227 research outputs found

    A rule based expert system to advise on air-filtering plants for indoor spaces in UAE

    Get PDF
    The purpose of this study was the development of an expert system that is able to recommend types of plants for the removal of toxic substances in a given artificial ecosystem. The domain was restricted to office environments within the United Arab Emirates (UAE). A literature review revealed a significant gap in research related to systems that help select plants based on a given environment. This eventually led to the creation of the Plant Recommender Expert System (PRES). PRES utilizes a set of inputs (for example expected humidity, average temperature, light quality, etc.). The system will then recommend the type(s) of plants that should be purchased to suit the given environment conditions. Horticultural experts usually give recommendations for these types of problem domains but such an expert may not always be available, and so the concept here is to encode the expertise knowledge in an intelligent system to ensure uninterrupted availability of the expert knowledge. The system was evaluated using several case studies with known outcomes. The PRES suggested plants for environments that were described via a set of inputs in these trials. The initial phase, being a prototype of PRES was created with the aim of helping non-expert users leverage the natural air-detoxification properties of plants. While in its current configuration the system is not capable of learning, it can at a later stage be integrated with other AI methods such as the use of decision trees to create further rules or data driven approaches such as the use of Neural Networks for the classification of plants relevant to a given domain. However, the latter approach will first necessitate the creation of a relevant data set

    National trends in emergency conditions through the Omicron COVID-19 wave in commercial and Medicare Advantage enrollees

    Get PDF
    Objective: To evaluate trends in emergency care sensitive conditions (ECSCs) from pre-COVID (March 2018–February 2020) through Omicron (December 2021–February 2022). Methods: This cross-sectional analysis evaluated trends in ECSCs using claims (OptumLabs Data Warehouse) from commercial and Medicare Advantage enrollees. Emergency department (ED) visits for ECSCs (acute appendicitis, aortic aneurysm/dissection, cardiac arrest/severe arrhythmia, cerebral infarction, myocardial infarction, pulmonary embolism, opioid overdose, pre-eclampsia) were reported per 100,000 person months from March 2018 to February 2022 by pandemic wave. We calculated the percent change for each pandemic wave compared to the pre-pandemic period. Results: There were 10,268,554 ED visits (March 2018−February 2022). The greatest increases in ECSCs were seen for pulmonary embolism, cardiac arrest/severe arrhythmia, myocardial infarction, and pre-eclampsia. For commercial enrollees, pulmonary embolism visit rates increased 22.7% (95% confidence interval [CI], 18.6%–26.9%) during Waves 2−3, 37.2% (95% CI, 29.1%–45.8%] during Delta, and 27.9% (95% CI, 20.3%–36.1%) during Omicron, relative to pre-pandemic rates. Cardiac arrest/severe arrhythmia visit rates increased 4.0% (95% CI, 0.2%–8.0%) during Waves 2−3; myocardial infarction rates increased 4.9% (95% CI, 2.1%–7.8%) during Waves 2−3. Similar patterns were seen in Medicare Advantage enrollees. Pre-eclampsia visit rates among reproductive-age female enrollees increased 31.1% (95% CI, 20.9%–42.2%), 23.7% (95% CI, 7.5%,–42.3%), and 34.7% (95% CI, 16.8%–55.2%) during Waves 2−3, Delta, and Omicron, respectively. ED visits for other ECSCs declined or exhibited smaller increases. Conclusions: ED visit rates for acute cardiovascular conditions, pulmonary embolism and pre-eclampsia increased despite declines or stable rates for all-cause ED visits and ED visits for other conditions. Given the changing landscape of ECSCs, studies should identify drivers for these changes and interventions to mitigate them

    Nonexistence of marginally trapped surfaces and geons in 2+1 gravity

    Full text link
    We use existence results for Jang's equation and marginally outer trapped surfaces (MOTSs) in 2+1 gravity to obtain nonexistence of geons in 2+1 gravity. In particular, our results show that any 2+1 initial data set, which obeys the dominant energy condition with cosmological constant \Lambda \geq 0 and which satisfies a mild asymptotic condition, must have trivial topology. Moreover, any data set obeying these conditions cannot contain a MOTS. The asymptotic condition involves a cutoff at a finite boundary at which a null mean convexity condition is assumed to hold; this null mean convexity condition is satisfied by all the standard asymptotic boundary conditions. The results presented here strengthen various aspects of previous related results in the literature. These results not only have implications for classical 2+1 gravity but also apply to quantum 2+1 gravity when formulated using Witten's solution space quantization.Comment: v3: Elements from the original two proofs of the main result have been combined to give a single proof, thereby circumventing an issue with the second proof associated with potential blow-ups of solutions to Jang's equation. To appear in Commun. Math. Phy

    Mutations of the BRAF gene in human cancer

    Get PDF
    Cancers arise owing to the accumulation of mutations in critical genes that alter normal programmes of cell proliferation, differentiation and death. As the first stage of a systematic genome-wide screen for these genes, we have prioritized for analysis signalling pathways in which at least one gene is mutated in human cancer. The RAS RAF MEK ERK MAP kinase pathway mediates cellular responses to growth signals. RAS is mutated to an oncogenic form in about 15% of human cancer. The three RAF genes code for cytoplasmic serine/threonine kinases that are regulated by binding RAS. Here we report BRAF somatic missense mutations in 66% of malignant melanomas and at lower frequency in a wide range of human cancers. All mutations are within the kinase domain, with a single substitution (V599E) accounting for 80%. Mutated BRAF proteins have elevated kinase activity and are transforming in NIH3T3 cells. Furthermore, RAS function is not required for the growth of cancer cell lines with the V599E mutation. As BRAF is a serine/threonine kinase that is commonly activated by somatic point mutation in human cancer, it may provide new therapeutic opportunities in malignant melanoma

    Origins of the Ambient Solar Wind: Implications for Space Weather

    Full text link
    The Sun's outer atmosphere is heated to temperatures of millions of degrees, and solar plasma flows out into interplanetary space at supersonic speeds. This paper reviews our current understanding of these interrelated problems: coronal heating and the acceleration of the ambient solar wind. We also discuss where the community stands in its ability to forecast how variations in the solar wind (i.e., fast and slow wind streams) impact the Earth. Although the last few decades have seen significant progress in observations and modeling, we still do not have a complete understanding of the relevant physical processes, nor do we have a quantitatively precise census of which coronal structures contribute to specific types of solar wind. Fast streams are known to be connected to the central regions of large coronal holes. Slow streams, however, appear to come from a wide range of sources, including streamers, pseudostreamers, coronal loops, active regions, and coronal hole boundaries. Complicating our understanding even more is the fact that processes such as turbulence, stream-stream interactions, and Coulomb collisions can make it difficult to unambiguously map a parcel measured at 1 AU back down to its coronal source. We also review recent progress -- in theoretical modeling, observational data analysis, and forecasting techniques that sit at the interface between data and theory -- that gives us hope that the above problems are indeed solvable.Comment: Accepted for publication in Space Science Reviews. Special issue connected with a 2016 ISSI workshop on "The Scientific Foundations of Space Weather." 44 pages, 9 figure

    XFEL structures of the human MT2 melatonin receptor reveal the basis of subtype selectivity

    Get PDF
    The human MT1 and MT2 melatonin receptors1,2 are G-protein-coupled receptors (GPCRs) that help to regulate circadian rhythm and sleep patterns3. Drug development efforts have targeted both receptors for the treatment of insomnia, circadian rhythm and mood disorders, and cancer3, and MT2 has also been implicated in type 2 diabetes4,5. Here we report X-ray free electron laser (XFEL) structures of the human MT2 receptor in complex with the agonists 2-phenylmelatonin (2-PMT) and ramelteon6 at resolutions of 2.8 Å and 3.3 Å, respectively, along with two structures of function-related mutants: H2085.46A (superscripts represent the Ballesteros–Weinstein residue numbering nomenclature7) and N862.50D, obtained in complex with 2-PMT. Comparison of the structures of MT2 with a published structure8 of MT1 reveals that, despite conservation of the orthosteric ligand-binding site residues, there are notable conformational variations as well as differences in [3H]melatonin dissociation kinetics that provide insights into the selectivity between melatonin receptor subtypes. A membrane-buried lateral ligand entry channel is observed in both MT1 and MT2, but in addition the MT2 structures reveal a narrow opening towards the solvent in the extracellular part of the receptor. We provide functional and kinetic data that support a prominent role for intramembrane ligand entry in both receptors, and suggest that there might also be an extracellular entry path in MT2. Our findings contribute to a molecular understanding of melatonin receptor subtype selectivity and ligand access modes, which are essential for the design of highly selective melatonin tool compounds and therapeutic agents. © 2019, The Author(s), under exclusive licence to Springer Nature Limited

    Structural basis of ligand recognition at the human MT1 melatonin receptor

    Get PDF
    Melatonin (N-acetyl-5-methoxytryptamine) is a neurohormone that maintains circadian rhythms1 by synchronization to environmental cues and is involved in diverse physiological processes2 such as the regulation of blood pressure and core body temperature, oncogenesis, and immune function3. Melatonin is formed in the pineal gland in a light-regulated manner4 by enzymatic conversion from 5-hydroxytryptamine (5-HT or serotonin), and modulates sleep and wakefulness5 by activating two high-affinity G-protein-coupled receptors, type 1A (MT1) and type 1B (MT2)3,6. Shift work, travel, and ubiquitous artificial lighting can disrupt natural circadian rhythms; as a result, sleep disorders affect a substantial population in modern society and pose a considerable economic burden7. Over-the-counter melatonin is widely used to alleviate jet lag and as a safer alternative to benzodiazepines and other sleeping aids8,9, and is one of the most popular supplements in the United States10. Here, we present high-resolution room-temperature X-ray free electron laser (XFEL) structures of MT1 in complex with four agonists: the insomnia drug ramelteon11, two melatonin analogues, and the mixed melatonin–serotonin antidepressant agomelatine12,13. The structure of MT2 is described in an accompanying paper14. Although the MT1 and 5-HT receptors have similar endogenous ligands, and agomelatine acts on both receptors, the receptors differ markedly in the structure and composition of their ligand pockets; in MT1, access to the ligand pocket is tightly sealed from solvent by extracellular loop 2, leaving only a narrow channel between transmembrane helices IV and V that connects it to the lipid bilayer. The binding site is extremely compact, and ligands interact with MT1 mainly by strong aromatic stacking with Phe179 and auxiliary hydrogen bonds with Asn162 and Gln181. Our structures provide an unexpected example of atypical ligand entry for a non-lipid receptor, lay the molecular foundation of ligand recognition by melatonin receptors, and will facilitate the design of future tool compounds and therapeutic agents, while their comparison to 5-HT receptors yields insights into the evolution and polypharmacology of G-protein-coupled receptors

    Publisher Correction: Structural basis of ligand recognition at the human MT1 melatonin receptor (Nature, (2019), 569, 7755, (284-288), 10.1038/s41586-019-1141-3)

    Get PDF
    Change history: In this Letter, the rotation signs around 90°, 135° and 15° were missing and in the HTML, Extended Data Tables 2 and 3 were the wrong tables; these errors have been corrected online. © 2019, The Author(s), under exclusive licence to Springer Nature Limited
    • 

    corecore