Modeling quasi-dark states with Temporal Coupled-Mode Theory

Coupled resonators are commonly used to achieve tailored spectral responses and allow novel functionalities in a broad range of applications, from optical modulation and filtering in integrated photonic circuits to the study of nonlinear dynamics in arrays of resonators. The Temporal Coupled-Mode Theory (TCMT) provides a simple and general tool that is widely used to model these devices and has proved to yield very good results in many different systems of low-loss, weakly coupled resonators. Relying on TCMT to model coupled resonators might however be misleading in some circumstances due to the lumped-element nature of the model. In this article, we report an important limitation of TCMT related to the prediction of dark states. Studying a coupled system composed of three microring resonators, we demonstrate that TCMT predicts the existence of a dark state that is in disagreement with experimental observations and with the more general results obtained with the Transfer Matrix Method (TMM) and the Finite-Difference Time-Domain (FDTD) simulations. We identify the limitation in the TCMT model to be related to the mechanism of excitation/decay of the supermodes and we propose a correction that effectively reconciles the model with expected results. A comparison with TMM and FDTD allows to verify both steady-state and transient solutions of the modified-TCMT model. The proposed correction is derived from general considerations, energy conservation and the non-resonant power circulating in the system, therefore it provides good insight on how the TCMT model should be modified to eventually account for the same limitation in a different coupled-resonator design. Moreover, our discussion based on coupled microring resonators can be useful for other electromagnetic resonant systems due to the generality and far-reach of the TCMT formalism.Comment: 7 pages, 4 figure

Interleukin-6 increases the expression and activity of insulin-degrading enzyme

FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOImpairment of the insulin-degrading enzyme (IDE) is associated with obesity and type 2 diabetes mellitus (T2DM). Here, we used 4-mo-old male C57BL/6 interleukin-6 (IL-6) knockout mice (KO) to investigate the role of this cytokine on IDE expression and activity. IL-6 KO mice displayed lower insulin clearance in the liver and skeletal muscle, compared with wild type (WT), due to reduced IDE expression and activity. We also observed that after 3-h incubation, IL-6, 50 and 100 ng ml(-1), increased the expression of IDE in HEPG2 and C2C12 cells, respectively. In addition, during acute exercise, the inhibition of IL-6 prevented an increase in insulin clearance and IDE expression and activity, mainly in the skeletal muscle. Finally, IL-6 and IDE concentrations were significantly increased in plasma from humans, after an acute exercise, compared to pre-exercise values. Although the increase in plasma IDE activity was only marginal, a positive correlation between IL-6 and IDE activity, and between IL-6 and IDE protein expression, was observed. Our outcomes indicate a novel function of IL-6 on the insulin metabolism expanding the possibilities for new potential therapeutic strategies, focused on insulin degradation, for the treatment and/or prevention of diseases related to hyperinsulinemia, such as obesity and T2DM.Impairment of the insulin-degrading enzyme (IDE) is associated with obesity and type 2 diabetes mellitus (T2DM). Here, we used 4-mo-old male C57BL/6 interleukin-6 (IL-6) knockout mice (KO) to investigate the role of this cytokine on IDE expression and act7112FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO2014/24719-7; 2015/12611-

Geometría y pérdidas de carga en inyectores Venturi mediante la dinámica de fluidos computacional

[EN] To determine the influence of geometry on the hydrodynamic behavior of Venturi injectors, using computational fluid dynamics techniques, we studied, at the Universitat Politècnica de València, Valencia, Spain, the geometric parameters that exert the most influence on head losses: the relationship between throat diameter and nozzle (β), nozzle angle (α1) and diffuser angle (α2). In addition, three throat morphologies (B1: nozzle-throat and throat-diffuser with a sharp edge; B2: nozzle-diffuser with a zero-length, sharp-edge throat; B3: nozzle-throat and throat-diffuser with rounded edge). We analyzed their influence on the velocity distribution and differential pressure between inlet and throat (DP/γ), throat and outlet (Δhv/γ), and outlet and throat ((P3-P2)/γ). The development of the velocity profile from the throat is slower the greater β is and the lower α2 is. DP/γ decreases with β, increases with α1 and varies little with α2. Δhv/γ decreases with β and increases with α1 and α2. (P3-P2)/γ decreases with β and increases with α1 and α2. Geometry B3 decreases the losses and delays the onset of cavitation. Thus, the lower β and the higher α2, the greater the losses; however, the influence of α1 is less clear. The rounded edges produce lower head losses.[ES] Estudio de la influencia de la geometría en el comportamiento hidrodinámico de inyectores Venturi mediante técnicas de dinámica de fluidos computacional. Para determinar la influencia de la geometría en el comportamiento hidrodinámico de inyectores Venturi, mediante técnicas de dinámica de fluidos computacional, se estudió, en la Universitat Politècnica de València, Valencia, España, los parámetros geométricos que más influencian las pérdidas de carga: relación entre diámetro de la garganta y tobera (β), ángulo de la tobera (α1) y ángulo del difusor (α2). Además, tres morfologías de la garganta (B1: tobera-garganta y garganta-difusor en arista viva; B2: tobera-difusor con garganta de longitud nula y en arista viva; B3: tobera-garganta y garganta-difusor en arista redondeadas). Se ha analizado su influencia en la distribución de velocidad y en la presión diferencial entre entrada y garganta (DP/γ), garganta y salida (∆hv/γ), y salida y garganta ((P3-P2)/γ). El desarrollo del perfil de velocidades a partir de la garganta es más lento cuanto mayor es β y menor es α2. DP/γ disminuye con β, aumenta con α1 y es poco variable con α2. ∆hv/γ disminuye con β y aumenta con α1 y α2. (P3-P2)/γ disminuye con β y α1, yaumenta con y α2. La geometría B3 disminuye las pérdidas y retarda la aparición de la cavitación. Así, cuanto menor es β y cuanto mayor es α2, mayores son las pérdidas de carga, sin embargo, la influencia de α1 no es tan clara. Las aristas redondeadas producen menores perdidas de cargaThe authors would like to thank the “Conselleria d'Empresa, Universitat i Ciència” of Generalitat Valenciana – Spain.Manzano Juarez, J.; Palau, CV.; De Azevedo, BM.; Do Bomfim, GV.; Vasconcelos, DV. (2016). Geometry and head loss in Venturi injectors through Computational Fluid Dynamics. Engenharia Agrícola. 36(3):482-491. doi:10.1590/1809-4430-Eng.Agric.v36n3p482-491/2016S482491363Baylar, A., Aydin, M., Unsal, M., & Ozkan, F. (2009). Numerical Modeling of Venturi Flows for Determining Air Injection Rates Using Fluent V6.2. Mathematical and Computational Applications, 14(2), 97-108. doi:10.3390/mca14020097Chan, L., Chin, C., Soria, J., & Ooi, A. (2014). Large eddy simulation and Reynolds-averaged Navier-Stokes calculations of supersonic impinging jets at varying nozzle-to-wall distances and impinging angles. International Journal of Heat and Fluid Flow, 47, 31-41. doi:10.1016/j.ijheatfluidflow.2014.02.005Dantas Neto, J., Maciel, J. L., Alves, A. de S., Azevedo, C. A. V. de, Fernandes, P. D., & Lima, V. L. A. de. (2013). Teores de macronutrientes em folhas de goiabeira fertirrigada com nitrogênio. Revista Brasileira de Engenharia Agrícola e Ambiental, 17(9), 962-968. doi:10.1590/s1415-43662013000900008Rezende, R., Helbel Júnior, C., Souza, R. S. de, Antunes, F. M., & Frizzone, J. A. (2010). Crescimento inicial de duas cultivares de cafeeiro em diferentes regimes hídricos e dosagens de fertirrigação. Engenharia Agrícola, 30(3), 447-458. doi:10.1590/s0100-69162010000300009Sanderse, B., Pijl, S. P., & Koren, B. (2011). Review of computational fluid dynamics for wind turbine wake aerodynamics. Wind Energy, 14(7), 799-819. doi:10.1002/we.458Santos, L. D. C., Zocoler, J. L., Justi, A. L., Silva, A. O., & Correia, J. D. S. (2012). ESTUDO COMPARATIVO DA TAXA DE INJEÇÃO EM INJETOR DO TIPO VENTURI COM E SEM VÁLVULA DE RETENÇÃO. IRRIGA, 1(01), 145. doi:10.15809/irriga.2012v1n01p145Sun, Y., & Niu, W. (2012). Simulating the Effects of Structural Parameters on the Hydraulic Performances of Venturi Tube. Modelling and Simulation in Engineering, 2012, 1-7. doi:10.1155/2012/458368Uribe, R. A. M., Gava, G. J. de C., Saad, J. C. C., & Kölln, O. T. (2013). Ratoon sugarcane yield integrated drip-irrigation and nitrogen fertilization. Engenharia Agrícola, 33(6), 1124-1133. doi:10.1590/s0100-69162013000600005Vasata, D., Galante, G., Rizzi, R. L., & Zara, R. A. (2011). Solução computacional do problema da cavidade cúbica através das equações de Navier-Stokes tridimensionais. Revista Brasileira de Ensino de Física, 33(2), 1-10. doi:10.1590/s1806-11172011000200013Yeoh, G. H., Liu, C., Tu, J., & Timchenko, V. (2012). Computational Fluid Dynamics and Its Applications 2012. Modelling and Simulation in Engineering, 2012, 1-2. doi:10.1155/2012/61061

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery