A study of a space-station-associated multiple spacecraft Michelson spatial interferometer

One approach to Michelson spatial interferometry at optical wavelengths involves use of an array of spacecraft in which two widely-separated telescopes collect light from a star and direct it to a third, centrally-located, device which combines the beams in order to detect and measure interference fringes. The original version of a spacecraft array for Michelson spatial interferometry (SAMSI) was modified so that the system uses the fuel resupply capability of a space station. The combination of this fuel resupply capability with a method of obtaining image Fourier transform phase information, necessary for full image reconstruction, permits SAMSI to be used to synthesize images equivalent to those produced by huge apertures in space. Synthesis of apertures in the 100 to 500 meter range is discussed. Reconstruction can be performed to a visual magnitude of at least 8 for a 100 A passband in 9 hours. Data are simultaneously collected for image generation from 0.1 micron to 18 microns. In the one-dimensional mode, measurements can be made every 90 minutes (including acquisition and repointing time) for objects as faint as 19th magnitude in the visible

Ozone Production and Loss Rate Measurements in the Middle Stratosphere

The first simultaneous measurements of HO(x), NO(x), and Cl(x) radicals in the middle stratosphere show that NO(x) catalytic cycles dominate loss of ozone (O3) for altitudes between 24 and 38 km; Cl(x) catalytic cycles are measured to be less effective than previously expected; and there is no 'ozone deficit' in the photochemically dominated altitude range from 31 and 38 km, contrary to some previous theoretical studies

Type I interferon responses of common carp strains with different levels of resistance to koi herpesvirus disease during infection with CyHV-3 or SVCV

Carp from breeding strains with different genetic background present diverse levels of resistance to viral pathogens. Carp strains of Asian origin, currently being treated as Cyprinus rubrofuscus L., especially Amur wild carp (AS), were proven to be more resistant to koi herpesvirus disease (KHVD; caused by cyprinid herpesvirus 3, CyHV-3) than strains originating from Europe and belonging to Cyprinus carpio L., like the Prerov scale carp (PS) or koi carp from a breed in the Czech Republic. We hypothesised that it can be associated with a higher magnitude of type I interferon (IFN) response as a first line of innate defence mechanisms against viral infections. To evaluate this hypothesis, four strains of common carp (AS, Rop, PS and koi) were challenged using two viral infection models: Rhabdovirus SVCV (spring viremia of carp virus) and alloherpesvirus CyHV-3. The infection with SVCV induced a low mortality rate and the most resistant was the Rop strain (no mortalities), whereas the PS strain was the most susceptible (survival rate of 78%). During CyHV-3 infection, Rop and AS strains performed better (survival rates of 78% and 53%, respectively) than PS and koi strains (survival rates of 35% and 10%, respectively). The evaluation of virus loads and virus replication showed significant differences between the carp strains, which correlated with the mortality rate. The evaluation of type I IFN responses showed that there were fundamental differences between the virus infection models. While responses to the SVCV were high, the CyHV-3 generally induced low responses. Furthermore, the results demonstrated that the magnitude of type I IFN responses did not correlate with a higher resistance in infected carp. In the case of a CyHV-3 infection, reduced type I IFN responses could be related to the potential ability of the virus to interfere with cellular sensing of foreign nucleic acids. Taken together, the results broaden our understanding of how common carp from different genetic lines interact with various viral pathogens

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)

Activation of tumor suppressor protein PP2A inhibits KRAS-driven tumor growth

Targeted cancer therapies, which act on specific cancer-associated molecular targets, are predominantly inhibitors of oncogenic kinases. While these drugs have achieved some clinical success, the inactivation of kinase signaling via stimulation of endogenous phosphatases has received minimal attention as an alternative targeted approach. Here, we have demonstrated that activation of the tumor suppressor protein phosphatase 2A (PP2A), a negative regulator of multiple oncogenic signaling proteins, is a promising therapeutic approach for the treatment of cancers. Our group previously developed a series of orally bioavailable small molecule activators of PP2A, termed SMAPs. We now report that SMAP treatment inhibited the growth of KRAS-mutant lung cancers in mouse xenografts and transgenic models. Mechanistically, we found that SMAPs act by binding to the PP2A Aα scaffold subunit to drive conformational changes in PP2A. These results show that PP2A can be activated in cancer cells to inhibit proliferation. Our strategy of reactivating endogenous PP2A may be applicable to the treatment of other diseases and represents an advancement toward the development of small molecule activators of tumor suppressor proteins

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

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