Synthesis, Biofunctionalization, and Application of Magnetic Nanomaterials

Since their inception in the late 1970\u27s magnetic nanomaterials have sparked heavy research into their use in the biomedical field. Their unique magnetic properties allow the magnetic particles to be the base for a large array of expiremental medical techniques, from treatments of disease, diagnostic tests, imaging aids, and more. In this manuscript, each stage starting from novel particle synthesis, functionalization with bioactive molecules, and innovative application is explored, specifically using the techniques magnetically mediated energy delivery, magnetophoresis, magnetic resonance imaging. The reproducible synthesis of nanomaterials is necessary if any further engineering application is going to be done. Using a novel extended LaMer approach where a precursor solution is consistently added to a reaction vessel allows for the linear volume growth of nanoparticles. This technique was originally used for the synthesis of magnetite (a simple ferrite) to control the volume of the particle indefinitely. Transferring it to a nonstoichiometric cobalt ferrite, it is shown that a linear volume growth is achieved up to 20nm. Secondary functionality of the magnetic particles has really opened up the application to sensing, selective treatment, and functional imaging. Surface modification with a bacterial strain discriminatory glycan allows for strain selective treatment of bacterial infection. Heparin functional particles show high pharmacokinetic activity for the treatment of neointimal hyperplasia due to high surface area to volume ratios. Gadolinium coated particles have distance dependent effects on the MRI relaxation rate of water, which may prove useful in functional imaging. Each of these complexes shows promise as a new way to treat or image malady. Although a small part in the large picture in developing a new generation of medicine, this research lays the foundation for each of these possible treatments. Be it the eradication of bacterial infection or the non-toxic prevention of restenosis, novel multifunctional nanomaterials such as the ones discussed in this manuscript, will be heavily relied on in the future of medicine

Ab initio RAFT emulsion polymerization mediated by small cationic RAFT agents to form polymers with low molar mass dispersity

We report on low molar mass cationic RAFT agents that provide predictable molar mass and low molar mass dispersities (Đm) in ab initio emulsion polymerization. Thus RAFT emulsion polymerization of styrene in the presence of the protonated RAFT agent, ((((cyanomethyl)thio)carbonothioyl)(methyl)amino)pyridin-1-ium toluenesulfonate (4), and the analogous methyl-quaternized RAFT agents, 4-((((cyanomethyl)thio)carbonothioyl)(methyl)amino)-1-methylpyridin-1-ium dodecyl sulfate (6), provide low dispersity polystyrene with Đm 1.2–1.4 for Mn ∼ 20 000. We postulate that the success of ab initio emulsion polymerization with 4 is due to the hydrophilicity of the pyridinium group, which is such that the water soluble RAFT agent partitions predominantly into the aqueous phase under the conditions of the experiment and that 4 provides little retardation. With 6, when the counterion is dodecyl sulfate, we can achieve “surfactant-free” RAFT emulsion polymerization to provide a low Đm polystyrene. However, the RAFT end-group is lost on isolation of the polymer. Preliminary results show that this class of RAFT agent is broadly applicable in ab initio emulsion polymerization of other more-activated monomers (e.g., butyl acrylate, butyl methacrylate). Furthermore, cyanomethyl(pyridin-4-yl)carbamodithioate (3, the RAFT agent in neutral form) provides molar mass control and Đm < 1.8 in ab initio emulsion polymerization of less activated monomers, specifically, the vinyl esters, vinyl acetate and vinyl benzoate.Published onlin

Writing in Britain and Ireland, c. 400 to c. 800

No abstract available

Use of ceragenins to create novel biofouling resistant water-treatment membranes.

Scoping studies have demonstrated that ceragenins, when linked to water-treatment membranes have the potential to create biofouling resistant water-treatment membranes. Ceragenins are synthetically produced molecules that mimic antimicrobial peptides. Evidence includes measurements of CSA-13 prohibiting the growth of and killing planktonic Pseudomonas fluorescens. In addition, imaging of biofilms that were in contact of a ceragenin showed more dead cells relative to live cells than in a biofilm that had not been treated with a ceragenin. This work has demonstrated that ceragenins can be attached to polyamide reverse osmosis (RO) membranes, though work needs to improve the uniformity of the attachment. Finally, methods have been developed to use hyperspectral imaging with multivariate curve resolution to view ceragenins attached to the RO membrane. Future work will be conducted to better attach the ceragenin to the RO membranes and more completely test the biocidal effectiveness of the ceragenins on the membranes

Maroon Archaeology Beyond the Americas: A View From Kenya

Archaeological research on Maroons—that is, runaway slaves—has been largely confined to the Americas. This essay advocates a more global approach. It specifically uses two runaway slave communities in 19th-century coastal Kenya to rethink prominent interpretive themes in the field, including “Africanisms,” Maroons’ connections to indigenous groups, and Maroon group cohesion and identity. This article’s analysis demonstrates that the comparisons enabled by a more globalized perspective benefit the field. Instead of eliding historical and cultural context, these comparisons support the development of more localized and historically specific understandings of individual runaway slave communities both in Kenya and throughout the New World

Evolution of the patellar sesamoid bone in mammals

The patella is a sesamoid bone located in the major extensor tendon of the knee joint, in the hindlimb of many tetrapods. Although numerous aspects of knee morphology are ancient and conserved among most tetrapods, the evolutionary occurrence of an ossified patella is highly variable. Among extant (crown clade) groups it is found in most birds, most lizards, the monotreme mammals and almost all placental mammals, but it is absent in most marsupial mammals as well as many reptiles. Here, we integrate data from the literature and first-hand studies of fossil and recent skeletal remains to reconstruct the evolution of the mammalian patella. We infer that bony patellae most likely evolved between four and six times in crown group Mammalia: in monotremes, in the extinct multituberculates, in one or more stem-mammal genera outside of therian or eutherian mammals and up to three times in therian mammals. Furthermore, an ossified patella was lost several times in mammals, not including those with absent hindlimbs: once or more in marsupials (with some re-acquisition) and at least once in bats. Our inferences about patellar evolution in mammals are reciprocally informed by the existence of several human genetic conditions in which the patella is either absent or severely reduced. Clearly, development of the patella is under close genomic control, although its responsiveness to its mechanical environment is also important (and perhaps variable among taxa). Where a bony patella is present it plays an important role in hindlimb function, especially in resisting gravity by providing an enhanced lever system for the knee joint. Yet the evolutionary origins, persistence and modifications of a patella in diverse groups with widely varying habits and habitats—from digging to running to aquatic, small or large body sizes, bipeds or quadrupeds—remain complex and perplexing, impeding a conclusive synthesis of form, function, development and genetics across mammalian evolution. This meta-analysis takes an initial step toward such a synthesis by collating available data and elucidating areas of promising future inquiry

Adjunctive rifampicin for Staphylococcus aureus bacteraemia (ARREST): a multicentre, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Staphylococcus aureus bacteraemia is a common cause of severe community-acquired and hospital-acquired infection worldwide. We tested the hypothesis that adjunctive rifampicin would reduce bacteriologically confirmed treatment failure or disease recurrence, or death, by enhancing early S aureus killing, sterilising infected foci and blood faster, and reducing risks of dissemination and metastatic infection. METHODS: In this multicentre, randomised, double-blind, placebo-controlled trial, adults (≥18 years) with S aureus bacteraemia who had received ≤96 h of active antibiotic therapy were recruited from 29 UK hospitals. Patients were randomly assigned (1:1) via a computer-generated sequential randomisation list to receive 2 weeks of adjunctive rifampicin (600 mg or 900 mg per day according to weight, oral or intravenous) versus identical placebo, together with standard antibiotic therapy. Randomisation was stratified by centre. Patients, investigators, and those caring for the patients were masked to group allocation. The primary outcome was time to bacteriologically confirmed treatment failure or disease recurrence, or death (all-cause), from randomisation to 12 weeks, adjudicated by an independent review committee masked to the treatment. Analysis was intention to treat. This trial was registered, number ISRCTN37666216, and is closed to new participants. FINDINGS: Between Dec 10, 2012, and Oct 25, 2016, 758 eligible participants were randomly assigned: 370 to rifampicin and 388 to placebo. 485 (64%) participants had community-acquired S aureus infections, and 132 (17%) had nosocomial S aureus infections. 47 (6%) had meticillin-resistant infections. 301 (40%) participants had an initial deep infection focus. Standard antibiotics were given for 29 (IQR 18-45) days; 619 (82%) participants received flucloxacillin. By week 12, 62 (17%) of participants who received rifampicin versus 71 (18%) who received placebo experienced treatment failure or disease recurrence, or died (absolute risk difference -1·4%, 95% CI -7·0 to 4·3; hazard ratio 0·96, 0·68-1·35, p=0·81). From randomisation to 12 weeks, no evidence of differences in serious (p=0·17) or grade 3-4 (p=0·36) adverse events were observed; however, 63 (17%) participants in the rifampicin group versus 39 (10%) in the placebo group had antibiotic or trial drug-modifying adverse events (p=0·004), and 24 (6%) versus six (2%) had drug interactions (p=0·0005). INTERPRETATION: Adjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with S aureus bacteraemia. FUNDING: UK National Institute for Health Research Health Technology Assessment

Optimizing magnetic particle image resolution using superferromagnetic nanoparticles modified through post-synthesis oxidation

Magnetic Particle Imaging (MPI) is a novel tracer-based imaging modality that allows for exquisitely sensitive celltherapy trackingin vivo, cancer imaging, lung ventilation/perfusion imaging, and hemorrhage detection. MPIuses superparamagnetic iron oxide Particles (SPIOs) as tracers with linear contrast, zero tissue attenuation, andmicromolar sensitivity, all with zero ionizing radiation and infinite reporter persistence. However, MPI’s poor spatialresolution (roughly 1 mm in a 7T/m gradient) is holding back clinical translation. Our lab recently reported theuse of superferromagnetic nanoparticles (SFMIOs) for MPI demonstrating a 10-fold improvement (?100?m) inresolution compared to the approximately mm for commercially available SPIOs. In the current work, we detail theproduction of SFMIO for MPI using a modified extended LaMer synthesis. We implement a post-oxidation step tothe process for repeated and reproducible production of high resolution SFMIO particles

Nitrate removal, denitrification and nitrous oxide production in the riparian zone of an ephemeral stream

Riparian zones are important features of the landscape that can buffer waterways from non-point sources of nitrogen pollution. Studies of perennial streams have identified denitrification as one of the dominant mechanisms by which this can occur. This study aimed to assess nitrate removal within the riparian zone of an ephemeral stream and characterise the processes responsible, particularly denitrification, using both in-situ and laboratory techniques. To quantify rates of groundwater nitrate removal and denitrification in-situ, nitrate was added to two separate injection–capture well networks in a perched riparian aquifer of a low order ephemeral stream in South East Queensland, Australia. Both networks also received bromide as a conservative tracer and one received acetylene to inhibit the last step of denitrification. An average of 77 ± 2% and 98 ± 1% of the added nitrate was removed within a distance of 40 cm from the injection wells (networks with acetylene and without, respectively). Based on rates of N2O production in the network with added acetylene, denitrification was not a major mechanism of nitrate loss, accounting for only 3% of removal. Reduction of nitrate to ammonium was also not a major pathway in either network, contributing <4%. Relatively high concentrations of oxygen in the aquifer following recent filling by stream water may have reduced the importance of these two anaerobic pathways. Alternatively, denitrification may have been underestimated using the in-situ acetylene block technique. In the laboratory, soils taken from two depths at each well network were incubated with four nitrate-N treatments (ranging from ambient concentration to an addition of 15 mg N l−1), with and without added acetylene. Potential rates of denitrification, N2O production and N2O:N2 ratios increased with nitrate additions, particularly in shallow soils. Potential rates of denitrification observed in the laboratory were equivalent in magnitude to nitrate removal measured in the field (mean 0.26 ± 0.12 mg N kg of dry soil−1 d−1), but were two orders of magnitude greater than denitrification measured in the field with added acetylene. The relative importance of assimilatory vs. dissimilatory processes of nitrate removal depends on environmental conditions in the aquifer, particularly hydrology and its effects on dissolved oxygen concentrations. Depending on seasonal conditions, aquifers of ephemeral streams like the study site are likely to fluctuate between oxic and anoxic conditions; nevertheless they may still function as effective buffers. While denitrification to N2 is a desirable outcome from a management perspective, assimilation into biomass can provide a rapid sink for nitrate, thus helping to reduce short-term delivery of nitrate downstream. Longer-term studies are needed to determine the overall effectiveness of riparian buffers associated with ephemeral streams in mitigating nitrate loads reaching downstream ecosystems