6,924 research outputs found
On the Narrative Features of British Sitcoms: Take The IT Crowd and Yes, Prime Minister as Examples
In recent years, British TV dramas have been a glaring phenomenon and the “new favorite” of fans who love watching overseas TV plays. This paper takes two TV dramas of The IT Crowd and Yes, Prime Minister for case studies, explores the narrative features of British sitcom from dramatic narrative tendency, core narration of “people”, self-deprecating humor, unity of conflict and social significance, concludes three points of inspiration for China’s film and television creation: “learn” instead of “imitate”, “serious” instead of “funny”, “modern” as well as “traditional.”
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Zika virus promotes CCN1 expression via the CaMKIIα-CREB pathway in astrocytes.
Zika virus (ZIKV) infection in the human central nervous system (CNS) causes Guillain-Barre syndrome, cerebellum deformity, and other diseases. Astrocytes are immune response cells in the CNS and an important component of the blood-brain barrier. Consequently, any damage to astrocytes facilitates the spread of ZIKV in the CNS. Connective tissue growth factor/Nephroblastoma overexpressed gene family 1 (CCN1), an important inflammatory factor secreted by astrocytes, is reported to regulate innate immunity and viral infection. However, the mechanism by which astrocyte viral infection affects CCN1 expression remains undefined. In this study, we demonstrate that ZIKV infection up-regulates CCN1 expression in astrocytes, thus promoting intracellular viral replication. Other studies revealed that the cAMP response element (CRE) in the CCN1 promoter is activated by the ZIKV NS3 protein. The cAMP-responsive element-binding protein (CREB), a transacting factor of the CRE, is also activated by NS3 or ZIKV. Furthermore,a specific inhibitor of CREB, i.e. SGC-CBP30, reduced ZIKV-induced CCN1 up-regulation and ZIKV replication. Moreover, co-immunoprecipitation, overexpression, and knockdown studies confirmed that the interaction between NS3 and the regulatory domain of CaMKIIα could activate the CREB pathway, thus resulting in the up-regulation of CCN1 expression and enhancement of virus replication. In conclusion, the findings of our investigations on the NS3-CaMKIIα-CREB-CCN1 pathway provide a foundation for understanding the infection mechanism of ZIKV in the CNS
Tick-borne encephalitis virus induces chemokine RANTES expression via activation of IRF-3 pathway.
BACKGROUND: Tick-borne encephalitis virus (TBEV) is one of the most important flaviviruses that targets the central nervous system (CNS) and causes encephalitides in humans. Although neuroinflammatory mechanisms may contribute to brain tissue destruction, the induction pathways and potential roles of specific chemokines in TBEV-mediated neurological disease are poorly understood. METHODS: BALB/c mice were intracerebrally injected with TBEV, followed by evaluation of chemokine and cytokine profiles using protein array analysis. The virus-infected mice were treated with the CC chemokine antagonist Met-RANTES or anti-RANTES mAb to determine the role of RANTES in affecting TBEV-induced neurological disease. The underlying signaling mechanisms were delineated using RANTES promoter luciferase reporter assay, siRNA-mediated knockdown, and pharmacological inhibitors in human brain-derived cell culture models. RESULTS: In a mouse model, pathological features including marked inflammatory cell infiltrates were observed in brain sections, which correlated with a robust up-regulation of RANTES within the brain but not in peripheral tissues and sera. Antagonizing RANTES within CNS extended the survival of mice and reduced accumulation of infiltrating cells in the brain after TBEV infection. Through in vitro studies, we show that virus infection up-regulated RANTES production at both mRNA and protein levels in human brain-derived cell lines and primary progenitor-derived astrocytes. Furthermore, IRF-3 pathway appeared to be essential for TBEV-induced RANTES production. Site mutation of an IRF-3-binding motif abrogated the RANTES promoter activity in virus-infected brain cells. Moreover, IRF-3 was activated upon TBEV infection as evidenced by phosphorylation of TBK1 and IRF-3, while blockade of IRF-3 activation drastically reduced virus-induced RANTES expression. CONCLUSIONS: Our findings together provide insights into the molecular mechanism underlying RANTES production induced by TBEV, highlighting its potential importance in the process of neuroinflammatory responses to TBEV infection
C-Terminus of Progranulin Interacts with the Beta-Propeller Region of Sortilin to Regulate Progranulin Trafficking
Progranulin haplo-insufficiency is a main cause of frontotemporal lobar degeneration (FTLD) with TDP-43 aggregates. Previous studies have shown that sortilin regulates progranulin trafficking and is a main determinant of progranulin level in the brain. In this study, we mapped the binding site between progranulin and sortilin. Progranulin binds to the beta-propeller region of sortilin through its C-terminal tail. The C-terminal progranulin fragment is fully sufficient for sortilin binding and progranulin C-terminal peptide displaces progranulin binding to sortilin. Deletion of the last 3 residues of progranulin (QLL) abolishes its binding to sortilin and also sortilin dependent regulation of progranulin trafficking. Since progranulin haplo-insufficiency results in FTLD, these results may provide important insights into future studies of progranulin trafficking and signaling and progranulin based therapy for FTLD
Characterization of High-Performance Organic Dyes for Dye-Sensitized Solar Cell: A DFT/TDDFT Study
Dye-sensitized solar cell (DSSC) is currently a promising technology that makes solar energy efficient and cost-effective to harness. In DSSC, metal free dyes, such indoline-containing D149 and D205, are proved to be potential alternatives for traditional metal organic dyes. In this work, a DFT/TDDFT characterization for D149 and D205 were carried out using different functionals, including B3LYP, MPW1K, CAM-B3LYP and PBE0. Three different conformers for D149 and four different conformers for D205 were identified and calculated in vacuum. The performance of different functionals on calculating the maximum absorbance of the dyes in vacuum and five common solvents (acetonitrile, chloroform, ethanol, methanol, and THF) were examined and compared to determine the suitable computational setting for predicting properties of these two dyes. Furthermore, deprotonated D149 and D205 in solvents were also considered, and the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) were calculated, which elucidates the substitution effect on the rhodanine ring of D149 and D205 dyes on their efficiency. Finally, D149 and D205 molecules were confirmed to be firmly anchored on ZnO surface by periodic DFT calculations. These results would shed light on the design of new highly efficiency metal-free dyes.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author
Radiative Transfer Modeling of Lyman Alpha Emitters. I. Statistics of Spectra and Luminosity
We combine a cosmological reionization simulation with box size of 100Mpc/h
on a side and a Monte Carlo Lyman-alpha (Lya) radiative transfer code to model
Lyman Alpha Emitters (LAEs) at z~5.7. The model introduces Lya radiative
transfer as the single factor for transforming the intrinsic Lya emission
properties into the observed ones. Spatial diffusion of Lya photons from
radiative transfer results in extended Lya emission and only the central part
with high surface brightness can be observed. Because of radiative transfer,
the appearance of LAEs depends on density and velocity structures in
circumgalactic and intergalactic media as well as the viewing angle, which
leads to a broad distribution of apparent (observed) Lya luminosity for a given
intrinsic Lya luminosity. Radiative transfer also causes frequency diffusion of
Lya photons. The resultant Lya line is asymmetric with a red tail. The peak of
the Lya line shifts towards longer wavelength and the shift is anti-correlated
with the apparent to intrinsic Lya luminosity ratio. The simple radiative
transfer model provides a new framework for studying LAEs. It is able to
explain an array of observed properties of z~5.7 LAEs in Ouchi et al. (2008),
producing Lya spectra, morphology, and apparent Lya luminosity function (LF)
similar to those seen in observation. The broad distribution of apparent Lya
luminosity at fixed UV luminosity provides a natural explanation for the
observed UV LF, especially the turnover towards the low luminosity end. The
model also reproduces the observed distribution of Lya equivalent width (EW)
and explains the deficit of UV bright, high EW sources. Because of the broad
distribution of the apparent to intrinsic Lya luminosity ratio, the model
predicts effective duty cycles and Lya escape fractions for LAEs.Comment: 28 pages, 22 figures, accepted for publication in ApJ, revised
according to the referee's comment
Measurement uncertainty relation for three observables
In this work we establish rigorously a measurement uncertainty relation (MUR)
for three unbiased qubit observables, which was previously shown to hold true
under some presumptions. The triplet MUR states that the uncertainty, which is
quantified by the total statistic distance between the target observables and
the jointly implemented observables, is lower bounded by an incompatibility
measure that reflects the joint measurement conditions. We derive a necessary
and sufficient condition for the triplet MUR to be saturated and the
corresponding optimal measurement. To facilitate experimental tests of MURs we
propose a straightforward implementation of the optimal joint measurements. The
exact values of incompatibility measure are analytically calculated for some
symmetric triplets when the corresponding triplet MURs are not saturated. We
anticipate that our work may enrich the understanding of quantum
incompatibility in terms of MURs and inspire further applications in quantum
information science. This work presents a complete theory relevant to a
parallel work [Y.-L. Mao, et al., Testing Heisenberg's measurement uncertainty
relation of three observables, arXiv:2211.09389] on experimental tests.Comment: arXiv admin note: substantial text overlap with arXiv:2211.0938
Chirality Effects in Peptide Assembly Structures
Peptide assembly structures have been widely exploited in fabricating biomaterials that are promising for medical applications. Peptides can self-organize into various highly ordered supramolecular architectures, such as nanofibril, nanobelt, nanotube, nanowire, and vesicle. Detailed studies of the molecular mechanism by which these versatile building blocks assemble can guide the design of peptide architectures with desired structure and functionality. It has been revealed that peptide assembly structures are highly sequence-dependent and sensitive to amino acid composition, the chirality of peptide and amino acid residues, and external factors, such as solvent, pH, and temperature. This mini-review focuses on the regulatory effects of chirality alteration on the structure and bioactivity of linear and cyclic peptide assemblies. In addition, chiral self-sorting and co-assembly of racemic peptide mixtures were discussed
cis-4-(Tosyloxymethyl)cyclohexanecarboxylic acid
The title compound, C15H20O5S, is an intermediate in the synthesis of novel aminocarboxylic acid derivatives. The cyclohexane ring exhibits a chair conformation. In the crystal structure, adjacent molecules form dimers via O—H⋯O hydrogen bonds
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