The FLT3/FLK2 receptor tyrosine kinase is closely related to two receptors, c-Kit and c-Fms, which function with their respective ligands, Kit ligand and macrophage colony-stimulating factor to control differentiation of haematopoietic and non-haematopoietic cells. FLT3/FLK2 is thought to be present on haematopoietic stem cells and found in brain, placenta and testis. We have purified to homogeneity and partially sequenced a soluble form of the FLT3/FLK2 ligand produced by mouse thymic stromal cells. We isolated several mouse and human complementary DNAs that encode polypeptides with identical N termini and different C termini. Some variants contain hydrophobic transmembrane segments, suggesting that processing may be required to release soluble ligand. The purified ligand enhances the response of mouse stem cells and a primitive human progenitor cell population to other growth factors such as interleukins IL-3 and IL-6 and to granulocyte-macrophage colony-stimulating factor, and also stimulates fetal thymocytes.
Progress toward the sanitation component of Millennium Development Goal (MDG) Target 7c was reassessed to account for the need to protect communities and the wider population from exposure to human excreta. We classified connections to sewerage as "improved sanitation" only if the sewage was treated before discharge to the environment. Sewerage connection data was available for 167 countries in 2010; of these, 77 had published data on sewage treatment prevalence. We developed an empirical model to estimate sewage treatment prevalence for 47 additional countries. We estimate that in 2010, 40% of the global population (2.8 billion people) used improved sanitation, as opposed to the estimate of 62% (4.3 billion people) from the WHO/UNICEF Joint Monitoring Programme (JMP), and that 4.1 billion people lacked access to an improved sanitation facility. Redefining sewerage-without-treatment as "unimproved sanitation" in MDG monitoring would raise the 1990 baseline population using unimproved sanitation from 53% to 64% and the corresponding 2015 target from 27% to 32%. At the current rate of progress, we estimate a shortfall of 28 percentage points (1.9 billion people) in 2010 and a projected 27 percentage point shortfall in 2015.
A cDNA sequence coding for a human granulocyte-macrophage colony-stimulating factor has been isolated from cDNA libraries prepared from mRNA derived from concanavalin A-activated human T-cell clones. The libraries constructed in the pcD vector system were screened by transfecting COS-7 monkey cells with DNA pools to express the products encoded by full-length cDNA inserts. By assaying the cell supernatants, we identified clones encoding a factor that stimulates the formation of granulocyte and macrophage colonies from human progenitor cells. These results demonstrate that identification of full-length cDNAs for many colonystimulating factors may be achieved entirely on the basis of detecting the functional polypeptide produced in mammalian cells.
Batch experiments were performed to study the kinetics of bromochloramine formation and decomposition from the reaction of monochloramine and bromide ion. The effects of pH, initial monochloramine and bromide ion concentrations, phosphate buffer concentration, and excess ammonia were evaluated. Results showed that the monochloramine decay rate increased with decreasing pH and increasing bromide ion concentration, and the concentration of bromochloramine increased to a maximum before decreasing gradually. The maximum bromochloramine concentration reached was found to decrease with increasing phosphate and ammonia concentrations. Previous models in the literature were not able to capture the decay of bromochloramine, and therefore we proposed an extended model consisting of reactions for monochloramine autodecomposition, the decay of bromamines in the presence of bromide, bromochloramine formation, and bromochloramine decomposition. Reaction rate constants were obtained through least-squares fitting to 11 data sets representing the effect of pH, bromide, monochloramine, phosphate, and excess ammonia. The reaction rate constants were then used to predict monochloramine and bromochloramine concentration profiles for all experimental conditions tested. In general, the modeled lines were found to provide good agreement with the experimental data under most conditions tested, with deviations occurring at low pH and high bromide concentrations.
We studied the volume-averaged chlorine (Cl) uptake into the bulk region of the aromatic polyamide active layer of a reverse osmosis membrane upon exposure to free chlorine. Volume-averaged measurements were obtained using Rutherford backscattering spectrometry with samples prepared at a range of free chlorine concentrations, exposure times, and mixing, rinsing, and pH conditions. Our volume-averaged measurements complement previous studies that have quantified Cl uptake at the active layer surface (top ≈ 7 nm) and advance the mechanistic understanding of Cl uptake by aromatic polyamide active layers. Our results show that surface Cl uptake is representative of and underestimates volume-averaged Cl uptake under acidic conditions and alkaline conditions, respectively. Our results also support that (i) under acidic conditions, N-chlorination followed by Orton rearrangement is the dominant Cl uptake mechanism with N-chlorination as the rate-limiting step; (ii) under alkaline conditions, N-chlorination and dechlorination of N-chlorinated amide links by hydroxyl ion are the two dominant processes; and (iii) under neutral pH conditions, the rates of N-chlorination and Orton rearrangement are comparable. We propose a kinetic model that satisfactorily describes Cl uptake under acidic and alkaline conditions, with the largest discrepancies between model and experiment occurring under alkaline conditions at relatively high chlorine exposures.
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