Sustainable Synthesis of Non‐Isocyanate Polyurethanes Based on Renewable 2,3‐Butanediol

In this work, three different cyclic carbonates are obtained from renewable diols and transformed into carbamates by reacting them with renewable 11-amino undecanoic acid methyl ester to synthesize non-isocyanate poly(ester urethane)s in a sustainable manner. A procedure using 2,3-butanediol (2,3-BDO) as a renewable starting material to synthesize a cyclic carbonate with dimethyl carbonate (DMC) is introduced, catalyzed by 1,5,7-triazabicylco[4.4.0]dec-5-ene (TBD). Three purification strategies, i.e., column chromatography, extraction, and distillation, are compared regarding their E-Factors. Propylene glycol (PG) and ethylene glycol (EG) are used as alternative starting materials to broaden the substrate scope and compare material properties, their cyclic carbonates likewise react to carbamates with 11-amino undecanoic acid methyl ester. All carbamates are then polymerized in a bulk polycondensation reaction, yielding non-isocyanate polyurethanes (NIPUs), specifically poly (ester urethane)s, with molecular weights (M$_n$) up to 10 kDa. Complete characterization is reported using differential scanning calorimetric (DSC), size exclusion chromatographic measurements (SEC), $^1$H-NMR as well as IR spectroscopy. The rheological properties of the poly(ester urethane)s are investigated in the framework of small amplitude oscillatory shear (SAOS) and uniaxial elongation

Introgression and repeated co-option facilitated the recurrent emergence of C4 photosynthesis among close relatives.

The origins of novel traits are often studied using species trees and modeling phenotypes as different states of the same character, an approach that cannot always distinguish multiple origins from fewer origins followed by reversals. We address this issue by studying the origin of C4 photosynthesis, an adaptation to warm and dry conditions, in the grass Alloteropsis. We dissect the C4 trait into its components, and show two independent origins of the C4 phenotype via different anatomical modifications, and the use of distinct sets of genes. Further, inference of enzyme adaptation suggests that one of the two groups encompasses two transitions to a full C4 state from a common ancestor with an intermediate phenotype that had some C4 anatomical and biochemical components. Molecular dating of C4 genes confirms the introgression of two key C4 components between species, while the inheritance of all others matches the species tree. The number of origins consequently varies among C4 components, a scenario that could not have been inferred from analyses of the species tree alone. Our results highlight the power of studying individual components of complex traits to reconstruct trajectories toward novel adaptations

Regional Fluid-Attenuated Inversion Recovery (FLAIR) at 7 Tesla correlates with amyloid beta in hippocampus and brainstem of cognitively normal elderly subjects

Background: Accumulation of amyloid beta (Aβ) may occur during healthy aging and is a risk factor for Alzheimer Disease (AD). While individual Aβ-accumulation can be measured non-invasively using Pittsburgh Compund-B positron emission tomography (PiB-PET), Fluid-attenuated inversion recovery (FLAIR) is a Magnetic Resonance Imaging (MRI) sequence, capable of indicating heterogeneous age-related brain pathologies associated with tissue-edema. In the current study cognitively normal elderly subjects were investigated for regional correlation of PiB- and FLAIR intensity. Methods: Fourteen healthy elderly subjects without known history of cognitive impairment received 11C-PiB-PET for estimation of regional Aβ-load. In addition, whole brain T1-MPRAGE and FLAIR-MRI sequences were acquired at high field strength of 7 Tesla (7T). Volume-normalized intensities of brain regions were assessed by applying an automated subcortical segmentation algorithm for spatial definition of brain structures. Statistical dependence between FLAIR- and PiB-PET intensities was tested using Spearman's rank correlation coefficient (rho), followed by Holm–Bonferroni correction for multiple testing. Results: Neuropsychological testing revealed normal cognitive performance levels in all participants. Mean regional PiB-PET and FLAIR intensities were normally distributed and independent. Significant correlation between volume-normalized PiB-PET signals and FLAIR intensities resulted for Hippocampus (right: rho = 0.86; left: rho = 0.84), Brainstem (rho = 0.85) and left Basal Ganglia vessel region (rho = 0.82). Conclusions: Our finding of a significant relationship between PiB- and FLAIR intensity mainly observable in the Hippocampus and Brainstem, indicates regional Aβ associated tissue-edema in cognitively normal elderly subjects. Further studies including clinical populations are necessary to clarify the relevance of our findings for estimating individual risk for age-related neurodegenerative processes such as AD

Insulin resistance causes inflammation in adipose tissue

Obesity is a major risk factor for insulin resistance and type 2 diabetes. In adipose tissue, obesity-mediated insulin resistance correlates with the accumulation of proinflammatory macrophages and inflammation. However, the causal relationship of these events is unclear. Here, we report that obesity-induced insulin resistance in mice precedes macrophage accumulation and inflammation in adipose tissue. Using a mouse model that combines genetically induced, adipose-specific insulin resistance (mTORC2-knockout) and diet-induced obesity, we found that insulin resistance causes local accumulation of proinflammatory macrophages. Mechanistically, insulin resistance in adipocytes results in production of the chemokine monocyte chemoattractant protein 1 (MCP1), which recruits monocytes and activates proinflammatory macrophages. Finally, insulin resistance (high homeostatic model assessment of insulin resistance [HOMA-IR]) correlated with reduced insulin/mTORC2 signaling and elevated MCP1 production in visceral adipose tissue from obese human subjects. Our findings suggest that insulin resistance in adipose tissue leads to inflammation rather than vice versa

Providing Information by Resource- Constrained Data Analysis

The Collaborative Research Center SFB 876 (Providing Information by Resource-Constrained Data Analysis) brings together the research fields of data analysis (Data Mining, Knowledge Discovery in Data Bases, Machine Learning, Statistics) and embedded systems and enhances their methods such that information from distributed, dynamic masses of data becomes available anytime and anywhere. The research center approaches these problems with new algorithms respecting the resource constraints in the different scenarios. This Technical Report presents the work of the members of the integrated graduate school

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Evaluation der Berufseinstiegsbegleitung nach § 421s SGB III: Zwischenbericht 2011

Die Anforderungen an Schülerinnen und Schüler zwei Jahre vor ihrem Schulabschluss sind hoch. Schulisch sind sie mit vielen Prüfungen gefordert. Daneben müssen sie Bewerbungen für Ausbildungsplätze schreiben. Wenn es zum Bewerbungsgespräch kommt, stehen sie vor einer unbekannten Situation. Viele sind unsicher darüber, wie es nach der Schule weitergeht. Das Berufsleben - später meist selbstverständlich - ist die große Unbekannte. In dieser Phase hilft die Berufseinstiegsbegleitung nach dem Arbeitsförderungsrecht derzeit in einer modellhaften Erprobung an rund 1.000 Schulen denjenigen, die besondere Schwierigkeiten beim Schulabschluss und beim Übergang in die berufliche Zukunft haben. Bisher wurden dabei rund 37.000 Schülerinnen und Schülern durch die Bundesagentur für Arbeit gefördert. Die begleitende Wirkungsforschung (Evaluation) zeigt nun, dass sich bei den Teilnehmenden leichte Verbesserungen der Noten in Mathematik, Deutsch und Englisch zeigen. Von denjenigen, die die Schule „in Begleitung“ verlassen haben, haben 22,8 % eine betriebliche und 5,1 % eine schulische Berufsausbildung begonnen. Vergleichszahlen zu Übergängen von der Schule in den Beruf von jungen Menschen "ohne entsprechende Begleitung" liegen noch nicht vor. Nach der Schule verteilen sich die Schülerinnen und Schüler auf verschiedene Betriebe, Berufsschulen und andere Einrichtungen. Für die Tätigkeit der Berufseinstiegsbegleiterinnen und -begleiter stellt dies eine räumliche und eine organisatorische Herausforderung dar. Denn die Berufseinstiegsbegleitung endet in der Berufsausbildung normalerweise erst nach sechs Monaten. Damit soll die kritische Anfangsphase, in der die meisten Abbrüche stattfinden, stabilisiert werden. Die bisherigen positiven Erfahrungen mit der Berufseinstiegsbegleitung haben die Bundesregierung dazu veranlasst, im Entwurf eines Gesetzes zur Verbesserung der Eingliederungschancen am Arbeitsmarkt die Entfristung der Berufseinstiegsbegleitung vorzuschlagen. Der Deutsche Bundestag hat dieses Gesetz am 23. September 2011 verabschiedet