Phosphazene-Catalyzed Desymmetrization of Cyclohexadienone by Dithiane Addition

We report a desymmetrization of cyclohexadienones by intramolecular conjugate addition of a tethered dithiane nucleophile. Mild reaction conditions allow the formation of diversely functionalized fused bicyclic lactones. The products participate in facially selective additions from the convex surface, leading to allylic alcohol derivative

Eikonal Approximation to 5D Wave Equations as Geodesic Motion in a Curved 4D Spacetime

We first derive the relation between the eikonal approximation to the Maxwell wave equations in an inhomogeneous anisotropic medium and geodesic motion in a three dimensional Riemannian manifold using a method which identifies the symplectic structure of the corresponding mechanics. We then apply an analogous method to the five dimensional generalization of Maxwell theory required by the gauge invariance of Stueckelberg's covariant classical and quantum dynamics to demonstrate, in the eikonal approximation, the existence of geodesic motion for the flow of mass in a four dimensional pseudo-Riemannian manifold. These results provide a foundation for the geometrical optics of the five dimensional radiation theory and establish a model in which there is mass flow along geodesics. Finally we discuss the case of relativistic quantum theory in an anisotropic medium as well. In this case the eikonal approximation to the relativistic quantum mechanical current coincides with the geodesic flow governed by the pseudo-Riemannian metric obtained from the eikonal approximation to solutions of the Stueckelberg-Schr\"odinger equation. This construction provides a model for an underlying quantum mechanical structure for classical dynamical motion along geodesics on a pseudo-Riemannian manifold. The locally symplectic structure which emerges is that of Stueckelberg's covariant mechanics on this manifold.Comment: TeX file. 17 pages. Rewritten for clarit

Academic freedom: in justification of a universal ideal

This paper examines the justification for, and benefits of, academic freedom to academics, students, universities and the world at large. The paper surveys the development of the concept of academic freedom within Europe, more especially the impact of the reforms at the University of Berlin instigated by Wilhelm von Humboldt. Following from this, the paper examines the reasons why the various facets of academic freedom are important and why the principle should continue to be supported

Relativistic Calculation of the Meson Spectrum: a Fully Covariant Treatment Versus Standard Treatments

A large number of treatments of the meson spectrum have been tried that consider mesons as quark - anti quark bound states. Recently, we used relativistic quantum "constraint" mechanics to introduce a fully covariant treatment defined by two coupled Dirac equations. For field-theoretic interactions, this procedure functions as a "quantum mechanical transform of Bethe-Salpeter equation". Here, we test its spectral fits against those provided by an assortment of models: Wisconsin model, Iowa State model, Brayshaw model, and the popular semi-relativistic treatment of Godfrey and Isgur. We find that the fit provided by the two-body Dirac model for the entire meson spectrum competes with the best fits to partial spectra provided by the others and does so with the smallest number of interaction functions without additional cutoff parameters necessary to make other approaches numerically tractable. We discuss the distinguishing features of our model that may account for the relative overall success of its fits. Note especially that in our approach for QCD, the resulting pion mass and associated Goldstone behavior depend sensitively on the preservation of relativistic couplings that are crucial for its success when solved nonperturbatively for the analogous two-body bound-states of QED.Comment: 75 pages, 6 figures, revised content

Toward a 21st-century health care system: Recommendations for health care reform

The coverage, cost, and quality problems of the U.S. health care system are evident. Sustainable health care reform must go beyond financing expanded access to care to substantially changing the organization and delivery of care. The FRESH-Thinking Project (www.fresh-thinking.org) held a series of workshops during which physicians, health policy experts, health insurance executives, business leaders, hospital administrators, economists, and others who represent diverse perspectives came together. This group agreed that the following 8 recommendations are fundamental to successful reform: 1. Replace the current fee-for-service payment system with a payment system that encourages and rewards innovation in the efficient delivery of quality care. The new payment system should invest in the development of outcome measures to guide payment. 2. Establish a securely funded, independent agency to sponsor and evaluate research on the comparative effectiveness of drugs, devices, and other medical interventions. 3. Simplify and rationalize federal and state laws and regulations to facilitate organizational innovation, support care coordination, and streamline financial and administrative functions. 4. Develop a health information technology infrastructure with national standards of interoperability to promote data exchange. 5. Create a national health database with the participation of all payers, delivery systems, and others who own health care data. Agree on methods to make de-identified information from this database on clinical interventions, patient outcomes, and costs available to researchers. 6. Identify revenue sources, including a cap on the tax exclusion of employer-based health insurance, to subsidize health care coverage with the goal of insuring all Americans. 7. Create state or regional insurance exchanges to pool risk, so that Americans without access to employer-based or other group insurance could obtain a standard benefits package through these exchanges. Employers should also be allowed to participate in these exchanges for their employees' coverage. 8. Create a health coverage board with broad stakeholder representation to determine and periodically update the affordable standard benefit package available through state or regional insurance exchanges

The Public Repository of Xenografts enables discovery and randomized phase II-like trials in mice

More than 90% of drugs with preclinical activity fail in human trials, largely due to insufficient efficacy. We hypothesized that adequately powered trials of patient-derived xenografts (PDX) in mice could efficiently define therapeutic activity across heterogeneous tumors. To address this hypothesis, we established a large, publicly available repository of well-characterized leukemia and lymphoma PDXs that undergo orthotopic engraftment, called the Public Repository of Xenografts (PRoXe). PRoXe includes all de-identified information relevant to the primary specimens and the PDXs derived from them. Using this repository, we demonstrate that large studies of acute leukemia PDXs that mimic human randomized clinical trials can characterize drug efficacy and generate transcriptional, functional, and proteomic biomarkers in both treatment-naive and relapsed/refractory disease