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Johnson Hall, 712 W. Franklin Street
No full textA photographic print of a building on 712 W. Franklin St. that is owned by the Scott Family, and used by Richmond Professional Institute (RPI) as a men\u27s dormitory, Johnson Hall.https://scholarscompass.vcu.edu/rg60/1142/thumbnail.jp
Adkins House, 824 Park Avenue
No full textA photographic print of Adkins House at 824 Park Avenue.https://scholarscompass.vcu.edu/rg60/1147/thumbnail.jp
Adopt a School Program
No full textA photographic print of a teacher presenting a lesson on a chalkboard, part of an Adopt a School program.https://scholarscompass.vcu.edu/rg60/1157/thumbnail.jp
VCU Health, Claudette McDaniel
No full textA photographic print focused on the face of Dr. Claudette McDaniel, who wears a name tag which also reads Section Chief, Special Activities. She looks at another individual who is out of focus. McDaniel worked in Therapeutic Recreation for the VCU Health System. She was also the first Black woman to serve as vice mayor in the city of Richmond.https://scholarscompass.vcu.edu/rg60/1169/thumbnail.jp
Portrait
No full textA photographic print of an individual sitting near a table with a plant in a pot on it. Originally in the subject folder labeled Airplanes.https://scholarscompass.vcu.edu/rg60/1181/thumbnail.jp
VCU Symphony, video
No full textEnsemble Performance, videoVCU Symphony presentsReformationconducted by Daniel MyssykwithTabatha Easley, fluteWednesday, December 3, 2025 at 7:00 p.m.Sonia Vlahcevic Concert HallW.E. Singleton Center for the Performing Arts922 Park Avenue | Richmond, Virgini
Saxophone Studio Recital, video
No full textStudio Recital videoSaxophone Studio Recital, videoStudents from the studio of Dr. Sheri Oyanwith James O\u27Brien and Russell Wilson, piano Tuesday, November 11, 2025 at 7:30 p.m.Recital HallJames W. Black Music Center1015 Grove Avenue | Richmond, Virgnini
Chamber Brass Ensembles, video
No full textStudio Recital, videoChamber Brass Ensembles, videocoached byDr. Ross WalterMonday, November 10, 2025 at 8:00 p.m.Recital HallJames W. Black Music Center1015 Grove Avenue | Richmond, Virgini
Predictive Inference for Ion Concentration with Machine Learning and Bayesian Methods
No full textUltraviolet--visible (UV--Vis) spectroscopy produces high-dimensional signals that are strongly collinear, shift with concentration, and exhibit heteroskedastic, non-Gaussian noise. These features make supervised regression from spectra to ionic concentrations statistically challenging and limit the reliability of methods that assume linear structure or homoscedastic errors.
This dissertation develops two complementary frameworks for prediction and uncertainty quantification in UV--Vis spectroscopic regression: (1) frequentist stacked ensembles combined with distribution-free conformal prediction, and (2) Bayesian hierarchical modeling and Bayesian stacking. Together, they provide a unified view of model-based and distribution-free uncertainty across nickel and nickel--cobalt datasets.
The frequentist component builds ensembles of Functional Data Analysis (FDA), Principal Component Regression (PCR), and Partial Least Squares (PLS) learners. Three ensemble strategies---non-negative least squares stacking, Dirichlet-regularized stacking, and a piecewise ensemble---improve point prediction by exploiting complementary structure in the spectral representations. Uncertainty is quantified with Split Conformal, CV+, Jackknife, and Jackknife+, which deliver finite-sample valid prediction intervals without distributional assumptions. A new kernel-weighted nonexchangeable conformal method incorporates spectral similarity, enabling locally adaptive intervals when observations are not exchangeable.
The Bayesian component develops hierarchical FDA, PCR, and PLS models with priors tailored to smooth functional structure and likelihoods suited to positive, heteroskedastic targets. Posterior predictive distributions supply coherent probabilistic uncertainty, and Bayesian stacking combines models by maximizing expected predictive performance.
Developed on the nickel dataset and evaluated on the mixed nickel--cobalt data for robustness, the two frameworks deliver strong predictive accuracy and complementary forms of uncertainty: conformal methods guarantee distribution-free coverage, while Bayesian models provide full probabilistic structure and interpretability
Drug-Like Properties of Synthetic Glycosaminoglycan Mimetics
No full textGlycosaminoglycans (GAGs) are a family of linear, highly negatively charged polydisperse polysaccharides composed of repeating disaccharide units, typically consisting of an amino sugar and either a uronic acid or galactose residue. These biomolecules are widely distributed throughout mammalian tissues and serve as essential components of the extracellular matrix. Through interactions with over 3,400 proteins, including growth factors, cytokines, and enzymes, GAGs play critical roles in regulating cell signaling, inflammation, angiogenesis, coagulation, and many other biological processes. Among natural GAGs, heparin is widely recognized for its clinical use as an anticoagulant. However, its complex and heterogeneous structure, along with the associated risk of bleeding, limits its broader therapeutic application. To address these limitations, researchers have developed synthetic glycosaminoglycan mimetics (NSGMs), compounds designed to mimic the biological activity of natural GAGs while offering improved pharmacological profiles and reduced side effects. Two promising examples are G2.2, a non-saccharide GAG mimetic that selectively inhibits cancer stem cells in colorectal cancer models, and sulfated chiro-inositol (SCI), which shows potent anticoagulant effects through inhibition of coagulation factor XIa.
Despite their biological efficacy, these mimetics diverge significantly from traditional small-molecule drugs. Their high charge density, extensive sulfation, and large polar surface areas violate standard drug-likeness rules (e.g., Lipinski’s Rule of Five, Veber criteria), raising concerns about oral bioavailability, membrane permeability, and pharmacokinetics. Determining whether these compounds, despite their unconventional structures, can be translated into viable therapeutics therefore requires detailed characterization of their physicochemical and absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties, as well as identification of their molecular targets. Understanding how their unique chemical features translate into drug-like behavior is critical for unlocking their therapeutic potential and for expanding the definition of what a “drug” can be in the context of complex diseases like cancer and thrombosis.
Although NSGMs such as G2.2 and SCI-derived scaffolds show strong promise in oncology and thrombosis, their clinical translation has been hindered by limited clarity regarding their drug-like behavior. Unlike conventional small molecules, NSGMs exhibit atypical physicochemical traits, high polarity, high charge, and extensive sulfation, that complicate the prediction of their ADMET. As a result, critical questions remain regarding their capacity to access biological compartments, engage targets selectively, and maintain stability in physiological environments. Addressing these gaps is essential not only for optimizing their therapeutic performance but also for broadening the chemical space considered “druggable.” This work addresses these questions through evaluation of G2.2, MQD1, their lipid-conjugated analogs, and the SCI-derived SB-series.
Analytical characterization of G2.2 and MQD1 using UPLC/MS and HR-MS confirmed that both molecules are chemically homogeneous, fully sulfated, and structurally intact, with monoisotopic masses identified within 7-9.9 ppm accuracy and characteristic multiply charged hexylamine adducts. Both scaffolds displayed extraordinarily high aqueous solubility (~500 mg/mL) and moderately hydrophilic experimental mlogP values (-1.0 to 3.0), showing a clear discrepancy from their computational clogP predictions (-10 to -15). They were chemically stable for at least 168 hours at 37 °C, exhibited high microsomal stability, and produced minimal inhibition across major CYP450 isoforms. ADMET studies also revealed \u3e96-99% plasma protein binding and no significant prolongation of PT or aPTT at concentrations up to 200 µM, indicating low anticoagulant risk. Pharmacokinetic evaluation of G2.2 demonstrated a terminal half-life of ~14 hours following IV dosing, while oral administration yielded a Cmax of 62.5 µg/mL, AUC0-8of 353 µg·h/mL, and ~4.3% bioavailability, demonstrating that limited absorption, rather than clearance, is the primary barrier to oral exposure.
To investigate whether targeted hydrophobic modification could improve pharmacokinetic performance, cholesterol-conjugated analogs of G2.2 (G2C, G5C, G8C) and MQD1 (MQD1-2C, MQD1-5C, MQD1-8C) were synthesized and fully characterized. Structures of these compounds are in Figure A. Lipidation increased hydrophobic surface area and chromatographic retention in a predictable chain-dependent fashion, yet these analogs remained highly water soluble (240-250 mg/mL) and structurally stable. Experimental mlogP values shifted modestly (-1.0 to -2.5) but remained within the hydrophilic range, confirming that dense sulfation continues to dominate physicochemical behavior. ADMET evaluation showed that lipid conjugation preserved high chemical stability, low CYP450 inhibition, and minimal anticoagulant activity. Preliminary PK analyses, however, revealed that addition of the cholesterol moiety did not substantially improve oral bioavailability; for example, G2C exhibited oral exposure nearly identical to G2.2. Likewise, the MQD1 lipid analogs showed no meaningful improvement in permeability or systemic exposure, indicating that cholesterol conjugation alone cannot overcome the intrinsic permeability limitations of highly sulfated NSGMs.
The SCI-derived SB-series, a panel of stereochemically distinct inositol analogs (SB-01: D-chiro; SB-02: L-chiro; SB-03: myo; SB-04: scyllo), was evaluated as a next-generation family of FXIa-targeted anticoagulants (Figure B). Analytical characterization confirmed chemical purity, homogeneous sulfation, and identical parent ions across the series. All SB analogs displayed extremely high solubility, uniformly high hydrophilicity, and experimental mlogP values in the -1.0 to -3.0 range, again highlighting the disparity between experimental measurements and overly negative clogP predictions. The compounds demonstrated excellent chemical stability at physiological pH for 168 hours, maintaining dominant fully sulfated species with only minor sulfate loss. Plasma protein binding was uniformly high (95-98%), with SB-04 showing slightly more time-dependent dissociation relative to SB-01 and SB-03. CYP450 inhibition across seven major isoforms was weak to moderate, with no potent inhibition observed, suggesting low risk of drug-drug interactions. Functionally, the series exhibited selective intrinsic-pathway anticoagulant activity: all four prolonged aPTT in a dose-dependent manner, with SB-03 approaching enoxaparin-like potency, while none affected PT. A 7-day repeat-dose toxicity study demonstrated excellent in vivo tolerability, including normal hematology, clinical chemistry, organ weights, and bone metrics.
Across anticancer (G2.2, MQD1) and anticoagulant (SB-series) NSGMs, this work demonstrates that highly sulfated, nontraditional scaffolds, despite falling far outside classical drug-likeness criteria, can exhibit robust chemical stability, favorable ADMET behavior, and excellent in vivo tolerability. While lipid conjugation provides a tunable means of modulating hydrophobicity, it does not fully overcome intrinsic absorption limitations imposed by extreme sulfation. The SB-series, in particular, combine superb solubility, chemical stability, selective FXIa inhibition, and minimal toxicity, positioning them as compelling next-generation anticoagulant candidates. Collectively, these findings broaden the boundaries of “drug-like” chemical space and support continued development of NSGMs as viable therapeutic scaffolds for oncology and thrombosis