Deuterium Kinetic Isotope Effects in Microsolvated Gas-Phase E2 Reactions

This work describes the first experimental studies of deuterium kinetic isotope effects (KIEs) for the gas-phase E2 reactions of microsolvated systems. The reactions of F−(H2O)n and OH−(H2O)n, where n = 0, 1, with (CH3)3CX (X = Cl, Br), as well as the deuterated analogs of the ionic and neutral reactants, were studied utilizing the flowing afterglow-selected ion flow tube technique. The E2 reactivity is found to decrease with solvation. Small, normal kinetic isotope effects are observed for the deuteration of the alkyl halide, while moderately inverse kinetic isotope effects are observed for the deuteration of the solvent. Minimal clustering of the product ions is observed, but there are intriguing differences in the nature and extent of the clustering process. Electronic structure calculations of the transition states provide qualitative insight into these microsolvated E2 reactions

Genetically predicted longer telomere length is associated with increased risk of B-cell lymphoma subtypes

Evidence from a small number of studies suggests that longer telomere length measured in peripheral leukocytes is associated with an increased risk of non-Hodgkin lymphoma (NHL). However, these studies may be biased by reverse causation, confounded by unmeasured environmental exposures and might miss time points for which prospective telomere measurement would best reveal a relationship between telomere length and NHL risk. We performed an analysis of genetically inferred telomere length and NHL risk in a study of 10 102 NHL cases of the four most common B-cell histologic types and 9562 controls using a genetic risk score (GRS) comprising nine telomere length-associated single-nucleotide polymorphisms. This approach uses existing genotype data and estimates telomere length by weighing the number of telomere length-associated variant alleles an individual carries with the published change in kb of telomere length. The analysis of the telomere length GRS resulted in an association between longer telomere length and increased NHL risk [four B-cell histologic types combined; odds ratio (OR) = 1.49, 95% CI 1.22–1.82, P-value = 8.5 × 10−5]. Subtype-specific analyses indicated that chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) was the principal NHL subtype contributing to this association (OR = 2.60, 95% CI 1.93–3.51, P-value = 4.0 × 10−10). Significant interactions were observed across strata of sex for CLL/SLL and marginal zone lymphoma subtypes as well as age for the follicular lymphoma subtype. Our results indicate that a genetic background that favors longer telomere length may increase NHL risk, particularly risk of CLL/SLL, and are consistent with earlier studies relating longer telomere length with increased NHL risk

Genome-wide association study identifies multiple susceptibility loci for diffuse large B cell lymphoma

Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma subtype and is clinically aggressive. To identify genetic susceptibility loci for DLBCL, we conducted a meta-analysis of three new genome-wide association studies (GWAS) and one prior scan, totaling 3,857 cases and 7,666 controls of European ancestry, with additional genotyping of nine promising SNPs in 1,359 cases and 4,557 controls. In our multi-stage analysis, five independent SNPs in four loci achieved genome-wide significance marked by rs116446171 at 6p25.3 (EXOC2; $P=2.33x10^{-21}$), rs2523607 at 6p21.33 (HLA-B; $2.40x10^{-10}$), rs79480871 at 2p23.3 (NCOA1; $P=4.23x10^{-8}$), and two independent SNPs, rs13255292 and rs4733601, at 8q24.21 (PVT1; $P=9.98x10^{-13}$ and $P=3.63x10^{-11}$, respectively). These data provide substantial new evidence for genetic susceptibility to this B-cell malignancy, and point towards pathways involved in immune recognition and immune function in the pathogenesis of DLBCL

High-Pressure Rate Rules for Alkyl + O₂ Reactions. 1. The Dissociation, Concerted Elimination, and Isomerization Channels of the Alkyl Peroxy Radical

The reactions of alkyl peroxy radicals (RO₂) play a central role in the low-temperature oxidation of hydrocarbons. In this work, we present high-pressure rate estimation rules for the dissociation, concerted elimination, and isomerization reactions of RO₂. These rate rules are derived from a systematic investigation of sets of reactions within a given reaction class using electronic structure calculations performed at the CBS-QB3 level of theory. The rate constants for the dissociation reactions are obtained from calculated equilibrium constants and a literature review of experimental rate constants for the reverse association reactions. For the concerted elimination and isomerization channels, rate constants are calculated using canonical transition state theory. To determine if the high-pressure rate expressions from this work can directly be used in ignition models, we use the QRRK/MSC method to calculate apparent pressure and temperature dependent rate constants for representative reactions of small, medium, and large alkyl radicals with O₂. A comparison of concentration versus time profiles obtained using either the pressure dependent rate constants or the corresponding high-pressure values reveals that under most conditions relevant to combustion/ignition problems, the high-pressure rate rules can be used directly to describe the reactions of RO₂

High-Pressure Rate Rules for Alkyl + O₂ Reactions. 2. The Isomerization, Cyclic Ether Formation, and β-Scission Reactions of Hydroperoxy Alkyl Radicals

The unimolecular reactions of hydroperoxy alkyl radicals (QOOH) play a central role in the low-temperature oxidation of hydrocarbons as they compete with the addition of a second O₂ molecule, which is known to provide chain-branching. In this work we present high-pressure rate estimation rules for the most important unimolecular reactions of the β-, γ-, and δ-QOOH radicals: isomerization to RO₂, cyclic ether formation, and selected β-scission reactions. These rate rules are derived from high-pressure rate constants for a series of reactions of a given reaction class. The individual rate expressions are determined from CBS-QB3 electronic structure calculations combined with canonical transition state theory calculations. Next we use the rate rules, along with previously published rate estimation rules for the reactions of alkyl peroxy radicals (RO₂), to investigate the potential impact of falloff effects in combustion/ignition kinetic modeling. Pressure effects are examined for the reaction of <i>n</i>-butyl radical with O₂ by comparison of concentration versus time profiles that were obtained using two mechanisms at 10 atm: one that contains pressure-dependent rate constants that are obtained from a QRRK/MSC analysis and another that only contains high-pressure rate expressions. These simulations reveal that under most conditions relevant to combustion/ignition problems, the high-pressure rate rules can be used directly to describe the reactions of RO₂ and QOOH. For the same conditions, we also address whether the various isomers equilibrate during reaction. These results indicate that equilibrium is established between the alkyl, RO₂, and γ- and δ-QOOH radicals