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Chronic alcohol abuse is a key component of alcohol use disorder and leads to adverse changes in localised regions of the human brain (Zahr & Pfefferbaum, 2017). The prefrontal cortex is particularly susceptible to damage following chronic alcohol abuse (Abernathy et al., 2010). Differential gene expression in the prefrontal cortex has been identified between alcoholics and controls, and includes genes related to immune/stress response (Liu et al., 2006). A chronic immune response in the central nervous system, termed neuroinflammation, has been implicated in the progression of alcohol-induced brain damage (Crews & Vetreno, 2014). Liver cirrhosis, a common co-morbid condition of chronic alcohol abuse, worsens alcohol-induced brain damage (Zahr & Pfefferbaum, 2017). Differential gene expression in the prefrontal cortex has been identified between alcoholics without liver cirrhosis (uncomplicated alcoholics) and alcoholics with liver cirrhosis (cirrhotic alcoholics) (Liu et al., 2007). Furthermore, females have more advanced neurodegeneration following chronic alcohol abuse (Ceylan-Isik et al., 2010). MicroRNAs (miRNAs) are a subclass of non-coding RNAs that regulate messenger RNA (mRNA) expression by binding to complementary seed sequences (O'Brien et al., 2018). Approximately 35 up-regulated miRNAs have been identified in the prefrontal cortex of human alcoholics (Lewohl et al., 2011). Dysregulation of miRNA expression following chronic alcohol abuse may result in the gene expression changes seen in alcoholics (Lewohl et al., 2011; Liu et al., 2007; Liu et al., 2006). As part of this thesis, original research articles related to α-synuclein, neuroinflammation, and alcoholism were reviewed and evaluated. The SNCA gene, which encodes α-synuclein, has been identified as a top candidate gene for alcoholism (Levey et al., 2014). No articles included information relating to all three of these topics, suggesting that the link between these three topics is yet to be identified. Toll-like receptor (TLR) 4, an innate immune receptor, was commonly studied in the field of alcoholism. Studies in humans used a variety of diagnostic criteria for the diagnosis of alcoholism. Studies in animals used a variety of alcohol exposure paradigms. Thus, a lack of consistency in diagnostic criteria for humans and animal models may complicate the interpretation of data derived from different studies. This thesis investigated differences in miRNA-7 (miR-7), miRNA-153 (miR-153), and miRNA-203 (miR-203) expression in the dorsolateral prefrontal cortex (prefrontal cortex) between controls, uncomplicated alcoholics, and cirrhotic alcoholics. Males and females were analysed separately to identify sex-specific changes in miRNA expression. Expression of miR-7, miR-153, and miR-203 was significantly higher in male uncomplicated alcoholics and cirrhotic alcoholics compared to controls. There were no differences in miR-7, miR-153, or miR-203 expression between controls, uncomplicated alcoholics, or cirrhotic alcoholics in females. MiR-153 has previously been validated to regulate the expression of wild-type α- synuclein (SNCA-140) (Doxakis, 2010). MiR-203 is predicted to target the α-synuclein splice variant SNCA-115 (McGeary et al., 2019). As part of my study, neuron-like cell cultures were treated with mimics or inhibitors of miR-153 or miR-203 to investigate their effect on SNCA-140, SNCA-112, and SNCA-115 expression. A 2.3-fold increase in SNCA-115 expression was identified 48 h after treatment with miR-203 inhibitor. The findings of this thesis highlight the effect of sex and liver cirrhosis in miRNA expression changes following chronic alcohol abuse. Regulation of α-synuclein splice variant expression by miRNAs may play a role in mediating the reward pathway (Butler et al., 2017) or alcohol-induced brain damage (Bennett, 2005). Understanding the mechanisms that underlie miRNA-mediated α-synuclein splice variant expression may enhance understanding of neuroinflammation and neuron function that results from chronic alcohol abuse.

Medulloblastoma is the most common malignant brain tumor in children. While survival has improved in high-income countries (HIC), the outcomes for patients in low-to-middle-income countries (LMIC) are unclear. Therefore, we sought to determine the survival of children with medulloblastoma at the Instituto Nacional de Enfermedades Neoplasicas (INEN) between 1997 and 2013 in Peru.Between 1997 and 2013, data from 103 children older than 3 years with medulloblastoma were analyzed. Fourteen patients were excluded. The patients were split into two distinct cohorts, 1997-2008 and 2009-2013, corresponding with chemotherapy regimen changes. Event-free (EFS) and overall survival (OS) were calculated using the Kaplan-Meier method, whereas prognostic factors were determined by univariate analysis (log-rank test).Eighty-nine patients were included; median age was 8.1 years (range: 3-13.9 years). The 5-year OS was 62% (95% CI: 53%-74%), while EFS was 57% (95% CI: 48%-69%). The variables adversely affecting survival were anaplastic histology (compared to desmoplastic; OS: HR = 3.4, p = .03), metastasis (OS: HR = 3.5, p = .01; EFS: HR = 4.3, p = .004), delay in radiation therapy of 31-60 days (compared to ≤30 days; EFS: HR = 2.1, p = .04), and treatment 2009-2013 cohort (OS: HR = 2.2, p = .02; EFS: HR = 2.0, p = .03).Outcomes for medulloblastoma at INEN were low compared with HIC. Anaplastic subtype, metastasis at diagnosis, delay in radiation therapy, and treatment in the period 2009-2013 negatively affected the outcomes in our study. Multidisciplinary teamwork, timely delivery of treatment, and partnerships with loco-regional groups and colleagues in HIC is likely beneficial.

Climate change threatens established communities on low-lying Pacific atoll islands by increasing their vulnerability to wave-driven flooding and shoreline instability. Atoll islands are dynamic features whose morphology can quickly respond to changing climate, sea level, and wave conditions. Results from this thesis provide new information about how future wave climates may change near Pacific atoll islands, specific projections for flooding and erosion at two particular atolls, and insights into how atoll morphology affects shoreline susceptibility to erosion. The first study projects how wave climates may change in the western tropical Pacific by 2100 at 25 island locations under two greenhouse gas emissions scenarios. Output from four global climate models were used to run a dynamically-downscaled numerical wave model. The mean of the top 5% of future boreal winter and summer wave heights, and their associated directions and frequencies, were calculated. Large winter wave heights were projected to decrease throughout the study area, and summer large wave directions were projected to change by as much as 30°. These changes were incorporated into the second study, which modeled run-up and erosion along island shorelines at Wake and Midway Atolls under differing oceanographic forcing conditions. Sea-level rise was projected to be the dominant control on flooding and morphological change on these two atolls, indicating that atoll islands are at great risk even if future wave heights decrease. Small changes in the direction of large incident waves also had a significant impact on shoreline flooding and erosion. Better-protected shorelines (e.g., lagoon shorelines) were disproportionately affected by increasing sea level and changing wave directions. While these findings were site specific for two atypical atolls, the third study involved modeling shoreline erosional change on a schematic atoll and evaluating how initial morphology affects shoreline response. Bathymetry for a generic atoll was generated with varying morphological parameters and wave-driven erosion was calculated. The parameters that had a significant impact on shoreline erosion were: reef flat width, reef flat depth, island width, and atoll diameter. Atolls with narrower, deeper reef flats, narrower islands, and smaller diameters were most susceptible to shoreline instability with sea level rise. Windward islands are projected to lengthen and migrate toward the lagoon, leeward islands are projected to lengthen and migrate toward the reef rim, and oblique islands are projected to migrate leeward and toward the lagoon. Findings from all three studies elucidate shoreline processes along atoll islands and provide critical information that can guide aid allocation and help communities plan for future hazards.

To investigate the influence of cell formats during a cell development programme, lithium-ion cells have been prepared in three different formats. Coin cells, single layer pouch cells, and stacked pouch cells gave a range of scales of almost three orders of magnitude. The cells used the same electrode coatings, electrolyte and separator. The performance of the different formats was compared in long term cycling tests and in measurements of resistance and discharge capacities at different rates. Some test results were common to all three formats. However, the stacked pouch cells had higher discharge capacities at higher rates. During cycling tests, there were indications of differences in the predominant degradation mechanism between the stacked cells and the other two cell formats. The stacked cells showed faster resistance increases, whereas the coin cells showed faster capacity loss. The difference in degradation mechanism can be linked to the different thermal and mechanical environments in the three cell formats. The correlation in the electrochemical performance between coin cells, single layer pouch cells, and stacked pouch cells shows that developments within a single cell format are likely to lead to improvements across all cell formats.

Metastasis is the leading cause of cancer related deaths for patients with solid tumors. While tumor genomic evolution is one possible mechanism whereby cancer cells acquire chemotherapy resistance during the metastatic process, increasing evidence demonstrates that non-cancerous cells within the secondary organ have crucial roles in mediating metastasis and therapy resistance. Therefore, disrupting tumor-stromal cell interactions is an exploitable therapeutic strategy to improve outcomes. Unfortunately, mechanistic insight into tumor-stromal interactions is limited for most cancers. Osteosarcoma, an aggressive bone tumor that primarily afflicts children and young adults, displays an overwhelming propensity for metastasis to the lungs, with overall survival plummeting to less than 20% at 5 years upon lung metastasis. Why osteosarcoma displays tropism for the lung and how it educates the lung to promote tumor growth in a vastly different microenvironment from the primary tumor remains poorly understood. In this study, we utilized single-cell RNA sequencing to define the cellular and molecular landscape of osteosarcoma metastases in immunocompetent mouse models. We unexpectedly found that alveolar epithelial cells are the most prominent non-immune stromal component within lung metastases. Not only are they present in significant numbers in lung metastases compared to unaffected lung, our molecular analysis demonstrated that tumor associated epithelial cells acquire a pro-fibrosis ‘wound-like’ phenotype, which was also observed in human metastasis samples. Furthermore, utilizing human and mouse culture systems, we found that osteosarcoma cells directly reprogramed epithelial cells through secretion of growth factors and cytokines such as FGF7 and IL6. These profibrotic epithelial cells in turn induced osteosarcoma cells to generate a complex, beta-1integrin (ITGB1)- dependent fibronectin matrix. The epithelial induced fibronectin matrix promoted osteosarcoma invasion and chemotherapy resistance. Accordingly, inhibition of ITGB1 sensitized osteosarcoma cells to chemotherapy. Collectively our results demonstrate that osteosarcoma cells educate the lung microenvironment into a ‘pro-wound’, pro-fibrosis state that is conducive to osteosarcoma lung colonization. Disruption of the lung metastatic niche is a promising therapeutic target for sensitizing osteosarcoma cells to chemotherapy. Citation Format: James Brandon Reinecke, Amy Gross, Maren Cam, Ryan Roberts. Tumor educated lung epithelial cells promote osteosarcoma metastasis and chemotherapy resistance by inducing integrin dependent fibronectin fibrillogenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3179.

Outcomes for young people diagnosed with osteosarcoma hinge almost exclusively on whether they develop lung metastasis. The striking predilection that osteosarcoma shows for metastatic spread to lung suggests properties and/or lung interactions that generate tissue-specific survival and proliferation advantages. While these mechanisms remain overall poorly defined, studies have begun to describe biological elements important to metastasis. Mechanisms described to date include both cell-autonomous adaptations that allow disseminated tumor cells to survive the stressors imposed by metastasis and intercellular signaling networks that tumor cells exploit to pirate needed signals from surrounding tissues or to recruit other cells that create a more favorable niche. Evidence suggests that cell-autonomous changes are largely driven by epigenetic reprogramming of disseminated tumor cells that facilitates resistance to late apoptosis, manages endoplasmic reticulum (ER) stressors, promotes translation of complex transcripts, and activates clotting pathways. Tumor-host signaling pathways important for lung colonization drive interactions with lung epithelium, mesenchymal stem cells, and mediators of innate and adaptive immunity. In this chapter, we highlight one particular pathway that integrates cell-autonomous adaptations with lung-specific tumor-host interactions. In this mechanism, aberrant ΔNp63 expression primes tumor cells to produce IL6 and CXCL8 upon interaction with lung epithelial cells. This tumor-derived IL6 and CXCL8 then initiates autocrine, osteosarcoma-lung paracrine, and osteosarcoma-immune paracrine interactions that facilitate metastasis. Importantly, many of these pathways appear targetable with clinically feasible therapeutics. Ongoing work to better understand metastasis is driving efforts to improve outcomes by targeting the most devastating complication of this disease.

The role and relative importance of vesicular arbuscular mycorrhiza (VAM), Rhizobium, weed competition, water stress and soil fertility (nitrogen, phosphorus and Ph) on early growth and establishment of leucaena were examined in a series of field and pot trials conducted in Central and Southeast Queensland from December 1987 to June 1990. Leucaena was found to be highly dependant on VAM for phosphorus extraction from the soil. Plants growing in soils low in mycorrhizal activity suffered a period of phosphorus deficiency until 15-20% root length was infected. Large differences in rate of infection were observed between soils. Activity of indigenous mycorrhiza able to infect leucaena varied among eight soils collected in Southeast and Central Queensland and accounted for over 65% of height differences in 4 and 6 week old leucaena grown in pots. This is the first documented evidence of growth differences in leucaena linked with varying levels of VAM in Australian soils. Other factors however appeared to have an over-riding importance in leucaena grown at 5 sites in the field. Phosphorous concentration in plant tissues were generally above critical nutrient concentrations 6-8 weeks after planting. Best final yield occurred in a well structured soil from Redland Bay (lowest in mycorrhizal activity). A soil higher in mycorrhizal activity on the other hand produced poor growth due to waterlogging. Early growth of leucaena in soils low in mycorrhizal activity could be increased by application of phosphorus fertilizer in pots and some field sites. Very high rates however were needed to stimulate early growth of plants. For example, 1200 kg P/ ha was required to significantly increase growth and tissue phosphorus concentration of leucaena prior to week 5 in a low activity podzolic soil from Mt. Cotton. As infection of the roots increased, however, response to phosphorus decreased and final yield at 75 kg P/ ha in the field and at 100 kg P/ ha in pots, was similar to that at the 1200 kg P/ ha rate. Very little response was found to application of nitrogen in either the field or in pots. A new Rhizobium strain CB3060 (TALI 145) was found to effectively nodulate leucaena in a number of soils. It was found to be persistent and accounted for greater than 90% nodules 12 months after planting at a site at Crows Nest.

Outcomes for young people diagnosed with osteosarcoma hinge almost exclusively on whether they develop lung metastasis. The striking predilection that osteosarcoma shows for metastatic spread to lung suggests properties and/or lung interactions that generate tissue-specific survival and proliferation advantages. While these mechanisms remain overall poorly defined, studies have begun to describe biological elements important to metastasis. Mechanisms described to date include both cell-autonomous adaptations that allow disseminated tumor cells to survive the stressors imposed by metastasis and intercellular signaling networks that tumor cells exploit to pirate needed signals from surrounding tissues or to recruit other cells that create a more favorable niche. Evidence suggests that cell-autonomous changes are largely driven by epigenetic reprogramming of disseminated tumor cells that facilitates resistance to late apoptosis, manages endoplasmic reticulum (ER) stressors, promotes translation of complex transcripts, and activates clotting pathways. Tumor-host signaling pathways important for lung colonization drive interactions with lung epithelium, mesenchymal stem cells, and mediators of innate and adaptive immunity. In this chapter, we highlight one particular pathway that integrates cell-autonomous adaptations with lung-specific tumor-host interactions. In this mechanism, aberrant ΔNp63 expression primes tumor cells to produce IL6 and CXCL8 upon interaction with lung epithelial cells. This tumor-derived IL6 and CXCL8 then initiates autocrine, osteosarcoma-lung paracrine, and osteosarcoma-immune paracrine interactions that facilitate metastasis. Importantly, many of these pathways appear targetable with clinically feasible therapeutics. Ongoing work to better understand metastasis is driving efforts to improve outcomes by targeting the most devastating complication of this disease.

Organic additives are typically used in the pulse electrodeposition of copper (Cu) to prevent void formation during the filling of high aspect ratio features. In this work, the role of bath chemistry as modified by organic additives was investigated for its effects on Cu trench microstructure. Polyethylene glycol (PEG), bis(3-sulfopropyl) disulfide (SPS), and Janus green b (JGB) concentrations were varied in the Cu electrodeposition bath. Results indicated a correlation between the JGB/SPS ratio and the surface roughness and residual stresses in the Cu. Electron backscattering diffraction (EBSD) and transmission Kikuchi diffraction (TKD) were used to study the cross-sectional microstructure in the trenches. Finer grain morphologies appeared in trenches filled with organic additives as compared to additive-free structures. Cu trench (111) texture also decreased with increasing organic additive concentrations due to more pronounced influence of sidewall seed layers on trench features. Twin density in the microstructure closely tracked calculated stresses in the Cu trenches. A comprehensive microstructural analysis was conducted in this study, on an area of focus that has garnered little attention from the literature, yet can have a major impact on microelectronic reliability.

Commercial lithium ion cells are now optimised for either high energy density or high power density. There is a trade off in cell design between the power and energy requirements. A tear down protocol has been developed, to investigate the internal components and cell engineering of nine cylindrical cells, with different power&ndash, energy ratios. The cells designed for high power applications used smaller particles of the active material in both the anodes and the cathodes. The cathodes for high power cells had higher porosities, but a similar trend was not observed for the anodes. In terms of cell design, the coat weights and areal capacities were lower for high power cells. The tag arrangements were the same in eight out of nine cells, with tags at each end of the anode, and one tag on the cathode. The thicknesses of the current collectors and separators were based on the best (thinnest) materials available when the cells were designed, rather than materials optimised for power or energy. To obtain high power, the resistance of each component is reduced as low as possible, and the lithium ion diffusion path lengths are minimised. This information illustrates the significant evolution of materials and components in lithium ion cells in recent years, and gives insight into designing higher power cells in the future.

This study focuses on identifying if the metastatic niche in osteosarcoma (OS) enriches for cells that have a survival advantage either from pre-defined genetic programs or adaptive responses to environmental cues. OS patients who develop metastases experience a dismal survival rate that is lower than twenty percent, a statistic that remains unchanged despite four decades of efforts to improve these outcomes. While therapies that treat metastasis could dramatically improve outcomes, we understand too little about the mechanisms of lung colonization to propose any rational intervention. To simultaneously evaluate changes in clonal diversity and phenotype during the metastatic bottleneck, cell by cell, we combined prospective lineage tracing with single cell transcriptomics in several murine models of metastatic OS. Single cell suspensions of metastatic tumor tissues were processed for single-cell RNA sequencing (scRNA-Seq). For lineage tracing studies, OS cells were virally-transduced to contain a high diversity, heritable and scRNA-Seq compatible lineage tag before inoculating mice. Single-cell libraries were processed bioinformatically to overlay phenotype and lineage information for each cell. Our findings support the following conclusions: First, that the metastatic bottleneck selects for certain clones with increased colonizing capacity, but this selection does not narrow the overall phenotypic diversity of those cells–clones of many different phenotypes can be found within the metastases. Second, the metastatic lung enriches for certain features that are conserved across different cell line and PDX models of metastatic OS. Gene set enrichment analysis of genes enriched within the surviving clones identified novel activated signaling pathways and upstream regulators that appear critical for metastatic progression. This signature includes activated IL6, TGF-β, PDGF signaling, response to a previously unidentified upstream regulator, IL-1β, and the acquisition of enhanced glycolytic activity. Whether each lesion becomes colonized by a phenotypically-distinct clone giving rise to phenotypically-diverse lesions or whether cooperation between phenotypically-distinct clones is required to effect colonization remains a point of active study. In summary, metastatic colonization of the lung by OS involves the selection of phenotypically-diverse tumor cell clones that share characteristics that engender fitness within the lung microenvironment. Citation Format: Sanjana Rajan, Maren Cam, Amy Gross, James Reinecke, Cenny Taslim, Ryan Roberts. Metastatic bottleneck in osteosarcoma selects for certain clonal populations, while metastatic lesions exhibit diverse phenotypes [abstract]. In: Proceedings of the AACR Virtual Special Conference on Tumor Heterogeneity: From Single Cells to Clinical Impact; 2020 Sep 17-18. Philadelphia (PA): AACR; Cancer Res 2020;80(21 Suppl):Abstract nr PO-012.

Four decades of intense multinational efforts to improve outcomes for children and teenagers with osteosarcoma have failed. Today, we still treat patients with a regimen first developed in 1982. The same 35-40% of young people diagnosed with osteosarcoma die from their disease, almost always from complications related to lung metastasis. Believing that therapies targeting lung metastasis could dramatically improve outcomes, we have sought to understand the mechanisms that drive lung colonization in this disease. We previously found that interactions with lung epithelium cause osteosarcoma cells to produce IL6 and CXCL8 and that this activity is necessary for metastasis. Inhibiting IL6 and CXCL8 signaling prevents metastasis entirely in 85% of mice with osteosarcoma. While conducting these studies, we learned that individual tumor cells react differently to signals from lung epithelium. Nearly all the IL6 and CXCL8 produced by osteosarcoma cells come from a small subset of cells. Interactions with pulmonary epithelium cause this discrete subset of tumor cells to produce large quantities of inflammatory cytokines, become strongly p21+, and stop proliferating. Early metastatic lesions consist almost entirely of cells with this phenotype, positioning them to orchestrate the development of the metastatic niche. Thus, we call these hypo-proliferative, cytokine-producing cells that survive early attrition "anchor cells." In the initial stages of metastasis, anchor cells alter the surrounding lung tissue in ways that facilitate subsequent colonization by tumor cells with proliferating phenotypes ("growth cells"). Growth cells then divide to create expanding, clinically-relevant metastasis. Importantly, one can leverage the biology of these anchor cells to develop rational targeting strategies. Anchor cells exhibit profound sensitivity to known senolytic agents. Combining these with conventional therapies (which effectively target growth cells) can eradicate established metastatic lesions and prevent new metastases from forming. These novel findings fundamentally alter our understanding of osteosarcoma and metastasis biology and have direct implications for approaches to treatment. Citation Format: James B. Reinecke, John M. Hinckley, Amy C. Gross, Maren Cam, Sanjana Rajan, Ryan D. Roberts. Distinct subpopulations of osteosarcoma cells cooperate to establish lung metastases [abstract]. In: Proceedings of the AACR Virtual Special Conference on Tumor Heterogeneity: From Single Cells to Clinical Impact; 2020 Sep 17-18. Philadelphia (PA): AACR; Cancer Res 2020;80(21 Suppl):Abstract nr PO-123.

Lymphatic filariasis is a neglected tropical disease caused by roundworm parasites such as Brugia malayi that spread via a mosquito vector. In vitro culture of these parasites provides controlled conditions to understand parasite biology and provides a cheaper way to screen potential micro- and macrofilaricides. Published studies have used a wide array of approaches and metrics regarding in vitro cultures of B. malayi; as a result, drawing comparisons and identifying the reasons why inability to reproduce outcomes are difficult. This study sought to determine conditions that ensure reproducible outcomes and used evaluation metrics that are easily measured and can be automated to ensure objectivity. We found culturing B. malayi third-stage larvae (L3) in endothelial basal media supplemented with 20% fetal bovine serum and 75 µ m ascorbic acid in a temperature- and humidity-controlled incubator produced better survival and molting rates as well as longer and more motile parasites than previously reported. The benefit of ascorbic acid seemed to be unique to L3 parasites, as the addition of ascorbic acid to adult parasites had no significant impact on survival or motility. The methods reported in this study will help in designing experiments for both parasite behaviour studies and drug screening applications for disease eradication.

In this study, the effect of thermal cycling on defect generation, microstructure, and RF signal integrity of blind Cu through-silicon vias (TSVs) were investigated. Three different thermal cycling profiles were used; each differentiated by their peak cycling temperature (100 °C, 150 °C, 200 °C) and the time needed to complete one cycle (cycle time). The study was performed on two Cu TSV wafer sample types; one containing large processing-induced voids (voided sample), the other without (non-voided sample). It was found that the RF signal return loss |S 11 | of the Cu TSVs increased upon thermal cycling for both the voided and the non-voided sample types. This was attributed to the increase in the void area due to the formation of new voids, rather than the growth of preexisting voids. On the other hand, the grain orientation and grain sizes of the Cu TSVs were found to be unaffected by all studied thermal cycling conditions and sample types.

The economic prosperity of a nation is a complex function of many factors, including its culture, geography, history, legal origins, ethnolinguistic fractionalization, resource endowment, leadership and religious homogeneity. However, economic prosperity is most robustly related to the quality of a nations institutions under which its resources are put to productive use. Institutions are the humanly devised constraints that structure political, economic and social interactions. Fundamental economic institutions, like property rights and the rule of law, structure the incentives that affect a nations productivity. Since at least the early 1990s, economists have quantified economic institutions and policies by aggregating economic policy variables into economic indexes. Of these indexes, the most popular is the Economic Freedom of the World, which measures the consistency of a nations institutions with the principles of economic freedom. After decades of study, we know that economic freedom is positively related to income, gender equality, civil liberty and happiness among other desirable economic outcomes. Despite the benefits of simplifying institutions into a single number, the implicit assumptions required to do so are costly. By summarizing institutional quality as a single quantity, scholars assume that the underlying institutional structure of two economies are identical as long as their summary scores are identical. This assumption is often false, and this research examines the costs of this assumption for modeling economic growth. The common methodology for measuring institutional quality ignores both institutional volatility and institutional imbalance. This research shows that both measures are robustly and negatively related to economic growth rates. Therefore, models that simply a nations institutions to a single value at a single period of time are assuming away valuable information that helps explain a nations prosperity or lack

Through-silicon vias (TSV) are copper (Cu) interconnects used in three dimensional integrated circuits (3D-IC) and other packaging to allow inter-chip communication. A thermo-mechanical reliability concern for Cu-TSVs, are the formation of voids, which are indicative of the stresses undergone by the structures. Voids can degrade signal propagation by acting as scattering centers and if large enough, can prevent the passage of current [1]. Simulations of fabrication conditions such as back-end-of-the-line (BEOL) addition, have been conducted by isothermal heating or minimal cycling [2-4]; however, few studies have focused on in-use conditions where chips undergo many cycles at lower temperatures, simulating environmental changes and joule heating from use. This study replicates these in-use conditions to evaluate defect evolution and distribution in thermally cycled Cu-TSVs. Silicon (Si) chips containing blind Cu-TSVs were cycled 2000 times from room temperature to maximum cycling temperatures of 100 °C, 150 °C, or 200 °C. Residual voiding from fabrication was considered by examining two sample types (shown in Fig. 1), specimens that contained Cu-TSVs with seams and large bottom voids and those that exhibited only microvoids. The S11 parameter was measured at 500 cycle increments and determined signal loss trended with maximum cycling temperature and initial void area, but not with number of cycles. To further investigate void development, the TSVs were cross-sectioned for internal evaluation using a combination of grinding, polishing, and ion beam milling. Voids were then studied using focus ion beam (FIB) and scanning electron microscope (SEM) images to record void dimensions and locations within the Cu of the TSVs. Void area was observed to increase with increasing maximum cycling temperature from 100 °C to 200 °C, however, this increase is a result of void nucleation as opposed to pre-existing void growth. While rapid cycling (~5 min/cycle) under in-use conditions for these Cu-TSVs did not allow diffusion and growth of voids, maximum cycling temperatures provided sufficient driving force for stresses to form new voids in the Cu. Fig. 1: SEM micrographs of the TSV cross-sections for the two as-received sample types: (a) containing seams and large bottom voids and (b) solely containing microvoids. References: 1. J. Kim, J. Cho, J. S. Pak, J. Kim, J. Yook, and J. C. Kim, Electrical Performance of Electronic Packaging and Systems (EPEPS), 2011 IEEE 20th Conference on 243-246 (2011). 2. H. Shin, B. Kim, J. Kim, S. Hwang, A. Budiman, H. Son, K. Byun, N. Tamura, M. Kunz, D. Kim and Y. Joo, Journal of Electronic Materials, 41 [4] 712-719 (2012). 3. L. W. Kong, J. R. Lloyd, K. B. Yeap, E. Zschech, A. Rudack, M. Liehr and A. Diebold, Journal of Applied Physics, 110 [5] 053502 (2011). 4. L. Kong, A. C. Rudack, P. Krueger, E. Zschech, S. Arkalgud and A. C. Diebold, Microelectronic Engineering, 92 [0] 24-28 (2012).

Applications like hybrid electric vehicles (HEV) require batteries with high volumetric and gravimetric power densities, in both charge and discharge modes. Lithium ion cells are now being designed with different power : energy ratios, for specific applications. Many cells are rated for high rate discharge (> 10 C), but not for high rate charge (< 2 C). However, even 10 C is not enough. A selection of commercial lithium ion cells, mainly cylindrical 18650 cells, were disassembled and characterised. The cells had a variety of different power : energy ratios, and this was correlated with key design parameters. For example, cells with a high power density had relatively low coat weights and areal capacities, and used active materials with a smaller particle size. However, most of the cells had the same tag arrangement, when high power cells were predicted to use more tags. Having disassembled the cells, the harvested electrodes were tested in coin cell half cells. The tests included resistance measurements, continuous discharge tests at relatively low rates, and pulse charge and discharge tests at high rates. During lithiation pulses, all the anode voltages went negative of zero volts vs. Li/Li+ by around 5 C. However, the reaction still appeared to be under solid state diffusion control, based on the linearity of the voltage vs. time0.5 GITT plots. These and other results will be presented at the meeting.