Abstract
This article examines the attempts at legislation in Ireland made by an elected assembly known as ‘Dáil Éireann’ in the revolutionary years between 1919 and 1922. These attempts at ...legislation, popularly known as ‘Dáil decrees’, have not been published or used as sources of law since the foundation of the Irish state on 6 December 1922. This analysis builds on a pioneering article on this subject published in 1975 by Brian Farrell and attempts to provide additional information on the final fate of the Dáil decrees. The conclusion argues that the fate of this legislation was not, as has been suggested, dictated by divisions created by the Irish civil war of 1922–23. Instead, this analysis concludes that the Dáil decrees faced insuperable practical barriers that could not be overcome after the foundation of the state in 1922.
This article examines the meaning of Irish “home rule” as a constitutional experiment and its relationship with other proposals for constitutional change in the British Empire of the late 19th and ...early 20th centuries. The concept of Irish home rule was seen as a major constitutional experiment and the United Kingdom had little experience of devolution or federal settlements. This article will examine the model that was finally selected for this constitutional experiment which was inspired by the constitution of the Dominion of Canada. The article will also examine the relationship between Irish home rule and other constitutional experiments. These included proposals to create a federal United Kingdom, a concept known as “home rule all round” and even a federal British Empire, a concept known as “Imperial federation”. The conclusion will assess the significance of these constitutional experiments in influencing the campaign for Irish home rule.
Endothelial cells represent major effectors in inflammation and angiogenesis, processes that drive a multitude of pathological states such as atherosclerosis and cancer. Both inflammation and ...angiogenesis are interconnected with each other in the sense that many pro-inflammatory proteins possess proangiogenic properties and vice versa. To elucidate this interplay further, we present a comparative proteome study of inflammatory and angiogenic activated endothelial cells. HUVEC were stimulated with interleukin 1-β and VEGF, respectively. Cultured primary cells were fractionated into secreted, cytoplasmic and nuclear protein fractions and processed for subsequent LC-MS/MS analysis. Obtained protein profiles were filtered for fraction-specific proteins to address potential cross fractional contamination, subjected to comparative computational biology analysis (GO-Term enrichment analysis, weighted gene co-expression analysis) and compared to published mRNA profiles of IL-1β respectively VEGF stimulated HUVEC. GO Term enrichment analysis and comparative pathway analysis revealed features such as NOD and NfkB signaling for inflammatory activated HUVEC and VEGF and ErB signaling for VEGF-activated HUVEC with potential crosstalk via map kinases MAP2K2. Weighted protein co-expression network analysis revealed several potential hub genes so far not associated with driver function in inflammation or angiogenesis such as HSPG2, ANXA3, and GPI. "Classical" inflammation or angiogenesis markers such as IL6, CXCL8 or CST1 were found in a less central position within the co-expression networks. In conclusion, this study reports a framework for the computational biology based analysis of proteomics data applied to cytoplasmic, nucleic and extracellular fractions of quiescent, inflammatory and angiogenic activated HUVEC. Novel potential hub genes relevant for these processes were successfully identified.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Groundwater contamination by cyclic ethers, 1,4-dioxane (dioxane), a probable human carcinogen, and tetrahydrofuran (THF), a co-contaminant at many chlorinated solvent release sites, are a growing ...concern. Cyclic ethers are readily transported in groundwater, yet little is known about their fate in environmental systems. High water solubility coupled with low Henry's law constants and octanol−water partition coefficients make their removal from groundwater problematic for both remedial and analytical purposes. A solid-phase extraction (SPE) method based on activated carbon disks was developed for the quantitative deter mination of dioxane and THF. The method requires 80 mL samples and a total of 1.2 mL of solvent (acetone). The number of steps is minimized due to the “in-vial” elution of the disks. Average recoveries for dioxane and THF were 98% and 95%, respectively, with precision, as indicated by the relative standard deviation of <2% to 6%. The method quantitation limits are 0.31 μg/L for dioxane and 3.1 μg/L for THF. The method was demonstrated by analyzing groundwater samples for dioxane and THF collected during a single sampling campaign at a TCA-impacted site. Dioxane concentrations and areal extent of dioxane in groundwater were greater than those of either TCA or THF.
Besides human red blood cells (RBC), a standard model used in AFM-single cell force spectroscopy (SCFS), little is known about apparent Young’s modulus (Ea) or adhesion of animal RBCs displaying ...distinct cellular features. To close this knowledge gap, we probed chicken, horse, camel, and human fetal RBCs and compared data with human adults serving as a repository for future studies. Additionally, we assessed how measurements are affected under physiological conditions (species-specific temperature in autologous plasma vs. 25 °C in aqueous NaCl solution). In all RBC types, Ea decreased with increasing temperature irrespective of the suspension medium. In mammalian RBCs, adhesion increased with elevated temperatures and scaled with reported membrane sialic acid concentrations. In chicken only adhesion decreased with higher temperature, which we attribute to the lower AE-1 concentration allowing more membrane undulations. Ea decreased further in plasma at every test temperature, and adhesion was completely abolished, pointing to functional cell enlargement by adsorption of plasma components. This halo elevated RBC size by several hundreds of nanometers, blunted the thermal input, and will affect the coupling of RBCs with the flowing plasma. The study evidences the presence of a RBC surface layer and discusses the tremendous effects when RBCs are probed at physiological conditions.
The purpose of this article is to assess the value of law journals as sources for a critical period of transition in modern Irish history. This is the years between 1916 and 1922 that witnessed the ...secession of most of the island of Ireland from the United Kingdom. The main source for this analysis is a journal known as the Irish Law Times which, in this period, was the only major law journal in existence on the island. A number of other publications, of lesser significance as historical sources, will also be included in this analysis such as the Irish Law Society Gazette, a minor publication that was exclusively aimed at Irish solicitors. The first purpose of this article is to introduce this useful source material for the years of upheaval in Ireland between 1916 and 1922 that has not previously come under close scholarly analysis. Historians and political scientists often overlook legal source material in analyses of particular historical periods. It is hoped that this interdisciplinary analysis will provide a general guide to these sources for scholars interested in particular aspects of this period of revolution. The second purpose of this analysis is to examine the response of the Irish legal professions to these important years of revolution and upheaval. This response is of wider historical interest because the Irish legal professions spanned traditional political divisions between Irish unionists, who wished to maintain links with the United Kingdom, and Irish nationalists, who wished for substantial autonomy or complete independence from the United Kingdom. Consequently, Irish law journals had to maintain a difficult balancing act between these viewpoints during a difficult period of bitter conflict.
Several pathways modulating longevity and stress resistance converge on translation by targeting ribosomal proteins or initiation factors, but whether this involves modifications of ribosomal RNA is ...unclear. Here, we show that reduced levels of the conserved RNA methyltransferase NSUN5 increase the lifespan and stress resistance in yeast, worms and flies. Rcm1, the yeast homologue of NSUN5, methylates C2278 within a conserved region of 25S rRNA. Loss of Rcm1 alters the structural conformation of the ribosome in close proximity to C2278, as well as translational fidelity, and favours recruitment of a distinct subset of oxidative stress-responsive mRNAs into polysomes. Thus, rather than merely being a static molecular machine executing translation, the ribosome exhibits functional diversity by modification of just a single rRNA nucleotide, resulting in an alteration of organismal physiological behaviour, and linking rRNA-mediated translational regulation to modulation of lifespan, and differential stress response.
This study examined data collected from U.S. public drinking water supplies in support of the recently-completed third round of the Unregulated Contaminant Monitoring Rule (UCMR3) to better ...understand the nature and occurrence of 1,4-dioxane and the basis for establishing drinking water standards. The purpose was to evaluate whether the occurrence data for this emerging but federally-unregulated contaminant fit with common conceptual models, including its persistence and the importance of groundwater contamination for potential exposure. 1,4-Dioxane was detected in samples from 21% of 4864 PWSs, and was in exceedance of the health-based reference concentration (0.35μg/L) at 6.9% of these systems. In both measures, it ranked second among the 28 UCMR3 contaminants. Although much of the focus on 1,4-dioxane has been its role as a groundwater contaminant, the detection frequency for 1,4-dioxane in surface water was only marginally lower than in groundwater (by a factor of 1.25; p<0.0001). However, groundwater concentrations were higher than those in surface water (p<0.0001) and contributed to a higher frequency of exceeding the reference concentration (by a factor of 1.8, p<0.0001), indicating that surface water sources tend to be more dilute. Sampling from large systems increased the likelihood that 1,4-dioxane was detected by a factor of 2.18 times relative to small systems (p<0.0001). 1,4-Dioxane detections in drinking water were highly associated with detections of other chlorinated compounds particularly 1,1-dichlorethane (odds ratio=47; p<0.0001), which is associated with the release of 1,4-dioxane as a chlorinated solvent stabilizer. Based on aggregated nationwide data, 1,4-dioxane showed evidence of a decreasing trend in concentration and detection frequency over time. These data suggest that the loading to drinking water supplies may be decreasing. However, in the interim, some water supply systems may need to consider improving their treatment capabilities in response to further regulatory review of this compound.
•1,4-Dioxane and other unregulated contaminants in drinking water were evaluated.•1,4-Dioxane exhibited relatively high rates of detection in public water systems.•1,4-Dioxane did not follow common assumptions about release and exposure routes.•Regulatory determinations on 1,4-dioxane will have significant implications.
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Tendinopathy, a prevalent overuse injury, lacks effective treatment options, leading to a significant impact on quality of life and socioeconomic burden. Mesenchymal stem/stromal cells (MSCs) and ...their secretome, including conditioned medium (CM) and extracellular vesicles (EVs), have shown promise in tissue regeneration and immunomodulation. However, it remains unclear which components of the secretome contribute to their therapeutic effects. This study aimed to compare the efficacy of CM, EVs, and the soluble protein fraction (PF) in treating inflamed tenocytes. CM exhibited the highest protein and particle concentrations, followed by PF and EVs. Inflammation significantly altered gene expression in tenocytes, with CM showing the most distinct separation from the inflamed control group. Treatment with CM resulted in the most significant differential gene expression, with both upregulated and downregulated genes related to inflammation and tissue regeneration. EV treatment also demonstrated a therapeutic effect, albeit to a lesser extent. These findings suggest that CM holds superior therapeutic efficacy compared with its EV fraction alone, emphasizing the importance of the complete secretome in tendon injury treatment.
OBJECTIVE:For patients in intensive care units, sepsis is a common and potentially deadly complication and prompt initiation of appropriate antimicrobial therapy improves prognosis. The objective of ...this trial was to determine whether a strategy of antimicrobial spectrum escalation, guided by daily measurements of the biomarker procalcitonin, could reduce the time to appropriate therapy, thus improving survival.
DESIGN:Randomized controlled open-label trial.
SETTING:Nine multidisciplinary intensive care units across Denmark.
PATIENTS:A total of 1,200 critically ill patients were included after meeting the following eligibility requirementsexpected intensive care unit stay of ≥24 hrs, nonpregnant, judged to not be harmed by blood sampling, bilirubin <40 mg/dL, and triglycerides <1000 mg/dL (not suspensive).
INTERVENTIONS:Patients were randomized either to the “standard-of-care-only arm,” receiving treatment according to the current international guidelines and blinded to procalcitonin levels, or to the “procalcitonin arm,” in which current guidelines were supplemented with a drug-escalation algorithm and intensified diagnostics based on daily procalcitonin measurements.
MEASUREMENTS AND MAIN RESULTS:The primary end point was death from any cause at day 28; this occurred for 31.5% (190 of 604) patients in the procalcitonin arm and for 32.0% (191 of 596) patients in the standard-of-care-only arm (absolute risk reduction, 0.6%; 95% confidence interval CI −4.7% to 5.9%). Length of stay in the intensive care unit was increased by one day (p = .004) in the procalcitonin arm, the rate of mechanical ventilation per day in the intensive care unit increased 4.9% (95% CI, 3.0–6.7%), and the relative risk of days with estimated glomerular filtration rate <60 mL/min/1.73 m was 1.21 (95% CI, 1.15–1.27).
CONCLUSIONS:Procalcitonin-guided antimicrobial escalation in the intensive care unit did not improve survival and did lead to organ-related harm and prolonged admission to the intensive care unit. The procalcitonin strategy like the one used in this trial cannot be recommended.
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