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

Apoptotic and stress markers are increased in the aged BACHD heart.

<p>A significant increase in Cleaved Caspase 3 (A) and Hsp-70 (B) protein levels was found in whole tissue lysate of the heart of aged BACHD mice. Values derived from the densitometric analysis were corrected for the background, normalized to GAPDH and are shown as a percentage of the value for the WT mice. (C) Protein levels of GAPDH did not differ between WT and BACHD. Insert shows representative immunoblots. Data are shown as the mean ± SEM, * <i>P</i><0.05 for genotypic differences (n = 4 per group).</p

Echocardiogram indicates structural and functional differences early in the disease progression.

<p>Structural (A) and functional (B, C) parameters of the heart from WT (n = 8) and BACHD (n = 9) mice were measured from 3 to 15 mo of age. ^ <i>P</i><0.05 within WT vs. 3 mo. ^#<i>P</i><0.05 within BACHD vs. 3 mo. * <i>P</i><0.05 for genotypic differences.</p

Microarray results were confirmed by probing expression of 4 genes using quantitative real-time PCR from ventricles from mice at 3 mo of age.

<p><i>Hspa1a</i> (A) and <i>Nppb</i> (B) are both involved in stress and pathological responses and were increased in the BACHD mice. Expression of <i>Kcnip2</i> (C), a voltage-gated potassium channel interacting protein responsive to changes in calcium, and <i>Acot1</i> (D) an enzyme involved in fatty acid metabolism were decreased in BACHD ventricles. Data are reported as ratios of the target gene expression to <i>Tbp</i>, and are shown as the mean ± SEM, * <i>P</i><0.05 for genotypic differences (n = 4 per group).</p

Histological analysis finds evidence of increased fibrosis in the BACHD hearts in response to the adrenoreceptor challenge.

<p>Examples of Masson’s Trichrome (A) stained heart sections from WT and BACHD mice treated with saline or ISO. Quantification of fibrosis by measurement of the optical density of blue staining confirmed increased fibrosis in the ISO-treated BACHD animals (B). Comparison of heart dimensions from H & E sections (C) and morphological measurements of WT and BACHD (D) mice indicated that the heart weight/body weight ratio was higher in both groups following ISO treatment. However, there were no significant differences between the genotypes. * P < 0.05 between genotypes; # <i>P</i><0.05 vs. saline within a genotype.</p

Network analysis of biologically relevant pathways altered in the heart of BACHD mice vs WT as measured by microarrays.

<p>Most altered gene networks in the comparison between young (3 mo) WT and BACHD hearts (A) and in the comparison between aged (15 mo) WT and aged BACHD (B). Grey boxes indicate that gene expression is increased in BACHD mice, while white boxes indicate decreased expression.</p

Histological analysis finds evidence of fibrosis and hypertrophy in the BACHD hearts.

<p>Examples of Masson’s Trichrome stained heart sections from 15 mo old WT and BACHD mice (A). Quantification of fibrosis by measuring the integrated density of fibrotic tissue and divided by tissue area detected significantly increased areas of fibrosis in BACHD mice (B). Examples of hematoxylin and eosin (H&E) stained heart sections from 15 mo old WT and BACHD mice (C). Morphometry measurements comparing heart weight relative to body weight between 15 mo old WT and BACHD mice (D). * <i>P</i><0.05 for genotypic differences.</p

The cardiovascular system of the BACHD mice responded adaptively to chronic treatment with an adrenoreceptor challenge (ISO, 0.96mg/kg per day for 30 days).

<p>Examples of ECG waveforms from WT (n = 10) (A) and BACHD (n = 8) mice (B). The ST segment range is shown by the black line. ISO increased HR (C) and elevated the ST segment voltage (D) in both genotypes indicating that the drug was effective in stimulating the heart also in BACHD mice. No significant difference in the response to ISO between genotypes was detected. ^#<i>P</i><0.05 vs. saline.</p

The CD44^high Tumorigenic Subsets in Lung Cancer Biospecimens Are Enriched for Low miR-34a Expression

<div><p>Cellular heterogeneity is an integral part of cancer development and progression. Progression can be associated with emergence of cells that exhibit high phenotypic plasticity (including “de-differentiation” to primitive developmental states), and aggressive behavioral properties (including high tumorigenic potentials). We observed that many biomarkers that are used to identify Cancer Stem Cells (CSC) can label cell subsets in an advanced clinical stage of lung cancer (malignant pleural effusions, or MPE). Thus, CSC-biomarkers may be useful for live sorting functionally distinct cell subsets from individual tumors, which may enable investigators to hone in on the molecular basis for functional heterogeneity. We demonstrate that the CD44^hi (CD44-high) cancer cell subsets display higher clonal, colony forming potential than CD44^lo cells (n = 3) and are also tumorigenic (n = 2/2) when transplanted in mouse xenograft model. The CD44^hi subsets express different levels of embryonal (de-differentiation) markers or chromatin regulators. In archived lung cancer tissues, ALDH markers co-localize more with CD44 in squamous cell carcinoma (n = 5/7) than Adeno Carcinoma (n = 1/12). MPE cancer cells and a lung cancer cell line (NCI-H-2122) exhibit chromosomal abnormalities and 1p36 deletion (n = 3/3). Since miR-34a maps to the 1p36 deletion site, low miR-34a expression levels were detected in these cells. The colony forming efficiency of CD44^hi cells, characteristic property of CSC, can be inhibited by mir-34a replacement in these samples. In addition the highly tumorigenic CD44^hi cells are enriched for cells in the G2 phase of cell cycle.</p></div

Expression of miR-34a in CD44^hi and CD44^lo cells evaluated by RT-qPCR and exogenous delivery of miR-34a into CD44^hi cells inhibits colony formation and anti- miR-34a into CD44^lo cells increases colony formation.

<p>(<b>A</b>) miR-34a expression in unsorted, CD44^hi and CD44^lo cells of two primary samples (M-1 and M-2), established NSCLC cell line NCI-H-2122 and normal human fibroblast cell line GM 05399. The miR-34a expression has been normalized with RNU48. (<b>B</b>) Sorted CD44^hi cells (samples M-1 and M-2) when transduced with miR-34a show decreased colony forming efficiency in comparison to miR-control transduced CD44^hi tumor cells; (Sample M-1: miR control = 131.6 (SD = 30.5),+miR-34a = 7 (SD = 2.6) and P = 0.002; Sample M-2: miR control = 75 (SD = 19.6),+miR-34a = 23 (SD = 5.5) and P = 0.01); The mean effect with miR-34a versus miR-control on CD44^hi cells is −88.3 (95% CI: −288.12, 111.45; P = 0.112) (<b>C</b>) Sorted CD44^hi tumor cells transduced with miR-34a exhibit small colony size (bottom panel) than miR-control transduced CD44^hi tumor cells (upper panel); (<b>D</b>) The CD44^lo cells from Sample M-1 and M-2 transduced with anti-miR34a show increased colony forming efficiency than tumor cells transduced with miR-control; (Sample M-1: miR control = 21 (SD = 4.5),+anti- miR-34a = 33 (SD = 5.2) and P = 0.04; Sample M-2: miR control = 24.6 (SD = 4.1),+anti-miR-34a = 39.3 (SD = 5.1) and P = 0.018); The mean effect with anti-miR-34a versus miR-control on CD44^lo cells is −13.3 (95% CI: −20.43, 47.10; P = 0.125). (<b>E</b>) Sorted CD44^lo cells transduced with anti-miR-34a exhibit bigger colony size (bottom panel) than miR-control transduced tumor cells (upper panel).</p