype for identifying patients with ATLI was 42% and the positive predictive value 5.9%. CT ATLI was more common among slow acetylators (prevalence ratio 2.0 (95% CI 0.95,4.20) )compared to rapid acetylators. There was no evidence that ATLI was associated with CYP2E1 RsaIc1/c1genotype, CYP2E1 RsaIc1/c2 or c2/c2 genotypes, or GSTM1/GSTT1 null genotypes. CONCLUSIONS: In Xinjiang Uyghur TB patients, liver injury was associated with the genetic variant NAT2*5, however the genetic markers studied are unlikely to be useful for screening patients due to the low sensitivity and low positive predictive values for identifying persons at risk of liver injury

    Super-resolution far-field ghost imaging via compressive sampling

    Full text link
    Much more image details can be resolved by improving the system's imaging resolution and enhancing the resolution beyond the system's Rayleigh diffraction limit is generally called super-resolution. By combining the sparse prior property of images with the ghost imaging method, we demonstrated experimentally that super-resolution imaging can be nonlocally achieved in the far field even without looking at the object. Physical explanation of super-resolution ghost imaging via compressive sampling and its potential applications are also discussed.Comment: 4pages,4figure

    Groupwise Multimodal Image Registration using Joint Total Variation

    Get PDF
    In medical imaging it is common practice to acquire a wide range of modalities (MRI, CT, PET, etc.), to highlight different structures or pathologies. As patient movement between scans or scanning session is unavoidable, registration is often an essential step before any subsequent image analysis. In this paper, we introduce a cost function based on joint total variation for such multimodal image registration. This cost function has the advantage of enabling principled, groupwise alignment of multiple images, whilst being insensitive to strong intensity non-uniformities. We evaluate our algorithm on rigidly aligning both simulated and real 3D brain scans. This validation shows robustness to strong intensity non-uniformities and low registration errors for CT/PET to MRI alignment. Our implementation is publicly available at https://github.com/brudfors/coregistration-njtv

    A natural product-like JAK2/STAT3 inhibitor induces apoptosis of malignant melanoma cells

    Get PDF
    The JAK2/STAT3 signaling pathway plays a critical role in tumorigenesis, and has been suggested as a potential molecular target for anti-melanoma therapeutics. However, few JAK2 inhibitors were being tested for melanoma therapy. In this study, eight amentoflavone analogues were evaluated for their activity against human malignant melanoma cells. The most potent analogue, compound 1, inhibited the phosphorylation of JAK2 and STAT3 in human melanoma cells, but had no discernible effect on total JAK2 and STAT3 levels. A cellular thermal shift assay was performed to identify that JAK2 is engaged by 1 in cell lysates. Moreover, compound 1 showed higher antiproliferative activity against human melanoma A375 cells compared to a panel of cancer and normal cell lines. Compound 1 also activated caspase-3 and cleaved PARP, which are markers of apoptosis, and suppressed the anti-apoptotic Bcl-2 level. Finally, compound 1 induced apoptosis in 80% of treated melanoma cells. To our knowledge, compound 1 is the first amentoflavone-based JAK2 inhibitor to be investigated for use as an anti-melanoma agent.published_or_final_versio

    Electrically-driven phase transition in magnetite nanostructures

    Full text link
    Magnetite (Fe3_{3}O4_{4}), an archetypal transition metal oxide, has been used for thousands of years, from lodestones in primitive compasses[1] to a candidate material for magnetoelectronic devices.[2] In 1939 Verwey[3] found that bulk magnetite undergoes a transition at TV_{V} \approx 120 K from a high temperature "bad metal" conducting phase to a low-temperature insulating phase. He suggested[4] that high temperature conduction is via the fluctuating and correlated valences of the octahedral iron atoms, and that the transition is the onset of charge ordering upon cooling. The Verwey transition mechanism and the question of charge ordering remain highly controversial.[5-11] Here we show that magnetite nanocrystals and single-crystal thin films exhibit an electrically driven phase transition below the Verwey temperature. The signature of this transition is the onset of sharp conductance switching in high electric fields, hysteretic in voltage. We demonstrate that this transition is not due to local heating, but instead is due to the breakdown of the correlated insulating state when driven out of equilibrium by electrical bias. We anticipate that further studies of this newly observed transition and its low-temperature conducting phase will shed light on how charge ordering and vibrational degrees of freedom determine the ground state of this important compound.Comment: 17 pages, 4 figure

    Infectious Disease Ontology

    Get PDF
    Technological developments have resulted in tremendous increases in the volume and diversity of the data and information that must be processed in the course of biomedical and clinical research and practice. Researchers are at the same time under ever greater pressure to share data and to take steps to ensure that data resources are interoperable. The use of ontologies to annotate data has proven successful in supporting these goals and in providing new possibilities for the automated processing of data and information. In this chapter, we describe different types of vocabulary resources and emphasize those features of formal ontologies that make them most useful for computational applications. We describe current uses of ontologies and discuss future goals for ontology-based computing, focusing on its use in the field of infectious diseases. We review the largest and most widely used vocabulary resources relevant to the study of infectious diseases and conclude with a description of the Infectious Disease Ontology (IDO) suite of interoperable ontology modules that together cover the entire infectious disease domain
    corecore