High resolution imaging at large telescopes

Image recovery at a resolution limited only by diffraction is now possible at large telescopes. The theory of speckle image reconstruction is explained and the current status of a video recording and digitization system for the reconstruction procedure is described. Potential applications of the process when used with very large telescopes are discussed. The constraints on telescope design imposed by these techniques are listed

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

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)

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

The history and evolution of the clinical effectiveness of haemophilia type a treatment: a systematic review.

First evidence of cases of haemophilia dates from ancient Egypt, but it was when Queen Victoria from England in the 19th century transmitted this illness to her descendants, when it became known as the "royal disease". Last decades of the 20th century account for major discoveries that improved the life expectancy and quality of life of these patients. The history and evolution of haemophilia healthcare counts ups and downs. The introduction of prophylactic schemes during the 1970s have proved to be more effective that the classic on-demand replacement of clotting factors, nevertheless many patients managed with frequent plasma transfusions or derived products became infected with the Human Immunodeficiency Virus (HIV) and Hepatitis C virus during the 1980s and 1990s. Recombinant factor VIII inception has decreased the risk of blood borne infections and restored back longer life expectancies. Main concerns for haemophilia healthcare are shifting from the pure clinical aspects to the economic considerations of long-term replacement therapy. Nowadays researchers' attention has been placed on the future costs and cost-effectiveness of costly long-term treatment. Equity considerations are relevant as well, and alternative options for less affluent countries are under the scope of further research. The aim of this review was to assess the evidence of different treatment options for haemophilia type A over the past four decades, focusing on the most important technological advances that have influenced the natural course of this "royal disease"

Greenland tidewater glacier advanced rapidly during era of Norse settlement

Our ability to improve prognostic modeling of the Greenland Ice Sheet relies on understanding the long-term relationships between climate and mass flux (via iceberg calving) from marine-terminating tidewater glaciers (TWGs). Observations of recent TWG behavior are widely available, but long-term records of TWG advance are currently lacking. We present glacial geomorphological, sedimentological, archaeological, and modeling data to reconstruct the ~20 km advance of Kangiata Nunaata Sermia (KNS; the largest tidewater glacier in southwest Greenland) during the first half of the past millennium. The data show that KNS advanced ~15 km during the 12th and 13th centuries CE at a rate of ~115 m a–1, contemporaneous with regional climate cooling toward the Little Ice Age and comparable to rates of TWG retreat witnessed over the past ~200 years. Presence of Norse farmsteads proximal to KNS demonstrates their resilience to climate change, manifest as a rapidly advancing TWG in a cooling climate. The results place limits on the magnitude of ice-margin advance and demonstrate TWG sensitivity to climate cooling as well as warming. These data combined with our grounding-line stability analysis provide a long-term record that validates approaches to numerical modeling aiming to link calving to climate

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

Mantle-driven dynamic uplift of the Rocky Mountains and Colorado Plateau and its surface response: Toward a unified hypothesis

The correspondence between seismic velocity anomalies in the crust and mantle and the differential incision of the continental-scale Colorado River system suggests that significant mantle-to-surface interactions can take place deep within continental interiors. The Colorado Rocky Mountain region exhibits low-seismic-velocity crust and mantle associated with atypically high (and rough) topography, steep normalized river segments, and areas of greatest differential river incision. Thermochronologic and geologic data show that regional exhumation accelerated starting ca. 6-10 Ma, especially in regions underlain by low-velocity mantle. Integration and synthesis of diverse geologic and geophysical data sets support the provocative hypothesis that Neogene mantle convection has driven long-wavelength surface deformation and tilting over the past 10 Ma. Attendant surface uplift on the order of 500-1000 m may account for ~25%-50% of the current elevation of the region, with the rest achieved during Laramide and mid-Tertiary uplift episodes. This hypothesis highlights the importance of continued multidisciplinary tests of the nature and magnitude of surface responses to mantle dynamics in intraplate settings