Washington, D.C. through the “Live. Learn. Intern” Program

In this essay, Andrew Waetzig reflects on a semester spent in Washington, D.C. studying at George Mason University and interning at the Association for Enterprise Opportunity

Does ESPN’s Total Quarterback Rating Help Explain an NFL Team’s Probability of Winning?

The purpose of this study is to examine the relationship between an NFL quarterback’s Total Quarterback Rating (TQR) and his team’s prospect of winning games. We use a binary-logit model to estimate the marginal effects of TQR on the probability of winning, controlling for teams’ power rankings and home-field advantage. We find that a 5-point improvement in the TQR score would lead to a 2% increase in the probability of winning the game. Our results suggest that NFL coaches could see an increase in the probability of winning through the improvement of their quarterbacks’ performance. This model can also be used to predict the outcome of NFL games in the coming seasons

Phosphate Tethers in Synthesis: The Total Synthesis of Dolabelide C.

The utilization of phosphate tethers in synthesis is the focus of the dissertation research described herein. Specifically, cross metathesis of various olefin partners with a phosphate tether has been demonstrated. These studies established the Type III olefin reactivity of the exocyclic olefin of the triply allylic bicyclic phosphate tether. Cross metathesis between the bicyclic phosphate and complex olefin partners allowed for rapid assembly of advanced polyol subunits. Understanding the reactivity of the bicyclic phosphate allowed for the application of this methodology toward the synthesis of a natural product. The target chosen was dolabelide C, a 24-membered macrolactone possessing cytotoxicity against HeLa-S3 cervical cancer cells. Retrosynthetic analysis of dolabelide C revealed two subunits that could be accessed by the developed bicyclic phosphate tether methodologies. In the synthesis of the C1-C14 subunit of dolabelide C the bicyclic phosphate tether mediates a selective cross metathesis with the terminal exocyclic olefin, differentiates the endocyclic and exocyclic olefins for selective hydrogenation, and serves as a leaving grouping for a regioselective palladium(0)-catalyzed hydride opening. Upon removal of the phosphate tether, the C1-C14 subunit of dolabelide C was completed in six subsequent steps. Studies toward the C15-C30 subunit of dolabelide C also utilized the bicyclic phosphate tether methodology. Three routes toward this subunit were realized, each took advantage of the latent leaving group ability of the phosphate tether to set the C23 stereocenter. These sequences supplied the C15-C30 of dolabelide C which was then prepared for pairing with the C1-C14 subunit. Final coupling of the C1-C14 and C15-C30 subunits of dolabelide C was accomplished and five more steps were successfully achieved, culminating in a macrocyclic ring-closing metathesis to completed the total synthesis of dolabelide C. The total synthesis of dolabelide C using our temporary phosphate tether methods was achieved in 24 steps (longest linear sequence from acetylacetone) and 54 total steps. The overall yield for this synthesis was 0.73% with an average yield per chemical step being 81.5%

Accessing Metastable Solid-Solution Nanoparticles from Solution-Phase Condensation Reactions: Applications in High-K Dielectrics, Geopolymerization, and X-Ray Phosphors

This dissertation focuses on the design, synthesis, and functional applications of ceramic materials prepared with precise compositional, dimensional, and structural control from molecular precursors using a versatile sol—gel condensation process. Three primary thrusts have stemmed from this central idea: (i) mapping the size-dependent phase diagram of HfOv2 and stabilizing the metastable tetragonal phase of HfOv2 at room temperature as a result of dimensional confinement, thereby obtaining a technologically important high-dielectric-constant polymorph that is only accessible above a temperature of 1720°C in the bulk; (ii) developing a method to cross-link plant fibers through creation of siloxane frameworks, resulting in the stabilization of a mechanically resilient load-bearing composite for roadworks in the Alberta Oil Sands; and (iii) stabilizing solid-solution rare earth oxychloride (REOCl) nanocrystals across a broad compositional range to obtain a full palette of X-ray phosphors, allowing for elucidation of activation channels, sensitization mechanisms, and recombination pathways underpinning X-ray-activated optical luminescence. The dissertation develops a versatile synthetic toolbox for defining oxide and oxyhalide frameworks. The choice of molecular precursors and ligands added during synthesis strongly influence kinetics of particle growth and allow for compositional control as well as tunability of particle dimensions. The metastable materials synthesized in this work have allowed for exploration of the size-dependent phase diagram of HfO2 and have enabled the development of quaternary and quintary solid-solution phosphors based on the PbFCl-type LaOCl and GdOCl frameworks

PREVENTION OF PROTEIN ADSORPTION ON BARE FUSED-SILICA CAPILLARY BY PEG IN CAPILLARY ZONE ELECTROPHORESIS

ABSTRACT The protein separation was studied in capillary zone electrophoresis for preventing protein adsorption on the capillary wall. /3-/actoglobulin(pI: 4.83-5.4, M,: 18.4kDa), cytochrome c (pI: 9.59, M,: 11.7kDa) and /3-casein(pI: 4.6, M,: 24 kDa) were used as protein models. Strong adsorption of the proteins occurred onto the capillary at a pH around their pIs. In order to prevent protein adsorption,PEG (Poly(ethyleneglycol» was investigated as an effective substance to stabilize the proteins native state and coat the bare fused-silica capillary surface. The presence of 32 mg/mL PEG in buffer solution in a pH range of 6.0 to 4.0 was successful to suppress protein adsorption during the separation. It can also be confirmed with the reproducibility of apparent EOF mobility with percentile RSD (Relative Standard Deviation) less than 2% in long-term measurement. Keywords: PEG, protein adsorption,CZ

Accurate and precise quantification of Cu,Zn-SOD in human red blood cells using species-specific double and triple IDMS

Acknowledgements This research was undertaken within the EMRP project HLT05. The EMRP was jointly funded by the EMRP participating countries within EURAMET and the European Union. We gratefully acknowledge support by the Braunschweig International Graduate School of Metrology B-IGSM.Peer reviewedPostprin

Modulation of autocrine TNF-α-stimulated matrix metalloproteinase 9 (MMP-9) expression by mitogenactivated protein kinases in THP-1 monocytic cells

Matrix metalloproteinase 9 (MMP-9) is implicated in various physiological processes by its ability to degrade the extracellular matrix (ECM) and process multiple regulatory proteins. Normally, MMP-9 expression is tightly controlled in cells. Sustained or enhanced MMP-9 secretion, however, has been demonstrated to contribute to the pathophysiology of numerous diseases, including arthritis and tumor progression, rendering this enzyme a major target for clinical interventions. Here we show that constitutive MMP-9 secretion was abrogated in THP-1 monocytic leukemia cells by addition of neutralizing antibodies against tumor necrosis factor alpha (TNF-α) or TNF receptor type 1 (TNF-R1), as well as by inhibition of TNF-α converting enzyme (TACE). This indicates that MMP-9 production in these cells is maintained by autocrine stimulation, with TNF-α acting via TNF-R1. To investigate the intracellular signaling routes involved in MMP-9 gene transcription, cells were treated with different inhibitors of major mitogen-activated protein kinase (MAPK) pathways. Interruption of the extracellular signal-regulated kinase pathway 1/2 (ERK1/2) using PD98059 significantly downregulated constitutive MMP-9 release. In contrast, blockage of p38 kinase activity by addition of SB203580 or SB202190, as well as inhibition of c-Jun N-terminal kinase (JNK) using L-JNK-I1, clearly augmented MMP-9 expression and secretion by an upregulation of ERK1/2 phosphorylation. Moreover, exogenously added TNF-α augmented MMP-9 synthesis and secretion in THP-1 cells via enhancement of ERK1/2 activity. Taken together, our results indicate that ERK1/2 activity plays a pivotal role in TNF-α-induced MMP-9 production and demonstrate its negative modulation by p38 and JNK activity. These findings suggest ERK1/2 rather than p38 and JNK as a reasonable target to specifically block MMP-9 expression using MAPK inhibitors in therapeutic applications

Total Synthesis of Dolabelide C: A Phosphate-Mediated Approach

The first synthesis of dolabelide C (1), a cytotoxic marine macrolide, is reported utilizing a phosphate tether-mediated approach. Bicyclic phosphates (S,S,SP)-5 and (R,R,RP)-5 serve as the central building blocks for the construction of two major 1,3-anti-diol subunits in 1 through selective cleavage pathways, regioselective olefin reduction and cross-metathesis. Overall, phosphate-mediated processes provided copious amounts of both major subunits allowing for a detailed RCM macrocyclization study to the 24-membered macrolactone 1

Real-time Atomistic Observation of Structural Phase Transformations in Individual Hafnia Nanorods

High-temperature phases of hafnium dioxide have exceptionally high dielectric constants and large bandgaps, but quenching them to room temperature remains a challenge. Scaling the bulk form to nanocrystals, while successful in stabilizing the tetragonal phase of isomorphous ZrO2, has produced nanorods with a twinned version of the room temperature monoclinic phase in HfO2. Here we use in situ heating in a scanning transmission electron microscope to observe the transformation of an HfO2 nanorod from monoclinic to tetragonal, with a transformation temperature suppressed by over 1000°C from bulk. When the nanorod is annealed, we observe with atomic-scale resolution the transformation from twinned-monoclinic to tetragonal, starting at a twin boundary and propagating via coherent transformation dislocation; the nanorod is reduced to hafnium on cooling. Unlike the bulk displacive transition, nanoscale size-confinement enables us to manipulate the transformation mechanism, and we observe discrete nucleation events and sigmoidal nucleation and growth kinetics

Oxide ceramic electrolytes for all-solid-state lithium batteries – cost-cutting cell design and environmental impact

All-solid-state batteries are a hot research topic due to the prospect of high energy density and higher intrinsic safety, compared to conventional lithium-ion batteries. Of the wide variety of solid-state electrolytes currently researched, oxide ceramic lithium-ion conductors are considered the most difficult to implement in industrial cells. Although their high lithium-ion conductivity combined with a high chemical and thermal stability make them a very attractive class of materials, cost-cutting synthesis and scalable processing into full batteries remain to be demonstrated. Additionally, they are Fluorine-free and can be processed in air but require one or more high temperature treatment steps during processing counteracting their ecological benefits. Thus, a viable cell design and corresponding assessment of its ecological impact is still missing. To close this gap, we define a target cell combining the advantages of the two most promising oxidic electrolytes, lithium lanthanum zirconium oxide (LLZO) and lithium aluminium titanium phosphate (LATP). Even though it has not been demonstrated so far, the individual components are feasible to produce with state-of-the-art industrial manufacturing processes. This model cell then allows us to assess the environmental impact of the ceramic electrolyte synthesis and cell component manufacturing not just on an abstract level (per kg of material) but also with respect to their contributions to the final cell. The in-depth life cycle assessment (LCA) analysis revealed surprising similarities between oxide-based all-solid-state batteries and conventional Li-ion batteries. The overall LCA inventory on the material level is still dominated by the cathode active material, while the fabrication through ceramic manufacturing processes is a major contributor to the energy uptake. A clear path that identifies relevant research and development directions in terms of economic benefits and environmental sustainability could thus be developed to promote the competitiveness of oxide based all-solid-state batteries in the market