The emerging inverse electron demand Diels-Alder (IEDDA) reaction stands out from other bioorthogonal reactions by virtue of its unmatchable kinetics, excellent orthogonality and biocompatibility. ...With the recent discovery of novel dienophiles and optimal tetrazine coupling partners, attention has now been turned to the use of IEDDA approaches in basic biology, imaging and therapeutics. Here we review this bioorthogonal reaction and its promising applications for live cell and animal studies. We first discuss the key factors that contribute to the fast IEDDA kinetics and describe the most recent advances in the synthesis of tetrazine and dienophile coupling partners. Both coupling partners have been incorporated into proteins for tracking and imaging by use of fluorogenic tetrazines that become strongly fluorescent upon reaction. Selected notable examples of such applications are presented. The exceptional fast kinetics of this catalyst-free reaction, even using low concentrations of coupling partners, make it amenable for in vivo radiolabelling using pretargeting methodologies, which are also discussed. Finally, IEDDA reactions have recently found use in bioorthogonal decaging to activate proteins or drugs in gain-of-function strategies. We conclude by showing applications of the IEDDA reaction in the construction of biomaterials that are used for drug delivery and multimodal imaging, among others. The use and utility of the IEDDA reaction is interdisciplinary and promises to revolutionize chemical biology, radiochemistry and materials science.
Enzymatic formation of supramolecular nanofibers is demonstrated as a novel approach to induce intracellular hydrogelation and control the fate of cells or cellular functions, which can lead to a new ...paradigm for developing biomaterials to manage cellular artificial nanostructures (CAN), understand cellular functions beyond the molecular level, and create novel therapeutics.
Both anti-PD1/PD-L1 therapy and oncolytic virotherapy have demonstrated promise, yet have exhibited efficacy in only a small fraction of cancer patients. Here we hypothesized that an oncolytic ...poxvirus would attract T cells into the tumour, and induce PD-L1 expression in cancer and immune cells, leading to more susceptible targets for anti-PD-L1 immunotherapy. Our results demonstrate in colon and ovarian cancer models that an oncolytic vaccinia virus attracts effector T cells and induces PD-L1 expression on both cancer and immune cells in the tumour. The dual therapy reduces PD-L1
cells and facilitates non-redundant tumour infiltration of effector CD8
, CD4
T cells, with increased IFN-γ, ICOS, granzyme B and perforin expression. Furthermore, the treatment reduces the virus-induced PD-L1
DC, MDSC, TAM and Treg, as well as co-inhibitory molecules-double-positive, severely exhausted PD-1
CD8
T cells, leading to reduced tumour burden and improved survival. This combinatorial therapy may be applicable to a much wider population of cancer patients.
Global manufacturing companies have some pressing needs to improve production visibility and decision-making performance by implementing effective production monitoring and scheduling. This paper ...proposes a radio frequency identification (RFID)-based intelligent decision support system architecture to handle production monitoring and scheduling in a distributed manufacturing environment. A pilot implementation of the architecture is reported in a distributed clothing manufacturing environment. RFID and cloud technologies were integrated for real-time and remote production capture and monitoring. Intelligent optimization techniques were also implemented to generate effective production scheduling solutions. A prototype system with remote monitoring and production scheduling functions was developed and implemented in a distributed manufacturing environment, which demonstrated the effectiveness of the architecture. The proposed architecture has good extensibility and scalability, which can easily be integrated with production decision-making as well as production and logistics operations in the supply chain. Lastly, this paper discusses the difficulties encountered and lessons learned during system implementation and the managerial implications of the proposed architecture.
•Integrate RFID, cloud technology and intelligent techniques for monitoring and scheduling.•RFID and cloud-based architecture improves production transparency and visibility.•Intelligent optimization techniques generate effective production scheduling solutions.•The architecture is helpful to increase production efficiency, and reduce wastes and costs.•Difficulties and lessons in implementation and managerial implications are discussed.
Origami structures are mechanical metamaterials with properties that arise almost exclusively from the geometry of the constituent folds and the constraint of piecewise isometric deformations. Here ...we characterize the geometry and planar and nonplanar effective elastic response of a simple periodically folded Miura-ori structure, which is composed of identical unit cells of mountain and valley folds with four-coordinated ridges, defined completely by two angles and two lengths. We show that the in-plane and out-of-plane Poisson's ratios are equal in magnitude, but opposite in sign, independent of material properties. Furthermore, we show that effective bending stiffness of the unit cell is singular, allowing us to characterize the two-dimensional deformation of a plate in terms of a one-dimensional theory. Finally, we solve the inverse design problem of determining the geometric parameters for the optimal geometric and mechanical response of these extreme structures.
Characterized by cyclic axisymmetric perturbations to both the magnetic and fluid parameters, magnetohydrodynamic fast sausage modes (FSMs) have proven useful for solar coronal seismology given their ...strong dispersion. This review starts by summarizing the dispersive properties of the FSMs in the canonical configuration where the equilibrium quantities are transversely structured in a step fashion. With this preparation we then review the recent theoretical studies on coronal FSMs, showing that the canonical dispersion features have been better understood physically, and further exploited seismologically. In addition, we show that departures from the canonical equilibrium configuration have led to qualitatively different dispersion features, thereby substantially broadening the range of observations that FSMs can be invoked to account for. We also summarize the advances in forward modeling studies, emphasizing the intricacies in interpreting observed oscillatory signals in terms of FSMs. All these advances notwithstanding, we offer a list of aspects that remain to be better addressed, with the physical connection of coronal FSMs to the quasi-periodic pulsations in solar flares particularly noteworthy.
The dynamic cylindrical cavity expansion model for a rate-dependent target material was previously derived by Warren to examine the effects of strain-rate sensitivity on the radial stress acting on a ...perforating projectile. However, the equations presented were largely analytical and were not further applied to predict the ballistic performance of ductile target plates. The current work expands on Warren’s derivation to model the dynamics of conical and ogival geometries, and the rate-dependent model is compared to prior experimental results of 7.62-mm APM2 rounds impacting 6061-T6511 aluminum alloy plates. Results show that including rate effects improves the ballistic performance prediction, even for a marginally strain-rate sensitive material such as Al6061-T651. However, existing semi-empirical variations of the cavity expansion model can provide the same degree of accuracy if target material rate-sensitivity parameters are not readily available.
We fabricate ultrasmall phosphorene quantum dots (PQDs) with an average size of 2.6 ± 0.9 nm using a liquid exfoliation method involving ultrasound probe sonication followed by bath sonication. By ...coupling the as-prepared PQDs with microfiber evanescent light field, the PQD-based saturable absorber (SA) device exhibits ultrafast nonlinear saturable absorption property, with an optical modulation depth of 8.1% at the telecommunication band. With the integration of the all-fiber PQD-based SA, a continuous-wave passively mode-locked erbium-doped (Er-doped) laser cavity delivers stable, self-starting pulses with a pulse duration of 0.88 ps and at the cavity repetition rate of 5.47 MHz. Our results contribute to the growing body of work studying the nonlinear optical properties of ultrasmall PQDs that present new opportunities of this two-dimensional (2D) nanomaterial for future ultrafast photonic technologies.
Abstract
Betatron acceleration, a plasma process obtaining particle energy in the perpendicular direction but reserving energy in the field-aligned direction, is the consequence of magnetic strength ...enhancement when the first adiabatic invariant is conserved. Such process has been widely reported in the terrestrial magnetosphere but is barely reported in other planetary environments. Here, based on the in situ measurements from the Mars Atmosphere and Volatile Evolution mission, we report two events of betatron acceleration upstream of the Martian bow shock. In both events, betatron accelerations increase the fluxes of suprathermal electrons. The acceleration processes in these events are quantitatively reproduced with an analytical model. Gratifyingly, we find the acceleration factors derived from the analytical model are well consistent with the observations of magnetic strength enhancement. These results for the first time show that the betatron acceleration is an active upstream of the Martian bow shock and is very useful to help us understand the generation of energetic electrons in the Martian environment.
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