Orally active Hsp90 inhibitors are of interest as potential chemotherapeutic agents. Recently, fully synthetic 8-benzyladenines and 8-sulfanyladenines such as 4 were disclosed as Hsp90 inhibitors, ...but these compounds are not water soluble and consequently have unacceptably low oral bioavailabilities. We now report that water-solubility can be achieved by inserting an amino functionality in the N(9) side chain. This results in compounds that are potent, soluble in aqueous media, and orally bioavailable. In an HER-2 degradation assay, the highest potency was achieved with the neopentylamine 42 (HER-2 IC50 = 90 nM). In a murine tumor xenograft model (using the gastric cancer cell line N87), the H3PO4 salts of the amines 38, 39, and 42 induced tumor growth inhibition when administered orally at 200 mg/kg/day. The amines 38, 39, and 42 are the first Hsp90 inhibitors shown to inhibit tumor growth upon oral dosage.
Rapidly involuting congenital hemangioma (RICH) is a recently recognized entity in which the vascular tumor is fully developed at birth and undergoes rapid involution. Angiographic findings in two ...infants with congenital hemangioma are reported and compared with a more common postnatal infantile hemangioma and a congenital infantile fibrosarcoma. Congenital hemangiomas differed from infantile hemangiomas angiographically by inhomogeneous parenchymal staining, large and irregular feeding arteries in disorganized patterns, arterial aneurysms, direct arteriovenous shunts, and intravascular thrombi. Both infants had clinical evidence of a high-output cardiac failure and intralesional bleeding. This congenital high-flow vascular tumor is difficult to distinguish angiographically from arteriovenous malformation and congenital infantile fibrosarcoma.
We use a 3-D chemical transport model and satellite observations to investigate Arctic ozone depletion in winter/spring 2019/20 and compare with earlier years. Persistently low temperatures caused ...extensive chlorine activation through to March. March-mean polar-cap-mean modelled chemical column ozone loss reached 78 DU (local maximum loss of ~108 DU in the vortex), similar to that in 2011. However, weak dynamical replenishment of only 59 DU from December to March was key to producing very low (<220 DU) column ozone values. The only other winter to exhibit such weak transport in the past 20 years was 2010/11, so this process is fundamental to causing such low ozone values. A model simulation with peak observed stratospheric total chlorine and bromine loading (from the mid-1990s) shows that gradual recovery of the ozone layer over the past two decades ameliorated the polar cap ozone depletion in March 2020 by ~20 DU.
An open incubation method has been used in many studies to directly estimate primary productivity and ecosystem functioning by measuring photosynthetic and respiratory rates in intertidal rockpool ...communities. The method measures changes in dissolved oxygen concentrations recorded in situ during an artificial dark period (respiration) and a natural light period (net primary productivity). Although this method has yielded interesting results, its advantages and limitations have yet to be thoroughly tested. The accuracy of the method was investigated in a controlled laboratory environment and compared with field incubations. Atmospheric oxygen diffusion across the air–water interface did not affect incubation measurements under low wind speed (<2 m s
−1). Temperature increases during incubations were not greater than in natural rockpools and did not affect primary productivity. The major problem was the oxygen supersaturation which inhibited photosynthesis, thus leading to an underestimation of primary production. To allow comparable measurements, net primary productivity needs to be recorded during the linear phase of the photosynthetic process (<30 min of light) before water reaches supersaturation (<160%). This method gives rapid and reliable estimates of primary productivity thereby allowing biodiversity and ecosystem functioning relationships to be tested using rockpools as natural mesocosms.
Tropospheric NO
2
columns derived from the data products of the Global Ozone Monitoring Experiment (GOME), deployed on the ESA ERS‐2 satellite, have been compared with model calculations from two ...global three‐dimensional chemistry transport models, IMAGES and MOZART. The main objectives of the study are an analysis of the tropospheric NO
2
data derived from satellite measurements, an interpretation of it and evaluation of its quality using global models, and an estimation the role of NO
2
in radiative forcing. The measured and modeled NO
2
columns show similar spatial and seasonal patterns, with large tropospheric column amounts over industrialized areas and small column amounts over remote areas. The comparison of the absolute values of the measured and modeled tropospheric column amounts are particularly dependent upon uncertainties in the derivation of the tropospheric NO
2
columns from GOME and the difficulty of modeling the boundary layer in global models, both of which are discussed below. The measured tropospheric column amounts derived from GOME data are of the same order as those calculated by the MOZART model over the industrialized areas of the United States and Europe, but a factor of 2–3 larger for Asia. The modeled tropospheric NO
2
columns from MOZART as well as the column amounts measured by GOME are in good agreement with NO
2
columns derived from observed NO
2
mixing ratios in the boundary layer in eastern North America. The comparison of the models to the GOME data illustrates the degree to which present models reproduce the hot spots seen in the GOME data. The radiative forcing of NO
2
has been estimated from the calculated tropospheric NO
2
columns. The local maxima in the radiative forcing of tropospheric NO
2
for cloud‐free conditions over the eastern United States and western Europe represent 0.1–0.15 W m
−2
, while values of 0.04–0.1 W m
−2
are estimated on a continental scale in these regions, of the same order of magnitude as the forcing of N
2
O and somewhat smaller than the regional forcing of tropospheric ozone. The globally averaged radiative forcing of tropospheric NO
2
is negligible, ∼0.005 W m
−2
.
Tropospheric NO2 columns derived from the data products of the Global Ozone Monitoring Experiment (GOME), deployed on the ESA ERS-2 satellite, have been compared with model calculations from two ...global 3D chemistry transport models, IMAGES and MOZART. The main objectives of the study are an analysis of the tropospheric NO2 data derived from satellite measurements, an interpretation of it and evaluation of its quality using global models, and an estimation the role of NO2 in radiative forcing. The measured and modeled NO2 columns show similar spatial and seasonal patterns, with large tropospheric column amounts over industrialized areas and small column amounts over remote areas. The comparison of the absolute values of the measured and modeled tropospheric column amounts are particularly dependent upon uncertainties in the derivation of the tropospheric NO2 columns from GOME and the difficulty of modeling the boundary layer in global models, both of which are discussed below. The measured tropospheric column amounts derived from GOME data are of the same order as those calculated by the MOZART model over the industrialized areas of the U.S. and Europe, but a factor of 2-3 larger for Asia. The modeled tropospheric NO2 columns from MOZART as well as the column amounts measured by GOME are in good agreement with NO2 columns derived from observed NO2 mixing ratios in the boundary layer in eastern North America. (Author)
On the spring 1995 cruise of the NOAA research vessel Malcolm Baldrige, we measured very large diurnal variations in ozone concentrations in the marine boundary layer. Average diurnal variations of ...about 32 percent of the mean were observed over the tropical Indian Ocean. We simulated these observations with the Model of Chemistry in Clouds and Aerosols, a photochemical box model with detailed aerosol chemistry. The model was constrained with photolysis rates, humidity, aerosol concentrations, NO, CO, and O3 specified by shipboard observations and ozonesondes. Conventional homogeneous chemistry, where ozone photolysis to O(1D) and HO(x) chemistry dominate ozone destruction, can account for a diurnal variation of only about 12 percent. On wet sea-salt aerosols (at humidities above the deliquescence point), absorption of HOBr leads to the release of BrCl and Br2, which photolyze to produce Br atoms that may provide an additional photochemical ozone sink. After eight days of simulation, these Br atoms reach a peak concentration of 1.2 x 10 exp 7/cu cm at noon and destroy ozone through a catalytic cycle involving BrO and HOBr. Reactive Br lost to HBr can be absorbed into the aerosol phase and reactivated. The model predicts a diurnal variation in O3 of 22 percent with aerosol-derived Br reaction explaining much, but not all, of the observed photochemical loss. The lifetime of ozone under these conditions is short, about two days. These results indicate that halogens play an important role in oxidation processes and the ozone budget in parts of the remote marine boundary layer. (Author)
Using the nadir-viewing Global Ozone Measuring Experiment (GOME) UV/VIS spectrometer on the ERS-2 satellite, we investigate short term variations in the vertical magnesium column densities in the ...atmosphere and any connection to possible enhanced mass deposition during a meteor shower. Time-dependent mass influx rates are derived for all the major meteor showers using published estimates of mass density and temporal profiles of meteor showers. An average daily sporadic background mass flux rate is also calculated and used as a baseline against which calculated shower mass flux rates are compared. These theoretical mass flux rates are then compared with GOME derived metal vertical column densities of Mg and Mg+ from the years 1996–2001. There is no correlation between theoretical mass flux rates and changes in the Mg and Mg+ metal column densities. A possible explanation for the lack of a shower related increase in metal concentrations may be differences in the mass regimes dominating the average background mass flux and shower mass flux.
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