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Symposium Introduction: A Tribute To Roberta Karmel, James A. Fanto

Brooklyn Journal of Corporate, Financial & Commercial Law

The Introduction provides the background to the symposium in honor of Professor Roberta Karmel

Full Of Questions And Wonder: Roberta Karmel's Legacy, Alan R. Palmiter

Brooklyn Journal of Corporate, Financial & Commercial Law

Roberta Karmel has been perhaps the keenest observer and commentator on the securities industry and its regulation for the past five decades. Her observations about securities regulation—during the SEC’s precocious adolescence and into its young adulthood—have framed the academic inquiry of all of us who have written on the subject during this period. But more valuable to us than her observations have been her questions, full of wonder and penetrating insight. We securities academics, the enterprise of securities regulation, and especially market capitalism, all owe an enormous debt of gratitude to Professor Karmel.

The Coming Shift In Shareholder Activism: From “Firm-Specific” To “Systematic Risk” Proxy Campaigns (And How To Enable Them), John C. Coffee, Jr.

Brooklyn Journal of Corporate, Financial & Commercial Law

This article distinguishes two types of shareholder activism: (1) firm-specific activism, which has a long history and focuses on changes at a specific target company, and (2) systematic risk activism, which seeks to reduce the systematic risk in a portfolio and thereby benefit diversified investors. Typically, such a systematic risk campaign may force a portfolio company to internalize negative externalities to benefit the other companies in the portfolio (such as by reducing carbon emissions or undertaking climate risk reforms). But, systematic risk activism faces an inherent difficulty: the party that leads this campaign and invests in the target company may …

“The Eu Challenge To The Sec”: A View From 2021, Howell E. Jackson

Brooklyn Journal of Corporate, Financial & Commercial Law

This essay offers a retrospective appreciation of Professor Roberta Karmel’s scholarship exploring the influence of securities regulation in the United States on developments in European capital markets regulation in the late 1990’s and early 2000’s. Professor Karmel’s writings document a fascinating evolution in this trans-Atlantic relationship as the Securities and Exchange Commission transitioned from the world’s dominant capital market regulator throughout most of the post-World War II era into a more collaborative posture by the end of the first decade of the Millennium. The essay concludes by suggesting that the trends that Professor Karmel chronicled in her scholarship have persisted …

Retail Investors: Why Online Investing Platforms Need More Regulation And Oversight, Christal Mccamy

Brooklyn Journal of Corporate, Financial & Commercial Law

Retail trading, in the age of the COVID-19 pandemic, has reached impressive and consequential levels, mostly due to the rise in popularity of online investing platforms. These platforms greatly increase the accessibility of the stock market and the ability to create wealth for young investors. However, this recent surge in activity has dramatically affected the stock market in various ways and led to many negative outcomes for retail investors themselves. This Note uses several examples, surrounding the use of the platform Robinhood, to argue for action by the SEC and FINRA to implement additional protections for retail investors who utilize …

The Means To Ending Ends: Electronic Nicotine Delivery Systems And America’S Youth, Megan C. Feeney

Brooklyn Journal of Corporate, Financial & Commercial Law

Electronic Nicotine Delivery Systems (ENDS) have risen in prominence amongst smokers and non-smokers as a way to inhale nicotine since their introduction to the United States in 2006. Often sold in a variety of mouth-watering flavors, ENDS are extremely enticing to both adolescents and adults. Though they are marketed as a safer alternative to combustible cigarettes, these devices have created a growing public health epidemic of nicotine addiction among adolescent users. Ultimately acknowledging the issue in 2020, the Food & Drug Administration (FDA) released guidelines to the nicotine industry and banned the sale of certain flavored ENDS. However, this flavor …

Let The Bots Be Bots: Why The Cfaa Must Be Clarified To Prevent The Selective Banning Of Data Collection Facilitating Private Social Media Information Monopolization, W. Connor Mcrory

Brooklyn Journal of Corporate, Financial & Commercial Law

In September 2019, the United States Court of Appeals for the Ninth Circuit granted plaintiff-startup hiQ Labs a preliminary injunction allowing it to “bot scrape” off of defendant-social networking service LinkedIn’s public profiles without triggering liability under Section 1030(a)(2)(C) of the Computer Fraud & Abuse Act (CFAA) for accessing a website “without authorization.” Differing judicial interpretations demonstrate the lack of clarity as to the legality of third-party bot scraping against the website owner’s consent, which causes irreparable harm to businesses that rely on such practices to operate, and antitrust issues when website owners like LinkedIn and Facebook can selectively ban …

When Your Apps Threaten National Security – A Review Of The Tiktok And Wechat Bans And Government Actions Under Ieepa And Firrma, Ru Hochen

Brooklyn Journal of Corporate, Financial & Commercial Law

Personal data can evolve into a national security issue. In August 2020, fears of foreign adversaries’ access to Americans’ personal data prompted President Trump to issue two executive orders that attempted to ban Chinese-owned social media applications TikTok and WeChat in the United States. In the last few years, the U.S. executive branch has acted against foreign entities that implicate national security interests via two primary tools: the presidential power under the International Economic Emergency Powers Act (IEEPA) and a foreign investment screening regime under the Foreign Investment Risk Review Modernization Act of 2018 (FIRRMA). However, the statutes were enacted …

Revising U.S. Privacy Laws: New Laws Are Required To Fill In The Gaps Of Current And Proposed Legislation To Account For New Technologies And Future Emergencies, Marissa Wong

Brooklyn Journal of Corporate, Financial & Commercial Law

With the ongoing expansion of internet services and increase in cyberattacks, Congress has long recognized the need for comprehensive federal privacy legislation, but no federal legislation has been passed. Currently, the scatter-shot of sector and state-specific privacy laws have proven to be ineffective. The authority of the Federal Trade Commission (FTC) has also been weak. The unexpected occurrence of the COVID-19 pandemic further exposed the dire need for comprehensive federal privacy legislation. Data-collection methods such as facial recognition, immunity passports, and contact tracing leave users’ health and location data vulnerable in the hands of the government and private companies. Technologies …

Investigating Therapeutic Strategies To Target Metabolic Vulnerabilities Of Nsclc Tumors With Mutant Keap1 Gene, Pranavi Koppula

Dissertations and Theses (Open Access)

The metabolic vulnerability of cancers has long been envisaged as an attractive window to develop novel therapeutic strategies. Metabolic flexibility at the cellular level encompasses the efficient rerouting of anabolic and catabolic pathways in response to varying environmental stimuli to maintain cellular homeostasis and sustain proliferation. The primary objective of this study is to identify metabolic vulnerabilities bestowed by KEAP1/NRF2 signaling axis through SLC7A11. SLC7A11 is a transcriptional target of NRF2, an essential regulator of cellular anti-oxidant response. Under unstressed basal conditions, NRF2 interacts with KEAP1, a tumor suppressor gene and a substrate adaptor protein of the Cullin3-dependent ubiquitin ligase …

Stat3 Inhibits Type I Interferon Signaling In Type I Conventional Dendritic Cells, Taylor Chrisikos

Dissertations and Theses (Open Access)

Conventional dendritic cells (cDCs) are an essential immune population, responsible for controlling adaptive immunity and tolerance. Recently, type I cDCs (cDC1s) have been delineated as a distinct cDC subset, uniquely responsible for coordinating T cell-mediated immunity against pathogens and tumors. Although the importance of cDC1s is now well established, the mechanisms that regulate cDC1 function remain largely unknown. Signal Transducer and Activator of Transcription 3 (STAT3) mediates the intracellular signaling of interleukin 10 (IL-10), an immunosuppressive cytokine. Therefore, we hypothesized that STAT3 and IL-10 inhibit cDC1 function and induction of T cell-mediated immunity. Herein, we show that IL-10 inhibits polyinosinic:polycytidylic …

Modulation Of The Receptor Gating Mechanism And Allosteric Communication In Ionotropic Glutamate Receptors, Nabina Paudyal, Nabina Paudyal

Dissertations and Theses (Open Access)

Ionotropic glutamate receptors (iGluRs) found in mammalian brain are primarily known to mediate excitatory synaptic transmission crucial for learning and memory formation. The family of iGluRs consists of AMPA receptors, NMDA receptors and kainate receptors with each member having distinct physiological role. In the recent years, significant progress has been made in understanding the biophysical, and functional properties of iGluRs. The development of Cryo-EM and X-Ray crystallography techniques have further facilitated in the structural understanding of these receptors. However, the multidomain nature, large size of the protein, complex gating mechanism and inadequate knowledge regarding the conformational dynamics of the receptors …

Mutant Kras Alters Extracellular Vesicle Microrna Sorting In Pancreatic Cystic Neoplasms, Rachel L. Dittmar

Dissertations and Theses (Open Access)

Pancreatic ductal adenocarcinoma (PDAC) is among the deadliest cancers by organ site with a 5-year survival rate of just 10.8%. This is largely because most patients do not experience symptoms until the disease has already metastasized. The best hope to cure PDAC is surgery, which can only be done with a curative intent at an early stage when the disease is localized. There are no reliable circulating, body-fluid-based biomarkers to detect early stage PDAC or its precursor lesions in a timely manner for effective surgical intervention. When potential PDAC precursor lesions, such as mucinous pancreatic cysts are found, there are …

Enhancing Adoptive Cell Therapy By Augmenting Fitness And Anti-Tumor Function Of Tumor-Infiltrating Lymphocytes, Parin Shah

Dissertations and Theses (Open Access)

The success of immune checkpoint inhibitors (ICIs) has established the importance of cancer immunotherapy in solid cancers, where it has been adopted as one of the standards of care for advanced melanoma and lung cancer. It is currently being investigated to treat other solid cancers. However, a large fraction of patients do not respond to ICIs and relapse. ICI therapy offers an in vivo approach to activate tumor-specific T cells, albeit in some cases, this modality does not create a sufficiently robust anti-tumor response. Thus, ex vivo approaches employing manipulation of immune cells, such as Adoptive Cell Therapy (ACT) using …

Cross-Seeding Potential Of Misfolded Amyloid-Beta Strains On Tau Protein: Examining The Puzzle Pieces Of Alzheimer's Disease, Sara Kelley

Dissertations and Theses (Open Access)

Alzheimer’s disease (AD) is a neurodegenerative disorder that will progressively impair cognitive function. AD is the leading source of dementia, and affects one third of the senior citizens in the United States. Aging is the primary risk factor for AD and due to the expected rise in human lifespan worldwide, the occurrence rate of AD diagnosis is projected to increase. This observation is increasingly alarming when considering there is no treatment for reversal or prevention of AD yet.

AD is characterized by gross pathological hallmarks in the brain. These include the extracellular accumulation of misfolded amyloid-beta (Aβ) and the intraneuronal …

Deciphering The Role Of Hsp110 Chaperones In Diseases Of Protein Misfolding, Unekwu M. Yakubu

Dissertations and Theses (Open Access)

Molecular chaperones maintain protein homeostasis (proteostasis) by ensuring the proper folding of polypeptides. Loss of proteostasis has been linked to the onset of numerous neurodegenerative disorders including Alzheimer’s, Parkinson’s, and Huntington’s disease. Hsp110 is a member of the Hsp70 class of molecular chaperones and acts as a nucleotide exchange factor (NEF) for Hsp70, the preeminent Hsp70-family protein folding chaperone. Hsp110 promotes rapid cycling of ADP for ATP, allowing Hsp70 to properly fold nascent or unfolded polypeptides in iterative cycles. In addition to its NEF activity, Hsp110 possesses an Hsp70-like substrate binding domain (SBD) whose biological roles are undefined. Previous work …

Agonist-Induced Conformational Changes In The Nmda Receptor, Ryan Durham, Ryan Durham

Dissertations and Theses (Open Access)

NMDA receptors are ligand-gated ion channels that mediate a number of physiological and pathological phenomena within the mammalian central nervous system. Under the typical course of activation, these receptors bind to glycine and glutamate molecules and undergo a series of conformational changes that results in the opening of a cation-permeable pore in the neuronal plasma membrane. Various aspects of NMDA receptor function are not fully understood, including the phenomenon of negative cooperativity between the glycine- and glutamate-binding sites of the receptor and the mechanism controlling partial agonism. Past studies utilizing static structural snapshots of the receptor or isolated domains of …

Mitochondrial Unfolded Protein Response Regulator Atf5 In Mitochondrial Targeted Therapies In Aml, Ran Zhao

Dissertations and Theses (Open Access)

Mitochondrial unfolded protein response (UPR^mt) is an adaptive transcriptional response induced by damaged proteins accumulated in mitochondria. UPR^mt signaling involves induction of mitochondrial specific chaperones and proteases such as HSP60, LonP1 and ClpP, aiding in the restoration of mitochondrial protein pool homeostasis. However, the cell-protective roles of UPR^mt in the context of mitochondrial stress-induced cell death in AML has not been well explored. We demonstrate that AML cells are susceptible to mitochondrial targeted agents such as ONC201, an agonist of the mitochondrial protease ClpP, and gamitrinib, an inhibitor of mitochondrial chaperone TRAP1, however, these agents also …

Atrx Inactivation And Idh1-R132h Drive Preferential Sensitivity To Proton Vs. X-Ray Radiotherapy In Glioma Stem Cells, Ángel Adrián Garcés

Dissertations and Theses (Open Access)

Background: Glioma Stem Cells (GSCs) are self-renewable, treatment resistant cells in the glioma tumor mass known to promote tumor development. In contrast to traditional photon-based radiation therapy (XRT), proton radiation therapy (PRT) may induce more complex DNA damage and therefore might have the potential to eliminate GSCs. Although previous studies have individually linked IDH mutations, specifically IDH1^R132H, and ATRX inactivating mutations to improved patient outcomes and suppressed DNA damage repair compared to their respective wild-types, the mechanisms by which these two genetic alterations interact in GSCs treated with PRT compared to XRT are currently unknown. We hypothesize that …

The Roberts Court, State Courts, And State Constitutions: Judicial Role Shopping, Ariel L. Bendor, Joshua Segev

Journal of Law and Policy

In this Article we reveal a dual dilemma, both material and institutional, that the Supreme Court in its current composition faces when reviewing liberal state court decisions based on the state constitution. The Article further describes substantive and procedural tactics that the Court adopts to address this dilemma, and illustrates the arguments by analyzing a number of recent Supreme Court decisions. The two dilemmas, the combination of which serve as a “power multiplier,” of sorts, have arisen following the last three appointments to the Supreme Court, which resulted in a solid majority of conservative Justices nominated by Republican presidents. One …

Section 230 And The Problem Of Social Cost, Stanley M. Besen, Philip L. Verveer

Journal of Law and Policy

This Article employs, with certain modifications, the framework developed in Ronald Coase’s classic article, “The Problem of Social Cost,” to analyze the current debate over Section 230 of the Communications Decency Act. This provision absolves interactive computer services, also known as platforms, from liability when they disseminate materials that cause “harm” to third parties, “harm” that can take the form of compensable damage of a sort found in ordinary tort cases but also can include broader injuries to social order and cohesion in the form of such things as hate speech and misinformation. The Article begins by pointing out that, …

The Historical Diagnosis Criterion Should Not Apply: Reasonable Accommodations In Standardized Testing For Individuals With A Later Diagnosis Of Adhd, Denise Elliot

Journal of Law and Policy

There is a growing number of adults being diagnosed with ADHD who were not diagnosed in childhood, misdiagnosed, or primarily exhibited symptoms in adulthood. Notably, most of the later diagnoses of ADHD in adults are individuals pursuing some level of higher education. Some of the reasons posited for this increase in ADHD diagnoses in higher education may be attributed to increased workloads, decreased structural and community supports, misdiagnosis in childhood, masking, and racial and socioeconomic factors that overlook subpopulations like children of color, female-presenting, and gender-nonbinary children with ADHD. Unfortunately, testing agencies that administer college entrance exams, graduate school entrance …

On The Outer Reaches Of The Marketplace Of Ideas: The Weaponization Of Title Vi Against Palestinian College Activists, Gavriella Fried

Journal of Law and Policy

On U.S. college campuses, Palestinian rights activists who are critical of Israel risk legal consequences. Title VI of the Civil Rights Act prohibits discrimination on the basis of race, color, or national origin in any program receiving federal funds. Over the past two decades, at least eighteen Title VI complaints have been filed against U.S. colleges and universities, alleging that Palestinian rights activists’ political expression is a form of anti-Semitism. In December 2019, President Trump promulgated Executive Order 13,899, which formally extended Title VI protections to Jews and directed enforcement agencies to investigate allegations of anti-Semitism using guidance that includes …

Big Dreams And Pyramid Schemes: The Ftc’S Path To Improving Multi-Level Marketing Consumer Protections In Light Of Amg Capital Management And The 2016 Herbalife Settlement, Camille H. Mangiaratti

Journal of Law and Policy

Multi-level marketing, also known as “MLM,” is a type of sales business that relies on both sales to consumers and recruitment of sellers into the company’s tiered commission structure. MLMs are wildly and enduringly popular, especially because they claim to be a flexible and easy source of income for people who need it most. However, almost everyone who joins an MLM will lose money, and many MLMs are illegal pyramid schemes. Millions of Americans are harmed by MLMs every year. Despite this, the government does very little to punish MLMs who lie to prospective participants about their odds of success. …

How Artificial Intelligence Machines Can Legally Become Inventors: An Examination Of And Solution To The Decision On Dabus, Justyn Millamena

Journal of Law and Policy

With proliferation of Artificial Intelligence research and development, it is foreseeable that these machines will invent many new patentable technologies. However, the United States Patent and Trademark Office recently deemed a patent application incomplete for listing an AI machine as the inventor. If the USPTO’s decision is not corrected, the patent system will be in danger because many fraudulent patent applications that list incorrect inventors will be filed. This would drastically change existing and settled inventorship jurisprudence and might endanger the patent protection over such patents. This Note argues that the USPTO’s reasons for not allowing the Artificial Intelligence machine …

Civil Asset Forfeitures: How Prosecutors Can Facilitate Community-Based Criminal Justice Reform, Lane Waples

Journal of Law and Policy

Criminal justice reform is elusive in the United States. Despite evidence that the system is broken, change remains ephemeral at best. This is partially attributable to the fact that most attempts to reform the criminal legal system have occurred through the political process. However, another method of criminal justice reform is to assist communities as they address the root causes of crime. Undergirding this approach is the belief that building stronger communities contributes to less crime and reduces recidivism. After seizing $250 million via prosecutions of financial crimes in 2016, the New York County District Attorney’s Office created a “first-of-its-kind” …

Cutaneous Melanocytic Tumor With Crtc1::Trim11 Fusion: Review Of The Literature Of A Potentially Novel Entity, Ourania Parra, Konstantinos Linos

Dartmouth Scholarship

“Cutaneous melanocytic tumor with CRTC1::TRIM11 fusion” (CMTCT) is a recently described entity belonging to the family of superficial tumors displaying melanocytic differentiation. Thirteen cases have been reported so far, on the head and neck, extremities, and trunk of adults of all ages (12 cases) and one in an 11-year-old child. Histopathologically, it is a nodular or multilobu-lated tumor composed of spindle and epithelioid cells arranged in nests, fascicles, or bundles that are surrounded by thin collagenous septa. By immunohistochemistry, the tumor shows variable immunoreactivity for S100-protein, SOX10, and MITF, as well as specific melanocytic markers such as MelanA and HMB-45. …

Methylation-Derived Inflammatory Measures And Lung Cancer Risk And Survival, Naisi Zhao, Mengyuan Ruan, Devin C. Koestler, Jiayun Lu, Lucas A. Salas, Karl T. Kelsey, Elizabeth A. Platz, Dominique S. Michaud

Dartmouth Scholarship

Background: Examining immunity-related DNA methylation alterations in blood could help elucidate the role of the immune response in lung cancer etiology and aid in discovering factors that are key to lung cancer development and progression. In a nested, matched case–control study, we estimated methylation-derived NLR (mdNLR) and quantified DNA methylation levels at loci previously linked with circulating concentrations of C-reactive protein (CRP). We examined associations between these measures and lung cancer risk and survival. Results: Using conditional logistic regression and further adjusting for BMI, batch effects, and a smoking-based methylation score, we observed a 47% increased risk of non-small cell …

A Close Association Of Freedom From Pain, Migraine-Related Functional Disability, And Other Outcomes: Results Of A Post Hoc Analysis Of Randomized Lasmiditan Studies Samurai And Spartan, Richard B. Lipton, Simin K. Baygani, Stewart J. Tepper, John H. Krege, Raghavendra Vasudeva, Eric M. Pearlman, Paula M. Hauck, Li Shen Loo

Dartmouth Scholarship

Background: While pain freedom at 2 h is a key primary outcome for current trials for acute treatment of migraine, the relationship between the degree of head pain and other efficacy measures at 2 h has rarely been explored. Following lasmiditan treatment of a migraine attack with moderate or severe head pain, we contrast those who achieve pain freedom with those who achieve mild pain but not pain freedom 2 h post dosing. Methods: Patient-level data were pooled across studies and treatment arms from two Phase 3 trials comparing lasmiditan and placebo, SAMURAI and SPARTAN. This post hoc analysis assessed …

Placental Dna Methylation Signatures Of Maternal Smoking During Pregnancy And Potential Impacts On Fetal Growth, Todd M. Everson, Marta Vives-Usano, Emie Seyve, Andres Cardenas, Marina Lacasaña, Jeffrey M. Craig, Corina Lesseur, Emily R. Baker, Nora Fernandez-Jimenez, Barbara Heude, Patrice Perron, Beatriz Gónzalez-Alzaga, Jane Halliday, Maya A. Deyssenroth, Margaret R. Karagas, Carmen Íñiguez, Luigi Bouchard, Pedro Carmona-Sáez, Yuk J. Loke, Ke Hao

Dartmouth Scholarship

Maternal smoking during pregnancy (MSDP) contributes to poor birth outcomes, in part through disrupted placental functions, which may be reflected in the placental epigenome. Here we present a meta-analysis of the associations between MSDP and placental DNA methylation (DNAm) and between DNAm and birth outcomes within the Pregnancy And Childhood Epigenetics (PACE) consortium (N = 1700, 344 with MSDP). We identify 443 CpGs that are associated with MSDP, of which 142 associated with birth outcomes, 40 associated with gene expression, and 13 CpGs are associated with all three. Only two CpGs have consistent associations from a prior meta-analysis of cord …