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Synthesis, Structure, and Optoelectronic Properties of Hybrid Metal Iodides
The focus of this dissertation was on the preparation and analysis of new materials related to hybrid halide perovskites, AMX3, where A = a small organic cation, M = a divalent heavy metal, and X = a halogen. It sought to understand the fundamental reasons for why the hybrid perovskites work as excellent optoelectronic materials, and to use this information to design new, stable, and less toxic materials.This dissertation first sought to understand whether disparate slabs of metaliodide octahedra could be electronically coupled using electronically functional organic molecules, as this could create more stable and potentially more functional materials. A well-known organic compound made famous during the advent of organic metals, tetrathiafulvalene, was used to prepare three new hybrid materials [(TTF)Pb2I5, (TTF)BiI4, and (TTF)4BiI6] with some found to behave like semiconductors with 3D electronic connectivity, even though they were structurally 1D or 2D materials. This discovery supported our original hypothesis that a more stable, layered, hybrid perovskite material could potentially exist using functional organic molecules as both structural and electronic components.This work then extended its focus to study platinum based hybrid perovskites, A2PtI6 (A = small organic cation), and examined the effect of increasing cation size in Pt based vacancy ordered hybrid perovskite materials (VOHPs). This study was pertinent to our fundamental understanding of VOHPs, as by establishing structural trends caused by the small organic cations, and how different metals (Pt) behaved in these systems, future avenues for material design could be opened. It was found that the hydrogen bonding of the small organic cation to the iodides of the [PtI6]2- octahedra were quite significant as cation size increased, as these interactions dictated final structure and subsequent optical properties of these materials.In the process of understanding iodide containing hybrid perovskites, serendipitous discoveries of polyiodides were made along the way. These works include understanding the effect of hydrogen bonding in the formation of hybrid platinum oligo- and polyiodides, as well as resolving the 200 years old mystery as to what happens when starch combines with iodine.In summary, the work presented herein is reflective of the many diverse preparation and characterization techniques needed to complete these projects: solution and solid state synthesis, and single crystal and bulk material characterization techniques ranging from crystallography, calorimetry, and optical spectroscopy. It is also a testament to the social aspect of science, as to complete this work, many collaborations needed to be formed
The single cell transcriptional landscape of esophageal adenocarcinoma and its modulation by neoadjuvant chemotherapy
Immune checkpoint blockade has recently proven effective in subsets of patients with esophageal adenocarcinoma (EAC) but little is known regarding the EAC immune microenvironment. We determined the single cell transcriptional profile of EAC in 8 patients who were treatment-naive (n =â4) or had received neoadjuvant chemotherapy (nâ=â4). Analysis of 52,387 cells revealed 10 major cell subsets of tumor, immune and stromal cells. Prior to chemotherapy tumors were heavy infiltrated by T regulatory cells and exhausted effector T cells whilst plasmacytoid dendritic cells were markedly expanded. Two dominant cancer-associated fibroblast populations were also observed whilst endothelial populations were suppressed. Pathological remission following chemotherapy associated with broad reversal of immune abnormalities together with fibroblast transition and an increase in endothelial cells whilst a chemoresistant epithelial stem cell population correlated with poor response. These findings reveal features that underlie and limit the response to current immunotherapy and identify a range of novel opportunities for targeted therapy. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12943-022-01666-x
On-stack replacement, distilled
On-stack replacement (OSR) is essential technology for adaptive optimization, allowing changes to code actively executing in a managed runtime. The engineering aspects of OSR are well-known among VM architects, with several implementations available to date. However, OSR is yet to be explored as a general means to transfer execution between related program versions, which can pave the road to unprecedented applications that stretch beyond VMs. We aim at filling this gap with a constructive and provably correct OSR framework, allowing a class of general-purpose transformation functions to yield a special-purpose replacement. We describe and evaluate an implementation of our technique in LLVM. As a novel application of OSR, we present a feasibility study on debugging of optimized code, showing how our techniques can be used to fix variables holding incorrect values at breakpoints due to optimizations
Genome evolution and hostâmicrobiome shifts correspond with intraspecific niche divergence within harmful algal bloomâforming Microcystis aeruginosa
Intraspecific niche divergence is an important driver of species range, population abundance and impacts on ecosystem functions. Genetic changes are the primary focus when studying intraspecific divergence; however, the role of ecological interactions, particularly hostâmicrobiome symbioses, is receiving increased attention. The relative importance of these evolutionary and ecological mechanisms has seen only limited evaluation. To address this question, we used Microcystis aeruginosa, the globally distributed cyanobacterium that dominates freshwater harmful algal blooms. These blooms have been increasing in occurrence and intensity worldwide, causing major economic and ecological damages. We evaluated 46 isolates of M. aeruginosa and their microbiomes, collected from 14 lakes in Michigan, USA, that vary over 20âfold in phosphorus levels, the primary limiting nutrient in freshwater systems. Genomes of M. aeruginosa diverged along this phosphorus gradient in genomic architecture and protein functions. Fitness in lowâphosphorus lakes corresponded with additional shifts within M. aeruginosa including genomeâwide reductions in nitrogen use, an expansion of phosphorus assimilation genes and an alternative life history strategy of nonclonal colony formation. In addition to host shifts, despite culturing in commonâgarden conditions, hostâmicrobiomes diverged along the gradient in taxonomy, but converged in function with evidence of metabolic interdependence between the host and its microbiome. Divergence corresponded with a physiological tradeâoff between fitness in lowâphosphorus environments and growth rate in phosphorusârich conditions. Coâoccurrence of genotypes adapted to different nutrient environments in phosphorusârich lakes may have critical implications for understanding how M. aeruginosa blooms persist after initial nutrient depletion. Ultimately, we demonstrate that the intertwined effects of genome evolution, host life history strategy and ecological interactions between a host and its microbiome correspond with an intraspecific niche shift with important implications for whole ecosystem function.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151861/1/mec15198_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151861/2/mec15198.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151861/3/mec15198-sup-0001-Supinfo.pd
The Human Gene Mutation Database: towards a comprehensive repository of inherited mutation data for medical research, genetic diagnosis and next-generation sequencing studies
The Human Gene Mutation Database (HGMDÂŽ) constitutes a comprehensive collection of published germline mutations in nuclear genes that underlie, or are closely associated with human inherited disease. At the time of writing (March 2017), the database contained in excess of 203,000 different gene lesions identified in over 8000 genes manually curated from over 2600 journals. With new mutation entries currently accumulating at a rate exceeding 17,000 per annum, HGMD represents de facto the central unified gene/disease-oriented repository of heritable mutations causing human genetic disease used worldwide by researchers, clinicians, diagnostic laboratories and genetic counsellors, and is an essential tool for the annotation of next-generation sequencing data. The public version of HGMD (http://www.hgmd.org) is freely available to registered users from academic institutions and non-profit organisations whilst the subscription version (HGMD Professional) is available to academic, clinical and commercial users under license via QIAGEN Inc
Trends in hospital admissions and surgical procedures for degenerative lumbar spine disease in England: a 15-year time-series study.
OBJECTIVES: Low back pain (LBP), from degenerative lumbar spine disease, represents a significant burden on healthcare resources. Studies worldwide report trends attributable to their country's specific demographics and healthcare system. Considering England's specific medico-socioeconomic conditions, we investigate recent trends in hospital admissions and procedures for LBP, and discuss the implications for the allocation of healthcare resources. DESIGN: Retrospective cohort study using Hospital Episode Statistics data relating to degenerative lumbar spine disease in England, between 1999 and 2013. Regression models were used to analyse trends. OUTCOME MEASURES: Trends in the number of admissions and procedures for LBP, mean patient age, gender and length of stay. RESULTS: Hospital admissions and procedures have increased significantly over the study period, from 127.09 to 216.16 and from 24.5 to 48.83 per 100â
000, respectively, (p<0.001). The increase was most marked in the oldest age groups with a 1.9 and 2.33-fold increase in admissions for patients aged 60-74 and âĽ75â
years, respectively, and a 2.8-fold increase in procedures for those aged âĽ60â
years. Trends in hospital admissions were characterised by a widening gender gap, increasing mean patient age, and decreasing mean hospital stay (p<0.001). Trends in procedures were characterised by a narrowing gender gap, increasing mean patient age (p=0.014) and decreasing mean hospital stay (p<0.001). Linear regression models estimate that each hospital admission translates to 0.27 procedures, per 100â
000 (95% CI 0.25 to 0.30, r 0.99, p<0.001; r, Pearson's correlation coefficient). Hospital admissions are increasing at 3.5 times the rate of surgical procedures (regression gradient 7.63 vs 2.18 per 100â
000/year). CONCLUSIONS: LBP represents a significant and increasing workload for hospitals in England. These trends demonstrate an increasing demand for specialists involved in the surgical and non-surgical management of this disease, and highlight the need for services capable of dealing with the increased comorbidity burden associated with an ageing patient group
Accountability : construct definition and measurement of a virtue vital to flourishing
This work was supported by a grant from the Templeton Religion Trust (TRT0171).Embracing accountability to others for oneâs responsibilities within relationships is important for flourishing, yet underexamined. An interdisciplinary team defined the construct of accountability and developed an 11-item single-factor Accountability Scale. In national samples with US census demographic representation (total N =Â 1257), we conducted psychometric analyses using methods from classical test theory (exploratory and confirmatory factor analyses) and item response theory. The Accountability Scale demonstrated internal consistency, construct validity, test-retest reliability, and incremental validity. Accountability correlated positively with relational variables (agreeableness, empathy) responsibility-oriented variables (conscientiousness, self-regulation), virtues (gratitude, forgiveness, limitations-owning humility), relational repair, perceived meaning presence, and flourishing, inversely with symptoms (personality disorders, temper, anxiety, depression), and weakly with searching for meaning and social desirability. Accountability scores superseded demographic variables, conscientiousness, and agreeableness to predict relational repair, perceived presence of meaning in life, and flourishing. We offer the accountability construct and scale to advance human flourishing research and applied work.Publisher PDFPeer reviewe
Risky Business: Rhesus Monkeys Exhibit Persistent Preferences for Risky Options
Rhesus monkeys have been shown to prefer risky over safe options in experiential decision-making tasks. These findings might be due, however, to specific contextual factors, such as small amounts of fluid reward and minimal costs for risk-taking. To better understand the factors affecting decision-making under risk in rhesus monkeys, we tested multiple factors designed to increase the stakes including larger reward amounts, distinct food items rather than fluid reward, a smaller number of trials per session, and risky options with greater variation that also included non-rewarded outcomes. We found a consistent preference for risky options, except when the expected value of the safe option was greater than the risky option. Thus, with equivalent mean utilities between the safe and risky options, rhesus monkeys appear to have a robust preference for the risky options in a broad range of circumstances, akin to the preferences found in human children and some adults in similar tasks. One account for this result is that monkeys make their choices based on the salience of the largest payoff, without integrating likelihood and value across trials. A related idea is that they fail to override an impulsive tendency to select the option with the potential to obtain the highest possible outcome. Our results rule out strict versions of both accounts and contribute to an understanding of the diversity of risky decision-making among primates
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