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Mechanisms of Circadian Clock Control of Rhythmic Translation in Neurospora crassa
The circadian clock in Neurospora crassa regulates daily rhythms in the phosphorylation and daytime inactivation of the conserved translation initiation factor eIF2��. Clock control of eIF2�� activity is responsible for the rhythmic translation of ~15% of mRNAs. Cycling phosphorylated eIF2�� levels require rhythmic activation of the eIF2�� kinase CPC-3 (the homolog of yeast and mammalian GCN2). However, how the clock controls the activity of CPC-3 is not known, and this information is critical to determine the mechanisms underlying rhythmic protein synthesis. To be activated, CPC-3 forms a complex with GCN1, which helps to bring uncharged tRNAs to the tRNA binding domain on CPC-3. In Saccharomyces cerevisiae, activation of GCN2 under stress conditions requires direct interaction of GCN1 and GCN2 with ribosomes. Furthermore, CPC-3 and GCN1 levels are clock-controlled in N. crassa. Based on these data, I hypothesized that N. crassa CPC-3 and GCN1 rhythmically interact with the ribosome, and that this interaction is necessary for rhythmic CPC-3 activity and eIF2��-controlled translation initiation. To test this hypothesis, the interaction of CPC-3 and GCN1 with ribosomes was examined in WT and the clock mutant ��frq. Ribosomes were pelleted from cultures grown in constant dark (DD) and harvested every 4 hours in a circadian time course. I found that CPC-3 and GCN1 interact with monosomes and polysomes, and that the interaction is clock-regulated with peak levels during the subjective day. We showed previously that rhythms in uncharged tRNA levels, and rhythms in CPC-3 activity are abolished in a valyl tRNA synthetase temperature sensitive mutant (un-3ts). The rhythmic interaction of CPC-3 and GCN1 with ribosomes was abolished in the un-3ts mutant, suggesting that rhythmic levels of uncharged tRNA drives the rhythmic interaction of CPC-3 and GCN1 with ribosomes. I found that disrupting the interaction between GCN1 and uncharged tRNA in the absence of GCN20, affects rhythmic CPC-3 activity. Taken together, these data support that clock regulation of rhythms in uncharged tRNA levels and rhythms in the interaction between CPC-3 and GCN1 with ribosomes are necessary for rhythmic CPC-3 activity that leads to rhythms in the translation of target mRNAs
Developing a Multiscale Modeling Approach Using Lumped Kinetics for Pyrolysis of Plastic Waste
Plastic waste poses a global environmental problem and one day the State of Qatar needs to address it in line with its 2030 vision. The pyrolysis of plastic waste is a thermochemical conversion process that has recently gained considerable attention for its potential to convert plastic waste while generating valuable chemicals. Despite extensive research on plastic waste pyrolysis, there is a notable gap in the literature regarding the exploration of connections between different scales���experimental, kinetic, reactor, and process scales. This thesis aims to address this gap by establishing a multiscale approach, bridging the transition from laboratory-scale experiments to process models for plastic waste pyrolysis by utilizing lumped kinetic models, demonstrated for the cases of polyolefins.
A methodology is developed to link the scales, followed by the creation of a sequence chart representing all the necessary steps to complete each stage. This approach is explored through three case studies that vary either in lumped kinetics, plastic feedstock, or component selection. For each case, a lump kinetic model is integrated into 1D pseudo-homogeneous tubular reactor model, that is developed using MATLAB. Parametric studies were conducted for residence time (0-2 hours), wall temperature (650-950 K), and overall heat transfer coefficients (300, 500, and 1000 W/m����K) within the reactor. With the insights gained from these parametric studies, selected scenarios based on the minimum reactor energy and maximum plastic consumption were integrated into Aspen Plus to construct process models for determining mass and energy requirements. Additionally, the fourth case was subjected to techno-economic analysis, where the total annualized cost, profit, and circularity indicators were calculated and compared with other thermochemical plastic waste routes.
Through this research, the gaps associated with multi-scale modeling aspects in literature are aimed to be addressed, and a framework is sought to be established that seamlessly connects information from each scale. By achieving this goal, a holistic understanding of the entire plastic waste pyrolysis chain is aimed to be provided to decision-makers, empowering them to be informed about implementing plastic waste pyrolysis as an effective and sustainable solution for waste management. The results are within the range of other plastic waste management processes, showcasing the practical implementation and gap-bridging capabilities of the approach
Effect of Bone Segementation Data of the Maxilla and Mandible on the Accuracy of Bone-Supported Surgical Guides
Purpose: The purpose of this study was to identify whether the quantity of Cone Beam Computed Tomography Scan (CBCT) image slices included in the jaw segmentation process has a significant effect on the accuracy of bone-supported guides and whether there is a minimum number of slices that can be identified as being needed to produce a surface model of the mandible and the maxilla that will yield an accurate bone-supported guide.
Materials and Methods: Dried human edentulous mandibles and maxillae, three of each, were selected. Each bone model was digitized using an intraoral scanner, and each scan was saved as a Standard Tessellation Language (STL). A bone-supported surgical guide was created on the surface scan of each jaw using a 3D implant planning software program, each serving as a reference guide for each specimen. CBCT images were then acquired once for each bone model, which were then imported into an implant planning software in digital imaging in communication in medicine (DICOM) format. A CBCT image segmentation procedure was then performed for each jaw to create a surface model of each bone with varying numbers of CBCT slices included for each segmentation: 10, 20, 30, 40, 50, 60, 70, 80, 90, and 100 slices. A surgical guide was then created on each surface model rendered from CBCT segmentations and saved as STL. Then the STL of each experimental guide and its corresponding reference guide were imported into an image analysis program and Root Mean Square (RMS) values and heat maps generated to study the internal fit deviation of each guide.
Results: There were statistically significant differences (P<0.001) between the guides created from different numbers of CBCT slices segmented. Additionally, there were statistically significant results between the mandibular and maxillary models, with the mandibular groups having a higher mean deviation (238 ��m) than the maxillary guides (230 ��m). For the mandibles combined, groups below 70 slices produced significant results, while for the maxillae combined, anything below 90 slices was significant.
Conclusions: The internal fit of bone-supported guides is affected by the number of CBCT slices used in the jaw segmentations process for rendering the bone model on which the guide is created. There is a difference in the minimum number of slices needed to create an accurate bone supported guide on the maxilla and mandible. The threshold number of slices is higher for the maxilla compared to the mandible. Although differences between the different guides were observed, the clinical implications are not as clear and should be further studied
The Impact of Preovulatory Estradiol on the Oviductal and Uterine Environments, and Profit per Pregnancy Associated with the Detection of Estrus
The expression of estrus and preovulatory estradiol concentrations influence pregnancy success in beef cattle; however, it is not clear how estrus and/or estradiol impact oviductal and uterine environments. The goals of this dissertation were to evaluate how preovulatory estradiol impacts oviductal gene and protein expression, how physiological estradiol exposure with/without estrus impacts pregnancy-associated factors, and how utilizing the detection of estrus with timed-artificial insemination (TAI) impacts expense and profit per pregnancy. In Chapter II, oviducts (n=6) were collected from synchronized beef cows with High (10.12��0.62 pg/ml, n=3) or Low (5.97��0.62 pg/ml, n=3) estradiol concentrations at fixed-time artificial insemination (FTAI), and differentially expressed genes were identified. Oviductal gene expression was hormonally regulated, with differential gene expression between High and Low cows. In Chapter III, oviducts and ovaries were collected from synchronized beef cows with High (���6.0 pg/mL; n=4) or Low (���4.5 pg/mL; n=5) estradiol concentrations. Oviducts were fixed and embedded for localization of prostaglandin E2 synthase (PTGES) and prostaglandin E2 receptor 2 (PTGER2) localization by immunofluorescence. There was no difference in immunoreactivity of PTGER2 protein; however, immunoreactivity of PTGES protein tended to be more intense in oviducts from High compared with Low cows. In Chapter IV, beef cows (n=603) were synchronized and grouped based on estrus by FTAI (day 0), or the administration of gonadotropin-releasing hormone (GnRH) and/or exogenous estradiol, and estrus by day 7. While estrus or physiological estradiol did not impact pregnancy or interferon-stimulated gene expression by day 19, pregnancy rate and pregnancy-associated glycoprotein abundance by day 24 differed between cows that did or did not express estrus by day 7. Differences in day 55 and 90 pregnancy were observed due to estrus by day 7, but not due to estradiol exposure without estrus. In Chapter V, beef cows and heifers were synchronized using a TAI protocol with (6d; n=437) or without (7d; n=429) estrus detection. Pregnancy rates did not differ; however, decreased expense and increased profit per pregnancy were observed with the 6d compared with the 7d protocol. These data indicate estrus supports pregnancy through maternal environment changes, and utilizing detection of estrus with TAI is more economical
De-Equivariantization in Fusion Categories from Quantum Groups at Roots of Unity
The representations of quantum groups at roots of unity lead to an important class of premodular tensor categories. We will discuss the construction and important properties of these categories. Then we will consider the categories of this kind associated to type D Lie Algebras and present explicit computations to demonstrate the fusion rules, grading and pointed subcategory. We will also discuss and provide examples of de-equivariantization. This process involves creating a new category by taking the category of modules over an algebra object, in some sense taking a ���quotient��� based on the tensor product with this object. More specifically, we identify a subcategory equivalent to Rep(G) for some finite group G and take the algebra object of functions on G in this subcategory. Then we take the modules over this algebra object in the centralizer of Rep(G), which ensures that the resulting category of modules retains the structure of a braided fusion category. Examples of de-equivariantization in the literature primarily consist of performing de-equivariantization with a cyclic group G. We provide an example of de-equivariantization by a non-cyclic group Z2 �� Z2 and discuss strategies to approach de-equivariantization by non-cyclic groups. Specifically, we show that the boson condensation of C(so(8), 10, q) by the full pointed subcategory Rep(Z2��Z2) is isomorphic to four copies of the integral subcategory of C(su(2), 5, q)
The Mental Well-Being of Students Enrolled in Dual Credit Courses at a West Texas Early College High School
The mental well-being of any adolescent is critical to how they think, feel and act in any environment. The purpose of the study was to measure the level of satisfaction with life of students enrolled in dual credit courses in a West Texas Early College High School (ECHS). The focus domains of life satisfaction were in these five areas: Family, Friends, School, Living Environment, and Self. The sample consisted of 152 ECHS students. The tool used was the Multidimensional Student Life Satisfaction Scale (MSLSS). The MSLSS revealed that although overall ECHS students have a positive satisfaction with life, ECHS students had a low satisfaction with the School domain, below 4.0, indicating a lower life satisfaction in this area. There was no statistically significant difference in life satisfaction among students between grade levels, but there was a statistical difference between genders in the Family domain. An intervention course that integrates resilience-building and social-emotional learning (SEL) is recommended to address these findings. Further research is also recommended towards the adolescent well-being of ECHS students enrolled in dual credit
The Genetic Basis of Seasonal Migration and Its Role in Reproductive Isolation
Seasonal migration has been suggested to play a role in speciation through environmentally induced selection against hybrids. Many migratory divides occur between groups that take different migratory routes. For example, the songbird Swainson���s thrush forms a migratory divide in western North America. This species includes two subspecies; coastal thrushes migrate along the west coast of North America while inland thrushes migrate east of the Rocky Mountains, through central North America to South America. These routes are largely genetically determined and involve navigation around geographic barriers. Hybrids in the divide have been shown to take intermediate routes that lead them through these barriers, potentially reducing their fitness. I used this system, spatial modeling, state-of-the-art tracking and genomic techniques to test the role migratory behavior plays in speciation.
First, I used spatial modeling and habitat preferences of birds on migration to show that hybrids taking intermediate routes have less access to highly suitable habitats and encounter more resistance on their routes compared to parental forms. These findings suggest that intermediate routes are inferior to routes taken by parental birds and there could be selection against hybrids contributing to speciation. Second, I individually tracked over 500 adult and juvenile Swainson���s thrushes from the center of the hybrid zone, obtaining detailed data on several migratory traits (e.g., orientation, timing, and wing morphology). Genomic mapping showed that most migratory traits are highly heritable and genetically correlated. I also mapped these traits to specific genomic regions, gaining insight into how these traits may be co-regulated and generating a list of candidate loci that are associated with these traits. Third, I used genomic data and analyses of viability selection to identify signatures of selection along the genome. I connected these regions with the genes associated with migration and showed that these loci are under selection. Combined, results from this dissertation provide one of the most comprehensive tests of seasonal migration as a driver of environmentally induced selection against hybrids in a free-living population that has ever been conducted. My results also provide insight into additional fields, including behavioral genetics and conservation biology
BATF3 and IRF4 Control iTreg Cell Fate Decisions
FOXP3 is the lineage-defining transcription factor for Tregs, a cell type critical to immune tolerance, but the mechanisms that control FOXP3 expression in Tregs remain incompletely defined- particularly as it relates to signals downstream of TCR and CD28 signaling. In this dissertation, I studied the role of IRF4 and BATF3, two transcription factors upregulated upon T cell activation, to the conversion of conventional CD4+ T cells to FOXP3+ T cells (iTregs) in vitro. I found that BATF3 is a potent inhibitor of FOXP3 expression and iTreg differentiation but is dependent on interactions with IRF4 to mediate this inhibition. BATF3 allows IRF4 to bind an upstream regulatory region within the Foxp3 super enhancer. I further demonstrate that interactions of these transcription factors are necessary for glycolytic reprogramming of activated T cells that is antagonistic to FOXP3 expression and stability. However, I also show that BATF3 and IRF4 play critical roles to iTreg function, demonstrating unique roles for these transcription factors in FOXP3 induction vs. in differentiated iTregs. Thus, my findings highlight how BATF3/IRF4 interactions contribute to the complex interplay between TCR signaling, FOXP3 expression and stability, and iTreg function while providing important insights to cellular mechanisms that govern expression of the Foxp3 locus
Ira Greenbaum field notebook: GK3001-GK3500.pdf
Bound book, each page corresponds to a karyotype slide data.Data pages for GK3001-GK3500 corresponding to unique identifiers of specimens/samples examined for biological research. Specimens are primarily housed at Texas A&M University; Biodiverstiy Research and Teaching Collection
New Directions in Indirect Detections: Gamma-Ray Observations of Globular Clusters and Dwarf Galaxies
One of the most elusive unknowns in particle physics and astrophysics today is the fundamental nature of dark matter. It is theoretically well-motivated that dark matter is a weakly interacting massive particle (WIMP) ��� a particle lying within the GeV to TeV energy ranges that interacts very weakly with Standard Model particles. Such behavior makes dark matter extremely difficult to detect with terrestrial detectors. However, there are still many ways to probe the fundamental nature of dark matter. One such way is by searching for astrophysical signatures of dark matter annihilation. Supposing that dark matter is a WIMP which self-annihilates, we can look for inexplicable excesses of Standard Model particles from astrophysical sources. In particular, we can look for high-energy gamma-rays with energies in the range of GeV to TeV. In this thesis, I will discuss recent results on both the dark matter distributions and gamma-ray emissions of a selection of Milky Way satellites and globular clusters with an emphasis on the Sagittarius dwarf galaxy system and the Omega Centauri globular cluster. In Chapter Two, I discuss an updated dynamical analysis of the Omega Centauri globular cluster. In Chapter Three, I discuss an in-depth analysis of the gamma-ray source associated with M54, the globular cluster at the center of the Sagittarius dwarf galaxy. In Chapter Four, I discuss a follow-up paper in which we use cosmological simulations to further test the physical origins of the M54/Sagittarius source. I conclude in Chapter Five by describing several unique ways in which it may be possible to differentiate between the signal of annihilating DM and that of astrophysical background sources