This dissertation explores questions in financial aid, student loans, and homework time use. In chapter one, I use quarter of birth instruments to estimate the relationship between calculated financial need and actual financial aid received. A dollar increase in financial need is associated with 15 cents in federal grants and 47 cents in loans. However, the relationship between financial need and institutional aid is, on average, small and statistically insignificant. In chapter two, I use instrumental variables to estimate the effect of student loans on fertility later in life. First, I exploit a FAFSA loan-eligibility rule along with state-level variation in the school-entrance age to instrument for differences in loan availability. Next, I exploit state-by-SAT-score variation in tuition at public universities to instrument for differences in loan demand. I find that an increase in undergraduate loans, due to an increase in loan availability, does not significantly affect fertility. However, an increase in loans, due to higher tuition, decreases the number of children the student has 10 years after graduation. Back of the envelope calculations suggest that doubling tuition at in- state public colleges will lead to a 14 percent decrease in total fertility 10 years after graduation. In chapter three, we use the American Time Use Survey (ATUS) to document that Asian- American high-school students, on average, spend 2.3 times more time on homework compared to white students and 3.9 times more time on homework compared to black students. Our estimates suggest that the Asian-white homework gap is approximately 7.4 hours per week. Contrary to certain stereotypes, Asian-American students do not spend less time on leisure or sleep compared to white students. Rather, Asian-American students spending less time working for pay, doing household chores, and playing sports account for the entire Asian-white homework gap. We hypothesize that the differences in time use across ethnic groups may be related to the differences in educational outcomes across ethnic group

Here, we provide revised gene models for D. ananassae, D. yakuba, and D. simulans, which include untranslated regions and empirically verified intron-exon boundaries, as well as ortholog groups identified using a fuzzy reciprocal-best-hit blast comparison. Using these revised annotations, we perform differential expression testing using the cufflinks suite to provide a broad overview of differential expression between reproductive tissues and the carcass. We identify thousands of genes that are differentially expressed across tissues in D. yakuba and D. simulans, with roughly 60% agreement in expression patterns of orthologs in D. yakuba and D. simulans. We identify several cases of putative polycistronic transcripts, pointing to a combination of transcriptional read-through in the genome as well as putative gene fusion and fission events across taxa. We furthermore identify hundreds of lineage specific genes in each species with no blast hits among transcripts of any other Drosophila species, which are candidates for neofunctionalized proteins and a potential source of genetic novelty.

Conducting polymers such as poly(3-hexylthiophene) (P3HT) can be used to convey electronic charge in battery electrodes. The electronic conductivity of P3HT (and other electronically conducting polymers) is potential-dependent. The main advance in this work is to quantify the effect of this potential dependency on battery performance. The discharge characteristics of a battery consisting of a cathode with LiFePO4 particles in a poly(3-hexylthiophene)-b-poly(ethylene oxide) (P3HT-PEO) copolymer matrix that conveys electrons and ions to the active particles, a polystyrene-b-poly(ethylene oxide) (PS-PEO) copolymer electrolyte layer, and a lithium metal anode were examined by experiments and macro-homogeneous modeling; lithium bis (trifluoromethanesulfonyl) imide was the salt in the cathode and the electrolyte. By comparing the model predictions with experiments, we conclude that the electronic conductivity of the polymer in the cathode is significantly lower than that obtained from measurements in the absence of active particles. The potential-dependent conductivity is manifested in the shape of the discharge curve wherein the slope increases continuously with capacity. The model provides insight into the underpinnings of the observed rate-dependency of electrode capacity, thereby guiding the design of the next generation of electrodes.

This describes a vertically-integrated exploration of NMC electrode rate limitations, combining experiments with corresponding macroscale (macro-homogeneous) and microscale models. Parameters common to both models were obtained from experiments or based on published results. Positive electrode tortuosity was the sole fitting parameter used in the macroscale model, while the microscale model used no fitting parameters, instead relying on microstructural domains generated from X-ray microtomography of pristine electrode material held under compression while immersed in electrolyte solution (additionally providing novel observations of electrode wetting). Macroscale simulations showed that the capacity decrease observed at higher rates resulted primarily from solution-phase diffusion resistance. This ability to provide such qualitative insights at low computational costs is a strength of macroscale models, made possible by neglecting electrode spatial details. To explore the consequences of such simplification, the corresponding, computationally-expensive microscale model was constructed. This was found to have limitations preventing quantitatively accurate predictions, for reasons that are discussed in the hope of guiding future work. Nevertheless, the microscale simulation results complement those of the macroscale model by providing a reality-check based on microstructural information; in particular, this novel comparison of the two approaches suggests a reexamination of salt diffusivity measurements.

We have used whole genome paired-end Illumina sequence data to identify tandem duplications in 20 isofemale lines of Drosophila yakuba and 20 isofemale lines of D. simulans and performed genome wide validation with PacBio long molecule sequencing. We identify 1,415 tandem duplications that are segregating in D. yakuba as well as 975 duplications in D. simulans, indicating greater variation in D. yakuba. Additionally, we observe high rates of secondary deletions at duplicated sites, with 8% of duplicated sites in D. simulans and 17% of sites in D. yakuba modified with deletions. These secondary deletions are consistent with the action of the large loop mismatch repair system acting to remove polymorphic tandem duplication, resulting in rapid dynamics of gain and loss in duplicated alleles and a richer substrate of genetic novelty than has been previously reported. Most duplications are present in only single strains, suggesting that deleterious impacts are common. Drosophila simulans shows larger numbers of whole gene duplications in comparison to larger proportions of gene fragments in D. yakuba. Drosophila simulans displays an excess of high-frequency variants on the X chromosome, consistent with adaptive evolution through duplications on the D. simulans X or demographic forces driving duplicates to high frequency. We identify 78 chimeric genes in D. yakuba and 38 chimeric genes in D. simulans, as well as 143 cases of recruited noncoding sequence in D. yakuba and 96 in D. simulans, in agreement with rates of chimeric gene origination in D. melanogaster. Together, these results suggest that tandem duplications often result in complex variation beyond whole gene duplications that offers a rich substrate of standing variation that is likely to contribute both to detrimental phenotypes and disease, as well as to adaptive evolutionary change.

One common hypothesis to explain the impacts of tandem duplications is that whole gene duplications commonly produce additive changes in gene expression due to copy number changes. Here, we use genome wide RNA-seq data from a population sample of Drosophila yakuba to test this 'gene dosage' hypothesis. We observe little evidence of expression changes in response to whole transcript duplication capturing 5' and 3' UTRs. Among whole gene duplications, we observe evidence that dosage sharing across copies is likely to be common. The lack of expression changes after whole gene duplication suggests that the majority of genes are subject to tight regulatory control and therefore not sensitive to changes in gene copy number. Rather, we observe changes in expression level due to both shuffling of regulatory elements and the creation of chimeric structures via tandem duplication. Additionally, we observe 30 de novo gene structures arising from tandem duplications, 23 of which form with expression in the testes. Thus, the value of tandem duplications is likely to be more intricate than simple changes in gene dosage. The common regulatory effects from chimeric gene formation after tandem duplication may explain their contribution to genome evolution.

We have used whole genome paired-end Illumina sequence data to identify tandem duplications in 20 isofemale lines of Drosophila yakuba and 20 isofemale lines of D. simulans and performed genome wide validation with PacBio long molecule sequencing. We identify 1,415 tandem duplications that are segregating in D. yakuba as well as 975 duplications in D. simulans, indicating greater variation in D. yakuba. Additionally, we observe high rates of secondary deletions at duplicated sites, with 8% of duplicated sites in D. simulans and 17% of sites in D. yakuba modified with deletions. These secondary deletions are consistent with the action of the large loop mismatch repair system acting to remove polymorphic tandem duplication, resulting in rapid dynamics of gain and loss in duplicated alleles and a richer substrate of genetic novelty than has been previously reported. Most duplications are present in only single strains, suggesting that deleterious impacts are common. Drosophila simulans shows larger numbers of whole gene duplications in comparison to larger proportions of gene fragments in D. yakuba. Drosophila simulans displays an excess of high-frequency variants on the X chromosome, consistent with adaptive evolution through duplications on the D. simulans X or demographic forces driving duplicates to high frequency. We identify 78 chimeric genes in D. yakuba and 38 chimeric genes in D. simulans, as well as 143 cases of recruited noncoding sequence in D. yakuba and 96 in D. simulans, in agreement with rates of chimeric gene origination in D. melanogaster. Together, these results suggest that tandem duplications often result in complex variation beyond whole gene duplications that offers a rich substrate of standing variation that is likely to contribute both to detrimental phenotypes and disease, as well as to adaptive evolutionary change.

Simulations are presented that result from incorporating dimensional and porosity changes in porous electrodes caused by volume changes in the active material during intercalation into a detailed lithium-ion battery model. Porosity and dimensional changes in an electrode can significantly affect the resistance of the battery during cycling, which in turn alters the reaction distributions in the porous electrodes. In addition, volume changes generate stresses in the electrode which can lead to premature failure of the battery. Here, material conservation equations are coupled with the mechanical properties of porous electrodes to link dimensional and porosity changes to stresses and the resulting resistances that occur during the intercalation processes. Through the use of porous rock mechanics, porosity and strain gradients can be predicted based on state of discharge and discharge rate. Several different battery casings and discharge rates are examined and operating curves are predicted.

Conjugated semiconducting polymers, such as poly(3-hexylthiophene) (P3HT), are poised to play an integral role in the development of organic electronic devices; however, their performance is governed by factors that are intrinsically coupled: dopant concentration, carrier mobility, crystal structure, and mesoscale morphology. We utilize synchrotron X-ray scattering and electrochemical impedance spectroscopy to probe the crystal structure and electronic properties of P3HT in situ during electrochemical doping. We show that doping strains the crystalline domains, coincident with an exponential increase in hole mobility. We believe these observations provide guidance for the development of improved theoretical models for charge transport in semiconducting polymers.

Background and aims

Colon cancer can occur sporadically or in the setting of chronic inflammation, such as in patients with inflammatory bowel disease. We previously showed that A20, a critical negative regulator of tumor necrosis factor signal transduction, could regulate sporadic colon cancer development. In this report, we investigate whether A20 also acts as a tumor suppressor in a model of colitis-associated cancer.

Methods

Colitis and colitis-associated tumors were induced in wild-type and A20 intestinal epithelial cell-specific knockout (A20dIEC) mice using dextran sodium sulfate and azoxymethane. Clinicopathologic markers of inflammation were assessed in conjunction with colonic tumor burden. Gene expression analyses and immunohistochemistry were performed on colonic tissue and intestinal enteroids. Nitric oxide (NO) production and activity were assessed in whole colonic lysates and mouse embryonic fibroblasts.

Results

A20dIEC mice develop larger tumors after treatment with dextran sodium sulfate and azoxymethane than wild-type mice. In addition to elevated markers of inflammation, A20dIEC mice have significantly enhanced expression of inducible nitric oxide synthase (iNOS), a well-known driver of neoplasia. Enhanced iNOS expression is associated with the formation of reactive nitrogen species and DNA damage. Loss of A20 also enhances NO-dependent cell death directly.

Conclusion

Mechanistically, we propose that A20 normally restricts tumor necrosis factor-induced nuclear factor kappa B-dependent production of iNOS in intestinal epithelial cells, thereby protecting against colitis-associated tumorigenesis. We also propose that A20 plays a direct role in regulating NO-dependent cell death.