An Unorthodox Introduction to QCD

These are lecture notes presented at the 2017 CTEQ Summer School at the University of Pittsburgh and the 2018 CTEQ Summer School at the University of Puerto Rico, Mayaguez. The title is a reference to hep-th/0309149 and introduces perturbative QCD and its application to jet substructure from a bottom-up perspective based on the approximation of QCD as a weakly-coupled, conformal field theory. Using this approach, a simple derivation of the Sudakov form factor with soft gluon emission modeled as a Poisson process is presented. Topics of the identification and discrimination of quark- versus gluon-initiated jets and jet grooming are also discussed.Comment: 16 pages, 18 figures. Comments welcome!, v2: updated to include both lectures from the 2018 CTEQ schoo

Plots of the log Cox Relative Hazard ratio for BOS against percent T regulatory lymphocyte subsets.

<p>The log of the Cox Relative Hazard (y-axis) decreases, i.e., less likely to develop BOS, as the percent of Treg, Treg subset or CCL21 protein level (x-axis) increases. The steeper the curve, as indicated by the blue line, the more protective the association with each Treg subset. The most significant effect is seen with the CCR7⁺ Treg subset. Confidence intervals are given by the gray bands. (top left) A plot for total BALF Treg, which demonstrates a non-significant protective effect. (top right) A plot of percent CCR4⁺ Treg, which demonstrates no significant protective effect. (bottom left) A plot of percent CCR7⁺ Treg, which demonstrates a significant protective effect. (botom right) A plot of BALF CCL21 protein level (pg) as determined by ELISA, which demonstrates a significant protective effect.</p

Density plots of chemokine receptor expression by Treg.

<p>Representative density plots of CCR4 and CCR7 expression by BALF Treg. The parent populations for determination of chemokine receptor positivity were singlet, live, CD3⁺CD4⁺CD25^hiFoxp3⁺ lymphocytes as shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0011354#pone-0011354-g001" target="_blank">Figure 1</a>. (left) Demonstrates the generally high level of CCR4 expression by Treg. The CCR4 gate was determined such that <0.1% of the cells were positive in the CCR4 FMO tube (see text for detail). (right) Demonstrates the variability of CCR7 expression by Treg. The CCR7 gate was determined such that <0.3% of the cells were positive in the CCR7 FMO tube.</p

Histopathology demonstrating CCL21 production in healthy lung allograft.

<p>Representative immunohistochemistry for (a) control antibody and (b) CCR7 ligand CCL21 on healthy lung allograft biopsy tissue. CCL21 protein expression is found in bronchial epithelial cells (red arrows) and alveolar macrophages (green arrows). Panels were photographed at 200× and 400× magnification.</p

Representative gating strategy for identification of CD3⁺CD4⁺CD25^hiFoxp3⁺ lymphocytes and subsets.

<p>Gated cells (selected cells) are purple, while non-gated cells (discarded cells) are blue or black. The gating involves sequential boolean filters and the sequence of filters is demonstrated here moving left to right and then top to bottom. Purple cell populations are selected in each scatterplot and this population is then used as the parent population in the subsequent scatterplot. (top row) First, singlets are identified in a forward scatter-area vs. forward scatter-height plot and gated on prior to logicle transformation of the data. Live/CD4⁺ cells are then identified in a CD4 vs. UV-Blue plot. CD3⁺ cells are then identified in a CD4 vs. CD3 plot. (bottom row) Lymphocytes within this population are identified in a side scatter-area vs. forward scatter-area plot. Treg are identified in a Foxp3 vs. CD25 plot. Determination of gates for CD25, CD45RA, Foxp3 and CCR7 utilized fluorescence minus-one (FMO) tubes.</p

Flow chart description of the number of samples and outcomes from each group.

<p>Forty-seven lung transplant recipients were in the study. Thirteen went on to develop BOS. Seventy BALF samples were collected and ten had insufficient cells to allow detection of Treg, thus 60 samples were used for total Treg analysis. Of the 60 samples, 27 were dropped from analysis for the Treg subsets due to inadequate number of Treg as explained in the <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0011354#s2" target="_blank">Methods</a>.</p

Descriptive statistics by BOS outcome for Treg subset analysis (CCR7⁺ and CCR4⁺ subsets).

<p>N is the number of non-missing values.</p><p>Numbers after percents are frequencies.</p><p>a[b, c] represents the median a, lower quartile b and the upper quartile c for continuous variables.</p><p>Tests used:</p>1<p>Pearson test;</p>2<p>Wilcoxon test.</p

ROC curve for CCR7⁺ Treg and BOS.

<p>The ROC curve is based upon a logistic regression model for CCR7+ Treg predicting BOS outcome, which excludes samples collected after the diagnosis of BOS. The p-value for the global null hypothesis is 0.04 and the area under the curve (AUC) is 0.75; the model has good predictive value.</p

Boxplots of T regulatory lymphocytes and BOS outcomes.

<p>(left) A boxplot of all 60 evaluable samples for total Treg. This plot demonstrates that there are no differences in total Treg frequencies between those recipients who eventually develop BOS and those that do not (p = 0.92). (middle) A boxplot of all 33 evaluable samples for Treg subsets. This plot demonstrates that there are no differences in CCR4⁺ Treg frequencies between those recipients who eventually develop BOS and those that do not (p = 0.12). (right) A boxplot of all 33 evaluable samples for Treg subsets. The CCR7⁺ subset is associated with protection against BOS (p = 0.04).</p

The prognostic importance of CXCR3 chemokine during organizing pneumonia on the risk of chronic lung allograft dysfunction after lung transplantation

<div><p>Rationale</p><p>Since the pathogenesis of chronic lung allograft dysfunction (CLAD) remains poorly defined with no known effective therapies, the identification and study of key events which increase CLAD risk is a critical step towards improving outcomes. We hypothesized that bronchoalveolar lavage fluid (BALF) CXCR3 ligand concentrations would be augmented during organizing pneumonia (OP) and that episodes of OP with marked chemokine elevations would be associated with significantly higher CLAD risk.</p><p>Methods</p><p>All transbronchial biopsies (TBBX) from patients who received lung transplantation between 2000 to 2010 were reviewed. BALF concentrations of the CXCR3 ligands (CXCL9, CXCL10 and CXCL11) were compared between episodes of OP and “healthy” biopsies using linear mixed-effects models. The association between CXCR3 ligand concentrations during OP and CLAD risk was evaluated using proportional hazards models with time-dependent covariates.</p><p>Results</p><p>There were 1894 bronchoscopies with TBBX evaluated from 441 lung transplant recipients with 169 (9%) episodes of OP and 907 (49%) non-OP histopathologic injuries. 62 (37%) episodes of OP were observed during routine surveillance bronchoscopy. Eight hundred thirty-eight (44%) TBBXs had no histopathology and were classified as “healthy” biopsies. There were marked elevations in BALF CXCR3 ligand concentrations during OP compared with “healthy” biopsies. In multivariable models adjusted for other injury patterns, OP did not significantly increase the risk of CLAD when BAL CXCR3 chemokine concentrations were not taken into account. However, OP with elevated CXCR3 ligands markedly increased CLAD risk in a dose-response manner. An episode of OP with CXCR3 concentrations greater than the 25^th, 50^th and 75^th percentiles had HRs for CLAD of 1.5 (95% CI 1.0–2.3), 1.9 (95% CI 1.2–2.8) and 2.2 (95% CI 1.4–3.4), respectively.</p><p>Conclusions</p><p>This study identifies OP, a relatively uncommon histopathologic finding after lung transplantation, as a major risk factor for CLAD development when considered in the context of increased allograft expression of interferon-γ inducible ELR- CXC chemokines. We further demonstrate for the first time, the prognostic importance of BALF CXCR3 ligand concentrations during OP on subsequent CLAD risk.</p></div