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Face Down In The Wishkah

This thesis will reexamine the life of America’s greatest unknown serial killer William (Billy) Gohl. Spanning an eight year period (1902-1910) Gohl was able to amass over one hundred victims in the port city of Aberdeen Washington. Gohl did this through taking advantage of people’s trust and integrating techniques from 19th century San Franciscan criminals to produce a systematic murder enterprise. It took a new mayor, chief of police, and over two years of investigation to finally bring Gohl to trial and conviction. Gohl’s story is one that covers a variety of historical studies and hinges on a fascinating narrative. The research and literature on Gohl is sparse but has been able to stay progressive and continuous throughout the years. Gohl’s history and tale is one that has been rarely seen and almost hidden in our Nation’s and Washington State History. But like Gohl’s victims his story will always surface

Habitable Zone Lifetime of Exoplanets around Main Sequence Stars

Funding: Dean's Scholarship at the University of East Anglia.The potential habitability of newly discovered exoplanets is initially assessed by determining whether their orbits fall within the circumstellar habitable zone of their star. However, the habitable zone (HZ) is not static in time or space, and its boundaries migrate outward at a rate proportional to the increase in luminosity of a star undergoing stellar evolution, possibly including or excluding planets over the course of the star’s main sequence lifetime. We describe the time that a planet spends within the HZ as its ‘‘habitable zone lifetime.’’ The HZ lifetime of a planet has strong astrobiological implications and is especially important when considering the evolution of complex life, which is likely to require a longer residence time within the HZ. Here, we present results from a simple model built to investigate the evolution of the ‘‘classic’’ HZ over time, while also providing estimates for the evolution of stellar luminosity over time in order to develop a ‘‘hybrid’’ HZ model. These models return estimates for the HZ lifetimes of Earth and 7 confirmed HZ exoplanets and 27 unconfirmed Kepler candidates. The HZ lifetime for Earth ranges between 6.29 and 7.79 · 109 years (Gyr). The 7 exoplanets fall in a range between ∼1 and 54.72 Gyr, while the 27 Kepler candidate planets’ HZ lifetimes range between 0.43 and 18.8 Gyr. Our results show that exoplanet HD 85512b is no longer within the HZ, assuming it has an Earth analog atmosphere. The HZ lifetime should be considered in future models of planetary habitability as setting an upper limit on the lifetime of any potential exoplanetary biosphere, and also for identifying planets of high astrobiological potential for continued observational or modeling campaigns.Peer reviewe

Festival City Futures: Reflections and Conclusions

This concluding chapter reflects on some of the key themes highlighted by previous chapters, but it also aims to look forward by examining how city festivals and festival cities may develop in the future. The chapter explores one of the most important dimensions of the book – the ways festivals and events might help to produce more inclusive public spaces. The authors explore whether the social and cultural value of festivals may be (re)prioritised over the economic agenda which has dominated in recent years. The contested nature of city festivals and urban festive spaces is also discussed at length, and the chapter also covers the importance of analyses that can capture the affective and sensorial effects of urban festivity. This provides the basis for a wider review of the methods employed by the authors of the chapters that feature in the book. Inevitably, given the timing of the book, there is also an attempt to highlight the implications of the Coronavirus pandemic, and the ways that urban festivity may be affected in the medium and longer terms. The chapter concludes by summarising the contribution of the book, and by making some suggestions for future research that would help us to better understand the relationships between festivals, public spaces and social inclusion

A linked data approach to publishing complex scientific workflows

Past data management practices in many fields of natural science, including climate research, have focused primarily on the final research output - the research publication - with less attention paid to the chain of intermediate data results and their associated metadata, including provenance. Data were often regarded merely as an adjunct to the publication, rather than a scientific resource in their own right. In this paper, we attempt to address the issues of capturing and publishing detailed workflows associated with the climate/research datasets held by the Climatic Research Unit (CRU) at the University of East Anglia. To this end, we present a customisable approach to exposing climate research workflows for the effective re-use of the associated data, through the adoption of linked-data principles, existing widely adopted citation techniques (Digital Object Identifier) and data exchange mechanisms (Open Archives Initiative Object Reuse and Exchange)

Nebulised surfactant in preterm infants with or at risk of respiratory distress syndrome

Nebulised surfactant has the potential to deliver surfactant to the infant lung with the goal of avoiding endotracheal intubation and ventilation, ventilator-induced lung injury and bronchopulmonary dysplasia (BPD). To determine the effect of nebulised surfactant administration either as prophylaxis or treatment compared to placebo, no treatment or intratracheal surfactant administration on morbidity and mortality in preterm infants with, or at risk of, respiratory distress syndrome (RDS). Searches were performed of CENTRAL (The Cochrane Library, January 2012), MEDLINE and PREMEDLINE (1950 to January 2012), EMBASE (1980 to January 2012) and CINAHL (1982 to January 2012), as well as proceedings of scientific meetings, clinical trial registries, Google Scholar and reference lists of identified studies. Expert informants and surfactant manufacturers were contacted. Randomised, cluster-randomised or quasi-randomised controlled trials of nebulised surfactant administration compared to placebo, no treatment, or other routes of administration (laryngeal, pharyngeal instillation of surfactant before the first breath, thin endotracheal catheter surfactant administration or intratracheal surfactant instillation) on morbidity and mortality in preterm infants at risk of RDS. We considered published, unpublished and ongoing trials. Two review authors independently assessed studies for eligibility and quality, and extracted data. No studies of prophylactic or early nebulised surfactant administration were found. A single small study of late rescue nebulised surfactant was included. The study is of moderate risk of bias. The study enrolled 32 preterm infants born < 36 weeks' gestation with RDS on nasal continuous positive airway pressure (nCPAP). The study reported no significant difference between nebulised surfactant administration compared to no treatment groups in chronic lung disease (risk ratio (RR) 5.00; 95% confidence interval (CI) 0.26 to 96.59) or other outcomes (oxygenation 1 to 12 hours after randomisation, need for mechanical ventilation, days of mechanical ventilation or continuous positive airways pressure (CPAP) or days of supplemental oxygen). No side effects of the nebulised surfactant therapy or aerosol inhalation were reported. There are insufficient data to support or refute the use of nebulised surfactant in clinical practice. Adequately powered trials are required to determine the effect of nebulised surfactant administration for prevention or early treatment of RDS in preterm infants. Nebulised surfactant administration should be limited to clinical trials

Festivals and the City: The Contested Geographies of Urban Events

This book explores how festivals and events affect urban places and public spaces, with a particular focus on their role in fostering inclusion. The ‘festivalisation’ of culture, politics and space in cities is often regarded as problematic, but this book examines the positive and negative ways that festivals affect cities by examining festive spaces as contested spaces. The book focuses on Western European cities, a particularly interesting context given the social and cultural pressures associated with high levels of in-migration and concerns over the commercialisation and privatisation of public spaces. The key themes of this book are the quest for more inclusive urban spaces and the contested geographies of festival spaces and places. Festivals are often used by municipal authorities to break down symbolic barriers that restrict who uses public spaces and what those spaces are used for. However, the rise of commercial festivals and ticketed events means that they are also responsible for imposing physical and financial obstacles that reduce the accessibility of city parks, streets and squares. Alongside addressing the contested effects of urban festivals on the character and inclusivity of public spaces, the book addresses more general themes including the role of festivals in culture-led regeneration. Several chapters analyse festivals and events as economic development tools, and the book also covers contested representations of festival cities and the ways related images and stories are used in place marketing. A range of cases from Western Europe are used to explore these issues, including chapters on some of the world’s most significant and contested festival cities: Venice, Edinburgh, London and Barcelona. The book covers a wide range of festivals, including those dedicated to music and the arts, but also events celebrating particular histories, identities and pastimes. A series of fascinating cases are discussed - from the Venice Biennale and Dublin Festival of History, to Rotterdam’s music festivals and craft beer festivals in Manchester. The diverse and innovative qualities of the book are also evident in the range of urban spaces covered: obvious examples of public spaces – such as parks, streets, squares and piazzas – are addressed, but the book includes chapters on enclosed public spaces (e.g., libraries) and urban blue spaces (waterways) too. This reflects the interpretation of public spaces as socio-material entities: they are produced informally through their use (including for festivals and events), as well as through their formal design and management

Evolutionary and Biochemical Studies of C₇-cyclitol Synthases and their Sunscreen Gene Clusters

Sugar phosphate cyclases (SPCs) are enzymes involved in the biosynthesis of many important natural products. SPCs form a unique cyclitol during the early steps in the biosynthesis of many natural products. These natural products include rifamycin, which is chemically modified to rifampicin and used clinically as an antituberculosis drug, and acarbose, an antidiabetic. Other natural products formed by SPCs have functions including but not limited to antifungal, antitumor, antioxidant, sunscreen, and wound healing activities. Thus, SPCs are useful genome mining probes for the discovery of novel natural products. One subset of SPCs are the sedoheptulose 7-phosphate cyclases (SH7PCs), which consists of three enzymes that each form a distinct cyclitol product from the same substrate, sedoheptulose 7-phosphate (SH7P). The three SH7PCs are 2-O-desmethyl-4-deoxygadusol synthases (DDGS), 2-epi-5-epi-valiolone synthases (EEVS), and 2-epi-valiolone synthases (EVS). DDGS is only involved in the biosynthesis of mycosporine-like amino acids (MAAs), which are sunscreen natural products. In contrast, EEVS and EVS are found in the biosynthesis of a variety of pseudosugars and aminocyclitols. This dissertation describes the identification, distribution, and evolution of SH7PCs and their use as probes for forming natural and unnatural sunscreens. SH7PCs are thought to descend from the shikimate pathway enzyme 3-dehydroquinate synthase (DHQS), which all vertebrates lack. However, genes encoding putative EEVS enzymes were identified in the genomes of non-mammalian vertebrates. Using Danio rerio (zebrafish) as a model, the vertebrate EEVS and an adjacent gene encoding a methyltransferase-oxidoreductase (MT-Ox) were shown to make a sunscreen called gadusol. Due to its similarity to MAAs, gadusol was originally thought to have dietary origins in marine fishes. However, the gadusol genes were expressed in D. rerio embryos and gadusol was identified in embryo extracts. Furthermore, gadusol was produced enzymatically and by heterologous production in Streptomyces coelicolor and Saccharomyces cerevisiae, establishing sustainable production routes for further development. One of the setbacks in the field was that SPCs were often misannotated in public databases due to their sequence similarity. In this thesis, two conserved active site amino acid motifs were identified by bioinformatics, allowing SPCs to be distinguished based off primary amino acid sequence. These sequences are more conserved in DDGS than other SPCs, possibly due to stringent spatial requirements needed for performing a dehydration reaction that other SPCs do not. Each motif contains a catalytic amino acid verified by protein crystallography and site-directed mutagenesis. Point mutation either of these catalytic amino acids in DDGS or EEVS disrupted catalysis. The bioinformatic analysis highlighted the distribution and evolution for DDGS and EEVS, suggesting their broad roles in nature. While EEVS genes are mostly found in Streptomyces spp. and non-mammalian vertebrates, DDGS genes are mostly distributed in cyanobacteria, fungi, and non-Streptomyces Actinobacteria. Through a genome mining study, an MAA gene cluster was also found in the nursery plant pathogen Rhodococcus fascians D188. This gene cluster was expressed in S. coelicolor M1152 and shinorine was produced as the primary MAA, whereas porphyra-334 and mycosporine-alanine-glycine were identified as minor products. This is the first demonstration that a bacterial pathogen encodes functional MAA genes, and MAAs may provide R. fascians D188 an advantage in its native environment. With functional MAA genes on hand, a synthetic pathway was designed for expression in S. coelicolor M1152 using ValA, the model EEVS from the validamycin pathway, the D. rerio MT-Ox, and the last two R. fascians D188 MAA biosynthetic enzymes to form unnatural gadusol and MAA analogs. These new compounds, called gadusporines, show unique UV absorbance at 340 nm, which is red-shifted compared to their natural counterparts. Gadusporine A, a hydroxylated shinorine analog, was the major analog produced and gadusporine B, a mycosporine-alanine-glycine analog, was also purified. The expression of gadusporines establishes a platform for further engineering of nature-inspired sunscreens

The Provider-Consumer Relationship and Individual Well-Being: Perspectives of Adults with Serious Mental Illness and their Mental Health Care Providers

Using a sample of 60 adults with mental illness in an inpatient state hospital, the present study examined the relative contribution of mental health consumers’ reports of working alliance and provider directiveness in consumers’ perceptions of recovery-oriented service delivery, personal loss from mental illness, and individual well-being. Using a subsample of mental health consumers (n = 19) and their mental health providers (n = 9) the present study examined the congruence of perception between providers’ and consumers’ views of working alliance and provider directiveness in understanding individual well-being for consumers and providers. Findings suggest that consumers’ reports of working alliance and provider directiveness accounted for a significant proportion of the variation in their reports of recovery-orientation of services. Consumers’ reports of working alliance accounted for a significant proportion of the variance in consumers’ reports of their individual well-being. However, consumers’ scores on relationship measures were not significantly related to their reports of personal loss from mental illness. In a subsample of providers and consumers, dyadic analyses suggest that consumers’ reports of a stronger working alliance were related to providers’ reports of higher levels of directive practices. Dyadic results also suggest that greater congruence of perceptions of working alliance among consumer-provider dyads was positively related to consumers’ perceptions of recovery-oriented service delivery. Implications of findings for research and clinical practice are discussed

Investigations of Pactamycin Biosynthesis

Pactamycin, a complex aminocyclitol compound produced by Streptomyces pactum, has significant antibiotic, antitumor, and antiplasmodial activity. However, this natural product has not been developed for clinical use due to its high cytotoxicity. Modulation of its biological properties by chemical synthesis has been difficult due to its complex chemical structure. Therefore, biosynthetic-based genetic engineering appears to be a feasible alternative approach to developing new analogs of pactamycin. While the pactamycin biosynthetic gene cluster is known, many parts of the pathway remain elusive. For example, the acyltransferase gene responsible for the transfer of 6-methylsalicyclic acid to the aminocyclitol core has not yet been identified. As part of our effort to identify this gene, we used gene disruption to inactivate 1) a putative acyltransferase gene, located outside of the pactamycin gene cluster but near the pactamycin resistance gene, and 2) a putative ketoacyl-(ACP) synthase (KAS)-III gene (ptmR), located within the cluster. The results showed that PtmR is the enzyme responsible for the attachment of 6-methylsalicylic acid. We also hypothesized that pactamycin production could be increased through the modulation of global regulators. Inactivation of the global regulatory genes afsA, arpA, and phoP, which are known to affect secondary metabolism, revealed that ArpA is directly involved in the regulation of pactamycin biosynthesis. On the other hand, inactivation of afsA and phoP did not affect pactamycin production