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At least 361 records · Page 20

Targeted inhibition of metastatic melanoma through interference with Pin1-FOXM1 signaling

Melanoma is the most lethal form of skin cancer and successful treatment of metastatic melanoma remains challenging. BRAF/MEK inhibitors only show a temporary benefit due to rapid occurrence of resistance, whereas immunotherapy is mainly effective in selected subsets of patients. Thus, there is a need to identify new targets to improve treatment of metastatic melanoma. To this extent, we searched for markers that are elevated in melanoma and are under regulation of potentially druggable enzymes. Here, we show that the pro-proliferative transcription factor FOXM1 is elevated and activated in malignant melanoma. FOXM1 activity correlated with expression of the enzyme Pin1, which we found to be indicative of a poor prognosis. In functional experiments, Pin1 proved to be a main regulator of FOXM1 activity through MEK-dependent physical regulation during the cell cycle. The Pin1-FOXM1 interaction was enhanced by BRAF V600E , the driver oncogene in the majority of melanomas, and in extrapolation of the correlation data, interference with\ Pin1 in BRAF V600E -driven metastatic melanoma cells impaired both FOXM1 activity and cell survival. Importantly, cell-permeable Pin1-FOXM1-blocking peptides repressed the proliferation of melanoma cells in freshly isolated human metastatic melanoma ex vivo and in three-dimensional-cultured patient-derived melanoids. When combined with the BRAF V600E -inhibitor PLX4032 a robust repression in melanoid viability was obtained, establishing preclinical value of patient-derived melanoids for prognostic use of drug sensitivity and further underscoring the beneficial effect of Pin1-FOXM1 inhibitory peptides as anti-melanoma drugs. These proof-of-concept results provide a starting point for development of therapeutic Pin1-FOXM1 inhibitors to target metastatic melanoma.

Biochemistry & Molecular Biology↗

Directly visualizing the sign change of d-wave superconducting gap in Bi 2 Sr 2 CaCu 2 O 8+δ by phase-referenced quasiparticle interference

The superconducting state is formed by the condensation of Cooper pairs and protected by the superconducting gap. The pairing interaction between the two electrons of a Cooper pair determines the gap function. Thus, it is pivotal to detect the gap structure for understanding the mechanism of superconductivity. In cuprate superconductors, it has been well established that the gap may have a d-wave function. This gap function has an alternative sign change in the momentum space. It is however hard to visualize this sign change. Here we report the measurements of scanning tunneling spectroscopy in Bi 2 Sr 2 CaCu 2 O 8+δ and conduct the analysis of phase-referenced quasiparticle interference (QPI). We see the seven basic scattering vectors that connect the octet ends of the banana-shaped contour of Fermi surface. The phase-referenced QPI clearly visualizes the sign change of the d -wave gap. Lastly, our results illustrate an effective way for determining the sign change of unconventional superconductors.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗

Multimodal interference-based imaging of nanoscale structure and macromolecular motion uncovers UV induced cellular paroxysm

Understanding the relationship between intracellular motion and macromolecular structure remains a challenge in biology. Macromolecular structures are assembled from numerous molecules, some of which cannot be labeled. Most techniques to study motion require potentially cytotoxic dyes or transfection, which can alter cellular behavior and are susceptible to photobleaching. Here in this paper, we present a multimodal label-free imaging platform for measuring intracellular structure and macromolecular dynamics in living cells with a sensitivity to macromolecular structure as small as 20 nm and millisecond temporal resolution. We develop and validate a theory for temporal measurements of light interference. In vitro, we study how higher-order chromatin structure and dynamics change during cell differentiation and ultraviolet (UV) light irradiation. Finally, we discover cellular paroxysms, a near-instantaneous burst of macromolecular motion that occurs during UV induced cell death. With nanoscale sensitive, millisecond resolved capabilities, this platform could address critical questions about macromolecular behavior in live cells.

59 BASIC BIOLOGICAL SCIENCES↗

Matter-wave interference of a native polypeptide

The de Broglie wave nature of matter is a paradigmatic example of quantum physics and it has been exploited in precision measurements of forces and fundamental constants. However, matter-wave interferometry has remained an outstanding challenge for natural polypeptides, building blocks of life, which are fragile and difficult to handle. Here, we demonstrate the wave nature of gramicidin, a natural antibiotic composed of 15 amino acids. Its center of mass is delocalized over more than 20 times the molecular size in our timedomain Talbot-Lau interferometer. We compare the observed interference fringes with a model that includes both a rigorous treatment of the peptide’s quantum wave nature as well as a quantum chemical assessment of its optical properties to distinguish our result from classical predictions. The realization of quantum optics with this prototypical biomolecule paves the way for quantum-assisted measurements on a large class of biologically relevant molecules.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

Hong-Ou-Mandel interference of single-photon-level pulses stored in independent room-temperature quantum memories

Abstract Quantum repeater networks require independent absorptive quantum memories capable of storing and retrieving indistinguishable photons to perform high-repetition entanglement swapping operations. The ability to perform these coherent operations at room temperature is of prime importance for the realization of scalable quantum networks. We perform Hong-Ou-Mandel (HOM) interference between photonic polarization states and single-photon-level pulses stored and retrieved from two sets of independent room-temperature quantum memories. We show that the storage and retrieval of polarization states from quantum memories does not degrade the HOM visibility for few-photon-level polarization states in a dual-rail configuration. For single-photon-level pulses, we measure the HOM visibility with various levels of background in a single polarization, single-rail QM, and investigate its dependence on the signal-to-background ratio. We obtain an HOM visibility of 43%, compared to the 48% no-memory limit of our set-up. These results allow us to estimate a 33% visibility for polarization qubits under the same conditions. These demonstrations lay the groundwork for future applications using large-scale memory-assisted quantum networks.

Physics↗

Quasi-particle interference of the van Hove singularity in Sr2RuO4

Abstract The single-layered ruthenate Sr 2 RuO 4 is one of the most enigmatic unconventional superconductors. While for many years it was thought to be the best candidate for a chiral p -wave superconducting ground state, desirable for topological quantum computations, recent experiments suggest a singlet state, ruling out the original p -wave scenario. The superconductivity as well as the properties of the multi-layered compounds of the ruthenate perovskites are strongly influenced by a van Hove singularity in proximity of the Fermi energy. Tiny structural distortions move the van Hove singularity across the Fermi energy with dramatic consequences for the physical properties. Here, we determine the electronic structure of the van Hove singularity in the surface layer of Sr 2 RuO 4 by quasi-particle interference imaging. We trace its dispersion and demonstrate from a model calculation accounting for the full vacuum overlap of the wave functions that its detection is facilitated through the octahedral rotations in the surface layer.

36 MATERIALS SCIENCE↗

Vortex-induced anomalies in the superconducting quantum interference patterns of topological insulator Josephson junctions

The superconducting quantum interference (SQI) patterns of Josephson junctions fabricated from hybrid structures that interface an s-wave superconductor with a topological insulator can be used to detect signatures of novel quasiparticle states. Here, we compare calculated and experimental SQI patterns obtained from hybrid junctions fabricated on cadmium arsenide, a two-dimensional topological insulator. The calculations account for the effects of Abrikosov (anti-) vortices in the superconducting contacts. They describe the experimentally observed deviations of the SQI from an ideal Fraunhofer pattern, including anomalous phase shifts, node lifting, even/odd modulations of the lobes, irregular lobe spacing, and an asymmetry in the positive/negative magnetic field. We also show that under a current bias, these vortices enter the electrodes even if there is no intentionally applied external magnetic field. The results show that Abrikosov vortices in the electrodes of the junctions can explain many of the observed anomalies in the SQI patterns of topological insulator Josephson junctions.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗

Ferroelectric quantum Hall phase revealed by visualizing Landau level wave function interference

States with spontaneously broken symmetry can form due to Coulomb interactions in electronic systems with multiple internal degrees of freedom. Materials with several degenerate regions in the Brillouin zone-called valleys-offer a rich setting for the emergence of such states, which have potential electronic and optical applications. To date, identification of these broken-symmetry phases has mostly relied on macroscopic transport or optical properties. Here we demonstrate a direct approach by visualizing the wavefunctions of bismuth surface states with a scanning tunnelling microscope. Strong spin-orbit coupling on the surface of bismuth leads to six degenerate, teardrop-shaped, hole valleys. Our spectroscopic measurements reveal that exchange interactions fully lift this degeneracy at high magnetic field, and we are able to determine the nature of the valley ordering by imaging the broken-symmetry Landau level wavefunctions. The spatial features of singly degenerate Landau level wavefunctions near isolated defects contain unique signatures of interference between spin-textured valleys, which identify the electronic ground state as a quantum Hall ferroelectric. As a result, our observations confirm the recent prediction that interactions in strongly anisotropic valley systems favour the occupation of a single valley, giving rise to emergent ferroelectricity in the surface state of bismuth.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

CRISPR interference to interrogate genes that control biofilm formation in Pseudomonas fluorescens

Bacterial biofilm formation involves signaling and regulatory pathways that control the transition from motile to sessile lifestyle, production of extracellular polymeric matrix, and maturation of the biofilm 3D structure. Biofilms are extensively studied because of their importance in biomedical, ecological and industrial settings. Gene inactivation is a powerful approach for functional studies but it is often labor intensive, limiting systematic gene surveys to the most tractable bacterial hosts. Here, we adapted the CRISPR interference (CRISPRi) system for use in diverse strain isolates of P. fluorescens, SBW25, WH6 and Pf0-1. We found that CRISPRi is applicable to study complex phenotypes such as cell morphology, motility and biofilm formation over extended periods of time. In SBW25, CRISPRi-mediated silencing of genes encoding the GacA/S two-component system and regulatory proteins associated with the cylic di-GMP signaling messenger produced swarming and biofilm phenotypes similar to those obtained after gene inactivation. Combined with detailed confocal microscopy of biofilms, our study also revealed novel phenotypes associated with extracellular matrix biosynthesis as well as the potent inhibition of SBW25 biofilm formation mediated by the PFLU1114 operon. We conclude that CRISPRi is a reliable and scalable approach to investigate gene networks in the diverse P. fluorescens group.

59 BASIC BIOLOGICAL SCIENCES↗

Microwave response in a topological superconducting quantum interference device

Abstract Photon detection at microwave frequency is of great interest due to its application in quantum computation information science and technology. Herein are results from studying microwave response in a topological superconducting quantum interference device (SQUID) realized in Dirac semimetal Cd 3 As 2 . The temperature dependence and microwave power dependence of the SQUID junction resistance are studied, from which we obtain an effective temperature at each microwave power level. It is observed the effective temperature increases with the microwave power. This observation of large microwave response may pave the way for single photon detection at the microwave frequency in topological quantum materials.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗

Spatial quantum-interference landscapes of multi-site-controlled quantum dots coupled to extended photonic cavity modes

Abstract A compact platform to integrate emitters in a cavity-like support is to embed quantum dots (QDs) in a photonic crystal (PhC) structure, making them promising candidates for integrated quantum photonic circuits. The emission properties of QDs can be modified by tailored photonic structures, relying on the Purcell effect or strong light-matter interactions. However, the effects of photonic states on spatial features of exciton emissions in these systems are rarely explored. Such effect is difficult to access due to random positions of self-assembled QDs in PhC structures, and the fact that quantum well excitons’ wavefunctions resemble photonic states in a conventional distributed Bragg reflector cavity system. In this work, we instead observe a spatial signature of exciton emission using site-controlled QDs embedded in PhC cavities. In particular, we observe the detuning-dependent spatial repulsion of the QD exciton emissions by polarized imaging of the micro-photoluminescence, dependent on the controlled QD’s position in a spatially extended photonic pattern. The observed effect arises due to the quantum interference between QD decay channel in a spatially-extended cavity mode. Our findings suggest that integration of site-controlled QDs in tailored photonic structures can enable spatially distributed single-photon sources and photon switches.

Physics↗

Defocused differential interference contrast microscopy imaging of single plasmonic anisotropic nanoparticles

We present the defocused differential interference contrast (DIC) imaging of gold nanorods. We found that the scattered light and the defocus aberration play an important role in the formation of orientation-dependent DIC image patterns of a gold nanorod. Interestingly, the scattered light from a gold nanorod aligned closer to the polarization directions enables us to directly resolve its spatial orientation under a defocused DIC microscope.

36 MATERIALS SCIENCE↗

Non-adiabatic quantum interference and complex formation in ultracold collisions of Rb with KRb

Ultracold elastic collisions of 87 Rb with 40 K 87 Rb in its ground vibrational and rotational state are investigated using a first principles based theoretical methodology. Full-dimensional ab initio computed potential energy surfaces are reported that include the two lowest-lying electronic states, their conical intersection, non-adiabatic couplings and an accurate long-range behavior. A numerically exact time-independent quantum dynamics method in hyperspherical coordinates is used to compute the elastic scattering cross sections, rate coefficients and collision lifetime spectrum. The quantum scattering calculations include all degrees of freedom and treat both electronic states and their non-adiabatic couplings using a two-state diabatic representation. The theoretically computed elastic rate coefficient is in good agreement with the recently reported experimental value. Significant non-adiabatic quantum interference effects are shown to originate from the unique properties of ultracold collisions and the geometric phase associated with the conical intersection. A high-resolution collision energy grid is used to investigate the origin of the experimentally reported long-lived 3-body collision complexes.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Superconducting quantum interference devices based set-up for probing current noise and correlations in three-terminal devices

We have implemented a new experimental set-up for precise measurements of current fluctuations in three-terminal devices. The system operates at very low temperatures (30 mK) and is equipped with three superconducting quantum interference devices (SQUIDs) as low noise current amplifiers. A SQUID input coil is connected to each terminal of a sample allowing the acquisition of time-dependent current everywhere in the circuit. From these traces, we can measure the current mean value, the noise, and cross-correlations between different branches of a device. In this paper, we present calibration results of noise and cross-correlations obtained using low impedance macroscopic resistors. From these results, we can extract the noise level of the set-up and show that there are no intrinsic correlations due to the measurement scheme. We also studied noise and correlations as a function of a dc current and estimated the electronic temperature of various macroscopic resistors.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

Tracking geomagnetic fluctuations to picotesla accuracy using two superconducting quantum interference device vector magnetometers

SQUIDs can be used to monitor the three vector components of the geomagnetic field to a high precision at very low frequencies, yet as they are susceptible to external interference, the accuracy to which they can track changes in the dc field over long periods has been unclear. We have carried out simultaneous measurements of the geomagnetic field recorded using two independent 3-axis SQUID magnetometers at the Laboratoire Souterrain a Bas Bruit (LSBB). We demonstrate a technique to take the difference between a linear transform of the three signals from one magnetometer, and a reference signal from the other, in order to account for any difference in alignment and calibration, and track local signals at a sub-nT level. We confirmed that both systems tracked the same signal with an RMS difference as low as 56pT over a period of 72 h. To our knowledge this is the first such demonstration of the long term accuracy of SQUID magnetometers for monitoring geomagnetic fields.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

Broadband calibrated scattering parameters characterization of a superconducting quantum interference device amplifier

In this work, we characterize the 2-port scattering parameters of a superconducting quantum interference device amplifier at {approx}20 mK over several gigahertz of bandwidth. The measurement reference plane is positioned on a 6.25 {Omega} microstrip line situated directly at the input and output of the device by means of a thru-reflect-line cryogenic calibration procedure. From the scattering parameters, we derive the device available power gain, isolation, and input impedance over the 2-8 GHz range. This measurement methodology provides a path towards designing wide-band matching circuits for low impedance superconducting amplifiers operating at dilution refrigerator temperatures.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗