50 research outputs found
Data Linkage to Improve Geriatric Oncology Research: A Feasibility Study
Older adults (aged 65 years and older) diagnosed with cancer account for most cancerârelated morbidity and mortality in the United States but are often underrepresented on clinical trials. Recent attention from a variety of professional, research, regulatory, and patient advocacy groups has centered on data linkage and data sharing as a means to capture patient information and outcomes outside of clinical trials to accelerate progress in the fight against cancer. The development of a more robust observational research data infrastructure would help to address gaps in the evidence base regarding optimal approaches to treating cancer among the growing and complex population of older adults. To demonstrate the feasibility of building such a resource, we linked information from a sample of older adults with cancer in North Carolina using three distinct, but complementary, data sources: (a) the Carolina Senior Registry, (b) the North Carolina Central Cancer Registry, and (c) North Carolina feeâforâservice Medicare claims data. A description of the linkage process, metrics, and characteristics of the final cohort is reported. This study highlights the potential for data linkage to improve the characterization of health status among older adults with cancer and the possibility to conduct passive followâup for outcomes of interest over time. Extensions of these linkage efforts in partnership with other institutions will enhance our ability to generate evidence that can inform the management of older adults with cancer
The Virtual Metabolic Human database: integrating human and gut microbiome metabolism with nutrition and disease
A multitude of factors contribute to complex diseases and can be measured with âomicsâ methods. Databases facilitate data interpretation for underlying mechanisms. Here, we describe the Virtual Metabolic Human (VMH, www.vmh.life) database encapsulating current knowledge of human metabolism within five interlinked resources âHuman metabolismâ, âGut microbiomeâ, âDiseaseâ, âNutritionâ, and âReconMapsâ. The VMH captures 5180 unique metabolites, 17 730 unique reactions, 3695 human genes, 255 Mendelian diseases, 818 microbes, 632 685 microbial genes and 8790 food items. The VMHâs unique features are (i) the hosting of the metabolic reconstructions of human and gut microbes amenable for metabolic modeling; (ii) seven human metabolic maps for data visualization; (iii) a nutrition designer; (iv) a user-friendly webpage and application-programming interface to access its content; (v) user feedback option for community engagement and (vi) the connection of its entities to 57 other web resources. The VMH represents a novel, interdisciplinary database for data interpretation and hypothesis generation to the biomedical community
Photodegradation of Ormetoprim in Aquaculture and Stream-Derived Dissolved Organic Matter
Ormetoprim (OMP) is an antibiotic approved for use in
the United
States to prevent the spread of disease in freshwater aquaculture.
It has been shown in the previous literature to be photochemically
stable to direct photolysis, but the role of photosensitization processes
in the presence of dissolved organic matter (DOM) on the rate of degradation
is not well understood. The present results show that water and DOM
(specifically the fulvic acid fraction) isolated from a eutrophic
aquaculture catfish pond and a nearby stream (Deer Creek) at the Mississippi
State University Delta Research and Extension Center facility in Stoneville,
MS, significantly increased the phototransformation of OMP relative
to direct photolysis. Similar results were reported for reference
fulvic acids obtained from the International Humic Substances Society.
Results from a combination of scavenging experiments and experiments
conducted under anoxic conditions indicate the indirect photodegradation
pathway occurs by hydroxyl radical, singlet oxygen attack, and reaction
with triplet excited-state DOM
Critical Evaluation of Implicit Solvent Models for Predicting Aqueous Oxidation Potentials of Neutral Organic Compounds
Quantum chemical implicit solvent
models are used widely to estimate
aqueous redox potentials. We compared the accuracy of several popular
implicit solvent models (SM8, SMD, C-PCM, IEF-PCM, and COSMO-RS) for
the prediction of aqueous single electron oxidation potentials of
a diverse test set of neutral organic compounds for which accurate
experimental oxidation potential and gas-phase ionization energy data
are available. Using a thermodynamic cycle, we decomposed the free
energy of oxidation into contributions arising from the gas-phase
adiabatic ionization energy, the solvation free energy of the closed-shell
neutral species, and the solvation free energy of the radical cation
species. For aqueous oxidation potentials, implicit solvent models
exhibited mean unsigned errors (MUEs) ranging from 0.27 to 0.50 V,
depending on the model. The principal source of error was attributed
to the computed solvation free energy of the oxidized radical cation.
Based on these results, a recommended implicit solvation approach
is the SMD model for the solvation free energy combined with CBS-QB3
for the gas-phase ionization energy. With this approach, the MUE in
computed oxidation potentials was 0.27 V, and the MUE in solvation
free energy of the charged open-shell species was 0.32 eV. This baseline
assessment provides a compiled benchmark test set of vetted experimental
data that may be used to judge newly developed solvation models for
their ability to produce improved predictions for aqueous oxidation
potentials and related properties
Explicit solvent simulations of the aqueous oxidation potential and reorganization energy for neutral molecules: Gas phase, linear solvent response, and non-linear response contributions
First principles simulations were used to predict aqueous one-electron oxidation potentials (E-ox) and associated half-cell reorganization energies (lambda(aq)) for aniline, phenol, methoxybenzene, imidazole, and dimethylsulfide. We employed quantum mechanical/molecular mechanical (QM/MM) molecular dynamics (MD) simulations of the oxidized and reduced species in an explicit aqueous solvent, followed by EOM-IP-CCSD computations with effective fragment potentials for diabatic energy gaps of solvated clusters, and finally thermodynamic integration of the non-linear solvent response contribution using classical MD. A priori predicted E-ox and lambda(aq) values exhibit mean absolute errors of 0.17 V and 0.06 eV, respectively, compared to experiment. We also disaggregate E-ox into several well-defined free energy properties, including the gas phase adiabatic free energy of ionization (7.73 to 8.82 eV), the solvent-induced shift in the free energy of ionization due to linear solvent response (-2.01 to -2.73 eV), and the contribution from non-linear solvent response (-0.07 to -0.14 eV). The linear solvent response component is further apportioned into contributions from the solvent-induced shift in vertical ionization energy of the reduced species (Delta VIEaq) and the solvent-induced shift in negative vertical electron affinity of the ionized species (Delta NVEA(aq)). The simulated Delta VIEaq and Delta NVEA(aq) are found to contribute the principal sources of uncertainty in computational estimates of E-ox and lambda(aq). Trends in the magnitudes of disaggregated solvation properties are found to correlate with trends in structural and electronic features of the solute. Finally, conflicting approaches for evaluating the aqueous reorganization energy are contrasted and discussed, and concluding recommendations are given
Exploring the aqueous vertical ionization of organic molecules by molecular simulation and liquid microjet photoelectron spectroscopy
To study the influence of aqueous solvent on the electronic energy levels of dissolved organic molecules, we conducted liquid microjet photoelectron spectroscopy (PES) measurements of the aqueous vertical ionization energies (VIEaq) of aniline (7.49 eV), veratrole alcohol (7.68 eV), and imidazole (8.51 eV). We also reanalyzed previously reported experimental PES data for phenol, phenolate, thymidine, and protonated imidazolium cation. We then simulated PE spectra by means of QM/MM molecular dynamics and EOM-IP-CCSD calculations with effective fragment potentials, used to describe the aqueous vertical ionization energies for six molecules, including aniline, phenol, veratrole alcohol, imidazole, methoxybenzene, and dimethylsulfide. Experimental and computational data enable us to decompose the VIEaq into elementary processes. For neutral compounds, the shift in VIE upon solvation, Delta VIEaq, was found to range from approximate to-0.5 to -0.91 eV. The Delta VIEaq was further explained in terms of the influence of deforming the gas phase solute into its solution phase conformation, the influence of solute hydrogen-bond donor and acceptor interactions with proximate solvent molecules, and the polarization of about 3000 outerlying solvent molecules. Among the neutral compounds, variability in Delta VIEaq appeared largely controlled by differences in solutesolvent hydrogen-bonding interactions. Detailed computational analysis of the flexible molecule veratrole alcohol reveals that the VIE is strongly dependent on molecular conformation in both gas and aqueous phases. Finally, aqueous reorganization energies of the oxidation half-cell ionization reaction were determined from experimental data or estimated from simulation for the six compounds aniline, phenol, phenolate, veratrole alcohol, dimethylsulfide, and methoxybenzene, revealing a surprising constancy of 2.06 to 2.35 eV
Controlling Factors in the Rates of Oxidation of Anilines and Phenols by Triplet Methylene Blue in Aqueous Solution
Anilines and phenols are structurally similar compound classes that both are susceptible to oxidation by excited state triplet sensitizers but undergo oxidation by different mechanisms. To gain an understanding of the factors that control the rate of oxidation of anilines and phenols by triplet excited states, a kinetic study was performed on the oxidation of substituted anilines and phenols by methylene blue. The rate constants of one-electron transfer from anilines to triplet state methylene blue and their dependence on the reaction free energy are well fit to a SandrosBoltzmann model. The observed rate constants are also well modeled when aniline oxidation potentials derived computationally are used. For phenols, the proton-coupled electron transfer rate constants were found to correlate primarily with O-H bond dissociation free energy and secondarily with phenol pK(a center dot) Rate constants for phenols could be modeled using computed bond dissociation free energies. These results provide a basis for predicting aniline and phenol oxidation rates, which could be valuable, for example, in assessing the likely persistence and fate of aniline- and phenol-based aqueous environmental pollutants
Exploring the Aqueous Vertical Ionization of Organic Molecules by Molecular Simulation and Liquid Microjet Photoelectron Spectroscopy
To
study the influence of aqueous solvent on the electronic energy
levels of dissolved organic molecules, we conducted liquid microjet
photoelectron spectroscopy (PES) measurements of the aqueous vertical
ionization energies (VIE<sub>aq</sub>) of aniline (7.49 eV), veratrole
alcohol (7.68 eV), and imidazole (8.51 eV). We also reanalyzed previously
reported experimental PES data for phenol, phenolate, thymidine, and
protonated imidazolium cation. We then simulated PE spectra by means
of QM/MM molecular dynamics and EOM-IP-CCSD calculations with effective
fragment potentials, used to describe the aqueous vertical ionization
energies for six molecules, including aniline, phenol, veratrole alcohol,
imidazole, methoxybenzene, and dimethylsulfide. Experimental and computational
data enable us to decompose the VIE<sub>aq</sub> into elementary processes.
For neutral compounds, the shift in VIE upon solvation, ÎVIE<sub>aq</sub>, was found to range from ââ0.5 to â0.91
eV. The ÎVIE<sub>aq</sub> was further explained in terms of
the influence of deforming the gas phase solute into its solution
phase conformation, the influence of solute hydrogen-bond donor and
acceptor interactions with proximate solvent molecules, and the polarization
of about 3000 outerlying solvent molecules. Among the neutral compounds,
variability in ÎVIE<sub>aq</sub> appeared largely controlled
by differences in soluteâsolvent hydrogen-bonding interactions.
Detailed computational analysis of the flexible molecule veratrole
alcohol reveals that the VIE is strongly dependent on molecular conformation
in both gas and aqueous phases. Finally, aqueous reorganization energies
of the oxidation half-cell ionization reaction were determined from
experimental data or estimated from simulation for the six compounds
aniline, phenol, phenolate, veratrole alcohol, dimethylsulfide, and
methoxybenzene, revealing a surprising constancy of 2.06 to 2.35 eV
Characterization of fulvic acid fractions of dissolved organic matter during ice-out in a hyper-eutrophic, coastal pond in Antarctica
Dissolved humic material (HDOM) is ubiquitous to all natural waters and its source material influences its chemical structure, reactivity, and bioavailability. While terrestrially derived HDOM reference materials distributed by the International Humic Substances Society (IHSS) have been readily available to engineering and scientific communities, a microbially derived reference HDOM was not, despite the well-characterized differences in the chemistry and reactivity of HDOM derived from terrestrial versus microbial sources. To address this gap, we collected a microbial reference fulvic acid from Pony Lake (PLFA) for distribution through the IHSS. Pony Lake is a saline coastal pond on Ross Island, Antarctica, where the landscape is devoid of terrestrial plants. Sample collection occurred over a 17-day period in the summer season at Pony Lake. During this time, the dissolved organic carbon (DOC) concentrations increased nearly two-fold, and the fulvic acid fraction (collected using the XAD-8 method) accounted for 14.6% of the DOC. During the re-concentration and desalting procedures we isolated two other chemically distinct fulvic acid fractions: (1) PLFA-2, which was high in carbohydrates and (2) PLFA-CER, which was high in nitrogen. The chemical characteristics (elemental analysis, optical characterization with UV-vis and fluorescence spectroscopy, and C-13 NMR spectroscopy) of the three fulvic acid fractions helped to explain their behavior during isolation