Dynamics of Wind Setdown at Suez and the Eastern Nile Delta

BACKGROUND: Wind setdown is the drop in water level caused by wind stress acting on the surface of a body of water for an extended period of time. As the wind blows, water recedes from the upwind shore and exposes terrain that was formerly underwater. Previous researchers have suggested wind setdown as a possible hydrodynamic explanation for Moses crossing the Red Sea, as described in Exodus 14. METHODOLOGY/PRINCIPAL FINDINGS: This study analyzes the hydrodynamic mechanism proposed by earlier studies, focusing on the time needed to reach a steady-state solution. In addition, the authors investigate a site in the eastern Nile delta, where the ancient Pelusiac branch of the Nile once flowed into a coastal lagoon then known as the Lake of Tanis. We conduct a satellite and modeling survey to analyze this location, using geological evidence of the ancient bathymetry and a historical description of a strong wind event in 1882. A suite of model experiments are performed to demonstrate a new hydrodynamic mechanism that can cause an angular body of water to divide under wind stress, and to test the behavior of our study location and reconstructed topography. CONCLUSIONS/SIGNIFICANCE: Under a uniform 28 m/s easterly wind forcing in the reconstructed model basin, the ocean model produces an area of exposed mud flats where the river mouth opens into the lake. This land bridge is 3-4 km long and 5 km wide, and it remains open for 4 hours. Model results indicate that navigation in shallow-water harbors can be significantly curtailed by wind setdown when strong winds blow offshore

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Colliding Worlds: Asteroid research and the legitimization of war in space

Accepted versio

A reference map of the human binary protein interactome.

Global insights into cellular organization and genome function require comprehensive understanding of the interactome networks that mediate genotype-phenotype relationships(1,2). Here we present a human 'all-by-all' reference interactome map of human binary protein interactions, or 'HuRI'. With approximately 53,000 protein-protein interactions, HuRI has approximately four times as many such interactions as there are high-quality curated interactions from small-scale studies. The integration of HuRI with genome(3), transcriptome(4) and proteome(5) data enables cellular function to be studied within most physiological or pathological cellular contexts. We demonstrate the utility of HuRI in identifying the specific subcellular roles of protein-protein interactions. Inferred tissue-specific networks reveal general principles for the formation of cellular context-specific functions and elucidate potential molecular mechanisms that might underlie tissue-specific phenotypes of Mendelian diseases. HuRI is a systematic proteome-wide reference that links genomic variation to phenotypic outcomes

FACT is recruited to the +1 nucleosome of transcribed genes and spreads in a Chd1-dependent manner

The histone chaperone FACT occupies transcribed regions where it plays prominent roles in maintaining chromatin integrity and preserving epigenetic information. How it is targeted to transcribed regions, however, remains unclear. Proposed models include docking on the RNA polymerase II (RNAPII) C-terminal domain (CTD), recruitment by elongation factors, recognition of modified histone tails, and binding partially disassembled nucleosomes. Here, we systematically test these and other scenarios in Saccharomyces cerevisiae and find that FACT binds transcribed chromatin, not RNAPII. Through a combination of high-resolution genome-wide mapping, single-molecule tracking, and mathematical modeling, we propose that FACT recognizes the +1 nucleosome, as it is partially unwrapped by the engaging RNAPII, and spreads to downstream nucleosomes aided by the chromatin remodeler Chd1. Our work clarifies how FACT interacts with genes, suggests a processive mechanism for FACT function, and provides a framework to further dissect the molecular mechanisms of transcription-coupled histone chaperoning

The GrADS project: Software support for high-level grid application development

Advances in networking technologies will soon make it possible to use the global information infrastructure in a qualitatively different way-as a computational as well as an information resource. As described in the recent book The Grid: Blueprint for a New Computing Infrastructure, this Grid will connect the nation's computers, databases, instruments, and people in a seamless web of computing and distributed intelligence, which can be used in an on-demand fashion as a problem-solving resource in many fields of human endeavor-and, in particular, science and engineering. The availability of grid resources will give rise to dramatically new classes of applications, in which computing resources are no longer localized but, rather, distributed, heterogeneous, and dynamic; computation is increasingly sophisticated and multidisciplinary; and computation is integrated into our daily lives and, hence, subject to stricter time constraints than at present. The impact of these new applications will be pervasive, ranging from new systems for scientific inquiry, through computing support for crisis management, to the use of ambient computing to enhance personal mobile computing environments. To realize this vision, significant scientific and technical obstacles must be overcome. Principal among these is usability. The goal of the Grid Application Development Software (GrADS) project is to simplify distributed heterogeneous computing in the same way that the World Wide Web simplified information sharing over the Internet. To that end, the project is exploring the scientific and technical problems that must be solved to make it easier for ordinary scientific users to develop, execute, and tune applications on the Grid. In this paper, the authors describe the vision and strategies underlying the GrADS project, including the base software architecture for grid execution and performance monitoring, strategies and tools for construction of applications from libraries of grid-aware components, and development of innovative new science and engineering applications that can exploit these new technologies to run effectively in grid environments