Global gyrokinetic simulations of ITG turbulence in the configuration space of the Wendelstein 7-X stellarator

We study the effect of turbulent transport in different magnetic configurations of the Weldenstein 7-X stellarator. In particular, we performed direct numerical simulations with the global gyrokinetic code GENE-3D, modeling the behavior of Ion Temperature Gradient turbulence in the Standard, High-Mirror, and Low-Mirror configurations of W7-X. We found that the Low-Mirror configuration produces more transport than both the High-Mirror and the Standard configurations. By comparison with radially local simulations, we have demonstrated the importance of performing global nonlinear simulations to predict the turbulent fluxes quantitatively

Overview of core impurity transport in the first divertor operation of Wendelstein 7-X

The impurity transport at Wendelstein 7-X during its most recent campaign is characterized and documented for a variety of different plasma scenarios. An overview of its dependence on several quantities is given, which allows identification of transport regimes and the major driver for impurity transport. Beyond this, a comparison with the impurity behavior in other fusion devices is now possible. In contrast to other stellarators, no density dependence of the impurity transport has been found. Additionally, the influence of the turbulence contribution to the overall transport is reflected in the dependence on various parameters, e.g. turbulent diffusion and density fluctuation amplitudes. With this database approach, one can now also apply scaling laws to make extrapolations about the impurity confinement in future plasma scenarios

Identification of Cisplatin-Regulated Metabolic Pathways in Pluripotent Stem Cells

The chemotherapeutic compound, cisplatin causes various kinds of DNA lesions but also triggers other pertubations, such as ER and oxidative stress. We and others have shown that treatment of pluripotent stem cells with cisplatin causes a plethora of transcriptional and post-translational alterations that, to a major extent, point to DNA damage response (DDR) signaling. The orchestrated DDR signaling network is important to arrest the cell cycle and repair the lesions or, in case of damage beyond repair, eliminate affected cells. Failure to properly balance the various aspects of the DDR in stem cells contributes to ageing and cancer. Here, we performed metabolic profiling by mass spectrometry of embryonic stem (ES) cells treated for different time periods with cisplatin. We then integrated metabolomics with transcriptomics analyses and connected cisplatin-regulated metabolites with regulated metabolic enzymes to identify enriched metabolic pathways. These included nucleotide metabolism, urea cycle and arginine and proline metabolism. Silencing of identified proline metabolic and catabolic enzymes indicated that altered proline metabolism serves as an adaptive, rather than a toxic response. A group of enriched metabolic pathways clustered around the metabolite S-adenosylmethionine, which is a hub for methylation and transsulfuration reactions and polyamine metabolism. Enzymes and metabolites with pro- or anti-oxidant functions were also enriched but enhanced levels of reactive oxygen species were not measured in cisplatin-treated ES cells. Lastly, a number of the differentially regulated metabolic enzymes were identified as target genes of the transcription factor p53, pointing to p53-mediated alterations in metabolism in response to genotoxic stress. Altogether, our findings reveal interconnecting metabolic pathways that are responsive to cisplatin and may serve as signaling modules in the DDR in pluripotent stem cells

A non-uniform semantic analysis of the Italian temporal connectives Prima and Dopo

In this paper, I argue that the temporal connective prima ('before') is a comparative adverb. The argument is based on a number of grammatical facts from Italian, showing that there is an asymmetry between prima and dopo ('after'). On the ground of their divergent behaviour, I suggest that dopo has a different grammatical status from prima. I propose a semantic treatment for prima that is based on an independently motivated analysis of comparatives which can be traced back to Seuren (1973). Dopo is analyzed instead as an atomic two-place predicate which contributes a binary relation over events to the sentence meaning. The different semantic treatments of the two connectives provide an explanation for the grammatical asymmetries considered at the outset; interestingly, it also sheds some light on other asymmetries between prima and dopo which are known to hold for the English temporal connectives before and after as well: these asymmetries are related to the veridicality properties, the distribution of NPIs, and the logical properties of these connectives first described in Anscombe (1964)

Global phosphoproteome profiling reveals unanticipated networks responsive to cisplatin treatment of embryonic stem cells

Cellular responses to DNA-damaging agents involve the activation of various DNA damage signaling and transduction pathways. Using quantitative and high-resolution tandem mass spectrometry, we determined global changes in protein level and phosphorylation site profiles following treatment of SILAC (stable isotope labeling by amino acids in cell culture)-labeled murine embryonic stem cells with the anticancer drug cisplatin. Network and pathway analyses indicated that processes related to the DNA damage response and cytoskeleton organization were significantly affected. Although the ATM (ataxia telangiectasia mutated) and ATR (ATM and Rad3-related) consensus sequence (S/T-Q motif) was significantly overrepresented among hyperphosphorylated peptides, about half of the >2-fold-upregulated phosphorylation sites based on the consensus sequence were not direct substrates of ATM and ATR. Eleven protein kinases mainly belonging to the mitogen-activated protein kinase (MAPK) family were identified as being regulated in their kinase domain activation loop. The biological importance of three of these kinases (cyclin-dependent kinase 7 [CDK7], Plk1, and KPCD1) in the protection against cisplatin-induced cytotoxicity was demonstrated by small interfering RNA (siRNA)-mediated knockdown. Our results indicate that the cellular response to cisplatin involves a variety of kinases and phosphatases not only acting in the nucleus but also regulating cytoplasmic targets, resulting in extensive cytoskeletal rearrangements. Integration of transcriptomic and proteomic data revealed a poor correlation between changes in the relative levels of transcripts and their corresponding proteins, but a large overlap in affected pathways at the levels of mRNA, protein, and phosphoprotein. This study provides an integrated view of pathways activated by genotoxic stress and deciphers kinases that play a pivotal role in regulating cellular processes other than the DNA damage response

Broadband Alfvénic excitation correlated to turbulence level in the Wendelstein 7-X stellarator plasmas

During the first operational phase (OP1) of the Wendelstein 7-X (W7-X) stellarator, poloidal magnetic field fluctuations, $\dot{B}_{\theta}$, were measured in several different plasma scenarios with a system of Mirnov coils. In the spectrograms, multiple frequency bands close together in frequency are observed below f = 600 kHz. Furthermore, a dominant feature is the appearance of a frequency band with the highest spectral amplitude centred between $f = 180-220$ kHz. The fluctuations are observed from the beginning of most W7-X plasmas of OP1, which were often operated solely with electron cyclotron resonance heating. The fluctuations show characteristics known from Alfvén waves and possibly Alfvén eigenmodes (AEs). However, the fast particle drive from heating sources, which is generally a driver necessary for the appearance of AEs in magnetic confinement plasmas, is absent in most of the analysed experiments. A characterization of the Alfvénic fluctuations measured during OP1 plasmas is possible using a newly developed tracking algorithm. In this paper, we extensively survey the different spectral properties of the fluctuations in correlation with plasma parameters and discuss possible driving mechanisms. The correlation studies of the dynamics of the possible ellipticity induced AEs indicate that Alfvén activity in the frequency interval between $f = 100-450$ kHz could be excited due to an interaction with turbulence, or profile effects also affecting the turbulence amplitude

Indefinites in comparatives

The goal of this paper is to explain the meaning and distribution of indefinites in comparatives, focusing on English some and any and German irgend-indefinites. We consider three competing theories of comparatives in combination with an alternative semantics of some and any, and a novel account of stressed irgend-indefinites. One of the resulting accounts, based on Heim’s analysis of comparatives, predicts all the relevant differences in quantificational force, and explains why free choice indefinites are licensed in comparatives