Echoes of the Past: Stylistic and Compositional Influences in the Music of Sergei Bortkiewicz

Despite the wide array of his compositional output in the first half of the twentieth century, the late Romantic composer, Sergei Bortkiewicz (1877-1952), remains relatively unknown. Bortkiewicz was born and raised near Kharkov, Ukraine, but considered himself Russian. Bortkiewicz studied in St. Petersburg and Leipzig, lived in Berlin, and later returned to Kharkov during World War I. During the Russian Revolution, he fled to Istanbul as a refugee. Eventually, he returned to Berlin and then to Vienna, where he would remain during World War II and for the rest of his life. Substantial modern-day recording efforts have rekindled interest in this composer who was faced with difficult circumstances throughout his life; however, a paucity of scholarly contributions exist. This project seeks to address some of these shortages. The first chapter provides historical perspective concerning Kharkov and Ukraine in the decades prior to the birth of Bortkiewicz. The second chapter presents a biography of Bortkiewicz against the backdrop of important events in world history. The third chapter contains commentary regarding Bortkiewicz’s compositional output which consisted primarily of works for the piano, but also included orchestral works, solo concerti, one opera, and several collections of songs. Unfortunately, some of these pieces have been lost as a result of World War II. The fourth chapter examines the compositional style of Sergei Bortkiewicz. Despite Bortkiewicz’s pro-Russian sentiments, some of his music appears to contain Ukrainian folk idioms. Other observations in this chapter supplement the work of Nils Franke regarding musical retrospection in Bortkiewicz’s works. These additional examples reaffirm harmonic and textural similarities and other stylistic connections in Bortkiewicz’s music. Ultimately, these similarities have pedagogical advantages notably through stylistic comparisons and might affect one’s approach to interpreting Bortkiewicz’s music

Light-Controlled Radical Polymerization: Mechanisms, Methods, and Applications

The use of light to mediate controlled radical polymerization has emerged as a powerful strategy for rational polymer synthesis and advanced materials fabrication. This review provides a comprehensive survey of photocontrolled, living radical polymerizations (photo-CRPs). From the perspective of mechanism, all known photo-CRPs are divided into either (1) intramolecular photochemical processes or (2) photoredox processes. Within these mechanistic regimes, a large number of methods are summarized and further classified into subcategories based on the specific reagents, catalysts, etc., involved. To provide a clear understanding of each subcategory, reaction mechanisms are discussed. In addition, applications of photo-CRP reported so far, which include surface fabrication, particle preparation, photoresponsive gel design, and continuous flow technology, are summarized. We hope this review will not only provide informative knowledge to researchers in this field but also stimulate new ideas and applications to further advance photocontrolled reactions.National Science Foundation (U.S.) (CHE-1334703

Visible-light-mediated, additive-free, and open-to-air controlled radical polymerization of acrylates and acrylamides

Oxygen tolerance in controlled radical polymerizations has been an active field of study in recent years. Herein, we report a photocontrolled, additive-free iniferter polymerization that operates in completely open vials utilizing the “polymerizing through oxygen” mechanism. Trithiocarbonates are directly activated with high intensity 450 nm light to produce narrowly dispersed (M[subscript w]/M[subscript n] = 1.1–1.6) polyacrylates and polyacrylamides. Living behavior is demonstrated through chain extension, block copolymer synthesis, and control over molecular weight through varying the monomer : iniferter ratio. A slight increase in induction period is observed for the open vial polymerization compared to the air-free reaction, but polymers with similar M[subscript n] and M[subscript w]/M[subscript n] values are produced after 30–60 minutes of irradiation. This system will provide a convenient platform for living additive manufacturing because of its fast reaction time, air tolerance, wide monomer scope, and lack of any additives beyond the monomer, iniferter, and DMSO solvent.National Science Foundation (U.S.) (CHE-1629358)National Science Foundation (U.S.). Materials Research Science and Engineering Centers (Program) (Award DMR 14-19807)National Institutes of Health (U.S.) (1F32GM126913-01A1

A novel mechanism of selectivity against AZT by the human mitochondrial DNA polymerase

Native nucleotides show a hyperbolic concentration dependence of the pre-steady-state rate of incorporation while maintaining concentration-independent amplitude due to fast, largely irreversible pyrophosphate release. The kinetics of 3′-azido-2′,3′-dideoxythymidine (AZT) incorporation exhibit an increase in amplitude and a decrease in rate as a function of nucleotide concentration, implying that pyrophosphate release must be slow so that nucleotide binding and incorporation are thermodynamically linked. Here we develop assays to measure pyrophosphate release and show that it is fast following incorporation of thymidine 5′-triphosphate (TTP). However, pyrophosphate release is slow (0.0009 s−1) after incorporation of AZT. Modeling of the complex kinetics resolves nucleotide binding (230 µM) and chemistry forward and reverse reactions, 0.38 and 0.22 s−1, respectively. This unique mechanism increases selectivity against AZT incorporation by allowing reversal of the reaction and release of substrate, thereby reducing kcat/Km (7 × 10−6 μ M−1 s−1). Other azido-nucleotides (AZG, AZC and AZA) and 8-oxo-7,8-dihydroguanosine-5′-triphosphate (8-oxo-dGTP) show this same phenomena

BRUSH-ARM STAR POLYMER IMAGING AGENTS AND USES THEREOF

Disclosed are methods, compositions, reagents, systems, and kits to prepare nitroxide-functionalized brush-arm star polymer organic radical contrast agent (BASP-ORCA) as well as compositions and uses thereof. Various embodiments show that BASP-ORCA display unprecedented per-nitrox-ide and per-molecule transverse relaxivities for organic radical contrast agents, exceptional stability, high water solubility, low in vitro and in vivo toxicity, and long blood compartment half-life. These materials have the potential to be adopted for tumor imaging using clinical high-field 1H MRI techniques

The PAS Domain-Containing Protein HeuR Regulates Heme Uptake in Campylobacter jejuni

Campylobacter jejuni is a leading cause of bacterially derived gastroenteritis. A previous mutant screen demonstrated that the heme uptake system (Chu) is required for full colonization of the chicken gastrointestinal tract. Subsequent work identified a PAS domain-containing regulator, termed HeuR, as being required for chicken colonization. Here we confirm that both the heme uptake system and HeuR are required for full chicken gastrointestinal tract colonization, with the hour mutant being particularly affected during competition with wild-type C. jejuni. Transcriptomic analysis identified the chu genes—and those encoding other iron uptake systems—as regulatory targets of HeuR. Purified HeuR bound the chuZA promoter region in electrophoretic mobility shift assays. Consistent with a role for HeuR in chu expression, heuR mutants were unable to efficiently use heme as a source of iron under iron-limiting conditions, and mutants exhibited decreased levels of cell-associated iron by mass spectrometry. Finally, we demonstrate that an heuR mutant of C. jejuni is resistant to hydrogen peroxide and that this resistance correlates to elevated levels of catalase activity. These results indicate that HeuR directly and positively regulates iron acquisition from heme and negatively impacts catalase activity by an as yet unidentified mechanism in C. jejuni

Drug-Loaded, Bivalent-Bottle-Brush Polymers by Graft-through ROMP

Graft through ring-opening metathesis polymerization (ROMP) using ruthenium N heterocyclic carbene catalysts has enabled the synthesis of bottle-brush polymers with unprecedented ease and control Here we report the first bivalent-brush polymers, these materials were prepared by graft through ROMP of drug-loaded poly(ethylene glycol) (PEG) based macromonomers (MMs) Anticancer drugs doxorubicin (DOX) and camptothecin (CT) were attached to a norbornene alkyne-PEG MM via a photocleavable linker ROMP of either or both drug loaded MMs generated brush homo and copolymers with low polydispersities and defined molecular weights. Release of free DOX and CT from these materials was initiated by exposure to 365 nm light All of the CT and DOX polymers were at least 10 fold more toxic to human cancer cells after photoinitiated drug release while a copolymer carrying both CT and DOX displayed 30-fold increased toxicity upon irradiation Graft through ROMP of drug loaded macromonomers provides a general method for the systematic study of structure function relationships for stimuli responsive polymers in biological systems

Tailoring the structure of polymer networks with iniferter-mediated photo-growth

Using dissipative particle dynamics (DPD), we developed a computational approach to capture the photo-controlled radical polymerization (“photo-growth”) of polymer gels containing trithiocarbonate (TTC) groups within the network strands. Using this model, we focused on a “primary gel” and illuminated the sample to activate the TTCs, which then interacted with monomer and cross-linker in the solution. At low TTC concentrations, gels composed of compatible monomers formed two distinct, spatially separated layers. Conversely, at high TTC concentration, gels formed from incompatible components displayed a well-intermixed structure. Hence, in the presence of light, variations in the TTC concentration provide a new approach for controllably tailoring the structure of polymer gels, and thereby tailoring the functionality of the network.National Science Foundation (U.S.). Designing Materials to Revolutionize and Engineer our Future (CHE-1334703

Universal Cyclic Topology in Polymer Networks

Polymer networks invariably possess topological defects: loops of different orders which have profound effects on network properties. Here, we demonstrate that all cyclic topologies are a universal function of a single dimensionless parameter characterizing the conditions for network formation. The theory is in excellent agreement with both experimental measurements of hydrogel loop fractions and Monte Carlo simulations without any fitting parameters. We demonstrate the superposition of the dilution effect and chain-length effect on loop formation. The one-to-one correspondence between the network topology and primary loop fraction demonstrates that the entire network topology is characterized by measurement of just primary loops, a single chain topological feature. Different cyclic defects cannot vary independently, in contrast to the intuition that the densities of all topological species are freely adjustable. Quantifying these defects facilitates studying the correlations between the topology and properties of polymer networks, providing a key step in overcoming an outstanding challenge in polymer physics.National Science Foundation (U.S.) (Award DMR-1253306

EPR Study of Spin Labeled Brush Polymers in Organic Solvents

Spin-labeled polylactide brush polymers were synthesized via ring-opening metathesis polymerization (ROMP), and nitroxide radicals were incorporated at three different locations of brush polymers: the end and the middle of the backbone, and the end of the side chains (periphery). Electron paramagnetic resonance (EPR) was used to quantitatively probe the macromolecular structure of brush polymers in dilute solutions. The peripheral spin-labels showed significantly higher mobility than the backbone labels, and in dimethylsulfoxide (DMSO), the backbone end labels were shown to be more mobile than the middle labels. Reduction of the nitroxide labels by a polymeric reductant revealed location-dependent reactivity of the nitroxide labels: peripheral nitroxides were much more reactive than the backbone nitroxides. In contrast, almost no difference was observed when a small molecule reductant was used. These results reveal that the dense side chains of brush polymers significantly reduce the interaction of the backbone region with external macromolecules, but allow free diffusion of small molecules