Increased CXCL10 (IP-10) is associated with advanced myeloproliferative neoplasms and its loss dampens erythrocytosis in mouse models.

Key studies in pre-leukemic disorders have linked increases in pro-inflammatory cytokines with accelerated phases of the disease, but the precise role of the cellular microenvironment in disease initiation and evolution remains poorly understood. In myeloproliferative neoplasms (MPNs), higher levels of specific cytokines have been previously correlated with increased disease severity (tumor necrosis factor-alpha [TNF-α], interferon gamma-induced protein-10 [IP-10 or CXCL10]) and decreased survival (interleukin 8 [IL-8]). Whereas TNF-α and IL-8 have been studied by numerous groups, there is a relative paucity of studies on IP-10 (CXCL10). Here we explore the relationship of IP-10 levels with detailed genomic and clinical data and undertake a complementary cytokine screen alongside functional assays in a wide range of MPN mouse models. Similar to patients, levels of IP-10 were increased in mice with more severe disease phenotypes (e.g., JAK2V617F/V617F TET2-/- double-mutant mice) compared with those with less severe phenotypes (e.g., CALRdel52 or JAK2+/V617F mice) and wild-type (WT) littermate controls. Although exposure to IP-10 did not directly alter proliferation or survival in single hematopoietic stem cells (HSCs) in vitro, IP-10-/- mice transplanted with disease-initiating HSCs developed an MPN phenotype more slowly, suggesting that the effect of IP-10 loss was noncell-autonomous. To explore the broader effects of IP-10 loss, we crossed IP-10-/- mice into a series of MPN mouse models and showed that its loss reduces the erythrocytosis observed in mice with the most severe phenotype. Together, these data point to a potential role for blocking IP-10 activity in the management of MPNs.

Persistent nucleation and size dependent attachment kinetics produce monodisperse PbS nanocrystals.

Modern syntheses of colloidal nanocrystals yield extraordinarily narrow size distributions that are believed to result from a rapid "burst of nucleation" (La Mer, JACS, 1950, 72(11), 4847-4854) followed by diffusion limited growth and size distribution focusing (Reiss, J. Chem. Phys., 1951, 19, 482). Using a combination of in situ X-ray scattering, optical absorption, and 13C nuclear magnetic resonance (NMR) spectroscopy, we monitor the kinetics of PbS solute generation, nucleation, and crystal growth from three thiourea precursors whose conversion reactivity spans a 2-fold range. In all three cases, nucleation is found to be slow and continues during >50% of the precipitation. A population balance model based on a size dependent growth law (1/r) fits the data with a single growth rate constant (k G) across all three precursors. However, the magnitude of the k G and the lack of solvent viscosity dependence indicates that the rate limiting step is not diffusion from solution to the nanoparticle surface. Several surface reaction limited mechanisms and a ligand penetration model that fits data our experiments using a single fit parameter are proposed to explain the results.

Growth kinetics determine the polydispersity and size of PbS and PbSe nanocrystals.

A library of thio- and selenourea derivatives is used to adjust the kinetics of PbE (E = S, Se) nanocrystal formation across a 1000-fold range (k r = 10-1 to 10-4 s-1), at several temperatures (80-120 °C), under a standard set of conditions (Pb : E = 1.2 : 1, [Pb(oleate)2] = 10.8 mM, [chalcogenourea] = 9.0 mM). An induction delay (t ind) is observed prior to the onset of nanocrystal absorption during which PbE solute is observed using in situ X-ray total scattering. Density functional theory models fit to the X-ray pair distribution function (PDF) support a Pb2(µ2-S)2(Pb(O2CR)2)2 structure. Absorption spectra of aliquots reveal a continuous increase in the number of nanocrystals over more than half of the total reaction time at low temperatures. A strong correlation between the width of the nucleation phase and reaction temperature is observed that does not correlate with the polydispersity. These findings are antithetical to the critical concentration dependence of nucleation that underpins the La Mer hypothesis and demonstrates that the duration of the nucleation period has a minor influence on the size distribution. The results can be explained by growth kinetics that are size dependent, more rapid at high temperature, and self limiting at low temperatures.

Au/TiO2-Catalyzed Benzyl Alcohol Oxidation on Morphologically Precise Anatase Nanoparticles.

Au nanoparticles (NP) on TiO2 have been shown to be effective catalysts for selective oxidation reactions by using molecular oxygen. In this work, we have studied the influence of support morphology on the catalytic activity of Au/TiO2 catalysts. Two TiO2 anatase supports, a nanoplatelet-shaped material with predominantly the {001} facet exposed and a truncated bipyramidal-shaped nanoparticle with predominantly the {101} facet exposed, were prepared by using a nonaqueous solvothermal method and characterized by using DRIFTS, XPS, and TEM. Au nanoparticles were deposited on the supports by using the deposition-precipitation method, and particle sizes were determined by using STEM. Au nanoparticles were smaller on the support with the majority of the {101} facet exposed. The resulting materials were used to catalyze the aerobic oxidation of benzyl alcohol and trifluoromethylbenzyl alcohol. Support morphology impacts the catalytic activity of Au/TiO2; reaction rates for reactions catalyzed by the predominantly {101} material were higher. Much of the increased reactivity can be explained by the presence of smaller Au particles on the predominantly {101} material, providing more Au/TiO2 interface area, which is where catalysis occurs. The remaining modest differences between the two catalysts are likely due to geometric effects as Hammett slopes show no evidence for electronic differences between the Au particles on the different materials.

The Trouble with ODE: Polymerization during Nanocrystal Synthesis.

1-Octadecene is a widely used solvent for high-temperature nanocrystal synthesis (120-320 °C). Here, we show that 1-octadecene spontaneously polymerizes under these conditions, and the resulting poly(1-octadecene) has a comparable solubility and size to nanocrystals stabilized by hydrophobic ligands. Typical purification procedures (precipitation/redispersion cycles or size exclusion chromatography) fail to separate the poly(1-octadecene) impurity from the nanocrystal product. To avoid formation of poly(1-octadecene), we replace 1-octadecene with saturated, aliphatic solvents. Alternatively, the nanocrystals' native ligands are exchanged for polar ligands, leading to significant solubility differences between nanocrystals and poly(1-octadecene), therefore allowing isolation of pure nanocrystals, free from polymer impurities. These results will help design superior syntheses and improve nanocrystal purity, an important factor in many applications.