Advanced Introduction to Family Law in the US

This Elgar Advanced Introduction provides key insights into family law in the US. In the midst of consequential changes wrought by the US Supreme Court, this book traces the evolution of the field from its origins in the law of domestic relations to the more modern regime of family law.Key features include:● Integrates state law, federal law, legal scholarship, and literature from other disciplines.● Identifies the regulation of sex and the policy of keeping dependency private as family law\u27\u27s principal enduring features.● Surveys different topics in family law including: marriage, nonmarriage, and dissolution; pregnancy; parentage; and children.● Reviews the impact of the US Supreme Court\u27\u27s Dobbs decision on all of family law in the US and looks ahead to the future of family law.Advanced Introduction to Family Law in the US is a valuable resource for teaching and learning family law, and also provides a sophisticated entry point for students and academics in gender studies and legal studies

Justifying the Fourth Amendment

Why does the Fourth Amendment belong in the Constitution? This question is not whether society should impose some legal restraints on government searches and seizures. Rather, why should such protections reside in our national charter, superior to other forms of law and insulated from change via ordinary majoritarian political processes? Despite major disputes about the Fourth Amendment’s content, Fourth Amendment theorists rarely ask this question. Almost all agree that the Fourth Amendment’s constitutional protections are critically important—even if no one can agree exactly what those protections are. This Article seeks a justification for the Fourth Amendment—the reason why search-and-seizure protections deserve to be enshrined in supreme and entrenched constitutional law. While this question might seem beside the point, identifying a justification for the Fourth Amendment should be seen as a critical step in choosing a theory of the Fourth Amendment’s meaning. Yet whether understood as freezing in place specific substantive rules, a broader value like privacy, or an institutional allocation of power, the reason to constitutionalize such a guarantee is surprisingly elusive. After canvassing all potential justifications for the Fourth Amendment as constitutional law, this Article finds that many are unappealing or unpersuasive; those that survive rest on uneasy premises. That conclusion poses a challenge to Fourth Amendment theorists, who must explain why their reading merits constitutional status. More generally, searching for the Fourth Amendment’s justification reveals how criminal procedure scholars can learn from constitutional theory. That investigation also deepens our understanding of constitutional interpretation and the very notion of constitutionalism itself

Privatising International (Organizations) Law

This essay explores the increasing role of private commercial actors within international organizations (IOs) and the implications for international law. Once conceived as state-centred institutions, IOs now routinely involve corporations, trade associations, and philanthropic foundations in lawmaking, policy-setting, financing, and implementation. These actors participate through multiple channels: as observers, delegates, stakeholders, funders, and partners. While private involvement has historical precedents, its contemporary scale and formalization mark a significant transformation in global governance. International law, however, offers little guidance on the boundary between public and private authority, leaving legitimacy concerns unresolved. To evaluate privatization, the article identifies two competing logics: a logic of representation, which grounds legitimacy in accountability and democratic participation, and a logic of production, which emphasizes outcomes, problem-solving capacity, and effectiveness. The challenge for international law is to hold these logics in tension by developing theories, rules, and categories that respond to conditions of hybridity in international organizations and shifts in the larger legal order

Space Enterprises as International Lawmakers: Nudges, Pledges, and Other Bottom-Up Modalities

Private entities are influencing the development of international space law. Space enterprises need regulatory certainty and consistent standards to attract capital and develop their plans for space. Yet, states have lagged in their capacity to make multilateral international space law in traditional public fora. Private entities have responded to this legal lag by attempting to create, develop, and nudge international space law in commerce-friendly ways. This chapter surveys a variety of modalities by which commercial actors can affect the development of international law, offers several examples of how commercial lawmaking effort

Expanding the druggable proteome by integrating deep learning with molecular simulations to predict cryptic pockets

Of the protein structures deposited in the Protein Data Bank, less than half have pockets suitable for the binding of drugs. Even when proteins contain pockets in their ground state structures (e.g., the nucleotide-binding active site in myosin motors), achieving specificity remains a central challenge in drug design as many protein families share common structural motifs. Cryptic pockets are cavities absent in ligand-free experimental structures that form due to protein fluctuations in solution. They provide a means to specifically target proteins currently considered undruggable. While cryptic pockets are alluring drug targets, it remains difficult to predict which proteins will form cryptic pockets. It is also unclear how certain compounds that bind at cryptic pockets discriminate between similar targets, even though those targets all have closed pockets in experimental structures. To address these problems, I develop a graph neural network called PocketMiner that predicts whether a protein is likely to form a cryptic pocket based on its ground state structure. I demonstrate that PocketMiner achieves improved performance (ROC-AUC: 0.87) compared to existing methods at \u3e1,000-fold faster run times. To further accelerate cryptic pocket discovery, I leverage the protein structure prediction algorithm AlphaFold to generate ensembles of structures. I show that AlphaFold-generated ensembles often sample cryptic pocket opening, and that using these ensembles as starting structures for molecular dynamics simulations can enhance sampling of a rare cryptic pocket opening in an antimalarial drug target. To connect cryptic pocket opening to drug specificity, I show that differences in the probability of cryptic pocket opening underpin the specificity of a myosin inhibitor known to bind at a cryptic site. By combining Markov state models with molecular docking, we accurately predict the affinity of blebbistatin for different myosin proteins. Finally, to demonstrate the utility of these methods for drug discovery applications, I use simulations of a cancer drug target, PPM1D phosphatase, to discover a novel cryptic pocket. Docked poses of compounds bound to this cryptic pocket can be fed to a neural network that predicts affinities to accurately rank compounds by their experimental affinities. Taken together, these results represent an important advancement towards rational drug design against previously undruggable targets

Mechanisms of Protective Humoral Immunity and Pathogenesis in Alphavirus Infection

Alphaviruses are enveloped, mosquito-transmitted, positive-sense RNA viruses of the Togaviridae family classified into Old and New World groups based on endemic regions and human disease characteristics. Old World alphaviruses, including chikungunya virus preferentially cause arthritogenic disease, whereas New World viruses like Venezuelan equine encephalitis virus (VEEV), Eastern equine encephalitis virus (EEEV), and Western equine encephalitis virus (WEEV) can cause neurological disease. Since the 1920s, VEEV has been responsible for major periodic outbreaks affecting hundreds of thousands of humans and equines in South and Central America. Expansion of mosquito vectors raises concern for possible VEEV reemergence. In addition, VEEV is a bioterrorism threat and was weaponized in the 1960s and 1970s for possible aerosol dissemination. Thus, alphaviruses, including VEEV, have been responsible for numerous worldwide epidemic outbreaks in the past century and yet, approved vaccines or treatments still do not exist. Here we investigate mechanisms of antibody-mediated protection against alphaviruses and how understanding alphavirus-host interactions leading to pathogenesis is critical for mitigating disease through antiviral therapeutic design. We describe the molecular basis of neutralization by murine and human monoclonal antibodies (mAbs) targeting several envelope protein epitopes. These mAbs inhibited multiple steps in the viral replication cycle including viral attachment, fusion to host membranes, and egress. Epitope mapping identified antigenically distinct sites on the VEEV E2 protein targeted by mAbs. Cryo-electron microscopy (cryo-EM) analysis of a potently neutralizing human mAb bound to VEEV defined a critical binding site within domain B of the E2 protein. Anti-VEEV mAbs targeting each antigenic site conferred robust protection and post-exposure therapeutic efficacy in mice challenged with aerosolized VEEV, highlighting targets for potential therapeutic development and vaccine immunogen design. Our studies link epitopes recognized by inhibitory anti-VEEV mAbs elicited after immunization with mechanisms of neutralization and thus further define the structural and functional components that contribute to protective efficacy against aerosolized VEEV infection. While neutralizing antibodies that inhibit individual alphaviruses have been described, broadly reactive antibodies that protect against both arthritogenic and encephalitic alphaviruses had not been reported. We screened and identified several candidate anti-WEEV cross-reactive mAbs and then developed an immunization and B cell sorting strategy to generate pan-alphavirus cross-reactive mAbs. Biosafety level 2 mouse models of EEEV, WEEV, and VEEV were developed for use in lethality and virological endpoints as a tool for screening these mAbs. Ultimately, two pan-protective yet poorly neutralizing human mAbs were identified, which bind to viral antigen on the surface of alphavirus-infected cells. These mAbs engage a conserved epitope in the E1 protein. Treatment with these mAbs protected against arthritogenic and encephalitic alphaviruses through various mechanisms including inhibition of viral egress and monocyte-dependent Fc effector functions. To better understand mechanisms of protective humoral immunity that might inform anti-alphavirus therapeutic development, we also defined key alphavirus receptors critical for pathogenesis in vivo. A VEEV-specific entry receptor, low-density lipoprotein receptor class A domain containing 3 (LDLRAD3), was identified using a loss-of-infection-based CRISPR-Cas9 genome-wide screen. LDLRAD3 is a highly conserved type I membrane protein of the LDL receptor superfamily and has been reported to regulate amyloid processing and auto-ubiquitination in neurons, although its endogenous ligand(s) are unknown. The most membrane-distal domain 1 (D1) of the three extracellular domains of LDLRAD3 was shown to be necessary and sufficient for VEEV infection, and a cryo-EM structure showed that LDLRAD3 D1 binds in a cleft formed between adjacent VEEV E2 and E1 proteins on the virion surface. We investigated the role of the entry receptor LDLRAD3 in VEEV pathogenesis using newly generated LDLRAD3-deficient mice. We found consistently lower levels of VEEV infection in all target tissues of LDLRAD3-deficient mice after subcutaneous inoculation, as early as 6 hours post-infection and at every timepoint tested thereafter. While VEEV entry into the brain occurred in the absence of LDLRAD3 expression, spread was delayed, infection accumulated at substantially lower levels, and animals did not sustain weight loss or lethality. Bone marrow chimera studies established that VEEV pathogenesis was largely dependent on LDLRAD3 expression in radioresistant stromal cells. Direct inoculation of VEEV into the brain via intracranial or intranasal inoculation resulted in uniform lethality in wild-type mice, whereas in LDLRAD3-deficient mice, animals lost weight but survived infection. This phenotype was associated with reduced central nervous system (CNS) viral burdens in LDLRAD3-deficient mice. Using in situ hybridization and immunohistochemistry, the absence of LDLRAD3 was associated with marked decreases in infection of neurons in adult mouse brains and in mixed primary neuron cultures isolated from embryos. Overall, we establish a key role for LDLRAD3 in the infection, dissemination, and pathogenesis of VEEV in peripheral and CNS tissues

Essays on Monetary Economics

Chapter I builds a quantitative New-Keynesian model with a central bank balance sheet, fiscal policy, and a representative financial intermediary facing uncertainty to show how interest rate policy has an additional counter-cyclical fiscal impact via central bank income when reserves are abundant as opposed to scarce. A counterfactual analysis between the US economies with small and large central bank balance sheets of 2005 and 2018 shows that in response to demand, supply, and government spending shocks, the real effects of identical interest rate changes are amplified in the abundant reserves economy. In response to a 1% preference shock, cumulative fluctuations are 4.5% lower in the output gap and 3.4% lower in inflation in the abundant reserves economy. Chapter II utilizes a panel dataset of central bank policy rates to provide evidence for asymmetric interest rate smoothing of central banks globally. During monetary easing interest rate cycles, central banks achieve the terminal policy rate at a faster pace than interest rate tightening cycles. This asymmetry is robust to real side factors in a Taylor type monetary rule. Policy rate cycles for central banks in countries that have higher levels of financial development display a stronger asymmetric smoothing than central banks in countries with less financial development. This finding provides evidence that central banks are cautious during interest rate tightening cycles to avoid financial stability risks which can have real economic impacts

Wavelet Representation of Singular Integral Operators

The idea of representing singular integral operators as averages dyadic shifts has proven fruitful since Petermichl\u27s representation of the Hilbert transform, and its generalization by Hyt\ onen to prove the $A_2$ conjecture. These results employ a random dyadic decomposition of the operator in terms of Haar shifts of all complexities. An alternate approach to wavelet representation was provided by Di Plinio, Wick, and Williams (2022) in which the random dyadic grids are replaced by zero-complexity wavelet projections, providing finer control of smooth operators and a more efficiently computable representation. The goal of this thesis is to provide two main generalizations of this continuous representation theorem; Both results are new and permit broader applications of the wavelet representation. First, we loosen the smoothness required of the Calder\\u27on--Zygmund operators to be Dini-type. This strengthens even the original statement for H\ older moduli of continuity by improving the loss of smoothness of the adapted wavelets to be precisely double-logarithmic. In general, the double log-Dini condition is likely not sharp, but is essential to the construction of a representation from wavelet averaging. We also consider operators in the ambient setting of spaces of homogeneous type, using wavelets adapted to dyadic grids constructed by Auscher and H\ ytonen. Because of the purely geometric nature of such spaces, this statement is made only in the case of fractional-order smoothness. Consequently, the statement is purely $T(1)$-type, which is still sufficient for proving new applications applications such as representations for compact Calder\\u27on-Zygmund operators

Weep No More, My Lady (Oh! Weep No More Today): Love, Violence, Printmaking, and Kentuckian Futurity

Situated within a regressive political climate, this essay considers the writer’s thesis artwork Weep No More, My Lady as a simultaneous account of Southern gendered violence and a desire for healing. Through personal and historical connections to Kentucky’s material culture, the work navigates binaries of class, race, and gender that have dictated the dominant contemporary conception of the region. Placing the competing forces of care and brutality in dialogue, Weep No More, My Lady translates these theoretical challenges into formal attributes. The work suggests modes of making — stitching, unraveling, tearing — can act against the construction and naturalization of hierarchy in the United States. Similarly, its use of printmaking mirrors historical discourse, since printmaking is both archival and able to meaningfully break from its own repetitive precedent. Therefore, Weep No More, My Lady attempts to reconcile a harmful past with sentimental longing, seeing a way forward in the process

Shell Quilt: Piecing Memory through Quilting, Collage, and Printmaking

Shell Quilt is a mixed media quilt and accompanying book which collect an amalgamation of found, hand dyed, and printed fabric pieces. This project serves as a visual tether and inquiry into my late grandmother Sylvia’s life and a way of piecing together memories of my time with her. As a conceptual frame for my thesis project, Shell Quilt, I have looked to the process of femmage, a term initially coined by Miriam Schapiro and Melissa Meyer, which I interpret as a portmanteau of feminism and collage. Through the lens of femmage, I explore the processes of collage, quilting, and print mediums and processes, in the work of the Folly Cove Designers, as well as artists like Margaret Kilgallen, Hương Ngô, Kiki Smith, and Faith Ringgold