Binary Targeting of siRNA to Hematologic Cancer Cells In Vivo Using Layer‐by‐Layer Nanoparticles

Using siRNA therapeutics to treat hematologic malignancies has been unsuccessful because blood cancer cells exhibit remarkable resistance to standard transfection methods. Herein, the successful delivery of siRNA therapeutics with a dual‐targeted, layer‐by‐layer nanoparticle (LbL‐NP) is reported. The LbL‐NP protects siRNA from nucleases in the bloodstream by embedding it within polyelectrolyte layers that coat a polymeric core. The outermost layer consists of hyaluronic acid (a CD44‐ligand) covalently conjugated to CD20 antibodies. The CD20/CD44 dual‐targeting outer layer provides precise binding to blood cancer cells, followed by receptor‐mediated endocytosis of the LbL‐NP. This siRNA delivery platform is used to silence B‐cell lymphoma 2 (BCL‐2), a pro‐survival protein, in vitro and in vivo. The dual‐targeting approach significantly enhances internalization of BCL‐2 siRNA in lymphoma and leukemia cells, which leads to significant downregulation of BCL‐2 expression. Systemic administration of the dual‐targeted, siRNA‐loaded nanoparticle induces apoptosis and hampers proliferation of blood cancer cells, both in cell culture and in orthotopic non‐Hodgkin's lymphoma animal models. These results provide the basis for approaches to targeting blood‐borne cancers and other diseases and suggest that LbL nanoassemblies are a promising approach for delivering therapeutic siRNA to hematopoetic cell types that are known to evade transfection by other means.     

Declining phosphorus as a potential driver for the onset of Didymosphenia geminata mats in North American rivers

Didymosphenia geminata is a stalk‐forming diatom capable of creating thick benthic mats in low‐nutrient streams. There are two hypotheses to explain the rapid worldwide increase in occurrence of nuisance D. geminata mats: (a) Cells are spread among rivers and across broad ecoregions through natural and anthropogenic vectors, or (2) pre‐existing D. geminata populations are forming mats in response to changing environmental conditions within the habitat. Low phosphorus (P) concentrations are a major trigger for stalk production by D. geminata cells. Although the environmental change hypothesis is gaining support among researchers, long‐term data sets demonstrating declining P concentrations prior to reported mat formation have been essentially absent from the literature. Here, we present long‐term datasets for two case studies for which long‐term P and D. geminata data coincide: the Matapedia River in Eastern Canada and the Kootenai River below Libby Dam in Montana, United States. Both rivers had declining P levels over time. However, there was a 2‐ and 20‐year lag time, respectively, between mat development and reaching the previously proposed average 2 μg/L soluble reactive P threshold for development. Although the Matapedia River provides some support of the environmental change hypothesis, the Kootenai River data set suggests other environmental factors may play a role in mat development. The data presented do not rule out the environmental change hypothesis but do suggest there may be conditions in addition to low P that must be met for mats to form and the environmental change hypothesis can likely be refined to include more parameters to better understand and mitigate the influence of mats.     

The influence of automation on tumor contouring

Fully or semi-automatic contouring tools are increasingly being used in the tumor contouring task for radiotherapy. While the fully automatic contouring tools have not reached sufficient efficiency, the semi-automatic contouring tools balance more effectively between the human interaction and automation. This study evaluates the influences of a semi-automation contouring tool, called between-slice interpolation, on the resulting contours and the contouring process. The tumor contouring study was conducted on three patient cases with five physicians in a naturalistic setting. The contouring task consisted of initiating the 2D contour manually or with the interpolation tool and correcting that initial contour. The similarity of the resulting contours was pairwise measured within the manual or the interpolated category. Interactions with the software were recorded, and variations in the contouring workflows steps were compared. Results indicated that using the between-slice interpolation tool for creating the initial contour, instead of initiating it manually, influenced both the contouring process and outcomes. First, it was identified that contours initiated by the interpolation tool showed an increased similarity among themselves compared to the manually initiated contours. At the same time, influences to the resulting contours were below clinical relevance, and toward the desired direction—improved consistency of contours. Second, when interpolation was used, in two cases out of three, the average contouring time also decreased significantly. Therefore, the use of such an automation tool can be encouraged.     

Tourism leads to wealth but increased vulnerability: a double-edged sword in Lijiang,South-West China

Tourism development in Lijiang, China, has helped lift many people out of poverty but has also led to increased pollution and water scarcity, which climate change is predicted to exacerbate. A shift towards tourism and cash crops has reduced the diversity of crops and livestock used by agrarian households. These effects are explored in two villages between 2008 and 2013 using a multi-method approach. It is found that local water governance does not follow any of the best practice principles outlined in the international literature. Improved water governance is urgently needed to reduce household vulnerability in the Lijiang area.     

Oil Quality Improvement in Soybeans-Glycine max (L.) Merr.

Plant breeding was used to reduce the linolenic acid content of soybean oil and improve oil stability. By crossing strains with the lowest linolenic acid content available, it was possible to produce offspring with amounts of linolenic acid 1 to 1.5% lower than the best parental strain. The selection of desirable strains was greatly accelerated by growing plants in Puerto Rico during the winter. Mutagenic agents (X-rays and ethyl methylsulfonate) were used in an attempt to introduce more variability for fatty acid composition into the population. Seed source has a small effect on the amount of linolenic acid produced in the next generation of seeds. A late planting date significantly increased the amount of linolenic and stearic acid in soybeans. There was a significant negative correlation between linolenic acid and both oleic and stearic acid.     

Fatty acid development in a soybean mutant with high stearic acid

The fatty acid composition of developing soybean (Glycine max [L.] Merrill) seeds was evaluated in the mutant line, A6, and its parent, FA8077. Seeds of both lines were harvested at 2-day intervals from 15 to 39 days after flowering (DAF) and at 4-day intervals from 39 DAF until maturity. Significant differences between the two lines were observed for stearic and oleic acid percentages at 19 DAF. The maximum difference between the lines was at 25 DAF, when A6 had 45.4% and FA8077 had 4.1% stearic acid. The increase in stearic acid percentage in A6 was accompanied by a decrease in oleic acid to 16.8% at 25 DAF, compared with 53.7% oleic acid for FA8077. The two lines did not differ in development of palmitic, linoleic and linolenic acids. The protein and oil content of mature seeds were similar for the two lines.     

Gas Discharge Lamps for Electrophotographic Exposure

The multitude of uses for lamps in the various steps of the xerographic process are enumerated. Particular emphasis is placed on the use of gas-discharge lamps for exposure, with their requirement of spectral control and adequate radiant power. The characteristics of various types of lamps are considered and the existence of a trouble-some ``power gap' is uncovered. The efficient performance of low-pressure arcs (such as fluorescent and low-pressure sodium lamps) is limited to low powers by electron de-excitation in the presence of self-absorption. On the other hand, high-pressure arc lamps perform efficiently at high powers, but it is difficult to operate these lamps at lower powers in the ``power gap' because of a complex set of interrelated reasons. Lamp designs which may fill this power gap are discussed. The radiant emission from various lamps is considered as well as techniques for manipulating the spectra, particularly the use of metallic halide additives. Overall, a major problem is that commercially available lamps reservice are designed for general illumination purposes while the electrophotographic requirements are different and more demanding.     

Specificity of lipase from several seeds andLeptospira pomona

The specificities of lipase preparation from oats,Leptospira pomona DM₂H, corn, soybeans, safflower seed and pinion nuts were examined by using cocoa butter, lard and corn oil as substrates. Oat lipase exhibited an acyl group specificity, favoring the hydrolysis of linoleyl groups and discriminating against stearoyl groups. TheL. pomona lipase exhibited a tendency to hydrolyze acyl groups on the 1 and 3 positions of glycerol preferentially. The hydrolysis by the other seed lipases was nonspecific. Journal Paper No. J-6316 of the Iowa Agriculture and Home Economics Experiment Station, Ames, Iowa, Project 1517.     

Polarity measurements in block copolymers (polyurethaneimides) and correlation with their pervaporation features

EtOH/ETBE azeotropic mixture was separated by pervaporation through films of polyurethaneimides (PUI), i. e., alternating block copolymers varying in their structure only by their oligomeric soft blocks. Pervaporation performances strongly depend on the flexible segments: fluxes on the molecular weight and selectivity towards ethanol on the chemical structure in the decreasing order: PEG, PCL, PCD, PTMG, PPG. In order to correlate selectivity with segment polarity, a new solvatochromic polarity probe that was well soluble in PUI was synthesized. Using 13 solvents covering a wide polarity range, Vis λ^max of the photochromic indicator open form was linearly correlated with the E_T(30) polarity scale. By illumination of the dissolved dye, PUI polarity was investigated in relation to soft segment nature and size. The very high PUI polarity values and their splitting for highest size segments were assigned to preferential probe solvation by interblock urethane junctions combined with phase segregation. Polarity values consistent with the chemical structure of the flexible segments were provided by similar measurements on suitably end-capped precursors of these segments and were then linearly correlated with the related PUI pervaporation selectivity. © 1995 John Wiley & Sons, Inc.     

Effects of Atmospheric Chemical and Climate Change on Tropospheric Ozone

Changes in atmospheric levels of certain pollutants (CH₄, CO, NO_X, nonmethane hydrocarbons) have the potential to affect tropospheric O₃ formation and the abundance of the free radical OH on a global scale. Perturbations to stratospheric O₃ and climate (temperature and moisture) also can influence tropospheric O3 and OH. We have used a tropospheric photochemical model with projections of CO, NO_X, and CH₄ to predict tropospheric ozone and OH changes from 1980-2030. The calculations simulate the background chemistry of various global regions and assume that increases in CH₄ and CO will continue at current rates. Predicted changes in tropospheric O₃ and OH are different in urban and nonurban areas, and in marine and continental regions.

Generally, increasing levels of CH₄ and CO at constant NO_X levels will increase O₃ and suppress OH. A rough estimate of possible global changes shows tropospheric O3 increasing ?10% from 1980 to 2030 and OH decreasing ?10% during that period. When calculations are performed assuming that stratospheric ozone depletion and climate warming occur at anticipated rates during the same period, tropospheric O₃ enhancement and OH loss in nonurban areas are both reduced relative to changes assuming that only CH₄ and CO emissions change.

Regional changes in surface-level O₃, OH and the water-soluble oxidant H₂O₂ are estimated for the year 2030. Increases in CO and CH₄ suppress OH and enhance O₃ and H₂O₂ in nonpolluted (low NO_X) areas. In urban environments (background NO_X > 1 ppbv), increases in CO and CH₄ add significantly to all three oxidants, O₃, OH and H₂O₂. Changes in and near urban areas may be of greatest magnitude, but the high levels of OH (and H₂O₂) found in the tropics indicate that perturbations in that region could dominate future global oxidant changes.