Characterizing Active Site Conformational Heterogeneity along the Trajectory of an Enzymatic Phosphoryl Transfer Reaction

States along the phosphoryl transfer reaction catalyzed by the nucleoside monophosphate kinase UmpK were captured and changes in the conformational heterogeneity of conserved active site arginine side-chains were quantified by NMR spin-relaxation methods. In addition to apo and ligand-bound UmpK, a transition state analog (TSA) complex was utilized to evaluate the extent to which active site conformational entropy contributes to the transition state free energy. The catalytically essential arginine side-chain guanidino groups were found to be remarkably rigid in the TSA complex, indicating that the enzyme has evolved to restrict the conformational freedom along its reaction path over the energy landscape, which in turn allows the phosphoryl transfer to occur selectively by avoiding side reactions

Executive Power and the Law of Nations in the Washington Administration

In this issue\u27s lead article, Professor Reinstein continueshis examination of the development of executive power over foreign affairs during the early history of the Republic. Re- cently, both legal scholars and the courts are looking to the actions of the first administrationas a potentialprecedent onhow to construe the scope and source of the President\u27s au- thority to determine and conduct the United States\u27 foreign policy. Last year, in an articlepublished in thisjournal,Pro-fessor Reinstein concluded that no originalistjustificationex-ists for a plenary executive recognitionpower. In this article, Professor Reinstein expands this discussion through an original historical and jurisprudential account of the Neutrality Crisis of 1792-1794 to draw three revisionist conclusions.First, he concludes that the Washington administration\u27s most plausible source of constitutional authority was the Executive\u27s duty, under the Take Care Clause, to obey the law of nations as expounded in the natural law treatises. Second, the Washington administration set a key precedent for the Executive\u27s duty to obey the constraints of international law. And third, since profound changes in the United States have shown that the founders\u27 way of thinking can be incompatible with our own, Professor Reinstein concludes that originalism is limited as a constitutional methodology and that theories of expansive executive powers must find foundations outside of the first President\u27s decision

Owning Outer Space

If exploitation of outer space\u27s bounty is our goal, we must establish a space property legal system that creates both incentives and predictability. Space development is a highly risky endeavor, as well as mind-bogglingly expensive. Who would expend the effort in developing a space colony, if they were not certain of the project\u27s legality? Valuable projects -- energy collection, mining, and colonization -- are by no means inevitable. If the law of outer space rejects such uses, or even makes their legality uncertain, it is unlikely that the nec-essary technology would ever be created. A promising solution to our ever-growing energy needs involves setting up giant banks of solar panels in Earth\u27s orbit and on the moon\u27s sunny side, using the solar energy to power space development projects, and then beaming the excess down to Earth as microwave energy for terrestrial use.2 Will a private electric company be willing to develop such a lunar solar collection system? Not without a field of space law that permits exploitation and a strong rate of return on investment. Unless we can impose a rule of law that eliminates uncertainty while permitting the highest possible rate of return, we may be denied access to the fruits of space for a long time to come

Owning Outer Space

If exploitation of outer space\u27s bounty is our goal, we must establish a space property legal system that creates both incentives and predictability. Space development is a highly risky endeavor, as well as mind-bogglingly expensive. Who would expend the effort in developing a space colony, if they were not certain of the project\u27s legality? Valuable projects -- energy collection, mining, and colonization -- are by no means inevitable. If the law of outer space rejects such uses, or even makes their legality uncertain, it is unlikely that the nec-essary technology would ever be created. A promising solution to our ever-growing energy needs involves setting up giant banks of solar panels in Earth\u27s orbit and on the moon\u27s sunny side, using the solar energy to power space development projects, and then beaming the excess down to Earth as microwave energy for terrestrial use.2 Will a private electric company be willing to develop such a lunar solar collection system? Not without a field of space law that permits exploitation and a strong rate of return on investment. Unless we can impose a rule of law that eliminates uncertainty while permitting the highest possible rate of return, we may be denied access to the fruits of space for a long time to come

Reliability of manual segmentation of cornea, contact lens and tear film using a high-resolution OCT

In this study, we aimed to evaluate the intra/inter-session and intra/inter-observer variability of manual segmentation of thickness of the pre-lens tear film, contact lens (CL), post-lens tear film, epithelium, bowman’s layer, stroma and the whole cornea and CLs with a flat and a steep fit, using a commercial high-resolution spectral domain optical coherence tomographer (OCT). Two different observers obtained three repeated measures in two separate sessions. A high correlation was found between the values obtained by the two different observers, except for the thinner layers, epithelium, and Bowman’s layer. Inter-observer analysis showed a high consistency in the measurements obtained by both observers (r 2 ≥ 0.80; p < 0.001) for the thicker layers: CL, stroma, and total cornea. Intra-observer analysis of measurements obtained by each observer within the same session displayed no statistically significant differences between the three repeated measures for both observers (p > 0.05). The present results suggest that manual segmentation of anterior segment OCT images in CL wearers provides acceptable levels of repeatability between observers and between different sessions for the thinner layers, while presenting a high level of repeatability for the thicker layers.This work was supported by FEDER through the COMPETE Program and by the Portuguese Foundation for Science and Technology (FCT) in the framework of the Strategic Project PEST-C/FIS/UI607/2011. Supported in part by research grants to A. Cervino from the Universitat de Valencia (UV-AE-20070225), the "Jose Castillejo" Research Grant from the Spanish Ministry of Science and Technology (JC2008-00078) and the Spanish Network for Research in Optometry (SAF2008-01114-E)

Listen to the market, hear the best policy decision, but don't always choose it

This is an updated version of the 20 February 2014 working paper of the same title, which is available in ORE at http://hdl.handle.net/10871/26685Policymakers often consider policies with (a) uncertain social benefits and (b) uncertain impacts on the value of private assets; we characterize six ways (a) and (b) may be inter-related. Where investors have private information over (b), policymakers may attempt to learn this through the response of asset markets to proposed policies. However, where this information is concentrated, an informed trader may profitably hide his information and “manipulate” the market. We show that it is nonetheless generically optimal for policymakers to listen and respond to asset markets, but under specified conditions they must commit (e.g., through “political capital”) to sometimes pursuing a policy even when the expected welfare effects are negative. Surprisingly, allowing traders to short-sell can make it easier for policymakers to induce truth-telling actions