We have examined doxorubicin's (DOX) physical state in solution and inside EPC/cholesterol liposomes that were loaded via a transmembrane pH gradient. Using cryogenic electron microscopy (cryo-EM) we noted that DOX loaded to 200-300 mM internal concentrations in citrate containing liposomes formed linear, curved, and circular bundles of fibers with no significant interaction/perturbation of the vesicle membrane. The individual DOX fibers are putatively comprised of stacked DOX molecules. From end-on views of bundles of fibers it appeared that they are aligned longitudinally in a hexagonal array with a separation between fibers of approx. 3-3.5 nm. Two distinct small angle X-ray diffraction patterns (oblique and simple hexagonal) were observed for DOX-citrate fiber aggregates that had been concentrated from solution at either pH 4 or 5. The doxorubicin fibers were also present in citrate liposomes loaded with only one-tenth the amount of doxorubicin used above (approx. 20 mM internal DOX concentration) indicating that the threshold concentration at which these structures form is relatively low. In fact, from cryo-EM and circular dichroism spectra, we estimate that the DOX-citrate fiber bundles can account for the vast majority (>99%) of DOX loaded via a pH gradient into citrate buffered liposomes. DOX loaded into liposomes containing lactobionic acid (LBA), a monoanionic buffer to control the internal pH, remained disaggregated at internal DOX concentrations of approx. 20 mM but formed uncondensed fibers (no bundles) when the internal DOX concentration was approx. 200 mM. This finding suggests that in the citrate containing liposomes the citrate multianion electrostatically bridged adjacent fibers to form the observed bundles. 13C-NMR measurements of [1,5-13C]citrate inside liposomes suggested that citrate 'bound' to the DOX complex and 'free' citrate rapidly exchange indicating that the citrate-DOX interaction is quite dynamic. DOX release into buffer was relatively slow (<4% at 1 h) from liposomes containing DOX fibers (in citrate loaded to a low or high DOX concentration or in LBA liposomes loaded to a high internal DOX concentration). LBA containing liposomes loaded with disaggregated DOX, where the internal DOX concentration was only approx. 20 mM, experienced an osmotic stress induced vesicle rupture with as much as 18% DOX leakage in less than 10 min. The possible implications for this in vivo are discussed.

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Temperature and precipitation time series datasets from 1961 to 2005 at 65 meteorological stations were used to reveal the spatial and temporal trends of climate change in Xinjiang, China. Annual and seasonal mean air temperature and total precipitation were analyzed using Mann-Kendall (MK) test, inverse distance weighted (IDW) interpolation, and R/S methods. The results indicate that: (1) both temperature and precipitation increased in the past 45 years, but the increase in temperature is more obvious than that of precipitation;(2) for temperature increase, the higher the latitude and the higher the elevation the faster the increase, though the latitude has greater influence on the increase. Northern Xinjiang shows a faster warming than southern Xinjiang, especially in summer; (3) increase of precipitation occurs mainly in winter in northern Xinjiang and in summer in southern Xinjiang. Ili, which has the most precipitation in Xinjiang, shows a weak increase of precipitation; (4) although both temperature and precipitation increased in general, the increase is different inside Xinjiang; (5) Hurst index (H) analysis indicates that climate change will continue the current trends.

Low‐elevation land areas and their populations are at risk globally from rising sea level. Global sea level has risen by about 2 millimeters per year over the past century. About half of this rise may be attributed to thermal expansion of the ocean and the melting of temperate‐latitude glaciers [Dyurgerov and Meier, 1997]. The remainder of the rise is believed to come from a net loss of mass from the Antarctic and Greenland ice sheets, although the exact contribution is unknown.

Abstract:The feasibility of simulating daily snowmelt runoff in an arid mountain watershed with limited hydro-meteorological measurements was explored with an enhanced temperature-index snowmelt runoff model (SRM) in which the degree-day factor (DDF) is varied on the basis of shortwave solar radiation and snow albedo. The model satisfactorily simulated snowmelt runoff with a model efficiency of 0Ð64 for the calibration year and efficiency values of 0Ð78 and 0Ð51 for two validation years. Analysis indicated that the model was sensitive to lapse rate and snow albedo parameterization. The distinct seasonal variation of lapse rate played a key role for successful simulation. Snow albedo parameterization, which directly scaled snow cover percentage into snow albedo, worked quite well for the watershed although further validation is needed. Eight-day snow cover data from the Moderate Resolution Imaging Spectroradiometer (MODIS) were used to feed the model. A frequency filter, which filtered out the clouds and large fluctuation of snow cover from the MODIS snow cover data, also improved model performance. The model, however, did not simulate peak stream flows well as most of the model runs underestimated them.

Future sea level rise caused by climate change would disrupt the physical processes, economic activities, and social systems in coastal regions. Based on a hypothetical global sea level increase of one to six meters, we developed GIS methods to assess and visualize the global impacts of potential inundation using the best available global datasets. After susceptible areas were delineated, we estimated that the size of the areas is between 1.055 (one meter) to 2.193 million km 2 (six meters). Population in the susceptible areas was estimated to range from 108 (one meter) to 431 million (six meters) people. Among the seven land-cover types in the susceptible areas, forest and grassland account for more than 60 percent for all the increments of sea level rise. A suite of interactive visualization products was also developed to understand and communicate the ramifications of potential sea level rise.

Lake ice is a robust indicator of climate change. The availability of information contained in Moderate Resolution Imaging Spectroradiometer daily snow products from 2000 to 2017 could be greatly improved after cloud removal by gap filling. Thresholds based on open water pixel numbers are used to extract the freezeup start and breakup end dates for 58 lakes on the Tibetan Plateau (TP); 18 lakes are also selected to extract the freezeup end and breakup start dates. The lake ice durations are further calculated based on freezeup and breakup dates. Lakes on the TP begin to freezeup in late October and all the lakes start the ice cover period in mid‐January of the following year. In late March, some lakes begin to break up, and all the lakes end the ice cover period in early July. Generally, the lakes in the northern Inner‐TP have earlier freezeup dates and later breakup dates (i.e., longer ice cover durations) than those in the southern Inner‐TP. Over 17 years, the mean ice cover duration of 58 lakes is 157.78 days, 18 (31%) lakes have a mean extending rate of 1.11 day/year, and 40 (69%) lakes have a mean shortening rate of 0.80 day/year. Geographical location and climate conditions determine the spatial heterogeneity of the lake ice phenology, especially the ones of breakup dates, while the physico‐chemical characteristics mainly affect the freezeup dates of the lake ice in this study. Ice cover duration is affected by both climatic and lake specific physico‐chemical factors, which can reflect the climatic and environmental change for lakes on the TP.

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