Event generation with SHERPA 1.1

In this paper the current release of the Monte Carlo event generator Sherpa, version 1.1, is presented. Sherpa is a general-purpose tool for the simulation of particle collisions at high-energy colliders. It contains a very flexible tree-level matrix-element generator for the calculation of hard scattering processes within the Standard Model and various new physics models. The emission of additional QCD partons off the initial and final states is described through a parton-shower model. To consistently combine multi-parton matrix elements with the QCD parton cascades the approach of Catani, Krauss, Kuhn and Webber is employed. A simple model of multiple interactions is used to account for underlying events in hadron--hadron collisions. The fragmentation of partons into primary hadrons is described using a phenomenological cluster-hadronisation model. A comprehensive library for simulating tau-lepton and hadron decays is provided. Where available form-factor models and matrix elements are used, allowing for the inclusion of spin correlations; effects of virtual and real QED corrections are included using the approach of Yennie, Frautschi and Suura.Comment: 47 pages, 21 figure

Future business and the role of purchasing and supply management: Opportunities for ‘business-not-as-usual’ PSM research

The raison d'être for this article is simple: traditional ways of researching, theorizing, and practicing purchasing and supply management (PSM) are no longer sufficient to ‘meet the moment’. Scholars need to advance a “business-not-as-usual” footing approach to their work, if they are to make a meaningful contribution to addressing the current and future emergencies, as highlighted by recent extreme weather and the COVID-19 pandemic. Yet, what can this, or should this, mean for a field rooted in traditional business thinking? This article builds on the Journal of Purchasing and Supply Management's (JPSM) 25th Anniversary Special Issue editorial (2019); members of the JPSM's editorial team advance their unique perspectives on what “business-not-as-usual” means for PSM. Specifically, we advocate both thinking much more widely, in scope and ambition, than we currently do, and simultaneously building our ability to comprehend supply chains in a more nuanced and granular way. We explore whether the bias toward positivist work has omitted potentially interesting findings, and viewpoints. This leads to a call to re-think how we approach our work: should the key criteria always be to focus on theory development or testing? Should academics “think bigger”? Turning to specific research themes, illustrations of how our current thinking can be challenged or broadened by addressing the circular economy, and role of purchasing and innovation. Specifically, the focus on the PSM function as an intrapreneur within the larger organization, and the role of innovation and technology in PSM work. Taken together, we hope the ideas and arguments presented here will inform and inspire ambitious and novel approaches to PSM research with significant and enduring impact on the transformation of business

Calmodulin Interaction with hEAG1 Visualized by FRET Microscopy

BACKGROUND: Ca(2+)-mediated regulation of ion channels provides a link between intracellular signaling pathways and membrane electrical activity. Intracellular Ca(2+) inhibits the voltage-gated potassium channel EAG1 through the direct binding of calmodulin (CaM). Three CaM binding sites (BD-C1: 674-683, BD-C2: 711-721, BD-N: 151-165) have been identified in a peptide screen and were proposed to mediate binding. The participation of the three sites in CaM binding to the native channel, however, remains unclear. METHODOLOGY/PRINCIPAL FINDINGS: Here we studied the binding of Ca(2+)/CaM to the EAG channel by visualizing the interaction between YFP-labeled CaM and Cerulean-labeled hEAG1 in mammalian cells by FRET. The results of our cellular approach substantiate that two CaM binding sites are predominantly involved; the high-affinity 1-8-14 based CaM binding domain in the N-terminus and the second C-terminal binding domain BD-C2. Mutations at these sites completely abolished CaM binding to hEAG1. CONCLUSIONS/SIGNIFICANCE: We demonstrated that the BD-N and BD-C2 binding domains are sufficient for CaM binding to the native channel, and, therefore, that BD-C1 is unable to bind CaM independently

Testing a communication assessment tool for ethically sensitive scenarios: Protocol of a validation study

Background: Although well-designed instruments to assess communication during medical interviews and complex encounters exist, assessment tools that differentiate between communication, empathy, decision-making, and moral judgment are needed to assess different aspects of communication during situations defined by ethical conflict. To address this need, we developed an assessment tool that differentiates competencies associated with practice in ethically challenging situations. The competencies are grouped into three distinct categories

Self‐pollination in island and mainland populations of the introduced hummingbird‐pollinated plant, Nicotiana glauca (Solanaceae)

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142032/1/ajb20672.pd

REST is a hypoxia-responsive transcriptional repressor

Cellular exposure to hypoxia results in altered gene expression in a range of physiologic and pathophysiologic states. Discrete cohorts of genes can be either up- or down-regulated in response to hypoxia. While the Hypoxia-Inducible Factor (HIF) is the primary driver of hypoxia-induced adaptive gene expression, less is known about the signalling mechanisms regulating hypoxia-dependent gene repression. Using RNA-seq, we demonstrate that equivalent numbers of genes are induced and repressed in human embryonic kidney (HEK293) cells. We demonstrate that nuclear localization of the Repressor Element 1-Silencing Transcription factor (REST) is induced in hypoxia and that REST is responsible for regulating approximately 20% of the hypoxia-repressed genes. Using chromatin immunoprecipitation assays we demonstrate that REST-dependent gene repression is at least in part mediated by direct binding to the promoters of target genes. Based on these data, we propose that REST is a key mediator of gene repression in hypoxia

Sequences Sufficient for Programming Imprinted Germline DNA Methylation Defined

Epigenetic marks are fundamental to normal development, but little is known about signals that dictate their placement. Insights have been provided by studies of imprinted loci in mammals, where monoallelic expression is epigenetically controlled. Imprinted expression is regulated by DNA methylation programmed during gametogenesis in a sex-specific manner and maintained after fertilization. At Rasgrf1 in mouse, paternal-specific DNA methylation on a differential methylation domain (DMD) requires downstream tandem repeats. The DMD and repeats constitute a binary switch regulating paternal-specific expression. Here, we define sequences sufficient for imprinted methylation using two transgenic mouse lines: One carries the entire Rasgrf1 cluster (RC); the second carries only the DMD and repeats (DR) from Rasgrf1. The RC transgene recapitulated all aspects of imprinting seen at the endogenous locus. DR underwent proper DNA methylation establishment in sperm and erasure in oocytes, indicating the DMD and repeats are sufficient to program imprinted DNA methylation in germlines. Both transgenes produce a DMD-spanning pit-RNA, previously shown to be necessary for imprinted DNA methylation at the endogenous locus. We show that when pit-RNA expression is controlled by the repeats, it regulates DNA methylation in cis only and not in trans. Interestingly, pedigree history dictated whether established DR methylation patterns were maintained after fertilization. When DR was paternally transmitted followed by maternal transmission, the unmethylated state that was properly established in the female germlines could not be maintained. This provides a model for transgenerational epigenetic inheritance in mice