Mechanisms of Metal Deposition on Gold Nanoparticle Substrates

Understanding the chemical mechanisms underlying multimetallic nanoparticle nucleation and growth is crucial for translating the unique properties that emerge on the nanoscale. However, limited knowledge of nanoscale nucleation and growth processes challenges our ability to synthesize and characterize these materials in a robust and reproducible fashion. This dissertation identifies and describes synthetic mechanisms that direct metal on metal growth processes for gold nanoparticle substrates with unprecedented chemical detail. In Chapter 1, the dissertation is introduced with a background on the processes that influence multimetallic nanoparticle formation in relation to classic thin film growth modes. Specifically, the chapter focuses on metal-on-metal nucleation and growth mechanisms and highlights current advances in the synthesis of multimetallic nanoparticles through island-type deposition pathways. Chapter 2 demonstrates homogeneous nucleation as a robust, scalable, and sustainable method to synthesize anisotropic Au nanorods and nanoprisms relative to traditional seed mediated strategies. With effective methods to synthesize anisotropic Au nanoparticles, Chapter 3 builds on these results and uses Au nanoparticles as substrates for secondary metal deposition and multimetallic nanoparticle formation. Specifically, Chapter 3 describes pathways of Pt island deposition and identifies chemical mechanisms impacting surface chemistry vs. redox mediated growth pathways. Building on these results, Chapter 4 identifies the use of metal-ligand surface chemistry to promote edge, facet, or vertex selective nucleation of Pd, Pt, and Au nanoparticles on anisotropic Au nanoparticle substrates. Finally, Chapter 5 describes the deposition of Cu on Au nanoprisms and the challenges of incorporating 3d transitions metals into traditional noble metal syntheses. Together, these chapters demonstrate metal-ligand surface chemistry as a robust and efficient means of influencing the morphology, composition, and properties of multimetallic transition metal nanostructures

Sustainable Bottom-Up Synthesis of Anisotropic Gold Nanoparticles

Anisotropic noble metal nanoparticles exhibit unique optical and catalytic properties that have the potential to revolutionize applications ranging from cancer therapy to hydrogen storage. While there is considerable drive for the commercial implementation of these materials, a significant barrier to industrial translation lies in the lack of rational synthetic methods to produce them. This gap introduces difficulties with both the reproducibility and the sustainability of anisotropic nanoparticle synthesis. Here, a robust approach for the solution-phase synthesis of gold nanoparticles of technological interest has been developed. Instead of using a seed template to access canonical gold nanomaterials such as nanorods and nanoprisms, a homogeneous nucleation approach has been developed where nucleation and growth occur in the same chemical environment. By regulating the stages of particle nucleation and growth, nanorods with lengths from 30 to 630 nm and triangular or hexagonal prisms with vertex-to-vertex lengths ranging from 120 to over 700 nm were produced in high yield. These results shed light on the factors that influence the growth of anisotropic nanomaterials, and allow for drastically more efficient synthetic routes. Specifically, this methodology allows for the reduction in the amount of reagents needed to synthesize nanorods and nanoprisms by as much as 90% by weight, and represent the first report of spectroscopically-discernible, colloidal gold nanoplates obtained using a seedless approach. Methods developed will facilitate future investigations concerning the formation of complex, hybrid nanoparticle architectures from anisotropic nanomaterial substrates

Evaluating the impact of air pollution on the incidence of out-of-hospital cardiac arrest in the Perth Metropolitan Region: 2000–2010

Background: Out-of-hospital cardiac arrest (OHCA) remains a major public health issue. Several studies have found that an increased level of ambient particulate matter (PM) smaller than 2.5 microns (PM2.5) is associated with an increased risk of OHCA. We investigated the relationship between air pollution levels and the incidence of OHCA in Perth, Western Australia.Methods: We linked St John Ambulance OHCA data of presumed cardiac aetiology with Perth air pollution data from seven monitors which recorded hourly levels of PM smaller than 2.5 and 10 microns (PM2.5/PM10), carbon monoxide (CO), sulfur dioxide (SO2), nitrogen dioxide (NO2) and ozone (O3). We used a case-crossover design to estimate the strength of association between ambient air pollution levels and risk of OHCA.Methods: We linked St John Ambulance OHCA data of presumed cardiac aetiology with Perth air pollution data from seven monitors which recorded hourly levels of PM smaller than 2.5 and 10 microns (PM2.5/PM10), carbon monoxide (CO), sulfur dioxide (SO2), nitrogen dioxide (NO2) and ozone (O3). We used a case-crossover design to estimate the strength of association between ambient air pollution levels and risk of OHCA.Conclusions: Elevated ambient PM2.5 and CO are associated with an increased risk of OHCA

Educational Outcomes of Childhood Survivors of Critical Illness-A Population-Based Linkage Study

OBJECTIVES Major postintensive care sequelae affect up to one in three adult survivors of critical illness. Large cohorts on educational outcomes after pediatric intensive care are lacking. We assessed primary school educational outcomes in a statewide cohort of children who survived PICU during childhood. DESIGN Multicenter population-based study on children less than 5 years admitted to PICU. Using the National Assessment Program-Literacy and Numeracy database, the primary outcome was educational achievement below the National Minimum Standard (NMS) in year 3 of primary school. Cases were compared with controls matched for calendar year, grade, birth cohort, sex, socioeconomic status, Aboriginal and Torres Strait Islander status, and school. Multivariable logistic regression models to predict educational outcomes were derived. SETTING Tertiary PICUs and mixed ICUs in Queensland, Australia. PATIENTS Children less than 5 years admitted to PICU between 1998 and 2016. INTERVENTIONS Not applicable. MEASUREMENTS AND MAIN RESULTS Year 3 primary school data were available for 5,017 PICU survivors (median age, 8.0 mo at first PICU admission; interquartile range, 1.9-25.2). PICU survivors scored significantly lower than controls across each domain (p < 0.001); 14.03% of PICU survivors did not meet the NMS compared with 8.96% of matched controls (p < 0.001). In multivariate analyses, socioeconomic status (odds ratio, 2.14; 95% CI, 1.67-2.74), weight (0.94; 0.90-0.97), logit of Pediatric Index of Mortality-2 score (1.11; 1.03-1.19), presence of a syndrome (11.58; 8.87-15.11), prematurity (1.54; 1.09-2.19), chronic neurologic conditions (4.38; 3.27-5.87), chronic respiratory conditions (1.65; 1.24-2.19), and continuous renal replacement therapy (4.20; 1.40-12.55) were independently associated with a higher risk of not meeting the NMS. CONCLUSIONS In this population-based study of childhood PICU survivors, 14.03% did not meet NMSs in the standardized primary school assessment. Socioeconomic status, underlying diseases, and severity on presentation allow risk-stratification to identify children most likely to benefit from individual follow-up and support

Origin and distribution of epipolythiodioxopiperazine (ETP) gene clusters in filamentous ascomycetes

<p>Abstract</p> <p>Background</p> <p>Genes responsible for biosynthesis of fungal secondary metabolites are usually tightly clustered in the genome and co-regulated with metabolite production. Epipolythiodioxopiperazines (ETPs) are a class of secondary metabolite toxins produced by disparate ascomycete fungi and implicated in several animal and plant diseases. Gene clusters responsible for their production have previously been defined in only two fungi. Fungal genome sequence data have been surveyed for the presence of putative ETP clusters and cluster data have been generated from several fungal taxa where genome sequences are not available. Phylogenetic analysis of cluster genes has been used to investigate the assembly and heredity of these gene clusters.</p> <p>Results</p> <p>Putative ETP gene clusters are present in 14 ascomycete taxa, but absent in numerous other ascomycetes examined. These clusters are discontinuously distributed in ascomycete lineages. Gene content is not absolutely fixed, however, common genes are identified and phylogenies of six of these are separately inferred. In each phylogeny almost all cluster genes form monophyletic clades with non-cluster fungal paralogues being the nearest outgroups. This relatedness of cluster genes suggests that a progenitor ETP gene cluster assembled within an ancestral taxon. Within each of the cluster clades, the cluster genes group together in consistent subclades, however, these relationships do not always reflect the phylogeny of ascomycetes. Micro-synteny of several of the genes within the clusters provides further support for these subclades.</p> <p>Conclusion</p> <p>ETP gene clusters appear to have a single origin and have been inherited relatively intact rather than assembling independently in the different ascomycete lineages. This progenitor cluster has given rise to a small number of distinct phylogenetic classes of clusters that are represented in a discontinuous pattern throughout ascomycetes. The disjunct heredity of these clusters is discussed with consideration to multiple instances of independent cluster loss and lateral transfer of gene clusters between lineages.</p

Prognostic accuracy of age-adapted SOFA, SIRS, PELOD-2, and qSOFA for in-hospital mortality among children with suspected infection admitted to the intensive care unit

PURPOSE:The Sepsis-3 consensus task force defined sepsis as life-threatening organ dysfunction caused by dysregulated host response to infection. However, the clinical criteria for this definition were neither designed for nor validated in children. We validated the performance of SIRS, age-adapted SOFA, quick SOFA and PELOD-2 scores as predictors of outcome in children. METHODS:We performed a multicentre binational cohort study of patients < 18 years admitted with infection to ICUs in Australia and New Zealand. The primary outcome was ICU mortality. SIRS, age-adapted SOFA, quick SOFA and PELOD-2 scores were compared using crude and adjusted area under the receiver operating characteristic curve (AUROC) analysis. RESULTS:Of 2594 paediatric ICU admissions due to infection, 151 (5.8%) children died, and 949/2594 (36.6%) patients died or experienced an ICU length of stay ≥ 3 days. A ≥ 2-point increase in the individual score was associated with a crude mortality increase from 3.1 to 6.8% for SIRS, from 1.9 to 7.6% for age-adapted SOFA, from 1.7 to 7.3% for PELOD-2, and from 3.9 to 8.1% for qSOFA (p < 0.001). The discrimination of outcomes was significantly higher for SOFA (adjusted AUROC 0.829; 0.791-0.868) and PELOD-2 (0.816; 0.777-0.854) than for qSOFA (0.739; 0.695-0.784) and SIRS (0.710; 0.664-0.756). CONCLUSIONS:SIRS criteria lack specificity to identify children with infection at substantially higher risk of mortality. We demonstrate that adapting Sepsis-3 to age-specific criteria performs better than Sepsis-2-based criteria. Our findings support the translation of Sepsis-3 into paediatric-specific sepsis definitions and highlight the importance of robust paediatric organ dysfunction characterization.Luregn J. Schlapbach, Lahn Straney, Rinaldo Bellomo, Graeme MacLaren, David Pilche

Burden of disease and change in practice in Critically Ill Infants with Bronchiolitis

Bronchiolitis represents the most common cause of non-elective admission to paediatric intensive care units (ICUs)

Effect of promoter architecture on the cell-to-cell variability in gene expression

According to recent experimental evidence, the architecture of a promoter, defined as the number, strength and regulatory role of the operators that control the promoter, plays a major role in determining the level of cell-to-cell variability in gene expression. These quantitative experiments call for a corresponding modeling effort that addresses the question of how changes in promoter architecture affect noise in gene expression in a systematic rather than case-by-case fashion. In this article, we make such a systematic investigation, based on a simple microscopic model of gene regulation that incorporates stochastic effects. In particular, we show how operator strength and operator multiplicity affect this variability. We examine different modes of transcription factor binding to complex promoters (cooperative, independent, simultaneous) and how each of these affects the level of variability in transcription product from cell-to-cell. We propose that direct comparison between in vivo single-cell experiments and theoretical predictions for the moments of the probability distribution of mRNA number per cell can discriminate between different kinetic models of gene regulation.Comment: 35 pages, 6 figures, Submitte

H-NS binds with high affinity to the Tn10 transpososome and promotes transpososome stabilization

H-NS is a bacterial DNA-binding protein that regulates gene expression and DNA transposition. In the case of Tn10, H-NS binds directly to the transposition machinery (i.e. the transpososome) to influence the outcome of the reaction. In the current work we evaluated the binding affinity of H-NS for two forms of the Tn10 transpososome, including the initial folded form and a pre-unfolded form. These two forms differ in that IHF is bound to the former but not the latter. IHF binding induces a bend (or fold) in the transposon end that facilitates transpososome formation. However, the continued presence of IHF in the transpososome inhibits intermolecular transposition events. We show that H-NS binds particularly strongly to the pre-unfolded transpososome with an apparent Kd of ∼0.3 nM. This represents the highest affinity interaction between H-NS and a binding partner documented to date. We also show that binding of H-NS to the transpososome stabilizes this structure and propose that both high-affinity binding and stabilization result from the combined interaction between H-NS and DNA and H-NS and transposase within the transpososome. Mechanistic implications for tight binding of H-NS to the transpososome and transpososome stabilization are considered