Enhanced sampling molecular dynamics simulations correctly predict the diverse activities of a series of stiff-stilbene G-quadruplex DNA ligands

Ligands with the capability to bind G-quadruplexes (G4s) specifically, and to control G4 structure and behaviour, offer great potential in the development of novel therapies, technologies and functional materials. Most known ligands bind to a pre-formed topology, but G4s are highly dynamic and a small number of ligands have been discovered that influence these folding equilibria. Such ligands may be useful as probes to understand the dynamic nature of G4 in vivo, or to exploit the polymorphism of G4 in the development of molecular devices. To date, these fascinating molecules have been discovered serendipitously. There is a need for tools to predict such effects to drive ligand design and development, and for molecular-level understanding of ligand binding mechanisms and associated topological perturbation of G4 structures. Here we study the G4 binding mechanisms of a family of stiff-stilbene G4 ligands to human telomeric DNA using molecular dynamics (MD) and enhanced sampling (metadynamics) MD simulations. The simulations predict a variety of binding mechanisms and effects on G4 structure for the different ligands in the series. In parallel, we characterize the binding of the ligands to the G4 target experimentally using NMR and CD spectroscopy. The results show good agreement between the simulated and experimentally observed binding modes, binding affinities and ligand-induced perturbation of the G4 structure. The simulations correctly predict ligands that perturb G4 topology. Metadynamics simulations are shown to be a powerful tool to aid development of molecules to influence G4 structure, both in interpreting experiments and to help in the design of these chemotypes

Progress in development of tapes and magnets made from Bi-2223 superconductors

Long lengths of (Bi,Pb)2Sr2Ca2Cu3O(x) tapes made by powder-in-tube processing have been wound into coils. Performance of the coils has been measured at temperatures of 4.2 to 77 K, and microstructures have been examined by x-ray diffraction and electron microscopy and then related to superconducting properties. A summary of recent results and an overview of future goals are presented

Visible-light photoswitching of ligand binding mode suggests G-quadruplex DNA as a target for photopharmacology

We report the selective targeting of telomeric G4 DNA with a dithienylethene ligand and demonstrate the robust visible-light mediated switching of the G4 ligand binding mode and G-tetrad structure in physiologically-relevant conditions. The toxicity of the ligand to cervical cancer cells is modulated by the photoisomeric state of the ligand, indicating for the first time the potential of G4 to serve as a target for photopharmacological strategies.MPO thanks the Bristol Chemical Synthesis Centre forDoctoral Training, funded by EPSRC (EP/L015366/1) and theUniversity of Bristol, for a PhD studentship, JRS acknowledges aMSCA fellowship (project 843720-BioNanoProbes). SH and AJMthanks EPSRC for support (grant numbers EP/M015378/1 andEP/M022609/1). This work was carried out using the computationalfacilities of the Advanced Computing Research Centre, University ofBristol – http://www.bris.ac.uk/acrc/ SS thanks the Bristol Centre ForFunctional Nanomaterials (EPSRC EP/L016648/1). JCMS thanks theSpanish Ministerio de Economı ́a y Competitividad (Grant CTQ2015-64275-P and RTI2018-099036-B-I00). MCG thanks the EuropeanResearch Council (ERC-COG: 64823

A novel, high-sensitivity, bacteriophage-based assay identifies low level Mycobacterium tuberculosis bacteraemia in immunocompetent patients with active and incipient tuberculosis

Haematogenous dissemination of M. tuberculosis (Mtb) is critical to pathogenesis of progressive tuberculous infection in animal models. Using a novel phage-based blood assay, we report the first concordant evidence in well-characterised immunocompetent human cohorts, demonstrating associations of Mtb bacteraemia with progressive phenotypes of latent infection and active pulmonary TB respectively

Fully on-chip photonic turnkey quantum source for entangled qubit/qudit state generation

Integrated photonics has recently become a leading platform for the realization and processing of optical entangled quantum states in compact, robust and scalable chip formats, with applications in long-distance quantum-secured communication, quantum-accelerated information processing and nonclassical metrology. However, the quantum light sources developed so far have relied on external bulky excitation lasers, making them impractical prototype devices that are not reproducible, hindering their scalability and transfer out of the laboratory into real-world applications. Here we demonstrate a fully integrated quantum light source that overcomes these challenges through the integration of a laser cavity, a highly efficient tunable noise suppression filter (>55 dB) exploiting the Vernier effect, and a nonlinear microring for entangled photon-pair generation through spontaneous four-wave mixing. The hybrid quantum source employs an electrically pumped InP gain section and a Si3N4 low-loss microring filter system, and demonstrates high performance parameters, that is, pair emission over four resonant modes in the telecom band (bandwidth of ~1 THz) and a remarkable pair detection rate of ~620 Hz at a high coincidence-to-accidental ratio of ~80. The source directly creates high-dimensional frequency-bin entangled quantum states (qubits/qudits), as verified by quantum interference measurements with visibilities up to 96% (violating Bell’s inequality) and by density matrix reconstruction through state tomography, showing fidelities of up to 99%. Our approach, leveraging a hybrid photonic platform, enables scalable, commercially viable, low-cost, compact, lightweight and field-deployable entangled quantum sources, quintessential for practical, out-of-laboratory applications such as in quantum processors and quantum satellite communications systems

Carbon Nanotubes for Space Photovoltaic Applications

Carbon nanotubes (CNTs) can be envisioned as an individual graphene sheet rolled into a seamless cylinder (single-walled, SWNT), or concentric sheets as in the case of a multi-walled carbon nanotube (MWNT) (1). The role-up vector will determine the hexagonal arrangement and "chirality" of the graphene sheet, which will establish the nanotube to be metallic or semiconducting. The optoelectronic properties will depend directly on this chiral angle and the diameter of the SWNT, with semiconductor types exhibiting a band gap energy (2). Characteristic of MWNTs are the concentric graphene layers spaced 0.34 nm apart, with diameters from 10-200 nm and lengths up to hundreds of microns (2). In the case of SWNTs, the diameters range from 0.4 - 2 nm and lengths have been reported up to 1.5 cm (3). SWNTs have the distinguishable property of "bundling" together due to van der Waal's attractions to form "ropes." A comparison of these different structural types is shown in Figure 1. The use of SWNTS in space photovoltaic (PV) applications is attractive for a variety of reasons. Carbon nanotubes as a class of materials exhibit unprecedented optical, electrical, mechanical properties, with the added benefit of being nanoscale in size which fosters ideal interaction in nanomaterial-based devices like polymeric solar cells. The optical bandgap of semiconducting SWNTs can be varied from approx. 0.4 - 1.5 eV, with this property being inversely proportional to the nanotube diameter. Recent work at GE Global Research has shown where a single nanotube device can behave as an "ideal" pn diode (5). The SWNT was bridged over a SiO2 channel between Mo contacts and exhibited an ideality factor of 1, based on a fit of the current-voltage data using the diode equation. The measured PV efficiency under a 0.8 eV monochromatic illumination showed a power conversion efficiency of 0.2 %. However, the projected efficiency of these junctions is estimated to be > 5 %, especially when one considers the enhanced absorption (from nanotubes whose bandgap is tailored to illumination) and electromagnetic coupling in a network of nanotubes

1-(3-Chloro-4-fluoro­phen­yl)-5-(2-diazo­acet­yl)-4-phenyl­pyrrolidin-2-one

In the title compound, C18H13ClFN3O2, the pyrrolidine ring adopts an envelope conformation and the planar part is rotated by 4.3 (6)° from the plane of the benzene ring and is almost perperdicular both to the diazo­acetyl unit [dihedral angle = 78.93 (7)°] and the phenyl ring [dihedral angle = 86.07 (7)°]. In the crystal, mol­ecules are linked into a three-dimensional framework by C—H⋯O inter­actions. The mol­ecular conformation is stabilized by an intra­molecular C—H⋯O hydrogen bond