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Development Of Chemical Tools To Identify Kinase-Substrate Pairs
No full textPost-translational modifications (PTMs) are important alterations made after translation that change protein interactions and functions in a cell. Phosphorylation is an important PTM that regulates cell biology by controlling the enzymatic function, localization, and molecular interactions of cellular proteins. Kinases catalyze the transfer of the γ-phosphoryl group from adenosine-5’-triphosphate (ATP) to a serine (Ser), threonine (Thr), or tyrosine (Tyr) residue of protein substrates (Figure 1).1, 2 Phosphorylation is a dynamic process and the phosphoryl can be cleaved by phosphatases, yielding the hydroxy residue. Together kinases and phosphatases regulate phosphorylation of their protein substrates. Kinase-mediated phosphorylation is highly regulated and crucial for proper cell function. Irregular kinase activity is linked to a variety of pathologies, including cancer and neurodegenerative diseases, making kinases a prominent drug target.3 Therefore, monitoring kinase mediated events in normal and diseased cellular conditions is essential to understand cell biology and identify potential drug targets. Due to the presence of more than 500 kinases and 20,000 phosphorylation sites, characterization of kinase-mediated signaling pathways remains a challenge. To remedy these challenges, The Pflum lab has developed γ-modified ATP analogs that can be used in kinase-catalyzed labeling to identify kinase-substrate pairs. K-CLIP is a method that utilizes γ-modified ATP analogs to identify upstream kinases of phosphoproteins of interest. K-CLIP was used in collaboration with two other labs to uncover unknown kinase biology. Next, K-CLIP was expanded with a new γ-modified ATP analog to identify the substrate scope of PKA. The new γ-modified ATP analogs allowed for a secondary enrichment step to separate upstream kinases and associated proteins from the kinase of interest and true substrates. Kinase-focused K-CLIP identified and validated SMC3 as a novel substrate of PKA. Finally, γ-modified ATP analogs were used in the K-BILDS and K-BIPS to identify substrate motifs of kinases and phosphatases respectively. Identifying substrate motifs in the context of full-length protein interactions will subsequently improve online databases that predict kinase-substrate pairs. In conclusion, γ-modified ATP analogs were developed and applied in methods to discover kinase-substrate pairs, which will expand the impact of kinase-mediated phosphorylation on cell biology
Flow Instabilities And Vortical Dynamics Analysis In The Wake Of Bluff Bodies: From Cylinders To Airfoils
No full textInstabilities in flow dynamics play a crucial role in understanding and predicting the behavior of fluids in various practical applications. Vortical structures are fundamental to the growth and saturation of these instabilities, making their study of paramount importance. In this regard, understanding the flow instabilities and the formation of vortical structures is of particular interest in the analysis of the flow dynamics. This research aims to study physical mechanisms responsible for the emergence of three-dimensional instability regimes in flow over cylinders, three-element high lift and National Advisory Committee for Aeronautics ``NACA\u27\u27 airfoils. The study carries out three-dimensional numerical simulations to analyze the wake flow instabilities and the associated vortical structures. The obtained results can contribute to the development of more accurate predictive models for the behavior and the impact of fluid flows over different engineering systems
Voicing Perspectives: Examining The Racialized Experiences Of Black Men Who Have Exited The Student Affairs Profession In Higher Education
No full textResearchers have discussed the significance of Black male educators in secondary and post-secondary education for decades. While there is extensive research on the impact of Black male teachers, education administrators, and those in the professoriate, there is a noticeable gap concerning the experiences of Black male student affairs staff in higher education. This qualitative study fills that void by analyzing the experiences of Black male student affairs professionals who have transitioned out of the higher education profession at American universities within the past decade. This research utilizes counter-storytelling as its methodology to offer fresh insights and alternative viewpoints. Employing Critical Race Theory as the primary analytical framework provides a comprehensive understanding of the racialized experiences of Black men in the student affairs profession. Additionally, this research examines these experiences\u27 impact on Black men\u27s career trajectories, uncovering significant barriers to advancement. It explores how Black men navigate the racialization of their bodies in the student affairs workspace, allowing a glimpse into the challenges they encounter in maintaining authenticity while conforming to professional norms. The recommendations include urging university leaders to foster inclusive workspaces and providing proactive pathways for Black men to thrive in student affairs despite systemic biases
The Relationship Of Empathy And Memory For Emotions With Social Integration Following Traumatic Brain Injury
No full textIntroduction: Although the high prevalence of poor social well-being after traumatic brain injury (TBI) is well documented, the underlying mechanisms remain unclear. Impairments in experienced and receptive emotion processing, such as empathy and facial affect recognition, are common after TBI. These abilities are thought to be critical to successful social outcomes. However, most research focuses on experimental tasks and questionnaires that are purported to assess these abilities, but these tasks and questionnaires are not directly connected to real-world social integration outcomes, such as community integration, companionship, emotional support, social isolation, and loneliness. Surprisingly, the role of memory for emotions in social integration has been overlooked. The present study examined the relationships among facial affect recognition and memory, empathy, and social outcomes after complicated-mild to severe TBI. Method: Participants were adults with complicated-mild to severe TBI (n = 53) and neurologically-healthy adults (NHA; n = 64). Main measures included the Facial Recognition and Memory for Emotions (FRAME)—a novel task measuring emotion perception and memory for facial affect—and self-report questionnaires assessing empathy and social integration outcomes including community integration, companionship, emotional support, social isolation, and loneliness. Group comparisons were conducted, and correlations evaluated the relationships among facial affect recognition and memory, empathy, and social integration outcomes. Multiple regression analyses investigated facial affect recognition, facial affect memory, and empathy as predictors of social integration outcomes. The moderating effect of awareness of deficit on the relationship between memory for emotions and social integration was analyzed via subgroup correlations and by Hayes’ PROCESS. Results: Overall, NHA exhibited better facial affect recognition and memory, as well as higher empathy levels than people with TBI, although cognitive empathy did not differ between groups, whereas affective empathy was significantly lower among persons with TBI. In terms of predicting social integration outcomes, cognitive empathy played a significant role in fostering community integration and reducing social isolation. Affective empathy, however, was primarily associated with loneliness, highlighting its role in subjective feelings of disconnectedness. There were no meaningful individual linear relationships between facial affect recognition and memory and social integration outcomes among the overall TBI group. However, multiple regression analyses indicated that memory for emotions showed an inverse relationship with social isolation and loneliness when combined with low empathy. Additionally, when self-awareness was examined as a moderator of the relationship between social integration outcomes and memory for emotions, there were significant associations among participants with impaired self-awareness via subgroup correlations; however, given small subgroup sizes, the Hayes’ PROCESS analyses were underpowered to detect interactions except for community integration. Unexpectedly, among NHA, there was an inverse relationship with memory for emotions and community integration. Conclusions: Memory for facial emotions and empathy are unique aspects of social cognition. Partial support was found for the associations of memory for emotions and empathy’s relationships with social integration outcomes. Both subjectively-experienced empathy and objective accuracy in recognizing and remembering emotions were associated with social integration, although the pattern of those relationships was complex and depended on cognitive status. Among adults with TBI, cognitive empathy but not affective empathy was positively associated with social integration outcomes including community integration, companionship, and emotional support; these associations were not observed among NHA. Additionally, among people with TBI, the combination of low empathy and low memory for emotions was associated with social isolation and loneliness. Noteworthy, among individuals with impaired self-awareness, memory for emotions appeared uniquely important for fostering meaningful social connections. The findings highlight the nuanced dynamic between emotion processing, social interaction, empathy, and awareness of deficits, providing insights regarding developing tailored interventions to support persons with TBI in navigating social interventions and enhancing emotional well-being
A Cyber-Physical System Approach For Collaborative Disassembly Automation
No full textThe increased interest in scarce raw materials for new technologies, such as batteries and electric motors, has created a risk to their supplier. Rapid demand intensification can lead to supplier disruption and damage national economies. Oppositely, enhancing these materials\u27 reverse cycles (i.e., recycling, repair, and remanufacturing) into the product lifecycle is fundamental to mitigate supply disruptions, a strategy defined under the Circular Economy philosophy. As the primary step, disassembly plays a critical role in material recovery and still needs advancement from Industry and Academia. Motivated by the recent introduction of sensing technologies allowing humans and robots to work safely in a shared workspace, this investigation aims to handle the automation gap in the recovery industries through human engagement in the robotic processes.Aiming to leverage high-volume disassembly lines, this investigation develops a systematic procedure for disassembly task recognition and disassembly sequence planning through human-robot interaction. Two primitive disassembly tasks are modeled and used to label collaborative robots (cobot) programs, which are used to output multiple robot trajectories. The human interaction in hand-guiding the cobot during the disassembly program is studied to improve the accuracy of the cobot\u27s positioning and disassembly of components. In addition, the impact of the product orientation on the physical workspace on disassembly sequence generation is studied and compared to CAD-simulated disassembly sequences. The disassembly framework has demonstrated practical potential in extracting disassembly information (e.g., disassembly tasks and sequence) from human-cobot interactions. This enhances the setup capabilities of other robots in both virtual and physical disassembly experiments. However, physical disassembly trials have indicated a need for a more robust trajectory prediction when improving the accuracy of hand-guided programs. In addition, the CAD-based disassembly sequence generation methodology has been tested over 1500 CAD models, showing great potential in use for disassembly sequence planning, and demonstrated how to modify the Interference Matrix to simulate the physical disassembly sequence space
A Complex Systems Approach To Identifying Risk Factors For Drinking Decision-Making In Black College Students
No full textObjective: This study utilized a transtheoretical framework, examining how personality traits, social cognitions (such as ethnic-racial identity, minority perception, and sense of belonging), and student role investments influence alcohol-related decision-making in Black and African American college students (N = 186). Participants indicated their attendance and alcohol consumption in scenarios with varying reward and punishment levels. It was hypothesized that neuroticism, behavioral activation (fun seeking), disengagement coping, experiences of discrimination, and drinking norms would positively affect high-risk scenario involvement. In contrast, self-control, spirituality, sense of belonging, ethnic-racial identity, majority/minority perceptions, and student role investment would have negative effects. Lower risk involvement was expected to be influenced by lower self-control, greater behavioral activation (fun seeking), and drinking norms. Exploratory analyses tested the effects of ethnic-racial identity subscales (private, public, and centrality) and group differences based on demographics. A pilot study (N = 51) examined responses to momentary, race-related stressors an experimentally tested the effect of microaggressions and microaffirmations on positive and negative affect.Methods: Structural equation modeling with bootstrapping procedures was used to test direct, indirect, and total effects on high and lower-risk scenario involvement. High and lower scenario involvement were identified as latent factors indicated by scenario responses. Exploratory analyses replicated the original model but indicated additional pathways involving ethnic-racial identity subscales and enhancement drinking motives on high-risk involvement. Results: Bivariate associations revealed significant correlations between predictors and demographics, which were used as covariates in the final model. The original model showed direct effects of self-control on lower high-risk involvement and behavioral activation and enhancement drinking motives on lower risk involvement. Enhancement was a significant mediator for the effect of behavioral activation (fun seeking) on lower risk involvement. While in the original model overall ethnic-racial identity did not affect either level of risk, exploratory analyses showed unique effects for greater ethnic-racial identity (private) on lower high-risk involvement and greater ethnic-racial identity (public) on lower risk involvement. The pilot study demonstrated significant mean differences in affect for students exposed to microaggression compared to both the neutral and role-affirming conditions. Conclusions: The results support various dispositional and environmental factors that contribute to varying levels of risk in decision-making for Black college students. Exploratory results suggest that ethnic-racial identity subscales should continue to be studied independently to examine predictors and pathways for risky decision-making. The pilot study suggests additional complexities in Black college student drinking behaviors that can further elucidate risky alcohol-related decision-making processes
The Effect Of Repetitive Sub-Concussive Head Impacts In A Rodent Model And Its Implication In Contact Sports
Get PDFTraumatic Brain Injury (TBI) is the damage caused to the brain by an external force causing rapid acceleration and deceleration of the brain, and a sub-concussive impact is defined as a bump, blow or jolt to the head not resulting in any apparent symptoms. Within the United States, around 1.7 million people suffer from TBI, of which sports-related injuries are the cause for one-third of the head injuries. It is estimated that approximately 20% of professional boxers experience at least one incidence of concussion or knockout in their careers and 40% of retired boxers suffer from lasting effects ranging from headaches, nausea and dizziness to Parkinson’s Disease, and dementia. Despite visible recovery from the initial injury, many individuals experience secondary neurodegeneration that can lead to gradual tissue deterioration and severe neurodegenerative diseases. The purpose of this research is to investigate the acute effects of repetitive sub-concussive impacts that are commonly seen in sports to study the progression neuropathology that would help advance the research and understanding of brain health among athletes worldwide. Since there are no existing models that adequately replicate the delivery of repetitive sub-concussive head impacts that is representative of head injuries in a sport, the first goal in this research was to develop a rodent model that delivered sub-concussive impacts and study its effects on behavior and on the resulting neuropathology in the brain. Following observations in an animal model, evoked response potential (ERP) of boxing participants were measured and compared after one year to study the effects of multiple sub-concussive impacts. Of the different types of wearable instrumentation that wirelessly measure head impact acceleration parameters, instrumented mouthguards (iMG) are preferred due to their tight coupling to the skull. Hence, this research investigated the accuracy of two different iMGs when subject to simulated punches as seen in boxing, on the jaws of post-mortem human subjects. The results from these studies provided important insights that help understand the acute effects of repetitive sub-concussive impacts in a rodent model. The lack of any difference in behavior accompanied by damage to the axonal structure in rats is similar to boxers returning to their daily routine after a match where no visual symptoms are seen, but this may underline a progression of deteriorating neuropathological cascade. Further experimental studies are needed to confirm the progression of this pathology, but it is well-known that retired boxers are susceptible to neurodegenerative effects. The lower ERP data in professional boxers who have more than 10 years of experience in the sport compared to amateur boxers with less than 5 years of experience also indicated a potential decline in cognition. Lastly, this study reported a contrast in performance of the iMGs in cadavers subject to jaw impacts compared to the close to perfect accuracy observed in idealistic tests in anthropometric test dummies (ATDs). This highlights that these iMGs may not be well suited to accurately measure impacts on the jaw. The findings from this research underscore the importance of understanding the acute effects of repetitive sub-concussive impacts and their potential long-term implications. The development of effective models and accurate measurement tools is crucial for advancing research in brain health among athletes and for developing preventive and therapeutic strategies
Skin Reaction Diagnosis In Breast Radiotherapy
Get PDFRadiotherapy plays an essential role in post-operative management of breast cancer. Unfortunately, the doses required to eradicate malignant tissue also cause radiation-induced skin damage. The more severe effects often require treatment postponement or cessation, which can impact the probability of local control and lasting negative effects.Acute skin reactions are subjectively evaluated by the clinician according to NCI’s CTC or RTOG scoring systems. The criteria for acute radiation morbidity ranges from grade 1 to 4 for adverse advents. The onset of symptoms typically occurs approximately two weeks into treatment and is dose dependent. Given radiation-induced skin injury remains a dose limiting complication, a means to detect skin changes prior to clinical manifestation for potential treatment adaptation is needed. If one could relate skin toxicity to a measurable quantity, the clinician could prophylactically adapt any number of parameters from the treatment to help reduce the patient’s risk. Utilizing microcirculation as a surrogate for this radiation skin response would provide quantitative metrics for the prediction of acute skin toxicity prior to clinical manifestation. We aim to identify an optical imaging technique to assess changes in microcirculation and identify patients at risk for impending skin reactions. As the blood flow changes are non-visible, signal post-processing methods are required to magnify these changes for visualization and quantification. Overall, the methods developed were able to use a simple digital camera to acquire videos of 10 second or less duration to capture cardiac signals. Accurate determination of a single heart rate was plausible in humans and limited to a broader range in mice. The Eulerian video magnification technique was built into a framework to amplify pixel values corresponding with extracted heart rates to depict nonvisible signals. The extracted heart rate was also utilized to determine the amplitude of this signal in the frequency-domain and plotted onto a two-dimensional pulse map. Various pre-clinical studies were utilized to fine tune workflows for these techniques. Ultimately, a breast radiotherapy clinical trial found agreement between EVM amplitude and pulse mapping with thermal imaging temperature results prior to the clinician noticing any toxicity, indicating their potential to predict impending reactions. Overall, both the EVM and pulse mapping techniques show promise as a means to diagnose skin reactions in breast radiotherapy prior to clinical manifestation
Development Of Zinc, Erbium, And Yttrium Metal Ald Precursors And Deposition Of Y2o3 Thin Films Using Thermal Ald
No full textALD stands out among numerous thin film deposition techniques due to its unique ability to deposit thin films layer by layer. This uniqueness is made possible by the self-limited growth behavior of ALD precursors. The layer-by-layer deposition enables precise thickness control at the Angstrom level and ensures 100% conformal coverage even on substrates with high aspect ratio features. ALD is becoming increasingly essential in the microelectronics industry due to the complexity of fabricating substrate surfaces. However, developing new ALD precursors presents challenges due to the specific requirements of volatility, thermal stability, and reactivity. The available library of ALD precursors is currently limited, necessitating efforts to expand and innovate to meet future demands in thin film depositions. To that end, this thesis contains three main chapters on developing Er, Y, and Zn metal ALD precursors and thin film deposition of Y2O3.
Late lanthanide oxide films exhibit valuable properties such as high dielectric constant, considerable band gap energy, high refractive index, and stability at high temperatures, making them attractive for potential dielectric applications. However, existing ALD precursors for late Ln films have drawbacks, including low reactivity with water, substrate oxidation with ozone, and variable thermal stability. Winter laboratory recently developed a series of volatile and thermally stable lanthanide tris(enaminolate) complexes. The synthetic studies focused on Er and Y precursor complexes, their ALD properties, and their use in depositing Er and Y oxide films using water as the co-reactant. This new class of ALD precursors has the potential to broaden the use of lanthanide oxide compounds, including multi-component complex oxides containing rare earths. The synthesis and characterization of Er(L1)3 and Y(L1)3 complexes, emphasizes the optimization of synthetic procedures and identification of their monomeric nature in the solid state. The unexpected formation of KErL14 and [KY(L1)4(L1H)] complexes are analyzed using various techniques, and detailed reaction roadmaps are developed to enhance the synthesis of Er and Y complexes. The chapter concludes with a comprehensive understanding of the chemistry of these complexes and strategies to overcome synthesis challenges.
Additionally, the growth of Y2O3 thin films was demonstrated using Y(L1)3 precursor and water as the co-reactant via thermal ALD on Si(100) and SiO2 substrates. Self-limited growth behavior is observed at 200°C, achieving a consistent growth rate of 0.33 Å per cycle within an ALD window of 175 to 225°C. Initial film analysis is performed using XRF and SE techniques, with further characterization using GI-XRD, AFM, XPS, and SEM. The Y2O3 films exhibit polycrystalline cubic phase deposition, with smooth and continuous morphologies and nearly stoichiometric compositions. This study highlights the effectiveness of lanthanide tris(enaminolate) precursors in the deposition of late Ln2O3 thin films. Additionally, it would be interesting to use lanthanide tris(enaminolate) precursors in early Ln2O3 depositions as well.
The chemistry of Zn(I) dimers is novel and important due to the reactivity of the Zn22+ ion. Zn(I) dimers have potential applications as reducing agents in metal thin film deposition and as precursors for Zn metal thin film deposition using ALD techniques, provided their chemical and physical properties are adequately adjusted. Winter laboratory developed several Zn complexes of β-ketoiminate and β-diketiminate ligands with simple and bulky alkyl groups to enhance the volatility, but their thermal stability was insufficient for ALD applications. To address this issue, two new ligand precursors were proposed with electron-rich alkyl groups containing adjustable bulkiness aiming to produce thermally stable Zn(I) precursors
Talent Management In Governmental Agencies: Employee Viewpoint
No full textTalent Management has become one of the major initiatives for Multinational Corporations as well as the federal government. Its primary focus is to hire the best and brightest individuals to be their innovators and leaders of the future. Talent Management from a Human Resources (HR) perspective includes the process of recruiting, nominating, developing, and retaining talented human capital. Although these talent management outcomes such as retention, engagement, and opportunities for advancement are key drivers for continued sustainability in promoting an engaged workforce, companies and the government are finding it challenging to maintain a talented and engaged workforce. The quest to reduce operational costs and increase profitability and efficiency has produced a silent disruption that causes employees to leave. The purpose of this study was to review talent management from a different lens that is nested in organizational theory, behavioral science, and research methods that examine behaviors associated with talent management outcomes. This study used the 2019 Federal Employee Viewpoint Survey (FEVS) to formulate a structural equation model (SEM) using selected survey items in examining the latent variables Talent Skills Development, the Work Environment and Engagement to explore the relationships associated with the talent management outcome Intent to Leave. A sample of 53,289 was partitioned from responses from Army respondents used to draw causal inferences. First, Principal Axis Factoring was used to validate the latent constructs. Second, Confirmatory Factor Analysis was used to determine if the prescribed factor model provided a good fit. Finally, SEM modeling was used to explore the relationships between the exogenous variable Talent Skills Development, and the endogenous variables Work Environment, Engagement, and Intent to Leave. The aim of this study investigated whether a positive work environment lessens an employee’s willingness to leave even if talent management is void, and if an employee’s perception of underutilized talent increases the likelihood to leave if talent management is thriving and explored the relationship between the work environment and intent to leave within the U.S. Army. The Army is investing in employee talent. This study contributes to the military psychology literature by expanding new definitions and contributes to the current Army People Strategy 2025. The federal government has had almost two decades in experience in trying to evaluate employee satisfaction and engagement as part of the work environment. This new approach of using the 2019 FEVS to formulate a SEM model brings them together to evaluate the talent employee possesses and the leave intentions that can be mitigated by a positive work environment