Development and Characterization of Plasma-based Sources for Ambient Desorption/Ionization Mass Spectrometry

Thesis (Ph.D.) - Indiana University, Chemistry, 2011A number of atmospheric-pressure ionization sources for mass spectrometry has recently appeared in the literature to yield a field that is collectively referred to as Ambient Desorption/Ionization-Mass Spectrometry (ADI-MS). These sources include, among others, Desorption ElectroSpray Ionization (DESI), Direct Analysis in Real Time (DART), the Flowing Atmospheric-Pressure Afterglow (FAPA), and the Low-Temperature Plasma (LTP) probe. Collectively, these ADI-MS sources offer numerous advantages over conventional ionization sources, including direct analysis of solid, liquid, and gaseous samples, high ionization efficiency, and soft ionization. Additionally, their ability to analyze samples directly with no pretreatment dramatically reduces analysis times. The ultimate ambient ionization source would be one that is capable of desorbing and ionizing a broad range of analytes (polar, non-polar, small molecules, biopolymers, etc.) while being minimally influenced by matrix effects. While the plasma-based ADI-MS sources, such as FAPA, DART, and LTP, have been shown to be capable of efficiently ionizing a range of small molecules, few investigations have been aimed at understanding desorption and ionization processes or matrix effects that occur with them. At present, the performance and fundamental characteristics of the FAPA source, developed in our research group, and the LTP probe, developed at Purdue University, are being evaluated through optical and mass-spectrometric methods. The FAPA source consists of a direct-current, atmospheric-pressure glow discharge in a pin-to-plate configuration. A hole in the plate allows ionized and excited plasma species to interact directly with a sample, while physically and electrically isolating the discharge from the sample-introduction region. Conversely, the LTP probe is a high-voltage, alternating-current, dielectric-barrier discharge that interacts directly with a sample. While the fundamental processes governing these discharges are quite different, mass spectra produced with both sources are very similar. The major differences are in achievable detection limits and susceptibility to matrix effects, with the FAPA sources routinely performing better. Direct, fundamental comparisons among the FAPA source, the LTP probe, and DART are made

Review: The Newsletter of the Literary Managers and Dramaturgs of the Americas, volume 15, issue 2

Contents include: Shopping=Theatre: Re-Staging Retail in NYC, LMDA\u27s Prez On Our Upcoming Extravaganza in the Lone Star State, Confessions of an Early Career Dramaturg, Dramablog, Dramaturging Education, Educating Dramturgs, Henier Muller on 42nd Street, LMDA\u27s Dramaturg Driven Project Gets Under Way, LMDA Regional Updates Issue editors: D.J. Hopkins, Shelley Orr, Megan Monaghan, Madeleine Oldhamhttps://soundideas.pugetsound.edu/lmdareview/1031/thumbnail.jp

Dipolar origin of the gas-liquid coexistence of the hard-core 1:1 electrolyte model

We present a systematic study of the effect of the ion pairing on the gas-liquid phase transition of hard-core 1:1 electrolyte models. We study a class of dipolar dimer models that depend on a parameter R_c, the maximum separation between the ions that compose the dimer. This parameter can vary from sigma_{+/-} that corresponds to the tightly tethered dipolar dimer model, to R_c --> infinity, that corresponds to the Stillinger-Lovett description of the free ion system. The coexistence curve and critical point parameters are obtained as a function of R_c by grand canonical Monte Carlo techniques. Our results show that this dependence is smooth but non-monotonic and converges asymptotically towards the free ion case for relatively small values of R_c. This fact allows us to describe the gas-liquid transition in the free ion model as a transition between two dimerized fluid phases. The role of the unpaired ions can be considered as a perturbation of this picture.Comment: 16 pages, 13 figures, submitted to Physical Review

Interaction of climate change with effects of conspecific and heterospecific density on reproduction

We studied the relationship between temperature and the coexistence of great titParus majorand blue titCyanistes caeruleus, breeding in 75 study plots across Europe and North Africa. We expected an advance in laying date and a reduction in clutch size during warmer springs as a general response to climate warming and a delay in laying date and a reduction in clutch size during warmer winters due to density-dependent effects. As expected, as spring temperature increases laying date advances and as winter temperature increases clutch size is reduced in both species. Density of great tit affected the relationship between winter temperature and laying date in great and blue tit. Specifically, as density of great tit increased and temperature in winter increased both species started to reproduce later. Density of blue tit affected the relationship between spring temperature and blue and great tit laying date. Thus, both species start to reproduce earlier with increasing spring temperature as density of blue tit increases, which was not an expected outcome, since we expected that increasing spring temperature should advance laying date, while increasing density should delay it cancelling each other out. Climate warming and its interaction with density affects clutch size of great tits but not of blue tits. As predicted, great tit clutch size is reduced more with density of blue tits as temperature in winter increases. The relationship between spring temperature and density on clutch size of great tits depends on whether the increase is in density of great tit or blue tit. Therefore, an increase in temperature negatively affected the coexistence of blue and great tits differently in both species. Thus, blue tit clutch size was unaffected by the interaction effect of density with temperature, while great tit clutch size was affected in multiple ways by these interactions terms.Peer reviewe

Hypothesis-driven genome-wide association studies provide novel insights into genetics of reading disabilities

Peer reviewe

Genome-wide analyses of individual differences in quantitatively assessed reading- and language-related skills in up to 34,000 people

The use of spoken and written language is a fundamental human capacity. Individual differences in reading- and language-related skills are influenced by genetic variation, with twin-based heritability estimates of 30 to 80% depending on the trait. The genetic architecture is complex, heterogeneous, and multifactorial, but investigations of contributions of single-nucleotide polymorphisms (SNPs) were thus far underpowered. We present a multicohort genome-wide association study (GWAS) of five traits assessed individually using psychometric measures (word reading, nonword reading, spelling, phoneme awareness, and nonword repetition) in samples of 13,633 to 33,959 participants aged 5 to 26 y. We identified genome-wide significant association with word reading (rs11208009, P = 1.098 x 10(-8)) at a locus that has not been associated with intelligence or educational attainment. All five reading-/language-related traits showed robust SNP heritability, accounting for 13 to 26% of trait variability. Genomic structural equation modeling revealed a shared genetic factor explaining most of the variation in word/nonword reading, spelling, and phoneme awareness, which only partially overlapped with genetic variation contributing to nonword repetition, intelligence, and educational attainment. A multivariate GWAS of word/nonword reading, spelling, and phoneme awareness maximized power for follow-up investigation. Genetic correlation analysis with neuroimaging traits identified an association with the surface area of the banks of the left superior temporal sulcus, a brain region linked to the processing of spoken and written language. Heritability was enriched for genomic elements regulating gene expression in the fetal brain and in chromosomal regions that are depleted of Neanderthal variants. Together, these results provide avenues for deciphering the biological underpinnings of uniquely human traits.Peer reviewe

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease