Common molecular determinants of local anesthetic, antiarrhythmic, and anticonvulsant block of voltage-gated Na+ channels.

Voltage-gated Na+ channels are the molecular targets of local anesthetics, class I antiarrhythmic drugs, and some anticonvulsants. These chemically diverse drugs inhibit Na+ channels with complex voltage- and frequency-dependent properties that reflect preferential drug binding to open and inactivated channel states. The site-directed mutations F1764A and Y1771A in transmembrane segment IVS6 of type IIA Na+ channel alpha subunits dramatically reduce the affinity of inactivated channels for the local anesthetic etidocaine. In this study, we show that these mutations also greatly reduce the sensitivity of Na+ channels to state-dependent block by the class Ib antiarrhythmic drug lidocaine and the anticonvulsant phenytoin and, to a lesser extent, reduce the sensitivity to block by the class Ia and Ic antiarrhythmic drugs quinidine and flecainide. For lidocaine and phenytoin, which bind preferentially to inactivated Na+ channels, the mutation F1764A reduced the affinity for binding to the inactivated state 24.5-fold and 8.3-fold, respectively, while Y1771A had smaller effects. For quinidine and flecainide, which bind preferentially to the open Na+ channels, the mutations F1764A and Y1771A reduced the affinity for binding to the open state 2- to 3-fold. Thus, F1764 and Y1771 are common molecular determinants of state-dependent binding of diverse drugs including lidocaine, phenytoin, flecainide, and quinidine, suggesting that these drugs interact with a common receptor site. However, the different magnitude of the effects of these mutations on binding of the individual drugs indicates that they interact in an overlapping, but nonidentical, manner with a common receptor site. These results further define the contributions of F1764 and Y1771 to a complex drug receptor site in the pore of Na+ channels.

Transmission and Transport of Energy in the Western U.S. and Canada: A Law and Policy Road Map

This collection of short essays arose from the inaugural meeting of the Idaho Symposium on Energy in the West, which was held in November, 2014. The topic for this first Symposium was Transmission and Transport of Energy in the Western U.S. and Canada: A Law and Policy Road Map. The essays in this collection provide a notable introduction to the major energy issues facing the West today. Topics include: building a resilient legal architecture for western energy production; natural gas flaring; transmission planning for wind energy; utilities and rooftop solar; special considerations for western states and the Clean Power Plan; the Clean Power Plan's implications for the western grid; siting renewable energy on public lands; and implications of utility reform in New York and Hawaii for the Northwest.

Solid Waste Management And Regulations in the Marshall Islands

The Marshall Islands, a small island developing nation, has a significant solid waste problem. The atoll environment of the Majuro, the capital of the Marshall Islands, is one of scarce land and overpopulation. Increasing Western influences has been a major factor in this solid waste problem. This problem has created health issues and is an impediment to the development of a tourism industry, which is essential to the development of economic opportunities. Responsibility for solid waste management in Majuro is divided between several governmental and non-governmental agencies. This system is dysfunctional as there is little or no cooperation between the agencies. Although many consultants have developed recommendations, no action has been taken. Developing an action plan to consolidate solid waste management under one authority is important to solving of this solid waste problem. This project proposes legislation creating a solid waste management authority that will have the power to regulate all aspects of solid waste and help implement education and awareness to the people of the Marshall Islands.

Effective Surface Water Quality Policies: A Contrast of Policies in the United States and the European Union

The United States and the European Union each have their own policy approach to protect surface water quality. Both policy approaches are similar in many ways. Both rely heavily on command and control. However, there are differences in the application of the details. Both the U.S. and E.U. began current efforts to protect surface water quality in the 1970s, yet quality continues to less than desired in both places. Both have reduced point source pollutants but have had difficulty controlling non-point source pollutants even though policies have been in place for many decades. The successes and failures of the two policies are studied in this project to determine which aspects of both policies will best protect surface water quality in an increasingly complex future.

Denver Water, Policy and Economics

An analysis of the Denver Water Department finds that it is charged with supplying water to over 1.1 million residents in the Denver Metropolitan area. With assets of over $1.2 billion dollars and a governing board of five appointed members who must make policy and financial decisions under unusual circumstances for most water districts. Those circumstances include; Colorado is the only State that has a single source of water, precipitation, State and Federal mandated water compacts that limits water resources further, and Colorado Constitutional mandated appropriation water laws. Combined together these circumstances create a difficult atmosphere for policy making and financial planning. When comparing the Denver Water Board with other water departments around the Country, the Denver Water Department seems to be competent in all areas.

Performance Septic Systems: Does an Advanced Septic System Provide Adequate Treatment on Black Hammock Island and is there Adequate Regulatory Policy to Ensure Integrity?

This project determined if the performance based septic system, proposed for a development on Black Hammock Island in Jacksonville, Florida, is the best choice to prevent environmental contamination from septic tanks and if adequate regulatory policy exists. Research shows a central wastewater treatment plant provides the most efficient pollutant removal but can be cost prohibitive. This project found performance based systems surpasses conventional septic system performance and are more suited and economical to remote areas without sewer service. This project finds current regulations to be inadequate and supports ordinance changes proposed by the Mayor of Jacksonville to enhance the current policy and provide more adequate and meaningful regulation.

Saint Mathew Law and Bonini Paradox in Textual Theory of Complex Models

The mathematical models of the complex reality are texts belonging to a certain literature that is written in a semi-formal language, denominated L(MT) by the authors whose laws linguistic mathematics have been previously defined. This text possesses linguistic entropy that is the reflection of the physical entropy of the processes of real world that said text describes. Through the temperature of information defined by Mandelbrot, the authors begin a text-reality thermodynamic theory that drives to the existence of information attractors, or highly structured point, settling down a heterogeneity of the space text, the same one that of ontologic space, completing the well-known law of Saint Mathew, of the General Theory of Systems and formulated by Margalef saying: “To the one that has more he will be given, and to the one that doesn't have he will even be removed it little that it possesses.

The eight hours day for wage earning women: United States Supreme Court upholds the California law : List of eight hours laws

National Consumers' League.

How one juvenile court helps to make child labor legislation effective

by Mabel Brown Ellis.

Abstracts of legislation relating to Harvard College governance (manuscript notebook), ca. 1723

Octavo-sized notebook containing handwritten abstracts of Massachusetts General Court legislation between 1650 and August 24, 1723 related to Harvard governance. The volume contains informal notes with extracts and summaries of legislation that established or amended the makeup and power of the Harvard Corporation. The authors of the volume are unidentified, but the notes appear to be in two different hands. The volume was presumably created during the fellowship controversy that erupted in the early 1720s after tutors Henry Flynt, Nicholas Sever, and Thomas Robie presented a memorial to the Board of Overseers calling for the tutors' right of fellowship in the Corporation.

Observations on the courts of law in Nova Scotia, Canada, 1775

Contains a discussion of the organization of the courts in Nova Scotia and recommends changes to allow for greater efficiency and logical administration of cases through the system of justice.