Combustion experiments in reduced gravity with two-component miscible droplets

The combustion of liquid fuels is a topic worthy of scientific attention on practical and fundamental grounds. Most practical applications of liquid-fuel combustion involve the formation of spray diffusion flames, where droplets frequently burn in groups rather than individually. The combustion is typically complex, with interactions occurring between various physical mechanisms. Many efforts to understand liquid sprays have focused upon studying isolated droplets. Information gained from these studies is often not directly transferable to spray situations. However, isolated-droplet studies are useful in that they allow certain phenomena (e.g., extinction) to be studied under well-controlled and simplified conditions. When theory and experiment agree for simplified situations, predictions for more complex cases (where accurate experimental data may not exist) may be made with more confidence. The simplest droplet combustion scenario is that of an isolated droplet undergoing spherically-symmetric combustion in an environment of infinite extent. The idealization is approached only when forced and buoyant convection are negligible, the droplet is unsupported, and all foreign objects are far-removed from the combustion zone. Appreciable gravity levels compromise spherical symmetry by inducing buoyant convection

Correlated emission and spin-down variability in radio pulsars

The recent revelation that there are correlated period derivative and pulse shape changes in pulsars has dramatically changed our understanding of timing noise as well as the relationship between the radio emission and the properties of the magnetosphere as a whole. Using Gaussian processes we are able to model timing and emission variability using a regression technique that imposes no functional form on the data. We revisit the pulsars first studied by Lyne et al. (2010). We not only confirm the emission and rotational transitions revealed therein, but reveal further transitions and periodicities in 8 years of extended monitoring. We also show that in many of these objects the pulse profile transitions between two well-defined shapes, coincident with changes to the period derivative. With a view to the SKA and other telescopes capable of higher cadence we also study the detection limitations of period derivative changes.Comment: 4 pages, 2 Figures, Proceedings of IAU Symposium 337 "Pulsar Astrophysics - The Next 50 Years" held at Jodrell Bank Observatory, UK Sept. 4-8 201

THE ECOTOXICOLOGY OF ENGINEERED NANOPARTICLES TO FRESHWATER FISH

The use of nanoscale materials is growing exponentially, but there are also concerns about the environmental hazard to aquatic biota. Metal-containing engineered nanoparticles (NPs) are an important group of these new materials, and whilst there are undoubtedly a plethora of beneficial uses for these NPs, it is essential that an appropriate risk assessment is carried out in order to protect the environment and human health, with the consumption of contaminated fish a distinct possibility. The current study aimed to assess the bioavailability, uptake and toxicological effects of two metal-NPs (TiO2 NPs and Cu-NPs) to fish from both dietary and waterborne exposure routes and where appropriate compare them to their bulk counterpart. Whole body system effects were assessed along with the influences of the life stage of exposed fish and abiotic factors on toxicity. A technique to improve the quantification of Ti from TiO2 NPs in fish tissue was also developed. Effects from exposure to dietary TiO2 NPs manifested similarly to traditional dietary metal exposure, with no reduction in growth, but some sublethal affects. Exposure to waterborne Cu-NPs showed that rainbow trout were more acutely sensitive to CuSO4 than the NPs, but that despite limited uptake several body systems were affected (most notably ionoregulation). Larvae were more sensitive to CuSO4 than Cu-NPs, but no differences were seen with embryos, whilst larvae were more sensitive than embryos. Abiotic factors did have an effect on acute Cu-NP toxicity, though not always in a predictable manner, with some effects more pronounced than with CuSO4. Overall, it appears that metal-NPs are not as acutely toxic as their bulk counterparts, but sublethal effects, were routinely observed. As TiO2 NPs appear more toxic than its bulk counterpart, current legislation governing safe environmental limits may have to be adjusted, though the situation with Cu-NPs isn’t as clear and further investigation is required. However, the risk of human exposure via the consumption of NP contaminated fish fillets is extremely low

Immunoregulatory Receptor Genetics, Expression, and Splicing Studies in Alzheimer’s Disease

Microglia are the resident immune cells of the brain, undertaking many critical tissue maintenance functions such as immune surveillance and phagocytosis. Microglial dysfunction has recently been identified as a multi-stage signature of many neurodegenerative diseases, including late-onset Alzheimer’s Disease (LOAD). Genome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) in over thirty genes that modulate risk of developing LOAD. In the central nervous system, roughly half of these LOAD-associated genes are primarily expressed in microglia. The proteins encoded by these genes include cell surface receptors that contain either immunomodulatory tyrosine-phosphorylated activating motifs (ITAMs) or inhibitory motifs (ITIMs), including TREM2, CD33, and SIGLEC14. Here, I studied the molecular genetics underlying these three genes and their respective contributions to LOAD risk. First, I found that TREM2 undergoes extensive alternative splicing in multiple tissues, including brain. Total TREM2 expression is not different as a function of LOAD diagnosis (p = 0.1268), but TREM2 expression is increased by 34% in tissues with higher National Institute on Aging/Reagan Institute (NIARI) scores (p = 0.0033). I also found that a novel TREM2 isoform lacking exon 2, D2-TREM2, accounts for 11% of the total TREM2 mRNA in human brain, and that this splicing efficiency is not altered as a function of AD status (p = 0.4909) or brain pathology (p = 0.9502). I also found that the D2-TREM2 protein has similar subcellular localization to its parent TREM2 protein, as both are primarily retained in the Golgi apparatus. Next, I studied the exon 2-lacking CD33 isoform, D2-CD33. I developed an in vitro model to study the function of the D2-CD33 using a CRISPR-Cas9 approach in the U937 human monocyte cell line. After validating this model with sequencing, qPCR, and flow cytometry, I found that a nearby pseudogene, SIGLEC22P, was used as a repair template in approximately 10% of edited cells. This finding also provided the highest resolution to date of the clinically relevant anti-CD33 P67.6 antibody clone, gemtuzumab. Finally, I combined a recent LOAD GWAS with a protein quantitative trait loci (pQTL) study to uncover SIGLEC14 as a potentially overlooked LOAD risk factor. I found that a previously described SIGLEC14 genetic deletion occurs within a 692 bp crossover region. I also found additional copy number variation not previously described using both qPCR-based and in silico assays, with copy numbers identified ranging from zero to four. While SIGLEC14 deletion does correlate well with a proxy single nucleotide polymorphism (SNP), rs1106476, additional SIGLEC14 genomic copies do not correlate with this SNP. Further, the SIGLEC14 genomic deletions correlate stepwise with decreased SIGLEC14 expression (p = 0.0002), and also correlate significantly with decreased SIGLEC5 expression (p = 0.0389). In conclusion, microglial cell surface receptors are heavily implicated in the risk of developing LOAD, and these studies advance the field by adding to the molecular mechanisms which underlie their risk contribution. Further studies will be needed to address whether these findings can be translated clinically to either potential druggable targets or biomarkers

A Novel Forensic DNA Profiling Method Based On Molecular Beacons Without Dna Purification

Analysis of polymorphisms in nucleic acid sequences provides the basis for identification of individuals and their genetic deficiencies. Currently, the accepted method of analysis for profiling is Short Tandem Repeat (STR) profiling. This is a lengthy process, typically taking up to 3 days. The time necessary to generate an STR profile, along with the ever-increasing reliance on DNA to solve crimes, has led to a large DNA sample backlog, with violent crime turnaround taking an average of 103 days. The time and resource investment required for STR analysis is significant, and not all samples generate useful profiles. The current methods for use of STR technologies require an isolated template sample. This isolation typically requires hours of extractions and incubations, followed by still more time for analysis. The considerable length of time necessary for this process makes it inherently expensive, while also increasing the backlog. A universal protocol allowing amplification from various, frequently used samples would allow extremely rapid sampling and results. Further, these templates are faster and easier to amplify than standard STRs, which reduces the risk of resources and time on a sample which may not amplify. Common forensic samples include blood, hair, saliva, and buccal swabs. Using a single, universal protocol to prepare these samples for analysis without extensive isolation allows the simultaneous preparation of multiple samples. Accordingly, this work explores the development of a preparatory method for multiple forensic samples coupled with the optimization of polymerase chain reaction conditions to facilitate the real-time monitoring of the interaction of molecular beacons (MBs) with the template. These MBs can then be used to identify the presence or absence of specific nucleotide polymorphisms. This increase in throughput has extensive application in forensic and medical applications

Jesus\u27 Resurrection: A Historical Investigation

This thesis will investigate Jesus\u27 resurrection from a historical perspective. This investigation will begin by evaluating historical criteria that help historians determine the authenticity of past events. The historical approach to this investigation will be the minimal facts approach as pioneered by Gary Habermas. Using this approach, twelve historical facts relevant to the resurrection will be explored. We will evaluate why these twelve facts are agreed upon by a large variety of critical scholars. Next, an argument will be made demonstrating that the earliest reporting of eyewitnesses who experienced the resurrection can be traced to within three years of Jesus\u27 death on the cross. Lastly, a chapter will be devoted to Bart Ehrman and his various objections regarding the historian\u27s ability to determine whether or not a miracle has occurred and other limitations of historical inquiry related to the resurrection of Jesus

Tractor Connections for Killing Tensors and Their Generalizations

We create new symbolic software tools for the analysis of Killing tensors. Central to our work is the construction of the tractor connection defined on the tractor bundle, which allows one to obtain information about the space of Killing tensors without solving the Killing equations–an approach termed the tractor approach. We give a new application of the tractor approach which allows one to more easily check explicitly for linear independence of a given set of Killing tensors. We develop software to implement such methods in the case of rank 2 Killing tensors; similarly, we develop software to implement analogous methods in the study of Killing-Yano tensors and conformal Killing vectors. Using our newly developed software, we find examples of rank 2 irreducible Killing tensors for exact solutions to Einstein’s field equations. We also make an in-depth study of various other methods of constructing Killing tensors of rank 2 and find that these algorithms most often do not produce Killing tensors which are linearly independent of the reducible Killing tensors and the metric, with the Kerr metric being one of the only known sources of examples