Precision Electroweak Tests of the Standard Model

The study of electron-positron collisions at LEP, together with additional measurements from other experiments, in particular those at SLC and at the Tevatron, has allowed for tests of the electroweak Standard Model with unprecedented accuracy. We review the results of the electroweak precision tests and their implications on the determination of the Standard Model parameters, in particular of the Higgs boson mass, and comment on the constraints for possible new physics effects.Comment: 16 pages 6 figures; to appear in a special issue of Physics Reports dedicated to CERN on the occasion of the laboratory's 50th anniversar

Electroweak Physics

The status of precision electroweak measurements as of summer 2002 is reviewed. The recent results on the anomalous magnetic moment of the muon and on neutrino-nucleon scattering are discussed. Precision results on the electroweak interaction obtained by the experiments at the SLC, LEP and TEVATRON colliders are presented. The experimental results are compared with the predictions of the minimal Standard Model and are used to constrain its parameters, including the mass of the Higgs boson. The final LEP results on the direct search for the Higgs boson of the Standard Model are presented.Comment: Plenary talk presented at the 31st ICHEP, Amsterdam, The Netherlands, July 24-31, 200

Electroweak corrections to γZ\gamma Z production at hadron colliders

In this paper we present the results from a calculation of the full electroweak one-loop corrections for $\gamma Z$ vector-boson pair production at hadron colliders. The cases of proton--antiproton as well as proton--proton collisions, at the Tevatron and the LHC, respectively, are considered. Results are presented for the distribution of the $\gamma Z$ invariant mass and for the transverse momentum of the final-state photon. The higher-order electroweak effects are numerically significant, in particular for probing possible anomalous gauge-boson couplings

Hypothermia and postconditioning after cardiopulmonary resuscitation reduce cardiac dysfunction by modulating inflammation, apoptosis and remodeling

Background: Mild therapeutic hypothermia following cardiac arrest is neuroprotective, but its effect on myocardial dysfunction that is a critical issue following resuscitation is not clear. This study sought to examine whether hypothermia and the combination of hypothermia and pharmacological postconditioning are cardioprotective in a model of cardiopulmonary resuscitation following acute myocardial ischemia. Methodology/Principal Findings: Thirty pigs (28–34 kg) were subjected to cardiac arrest following left anterior descending coronary artery ischemia. After 7 minutes of ventricular fibrillation and 2 minutes of basic life support, advanced cardiac life support was started according to the current AHA guidelines. After successful return of spontaneous circulation (n = 21), coronary perfusion was reestablished after 60 minutes of occlusion, and animals were randomized to either normothermia at 38°C, hypothermia at 33°C or hypothermia at 33°C combined with sevoflurane (each group n = 7) for 24 hours. The effects on cardiac damage especially on inflammation, apoptosis, and remodeling were studied using cellular and molecular approaches. Five animals were sham operated. Animals treated with hypothermia had lower troponin T levels (p<0.01), reduced infarct size (34±7 versus 57±12%; p<0.05) and improved left ventricular function compared to normothermia (p<0.05). Hypothermia was associated with a reduction in: (i) immune cell infiltration, (ii) apoptosis, (iii) IL-1beta and IL-6 mRNA up-regulation, and (iv) IL-1beta protein expression (p<0.05). Moreover, decreased matrix metalloproteinase-9 activity was detected in the ischemic myocardium after treatment with mild hypothermia. Sevoflurane conferred additional protective effects although statistic significance was not reached. Conclusions/Significance: Hypothermia reduced myocardial damage and dysfunction after cardiopulmonary resuscitation possible via a reduced rate of apoptosis and pro-inflammatory cytokine expression

Determination of the full deformation tensor by multi-Bragg fast scanning nano X-ray diffraction

International audienceThis work showcases a method to map the full deformation tensor in a single micro-sized crystal. It is shown that measuring the position of two Bragg reflections in reciprocal space is sufficient to obtain the full deformation tensor, if the condition of incompressibility of the material is imposed. This method is used to reveal the surface tension induced deformation at the edges of an as-grown single-crystal VO 2 microwire. All components of the deformation tensor of the microwire were measured down to an absolute value of 10 À4 in an 8 Â 14 mm projected area of the wire. With a beam-defined spatial resolution of 150 Â 150 nm, the measurement time was merely 2.5 h

Tribological and mechanical properties of lubricant filled microcapsules in thermoplastic composites

Polymeric materials with long lifetime and low frictional energy loss are frequently required for a broad range of applications. Microencapsulation of lubricating oils by in-situ polymerization (melamine-formaldehyde) and interfacial polymerization (polyurethane/polyurea) was used to obtain free-flowing powders, which can be used as additive for thermoplastic materials resulting in microcapsule-containing self-lubricating composites. The specific functionality of such composites is achieved via portioned and localised release of the lubricant in the areas of the interface, which experiences the highest degrees of stress and wear due to the friction. Friction-triggered on-demand release of the lubricating oil results in materials with higher wear resistance and potentially leading to new products with prolonged lifetime. In this study, different ratios of microcapsules were added in polyoxymethylene (POM) and polybutylterephthalat (PBT) matrices by using laboratory scale twin-screw extruder resulting in self-lubricating composite materials. The effect of such modification on the tribological and mechanical properties of the thermoplastic composites were investigated. Rotational ball on disc tests were used to investigate the wear loss and coefficient of friction for the composites with varied microcapsule concentrations. Tensile tests revealed decreased mechanical stability for the composites with higher microcapsule content regardless of microcapsule wall material composition. Addition of 5&nbsp;wt.-&nbsp;% of encapsulated lubricant oil led to the substantial decrease of the frictional and wear coefficients. Further increase of encapsulated lubricant oil content to 10&nbsp;wt.-% had a major decreasing impact on the mechanical properties, whilst the effect on the tribological performance was rather small

Integrative clinical transcriptome analysis reveals TMPRSS2-ERG dependency of prognostic biomarkers in prostate adenocarcinoma

In prostate adenocarcinoma (PCa), distinction between indolent and aggressive disease is challenging. Around 50% of PCa are characterized by TMPRSS2-ERG (T2E)-fusion oncoproteins defining two molecular subtypes (T2E-positive/negative). However, current prognostic tests do not differ between both molecular subtypes, which might affect outcome prediction. To investigate gene-signatures associated with metastasis in T2E-positive and T2E-negative PCa independently, we integrated tumor transcriptomes and clinicopathological data of two cohorts (total n = 783), and analyzed metastasis-associated gene- signatures regarding the T2E-status. Here, we show that the prognostic value of biomarkers in PCa critically depends on the T2E-status. Using gene-set enrichment analyses, we uncovered that metastatic T2E-positive and T2E-negative PCa arecharacterized by distinct gene-signatures. In addition, by testing genes shared by several functional gene-signatures for theirassociation with event-free survival in a validation cohort (n=272), we identifiedfive genes (ASPN,BGN,COL1A1,RRM2andTYMS)—three of which are included in commercially available prognostic tests—whose high expression was significantlyassociated with worse outcome exclusively in T2E-negative PCa. Among these genes,RRM2andTYMSwere validated byimmunohistochemistry in another validation cohort (n=135), and several of them proved to add prognostic information tocurrent clinicopathological predictors, such as Gleason score, exclusively for T2E-negative patients. No prognostic biomarkerswere identified exclusively for T2E-positive tumors. Collectively, our study discovers that the T2E-status, which ispersenot astrong prognostic biomarker, crucially determines the prognostic value of other biomarkers. Our data suggest that themolecular subtype needs to be considered when applying prognostic biomarkers for outcome prediction in PCa. What’s new? Genetic rearrangements involving androgen-regulated transmembrane protease serine 2 and genes from the ETS transcription factor family (T2E), most commonly ERG and ETV1, occur in half of prostate cancers but are currently not considered in risk predictions. The authors integrate clinical and transcriptomic data from multiple studies and show that the prognostic value of biomarkers critically depends on the T2E-status. They identify five biomarkers that predict negative outcome exclusively in T2E-negative prostate cancers, which has implications for outcome prediction based on the molecular subtype.Deutsche Forschungsgemeinschaft 391665916Deutsche Krebshilfe 70112257Dr Leopold and Carmen Ellinger FoundationDr Rolf M. Schwiete FoundationFriedrich-Baur FoundationGert and Susanna Mayer FoundationKind-Philipp FoundationMatthias-Lackas FoundationMehr LEBEN fur Krebskranke Kinder-Bettina-Brau-StiftungWilhelm Sander-Stiftung 2016.167.

Therapeutic targeting of the PLK1-PRC1-axis triggers cell death in genomically silent childhood cancer

Chromosomal instability (CIN) is a hallmark of cancer1. Yet, many childhood cancers, such as Ewing sarcoma (EwS), feature remarkably ‘silent’ genomes with minimal CIN2. Here, we show in the EwS model how uncoupling of mitosis and cytokinesis via targeting protein regulator of cytokinesis 1 (PRC1) or its activating polo-like kinase 1 (PLK1) can be employed to induce fatal genomic instability and tumor regression. We find that the EwS-specific oncogenic transcription factor EWSR1-FLI1 hijacks PRC1, which physiologically safeguards controlled cell division, through binding to a proximal enhancer-like GGAA-microsatellite, thereby promoting tumor growth and poor clinical outcome. Via integration of transcriptome-profiling and functional in vitro and in vivo experiments including CRISPR-mediated enhancer editing, we discover that high PRC1 expression creates a therapeutic vulnerability toward PLK1 inhibition that can repress even chemo-resistant EwS cells by triggering mitotic catastrophe. Collectively, our results exemplify how aberrant PRC1 activation by a dominant oncogene can confer malignancy but provide opportunities for targeted therapy, and identify PRC1 expression as an important determinant to predict the efficacy of PLK1 inhibitors being used in clinical trials

High specificity of BCL11B and GLG1 for EWSR1-FLI1 and EWSR1-ERG positive Ewing sarcoma

Ewing sarcoma (EwS) is an aggressive cancer displaying an undifferentiated small-round-cell histomorphology that can be easily confused with a broad spectrum of differential diagnoses. Using comparative transcriptomics and immunohistochemistry (IHC), we previously identified BCL11B and GLG1 as potential specific auxiliary IHC markers for EWSR1-FLI1-positive EwS. Herein, we aimed at validating the specificity of both markers in a far larger and independent cohort of EwS (including EWSR1-ERG-positive cases) and differential diagnoses. Furthermore, we evaluated their intra-tumoral expression heterogeneity. Thus, we stained tissue microarrays from 133 molecularly confirmed EwS cases and 320 samples from morphological mimics, as well as a series of patient-derived xenograft (PDX) models for BCL11B, GLG1, and CD99, and systematically assessed the immunoreactivity and optimal cut-offs for each marker. These analyses demonstrated that high BCL11B and/or GLG1 immunoreactivity in CD99-positive cases had a specificity of 97.5% and an accuracy of 87.4% for diagnosing EwS solely by IHC, and that the markers were expressed by EWSR1-ERG-positive EwS. Only little intra-tumoral heterogeneity in immunoreactivity was observed for differential diagnoses. These results indicate that BCL11B and GLG1 may help as specific auxiliary IHC markers in diagnosing EwS in conjunction with CD99, especially if confirmatory molecular diagnostics are not available.Barbara und Hubertus Trettner foundationDeutsche Forschungsgemeinschaft DFG 391665916Deutsche Stiftung fur junge Erwachsene mit KrebsDr. Leopold und Carmen Ellinger foundationDr. Rolf M. Schwiete foundationDr. Rudolf und Brigitte Zenner StiftungFriedrich-Baur foundationGerman Cancer Aid DKH-70112257German Cancer Aid DKH-108128German Cancer Aid DKH-70112018German Cancer Aid DKH-70113421

Characterization of encapsulated graphene layers using extreme ultraviolet coherence tomography

Many applications of two-dimensional materials such as graphene require the encapsulation in bulk material. While a variety of methods exist for the structural and functional characterization of uncovered 2D materials, there is a need for methods that image encapsulated 2D materials as well as the surrounding matter. In this work, we use extreme ultraviolet coherence tomography to image graphene flakes buried beneath 200 nm of silicon. We show that we can identify mono-, bi-, and trilayers of graphene and quantify the thickness of the silicon bulk on top by measuring the depth-resolved reflectivity. Furthermore, we estimate the quality of the graphene interface by incorporating a model that includes the interface roughness. These results are verified by atomic force microscopy and prove that extreme ultraviolet coherence tomography is a suitable tool for imaging 2D materials embedded in bulk materials