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Figure S1. Boxplot summarising sequencing statistics including total purity-filtered reads, uniquely aligned reads, multimapping reads, unaligned reads and reads that were removed due to a very short insert size (

Aims/hypothesis The aim of this study was to examine the effect of cord blood autoantibodies on the risk for type 1 diabetes in children followed prospectively from birth. Methods The Diabetes Prediction in Skane (DiPiS) study consists of 35,853 children from the general population born during 2000-2004. Samples were collected at birth and analysed for HLA genotypes and autoantibodies to glutamate decarboxylase 65 (GAD65), insulin and insulinoma-associated protein 2 (IA-2). After adjusting for HLA, sex, maternal age and parental type 1 diabetes, independent associations with risk of diabetes were assessed using multivariate Cox proportional hazards models. Results In total, 151 children (0.4%) had developed type 1 diabetes by the end of 2013 at a median age of 5.8 years (0.8-12.2 years). In the multivariate analysis, the presence of IA-2 autoantibodies (IA-2A) in cord blood (HR 6.88, 95% CI 1.46,32.4; p = 0.003), but not maternal diabetes (HR 1.38, 95% CI 0.24,7.84; p = 0.71), was associated with risk of developing type 1 diabetes. No increased risk could be seen for the presence of autoantibodies to GAD65 or insulin. Conclusions/interpretation Our study indicates that the presence of cord blood IA-2A superimposes maternal diabetes and other cord blood islet autoantibodies as a predictor of type 1 diabetes development in the child. These findings may be of significance for future screening and study protocols on type 1 diabetes prediction.

Laser Microdissection. Representative pictures of a cresyl violet stained triple-negative breast tumor (A), marked (B) and dissected (C) for inflammatory stromal compartment. (PDF 164Â kb)

TCGA data sets. (PDF 25Â kb)

ID of TaqManÂŽ gene expression assays. (PDF 41Â kb)

Histological analysis of TCGA breast tumors. Tumors with distinct and compactly organized stroma surrounding a bulk tumorous structure and were classified as tumors with “separated” stroma (A) whereas tumors with a more integrated pattern of stroma and cancer cells were classified as “mixed” (B). (PDF 256 kb)

Expanded endothelial gene set used for identification of compact endothelial cluster. (PDF 28Â kb)

TCGA data sets. (PDF 25Â kb)

Breast cancer data sets. (PDF 26Â kb)

Histological analysis of TCGA breast tumors. Tumors with distinct and compactly organized stroma surrounding a bulk tumorous structure and were classified as tumors with “separated” stroma (A) whereas tumors with a more integrated pattern of stroma and cancer cells were classified as “mixed” (B). (PDF 256 kb)

Levels of ECM and endothelial metagenes in different cancer types. The expression levels of the ECM (A) and endothelial (B) metagenes were quantified in TCGA RNA-seq cancer sets (BRCA – breast adenocarcinoma, COAD – colon adenocarcinoma, HNSC – head and neck squamous cell carcinoma, KIRC – kidney renal clear cell carcinoma, LUAD – lung adenocarcinoma, LUSC – lung squamous cell carcinoma). (PDF 121 kb)

Expanded ECM gene set used for identification of compact ECM cluster. (PDF 30Â kb)

ID of TaqManÂŽ gene expression assays. (PDF 41Â kb)

Laser Microdissection. Representative pictures of a cresyl violet stained triple-negative breast tumor (A), marked (B) and dissected (C) for inflammatory stromal compartment. (PDF 164Â kb)

Breast cancer data sets. (PDF 26Â kb)

Expanded ECM gene set used for identification of compact ECM cluster. (PDF 30Â kb)

Tables S1–S5. Sugars released from the hydrolysis of lignocellulose materials. Sugars released from the enzymatic hydrolysis of lignocelluloses non-treated and treated with either H2SO4 (205 °C for 10 min) or (S)IL solvents at (A) 120 °C for 90 min (B) 160 °C for 90 min and (C) 180 °C for 60 min. Sugars released from the acid pre-hydrolysis are also shown. AH is acid hydrolysate and EH is enzymatic hydrolysate

Chapitre 6; Written by researchers representing six countries and 28 institutions, this book highlights the development of the genus Populus as a model organism for tree genomics. Reflecting an impressive depth of coverage, the contributors' thorough reviews and analyses of Populus genomics provide insight into future discoveries about the basic biology of this fascinating genus and paves the way for applied breeding and genetic improvement of poplars.

Whole-genome sequencing (WGS) brings comprehensive insights to cancer genome interpretation. To explore the clinical value of WGS, we sequenced 254 triple-negative breast cancers (TNBCs) for which associated treatment and outcome data were collected between 2010 and 2015 via the population-based Sweden Cancerome Analysis Network-Breast (SCAN-B) project (ClinicalTrials.gov ID:NCT02306096). Applying the HRDetect mutational-signature-based algorithm to classify tumors, 59% were predicted to have homologous-recombination-repair deficiency (HRDetect-high): 67% explained by germline/somatic mutations of BRCA1/BRCA2, BRCA1 promoter hypermethylation, RAD51C hypermethylation or biallelic loss of PALB2. A novel mechanism of BRCA1 abrogation was discovered via germline SINE-VNTR-Alu retrotransposition. HRDetect provided independent prognostic information, with HRDetect-high patients having better outcome on adjuvant chemotherapy for invasive disease-free survival (hazard ratio (HR) = 0.42; 95% confidence interval (CI) = 0.2-0.87) and distant relapse-free interval (HR = 0.31, CI = 0.13-0.76) compared to HRDetect-low, regardless of whether a genetic/epigenetic cause was identified. HRDetect-intermediate, some possessing potentially targetable biological abnormalities, had the poorest outcomes. HRDetect-low cancers also had inadequate outcomes: ~4.7% were mismatch-repair-deficient (another targetable defect, not typically sought) and they were enriched for (but not restricted to) PIK3CA/AKT1 pathway abnormalities. New treatment options need to be considered for now-discernible HRDetect-intermediate and HRDetect-low categories. This population-based study advocates for WGS of TNBC to better inform trial stratification and improve clinical decision-making.

A review with 48 refs. The topics discussed include mass and energy balances for open and non-steady state systems, calcn. of reaction enthalpies, and enthalpy balance in aerobic and anaerobic growth. [on SciFinder (R)]

Breast tumors of the basal-like, hormone receptor-negative subtype remain an unmet clinical challenge, as there is high rate of recurrence and poor survival in patients following treatment. Coevolution of the malignant mammary epithelium and its underlying stroma instigates cancer-associated fibroblasts (CAFs) to support most, if not all, hallmarks of cancer progression. Here we delineate a previously unappreciated role for CAFs as determinants of the molecular subtype of breast cancer. We identified paracrine crosstalk between cancer cells expressing platelet-derived growth factor (PDGF)-CC and CAFs expressing the cognate receptors in human basal-like mammary carcinomas. Genetic or pharmacological intervention of PDGF-CC activity in mouse models of cancer resulted in conversion of basal-like breast cancers into a hormone receptor-positive state that enhanced sensitivity to endocrine therapy in previously resistant tumors. We conclude that specification of breast cancer to the basal-like subtype is under microenvironmental control and is therapeutically actionable.