Regulatory Entrepreneurship

Numerous corporations, ranging from Airbnb to Tesla, and from DraftKings to Uber, have built huge businesses that reside in legal gray areas. Instead of taking the law as a given, these companies have become agents of legal change, focusing major parts of their business plans on changing the law. To achieve their political goals, these companies employ conventional lobbying techniques, but also more innovative tactics. In particular, some attempt to enter markets quickly, then grow too big to ban before regulators can respond. If regulators do take aim at them, they respond by mobilizing their users for political support. This Article offers the first focused study of what we term regulatory entrepreneurship — entering a line of business in which changing the law is a significant part of the business plan. We provide a framework for understanding this combination of business and political activity and a detailed account of the techniques that these companies employ. Further, the Article identifies and considers the conditions that are most likely to foster regulatory entrepreneurship, the prospects for regulatory entrepreneurship going forward, and its likely positive and negative implications for lawmaking

The Derivative Nature of Corporate Constitutional Rights

This Article engages the two-hundred-year history of corporate constitutional rights jurisprudence to show that the Supreme Court has long accorded rights to corporations based on the rationale that corporations represent associations of people from whom such rights are derived. The Article draws on the history of business corporations in America to argue that the Court’s characterization of corporations as associations made sense throughout most of the nineteenth century. By the late nineteenth century, however, when the Court was deciding several key cases involving corporate rights, this associational view was already becoming a poor fit for some corporations. The Court’s failure to account for the wide spectrum of organizations labeled “corporations” became increasingly problematic with the rise of modern business corporations that could no longer be fairly characterized as an identifiable group of people acting in association. Nonetheless, the Court continued to apply the associational rationale from early case law and expand corporate rights into the realm of speech and political spending without careful analysis of when the associational approach would be appropriate. We set forth a theoretical framework that we believe is consistent with the underlying logic of the Court’s jurisprudence, based on the concepts of derivative and instrumental rights. Specifically, we argue that the Court, to date, has not granted constitutional rights to corporations in their own right. Instead, it has granted rights to corporations either derivatively, when necessary to protect the rights of natural persons assumed to be represented by the corporation, or instrumentally, when necessary to protect the rights of parties outside the corporation. Further, we consider the implications that this framework, with a more nuanced view of the spectrum of corporations in existence, would have if applied to recent corporate rights cases, such as Citizens United. We believe this framework provides a principled path forward for the difficult line drawing between corporations that needs to be done

Modeling of a Building Scale Liquid Air Energy Storage and Expansion System with ASPEN HYSYS

Liquid Air Energy Storage (LAES) is a potential solution to mitigate renewable energy intermittency on islanded microgrids. Renewable microgrid generation in excess of the immediate load runs a cryogenic cycle to create and store liquid air. LAES systems can be combined with an expansion turbine to recover the stored energy. Using analytic methods to design a LAES and expansion system is complex and time consuming, suggesting modeling and simulation as a more efficient approach. Aspen HYSYS, an industrial process modeling software package, was used to model a combined Linde- Hampson cryogenic cycle (for liquefaction of air) and an expansion cycle (to convert the energy from liquid air vaporization to mechanical energy). The model was validated against previous analytic work. The validated model will be used to implement a model-based systems engineering (MBSE) approach to design an LAES and expansion system to reduce intermittency on an experimental microgrid at the Naval Postgraduate School in Monterey, CA, USA. Data from this facility will be used to further modify and validate the HYSYS model

Krylov Subspace Method for Molecular Dynamics Simulation based on Large-Scale Electronic Structure Theory

For large scale electronic structure calculation, the Krylov subspace method is introduced to calculate the one-body density matrix instead of the eigenstates of given Hamiltonian. This method provides an efficient way to extract the essential character of the Hamiltonian within a limited number of basis set. Its validation is confirmed by the convergence property of the density matrix within the subspace. The following quantities are calculated; energy, force, density of states, and energy spectrum. Molecular dynamics simulation of Si(001) surface reconstruction is examined as an example, and the results reproduce the mechanism of asymmetric surface dimer.Comment: 7 pages, 3 figures; corrected typos; to be published in Journal of the Phys. Soc. of Japa

Bcl-2 protein family: Implications in vascular apoptosis and atherosclerosis

Apoptosis has been recognized as a central component in the pathogenesis of atherosclerosis, in addition to the other human pathologies such as cancer and diabetes. The pathophysiology of atherosclerosis is complex, involving both apoptosis and proliferation at different phases of its progression. Oxidative modification of lipids and inflammation differentially regulate the apoptotic and proliferative responses of vascular cells during progression of the atherosclerotic lesion. Bcl-2 proteins act as the major regulators of extrinsic and intrinsic apoptosis signalling pathways and more recently it has become evident that they mediate the apoptotic response of vascular cells in response to oxidation and inflammation either in a provocative or an inhibitory mode of action. Here we address Bcl-2 proteins as major therapeutic targets for the treatment of atherosclerosis and underscore the need for the novel preventive and therapeutic interventions against atherosclerosis, which should be designed in the light of molecular mechanisms regulating apoptosis of vascular cells in atherosclerotic lesions

Model based analysis of fMRI-data: Applying the sSoTS framework to the neural basic of preview search.

The current work aims to unveil the neural circuits under- lying visual search over time and space by using a model-based analysis of behavioural and fMRI data. It has been suggested by Watson and Humphreys [31] that the prioritization of new stimuli presented in our visual field can be helped by the active ignoring of old items, a process they termed visual marking. Studies using fMRI link the marking pro- cess with activation in superior parietal areas and the precuneus [4, 18, 27, 26]. Marking has been simulated previously using a neural-level ac- count of search, the spiking Search over Time and Space (sSoTS) model, which incorporates inhibitory as well as excitatory mechanisms to guide visual selection. Here we used sSoTS to help decompose the fMRI signals found in a preview search procedure, when participants search for a new target whilst ignoring old distractors. The time course of activity linked to inhibitory and excitatory processes in the model was used as a regres- sor for the fMRI data. The results showed that different neural networks were correlated with top-down excitation and top-down inhibition in the model, enabling us to fractionate brain regions previously linked to vi- sual marking. We discuss the contribution of model-based analysis for decomposing fMRI data

Sirolimus inhibits key events of restenosis in vitro/ex vivo: evaluation of the clinical relevance of the data by SI/MPL- and SI/DES-ratio's

<p>Abstract</p> <p>Background</p> <p>Sirolimus (SRL, Rapamycin) has been used successfully to inhibit restenosis both in drug eluting stents (DES) and after systemic application. The current study reports on the effects of SRL in various human in vitro/ex vivo models and evaluates the theoretical clinical relevance of the data by SI/MPL- and SI/DES-ratio's.</p> <p>Methods</p> <p>Definition of the SI/MPL-ratio: relation between <b>s</b>ignificant <b>i</b>nhibitory effects in vitro/ex vivo and the <b>m</b>aximal <b>p</b>lasma <b>l</b>evel after systemic administration in vivo (6.4 ng/ml for SRL). Definition of the SI/DES-ratio: relation between <b>s</b>ignificant <b>i</b>nhibitory effects in vitro/ex vivo and the drug concentration in <b>DES </b>(7.5 mg/ml in the ISAR drug-eluting stent platform). Part I of the study investigated in cytoflow studies the effect of SRL (0.01–1000 ng/ml) on TNF-α induced expression of intercellular adhesion molecule 1 (ICAM-1) in human coronary endothelial cells (HCAEC) and human coronary smooth muscle cells (HCMSMC). Part II of the study analysed the effect of SRL (0.01–1000 ng/ml) on cell migration of HCMSMC. In part III, IV, and V of the study ex vivo angioplasty (9 bar) was carried out in a human organ culture model (HOC-model). SRL (50 ng/ml) was added for a period of 21 days, after 21 and 56 days cell proliferation, apoptosis, and neointimal hyperplasia was studied.</p> <p>Results</p> <p>Expression of ICAM-1 was significantly inhibited both in HCAEC (SRL ≥ 0.01 ng/ml) and HCMSMC (SRL ≥ 10 ng/ml). SRL in concentrations ≥ 0.1 ng/ml significantly inhibited migration of HCMSMC. Cell proliferation and neointimal hyperplasia was inhibited at day 21 and day 56, significance (p < 0.01) was achieved for the inhibitory effect on cell proliferation in the media at day 21. The number of apoptotic cells was always below 1%.</p> <p>Conclusion</p> <p>SI/MPL-ratio's ≤ 1 (ICAM-1 expression, cell migration) characterize inhibitory effects of SRL that can be theoretically expected both after systemic and local high dose administration, a SI/MPL-ratio of 7.81 (cell proliferation) represents an effect that was achieved with drug concentrations 7.81-times the MPL. SI/DES-ratio's between 10^-6and 10^-8indicate that the described inhibitory effects of SRL have been detected with micro to nano parts of the SRL concentration in the ISAR drug-eluting stent platform. Drug concentrations in DES will be a central issue in the future.</p

Inhibition of STAT3 signaling prevents vascular smooth muscle cell proliferation and neointima formation

Dedifferentiation, migration, and proliferation of resident vascular smooth muscle cells (SMCs) are key components of neointima formation after vascular injury. Activation of signal transducer and activator of transcription-3 (STAT3) is suggested to be critically involved in this process, but the complex regulation of STAT3-dependent genes and the functional significance of inhibiting this pathway during the development of vascular proliferative diseases remain elusive. In this study, we demonstrate that STAT3 was activated in neointimal lesions following wire-induced injury in mice. Phosphorylation of STAT3 induced trans-activation of cyclin D1 and survivin in SMCs in vitro and in neointimal cells in vivo, thus promoting proliferation and migration of SMCs as well as reducing apoptotic cell death. WP1066, a highly potent inhibitor of STAT3 signaling, abrogated phosphorylation of STAT3 and dose-dependently inhibited the functional effects of activated STAT3 in stimulated SMCs. The local application of WP1066 via a thermosensitive pluronic F-127 gel around the dilated arteries significantly inhibited proliferation of neointimal cells and decreased the neointimal lesion size at 3 weeks after injury. Even though WP1066 application attenuated the injury-induced up-regulation of the chemokine RANTES at 6 h after injury, there was no significant effect on the accumulation of circulating cells at 1 week after injury. In conclusion, these data identify STAT3 as a key molecule for the proliferative response of SMC and neointima formation. Moreover, inhibition of STAT3 by the potent and specific compound WP1066 might represent a novel and attractive approach for the local treatment of vascular proliferative diseases

Digitalized service multinationals and international business theory

Banalieva and Dhanaraj argue that digital service multinationals (DSMNCs) possess a new category of firm-specific advantage (FSA), the network advantage, and that, contrary to extant theory, they use networks as a mode of governance. I review the business models used by DSMNCs, compare them to non-digital ones, and explore what we can learn about them from extant IB theory. I conclude that network advantages are not a new category of FSAs, that networks are not a mode of governance, and that their use by DSMNCs is well explained by extant theory