Yes-associated protein (YAP) is a downstream effector of the Hippo signaling pathway, which controls organ expansion and tissue development. We have recently defined the tumorigenic potential and ...clinical significance of the YAP1 oncogene in human hepatocellular carcinoma (HCC). The present study aims to define the tumorigenic properties of YAP in HCC and elucidate the related downstream signaling mechanism. In a gain-of-function study, we demonstrated that ectopic increased expression of YAP in the immortalized non-tumorigenic hepatocyte cell line MIHA confers tumorigenic and metastatic potentials, as evidenced by (1) enhanced aptitudes in cell viability, anchorage-independent growth, migration and invasion; (2) tumor formation in a xenograft mouse model; and (3) induction of HCC biomarker α-fetoprotein and activation of mitogen-activated protein kinase. Furthermore, we have identified AXL, a receptor tyrosine kinase, as a key downstream target that drives YAP-dependent oncogenic functions. RNAi-mediated knockdown of AXL expression decreased the ability of YAP-expressing MIHA cells and of the primary HCC cell line to proliferate and invade. These results indicate that AXL is a mediator of YAP-dependent oncogenic activities and implicates it as a potential therapeutic target for HCC.
ASASSN-15lh: A highly super-luminous supernova Dong, Subo; Shappee, B. J.; Prieto, J. L. ...
Science (American Association for the Advancement of Science),
01/2016, Letnik:
351, Številka:
6270
Journal Article
Recenzirano
Odprti dostop
We report the discovery of ASASSN-15lh (SN 2015L), which we interpret as the most luminous supernova yet found. At redshift z = 0.2326, ASASSN-15lh reached an absolute magnitude of Mu,AB = −23.5 ± ...0.1 and bolometric luminosity Lbol = (2.2 ± 0.2) × 10⁴⁵ ergs s⁻¹, which is more than twice as luminous as any previously known supernova. It has several major features characteristic of the hydrogen-poor super-luminous supernovae (SLSNe-l), whose energy sources and progenitors are currently poorly understood. In contrast to most previously known SLSNe-l that reside in star-forming dwarf galaxies, ASASSN-15lh appears to be hosted by a luminous galaxy (MK ≈ −25.5) with little star formation. In the 4 months since first detection, ASASSN-15lh radiated (1.1 ± 0.2) × 10⁵² ergs, challenging the magnetar model for its engine.
The associations between long-term risk of hepatocellular carcinoma (HCC) and spontaneous seroclearance of HBV e antigen (HBeAg), HBV DNA and HBV surface antigen (HBsAg) have never been examined by a ...prospective study using serially measured seromarkers. This study aimed to assess the importance of spontaneous HBeAg, HBV DNA and HBsAg seroclearance in the prediction of HCC risk.
This study included 2946 HBsAg seropositive individuals who were seronegative for antibodies against HCV and free of liver cirrhosis. Serial serum samples collected at study entry and follow-up health examinations were tested for HBeAg, HBV DNA and HBsAg. Cox proportional hazards models were used to calculate the HRs of developing HCC after seroclearance of HBV markers.
The HR (95% CI) of developing HCC after seroclearance of HBeAg, HBV DNA and HBsAg during follow-up was 0.63 (0.38 to 1.05), 0.24 (0.11 to 0.57) and 0.18 (0.09 to 0.38), respectively, after adjustment for age, gender and serum level of alanine aminotransferase at study entry. High HBV DNA levels at the seroclearance of HBeAg (mean±SD, 4.35±1.64 log10 IU/mL) may explain the non-significant association between HBeAg seroclearance and HCC risk. Among HBeAg seronegative participants with detectable serum HBV DNA at study entry, the lifetime (30-75-years-old) cumulative incidence of HCC was 4.0%, 6.6% and 14.2%, respectively, for those with seroclearance of both HBV DNA and HBsAg, seroclearance of HBV DNA only, and seroclearance of neither.
Spontaneous seroclearance of HBV DNA and HBsAg are important predictors of reduced HCC risk.
Abstract
Topological superconductors (TSCs) are unconventional superconductors with bulk superconducting gap and in-gap Majorana states on the boundary that may be used as topological qubits for ...quantum computation. Despite their importance in both fundamental research and applications, natural TSCs are very rare. Here, combining state of the art synchrotron and laser-based angle-resolved photoemission spectroscopy, we investigated a stoichiometric transition metal dichalcogenide (TMD), 2M-WS
2
with a superconducting transition temperature of 8.8 K (the highest among all TMDs in the natural form up to date) and observed distinctive topological surface states (TSSs). Furthermore, in the superconducting state, we found that the TSSs acquired a nodeless superconducting gap with similar magnitude as that of the bulk states. These discoveries not only evidence 2M-WS
2
as an intrinsic TSC without the need of sensitive composition tuning or sophisticated heterostructures fabrication, but also provide an ideal platform for device applications thanks to its van der Waals layered structure.
Alloys with ultra-high strength and sufficient ductility are highly desired for modern engineering applications but difficult to develop. Here we report that, by a careful controlling alloy ...composition, thermomechanical process, and microstructural feature, a Co-Cr-Ni-based medium-entropy alloy (MEA) with a dual heterogeneous structure of both matrix and precipitates can be designed to provide an ultra-high tensile strength of 2.2 GPa and uniform elongation of 13% at ambient temperature, properties that are much improved over their counterparts without the heterogeneous structure. Electron microscopy characterizations reveal that the dual heterogeneous structures are composed of a heterogeneous matrix with both coarse grains (10∼30 μm) and ultra-fine grains (0.5∼2 μm), together with heterogeneous L1
-structured nanoprecipitates ranging from several to hundreds of nanometers. The heterogeneous L1
nanoprecipitates are fully coherent with the matrix, minimizing the elastic misfit strain of interfaces, relieving the stress concentration during deformation, and playing an active role in enhanced ductility.
Talaromyces marneffei
(
T. marneffei
) can cause talaromycosis, a fatal systemic mycosis, in patients with AIDS. With the increasing number of talaromycosis cases in Guangdong, China, we aimed to ...investigate the susceptibility of 189
T. marneffei
clinical strains to eight antifungal agents, including three echinocandins (anidulafungin, micafungin, and caspofungin), four azoles (posaconazole, itraconazole, voriconazole, and fluconazole), and amphotericin B, with determining minimal inhibition concentrations (MIC) by Sensititre YeastOne™ YO10 assay in the yeast phase. The MICs of anidulafungin, micafungin, caspofungin, posaconazole, itraconazole, voriconazole, fluconazole, and amphotericin B were 2 to > 8 μg/ml, >8 μg/ml, 2 to > 8 μg/ml, ≤ 0.008 to 0.06 μg/ml, ≤ 0.015 to 0.03 μg/ml, ≤ 0.008 to 0.06 μg/ml, 1 to 32 μg/ml, and ≤ 0.12 to 1 μg/ml, respectively. The MICs of all echinocandins were very high, while the MICs of posaconazole, itraconazole, and voriconazole, as well as amphotericin B were comparatively low. Notably, fluconazole was found to have a higher MIC than other azoles, and exhibited particularly weak activity against some isolates with MICs over 8 μg/ml. Our data in vitro support the use of amphotericin B, itraconazole, voriconazole, and posaconazole in management of talaromycosis and suggest potential resistance to fluconazole.
High-temperature superconductivity emerges on doping holes or electrons into antiferromagnetic copper oxides. The large energy scale of magnetic excitations, for example, compared with phonon ...energies, is thought to drive superconductivity with high transition temperatures (Tc). Comparing high-energy magnetic excitations of hole- and electron-doped superconductors provides an opportunity to test this hypothesis. Here, we use resonant inelastic X-ray scattering at the Cu L3-edge to reveal collective excitations in the electron-doped cuprate Nd2xCexCuO4. Surprisingly, magnetic excitations harden signicantly across the antiferromagnetic high-temperature superconductivity phase boundary despite short-ranged antiferromagnetic correlations, in contrast to the hole-doped cuprates. Furthermore, we nd an unexpected branch of collective modes in superconducting compounds, absent in hole-doped cuprates. These modes emanate from the zone centre and possess a higher temperature scale than Tc, signalling a distinct quantum phase. Despite their dierences, the persistence of magnetic excitations and the existence of a distinct quantum phase are apparently universal in both hole- and electron-doped cuprates.
The objective of this study was to determine the usefulness of augmented reality (AR) in teaching. An experiment was conducted to examine children's learning performances, which included the number ...of errors they made, their ability to remember the content of what they had read and their satisfaction with the three types of teaching materials, including a picture book, physical interactions and an AR graphic book. The three teaching materials were aimed to respectively demonstrate the characteristics of six bacteria with 2D graphics, 3D physical objects, and 3D virtual objects. Seventy‐two fifth‐grade children were randomly selected to participate in the study, and they were divided into three groups, each of which used the assigned teaching material to learn the name of the six different bacteria in intervals of 1, 2 and 3 min. Results showed that the AR graphic book offers a practical and hands‐on way for children to explore and learn about the bacteria. Follow‐up interviews indicated that the children liked the AR graphic book the most, and they preferred it to the other materials.
Lay Description
What is currently known about Augmented Reality and learning?
Augmented reality (AR) provides a new perspective for learning by allowing learners to visualize complex spatial relationships and concepts.
What the paper adds to the subject matter?
AR improves learning performances to a similar extent as the most used teaching materials (both picture books and physical interactions) do.
AR not only facilitates learning but also increases learning motivations better than conventional teaching materials do.
The implications of study findings for practitioners.
If children feel bored about reading textbooks, give them AR (because AR effectively enhances learning and children are more motivated when using AR).
AR teaching material is a good alternative to conventional picture book and physical interactions.
ABSTRACT
We present photometric and spectroscopic observations of the unusual Type Ia supernova ASASSN-18tb, including a series of Southern African Large Telescope spectra obtained over the course of ...nearly six months and the first observations of a supernova by the Transiting Exoplanet Survey Satellite. We confirm a previous observation by Kollmeier et al. showing that ASASSN-18tb is the first relatively normal Type Ia supernova to exhibit clear broad (∼1000 km s−1) H α emission in its nebular-phase spectra. We find that this event is best explained as a sub-Chandrasekhar mass explosion producing $M_{\mathrm{ Ni}} \approx 0.3\,\, \rm {M}_\odot$. Despite the strong H α signature at late times, we find that the early rise of the supernova shows no evidence for deviations from a single-component power-law and is best fit with a moderately shallow power law of index 1.69 ± 0.04. We find that the H α luminosity remains approximately constant after its initial detection at phase +37 d, and that the H α velocity evolution does not trace that of the Fe iii λ4660 emission. These suggest that the H α emission arises from a circumstellar medium (CSM) rather than swept-up material from a non-degenerate companion. However, ASASSN-18tb is strikingly different from other known CSM-interacting Type Ia supernovae in a number of significant ways. Those objects typically show an H α luminosity two orders of magnitude higher than what is seen in ASASSN-18tb, pushing them away from the empirical light-curve relations that define ‘normal’ Type Ia supernovae. Conversely, ASASSN-18tb exhibits a fairly typical light curve and luminosity for an underluminous or transitional SN Ia, with MR ≈ −18.1 mag. Moreover, ASASSN-18tb is the only SN Ia showing H α from CSM interaction to be discovered in an early-type galaxy.
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