Structural Simplification of Bedaquiline: the Discovery of 3-(4-(N,N-dimethylaminomethyl)phenyl)quinoline Derived Antitubercular Lead Compounds

Bedaquiline (BDQ) is a novel and highly potent last-line antituberculosis drug that was approved by the US FDA in 2013. Owing to its stereo-structural complexity, chemical synthesis and compound optimization are rather difficult and expensive. This study describes the structural simplification of bedaquiline while preserving antitubercular activity. The compound's structure was split into fragments and reassembled in various combinations while replacing the two chiral carbon atoms with an achiral linkage instead. Four series of analogues were designed; these candidates retained their potent antitubercular activity at sub-microgram per mL concentrations against both sensitive and multidrug-resistant (MDR) Mycobacterium tuberculosis strains. Six out of the top nine MIC-ranked candidates were found to inhibit mycobacterial ATP synthesis activity with IC50 values between 20 and 40 μm, one had IC50>66 μm, and two showed no inhibition, despite their antitubercular activity. These results provide a basis for the development of chemically less complex, lower-cost bedaquiline derivatives and describe the identification of two derivatives with antitubercular activity against non-ATP synthase related targets

Large, high quality single-crystals of the new Topological Kondo Insulator, SmB6

SmB6 has recently been predicted to be a Topological Kondo Insulator, the first strongly correlated heavy fermion material to exhibit topological surface states. High quality crystals are necessary to investigate the topological properties of this material. Single crystal growth of the rare earth hexaboride, SmB6, has been carried out by the floating zone technique using a high power xenon arc lamp image furnace. Large, high quality single-crystals are obtained by this technique. The crystals produced by the floating zone technique are free of contamination from flux materials and have been characterised by resistivity and magnetisation measurements. These crystals are ideally suited for the investigation of both the surface and bulk properties of SmB6

The clock genes Period 2 and Cryptochrome 2 differentially balance bone formation

Background: Clock genes and their protein products regulate circadian rhythms in mammals but have also been implicated in various physiological processes, including bone formation. Osteoblasts build new mineralized bone whereas osteoclasts degrade it thereby balancing bone formation. To evaluate the contribution of clock components in this process, we investigated mice mutant in clock genes for a bone volume phenotype. Methodology/Principal Findings: We found that Per2Brdm1 mutant mice as well as mice lacking Cry2-/- displayed significantly increased bone volume at 12 weeks of age, when bone turnover is high. Per2Brdm1 mutant mice showed alterations in parameters specific for osteoblasts whereas mice lacking Cry2-/- displayed changes in osteoclast specific parameters. Interestingly, inactivation of both Per2 and Cry2 genes leads to normal bone volume as observed in wild type animals. Importantly, osteoclast parameters affected due to the lack of Cry2, remained at the level seen in the Cry2-/- mutants despite the simultaneous inactivation of Per2. Conclusions/Significance: This indicates that Cry2 and Per2 affect distinct pathways in the regulation of bone volume with Cry2 influencing mostly the osteoclastic cellular component of bone and Per2 acting on osteoblast parameters

Transport Through Andreev Bound States in a Graphene Quantum Dot

Andreev reflection-where an electron in a normal metal backscatters off a superconductor into a hole-forms the basis of low energy transport through superconducting junctions. Andreev reflection in confined regions gives rise to discrete Andreev bound states (ABS), which can carry a supercurrent and have recently been proposed as the basis of qubits [1-3]. Although signatures of Andreev reflection and bound states in conductance have been widely reported [4], it has been difficult to directly probe individual ABS. Here, we report transport measurements of sharp, gate-tunable ABS formed in a superconductor-quantum dot (QD)-normal system, which incorporates graphene. The QD exists in the graphene under the superconducting contact, due to a work-function mismatch [5, 6]. The ABS form when the discrete QD levels are proximity coupled to the superconducting contact. Due to the low density of states of graphene and the sensitivity of the QD levels to an applied gate voltage, the ABS spectra are narrow, can be tuned to zero energy via gate voltage, and show a striking pattern in transport measurements.Comment: 25 Pages, included SO

Measurement of the Branching Fraction of J/psi --> pi+ pi- pi0

Using 58 million J/psi and 14 million psi' decays obtained by the BESII experiment, the branching fraction of J/psi --> pi+ pi- pi0 is determined. The result is (2.10+/-0.12)X10^{-2}, which is significantly higher than previous measurements.Comment: 9 pages, 8 figures, RevTex

First observation of psi(2S)-->K_S K_L

The decay psi(2S)-->K_S K_L is observed for the first time using psi(2S) data collected with the Beijing Spectrometer (BESII) at the Beijing Electron Positron Collider (BEPC); the branching ratio is determined to be B(psi(2S)-->K_S K_L) = (5.24\pm 0.47 \pm 0.48)\times 10^{-5}. Compared with J/psi-->K_S K_L, the psi(2S) branching ratio is enhanced relative to the prediction of the perturbative QCD ``12%'' rule. The result, together with the branching ratios of psi(2S) decays to other pseudoscalar meson pairs (\pi^+\pi^- and K^+K^-), is used to investigate the relative phase between the three-gluon and the one-photon annihilation amplitudes of psi(2S) decays.Comment: 5 pages, 4 figures, 2 tables, submitted to Phys. Rev. Let

Self-Assembled 3D Flower-Like Hierarchical β-Ni(OH)2Hollow Architectures and their In Situ Thermal Conversion to NiO

Three-dimensional (3D) flower-like hierarchicalβ-Ni(OH)2hollow architectures were synthesized by a facile hydrothermal route. The as-obtained products were well characterized by XRD, SEM, TEM (HRTEM), SAED, and DSC-TGA. It was shown that the 3D flower-like hierarchicalβ-Ni(OH)2hollow architectures with a diameter of several micrometers are assembled from nanosheets with a thickness of 10–20 nm and a width of 0.5–2.5 μm. A rational mechanism of formation was proposed on the basis of a range of contrasting experiments. 3D flower-like hierarchical NiO hollow architectures with porous structure were obtained after thermal decomposition at appropriate temperatures. UV–Vis spectra reveal that the band gap of the as-synthesized NiO samples was about 3.57 eV, exhibiting obviously red shift compared with the bulk counterpart

Fully gapped topological surface states in Bi2_2Se3_3 films induced by a d-wave high-temperature superconductor

Topological insulators are a new class of materials, that exhibit robust gapless surface states protected by time-reversal symmetry. The interplay between such symmetry-protected topological surface states and symmetry-broken states (e.g. superconductivity) provides a platform for exploring novel quantum phenomena and new functionalities, such as 1D chiral or helical gapless Majorana fermions, and Majorana zero modes which may find application in fault-tolerant quantum computation. Inducing superconductivity on topological surface states is a prerequisite for their experimental realization. Here by growing high quality topological insulator Bi$_2$Se$_3$ films on a d-wave superconductor Bi$_2$Sr$_2$CaCu$_2$O$_{8+\delta}$ using molecular beam epitaxy, we are able to induce high temperature superconductivity on the surface states of Bi$_2$Se$_3$ films with a large pairing gap up to 15 meV. Interestingly, distinct from the d-wave pairing of Bi$_2$Sr$_2$CaCu$_2$O$_{8+\delta}$, the proximity-induced gap on the surface states is nearly isotropic and consistent with predominant s-wave pairing as revealed by angle-resolved photoemission spectroscopy. Our work could provide a critical step toward the realization of the long sought-after Majorana zero modes.Comment: Nature Physics, DOI:10.1038/nphys274

Microwave studies of the fractional Josephson effect in HgTe-based Josephson junctions

The rise of topological phases of matter is strongly connected to their potential to host Majorana bound states, a powerful ingredient in the search for a robust, topologically protected, quantum information processing. In order to produce such states, a method of choice is to induce superconductivity in topological insulators. The engineering of the interplay between superconductivity and the electronic properties of a topological insulator is a challenging task and it is consequently very important to understand the physics of simple superconducting devices such as Josephson junctions, in which new topological properties are expected to emerge. In this article, we review recent experiments investigating topological superconductivity in topological insulators, using microwave excitation and detection techniques. More precisely, we have fabricated and studied topological Josephson junctions made of HgTe weak links in contact with two Al or Nb contacts. In such devices, we have observed two signatures of the fractional Josephson effect, which is expected to emerge from topologically-protected gapless Andreev bound states. We first recall the theoretical background on topological Josephson junctions, then move to the experimental observations. Then, we assess the topological origin of the observed features and conclude with an outlook towards more advanced microwave spectroscopy experiments, currently under development.Comment: Lectures given at the San Sebastian Topological Matter School 2017, published in "Topological Matter. Springer Series in Solid-State Sciences, vol 190. Springer

Dimensionality of Carbon Nanomaterials Determines the Binding and Dynamics of Amyloidogenic Peptides: Multiscale Theoretical Simulations

Experimental studies have demonstrated that nanoparticles can affect the rate of protein self-assembly, possibly interfering with the development of protein misfolding diseases such as Alzheimer's, Parkinson's and prion disease caused by aggregation and fibril formation of amyloid-prone proteins. We employ classical molecular dynamics simulations and large-scale density functional theory calculations to investigate the effects of nanomaterials on the structure, dynamics and binding of an amyloidogenic peptide apoC-II(60-70). We show that the binding affinity of this peptide to carbonaceous nanomaterials such as C60, nanotubes and graphene decreases with increasing nanoparticle curvature. Strong binding is facilitated by the large contact area available for π-stacking between the aromatic residues of the peptide and the extended surfaces of graphene and the nanotube. The highly curved fullerene surface exhibits reduced efficiency for π-stacking but promotes increased peptide dynamics. We postulate that the increase in conformational dynamics of the amyloid peptide can be unfavorable for the formation of fibril competent structures. In contrast, extended fibril forming peptide conformations are promoted by the nanotube and graphene surfaces which can provide a template for fibril-growth