Total Synthesis of Strempeliopidine and Non-Natural Stereoisomers through a Convergent Petasis Borono-Mannich Reaction.

Strempeliopidine is a member of the monoterpenoid bisindole alkaloid family, a class of natural products that have been shown to elicit an array of biological responses including modulating protein-protein interactions in human cancer cells. Our synthesis of strempeliopidine leverages palladium-catalyzed decarboxylative asymmetric allylic alkylations to install the requisite all-carbon quaternary centers found in each of the two monomeric natural products, aspidospermidine and eburnamine. Initial studies employing Suzuki-Miyaura cross-coupling followed by diastereoselective hydrogenation provided evidence for a structural reassignment of the natural product.

Development of a Non-Directed Petasis-Type Reaction by an Aromaticity-Disrupting Strategy.

The Petasis-type reaction, which couples an imine and boronic acid, is an important tool for C-C bond formation in organic synthesis. However, the generality of this transformation has been limited by the requirement for a directing heteroatom to enable reactivity. Herein, we report the development of a non-directed Petasis-type reaction that allows for the coupling of trifluoroborate salts with α-hydroxyindoles.

What is a Cross-Coupling? An Argument for a Universal Definition.

Despite amazing advances in cross-coupling technologies over the past several decades, there is not a consistent definition of what a cross-coupling reaction is. Often, definitions rely on comparison to "traditional" palladium-catalyzed cross-couplings pioneered in the 1970s by chemists such as Suzuki, Negishi, and Heck. While these reactions provide a basis for a cross-coupling definition, they do not define this type of transformation, originally described by Linstead almost 20 years prior.

Investigations into mechanism and origin of regioselectivity in the metallaphotoredox-catalyzed α-arylation of -alkylbenzamides.

A mechanistic study on the α-arylation of -alkylbenzamides catalyzed by a dual nickel/photoredox system using aryl bromides is reported herein. This study elucidates the origins of site-selectivity of the transformation, which is controlled by the generation of a hydrogen atom transfer (HAT) agent by a photocatalyst and bromide ions in solution. Tetrabutylammonium bromide was identified as a crucial additive and source of a potent HAT agent, which led to increases in yields and a lowering of the stoichiometries of the aryl bromide coupling partner.

Catalytic reduction of aryl trialkylammonium salts to aryl silanes and arenes.

A new approach for the reduction of aryl ammonium salts to arenes or aryl silanes using nickel catalysis is reported. This method displays excellent ligand-controlled selectivity based on the N-heterocyclic carbene (NHC) ligand employed. Utilizing a large NHC in non-polar solvents generates aryl silanes, while small NHCs in polar solvents promote reduction to arenes.

The Radiation Oncology Mentorship Initiative: Analysis of a Formal Mentoring Initiative for Medical Students Interested in Radiation Oncology.

The importance of mentorship in medicine and its impact on academic and professional development has been widely studied. However, mentorship for medical students in the field of radiation oncology is limited. Our radiation oncology department developed a formal medical student mentorship program in 2004.

Impact of patient demographics, tumor characteristics, and treatment type on treatment delay throughout breast cancer care at a diverse academic medical center.

Purpose And Objective: The aim of this study was to examine the impact of patient demographics, tumor characteristics, and treatment type on time to treatment (TTT) in patients with breast cancer treated at a safety net medical center with a diverse patient population.

Patients And Methods: A total of 1,130 patients were diagnosed and treated for breast cancer between 2004 and 2014 at our institution. We retrospectively collected data on patient age at diagnosis, race/ethnicity, primary language spoken, marital status, insurance coverage, American Joint Committee on Cancer (AJCC) stage, hormone receptor status, and treatment dates.

CONSTRUCTION OF SCALAR AND VECTOR FINITE ELEMENT FAMILIES ON POLYGONAL AND POLYHEDRAL MESHES.

We combine theoretical results from polytope domain meshing, generalized barycentric coordinates, and finite element exterior calculus to construct scalar- and vector-valued basis functions for conforming finite element methods on generic convex polytope meshes in dimensions 2 and 3. Our construction recovers well-known bases for the lowest order Nédélec, Raviart-Thomas, and Brezzi-Douglas-Marini elements on simplicial meshes and generalizes the notion of Whitney forms to non-simplicial convex polygons and polyhedra. We show that our basis functions lie in the correct function space with regards to global continuity and that they reproduce the requisite polynomial differential forms described by finite element exterior calculus.

Accelerated Molecular Mechanical and Solvation Energetics on Multicore CPUs and Manycore GPUs.

Motivation: Despite several reported acceleration successes of programmable GPUs (Graphics Processing Units) for molecular modeling and simulation tools, the general focus has been on fast computation with small molecules. This was primarily due to the limited memory size on the GPU. Moreover simultaneous use of CPU and GPU cores for a single kernel execution - a necessity for achieving high parallelism - has also not been fully considered.

Microwave-assisted synthesis of 3-aminobenzo[b]thiophene scaffolds for the preparation of kinase inhibitors.

Microwave irradiation of 2-halobenzonitriles and methyl thioglycolate in the presence of triethylamine in DMSO at 130 °C provides rapid access to 3-aminobenzo[b]thiophenes in 58-96% yield. This transformation has been applied in the synthesis of the thieno[2,3-b]pyridine core motif of LIMK1 inhibitors, the benzo[4,5]thieno[3,2-e][1,4]diazepin-5(2H)-one scaffold of MK2 inhibitors and a benzo[4,5]thieno[3,2-d]pyrimidin-4-one inhibitor of the PIM kinases.

Effect of Patient Demographic Characteristics and Radiation Timing on PSA Reduction in Patients Treated With Definitive Radiation Therapy for Prostate Cancer.

Introduction: The purpose of this study was to assess how demographic characteristics and temporal factors including time to treatment (TTT) and elapsed time of treatment (ETT) affect prostate-specific antigen (PSA) levels during and after radiation treatment for low- and intermediate-risk prostate cancer.

Patients And Methods: A retrospective review of 1584 patients was conducted on patients diagnosed with prostate cancer between 2005 and 2013, from which 147 patients were found to have completed definitive external beam radiation therapy (EBRT) monotherapy. Demographic data, TTT (days between diagnosis and EBRT start date), ETT (days between EBRT start and stop date), and Gleason score were collected on these patients and analysis of variance was performed to analyze the relationship of these factors with PSA changes.

Medical student mentorship in radiation oncology at a single academic institution: A 10-year analysis.

Purpose: Mentorship has been identified by medical students, residents, and faculty as an important component of specialty selection and research productivity in radiation oncology. This study quantitatively analyzes the impact of a mentorship program in radiation oncology targeted to medical students at our institution.

Methods And Materials: We performed a retrospective review of 76 current or former medical students who were mentored by faculty radiation oncologists at our institution between 2004 and 2013.

QUADRATIC SERENDIPITY FINITE ELEMENTS ON POLYGONS USING GENERALIZED BARYCENTRIC COORDINATES.

We introduce a finite element construction for use on the class of convex, planar polygons and show it obtains a quadratic error convergence estimate. On a convex -gon, our construction produces 2 basis functions, associated in a Lagrange-like fashion to each vertex and each edge midpoint, by transforming and combining a set of ( + 1)/2 basis functions known to obtain quadratic convergence. The technique broadens the scope of the so-called 'serendipity' elements, previously studied only for quadrilateral and regular hexahedral meshes, by employing the theory of generalized barycentric coordinates.

Patient demographic characteristics and disease stage as drivers of disparities in mortality in prostate cancer patients who receive care at a safety net academic medical center.

Introduction: The purpose of this study was to examine the effect of patient demographic characteristics and tumor stage at diagnosis on mortality in prostate cancer patients who receive care at a safety net, academic medical center with a diverse patient population.

Patients And Methods: Eight hundred sixty-nine patients were diagnosed with prostate cancer at our institution between August 2004 and October 2011. Patient demographic characteristics were determined as follows: race and/or ethnicity, primary language, insurance type, age at diagnosis, marital status, income (determined by zip code), and American Joint Committee on Cancer (AJCC) tumor stage.

Interpolation Error Estimates for Mean Value Coordinates over Convex Polygons.

In a similar fashion to estimates shown for Harmonic, Wachspress, and Sibson coordinates in [Gillette et al., AiCM, to appear], we prove interpolation error estimates for the mean value coordinates on convex polygons suitable for standard finite element analysis. Our analysis is based on providing a uniform bound on the gradient of the mean value functions for all convex polygons of diameter one satisfying certain simple geometric restrictions.

Error Estimates for Generalized Barycentric Interpolation.

We prove the optimal convergence estimate for first order interpolants used in finite element methods based on three major approaches for generalizing barycentric interpolation functions to convex planar polygonal domains. The Wachspress approach explicitly constructs rational functions, the Sibson approach uses Voronoi diagrams on the vertices of the polygon to define the functions, and the Harmonic approach defines the functions as the solution of a PDE. We show that given certain conditions on the geometry of the polygon, each of these constructions can obtain the optimal convergence estimate.

AN EFFICIENT HIGHER-ORDER FAST MULTIPOLE BOUNDARY ELEMENT SOLUTION FOR POISSON-BOLTZMANN BASED MOLECULAR ELECTROSTATICS.

In order to compute polarization energy of biomolecules, we describe a boundary element approach to solving the linearized Poisson-Boltzmann equation. Our approach combines several important features including the derivative boundary formulation of the problem and a smooth approximation of the molecular surface based on the algebraic spline molecular surface. State of the art software for numerical linear algebra and the kernel independent fast multipole method is used for both simplicity and efficiency of our implementation.