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Applied, Admitted, And Accepted? An Analysis Of Black Women’s Experiences At Predominately White Institutions
No full textThis qualitative study explored strategies to improve Black women\u27s experiences at predominately white colleges and universities. The study used intersectionality as the lens and a narrative inquiry approach. The study sought to determine the usefulness of extracurricular activities and how they aid Black women’s retention and graduation. This study aimed to increase attention to the unique needs of Black women while in college. There is a surplus of research and acknowledgment regarding Black women\u27s success and postsecondary graduation, but that is only part of the story. Little is known about the authentic experiences of Black women while at college. The study will fill this gap by exploring the role of student organizations and programs in shaping the college experiences of Black women. Keywords: Black women, African American women, higher education, student organizations, graduation, intersectionality, social reproduction, narrative inquir
Cyclin Dependent Kinase 4/6 as a Therapeutic Target in the Treatment of Glioblastoma
No full textGlioblastoma, a grade IV astrocytoma, is the most aggressive primary malignant brain tumor. Its genomic heterogeneity and diverse oncogenic alterations often lead to aberrant regulation of the cell cycle, making it an appealing target for therapy. Among the pivotal regulators of the G1 phase of the cell cycle is the Cyclin-Dependent Kinase 4/6 (CDK4/6) - Retinoblastoma (Rb) signaling axis, which is deregulated in 82% of GBMs, according to the TCGA. Pharmacological inhibition of CDK4/6, demonstrated by FDA-approved small molecule inhibitors including abemaciclib, ribociclib, and palbociclib, initially approved for breast cancer, shows promise in Glioblastoma treatment. However, a poor GBM clinical trial track necessitates the identification of predictive markers to enhance treatment outcomes. Two CDK4/6 inhibitors, abemaciclib, and ribociclib, were employed to assess response to CDK4/6 inhibitors in a panel of GBM cohorts. We show that MYC amplification co-occurring with deregulation of growth factor signaling including amplifications in EGFR or PIK3CA is indicative of a refractory phenotype to CDK4/6 inhibitors (CDK4/6i) in GBM patients. Our findings also challenge the efficacy of current monogenic biomarkers, including CDK4 amplification and CDKN2A deep deletion, in effectively stratifying CDK4/6i responsiveness among GBM cohorts. To comprehensively interrogate resistance to G1 blockade, the study explored the potential of CDK2/4/6 inhibition using ebvaciclib and combination therapy of an EGFR inhibitor (dacomatinib) with ribociclib. Combination therapy was decidedly more efficacious in inducing an anti-proliferative phenotype across all CSC lines, even in the recovery period post-treatment; however, ebvaciclib demonstrated high anti-proliferative efficacy in select CSC models. Furthermore, transcriptomic analysis implicated MYC and mTOR signaling as critical drivers of CDK4/6i refractory phenotype in GBMs. Additionally, deregulation of ribosomal processes and activation of non-canonical translation mechanisms emerged as contributors to resistance. Finally, we combined CDK4/6i with ionizing radiation in a large-scale in vitro pharmaco-radiogenomic study. We found that CDK4/6 inhibitors antagonize the cytotoxic effects of ionizing radiation in GBM CSCs. While the utilization of CDK4/6i remains promising in GBMs, our findings have important implications for developing more precise therapeutic strategies, offering new avenues for enhancing the stratification and efficacy of CDK4/6i treatments in GBM
Synthesis And Reactivity Of Xanthene-Based Heterobimetallic Systems For Co Oxidation
Get PDFNature provides a useful guideline for the design of an efficient earth-abundant catalyst for CO oxidation that relies on bimodal heterobimetallic cooperativity. Molybdenum-copper carbon monoxide dehydrogenase (Mo-Cu CODH) is an enzyme of the xanthine oxidoreductase family that catalyzes reversible oxidation of CO; it is inhibited by cyanide CN- and inserts isocyanide CNR between Cu and O/S. The active site contains molybdenum(VI) in a square pyramidal configuration with apical oxo and basal dithiolene, oxo, and sulfide ligands. The two-coordinate Cu(I) is coordinated by cysteinate and Mo-sulfide to form Mo-S-Cu bridge.While several groups have reported structural models of the active site of Mo-Cu CODH, none of the models were able to demonstrate reactivity with CO or isocyanide. We believe that the lack of reactivity in the prior models can be attributed to model instability in the absence of the supporting protein environment. We hypothesize that the inherent instability of the active site model can be remedied by the application of the robust heterodinucleating ligand which would hold the metals together. My dissertation focuses on the development of structural and functional models of the Mo-Cu CODH active site on a xanthene-based heterodinucleating ligand platform to serve as structural and functional models of Mo-Cu CODH. Specific objectives of my research include: (1) design and synthesis of xanthene-based heterodinucleating ligands capable of selective coordination of an early and a late metal; (2) synthesis and characterization of the respective Mo(VI)/Cu(I) complexes with these ligands, and the study of their biomimetic reactivity with CO, CNR, and other relevant substrates; and (3) synthesis and investigation of CO oxidation by heterobimetallic compelxes containing with [M0(CO)3] (M = Mo, Cr) fixed in the proximity of [MoVIO3] . A significant part of my work focused on synthesis of two new heterodinucleating ligands. The synthesis of dipyridylamine ligand (L2H2) involved initial protection of one of the amine sites by tert-butyloxycarbonyl (BOC), followed by double alkylation of the unprotected site, deprotection, and imine formation. L2H2 was isolated in a 28% overall yield. This new heterodinucleating ligand (L2H2) features two different chelating sites, bis(pyridyl) amine for soft low-oxidation-state transition metals and catecholate for hard high-oxidation-state transition metals bridged by a xanthene linker. Similarly, pyridylamine ligand (L3H2) can be synthesized by the methylation of the unprotected amine, followed by imine formation; this ligand was isolated in 38% overall yield. The L3H2 retains the catecholate site for chelating hard high-oxidation-state early transition metals, but its soft site has been modified to a pyridylamine site. Next, we investigated the reactivity of dipyridylamine ligand with Cu(I) and Mo(VI) precursors, as well as conducting studies pertaining to the functional modeling of Mo-Cu CODH activity. The reaction of L2H2 with [Cu(NCMe)4]+ led to the tetradentate coordination of Cu(I) via all nitrogen donors of the ligand, including the imine. Cu(I) complex was characterized by multinuclear NMR spectroscopy, high-resolution mass spectrometry (HRMS), X-ray crystallography, and DFT calculations. The reaction of the Cu(I) complex with a variety of monodentate ligands X (Cl-, SCN-, CN-) released the metal from coordination to the imine. The release of the imine from metal coordination is facilitated by the formation of the hydrogen bond with nearby catechol proton. The second catechol proton engages in H-bonding with Cu-X (X = Cl, CN, SCN), which can be intermolecular (XRD) or intramolecular (DFT). The protonolysis reaction of LH2 with molybdate [MoO4]2- led to insertion of [MoVIO3] at the catecholate position, producing [MoO3(L)]2-. Similarly, the reaction of [Cu(LH2)]+ with [MoO4]2- formed the heterodinuclear [CuMoO3(L)]- complex. The desired heterobimetallic complex was characterized by multinuclear NMR, UV-vis, and HRMS. HRMS in both cases confirmed the constitution of the complexes, containing molecular ions with the expected isotopic distribution. However, this complex showed limited stability in solution and a more stable variant of the heterobimetallic complex was obtained by reacting the silylated Mo(VI) precursor (Et4N)(MoO3(OSiPh3)) with L2H2, followed by the addition of [Cu(NCMe)4]+. This complex showed increased stability and it was characterized by NMR spectroscopy, high-resolution mass spectrometry, and X-ray crystallography. The oxidation capability of Cu(I) phosphine and isocyanide complexes with molybdate was interrogated. IR (for isocyanide) and 31P NMR (for PPh3/PMe3) spectroscopy demonstrates the lack of oxidation reactivity. The lack of oxidation can be attributed to the presence of coordinately saturated Cu(I) and anti conformation of two metal centers. Finally, we described synthesis, characterization, and reactivity of a heterobimetallic complex combining Mo(VI) trioxo with Mo(0) tricarbonyl. The formation of the heterobimetallic complex is facilitated by the xanthene-bridged heterodinucleating ligand (L1H2) containing hard catecholate chelate and soft iminopyridine chelate. The iminopyridine-bound [Mo0(CO)3] fragment coordinated to catechol-bound square-pyramidal [MoVIO3] fragment with a single (oxo) bridge. The overall arrangement of this unit is related to the proposed first step in the CODH mechanism where square-pyramidal [MoVIO2S] interacts with the [Cu-CO] via a single sulfido bridge. Our attempt to obtain a sulfido-bridge analogue (using [MoO3S]2- precursor) led to a mixture of products possibly containing different (oxo and sulfido) bridges. No internal CO oxidation is observed even though a direct interaction between Mo(VI) and Mo(0) segments were observed. The low-lying unoccupied MOs being d-π orbitals at MoVIO3 and the high-lying occupied MOs being mostly d-π orbitals at Mo0(CO)3. This heterobimetallic complex was found to be stable in DMF-d7 up to 100 °C due to its overall rigid structure (based on 1H NMR). Above this temperature, the complex dissociates to form stable Mo(CO)3(DMF)3 (according to IR) without producing CO2 (according to GC). We have also synthesized and studied the reactivity of the Mo(VI)/Cr(0) analogue. While this complex demonstrated more facile decomposition, no CO2 production was observed as well. DFT calculations suggest that the formation of [CO2]2- and its subsequent reductive elimination is endergonic in the present system, likely due to the stability of fac-Mo0(CO)3 and nucleophilic character of the carbonyl carbon engendered by Mo(0). The calculations also indicate that the replacement of one oxo by sulfido (both terminal and bridging), replacement of catechol with dithiolene, and replacement of Mo(0) with Cr(0) does not affect significantly the energetics of the process, likely requiring the use a less stable and less π-basic CO anchor
Usage Of Less Lethal Impact Munitions To Identify Risk Predictors For Skin Penetration
No full textLaw enforcement sometimes use less lethal impact munitions (LLIM) as an alternative to lethal force. Although marketed as safe, there have been many reports of injuries with these projectiles when the LLIM penetrates through the skin. To better understand the skin’s penetration response to these projectiles, eight fresh, unembalmed, whole-body postmortem human specimens (PMHS) underwent impact testing with a rubber spherical projectile. Each PMHS was impacted in a variety of body regions to span across different body compositions (e.g., bone backed vs no bone). A variety of skin surrogates also underwent testing for comparison to the PMHS data to help identify a biofidelic skin surrogate. PMHS testing revealed that energy density was a suitable predictor for risk of skin penetration in many body regions, and the threshold for 50% risk varied greatly throughout the body. Surrogates were identified and can be potential biofidelic skin surrogates
High-Power, High-Efficiency, High-Power-Density, Non-Isolated Dc-Dc Converter For Fuel Cell Vehicles
No full textThis work proposes various solutions for performance, efficiency, and power density improvements of high-power interleaved boost converters (IBCs) in electrified powertrains, namely, use of SiC, LCIs, improved controller, and soft-switching. A relationship was developed for the output current calculation of an n-phase interleaved boost converter (IBC) and output DC link capacitance sizing. The semiconductor losses and efficiency in an n-phase SiC-based IBC were calculated and analyzed. The trade-off in design of an n-phase SIBC with regards to passive components requirements and sizing, passive components volume, losses, and efficiency were analytically investigated from different aspects. An n-phase SIBC was simulated at high power for different number of phases and duty cycles to demonstrate the operation of the aforementioned converter and trade-offs. In the magnetics aspect of IBC performance optimization, Loosely-coupled inductors (LCIs) current ripples in an n-phase LCI-based IBC (LIBC) were analyzed and their expressing relationships were developed. Furthermore, an analysis and relationship for sizing n-phase LIBCs based on the maximum allowed input current ripple were developed. Additionally, analysis and relationship for output current in n-phase LIBC were developed and used for output DC link capacitance sizing. An optimization scheme for design of the LCIs was proposed which could be used for optimization of volume, efficiency, weight, cost, or a combination of these objective functions. Detailed results for use of the optimization scheme for volumetric optimization under various constraints including a \u3e99% efficiency were provided and analyzed to identify the optimal number of phases and switching frequency. An n-phase SiC-based LCI-based IBC (SLIBC) for high-power, high-efficiency, high-power applications was proposed in this work. Passive component sizing, passive components volume, losses, efficiency, and weight of the proposed converter and associated trade-offs were discussed in detail with focus on real-world applications constraints. Simulation results for n-phase SLIBC for various number of phases and operation points were provided to better demonstrate the advantages and trade-offs in the aforementioned converter. Additionally, a small-signal model for the proposed 2N-phase LIBC was developed taking into account the ESRs of the LCIs and DC link capacitors. The transfer functions of the converter were extracted and used to perform a stability analysis and investigation of the poles. the impact of coupled inductors coupling coefficients, ESR and terms generated from the linearization of equations could be shown as the disturbance signal in the state equations. These disturbance signals are functions of the state space variables of the system. Therefore, the conventional controllers like PI and cascaded (nested) loop PI controllers which control the system around its equilibrium point show weak performance in presence of these disturbances. To solve this problem, a novel cascaded loop Lyapunov-based PI controller was developed. The proposed cascaded loop structure has a simple structure which makes its implementation possible at low-cost-microcontrollers. Furthermore, the presented controller has a clear structure which helps make it easier for engineers to design and analyze the system behavior. The proposed controller was designed, simulated and compared with the traditional cascaded PI controller at real-world application operation points. The comparison showed improved response time, tracking, and lower distortions in duty cycle, phase inductor current, and output voltage. Soft-switching is another method for improvements of efficiency, power density, and EMI levels in high-power automotive non-isolated DC-DC converters. The analysis and theoretical design procedure was developed for the unidirectional version of the single-phase soft-switching boost converter presented in [133] without reverse blocking diode and based on use of SiC semiconductor devices, which was previously not conducted in the literature. Moreover, an n-phase SiC-based LCI-based IBC (SSLIBC) using the aforementioned soft-switching topology as the base module was proposed. Numerical example and simulation results were provided for the proposed SSLIBC. Finally, the experimental results were provided for an 8-phase demo of the proposed n-phase SSLIBC achieving a rated efficiency of 98.5%, peak efficiency of 99.29%, power density of 15kW/L, and weight density of 9.8kW/kg
Crying Conspiracy: White Discourses On Black Rebellion In Spanish Colonial Cuba, 1832-1845
No full textThis dissertation examines discourses that were produced and disseminated by the Spanish colonial administrations that controlled Cuba between 1832 and 1845. As uprisings among enslaved Africans threatened Spanish supremacy, the Spanish Crown granted capitanes generales, or governors, full political and military authority over the island. The capitanes generales, all of whom were high-ranking Spanish military personnel, were tasked with consolidating control over all subjects. The desperation of the capitanes as they attempted to fulfill their duties to the crown is evident in the decrees, letters, and news publications they created, endorsed, and circulated. This dissertation approaches administrative texts as a specific genre: Colonial discourses, which are fictions deployed in service of a colonial agent or administrative body. The capitanes generales and other administrators were steeped in the symbolic cultural realities formed through the forces of empire, white supremacy, and capitalism, which were reflected in the discourses they produced. This dissertation uses rhetorical and “microtextual” methods to formulate a critique of those systems of power. Constitutive rhetoric explains how texts interpellated audiences in the symbolic reality of loyalty to Spain—even as political dissent flourished. In addition, the rhetorical situation accounts for the complex relationships between individual rhetors and the exigencies they attempted to overcome. The conflation of an individual administrator’s identity with the authority bestowed on him by the Spanish Crown can be understood through the rhetoric of identity construction. Finally, the “microtextual” approach, a method derived from microhistory, describes this dissertation’s focus on historical events and individuals as well as the implications of administrators’ grammatical constructions and word choices. The first of the Spanish capitanes generales examined in this dissertation is Mariano Ricafort (1832-1834), who annulled freedom of the press and issued decrees regulating the migration of people of African descent to Cuba. The next capitán, Miguel Tacón (1834-1838), was an avowed enemy of white criollos (of European descent and born in Cuba) and expanded Spanish military presence to curtail “vagrancy.” The third capitán examined in this dissertation, Gerónimo Valdés (1841-1843), reformed the Cuban slave code to regulate the physical punishment of enslaved people. While this was considered a relatively progressive measure, Valdés’ 1842 Edict reinforced slavery as an institution and continued the marginalization of people of African descent. Finally, Leopoldo O’Donnell (1843-1848) wrote letters to other colonial administrators about the threat of Black rebellion. After discovering conspiracies on plantations in Matanzas, O’Donnell altered Cuba’s judicial systems to more effectively locate, arrest, torture, sentence, and execute those suspected of rebellion. O’Donnell’s brutal repression of anti-slavery and anti-colonial movements in 1844 became known as La Conspiración de la Escalera, the Ladder Conspiracy. In the decades leading up to La Escalera, colonial administrations deployed rhetoric that stereotyped and blamed people of African descent for political and social unrest, and absolved individuals of the violence they committed by referencing the authority of Spanish and colonial law. As people with various amounts of African and European ancestry protested slavery and Spanish rule, the authorities collapsed Cuba’s complex racial hierarchy into a false binary of “people of color,” an umbrella term for people with various amounts of African heritage, versus whites—or rather, the colonial elite. This dissertation views La Escalera as the culmination of decades of distortive colonial rhetorics, which represented Black rebellion as a threat that could only be contained by absolute loyalty to the Spanish Empire and Cuban capitanes generales
Subdifferentials Calculus For Ordered Set-Valued Mappings And Applications To Set-Valued Optimizations
No full textThe dissertation studies calculus (sum and chain) rules for subdifferentials of ordered set-valued mappings with their applications to set-valued optimizations. Particularly, by using the obtained calculus rules, we derive the existence condition for optimal solutions and necessary optimality conditions in various classses of constrained set-valued optimization problems in infinite-dimensonal settings. Many examples are given and discussed in finite-dimensional settings as well
The Communication Theory Of Racially Motivated Ostracism: Exploring How People Of Color Experience Ostracism
No full textThis study examined the everyday, underreported lived experiences that people of color have with racially motivated acts of ostracism. Ostracism is a phenomenon and umbrella term that encapsulates how people of color experience ostracism, including social rejection, social exclusion, offensive humor, microaggressions, stereotyping, and silencing/ignoring. Using a grounded, social constructivist approach, 22 participants were recruited for one-on-one and group interview sessions exploring their experiences with racially motivated ostracism. Three communication theories provided the foundation for my theory, titled The Communication of Racially Motivated Ostracism. I define racially motivated ostracism acts as the intentional act of marginalizing, excluding, rejecting, isolating, and/or silencing people of color, reinforcing their vulnerable positions in racialized societies. Expectancy Violations Theory served to theorize and explain the reflexive stage of an ostracism experience, while Standpoint Theory served as a theoretical framework to understand a target’s sense-making process and communication strategies enacted in response to the source of ostracism. Communication Accommodation Theory provided a background on the different ways that targets adjust or don\u27t adjust their behaviors in response to their ostracism experiences. After the analysis, it was found that a plethora of emotions and feelings were experienced during the ostracism act and after reflection. Feelings and emotions described during and after the ostracism experiences included: anger/frustration, sadness, disappointment, shock, acceptance/resignation, confusion, and embarrassment. The sense-making factors that influenced how participants processed racially motivated ostracism experiences during childhood, adolescence and adulthood included racial stigmas/stereotypes, historical events and their perceived connection to religion, media representation, family/friend/other advice and thoughts, past experiences with racially motivated ostracism, and immigration status/language differences. Participants engaged in a variety of communication strategies in response to their experiences, including accommodation, divergence/differentiation, maintenance, and support seeking. Implications are discussed regarding the need to pay closer attention to these everyday, underreported experiences with racially motivated ostracism
Gas Sensor Development For Environmental And Soil Monitoring
No full textThis dissertation introduces the development of 3 type of gas sensors for different applications.Chapter 2 reports a simple but effective methane sensor based on off-the-shelf quartz tuning forks (QTFs). It has been experimentally demonstrated that the presence of methane increases the resonant frequency of a single QTF with a sensitivity of 0.0063 Hz/1% or 0.19 ppm/1% and a detection limit of 0.025% at 0.5 Hz sampling rate. For the differential device with 2 QTFs, the values reach to 0.0050 Hz/1% and \u3c0.0386% at 0.25 Hz sampling rate. An excellent selectivity to carbon dioxide, which causes a decrease of the resonant frequency, has been illustrated. Temperature, pressure and humidity responses have been characterized. This new methane sensor is expected to meet the requirements of cost, power, size, reliability and explosion permissibility for coal mine safety applications. Chapter 3 illustrates an in-situ soil probe prototype development for Arctic area underground greenhouse monitoring utilizing commercially available CO2 sensors. Several single and double measurement site prototypes indoor and outdoor test results show the reliability and robustness. These prototypes are ready for real field test to provide long-term Arctic soil information in harsh environments. Chapter 4 uses a simple, surfactant-free solvothermal method to synthesize spherical Pt−Ni NPs which was coated onto a planar electrochemical sensor device as the electrode material. With BmpyNTf2 as the electrolyte, O2 and H2 sensing reaction were investigated. The sensor exhibited a high sensitivity to O2 ((3.04 ± 0.18) × 10−5 mA cm−2 ppm−1) compared to commercial Pt/C-based sensor ((2.57 ± 0.22) × 10−5 mA cm−2 ppm−1), and H2 sensitivity for (0.331 ± 0.014) × 10−4 mA cm−2 ppm−1. Other feature such as rapid gas response, high selectivity and superior reproducibility were also demonstrated
Optimal Drawbead Restraining Force Design With Physical-Artificial Intelligence Method
No full textIn sheet metal forming processing, the drawbead plays an important role in the manufacturing feasibility. However, the design of optimal drawbead restraining force (DBRF) remains a challenging problem. This paper introduces an innovative methodology for the optimization of DBRF design that enhances both efficiency and accuracy. This approach involves a hybrid physical-artificial intelligence (AI) method to establish an initial design that aligns closely with the acceptable range. Initially, a mechanics analysis of metal forming is undertaken to discern part features correlated with the DBRF. Subsequently, multiple AI methods are deployed to create an initial DBRF design, utilizing features gleaned from pre-existing designs of analogous parts. The DBRF design is then modelled as an optimization problem. To streamline this process, we introduce the Nearest Point Adjustment (NPA) method, designed to narrow the variable domain for ensuing iterations. By determining dominant bead sections in relation to the location of critical strains, the NPA method facilitates the identification of the optimal DBRF design with fewer iterations. The developed methods were applied to the DBRF design of an automobile hood outer panel, and the results reveal significant improvements in both computational efficiency and accuracy