Simultaneous enhancement of out-coupling efficiency, internal quantum efficiency, and color purity in thermally activated delayed fluorescence (TADF) emitters is highly desired for the practical ...application of these materials. We designed and synthesized two isomeric TADF emitters, 2DPyM-mDTC and 3DPyM-pDTC, based on di(pyridinyl)methanone (DPyM) cores as the new electron-accepting units and di(tert-butyl)carbazole (DTC) as the electron-donating units. 3DPyM-pDTC, which is structurally nearly planar with a very small ΔE ST, shows higher color purity, horizontal ratio, and quantum yield than 2DPyM-mDTC, which has a more flexible structure. An electroluminescence device based on 3DPyM-pDTC as the dopant emitter can reach an extremely high external quantum efficiency of 31.9% with a pure blue emission. This work also demonstrates a way to design materials with a high portion of horizontal molecular orientation to realize a highly efficient pure-blue device based on TADF emitters.
MicroRNAs (miRNAs) are involved in tumorigenecity by regulating specific oncogenes and tumor suppressor genes, and their roles in breast cancer stem cells (BCSCs) are becoming apparent. Distinct from ...the CD44(+)/CD24(-/low) sub-population, we have isolated a novel PROCR(+)/ESA(+) BCSC sub-population. To explore miRNA-regulatory mechanisms in this sub-population, we performed miRNA expression profiling and found miR-495 as the most highly upegulated miRNA in PROCR(+)/ESA(+) cells. Coincidently, high upregulation of miR-495 was also found in CD44(+)/CD24(-/low) BCSCs, reflecting its potential importance in maintaining common BCSC properties. Ectopic expression of miR-495 in breast cancer cells promoted their colony formation in vitro and tumorigenesis in mice. miR-495 directly suppressed E-cadherin expression to promote cell invasion and inhibited REDD1 expression to enhance cell proliferation in hypoxia through post-transcriptional mechanism. miR-495 expression was directly modulated by transcription factor E12/E47, which itself is highly expressed in BCSCs. These findings reveal a novel regulatory pathway centered on miR-495 that contributes to BCSC properties and hypoxia resistance.
The rotation curve (RC) of the Milky Way out to ~100 kpc has been constructed using ~16,000 primary red clump giants (PRCGs) in the outer disc selected from the LAMOST Spectroscopic Survey of the ...Galactic Anti-centre (LSS-GAC) and the Sloan Digital Sky Survey (SDSS)-III/APOGEE survey, combined with ~5700 halo K giants (HKGs) selected from the SDSS/SEGUE survey. To derive the RC, the PRCG sample of the warm disc population and the HKG sample of halo stellar population are, respectively, analysed using a kinematical model allowing for the asymmetric drift corrections and re-analysed using the spherical Jeans equation along with measurements of the anisotropic parameter beta currently available. The typical uncertainties of RC derived from the PRCG and HKG samples are, respectively, 5-7 km s super( -1) and several tens km s super( -1). We determine a circular velocity at the solar position, ... and an azimuthal peculiar speed of the Sun, ..., both in good agreement with the previous determinations. The newly constructed RC has a generally flat value of 240 km s super( -1) within a Galactocentric distance rof 25 kpc and then decreases steadily to 150 km s super( -1) at r ~ 100 kpc. On top of this overall trend, the RC exhibits two prominent localized dips, one at r ~ 11 kpc and another at r ~ 19 kpc. From the newly constructed RC, combined with other constraints, we have built a parametrized mass model for the Galaxy, yielding a virial mass of the Milky Way's dark matter halo of ... and a local dark matter density, ... (ProQuest: ... denotes formulae/symbols omitted.)
Previous mass screening studies have shown that IgA antibodies against Epstein–Barr Virus (EBV) can facilitate early detection of nasopharyngeal carcinoma (NPC), but the impact of EBV-antibody ...screening for NPC-specific mortality remains unknown.
A prospective, cluster randomized, controlled trial for NPC screening (PRO-NPC-001) was conducted in 3 selected towns of Zhongshan City and 13 selected towns of Sihui City in southern China beginning in 2008. Serum samples of the screening group were tested for two previously selected anti-EBV antibodies. Subjects with serological medium risk were subsequently retested annually for 3 years, and those with serological high risk were referred to otorhinolaryngologists for diagnostic check-up. An interim analysis was carried out to evaluate the primary end points of the NPC-specific mortality and the early diagnostic rate, and the secondary end point of the NPC incidence, through linkage with the database of Zhongshan City.
Among 70 296 total subjects, 29 413 screened participants (41.8% of the total subjects) in the screening group and 50 636 in the control group, 153 (43.3 per 100 000 person-year), 62 (55.3 per 100 000 person-year) and 99 (33.1 per 100 000 person-year) NPC cases were identified. The early diagnostic rates of NPC were significantly higher in the participants (79.0%, P < 0.0001) and the screening group (45.9%, P < 0.0001) compared with the control group (20.6%). Although no differences were found between NPC-specific mortality of the screening group and the control group relative risk (RR)= 0.82, 95% confidence interval (CI) 0.37–1.79, lower NPC-specific mortality was noticed among participants from the screening group versus the control group (RR = 0.22, 95% CI 0.09–0.49).
IgA antibodies against EBV can identify high-risk population and was effective in screening for early asymptomatic NPC. Although the mortality reduction was not significant in the primary end point, we noted encouraging evidence of a mortality reduction in screening participants in this interim analysis.
NCT00941538.
A 36‐year‐old woman who presented with upper limb distal weakness since the age of 15 years, with gradual progression to the lower limbs, is reported. Hereditary motor neuropathy was initially ...suspected based on distal weakness and hyporeflexia; however, whole exome sequencing accidentally revealed a compound heterozygous variant in the GNE gene, and ultrasound revealed increased homogeneous echogenicity in the involved muscles, which is characteristic of myopathic changes. Muscle magnetic resonance imaging revealed fatty infiltration in all limb muscles, sparing the triceps brachii, vastus lateralis and vastus medialis. Muscle biopsy revealed intracytoplasmic rimmed vacuole, supporting the diagnosis of GNE myopathy.
As a major component of the LAMOST Galactic surveys, the LAMOST Spectroscopic Survey of the Galactic Anticentre (LSS-GAC) aims to survey a significant volume of the Galactic thin/thick discs and halo ...for a contiguous sky area of over 3400 deg2 centred on the Galactic anticentre (|b| ≤ 30°, 150 ≤ l ≤ 210°), and obtain λλ3700–9000 low-resolution (R ∼ 1800) spectra for a statistically complete sample of ∼3 M stars of all colours down to a limiting magnitude of r ∼ 17.8 mag (to 18.5 mag for limited fields). Together with Gaia, the LSS-GAC will yield a unique data set to advance our understanding of the structure and assemblage history of the Galaxy, in particular its disc(s). In addition to the main survey, the LSS-GAC will also target hundreds of thousands objects in the vicinity fields of M 31 and M 33 and survey a significant fraction (over a million) of randomly selected very bright stars (r ≤ 14 mag) in the Northern hemisphere. During the Pilot and the first year Regular Surveys of LAMOST, a total of 1042 586 750 867 spectra of a signal-to-noise ratio S/N(7450 Å) ≥ 10 S/N(4650 Å) ≥ 10 have been collected. In this paper, we present a detailed description of the target selection algorithm, survey design, observations and the first data release of value-added catalogues (including radial velocities, effective temperatures, surface gravities, metallicities, values of interstellar extinction, distances, proper motions and orbital parameters) of the LSS-GAC.
The particulate methane monooxygenase (pMMO) is the first enzyme in the C1 metabolic pathway in methanotrophic bacteria. As this enzyme converts methane into methanol efficiently near room ...temperature, it has become the paradigm for developing an understanding of this difficult C1 chemistry. pMMO is a membrane-bound protein with three subunits (PmoB, PmoA, and PmoC) and 12–14 coppers distributed among different sites. X-ray crystal structures that have revealed only three mononuclear coppers at three sites have neither disclosed the location of the active site nor the catalytic mechanism of the enzyme. Here we report a cyro-EM structure of holo-pMMO from Methylococcus capsulatus (Bath) at 2.5 Å, and develop quantitative electrostatic-potential profiling to scrutinize the nonprotein densities for signatures of the copper cofactors. Our results confirm a mononuclear CuI at the A site, resolve two CuIs at the B site, and uncover additional CuI clusters at the PmoA/PmoC interface within the membrane (D site) and in the water-exposed C-terminal subdomain of the PmoB (E clusters). These findings complete the minimal set of copper factors required for catalytic turnover of pMMO, offering a glimpse of the catalytic machinery for methane oxidation according to the chemical principles underlying the mechanism proposed earlier.
Our current knowledge of cosmic star-formation history during the first two billion years (corresponding to redshift z > 3) is mainly based on galaxies identified in rest-frame ultraviolet light
. ...However, this population of galaxies is known to under-represent the most massive galaxies, which have rich dust content and/or old stellar populations. This raises the questions of the true abundance of massive galaxies and the star-formation-rate density in the early Universe. Although several massive galaxies that are invisible in the ultraviolet have recently been confirmed at early epochs
, most of them are extreme starburst galaxies with star-formation rates exceeding 1,000 solar masses per year, suggesting that they are unlikely to represent the bulk population of massive galaxies. Here we report submillimetre (wavelength 870 micrometres) detections of 39 massive star-forming galaxies at z > 3, which are unseen in the spectral region from the deepest ultraviolet to the near-infrared. With a space density of about 2 × 10
per cubic megaparsec (two orders of magnitude higher than extreme starbursts
) and star-formation rates of 200 solar masses per year, these galaxies represent the bulk population of massive galaxies that has been missed from previous surveys. They contribute a total star-formation-rate density ten times larger than that of equivalently massive ultraviolet-bright galaxies at z > 3. Residing in the most massive dark matter haloes at their redshifts, they are probably the progenitors of the largest present-day galaxies in massive groups and clusters. Such a high abundance of massive and dusty galaxies in the early Universe challenges our understanding of massive-galaxy formation.
Past studies on the issue of learning‐theory foundations in game‐based learning stressed the importance of establishing learning‐theory foundation and provided an exploratory examination of ...established learning theories. However, we found research seldom addressed the development of the use or failure to use learning‐theory foundations and categorized these learning theories into relative types and synthesized their development. We investigate this issue from the perspective of learning theories invoked to underpin educational computer game design and use based on the four types of learning theories: behaviourism, cognitivism, humanism and constructivism. Because the investigation needs to examine and analyse the results from a large number of independent previous studies, this study applied the meta‐analysis method to present a more comprehensive description and discussion of the influence and implications of the findings. This study shows the distribution of development trends for the use of learning theory as a theoretical foundation, as opposed to those that fail to use learning theory in game‐based learning, along with the distribution of types and principles of learning theories that used a learning‐theory foundation. These new findings can supplement the results of previous studies with regard to the issue of learning‐theory foundations in game‐based learning. The contributions of this study for the issue of learning‐theory foundations in game‐based learning are discussed.
Background
Pulsed radiofrequency (PRF) has been widely used to treat chronic pain, but the effectiveness and mechanisms in preventing early neuropathic pain have not been well explored. Even fewer ...knowledge is available in its impact on glia‐mediated nociceptive sensitization. This study aims to elucidate the modulation of PRF on nerve injury‐induced pain development and activation of spinal mitogen‐activated protein kinases (MAPKs).
Methods
In a rat spinal nerve ligation (SNL) model, a low‐volt PRF treatment was applied to the L5 dorsal root ganglion after nerve injury. Nociceptive behaviours were measured by von Frey and heat withdrawal tests at multiple time points. MAPK activations, including p‐ERK and p‐p38, as well as TNF‐α level in the spinal dorsal horn were assessed and the cell types that expressed MAPK activation were identified by double immunofluorescence staining.
Results
We found that SNL promptly induced neuropathic pain in the affected hind limb for over 1 week as well as increased p‐ERK and p‐p38 in the spinal dorsal horn. PRF significantly attenuated SNL‐induced mechanical allodynia and thermal hyperalgesia for 5–7 days. PRF also inhibited ERK and p38 activations, which were found majorly located within neurons and microglia, respectively. Besides, PRF significantly suppressed expression of TNF‐α in the spinal dorsal horn throughout the course.
Conclusions
Low‐volt PRF significantly ameliorated SNL‐induced acute pain. Inferentially, PRF may inhibit spinal sensitization by down‐regulating spinal MAPK activations and activation‐mediated cytokine release. We demonstrated that early PRF treatment in acute nerve injury helps to ameliorate neuropathic pain development.
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