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Membrane lipids control the cellular activity of kinases containing the Src homology 2 (SH2) domain through direct lipid-SH2 domain interactions. Here we report development of novel non-lipidic small molecule inhibitors of the lipid-SH2 domain interaction that block the cellular activity of their host proteins. As a pilot study, we evaluated the efficacy of lipid-SH2 domain interaction inhibitors for spleen tyrosine kinase (Syk), which is implicated in hematopoietic malignancies, including acute myeloid leukemia (AML). An optimized inhibitor (WC36) specifically and potently suppressed oncogenic activities of Syk in AML cell lines and patient-derived AML cells. Unlike ATP-competitive Syk inhibitors, WC36 was refractory to de novo and acquired drug resistance due to its ability to block not only the Syk kinase activity but also its non-catalytic scaffolding function that is linked to drug resistance. Collectively, our study shows that targeting lipid-protein interaction is a powerful approach to developing novel small molecule drugs.

Phospholipid extrusion by ABC subfamily A (ABCA) exporters is central to cellular physiology, although the specifics of the underlying substrate interactions and transport mechanisms remain poorly resolved at the molecular level. Here we report cryo-EM structures of lipid-embedded human ABCA7 in an open state and in a nucleotide-bound, closed state at resolutions between 3.6 and 4.0 Å. The former reveals an ordered patch of bilayer lipids traversing the transmembrane domain (TMD), while the latter reveals a lipid-free, closed TMD with a small extracellular opening. These structures offer a structural framework for both substrate entry and exit from the ABCA7 TMD and highlight conserved rigid-body motions that underlie the associated conformational transitions. Combined with functional analysis and molecular dynamics (MD) simulations, our data also shed light on lipid partitioning into the ABCA7 TMD and localized membrane perturbations that underlie ABCA7 function and have broader implications for other ABCA family transporters.

P-glycoprotein (Pgp) is a major efflux pump in humans, overexpressed in a variety of cancers and associated with the development of multi-drug resistance. Allosteric modulation by various ligands (e.g., transport substrates, inhibitors, and ATP) has been biochemically shown to directly influence structural dynamics, and thereby, the function of Pgp. However, the molecular details of such effects, particularly with respect to the role and involvement of the surrounding lipids, are not well established. Here, we employ all-atom molecular dynamics (MD) simulations to study the conformational landscape of Pgp in the presence of a high-affinity, third-generation inhibitor, tariquidar, in comparison to the nucleotide-free (APO) and the ATP-bound states, in order to characterize the mechanical effects of the inhibitor that might be of relevance to its blocking mechanism of Pgp. Simulations in a multi-component lipid bilayer show a dynamic equilibrium between open(er) and more closed inward-facing (IF) conformations in the APO state, with binding of ATP shifting the equilibrium towards conformations more prone to ATP hydrolysis and subsequent events in the transport cycle. In the presence of the inhibitor bound to the drug-binding pocket within the transmembrane domain (TMD), Pgp samples more open IF conformations, and the nucleotide binding domains (NBDs) become highly dynamic. Interestingly, and reproduced in multiple independent simulations, the inhibitor is observed to facilitate recruitment of lipid molecules into the Pgp lumen through the two proposed drug-entry portals, where the lipid head groups from the cytoplasmic leaflet penetrate into and, in some cases, translocate inside the TMD, while the lipid tails remain extended into the bulk lipid environment. These “wedge” lipids likely enhance the inhibitor-induced conformational restriction of the TMD leading to the differential modulation of coupling pathways observed with the NBDs downstream. We suggest a novel inhibitory mechanism for tariquidar, and potentially for related third-generation Pgp inhibitors, where lipids are seen to enhance the inhibitory role in the catalytic cycle of membrane transporters., Lipid invasion of P-glycoprotein, enhanced by binding of an inhibitor.

Glutamate is the predominant excitatory neurotransmitter in the mammalian central nervous system (CNS). Excitatory Amino Acid Transporters (EAATs) regulate extracellular glutamate by transporting it into cells, mostly glia, to terminate neurotransmission and to avoid neurotoxicity. EAATs are also chloride (Cl−) channels, but the physiological role of Cl− conductance through EAATs is poorly understood. Mutations of human EAAT1 (hEAAT1) have been identified in patients with episodic ataxia type 6 (EA6). One mutation showed increased Cl− channel activity and decreased glutamate transport, but the relative contributions of each function of hEAAT1 to mechanisms underlying the pathology of EA6 remain unclear. Here we investigated the effects of five additional EA6-related mutations on hEAAT1 function in Xenopus laevis oocytes, and on CNS function in a Drosophila melanogaster model of locomotor behavior. Our results indicate that mutations with decreased hEAAT1 Cl− channel activity and functional glutamate transport can also contribute to the pathology of EA6, highlighting the importance of Cl− homeostasis in glial cells for proper CNS function. We also identified a novel mechanism involving an ectopic sodium (Na+) leak conductance in glial cells. Together, these results strongly support the idea that EA6 is primarily an ion channelopathy of CNS glia.

Excitatory amino acid transporters (EAATs) are glutamate transporters that belong to the solute carrier 1A (SLC1A) family. They couple glutamate transport to the co-transport of three sodium (Na+) ions and one proton (H+) and the counter-transport of one potassium (K+) ion. In addition to this coupled transport, binding of substrate and Na+ ions to EAATs activates a thermodynamically uncoupled chloride (Cl−) conductance. Structures of SLC1A family members have revealed that these transporters use a twisting elevator mechanism of transport, where a mobile transport domain carries substrate and coupled ions across the membrane, while a static scaffold domain anchors the transporter in the membrane. We have recently demonstrated that the uncoupled Cl− conductance is activated by the formation of an aqueous pore at the domain interface during the transport cycle in archaeal GltPh. However, a pathway for the uncoupled Cl− conductance has not been reported for the EAATs and it is unclear if such a pathway is conserved. Here, we employ all-atom molecular dynamics (MD) simulations combined with enhanced sampling, free-energy calculations, and experimental mutagenesis to approximate large-scale conformational changes during the transport process and identified a Cl− conducting conformation in human EAAT1. We were able to extensively sample the large-scale structural transitions, allowing us to capture an intermediate conformation formed during the transport cycle with a continuous aqueous pore at the domain interface. The free-energy calculations performed for the conduction of Cl− and Na+ ions through the captured conformation, highlight the presence of two hydrophobic gates which control the selective movement of Cl− through the aqueous pathway. Overall, our findings provide insights into the mechanism by which a human glutamate transporter can support the dual functions of active transport and passive Cl− permeation and confirming the commonality of this mechanism in different members of the SLC1A family.

Phosphatidylinositol-4,5-bisphosphate (PIP2) is a signaling lipid which regulates voltage-gated Kv7/KCNQ potassium channels. Altered PIP2 sensitivity of neuronal Kv7.2 channel is involved in KCNQ2 epileptic encephalopathy. However, the molecular action of PIP2 on Kv7.2 gating remains largely elusive. Here, we use molecular dynamics simulations and electrophysiology to characterize PIP2 binding sites in a human Kv7.2 channel. In the closed state, PIP2 localizes to the periphery of the voltage-sensing domain (VSD). In the open state, PIP2 binds to 4 distinct interfaces formed by the cytoplasmic ends of the VSD, the gate, intracellular helices A and B and their linkers. PIP2 binding induces bilayer-interacting conformation of helices A and B and the correlated motion of the VSD and the pore domain, whereas charge-neutralizing mutations block this coupling and reduce PIP2 sensitivity of Kv7.2 channels by disrupting PIP2 binding. These findings reveal the allosteric role of PIP2 in Kv7.2 channel activation.

Fatty acid (FA) transfer proteins extract FA from membranes and sequester their ligand to facilitate its movement through the cytosol. While detailed views of soluble protein-FA complexes are available, how FA exchange occurs at the membrane has remained unknown. Staphylococcus aureus FakB1 is a prototypical bacterial FA transfer protein that binds palmitate within a narrow, buried tunnel. Here, we determine the conformational change from this closed state to an open state that engages the phospholipid bilayer. Upon membrane binding, a dynamic loop in FakB1 that covers the FA binding site disengages and folds into an amphipathic helix. This helix inserts below the phosphate plane of the bilayer to create a diffusion channel for the FA to exchange between the protein and the membrane. The structure of the bilayer-associated conformation of FakB1 has local similarities with mammalian FA binding proteins and provides a general conceptual framework for how these proteins interact with the membrane to promote lipid transfer.

Phosphatidylinositol-4,5-bisphosphate (PIP2) is a signaling lipid which regulates voltage-gated Kv7/KCNQ potassium channels. Altered PIP2 sensitivity of neuronal Kv7.2 channel is involved in KCNQ2 epileptic encephalopathy. However, the molecular action of PIP2 on Kv7.2 gating remains largely elusive. Here, we use molecular dynamics simulations and electrophysiology to characterize PIP2 binding sites in a human Kv7.2 channel. In the closed state, PIP2 localizes to the periphery of the voltage-sensing domain (VSD). In the open state, PIP2 binds to 4 distinct interfaces formed by the cytoplasmic ends of the VSD, the gate, intracellular helices A and B and their linkers. PIP2 binding induces bilayer-interacting conformation of helices A and B and the correlated motion of the VSD and the pore domain, whereas charge-neutralizing mutations block this coupling and reduce PIP2 sensitivity of Kv7.2 channels by disrupting PIP2 binding. These findings reveal the allosteric role of PIP2 in Kv7.2 channel activation.

Diagnosis and prognosis of failures for aircrafts’ integrity are some of the most important regular functionalities in complex and safety-critical aircraft structures. Further, development of failure diagnostic tools such as Non-Destructive Testing (NDT) techniques, in particular, for aircraft composite materials, has been seen as a subject of intensive research over the last decades. The need for diagnostic and prognostic tools for composite materials in aircraft applications rises and draws increasing attention. Yet, there is still an ongoing need for developing new failure diagnostic tools to respond to the rapid industrial development and complex machine design. Such tools will ease the early detection and isolation of developing defects and the prediction of damages propagation; thus allowing for early implementation of preventive maintenance and serve as a countermeasure to the potential of catastrophic failure. This paper provides a brief literature review of recent research on failure diagnosis of composite materials with an emphasis on the use of active thermography techniques in the aerospace industry. Furthermore, as the use of unmanned aerial vehicles (UAVs) for the remote inspection of large and/or difficult access areas has significantly grown in the last few years thanks to their flexibility of flight and to the possibility to carry one or several measuring sensors, the aim to use a UAV active thermography system for the inspection of large composite aeronautical structures in a continuous dynamic mode is proposed., Thermosense: Thermal Infrared Applications XLIII, April 12-16, 2021, Online Only, United States, Series: Proceedings of SPIE

Phospholipid extrusion by ABC subfamily A (ABCA) exporters is central to cellular physiology, although the specifics of the underlying substrate interactions and transport mechanisms remain poorly resolved at the molecular level. Here we report cryo-EM structures of lipid-embedded human ABCA7 in an open state and a nucleotide-bound, closed state at resolutions between 3.6-4.0 Å. The former reveals an ordered patch of bilayer lipids traversing the transmembrane domain (TMD), while the latter reveals a lipid-free, closed TMD with a small extracellular opening. These structures offer a structural framework for both substrate entry and exit from the ABCA7 TMD and highlight conserved rigid-body motions that underlie the associated conformational transitions. Combined with functional analysis and molecular dynamics (MD) simulations, our data also shed light on lipid partitioning into the ABCA7 TMD and localized membrane perturbations that underlie ABCA7 function and have broader implications for other ABCA family transporters.

This chapter provides an overview of the common types of defects found in various structural materials and joints in aircraft. Materials manufacturing methods (including large-scale production) have been established in the aircraft industry. However, as will be seen in this chapter, manufacturing defects and defects during in-service conditions are very common across all material types. The structural material types include metals, composites, coatings, adhesively bonded and stir-welded joints. This chapter describes the defect types as a baseline for the description of their detection with the methods of Chap. 5 to 8. Based on the understanding of the defect types, there is great expectation for a technical breakthrough for the application of structural health monitoring (SHM) damage detection systems, where continuous monitoring and assessment with high throughput and yield will produce the desired structural integrity., Series: Springer Aerospace Technology

Phosphatidylinositol-4,5-bisphosphate (PIP2) is a signaling lipid which regulates voltage-gated Kv7/KCNQ potassium channels. Altered PIP2 sensitivity of neuronal Kv7.2 channel is involved in KCNQ2 epileptic encephalopathy. However, the molecular action of PIP2 on Kv7.2 gating remains largely elusive. Here, we use molecular dynamics simulations and electrophysiology to characterize PIP2 binding sites in a human Kv7.2 channel. In the closed state, PIP2 localizes to the periphery of the voltage-sensing domain (VSD). In the open state, PIP2 binds to 4 distinct interfaces formed by the cytoplasmic ends of the VSD, the gate, intracellular helices A and B and their linkers. PIP2 binding induces bilayer-interacting conformation of helices A and B and the correlated motion of the VSD and the pore domain, whereas charge-neutralizing mutations block this coupling and reduce PIP2 sensitivity of Kv7.2 channels by disrupting PIP2 binding. These findings reveal the allosteric role of PIP2 in Kv7.2 channel activation., Pant et al. describe the mechanism by which PIP2 might regulate homomeric Kv7.2 channels. They identify sites important in the binding of the PIP2 lipid to Kv7.2 channels and propose that the PIP2 binding to a specific site results in the coupling between the voltage sensor domain (VSD) and pore domain (PD), which stabilizes the open state of the channel.

Artificial intelligence (AI) based approaches have had indubitable impact across the sciences through the ability to extract relevant information from raw data. Recently AI has also seen use for enhancing the efficiency of molecular simulations, wherein AI derived slow modes are used to accelerate the simulation in targeted ways. However, while typical fields where AI is used are characterized by a plethora of data, molecular simulations per construction suffer from limited sampling and thus limited data. As such the use of AI in molecular simulations can suffer from a dangerous situation where the AI optimization could get stuck in spurious regimes, leading to incorrect characterization of the reaction coordinate (RC) for the problem at hand. When such an incorrect RC is then used to perform additional simulations, one could start to deviate progressively from the ground truth. To deal with this problem of spurious AI solutions, here we report a novel and automated algorithm using ideas from statistical mechanics. It is based on the notion that a more reliable AI solution for many problems in chemistry and biophysics will be one that maximizes the time scale separation between slow and fast processes. To learn this timescale separation even from limited data, we use a maximum path entropy or caliber-based framework. We show the applicability of this automatic protocol for 3 classic benchmark problems, namely capturing the conformational dynamics of a model peptide (alanine dipeptide), ligand unbinding dynamics from a protein, and extensive sampling of the folding/unfolding energy landscape of the C-terminal domain of protein G (GB1-C16). We believe our work will lead to increased and robust use of trustworthy AI in molecular simulations of complex systems.

Glutamate is the most abundant excitatory neurotransmitter in the central nervous system, therefore its precise control is vital for maintaining normal brain function and preventing excitotoxicity1. Removal of extracellular glutamate is achieved by plasma membrane-bound transporters, which couple glutamate transport to sodium, potassium and pH gradients using an elevator mechanism2–5. Glutamate transporters also conduct chloride ions via a channel-like process that is thermodynamically uncoupled from transport6–8. However, the molecular mechanisms that allow these dual-function transporters to carry out two seemingly contradictory roles are unknown. Here we report the cryo-electron microscopy structure of a glutamate transporter homologue in an open-channel state, revealing an aqueous cavity that is formed during the transport cycle. Using functional studies and molecular dynamics simulations, we show that this cavity is an aqueous-accessible chloride permeation pathway gated by two hydrophobic regions, and is conserved across mammalian and archaeal glutamate transporters. Our findings provide insight into the mechanism by which glutamate transporters support their dual function and add a crucial piece of information to aid mapping of the complete transport cycle shared by the SLC1A transporter family.

Proton-coupled transporters use transmembrane proton gradients to power active transport of nutrients inside the cell. High-resolution structures often fail to capture the coupling between proton and ligand binding, and conformational changes associated with transport. We combine HDX-MS with mutagenesis and MD simulations to dissect the molecular mechanism of the prototypical transporter XylE. We show that protonation of a conserved aspartate triggers conformational transition from outward-facing to inward-facing state. This transition only occurs in the presence of substrate xylose, while the inhibitor glucose locks the transporter in the outward-facing state. MD simulations corroborate the experiments by showing that only the combination of protonation and xylose binding, and not glucose, sets up the transporter for conformational switch. Overall, we demonstrate the unique ability of HDX-MS to distinguish between the conformational dynamics of inhibitor and substrate binding, and show that a specific allosteric coupling between substrate binding and protonation is a key step to initiate transport., SCOPUS: ar.j, info:eu-repo/semantics/published

Kv7 channels are enriched at the axonal plasma membrane where their voltage-dependent potassium currents suppress neuronal excitability. Mutations in Kv7.2 and Kv7.3 subunits cause epileptic encephalopathy (EE), yet the underlying pathogenetic mechanism is unclear. Here, we used novel statistical algorithms and structural modeling to identify EE mutation hotspots in key functional domains of Kv7.2 including voltage sensing S4, the pore loop and S6 in the pore domain, and intracellular calmodulin-binding helix B and helix B-C linker. Characterization of selected EE mutations from these hotspots revealed that L203P at S4 induces a large depolarizing shift in voltage dependence of Kv7.2 channels and L268F at the pore decreases their current densities. While L268F severely reduces expression of heteromeric channels in hippocampal neurons without affecting internalization, K552T and R553L mutations at distal helix B decrease calmodulin-binding and axonal enrichment. Importantly, L268F, K552T, and R553L mutations disrupt current potentiation by increasing phosphatidylinositol 4,5-bisphosphate (PIP2), and our molecular dynamics simulation suggests PIP2 interaction with these residues. Together, these findings demonstrate that each EE variant causes a unique combination of defects in Kv7 channel function and neuronal expression, and suggest a critical need for both prediction algorithms and experimental interrogations to understand pathophysiology of Kv7-associated EE.

Fatty acid (FA) transfer proteins extract FA from membranes and sequester them to facilitate their movement through the cytosol. Detailed structural information is available for these soluble protein-FA complexes, but the structure of the protein conformation responsible for FA exchange at the membrane is unknown. Staphylococcus aureus FakB1 is a prototypical bacterial FA transfer protein that binds palmitate within a narrow, buried tunnel. Here, we define the conformational change from a "closed" FakB1 state to an "open" state that associates with the membrane and provides a path for entry and egress of the FA. Using NMR spectroscopy, we identified a conformationally flexible dynamic region in FakB1, and X-ray crystallography of FakB1 mutants captured the conformation of the open state. In addition, molecular dynamics simulations show that the new amphipathic α-helix formed in the open state inserts below the phosphate plane of the bilayer to create a diffusion channel for the hydrophobic FA tail to access the hydrocarbon core and place the carboxyl group at the phosphate layer. The membrane binding and catalytic properties of site-directed mutants were consistent with the proposed membrane docked structure predicted by our molecular dynamics simulations. Finally, the structure of the bilayer-associated conformation of FakB1 has local similarities with mammalian FA binding proteins and provides a conceptual framework for how these proteins interact with the membrane to create a diffusion channel from the FA location in the bilayer to the protein interior.

Nondestructive testing and evaluation (NDT&E) are commonly used in the industry for their ability to identify damage and assess material conditions. Ultrasonic testing (UT) is one of the most popular NDT&E techniques. A variant of ultrasonic testing known as nonlinear ultrasonic testing (NUT) has some advantages over conventional (linear) UT as it is more sensitive to damages in their early stages; even at the microscopic levels. Furthermore, the nonlinear characteristics of ultrasonic waves can be correlated to several material properties. In the last two decades, the NUT method has been investigated from two aspects, namely the direct (modeling) problem and the inverse (NUT testing) problem. The direct problem aims to establish the nonlinear mechanism and analyze the behavior of wave-damage interaction. The inverse problem is investigated under three headings: (1) data acquisition with NUT techniques, (2) signal pre-processing and feature extraction, and (3) parameter analysis for damage characterization. The conventional data analytical methods extract nonlinear features from noisy signals and build a damage index to characterize damages. However, damage index-based analyzing model can be challenging, as other factors affect the overall system nonlinearity such as complex specimen geometry, different damage characteristics, varying ambient conditions, and measurement uncertainties. To overcome these shortcomings, machine learning (ML) methods appear promising for the analysis of complex nonlinear ultrasonic signals by exploiting data mining and pattern recognition capabilities. Therefore, this paper aims to provide a comprehensive review of the state-of-the-art ML-enriched NUT for damage characterization. Other NUT-based technologies are also reviewed, including modeling of wave-damage interaction, different NUT techniques for data acquisition, signal pre-processing methods, and damage index-based parameter analysis strategies for damage characterization. Major emphasis is placed on the application of ML methods for NDT&E applications. Additionally, future research trends on data augmentation, complex damage characterization, and baseline-free methods using NUT are also discussed.

The pleckstrin homology (PH) domain of general receptor for phosphoionositides 1 (GRP1-PHD) binds specifically to phosphatidylinositol (3,4,5)-triphosphate (PIP3 ), and acts as a second messenger. Using an extensive array of molecular dynamics (MD) simulations employing highly mobile membrane mimetic (HMMM) model as well as complementary full membrane simulations, we capture differentiable binding and dynamics of GRP1-PHD in the presence of membranes containing PC, PS, and PIP3 lipids in varying compositions. While GRP1-PHD forms only transient interactions with pure PC membranes, incorporation of anionic lipids resulted in stable membrane-bound configurations. We report the first observation of two distinct PIP3 binding modes on GRP1-PHD, involving PIP3 interactions at a "canonical" and at an "alternate" site, suggesting the possibility of simultaneous binding of multiple anionic lipids. The full membrane simulations confirmed the stability of the membrane bound pose of GRP1-PHD as captured from our HMMM membrane binding simulations. By performing additional steered membrane unbinding simulations and calculating nonequilibrium work associated with the process, as well as metadynamics simulations, on the protein bound to full membranes, allowing for more quantitative examination of the binding strength of the GRP1-PHD to the membrane, we demonstrate that along with the bound PIP3 , surrounding anionic PS lipids increase the energetic cost of unbinding of GRP1-PHD from the canonical mode, causing them to dissociate more slowly than the alternate mode. Our results demonstrate that concurrent binding of multiple anionic lipids by GRP1-PHD contributes to its membrane affinity, which in turn control its signaling activity. © 2019 Wiley Periodicals, Inc.

We investigate the role of the length scale of attraction on the dynamical heterogeneity in three-dimensional core-softened (CS) model liquid having interaction potential of two different length scales. Using the simple CS model, we have shown that the presence of heterogeneity is attributed to the existence of attractive interactions in a system. The time scale associated with the peak position of the non-Gaussian parameter is found to be strongly dependent on the temperature for different length scale of attraction. The dynamical heterogeneity dramatically decreases with the increase in temperature. We further characterize dynamical heterogeneity by calculating new non-Gaussian parameter which indicates the existence of much longer relaxation timescale than that suggested by the peak position in the non-Gaussian parameter. Furthermore, we have shown the presence of particles, whose displacement distribution deviates from the Gaussian distribution and contributes towards the origin/presence of heterogeneity. Dynamical heterogeneity strongly depends on the length scale as well as the strength of attraction. System A which does not show that dynamical heterogeneity corresponds to repulsive interaction with large interaction length scale. System B which corresponds to attractive interaction with a small length scale of interaction shows dynamical heterogeneity. Non-Gaussian parameter $$[\alpha _2 ( t )]$$ for system A and system B at different temperatures

Thermodynamic and structural properties of core-softened fluid inside a (6,6) carbon nanotube (CNT) nanopore with tunable well depth, temperature and density have been carried out by molecular dynamic simulations. Methods of analysis include the radial distribution function, translational order parameter, excess entropy and derivative of excess entropy with respect to the density. We observe strong positional ordering of core-softened fluid inside the CNT and this ordering strongly depends on temperature and density of the system. On increasing density, we observe new peaks in the positional ordering. Translational order parameter and excess entropy indicate presence of a new anomalous region. On increasing the well depth and change in slope between the attractive well and repulsive shoulder in the potential, we hardly observe any change in the anomalous regions that are drastically different from that of the bulk core-softened fluids.

Detecting and identifying drones is of great interest due to the proliferation of highly manoeuverable drones with on-board sensors of increasing sensing capabilities. In this paper, we investigate the use of radars for tackling this problem. In particular, we focus on the problem of detecting rotary drones and distinguishing between single-propeller and multi-propeller drones using a micro-Doppler analysis. Two different radars were used, an ultra wideband (UWB) continuous wave (CW) C-band radar and an automotive frequency modulated continuous wave (FMCW) W-band radar, to collect micro-Doppler signatures of the drones. By taking a closer look at HElicopter Rotor Modulation (HERM) lines, the spool and chopping lines are identified for the first time in the context of drones to determine the number of propeller blades. Furthermore, a new multi-frequency analysis method using HERM lines is developed, which allows the detection of propeller rotation rates (spool and chopping frequencies) of single and multi-propeller drones. Therefore, the presented method is a promising technique to aid in the classification of drones.

Lamb waves are useful for detecting changes in material properties, as their propagation characteristics are sensitive to changes in the medium through which they travel. Defects and damage in materials/structures can be detected by analyzing the difference between the phase and/or group velocity amplitude and mode changes of Lamb waves’ propagation in damaged versus un-damaged specimens. The propagation characteristics of Lamb waves are described in the form of dispersion curves, relating phase and/or group velocities to the product of frequency and thickness, with these curves being generated by solving the Lamb wave equations. In this article, the effect on the Lamb wave propagation/dispersion due to changes in the material properties such as E 11 , E 22 , G 12 , and density were analyzed for three different composite laminate types – unidirectional, cross-ply, and quasi-isotropic, all constructed out of 16-plies of unidirectional carbon-fiber epoxy prepregs. The analysis was performed by obtaining the characteristic Lamb waves’ phase velocity dispersion and slowness curves for each laminate type. This was done by reducing E 11 , E 22 , and G 12 by 5%, 10%, 15% and 30%, and density by 1%, 2%, 5% and 10% with the intent of representing manufacturing and in-service defects. Since the Lamb waves’ velocity in a composite laminate varies with the propagation direction, the laminates were analyzed at 0°, 20°, 45°, 70°, and 90° propagation angles, with all the aforementioned variations. A program developed in MATLAB was used to generate the dispersion curves for the fundamental anti-symmetric and symmetric Lamb wave. The information provided in this paper can be used to select the proper Lamb wave modes, excitation frequency, which in turn governs sensor selection, data acquisition hardware, and damage detection algorithm for structural health monitoring of composite structures.

Using Molecular Dynamics approach we investigated the structure, dynamics of water confined inside pristine and charged 6,6 carbon nanotubes (CNTs). This study reports the breakdown of 1D water wires and the emergence of triangular faced water on incorporating charges in 6,6 CNTs. Incorporation of charges results in high potential barriers to the flipping of water molecules due to the formation of a large number of hydrogen bonds. The PMF analyses show the presence of ~2 kcal/mol barrier for the movement of water inside pristine CNT and almost negligible barrier in charged CNTs., Comment: 12 Pages, 21 figures

We present a detailed molecular dynamics simulation investigation on hydration of C60 fullerene in a coarse-grained water-like solvent. Based on our recent study (J. Chem. Phys. 2013), which has demonstrated the capability of a coarse-grained, core-soft model of water to describe water-like anomalies, we report here the applicability of this model to describe hydration characteristic of C60 fullerenes. Molecular dynamics simulation has been performed in NVE ensemble and structural characteristics of water around C60 fullerene have been analyzed by calculating C60-water radial distribution function. The computational economy and simplicity of the coarse-grained model will allow us to investigate self-assembly processes that require simulations of a much larger system over a longer period of time.

Understanding the origin of anomalous properties of water is of prime importance. A pertinent question in this respect is: whether tetrahedral orientational interaction is a prerequisite for the manifestation of water-like anomalies. Recently it is shown that spherically symmetric potentials with two length scales, popularly known as coresoftened potentials yield water-like anomalies. In the present study, we investigate the effect of attractive interactions among the particles on the existence and location of density anomaly in the temperature-density (T-ρ) plane. Using a suitable form of the core-softened potential, we employ extensive molecular dynamic simulations to understand microscopic origin of the density anomaly in terms of local structure of the model fluid. We observe that with the increase of the attractive interaction, the density anomaly region shifts towards higher densities and higher temperatures.

We report a simple, rapid and green route for synthesis of fluorescent carbon quantum dots (CQDs) by microwave assisted pyrolysis method using polyleucine polymer (Boc-L-Leu-HEMA) as precursor and self-passivating agent. The as synthesized CQDs were found to possess low cytotoxicity, thus making them suitable candidates for bioimaging and bio-labelling. Moreover, nanocomposites of as prepared CQDs with [α−PW12O403−] polyoxometalate were synthesized and were shown to possess excellent photocatalytic properties under visible light towards degradation of organic dye pollutants. Based on the control experiments, a suitable mechanism has been proposed to explain the remarkable photoactivity of the CQD/[α−PW12O403−] composites.

It is now well established that water-like anomalies can be reproduced by a spherically symmetric potential with two length scales, popularly known as core-softened potential. In the present study we aim to investigate the effect of attractive interactions among the particles in a model fluid interacting with core-softened potential on the existence and location of various water-like anomalies in the temperature-pressure plane. We employ extensive molecular dynamic simulations to study anomalous nature of various order parameters and properties under isothermal compression. Order map analyses have also been done for all the potentials. We observe that all the systems with varying depth of attractive wells show structural, dynamic, and thermodynamic anomalies. As many of the previous studies involving model water and a class of core softened potentials have concluded that the structural anomaly region encloses the diffusion anomaly region, which in turn, encloses the density anomaly region, the same pattern has also been observed in the present study for the systems with less depth of attractive well. For the systems with deeper attractive well, we observe that the diffusion anomaly region shifts toward higher densities and is not always enclosed by the structural anomaly region. Also, density anomaly region is not completely enclosed by diffusion anomaly region in this case.

Reversible addition-fragmentation chain transfer (RAFT) polymerization was employed to afford two different chiral copolymer series having opposite chiroptical properties based on 2-(2-methoxyethoxy)ethyl methacrylate (MEO2MA) and Boc-L/D-leucine methacryloyloxyethyl ester (Boc-L/D-Leu-HEMA) with varying co-monomer proportions. The random nature of the copolymers was indicated by the reactivity ratios of the two monomers for the two systems (MEO2MA with Boc-L-Leu-HEMA and Boc-D-Leu-HEMA), and further supported by smooth variation of the single glass transition temperature (Tg) determined from differential scanning calorimetry (DSC). With an increasing amino acid content in the copolymer, the specific rotation and molar ellipticity values increased, as examined by polarimeter and circular dichroism (CD) spectroscopy, respectively. After Boc-group cleavage under acidic conditions, all the copolymers exhibited cationic nature, as confirmed by dynamic light scattering (DLS), as well as the dual thermo and pH-dependent solubility behaviour in aqueous solution. The temperature induced phase transition of these copolymers was investigated as a function of the copolymer compositions over the pH range from 5.5 to 6.5 using a UV-Vis spectrophotometer. Furthermore, the chiral recognition ability of the synthesized monomers and homopolymers towards 1,1′-bi-2-naphthol (rac-BINOL) was studied by 1H NMR spectroscopy.

In Acoustic Emissions (AE) Hsu-Nielsen Pencil-Lead Breaks (PLB) are used to generate sound waves enabling the characterization of acoustic wave speed in complex structures. The broadband signal of a PLB represents a repeatable emission, which can be applied at different regions of the structure, and therefore can be used to calibrate the localization algorithms of the AE system. In recent years, the use of Finite Element Method (FEM) has flourished for modelling acoustic Lamb wave propagation, which is present in thin plate-like structures. The primary challenge faced by the AE community is the lack of a well-known mathematical function of a PLB signal that can be applied in numerical simulations. This study makes use of a Time Reversal (TR) approach to identify the emission source of the PLB on a 7075-T651 aluminum plate. An ABAQUS CAETM model with piezoelectric actuators and sensors was developed. In order to avoid edge reflections, absorbing boundaries based on the Stiffness Reduction Method (SRM) were considered. The captured PLB signals were used as input to the FEM and was time-reversed. Furthermore, a band-limited white noise signal was used to calibrate the contribution of the broadband frequencies found in the transmitted wave packet. Preliminary results indicate that the TR approach can be used to understand the shape and function of the original transmitted signal.