DESIGN AND SYNTHESIS OF POLYMER - MAGNETIC NANOPARTICLE COMPOSITES FOR USE IN BIOMEDICAL APPLICATIONS

The future of diagnostics and therapeutic drugs in biomedicine is nanoparticles. These nanoparticles come in many different shapes, sizes, and combination of materials. Magnetic nanoparticles have been studied for many years for use in biomedicine, not only for their high surface area, but also because of its unique magnetic properties. They can magnetically interact with their environment, be guided to a specific location, and manipulated to release energy in the form of heat. To ensure that these magnetic nanoparticles survive in the circulatory system, they must be modified with materials to make them colloidally stable in water and shield them from the body\u27s immune response to foreign objects. The purpose of this project is to design and synthesize a ligand for the modification of iron oxide nanoparticles with three important characteristics: 1) water-dispersable, 2) biologically stable, and 3) functional surface. This was accomplished by synthesizing specialized heterobifunctional polyethylene oxide (PEO) that has a catechol on one end to bind strongly to iron oxide nanoparticles and an alkyne on the other end to provide further functionality. This design allows for easy customization of the particles surface, using click chemistry, with targeting and fluorescent moieties for any desired application. The work reported discusses the techniques used for synthesizing a variety of heterobifunctional PEO via anionic ring opening polymerization of ethylene oxide and subsequent end group modifications that ultimately led to the design of a universal ligand for iron oxide nanoparticles, with improved stability in biological environments, that can be used in many biomedical applications. These universal magnetic nanoparticles were modified with different fluorescent dyes for imaging biofilms, carbohydrates for targeting bacteria, and radiotracers for multifunctional diagnostic probes to demonstrate the versatility of this surface

Maximizing the benefits and minimizing the risks of intervention programs to address micronutrient malnutrition: symposium report.

Interventions to address micronutrient deficiencies have large potential to reduce the related disease and economic burden. However, the potential risks of excessive micronutrient intakes are often not well determined. During the Global Summit on Food Fortification, 9-11 September 2015, in Arusha, a symposium was organized on micronutrient risk-benefit assessments. Using case studies on folic acid, iodine and vitamin A, the presenters discussed how to maximize the benefits and minimize the risks of intervention programs to address micronutrient malnutrition. Pre-implementation assessment of dietary intake, and/or biomarkers of micronutrient exposure, status and morbidity/mortality is critical in identifying the population segments at risk of inadequate and excessive intake. Dietary intake models allow to predict the effect of micronutrient interventions and their combinations, e.g. fortified food and supplements, on the proportion of the population with intakes below adequate and above safe thresholds. Continuous monitoring of micronutrient intake and biomarkers is critical to identify whether the target population is actually reached, whether subgroups receive excessive amounts, and inform program adjustments. However, the relation between regular high intake and adverse health consequences is neither well understood for many micronutrients, nor do biomarkers exist that can detect them. More accurate and reliable biomarkers predictive of micronutrient exposure, status and function are needed to ensure effective and safe intake ranges for vulnerable population groups such as young children and pregnant women. Modelling tools that integrate information on program coverage, dietary intake distribution and biomarkers will further enable program makers to design effective, efficient and safe programs

Compliant Surgical Adhesive

Surgical adhesives that include a blend of two different thermoreversible gelling polymers and a crosslinking agent are described. The first thermoreversible gelling polymer is partially or fully acrylated and the second thermoreversible gelling polymer includes dual functionality including acrylate functionality and amine-reactive functionality. The adhesives can provide gelling and covalent crosslinking within the polymers of the adhesive as well as crosslinking with surrounding tissue

Magnetic Field Evolution in Merging Clusters of Galaxies

We present initial results from the first 3-dimensional numerical magnetohydrodynamical (MHD) simulations of magnetic field evolution in merging clusters of galaxies. Within the framework of idealized initial conditions similar to our previous work, we look at the gasdynamics and the magnetic field evolution during a major merger event in order to examine the suggestion that shocks and turbulence generated during a cluster/subcluster merger can produce magnetic field amplification and relativistic particle acceleration and, as such, may play a role in the formation and evolution of cluster-wide radio halos. The ICM, as represented by the equations of ideal MHD, is evolved self-consistently within a changing gravitational potential defined largely by the collisionless dark matter component represented by an N-body particle distribution. The MHD equations are solved by the Eulerian, finite-difference code, ZEUS. The particles are evolved by a standard particle-mesh (PM) code. We find significant evolution of the magnetic field structure and strength during two distinct epochs of the merger evolution.Comment: 21 pages, 7 figures, Figure 2 is color postscript. Accepted for publication in Ap

The influence of mixing on the stratospheric age of air changes in the 21st century

Climate models consistently predict an acceleration of the Brewer–Dobson circulation (BDC) due to climate change in the 21st century. However, the strength of this acceleration varies considerably among individual models, which constitutes a notable source of uncertainty for future climate projections. To shed more light upon the magnitude of this uncertainty and on its causes, we analyse the stratospheric mean age of air (AoA) of 10 climate projection simulations from the Chemistry-Climate Model Initiative phase 1 (CCMI-I), covering the period between 1960 and 2100. In agreement with previous multi-model studies, we find a large model spread in the magnitude of the AoA trend over the simulation period. Differences between future and past AoA are found to be predominantly due to differences in mixing (reduced aging by mixing and recirculation) rather than differences in residual mean transport. We furthermore analyse the mixing efficiency, a measure of the relative strength of mixing for given residual mean transport, which was previously hypothesised to be a model constant. Here, the mixing efficiency is found to vary not only across models, but also over time in all models. Changes in mixing efficiency are shown to be closely related to changes in AoA and quantified to roughly contribute 10 % to the long-term AoA decrease over the 21st century. Additionally, mixing efficiency variations are shown to considerably enhance model spread in AoA changes. To understand these mixing efficiency variations, we also present a consistent dynamical framework based on diffusive closure, which highlights the role of basic state potential vorticity gradients in controlling mixing efficiency and therefore aging by mixing.Helmholtz Association | Ref. VH-NG-1014Australian Research Council’s Centre of Excellence for Climate System Science | Ref. CE110001028Australian Government’s National Computational Merit Allocation Scheme | Ref. FUERZAS 4012Ministerio de Ciencia e Innovación | Ref. CGL2015-71575-PNew Zealand Royal Society Marsden Fund | Ref. 12-NIW-00

Identification of Driver and Passenger Mutations of FLT3 by High-Throughput DNA Sequence Analysis and Functional Assessment of Candidate Alleles

SummaryMutations in the juxtamembrane and kinase domains of FLT3 are common in AML, but it is not known whether alterations outside these regions contribute to leukemogenesis. We used a high-throughput platform to interrogate the entire FLT3 coding sequence in AML patients without known FLT3 mutations and experimentally tested the consequences of each candidate leukemogenic allele. This approach identified gain-of-function mutations that activated downstream signaling and conferred sensitivity to FLT3 inhibition and alleles that were not associated with kinase activation, including mutations in the catalytic domain. These findings support the concept that acquired mutations in cancer may not contribute to malignant transformation and underscore the importance of functional studies to distinguish “driver” mutations underlying tumorigenesis from biologically neutral “passenger” alterations

The Influence of Mixing on Stratospheric Age of Air Changes in the 21st Century

Climate models consistently predict an acceleration of the BrewerDobson circulation (BDC) due to climate change in the 21st century. However, the strength of this acceleration varies considerably among individual models, which constitutes a notable source of uncertainty for future climate projections. To shed more light upon the magnitude of this uncertainty and on its causes, we analyse the stratospheric mean age of air (AoA) of 10 climate projection simulations from the Chemistry-Climate Model Initiative phase 1 (CCMI-I), covering the period between 1960 and 2100. In agreement with previous multi-model studies, we find a large model spread in the magnitude of the AoA trend over the simulation period. Differences between future and past AoA are found to be predominantly due to differences in mixing (reduced aging by mixing and recirculation) rather than differences in residual mean transport. We furthermore analyse the mixing efficiency, a measure of the relative strength of mixing for given residual mean transport, which was previously hypothesised to be a model constant. Here, the mixing efficiency is found to vary not only across models, but also over time in all models. Changes in mixing efficiency are shown to be closely related to changes in AoA and quantified to roughly contribute 10 % to the long-term AoA decrease over the 21st century. Additionally, mixing efficiency variations are shown to considerably enhance model spread in AoA changes. To understand these mixing efficiency variations, we also present a consistent dynamical framework based on diffusive closure, which highlights the role of basic state potential vorticity gradients in controlling mixing efficiency and therefore aging by mixing

Quantum state preparation and macroscopic entanglement in gravitational-wave detectors

Long-baseline laser-interferometer gravitational-wave detectors are operating at a factor of 10 (in amplitude) above the standard quantum limit (SQL) within a broad frequency band. Such a low classical noise budget has already allowed the creation of a controlled 2.7 kg macroscopic oscillator with an effective eigenfrequency of 150 Hz and an occupation number of 200. This result, along with the prospect for further improvements, heralds the new possibility of experimentally probing macroscopic quantum mechanics (MQM) - quantum mechanical behavior of objects in the realm of everyday experience - using gravitational-wave detectors. In this paper, we provide the mathematical foundation for the first step of a MQM experiment: the preparation of a macroscopic test mass into a nearly minimum-Heisenberg-limited Gaussian quantum state, which is possible if the interferometer's classical noise beats the SQL in a broad frequency band. Our formalism, based on Wiener filtering, allows a straightforward conversion from the classical noise budget of a laser interferometer, in terms of noise spectra, into the strategy for quantum state preparation, and the quality of the prepared state. Using this formalism, we consider how Gaussian entanglement can be built among two macroscopic test masses, and the performance of the planned Advanced LIGO interferometers in quantum-state preparation

A Search for Dark Higgs Bosons

Recent astrophysical and terrestrial experiments have motivated the proposal of a dark sector with GeV-scale gauge boson force carriers and new Higgs bosons. We present a search for a dark Higgs boson using 516 fb-1 of data collected with the BABAR detector. We do not observe a significant signal and we set 90% confidence level upper limits on the product of the Standard Model-dark sector mixing angle and the dark sector coupling constant.Comment: 7 pages, 5 postscript figures, published version with improved plots for b/w printin

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO