Chemistry of 4-alkylaryloxenium ion "precursors": Sound and fury signifying something?

Quinol esters '2b', '2c', and '3b' and sulfonamide '4c' were investigated as possible precursors to 4-alkylaryloxenium ions, reactive intermediates that have not been previously detected. These compounds exhibit a variety of interesting reactions, but with one possible exception, they do not generate oxenium ions. The 4-isopropyl ester '2b' predominantly undergoes ordinary acid- and base-catalyzed ester hydrolysis. The 4-tert-butyl ester '2c' decomposes under both acidic and neutral conditions to generate tert-butanol and 1-acetyl-1,4-hydroquinone, '8', apparently by an S(N)1 mechanism. This is also a minor decomposition pathway for '2b', but the mechanism in that case is not likely to be S(N)1. Decomposition of '2c' in the presence of N₃⁻ leads to formation of the explosive 2,3,5,6-tetraazido-1,4-benzoquinone, '14', produced by N₃⁻-induced hydrolysis of '8', followed by a series of oxidations and nucleophilic additions by N₃⁻. No products suggestive of N₃⁻-trapping of an oxenium ion were detected. The 4-isopropyl dichloroacetic acid ester '3b' reacts with N₃⁻ to generate the two adducts 2-azido-4-isopropylphenol, '5b', and 3-azido- 4-isopropylphenol, '11b'. Although '5b' is the expected product of N₃⁻ trapping of the oxenium ion, kinetic analysis shows that it is produced by a kinetically bimolecular reaction of N₃⁻ with '3b'. No oxenium ion is involved. The sulfonamide '4c' predominantly undergoes a rearrangement reaction under acidic and neutral conditions, but a minor component of the reaction yields 4-tert-butylcresol, '17', and 2-azido-4- tert-butylphenol, '5c', in the presence of N₃⁻. These products may indicate that '4c' generates the oxenium ion '1c', but they are generated in very low yields (ca. 10%) so it is not possible to definitively conclude that '1c' has been produced. If '1c' has been generated, the N₃⁻-trapping data indicate that it is a very short-lived and reactive species in H₂O. Comparisons with similarly reactive nitrenium ions indicate that the lifetime of '1c' is ca. 20-200 ps if it is generated, so it must react by a preassociation process. Density functional theory calculations at the B3LYP/6-31G*//HF/6-31G* level coupled with kinetic correlations also indicate that the aqueous solution lifetimes of '1a-c' are in the picosecond range

The systemic inflammatory response to Clostridium difficile infection.

The systemic inflammatory response to Clostridium difficile infection (CDI) is incompletely defined, particularly for patients with severe disease.Analysis of 315 blood samples from 78 inpatients with CDI (cases), 100 inpatients with diarrhea without CDI (inpatient controls), and 137 asymptomatic outpatient controls without CDI was performed. Serum or plasma was obtained from subjects at the time of CDI testing or shortly thereafter. Severe cases had intensive care unit admission, colectomy, or death due to CDI within 30 days after diagnosis. Thirty different circulating inflammatory mediators were quantified using an antibody-linked bead array. Principal component analysis (PCA), multivariate analysis of variance (MANOVA), and logistic regression were used for analysis.Based on MANOVA, cases had a significantly different inflammatory profile from outpatient controls but not from inpatient controls. In logistic regression, only chemokine (C-C motif) ligand 5 (CCL5) levels were associated with cases vs. inpatient controls. Several mediators were associated with cases vs. outpatient controls, especially hepatocyte growth factor, CCL5, and epithelial growth factor (inversely associated). Eight cases were severe and associated with elevations in IL-8, IL-6, and eotaxin.A broad systemic inflammatory response occurs during CDI and severe cases appear to differ from non-severe infections

Climate change decreases the cooling effect from postfire albedo in boreal North America

Fire is a primary disturbance in boreal forests and generates both positive and negative climate forcings. The influence of fire on surface albedo is a predominantly negative forcing in boreal forests, and one of the strongest overall, due to increased snow exposure in the winter and spring months. Albedo forcings are spatially and temporally heterogeneous and depend on a variety of factors related to soils, topography, climate, land cover/vegetation type, successional dynamics, time since fire, season, and fire severity. However, how these variables interact to influence albedo is not well understood, and quantifying these relationships and predicting postfire albedo becomes increasingly important as the climate changes and management frameworks evolve to consider climate impacts. Here we developed a MODIS-derived ‘blue sky’ albedo product and a novel machine learning modeling framework to predict fire-driven changes in albedo under historical and future climate scenarios across boreal North America. Converted to radiative forcing (RF), we estimated that fires generate an annual mean cooling of −1.77 ± 1.35 W/m 2 from albedo under historical climate conditions (1971–2000) integrated over 70 years postfire. Increasing postfire albedo along a south–north climatic gradient was offset by a nearly opposite gradient in solar insolation, such that large-scale spatial patterns in RF were minimal. Our models suggest that climate change will lead to decreases in mean annual postfire albedo, and hence a decreasing strength of the negative RF, a trend dominated by decreased snow cover in spring months. Considering the range of future climate scenarios and model uncertainties, we estimate that for fires burning in the current era (2016) the cooling effect from long-term postfire albedo will be reduced by 15%–28% due to climate change

Global systemic inflammatory responses in <i>C. difficile</i> infection (CDI) cases and inpatient controls.

<p>Principal component analysis (PCA) (panel A) results are shown for CDI cases and inpatient controls. The individual inflammatory mediators’ effects on the PCA were plotted as biplots (panel B). In biplots the arrows indicate the direction of maximum change while the length of arrows represents the magnitude of the change. The PCA centroids were not significantly different by permutational MANOVA testing (<i>P</i> = .051).</p

Thirty inflammatory mediators (cytokines, chemokines, and growth factors) measured in the circulation of study subjects.

<p>Thirty inflammatory mediators (cytokines, chemokines, and growth factors) measured in the circulation of study subjects.</p

Simple logistic regression results for serum inflammatory mediators (cytokines, chemokines, and growth factors) in patients with <i>Clostridium difficile</i> infection (CDI) vs. matched inpatient controls who tested negative for CDI and asymptomatic outpatient controls (all units in log^­₁₀ pg/mL).

1<p>Versus patients with CDI.</p

Global systemic inflammatory responses in <i>C. difficile</i> infection (CDI) cases and outpatient controls.

<p>Principal component analysis (PCA) (panel A) results are shown for CDI cases and outpatient controls. The individual inflammatory mediators’ effects on the PCA were plotted as biplots (panel B). In biplots the arrows indicate the direction of maximum change while the length of arrows represents the magnitude of the change. The PCA centroids were different by permutational MANOVA testing (<i>P</i><.001).</p

Patient characteristics.

<p><i>Abbreviations</i>: CDI, <i>Clostridium difficile</i> infection; IQR, interquartile range; NA, not applicable; PPI, proton pump inhibitor; SD, standard deviation; WBC, white blood cell count. Missing data is indicated by a hyphen.</p>1<p>Diarrhea, but no CDI.</p>2<p>Healthy patients without diarrhea or CDI.</p>3<p><i>P</i> values compare control groups to cases and use the unpaired t-test for means/Mann-Whitney test for medians (continuous variables) or the two sample z-test for proportions (categorical variables).</p>4<p>Temperature > 38°C.</p>5<p>thousands of cells per mm³_.</p>6<p>Intensive care unit admission, colectomy, or death attributed to CDI within 30 days of diagnosis.</p>7<p>All-cause 30-day mortality.</p