University of Illinois at Chicago
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Uncovering Mechanisms of Cell Envelope Integrity and Nutrient Acquisition in Acinetobacter baumannii
No full textAcinetobacter baumannii is an emerging bacterial pathogen of critical concern due to increasing multidrug resistance. The outer membrane (OM) of A. baumannii is a key barrier to antimicrobials and stressors but must also allow the entry of essential nutrients. The maintenance of lipid asymmetry (Mla) system is the primary homeostatic mechanism in Gram-negative bacteria to maintain lipid asymmetry by removing mislocalized phospholipids from the OM. In A. baumannii and other bacteria, loss of the Mla system results in increased sensitivity to membrane stressors and some antibiotics as well as attenuated virulence. In A. baumannii lacking the Mla system, we show that the cellular levels of the essential glycan carrier undecaprenyl phosphate (Und-P) are critically important for maintaining cell envelope integrity and promoting pathogenicity. In an independent study, we characterize a family of OM porins required for growth on carboxylates. The dicarboxylic acid porin (DcaP) was putatively assigned dicarboxylate specificity based on genomic context. We show that major A. baumannii vaccine candidate DcaP3 is important for growth on tricarboxylates and dicarboxylates as sole carbon sources including the citric acid cycle intermediate, citrate. Loss of DcaP3 resulted in reduced bacterial burden from the liver and spleen of mice, suggesting one of the DcaP3-associated carbon sources is important during infection. Altogether, this thesis uncovers synergy between the Mla system and Und-P that is important for cell envelope integrity and characterizes a family of porins critical for nutrient acquisition in the bacterial pathogen A. baumannii
Synthesis of N-Heterocycles and Thiocines via Electrophilic Divalent Reactive Intermediates
No full textThe formation of C–N bonds is a critical transformation in organic chemistry due to their high prevalence in structurally diverse natural products and pharmacologically active compounds. The synthesis of N-heterocycles is interesting and synthetically challenging which has motivated the work of the Driver group. My research has focused on using aryl amines and azides as the N-atom source to synthesize these complex organic scaffolds that possess biological activity such as dibenzazepines, benzimidazoles, and 3H-indoles by accessing electrophilic divalent intermediates. I found that exposure of ortho-substituted aryl amines to either 1.1 equivalents of PIFA or PhIO at room temperature triggered iminoiodinane formation, followed by C–NAr bond formation to yield dibenzazepines. The use of hypervalent iodine reagents motivated me to examine the possibility of using the same reactivity to achieve sp3-C–NAr bond formation. An iodine(III)-catalyzed process was developed using 0.5 mol % of iodobenzene, 2.3 equivalents of Selectfluor, and 2.3 equivalents of trifluoracetic acid to promote the formation of benzimidazoles. Kinetic isotope effect mechanistic studies suggested that benzimidazole formation occurs through oxidation of the piperidine nitrogen followed by an intramolecular product-determining E2 elimination. The emergence of electrochemistry as a novel way to achieve chemical transformations replacing chemical oxidants with electricity intrigued me to explore this new method. I discovered that 3H-indoles could be formed from ortho-substituted azides using graphite as both the cathode and anode and triethyl amine as an electrolyte in an undivided chemical cell. Another focus of my PhD research was to leverage the reactivity of electron-rich carbenes to construct medium-sized heterocycles. A Ru(II)-catalyzed carbene transfer reaction was discovered to construct thiocines from diazo compounds and 2-vinyltetrahydrothiophenes. Together, I was able to harness the reactivity of electrophilic divalent intermediates to develop a suite of methods to construct important N-heterocycles and carbocycles
Design of the What's On Your Plate SNAP Study
No full textThis research brief describes the design of the What’s On Your Plate study that aims to evaluate the impact of the Rhode Island Eat Well, Be Well nutrition incentive program on fruit and vegetable intake using a difference-in-differences approach with Connecticut (CT) serving as a comparison state.</p
Enhancing rufomycin production by CRISPR/Cas9-based genome editing and promoter engineering in Streptomyces sp. MJM3502
No full textStreptomyces sp. MJM3502 is a promising producer of rufomycins, which are a class of potent anti-tuberculosis lead compounds. Although the structure, activity, and mechanism of the main rufomycin 4/6 and its analogs have been extensively studied, a significant gap remains in our understanding of the genome sequence and biosynthetic pathway of Streptomyces sp. MJM3502, and its metabolic engineering has not yet been reported. This study established the genetic manipulation platform for the strain. Using CRISPR/Cas9-based technology to in-frame insert the strong kasO∗p promoter upstream of the rufB and rufS genes of the rufomycin BGC, we increased rufomycin 4/6 production by 4.1-fold and 2.8-fold, respectively. Furthermore, designing recombinant strains by inserting the kasO∗p promoter upstream of the biosynthetic genes encoding cytochrome P450 enzymes led to new rufomycin derivatives. These findings provide the basis for enhancing the production of valuable natural compounds in Streptomyces and offer insights into the generation of novel active natural products via synthetic biology and metabolic engineering.</p
Heat Safety Resources
No full textThis slide deck previews resources related to heat safety, including a pilot project using WhatsApp to reach farmworkers, a process for designing and testing visual trainings, and a pilot project investigating farmworkers' experiences with heat-protective clothing.</p
African American English in Urban Education: A Multimethodological Approach to Understanding Classroom Discourse Strategies
No full textDiscrepancies between 'home English' and 'school English' for urban students have been addressed for decades by a number of scholars in the fields of linguistics, education, and sociology (Baratz 1969, Baugh 1995, Charity et al 2004, Alim 2009, Edwards 2010). Those students who speak prestige varieties of English tend to do better in school settings, in which the teacher's language is that of the mainstream middle class. Charity Hudley and Mallinson (2011: 77) note, '[e]ducators and students who come from different racial, ethnic, and cultural backgrounds may be unaware of, confused by, or ill equipped to understand each other's linguistic and cultural behaviors.' Some researchers have examined teachers' contrastive analysis of non-prestige varieties of English with that of the prestige variety (Pandey 2000, Wheeler and Swords 2006), but rarely has the teachers' acquisition of non-prestige forms been examined in any form (a notable exception is Fogel and Ehri 2006). Furthermore, no study to date has taken a multimethodological approach to understanding both student and teacher discourse strategies in the urban classroom. Citation reproduced with permission of ProQuest LLC. Abridged abstract reproduced with permission of ProQuest LLC. Full text available at URL below.</p
A Linear Programming Framework for Converse Bounds in Coded Caching with Linear Placement
No full textIn the coded caching model, a server stores a library of N files and serves K users over a shared broadcast link. Each user has a cache of size M files. The goal is to design placement and delivery strategies that minimize the worst-case broadcast rate across all possible user demands.
While uncoded placements are well understood, it is known that in the small-memory regime, when M ≪ N, optimal performance often requires coded placements. However, the theoretical understanding of such strategies remains limited.
This thesis aims to close this gap by developing a computational framework for deriving converse bounds, which characterize the fundamental limits of coded caching with coded placement.
These bounds can be formulated as linear programs (LPs) using information-theoretic inequalities, but their size grows doubly exponentially with K and N, making even small instances (e.g., 3 users and 3 files) challenging to solve.
To address this, we introduce a scalable C++ framework that automates LP construction and solution, leveraging both Shannon and non-Shannon inequalities. By exploiting problem symmetries and sparsity, we significantly reduce the number of variables and constraints.
The implementation uses OpenMP for parallelism and integrates Gurobi for efficient optimization.
Our tool enables automated computation of converse bounds for arbitrary (K, N) values, overcoming previous scalability barriers and providing a powerful platform to explore the memory-rate tradeoff in coded caching
Structure-Based Mechano-Chemical Modeling of Microtubule Nucleation
No full textMicrotubule (MT) nucleation is essential for organizing and regulating the cellular MT network. Nucleation begins from two types of templates: 1) Seed MTs – tubelike templates resembling normal MTs, and 2) γ-tubulin ring complexes (γTuRCs) – dynamic templates that must undergo closure to become tubelike. While nucleation from seed MTs is the foundation of the process, nucleation from γTuRCs involves additional complexity. The underlying mechanisms in both cases have remained elusive. Here, we present a structure-based mechano-chemical model that integrates MT dynamic instability with stepwise γTuRC closure, offering a comprehensive view of MT nucleation. Contrary to the prevailing “critical nucleus” framework, we found that nascent MTs do not need to form a specific structure to initiate growth. However, catastrophes (stochastic switches from growth to shortening) reduce the chance that nucleation can be detected. In contrast to the commonly held view of γTuRC as a simple activation switch, γTuRC actually functions as an active extension of the MT lattice, directing the construction of the nascent MT. Conformational changes in γTuRC subunits during closure are analogous to the structural transitions of tubulins within the MT. These changes maintain a sheetlike structure during the nascent MT formation, which resists catastrophes and thereby promotes successful nucleation. This unified framework resolves many longstanding experimental puzzles and opens new paths for understanding cellular functions, enabling new strategies for drug developments
Novel Transition-Metal Oxides Under Pressure
No full textTransition-metal oxides have been the focus of multiple experimental and theoretical research efforts because of their versatility and applicability to new technology. These characteristics mostly owe to our ability to adjust valence states and crystal fields, among others, by fine-tuning thermodynamic variables. From this tuning, interesting and sometimes competing properties emerge; but it is often necessary to take these oxides to extremes conditions of pressure, temperature or magnetic field so novel phenomena arise (e.g. P ∼100 GPa = 1 Mbar, T ∼1 K, µ0H ∼10 T), which is the case for some high-temperature superconductors and Kitaev quantum spin liquids (KQSLs). In particular, the latter is a frustrated state of matter, modeled for 2D honeycomb lattices, that hosts topologically protected excitations and presents immense potential for application to fault-tolerant quantum computing. However, reliable stabilization of this state in real materials has been challenging. Therefore, this work aimed at unraveling atomic, electronic and magnetic structures of KQSL-candidate Na3Co2SbO6 at thermodynamic extremes, by combining multiple techniques and diamond anvil cells. Na3Co2SbO6 shows no structural dimerization up to 1 Mbar, likely due to the reduced spatial extent of Co 3d orbitals compared to Rh 4d and Ir 5d bands in other Kitaev candidates. Pressure suppresses this cobaltate’s magnetic response, which vanishes above 100 GPa in good agreement with induced frustration. Although a high-to-low-spin transition at ∼70 GPa quenches the orbital momentum required in KQSLs, other models predict that honeycomb lattices of low-spin Co2+ ions can host a spin-liquid phase, which is of great interest for related research. Contributions to the study of another Kitaev-candidate material, Ag3LiRh2O6, are also highlighted. Furthermore, superconducting transitions were explored on nickelates. For the first time, a temperature-dependent resistivity drop was reported for compressed Pr4Ni3O10, suggesting that bulk superconductivity is a more general property of Ruddlesden-Popper Ni-O stacks under pressure
Perspectives of Black Women with Emotional Behavior Disabilities Regarding Special Education Experiences
No full textThis phenomenological study explores the unique experiences of Black girls diagnosed with Emotional and Behavioral Disabilities (EBD) within special education systems. Often overlooked in the referral process, girls typically internalize their feelings, which contrasts with boys who externalize behaviors. Consequently, when girls are identified as having EBD, they are perceived as exhibiting worse behaviors than their male counterparts, challenging traditional gender stereotypes. This research aims to address the significant gap in the literature regarding Black girls' educational experiences and the intersections of race, gender, and disability. Using a qualitative, descriptive approach, narrative interviews were conducted with former Black female students previously labeled EBD and involved in Individual Education Programs. Participants shared their recollections of the referral process and their relationships with teachers and peers. Findings reveal how systemic biases shape their educational trajectories and underscore the urgent need for culturally responsive interventions tailored to their unique needs. This study advocates for educational reforms that prioritize the voices of Black girls with EBD, promoting equitable learning environments. Implications for future research are discussed, emphasizing the need to further understand the multifaceted identities impacting educational outcomes for marginalized students
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