400 research outputs found
Quantum walk on a line for a trapped ion
We show that a multi-step quantum walk can be realized for a single trapped
ion with interpolation between quantum and random walk achieved by randomizing
the generalized Hadamard coin flip phase. The signature of the quantum walk is
manifested not only in the ion's position but also its phonon number, which
makes an ion trap implementation of the quantum walk feasible.Comment: 5 pages, 3 figure
Steps Toward Determination of the Size and Structure of the Broad-Line Region in Active Galactic Nuclei. XV. Long-Term Optical Monitoring of NGC 5548
We present the results of three years of ground-based observations of the
Seyfert 1 galaxy NGC 5548, which combined with previously reported data, yield
optical continuum and broad-line H-beta light curves for a total of eight
years. The light curves consist of over 800 points, with a typical spacing of a
few days between observations. During this eight-year period, the nuclear
continuum has varied by more than a factor of seven, and the H-beta emission
line has varied by a factor of nearly six. The H-beta emission line responds to
continuum variations with a time delay or lag of 10-20 days, the precise value
varying somewhat from year to year. We find some indications that the lag
varies with continuum flux in the sense that the lag is larger when the source
is brighter.Comment: 29 pages, 6 figures. Accepted for publication in ApJ (1999 Jan 10
Strain induced exciton fine-structure splitting and shift in bent ZnO microwires
Lattice strain is a useful and economic way to tune the device performance and is commonly present in nanostructures. Here, we investigated for the first time the exciton spectra evolution in bent ZnO microwires along the radial direction via high spatial/energy resolution cathodeluminescence spectroscopy at 5.5â
K. Our experiments show that the exciton peak splits into multi fine peaks towards the compressive part while retains one peak in the tensile part and the emission peak displays a continuous blue-shift from tensile to compressive edges. In combination with first-principles calculations, we show that the observed NBE emission splitting is due to the valence band splitting and the absence of peak splitting in the tensile part maybe due to the highly localized holes in the A band and the carrier density distribution across the microwire. Our studies may pave the way to design nanophotonic and electronic devices using bent ZnO nanowires
The long non-coding RNA HOTAIR is transcriptionally activated by HOXA9 and is an independent prognostic marker in patients with malignant glioma
The lncRNA HOTAIR has been implicated in several human cancers. Here, we evaluated the molecular alterations and upstream regulatory mechanisms of HOTAIR in glioma, the most common primary brain tumors, and its clinical relevance. HOTAIR gene expression, methylation, copy-number and prognostic value were investigated in human gliomas integrating data from online datasets and our cohorts. High levels of HOTAIR were associated with higher grades of glioma, particularly IDH wild-type cases. Mechanistically, HOTAIR was overexpressed in a gene dosage-independent manner, while DNA methylation levels of particular CpGs in HOTAIR locus were associated with HOTAIR expression levels in GBM clinical specimens and cell lines. Concordantly, the demethylating agent 5-Aza-2'-deoxycytidine affected HOTAIR transcriptional levels in a cell line-dependent manner. Importantly, HOTAIR was frequently co-expressed with HOXA9 in high-grade gliomas from TCGA, Oncomine, and our Portuguese and French datasets. Integrated in silico analyses, chromatin immunoprecipitation, and qPCR data showed that HOXA9 binds directly to the promoter of HOTAIR. Clinically, GBM patients with high HOTAIR expression had a significantly reduced overall survival, independently of other prognostic variables. In summary, this work reveals HOXA9 as a novel direct regulator of HOTAIR, and establishes HOTAIR as an independent prognostic marker, providing new therapeutic opportunities to treat this highly aggressive cancer.Fundação Para A CiĂȘncia e Tecnologia (PTDC/ SAU-GMG/113795/2009; SFRH/BPD/33612/2009 and IF/00601/2012 to B.M.C.; SFRH/BD/88220/2012 to A.X.M.; SFRH/BD/92786/2013 to C.S.G; SFRH/BD/81042/2011 to M.P.; and SFRH/BD/51996/2012 to T.L.), Project co-financed by Programa Operacional Regional do Norte (ON.2 â O Novo Norte), Quadro de ReferĂȘncia EstratĂ©gico Nacional (QREN), Fundo Europeu de Desenvolvimento Regional (FEDER); Fundação Calouste Gulbenkian (B.M.C.); and Liga Portuguesa Contra o Cancro, Portugal (B.M.C.). This article has been developed under the scope of the projects NORTE-01-0246-FEDER-000012, NORTE-01-0145-FEDER-000023 and NORTE-01-0145FEDER-000013, supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER). This work has been funded by FEDER funds, through the Competitiveness Factors Operational Programme (COMPETE), and by National funds, through the Foundation for Science and Technology (FCT), under the scope of the project POCI01-0145-FEDER-007038. C.J. acknowledges NHS funding to the Biomedical Research Centre. P.A. acknowledges the Plan Cancer-INSERM (CS14085CSâGliobivâ, PA), the CancĂ©ropole CLARA (Oncostarter «Gliohoxas»; PA), Fonds de dotation Patrick Brou de LauriĂ©re (PA).info:eu-repo/semantics/publishedVersio
CD133 in brain tumor: the prognostic factor
CD133 has been shown to be an important stem cell factor that promotes glioma progression. However, the mechanism for CD133-mediated glioma progression has yet to be fully elucidated. In this study, we found that CD133 mRNA expression was a prognostic marker in three independent glioma patient cohorts, corroborating a putative role for CD133 in glioma progression. Importantly, we found that CD133 expression in glioma was highly correlated with the expression of HOX gene stem cell factors (HOXA5, HOXA7, HOXA10, HOXC4 and HOXC6). The expression of these HOX genes individually was significantly associated with survival. Interestingly, the prognostic significance of CD133 was dependent on the expression level of HOX genes, and vice versa. CD133 (p = 0.021) and HOXA7 (p = 0.001) were independent prognostic markers when the three glioma patient cohorts were combined (n = 231). Our results suggest that HOX genes may play a more important role in progression of glioma when CD133 expression is low. Furthermore, we showed that low-level expression of LIM2 in CD133-high glioma was associated with poorer survival, suggesting that LIM2 could be a therapeutic target for glioma expressing a high level of CD133. Connectivity mapping identified vinblastine and vincristine as agents that could reverse the CD133/HOX genes/LIM2-signature, and we confirmed this by in vitro analysis in glioma cell lines, demonstrating that CD133 and HOX genes were co-expressed and could be downregulated by vincristine. In conclusion, our data show that CD133 and HOX genes are important prognostic markers in glioma and shed light on possible treatment strategies for glioma expressing a high level of CD133
Cadm1-Expressing Synapses on Purkinje Cell Dendrites Are Involved in Mouse Ultrasonic Vocalization Activity
Foxp2(R552H) knock-in (KI) mouse pups with a mutation related to human speechâlanguage disorders exhibit poor development of cerebellar Purkinje cells and impaired ultrasonic vocalization (USV), a communication tool for mother-offspring interactions. Thus, human speech and mouse USV appear to have a Foxp2-mediated common molecular basis in the cerebellum. Mutations in the gene encoding the synaptic adhesion molecule CADM1 (RA175/Necl2/SynCAM1/Cadm1) have been identified in people with autism spectrum disorder (ASD) who have impaired speech and language. In the present study, we show that both Cadm1-deficient knockout (KO) pups and Foxp2(R552H) KI pups exhibit impaired USV and smaller cerebellums. Cadm1 was preferentially localized to the apicalâdistal portion of the dendritic arbor of Purkinje cells in the molecular layer of wild-type pups, and VGluT1 level decreased in the cerebellum of Cadm1 KO mice. In addition, we detected reduced immunoreactivity of Cadm1 and VGluT1 on the poorly developed dendritic arbor of Purkinje cells in the Foxp2(R552H) KI pups. However, Cadm1 mRNA expression was not altered in the Foxp2(R552H) KI pups. These results suggest that although the Foxp2 transcription factor does not target Cadm1, Cadm1 at the synapses of Purkinje cells and parallel fibers is necessary for USV function. The loss of Cadm1-expressing synapses on the dendrites of Purkinje cells may be associated with the USV impairment that Cadm1 KO and Foxp2(R552H) KI mice exhibit
Current trends in drug metabolism and pharmacokinetics.
Pharmacokinetics (PK) is the study of the absorption, distribution, metabolism, and excretion (ADME) processes of a drug. Understanding PK properties is essential for drug development and precision medication. In this review we provided an overview of recent research on PK with focus on the following aspects: (1) an update on drug-metabolizing enzymes and transporters in the determination of PK, as well as advances in xenobiotic receptors and noncoding RNAs (ncRNAs) in the modulation of PK, providing new understanding of the transcriptional and posttranscriptional regulatory mechanisms that result in inter-individual variations in pharmacotherapy; (2) current status and trends in assessing drug-drug interactions, especially interactions between drugs and herbs, between drugs and therapeutic biologics, and microbiota-mediated interactions; (3) advances in understanding the effects of diseases on PK, particularly changes in metabolizing enzymes and transporters with disease progression; (4) trends in mathematical modeling including physiologically-based PK modeling and novel animal models such as CRISPR/Cas9-based animal models for DMPK studies; (5) emerging non-classical xenobiotic metabolic pathways and the involvement of novel metabolic enzymes, especially non-P450s. Existing challenges and perspectives on future directions are discussed, and may stimulate the development of new research models, technologies, and strategies towards the development of better drugs and improved clinical practice
Reactive spreading: adsorption, ridging and compound formation
Reactive spreading, in which a chemically active element is added to promote wetting of noble metals on nonmetallic materials, is evaluated. Theories for the energetics and kinetics of the necessary steps involved in spreading are outlined and compared to the steps in compound formation that typically accompany reactive wetting. These include: fluid flow, active metal adsorption, including nonequilibrium effects, and triple line ridging. All of these can be faster than compound nucleation under certain conditions. Analysis and assessment of recently reported experiments on metal/ceramic systems lead to a focus on those conditions under which spreading proceeds ahead of the actual formation of a new phase at the interface. This scenario may be more typical than believed, and perhaps the most effective situation leading to enhanced spreading. A rationale for the pervasive variability and hysteresis observed during high temperature wetting also emerges
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