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Rhesus Monkey Rhadinovirus Uses Eph Family Receptors for Entry into B Cells and Endothelial Cells but Not Fibroblasts
Cellular Ephrin receptor tyrosine kinases (Ephrin receptors, Ephs) were found to interact efficiently with the gH/gL glycoprotein complex of the rhesus monkey rhadinovirus (RRV). Since EphA2 was recently identified as a receptor for the Kaposi's sarcoma-associated herpesvirus (KSHV) (Hahn et al., Nature Medicine 2012), we analyzed RRV and KSHV in parallel with respect to Eph-binding and Eph-dependent entry. Ten of the 14 Eph proteins, including both A- and B-type, interacted with RRV gH/gL. Two RRV strains with markedly different gH/gL sequences exhibited similar but slightly different binding patterns to Ephs. gH/gL of KSHV displayed high affinity towards EphA2 but substantially weaker binding to only a few other Ephs of the A-type. Productive entry of RRV 26-95 into B cells and into endothelial cells was essentially completely dependent upon Ephs since expression of a GFP reporter cassette from recombinant virus could be blocked to greater than 95% by soluble Eph decoys using these cells. In contrast, entry of RRV into fibroblasts and epithelial cells was independent of Ephs by these same criteria. Even high concentrations and mixtures of soluble Eph decoys were not able to reduce by any appreciable extent the number of fibroblasts and epithelial cells productively entered by RRV. Thus, RRV is similar to its close relative KSHV in the use of Eph family receptors for productive entry into B cells and endothelial cells. However, RRV uses a separate, distinct, Eph-independent pathway for productive entry into fibroblasts and epithelial cells. Whether KSHV also uses an Eph-independent pathway in some circumstances or to some extent remains to be determined
New Coordinate Systems for Axisymmetric Black Hole Collisions
We describe a numerical grid generating procedure to construct new classes of
orthogonal coordinate systems that are specially adapted to binary black hole
spacetimes. The new coordinates offer an alternative approach to the
conventional \v{C}ade\v{z} coordinates, in addition to providing a potentially
more stable and flexible platform to extend previous calculations of binary
black hole collisions.Comment: 3 pages, 5 postscript figures, LaTeX, uses mprocl.sty (available at
http://shemesh.fiz.huji.ac.il/MG8/submission.html) To appear in the
proceedings of the Marcel Grossmann 8 (Jerusalem, 1997
Genome-scale analysis identifies paralog lethality as a vulnerability of chromosome 1p loss in cancer.
Functional redundancy shared by paralog genes may afford protection against genetic perturbations, but it can also result in genetic vulnerabilities due to mutual interdependency1-5. Here, we surveyed genome-scale short hairpin RNA and CRISPR screening data on hundreds of cancer cell lines and identified MAGOH and MAGOHB, core members of the splicing-dependent exon junction complex, as top-ranked paralog dependencies6-8. MAGOHB is the top gene dependency in cells with hemizygous MAGOH deletion, a pervasive genetic event that frequently occurs due to chromosome 1p loss. Inhibition of MAGOHB in a MAGOH-deleted context compromises viability by globally perturbing alternative splicing and RNA surveillance. Dependency on IPO13, an importin-β receptor that mediates nuclear import of the MAGOH/B-Y14 heterodimer9, is highly correlated with dependency on both MAGOH and MAGOHB. Both MAGOHB and IPO13 represent dependencies in murine xenografts with hemizygous MAGOH deletion. Our results identify MAGOH and MAGOHB as reciprocal paralog dependencies across cancer types and suggest a rationale for targeting the MAGOHB-IPO13 axis in cancers with chromosome 1p deletion
Software engineering to sustain a high-performance computing scientific application: QMCPACK
We provide an overview of the software engineering efforts and their impact
in QMCPACK, a production-level ab-initio Quantum Monte Carlo open-source code
targeting high-performance computing (HPC) systems. Aspects included are: (i)
strategic expansion of continuous integration (CI) targeting CPUs, using GitHub
Actions runners, and NVIDIA and AMD GPUs in pre-exascale systems, using
self-hosted hardware; (ii) incremental reduction of memory leaks using
sanitizers, (iii) incorporation of Docker containers for CI and
reproducibility, and (iv) refactoring efforts to improve maintainability,
testing coverage, and memory lifetime management. We quantify the value of
these improvements by providing metrics to illustrate the shift towards a
predictive, rather than reactive, sustainable maintenance approach. Our goal,
in documenting the impact of these efforts on QMCPACK, is to contribute to the
body of knowledge on the importance of research software engineering (RSE) for
the sustainability of community HPC codes and scientific discovery at scale.Comment: Accepted at the first US-RSE Conference, USRSE2023,
https://us-rse.org/usrse23/, 8 pages, 3 figures, 4 table
Recommendations of the LHC Dark Matter Working Group: Comparing LHC searches for heavy mediators of dark matter production in visible and invisible decay channels
Weakly-coupled TeV-scale particles may mediate the interactions between
normal matter and dark matter. If so, the LHC would produce dark matter through
these mediators, leading to the familiar "mono-X" search signatures, but the
mediators would also produce signals without missing momentum via the same
vertices involved in their production. This document from the LHC Dark Matter
Working Group suggests how to compare searches for these two types of signals
in case of vector and axial-vector mediators, based on a workshop that took
place on September 19/20, 2016 and subsequent discussions. These suggestions
include how to extend the spin-1 mediated simplified models already in
widespread use to include lepton couplings. This document also provides
analytic calculations of the relic density in the simplified models and reports
an issue that arose when ATLAS and CMS first began to use preliminary numerical
calculations of the dark matter relic density in these models.Comment: 19 pages, 4 figures; v2: author list and LaTeX problem fixe
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