Superconducting Dome in a Gate-Tuned Band Insulator Ye, J. T.; Zhang, Y. J.; Akashi, R. ...
Science (American Association for the Advancement of Science),
11/2012, Volume:
338, Issue:
6111
Journal Article
Peer reviewed
A dome-shaped superconducting region appears in the phase diagrams of many unconventional superconductors. In doped band insulators, however, reaching optimal superconductivity by the fine-tuning of ...carriers has seldom been seen. We report the observation of a superconducting dome in the temperature—carrier density phase diagram of MoS₂, an archetypal band insulator. By quasi-continuous electrostatic carrier doping achieved through a combination of liquid and solid gating, we revealed a large enhancement in the transition temperature T c occurring at optimal doping in the chemically inaccessible low-carrier density regime. This observation indicates that the superconducting dome may anse even in doped band insulators.
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Summary
Background
Autophagy and neutrophil extracellular DNA traps (NETs) are implicated in asthma; however, their roles in asthma pathogenesis have not been elucidated.
Objectives
We compared ...autophagy and NET production levels from peripheral blood neutrophils (PBNs) of patients with severe asthma (SA) and non‐severe asthma (NSA). Additionally, we investigated the inflammatory effects of NETs on human airway epithelial cells (AECs) and peripheral blood eosinophils (PBEs).
Methods
Peripheral blood neutrophils from patients with SA (n = 30) and NSA (n = 38) were treated with interleukin (IL)‐8 (100 ng/mL). Autophagy (light chain 3‐II expression) and NET production levels were evaluated by Western blot, immunofluorescence microscopy, and PicoGreen assay. The effects of NETs on AECs were assessed by investigating cell death, cell detachment, expression of occludin and claudin‐1, and IL‐8 production; the effects of NETs on PBEs were examined by investigating the activation and release of eosinophil cationic protein (ECP) and eosinophil‐derived neurotoxin (EDN).
Results
Untreated and IL‐8‐treated PBNs from the SA group produced higher autophagy and NET levels compared with those from the NSA group (P < 0.01). IL‐8 increased autophagy and NET levels in PBNs from the SA group, but not from the NSA group. NET levels were correlated with autophagy levels in PBNs (P < 0.001). IL‐8‐induced NET production levels negatively were correlated with FEV1/FVC (r = −0.700, P = 0.016). NETs induced cell death, detachment, degradation of occludin and claudin‐1, and IL‐8 production from AECs. Higher levels of NET‐induced ECP and EDN were released from PBEs in SA compared with NSA groups.
Conclusions and Clinical Relevance
Neutrophil autophagy and NETs could enhance asthma severity by damaging airway epithelium and triggering inflammatory responses of AECs and PBEs. Modulating neutrophil autophagy and NET production may be a new target therapy for SA.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
The accumulation of myeloid-derived suppressor cells (MDSCs) has been observed in solid tumors and is correlated with tumor progression; however, the underlying mechanism is still poorly understood. ...In this study, we identified a mechanism by which tumor cells induce MDSC accumulation and expansion in the bladder cancer (BC) microenvironment via CXCL2/MIF-CXCR2 signaling. Elevated expression of CXCL2 and MIF and an increased number of CD33
MDSCs were detected in BC tissues, and these increases were significantly associated with advanced disease stage and poor patient prognosis (P<0.01). A positive association was observed between CXCL2 or MIF expression and the number of tumor-infiltrating CD33
MDSCs (P<0.01). Subsequently, we demonstrated that CD45
CD33
CD11b
HLA-DR
MDSCs from fresh BC tissues displayed high levels of suppressive molecules, including Arg1, iNOS, ROS, PDL-1 and P-STAT3, and stronger suppression of T-cell proliferation. Interestingly, these CD45
CD33
CD11b
HLA-DR
MDSCs exhibited increased CXCR2 expression compared with that in peripheral blood from BC patients or healthy controls (P<0.05). Chemotaxis assay revealed that bladder cancer cell line J82 induced MDSC migration via CXCL2/MIF-CXCR2 signaling in vitro. Mechanistic studies demonstrated that J82-induced MDSC trafficking and CXCR2 expression were associated with increased phosphorylation of p38, ERK and p65. Conversely, inhibition of the phosphorylation of p38, ERK or p65 decreased J82-induced MDSC trafficking and CXCR2 expression. CXCL2/MIF-stimulated activation of the mitogen-activated protein kinase and nuclear factor kappa B pathways in MDSCs was MyD88 dependent. Overall, our results identify the CXCL2/MIF-CXCR2 axis as an important mediator in MDSC recruitment and as predictors and potential therapeutic targets in BC patients.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Tungsten diselenide (WSe2) and related transition metal dichalcogenides exhibit interesting optoelectronic properties owing to their peculiar band structures originating from the valley degree of ...freedom. Although the optical generation and detection of valley polarization has been demonstrated, it has been difficult to realize active valley-dependent functions suitable for device applications. We report an electrically switchable, circularly polarized light source based on the material's valley degree of freedom. Our WSe2-based ambipolar transistors emit circularly polarized electroluminescence from p-i-n junctions electrostatically formed in transistor channels. This phenomenon can be explained qualitatively by the electron-hole overlap controlled by the in-plane electric field. Our device demonstrates a route to exploit the valley degree of freedom and the possibility to develop a valley-optoelectronics technology.
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Molybdenum disulfide (MoS2) has gained attention because of its high mobility and circular dichroism. As a crucial step to merge these advantages into a single device, we present a method that ...electronically controls and locates p–n junctions in liquid-gated ambipolar MoS2 transistors. A bias-independent p–n junction was formed, and it displayed rectifying I–V characteristics. This p–n diode could perform a crucial role in the development of optoelectronic valleytronic devices.
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IJS, KILJ, NUK, PNG, UL, UM
Leptomeningeal metastases (LM) are more frequent in non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations. Due to limited access to leptomeningeal lesions, the ...purpose of this study was to explore the potential role of cerebrospinal fluid (CSF) as a source of liquid biopsy in patients with LM.
Primary tumor, CSF, and plasma in NSCLC with LM were tested by next-generation sequencing. In total, 45 patients with suspected LM underwent lumbar puncture, and those with EGFR mutations diagnosed with LM were enrolled.
A total of 28 patients were enrolled in this cohort; CSF and plasma were available in 26 patients, respectively. Driver genes were detected in 100% (26/26), 84.6% (22/26), and 73.1% (19/26) of samples comprising CSF cell-free DNA (cfDNA), CSF precipitates, and plasma, respectively; 92.3% (24/26) of patients had much higher allele fractions in CSF cfDNA than the other two media. Unique genetic profiles were captured in CSF cfDNA compared with those in plasma and primary tissue. Multiple copy number variations (CNVs) were mainly identified in CSF cfDNA, and MET copy number gain identified in 47.8% (11/23) of patients was the most frequent one, while other CNVs included ERBB2, KRAS, ALK, and MYC. Moreover, loss of heterozygosity (LOH) of TP53 was identified in 73.1% (19/26) CSF cfDNA, which was much higher than that in plasma (2/26, 7.7%; P<0.001). There was a trend towards a higher frequency of concomitant resistance mutations in patients with TP53 LOH than those without (70.6% versus 33.3%; P=0.162). EGFR T790M was identified in CSF cfDNA of 30.4% (7/23) of patients who experienced TKI progression.
CSF cfDNA could reveal the unique genetic profiles of LM and should be considered as the most representative liquid biopsy medium for LM in EGFR-mutant NSCLC.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
During insect larval–pupal metamorphosis, the obsolete larval organs and tissues undergo histolysis and programmed cell death to recycle cellular materials. It has been demonstrated that some ...cathepsins are essential for histolysis in larval tissues, but the process of tissue destruction is not well documented. Fat body, the homologous organ to mammalian liver and adipose tissue, goes through a distinct destruction process during larval–pupal transition. Herein, we found that most of the Bombyx proteases – including Bombyx cathepsin B (BmCatB) (BmCatLL-2), Bombyx cathepsin D (BmCatD), Bombyx cathepsin L like‐1 (BmCatLL-1) and –2(BmCatLL-2), Bombyx fibroinase (BmBcp), Bombyx matrix metalloprotease (BmMmp), Bombyx A disintegrin and metalloproteinase with thrombospondin motifs 1 (BmAdamTS‐1), Bombyx A disintegrin and metalloproteinase with thrombospondin motifs like (BmAdamTS L) and Bombyx cysteine protease inhibitor (Bmbcpi)– were expressed highly in fat body during feeding and metamorphosis, with a peak occurring during the nonfeeding moulting or prepupal stage, as well as being responsive to 20‐hydroxyecdysone (20E). The aforementioned protease genes expression was upregulated by injection of 20E into the feeding larvae, while blocking 20E signalling transduction led to downregulation. Western blotting and immunofluorescent staining of BmCatB and BmBcp confirmed the coincident variation of their messenger RNA (mRNA) and protein level during the development and after the treatments. Moreover, BmCatB, BmBcp, BmMmp and BmAdamTS‐1 RNA interference all led to blockage of larval fat body destruction. Taken together, we conclude that 20E regulates larval fat body destruction by upregulating related protease gene expression and protein levels during larval–pupal transition.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
High-energy photons from the Crab Nebula
The Crab Nebula contains a pulsar that excites the surrounding gas to emit high-energy radiation. The combination of the pulsar's youth and nearby location ...makes the nebula the brightest gamma-ray source in the sky. The LHAASO Collaboration report observations of this source at energies of tera– to peta–electron volts, extending the spectrum of this prototypical object. They combine these data with observations at lower energies to model the physics of the emission process. The multiwave-length data can be explained by a combination of synchrotron radiation and inverse Compton scattering.
Science
, abg5137, this issue p.
425
Detection of the Crab Nebula at peta–electron volt energies constrains the gamma-ray emission mechanism.
The Crab Nebula is a bright source of gamma rays powered by the Crab Pulsar’s rotational energy through the formation and termination of a relativistic electron-positron wind. We report the detection of gamma rays from this source with energies from 5 × 10
−4
to 1.1 peta–electron volts with a spectrum showing gradual steepening over three energy decades. The ultrahigh-energy photons imply the presence of a peta–electron volt electron accelerator (a pevatron) in the nebula, with an acceleration rate exceeding 15% of the theoretical limit. We constrain the pevatron’s size between 0.025 and 0.1 parsecs and the magnetic field to ≈110 microgauss. The production rate of peta–electron volt electrons, 2.5 × 10
36
ergs per second, constitutes 0.5% of the pulsar spin-down luminosity, although we cannot exclude a contribution of peta–electron volt protons to the production of the highest-energy gamma rays.
Summary
Background
Autophagy and genetic predisposition have been suggested to potentially play roles in the development of asthma. However, little is known about the role of autophagy in the ...pathogenesis of severe asthma.
Objective
We compared autophagy in the sputum granulocytes, peripheral blood cells (PBCs) and peripheral blood eosinophils (PBEs) between patients with severe asthma and those with non‐severe asthma and investigated the functional effects of autophagy.
Methods
We enrolled 36 patients with severe asthma, 14 with non‐severe asthma and 23 normal healthy controls in this study. Sputum granulocytes, PBCs and PBEs were isolated from each subject. Autophagy was evaluated based on the expression of microtubule‐associated protein light chain 3 (LC3) by Western blot, confocal microscopy, transmission electron microscopy and flow cytometry. IL‐8 levels were measured by ELISA. To induce autophagy, HL‐60 cells, human primary small airway epithelial cells (SAECs) and A549 cells were treated with IL‐5, IL‐1β and TNF‐α. To inhibit autophagy, PI3K inhibitors (LY29400 and 3‐methyladenine 3‐MA) and hydroxychloroquine (HCQ) were used. Knockdown of ATG5 and Beclin‐1 was performed in A549 cells, and the therapeutic effects of dexamethasone were evaluated.
Results
Higher autophagy levels were noted in sputum granulocytes, PBCs and PBEs from patients with severe asthma than from patients with non‐severe asthma and healthy controls (P < 0.05 for all). IL‐5 increased autophagy levels in both PBCs and PBEs (P < 0.05). 3‐MA attenuated the increased expression of LC3‐II and eosinophil cationic protein in HL‐60 cells induced by IL‐5 (P = 0.034 for both). Dexamethasone did not affect autophagy levels in PBEs. IL‐1β increased LC3‐II expression and IL‐8 production (P < 0.01) in SAECs, and this was attenuated by LY294002, 3‐MA, HCQ and knockdown of ATG5 and Beclin‐1 (in A549 cells) (P < 0.01).
Conclusions and Clinical Relevance
Autophagy could play a role in the pathogenesis of severe asthma. Autophagy modulation may be a novel therapeutic target for conventional therapy‐resistant severe asthma.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Sonoporation is the membrane disruption generated by ultrasound and has been exploited as a non-viral strategy for drug and gene delivery. Acoustic cavitation of microbubbles has been recognized to ...play an important role in sonoporation. However, due to the lack of adequate techniques for precise control of cavitation activities and real-time assessment of the resulting sub-micron process of sonoporation, limited knowledge has been available regarding the detail processes and correlation of cavitation with membrane disruption at the single cell level. In the current study, we developed a combined approach including optical, acoustical, and electrophysiological techniques to enable synchronized manipulation, imaging, and measurement of cavitation of single bubbles and the resulting cell membrane disruption in real-time. Using a self-focused femtosecond laser and high frequency ultrasound (7.44
MHz) pulses, a single microbubble was generated and positioned at a desired distance from the membrane of a Xenopus oocyte. Cavitation of the bubble was achieved by applying a low frequency (1.5
MHz) ultrasound pulse (duration 13.3 or 40
μs) to induce bubble collapse. Disruption of the cell membrane was assessed by the increase in the transmembrane current (TMC) of the cell under voltage clamp. Simultaneous high-speed bright field imaging of cavitation and measurements of the TMC were obtained to correlate the ultrasound-generated bubble activities with the cell membrane poration. The change in membrane permeability was directly associated with the formation of a sub-micrometer pore from a local membrane rupture generated by bubble collapse or bubble compression depending on ultrasound amplitude and duration. The impact of the bubble collapse on membrane permeation decreased rapidly with increasing distance (D) between the bubble (diameter
d) and the cell membrane. The effective range of cavitation impact on membrane poration was determined to be
D/d
=
0.75. The maximum mean radius of the pores was estimated from the measured TMC to be 0.106
±
0.032
μm (n
=
70) for acoustic pressure of 1.5
MPa (duration 13.3
μs), and increased to 0.171
±
0.030
μm (n
=
125) for acoustic pressure of 1.7
MPa and to 0.182
±
0.052
μm (n
=
112) for a pulse duration of 40
μs (1.5
MPa). These results from controlled cell membrane permeation by cavitation of single bubbles revealed insights and key factors affecting sonoporation at the single cell level.
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