Multimodal X-ray imaging of nanocontainer-treated macrophages and calcium distribution in the perilacunar bone matrix

Studies of biological systems typically require the application of several complementary methods able to yield statistically-relevant results at a unique level of sensitivity. Combined X-ray fluorescence and ptychography offer excellent elemental and structural imaging contrasts at the nanoscale. They enable a robust correlation of elemental distributions with respect to the cellular morphology. Here we extend the applicability of the two modalities to higher X-ray excitation energies, permitting iron mapping. Using a long-range scanning setup, we applied the method to two vital biomedical cases. We quantified the iron distributions in a population of macrophages treated with Mycobacterium-tuberculosis-targeting iron-oxide nanocontainers. Our work allowed to visualize the internalization of the nanocontainer agglomerates in the cytosol. From the iron areal mass maps, we obtained a distribution of antibiotic load per agglomerate and an average areal concentration of nanocontainers in the agglomerates. In the second application we mapped the calcium content in a human bone matrix in close proximity to osteocyte lacunae (perilacunar matrix). A concurrently acquired ptychographic image was used to remove the mass-thickness effect from the raw calcium map. The resulting ptychography-enhanced calcium distribution allowed then to observe a locally lower degree of mineralization of the perilacunar matrix

Validation of the Aura Microwave Limb Sounder HNOmeasurements

We assess the quality of the version 2.2 (v2.2) HNO3 measurements from the Microwave Limb Sounder (MLS) on the Earth Observing System Aura satellite. The MLS HNO3 product has been greatly improved over that in the previous version (v1.5), with smoother profiles, much more realistic behavior at the lowest retrieval levels, and correction of a high bias caused by an error in one of the spectroscopy files used in v1.5 processing. The v2.2 HNO3 data are scientifically useful over the range 215 to 3.2 hPa, with single-profile precision of ∼0.7 ppbv throughout. Vertical resolution is 3–4 km in the upper troposphere and lower stratosphere, degrading to ∼5 km in the middle and upper stratosphere. The impact of various sources of systematic uncertainty has been quantified through a comprehensive set of retrieval simulations. In aggregate, systematic uncertainties are estimated to induce in the v2.2 HNO3 measurements biases that vary with altitude between ±0.5 and ±2 ppbv and multiplicative errors of ±5–15% throughout the stratosphere, rising to ∼±30% at 215 hPa. Consistent with this uncertainty analysis, comparisons with correlative data sets show that relative to HNO3 measurements from ground-based, balloon-borne, and satellite instruments operating in both the infrared and microwave regions of the spectrum, MLS v2.2 HNO3 mixing ratios are uniformly low by 10–30% throughout most of the stratosphere. Comparisons with in situ measurements made from the DC-8 and WB-57 aircraft in the upper troposphere and lowermost stratosphere indicate that the MLS HNO3 values are low in this region as well, but are useful for scientific studies (with appropriate averaging)

Triggered crustal earthquake swarm across subduction segment boundary after the 2016 Pedernales, Ecuador megathrust earthquake

Megathrust ruptures and the ensuing postseismic deformation cause stress changes that may induce seismicity on upper plate crustal faults far from the coseismic rupture area. In this study, we analyze seismic swarms that occurred in the north Ecuador area of Esmeraldas, beginning two months after the 2016 M$_{w}$ 7.8 Pedernales, Ecuador megathrust earthquake. The Esmeraldas region is 70 km from the Pedernales rupture area in a separate segment of the subduction zone. We characterize the Esmeraldas sequence, relocating the events using manual arrival time picks and a local a-priori 3D velocity model. The earthquake locations from the Esmeraldas sequence outline an upper plate fault or shear zone. The sequence contains one major swarm and several smaller swarms. Moment tensor solutions of several events include normal and strike-slip motion and non-double-couple components. During the main swarm, earthquake hypocenters increase in distance from the first event over time, at a rate of a few hundred meters per day, consistent with fluid diffusion. Events with similar waveforms occur within the sequence, and a transient is seen in time series of nearby GPS stations concurrent with the seismicity. The events with similar waveforms and the transient in GPS time series suggest that slow aseismic slip took place along a crustal normal fault during the sequence. Coulomb stress calculations show a positive Coulomb stress change in the Esmeraldas region, consistent with seismicity being triggered by the Pedernales mainshock and large aftershocks. The characteristics of the seismicity indicate that postseismic deformation involving fluid flow and slow slip activated upper plate faults in the Esmeraldas area. These findings suggest the need for further investigation into the seismic hazard potential of shallow upper plate faults and the potential for megathrust earthquakes to trigger slow-slip and shallow seismicity across separate segments of subduction zones

Bodily tides near spin-orbit resonances

Spin-orbit coupling can be described in two approaches. The method known as "the MacDonald torque" is often combined with an assumption that the quality factor Q is frequency-independent. This makes the method inconsistent, because the MacDonald theory tacitly fixes the rheology by making Q scale as the inverse tidal frequency. Spin-orbit coupling can be treated also in an approach called "the Darwin torque". While this theory is general enough to accommodate an arbitrary frequency-dependence of Q, this advantage has not yet been exploited in the literature, where Q is assumed constant or is set to scale as inverse tidal frequency, the latter assertion making the Darwin torque equivalent to a corrected version of the MacDonald torque. However neither a constant nor an inverse-frequency Q reflect the properties of realistic mantles and crusts, because the actual frequency-dependence is more complex. Hence the necessity to enrich the theory of spin-orbit interaction with the right frequency-dependence. We accomplish this programme for the Darwin-torque-based model near resonances. We derive the frequency-dependence of the tidal torque from the first principles, i.e., from the expression for the mantle's compliance in the time domain. We also explain that the tidal torque includes not only the secular part, but also an oscillating part. We demonstrate that the lmpq term of the Darwin-Kaula expansion for the tidal torque smoothly goes through zero, when the secondary traverses the lmpq resonance (e.g., the principal tidal torque smoothly goes through nil as the secondary crosses the synchronous orbit). We also offer a possible explanation for the unexpected frequency-dependence of the tidal dissipation rate in the Moon, discovered by LLR

Surface-wave imaging of the weakly-extended Malawi Rift from ambient-noise and teleseismic Rayleigh waves from onshore and lake-bottom seismometers

Located at the southernmost sector of the Western Branch of the East African Rift System, the Malawi Rift exemplifies an active, magma-poor, weakly extended continental rift. To investigate the controls on rifting, we image crustal and uppermost mantle structure beneath the region using ambient-noise and teleseismic Rayleigh-wave phase velocities between 9 and 100 s period. Our study includes six lake-bottom seismometers located in Lake Malawi (Nyasa), the first time seismometers have been deployed in any of the African rift lakes. Noise-levels in the lake are lower than that of shallow oceanic environments and allow successful application of compliance corrections and instrument orientation determination. Resulting phase-velocity maps reveal slow velocities primarily confined to Lake Malawi at short periods (T 25 s) a prominent low-velocity anomaly exists beneath the Rungwe Volcanic Province at the northern terminus of the rift basin. Estimates of phase-velocity sensitivity indicates these low velocities occur within the lithospheric mantle and potentially uppermost asthenosphere, suggesting that mantle processes may control the association of volcanic centers and the localization of magmatism. Beneath the main portion of the Malawi Rift, a modest reduction in velocity is also observed at periods sensitive to the crust and upper mantle, but these velocities are much higher than those observed beneath Rungwe

Prenylation Inhibition-Induced Cell Death in Melanoma: Reduced Sensitivity in BRAF Mutant/PTEN Wild-Type Melanoma Cells.

While targeted therapy brought a new era in the treatment of BRAF mutant melanoma, therapeutic options for non-BRAF mutant cases are still limited. In order to explore the antitumor activity of prenylation inhibition we investigated the response to zoledronic acid treatment in thirteen human melanoma cell lines with known BRAF, NRAS and PTEN mutational status. Effect of zoledronic acid on proliferation, clonogenic potential, apoptosis and migration of melanoma cells as well as the activation of downstream elements of the RAS/RAF pathway were investigated in vitro with SRB, TUNEL and PARP cleavage assays and videomicroscopy and immunoblot measurements, respectively. Subcutaneous and spleen-to-liver colonization xenograft mouse models were used to evaluate the influence of zoledronic acid treatment on primary and disseminated tumor growth of melanoma cells in vivo. Zoledronic acid more efficiently decreased short-term in vitro viability in NRAS mutant cells when compared to BRAF mutant and BRAF/NRAS wild-type cells. In line with this finding, following treatment decreased activation of ribosomal protein S6 was found in NRAS mutant cells. Zoledronic acid demonstrated no significant synergism in cell viability inhibition or apoptosis induction with cisplatin or DTIC treatment in vitro. Importantly, zoledronic acid could inhibit clonogenic growth in the majority of melanoma cell lines except in the three BRAF mutant but PTEN wild-type melanoma lines. A similar pattern was observed in apoptosis induction experiments. In vivo zoledronic acid did not inhibit the subcutaneous growth or spleen-to-liver colonization of melanoma cells. Altogether our data demonstrates that prenylation inhibition may be a novel therapeutic approach in NRAS mutant melanoma. Nevertheless, we also demonstrated that therapeutic sensitivity might be influenced by the PTEN status of BRAF mutant melanoma cells. However, further investigations are needed to identify drugs that have appropriate pharmacological properties to efficiently target prenylation in melanoma cells