Apple production potential in Interior Alaska within a state of amplified climatic change

Master's Project (M.N.R.E.) University of Alaska Fairbanks, 2021Successful apple (Malus Domestica) tree and fruit growing have been ongoing in Alaska for over 100 years. At the outset, crabapples were the only varieties produced, but as agriculturalists, orchardists, and farmers began to experiment with grafting coldhardy rootstock with scions, new cultivars began to emerge, with varying degrees of success, throughout the state. In addition to experimental cultivars, the climate began to change, with an overall warming trend emerging. Together these variables could be the winning combination to large-scale apple orchards being started in the state of Alaska. More fruit production in the state would strengthen both the small agricultural industry and the state’s food security posture. If raw fruit products can be produced, then possibly other related business and commerce will become possible, such as production of apple cider, apple sauce, fruit leather, and preserves. The state of Washington, particularly the Eastern side, has prime apple-growing weather and climate. Of all the states, Washington produces the most apples annually. The national top ten most consumed apples are grown there. The Eastern Washington climatic region was chosen for comparison and a point of reference versus the projected interior Alaska region climate. Long-season, later-harvest apples are grown in Eastern Washington, but not in Alaska. This type of apple is valuable and desirable due to its potential for stable, long-term storage. Currently, Alaska-grown apples can be of high quality but are smaller to medium-sized, in general, and not conducive to long-term storage. Long-term storage compatible apples are desirable because that trait makes year-round apple eating possible. The purpose of this research project is to evaluate whether longer growing seasons, due to climate change, will potentially allow production, in interior Alaska, of late season apples. The analysis approach includes a combination of personal observations, literature review, climatic modeling, evaluation, and synthesis of data from multiple sources. Climatic trends and data from both past and future years were examined. Environmental variables such as atmospheric temperatures, precipitation, first and last frost dates, plant hardiness zones, and growing degree days were included in the analysis. It was found that within the next two to three decades, or sooner, with some model predictions, that the interior Alaska climate will be approaching that of Eastern Washington, although still cooler in both the winter and summer. Nevertheless, hardiness zone compatibility indicates that interior Alaska will have a climate that is conducive to growing both the shorter season apples (generally used for cider) and later-harvest, long-term storage apple varieties (mainly used for direct consumption). Interior Alaska average annual air temperatures have been slowly but steadily climbing over time, with increases evident year-round. Precipitation has also been found to be increasing, with rain in some locations during the winter (where previously there was no rainfall) melting the snow and affecting the snow coverage of an area. Rainfall has been increasing in the shoulder seasons too, affecting the growing season. Evapotranspiration has also been projected to increase, potentially nullifying the benefit of increased precipitation for natural crop irrigation purposes. With permafrost also degrading statewide, soil conditions may naturally get drier. Irrigation and on-farm water storage may prove to be a short-term method to overcome more arid environmental conditions

Effect of remote ischaemic conditioning on clinical outcomes in patients with acute myocardial infarction (CONDI-2/ERIC-PPCI): a single-blind randomised controlled trial.

BACKGROUND: Remote ischaemic conditioning with transient ischaemia and reperfusion applied to the arm has been shown to reduce myocardial infarct size in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). We investigated whether remote ischaemic conditioning could reduce the incidence of cardiac death and hospitalisation for heart failure at 12 months. METHODS: We did an international investigator-initiated, prospective, single-blind, randomised controlled trial (CONDI-2/ERIC-PPCI) at 33 centres across the UK, Denmark, Spain, and Serbia. Patients (age >18 years) with suspected STEMI and who were eligible for PPCI were randomly allocated (1:1, stratified by centre with a permuted block method) to receive standard treatment (including a sham simulated remote ischaemic conditioning intervention at UK sites only) or remote ischaemic conditioning treatment (intermittent ischaemia and reperfusion applied to the arm through four cycles of 5-min inflation and 5-min deflation of an automated cuff device) before PPCI. Investigators responsible for data collection and outcome assessment were masked to treatment allocation. The primary combined endpoint was cardiac death or hospitalisation for heart failure at 12 months in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02342522) and is completed. FINDINGS: Between Nov 6, 2013, and March 31, 2018, 5401 patients were randomly allocated to either the control group (n=2701) or the remote ischaemic conditioning group (n=2700). After exclusion of patients upon hospital arrival or loss to follow-up, 2569 patients in the control group and 2546 in the intervention group were included in the intention-to-treat analysis. At 12 months post-PPCI, the Kaplan-Meier-estimated frequencies of cardiac death or hospitalisation for heart failure (the primary endpoint) were 220 (8·6%) patients in the control group and 239 (9·4%) in the remote ischaemic conditioning group (hazard ratio 1·10 [95% CI 0·91-1·32], p=0·32 for intervention versus control). No important unexpected adverse events or side effects of remote ischaemic conditioning were observed. INTERPRETATION: Remote ischaemic conditioning does not improve clinical outcomes (cardiac death or hospitalisation for heart failure) at 12 months in patients with STEMI undergoing PPCI. FUNDING: British Heart Foundation, University College London Hospitals/University College London Biomedical Research Centre, Danish Innovation Foundation, Novo Nordisk Foundation, TrygFonden

A comparison between 2010 and 2006 air quality and meteorological conditions, and emissions and boundary conditions used in simulations of the AQMEII-2 North American domain

Several participants in Phase 2 of the Air Quality Model Evaluation International Initiative (AQMEII-2) who are applying coupled models to the North American domain are comparing model results for two years, 2006 and 2010, with the goal of performing dynamic model evaluation. From a modeling perspective, the differences of interest are the large reductions in domain total emissions of NOx (21%) and SO2 (37%) from 2006 to 2010 and significant differences in meteorological conditions between these two years. The emission reductions occurred mostly in the eastern U.S, with some reduction in emissions from western wildfires in 2010. Differences in meteorological conditions both confound the impact of emission reductions on ambient air quality and provide an opportunity to examine how models respond to changing meteorology. This study is aimed at documenting changes in emissions, modeled large-scale background concentrations used as boundary conditions for the regional models, and observed meteorology and air quality to provide a context for the dynamic model evaluation studies performed within AQMEII-2. In addition to warmer summer temperatures, conditions in the eastern U.S. summer of 2010 were characterized by less precipitation than in 2006, while western portions of the U.S. and Canada were much cooler in 2010 due to a strengthening of the thermal trough over the Southwest and associated onshore flow. Summer ozone levels in many portions of the Northeast and Midwest were largely unchanged in 2010 despite reductions in precursor emissions. Normalization of the ozone trend, to account for differences in meteorological conditions, including warmer summer temperatures in 2010, shows that the emission reductions would have resulted in lower ozone levels at these locations if not for the countervailing influence of meteorological conditions. Winter mean surface temperatures were generally above average in 2006 whereas below average temperatures were noted in the Southeast and northern plains in 2010, consistent with a greater frequency of cold arctic air outbreaks. In general, changes in observed air quality as measured at U.S. monitoring sites appear to be consistent with differences in emissions and meteorological conditions between 2006 and 2010. Two potential inconsistencies were noted which warrant further investigation: 1) an increase in particulate nitrate during the winter in the Midwest despite lower emissions of NOx and 2) lower than expected SO2 reductions in the Southeast during the winter

Uridine Depletion and Chemical Modification Increase Cas9 mRNA Activity and Reduce Immunogenicity without HPLC Purification

The Cas9/guide RNA (Cas9/gRNA) system is commonly used for genome editing. mRNA expressing Cas9 can induce innate immune responses, reducing Cas9 expression. First-generation Cas9 mRNAs were modified with pseudouridine and 5-methylcytosine to reduce innate immune responses. We combined four approaches to produce more active, less immunogenic second-generation Cas9 mRNAs. First, we developed a novel co-transcriptional capping method yielding natural Cap 1. Second, we screened modified nucleotides in Cas9 mRNA to identify novel modifications that increase Cas9 activity. Third, we depleted the mRNA of uridines to improve mRNA activity. Lastly, we tested high-performance liquid chromatography (HPLC) purification to remove double-stranded RNAs. The activity of these mRNAs was tested in cell lines and primary human CD34+ cells. Cytokines were measured in whole blood and mice. These approaches yielded more active and less immunogenic mRNA. Uridine depletion (UD) most impacted insertion or deletion (indel) activity. Specifically, 5-methoxyuridine UD induced indel frequencies as high as 88% (average ± SD = 79% ± 11%) and elicited minimal immune responses without needing HPLC purification. Our work suggests that uridine-depleted Cas9 mRNA modified with 5-methoxyuridine (without HPLC purification) or pseudouridine may be optimal for the broad use of Cas9 both in vitro and in vivo. Keywords: mRNA, capping, Cas9, innate immunity, CRISPR, CleanCap, mRNA, uridine depletion, ARCA, Cap