We have simulated the formation of a galaxy cluster in a Λ cold dark matter universe using 13 different codes modelling only gravity and non-radiative hydrodynamics (ramses, ART, arepo, hydra and ...nine incarnations of gadget). This range of codes includes particle-based, moving and fixed mesh codes as well as both Eulerian and Lagrangian fluid schemes. The various gadget implementations span classic and modern smoothed particle hydrodynamics (SPH) schemes. The goal of this comparison is to assess the reliability of cosmological hydrodynamical simulations of clusters in the simplest astrophysically relevant case, that in which the gas is assumed to be non-radiative. We compare images of the cluster at z = 0, global properties such as mass and radial profiles of various dynamical and thermodynamical quantities. The underlying gravitational framework can be aligned very accurately for all the codes allowing a detailed investigation of the differences that develop due to the various gas physics implementations employed. As expected, the mesh-based codes ramses, art and arepo form extended entropy cores in the gas with rising central gas temperatures. Those codes employing classic SPH schemes show falling entropy profiles all the way into the very centre with correspondingly rising density profiles and central temperature inversions. We show that methods with modern SPH schemes that allow entropy mixing span the range between these two extremes and the latest SPH variants produce gas entropy profiles that are essentially indistinguishable from those obtained with grid-based methods.
Building on the initial results of the nIFTy simulated galaxy cluster comparison, we compare and contrast the impact of baryonic physics with a single massive galaxy cluster, run with 11 ...state-of-the-art codes, spanning adaptive mesh, moving mesh, classic and modern smoothed particle hydrodynamics (SPH) approaches. For each code represented we have a dark-matter-only (DM) and non-radiative (NR) version of the cluster, as well as a full physics (FP) version for a subset of the codes. We compare both radial mass and kinematic profiles, as well as global measures of the cluster (e.g. concentration, spin, shape), in the NR and FP runs with that in the DM runs. Our analysis reveals good consistency ⪅20 per cent) between global properties of the cluster predicted by different codes when integrated quantities are measured within the virial radius R
200. However, we see larger differences for quantities within R
2500, especially in the FP runs. The radial profiles reveal a diversity, especially in the cluster centre, between the NR runs, which can be understood straightforwardly from the division of codes into classic SPH and non-classic SPH (including the modern SPH, adaptive and moving mesh codes); and between the FP runs, which can also be understood broadly from the division of codes into those that include active galactic nucleus feedback and those that do not. The variation with respect to the median is much larger in the FP runs with different baryonic physics prescriptions than in the NR runs with different hydrodynamics solvers.
Drawing on literary examples, this book helps readers better understand the full range of issues that older men face--from legacy and loss to health issues and grace. Looking at how older men's lives ...are documented in American fiction, the author examines works by some of the most important names in contemporary literature including Don DeLillo, Jonathan Franzen, Cormac McCarthy, Marilynne Robinson, Philip Roth, Jane Smiley, Anne Tyler, and John Updike.
In contrast to feminist theory or women’s studies, masculinity studies is a relatively new approach to analysing literature. This article discusses the state of literary masculinity studies and its ...relationship to sociological men’s studies and feminism. It highlights the intention of masculinity studies scholarship to expose the damaging impact of patriarchy on men (as well as women), and its aim to celebrate alternative masculinities over hegemonic ideals through an analysis of male protagonists. It also notes the criticisms brought against the theoretical approach: that men are already adequately represented in literary theory; that the approach can be either universalist or too fragmented by sub‐categorisations of masculinity according to class, race, sexuality, etc. Giving an overview of the scholarship in the field, the article notes that while sexuality and ethnicity are becoming more frequent subjects for critics, issues of age – both youth and senescence – are relatively ignored, and suggests that this theme requires further examination in literary masculinity studies and in men’s studies more widely.
Although Philip Roth typically writes characters who are intent on pursuing lust rather than love, Sabbath's Theater (1995), while sexually explicit, portrays a protagonist who reveals a longing for ...attachment. Analyzed against other recent novels and Leslie Fiedler's thesis that fictional American men eschew family responsibilities and women, this article indicates that far from celebrating infidelity, the novel suggests that this immature masculine identity brings only isolation and regret.
Equally influential in this decision might be the older actors, writers, and directors working in the industry; as Sally Chivers explains, The ongoing influence of the famous among aging boomers-and ...the latter's demographic weight-has resulted in a growing number of notable actors, like Harrison Ford, remaining onscreen later into their lives, unafraid to look if not act their ages, and changing the "face" of Hollywood, (xv) Clearly, then, Hollywood is motivated, as ever, by monetary gain, but this notwithstanding the fact remains that the demographics of stars and storylines are diversifying to include those in older age. ...while the female protagonists in these films have issues of self-confidence and are clearly aware of the social stigma against mature women, they subvert it through creativity and independence.
This article considers the negotiation of masculinity that takes place within a family context, juxtaposing Raewyn Connell's concept of hegemonic masculinity with one that is more aligned with the ...collective. Taking Philip Roth's 2003 novel The Plot Against America, the article uses the character of Herman Roth as a case study. Despite Roth's reputation as a fundamentally masculine writer, and one who has not always represented the family as a positive force on individual masculine identity, this novel portrays a father who is responsive to circumstance and whose masculinity evolves according to his family's needs.
Since these critics' work on the body spans several texts and has developed over time, it is difficult to encapsulate the ideas of either Baudrillard or Butler in a simple summary, but the statting ...points of their theses can nonetheless be identified. The Swede's youthful athleticism therefore carries the suggestion of success later in life. ...his sign value (the social status afforded to his handsome appearance) is strengthened because it is juxtaposed against the image of his brother. ...it shows that perfection cannot be continued indefinitely, that either the illusion breaks or the individual does. ...his initial image of physical difference is an indicator of what is to come.
Employing the work of Jean Baudrillard and Judith Butler, this article considers the body as a site of meaning in Philip Roth'sAmerican Pastoral(1997). Concentrating on Seymour “the Swede” Levov, the ...analysis discusses the impact of appearance on the formation of masculine identity. Also addressed are notions of ownership and interpretation within this process, and the article pays particular attention to evaluating the role that outside agency has on creating an individual's sense of self.
Tumors exhibit intratumor heterogeneity in both genetic make-up and phenotypic traits such as morphology, cell cycle status and gene expression. Although heterogeneity has been long recognized, its ...biological and clinical significance is not fully understood. To determine the relative contribution of genetic versus epigenetic heterogeneity to therapeutic resistance and relapse in childhood acute lymphoblastic leukemia (cALL), we have developed a mouse model that affords "real-time" longitudinal analysis of subclonal dynamics.
The mouse model allows the engraftment of primary leukemic cells from an individual patient into multiple xenograft recipients, half of which are then treated with a combination of vincristine and dexamethasone. By assessing the reproducibility of independent outcomes, one can distinguish between deterministic and stochastic mechanisms of selection during therapy. We have used automated multicolor fluorescence in situ hybridization (mFISH) for the most frequent drivers of the leukemia (ETV6, RUNX1, PAX5, P16) to track the fate of individual genetic subclones. By comparing clonal composition in control and treated mice pre- and post-chemotherapy we demonstrate that, while treatment of sensitive ALLs results in a striking reduction in leukemic burden, the overall extent of genetic diversity (measured by mean of the Shannon index of diversity) is unaffected. This suggests that resistance in ALL may be largely independent of genetic variegation. In light of recent data demonstrating aberrant RAG activation in ETV6-RUNX1 leukemia, we reasoned that our results could reflect convergent evolution. Because RAG mediated deletions recurrently target the same key B-cell pathways, it is possible that genetically distinct clones could display convergent phenotypes. To test this hypothesis, and extend our mutational analysis to whole genome resolution, we performed single-cell whole genome sequencing. We sequenced matching diagnostic and relapse samples, and further validated our mFISH data. This reveals unprecedented levels of intratumor heterogeneity, with individual cells carrying on average 37 copy number variations (CNVs), a large number of which are private. By resolving the genomic breakpoints of lesions to known drivers of disease we formally proved that convergent evolution can happen. Thus, we identified clones carrying the same lesion but distinct breakpoints, highlighting their independent origins.
Functional analysis based on limiting dilution secondary transplantation assays showed that chemotherapy enriches for cells with tumor propagating potential. Transcriptome analysis (RNAseq) of treated and untreated cells revealed that the former have distinct signatures shared amongst metastatic sites. Chemo-resistant cells displayed differences in cell cycle status and transcription rate, as well as differential activation of key signaling pathways (MAPK, Rap1 and Jak-Stat), and expression of cell adhesion molecules. Through gene set enrichment analysis we observed that resistant cells have features characteristic of more primitive hematopoietic cells, including concomitant up-regulation of hematopoietic stem cells and lympho-myeloid progenitors markers. Interestingly, following secondary transplantation global gene expression of treated cells largely reverted to a treatment-naïve signature.
Overall this analysis provides novel insight into the contribution of genetic and epigenetic heterogeneity to resistance to cytotoxic chemotherapy. In the case of cALL phenotypic heterogeneity appears to play a larger role than genetic diversity, particularly with regards to cell cycle state and developmental stage. Our data suggest that resistance is driven by a pre-existing population of immature cells with a distinct global gene expression signature and higher tumor propagating potential, and that genetic heterogeneity in cALL arises through independent acquisition of CNVs affecting the same gene or genes within the same pathway, thereby driving convergent phenotypic evolution. Such a view is consistent with the observation that distinct subclones appear to respond to chemotherapy-derived environmental pressure in a similar manner.
No relevant conflicts of interest to declare.
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