MRC Laboratory of Molecular Biology
CUED - Cambridge University Engineering DepartmentNot a member yet
45551 research outputs found
Sort by
Compositional and entropy indirect noise generated in subsonic non-isentropic nozzles
Indirect noise generated by the acceleration of synthetic compositional and entropic perturbations through non-isentropic nozzles is measured experimentally. A physics-based analytical low-order model to evaluate the indirect noise generated by non-isentropic compact nozzles is developed and validated with experimental measurements. A one-dimensional model for describing the waves generated by the addition of mass, momentum, energy and species to a steady flow in an entropy and composition wave generator is presented. The transfer functions describing the multiple reflections of acoustic waves in an enclosed environment are derived. This analytical framework allows unambiguous identification and isolation of the experimental direct and indirect noise generated by the injection of helium, methane, argon or carbon dioxide into a flow duct. Experimental data show that entropic and compositional noise make a significant contribution to the overall pressure traces acquired in the entropy generator. Moreover, it is demonstrated that the isentropic modelling assumption is inadequate to capture the experimental behaviour, while the analytical model for non-isentropic nozzles successfully describes the direct and indirect noise transfer functions. The disregard for the compositional contribution and the unjustified use of the isentropic assumption can provide significantly inaccurate noise predictions. This work shows that compositional noise, as well as non-isentropicity in the system, should be considered in future thermoacoustic and combustion noise models
Systematic Activity Maturation of a Single-Domain Antibody with Non-canonical Amino Acids through Chemical Mutagenesis
Great advances have been made over the last four decades in therapeutic and diagnostic applications of antibodies. The activity maturation of antibody candidates, however, remains a significant challenge. To address this problem, we present a method that enables the systematic enhancement of the activity of a single-domain antibody through the post-translational installation of non-canonical side chains by chemical mutagenesis. We illustrate this approach by performing a structure-activity relationship study beyond the 20 naturally occurring amino acids on a single-domain antibody designed in silico to inhibit the aggregation of the amyloid-β peptide, a process closely linked to Alzheimer's disease. We found that this approach can improve, by five orders of magnitude, the anti-aggregation activity of the starting single-domain antibody, without affecting its stability. These results show that the expansion of the chemical space available to antibodies through chemical mutagenesis can be exploited for the systematic enhancement of the activity of these molecules
In Vivo Pretargeting Based on Cysteine-Selective Antibody Modification with IEDDA Bioorthogonal Handles for Click Chemistry
Pretargeted imaging has emerged as an effective multistep strategy aiming to improve imaging contrast and reduce patient radiation exposure through decoupling of the radioactivity from the targeting vector. The inverse electron-demand Diels-Alder (IEDDA) reaction between a trans-cyclooctene (TCO)-conjugated antibody and a labeled tetrazine holds great promise for pretargeted imaging applications due to its bioorthogonality, rapid kinetics under mild conditions, and formation of stable products. Herein, we describe the use of functionalized carbonylacrylic reagents for site-specific incorporation of TCO onto a human epidermal growth factor receptor 2 (HER2) antibody (THIOMAB) containing an engineered unpaired cysteine residue, generating homogeneous conjugates. Precise labeling of THIOMAB-TCO with a fluorescent or radiolabeled tetrazine revealed the potential of the TCO-functionalized antibody for imaging the HER2 after pretargeting in a cellular context in a HER2 positive breast cancer cell line. Control studies with MDA-MD-231 cells, which do not express HER2, further confirmed the target specificity of the modified antibody. THIOMAB-TCO was also evaluated in vivo after pretargeting and subsequent administration of an 111In-labeled tetrazine. Biodistribution studies in breast cancer tumor-bearing mice showed a significant activity accumulation on HER2+ tumors, which was 2.6-fold higher than in HER2- tumors. Additionally, biodistribution studies with THIOMAB without the TCO handle also resulted in a decreased uptake of 111In-DOTA-Tz on HER2+ tumors. Altogether, these results clearly indicate the occurrence of the click reaction at the tumor site, i.e., pretargeting of SK-BR-3 HER2-expressing cells with THIOMAB-TCO and reaction through the TCO moiety present in the antibody. The combined advantages of site-selectivity and stability of TCO tagged-antibodies could allow application of biorthogonal chemistry strategies for pretargeting imaging with minimal side-reactions and background
Spin-valley dynamics in alloy-based transition metal dichalcogenide heterobilayers
Van der Waals heterobilayers based on 2D transition metal dichalcogenides have been recently shown to support robust and long-lived valley polarization for potential valleytronic applications. However, the roles of the chemical composition and geometric alignment of the constituent layers in the underlying dynamics remain largely unexplored. Here we study spin-valley relaxation dynamics in heterobilayers with different structures and optical properties engineered via the use of alloyed monolayer semiconductors. Through a combination of time-resolved Kerr rotation spectroscopic measurements and theoretical modeling for Mo1 − xWxSe2/WSe2 samples with different chemical compositions and stacking angles, we uncover the contributions of the interlayer exciton recombination and charge carrier spin depolarization to the overall valley dynamics. We show that the corresponding decay rates can be tuned in a wide range in transitions from a misaligned to an aligned structure, and from a hetero- to a homo-bilayer. Our results provide insights into the microscopic spin-valley polarization mechanisms in van der Waals heterostructures for the development of future 2D valleytronic devices
The use of strontium ferrite perovskite as an oxygen carrier in the chemical looping epoxidation of ethylene
In the epoxidation of ethylene to ethylene oxide using chemical looping, Ag is supported on strontium ferrite perovskite, where Ag acts as the catalyst while the perovskite acts as an oxygen carrier. This study explores how various oxygen carriers based on strontium ferrite affect chemical looping epoxidation. The structure of the oxygen carrier was varied by incorporating different ratios of two perovskite phases: cubic SrFeO3, and a layered Ruddlesden-Popper (RP) phase: Sr3Fe2O7. Maximum yield of ethylene oxide was obtained for the sample with 1:1 SrFeO3:RP ratio, leading to an increase in the yield of ethylene oxide around 4 times, compared to only SrFeO3 (i.e. 0.4–1.6% ethylene oxide yield). These results confirm a possibility of designing the oxygen carriers used in chemical looping epoxidation towards optimal performance. Such a design approach can be expanded to other chemical looping processes to tune the performance of oxygen carrier for the reaction in question
Printed subthreshold organic transistors operating at high gain and ultralow power
Overcoming the trade-offs between power consumption, fabrication-cost and signal-amplification has been a long-standing question for wearable electronics. We report a high-gain, fully inkjet-printed Schottky-barrier organic thin-film transistor amplifier circuit. The transistor signal amplification efficiency is 38.2 siemens per ampere, which is near the theoretical thermionic limit and an ultralow power consumption of 60 decibels and noise voltage <0.3 microvolt per hertz1/2at 100 hertz
S-Nav: Safety-Aware IoT Navigation Tool for Avoiding COVID-19 Hotspots
In this article, we present a Q -learning-enabled safe navigation system - S-Nav - that recommends routes in a road network by minimizing traveling through categorically demarcated COVID-19 hotspots. S-Nav takes the source and destination as inputs from the commuters and recommends a safe path for traveling. The S-Nav system dodges hotspots and ensures minimal passage through them in unavoidable situations. This feature of S-Nav reduces the commuter's risk of getting exposed to these contaminated zones and contracting the virus. To achieve this, we formulate the reward function for the reinforcement learning model by imposing zone-based penalties and demonstrate that S-Nav achieves convergence under all conditions. To ensure real-time results, we propose an Internet of Things (IoT)-based architecture by incorporating the cloud and fog computing paradigms. While the cloud is responsible for training on large road networks, the geographically aware fog nodes take the results from the cloud and retrain them based on smaller road networks. Through extensive implementation and experiments, we observe that S-Nav recommends reliable paths in near real time. In contrast to state-of-the-art techniques, S-Nav limits passage through red/orange zones to almost 2% and close to 100% through green zones. However, we observe 18% additional travel distances compared to precarious shortest paths
Supply chain resilience reactive strategies for food SMEs in coping to COVID-19 crisis
Background: The ability of small- and medium-sized enterprises in the food industry (FSMEs) in cultivating resilience against the COVID-19 pandemic is vital food security. However, there is limited supply chain resilience literature to guide FSMEs in overcoming disruptions caused by pandemic. Scope and approach: This review aims to provide a broad view of SCRes reactive strategies for FSMEs in dealing with crises in the context of COVID-19. Attention is given to the literature on resilience in other types of supply chain and situated in the context of food settings. The factors are monitored or controlled to contribute to FSME resiliency. Key findings and conclusion: Four quadrants, i.e., (1) rapid with low cost, (2) rapid with high cost, (3) slow with low cost and (4) slow with high cost, are offered based on the limitations and the time needed to react, and the strategies of each quadrant are explained in depth. This review also provides a better understanding of and guidance on reactive strategies for SCRes as options for FSMEs in dealing with the COVID-19 pandemic. This review suggests future directions as extensions based on the logical flow of this review
PCM-net: A refractive index database of chalcogenide phase change materials for tunable nanophotonic device modelling
The growing demand for multifunctional nanophotonic devices has led to the exploration, and utilization, of a plethora of exotic electro-optical materials. Recently, chalcogenide glass based phase change materials (PCMs) have shown utility as a tuning material for a range of nanophotonic devices. Owing to their low loss, ultrafast switching speeds and wide waveband operation, PCMs are integrated in an increasing number of next-generation tunable components, including integrated photonic switches, metasurface optics and tunable spectral filters. Nonetheless, modelling of PCM-based devices is challenging-both in terms of accurate representation of experimentally derived material properties in different phase states, and standardization of results across the research community. Further, as each device requires optimization of specific performance metrics dependent on their respective application, any inaccuracies will lead to erroneous outcomes. In this work, we introduce PCM-net (http://nekocloud.com/pnet/): an online database of the complex refractive indices of a variety of chalcogenide glass PCMs (such as GeSbTe), as an accessible and indexed repository for data sharing across the PCM community. Refractive indices (n) and extinction coefficients (k) between amorphous and crystalline states are directly extracted from experimentally derived data in numerous academic research articles, and collated into the material resource database. Due to the inaccuracies associated with our data collection methods, this data is supplemented with additional computationally generated data, obtained through WVASE® -a commercial ellipsometry analysis software package. To demonstrate the utility of PCM-net, we provide a NASA application-driven device optimization example using the optical properties of PCMs collected with our database. We anticipate the database providing great use to the PCM community and coordinated research efforts enabled by PCM-net will promote the shared repository for the selection of appropriate PCMs for tunable nanophotonic device design for a range of applications
Observed Performance of a Deep Excavation in the Historical Center of Rome
The C Line of the Rome underground underpasses the historical city center, facing significant problems for the presence of archaeological artefacts and the necessity to prevent damage to the historical and monumental heritage. This paper describes the field performance of a 30-m-deep excavation that has been constructed at a short distance from the Aurelian Walls at Porta Asinaria (third century). An extensive instrumentation program was conducted during construction, as well as field observations including deflection of the diaphragm walls, ground movements, pore water pressures, settlements, and rotation of the Aurelian Walls. Observed ground settlements and diaphragm wall displacements were smaller than those monitored in other case histories worldwide, inducing no damage to the Aurelian Walls. The lessons learned from this case study showed that a stiff retaining system and a strict control of the construction sequence were the key to minimize the effects of a deep excavation with millennia of history at risk