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A Structural Ensemble of a Tau-Microtubule Complex Reveals Regulatory Tau Phosphorylation and Acetylation Mechanisms
No full textAbstract Tau is a microtubule-associated protein that regulates the stability of microtubules. The affinity of tau for microtubules is modulated by post-translational modifications, and the dysregulation of these events has been associated with the aberrant aggregation of tau in Alzheimer's disease and related tauopathies. Here, we use the metainference cryo-electron microscopy approach to determine an ensemble of structures representing the structure and dynamics of a tau-microtubule complex comprising an extended microtubule-binding region of tau (residues 202-395). We thus identify the ground state of the complex and a series of excited states of lower populations. An analysis of the interactions in these states of structures reveals positions in the tau sequence that are important to determine the overall stability of the tau-microtubule complex. This analysis leads to the identification of positions where phosphorylation and acetylation events have destabilising effects, which we validate by using site-specific post-translationally modified tau variants obtained by chemical mutagenesis. Taken together, these results illustrate how the simultaneous determination of ground and excited states of macromolecular complexes reveals functional and regulatory mechanisms
Construction with digital twin information systems
No full textAbstract The concept of a “digital twin” as a model for data-driven management and control of physical systems has emerged over the past decade in the domains of manufacturing, production, and operations. In the context of buildings and civil infrastructure, the notion of a digital twin remains ill-defined, with little or no consensus among researchers and practitioners of the ways in which digital twin processes and data-centric technologies can support design and construction. This paper builds on existing concepts of Building Information Modeling (BIM), lean project production systems, automated data acquisition from construction sites and supply chains, and artificial intelligence to formulate a mode of construction that applies digital twin information systems to achieve closed loop control systems. It contributes a set of four core information and control concepts for digital twin construction (DTC), which define the dimensions of the conceptual space for the information used in DTC workflows. Working from the core concepts, we propose a DTC information system workflow—including information stores, information processing functions, and monitoring technologies—according to three concentric control workflow cycles. DTC should be viewed as a comprehensive mode of construction that prioritizes closing the control loops rather than an extension of BIM tools integrated with sensing and monitoring technologies.</jats:p
Self-supervised Learning Through Scene Observation for Selective Item Identification in Conveyor Belt Systems
No full textConveyor belts are core components in several industries. Often, workers need to operate on conveyor belts, selectively picking objects based on visual features following inspection. In such cases it is desirable to be able to selectively identify such items automatically. The need of tailored systems discourages solutions based on common data collection and labeling, as well as vision systems based on known object features. We device a novel framework to learn from existing human labor, without need of explicit data gathering or labeling. The framework autonomously detects, tracks and learns the visual features of salient objects in conveyor belt-based systems. The system is comprised of two cameras, a Convolutional Neural Network and a novel training regime, devised to support learning on on-line visual feeds. We show the framework is capable of autonomously learning the visual features of the objects picked by human operators. The system trains entirely through visual observation of human labor and achieves detection accuracy of over 97% on a set of 7 different objects after only 10 min of operation, without any knowledge of the objects at priori
A phase field formulation for dissolution-driven stress corrosion cracking
No full textWe present a new theoretical and numerical framework for modelling mechanically-assisted corrosion in elastic-plastic solids. Both pitting and stress corrosion cracking (SCC) can be captured, as well as the pit-to crack transition. Localised corrosion is assumed to be dissolution-driven and a formulation grounded upon the film rupture-dissolution repassivation mechanism is presented to incorporate the influence of film passivation. The model incorporates, for the first time, the role of mechanical straining as the electrochemical driving force, accelerating corrosion kinetics. The computational complexities associated with tracking the evolving metal-electrolyte interface are resolved by making use of a phase field paradigm, enabling an accurate approximation of complex SCC morphologies. The coupled electro-chemo-mechanical formulation is numerically implemented using the finite element method and an implicit time integration scheme; displacements, phase field order parameter and concentration are the primary variables. Five case studies of particular interest are addressed to showcase the predictive capabilities of the model, revealing an excellent agreement with analytical solutions and experimental measurements. By modelling these paradigmatic 2D and 3D boundary value problems we show that our formulation can capture: (i) the transition from activation-controlled corrosion to diffusion-controlled corrosion, (ii) the sensitivity of interface kinetics to mechanical stresses and strains, (iii) the role of film passivation in reducing corrosion rates, and (iv) the dependence of the stability of the passive film to local strain rates. The influence of these factors in driving the shape change of SCC defects, including the pit-to-crack transition, is a natural outcome of the model, laying the foundations for a mechanistic assessment of engineering materials and structures
Terahertz Frequency Combs Exploiting an On-Chip, Solution-Processed, Graphene-Quantum Cascade Laser Coupled-Cavity.
No full textThe ability to engineer quantum-cascade-lasers (QCLs) with ultrabroad gain spectra, and with a full compensation of the group velocity dispersion, at terahertz (THz) frequencies, is key for devising monolithic and miniaturized optical frequency-comb-synthesizers (FCSs) in the far-infrared. In THz QCLs four-wave mixing, driven by intrinsic third-order susceptibility of the intersubband gain medium, self-locks the optical modes in phase, allowing stable comb operation, albeit over a restricted dynamic range (∼20% of the laser operational range). Here, we engineer miniaturized THz FCSs, comprising a heterogeneous THz QCL, integrated with a tightly coupled, on-chip, solution-processed, graphene saturable-absorber reflector that preserves phase-coherence between lasing modes, even when four-wave mixing no longer provides dispersion compensation. This enables a high-power (8 mW) FCS with over 90 optical modes, through 55% of the laser operational range. We also achieve stable injection-locking, paving the way to a number of key applications, including high-precision tunable broadband-spectroscopy and quantum-metrology
Quantum dot mode-locked frequency comb with ultra-stable 25.5 GHz spacing between 20°C and 120°C
No full text© 2020 Chinese Laser Press. Semiconductor mode-locked lasers (MLLs) are promising frequency comb sources for dense wavelength-divisionmultiplexing (DWDM) data communications. Practical data communication requires a frequency-stable comb source in a temperature-varying environment and a minimum tone spacing of 25 GHz to support high-speed DWDM transmissions. To the best of our knowledge, however, to date, there have been no demonstrations of comb sources that simultaneously offer a high repetition rate and stable mode spacing over an ultrawide temperature range. Here, we report a frequency comb source based on a quantum dot (QD) MLL that generates a frequency comb with stable mode spacing over an ultrabroad temperature range of 20-120°C. The two-section passively mode-locked InAs QD MLL comb source produces an ultra-stable fundamental repetition rate of 25.5 GHz (corresponding to a 25.5 GHz spacing between adjacent tones in the frequency domain) with a variation of 0.07 GHz in the tone spacing over the tested temperature range. By keeping the saturable absorber reversely biased at -2 V, stable mode-locking over the whole temperature range can be achieved by tuning the current of the gain section only, providing easy control of the device. At an elevated temperature of 100°C, the device shows a 6 dB comb bandwidth of 4.81 nm and 31 tones with >36 dB optical signal-to-noise ratio. The corresponding relative intensity noise, averaged between 0.5 GHz and 10 GHz, is -146 dBc/Hz. Our results show the viability of the InAs QD MLLs as ultra-stable, uncooled frequency comb sources for low-cost, large-bandwidth, and low-energy-consumption optical data communications
Design considerations for high-power-density IPT pads using nanocrystalline ribbon cores
No full textIn inductive power transfer, ferrite cores present several drawbacks such as brittleness, low permeability and saturation point, and sensitivity to temperature variation. Other materials such as nanocrystalline alloys are being considered as substitutes. They offer a higher permeability and saturation point. Also, they are more robust and stable with temperature. This paper reviews the design considerations that should be taken into account when designing nanocrystalline cores for IPT applications. Bespoke designs are required to mitigate the eddy-current losses which arise due to the high conductivity of the material. A WPT3 pad, 11 kW, is designed and compared to and identical pad with ferrite cores. Using nanocrystalline ribbon cores, a higher coupling factor, 11%, was achieved. Also, a 2% improvement in efficiency was measured. This is attributed to the lower hysteresis losses and higher coupling factor. Finally, the saturation limits were tested for both materials. Results confirm that, with nanocrystalline ribbon cores, higher power ratings and power densities can be achieved
Application of immersed boundary method on instrumented turbine blade with LES
No full textLeading edge instrumentation used in compressor and turbine blades for jet-engine test rigs can cause significant obstruction and lead to a marked increase in downstream pressure loss. Typical instrumentation used in such a scenario could be a Kiel-shrouded probe with either a thermocouple or pitot-static tube for temperature/pressure measurement. High fidelity analysis of a coupled blade and probe requires the generation of a high quality mesh which can take a significant amount of an engineers time. The application of Immersed Boundary Method (IBM) and Large Eddy Simulation is shown in this paper to enable the use of an extremely simple mesh to observe the primary flow features generated due to the blade and probe interaction effects, as well as quantify downstream pressure loss to within a high level of accuracy. IBM is utilised to approximately model the probe, while fully resolving the blade itself through a series of LES simulations. This method has shown to be able to capture downstream loss profiles as well as integral quantities compared to both experiment and fully wall-resolved LES without the need to spend a significant amount of time generating the ideal mesh. Additionally, it is also able to capture the turbulence anisotropy surrounding the probe and blade regions
The impact of combustor turbulence on turbine loss mechanisms
No full textA blade row that is located downstream of a combustor has an extremely high turbulence intensity at the inlet, typically above 10%. The peak turbulent length scale is also high, at around 20% of the chord of the downstream blade row. In a combustor, the turbulence is created by impinging jets in crossflow. This may result in the turbulence being anisotropic in nature. The aim of this paper is to investigate the effect of combustor turbulence on the loss mechanisms which occur in a turbine blade row. The paper has a number of important findings. The combustor turbulence is characterized and is shown to be isotropic in nature. It shows that, when no pressure gradient is present, combustor turbulence increases the loss of a turbulent boundary layer by 22%. The mechanism responsible for this change is shown to be a deep penetration of the turbulence into the boundary layer. It shows that the presence of combustor turbulence increases the profile loss and endwall loss in the turbine cascade studied by 37% and 47%, respectively. The presence of combustor turbulence also introduces a freestream loss resulting in the total loss of the turbine cascade rising by 47%. When these loss mechanisms were applied to the vane alone, of an engine representative high-pressure turbine, it was found to result in a 1.3% reduction in stage efficiency
Role of the third metal oxide in In-Ga-Zn-O<inf>4</inf>amorphous oxide semiconductors: Alternatives to gallium
No full textWe study the role of the third metal oxide in In-Ga-Zn-type oxides (IGZO), Ga2O3, by comparing the calculated electronic properties of various alternatives (Al, Y, Hf, Ti, Si, and W) with Ga. It is found that Ga2O3 causes little disorder in the conduction band minimum (CBM) energy based on In or Zn oxides, and it has a large O vacancy suppression effect, which benefits both a high mobility and a low OFF current of IGZO. However, other alternatives give a pronounced conduction band disorder potential due to their higher CBM energies and thus are not ideal components in amorphous oxide semiconductors. Si and W may reduce the negative bias illumination stress instability by lowering hydrogen-induced states to below the bulk valence band maximum, but Si is not beneficial for mobility. Their role in back-end-of-line transistors is also noted