Smart Contracts in Traditional Contract Law, Or: The Law of the Vending Machine

Smart contracts are the new norm, yet state legislatures and courts have not developed set rules and answers to legal disputes that these contracts create. Is traditional contract law sufficient? Or should we create an entirely new legislative or common law scheme to deal with these disputes? The common law has proven to be successful in dealing with new technologies and contracts, particularly because of its flexibility. Although a major overhaul may be in the future, there are still solutions that we can find today with the current legal landscape given the state of contract law and its evolution over time. One particularly analogous body of case law is instructive: the law of the vending machine. In the end, thinking about smart contracts as vending machines may be fruitful for the future of this evolving area of the law

Blockchain-Based Token Sales, Initial Coin Offerings, and the Democratization of Public Capital Markets

Best known for their role in the creation of cryptocurrencies like bitcoin, blockchains are revolutionizing the way technology entrepreneurs finance their business enterprises. In 2017 alone, tech entrepreneurs raised over $6 billion through the sale of blockchain-based digital tokens, with some sales lasting mere seconds before selling out. In a token sale, also referred to as an “initial coin offering” or “ICO,” organizers of a project sell digital tokens to members of the public to finance the development of new technological platforms and services. After the initial sale, cryptocurrency exchanges scattered across the globe list tokens for trading and facilitate an active secondary market in which wild price fluctuations are common. The recent explosion of token sales could mark the beginning of a broader shift in public capital markets. Blockchains drastically reduce the cost of exchanging value and enable anyone to transmit digitized assets around the globe in a highly trusted manner, stoking dreams of truly global capital markets that leverage the power of a blockchain and the Internet to facilitate capital formation. Lacking homogeneity, the status of tokens under U.S. securities laws is unclear. Although the SEC recently issued a Report of Investigation and has initiated several enforcement actions in which it has found that tokens are securities, confusion still surrounds the boundaries between the types of tokens that will be treated as securities and those that will not. In this Article, we argue that the SEC and Congress should provide token sellers and the exchanges that facilitate token sales with additional regulatory certainty and a sensible path to compliance. Specifically, we outline extrinsic and intrinsic factors that courts and regulators should consider when applying the Howey test to digital tokens, adoption of which would help resolve the uncertainty surrounding tokens that mix aspects of consumption and use with the potential for profit. We further propose that lawmakers adopt both a compliance-driven safe harbor for online exchanges that list tokens with a reasonable belief that the public sale of such tokens is not a violation of section 5 of the Securities Act of 1933 as well as an exemption to the section 5 registration requirement that has been tailored to digital tokens

Blockchain-Based Token Sales, Initial Coin Offerings, and the Democratization of Public Capital Markets

Best known for their role in the creation of cryptocurrencies like bitcoin, blockchains are revolutionizing the way technology entrepreneurs finance their business enterprises. In 2017 alone, tech entrepreneurs raised over $6 billion through the sale of blockchain-based digital tokens, with some sales lasting mere seconds before selling out. In a token sale, also referred to as an “initial coin offering” or “ICO,” organizers of a project sell digital tokens to members of the public to finance the development of new technological platforms and services. After the initial sale, cryptocurrency exchanges scattered across the globe list tokens for trading and facilitate an active secondary market in which wild price fluctuations are common. The recent explosion of token sales could mark the beginning of a broader shift in public capital markets. Blockchains drastically reduce the cost of exchanging value and enable anyone to transmit digitized assets around the globe in a highly trusted manner, stoking dreams of truly global capital markets that leverage the power of a blockchain and the Internet to facilitate capital formation. Lacking homogeneity, the status of tokens under U.S. securities laws is unclear. Although the SEC recently issued a Report of Investigation and has initiated several enforcement actions in which it has found that tokens are securities, confusion still surrounds the boundaries between the types of tokens that will be treated as securities and those that will not. In this Article, we argue that the SEC and Congress should provide token sellers and the exchanges that facilitate token sales with additional regulatory certainty and a sensible path to compliance. Specifically, we outline extrinsic and intrinsic factors that courts and regulators should consider when applying the Howey test to digital tokens, adoption of which would help resolve the uncertainty surrounding tokens that mix aspects of consumption and use with the potential for profit. We further propose that lawmakers adopt both a compliance-driven safe harbor for online exchanges that list tokens with a reasonable belief that the public sale of such tokens is not a violation of section 5 of the Securities Act of 1933 as well as an exemption to the section 5 registration requirement that has been tailored to digital tokens

Modelling the effect of gap junctions on tissue-level cardiac electrophysiology

When modelling tissue-level cardiac electrophysiology, continuum approximations to the discrete cell-level equations are used to maintain computational tractability. One of the most commonly used models is represented by the bidomain equations, the derivation of which relies on a homogenisation technique to construct a suitable approximation to the discrete model. This derivation does not explicitly account for the presence of gap junctions connecting one cell to another. It has been seen experimentally [Rohr, Cardiovasc. Res. 2004] that these gap junctions have a marked effect on the propagation of the action potential, specifically as the upstroke of the wave passes through the gap junction. In this paper we explicitly include gap junctions in a both a 2D discrete model of cardiac electrophysiology, and the corresponding continuum model, on a simplified cell geometry. Using these models we compare the results of simulations using both continuum and discrete systems. We see that the form of the action potential as it passes through gap junctions cannot be replicated using a continuum model, and that the underlying propagation speed of the action potential ceases to match up between models when gap junctions are introduced. In addition, the results of the discrete simulations match the characteristics of those shown in Rohr 2004. From this, we suggest that a hybrid model -- a discrete system following the upstroke of the action potential, and a continuum system elsewhere -- may give a more accurate description of cardiac electrophysiology.Comment: In Proceedings HSB 2012, arXiv:1208.315

Praziquantel activates a native cation current in Schistosoma mansoni

IntroductionPraziquantel (PZQ), an anthelmintic drug discovered in the 1970s, is still used to treat schistosomiasis and various other infections caused by parasitic flatworms. PZQ causes a triad of phenotypic effects on schistosome worms – rapid depolarization, muscle contraction, and damage throughout the worm tegument. The molecular target mediating these effects has been intimated as a Ca2+-permeable ion channel, but native currents evoked by PZQ have not been reported in any schistosome cell type. The properties of the endogenous PZQ activated conductance therefore remain unknown. MethodsHere, invasive electrophysiology was used to probe for responses to PZQ from different locales in a living schistosome worm.Results and discussionNo direct response was seen in tegument-derived vesicles, or from the sub-tegumental muscle layer despite the presence of voltage-operated currents. However, PZQ rapidly triggered a sustained, non-selective cation current in recordings from neuronal tissue, targeting both the anterior ganglion and the main longitudinal nerve cord. The biophysical signature of this PZQ-evoked current resolved at single channel resolution matched that of a transient receptor potential ion channel named TRPMPZQ, recently proposed as the molecular target of PZQ. The endogenous PZQ-evoked current was also inhibited by a validated TRPMPZQ antagonist. PZQ therefore is a neuroactive anthelmintic, causing a sustained depolarization through ion channels with the characteristics of TRPMPZQ

TRP drop, TRP drop: a steady patter of anti-schistosomal target illumination

Infections caused by parasitic flatworms impart a significant disease burden. This is well exemplified by the neglected tropical disease schistosomiasis, which afflicts millions of people worldwide. The anti-schistosomal activity of various chemotypes has been known for decades, but the parasite targets of many of these remain undefined. Until recently, this included the current clinical therapy, praziquantel (PZQ). However, the tempo of target discovery has recently gathered pace, with discoveries of schistosome targets for praziquantel (PZQ) and the anthelmintic benzodiazepine, meclonazepam (MCLZ). This steady patter of target illumination has also revealed a pattern in that both PZQ and MCLZ target members of the same ion channel subgroup—transient receptor potential ion channels of the melastatin family (TRPM channels). PZQ activates one member of this family (TRPMPZQ) and MCLZ activates a different channel (TRPMMCLZ). Here, similarities and differences between these two new targets are discussed. These data highlight the need for further study of TRPM channels in parasitic flatworms given their vulnerability to chemotherapeutic attack

The Anthelmintic Activity of Praziquantel Analogs Correlates with Structure-Activity Relationships at TRPMPZQ Orthologs.

The anthelmintic drug praziquantel remains a key clinical therapy for treating various diseases caused by parasitic flatworms. The parasite target of praziquantel has remained undefined despite longstanding usage in the clinic, although a candidate ion channel target, named TRPMPZQ, has recently been identified. Intriguingly, certain praziquantel derivatives show different activities against different parasites: for example, some praziquantel analogs are considerably more active against cestodes than against schistosomes. Here we interrogate whether the different activities of praziquantel analogs against different parasites are also reflected by unique structure-activity relationships at the TRPMPZQ channels found in these different organisms. To do this, several praziquantel analogs were synthesized and functionally profiled against schistosome and cestode TRPMPZQ channels. Data demonstrate that structure-activity relationships are closely mirrored between parasites and their TRPMPZQ orthologs, providing further support for TRPMPZQ as the therapeutically relevant target of praziquantel

Biodiversity loss underlies the dilution effect of biodiversity

The dilution effect predicts increasing biodiversity to reduce the risk of infection, but the generality of this effect remains unresolved. Because biodiversity loss generates predictable changes in host community competence, we hypothesised that biodiversity loss might drive the dilution effect. We tested this hypothesis by reanalysing four previously published meta-analyses that came to contradictory conclusions regarding generality of the dilution effect. In the context of biodiversity loss, our analyses revealed a unifying pattern: dilution effects were inconsistently observed for natural biodiversity gradients, but were commonly observed for biodiversity gradients generated by disturbances causing losses of biodiversity. Incorporating biodiversity loss into tests of generality of the dilution effect further indicated that scale-dependency may strengthen the dilution effect only when biodiversity gradients are driven by biodiversity loss. Together, these results help to resolve one of the most contentious issues in disease ecology: the generality of the dilution effect.Non peer reviewe

Selection on stability across ecological scales

Much of the focus in evolutionary biology has been on the adaptive differentiation among organisms. It is equally important to understand the processes that result in similarities of structure among systems. Here, we discuss examples of similarities occurring at different ecological scales, from predator–prey relations (attack rates and handling times) through communities (food-web structures) to ecosystem properties. Selection among systemic configurations or patterns that differ in their intrinsic stability should lead generally to increased representation of relatively stable structures. Such nonadaptive, but selective processes that shape ecological communities offer an enticing mechanism for generating widely observed similarities, and have sparked new interest in stability properties. This nonadaptive systemic selection operates not in opposition to, but in parallel with, adaptive evolution