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At least 1,765 records · Page 98

Design of the First-in-Class, Highly Potent Irreversible Inhibitor Targeting the Menin-MLL Protein–Protein Interaction

The structure-based design of M-525 as the first-in-class, highly potent, irreversible small-molecule inhibitor of the menin-MLL interaction is presented. M-525 targets cellular menin protein at sub-nanomolar concentrations and achieves low nanomolar potencies in cell growth inhibition and in the suppression of MLL-regulated gene expression in MLL leukemia cells. M-525 demonstrates high cellular specificity over non-MLL leukemia cells and is more than 30 times more potent than its corresponding reversible inhibitors. Mass spectrometric analysis and co-crystal structure of M-525 in complex with menin firmly establish its mode of action. A single administration of M-525 effectively suppresses MLL-regulated gene expression in tumor tissue. An efficient procedure was developed to synthesize M-525. This study demonstrates that irreversible inhibition of menin may be a promising therapeutic strategy for MLL leukemia.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Spectral sum rules and magneto-roton as emergent graviton in fractional quantum Hall effect

Here, we consider gapped fractional quantum Hall states on the lowest Landau level when the Coulomb energy is much smaller than the cyclotron energy. We introduce two spectral densities, ρ T (ω) and $\bar{p}$ T (ω), which are proportional to the probabilities of absorption of circularly polarized gravitons by the quantum Hall system. We prove three sum rules relating these spectral densities with the shift S, the q 4 coefficient of the static structure factor S 4 , and the high-frequency shear modulus of the ground state μ ∞ , which is precisely defined. We confirm an inequality, first suggested by Haldane, that S 4 is bounded from below by |S–1|/8. The Laughlin wavefunction saturates this bound, which we argue to imply that systems with ground state wavefunctions close to Laughlin’s absorb gravitons of predominantly one circular polarization. We consider a nonlinear model where the sum rules are saturated by a single magneto-roton mode. In this model, the magneto-roton arises from the mixing between oscillations of an internal metric and the hydrodynamic motion. Implications for experiments are briefly discussed.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗

Electron–Phonon Coupling in Ti/TiN MKIDs Multilayer Microresonator

Over the last few years, there has been a growing interest toward the use of superconducting microwave microresonators operated in quasi-thermal equilibrium mode, especially applied to single particle detection. Indeed, previous devices designed and tested by our group with X-ray sources in the keV range evidenced that several issues arise from the attempt of detection through athermal quasiparticles produced within direct strikes of X-rays in the superconductor material of the resonator. In order to prevent issues related to quasiparticles self-recombination and to avoid exchange of athermal phonons with the substrate, our group focused on the development of thermal superconducting microresonators. In this configuration, resonators composed of multilayer films of Ti/TiN sense the temperature of an absorbing material. To maximize the thermal response, low-critical-temperature films are preferable. By lowering the critical temperature, though, the maximum probing power bearable by the resonators decreases abruptly because of the weakening of the electron–phonon coupling. A proper compromise between the value of critical temperature (and hence sensitivity to energy deposition) and readout power bearable by the device has to be found in order to avoid signal-to-noise ratio degradation. In this contribution, we report the latest measurement of the electron–phonon coupling.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗

Development of a multidimensional gamma-spectrometer

A high-sensitivity multidimensional gamma-spectrometer is being developed within the shallow underground laboratory at Pacific Northwest National Laboratory (PNNL, USA). The system consists of two Broad Energy Germanium (BEGe) detectors, inside a low-background lead and copper shield, fitted with a cosmic veto background reduction system. The detector has advanced functionality, including operation in single or combined detector mode, with reductions in the cosmic background by 49.6% and Compton suppression of 6.5%. For selected radionuclides this provides an overall MDA improvement of 52.7%. Utilizing both detectors for simultaneous measurements of thermally irradiated highly enriched uranium (HEU) increased peak identification and reduced uncertainty by 27.6%. The design uses commercially off-the-shelf (COTS) components, for which the configuration is described, to provide a practical and powerful solution for low-level nuclear measurements.

Compton suppression↗

In situ investigation of the tensile deformation of laser welded Ti{sub 2}AlNb joints

The tensile deformation behavior of laser welded Ti{sub 2}AlNb joints was investigated using in situ analysis methods. The fracture mode of the single-B2-phase fusion zone was quasi-cleavage at room temperature and intergranular at 650 °C, while that of base metal was microvoid coalescence at both room temperature and 650 °C. Tensile deformation at room temperature was observed using in situ SEM tensile testing. In base metal, microcracks nucleated and propagated mainly within the O phase or along O/B2 phase boundaries. While both the cross- and multi-slips were found in the single-B2-phase fusion zone, a confocal laser scanning microscopy was used to observe the crack initiation and propagation process in situ at 650 °C. Cracks mainly formed along the B2/O phase boundaries in base metal, along the fragile grain boundaries of B2 phase in the fusion zone. The thermal simulation experiment and following TEM analysis indicated that the precipitation of continuous O-phase films along the B2 grain boundaries resulted in the high temperature brittleness of laser welded Ti{sub 2}AlNb joints. - Highlights: •Cracks formed within O phase or along B2/O boundaries in the base metal. •Cross- and multi-slips relieved stress in the fusion zone at room temperature. •Cracks mainly formed along the B2/O boundaries at 650 °C. •In the fusion zone, intergranular cracks were in situ observed at 650 °C. •O-phase films along B2 grain boundaries caused the high temperature brittleness.

36 MATERIALS SCIENCE↗

Performance testing of a Compton suppressed coincidence measurements using the Advanced Radionuclide Gamma-spectrOmeter

A Compton-suppressed multidimensional gamma-spectrometer is being developed within the Shallow Underground Laboratory (SUL) at Pacific Northwest National Laboratory (PNNL, USA). This Advanced Radionuclide Gamma-spectrOmeter (ARGO) system consists of two Broad Energy Germanium (BEGe) detectors, surrounded by a 12-detector sodium iodide (NaI) Compton suppression shield, situated inside a low-background lead and copper shield, fitted with a cosmic veto background reduction system. The detector has advanced functionality, including operation in single or combined detector mode, coincidence mode and Compton suppressed coincidence mode. Validation experiments measuring a neutron irradiated natural uranium sample, have demonstrated order of magnitude improvements in gamma detection sensitivity compared to conventional gamma-spectrometry techniques. Importantly this research demonstrates the feasibility of processing and analysing high-multiplicity datasets and the potential for high-sensitivity radionuclide measurements.

ARGO↗

Modal dynamics of high-frequency transverse combustion instabilities

This paper investigates the modal dynamics of self-excited high frequency transverse instabilities in a multi-nozzle, swirl-stabilized can combustor. It utilizes results from multiple pressure sensors to decompose the disturbance into clockwise (CW) and counter-clockwise (CCW) waves, enabling a reconstruction of the pressure amplitude, phase, anti-nodal line location, and spin ratio. While these types of decompositions have been demonstrated on small scale combustors, particularly annular combustors, this is the first study to analyze these results for a high power, multi-nozzle can combustor. Its particular focus is in characterizing the system evolution in phase space and the nature of the system attractors under linearly unstable conditions; results are presented in spin ratio-phase difference space, so that limit cycle oscillations appear as fixed points. Results are shown for conditions where three different attractors dominate (standing, CW, and CCW) but are taken for very long time periods (~50,000 cycles) so that the system's interaction with these attractors can be observed. For the standing mode-dominated case, the phase portrait shows spiral trajectories converging to a single fixed point. For the spinning mode dominated cases, however, multiple fixed points and saddle points were observed, and the trajectories showed a more complicated structure. It was also shown that even though the CW mode is dominant, this mode intermittently switches to standing or CCW modes for short period. These results suggest that the strength of each attractor depends on test conditions and that random noise stochastically perturbs the system so that large regions of the phase space are explored. Lastly, one interesting observation is that the angular velocity of the anti-nodal line linearly varies with the spin ratio under standing-mode dominant conditions.

42 ENGINEERING↗

Self-Assembly of Metallo-Supramolecules with Dissymmetrical Ligands and Characterization by Scanning Tunneling Microscopy

Asymmetrical and dissymmetrical structures are widespread and play a critical role in nature and life systems. In the field of metallo-supramolecular assemblies, it is still in its infancy for constructing artificial architectures using dissymmetrical building blocks. Herein, we report the self-assembly of supramolecular systems based on two dissymmetrical double-layered ligands. With the aid of ultra-high-vacuum, low-temperature scanning tunneling microscopy (UHV-LT-STM), we were able to investigate four isomeric structures corresponding to four types of binding modes of ligand LA with two major conformations complexes A. The distribution of isomers measured by STM and total binding energy of each isomer obtained by density functional theory (DFT) calculations suggested that the most abundant isomer could be the most stable one with highest total binding energy. Lastly, through shortening the linker between inner and outer layers and the length of arms, the arrangement of dissymmetrical ligand LB could be controlled within one binding mode corresponding to the single conformation for complexes B.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Double-pulse speckle contrast correlations with near Fourier transform limited free-electron laser light using hard X-ray split-and-delay

Abstract The ability to deliver two coherent X-ray pulses with precise time-delays ranging from a few femtoseconds to nanoseconds enables critical capabilities of probing ultra-fast phenomena in condensed matter systems at X-ray free electron laser (FEL) sources. Recent progress made in the hard X-ray split-and-delay optics developments now brings a very promising prospect for resolving atomic-scale motions that were not accessible by previous time-resolved techniques. Here, we report on characterizing the spatial and temporal coherence properties of the hard X-ray FEL beam after propagating through split-and-delay optics. Speckle contrast analysis of small-angle scattering measurements from nanoparticles reveals well-preserved transverse coherence of the beam. Measuring intensity fluctuations from successive X-ray pulses also reveals that only single or double temporal modes remain in the transmitted beam, corresponding to nearly Fourier transform limited pulses.

42 ENGINEERING↗

Nanograting formation through surface plasmon fields induced by femtosecond laser pulses

Ablation of solid surfaces irradiated with superimposed multiple shots of low fluence femtosecond (fs) laser pulses often results in the formation of periodic nanostructures on the target surface. We demonstrate that the self-organization process of nanostructuring can be regulated to fabricate a homogeneous nanograting on the target surface in air. A simple two-step ablation process was used to control the nanoscale energy deposition that should be developed through the excitation of surface plasmon polaritons (SPPs) during the fs laser-surface interaction. The results obtained for crystalline gallium nitride represent exactly the nature of a single spatial standing wave mode of SPPs of which periodically enhanced near-fields ablate the target surface to form the nanograting with a period of ∼200 nm. The calculated results for a model target reproduce well the observed nanograting period and explain the origin of its characteristic properties.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

Cavity-photon-switched coherent transient transport in a double quantum waveguide

We study a cavity-photon-switched coherent electron transport in a symmetric double quantum waveguide. The waveguide system is weakly connected to two electron reservoirs, but strongly coupled to a single quantized photon cavity mode. A coupling window is placed between the waveguides to allow electron interference or inter-waveguide transport. The transient electron transport in the system is investigated using a quantum master equation. We present a cavity-photon tunable semiconductor quantum waveguide implementation of an inverter quantum gate, in which the output of the waveguide system may be selected via the selection of an appropriate photon number or “photon frequency” of the cavity. In addition, the importance of the photon polarization in the cavity, that is, either parallel or perpendicular to the direction of electron propagation in the waveguide system is demonstrated.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

Time-domain self-consistent theory of frequency-locking regimes in gyrotrons with low-Q resonators

A time-domain theory of frequency-locking gyrotron oscillators with low-Q resonators has been developed. The presented theory is based on the description of wave propagation by a parabolic equation taking into account the external signal by modification of boundary conditions. We show that the developed model can be effectively used for simulations of both single- and multi-mode operation regimes in gyrotrons driven by an external signal. For the case of low-Q resonators typical for powerful gyrotrons, the external signal can influence the axial field profile inside the interaction space significantly and, correspondingly, the value of the electron orbital efficiency.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗

Relativistic electron motion in cylindrical waveguide with strong guiding magnetic field and high power microwave

In O-type high power microwave (HPM) devices, the annular relativistic electron beam is constrained by a strong guiding magnetic field and propagates through an interaction region to generate HPM. Some papers believe that the E × B drift of electrons may lead to beam breakup. This paper simplifies the interaction region with a smooth cylindrical waveguide to research the radial motion of electrons under conditions of strong guiding magnetic field and TM{sub 01} mode HPM. The single-particle trajectory shows that the radial electron motion presents the characteristic of radial guiding-center drift carrying cyclotron motion. The radial guiding-center drift is spatially periodic and is dominated by the polarization drift, not the E × B drift. Furthermore, the self fields of the beam space charge can provide a radial force which may pull electrons outward to some extent but will not affect the radial polarization drift. Despite the radial drift, the strong guiding magnetic field limits the drift amplitude to a small value and prevents beam breakup from happening due to this cause.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗

Edge cracks in nickel and aluminium single crystals: A molecular dynamics study

A molecular dynamics study of edge cracks in Ni and Al single crystals under mode-I loading conditions is presented. Simulations are performed using embedded-atom method potentials for Ni and Al at a temperature of 0.5 K. The results reveal that Ni and Al show different fracture mechanisms. Overall failure behavior of Ni is brittle, while fracture in Al proceeds through void nucleation and coalescence with a zig-zag pattern of crack growth. The qualitative nature of results is discussed in the context of vacancy-formation energies and surface energies of the two FCC metals.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗

Absorptive lasing mode suppression in ZnO nano- and microcavities

We conclusively explain the different lasing mode energies in ZnO nano- and microcavities observed by us and reported in literature. The limited penetration depth of usually used excitation lasers results in an inhomogeneous spatial gain region depending on the structure size and geometry. Hence, weakly or even nonexcited areas remain present after excitation, where modes are instantaneously suppressed by excitonic absorption. We compare the effects for ZnO microwires, nanowires, and tetrapod-like structures at room temperature and demonstrate that the corresponding mode selective effect is most pronounced for whispering-gallery modes in microwires with a hexagonal cross section. Furthermore, the absorptive lasing mode suppression will be demonstrated by correlating the spot size of the excitation laser and the lasing mode characteristic of a single ZnO nanowire.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

Control over the performance characteristics of a passively mode-locked erbium-doped fibre ring laser

We report an all-fibre ultrashort pulse erbium-doped ring laser passively mode-locked by single-wall carbon nanotubes dispersed in carboxymethylcellulose-based polymer films. Owing to intracavity dispersion management and controlled absorption in the polymer films, the laser is capable of generating both femto- and picosecond pulses of various shapes in the spectral range 1.53 – 1.56 μm. We have demonstrated and investigated the generation of almost transform- limited, inversely modified solitons at a high normal cavity dispersion. (control of laser radiation parameters)

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗

Parametric generation in a PPLN crystal pumped by a Q-switched mode-locked Nd : YAG laser: comparison of the superluminescent and singly resonant operation regimes

The output characteristics of light in two parametric generation regimes [parametric superluminescence and parametric generation in a singly resonant optical parametric oscillator (OPO) based on a 50-mm long PPLN crystal, synchronously pumped by a 50-ps Nd : YAG laser] are compared. The total average output power at the wavelengths of signal (λ = 1475 nm) and idler (λ = 3820 nm) waves in the superluminescence regime is ∼120 mW (peak power ∼120 kW). The maximum total conversion efficiency with respect to the absorbed power in the superluminescence regime is ∼60%. The maximum conversion efficiency into the idler wave with respect to the absorbed pump power is 15% and 25% (quantum efficiencies of 54% and 90%) for the superluminescence and singly resonant OPO regimes, respectively. The maximum values of the average output power at the idler wavelength are ∼30 and ∼60 mW at degrees of pump depletion of 47% and 55% for the superluminescence and singly resonant OPO regimes, respectively. (paper)

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗