Dependent Types In Haskell: Theory And Practice

Haskell, as implemented in the Glasgow Haskell Compiler (GHC), has been adding new type-level programming features for some time. Many of these features---generalized algebraic datatypes (GADTs), type families, kind polymorphism, and promoted datatypes---have brought Haskell to the doorstep of dependent types. Many dependently typed programs can even currently be encoded, but often the constructions are painful. In this dissertation, I describe Dependent Haskell, which supports full dependent types via a backward-compatible extension to today\u27s Haskell. An important contribution of this work is an implementation, in GHC, of a portion of Dependent Haskell, with the rest to follow. The features I have implemented are already released, in GHC 8.0. This dissertation contains several practical examples of Dependent Haskell code, a full description of the differences between Dependent Haskell and today\u27s Haskell, a novel dependently typed lambda-calculus (called Pico) suitable for use as an intermediate language for compiling Dependent Haskell, and a type inference and elaboration algorithm, Bake, that translates Dependent Haskell to type-correct Pico. Full proofs of type safety of Pico and the soundness of Bake are included in the appendix

Synergistic effects of oncolytic reovirus and docetaxel chemotherapy in prostate cancer

Reovirus type 3 Dearing (T3D) has demonstrated oncolytic activity in vitro, in in vivo murine models and in early clinical trials. However the true potential of oncolytic viruses may only be realized fully in combination with other modalities such as chemotherapy, targeted therapy and radiotherapy. In this study, we examine the oncolytic activity of reovirus T3D and chemotherapeutic agents against human prostate cancer cell lines, with particular focus on the highly metastatic cell line PC3 and the chemotherapeutic agent docetaxel. Docetaxel is the standard of care for metastatic prostate cancer and acts by disrupting the normal process of microtubule assembly and disassembly. Reoviruses have been shown to associate with microtubules and may require this association for efficient viral replication

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

Platinum(II) polypyridyl complexes for visible light-driven hydrogen production from water

Thesis (Ph. D.)--University of Rochester. Dept. of Chemistry, 2009.This thesis employs Pt(II) terpyridyl and cyclometalated complexes as the chromophores to construct photoactive systems for hydrogen production from water. Several catalysts, including Pt nanoparticles, Pt(II) bi- and terpyridyl chloro complexes, and cobalt dimethylglyoximate complexes, were investigated to catalyze the hydrogen production reactions. Chapter 1, as an introduction part, describes the recent progress in photoinduced hydrogen production from water, including heterogeneous multiple-component systems, homogeneous multiple-component systems and an integrated approach to artificial photosynthesis for photoinduced hydrogen production. Chapter 2 studies a multiple-component system containing a platinum(II) terpyridyl acetylide chromophore, a sacrificial donor (TEOA), an electron relay (MV2+ and diquats) and colloidal platinum catalyst for photocatalytic generation of hydrogen from water. Hydrogen efficiency varies by using different Pt(II) photosensitizers and electron relays, as well as the different concentrations of each species. Chapter 3 discusses the real role of [Pt(ttpy)Cl]+ and Pt(dcbpy)Cl2 as the hydrogen production catalysts. TEM, EDAX and mecury tests show the Pt(II) chloro complexes are only the precursors to form colloidal platinum, which is the real catalyst for hydrogen generation. Chapter 4 and chapter 5 study a novel homogeneous system for photochemical hydrogen production using a cobalt(III) dimethylglyoximate complex as the hydrogen production catalyst and a Pt(II) terpyridyl acetylide complex as the photosensitizer. Cobalt(III) dimethylglyoximate has been used for hydrogen generation by electrochemical method. But very few examples have been reported in photochemical way. The variation of the photosensitizers and cobaloximes are also discussed, as well as the reaction mechanism. Chapter 6 discusses a novel terpyridyl cationic complex [Pt(TPPPB)Cl]Cl, containing a bulky terpyridyl ligand (1-terpyridyl-2,3,4,5,6-pentaphenyl-benzene (TPPPB)). The complex exhibits reversible vapochromic behavior upon exposure to methylene chloride vapors, changing color from red to green. The shift to higher energy in the emission maximum from 654 nm to 514 nm is the largest vapochromic shift (140 nm) yet reported. The [Pt(TPPPB)Cl]Cl complex exhibits high selectivity for certain volatile organic compounds (VOCs) including only methylene chloride, ethanol, ethyl acetate and acetonitrile. The crystal structures of both the green and red forms have been determined by single crystal X-ray diffraction. Chapter 7 describes the perspectives and future directions in this project. More potential efficient and stable cobalt complexes are designed and discussed. The platinum-cobalt supramolecular assemblies towards photochemical molecular devices show interesting properties for hydrogen production

Structural and luminescence properties of gold(I) benzimidazolethiolate complexes

Thesis (Ph. D.)--University of Rochester. Dept. of Chemistry, 2008.The research presented in this thesis has been written in two parts. The first involves the structural and luminescence properties of gold(I) benzimidazolethiolate complexes, discussed in chapters 1-3, and the second examines cyclometalated platinum(II) coordination compounds as potential chromophores for the photogeneration of hydrogen from water, discussed in chapter 4 - 7. Chapter 1 describes the underlying principles of gold---gold bonding interactions, as well as the effect thiolate donors have on the excited states. Chapters 2 and 3 build on the theories of gold---gold bonding. Chapter 2 examines the structural and photophysical properties of a new series of cationic and neutral Au(I) dinuclear compounds bridged by bis(diphenylphosphino)methane (dppm) and substituted benzimidazolethiolate (X-BIT) ligands, where X = H, Me, OMe, and Cl. The monocationic and neutral complexes have relatively short Au(I)---Au(I) separations ranging between 2.8597(3) and 2.9822(8) Å. The complexes exhibit excited state transitions assigned to IL, MC, LMCT, and LMMCT states. Three of the cationic complexes exhibit unusual luminescence tribochromism in the solid-state. Chapter 3 describes a high-nuclearity cluster composed of twelve Au(I) nuclei, four sulfur donors, and one Ag(I) ion. The cluster, [AgAu12(µ-H-BIT)8(µ-dppm)4][CF3CO2]4[Cl], has an eight-coordinate Ag(I) ion at the core that is bound to four Au(I) nuclei and four sulfur donors. It possesses exceptionally high extinction coefficients in the UV-vis spectrum and has emission maxima of 595, 503, and 464 nm in fluid CH2Cl2 solution at room temperature, frozen glass (77 K), and in the solid state at room temperature, respectively. Chapter 4 provides an introduction to the light-driven reduction of water using multiple component systems that contain a visible light sensitizer, an electron transfer mediator, a hydrogen evolving catalyst, and an electron source. Chapter 5 presents a new group of cyclometalated 6-phenyl-4-(p-R-phenyl)-2,2´-bipyridyl (C^N^N) Pt(II) thiophenolate complexes (R = CH3, COOCH3, and P(O)(OEt)2) with two charge-transfer bands in their electronic spectra tentatively assigned to a MLCT (λabs ~ 415 nm) transition and a mixed metal - ligand-to-ligand´ charge-transfer (MMLL´CT, λabs ~ 555 nm) transition, respectively. The MMLL´CT band is solvatochromic with absorption maxima in the range of 496 nm in MeOH to 590 nm in toluene. Chapter 6 is a detailed study on the photochemical properties of cyclometalated Pt(II) acetylide complexes, Pt(C^N^N-Ph-R)(CCPh) where R = Me, COOMe, and P(O)(OEt)2. The compounds undergo oxidative quenching by MV2+ and reductive quenching by several aryl amine donors with quenching rate constants on the order of the diffusion-controlled limit. When the complexes are employed as the sensitizer in multiple component system, approximately 1 turnover of H2 (TN vs mol chromophore) is produced per hour upon irradiation with λ > 410 nm, but only after at least a 2 h induction period. Chapter 7 examines the nature of several platinum (II) bipyridyl chloro complexes as the active catalyst for the photocatalytic production of hydrogen from water. Specifically, the question of whether Pt(II) complexes can serve as molecular catalysts for light-driven generation of H2 or whether they act solely as precursors for colloidal Pt as the actual catalyst