Coupling a two-dimensional (2D) semiconductor heterostructure to a superconductor opens new research and technology opportunities, including fundamental problems in mesoscopic superconductivity, ...scalable superconducting electronics, and new topological states of matter. One route towards topological matter is by coupling a 2D electron gas with strong spin-orbit interaction to an s-wave superconductor. Previous efforts along these lines have been adversely affected by interface disorder and unstable gating. Here we show measurements on a gateable InGaAs/InAs 2DEG with patterned epitaxial Al, yielding devices with atomically pristine interfaces between semiconductor and superconductor. Using surface gates to form a quantum point contact (QPC), we find a hard superconducting gap in the tunnelling regime. When the QPC is in the open regime, we observe a first conductance plateau at 4e
/h, consistent with theory. The hard-gap semiconductor-superconductor system demonstrated here is amenable to top-down processing and provides a new avenue towards low-dissipation electronics and topological quantum systems.
Nitrogen oxides (NOx) have fallen steadily across the US over the last 15 years. At the same time, NOx concentrations decrease on weekends relative to weekdays, largely without co-occurring changes ...in other gas-phase emissions, due to patterns of diesel truck activities. These trends taken together provide two independent constraints on the role of NOx in the nonlinear chemistry of atmospheric oxidation. In this context, we interpret interannual trends in wintertime ammonium nitrate (NH4NO3) in the San Joaquin Valley of California, a location with the worst aerosol pollution in the US and where a large portion of aerosol mass is NH4NO3. Here, we show that NOx reductions have simultaneously decreased nighttime and increased daytime NH4NO3 production over the last decade. We find a substantial decrease in NH4NO3 since 2000 and conclude that this decrease is due to reduced nitrate radical-initiated production at night in residual layers that are decoupled from fresh emissions at the surface. Further reductions in NOx are imminent in California, and nationwide, and we make a quantitative prediction of the response of NH4NO3. We show that the combination of rapid chemical production and efficient NH4NO3 loss via deposition of gas-phase nitric acid implies that high aerosol days in cities in the San Joaquin Valley air basin are responsive to local changes in NOx within those individual cities. Our calculations indicate that large decreases in NOx in the future will not only lower wintertime NH4NO3 concentrations but also cause a transition in the dominant NH4NO3 source from nighttime to daytime chemistry.
We present measurements of methane (CH4) taken aboard a NOAA WP‐3D research aircraft in 2013 over the Haynesville shale region in eastern Texas/northwestern Louisiana, the Fayetteville shale region ...in Arkansas, and the northeastern Pennsylvania portion of the Marcellus shale region, which accounted for the majority of Marcellus shale gas production that year. We calculate emission rates from the horizontal CH4 flux in the planetary boundary layer downwind of each region after subtracting the CH4 flux entering the region upwind. We find 1 day CH4 emissions of (8.0 ± 2.7) × 107 g/h from the Haynesville region, (3.9 ± 1.8) × 107 g/h from the Fayetteville region, and (1.5 ± 0.6) × 107 g/h from the Marcellus region in northeastern Pennsylvania. Finally, we compare the CH4 emissions to the total volume of natural gas extracted from each region to derive a loss rate from production operations of 1.0–2.1% from the Haynesville region, 1.0–2.8% from the Fayetteville region, and 0.18–0.41% from the Marcellus region in northeastern Pennsylvania. The climate impact of CH4 loss from shale gas production depends upon the total leakage from all production regions. The regions investigated in this work represented over half of the U.S. shale gas production in 2013, and we find generally lower loss rates than those reported in earlier studies of regions that made smaller contributions to total production. Hence, the national average CH4 loss rate from shale gas production may be lower than values extrapolated from the earlier studies.
Key Points
CH4 emissions from Haynesville, Fayetteville, and Marcellus regions quantified
CH4 emissions similar to previously studied gas‐producing regions
CH4 loss rates lower than previously studied gas‐producing regions
Analysis of in situ airborne measurements from the CalNex 2010 field experiment (Research at the Nexus of Air Quality and Climate Change) show that ozone in the boundary layer over Southern ...California was increased by downward mixing of air from the free troposphere (FT). The chemical composition, origin, and transport of air upwind and over Los Angeles, California, were studied using measurements of carbon monoxide (CO), ozone, reactive nitrogen species, and meteorological parameters from the National Oceanic and Atmospheric Administration WP‐3D aircraft on 18 research flights in California in May and June 2010. On six flights, multiple vertical profiles from 0.2–3.5 km above ground level were conducted throughout the Los Angeles (LA) basin and over the Pacific Ocean. Gas phase compounds measured in 32 vertical profiles are used to characterize air masses in the FT over the LA basin, with the aim of determining the source of increased ozone observed above the planetary boundary layer (PBL). Four primary air mass influences were observed regularly in the FT between approximately 1 and 3.5 km altitude: upper tropospheric air, long‐range transport of emissions, aged regional emissions, and marine air. The first three air mass types accounted for 89% of the FT observations. Ozone averaged 71 ppbv in air influenced by the upper troposphere, 69 ppbv in air containing emissions transported long distances, and 65 ppbv in air with aged regional emissions. Correlations between ozone and CO, and ozone and nitric acid, demonstrate entrainment of ozone from the FT into the LA PBL. Downward transport of ozone‐rich air from the FT into the PBL contributes to the ozone burden at the surface in this region and makes compliance with air quality standards challenging.
Key Points
Air mass chemical composition over Los Angeles Basin measured from aircraft
Upper tropospheric influence increased ozone in the lower free troposphere
Downward mixing of ozone‐rich air increased ozone in California
The fate of deepwater releases of gas and oil mixtures is initially determined by solubility and volatility of individual hydrocarbon species; these attributes determine partitioning between air and ...water. Quantifying this partitioning is necessary to constrain simulations of gas and oil transport, to predict marine bioavailability of different fractions of the gas‐oil mixture, and to develop a comprehensive picture of the fate of leaked hydrocarbons in the marine environment. Analysis of airborne atmospheric data shows massive amounts (∼258,000 kg/day) of hydrocarbons evaporating promptly from the Deepwater Horizon spill; these data collected during two research flights constrain air‐water partitioning, thus bioavailability and fate, of the leaked fluid. This analysis quantifies the fraction of surfacing hydrocarbons that dissolves in the water column (∼33% by mass), the fraction that does not dissolve, and the fraction that evaporates promptly after surfacing (∼14% by mass). We do not quantify the leaked fraction lacking a surface expression; therefore, calculation of atmospheric mass fluxes provides a lower limit to the total hydrocarbon leak rate of 32,600 to 47,700 barrels of fluid per day, depending on reservoir fluid composition information. This study demonstrates a new approach for rapid‐response airborne assessment of future oil spills.
Key Points
Atmospheric hydrocarbon data define air‐water partitioning of marine oil spills
Air‐water partitioning determines oil fate and extent in the marine environment
These data permit a unique and robust calculation of oil leak rate
The PROTAC (proteolysis-targeting chimera) ARV-825 recruits bromodomain and extraterminal (BET) proteins to the E3 ubiquitin ligase cereblon, leading to degradation of BET proteins, including BRD4. ...Although the BET-protein inhibitor (BETi) OTX015 caused accumulation of BRD4, treatment with equimolar concentrations of ARV-825 caused sustained and profound depletion (>90%) of BRD4 and induced significantly more apoptosis in cultured and patient-derived (PD) CD34+ post-MPN sAML cells, while relatively sparing the CD34+ normal hematopoietic progenitor cells. RNA-Seq, Reverse Phase Protein Array and mass cytometry 'CyTOF' analyses demonstrated that ARV-825 caused greater perturbations in messenger RNA (mRNA) and protein expressions than OTX015 in sAML cells. Specifically, compared with OTX015, ARV-825 treatment caused more robust and sustained depletion of c-Myc, CDK4/6, JAK2, p-STAT3/5, PIM1 and Bcl-xL, while increasing the levels of p21 and p27. Compared with OTX015, PROTAC ARV-771 treatment caused greater reduction in leukemia burden and further improved survival of NSG mice engrafted with luciferase-expressing HEL92.1.7 cells. Co-treatment with ARV-825 and JAK inhibitor ruxolitinib was synergistically lethal against established and PD CD34+ sAML cells. Notably, ARV-825 induced high levels of apoptosis in the in vitro generated ruxolitinib-persister or ruxolitinib-resistant sAML cells. These findings strongly support the in vivo testing of the BRD4-PROTAC based combinations against post-MPN sAML.
Non-ribosomal peptide synthetases (NRPSs) are giant enzyme machines that activate amino acids in an assembly line fashion. As NRPSs are not restricted to the incorporation of the 20 proteinogenic ...amino acids, their efficient manipulation would enable microbial production of a diverse range of peptides; however, the structural requirements for reprogramming NRPSs to facilitate the production of new peptides are not clear. Here we describe a new fusion point inside the condensation domains of NRPSs that results in the development of the exchange unit condensation domain (XUC) concept, which enables the efficient production of peptides, even containing non-natural amino acids, in yields up to 280 mg l
. This allows the generation of more specific NRPSs, reducing the number of unwanted peptide derivatives, but also the generation of peptide libraries. The XUC might therefore be suitable for the future optimization of peptide production and the identification of bioactive peptide derivatives for pharmaceutical and other applications.
We present the first systematic analysis of the X-ray variability of Sgr A* during the Chandra X-ray Observatory's 2012 Sgr A* X-ray Visionary Project. With 38 High Energy Transmission Grating ...Spectrometer observations spaced an average of 7 days apart, this unprecedented campaign enables detailed study of the X-ray emission from this supermassive black hole at high spatial, spectral and timing resolution. In 3 Ms of observations, we detect 39 X-ray flares from Sgr A*, lasting from a few hundred seconds to approximately 8 ks, and ranging in 2-10 keV luminosity from ~10 super(34) erg s super(-1) to 2 x 10 super(35) erg s super(-1). Despite tentative evidence for a gap in the distribution of flare peak count rates, there is no evidence for X-ray color differences between faint and bright flares. Our preliminary X-ray flare luminosity distribution dN/dL is consistent with a power law with index -19 super(+0.3) sub(-0.4); this is similar to some estimates of Sgr A*'s near-IR flux distribution. The observed flares contribute one-third of the total X-ray output of Sgr A* during the campaign, and as much as 10% of the quiescent X-ray emission could be comprised of weak, undetected flares, which may also contribute high-frequency variability. We argue that flares may be the only source of X-ray emission from the inner accretion flow.
Bromodomain extraterminal protein (BETP) inhibitors transcriptionally repress oncoproteins and nuclear factor-κB (NF-κB) target genes that undermines the growth and survival of mantle cell lymphoma ...(MCL) cells. However, BET bromodomain inhibitor (BETi) treatment causes accumulation of BETPs, associated with reversible binding and incomplete inhibition of BRD4 that potentially compromises the activity of BETi in MCL cells. Unlike BETi, BET-PROTACs (proteolysis-targeting chimera) ARV-825 and ARV-771 (Arvinas, Inc.) recruit and utilize an E3-ubiquitin ligase to effectively degrade BETPs in MCL cells. BET-PROTACs induce more apoptosis than BETi of MCL cells, including those resistant to ibrutinib. BET-PROTAC treatment induced more perturbations in the mRNA and protein expressions than BETi, with depletion of c-Myc, CDK4, cyclin D1 and the NF-κB transcriptional targets Bcl-xL, XIAP and BTK, while inducing the levels of HEXIM1, NOXA and CDKN1A/p21. Treatment with ARV-771, which possesses superior pharmacological properties compared with ARV-825, inhibited the in vivo growth and induced greater survival improvement than the BETi OTX015 of immune-depleted mice engrafted with MCL cells. Cotreatment of ARV-771 with ibrutinib or the BCL2 antagonist venetoclax or CDK4/6 inhibitor palbociclib synergistically induced apoptosis of MCL cells. These studies highlight promising and superior preclinical activity of BET-PROTAC than BETi, requiring further in vivo evaluation of BET-PROTAC as a therapy for ibrutinib-sensitive or -resistant MCL.
ABSTRACT We present spectral analyses of five Nuclear Spectroscopic Telescope Array and Swift observations of GX 339-4 taken during a failed outburst during the summer of 2013. These observations ...cover Eddington luminosity fractions in the range 0.9%-6%. Throughout this outburst GX 339-4 stayed in the hard state and all five observations show similar X-ray spectra, with a hard power law with a photon index near 1.6, and significant contribution from reflection. Using simple reflection models we find unrealistically high iron abundances. Allowing for different photon indices for the continuum incident on the reflector relative to the underlying observed continuum results in a statistically better fit and reduced iron abundances. With a photon index around 1.3, the input power law on the reflector is significantly harder than that which is directly observed. We study the influence of different emissivity profiles and geometries and consistently find an improvement when using separate photon indices. The inferred inner accretion disk radius is strongly model dependent, but we do not find evidence for a truncation radius larger than in any model. The data do not allow independent spin constraints, but the results are consistent with the literature (i.e., ). Our best-fit models indicate an inclination angle in the range 40°-60°, consistent with limits on the orbital inclination but higher than reported in the literature using standard reflection models. The iron line around 6.4 keV is clearly broadened, and we detect a superimposed narrow core as well. This core originates from a fluorescent region outside the influence of the strong gravity of the black hole. Additionally, we discuss possible geometries.
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