Quantifying the influence of surface processes on subsurface geometry in deltaic environments

River deltas are densely populated and dynamically changing environments located at the boundary between land and sea. Population demands for water as well as rising sea levels are increasingly threatening aquifer water quality in deltaic regions. The rate at which aquifer contamination by salt water or other contaminants occurs is dictated, in part, by the arrangement of sediment within the subsurface. In this work, we examine the heterogeneity of the subsurface from a structural vantage to better understand how surface processes and geometry are linked to subsurface architecture. The numerical model, DeltaRCM, is applied to simulate delta evolution under a variety of input conditions. The resulting model outputs simulate 800 years during which the growing delta generates a subsurface volume that is over 40m deep. Surface channel properties and behavior, such as channel depths and channel planform decay rates are measured. Similarly, the structure of the sand bodies in the subsurface domain is evaluated. These different types of analyses, surface and subsurface, are ultimately compared to take a first-look at how channel properties in a deltaic environment may relate to subsurface structure and form. Broadly, expectations about channel trends and subsurface structure from the field of geomorphology are supported. Channel depths decrease with distance from the inlet, and as the input sand proportion increases. Similarly, the channelized fraction of the delta surface increases with higher input sand fraction values. In the subsurface, different types of channel behavior on the surface correspond to different structures. The sand bodies are larger when the surface channels are shallower and more mobile. In addition, the spatial continuity within strike sections (sections taken perpendicular to the inlet channel) increases with channel depth. Comparisons of the modeled subsurface with stochastically re-arranged replicates have confirmed the assertion that surface processes create unique subsurface structures. When the input proportion of sediment contains at least 40% sand by volume, the average size of the subsurface sand bodies follows a power-law relation with respect to surface channel depths and the average channelized fraction of the delta platform. The range of spatial entropy (disorder) also increases with channel depth. Within models, with increasing distance from the inlet both channel depths and spatial entropy ranges decrease. Changing the input sediment proportions over the course of the delta evolution provides mixed results. Some channel parameters like channel depth are indistinguishable from steady input cases, while others are influenced by the initial topographic setup. In the subsurface, variable sediment input proportions create vastly different sand body geometries depending on the rate of variation of the input sand proportion. When the input sand proportion is gradually increased, the average sand body size becomes very large; however when the sand input is abruptly increased, the mean sand body value is less than a steady sand input analog.Civil, Architectural, and Environmental Engineerin

Separate Ion Pathways in a Cl−/H+ Exchanger

CLC-ec1 is a prokaryotic CLC-type Cl−/H+ exchange transporter. Little is known about the mechanism of H+ coupling to Cl−. A critical glutamate residue, E148, was previously shown to be required for Cl−/H+ exchange by mediating proton transfer between the protein and the extracellular solution. To test whether an analogous H+ acceptor exists near the intracellular side of the protein, we performed a mutagenesis scan of inward-facing carboxyl-bearing residues and identified E203 as the unique residue whose neutralization abolishes H+ coupling to Cl− transport. Glutamate at this position is strictly conserved in all known CLCs of the transporter subclass, while valine is always found here in CLC channels. The x-ray crystal structure of the E203Q mutant is similar to that of the wild-type protein. Cl− transport rate in E203Q is inhibited at neutral pH, and the double mutant, E148A/E203Q, shows maximal Cl− transport, independent of pH, as does the single mutant E148A. The results argue that substrate exchange by CLC-ec1 involves two separate but partially overlapping permeation pathways, one for Cl− and one for H+. These pathways are congruent from the protein's extracellular surface to E148, and they diverge beyond this point toward the intracellular side. This picture demands a transport mechanism fundamentally different from familiar alternating-access schemes

Reproducibility Starts at the Source: R, Python, and Julia Packages for Retrieving USGS Hydrologic Data

Much of modern science takes place in a computational environment, and, increasingly, that environment is programmed using R, Python, or Julia. Furthermore, most scientific data now live on the cloud, so the first step in many workflows is to query a cloud database and load the response into a computational environment for further analysis. Thus, tools that facilitate programmatic data retrieval represent a critical component in reproducible scientific workflows. Earth science is no different in this regard. To fulfill that basic need, we developed R, Python, and Julia packages providing programmatic access to the U.S. Geological Survey’s National Water Information System database and the multi-agency Water Quality Portal. Together, these packages create a common interface for retrieving hydrologic data in the Jupyter ecosystem, which is widely used in water research, operations, and teaching. Source code, documentation, and tutorials for the packages are available on GitHub. Users can go there to learn, raise issues, or contribute improvements within a single platform, which helps foster better engagement and collaboration between data providers and their users

Molecular Pathogenesis of Post-Transplant Acute Kidney Injury: Assessment of Whole-Genome mRNA and MiRNA Profiles.

Acute kidney injury (AKI) affects roughly 25% of all recipients of deceased donor organs. The prevention of post-transplant AKI is still an unmet clinical need. We prospectively collected zero-hour, indication as well as protocol kidney biopsies from 166 allografts between 2011 and 2013. In this cohort eight cases with AKI and ten matched allografts without pathology serving as control group were identified with a follow-up biopsy within the first twelve days after engraftment. For this set the zero-hour and follow-up biopsies were subjected to genome wide microRNA and mRNA profiling and analysis, followed by validation in independent expression profiles of 42 AKI and 21 protocol biopsies for strictly controlling the false discovery rate. Follow-up biopsies of AKI allografts compared to time-matched protocol biopsies, further baseline adjustment for zero-hour biopsy expression level and validation in independent datasets, revealed a molecular AKI signature holding 20 mRNAs and two miRNAs (miR-182-5p and miR-21-3p). Next to several established biomarkers such as lipocalin-2 also novel candidates of interest were identified in the signature. In further experimental evaluation the elevated transcript expression level of the secretory leukocyte peptidase inhibitor (SLPI) in AKI allografts was confirmed in plasma and urine on the protein level (p<0.001 and p = 0.003, respectively). miR-182-5p was identified as a molecular regulator of post-transplant AKI, strongly correlated with global gene expression changes during AKI. In summary, we identified an AKI-specific molecular signature providing the ground for novel biomarkers and target candidates such as SLPI and miR-182-5p in addressing AKI

Connecting delta morphology, surface processes, and subsurface structure

Home to a disproportionate population relative to their areas, river deltas are critically important landscapes. Their locations at the interface of the land and sea make them particularly susceptible to sea level rise, while their vast extents limit characterization based on in situ observations alone. Consequently, remote sensing and numerical modeling methods and studies are needed to better understand the current processes occurring within these systems, as well as to estimate their future evolution. In this dissertation, a suite of remote sensing and numerical modeling methods are developed and applied to better understand current processes within deltas, and to project future changes. The first study is an assessment of the accuracy of discharge partitioning estimation from remotely sensed imagery of river delta networks. This analysis aggregates data from 15 site-specific studies to find that errors associated with graph-theoretic estimates of discharge partitioning are consistent across a diverse set of delta landscapes. In the second study, reduced-complexity modeling simulates the evolution and anthropogenic modification of idealized river deltas. Simulation of different hydrodynamic scenarios, and routing of passive particles through the landscape, enables characterizations of the impact that natural morphological differences, anthropogenic modifications, and different flow conditions have on material transport. The results suggest that material type exerts a first-order control over particle behavior, and human modifications to the landscape reduce hydrological connectivity. The third and fourth studies present reduced complexity modeling of deltaic evolution over hundreds of years to investigate the relationship between surface processes and subsurface form within deltaic environments in the context of their future evolution. In the third study, testing of different input sediment compositions and steady rates of sea level rise suggests that both variables influence surface morphology and subsurface connectivity. The fourth study considers the impact of sea level rise acceleration, and finds that the dynamic response of surface channels to an unsteady rate of sea level rise changes based on its magnitude and trajectory. These changes on the surface are mirrored to an extent in the subsurface, which can only be estimated from surface information if the sea level change is relatively steady for some period of time. The results of these studies provide guidance for both policy makers and managers of deltas, as it is clear that humans are significantly impacting the natural processes of these landscapes. Taken together, research conducted as part of this dissertation provides information about current processes and potential future evolution of delta landscapes.Civil, Architectural, and Environmental Engineerin

X-Ray Structures of the N- and C-Terminal Domains of a Coronavirus Nucleocapsid Protein: Implications for Nucleocapsid Formation

Coronaviruses cause a variety of respiratory and enteric diseases in animals and humans including severe acute respiratory syndrome. In these enveloped viruses, the filamentous nucleocapsid is formed by the association of nucleocapsid (N) protein with single-stranded viral RNA. The N protein is a highly immunogenic phosphoprotein also implicated in viral genome replication and in modulating cell signaling pathways. We describe the structure of the two proteolytically resistant domains of the N protein from infectious bronchitis virus (IBV), a prototype coronavirus. These domains are located at its N- and C-terminal ends (NTD and CTD, respectively). The NTD of the IBV Gray strain at 1.3-Å resolution exhibits a U-shaped structure, with two arms rich in basic residues, providing a module for specific interaction with RNA. The CTD forms a tightly intertwined dimer with an intermolecular four-stranded central β-sheet platform flanked by α helices, indicating that the basic building block for coronavirus nucleocapsid formation is a dimeric assembly of N protein. The variety of quaternary arrangements of the NTD and CTD revealed by the analysis of the different crystal forms delineates possible interfaces that could be used for the formation of a flexible filamentous ribonucleocapsid. The striking similarity between the dimeric structure of CTD and the nucleocapsid-forming domain of a distantly related arterivirus indicates a conserved mechanism of nucleocapsid formation for these two viral families

Cryoelectron Microscopy Structures of Rotavirus NSP2-NSP5 and NSP2-RNA Complexes: Implications for Genome Replication

The replication and packaging of the rotavirus genome, comprising 11 segments of double-stranded RNA, take place in specialized compartments called viroplasms, which are formed during infection and involve a coordinated interplay of multiple components. Two rotavirus nonstructural proteins, NSP2 (with nucleoside triphosphatase, single-stranded RNA [ssRNA] binding and helix-destabilizing activities) and NSP5, are essential in these events. Previous structural analysis of NSP2 showed that it is an octamer in crystals, obeying 4-2-2 crystal symmetry, with a large 35-Å central hole along the fourfold axis and deep grooves at one of the twofold axes. To ascertain that the solution structure of NSP2 is the same as that in the crystals and investigate how NSP2 interacts with NSP5 and RNA, we carried out single-particle cryoelectron microscopy (cryo-EM) analysis of NSP2 alone and in complexes with NSP5 and ssRNA at subnanometer resolution. Because full-length NSP5 caused severe aggregation upon mixing with NSP2, the deletion construct NSP5(66-188) was used in these studies. Our studies show that the solution structure of NSP2 is same as the crystallographic octamer and that both NSP5(66-188) and ssRNA bind to the grooves in the octamer, which are lined by positively charged residues. The fitting of the NSP2 crystal structure to cryo-EM reconstructions of the complexes indicates that, in contrast to the binding of NSP5(66-188), the binding of RNA induces noticeable conformational changes in the NSP2 octamer. Consistent with the observation that both NSP5 and RNA share the same binding site on the NSP2 octamer, filter binding assays showed that NSP5 competes with ssRNA binding, indicating that one of the functions of NSP5 is to regulate NSP2-RNA interactions during genome replication