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Oral squamous cell carcinoma (OSCC) is one of the most painful cancers, which interferes with orofacial function including talking and eating. We report that legumain (Lgmn) cleaves protease-activated receptor-2 (PAR2) in the acidic OSCC microenvironment to cause pain. Lgmn is a cysteine protease of late endosomes and lysosomes that can be secreted; it exhibits maximal activity in acidic environments. The role of Lgmn in PAR2-dependent cancer pain is unknown. We studied Lgmn activation in human oral cancers and oral cancer mouse models. Lgmn was activated in OSCC patient tumors, compared with matched normal oral tissue. After intraplantar, facial or lingual injection, Lgmn evoked nociception in wild-type (WT) female mice but not in female mice lacking PAR2in NaV1.8-positive neurons (Par2Nav1.8), nor in female mice treated with a Lgmn inhibitor, LI-1. Inoculation of an OSCC cell line caused mechanical and thermal hyperalgesia that was reversed by LI-1.Par2Nav1.8andLgmndeletion attenuated mechanical allodynia in female mice with carcinogen-induced OSCC. Lgmn caused PAR2-dependent hyperexcitability of trigeminal neurons from WT female mice.Par2deletion, LI-1, and inhibitors of adenylyl cyclase or protein kinase A (PKA) prevented the effects of Lgmn. Under acidified conditions, Lgmn cleaved within the extracellular N terminus of PAR2at Asn30↓Arg31, proximal to the canonical trypsin activation site. Lgmn activated PAR2by biased mechanisms in HEK293 cells to induce Ca2+mobilization, cAMP formation, and PKA/protein kinase D (PKD) activation, but not β-arrestin recruitment or PAR2endocytosis. Thus, in the acidified OSCC microenvironment, Lgmn activates PAR2by biased mechanisms that evoke cancer pain.SIGNIFICANCE STATEMENTOral squamous cell carcinoma (OSCC) is one of the most painful cancers. We report that legumain (Lgmn), which exhibits maximal activity in acidic environments, cleaves protease-activated receptor-2 (PAR2) on neurons to produce OSCC pain. Active Lgmn was elevated in OSCC patient tumors, compared with matched normal oral tissue. Lgmn evokes pain-like behavior through PAR2. Exposure of pain-sensing neurons to Lgmn decreased the current required to generate an action potential through PAR2. Inhibitors of adenylyl cyclase and protein kinase A (PKA) prevented the effects of Lgmn. Lgmn activated PAR2to induce calcium mobilization, cAMP formation, and activation of protein kinase D (PKD) and PKA, but not β-arrestin recruitment or PAR2endocytosis. Thus, Lgmn is a biased agonist of PAR2that evokes cancer pain.

The generalized Langevin equation (GLE) is a stochastic integro-differential equation that has been used to describe the velocity of microparticles in viscoelastic fluids. In this work, we consider the large-time asymptotic properties of a Markovian approximation to the GLE in the presence of a wide class of external potential wells. The qualitative behavior of the GLE is largely determined by its memory kernel K, which summarizes the delayed response of the fluid medium on the particles past movement. When K can be expressed as a finite sum of exponentials, it has been shown that long-term time-averaged properties of the position and velocity do not depend on K at all. In certain applications, however, it is important to consider the GLE with a power law memory kernel. Using the fact that infinite sums of exponentials can have power law tails, we study the infinite-dimensional version of the Markovian GLE in a potential well. In the case where the memory kernel K is integrable (i.e. in the asymptotically diffusive regime), we are able to extend previous results and show that there is a unique stationary distribution for the GLE system and that the long-term statistics of the position and velocity do not depend on K. However, when K is not integrable (i.e. in the asymptotically subdiffusive regime), we are able to show the existence of an invariant probability measure but uniqueness remains an open question. In particular, the method of asymptotic coupling used in the integrable case to show uniqueness does not apply when K fails to be integrable.

The interfacial passivation technique is an effective method to improve the stability and photovoltaic performance of perovskite solar cells. Here, we demonstrate the importance of passivating undercoordinated halide ions in minimizing carrier losses at the perovskite/spiro-OMeTAD interface. 4-Chlorobenzene sulfonyl chloride (CBSC) has been utilized as a Lewis acid passivation material. CBSC molecules act as electron acceptors, which bind to the negatively charged undercoordinated halide ions and Pb-I antisite defects (PbI3−). The champion CBSC-passivated perovskite device shows a high power conversion efficiency (PCE) of 20.02%, unlike the pristine device with an efficiency of 18.29%. Significant long term-stability in the CBSC passivated device is also observed, maintaining 93% of the initial PCE after 768 h stored in ambient conditions with 30% relative humidity. Energy Market Authority (EMA) Ministry of Education (MOE) National Research Foundation (NRF) Published version The research is supported by an AcRF Tier2 grant (MOET2EP50121-0012) from Singapore Ministry of Education, and EMA-EP004-EKJGC-0003 grant from the Energy Market Authority (EMA) and National Research Foundation (NRF) Singapore and NRF2018-ITC001-001.

The chance-constrained optimal power flow (CC-OPF) has gained prominence due to increased uncertainty in the power system. However, solving CC-OPF for general uncertainty distribution classes is challenging due to lack of analytical formulation of probabilistic constraints and cost-complexity trade-off issues. This work proposes a novel joint chance-constrained optimal power flow (JCC-OPF) via maximum mean discrepancy (MMD) penalization to obtain a probabilistically feasible low-cost solution. The idea is to view the JCC-OPF problem as a distribution matching problem. The MMD quantifies the distance between two probability distributions embedded into reproducing kernel Hilbert space (RKHS) and thus provides an efficient way to minimize the distance between distributions. The RKHS embedding, also called kernel mean embedding (KME), is a non-parametric method that does not require any information about the random injection's distribution while performing the embedding. Furthermore, the proposed method is based on a point-wise evaluation of the constraint functions and has the same complexity as a deterministic OPF problem. The proposed penalization-based formulation handles JCC directly and does not require the conversion of joint chance constraints into individual ones. Simulations on IEEE 24-Bus, 30-Bus, and 57-Bus systems validate the proposed method's non-parametric nature and ability to obtain a probabilistically feasible solution. Benchmarking results against existing approaches indicate the better computational performance of the proposed method. Energy Market Authority (EMA) Nanyang Technological University National Research Foundation (NRF) Submitted/Accepted version Authors are supported in part by the NTU SUG, Singapore, in part by the Academic Research Fund, Singapore TIER 1 2019-T1-001-119 (RG 79/19), and in part by the EMA and NRF Singapore under Grant EMA-EP004-EKJGC-000.

This paper discusses the physical dynamics of the use of the Active Flow Control (AFC) actuators embedded in a Vertical Take-Off and Landing (VTOL) aircraft. Results of High-Fidelity numerical simulations are examined at near stall conditions. Different approaches of AFC are proposed to suppress the flow separation at these conditions. First the flow around the VTOL aircraft at high angle of attack in the take-off and landing configurations in real flight conditions at high Reynolds number are examined, then different flow control strategies are investigated. It was found that at these flow condition a flow separation travels along the spanwise direction in the near trailing-edge region of the wing with additional corner vortices between the wing-nacelle and the wing-fuselage junctions. Zero Net Mass Flux (ZNMF) actuators, also called synthetic jets, were then used for Active Flow Control. It was found that these ZNMF devices, when operating at the optimal blowing velocity and activation frequency, and when placed at the correct location enable the flow to re-attach and to delay the flow separation, resulting in an increase in aerodynamic efficiency of the aircraft. This work presented in this paper has been carried out in the context of the European project CleanSky2 Active Flow Control for TiltRotor aircraft (AFC4TR), Grant Agreement 886718.

This paper attempts to model both static and dynamic dependence structures and measure impacts of energy consumptions (both renewable (EC) and non-renewable (REN) energies), economic globalization (GLO), and economic growth (GDP) on carbon dioxide (CO

π-stacked organic electronic materials are tunable light absorbers with many potential applications in optoelectronics. The optical properties of such molecules are highly dependent on the nature and energy of electron-hole pairs or excitons formed upon light absorption, which in turn are determined by intra- and intermolecular electronic and vibrational excitations. Here, we present a first-principles approach for describing the optical spectrum of stacked organic molecules with strong vibronic coupling. For stacked perylene tetracarboxylic acid diimides, we describe optical excitations by using the time-dependent density functional theory with a Franck-Condon Herzberg-Teller approximation of vibronic effects and validate our approach with comparison to experimental ultraviolet-visible (UV-vis) absorption measurements of solvated model systems. We determine that for larger macromolecules, unlike for single molecules, the sampling of the ground-state potential energy surface significantly influences the optical absorption spectrum. We account for this effect by applying our analysis to ∼100 structures extracted from equilibrated molecular dynamics simulations and averaging the optical spectrum over the entire ensemble. Additionally, we demonstrate that intermolecular electronic coupling within the stacks results in multiple low-energy electronically excited states that all contribute to the optical spectrum. This study provides a computationally feasible recipe for describing the spectroscopic properties of stacked organic chromophores via first-principles density functional theory.

Perylene-3,4,9,10-tetracarboxylic diimides (PTCDIs) have been extensively studied for organic electronics applications. Additionally, PTCDI-based supramolecular architectures have been used as platforms for the investigation of various charge transfer/transport phenomena. For these systems, the study of their structural characteristics and self-assembly behavior with molecular dynamics simulations has remained relatively limited. Herein, we describe a detailed molecular dynamics investigation of the intramolecular self-assembly of DNA-inspired columnar macromolecules, which consist of multiple hexaethyleneglycol-substituted PTCDIs that are covalently appended to a phosphoalkane backbone. By evaluating relevant geometric and energetic parameters obtained from our simulations, we determine the factors underpinning the dynamics of PTCDI stacking for our constructs. Our findings may shed insight into the structure of biomimetic one-dimensional molecular wires from PTCDIs and other related materials.

In this study, we investigated ostracod assemblages from the Co To Islands in northeastern Vietnam. We identified 77 ostracod species belonging to 46 genera in nine surface sediment samples and recognized three biofacies (I, II, and III) based on Q-mode cluster analysis. The dominant species of biofacies I and II were Aurila hataii, Loxoconcha japonica, and Xestoleberis hanaii, which commonly occur in seaweed beds from southern China to Japan. This is the first report on the ostracod assemblage from the open-sea area in northeastern Vietnam. We clarified that the ostracod assemblages in the Gulf of Tongking, including northern Vietnam, have a strong biogeographical relationship with East Asia seas. A new species, Loxoconcha cotoensis sp. nov., was described herein from the Co To Islands (http://www.zoobank.org/NomenclaturalActs/41d3fb9f-ae17-4215-82c1-0874a8bf1a30, last access: 3 June 2019).

Two new polyisoprenylated benzophenones, planchoniones A (