Showing papers by "National Physical Laboratory published in 2021"

Antiviral surfaces and coatings and their mechanisms of action

Abstract: Viral infections are a serious health challenge, and the COVID-19 pandemic has increased the demand for antiviral measures and treatments for clean surfaces, especially in public places. Here, we review a range of natural and synthetic surface materials and coatings with antiviral properties, including metals, polymers and biopolymers, graphene and antimicrobial peptides, and their underpinning antiviral mechanisms. We also discuss the physico-chemical properties of surfaces which influence virus attachment and persistence on surfaces. Finally, an overview is given of the current practices and applications of antiviral and virucidal materials and coatings in consumer products, personal protective equipment, healthcare and public settings. The COVID-19 pandemic has highlighted the importance of materials and coatings for antiviral surfaces. Here, a comprehensive review is performed for natural and synthetic antiviral and virucidal materials, including a discussion of their underpinning mechanisms.

The amino acid transporter SLC7A5 is required for efficient growth of KRAS-mutant colorectal cancer.

Abstract: Oncogenic KRAS mutations and inactivation of the APC tumor suppressor co-occur in colorectal cancer (CRC). Despite efforts to target mutant KRAS directly, most therapeutic approaches focus on downstream pathways, albeit with limited efficacy. Moreover, mutant KRAS alters the basal metabolism of cancer cells, increasing glutamine utilization to support proliferation. We show that concomitant mutation of Apc and Kras in the mouse intestinal epithelium profoundly rewires metabolism, increasing glutamine consumption. Furthermore, SLC7A5, a glutamine antiporter, is critical for colorectal tumorigenesis in models of both early- and late-stage metastatic disease. Mechanistically, SLC7A5 maintains intracellular amino acid levels following KRAS activation through transcriptional and metabolic reprogramming. This supports the increased demand for bulk protein synthesis that underpins the enhanced proliferation of KRAS-mutant cells. Moreover, targeting protein synthesis, via inhibition of the mTORC1 regulator, together with Slc7a5 deletion abrogates the growth of established Kras-mutant tumors. Together, these data suggest SLC7A5 as an attractive target for therapy-resistant KRAS-mutant CRC.

Report on G4‐Med, a Geant4 benchmarking system for medical physics applications developed by the Geant4 Medical Simulation Benchmarking Group

Abstract: Background: Geant4 is a Monte Carlo code extensively used in medical physics for a wide range of applications, such as dosimetry, micro- and nanodosimetry, imaging, radiation protection, and nuclear medicine. Geant4 is continuously evolving, so it is crucial to have a system that benchmarks this Monte Carlo code for medical physics against reference data and to perform regression testing. Aims: To respond to these needs, we developed G4-Med, a benchmarking and regression testing system of Geant4 for medical physics. Materials and Methods: G4-Med currently includes 18 tests. They range from the benchmarking of fundamental physics quantities to the testing of Monte Carlo simulation setups typical of medical physics applications. Both electromagnetic and hadronic physics processes and models within the prebuilt Geant4 physics lists are tested. The tests included in G4-Med are executed on the CERN computing infrastructure via the use of the geant-val web application, developed at CERN for Geant4 testing. The physical observables can be compared to reference data for benchmarking and to results of previous Geant4 versions for regression testing purposes. Results: This paper describes the tests included in G4-Med and shows the results derived from the benchmarking of Geant4 10.5 against reference data. Discussion: Our results indicate that the Geant4 electromagnetic physics constructor G4EmStandardPhysics_option4 gives a good agreement with the reference data for all the tests. The QGSP_BIC_HP physics list provided an overall adequate description of the physics involved in hadron therapy, including proton and carbon ion therapy. New tests should be included in the next stage of the project to extend the benchmarking to other physical quantities and application scenarios of interest for medical physics. Conclusion: The results presented and discussed in this paper will aid users in tailoring physics lists to their particular application. (Less)

Selenium in soil-microbe-plant systems: Sources, distribution, toxicity, tolerance, and detoxification

Abstract: Selenium is an essential micronutrient required for natural biological systems such as anti-oxidative systems. Despite such beneficial aspect, contamination of selenium and its subsequent bioaccumu...

Integrated contact lens sensor system based on multifunctional ultrathin MoS2 transistors.

Abstract: Summary Smart contact lenses attract extensive interests due to their capability of directly monitoring physiological and ambient information. However, previous demonstrations usually lacked efficient sensor modalities, facile fabrication process, mechanical stability, or biocompatibility. Here, we demonstrate a flexible approach for fabrication of multifunctional smart contact lenses with an ultrathin MoS2 transistors-based serpentine mesh sensor system. The integrated sensor systems contain a photodetector for receiving optical information, a glucose sensor for monitoring glucose level directly from tear fluid, and a temperature sensor for diagnosing potential corneal disease. Unlike traditional sensors and circuit chips sandwiched in the lens substrate, this serpentine mesh sensor system can be directly mounted onto the lenses and maintain direct contact with tears, delivering high detection sensitivity, while being mechanically robust and not interfering with either blinking or vision. Furthermore, the in vitro cytotoxicity tests reveal good biocompatibility, thus holding promise as next-generation soft electronics for healthcare and medical applications.

Evaluating the noise resilience of variational quantum algorithms

Abstract: We simulate the effects of different types of noise in state preparation circuits of variational quantum algorithms. We first use a variational quantum eigensolver to find the ground state of a Hamiltonian in the presence of noise and adopt two quality measures in addition to the energy, namely, fidelity and concurrence. We then extend the task to the one of constructing, with a layered quantum circuit ansatz, a set of general random target states. We determine the optimal circuit depth for different types and levels of noise, and observe that the variational algorithms mitigate the effects of noise by adapting the optimized parameters. We find that the inclusion of redundant parameterized gates makes the quantum circuits more resilient to noise. For such overparameterized circuits, different sets of parameters can result in the same final state in the noiseless case, which we denote as parameter degeneracy. Numerically, we show that this degeneracy can be lifted in the presence of noise, with some states being significantly more resilient to noise than others. We also show that the average deviation from the target state is linear in the noise level, as long as this is small compared to a circuit-dependent threshold. In this region, the deviation is well described by a stochastic model. Above the threshold, the optimization can converge to states with largely different physical properties from the true target state, so for practical applications it is critical to ensure that noise levels are below this threshold.

REMBI: Recommended Metadata for Biological Images-enabling reuse of microscopy data in biology.

Abstract: Bioimaging data have significant potential for reuse, but unlocking this potential requires systematic archiving of data and metadata in public databases. We propose draft metadata guidelines to begin addressing the needs of diverse communities within light and electron microscopy. We hope this publication and the proposed Recommended Metadata for Biological Images (REMBI) will stimulate discussions about their implementation and future extension.

Angular momentum generation in nuclear fission.

Abstract: When a heavy atomic nucleus splits (fission), the resulting fragments are observed to emerge spinning1; this phenomenon has been a mystery in nuclear physics for over 40 years2,3. The internal generation of typically six or seven units of angular momentum in each fragment is particularly puzzling for systems that start with zero, or almost zero, spin. There are currently no experimental observations that enable decisive discrimination between the many competing theories for the mechanism that generates the angular momentum4–12. Nevertheless, the consensus is that excitation of collective vibrational modes generates the intrinsic spin before the nucleus splits (pre-scission). Here we show that there is no significant correlation between the spins of the fragment partners, which leads us to conclude that angular momentum in fission is actually generated after the nucleus splits (post-scission). We present comprehensive data showing that the average spin is strongly mass-dependent, varying in saw-tooth distributions. We observe no notable dependence of fragment spin on the mass or charge of the partner nucleus, confirming the uncorrelated post-scission nature of the spin mechanism. To explain these observations, we propose that the collective motion of nucleons in the ruptured neck of the fissioning system generates two independent torques, analogous to the snapping of an elastic band. A parameterization based on occupation of angular momentum states according to statistical theory describes the full range of experimental data well. This insight into the role of spin in nuclear fission is not only important for the fundamental understanding and theoretical description of fission, but also has consequences for the γ-ray heating problem in nuclear reactors13,14, for the study of the structure of neutron-rich isotopes15,16, and for the synthesis and stability of super-heavy elements17,18. γ-ray spectroscopy experiments on the origin of spin in the products of nuclear fission of spin-zero nuclei suggest that the fission fragments acquire their spin after scission, rather than before.

Recent advances in the application of noble metal nanoparticles in colorimetric sensors for lead ions

Abstract: Recent developments in nanotechnology and engineering have produced a plethora of nanomaterials with amazing physical/chemical properties and enhanced sensing potential for various heavy metals in the environment. Noble metal nanoparticles (NPs), particularly those made from gold and silver, have attracted a great deal of attention mainly due to ease of synthesis, a high degree of surface functionalization, biocompatibility, and tunable physico-chemical properties. The use of noble metal nanoparticles has enabled fast and multiplexed detection of metal ions with excellent sensitivity and selectivity. The optical characteristics of Au–Ag NPs and noble metal-based nanozymes enable the detection of metals based on colorimetry. Color changes of these metal nanoparticles upon interaction with lead ions are based on inter-particle interactions (aggregation/dis-aggregation) and changes in surface modification. This review presents up-to-date information on the applications of noble metal NPs in the colorimetric sensing of lead (Pb2+) ions with special attention on selectivity, sensitivity, and practicality. The extensive potential of noble metal nanomaterials as the next-generation and on-site sensing tools has been explored for the rapid detection of lead ions in environmental matrices.

Comparison of Measurement Methods for 2–150-kHz Conducted Emissions in Power Networks

Abstract: This article presents a comparison of measurement methods for current and voltage distortions in low-voltage networks in the frequency range from 2 to 150 kHz (supraharmonics). The comparison encompasses the methods informatively described in IEC and CISPR international standards, as well as other innovative techniques presented in the literature. This work is carried out within a novel framework that includes advanced and complex synthetic test signals, as well as real grid recordings that allow an accurate comparison of the performance of the tested methods. Specifically designed indices are employed to characterize the accuracy of the tested methods in the frequency and amplitude assessments. In light of that, the strengths and weaknesses of the methods are identified. The results of this article contribute to the ongoing standardization work carried out by the IEC SC77A/WG9 with the purpose of defining a normative measurement method suitable for assessing grid disturbance levels in the range from 2 to 150 kHz.

Spontaneous symmetry breaking of dissipative optical solitons in a two-component Kerr resonator.

Abstract: Dissipative solitons are self-localized structures that can persist indefinitely in open systems driven out of equilibrium. They play a key role in photonics, underpinning technologies from mode-locked lasers to microresonator optical frequency combs. Here we report on experimental observations of spontaneous symmetry breaking of dissipative optical solitons. Our experiments are performed in a nonlinear optical ring resonator, where dissipative solitons arise in the form of persisting pulses of light known as Kerr cavity solitons. We engineer symmetry between two orthogonal polarization modes of the resonator and show that the solitons of the system can spontaneously break this symmetry, giving rise to two distinct but co-existing vectorial solitons with mirror-like, asymmetric polarization states. We also show that judiciously applied perturbations allow for deterministic switching between the two symmetry-broken dissipative soliton states. Our work delivers fundamental insights at the intersection of multi-mode nonlinear optical resonators, dissipative structures, and spontaneous symmetry breaking, and expands upon our understanding of dissipative solitons in coherently driven Kerr resonators.

Advancements of nanotechnologies in crop promotion and soil fertility: Benefits, life cycle assessment, and legislation policies

Abstract: Increasing agricultural production has become one of the key components to bridge the gap between securing food resources and sustainable development goals (SDGs), namely, no poverty, zero hunger, preservation of natural resources (water and energy), combating climate change and its impacts, and halting the loss of biodiversity in terrestrial ecosystems. In this regard, the crucial role of nanotechnology in modern farming is emphasized as an efficient means to develop “precision farming” systems. It can play a potent role in promoting sustainable agriculture, improving nutrient utilization, and mitigating climate change and environmental pollution. Particularly, nanotechnology-enabled products such as “smart nano-delivery capsules” offer new opportunities for controlled slow release of diverse deliverables (e.g., pesticides, herbicides, fertilizers, and micronutrients) in compliance with the needs of plants under specific environmental stimuli responses. In this framework, this review explores the basic properties, application benefits, and future directions of nanotechnology in agricultural economics, particularly for promoting crop growth and soil reclamation under the umbrella of SDG targets. All obstacles for applying agri-nanotech products (agri-NPs) in farming have been identified and discussed, considering their life cycle assessment (LCA) in soil and plants. Emphasis has been made on evaluating the impacts of various nanotech products on crop growth in reference to traditional market technologies. Besides, this review work discusses the benefits of nanobiochar and nanobubbles as viable alternative natural nanotech products to promote crop physiology, alleviate environmental pollution, and sequester carbon in the soil. This work also summarizes the technical aspects associated with the conversion of agricultural biomass wastes into affordable biofuels. It also highlights regulations, legislative policies, and economic outputs to strengthen the public awareness and acceptance of nanotechnologies in agro-environmental fields. The opportunities and challenges in these topics are discussed to help actively develop and implement nano-enabled products in agriculture and related industries.

QUAREP-LiMi: A community-driven initiative to establish guidelines for quality assessment and reproducibility for instruments and images in light microscopy

Abstract: A modern day light microscope has evolved from a tool devoted to making primarily empirical observations to what is now a sophisticated, quantitative device that is an integral part of both physical and life science research. Nowadays, microscopes are found in nearly every experimental laboratory. However, despite their prevalent use in capturing and quantifying scientific phenomena, neither a thorough understanding of the principles underlying quantitative imaging techniques nor appropriate knowledge of how to calibrate, operate and maintain microscopes can be taken for granted. This is clearly demonstrated by the well-documented and widespread difficulties that are routinely encountered in evaluating acquired data and reproducing scientific experiments. Indeed, studies have shown that more than 70% of researchers have tried and failed to repeat another scientist's experiments, while more than half have even failed to reproduce their own experiments1 . One factor behind the reproducibility crisis of experiments published in scientific journals is the frequent underreporting of imaging methods caused by a lack of awareness and/or a lack of knowledge of the applied technique2,3 . Whereas quality control procedures for some methods used in biomedical research, such as genomics (e.g., DNA sequencing, RNA-seq) or cytometry, have been introduced (e.g. ENCODE4 ), this issue has not been tackled for optical microscopy instrumentation and images. Although many calibration standards and protocols have been published, there is a lack of awareness and agreement on common standards and guidelines for quality assessment and reproducibility5 . In April 2020, the QUality Assessment and REProducibility for instruments and images in Light Microscopy (QUAREP-LiMi) initiative6 was formed. This initiative comprises imaging scientists from academia and industry who share a common interest in achieving a better understanding of the performance and limitations of microscopes and improved quality control (QC) in light microscopy. The ultimate goal of the QUAREP-LiMi initiative is to establish a set of common QC standards, guidelines, metadata models7,8 , and tools9,10 , including detailed protocols, with the ultimate aim of improving reproducible advances in scientific research. This White Paper 1) summarizes the major obstacles identified in the field that motivated the launch of the QUAREP-LiMi initiative; 2) identifies the urgent need to address these obstacles in a grassroots manner, through a community of stakeholders including, researchers, imaging scientists11 , bioimage analysts, bioimage informatics developers, corporate partners, funding agencies, standards organizations, scientific publishers, and observers of such; 3) outlines the current actions of the QUAREP-LiMi initiative, and 4) proposes future steps that can be taken to improve the dissemination and acceptance of the proposed guidelines to manage QC. To summarize, the principal goal of the QUAREP-LiMi initiative is to improve the overall quality and reproducibility of light microscope image data by introducing broadly accepted standard practices and accurately captured image data metrics.

Multi-length scale microstructural design of lithium-ion battery electrodes for improved discharge rate performance

Abstract: Fast discharge capability of automotive batteries not only affects the acceleration and climbing performance of electric vehicles, but also the accessible driving range under complex driving cycles. Understanding the intricate physical and chemical processes across multiple length-scales is critical to assist the strategic design of electrodes for improved rate performance. Here, we correlate the discharge rate performance of Ni-rich LiNi1−x−yCoxMnyO2 (NMC) cathodes to the electrode architectures, ranging from the crystallographic orientations, surface morphology and cracks at single particle level, to the factors that affect the dominance of the solid and liquid-state transport (SST and LST) at electrode level. A random orientation of the primary particles is found to incur an increase of the SST resistance by a factor of 2.35 at 5C and a heterogeneous intra-particle lithiation. Internal cracks significantly restrict the accessibility to the active material. Double-layered particles are proved to be a more promising candidate than single-crystal particles. At electrode level, the SST-dominance depth is quantified for the first time to guide the microstructural tuning and rational operating windows are proposed for electrodes of various architectures. The reaction front is observed to shuttle across the electrode depth to mitigate the polarization, which can provide valuable insights into the battery management development. Finally, by comparing the performance of single crystal and polycrystalline NMC811 electrodes, it is suggested that electrode thickness and porosity are more critical in the former for enhanced discharge rate performance, in contrast to polycrystalline electrodes, in which a gradient particle fraction and size distribution are recommended.

Phase separation in the outer membrane of Escherichia coli

Abstract: Gram-negative bacteria are surrounded by a protective outer membrane (OM) with phospholipids in its inner leaflet and lipopolysaccharides (LPS) in its outer leaflet. The OM is also populated with many β-barrel outer-membrane proteins (OMPs), some of which have been shown to cluster into supramolecular assemblies. However, it remains unknown how abundant OMPs are organized across the entire bacterial surface and how this relates to the lipids in the membrane. Here, we reveal how the OM is organized from molecular to cellular length scales, using atomic force microscopy to visualize the OM of live bacteria, including engineered Escherichia coli strains and complemented by specific labeling of abundant OMPs. We find that a predominant OMP in the E. coli OM, the porin OmpF, forms a near-static network across the surface, which is interspersed with barren patches of LPS that grow and merge with other patches during cell elongation. Embedded within the porin network is OmpA, which forms noncovalent interactions to the underlying cell wall. When the OM is destabilized by mislocalization of phospholipids to the outer leaflet, a new phase appears, correlating with bacterial sensitivity to harsh environments. We conclude that the OM is a mosaic of phase-separated LPS-rich and OMP-rich regions, the maintenance of which is essential to the integrity of the membrane and hence to the lifestyle of a gram-negative bacterium.

Reference dosimetry in MRI-linacs: evaluation of available protocols and data to establish a Code of Practice.

Abstract: With the rapid increase in clinical treatments with MRI-linacs, a consistent, harmonized and sustainable ground for reference dosimetry in MRI-linacs is needed Specific for reference dosimetry in MRI-linacs is the presence of a strong magnetic field Therefore, existing Code of Practices (CoPs) are inadequate In recent years, a vast amount of papers have been published in relation to this topic The purpose of this review paper is twofold: to give an overview and evaluate the existing literature for reference dosimetry in MRI-linacs and to discuss whether the literature and datasets are adequate and complete to serve as a basis for the development of a new or to extend existing CoPs This review is prefaced with an overview of existing MRI-linac facilities Then an introduction on the physics of radiation transport in magnetic fields is given The main part of the review is devoted to the evaluation of the literature with respect to the following subjects: • beam characteristics of MRI-linac facilities; • formalisms for reference dosimetry in MRI-linacs; • characteristics of ionization chambers in the presence of magnetic fields; • ionization chamber beam quality correction factors; and • ionization chamber magnetic field correction factors The review is completed with a discussion as to whether the existing literature is adequate to serve as basis for a CoP In addition, it highlights subjects for future research on this topic

Self-Switching Kerr Oscillations of Counterpropagating Light in Microresonators

Abstract: We report the experimental and numerical observation of oscillatory antiphase switching between counterpropagating light beams in Kerr ring microresonators, where dominance between the intensities of the two beams is periodically or chaotically exchanged. Self-switching occurs in balanced regimes of operation and is well captured by a simple coupled dynamical system featuring only the self- and cross-phase Kerr nonlinearities. Switching phenomena are due to temporal instabilities of symmetry-broken states combined with attractor merging, which restores the broken symmetry on average. Self-switching of counterpropagating light is robust for realizing controllable, all-optical generation of waveforms, signal encoding, and chaotic cryptography.

Particle size distributions for cellulose nanocrystals measured by atomic force microscopy: an interlaboratory comparison

Abstract: Particle size measurements of cellulose nanocrystals (CNCs) are challenging due to their broad size distribution, irregular shape and propensity to agglomerate. Particle size is one of the key parameters that must be measured for quality control purposes and to differentiate materials with different properties. We report the results of an interlaboratory comparison (ILC) which examined atomic force microscopy (AFM) data acquisition and data analysis protocols. Samples of CNCs deposited on poly-L-lysine coated mica were prepared in the pilot laboratory and sent to 10 participating laboratories including academic, government and industrial organizations with varying levels of experience with imaging CNCs. The participant data sets indicated that the central location, width and asymmetry varied considerably for both length and height distributions. To deal with this variability we used a skew normal distribution to model the data from each laboratory and to obtain the consensus distribution that describes the CNC particle size. The skew normal distribution has 3 parameters: a central location (mean), distribution width (standard deviation) and asymmetry (shape) factor. This approach gave consensus distributions with mean, standard deviation and asymmetry factor of 94.9 nm, 37.3 nm and 6.0 for length and 3.4 nm, 1.2 nm and 2.8 for height, respectively. The use of multiple probes and/or deterioration of the probe with increased use are significant contributing factors to the variability in mean length between laboratories. There is less variability in height across participating laboratories and tests of applied imaging force indicate that it is possible to image without significant compression of the CNCs. The number of CNCs necessary to obtain a reliable data set depends on the probes and operating conditions, but with careful control of various parameters analysis of 250 and 300 CNCs should provide consistent data sets for height and length, respectively for one sample. Comparison of AFM with transmission electron microscopy (TEM) data obtained in the same ILC demonstrated excellent agreement between measured lengths for the 2 methods. By contrast AFM height was approximately one half the TEM width, a result that indicates the presence of a significant number of laterally agglomerated particles, consistent with literature data.

Deep Learning-Based Annotation Transfer between Molecular Imaging Modalities: An Automated Workflow for Multimodal Data Integration.

Abstract: An ever-increasing array of imaging technologies are being used in the study of complex biological samples, each of which provides complementary, occasionally overlapping information at different length scales and spatial resolutions. It is important to understand the information provided by one technique in the context of the other to achieve a more holistic overview of such complex samples. One way to achieve this is to use annotations from one modality to investigate additional modalities. For microscopy-based techniques, these annotations could be manually generated using digital pathology software or automatically generated by machine learning (including deep learning) methods. Here, we present a generic method for using annotations from one microscopy modality to extract information from complementary modalities. We also present a fast, general, multimodal registration workflow [evaluated on multiple mass spectrometry imaging (MSI) modalities, matrix-assisted laser desorption/ionization, desorption electrospray ionization, and rapid evaporative ionization mass spectrometry] for automatic alignment of complex data sets, demonstrating an order of magnitude speed-up compared to previously published work. To demonstrate the power of the annotation transfer and multimodal registration workflows, we combine MSI, histological staining (such as hematoxylin and eosin), and deep learning (automatic annotation of histology images) to investigate a pancreatic cancer mouse model. Neoplastic pancreatic tissue regions, which were histologically indistinguishable from one another, were observed to be metabolically different. We demonstrate the use of the proposed methods to better understand tumor heterogeneity and the tumor microenvironment by transferring machine learning results freely between the two modalities.