Data-driven analysis of the simulations of the spread of COVID-19 under different interventions of China.

Since February 2020, COVID-19 has spread rapidly to more than 200 countries in the world. During the pandemic, local governments in China have implemented different interventions to efficiently control the spread of the epidemic. Characterizing transmission of COVID-19 under some typical interventions is essential to help countries develop appropriate interventions. Based on the pre-symptomatic transmission patterns of COVID-19, we established a novel compartmental model: Susceptible-Infectious-Confirmed-Removed (SICR) model, which allowed the effective reproduction number to change over time, thus the effects of policies could be reasonably estimated. Using the epidemic data of Wuhan, Wenzhou, and Shenzhen, we migrated the corresponding estimated policy modes to South Korea, Italy, and the United States and simulated the potential outcomes for these countries when they adopted similar policy strategies to China. We found that the mild interventions implemented in Shenzhen were effective in controlling the epidemic in the early stage, while more stringent policies which were implemented in Wuhan and Wenzhou were necessary if the epidemic became severe and needed to be controlled in a short time.

App-Free Method for Visualization of Polymers in 3D and Augmented Reality.

The rise of virtual and online education in recent years has led to the development and popularization of many online tools, notably three-dimensional (3D) models and augmented reality (AR), for visualizing various structures in chemical sciences. The majority of the developed tools focus on either small molecules or biological systems, as information regarding their structure can be easily accessed from online databases or obtained through relatively quick calculations. As such, due to a lack of crystallographic and theoretical data available for nonbiological macromolecules, there is a noticeable lack of accessible online tools for the visualization of polymers in 3D. Herein, using a few sample polymers, we showcase a workflow for the generation of 3D models using molecular dynamics and Blender. The 3D structures can then be hosted on p3d.in, where AR models can be generated automatically. Furthermore, the hosted 3D models can then be shared via quick response (QR) codes and used in various settings without the need to download any applications.

Research on biomimetic design and impact characteristics of periodic multilayer helical structures.

Osteons are composed of concentric lamellar structure, the concentric lamellae are composed of periodic thin and thick sub-lamellae, and every 5 sub-lamellae is a cycle, the periodic helix angle of mineralized collagen fibers in two adjacent sub-lamellae is 30°. Four biomimetic models with different fiber helix angles were established and fabricated according to the micro-nano structure of osteon. The effects of the fiber periodic helical structure on impact characteristic and energy dissipation of multi-layer biomimetic composite were investigated. The calculation results indicated that the stress distribution, contact characteristics and fiber failur during impact, and energy dissipation of the composite are affected by the fiber helix angle. The stress concentration of composite materials under external impact can be effectively improved by adjusting the fiber helix angle when the material composition and material performance parameters are same. Compared with the sample30, the maximum stress of sample60 and sample90 increases by 38.1% and 69.8%, respectively. And the fiber failure analysis results shown that the model with a fiber helix angle of 30° has a better resist impact damage. The drop-weight test results shown that the impact damage area of the specimen with 30° helix angle is smallest among the four types of biomimetic specimens. The periodic helical structure of mineralized collagen fibers in osteon can effectively improve the impact resistance of cortical bone. The research results can provide useful guidance for the design and manufacture of high-performance, impact-resistant biomimetic composite materials.

Computational Analysis of Pathological Image Enables Interpretable Prediction for Microsatellite Instability.

Background: Microsatellite instability (MSI) is associated with several tumor types and has become increasingly vital in guiding patient treatment decisions; however, reasonably distinguishing MSI from its counterpart is challenging in clinical practice. Methods: In this study, interpretable pathological image analysis strategies are established to help medical experts to identify MSI. The strategies only require ubiquitous hematoxylin and eosin-stained whole-slide images and perform well in the three cohorts collected from The Cancer Genome Atlas. Equipped with machine learning and image processing technique, intelligent models are established to diagnose MSI based on pathological images, providing the rationale of the decision in both image level and pathological feature level. Findings: The strategies achieve two levels of interpretability. First, the image-level interpretability is achieved by generating localization heat maps of important regions based on deep learning. Second, the feature-level interpretability is attained through feature importance and pathological feature interaction analysis. Interestingly, from both the image-level and feature-level interpretability, color and texture characteristics, as well as their interaction, are shown to be mostly contributed to the MSI prediction. Interpretation: The developed transparent machine learning pipeline is able to detect MSI efficiently and provide comprehensive clinical insights to pathologists. The comprehensible heat maps and features in the intelligent pipeline reflect extra- and intra-cellular acid-base balance shift in MSI tumor.

Catechol Moiety Integrated Tri-Aryl Type AIEgen for Visual and Quantitative Boronic Acid Detection.

Novel functional AIEgen based on three compact bound aryl skeletons is designed and synthesized. This tri-aryl type luminogen (TA-Catechol) embedded with catechol moiety responds rapidly to series of boronic acids. Real-time visual and quantitative dual-mode detection method is established for the first time with modest precision and low detection limit (8.0 µM). Detailed mechanistic discussion identifies tetra-coordinated boronic species as the key intermediate within sensing procedure. Wide range of organic boronic acids compatible with this strategy is displayed which is promising in high throughput screening technology. Furthermore, solid-state sensing capability of TA-Catechol is also demonstrated.

Thermally activated delayed fluorescence materials with aggregation-induced emission properties: a QM/MM study.

Organic molecules with thermally activated delayed fluorescence (TADF) and aggregation induced emission (AIE) properties have attracted increasing research interest due to their great potential applications in organic light emitting diodes (OLEDs), especially for those with multicolor mechanochromic luminescence (MCL) features. Theoretical research on the luminescence characteristics of organic TADF emitters based on the aggregation states is highly desired to quantify the relationship between the TADF properties and aggregation states. In this work, we study the 4,4'-(6-(9,9-dimethylacridine-10(9H)-yl)quinoline-2,3-dibenzonitrile (DMAC-CNQ) emitter with TADF and AIE properties, and calculate the photophysical properties in gas, solid and amorphous states by using the quantum mechanics and molecular mechanics (QM/MM) method. Our simulations demonstrate that the aggregation states enhance obviously the reverse intersystem crossing rates and transition dipole moments of the DMAC-CNQ emitter, and suppress the non-radiative rates from the lowest excited singlet state (S1) to ground state (S0). Specifically, the molecular stacking of DMAC-CNQ in solid phases can mainly restrict the geometric torsion of the DMAC moiety for decreasing non-radiative decay rates, and the torsion of the CNQ moiety for increasing the reverse intersystem crossing rates. As a result, the calculated fluorescence efficiencies of the DMAC-CNQ emitter in the crystal and amorphous states are 67% and 26% respectively, and in good agreement with the experimental results.

Aggregation-Enhanced Thermally Activated Delayed Fluorescence Efficiency for Two-Coordinate Carbene-Metal-Amide Complexes: A QM/MM Study.

The two-coordinate carbene-metal-amide complexes have attracted a great deal of attention due to their remarkable thermally activated delayed fluorescence (TADF) properties, giving them promise in organic light-emitting diode application. To reveal the inherent mechanism, we take CAAC-Cu(I)-Cz and CAAC-Au(I)-Cz as examples to investigate the photophysical properties in solution and solid phases by combining quantum mechanics/molecular mechanics approaches for the electronic structure and the thermal vibration correlation function formalism for the excited-state decay rates. We found that both intersystem crossing (ISC) and its reverse (rISC) are enhanced by 2-4 orders of magnitude upon aggregation, leading to highly efficient TADF, because (i) the metal proportion in the frontier molecular orbitals increases, leading to an enhanced spin-orbit coupling strength between S1 and T1, and (ii) the reaction barriers for ISC and rISC are much lower in solution than in aggregate phases through a decrease in energy gap ΔEST and an increase in the relative reorganization energy through bending the angle ∠C2-Cu-N1 for T1. We propose a pump-probe time-resolved infrared spectroscopy study to verify the mechanism. These findings can clarify the ongoing dispute over the understanding of the high TADF quantum efficiency for two-coordinate metal complexes.

Finite element analysis on multi-toughening mechanism of microstructure of osteon.

The toughening mechanism of cortical bone is closely related to its hierarchical microstructure. Osteon is the most important microstructure of cortical bone. Therefore, it is very important to study the toughening mechanism of the microstructure of osteon. There are three main kinds of cracks in cortical bone: external crack of osteon, internal radial cracks of osteon and microporous damage cracks. Numerical models for these three kinds of cracks are established by XFEM and the progressive damage approach, respectively. The multi-toughening mechanisms of microstructure of osteon are found. The cement line on the outside of osteon is its first toughening mechanism, which can make the crack deflection and improve the fracture resistance of osteon. The resistance of cement line to fracture increases with the decrease of the strength and the increase of the thickness. The second toughening mechanism is elliptical osteocyte lacunae, which can attract the crack into the elliptical lacunae and cause stress redistribution to prevent the crack propagation. The annularly elliptical lacuna structure is an optimized arrangement and shape of microstructure, which is the third toughening mechanism of osteon. This microstructure can determine the location of the crack initiation and make the microcracks propagate along the annular direction rather than penetrating into the haversian cannal to protect the integrity of the osteon. The study of these toughening mechanisms provides new ideas for the research and design of synthetic composite structures.

Graph analysis of proton conduction pathways in scandium-doped barium zirconate.

Understanding the relationship between the acceptor dopant size and proton conductivity in barium zirconate, BaZrO3, is important for maximizing efficiency in this promising fuel cell material. While proton conduction pathways with larger YZr ' and smaller AlZr ' defects have been explored, proton pathways with ScZr ', a defect of comparable size to the replaced ion, have not been investigated using centrality measures, periodic pathway searches, and kinetic Monte Carlo (KMC). Centrality measures in BaSc0.125Zr0.875O3 highlight a trapping region by ScZr ' and scattered high centrality regions on undoped planes. Connected long-range high centrality regions are found mainly in undoped planes for BaAl0.125Zr0.875O3 and in the dopant planes for BaY0.125Zr0.875O3. The best long-range proton conduction periodic pathways in AlZr ' and ScZr ' systems travel between dopant planes, while those for yttrium-doped BaZrO3 remained on dopant planes. KMC trajectories at 1000 K show long-range proton conduction barriers of 0.86 eV, 0.52 eV, and 0.25 eV for AlZr ', ScZr ', and YZr ' systems, respectively. Long-range periodic conduction highway limiting barrier averages correlate well with the connectivity of the most central regions in each system but ignore diffusion around the dopant and through other high centrality regions. BaSc0.125Zr0.875O3 shows an intermediate overall conduction barrier limited by trapping, which earlier experiments and simulations suggest that it can be mitigated with increased oxygen vacancy concentration.

MTIF2 impairs 5 fluorouracil-mediated immunogenic cell death in hepatocellular carcinoma in vivo: Molecular mechanisms and therapeutic significance.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related morbidity and mortality; it has been reported that immune cell infiltration is a prognosis factor. Here we identified genes that associated with tumor immune cell infiltrate; the underlying mechanism was verified by in vivo and in vitro experiment. In this study, Weighted correlation network analysis (WGCNA) and CIBERSORT tool were used to identify MTIF2 as the hub tumor immune infiltrating gene in HCC. To investigate the underlying role played by MTIF2, MTIF2 was knocked down by transfection of shRNA targeting MTIF2, CCK8, and EdU incorporation assay was used to evaluate the effect of MTIF2 on proliferation, wound heal assay and transwell assay was used to confirm its effect on cell migration. Ecto-calreticulin on the cell surface was evaluated by flow cytometry, ATP, and HMGB1 secretion were tested to the investigated effect of MTIF2 on the immunogenic cell death (ICD) process. We found that down-regulation of MTIF2 impaired proliferation and migration capacity of HCC cells, chemoresistance to 5-Fluorouracil (5-FU) weakened after MTIF2 was knocked down. Reduced release of damage-associated molecular patterns (DAMP) was observed after MTIF2 was overexpressed, which subsequently impaired dendritic cell (DC) maturation and proliferation of CD8 + T cells. Mechanically, the co-IP experiment confirmed that MTIF2 could interact with AIFM1, prevents AIFM1 induced transcription of caspase3, and finally suppress apoptosis. In vivo experiment also used to confirm our previously conclusion, our result indicated that MTIF2 overexpression suppresses tumor apoptosis and immune cell activity in the 5-FU therapy in vivo model, by suppression maturation of tumor-infiltrated DC. Collectively, our study confirmed that MTIF2 impair drug-induced immunogenic cell death in hepatocellular carcinoma cells.

Strong Solid-State Fluorescence Induced by Restriction of the Coordinate Bond Bending in Two-Coordinate Copper(I)-Carbene Complexes.

The photophysical properties of two-coordinate copper(I) complexes have become a new research hotspot due to their nearly perfect luminescent properties and low price and promising applications in organic light-emitting diodes (OLEDs). In this work, we employ the hybrid quantum mechanics and molecular mechanics (QM/MM) approach, coupled with our early developed thermal vibration correlation function (TVCF) rate formalism, to study the aggregation effect on the luminescent properties of the cyclic (alkyl)(amino)carbene-copper(I)-Cl complex. Our calculations reveal that the transition properties changes from metal-ligand-charge-transfer (MLCT) in solution to hybrid halogen ligand charge-transfer (XLCT) and MLCT in solid state, which induces the blue-shifted emission spectra from solution to solid phase. Upon aggregation, the restriction of the bending vibrations of the C-Cu-Cl and Cu-C-N bonds largely slow down the nonradiative decay, which induces strong fluorescence. This study provides a clear rationalization for the highly efficient fluorescence character of two-coordinate Cu(I) complexes.

Investigation of inner mechanism of anisotropic mechanical property of antler bone.

Bones have different functions and various applications depending on the roles they play in different mammal bodies. The internal relationships between the functions and microstructures of bones need further expounding to understand their specific mechanical properties. In this study, the relationships between the mechanical properties and microstructures of the compact bone of antler (called as antler bone for short) along its three different orientations are investigated. First, the bending mechanical properties of the specimens of the antler bone along its three different orientations are tested with material-testing machine, followed by the observations of the crack-extending routes and the fracture surfaces of the three different orientations with a scanning electron microscope (SEM). The results of the tests reveal that the antler bone possesses anisotropic mechanical property. Namely, the mechanical properties of the antler bone are closely related to its orientations. Concretely, the fracture strength, elastic modulus and work-of-fracture along the transversal orientation of the bone are remarkably larger than those of the longitudinal and radial orientations. The results of the observation of the SEM show that there are different crack-extending routes and fracture-surface characteristics along the three different fracture orientations of the bone. Specifically, there are crack deflections and crack twists along the transversal fracture orientation, crack bridging along the longitudinal fracture orientation and crack rounding of osteons along the radial fracture orientation. Based on the tested and observed results, the fractal models of the crack-extending routes along the three different fracture orientations are presented. The fractal dimensions and critical crack extension forces along the three different fracture directions are calculated based on the fractal models. Further, the box-counting method is adopted to verify the correctness of the models. It is indicated that the fractal dimension and fracture energy of the transversal orientation are obviously larger than those of the longitudinal and radial orientations, which are in accordance with the experimental results.

Effects of Shape and Orientation of Pore Canals on Mechanical Behaviors of Lobster Cuticles.

The work is to investigate the relationships between the microstructures and mechanical behaviors of lobster cuticles and reveal the inner mechanisms of the anisotropic mechanical properties of the cuticles and give the helpful guidance for the design of high-performance man-made composites. First, the tensile mechanical properties of the longitudinal and transverse specimens of the cuticles of American lobsters were tested with a mechanical-testing instrument. It is was found that the fracture strength and elastic modulus of the longitudinal specimens are distinctly larger than those of the transverse specimens. Then, the microstructural characteristics of the fracture surfaces of the specimens were observed with scanning electron microscope. It was observed that the pore canals in the cuticles are elliptic and their orientations are along the longitudinal orientation of the cuticles. Furthermore, the stresses and micro-damage of the longitudinal and transverse specimens were calculated with the rule of progressive damage by finite element method. It was revealed that the shape and orientation of the pore canals in the cuticles give rise to the anisotropic mechanical property of the cuticles and ensure that the cuticles possess the largest fracture strength and elastic modulus along their largest main-stress orientation.

Efficient, tunable flip-chip-integrated III-V/Si hybrid external-cavity laser array.

We demonstrate a surface-normal coupled tunable hybrid silicon laser array for the first time using passively-aligned, high-accuracy flip chip bonding. A 2x6 III-V reflective semiconductor optical amplifier (RSOA) array with integrated total internal reflection mirrors is bonded to a CMOS SOI chip with grating couplers and silicon ring reflectors to form a tunable hybrid external-cavity laser array. Waveguide-coupled wall plug efficiency (wcWPE) of 2% and output power of 3 mW has been achieved for all 12 lasers. We further improved the performance by reducing the thickness of metal/dielectric stacks and achieved 10mW output power and 5% wcWPE with the same integration techniques. This non-invasive, one-step back end of the line (BEOL) integration approach provides a promising solution to high density laser sources for future large-scale photonic integrated circuits.

QM/MM Study on Mechanistic Photophysics of Alloxazine Chromophore in Aqueous Solution.

Compared with isoalloxazine, the core chromophore of biologically important flavins, alloxazine exhibits much lower fluorescence quantum yield and larger intersystem-crossing quantum yield. However, its efficient radiationless relaxation pathways are still elusive. In this work, we have used the QM(MS-CASPT2//CASSCF)/MM method to explore the mechanistic photophysics of alloxazine chromophore in aqueous solution. On the basis of the optimized minima, conical intersections, and crossing points in the lowest (1)ππ*, (1)nπ*, (3)ππ*, and (3)nπ* states, we have proposed three energetically possible nonadiabatic relaxation pathways populating the lowest (3)ππ* triplet state from the initially populated excited (1)ππ* singlet state. The first is the direct (1)ππ*→ (3)ππ* intersystem crossing via the (1)ππ*/(3)ππ* crossing point. The second is an indirect (1)ππ* → (3)ππ* intersystem crossing relayed by the dark (1)nπ* singlet state. In this route, the (1)ππ* system first decays to the (1)nπ* state via the (1)ππ*/(1)nπ* conical intersection, followed by an (1)nπ*→ (3)ππ* intersystem crossing at the (1)nπ*/(3)ππ* crossing point to arrive at the final (3)ππ* state. The third is similar to the second one; but its intersystem crossing is relayed by the (3)nπ* triplet state. The (1)ππ* system first decays to the (3)nπ* state via the (1)ππ*/(3)nπ* crossing point; the generated (3)nπ* state is then de-excited to the (3)ππ* state through the (3)nπ*→ (3)ππ* internal conversion at the (3)nπ*/(3)ππ* conical intersection. According to the classical El-Sayed rule, we suggest the second and third paths play a much more important role than the first one in the formation of the lowest (3)ππ* state.

Error-free operation of a polarization-insensitive 4λ x 25 Gbps silicon photonic WDM receiver with closed-loop thermal stabilization of Si microrings.

We report the first closed-loop operation of a 100 Gbps polarization-insensitive, 4-channel wavelength-tracking WDM receiver in silicon photonics platform. Error-free operation is achieved with input polarization scrambling over input wavelength change of 4.5 nm using efficient thermal tuning of Si microring demux, corresponding to greater than 60°C fluctuation in temperature.

Albuterol in the treatment of acute respiratory distress syndrome: A meta-analysis of randomized controlled trials.

BACKGROUND: This meta-analysis of randomized controlled trials aimed to systematically evaluate the value of albuterol in the treatment of patients with acute respiratory distress syndrome (ARDS). DATA SOURCES: Randomized controlled trials on albuterol treatment of ARDS from its inception to October 2014 were searched systematically. The databases searched included: PubMed, Ovid EMBASE, Ovid Cochrane, CNKI, WANFANG and VIP. The trials were screened according to the pre-designed inclusion and exclusion criteria. We performed a systematic review and meta-analysis of the randomized controlled trials (RCTs) on albuterol treatment, attempting to improve outcomes, i.e. lowering the 28-day mortality and ventilator-free days. RESULTS: Three RCTs involving 646 patients met the inclusion criteria. There was no significant decrease in the 28-day mortality (risk difference=0.09; P=0.07, P for heterogeneity=0.22, I (2)=33%). The ventilator-free days and organ failure-free days were significantly lower in the patients who received albuterol (mean difference=-2.20; P<0.001, P for heterogeneity=0.49, I (2)=0% and mean difference=-1.71, P<0.001, P for heterogeneity=0.60, I (2)=0%). CONCLUSIONS: Current evidences indicate that treatment with albuterol in the early course of ARDS was not effective in increasing the survival, but significantly decreasing the ventilator-free days and organ failure-free days. Owing to the limited number of included trails, strong recommendations cannot be made.

An all-solid-state, WDM silicon photonic digital link for chip-to-chip communications.

We describe a multiwavelength hybrid-integrated solid-state link on a 3 µm silicon-on-insulator (SOI) nanophotonic platform. The link spans three chips and employs germanium-silicon electroabsorption waveguide modulators, silicon transport waveguides, echelle gratings for multiplexing and demultiplexing, and pure germanium waveguide photo-detectors. The 8λ WDM Tx and Rx components are interconnected via a routing "bridge" chip using edge-coupled optical proximity communication. The packaged, retimed digital WDM link is demonstrated at 10 Gb/s and 10(-12) BER, with three wavelength channels consuming an on-chip power below 1.5 pJ/bit, excluding the external laser power.

Microring-based multi-chip WDM photonic module.

We report on a packaged prototype of a WDM photonic transceiver. It is an all-solid state hybrid assembly based on 130nm SOI photonic circuitry integrated with a 40nm CMOS VLSI driver. Our prototype supports eight tunable WDM channels operating at 10Gb/s, each capable of both transmitting and receiving data on the same chip. We discuss two options to close the link using the optical fiber or a waveguide bridge chip. We provide integration details and supporting link measurement data to describe packaged photonic module and its power efficient functionality with its on-chip power per channel averaging 1.3pJ/bit, excluding off-chip laser electrical power.

Demonstration of 12.2% wall plug efficiency in uncooled single mode external-cavity tunable Si/III-V hybrid laser.

A Si/III-V hybrid laser has been a highly sought after device for energy-efficient and cost-effective high-speed silicon photonics communication. We present a high wall-plug efficiency external-cavity hybrid laser created by integrating an independently optimized SOI ring reflector and a III-V gain chip. In our demonstration, the uncooled integrated laser achieved a waveguide-coupled wall-plug efficiency of 12.2% at room temperature with an optical output power of ~10 mW. The laser operated single-mode near 1550 nm with a linewidth of 0.22 pm. This is a tunable light source with 8 nm wavelength tuning range. A proof-of-concept laser wavelength stabilization technique has also been demonstrated. Using a simple feedback loop, we achieved mode-hop-free operation in a packaged external-cavity hybrid laser as bias current was varied by 60mA.