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This thesis consists of three essays on shareholder activism. Chapter 2 uses US share- holder activism data to show that activists are significantly more likely to target female rather than male CEOs. We use both matching and an instrumental variable approach to provide evidence of the difference in targeting. We also show that campaigns targeting female-led firms are more likely to aim for board representation, more hostile, but not more likely to attain a goal success. The high hostility in female-CEO campaigns leads to a higher propensity for activists to ask for reimbursement. Despite these campaign differences, we find no gender dif- ferences in the market reaction to activist 13D filings, in post-campaign firm performance, or merger activity. Chapter 3 studies career changes of CEOs following activism campaigns in their compa- nies. Compared to otherwise similar peers, targeted CEOs experience a significant decline not only in the number of executive and director positions held, but also in the level of compensa- tion received. For executive and board positions, the results are driven by the internal slot at the targeted companies; for compensation, the results are driven by both the equity-based and nonequity-based portion of compensation. Furthermore, the career consequences are particu- larly pronounced for male CEOs. Activist tactics and campaign outcomes are also associated with CEO career changes. Using a unique and comprehensive hand-collected sample of activist-nominated direc- tors, Chapter 4 examines the attributes and careers of these directors. The group of activist directors is dominated by young men who possess less board and executive experience than target board members, but are more experienced and better educated than other individuals in the director labor pool. Additionally, activist directors are rewarded by the labor market. Compared to their non-activist colleagues, activist directors are more likely to retain their current seats and gain more new seats following the campaigns.

Both cancer and rheumatoid arthritis (RA) are intricate diseases that pose significant threats to human health. Targeted therapy is a treatment approach that delivers drugs specifically to the disease site, leading to maximum efficacy and minimized toxicity and adverse effects. Peptides are a promising targeting molecule for scientific exploration, among the numerous available treatment methods for these two diseases. Chapter 2 describes the design of a thermosensitive hydrogel formulation to deliver peptide-functionalized drugs subcutaneously for a more patient-friendly method and controlled drug release. Dexamethasone (DEX) is commonly used to decrease inflammation and relieve pain, but it often causes adverse effects due to nonspecific biodistribution. A solution to this problem is the conjugation of DEX with an inflammation-targeting peptide, CRV, which increases DEX accumulation in inflamed joints while decreasing it in healthy organs. Chapter 2 of this work described the design of a thermosensitive hydrogel formulation that delivered peptide-functionalized drug subcutaneously, allowing for controlled drug release and a more patient-friendly treatment method. The HP hydrogel forms a sol state at room temperature and transfers to a gel state at 31 °C, exhibiting shear-thinning behavior and robust solid-like properties. Gel erosion induces drug predominant release and presents good correlation under zero-order kinetics. Subcutaneous injection of CRV loaded-HP hydrogel in mice shows the systemic circulation time of CRV is prolonged to 48 hours attributed to the sustained release behavior of HP hydrogel. Although the biodistribution of CRV-DEX decreases DEX concentration in non-targeted organs, compared to DEX alone, there is currently no evidence indicating its efficacy in targeting joints. Further investigation is needed to explore how CRV peptide can target to joints via subcutaneous injection with hydrogel. In Chapter 3, recent studies showed that a significant portion of NPs are transferred inside extracellular vesicles (EVs), and inhibition of EV biogenesis significantly reduces tumor accumulation and vascular penetration of NPs in vivo. A manual chemical screen identified LDN-214117, an activin receptor-like kinase-2 (ALK-2) inhibitor, as an agonist of NP intercellular exchange that increases EV biogenesis via the BMP (bone morphogenetic protein)-MAPK (mitogen-activated protein kinase) signaling pathway. LDN-214117 treatment in vivo enhances the tumor accumulation and vascular penetration of various NPs, improving their antitumor efficacy. This study showcases the identification of a novel chemical compound with intercellular exchange assays to modulate EV biogenesis and EV-mediated transport, thus boosting the delivery and therapeutic efficacy of nanomaterial. Overall, this work shows improved drug delivery to treat RA and solid tumor by CRV peptide targeting and EV modulation.

Abstract: In this thesis we study X-ray millisecond pulsars (MSPs) in the Galactic globular clusters (GCs) to better understand the X-ray emission from them. We analyze 55 ks and 290 ks of Chandra X-ray observations of the clusters M13 and Omega Cen, respectively. We find confident X-ray counterparts to five of the six MSPs recently discovered in M13, while we place an upper limit of the X-ray luminosity for the sixth. We also find optical counterparts to two M13 pulsars, which are likely white dwarfs, using the Hubble Space Telescope. In addition, we detect X-ray counterparts to two newly found MSPs in the GC Omega Cen. We then compile previous X-ray studies of MSPs to present a comprehensive census of X-ray MSPs in 29 GCs, including 64 MSPs with detected X-ray luminosities and 111 MSPs with X-ray upper limits. We find most detected X-ray MSPs have luminosities between $\\sim 10^{30}$ erg s$^{-1}$ to $3 \\times 10^{31}$ erg s$^{-1}$ (0.3--8 keV). We estimate the total number of MSPs in 36 GCs based on the correlation between the number of MSPs and stellar encounter rate in GCs, and suggest that around 600 to 1500 MSPs exist in those GCs. Finally, we estimate the number of X-ray-detectable MSPs in the Galactic bulge, and suggest there are between 1--90 MSPs with $L_X > 10^{33}$ erg s$^{-1}$ and $\\sim$ 20--900 MSPs with $L_X > 10^{32}$ erg s$^{-1}$ in the bulge.

Due to their adjustable physiochemical properties and proven biocompatibility, iron oxide (Fe3O4) magnetic nanoparticles are promising in drug delivery, magnetic resonance imaging and catalysis. In this thesis, we have utilized two types of iron oxide nanoparticles: i) superparamagnetic iron oxide nanoparticles (SPION) for targeted destruction of cancer cells, and ii) poly(N-isopropylacrylamide) (pNIPAM) coated magnetic particles (MNP) for multistage cell separation. SPION are generally considered as drug delivery vehicles for the enhanced permeability and retention (EPR) effect. SPION possess the intrinsic peroxidase-like activity as Horseradish peroxidase (HRP), which can generate reactive oxygen species (ROS) from H2O2 via Fenton’s reaction. ROS regulate cell signaling, but a significant ROS stress can disrupt the redox homeostasis of cancer cells leading to selective tumor cell toxicity and destruction. Hereby, we developed ROS-induced targeted cell destruction with SPION-GOx bioconjugates platform. GOx catalyzes glucose oxidation in cancer cells to produce H2O2. 24 h incubation with 10 μg/mL SPION-GOx on 4T1 cells resulted in almost zero cell viability. In vivo evaluation showed SPION-GOx led to a much slower tumor growth compared to control groups. Additionally, magnetic activated cell sorting (MACS) has become a common technique for the separation of target cell populations from biological suspensions. A major obstacle preventing current single stage MACS from achieving satisfying separation efficiency is the non-specific interactions between the cells and MNP. Thus, we designed a multistage separation platform similar to distillation concept in chemical engineering. The repeated capture-and-release separation process is enabled by attaching the temperature responsive polymer- pNIPAM to both MNP and target cells. We manipulate the reversible hydrophobic-hydrophilic interactions between such functionalized MNP and target cells through temperature cycling to capture and release target cells at a higher efficiency than non-target. After several temperature cycles, target cells are enriched in the product. Flow cytometry results suggest that A431 cells (target) could be effectively separated from HeLa cells (non-target) after three separation stages resulting in an enrichment factor of 3.69 when the starting ratio of target to non-target is 1:2.