Rationally designed chimeric PI3K-BET bromodomain inhibitors elicit curative responses in MYC-driven lymphoma.

Targeted inhibitors of bromodomain and extraterminal (BET)-bromodomains and phosphatidylinositol-3-kinase (PI3K) signaling demonstrate potent but self-limited antilymphoma activity as single agents in the context of cellular Myelocytomatosis () oncogene-dysregulation. However, combined PI3K and BET inhibition imparts synergistic anticancer activity with the potential for more sustained disease responses due to the mutual antagonism of compensatory epigenetic and signaling networks. Here, we describe the mechanistic and therapeutic validation of rationally designed dual PI3K/BET bromodomain inhibitors, built by linkage of established PI3K and BET inhibitor pharmacophores.

Molecular Mechanisms of Cereblon-Interacting Small Molecules in Multiple Myeloma Therapy.

Thalidomide analogues (or immunomodulatory imide drugs, IMiDs) are cornerstones in the treatment of multiple myeloma (MM). These drugs bind Cereblon (CRBN), a receptor for the Cullin-ring 4 ubiquitin-ligase (CRL4) complex, to modify its substrate specificity. IMiDs mediate CRBN-dependent engagement and proteasomal degradation of 'neosubstrates', Ikaros (IKZF1) and Aiolos (IKZF3), conveying concurrent antimyeloma activity and T-cell costimulation.

A Raman probe of phonons and electron-phonon interactions in the Weyl semimetal NbIrTe.

There is tremendous interest in measuring the strong electron-phonon interactions seen in topological Weyl semimetals. The semimetal NbIrTe has been proposed to be a Type-II Weyl semimetal with 8 pairs of opposite Chirality Weyl nodes which are very close to the Fermi energy. We show using polarized angular-resolved micro-Raman scattering at two excitation energies that we can extract the phonon mode dependence of the Raman tensor elements from the shape of the scattering efficiency versus angle.

Ultrafast photoinduced band splitting and carrier dynamics in chiral tellurium nanosheets.

Trigonal tellurium (Te) is a chiral semiconductor that lacks both mirror and inversion symmetries, resulting in complex band structures with Weyl crossings and unique spin textures. Detailed time-resolved polarized reflectance spectroscopy is used to investigate its band structure and carrier dynamics. The polarized transient spectra reveal optical transitions between the uppermost spin-split H and H and the degenerate H valence bands (VB) and the lowest degenerate H conduction band (CB) as well as a higher energy transition at the L-point.

Strong Hot Carrier Effects in Single Nanowire Heterostructures.

We use transient Rayleigh scattering to study the thermalization of hot photoexcited carriers in single GaAsSb/InP nanowire heterostructures. By comparing the energy loss rate in single core-only GaAsSb nanowires which do not show substantial hot carrier effects with the core-shell nanowires, we show that the presence of an InP shell substantially suppresses the longitudinal optical phonon emission rate at low temperatures which then leads to strong hot carrier effects.

Revealing Optical Transitions and Carrier Recombination Dynamics within the Bulk Band Structure of BiSe.

Bismuth selenide (BiSe) is a prototypical 3D topological insulator whose Dirac surface states have been extensively studied theoretically and experimentally. Surprisingly little, however, is known about the energetics and dynamics of electrons and holes within the bulk band structure of the semiconductor. We use mid-infrared femtosecond transient reflectance measurements on a single nanoflake to study the ultrafast thermalization and recombination dynamics of photoexcited electrons and holes within the extended bulk band structure over a wide energy range (0.

Thermal Delocalization of Excitons in GaAs/AlGaAs Quantum Well Tube Nanowires.

We use temperature-dependent photoluminescence (PL), photoluminescence imaging, and time-resolved photoluminescence measurements to gain insights into the localization of excitons in single 2 nm GaAs/AlGaAs quantum well tube nanowires. PL spectra reveal the coexistence of localized and delocalized states at low temperatures, with narrow quantum dot-like emission lines on the high energy side of a broad emission band, and delocalized states on the low energy side. We find that the high energy QD-like emissions are metastable, disappearing at higher temperatures with only delocalized states (quantum well tube ground states) surviving.

Quantum Confined Stark Effect in a GaAs/AlGaAs Nanowire Quantum Well Tube Device: Probing Exciton Localization.

In this Letter, we explore the nature of exciton localization in single GaAs/AlGaAs nanowire quantum well tube (QWT) devices using photocurrent (PC) spectroscopy combined with simultaneous photoluminescence (PL) and photoluminescence excitation (PLE) measurements. Excitons confined to GaAs quantum well tubes of 8 and 4 nm widths embedded into an AlGaAs barrier are seen to ionize at high bias levels. Spectroscopic signatures of the ground and excited states confined to the QWT seen in PL, PLE, and PC data are consistent with simple numerical calculations.

Adaxial cell migration in the zebrafish embryo is an active cell autonomous property that requires the Prdm1a transcription factor.

Adaxial cells, the progenitors of slow-twitch muscle fibres in zebrafish, exhibit a stereotypic migratory behaviour during somitogenesis. Although this process is known to be disrupted in various mutants, its precise nature has remained unclear. Here, using in vivo imaging and chimera analysis, we show that adaxial cell migration is a cell autonomous process, during which cells become polarised and extend filopodia at their leading edge.

Emergence of localized states in narrow GaAs/AlGaAs nanowire quantum well tubes.

We use low-temperature photoluminescence, photoluminescence excitation, and photoluminescence imaging spectroscopy to explore the optical and electronic properties of GaAs/AlGaAs quantum well tube (QWT) heterostructured nanowires (NWs). We find that GaAs QWTs with widths >5 nm have electronic states which are delocalized and continuous along the length of the NW. As the NW QWT width decreases from 5 to 1.

The role of Sox6 in zebrafish muscle fiber type specification.

Background: The transcription factor Sox6 has been implicated in regulating muscle fiber type-specific gene expression in mammals. In zebrafish, loss of function of the transcription factor Prdm1a results in a slow to fast-twitch fiber type transformation presaged by ectopic expression of sox6 in slow-twitch progenitors. Morpholino-mediated Sox6 knockdown can suppress this transformation but causes ectopic expression of only one of three slow-twitch specific genes assayed.

Effects of surface passivation on twin-free GaAs nanosheets.

Unlike nanowires, GaAs nanosheets exhibit no twin defects, stacking faults, or dislocations even when grown on lattice mismatched substrates. As such, they are excellent candidates for optoelectronic applications, including LEDs and solar cells. We report substantial enhancements in the photoluminescence efficiency and the lifetime of passivated GaAs nanosheets produced using the selected area growth (SAG) method with metal organic chemical vapor deposition (MOCVD).

Zn3As2 nanowires and nanoplatelets: highly efficient infrared emission and photodetection by an earth abundant material.

The development of earth abundant materials for optoelectronics and photovoltaics promises improvements in sustainability and scalability. Recent studies have further demonstrated enhanced material efficiency through the superior light management of novel nanoscale geometries such as the nanowire. Here we show that an industry standard epitaxy technique can be used to fabricate high quality II-V nanowires (1D) and nanoplatelets (2D) of the earth abundant semiconductor Zn3As2.

Carrier thermalization dynamics in single zincblende and wurtzite InP Nanowires.

Using transient Rayleigh scattering (TRS) measurements, we obtain photoexcited carrier thermalization dynamics for both zincblende (ZB) and wurtzite (WZ) InP single nanowires (NW) with picosecond resolution. A phenomenological fitting model based on direct band-to-band transition theory is developed to extract the electron-hole-plasma density and temperature as a function of time from TRS measurements of single nanowires, which have complex valence band structures. We find that the thermalization dynamics of hot carriers depends strongly on material (GaAs NW vs InP NW) and less strongly on crystal structure (ZB vs WZ).

Illuminating the second conduction band and spin-orbit energy in single wurtzite InP nanowires.

We use polarized photoluminescence excitation spectroscopy to observe the energy and symmetry of the predicted second conduction band in 130 nm diameter wurtzite InP nanowires. We find direct spectroscopic signatures for optical transitions among the A, B, and C hole bands and both the first and the second conduction bands. We determine that the splitting between the first and second conduction bands is 228 ± 7 meV in excellent agreement with theory.

Control of muscle fibre-type diversity during embryonic development: the zebrafish paradigm.

Vertebrate skeletal muscle is composed of distinct types of fibre that are functionally adapted through differences in their physiological and metabolic properties. An understanding of the molecular basis of fibre-type specification is of relevance to human health and fitness. The zebrafish provides an attractive model for investigating fibre type specification; not only are their rapidly developing embryos optically transparent, but in contrast to amniotes, the embryonic myotome shows a discrete temporal and spatial separation of fibre type ontogeny that simplifies its analysis.

Retiree out-of-pocket healthcare spending: a study of consumer expectations and policy implications.

Even though most American retirees benefit from Medicare coverage, a mounting body of research predicts that many will face large and increasing out-of-pocket expenditures for healthcare costs in retirement and that many already struggle to finance these costs. It is unclear, however, whether the general population understands the likely magnitude of these out-of-pocket expenditures well enough to plan for them effectively. This study is the first comprehensive examination of Americans' expectations regarding their out-of-pocket spending on healthcare in retirement.

Optical, structural, and numerical investigations of GaAs/AlGaAs core-multishell nanowire quantum well tubes.

The electronic properties of thin, nanometer scale GaAs quantum well tubes embedded inside the AlGaAs shell of a GaAs core-multishell nanowire are investigated using optical spectroscopies. Using numerical simulations to model cylindrically and hexagonally symmetric systems, we correlate these electronic properties with structural characterization by aberration-corrected scanning transmission electron microscopy of nanowire cross sections. These tubular quantum wells exhibit extremely high quantum efficiency and intense emission for extremely low submicrowatt excitation powers in both photoluminescence and photoluminescence excitation measurements.

Transient Rayleigh scattering: a new probe of picosecond carrier dynamics in a single semiconductor nanowire.

Using a new technique, transient Rayleigh scattering, we show that measurements from a single GaAs/AlGaAs core-shell semiconductor nanowire provide sensitive and detailed information on the time evolution of the density and temperature of the electrons and holes after photoexcitation by an intense laser pulse. Through band filling, band gap renormalization, and plasma screening, the presence of a dense and hot electron-hole plasma directly influences the real and imaginary parts of the complex index of refraction that in turn affects the spectral dependence of the Rayleigh scattering cross-section in well-defined ways. By measuring this spectral dependence as a function of time, we directly determine the thermodynamically independent density and temperature of the electrons and holes as a function of time after pulsed excitation as the carriers thermalize to the lattice temperature.

Photomodulated rayleigh scattering of single semiconductor nanowires: probing electronic band structure.

The internal electronic structures of single semiconductor nanowires can be resolved using photomodulated Rayleigh scattering spectroscopy. The Rayleigh scattering from semiconductor nanowires is strongly polarization sensitive which allows a nearly background-free method for detecting only the light that is scattered from a single nanowire. While the Rayleigh scattering efficiency from a semiconductor nanowire depends on the dielectric contrast, it is relatively featureless as a function of energy.

The morphology and evolution of bipyramidal gold nanoparticles.

We examine the growth and evolution with time of bipyramidal gold nanoparticles grown by a seed-mediated process. The nanoparticles are characterized both by their physical dimensions determined by transmission electron microscopy and by the wavelength position of their localized surface plasmon resonance. Each growth's physical dimensions correspond to particular initial conditions, and we observe two distinct modes of temporal evolution during growth.

Direct measure of strain and electronic structure in GaAs/GaP core-shell nanowires.

Highly strained GaAs/GaP nanowires of excellent optical quality were grown with 50 nm diameter GaAs cores and 25 nm GaP shells. Photoluminescence from these nanowires is observed at energies dramatically shifted from the unstrained GaAs free exciton emission energy by 260 meV. Using Raman scattering, we show that it is possible to separately measure the degree of compressive and shear strain of the GaAs core and show that the Raman response of the GaP shell is consistent with tensile strain.

Novel growth and properties of GaAs nanowires on Si substrates.

Straight, vertically aligned GaAs nanowires were grown on Si(111) substrates coated with thin GaAs buffer layers. We find that the V/III precursor ratio and growth temperature are crucial factors influencing the morphology and quality of buffer layers. A double layer structure, consisting of a thin initial layer grown at low V/III ratio and low temperature followed by a layer grown at high V/III ratio and high temperature, is crucial for achieving straight, vertically aligned GaAs nanowires on Si(111) substrates.

Observation of the naive-T-odd Sivers effect in deep-inelastic scattering.

Azimuthal single-spin asymmetries of leptoproduced pions and charged kaons were measured on a transversely polarized hydrogen target. Evidence for a naive-T-odd, transverse-momentum-dependent parton distribution function is deduced from nonvanishing Sivers effects for pi(+), pi(0), and K(+/-), as well as in the difference of the pi(+) and pi(-) cross sections.