Photochemically Produced Aminocyclobutanes as Masked Dienes in Thermal Electrocyclic Cascade Reactions

Cyclobutane products of a triplet sensitized enamide-alkene intramolecular [2 + 2] photocycloaddition have been shown to undergo fragmentation under acidic conditions. This lability has been exploited by inducing a complexity-generating thermal electrocyclic cascade sequence involving the <i>in situ</i> formation of a cyclobutene, followed by electrocyclic ring opening, Diels–Alder cycloaddition, and subsequent lactamization. This combination of excited state photochemistry and thermal electrocyclic cascade reactions allows simple planar molecules to be rapidly transformed into sp³-rich scaffolds

Toward optimal implementation of cancer prevention and control programs in public health: A study protocol on mis-implementation

Abstract Background Much of the cancer burden in the USA is preventable, through application of existing knowledge. State-level funders and public health practitioners are in ideal positions to affect programs and policies related to cancer control. Mis-implementation refers to ending effective programs and policies prematurely or continuing ineffective ones. Greater attention to mis-implementation should lead to use of effective interventions and more efficient expenditure of resources, which in the long term, will lead to more positive cancer outcomes. Methods This is a three-phase study that takes a comprehensive approach, leading to the elucidation of tactics for addressing mis-implementation. Phase 1: We assess the extent to which mis-implementation is occurring among state cancer control programs in public health. This initial phase will involve a survey of 800 practitioners representing all states. The programs represented will span the full continuum of cancer control, from primary prevention to survivorship. Phase 2: Using data from phase 1 to identify organizations in which mis-implementation is particularly high or low, the team will conduct eight comparative case studies to get a richer understanding of mis-implementation and to understand contextual differences. These case studies will highlight lessons learned about mis-implementation and identify hypothesized drivers. Phase 3: Agent-based modeling will be used to identify dynamic interactions between individual capacity, organizational capacity, use of evidence, funding, and external factors driving mis-implementation. The team will then translate and disseminate findings from phases 1 to 3 to practitioners and practice-related stakeholders to support the reduction of mis-implementation. Discussion This study is innovative and significant because it will (1) be the first to refine and further develop reliable and valid measures of mis-implementation of public health programs; (2) bring together a strong, transdisciplinary team with significant expertise in practice-based research; (3) use agent-based modeling to address cancer control implementation; and (4) use a participatory, evidence-based, stakeholder-driven approach that will identify key leverage points for addressing mis-implementation among state public health programs. This research is expected to provide replicable computational simulation models that can identify leverage points and public health system dynamics to reduce mis-implementation in cancer control and may be of interest to other health areas

The Majorana Project

Building a \BBz experiment with the ability to probe neutrino mass in the inverted hierarchy region requires the combination of a large detector mass sensitive to \BBz, on the order of 1-tonne, and unprecedented background levels, on the order of or less than 1 count per year in the \BBz signal region. The MAJORANA Collaboration proposes a design based on using high-purity enriched Ge-76 crystals deployed in ultra-low background electroformed Cu cryostats and using modern analysis techniques that should be capable of reaching the required sensitivity while also being scalable to a 1-tonne size. To demonstrate feasibility, the collaboration plans to construct a prototype system, the MAJORANA DEMONSTRATOR, consisting of 30 kg of 86% enriched \Ge-76 detectors and 30 kg of natural or isotope-76-depleted Ge detectors. We plan to deploy and evaluate two different Ge detector technologies, one based on a p-type configuration and the other on n-type.Comment: paper submitted for the 2008 Carolina International Symposium on Neutrino Physic

Multi-Messenger Gravitational Wave Searches with Pulsar Timing Arrays: Application to 3C66B Using the NANOGrav 11-year Data Set

When galaxies merge, the supermassive black holes in their centers may form binaries and, during the process of merger, emit low-frequency gravitational radiation in the process. In this paper we consider the galaxy 3C66B, which was used as the target of the first multi-messenger search for gravitational waves. Due to the observed periodicities present in the photometric and astrometric data of the source of the source, it has been theorized to contain a supermassive black hole binary. Its apparent 1.05-year orbital period would place the gravitational wave emission directly in the pulsar timing band. Since the first pulsar timing array study of 3C66B, revised models of the source have been published, and timing array sensitivities and techniques have improved dramatically. With these advances, we further constrain the chirp mass of the potential supermassive black hole binary in 3C66B to less than $(1.65\pm0.02) \times 10^9~{M_\odot}$ using data from the NANOGrav 11-year data set. This upper limit provides a factor of 1.6 improvement over previous limits, and a factor of 4.3 over the first search done. Nevertheless, the most recent orbital model for the source is still consistent with our limit from pulsar timing array data. In addition, we are able to quantify the improvement made by the inclusion of source properties gleaned from electromagnetic data to `blind' pulsar timing array searches. With these methods, it is apparent that it is not necessary to obtain exact a priori knowledge of the period of a binary to gain meaningful astrophysical inferences.Comment: 14 pages, 6 figures. Accepted by Ap

A laboratory-scale annular continuous flow reactor for UV photochemistry using excimer lamps for discrete wavelength excitation and its use in a wavelength study of a photodecarboxlyative cyclisation

This paper describes a new annular reactor for continuous UV photochemistry, which uses easily interchangeable excimer lamps of different wavelengths. The reactor has narrow clearance to form thin films of material for efficient irradiation of molecules. Its use is demonstrated by investigating the effect of discrete wavelength lamps (222, 282 and 308 nm) on the reaction of potassium N-phthalimidobutanoate 1. The ability of the reactor to be integrated into multistep processes is illustrated by combining it with an Amberlyst scavenger and a solid acid catalyst, NbOPO4, to access a second product 3 that is obtained in a single telescoped process. The tricyclic scaffold in 3 is a motif found in several biologically active compounds and has possibilities as a synthon for new pharmaceutical products

Astroparticle Physics with a Customized Low-Background Broad Energy Germanium Detector

The MAJORANA Collaboration is building the MAJORANA DEMONSTRATOR, a 60 kg array of high purity germanium detectors housed in an ultra-low background shield at the Sanford Underground Laboratory in Lead, SD. The MAJORANA DEMONSTRATOR will search for neutrinoless double-beta decay of 76Ge while demonstrating the feasibility of a tonne-scale experiment. It may also carry out a dark matter search in the 1-10 GeV/c^2 mass range. We have found that customized Broad Energy Germanium (BEGe) detectors produced by Canberra have several desirable features for a neutrinoless double-beta decay experiment, including low electronic noise, excellent pulse shape analysis capabilities, and simple fabrication. We have deployed a customized BEGe, the MAJORANA Low-Background BEGe at Kimballton (MALBEK), in a low-background cryostat and shield at the Kimballton Underground Research Facility in Virginia. This paper will focus on the detector characteristics and measurements that can be performed with such a radiation detector in a low-background environment.Comment: Submitted to NIMA Proceedings, SORMA XII. 9 pages, 4 figure

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy