Harmful algal blooms (HABs) have been documented to harbor algae capable of producing toxins harmful to both humans and marine life. Lingulodinium polyedrum, the major dinoflagellate species in the recent algal blooms in southern California in 2011 and 2013, has been shown to induce allergic responses in humans exposed to the bloom. The chemical natures of the compounds produced by L. polyedrum which induce this response are as of yet unknown. This study had the goal of determining whether L. polyedrum contains any pro-inflammatory compounds and to discern whether these compounds could induce an allergic reaction. Bioassay guided fractionation and chemical separation of cultured L. polyedrum has led to the isolation of a glycolipid produced by L. polyedrum, monogalactosyldiacylglycerol (20:5/18:5). Evaluation of the pro-inflammatory capacity of this glycolipid revealed that this glycolipid does not induce a pro-inflammatory response.

Gate sizing is one of the most flexible and powerful methods available for the timing and power optimization of digital circuits. As such, it has been a very well-studied topic over the past few decades. However, developments in modern semiconductor technologies have changed the context in which gate sizing is performed. The focus has shifted from custom design methods to standard cell based designs, which has been an enabler in the design of modern, large-scale designs. We start by providing benchmarking efforts to show where the state-of-the-art is in standard cell based gate sizing. Next, we develop a framework to assess the impact of the limited precision and range available in the standard cell library on the power-delay tradeoffs.

In addition, shrinking dimensions and decreased manufacturing process control has led to variations in the performance and power of the resulting designs. We provide methods for gate sizing with statistical delay, and compute bounds to show that full statistical power optimization is not essential. Lastly, to address the complexities of doing in design in a yet immature process, we provide a method to perform incremental discrete gate sizing to account for both anticipated and unanticipated changes in the manufacturing process parameters.

Purpose of the review

Recent findings

Metal-air batteries (MAB) is becoming a revived interest because of its high theoretical energy density, low-cost, and environmentally friendly nature. It has wide range of applications from portable transportation to stationary applications. However, commercialization of this technology is hindered by the limitations associated with the metal anode, air cathode, and electrolyte.Commercial benchmark catalysts at the cathode and anode are platinum nanoparticles over carbon-based supports and iridium oxide particles, respectively. However, carbon supports are highly susceptible to corrosion resulting in major performance losses. These metals are also expensive, limited, and difficult to obtain. Hence, corrosion-resistant support materials or an alternative metal are needed. In this study, catalytic activity of a library of transition metal oxides with various supports is explored. All the catalysts were characterized physically and electrochemically to understand their morphological and electrocatalytic properties towards oxygen reduction reaction and oxygen evolution reaction. The oxygen reduction reaction activity, investigated in aqueous 1 M KOH electrolyte, using rotating disk electrode showed worse performance than benchmark Pt/C. However, the oxygen evolution reaction activity surpassed performance of industrial catalyst IrOx. The best performing catalyst in nickel iron oxides and nickel cobalt oxides, neglecting carbon supports, are also investigated in MABs. This thesis provides an exploration of novel bifunctional catalysts tested electrochemically in aqueous 1 M KOH and aqueous 2 M NaCl. The best performing catalysts are then tested in a Zinc-Air battery in aqueous 1 M KOH.

My dissertation focuses on weaponry in the Achaemenid Persian Empire (ca. 550-330 BC), with an emphasis on bows and spears. Scholars have long recognized the importance of archery in the ancient Near East generally, and the Achaemenid Empire more specifically, but no thorough study of archery has been undertaken.

In the opening chapters, I examine weapons as physical objects. Chapter one describes the shape and size of the Elamite and Scythian style bows which the Persians used. I also consider other aspects of archery tackle, in particular arrows. Arrowheads are often the only evidence for arrows that remain, and their shape, size, and weight can reveal their purpose, the type of bow from which they were fired, and the potential range they could travel.

Chapter two discusses the physical properties of Achaemenid spears. Evidence suggests that Persians used both throwing and thrusting spears. The Persians may have used a single versatile type of spear, called in Greek a palton, that could be used either way, and is often associated with Persian cavalry. Evidence suggests the Persians used a fairly long spear, perhaps seven feet, which contradicts Herodotus’ description of short spears. Chapter three focuses on the logistics of military archery, and to a lesser extent spearmanship, in an Achaemenid context. The study of archery is especially relevant to this topic due to the increased logistical needs involved in the manufacture of composite bows, and the constant need to supply arrows to soldiers while on campaign. I also examine the recruitment, training, and armament of spearmen in this section. Documentary evidence describes that the state distributed arable land in exchange for military service. This practice was carried over from the earlier empires that ruled in this region. Another source of recruitment attested in Mesopotamia, but perhaps used elsewhere, were the temples. Temple dependants worked these lands for the temple, but were also liable for military service. Temples also employed weapon manufacturing specialists, including bowyers and blacksmiths, who produced the weapons that armed the conscripted soldiers.

In chapter four, I examine the gerrhon, a rectangular shield which the Persians are said to have used at the battle of Plataea and Mycale. The Greek term for these shields, gerrhon, can be translated as “wicker.” Many modern historians have taken this translation literally, and suggest that a wicker shield could not have been an effective form of defense. I challenge this hypothesis, and built shields using the same techniques as the Persians, and with materials that have similar properties to those available to the ancient Achaemenids. Finally, I consider how these shields were used on the battlefield, whether they formed a solid defensive wall or were arranged in an open pattern, and how many archers could have been protected by each shield.

In the final chapter, I move away from bows and spears as weapons to discuss their symbolic value within the Achaemenid Empire. Both weapons appear as symbols of royal power on Achaemenid reliefs, coins, and seals, and in inscriptions. The bow is also used as an ethical symbol in many cultures, and may have been particularly suitable as a symbol of Persian morality. Bows produce power through the tension of opposing forces, the limbs. This source of power may have resonated with the Achaemenids, as their cosmology was based on opposition. Finally, I consider the possibility that the Achaemenids used weapons in rituals. There is no direct evidence for this practice, but some passages in Greek literature could reflect a misunderstanding of actual Achaemenid ritual practice.

Prostate cancer is a heterogeneous disease arising from the epithelial cells of the prostate gland. While most prostate cancers are considered to be indolent, subsets of these cancers are or will evolve to become aggressive with heightened proliferative and invasive capacity. Two features that accompany this lethal prostate cancer phenotype are (1) androgen-independent growth and, in many cases, (2) the acquisition of neuroendocrine differentiation. Few treatments are effective at this stage and a better understanding of the disease biology is required to develop therapeutics that extend and enhance life. To this end, we set out to characterize determinants of aggressive prostate cancer, with specific focus on the epithelial cell of origin of cancer, active kinase signaling networks, and the genetics of neuroendocrine prostate cancer (NEPC).

Our group has developed technology to isolate and transform basal cells from the human prostate epithelium using lentivirus to introduce defined oncogenic alterations into benign cells prior to transplantation in mouse hosts. However, we were previously unable to assess the effect of oncogenic stress on luminal cells of the human prostate epithelium. We therefore adapted the human prostate transformation assay to use an intermediate organoid culture step to show that basal- and luminal-derived tumors arising from c-Myc overexpression and PI3K pathway activation exhibit distinct cancer differentiation states.

We have previously shown that global phosphorylation levels of tyrosine residues are increased in advanced prostate cancer relative to primary prostate cancer. To understand the active tyrosine kinase signaling networks in aggressive prostate cancer, we performed liquid chromatography tandem mass spectrometry to profile the tyrosine phosphoproteome of metastatic prostate cancer tissues obtained at rapid autopsy. We identified active and druggable targets/pathways including SRC, epidermal growth factor receptor (EGFR), rearranged during transfection (RET), anaplastic lymphoma kinase (ALK), and MAPK1/3 that may form the basis for future kinase inhibition studies in prostate cancer.

Finally, we used the human prostate transformation assay to define an important functional role for aberrant N-Myc expression in the setting of PI3K pathway activation in the initiation of NEPC. With this human NEPC model system, we established that epithelial cells can give rise to neuroendocrine cancer in the prostate gland and provided direct evidence of in vivo prostate cancer plasticity. Furthermore, N-Myc expression is required for maintenance of the cancer state and destabilizing N-Myc through inhibition of a kinase-independent interaction with Aurora A kinase may be a promising therapeutic strategy for NEPC.

Organometallic chemists have historically studied the influence of ligands and counteranions on homogeneous transition metal catalysts in order to improve their selectivities and reactivities. Recently, these interests have expanded to incorporate supramolecular hosts and heterogeneous porous materials as supports which can influence catalyst properties. This work encompasses such an integration of catalysts with heterogeneous supports, wherein two types of chiral porous materials are evaluated for their abilities to induce enantioselectivity with nano- and molecular- scale catalysts. Furthermore, the strategy of architectural stabilization is developed to improve a gold(III) catalyst via introduction into robust metal-organic frameworks.

Chapter 1. A variety of catalysts were immobilized in chiral mesoporous silica, and their reactivities were evaluated. Efforts towards the enantioenrichment of MOF-520 are described. Additionally, a novel post-synthetic metalation strategy is described for the introduction of a transition metal catalysts into metal-organic frameworks via oxidative addition.

Chapter 2. A novel architectural stabilization strategy is described with a structurally well- defined gold(III) catalyst in metal-organic frameworks. The robustness of IRMOF-10 and bio- MOF-100 were used to rigidify a gold(III) catalyst to suppress a unimolecular decomposition pathway – reductive elimination. Through this architectural stabilization strategy, decomposition of the incorporated gold(III) catalyst in the metal-organic frameworks was not observed; in contrast, the homogeneous analogue was prone to decomposition in solution. Stabilization of the gold(III) catalyst in these metal-organic frameworks precluded leaching and enabled recyclability, which is crucial for productive heterogeneous catalysis.