Towards extracting the timelike pion form factor on CLS two-flavour ensembles

Results are presented from an ongoing study of the $\rho$ resonance. The focus is on CLS 2-flavour ensembles generated using $\mathcal{O}(a)$ improved Wilson fermions with pion masses ranging from $265$ to $437$ $\mathrm{MeV}$. The energy levels are extracted by solving the GEVP of correlator matrices, created with the distillation approach involving $\rho$ and $\pi\pi$ interpolators. The study is done in the centre-of-mass frame and several moving frames. One aim of this work is to extract the timelike pion form factor after applying the L\"uscher formalism. We therefore plan to integrate this study with the existing Mainz programme for the calculation of the hadronic vacuum polarization contribution to the muon $g-2$.Comment: proceedings to conference: Lattice 2017, Granada, Spai

Studying the Nature of Dark Energy with Galaxy Clusters

We report on the status of our effort to constrain the nature of dark energy through the evolution of the cluster mass function. Chandra temperature profiles for 31 clusters from a local cluster sample are shown. The X-ray appearance of the proto supermassive binary black hole at the center of the cluster Abell 400 is described. Preliminary weak lensing results obtained with Megacam@MMT for a redshift z=0.5 cluster from a distant cluster sample are given.Comment: 5 pages, to appear in: Aschenbach, B., Burwitz, V., Hasinger, G., Leibundgut, B. (eds.), Relativistic Astrophysics and Cosmology - Einstein's Legacy. ESO Astrophysics Symposia, Springer Verlag, Berlin, German

Quantum-dot-like states in molybdenum disulfide nanostructures due to the interplay of local surface wrinkling, strain, and dielectric confinement

The observation of quantum light emission from atomically thin transition metal dichalcogenides has opened a new field of applications for these material systems. The corresponding excited charge-carrier localization has been linked to defects and strain, while open questions remain regarding the microscopic origin. We demonstrate that the bending rigidity of these materials leads to wrinkling of the two-dimensional layer. The resulting strain field facilitates strong carrier localization due to its pronounced influence on the band gap. Additionally, we consider charge carrier confinement due to local changes of the dielectric environment and show that both effects contribute to modified electronic states and optical properties. The interplay of surface wrinkling, strain-induced confinement, and local changes of the dielectric environment is demonstrated for the example of nanobubbles that form when monolayers are deposited on substrates or other two-dimensional materials

A potential role for a novel ZC3H5 complex in regulating mRNA translation in Trypanosoma brucei

In Trypanosoma brucei and related kinetoplastids, gene expression regulation occurs mostly post-transcriptionally. Consequently, RNA-binding proteins play a critical role in the regulation of mRNA and protein abundance. Yet, the roles of many RNA-binding proteins are not understood. Our previous research identified the RNA-binding protein ZC3H5 as possibly involved in gene repression, but its role in controlling gene expression was unknown. We here show that ZC3H5 is an essential cytoplasmic RNA-binding protein: RNAi targeting ZC3H5 causes accumulation of pre-cytokinetic cells followed by rapid cell death. Affinity purification and pair-wise yeast 2-hybrid analysis suggest that ZC3H5 forms a complex with three other proteins, encoded by genes Tb927.11.4900, Tb927.8.1500 and Tb927.7.3040. RNA immunoprecipitation revealed that ZC3H5 is preferentially associated with poorly translated, low-stability mRNAs, the 5´-untranslated regions and coding regions of which are enriched in the motif (U/A)UAG(U/A). As previously found in high-throughput analyses, artificial tethering of ZC3H5 to a reporter mRNA or other complex components repressed reporter expression. However, depletion of ZC3H5 in vivo caused only very minor decreases in a few targets, marked increases in the abundances of very stable mRNAs, an increase in monosomes at the expense of large polysomes, and appearance of "halfmer" disomes containing two 80S subunits and one 40S subunit. We speculate that the ZC3H5 complex might be implicated in quality control during the translation of sub-optimal open reading frames.Fil: Bajak, Kathrin. Universität Heidelberg; AlemaniaFil: Leiss, Kevin. Universität Heidelberg; AlemaniaFil: Clayton, Christine. Universität Heidelberg; AlemaniaFil: Erben, Esteban Daniel. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; Argentin

Insights into the functions and RNA binding of Trypanosoma brucei ZC3H22, RBP9 and DRBD7

Trypanosoma brucei is unusually reliant on mRNA-binding proteins to control mRNA fate, because its protein-coding genes lack individual promoters. We here focus on three trypanosome RNA-binding proteins. ZC3H22 is specific to Tsetse fly forms, RBP9 is preferentially expressed in bloodstream forms; and DRBD7 is constitutively expressed. Depletion of RBP9 or DRBD7 did not affect bloodstream-form trypanosome growth. ZC3H22 depletion from procyclic forms caused cell clumping, decreased expression of genes required for cell growth and proliferation, and increased expression of some epimastigote markers. Apart from decreases in mRNAs encoding enzymes of glucose metabolism, levels of most ZC3H22-bound transcripts were unaffected by ZC3H22 depletion. We compared ZC3H22, RBP9 and DRBD7 RNA binding with that of 16 other RNA-binding proteins. ZC3H22, PUF3 and ERBP1 show a preference for ribosomal protein mRNAs. RBP9 preferentially binds mRNAs that are more abundant in bloodstream forms than in procyclic forms. RBP9, ZC3H5, ZC3H30 and DRBD7 prefer mRNAs with long coding regions; UBP1-associated mRNAs have long 3′-untranslated regions; and RRM1 prefers mRNAs with long 3′or 5′-untranslated regions. We suggest that proteins that prefer long mRNAs may have relatively short or degenerate binding sites, and that preferences for A or U increase binding in untranslated regions.Fil: Erben, Esteban Daniel. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; Argentina. Ruprecht Karls Universitat Heidelberg; AlemaniaFil: Leiss, Kevin. Ruprecht Karls Universitat Heidelberg; AlemaniaFil: Liu, Bin. Ruprecht Karls Universitat Heidelberg; AlemaniaFil: Gil, Diana Inchaustegui. Ruprecht Karls Universitat Heidelberg; AlemaniaFil: Helbig, Claudia. Ruprecht Karls Universitat Heidelberg; AlemaniaFil: Clayton, Christine. Ruprecht Karls Universitat Heidelberg; Alemani

Functional insights from a surface antigen mRNA-bound proteome

Trypanosoma brucei is the causative agent of human sleeping sickness. The parasites' Variant Surface Glycoprotein (VSG) enables them to evade adaptive immunity via anti-genic variation. VSG comprises 10% of total cell protein and the high stability of VSG mRNA is essential for trypanosome survival. To determine how VSG mRNA stability is maintained, we used mRNA affinity purification to identify all its associated proteins. CFB2, an unconventional RNA-binding protein with an F-box domain, was specifically enriched with VSG mRNA. We demonstrate that CFB2 is essential for VSG mRNA stabil-ity, describe cis acting elements within the VSG 3'-untranslated region that regulate the interaction, identify trans-acting factors that are present in the VSG messenger ribonu-cleoprotein particle and mechanistically explain how CFB2 stabilizes the mRNA of this key pathogenicity factor. Beyond T. brucei, the mRNP purification approach has the potential to supply detailed biological insight into metabolism of relatively abundant mRNAs in any eukaryote.Fil: do Nascimento, Larissa Melo. Ruprecht Karls Universitat Heidelberg; AlemaniaFil: Egler, Franziska. Ruprecht Karls Universitat Heidelberg; AlemaniaFil: Arnold, Katharina. Ruprecht Karls Universitat Heidelberg; AlemaniaFil: Papavasiliou, Nina. Ruprecht Karls Universitat Heidelberg; Alemania. Deutsche Krebsforschungszentrum; AlemaniaFil: Clayton, Christine. Ruprecht Karls Universitat Heidelberg; AlemaniaFil: Erben, Esteban Daniel. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; Argentina. Ruprecht Karls Universitat Heidelberg; Alemania. Deutsche Krebsforschungszentrum; Alemani

Molecular analysis of desmoid tumors with a high-density single-nucleotide polymorphism array identifies new molecular candidate lesions

Background: Desmoid tumors are neoplastic proliferations of connective tissues. The mutation status of the gene coding for catenin (cadherin-associated protein) beta 1 (CTNNB1) and trisomy 8 on the chromosomal level have been described to have prognostic relevance. Patients and Methods: In order to elucidate new molecular mechanisms underlying these tumors, we carried out a molecular analysis with a genome-wide human high-density single-nucleotide polymorphism (SNP) array, in 9 patients. Results: Single samples showed numerical aberrations on chromosomes (Chrs) 20 and 6 with either trisomy 20 or monosomy 6. No trisomy 8 could be detected. Recurrent heterozygous deletions were found in Chr 5q (including the APC gene locus, n = 3) and Chr 8p23 (n = 4, containing coding regions for the potential tumor suppressor gene CSMD1). This novel deletion in 8p23 showed an association with local recurrence. In addition, structural chromosomal changes (gain of Chrs 8 and 20) were found in a minority of cases. Conclusion: The genomic alteration affecting the candidate gene CSMD1 could be important in the development of desmoid tumors

Visually narrating post-colonial lives: ghosts of war and empire

This paper is about two journeys: the first through the memories of an old soldier captured by the Japanese in the Second World War; the second through the present life to which this past gave rise, in which the old soldier tends the graves of his fellow soldiers as part of his current navigation by bus and taxi of the post-colonial landscape of Hong Kong

Self-Calibration Technique for 3-point Intrinsic Alignment Correlations in Weak Lensing Surveys

The intrinsic alignment (IA) of galaxies has been shown to be a significant barrier to precision cosmic shear measurements. (Zhang, 2010, ApJ, 720, 1090) proposed a self-calibration technique for the power spectrum to calculate the induced gravitational shear-galaxy intrinsic ellipticity correlation (GI) in weak lensing surveys with photo-z measurements which is expected to reduce the IA contamination by at least a factor of 10 for currently proposed surveys. We confirm this using an independent analysis and propose an expansion to the self-calibration technique for the bispectrum in order to calculate the dominant IA gravitational shear-gravitational shear-intrinsic ellipticity correlation (GGI) contamination. We first establish an estimator to extract the galaxy density-density-intrinsic ellipticity (ggI) correlation from the galaxy ellipticity-density-density measurement for a photo-z galaxy sample. We then develop a relation between the GGI and ggI bispectra, which allows for the estimation and removal of the GGI correlation from the cosmic shear signal. We explore the performance of these two methods, compare to other possible sources of error, and show that the GGI self-calibration technique can potentially reduce the IA contamination by up to a factor of 5-10 for all but a few bin choices, thus reducing the contamination to the percent level. The self-calibration is less accurate for adjacent bins, but still allows for a factor of three reduction in the IA contamination. The self-calibration thus promises to be an efficient technique to isolate both the 2-point and 3-point intrinsic alignment signals from weak lensing measurements.Comment: 22 pages, 5 figures, matches version published in MNRAS. Published online December 5, 201

Prognostic significance of EGFR, AREG and EREG amplification and gene expression in muscle invasive bladder cancer

IntroductionMuscle invasive bladder cancer (MIBC) remains a prevalent cancer with limited therapeutic options, obviating the need for innovative therapies. The epidermal growth factor receptor (EGFR) is a linchpin in tumor progression and presents a potential therapeutic target in MIBC. Additionally, the EGFR ligands AREG and EREG have shown associations with response to anti-EGFR therapy and improved progression-free survival in colorectal carcinoma.Materials and methodsWe investigated the prognostic significance of EGFR, AREG, and EREG in MIBC. Gene expression and copy number analyses were performed via qRT-PCR on tissue samples from 100 patients with MIBC who underwent radical cystectomy at the University Hospital Mannheim (MA; median age 72, interquartile range [IQR] 64–78 years, 25% female). Results were validated in 361 patients from the 2017 TCGA MIBC cohort (median age 69, IQR 60–77 years, 27% female), in the Chungbuk and MDACC cohort. Gene expressions were correlated with clinicopathologic parameters using the Mann-Whitney test, Kruskal-Wallis- test and Spearman correlation. For overall survival (OS), cancer-specific survival (CSS) and disease-free survival (DFS) gene expression was analyzed with Kaplan-Meier and Cox-proportional hazard models.ResultsSignificant gene expression differences in EGFR, AREG, and EREG could be detected in all cohorts. In the TCGA cohort, EGFR expression was significantly elevated in patients with EGFR amplification and KRAS wildtype. High AREG expression independently predicted longer OS (HR = 0.35, CI 0.19 - 0.63, p = 0.0004) and CSS (HR = 0.42, CI 0.18 – 0.95, p = 0.0378) in the MA cohort. In the TCGA cohort, high EGFR, AREG, and EREG expression correlated with shorter OS (AREG: HR = 1.57, CI 1.12 – 2.20, p = 0.0090) and DFS (EGFR: HR = 1.91, CI 1.31 – 2.8, p = 0.0008). EGFR amplification was also associated with reduced DFS.DiscussionHigh EGFR and EREG indicate worse survival in patients with MIBC. The prognostic role of AREG should further be investigated in large, prospective series. Divergent survival outcomes between the four cohorts should be interpreted cautiously, considering differences in analysis methods and demographics. Further in vitro investigations are necessary to elucidate the functional mechanisms underlying the associations observed in this study