Unbound by Law: Association and Autonomy in the Early American Republic

This dissertation examines how the concept of voluntary membership evolved between the 1780s and the 1830s, a period in which men and women created thousands of groups seeking everything from fraternity to profit to social reform. Before observers foreign and domestic would begin to identify the voluntary association as a defining characteristic of post-Revolutionary American culture, Americans who organized and joined such groups had struggled for decades to determine what membership ought to look like, what rights and duties the act of joining should entail. By the time Alexis de Tocqueville famously noted in 1831 that Americans were forever forming associations, they had come to some answers. A revolutionary idea evolved unsteadily through the practical, day-to-day experiences of membership, as men and women began to insist upon basic principles of procedural fairness: the idea that people carried rights into every social relationship. Historians have yet to examine these debates over the norms of belonging, largely owing to the long-lasting influence of Tocqueville\u27s rosy picture of spontaneous cooperation and, more recently, J├╝rgen Habermas\u27s theory of associations in the public sphere. But Americans of the post-Revolutionary generations were anxious and uncertain about private governing power and the potential abuses of even voluntary commitments. In groups as diverse as women\u27s literary societies, men\u27s political fraternities, business corporations, and mutual benefit societies, Americans responded to the challenges they perceived by erecting procedural protections for members and by embracing a legalistic rather than an affective understanding of what it meant to belong. For they were anxious, too, about how they could make these groups work, how they could make collective action a reality in an age when even the survival of the new republic appeared tenuous. Innovation born of conflict within the groups--especially, efforts to forestall and to resolve disputes over the meanings, burdens, and benefits of voluntary membership, many of which wound up in court--shaped the post-Revolutionary associational landscape. While there continued to be encomia about the natural sociability of man and the tender ties of affection, in practice the American joiners that Tocqueville described had embraced a wholly different model of associated action. The rules by which the joiners organized themselves evinced a trend toward greater precision and an increasing emphasis on legalistic formalities. What is more, law-making and judicial institutions became comfortable assuming a role as superintendent over the actions within private societies, holding them to broad standards of justice and resolving the conflicts that arose within them, such as contested expulsions, and thereby setting the furthest limits of private governing authority. They created a substructure for Americans\u27 efforts at collective action, one that evinced a pervasive liberalism, in that it was grounded in an individualistic common law, legal guarantees of the rights of individual members, and a reliance on adversarial legalism and procedural formalities to reconcile conflict, even in these ostensibly private, wholly voluntary groups. The conflict-driven process of defining voluntary membership had a second effect: Americans of this period came to accept the pluralist makeup of their society, in which myriad groups pursued divergent ends rather than a singular, public good. They could do so because, internally, most of these groups had begun to look the same, and those few associations that did appear to threaten the autonomy of their members, such as the Freemasons, came to stand out in ways they had not just a generation before. By about 1840, certain conceptions of voluntary membership had become so generally accepted that the judicial superintendence of private associations would become less direct, resting on broad schema of procedural expectations

Enhancing and Implementing Fully Transparent Internet Voting

Voting over the internet has been the focus of significant research with the potential to solve many problems. Current implementations typically suffer from a lack of transparency, where the connection between vote casting and result tallying is seen as a black box by voters. A new protocol was recently proposed that allows full transparency, never obfuscating any step of the process, and splits authority between mutually-constraining conflicting parties. Achieving such transparency brings with it challenging issues. In this paper we propose an efficient algorithm for generating unique, anonymous identifiers (voting locations) that is based on the Chinese Remainder Theorem, we extend the functionality of an election to allow for races with multiple winners, and we introduce a prototype of this voting system implemented as a multiplatform web application

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Community Structure of Lithotrophically-Driven Hydrothermal Microbial Mats from the Mariana Arc and Back-Arc

The Mariana region exhibits a rich array of hydrothermal venting conditions in a complex geological setting, which provides a natural laboratory to study the influence of local environmental conditions on microbial community structure as well as large-scale patterns in microbial biogeography. We used high-throughput amplicon sequencing of the bacterial small subunit (SSU) rRNA gene from 22 microbial mats collected from four hydrothermally active locations along the Mariana Arc and back-arc to explore the structure of lithotrophically-based microbial mat communities. The vent effluent was classified as iron- or sulfur-rich corresponding with two distinct community types, dominated by either Zetaproteobacteria or Epsilonproteobacteria, respectively. The Zetaproteobacterial-based communities had the highest richness and diversity, which supports the hypothesis that Zetaproteobacteria function as ecosystem engineers creating a physical habitat within a chemical environment promoting enhanced microbial diversity. Gammaproteobacteria were also high in abundance within the iron-dominated mats and some likely contribute to primary production. In addition, we also compare sampling scale, showing that bulk sampling of microbial mats yields higher diversity than micro-scale sampling. We present a comprehensive analysis and offer new insights into the community structure and diversity of lithotrophically-driven microbial mats from a hydrothermal region associated with high microbial biodiversity. Our study indicates an important functional role of for the Zetaproteobacteria altering the mat habitat and enhancing community interactions and complexity

Comparative Proteomic Analyses of the Parietal Lobe from Rhesus Monkeys Fed a High-Fat/Sugar Diet With and Without Resveratrol Supplementation, Relative to a Healthy Diet: Insights Into the Roles of Unhealthy Diets and Resveratrol on Function

A diet consisting of a high intake of saturated fat and refined sugars is characteristic of a Western-diet and has been shown to have a substantial negative effect on human health. Expression proteomics were used to investigate changes to the parietal lobe proteome of rhesus monkeys consuming either a high fat and sugar (HFS) diet, a HFS diet supplemented with resveratrol (HFS+RSV), or a healthy control diet for 2 years. Here we discuss the modifications in the levels of 12 specific proteins involved in various cellular systems including metabolism, neurotransmission, structural integrity, and general cellular signaling following a nutritional intervention. Our results contribute to a better understanding of the mechanisms by which resveratrol functions through the up- or down-regulation of proteins in different cellular sub-systems to affect the overall health of the brain

The need for a network to establish and validate predictive biomarkers in cancer immunotherapy.

Immunotherapies have emerged as one of the most promising approaches to treat patients with cancer. Recently, the entire medical oncology field has been revolutionized by the introduction of immune checkpoints inhibitors. Despite success in a variety of malignancies, responses typically only occur in a small percentage of patients for any given histology or treatment regimen. There are also concerns that immunotherapies are associated with immune-related toxicity as well as high costs. As such, identifying biomarkers to determine which patients are likely to derive clinical benefit from which immunotherapy and/or be susceptible to adverse side effects is a compelling clinical and social need. In addition, with several new immunotherapy agents in different phases of development, and approved therapeutics being tested in combination with a variety of different standard of care treatments, there is a requirement to stratify patients and select the most appropriate population in which to assess clinical efficacy. The opportunity to design parallel biomarkers studies that are integrated within key randomized clinical trials could be the ideal solution. Sample collection (fresh and/or archival tissue, PBMC, serum, plasma, stool, etc.) at specific points of treatment is important for evaluating possible biomarkers and studying the mechanisms of responsiveness, resistance, toxicity and relapse. This white paper proposes the creation of a network to facilitate the sharing and coordinating of samples from clinical trials to enable more in-depth analyses of correlative biomarkers than is currently possible and to assess the feasibilities, logistics, and collated interests. We propose a high standard of sample collection and storage as well as exchange of samples and knowledge through collaboration, and envisage how this could move forward using banked samples from completed studies together with prospective planning for ongoing and future clinical trials

Polycation-π Interactions Are a Driving Force for Molecular Recognition by an Intrinsically Disordered Oncoprotein Family

Molecular recognition by intrinsically disordered proteins (IDPs) commonly involves specific localized contacts and target-induced disorder to order transitions. However, some IDPs remain disordered in the bound state, a phenomenon coined "fuzziness", often characterized by IDP polyvalency, sequence-insensitivity and a dynamic ensemble of disordered bound-state conformations. Besides the above general features, specific biophysical models for fuzzy interactions are mostly lacking. The transcriptional activation domain of the Ewing's Sarcoma oncoprotein family (EAD) is an IDP that exhibits many features of fuzziness, with multiple EAD aromatic side chains driving molecular recognition. Considering the prevalent role of cation-π interactions at various protein-protein interfaces, we hypothesized that EAD-target binding involves polycation- π contacts between a disordered EAD and basic residues on the target. Herein we evaluated the polycation-π hypothesis via functional and theoretical interrogation of EAD variants. The experimental effects of a range of EAD sequence variations, including aromatic number, aromatic density and charge perturbations, all support the cation-π model. Moreover, the activity trends observed are well captured by a coarse-grained EAD chain model and a corresponding analytical model based on interaction between EAD aromatics and surface cations of a generic globular target. EAD-target binding, in the context of pathological Ewing's Sarcoma oncoproteins, is thus seen to be driven by a balance between EAD conformational entropy and favorable EAD-target cation-π contacts. Such a highly versatile mode of molecular recognition offers a general conceptual framework for promiscuous target recognition by polyvalent IDPs. © 2013 Song et al