Mastering dynamic free-space spectral control and modulation in the near-infrared (NIR) and optical regimes remains a challenging task that is hindered by the available functional materials at high ...frequencies. In this work, we have realized an efficient metadevice capable of spectral control by minimizing the thermal mass of a vanadium dioxide phase-change material (PCM) and placing the PCM at the feed gap of a bow-tie field antenna. The device has an experimentally measured tuning range of up to 360 nm in the NIR and a modulation depth of 33% at the resonant wavelength. The metadevice is configured for integrated and local heating, leading to faster switching and more precise spatial control compared with devices based on phase-change thin films. We envisage that the combined advantages of this device will open new opportunities for signal processing, memory, security, and holography at optical frequencies.
Abstract
Smart grid solutions enable utilities and customers to better monitor and control energy use via information and communications technology. Information technology is intended to improve the ...future electric grid’s reliability, efficiency, and sustainability by implementing advanced monitoring and control systems. However, leveraging modern communications systems also makes the grid vulnerable to cyberattacks. Here we report the first use of quantum key distribution (QKD) keys in the authentication of smart grid communications. In particular, we make such demonstration on a deployed electric utility fiber network. The developed method was prototyped in a software package to manage and utilize cryptographic keys to authenticate machine-to-machine communications used for supervisory control and data acquisition (SCADA). This demonstration showcases the feasibility of using QKD to improve the security of critical infrastructure, including future distributed energy resources (DERs), such as energy storage.
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Ligands for the bromodomain and extra-terminal domain (BET) family of bromodomains have shown promise as useful therapeutic agents for treating a range of cancers and inflammation. ...Here we report that our previously developed 3,5-dimethylisoxazole-based BET bromodomain ligand (OXFBD02) inhibits interactions of BRD4(1) with the RelA subunit of NF-κB, in addition to histone H4. This ligand shows a promising profile in a screen of the NCI-60 panel but was rapidly metabolised (t½ = 39.8 min). Structure-guided optimisation of compound properties led to the development of the 3-pyridyl-derived OXFBD04. Molecular dynamics simulations assisted our understanding of the role played by an internal hydrogen bond in altering the affinity of this series of molecules for BRD4(1). OXFBD04 shows improved BRD4(1) affinity (IC50 = 166 nM), optimised physicochemical properties (LE = 0.43; LLE = 5.74; SFI = 5.96), and greater metabolic stability (t½ = 388 min).
Practical quantum networking architectures are crucial for scaling the connection of quantum resources. Yet quantum network testbeds have thus far underutilized the full capabilities of modern ...lightwave communications, such as flexible-grid bandwidth allocation. In this work, we implement flex-grid entanglement distribution in a deployed network for the first time, connecting nodes in three distinct campus buildings time synchronized via the Global Positioning System. We quantify the quality of the distributed polarization entanglement via log-negativity, which offers a generic metric of link performance in entangled bits per second. After demonstrating successful entanglement distribution for two allocations of our eight dynamically reconfigurable channels, we realize the first deployed fiber network demonstration of remote state preparation (RSP), a fundamental quantum communications protocol with utility for performing remote private “blind” quantum computing. We further demonstrate RSP not only at one location but over three nodes in three locations. In general, our results highlight an advanced paradigm for managing entanglement resources in quantum networks of ever-increasing complexity and service demands.
The epidemic of opioid abuse is increasing, and the number of deaths secondary to opioid overdose is also increasing. Recent attention has focused on opioid prescribing and management of chronic ...pain. However, opioid use in perioperative and periprocedural patients, whether they have chronic pain or exhibit new persistent opioid abuse after a procedure, has received little attention.
We present an evidence-based technique that combines subanesthetic infusions of lidocaine and dexmedetomidine supplemented with other intravenous agents and a low dose of inhaled anesthetic.
Based on evidence of drug action and interaction, an opioid-free anesthetic can be delivered successfully. We present the cases of 2 patients in whom the opioid-free anesthetic technique was used with a successful outcome, adequate pain management, and avoidance of opioid drugs.
This anesthetic prescription can be useful for opioid-naïve patients as well as for patients with chronic pain that is managed with opioids.
Theileria parva causes an acute fatal disease in cattle, but infections are asymptomatic in the African buffalo (Syncerus caffer). Cattle can be immunized against the parasite by infection and ...treatment, but immunity is partially strain specific. Available data indicate that CD8(+) T lymphocyte responses mediate protection and, recently, several parasite antigens recognised by CD8(+) T cells have been identified. This study set out to determine the nature and extent of polymorphism in two of these antigens, Tp1 and Tp2, which contain defined CD8(+) T-cell epitopes, and to analyse the sequences for evidence of selection.
Partial sequencing of the Tp1 gene and the full-length Tp2 gene from 82 T. parva isolates revealed extensive polymorphism in both antigens, including the epitope-containing regions. Single nucleotide polymorphisms were detected at 51 positions (∼12%) in Tp1 and in 320 positions (∼61%) in Tp2. Together with two short indels in Tp1, these resulted in 30 and 42 protein variants of Tp1 and Tp2, respectively. Although evidence of positive selection was found for multiple amino acid residues, there was no preferential involvement of T cell epitope residues. Overall, the extent of diversity was much greater in T. parva isolates originating from buffalo than in isolates known to be transmissible among cattle.
The results indicate that T. parva parasites maintained in cattle represent a subset of the overall T. parva population, which has become adapted for tick transmission between cattle. The absence of obvious enrichment for positively selected amino acid residues within defined epitopes indicates either that diversity is not predominantly driven by selection exerted by host T cells, or that such selection is not detectable by the methods employed due to unidentified epitopes elsewhere in the antigens. Further functional studies are required to address this latter point.
An experimental Quantum Key Distribution (QKD) implementation requires advanced costly hardware, unavailable in most research environments, making protocol testing and performance evaluation ...complicated. This has been a major motivation for the development of QKD simulation frameworks, to allow researchers to obtain insight before proceeding into practical implementations. Several simulators have been introduced over the recent years. However, only four are publicly available, only one of which models equipment imperfections. Currently, no open‐source simulator includes all following capabilities: channel attenuation modelling, equipment imperfections and effects on key rates, estimation of elapsed time during classical and quantum‐ channel processes, use of truly random binary sequences for qubits and measurement bases, shared ‐bit fraction customization. In this paper, we present NuQKD, an open‐ source modular, intuitive simulator, featuring all the above capabilities. NuQKD establishes communication between two computer terminals, accepts custom user inputs (iterations, raw key size, attacker interception rate etc.) and evaluates the sifted key, Quantum Bit Error Rate (QBER), elapsed communication time, and more. NuQKD capabilities include optical fiber and free ‐space simulation, modeling of equipment/channel imperfections, bitstrings from True Random Number Generators, decoy‐state protocol support, and automated evaluation of performance metrics. We expect NuQKD to enable convenient and accurate representation of actual experimental conditions.
QKD experimentation requires advanced, expensive equipment, while most publicly available simulators assume ideal conditions. NuQKD is a novel simulator bridging the gap between theory and practice, offering unique features as real‐time truly random number generation, precise modelling of equipment/channel imperfections and advanced input/output user customization. NuQKD is envisioned as a beneficial tool for both experienced researchers and newcomers to the field.
The bromodomain and extraterminal (BET) family of bromodomain-containing proteins are important regulators of the epigenome through their ability to recognize N-acetyl lysine (KAc) post-translational ...modifications on histone tails. These interactions have been implicated in various disease states and, consequently, disruption of BET–KAc binding has emerged as an attractive therapeutic strategy with a number of small molecule inhibitors now under investigation in the clinic. However, until the utility of these advanced candidates is fully assessed by these trials, there remains scope for the discovery of inhibitors from new chemotypes with alternative physicochemical, pharmacokinetic, and pharmacodynamic profiles. Herein, we describe the discovery of a candidate-quality dimethylpyridone benzimidazole compound which originated from the hybridization of a dimethylphenol benzimidazole series, identified using encoded library technology, with an N-methyl pyridone series identified through fragment screening. Optimization via structure- and property-based design led to I-BET469, which possesses favorable oral pharmacokinetic properties, displays activity in vivo, and is projected to have a low human efficacious dose.
Challenges facing the deployment of quantum key distribution (QKD) systems in critical infrastructure protection applications include the optical loss-key rate tradeoff, addition of network clients, ...and interoperability of vendor-specific QKD hardware. Here, we address these challenges and present results from a recent field demonstration of three QKD systems on a real-world electric utility optical fiber network.
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