Acute Respiratory Distress Syndrome (ARDS) following hemorrhagic shock/resuscitation (S/R) is an important contributor to late morbidity and mortality in trauma patients. S/R promotes ARDS by inducing oxidative stress that primes cells of the innate immune system for excessive responsiveness to small inflammatory stimuli, termed the “twohit” hypothesis. Activated alveolar macrophages (AM) play a central role and when recovered from S/R animals exhibit an exaggerated responsiveness to lipopolysaccharide (LPS) with increased activation of the proinflammatory transcription factor NF-κB, and augmented expression of cytokines. LPS triggers AM signalling through Toll like receptor 4 (TLR4), which resides in plasma membrane lipid rafts. The objective of this work is to define cellular mechanisms of macrophage priming by oxidative stress following shock resuscitation. The main hypothesis investigated is that altered cellular distribution of TLR4 can lead to macrophage priming and antioxidant resuscitation strategies can diminish these effects. AM of rodents, exposed in vivo to oxidant stress following S/R, increase their surface levels of TLR4, which in turn results in augmented NF-κB translocation in response to small doses of LPS. Furthermore, in vitro H2O2 treatment of RAW 264.7 macrophages results in similar TLR4 surface translocation. Depletion of intracellular calcium, disruption of the cytoskeleton or inhibition of the Src kinases prevents the H2O2-induced TLR4 translocation, suggesting the involvement of receptor exocytosis. Further, fluorescent resonance energy iii transfer between TLR4 and lipid rafts as well as biochemical raft analysis demonstrated that oxidative stress redistributes TLR4 to surface lipid rafts. Preventing the oxidant-induced movement of TLR4 to lipid rafts using methyl-ß-cyclodextrin precluded the increased responsiveness of cells to LPS after H2O2 treatment. Further, AM priming by oxidative stress can be diminished by early exposure to resuscitation regimens with direct or indirect systemic antioxidant effects, such as 25% albumin, N-acetylcysteine and hypertonic saline. Hyperosmolarity was found to modulate AM TLR4 gene and protein expression. Collectively, these studies suggest a novel mechanism whereby oxidative stress might prime the responsiveness of cells of the innate immune system. Targeting the TLR4 signalling pathway early during shock resuscitation may represent an anti-inflammatory strategy able to ameliorate late morbidity and mortality following S/R.

In 2013 around 289,000 women died from what was categorised as maternal complications. This figure is likely to be higher as only 40% of the world has an adequately function health reporting system (WHO et al 2014, p.1). Severe bleeding causes around 27% of all maternal deaths; this is the single biggest threat to pregnancy and childbirth. Moreover, maternal complications are the second biggest cause of death for women of reproductive age globally. The risks women and girls face through pregnancy and childbirth are the outcome of socio-cultural structures and norms, which increase the inequalities in many societies. The decisions we make, the choices we have, and the actions we carry out are a product of our social system’s structures and norms. Humanitarian crises painfully display the divisiveness and destruction that these structures and norms can have on the members of that system. But, crises also offer an opportunity to either, rebuild structures and norms in a way that reduces inequality and protects the vulnerable, or a regression to more traditional, more patriarchal and more hierarchical structures and norms which will ultimately disadvantage women and girls further in their plight for equality. There is a vicious circle of poverty and mortality that can be triggered by maternal death. In order to prevent these cycles from continuing, creative, simple and appropriate strategies need to be developed for humanitarian response that build on the knowledge systems and capacities of those affected, as well as the experience and expertise of practitioners. Instead of a discussion between development or humanitarian, the conversation should try to find ways for all interventions to be more homophilious with those affected and ensure that they do not worsen the structures protecting the most vulnerable. Innovation has long since been seen as a process for those who ‘have’, and not for those who ‘have not’. Criticisms of increasing inequality through a division based on socio-economic markers have only led to self-fulfilling stereotypes of who is innovative and who is not. This research is trying to shift the focus from one that is divisive to a more inclusionary approach. To address maternal mortality caused by severe bleeding, it is imperative to understand the context in which it is happening. Who is affected? Why? What do they think and believe? What happens to the family, the community? How are the structures and norms of the society affecting it? What solutions have been offered? In answering these questions it is clear how far the impact of maternal mortality can reach. It is the hope of this research, that its can be used to reduce and lessen this impact through better-targeted and tailored responses using appropriate tools – such as the non-pneumatic anti-shock garment, implemented in a mind frame of sustainability and resilience in an environment receptive to innovation. There is a need for fresh ideas and approaches to reduce a burden that does not exist in resource stable parts of the world, and a burden that has come to be seen as a problem of the poor. The non-pneumatic anti-shock garment is a game changer. It has the potential to inspire interest and access health systems, yet implementation thus far has been limited in humanitarian response. This research investigates maternal mortality caused by postpartum haemorrhage in humanitarian crises, in an endeavour to improve the discussion on including the NASG into the MISP as an appropriate tool to fight maternal mortality and the inequality that is found at its root.

In this study, it is determined that excess returns on the OMX 30 are confirmed to rise in anticipation of monetary policy decisions made by the central banks of Sweden and The United States of America. Those findings were manifested at a greater magnitude on the first day prior to the announcements and on a statistically significant level one day prior to monetary policy decisions from the Federal Open Market Committee. Moreover, excess returns beyond the average rate were found to be substantially higher on the first and third day prior monetary policy decisions from the Swedish Central bank (Riksbanken) albeit not on a statistically significant level. The results drawn from the data in the study were reinforced by findings in similar tests conducted during times of global recession.

Simulating transient compressible flows involving shock waves presents challenges to the CFD practitioner in terms of the mesh quality required to resolve discontinuities and prevent smearing. This document discusses a novel two-dimensional Cartesian anisotropic mesh adaptation technique implemented for transient compressible flow. This technique, originally developed for laminar incompressible flow, is efficient because it refines and coarsens cells using criteria that consider the solution in each of the cardinal directions separately. In this document the method will be applied to compressible flow. The procedure shows promise in its ability to deliver good quality solutions while achieving computational savings. Transient shock wave diffraction over a backward step and shock reflection over a forward step are considered as test cases because they demonstrate that the quality of the solution can be maintained as the mesh is refined and coarsened in time. The data structure is explained in relation to the computational mesh, and the object-oriented design and implementation of the code is presented. Refinement and coarsening algorithms are outlined. Computational savings over uniform and isotropic mesh approaches are shown to be significant.

The heat shock or stress response is a transient response to stressful stimuli that protects vital cellular proteins from damage and irreversible aggregation. Heat shock proteins (Hsps) are molecular chaperones that bind to unfolded protein and inhibit their aggregation, thereby maintaining their solubility until they can be refolded to their native conformation. Hsp47 is an endoplasmic reticulum (ER)-resident protein that serves as a molecular chaperone during collagen production. Collagen is the major class of insoluble fibrous protein found in the extracellular matrix and in connective tissues. It is the single most abundant protein of the animal kingdom; at least 14 different forms exist, each with distinct structures and binding properties. The various types of collagen all possess protein regions with the distinct triple helical conformation. This complex physical structure requires very organized assembly and HSP47 has been established as an integral component of this process for collagen types I-V. Most of the previous studies examining the expression and function of hsp47 have been conducted with mammalian cultured cells. The present study represented the first investigation of the expression of hsp47 in the poikilothermic vertebrate, <i>Xenopus laevis</i>. Full-length <i>Xenopus</i> hsp47 nucleotide and amino acid sequences were obtained from Genbank and compared with hsp47 from chicken, mouse, rat, human and zebrafish. <i>Xenopus</i> HSP47 protein had an identity of approximately 77% with chicken, 73% with mouse, 72% with rat and human, and 70% with zebrafish. Most of the sequence identity between HSP47 from all investigated organisms occurred centrally in the amino acid sequence and in several carboxyl terminal regions. Three key features were conserved between HSP47 proteins from most species investigated: a hydrophobic leader sequence, two potential glycosylation sites and the ER-retention signal, RDEL. A partial cDNA clone encoding <i>Xenopus</i> hsp47 was obtained from the American Type Culture Collection (ATCC) and used to generate hsp47 antisense riboprobe for the purpose of investigating hsp47 mRNA accumulation in <i>Xenopus</i> A6 kidney epithelial cells and embryos. Northern blot analysis detected hsp47 mRNA constitutively in A6 cells. The expression pattern for hsp47 mRNA was compared with two other <i>Xenopus</i> heat shock proteins that have been previously characterized in our laboratory: hsp70, a cystolic/nuclear hsp and BiP, an ER-resident hsp. The results of hsp47 mRNA accumulation in A6 cells suggested that the expression pattern for <i>Xenopus</i> hsp47 was unique but, with respect to some stressors, resembled that of a cytosolic hsp rather than an ER-resident hsp. HSP47 protein levels were also examined in A6 cells. Heat shock, sodium arsenite and b-aminopropionitrile fumerate treatments enhanced hsp47 accumulation. In some experiments, western blot analysis revealed the presence of two closely sized protein bands. It is possible that minor differences in HSP47 protein size may be due to post-translational modification, namely phosphorylation or glycosylation. The present study also examined the accumulation and spatial pattern of hsp47 mRNA accumulation during <i>Xenopus laevis</i> early development. Hsp47 was constitutively expressed throughout <i>Xenopus</i> early development. Constitutive levels of hsp47 mRNA in unfertilized eggs, fertilized eggs and cleavage stage embryos indicated that these transcripts were maternally inherited. Constitutive hsp47 mRNA accumulation was enhanced in neurula and tailbud embryos compared to earlier stages. This finding may be explained by the shift towards organogenesis during these stages. Whole mount <i>in situ</i> hybridization revealed hsp47 message along the dorsal region of the embryo, in the notochord and somites, as well as in the head region including the eye vesicle. Hsp47 mRNA induction in <i>Xenopus</i> embryos was also examined in response to heat shock. Hsp47 mRNA accumulated in response to heat shock immediately following the midblastula transition (MBT). In tailbud stages, hsp47 mRNA accumulated in the notochord, somites and head region. Northern blot analysis and whole mount <i>in situ</i> hybridization results revealed an expression pattern that coincided well with the development of collagen-rich tissues thereby substantiating the proposed role of HSP47 as a procollagen molecular chaperone.

The performance of an MBR under chemical shock loading conditions was investigated, to ascertain the robustness of the treatment system for urban water reuse. 32 household products and industrial substances, likely to be found in urban wastewater were assessed for toxicity, using Microtox and respirometry to obtain EC50 values. Six of these toxins were dosed into bench scale porous pots to observe any detrimental effects on the treatment system, in terms of effluent quality and potential foulant release. Four toxins were dosed into a pilot scale MBR to observe the effects of scale and enhanced biomass retention on the perturbations seen at bench scale. Mitigation of the foulants observed was investigated by the addition of ancillary chemicals. 10 household products and 6 industrial products were identified as being of risk to a biological treatment system with EC50 concentrations of the order that could be present in urban wastewater. 2 of the 6 toxins dosed into the porous pots caused a serious impact on the system reducing COD removal rates to 45%, compared with 92% average for the control pots, and increasing SMP turbidity to 11 NTU. 1 of the 4 toxins dosed into the MBR caused an impact, although less than observed in the porous pots, with the COD removal rate reducing to 77% and SMP turbidity increasing to a maximum of 9 NTU. Jar tests carried out to investigate mitigation potential of SMP turbidity found the cationic polymers MPE50 and high molecular weight polyDADMAC most efficient with reductions of SMP turbidity to <1 NTU possible although the toxins increased the dose necessary to achieve this.

Biological systems of bacteria were investigated at the single-cell and single-molecule level. Additionally, aspects of the techniques employed were studied. A unifying theme in each project is the reliance on optical imaging techniques coupled to microfluidic devices. Hypo-osmotic shock experiments with an Escherichia coli mechanosensitive channel deletion mutant were carried out at the single-cell level. E. coli MJF465 cells in which the three major mechanosensitive channel genes are deleted (∆mscL, ∆mscS, ∆mscK) show only 10% cell viability upon hypo-osmotic shock (from LB + 0.5 M NaCl into distilled water), compared to 90% viability of the wild-type strain. Bacterial cells were trapped with optical tweezers in microfluidic devices, enabling the first direct observation of single-cell behaviour upon hypo-osmotic shock. Phase-contrast microscopy revealed intra-population diversity in the cells response: Different features of lysis included cells bursting rapidly and leakage of ribosomes, DNA and protein from the cytoplasm. Fluorescence microscopy of hypo-osmotically-shocked GFP-expressing MJF465 cells showed either bursting of cells, which was a rare event, or fast leakage of GFP, indicating cell membrane ruptures. Data were analysed in terms of their kinetic behaviour and showed that lysis occurs on a timescale of milliseconds to seconds. The implications of these findings for the bacterial cell wall and cell membranes are discussed. Enzymes involved in homologous recombination and repair of double-stranded DNA (dsDNA) breaks are essential for maintaining genomic integrity in both eukaryotes and prokaryotes. RecBCD of E. coli and AddAB, found widely in bacteria, are involved in these processes, carrying out the same function. Both enzymes were studied kinetically with single-molecule total internal reflection fluorescence microscopy (TIRFM). Surface-tethered, hydrodynamically stretched lambda-DNA molecules, stained with YOYO-1, were imaged with TIRFM in a microfluidic flowcell. The RecBCD enzyme is a well characterised DNA helicase and was introduced to this system for method validation purposes. The AddAB enzyme of Bacteroides fragilis was then characterised as a helicase acting on lambda-DNA. It was found that AddAB helicase unwinds dsDNA with high processivity of on average 14,000 bp and up to 40,000 bp for individual enzyme complexes at an ATP-dependent rate ranging from 50-250 bp s−1 (for Mg2+-ATP concentrations larger or equal than 0.1 mM). This activity was detected by DNA binding dye (YOYO-1) displacement from the dsDNA and studied for different Mg2+-ATP concentrations, flow (shear) rates and different YOYO-1 staining ratios of DNA. Aspects of this last experimental setup were investigated. A kinetic analysis of intercalation of YOYO-1 into lambda-DNA is presented, occurring on a timescale of minutes. Different flow rates and staining ratios that influence the apparent (stretched) DNA molecule length were also examined. Several image analysis techniques were employed to enhance the data quality in images showing stretched lambda-DNA molecules. The Singular Value Decomposition was found to be the most effective technique which strongly reduces the noise in the obtained kymograph images.

We have surveyed 84 Class 0, Class I, and flat-spectrum protostars in mid-infrared [Si II], [Fe II], and [S I] line emission, and 11 of these in far-infrared [O I] emission. We use the results to derive their mass. outflow rates, (M) over dot(w). Thereby we observe a strong correlation of (M) over dot(w) with bolometric luminosity, and with the inferred mass accretion rates of the central objects, (M) over dot(a), which continues through the Class 0 range the trend observed in Class II young stellar objects. Along this trend from large to small mass. flow rates, the different classes of young stellar objects lie in the sequence Class 0-Class I/flat-spectrum-Class II, indicating that the trend is an evolutionary sequence in which (M) over dot(a) and (M) over dot(w) decrease together with increasing age, while maintaining rough proportionality. The survey results include two that. are key tests of magnetocentrifugal outflow-acceleration mechanisms: the distribution of the outflow/accretion branching ratio b = (M) over dot(w)/(M) over dot(a), and limits on the distribution of outflow speeds. Neither rules out any of the three leading outflow-acceleration, angular-momentum-ejection mechanisms, but they provide some evidence that disk winds and accretion-powered stellar winds (APSWs) operate in many protostars. An upper edge observed in the branching-ratio distribution is consistent with the upper bound of b = 0.6 found in models of APSWs, and a large fraction (31%) of the sample have a. branching ratio sufficiently small that only disk winds, launched on scales as large as several au, have been demonstrated to account for them.

Supernovae (SNe) are energetic explosions that signal the end of a star's life. These events and the supernova remnants (SNRs) they leave behind play a central role in stellar feedback by adding energy and momentum and metals to the interstellar medium (ISM). Emission associated with these feedback processes, especially atomic and molecular line emission as well as thermal and nonthermal continuum emission is known to be enhanced in regions of high density, such as dense circumstellar matter (CSM) around SNe and molecular clouds (MCs). In this thesis, I begin with a brief overview of the physics of SN shocks in Chapter 1, focusing on a foundation for studying pan-chromatic signatures of interactions between SNe and dense environments. In Chapter 2, I examine an unusual SN with signatures of CSM interaction in the form of narrow lines of hydrogen (Type IIn) and thermal continuum emission. This SN appears to belong to a class of Type Ia SNe that shares spectroscopic features with Type IIn SNe. I discuss the difficulties of decomposing spectra in a regime where interaction occurs between SN ejecta and CSM, potentially confusing the underlying SN type. This is followed by a discussion of rebrightening that occurred at late-time in 𝐵 and 𝑉 band photometry of this SN, possibly associated with clumpy or dense CSM at large distances from the progenitor. In Chapter 3, I examine synchrotron emission from Cassiopeia A, observed in the 𝐾ₛ band over multiple epochs. The synchrotron emission is generally diffuse over the remnant, but there is one location in the southwest portion of the remnant where it appears to be enhanced and entrained as knots of emission in the SNR ejecta. I evaluate whether the 𝐾ₛ band knots are dominated by synchrotron emission by comparing them to other infrared and radio imaging that is known to be dominated by synchrotron emission. Concluding that they are likely synchrotron-emitting knots, I measure the magnetic field strength and electron density required for their evolution over the ~ 10 yr baseline they were observed and find 𝐵 ≈ 1.3-5.8 mG and 𝑛ₑ≈ 1,000-15,000 cm⁻³. The magnetic field strengths appear enhanced beyond values required by the adiabatic strong shock limit, arguing in favor of other forms of magnetic field amplification in the shock. In Chapter 4, I again discuss Cassiopeia A and interaction between the remnant and nearby MCs as seen at mid-infrared and millimeter wavelengths. I report detection of a SNR-MC interaction and analyze its signatures in broadened molecular lines. I extend this analysis in Chapter 5 to a large survey for SNR-MC interactions in the ¹²CO 𝐽=2-1 line. Although broadened ¹²CO 𝐽=2-1 line emission should be detectable toward virtually all SNR-MC interactions, I find relatively few examples; therefore, the number of interactions is low. This result favors mechanisms other than supernova feedback as the basic trigger for star formation. In addition, I find no significant association between TeV gamma-ray sources and MC interactions, contrary to predictions that SNR-MC interfaces are the primary venues for cosmic ray acceleration. I end this dissertation in Chapter 6 with a brief summary of my results and two extensions of this work: examining the late-time radio light curves of CSM-interacting SNe for signatures of radio synchrotron emission and dense or clumpy CSM at large distances from the progenitor and re-observing SNR-MC interactions in ¹²CO 𝐽=3-2 in order to verify the presence of shock-heated molecular gas and perform a census on the densities and temperatures of post-shock molecular gas.

This paper offers grounded evidence in support of the elaboration of Kim's [(2001). Becoming intercultural: An integrative theory of communication and cross-cultural adaptation. Thousand Oaks, CA: Sage] integrative theory of communication and cross-cultural adaptation (ITCCA) to include sojourner reentry. Findings from 24 intensive interviews validate the heuristic value of ITCCA in the reentry context, but also reveal unique features that set reentry adaptation apart from cross-cultural adaptation. Key theoretical contributions include (1) a nuanced description of the role of reentry communication competence, (2) greater complexity of the roles and networks of interpersonal and mediated communication upon return, (3) an expansion to the environment domain to include home environment, and (4) a long-range perspective on the development of functional fitness, psychological health, and intercultural personhood. Implications for sojourner reentry training are addressed.