Best Selling Books by Andrew David

The purpose of this study was to determine if the Summit Learning Platform, a type of Intelligent Tutoring System, has a positive association with mathematics achievement of high school students in grades nine through eleven. The study was conducted in a Midwest suburban school district among three high schools within the same district. Further, a quasi-experimental research design was used with a sample size of 2000 students in the control group and 450 students in the treatment group. Data were compiled from the 2018-2019 school year and applied a combination of t-tests and analysis of variance (ANOVA) to compare the mean scores of the two groups. As comparison points, the Northwest Evaluation Association (NWEA), pre-ACT, and ACT were used in this Midwest district as measures among all students. The results demonstrated that students using the Summit Learning Platform showed significant gains when using their pre-test and post-test scores, but there was not statistical significance when analyzing the measures between the control and treatment groups. As more school districts utilize technological tools in far-reaching efforts to raise achievement levels in math, the intent of the study was to demonstrate potential benefits of the Summit Learning Platform for districts across the nation.

Drug-eluting stents have emerged as the most effective method for treating restenosis following percutaneous coronary interventions. This thesis investigates how drugs with similar physiochemical properties but different specific binding targets yield drastically different tissue transport, retention and ultimately efficacy independent of their putative biological effects. Our central hypothesis is that both specific and general binding of drugs to tissue proteins, as mediated by drug-specific physiochemical properties, plays a central role in arterial transport and distribution. We define and compare the kinetic and transport properties of clinically implemented compounds with different binding modes. While hydrophilic compounds are rapidly cleared, hydrophobic ones are retained with an arterial transmural distribution dependent upon the distribution of specific and general binding sites. Common systemically administered cardiac drugs compete with locally delivered agents through displacement of general binding sites. Exploration of drug binding in thrombus indicates significant specific and general binding capacity. Stent-to- arterial wall drug transfer is acutely sensitive to stent strut position in clot relative to the wall due to thrombus binding capacity. A poorly controlled microthrombotic environment around a stent strut can drastically enhance systemic washout while reducing delivery to the tissue. Together this body of work implies that specific and general binding plays a critical role in the clinical efficacy of locally delivered drugs, and must be a consideration in the rational design of stent-based delivery devices.

The eukaryotic ribosome is a large molecular machine consisting of ~80 ribosomal proteins and 4 rRNAs. The 40S and 60S ribosomal subunits are assembled in the nucleolus by ~200 helper proteins then shipped into the cytoplasm or to the endoplasmic reticulum where protein translation takes place. Eventually ribosomes are removed from the cytoplasm and recycled through ribophagy, however, very is little is known about ribosomal protein exchange after assembly but before ribophagy. Using kinetic turnover measurements of ribosomal proteins and rRNA in vivo we determined ribosomal protein replacement rates are diverse suggesting ribosomal components may be replaced without destruction of the entire ribosome. Measurements from ad libitum fed and dietary restricted mice provide strong evidence that RPL10 exchanges rates are dramatically different between AL and DR while synthesis and degradation do ont change. RPL10 turnover can be described using a two-pool kinetic model, which may be applied to many ribosomal proteins.

Central sensitization refers to abnormal pain modulation present which is characterized by non-aversive or mildly aversive stimuli promoting feelings of pain. Many conditions referred to as Functional Somatic Syndromes (FSS)s are characterized by abnormal pain modulation, including pain in areas of the body not thought to be related to the specific FSS with which the patient has been diagnosed. Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS) is a diagnosis of exclusion characterized by pelvic pain and urologic symptoms that shares many environmental and psychosocial correlates with FSSs. Treatment is generally non-satisfactory for patients despite substantial healthcare expenditures. Preliminary evidence suggests abnormal pain modulation in IC/BPS. Inflammatory dysregulation is an underexplored mechanism in the pain experience in IC/BPS and FSSs. The purpose of the current project is to explore the role of dysregulated inflammatory processes in IC/BPS with an emphasis on painful symptoms in three distinct papers. Paper one examines the role of inflammation in IC/BPS patients with particular emphasis on the association of Toll-Like Receptor (TLR) - 4 mediated inflammation with symptoms of pelvic pain. Paper two expands on the findings of paper one by exploring the association of TLR-4 mediated inflammation with the presence of comorbid FSSs and widespread pain. Paper three evaluates the predictive ability of these previously explored baseline inflammatory measures by testing the association between TLR-2 and 4-mediated inflammation and diurnal cortisol rhythms with symptom trajectories and symptom flares over one year of observation. Finally, the significance of these novel findings is explored.

The environmental impact of the beef industry has recently become an area of increasing scientific investigation. One of the objectives of this thesis was to examine how genetic selection and breeding could influence the environmental sustainability of the beef sector by estimating genetic variance parameters and discovering loci associated with predicted methane traits. Observed feed intake of 830 crossbred steers was used to calculate predicted methane traits via three enteric methane estimation equations from Ellis et al. (2007), Mills et al. (2001), and IPCC (2019). Variance components were estimated using genomic best linear unbiased prediction (GBLUP). Heritabilities for each predicted methane trait ranged from 0.70 to 0.74. Spearman correlations of estimated breeding values for each trait were 0.99. Together, these results suggest any of the three predicted methane, if used for selection, would rank animals very similarly in addition to making genetic progress in a relatively short amount of time. A genome-wide association study was also performed for each predicted methane trait. While none of the single nucleotide polymorphisms (SNP) reached the set significance threshold, an analysis of the 25 SNP nearest to the threshold showed each predicted methane trait was associated with the same genetic loci. Candidate genes found near the top 25 SNP indicate collagen related genes could be tied to predicted methane traits. Another objective of this thesis was to use a stochastic model to simulate a 100 head cow-calf operation to determine land, water, and fertilizer requirements as well as methane emissions for various regional beef production scenarios. The simulations were parameterized to replicate 74 different land regions in the Great Plains and six varying genetic potentials for mature body weight and peak lactation for cattle within those regions for a total of 444 unique scenarios. Further, the resource inputs of diets including corn products were compared to diets including grain sorghum products in regions where grains are often fed by cow-calf producers. Lastly, total herd weaning weights for each scenario were estimated based on differences in mature body weight and lactation potential. These weaning weights were used to evaluate resource use efficiency of each genetic potential. The average amount of land use for each herd was 711 hectares when corn products were used and 714 hectares when sorghum products were used. Corn-based diets required an average of 30,588,948 liters of total (irrigation and drinking) water per herd per year, while sorghum-based diets required an average of 42,776,720 liters per herd per year. There were negligible differences in fertilizer estimates between corn and sorghum-based diets (26,532 and 26,523 kilograms of nitrogen per year, respectively). The average enteric methane production for all scenarios was 8,898 and 8,925 kilograms per herd per year for corn and sorghum-based diets, respectively. In general, large, high lactation cattle had the largest environmental footprint, whereas small, low lactation cattle had the slightest. Depending on the variable evaluated, the impact of body size and lactation potential varied in importance. However, animals with a higher lactation potential required more land to grow feedstuffs regardless of size. Although heavier animals had a larger environmental impact than lighter animals with the same lactation potential for total land, blue water, fertilizer, and enteric methane production. When resource use was scaled by kilograms of weaning weight, small, high lactation animals tended to be the most efficient, provided adequate resources can be provided in a cost-effective manner to achieve their genetic potential.

Initial margin requirements are becoming an increasingly common feature of derivative markets. However, while the valuation of derivatives under collateralisation (Piterbarg, 2010, 2012a), under counterparty risk with unsecured funding costs (FVA) (Burgard and Kjaer, 2011a, 2011b, 2013) and in the presence of regulatory capital (KVA) (Green, Kenyon and Dennis, 2014) are established through valuation adjustments, hitherto initial margin has not been considered. This paper further extends the semi-replication framework of Burgard and Kjaer (2013), itself later extended by Green, Kenyon and Dennis (2014), to cover the cost of initial margin, leading to Margin Valuation Adjustment (MVA). Initial margin requirements are typically generated through the use of VAR or CVAR models. Given the form of MVA as an integral over the expected initial margin profile this would lead to excessive computational costs if a brute force calculation were to be used. Hence we also propose a computationally efficient approach to the calculation of MVA through the use of regression techniques, Longstaff-Schwartz Augmented Compression (LSAC).

The simultaneous production of two J/psi mesons has been significantly observed in proton-proton collisions at a center-of-mass energy of 7 TeV with the CMS detector. The two J/psi mesons are fully reconstructed in their decay to muons. The signal yield is extracted with an extended maximum likelihood fit based on four event variables. A method was developed to correct for detector acceptances and efficiencies based on the measured momenta of the J/psi and their decay muons to maintain the least model dependence possible. The measurement is performed in an acceptance region defined by the individual J/psi transverse momentum and rapidity. From the measured signal yield of 446 events corresponding to an integrated luminosity of 4:7 inverse femtobarn. The total cross section is found to be 1:49 nanobarn, with 0:07 statistical and 0:13 nb systematic error, and unpolarizaed production was assumed. Most predictions for particle production at the LHC assume dominance of single parton interaction for proton-proton collisions, which can be tested with the final state measured in this analysis. The differential cross section is measured in bins of the double J/psi invariant mass, the double J/psi transverse momentum, and the absolute difference in rapidity of the two J/psi. The reconstruction of the four charged muon trajectories heavily relies on the Pixel subdetector located close to the beampipe. Systematic studies with cosmic muons and tracks from collision events are presented. The development of the Pixel RawToDigi package, data quality monitoring packages, commissioning studies of Pixel data and tracks in first collisions, and realistic simulations of decay signals in the pixel subdetector were all performed as a part of this dissertation work.

Furthermore, lcla1 was resistant to treatment with cerulenin, a plastid fatty acid synthesis inhibitor, in high light suggesting the high light sensitivity was due to lipotoxicity. The insertional cassette in lcla1 was mapped to Cre07.g329861, predicted to encode a large protein with numerous low complexity regions but without any conserved domains suggestive of a biological function. Introduction of an epitope tag facilitated detection of the encoded isoforms at the expected sizes and the gene renamed LCLA1 for Low Complexity protein in Lipid Accumulation. The N-terminus of one isoform was sufficient to direct a chimeric reporter to the ER in mixotrophic conditions (light plus acetate), the site of de novo peroxisome biogenesis. Shifting cultures to respiratory conditions, the reporter redistributed to puncta resembling peroxisomes. Due to these observations and the compartmentation of glyoxylate cycle and fatty acid oxidation enzymes in peroxisomes, an intriguing possibility is for a role of LCLA1 in peroxisome biogenesis. Indeed, only ~1/3 of the proteins involved in peroxisome biogenesis are conserved in Chlamydomonas. While the precise function of LCLA1 remains to be elucidated, here we provide support for a role in lipid metabolism, indirectly through peroxisome function. In summary, from an insertional mutagenic screen for mitochondrial CI deficiency, two nuclear mutants encoding subunits of CI were obtained as well as two additional mutants disrupted for novel genes. The first, AMC1, was shown to encode a novel CI biogenesis factor controlling expression of the mitochondrial-encoded nd4 transcript. The second, LCLA1, encoding at least two isoforms that participate in lipid homeostasis, possibly through peroxisome biogenesis, an organelle central to lipid metabolism and acetate assimilation. Interestingly, from this screen we have identified two novel genes encoding large, low complexity proteins participating in diverse biological processes.