Small-cell lung cancer (SCLC) is a highly malignant type of lung cancer with no effective second-line chemotherapy drugs. Arsenic trioxide (As2O3) was reported to exert antiangiogenesis activities ...against lung cancer and induce poor development of vessel structures, similar to the effect observed following the blockade of Notch signaling. However, there are no direct evidences on the inhibitory effects of As2O3 on tumor growth and angiogenesis via blockade of Notch signaling in SCLC. Here, we found that As2O3 significantly inhibited the tumor growth and angiogenesis in SCLC and reduced the microvessel density. As2O3 disturbed the morphological development of tumor vessels and downregulated the protein levels of delta-like canonical Notch ligand 4 (Dll4), Notch1, and Hes1 in vivo. DAPT, a Notch signaling inhibitor, exerted similar effects in SCLC. We found that both As2O3 treatment and Notch1 expression knockdown resulted in the interruption of tube formation by human umbilical vein endothelial cells (HUVECs) on Matrigel. As2O3 had no effects on Dll4 level in HUVECs but significantly inhibited the expression of Notch1 and its downstream gene Hes1 regardless of Dll4 overexpression or Notch1 knockdown. These findings suggest that the antitumor activity of As2O3 in SCLC was mediated via its antiangiogenic effect through the blockade of Notch signaling, probably owing to Notch1 targeting.
In 1816, Robert Stirling proposed the first beta-type Stirling engine (BTSE) which have been extensively used in renewable energy. In BTSEs, the displacer and piston are coaxially arranged, resulting ...in a more compact design and a higher power density. In this study, the dynamic characteristics and performance of BTSEs with five driving mechanisms, namely, slider crank, rhombic drive, Ross yoke, bell crank, and Scotch yoke mechanisms, were investigated. Variations in the thermal properties of the working fluid in BTSEs were predicted using a thermodynamic model. The dynamic models of the five mechanisms were presented, and friction losses due to the piston rings, sliders, bearings, and seals were considered. The thermal properties of the working fluid and the dynamic behavior of the driving mechanisms were investigated. The instantaneous variations in the displacement of the moving components and engine speed were obtained, and the indicated power, shaft power, total friction loss, and mechanical efficiency of BTSEs with the five mechanisms were compared. The results indicated that the trajectories of the piston and displacer considerably affected the performance of BTSEs. Additionally, BTSEs with the bell crank mechanism produced the highest shaft power (1533 W) at 550 rpm, with a mechanical efficiency of 80.5%.
•A complete model for analyzing beta-type Stirling engines is proposed.•The performance of the engines with different driving mechanisms is studied.•The transient behaviors and performance of the engines are simulated.•The engine with bell crank mechanism can produce the highest power 1533 W.
The tolerance of adjustable speed drive (ASD) under voltage sag is important for users to select equipment and take mitigation methods. However, it is not easy for users to obtain the tolerance ...information of ASD. To address this issue, this paper proposes practical tables for tolerance assessment of ASD under voltage sag, providing a simpler and faster way for an approximate understanding of the tolerance of ASD. First, this paper proposes a calculation method for three trip characteristics to describe the tolerance of ASD. Second, this paper presents a voltage tolerance curve (VTC) assessment model based on the three trip characteristics, and the coordinate of the “knee point” of VTC can be assessed straightforwardly. Furthermore, the practical tables for tolerance assessment of ASD are formed based on the studies mentioned above. Users can obtain the tolerance of ASDs by looking up the table when they know several key parameters. Simulations tests verify the effectiveness of the calculation method and practical tables.
Synthetic two-dimensional (2D) materials without layered bulk allotropes are approaching a new frontier of materials flatland, one with properties richer than those of graphene-like materials. This ...is the case even as only a few chemical elements and blends have shown synthetic 2D forms. While hydrogen and metals are earth-abundant and form numerous compounds, rarely are 2D materials with only robust metal–hydrogen bonds. Here, a large new family of 2D materials is found from metal hydrides by high-throughput computational search augmented with first-principles calculations. There are 110 thermally and dynamically stable 2D materials that range from metallic materials to wide-gap semiconductors. A subgroup of these materials even varies from topological insulators to nodal-loop semimetals as well as from antiferromagnetic semiconductors to ferromagnetic half-metals. Unexpectedly, these monolayers resemble graphene in an ability to form weak interlayer interaction due to the variable multicenter bonding of hydrogen that eliminates the otherwise prevalent dangling bonds, rather than the covalent bonds between stacked layers as in previously reported synthetic 2D materials. This feature will favor potential experimental synthesis of these metal hydride monolayers.
A novel series of peptidomimetic aldehydes was designed and synthesized to target 3C protease (3Cpro) of enterovirus 71 (EV71). Most of the compounds exhibited high antiviral activity, and among ...them, compound 18p demonstrated potent enzyme inhibitory activity and broad-spectrum antiviral activity on a panel of enteroviruses and rhinoviruses. The crystal structure of EV71 3Cpro in complex with 18p determined at a resolution of 1.2 Å revealed that 18p covalently linked to the catalytic Cys147 with an aldehyde group. In addition, these compounds also exhibited good inhibitory activity against the 3CLpro and the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), especially compound 18p (IC50 = 0.034 μM, EC50 = 0.29 μM). According to our previous work, these compounds have no reasons for concern regarding acute toxicity. Compared with AG7088, compound 18p also exhibited good pharmacokinetic properties and more potent anticoronavirus activity, making it an excellent lead for further development.
Let K_{\nu } be the modified Bessel functions of the second kind of order \nu. The ratio Q_{\nu }\left ( x\right ) =xK_{\nu -1}\left ( x\right ) /K_{\nu }\left ( x\right ) appeared in physics and ...probability. In this paper, we collate properties of this ratio, and prove the conjecture that \left ( -1\right ) ^{n}Q_{\nu }^{\left ( n\right ) }\left ( x\right ) >\left ( <\right ) 0 for x>0 and n=2,3 if \left \vert \nu \right \vert >\left ( <\right ) 1/2 holds for n=2. This yields several new consequences and improves some known results. Finally, two conjectures are proposed.
Boron, as a unique element nearest to carbon in the periodic table, has been predicted to form many distinctive two‐dimensional (2D) structures that significantly differ from other well‐studied 2D ...materials, owning to its exceptional ability to form strong covalent two‐center‐two‐electron bonds as well as stable electron‐deficient multi‐center‐two‐electron bonds. Until recently, the successful syntheses of atomically thin crystalline 2D boron sheets (i.e., borophenes) provoked growing passion in 2D boron crystals. In this feature article, we present a survey of the latest achievements on 2D boron structures, starting from a concise introduction of the structures and properties of the bulk allotropes of boron, boron clusters, and especially potential building blocks for 2D boron crystals. Then we review important achievements and the current status of research on single‐layered metallic borophene, and discuss 2D few‐layered boron sheets, from their possible structures to tunable properties and potential applications in electronics, spintronics, and photoelectronics. We also systematically investigate the stability and functionalization of 2D icosahedral boron sheets in comparison with borophenes through first‐principles studies. Finally, we present an outlook on the advance in fabrications of 2D boron sheets, and the challenges and prospects in the realm of 2D boron crystals.
Boron bulk allotropes and clusters with unique bonding and structures have drawn long‐standing interest. Now, boron of a new dimensionality, namely 2D boron crystals, has emerged into the vision of scientific communities, especially with the success of their experimental synthesis achieved in the last year. Here, we review state‐of‐the‐art experimental and theoretical achievements on 2D boron crystals, with special attention paid to their possible structures, tunable properties, and potential applications.
•Three coactivation patterns (CAPs) pairs with opposite coactivation profiles were identified, and the between-state transition probability was positively correlated with their spatial ...similarity.•Good spatial/temporal reproducibility and generalizability of CAPs were achieved under varied analytic methods and independent cohorts.•Schizophrenia patients showed altered temporal dynamics related to not only the triple-network but also other primary and higher-order networks.
It is well documented that massive dynamic information is contained in the resting-state fMRI. Recent studies have identified recurring states dominated by similar coactivation patterns (CAPs) and revealed their temporal dynamics. However, the reproducibility and generalizability of the CAP analysis are unclear. To address this question, the effects of methodological pipelines on CAP are comprehensively evaluated in this study, including the preprocessing, network construction, cluster number and three independent cohorts. The CAP state dynamics are characterized by the fraction of time, persistence, counts, and transition probability. Results demonstrate six reliable CAP states and their dynamic characteristics are also reproducible. The state transition probability is found to be positively associated with the spatial similarity. Furthermore, the aberrant CAP states in schizophrenia have been investigated by using the reproducible method on three cohorts. Schizophrenia patients spend less time in CAP states that involve the fronto-parietal network, but more time in CAP states that involve the default mode and salience network. The aberrant dynamic characteristics of CAP states are correlated with the symptom severity. These results reveal the reproducibility and generalizability of the CAP analysis, which can provide novel insights into the neuropathological mechanism associated with aberrant brain network dynamics of schizophrenia.
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This paper presents the first experimental demonstration of an energy-efficient electronic-photonic co-designed transceiver circuit heterogeneously 3D co-integrated with high-density, low-parasitic ...Direct Bond Interconnect (DBI ® ) featuring 32-channel microdisk modulator/filter based optical transceivers for Wavelength Division Multiplexing (WDM) scheme. The silicon photonic chip is fabricated in AIM Photonics' integrated photonic technology, and the optical transceiver chip is fabricated in GlobalFoundries 12 nm FinFET process. The optical transmitter consumes 2.823 mW at 18 Gb/s, with 1.2 V ppd electrical modulation differential swing, and achieves an extinction ratio of 7 dB. The optical receiver utilized quarter-rate sampling via Injection-Locked Oscillator (ILO) and forward clocking architecture, consumes 6.11 mW, and achieves the Optical Modulation Amplitude (OMA) sensitivity of -20.3 dBm at 12 Gb/s under the photodiode responsivity of 0.8 A/W. The receiver can further operate at 25 Gb/s with a sensitivity of -17.01 dBm and 191 fJ/bit. The transceiver pair at 18 Gb/s achieves 496 fJ/bit link efficiency.
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