cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.7274/25872196.v1
title: Exploring Actinide Bonding and Crystal Chemistry in Acidic Media with Borate, Sulfate, Phosphate, and Arsenate Ligands

description: Herein we explore the vast coordination and crystal chemistry of the actinides by probing various ligand systems in acidic media. Unique solvothermal synthetic techniques were developed and implemented in order to synthesize new crystals yielding a variety of new structures containing the acidic solvent of choice. The main reaction medium used was oleum, or fuming sulfuric acid, which presented an uncommon avenue of study in the solid-state, given the lack of literature using these methods with actinide-bearing compounds. Additional research was done on the hydronium cation, a common cation in acidic aqueous systems, and the radiation stability of hydronium in uranium-bearing compounds.
The first area of research explored the development of methods required to synthesize new compounds in oleum, SO3 enriched sulfuric acid. The use of 20% free SO3 H2SO4 presented various unique challenges when combining with the safety necessary in handling the actinides. Once established, these methods were executed in order to synthesize the first actinide borosulfate compounds. The first two actinide borosulfate compounds were both synthesized using solvothermal techniques with oleum and are both uranium-bearing compounds. Two out of the three unique bridging modes within borosulfate chemistry were targeted in these structures, the conventional borate-to-sulfate (B-O-S) and the unconventional borate-to-borate (B-O-B) bridging modes.
The second area of research further expanded the synthetic methods of acidic media and the actinides by exploring with transuranic elements, neptunium and plutonium. These two elements have an extensive redox landscape and introduced more precautionary measures given the higher activity of the isotopes. Exploring neptunium and plutonium sulfate syntheses with oleum, concentration sulfuric acid, and H5[B(SO4)4] yielded some of the first anhydrous transuranic sulfates, as well as targeted an uncommon oxidation state sulfate, plutonium(III) sulfate.
The third area of study investigated the environmentally relevant minerals, hydronium uranyl phosphate (HUP) and hydronium uranyl arsenate (HUAs). Hydronium, H3O+, is extremely prevalent in acidic aqueous solutions, but is far less common in solid-state compounds. The presence and placement of hydronium in HUP was analyzed with neutron powder diffraction and was compared to density functional perturbation theory calculations. Radiation stability of these low solubility compounds was also explored.
DOI: 10.7274/26061361
title: Synthesis of Small Molecule Adjuvants to Combat Antibiotic Resistance Mechanisms

description: According to the Centers for Disease Control and Prevention (CDC), the U.S. lost a lot of the progress made towards combating the antibiotic resistance crisis back in 2020 due to the effects of the COVID-19 pandemic. They state that during the first year of the pandemic, more than 29,400 people died from a bacterial infection, with 40% of those infections being acquired during a hospital stay. Although determination of the full extent of the national burden of deaths from antimicrobial infections may be hindered from the statistical gaps caused by the pandemic, the 2019 CDC estimate of 2.8 million infections/year resulting in approximately 35,000 deaths, remains some of the strongest data obtained to date. These statistics, the loss of progress made, and the dearth of new antibiotics in the drug pipeline highlight the urgent need for novel ways to treat such infections. 
The work presented in this document describes multiple projects focusing on the development of antibiotic adjuvants to combat this issue. In-depth discussions detail initial hits found for each project, followed by a structure activity relationship (SAR) study to reveal lead adjuvants. The first two projects focus on utilizing adjuvants to sensitize gram-negative pathogens to gram-positive selective antibiotics. Gram-negative bacteria are more resistant to many antibiotics than gram-positive bacteria, since they possess an outer membrane that acts as a first line of defense to many antibiotics by preventing their entry into the cell. 
We identified a class of dimeric 2-aminoimidazole (2-AI) adjuvants that dramatically enhance the sensitivity of Acinetobacter baumannii to the macrolide antibiotic clarithromycin, with reductions of minimum inhibitory concentrations (MICs) as high as =512-fold. Activity for these adjuvants was seen across a variety of A. baumannii clinical isolates and among other gram-negative pathogens including: Klebsiella pneumoniae (KP2146), Pseudomonas aeruginosa PAO1, and Escherichia coli (EC25922). Furthermore, the dimeric 2-AI analogs exhibited highly reduced mammalian cell toxicity compared to earlier adjuvants, with IC50 values &gt;200 µg/mL against HepG2 cells, which corresponds to therapeutic indices (TIs) &gt;200. Another project identifies preliminary trends for a second-generation set of 2-AI dimer adjuvants for clarithromycin potentiation against A. baumannii. Lastly, this document describes the efforts made toward synthesizing a set of quinuclidine based natural products for the potentiation of oxacillin against Staphylococcus aureus.
DOI: 10.7274/26061361.v1
title: Synthesis of Small Molecule Adjuvants to Combat Antibiotic Resistance Mechanisms

description: According to the Centers for Disease Control and Prevention (CDC), the U.S. lost a lot of the progress made towards combating the antibiotic resistance crisis back in 2020 due to the effects of the COVID-19 pandemic. They state that during the first year of the pandemic, more than 29,400 people died from a bacterial infection, with 40% of those infections being acquired during a hospital stay. Although determination of the full extent of the national burden of deaths from antimicrobial infections may be hindered from the statistical gaps caused by the pandemic, the 2019 CDC estimate of 2.8 million infections/year resulting in approximately 35,000 deaths, remains some of the strongest data obtained to date. These statistics, the loss of progress made, and the dearth of new antibiotics in the drug pipeline highlight the urgent need for novel ways to treat such infections. 
The work presented in this document describes multiple projects focusing on the development of antibiotic adjuvants to combat this issue. In-depth discussions detail initial hits found for each project, followed by a structure activity relationship (SAR) study to reveal lead adjuvants. The first two projects focus on utilizing adjuvants to sensitize gram-negative pathogens to gram-positive selective antibiotics. Gram-negative bacteria are more resistant to many antibiotics than gram-positive bacteria, since they possess an outer membrane that acts as a first line of defense to many antibiotics by preventing their entry into the cell. 
We identified a class of dimeric 2-aminoimidazole (2-AI) adjuvants that dramatically enhance the sensitivity of Acinetobacter baumannii to the macrolide antibiotic clarithromycin, with reductions of minimum inhibitory concentrations (MICs) as high as =512-fold. Activity for these adjuvants was seen across a variety of A. baumannii clinical isolates and among other gram-negative pathogens including: Klebsiella pneumoniae (KP2146), Pseudomonas aeruginosa PAO1, and Escherichia coli (EC25922). Furthermore, the dimeric 2-AI analogs exhibited highly reduced mammalian cell toxicity compared to earlier adjuvants, with IC50 values &gt;200 µg/mL against HepG2 cells, which corresponds to therapeutic indices (TIs) &gt;200. Another project identifies preliminary trends for a second-generation set of 2-AI dimer adjuvants for clarithromycin potentiation against A. baumannii. Lastly, this document describes the efforts made toward synthesizing a set of quinuclidine based natural products for the potentiation of oxacillin against Staphylococcus aureus.
DOI: 10.7274/26182112
title: Towards Iodine and Lead Determination in Field Settings

description: Field testing has several advantages including the elimination of sample
transportation time and cost, opportunity to educate participants, and rapid determination
of remedial action on site. Iodine, an essential micronutrient that is required to be
determined at the population level, lacks a field test. The Sandell-Kolthoff urinary iodine
reaction is the gold-standard laboratory test whose pretreatment step is not field-friendly.
To aid the development of a field test, I completed an interference study, identifying most
significant interference from urobilin.
Lead is a neurotoxin with major exposure pathways through dust and water but
lacks sensitive field screening tests for these matrices. The portable X-ray fluorescence
analyzer (XRF) is currently used in the health department gold-standard lead risk
assessment (LRA) for determining lead in paint. I have built upon previous work from
our lab for deploying the XRF as a screening tool for lead in dust and water, with
increased sensitivity and robustness.
DOI: 10.7274/26182112.v1
title: Towards Iodine and Lead Determination in Field Settings

description: Field testing has several advantages including the elimination of sample
transportation time and cost, opportunity to educate participants, and rapid determination
of remedial action on site. Iodine, an essential micronutrient that is required to be
determined at the population level, lacks a field test. The Sandell-Kolthoff urinary iodine
reaction is the gold-standard laboratory test whose pretreatment step is not field-friendly.
To aid the development of a field test, I completed an interference study, identifying most
significant interference from urobilin.
Lead is a neurotoxin with major exposure pathways through dust and water but
lacks sensitive field screening tests for these matrices. The portable X-ray fluorescence
analyzer (XRF) is currently used in the health department gold-standard lead risk
assessment (LRA) for determining lead in paint. I have built upon previous work from
our lab for deploying the XRF as a screening tool for lead in dust and water, with
increased sensitivity and robustness.
DOI: 10.15468/dl.yqg7dd
title: Occurrence Download

description: A dataset containing 0 species occurrences available in GBIF matching the query:
{
 "and" : [
 "TaxonKey is Vanessa atalanta (Linnaeus, 1758)",
 "Year is 46",
 "Country is Netherlands"
 ]
}

 The dataset includes 0 records from 0 constituent datasets; see https://api.gbif.org/v1/occurrence/download/0008075-241107131044228/datasets/export for details.
DOI: 10.7274/26793658
title: Structure and Function of Pattern D Streptococcus Pyogenes Surface Exposed Plasminogen Receptors

description: One important process governing the pathogenesis of Group A Streptococcus (GAS) involves its conscription of human host plasminogen (hPg) by a multicopy surface-resident M-protein (M-Prt) direct binding hPg receptor (PAM), or other surface moonlighting proteins such as the homooctameric glycolytic enzyme enolase (SEN). hPg is a single chain multi-modular zymogen containing five kringle domains (K1-K5), four of which interact with lysine. This characteristic is utilized by hPg/hPm to interact with receptors containing COOH-terminal lysine residues or through-space isosteric pseudo lysine residues. On the GAS exterior, hPg is readily activated to the serine protease, plasmin (hPm), by bacterial and host activators. Enabling such a proteolytic surface on GAS aids in its survival and dissemination. The ectodomains of evolutionary-related M-Prts are assumed to form extended alpha-helical coiled-coil projections without tertiary structure, while SEN has no features that suggest the mechanism of its translocation from its normal location in the cytoplasm to the cell surface. In this thesis, there are two conclusions drawn for these Pg receptors (PgRs). First, PAM is anchored in membranes of secreted microvesicular (MV) projections both on the GAS surface and in the surrounding medium where it is fully capable of binding hPg/hPm. Secondly, SEN is also found to translocate to the cell surface by lipid microvesicles (MV) most likely originating from the cytosolic membrane. Using cryogenic-electron microscopy, a high-resolution structure of PAM on lentiviral membrane, SEN, and SEN-hPg embedded in small DOPG unilamellar vesicles. (PL), is provided as a model system for MV-PgRs. We found that the ectodomain of PAM in complex with hPg is folded through intra- and inter-domain interactions to a more compact form on the cell surface, thus establishing a new paradigm for membrane-bound M-Prt/ligand structures. While the PL-SEN structure predominantly shows that two subunits of the SEN octamer are exposed to the extracellular medium and six subunits are buried within the membrane and vesicular interior. While soluble SEN does not meaningfully interact with hPg, due to the steric unavailability of the COOH-terminal lysine residue of SEn, hPg can interact with SEN in DOPG vesicles, primarily via the hPg-K1 lysine binding site. Nonetheless, SEN does not place hPg in a favorable conformation for facile activation and this lack of conformational rearrangement is the primary reason for the attenuated enhancement of hPg activation when bound to the SEN octamer. These studies provide a molecular framework for addressing the need for new treatments of GAS disease by providing a platform to solve structures of virulence-determining membrane proteins.
DOI: 10.7274/26793658.v1
title: Structure and Function of Pattern D Streptococcus Pyogenes Surface Exposed Plasminogen Receptors

description: One important process governing the pathogenesis of Group A Streptococcus (GAS) involves its conscription of human host plasminogen (hPg) by a multicopy surface-resident M-protein (M-Prt) direct binding hPg receptor (PAM), or other surface moonlighting proteins such as the homooctameric glycolytic enzyme enolase (SEN). hPg is a single chain multi-modular zymogen containing five kringle domains (K1-K5), four of which interact with lysine. This characteristic is utilized by hPg/hPm to interact with receptors containing COOH-terminal lysine residues or through-space isosteric pseudo lysine residues. On the GAS exterior, hPg is readily activated to the serine protease, plasmin (hPm), by bacterial and host activators. Enabling such a proteolytic surface on GAS aids in its survival and dissemination. The ectodomains of evolutionary-related M-Prts are assumed to form extended alpha-helical coiled-coil projections without tertiary structure, while SEN has no features that suggest the mechanism of its translocation from its normal location in the cytoplasm to the cell surface. In this thesis, there are two conclusions drawn for these Pg receptors (PgRs). First, PAM is anchored in membranes of secreted microvesicular (MV) projections both on the GAS surface and in the surrounding medium where it is fully capable of binding hPg/hPm. Secondly, SEN is also found to translocate to the cell surface by lipid microvesicles (MV) most likely originating from the cytosolic membrane. Using cryogenic-electron microscopy, a high-resolution structure of PAM on lentiviral membrane, SEN, and SEN-hPg embedded in small DOPG unilamellar vesicles. (PL), is provided as a model system for MV-PgRs. We found that the ectodomain of PAM in complex with hPg is folded through intra- and inter-domain interactions to a more compact form on the cell surface, thus establishing a new paradigm for membrane-bound M-Prt/ligand structures. While the PL-SEN structure predominantly shows that two subunits of the SEN octamer are exposed to the extracellular medium and six subunits are buried within the membrane and vesicular interior. While soluble SEN does not meaningfully interact with hPg, due to the steric unavailability of the COOH-terminal lysine residue of SEn, hPg can interact with SEN in DOPG vesicles, primarily via the hPg-K1 lysine binding site. Nonetheless, SEN does not place hPg in a favorable conformation for facile activation and this lack of conformational rearrangement is the primary reason for the attenuated enhancement of hPg activation when bound to the SEN octamer. These studies provide a molecular framework for addressing the need for new treatments of GAS disease by providing a platform to solve structures of virulence-determining membrane proteins.
DOI: 10.7274/26858434
title: Advancing chemical synthesis with machine learning: opportunities and limitations

description: With advancements in computational power and increased data availability, machine learning (ML) has been applied in predicting chemical reactions and proposing synthetic pathways. This thesis contributes to advancing chemical reaction discovery through ML across three primary domains. Initially, computational methods were used to analyze transition states in reaction routes generated by the Sarpong group using Synthia™, evaluating their computational feasibility. Then, industrial electronic lab notebook (ELN) data, supported by AZ, were processed and featurized. Various ML techniques, including Random Forests (RF), k-Nearest Neighbors (KNN), Neural Networks (NN), and Graph Neural Networks (GNN), were applied to predict reaction yields. Yield imbalances in HTE and ELN were addressed to enhance yield prediction in critical regions using imbalanced regression methods. Large Language Models (LLMs) were integrated for data extraction, solving inconsistencies in USPTO datasets from multiple sources, and investigating the intricate information space of reaction procedure through a specific study on t-butyl ester deprotection. In the second part, substantial advancements were achieved in Molecular Representation Learning (MRL) to accurately capture molecular structures and physical behavior. By evaluating 3D GNNs and conformer ensemble-based models, this research extends beyond traditional SMILES, fingerprints, and 2D molecular graphs, enhancing the precision of predictions for molecule and reaction-level properties. These improvements are crucial for tasks such as enantiomeric excess (ee) selectivity prediction and binding energy (BE) prediction studies.
DOI: 10.7274/26858434.v1
title: Advancing chemical synthesis with machine learning: opportunities and limitations

description: With advancements in computational power and increased data availability, machine learning (ML) has been applied in predicting chemical reactions and proposing synthetic pathways. This thesis contributes to advancing chemical reaction discovery through ML across three primary domains. Initially, computational methods were used to analyze transition states in reaction routes generated by the Sarpong group using Synthia™, evaluating their computational feasibility. Then, industrial electronic lab notebook (ELN) data, supported by AZ, were processed and featurized. Various ML techniques, including Random Forests (RF), k-Nearest Neighbors (KNN), Neural Networks (NN), and Graph Neural Networks (GNN), were applied to predict reaction yields. Yield imbalances in HTE and ELN were addressed to enhance yield prediction in critical regions using imbalanced regression methods. Large Language Models (LLMs) were integrated for data extraction, solving inconsistencies in USPTO datasets from multiple sources, and investigating the intricate information space of reaction procedure through a specific study on t-butyl ester deprotection. In the second part, substantial advancements were achieved in Molecular Representation Learning (MRL) to accurately capture molecular structures and physical behavior. By evaluating 3D GNNs and conformer ensemble-based models, this research extends beyond traditional SMILES, fingerprints, and 2D molecular graphs, enhancing the precision of predictions for molecule and reaction-level properties. These improvements are crucial for tasks such as enantiomeric excess (ee) selectivity prediction and binding energy (BE) prediction studies.
DOI: 10.7274/27184629
title: Analyzing Murine Primary Mesothelial Cell Proteomics to Identify Candidate Proteins Contributing to Gender Differences in Colorectal Cancer Peritoneal Metastatic Receptivity with Aging

description: Cancer is a disease that predominantly affects older individuals. While age remains one of the most significant risk factors for cancer and metastasis, the biological sex of the host also plays a crucial role in influencing metastasis and survival outcomes.. Specifically in colorectal cancer (CRC), both cancer incidence and deaths from metastatic disease are higher in males relative to females. The study hypothesizes that gender- and/or age-related differences in peritoneal mesothelial cells impact the interaction between tumor and mesothelial cells (MC) early in metastatic dissemination, influencing CRC metastasis success. 
In a comparative analysis using female or male young mice (3-6 months, equivalent to human 20-30 years old, FY and MY) and aged mice (20-23 months, equivalent to human 60-67 years old, FA and MA) in an intra-peritoneal (ip) metastasis model, results show that aged males exhibit the highest metastatic tumor burden which aligns with human epidemiological data. The results also show CRC selectively targets adipose tissues covered by visceral peritoneum. Additionally, the omentum shows gender-specific differences in aged groups.
To further explore these gender and age effects, the study investigates the proteome of murine primary peritoneal mesothelial cells (MPPMCs) isolated from young and aged male and female mice. In each cohort, ~2000 proteins and ~1000 protein groups were identified. Proteomic analysis revealed differences in protein expression based on gender and age, providing baseline data for future studies on how these factors regulate MC homeostasis and influence the initiation of peritoneal diseases. 
One of the candidate proteins identified, protein tyrosine phosphatase type IVA 1 (Prl-1), has been characterized in its function in CRC metastasis. Prl-1, expressed exclusively in aged male mice, is found to promote CRC metastasis by aiding initial adhesion of tumor cells to mesothelial cells. The study identifies key signaling pathways, including RhoA-GTPase and src-FAK/p130cas, that are activated by Prl-1. A Prl-1 inhibitor, CMPD-43, shows promise in reducing cell adhesion and migration. The findings suggest that targeting Prl-1 could offer new therapeutic avenues to impede CRC progression and metastasis.