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- Archfield, Stacey A., et al.
(author)
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Accelerating advances in continental domain hydrologic modeling
- 2015
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In: Water resources research. - 0043-1397 .- 1944-7973. ; 51:12, s. 10078-10091
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Journal article (peer-reviewed)abstract
- In the past, hydrologic modeling of surface water resources has mainly focused on simulating the hydrologic cycle at local to regional catchment modeling domains. There now exists a level of maturity among the catchment, global water security, and land surface modeling communities such that these communities are converging toward continental domain hydrologic models. This commentary, written from a catchment hydrology community perspective, provides a review of progress in each community toward this achievement, identifies common challenges the communities face, and details immediate and specific areas in which these communities can mutually benefit one another from the convergence of their research perspectives. Those include: (1) creating new incentives and infrastructure to report and share model inputs, outputs, and parameters in data services and open access, machine-independent formats for model replication or reanalysis; (2) ensuring that hydrologic models have: sufficient complexity to represent the dominant physical processes and adequate representation of anthropogenic impacts on the terrestrial water cycle, a process-based approach to model parameter estimation, and appropriate parameterizations to represent large-scale fluxes and scaling behavior; (3) maintaining a balance between model complexity and data availability as well as uncertainties; and (4) quantifying and communicating significant advancements toward these modeling goals.
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- Over, Bjorn, et al.
(author)
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Structural and conformational determinants of macrocycle cell permeability
- 2016
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In: Nature Chemical Biology. - New York : Nature Publishing Group. - 1552-4450 .- 1552-4469. ; 12:12, s. 1065-1074
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Journal article (peer-reviewed)abstract
- Macrocycles are of increasing interest as chemical probes and drugs for intractable targets like protein-protein interactions, but the determinants of their cell permeability and oral absorption are poorly understood. To enable rational design of cell-permeable macrocycles, we generated an extensive data set under consistent experimental conditions for more than 200 nonpeptidic, de novo-designed macrocycles from the Broad Institute's diversity-oriented screening collection. This revealed how specific functional groups, substituents and molecular properties impact cell permeability. Analysis of energy-minimized structures for stereo- and regioisomeric sets provided fundamental insight into how dynamic, intramolecular interactions in the 3D conformations of macrocycles may be linked to physicochemical properties and permeability. Combined use of quantitative structure-permeability modeling and the procedure for conformational analysis now, for the first time, provides chemists with a rational approach to design cell-permeable non-peptidic macrocycles with potential for oral absorption.
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- Slieker, Roderick C, et al.
(author)
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Identification of biomarkers for glycaemic deterioration in type 2 diabetes
- 2023
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In: Nature Communications. - 2041-1723. ; 14, s. 1-18
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Journal article (peer-reviewed)abstract
- We identify biomarkers for disease progression in three type 2 diabetes cohorts encompassing 2,973 individuals across three molecular classes, metabolites, lipids and proteins. Homocitrulline, isoleucine and 2-aminoadipic acid, eight triacylglycerol species, and lowered sphingomyelin 42:2;2 levels are predictive of faster progression towards insulin requirement. Of ~1,300 proteins examined in two cohorts, levels of GDF15/MIC-1, IL-18Ra, CRELD1, NogoR, FAS, and ENPP7 are associated with faster progression, whilst SMAC/DIABLO, SPOCK1 and HEMK2 predict lower progression rates. In an external replication, proteins and lipids are associated with diabetes incidence and prevalence. NogoR/RTN4R injection improved glucose tolerance in high fat-fed male mice but impaired it in male db/db mice. High NogoR levels led to islet cell apoptosis, and IL-18R antagonised inflammatory IL-18 signalling towards nuclear factor kappa-B in vitro. This comprehensive, multi-disciplinary approach thus identifies biomarkers with potential prognostic utility, provides evidence for possible disease mechanisms, and identifies potential therapeutic avenues to slow diabetes progression.
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- Zhu, B., et al.
(author)
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X-ray emission associated with radiative recombination for Pb82+ ions at threshold energies
- 2022
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In: Physical Review A: covering atomic, molecular, and optical physics and quantum information. - 2469-9926 .- 2469-9934. ; 105:5
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Journal article (peer-reviewed)abstract
- For decelerated bare lead ions at a low beam energy of 10 MeV/u, the x-ray emission associated with radiative recombination (RR) at threshold energies has been studied at the electron cooler of CRYRING@ESR at GSI, Darmstadt. In our experiment, we observed the full x-ray emission pattern by utilizing dedicated x-ray detection chambers installed at 0∘ and 180∘ observation geometry. Most remarkably, no line distortion effects due to delayed emission are present in the well-defined x-ray spectra, spanning a wide range of x-ray energies (from about 5 to 100 keV), which enables us to identify fine-structure resolved Lyman, Balmer, and Paschen x-ray lines along with the RR transitions into the K, L, and M shells of the ions. For comparison with theory, an elaborate theoretical model is established taking into account the initial population distribution via RR for all atomic levels up to Rydberg states with principal quantum number n=165 in combination with time-dependent feeding transitions. Within the statistical accuracy, the experimental data are in very good agreement with the results of rigorous relativistic predictions. Most notably, this comparison sheds light on the contribution of prompt and delayed x-ray emission (up to 70 ns) to the observed x-ray spectra, originating in particular from yrast transitions into inner shells.
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