Inclusion of tetramethylpyrazine in channels of the organic zeolite 2,4,6-tris(4-bromophenoxy)-1,3,5-triazine

2,4,6-tris(4-bromophenoxy)-1,3,5-triazine (BrPOT) features a channel size (11-12Å) allowing the inclusion of large guest molecules such as tetramethylpyrazine (TMPZ). TMPZ forms π-stacks (d: 3.5Å) along channels of BrPOT and shows rotational disorder for methyl positions. Co-inclusions of I2 resulted in a doped state where I2 molecules are oriented perpendicular to the channel axis with positional disorder as well. The particular orientation of I2 molecules is evident from the observed dichrois

Halo Retention and Evolution of Coalescing Compact Binaries in Cosmological Simulations of Structure Formation: Implications for Short Gamma-Ray Bursts

Merging compact binaries are the one source of gravitational radiation so far identified. Because short-period systems which will merge in less than a Hubble time have already been observed as binary pulsars, they are important both as gravitational wave sources for observatories such as LIGO but also as progenitors for short gamma-ray bursts (SGRBs). The fact that these systems must have large systemic velocities implies that by the time they merge, they will be far from their formation site. The locations of merging sites depend sensitively on the gravitational potential of the galaxy host, which until now has been assumed to be static. Here we refine such calculations to incorporate the temporal evolution of the host's gravitational potential as well as that of its nearby neighbors using cosmological simulations of structure formation. This results in merger site distributions that are more diffusively distributed with respect to their putative hosts, with locations extending out to distances of a few Mpc for lighter halos. The degree of mixing between neighboring compact binary populations computed in this way is severely enhanced in environments with a high number density of galaxies. We find that SGRB redshift estimates based solely on the nearest galaxy in projection can be very inaccurate, if progenitor systems inhere large systematic kicks at birth.Comment: 7 pages, 3 figures, accepted for publication in ApJ

Crossing the Midline Roles and Regulation of Robo Receptors

AbstractIn the Drosophila CNS, the midline repellent Slit acts at short range through its receptor Robo to control midline crossing. Longitudinal axons express high levels of Robo and avoid the midline; commissural axons that cross the midline express only low levels of Robo. Robo levels are in turn regulated by Comm. Here, we show that the Slit receptors Robo2 and Robo3 ensure the fidelity of this crossing decision: rare crossing errors occur in both robo2 and robo3 single mutants. In addition, low levels of either Robo or Robo2 are required to drive commissural axons through the midline: only in robo,robo2 double mutants do axons linger at the midline as they do in slit mutants. Robo2 and Robo3 levels are also tightly regulated, most likely by a mechanism similar to but distinct from the regulation of Robo by Comm

Shear-thinning, Coulomb friction and grain collisions in debris-flow waterfalls: Applications of a 3D phase mixture model with a single calibration parameter and a complex 4-way coupled resolved CFD-DEM approach

Shear-thinning is a common flow-feature of fine sediment suspensions. Mixed with gravel, Coulomb friction drives the energy dissipation between small grains while collisions become more and more important with larger grains. The interaction of the flow with local geometries of the channel can enforce each of these three key features, making the design analysis of channel sections with obstacles a highly back-coupled system. This paper addresses the numerical simulation of debris flow material under extreme flow conditions at planned protection measures. Mixtures with small grain sizes are modelled with a single calibration parameter using the 3D CFD phase mixture software debrisInterMixing and compared with laboratory experiments. To further investigate the scaling of the results, a coupled code of YADE and debrisInterMixingLP is applied accounting for the 4-way coupling to the coarse boulders at the front with resolved CFD-DEM, reaching beyond the possibilities of debris flow experiments

Zebularine reactivates silenced E-cadherin but unlike 5-Azacytidine does not induce switching from latent to lytic Epstein-Barr virus infection in Burkitt's lymphoma Akata cells

Epigenetic silencing of regulatory genes by aberrant methylation contributes to tumorigenesis. DNA methyltransferase inhibitors (DNMTI) represent promising new drugs for anti-cancer therapies. The DNMTI 5-Azacytidine is effective against myelodysplastic syndrome, but induces switching of latent to lytic Epstein-Barr virus (EBV) in vitro and results in EBV DNA demethylation with the potential of induction of lytic EBV in vivo. This is of considerable concern given that recurrent lytic EBV has been linked with an increased incidence of EBV-associated lymphomas. Based on the distinct properties of action we hypothesized that the newer DNMTI Zebularine might differ from 5-Azacytidine in its potential to induce switching from latent to lytic EBV. Here we show that both 5-Azacytidine and Zebularine are able to induce expression of E-cadherin, a cellular gene frequently silenced by hypermethylation in cancers, and thus demonstrate that both DNMTI are active in our experimental setting consisting of EBV-harboring Burkitt's lymphoma Akata cells. Quantification of mRNA expression of EBV genes revealed that 5-Azacytidine induces switching from latent to lytic EBV and, in addition, that the immediate-early lytic infection progresses to early and late lytic infection. Furthermore, 5-Azacytidine induced upregulation of the latent EBV genes LMP2A, LMP2B, and EBNA2 in a similar fashion as observed following switching of latent to lytic EBV upon cross-linking of the B-cell receptor. In striking contrast, Zebularine did not exhibit any effect neither on lytic nor on latent EBV gene expression. Thus, Zebularine might be safer than 5-Azacytidine for the treatment of cancers in EBV carriers and could also be applied against EBV-harboring tumors, since it does not induce switching from latent to lytic EBV which may result in secondary EBV-associated malignancies

Quantitative profiling of housekeeping and Epstein-Barr virus gene transcription in Burkitt lymphoma cell lines using an oligonucleotide microarray

BACKGROUND: The Epstein-Barr virus (EBV) is associated with lymphoid malignancies, including Burkitt's lymphoma (BL), and can transform human B cells in vitro. EBV-harboring cell lines are widely used to investigate lymphocyte transformation and oncogenesis. Qualitative EBV gene expression has been extensively described, but knowledge of quantitative transcription is lacking. We hypothesized that transcription levels of EBNA1, the gene essential for EBV persistence within an infected cell, are similar in BL cell lines. RESULTS: To compare quantitative gene transcription in the BL cell lines Namalwa, Raji, Akata, Jijoye, and P3HR1, we developed an oligonucleotide microarray chip, including 17 housekeeping genes, six latent EBV genes (EBNA1, EBNA2, EBNA3A, EBNA3C, LMP1, LMP2), and four lytic EBV genes (BZLF1, BXLF2, BKRF2, BZLF2), and used the cell line B95.8 as a reference for EBV gene transcription. Quantitative polymerase chain reaction assays were used to validate microarray results. We found that transcription levels of housekeeping genes differed considerably among BL cell lines. Using a selection of housekeeping genes with similar quantitative transcription in the tested cell lines to normalize EBV gene transcription data, we showed that transcription levels of EBNA1 were quite similar in very different BL cell lines, in contrast to transcription levels of other EBV genes. As demonstrated with Akata cells, the chip allowed us to accurately measure EBV gene transcription changes triggered by treatment interventions. CONCLUSION: Our results suggest uniform EBNA1 transcription levels in BL and that microarray profiling can reveal novel insights on quantitative EBV gene transcription and its impact on lymphocyte biology

Einfluss der Fellbach-Wasserfälle auf das Fliessverhalten von Murgängen und auf mögliche Schutzmassnahmen

Aufsatz veröffentlicht in: "Wasserbau-Symposium 2021: Wasserbau in Zeiten von Energiewende, Gewässerschutz und Klimawandel, Zurich, Switzerland, September 15-17, 2021, Band 1" veröffentlicht unter: https://doi.org/10.3929/ethz-b-00049975

Impact of medical practice guidelines on the assessment of patients with acute coronary syndrome without persistent ST segment elevation

Objective. To assess the impact of introducing clinical practice guidelines on acute coronary syndrome without persistent ST segment elevation (ACS) on patient initial assessment. Design. Prospective before-after evaluation over a 3-month period. Setting. The emergency ward of a tertiary teaching hospital. Patients. All consecutive patients with ACS evaluated in the emergency ward over the two 3-month periods. Intervention. Implementation of the practice guidelines, and the addition of a cardiology consultant to the emergency team. Main outcome measures. Diagnosis, electrocardiogram interpretation, and risk stratification after the initial evaluation. Results. The clinical characteristics of the 328 and 364 patients evaluated in the emergency ward for suspicion of ACS before and after guideline implementation were similar. Significantly more patients were classified as suffering from atypical chest pain (39.6% versus 47.0%; P = 0.006) after guideline implementation. Guidelines availability was associated with significantly more formal diagnoses (79.9% versus 92.9%; P < 0.0001) and risk stratification (53.7% versus 65.4%, P < 0.0001) at the end of initial assessment. Conclusion. Guidelines implementation, along with availability of a cardiology consultant in the emergency room had a positive impact on initial assessment of patients evaluated for suspicion of ACS. It led to increased confidence in diagnosis and stratification by risk, which are the first steps in initiating effective treatment for this common conditio

FLYSNPdb: a high-density SNP database of Drosophila melanogaster

FLYSNPdb provides high-resolution single nucleotide polymorphism (SNP) data of Drosophila melanogaster. The database currently contains 27 367 polymorphisms, including >3700 indels (insertions/deletions), covering all major chromsomes. These SNPs are clustered into 2238 markers, which are evenly distributed with an average density of one marker every 50.3 kb or 6.6 genes. SNPs were identified automatically, filtered for high quality and partly manually curated. The database provides detailed information on the SNP data including molecular and cytological locations (genome Releases 3–5), alleles of up to five commonly used laboratory stocks, flanking sequences, SNP marker amplification primers, quality scores and genotyping assays. Data specific for a certain region, particular stocks or a certain genome assembly version are easily retrievable through the interface of a publicly accessible website (http://flysnp.imp.ac.at/flysnpdb.php)

Endothelial mineralocorticoid receptor activation mediates endothelial dysfunction in diet-induced obesity

Received 22 July 2012; revised 29 January 2013; accepted 4 March 2013Aims Aldosterone plays a crucial role in cardiovascular disease. ‘Systemic' inhibition of its mineralocorticoid receptor (MR) decreases atherosclerosis by reducing inflammation and oxidative stress. Obesity, an important cardiovascular risk factor, is an inflammatory disease associated with increased plasma aldosterone levels. We have investigated the role of the ‘endothelial' MR in obesity-induced endothelial dysfunction, the earliest stage in atherogenesis. Methods and results C57BL/6 mice were exposed to a normal chow diet (ND) or a high-fat diet (HFD) alone or in combination with the MR antagonist eplerenone (200 mg/kg/day) for 14 weeks. Diet-induced obesity impaired endothelium-dependent relaxation in response to acetylcholine, whereas eplerenone treatment of obese mice prevented this. Expression analyses in aortic endothelial cells isolated from these mice revealed that eplerenone attenuated expression of pro-oxidative NADPH oxidase (subunits p22phox, p40phox) and increased expression of antioxidative genes (glutathione peroxidase-1, superoxide dismutase-1 and -3) in obesity. Eplerenone did not affect obesity-induced upregulation of cyclooxygenase (COX)-1 or prostacyclin synthase. Endothelial-specific MR deletion prevented endothelial dysfunction in obese (exhibiting high ‘endogenous' aldosterone) and in ‘exogenous' aldosterone-infused lean mice. Pre-incubation of aortic rings from aldosterone-treated animals with the COX-inhibitor indomethacin restored endothelial function. Exogenous aldosterone administration induced endothelial expression of p22phox in the presence, but not in the absence of the endothelial MR. Conclusion Obesity-induced endothelial dysfunction depends on the ‘endothelial' MR and is mediated by an imbalance of oxidative stress-modulating mechanisms. Therefore, MR antagonists may represent an attractive therapeutic strategy in the increasing population of obese patients to decrease vascular dysfunction and subsequent atherosclerotic complication