FUNCTIONAL PHOSPHORYLCHOLINE POLYMERS: PRODRUGS AND BIOMATERIALS

This thesis describes the synthesis and applications of multifunctional, hydrophilic polymers consisting of a methacrylate backbone and zwitterionic phosphorylcholine (PC) pendent groups, prepared by free radical polymerization of the zwitterionic monomer, 2-methacryloyloxyethyl phosphorylcholine (MPC). Advances in polymer chemistry, applied to PC polymers, allowed for the preparation of well-defined structures with controlled molecular weight, narrow polydispersity, and facile incorporation of functional comonomers, giving breadth to the range of materials accessible for different applications. Built-in functionality included fluorophores and reactive groups for post-polymerization transformations, such as drug conjugation or cross-linking. The ability to form well-defined structures based on the polyMPC backbone is attractive to the fields of polymer therapeutics and biomaterials, due to the high level of biocompatibility associated with PC polymers. The work presented here examines methacrylate-based PC polymers as (1) polymer-protein conjugates, (2) polymer prodrugs, and (3) polymeric hydrogels. In Chapter 2, synthetic advances center on tailoring chain-end functionality and utilizing such structures as polymer-protein conjugates. The design of new ATRP initiators containing specific functionality allowed for polymer conjugation to lysozyme as a model protein. PolyMPC-lysozyme conjugates retained their native enzymatic activity, and pharmacokinetic profiles of the conjugates in mice revealed increased circulation half-life compared to lysozyme alone. Chapter 3 describes PC-polymers that enhance intravenous drug delivery of potent chemotherapeutic agents. Functionalized methacrylates for copolymerization with MPC were designed, such that multiple copies of a drug can be loaded onto the polymer backbone, affording highly water soluble polymer prodrugs with unprecedented drug loading (\u3e30 wt %). PolyMPC prodrugs of camptothecin (CPT) and doxorubicin (DOX) demonstrated cytotoxicity against several human cancer cell lines in vitro. PolyMPC-DOX prodrugs displayed prolonged circulation half-lives, and reduced uptake in healthy tissue, enhanced accumulation in tumors, and superior treatment efficacy in 4T1-tumor bearing mice. Chapter 4 highlights multifunctional polyMPC as a precursor to new phosphorylcholine hydrogels. Two cell lines, live mouse skeletal muscle myoblasts (C2C12) and human ovarian cancer (SKOV3) cells, were observed to specifically attach, spread, and proliferate on PC-hydrogels containing the GRGDS peptide sequence, with a notable dependence on peptide concentration. The remarkable hydrophilicity and biocompatibility attributed to polyMPC combined with facile gelation conditions affords a platform of new bio-cooperative materials suitable for cell studies

Gibbs' paradox and black-hole entropy

In statistical mechanics Gibbs' paradox is avoided if the particles of a gas are assumed to be indistinguishable. The resulting entropy then agrees with the empirically tested thermodynamic entropy up to a term proportional to the logarithm of the particle number. We discuss here how analogous situations arise in the statistical foundation of black-hole entropy. Depending on the underlying approach to quantum gravity, the fundamental objects to be counted have to be assumed indistinguishable or not in order to arrive at the Bekenstein--Hawking entropy. We also show that the logarithmic corrections to this entropy, including their signs, can be understood along the lines of standard statistical mechanics. We illustrate the general concepts within the area quantization model of Bekenstein and Mukhanov.Comment: Contribution to Mashhoon festschrift, 13 pages, 4 figure

Illicit substance use among university students from seven European countries: A comparison of personal and perceived peer use and attitudes towards illicit substance use

Objective: To compare European students' personal use and approval of illicit substance use with their perceptions of peer behaviours and attitudes, and investigate whether perceptions of peer norms are associated with personal use of illicit substances and attitudes. Method: This study used baseline data fromthe Social Norms Intervention for the prevention of Polydrug usE (SNIPE) project involving 4482 students from seven European countries in 2012. Students completed an online surveywhich included questions on personal and perceived peer illicit substance use and personal and perceived peer attitude towards illicit substances. Results: 8.3% of students reported having used illicit substances at least once in their life. 49.7% of students perceived that the majority of their peers have used illicit substances more frequently than themselves. The perception was significantly associated with higher odds for personal illicit substance use (OR: 1.97, 95% CI: 1.53–2.54). The perception that the majority of peers approve illicit substance use was significantly associated with higher odds for personal approval of illicit substance use (OR: 3.47, 95% CI: 2.73–4.41). Conclusion: Students commonly perceived that their peers used illicit subtances more often than themselves. We found an association between the perceived peer norms/attitudes and reported individual behaviour/ attitudes

Many body physics from a quantum information perspective

The quantum information approach to many body physics has been very successful in giving new insight and novel numerical methods. In these lecture notes we take a vertical view of the subject, starting from general concepts and at each step delving into applications or consequences of a particular topic. We first review some general quantum information concepts like entanglement and entanglement measures, which leads us to entanglement area laws. We then continue with one of the most famous examples of area-law abiding states: matrix product states, and tensor product states in general. Of these, we choose one example (classical superposition states) to introduce recent developments on a novel quantum many body approach: quantum kinetic Ising models. We conclude with a brief outlook of the field.Comment: Lectures from the Les Houches School on "Modern theories of correlated electron systems". Improved version new references adde

Effective Functional Form of Regge Trajectories

We present theoretical arguments and strong phenomenological evidence that hadronic Regge trajectories are essentially nonlinear and can be well approximated, for phenomenological purposes, by a specific square-root form.Comment: 29 pages, LaTeX. Published versio

Magnetic Fields in the Milky Way

This chapter presents a review of observational studies to determine the magnetic field in the Milky Way, both in the disk and in the halo, focused on recent developments and on magnetic fields in the diffuse interstellar medium. I discuss some terminology which is confusingly or inconsistently used and try to summarize current status of our knowledge on magnetic field configurations and strengths in the Milky Way. Although many open questions still exist, more and more conclusions can be drawn on the large-scale and small-scale components of the Galactic magnetic field. The chapter is concluded with a brief outlook to observational projects in the near future.Comment: 22 pages, 5 figures, to appear in "Magnetic Fields in Diffuse Media", eds. E.M. de Gouveia Dal Pino and A. Lazaria

PSR J1119-6127 and the X-ray Emission from High Magnetic Field Radio Pulsars

The existence of radio pulsars having inferred magnetic elds in the magnetar regime suggests that possible transition objects could be found in the radio pulsar population. The discovery of such an object would contribute greatly to our understanding of neutron star physics. Here we report on unusual X-ray emission detected from the radio pulsar PSR J1119-6127 using XMM-Newton. The pulsar has a characteristic age of 1,700 yrs and inferred surface dipole magnetic eld strength of 4.1x10^13 G. In the 0.5-2.0 keV range, the emission shows a single, narrow pulse with an unusually high pulsed fraction of ~70%. No pulsations are detected in the 2.0-10.0 keV range, where we derive an upper limit at the 99% level for the pulsed fraction of 28%. The pulsed emission is well described by a thermal blackbody model with a high temperature of 2.4x10^6 K. While no unambiguous signature of magnetar-like emission has been found in high-magnetic-eld radio pulsars, the X-ray characteristics of PSR J1119-6127 require alternate models from those of conventional thermal emission from neutron stars. In addition, PSR J1119-6127 is now the radio pulsar with the smallest characteristic age from which thermal X-ray emission has been detected

Formaldehyde production from isoprene oxidation across NOx regimes

The chemical link between isoprene and formaldehyde (HCHO) is a strong, nonlinear function of NOx (i.e., NO + NO2). This relationship is a linchpin for top-down isoprene emission inventory verification from orbital HCHO column observations. It is also a benchmark for overall photochemical mechanism performance with regard to VOC oxidation. Using a comprehensive suite of airborne in situ observations over the southeast US, we quantify HCHO production across the urban&ndash;rural spectrum. Analysis of isoprene and its major first-generation oxidation products allows us to define both a "prompt" yield of HCHO (molecules of HCHO produced per molecule of freshly emitted isoprene) and the background HCHO mixing ratio (from oxidation of longer-lived hydrocarbons). Over the range of observed NOx&nbsp;values (roughly 0.1&ndash;2 ppbv), the prompt yield increases by a factor of 3 (from 0.3 to 0.9 ppbv ppbv-1), while background HCHO increases by a factor of 2 (from 1.6 to 3.3 ppbv). We apply the same method to evaluate the performance of both a global chemical transport model (AM3) and a measurement-constrained 0-D steady-state box model. Both models reproduce the NOx&nbsp;dependence of the prompt HCHO yield, illustrating that models with updated isoprene oxidation mechanisms can adequately capture the link between HCHO and recent isoprene emissions. On the other hand, both models underestimate background HCHO mixing ratios, suggesting missing HCHO precursors, inadequate representation of later-generation isoprene degradation and/or underestimated hydroxyl radical concentrations. Detailed process rates from the box model simulation demonstrate a 3-fold increase in HCHO production across the range of observed NOx&nbsp;values, driven by a 100 % increase in OH and a 40 % increase in branching of organic peroxy radical reactions to produce HCHO.</p

Reactive nitrogen partitioning and its relationship to winter ozone events in Utah

High wintertime ozone levels have been observed in the Uintah Basin, Utah, a sparsely populated rural region with intensive oil and gas operations. The reactive nitrogen budget plays an important role in tropospheric ozone formation. Measurements were taken during three field campaigns in the winters of 2012, 2013 and 2014, which experienced varying climatic conditions. Average concentrations of ozone and total reactive nitrogen were observed to be 2.5 times higher in 2013 than 2012, with 2014 an intermediate year in most respects. However, photochemically active NOx (NO + NO2) remained remarkably similar all three years. Nitric acid comprised roughly half of NOz ( ≡  NOy − NOx) in 2013, with nighttime nitric acid formation through heterogeneous uptake of N2O5 contributing approximately 6 times more than daytime formation. In 2012, N2O5 and ClNO2 were larger components of NOz relative to HNO3. The nighttime N2O5 lifetime between the high-ozone year 2013 and the low-ozone year 2012 is lower by a factor of 2.6, and much of this is due to higher aerosol surface area in the high-ozone year of 2013. A box-model simulation supports the importance of nighttime chemistry on the reactive nitrogen budget, showing a large sensitivity of NOx and ozone concentrations to nighttime processes