WireWall: a new approach to coastal wave hazard monitoring

WireWall will be the first agile in situ system to make field measurements of overtopping on a wave-by-wave basis. Such data will enable site-specific calibration of (i) numerical tools used in sea defence design, (ii) flood forecasting models and (iii) public safety tolerances used by shoreline managers. The new approach transfers existing laboratory and offshore wave monitoring capabilities to the problem of coastal hazard monitoring. The capacitance wire system will collect high frequency field data to quantify wave overtopping velocity and volume. Our approach will replace the use of water collection tanks, which provide very limited information, are cumbersome, and hence rarely deployed. The method will use a coupled modelling-observational-modelling approach. Industry standard overtopping tools will generate a numerical dataset of plausible overtopping conditions at our study site Crosby (NW England). This data will inform the configuration of the wire units to be used in dockside and flume tests prior to the design of the field rig. The newly collected field observations will allow site-specific calibration and validation of the numerical tools, which will then be applied for a range of storm and beach conditions to develop site-specific overtopping safety tolerances and identify overtopping trigger levels for the existing sea wall

Pancreatic cancer 3D cell line organoids (CLOs) maintain the phenotypic characteristics of organoids and accurately reflect the cellular architecture and heterogeneity In vivo

Pancreatic cancer is a highly lethal disease. Therapeutic resistance to chemotherapy is a major cause of treatment failure and recurrence in pancreatic cancer. Organoids derived from cancer stem cells (CSC) are promising models for the advancement of personalised therapeutic responses to inform clinical decisions. However, scaling-up of 3D organoids for high-throughput screening is time-consuming and costly. Here, we successfully developed organoid-derived cell lines (2.5D) from 3D organoids; the cells were then expanded and recapitulated back into organoids known as cell line organoids (CLOs). The 2.5D lines were cultured long term into 2D established cell lines for downstream comparison analysis. Experimental characterisation of the models revealed that the proliferation of CLOs was slightly faster than that of parental organoids. The therapeutic response to chemotherapeutic agents in 3D CLOs and organoids showed a similar responsive profile. Compared to 3D CLOs and organoids, 2D cell lines tended to be less responsive to all the drugs tested. Stem cell marker expression was higher in either 3D CLOs or organoids compared to 2D cell lines. An in vivo tumorigenicity study found CLOs form tumours at a similar rate to organoids and retain enhanced CSC marker expression, indicating the plasticity of CSCs within the in vivo microenvironment

Rich-Club Phenomenon in the Interactome of P. falciparum—Artifact or Signature of a Parasitic Life Style?

Recent advances have provided a first experimental protein interaction map of the human malaria parasite P. falciparum, which appears to be remotely related to interactomes of other eukaryotes. Here, we present a comparative topological analysis of this experimentally determined web with a network of conserved interactions between proteins in S. cerevisiae, C. elegans and D. melanogaster that have an ortholog in Plasmodium. Focusing on experimental interactions, we find a significant presence of a “rich-club,” a topological characteristic that features an “oligarchy” of highly connected proteins being intertwined with one another. In complete contrast, the network of interologs and particularly the web of evolutionary-conserved interactions in P. falciparum lack this feature. This observation prompts the question of whether this result points to a topological signature of the parasite's biology, since experimentally obtained interactions widely cover parasite-specific functions. Significantly, hub proteins that appear in such an oligarchy revolve around invasion functions, shaping an island of parasite-specific activities in a sea of evolutionary inherited interactions. This presence of a biologically unprecedented network feature in the human malaria parasite might be an artifact of the quality and the methods to obtain interaction data in this organism. Yet, the observation that rich-club proteins have distinctive and statistically significant functions that revolve around parasite-specific activities point to a topological signature of a parasitic life style

Gene content evolution in the arthropods

Arthropods comprise the largest and most diverse phylum on Earth and play vital roles in nearly every ecosystem. Their diversity stems in part from variations on a conserved body plan, resulting from and recorded in adaptive changes in the genome. Dissection of the genomic record of sequence change enables broad questions regarding genome evolution to be addressed, even across hyper-diverse taxa within arthropods. Using 76 whole genome sequences representing 21 orders spanning more than 500 million years of arthropod evolution, we document changes in gene and protein domain content and provide temporal and phylogenetic context for interpreting these innovations. We identify many novel gene families that arose early in the evolution of arthropods and during the diversification of insects into modern orders. We reveal unexpected variation in patterns of DNA methylation across arthropods and examples of gene family and protein domain evolution coincident with the appearance of notable phenotypic and physiological adaptations such as flight, metamorphosis, sociality, and chemoperception. These analyses demonstrate how large-scale comparative genomics can provide broad new insights into the genotype to phenotype map and generate testable hypotheses about the evolution of animal diversity

Space Based Gravitational Wave Astronomy Beyond LISA

The Laser Interferometer Space Antenna (LISA) will open three decades of gravitational wave(GW) spectrum between 0.1 and 100 mHz, the mHz band [1]. This band is expected to be the richest part of the GW spectrum, in types of sources, numbers of sources, signal-to-noise ratios and discovery potential. When LISA opens the low-frequency window of the gravitational wave spectrum,around 2034, the surge of gravitational-wave astronomy will strongly compel a subsequent mission to further explore the frequency bands of the GW spectrum that can only be accessed from space. The 2020's is the time to start developing technology and studying mission concepts for a large-scale mission to be launched in the 2040's. The mission concept would then be proposed to Astro2030. Only space-based missions can access the GW spectrum between 108 and 1 Hz because of the Earth's seismic noise. This white paper surveys the science in this band and mission concepts that could accomplish that science. The proposed small scale activity is a technology development program that would support a range of concepts and a mission concept study to choose a specific mission concept for Astro2030. In this white paper, we will refer to a generic GW mission beyond LISA as bLISA

The NANOGrav Nine-year Data Set:Observations, Arrival Time Measurements, and Analysis of 37 Millisecond Pulsars

We present high-precision timing observations spanning up to nine years for 37 millisecond pulsars monitored with the Green Bank and Arecibo radio telescopes as part of the North American Nanohertz Observatory for Gravitational Waves (NANOGrav) project. We describe the observational and instrumental setups used to collect the data, and methodology applied for calculating pulse times of arrival; these include novel methods for measuring instrumental offsets and characterizing low signal-to-noise ratio timing results. The time of arrival data are fit to a physical timing model for each source, including terms that characterize time-variable dispersion measure and frequency-dependent pulse shape evolution. In conjunction with the timing model fit, we have performed a Bayesian analysis of a parameterized timing noise model for each source, and detect evidence for excess low-frequency, or "red," timing noise in 10 of the pulsars. For 5 of these cases this is likely due to interstellar medium propagation effects rather than intrisic spin variations. Subsequent papers in this series will present further analysis of this data set aimed at detecting or limiting the presence of nanohertz-frequency gravitational wave signals

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin