Anion Distribution, Structural Distortion, and Symmetry-Driven Optical Band Gap Bowing in Mixed Halide Cs2SnX6 Vacancy Ordered Double Perovskites.

Mixed anion compounds in the Fm3̅m vacancy ordered perovskite structure were synthesized and characterized experimentally and computationally with a focus on compounds where A = Cs+. Pure anion Cs2SnX6 compounds were formed with X = Cl, Br, and I using a room temperature solution phase method. Mixed anion compounds were formed as solid solutions of Cs2SnCl6 and Cs2SnBr6 and a second series from Cs2SnBr6 and Cs2SnI6. Single phase structures formed across the entirety of both composition series with no evidence of long-range anion ordering observed by diffraction. A distortion of the cubic A2BX6 structure was identified in which the spacing of the BX6 octahedra changes to accommodate the A site cation without reduction of overall symmetry. Optical band gap values varied with anion composition between 4.89 eV in Cs2SnCl6 to 1.35 eV in Cs2SnI6 but proved highly nonlinear with changes in composition. In mixed halide compounds, it was found that lower energy optical transitions appeared that were not present in the pure halide compounds, and this was attributed to lowering of the local symmetry within the tin halide octahedra. The electronic structure was characterized by photoemission spectroscopy, and Raman spectroscopy revealed vibrational modes in the mixed halide compounds that could be assigned to particular mixed halide octahedra. This analysis was used to determine the distribution of octahedra types in mixed anion compounds, which was found to be consistent with a near-random distribution of halide anions throughout the structure, although some deviations from random halide distribution were noted in mixed iodide-bromide compounds, where the larger iodide anions preferentially adopted trans configurations

Modifying executive function and self-regulatory behaviours in developmental dyslexia: cognitive and neural bases of response inhibition

Dyslexia is characterised by impaired reading, but socio-emotional problems typically co-occur (1). It is also associated with response inhibition (RI) impairments at the behavioural (2,3) and neural levels as indexed by reduced response-inhibition related P3 amplitude (4). Studies have shown that variability in RI is predictive of the severity of reading and socio-emotional problems in dyslexia (2,5), suggesting that RI may underpin these issues. RI appears modifiable at the behavioural and neural levels with training (6,7). Therefore, RI training may improve RI (behavioural & neural), and reduce reading and socio-emotional problems in dyslexia. No study to date has explored whether RI is modifiable in dyslexia and whether training transfers to reduced symptoms

Five Geneseo Monuments: Exhibition Catalog

SUNY Geneseo Museum Studies Class Exhibition, Fall 2019. Bridge Gallery, December 4, 2019. The Big Tree The Bear Fountain Monument: A Symbol of Community James Samuel Wadsworth Statue Progression Toward Modernity: Geneseo’s Suffragists, The Shaw Sisters The Geneseo Fire Department Memorialhttps://knightscholar.geneseo.edu/geneseo-authors/1009/thumbnail.jp

A Novel Plaque Enriched Long Noncoding RNA in Atherosclerotic Macrophage Regulation (PELATON)

Objective: Long noncoding RNAs (lncRNAs) are an emergent class of molecules with diverse functional roles, widely expressed in human physiology and disease. Although some lncRNAs have been identified in cardiovascular disease, their potential as novel targets in the prevention of atherosclerosis is unknown. We set out to discover important lncRNAs in unstable plaque and gain insight into their functional relevance. Approach and Results: Analysis of RNA sequencing previously performed on stable and unstable atherosclerotic plaque identified a panel of 47 differentially regulated lncRNAs. We focused on LINC01272, a lncRNA upregulated in unstable plaque previously detected in inflammatory bowel disease, which we termed PELATON (plaque enriched lncRNA in atherosclerotic and inflammatory bowel macrophage regulation). Here, we demonstrate that PELATON is highly monocyte- and macrophage-specific across vascular cell types, and almost entirely nuclear by cellular fractionation (90%-98%). In situ hybridization confirmed enrichment of PELATON in areas of plaque inflammation, colocalizing with macrophages around the shoulders and necrotic core of human plaque sections. Consistent with its nuclear localization, and despite containing a predicted open reading frame, PELATON did not demonstrate any protein-coding potential in vitro. Functionally, knockdown of PELATON significantly reduced phagocytosis, lipid uptake and reactive oxygen species production in high-content analysis, with a significant reduction in phagocytosis independently validated. Furthermore, CD36, a key mediator of phagocytic oxLDL (oxidized low-density lipoprotein) uptake was significantly reduced with PELATON knockdown. Conclusions: PELATON is a nuclear expressed, monocyte- and macrophage-specific lncRNA, upregulated in unstable atherosclerotic plaque. Knockdown of PELATON affects cellular functions associated with plaque progression

CARMN loss regulates smooth muscle cells and accelerates atherosclerosis in mice

[Figure: see text]

Conceptual responsibility

Conceptual engineering is concerned with the improvement of our concepts. The motivating thought behind many such projects is that some of our concepts are defective. But, if to use a defective concept is to do something wrong, and if to do something wrong one must be in control of what one is doing, there might be no defective concepts, since we typically are not in control of our concept use. To address this problem, this paper turns from appraising the concepts we use to appraising the people who use them. First, I outline several ways in which the use of a concept can violate moral standards. Second, I discuss three accounts of moral responsibility, which I call voluntarism, rationalism, and psychologism, arguing that each allows us to find at least some cases where we are responsible for using defective concepts. Third, I answer an objection that because most of our concepts are acquired through processes for which we are not responsible, our use of defective concepts is a matter of bad luck, and not something for which we are responsible after all. Finally, I conclude by discussing some of the ways we may hold people accountable for using defective concepts

The moral obligation to be vaccinated: utilitarianism, contractualism, and collective easy rescue

Despite the success of vaccines in preventing and sometimes eradicating infectious diseases, and despite their demonstrated safety (Navin 2015, p. 6; CDC 2015a; Andre et al 2008), many people today refuse vaccination for themselves or their children. In the U.S. there has been a significant increase in cases of measles over the last few years due to increasingly widespread non-vaccination: in 2014, for example, there were 667 reported cases, the highest number since measles elimination was documented in the U.S. in 2000 (CDC 2016a). Similarly, in different parts of Europe there were measles outbreaks in 2016 and 2017, due to a significant decrease in measles vaccination rates; for example, in Italy there were more than 3,300 cases of measles in the first half of 2017, 88% of which were not vaccinated and 7% of which received just one dose of vaccine (ECDC 2017). Before the introduction of the measles vaccination program in 1963, 3-4 million people in the US were infected by measles every year, and 4-500 of them died (CDC, 2015b)

Hypoxyprobe™ reveals dynamic spatial and temporal changes in hypoxia in a mouse model of endometrial breakdown and repair

BACKGROUND: Menstruation is the culmination of a cascade of events, triggered by the withdrawal of progesterone at the end of the menstrual cycle. Initiation of tissue destruction and endometrial shedding causes spiral arteriole constriction in the functional layer of the endometrium. Upregulation of genes involved in angiogenesis and immune cell recruitment, two processes that are essential to successful repair and remodelling of the endometrium, both thought to be induced by reduced oxygen has been reported. Evidence for stabilisation/increased expression of the transcriptional regulator hypoxia inducible factor in the human endometrium at menses has been published. The current literature debates whether hypoxia plays an essential role during menstrual repair, therefore this study aims to delineate a role for hypoxia using a sensitive detection method (the Hypoxyprobe™) in combination with an established mouse model of endometrial breakdown and repair. RESULTS: Using our mouse model of menses, during which documented breakdown and synchronous repair occurs in a 24 h timeframe, in combination with the Hypoxyprobe™ detection system, oxygen tensions within the uterus were measured. Immunostaining revealed striking spatial and temporal fluctuations in hypoxia during breakdown and showed that the epithelium is also exposed to hypoxic conditions during the repair phase. Furthermore, time-dependent changes in tissue hypoxia correlated with the regulation of mRNAs encoding for the angiogenic genes vascular endothelial growth factor and stromal derived factor (Cxcl12). CONCLUSIONS: Our findings are consistent with a role for focal hypoxia during endometrial breakdown in regulating gene expression during menses. These data have implications for treatment of endometrial pathologies such as heavy menstrual bleeding

The Human-Specific and Smooth Muscle Cell-Enriched LncRNA SMILR Promotes Proliferation by Regulating Mitotic CENPF mRNA and Drives Cell-Cycle Progression Which Can Be Targeted to Limit Vascular Remodeling.

RATIONALE: In response to blood vessel wall injury, aberrant proliferation of vascular smooth muscle cells (SMCs) causes pathological remodeling. However, the controlling mechanisms are not completely understood. OBJECTIVE: We recently showed that the human long noncoding RNA, SMILR, promotes vascular SMCs proliferation by a hitherto unknown mechanism. Here, we assess the therapeutic potential of SMILR inhibition and detail the molecular mechanism of action. METHODS AND RESULTS: We used deep RNA-sequencing of human saphenous vein SMCs stimulated with IL (interleukin)-1α and PDGF (platelet-derived growth factor)-BB with SMILR knockdown (siRNA) or overexpression (lentivirus), to identify SMILR-regulated genes. This revealed a SMILR-dependent network essential for cell cycle progression. In particular, we found using the fluorescent ubiquitination-based cell cycle indicator viral system that SMILR regulates the late mitotic phase of the cell cycle and cytokinesis with SMILR knockdown resulting in ≈10% increase in binucleated cells. SMILR pulldowns further revealed its potential molecular mechanism, which involves an interaction with the mRNA of the late mitotic protein CENPF (centromere protein F) and the regulatory Staufen1 RNA-binding protein. SMILR and this downstream axis were also found to be activated in the human ex vivo vein graft pathological model and in primary human coronary artery SMCs and atherosclerotic plaques obtained at carotid endarterectomy. Finally, to assess the therapeutic potential of SMILR, we used a novel siRNA approach in the ex vivo vein graft model (within the 30 minutes clinical time frame that would occur between harvest and implant) to assess the reduction of proliferation by EdU incorporation. SMILR knockdown led to a marked decrease in proliferation from ≈29% in controls to ≈5% with SMILR depletion. CONCLUSIONS: Collectively, we demonstrate that SMILR is a critical mediator of vascular SMC proliferation via direct regulation of mitotic progression. Our data further reveal a potential SMILR-targeting intervention to limit atherogenesis and adverse vascular remodeling