Electrospray ionization mass spectrometric techniques for the study of molecular recognition

The ability of electrospray ionization mass spectrometry (ESI-MS) to quantitatively analyze the distribution of complexes resulting from molecular recognition in solution was modeled, and ESI-MS techniques were developed to analyze complexes involving several different types of novel compounds in different areas of molecular recognition and supramolecular chemistry. To better understand the relationship between ion abundances observed by ESI-MS and concentrations of host-guest complexes in solution, mathematical models based on equilibrium partitioning theory were developed to relate ESI-MS ion abundances to relative solution concentrations of complexes resulting from host-guest binding. The predictions of these new models were evaluated and experimentally confirmed through the analysis of complexes of crown ethers with alkali metal cations in an ESI quadrupole ion trap mass spectrometer, yielding a greater understanding of the behavior of host-guest complexes in ESI-MS, allowing for more accurate measurements of solution binding interactions. The self-assembly of ligand-metal-ligand sandwich complexes involving a novel quinoxaline-containing crown ether was studied to evaluate the contribution of pi-stacking interactions between the ligands towards the overall stability of the complexes. Donor-acceptor pi-stacking interactions between the electron-poor quinoxaline group and electron-rich benzene groups from benzo- or dibenzo-18-crown-6 were found to significantly enhance the formation of mixed-ligand sandwich complexes. A synthetic pyrrole-inosine nucleoside, capable of forming an extended three-point Hoogsteen-type hydrogen-bonding interaction with guanine, was shown to bind guanosine selectively over other individual nucleosides, and ESI-MS results indicated the formation of specific complexes between the pyrrole-inosine nucleoside and two different quadruplex DNA structures. The specificity of the pyrrole-inosine nucleoside for quadruplex DNA suggests that it or similar structures based on this binding modality may ultimately demonstrate utility as anti-tumor agents. The interactions between a novel enediyne drug and various cytidine-containing oligonucleotides were studied, and the structures of the DNA-enediyne adducts known to lead to cytidine-specific DNA cleavage were examined. Collisionally activated dissociation of the adducts confirmed their strength and suggest a direct linkage between the enediyne and the cytidine nucleobase, likely the result of a nucleophilic attack by the cytidine amine.Chemistry and BiochemistryChemistr

Liver transplantation for hepatocellular carcinoma: Management after the transplant

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153700/1/ajt15697.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/153700/2/ajt15697_am.pd

The context, influences and challenges for undergraduate nurse clinical education: Continuing the dialogue

Introduction – Approaches to clinical education are highly diverse and becoming increasingly complex to sustain in complex milieu Objective – To identify the influences and challenges of providing nurse clinical education in the undergraduate setting and to illustrate emerging solutions. Method: A discursive exploration into the broad and varied body of evidence including peer reviewed and grey literature. Discussion - Internationally, enabling undergraduate clinical learning opportunities faces a range of challenges. These can be illustrated under two broad themes: (1) Legacies from the past and the inherent features of nurse education and (2) Challenges of the present, including, population changes, workforce changes, and the disconnection between the health and education sectors. Responses to these challenges are triggering the emergence of novel approaches, such as collaborative models. Conclusion(s) – Ongoing challenges in providing accessible, effective and quality clinical learning experiences are apparent

Learning to treat the climate emergency together: social tipping interventions by the health community

Accelerating the decarbonisation of local and national economies is a profound public health imperative. As trusted voices within communities around the world, health professionals and health organisations have enormous potential to influence the social and policy landscape in support of decarbonisation. We assembled a multidisciplinary, gender-balanced group of experts from six continents to develop a framework for maximising the social and policy influence of the health community on decarbonisation at the micro levels, meso levels, and macro levels of society. We identify practical, learning-by-doing approaches and networks to implement this strategic framework. Collectively, the actions of health-care workers can shift practice, finance, and power in ways that can transform the public narrative and influence investment, activate socioeconomic tipping points, and catalyse the rapid decarbonisation needed to protect health and health systems

Condensation of zinc vapor in a supersonic carrier gas

A study of the condensation of a metal vapor in an inert carrier gas is made. Superheated zinc vapor is generated in a hot shot wind tunnel in a helium carrier gas and expanded in a converging-diverging nozzle. Static pressure measurements along the length of the nozzle are made to determine the location of the onset of condensation. A conical nominal Mach 5 (helium) nozzle is employed. The amount of supercooling before the onset of condensation is found to be approximately 430 K, measured along the isentrope over a range of initial zinc mass fractions of .35 to .70 for saturation partial pressures of zinc between 10 psia and 70 psia. The measurements are compared with results of an analysis based on the classical liquid drop model of nucleation. The computed results agree reasonably well with the measurements.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41794/1/10494_2004_Article_BF00382286.pd

p53 and ovarian carcinoma survival: an Ovarian Tumor Tissue Analysis consortium study

Our objective was to test whether p53 expression status is associated with survival for women diagnosed with the most common ovarian carcinoma histotypes (high-grade serous carcinoma [HGSC], endometrioid carcinoma [EC], and clear cell carcinoma [CCC]) using a large multi-institutional cohort from the Ovarian Tumor Tissue Analysis (OTTA) consortium. p53 expression was assessed on 6,678 cases represented on tissue microarrays from 25 participating OTTA study sites using a previously validated immunohistochemical (IHC) assay as a surrogate for the presence and functional effect of TP53 mutations. Three abnormal expression patterns (overexpression, complete absence, and cytoplasmic) and the normal (wild type) pattern were recorded. Survival analyses were performed by histotype. The frequency of abnormal p53 expression was 93.4% (4,630/4,957) in HGSC compared to 11.9% (116/973) in EC and 11.5% (86/748) in CCC. In HGSC, there were no differences in overall survival across the abnormal p53 expression patterns. However, in EC and CCC, abnormal p53 expression was associated with an increased risk of death for women diagnosed with EC in multivariate analysis compared to normal p53 as the reference (hazard ratio [HR] = 2.18, 95% confidence interval [CI] 1.36-3.47, p = 0.0011) and with CCC (HR = 1.57, 95% CI 1.11-2.22, p = 0.012). Abnormal p53 was also associated with shorter overall survival in The International Federation of Gynecology and Obstetrics stage I/II EC and CCC. Our study provides further evidence that functional groups of TP53 mutations assessed by abnormal surrogate p53 IHC patterns are not associated with survival in HGSC. In contrast, we validate that abnormal p53 IHC is a strong independent prognostic marker for EC and demonstrate for the first time an independent prognostic association of abnormal p53 IHC with overall survival in patients with CCC