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Endothelin-1 (ET-1) is elevated in patients with systemic lupus erythematosus (SLE), an autoimmune disease characterized by high rates of hypertension, renal injury, and cardiovascular disease. SLE is also associated with increased prevalence of obesity and insulin resistance compared to the general population. In the present study, we tested the hypothesis that elevated ET-1 in SLE is contributes to obesity and insulin resistance. For these studies, we used the NZBWF1 mouse model of SLE, which develops obesity and insulin resistance on a normal chow diet. To test this hypothesis, we treated control (NZW) and SLE (NZBWF1) mice with vehicle, atrasentan (ET

The fungal kingdom represents an extraordinary diversity of organisms with profound impacts across animal, plant, and ecosystem health. Fungi simultaneously support life, by forming beneficial symbioses with plants and producing life-saving medicines, and bring death, by causing devastating diseases in humans, plants, and animals. With climate change, increased antimicrobial resistance, global trade, environmental degradation, and novel viruses altering the impact of fungi on health and disease, developing new approaches is now more crucial than ever to combat the threats posed by fungi and to harness their extraordinary potential for applications in human health, food supply, and environmental remediation. To address this aim, the Canadian Institute for Advanced Research (CIFAR) and the Burroughs Wellcome Fund convened a workshop to unite leading experts on fungal biology from academia and industry to strategize innovative solutions to global challenges and fungal threats. This report provides recommendations to accelerate fungal research and highlights the major research advances and ideas discussed at the meeting pertaining to 5 major topics: (1) Connections between fungi and climate change and ways to avert climate catastrophe; (2) Fungal threats to humans and ways to mitigate them; (3) Fungal threats to agriculture and food security and approaches to ensure a robust global food supply; (4) Fungal threats to animals and approaches to avoid species collapse and extinction; and (5) Opportunities presented by the fungal kingdom, including novel medicines and enzymes.

The first meeting of the CIFAR Fungal Kingdom: Threats & Opportunities research program saw the congregation of experts on fungal biology to address the most pressing threats fungi pose to global health, agriculture, and biodiversity. This report covers the research discussed during the meeting and the advancements made toward mitigating the devastating impact of fungi on plants, animals, and humans.

Using the Parker Solar Probe FIELDS bandpass-filter data and SWEAP electron data from Encounters 1 through 9, we show statistical properties of narrowband whistlers from ∼16 R s to ∼130 R s, and compare wave occurrence to electron properties including beta, temperature anisotropy, and heat flux. Whistlers are very rarely observed inside ∼28 R s (∼0.13 au). Outside 28 R s, they occur within a narrow range of parallel electron beta from ∼1 to 10, and with a beta-heat flux occurrence consistent with the whistler heat flux fan instability. Because electron distributions inside ∼30 R s display signatures of the ambipolar electric field, the lack of whistlers suggests that the modification of the electron distribution function associated with the ambipolar electric field or changes in other plasma properties must result in lower instability limits for the other modes (including the observed solitary waves and ion acoustic waves) that are observed close to the Sun. The lack of narrowband whistler-mode waves close to the Sun and in regions of either low (10) beta is also significant for the understanding and modeling of the evolution of flare-accelerated electrons and the regulation of heat flux in astrophysical settings including other stellar winds, the interstellar medium, accretion disks, and the intragalaxy cluster medium.

SUMMARY Evasion of killing by immune cells is crucial for fungal survival in the host. For the human fungal pathogen Candida albicans, internalization by macrophages induces a transition from yeast to filaments that promotes macrophage death and fungal escape. Nutrient deprivation, alkaline pH, and oxidative stress have been implicated as triggers of intraphagosomal filamentation; however, the impact of other host-derived factors remained unknown. Here, we show that lysates prepared from macrophage-like cell lines and primary macrophages robustly induce C. albicans filamentation. Enzymatic treatment of lysate implicates a phosphorylated protein, and bioactivity-guided fractionation coupled to mass spectrometry identifies the immunomodulatory phosphoprotein PTMA as a candidate trigger of C. albicans filamentation. Immunoneutralization of PTMA within lysate abolishes its activity, strongly supporting PTMA as a filament-inducing component of macrophage lysate. Adding to the known repertoire of physical factors, this work implicates a host protein in the induction of C. albicans filamentation within immune cells., Graphical Abstract, In brief The human fungal pathogen Candida albicans filaments within host macrophages, enabling its escape. Case et al. demonstrate that lysates prepared from macrophage-like cell lines and primary macrophages induce C. albicans filamentation and implicate the immunomodulatory protein prothymosin alpha (PTMA) as a trigger of filamentation produced by host immune cells.

Observations of plasma waves by the Fields Suite and of electrons by the Solar Wind Electrons Alphas and Protons Investigation (SWEAP) on Parker Solar Probe provide strong evidence for pitch angle scattering of strahl-energy electrons by narrowband whistler-mode waves at radial distances less than ~0.3 AU. We present two example intervals of a few hours that include 8 waveform captures with whistler-mode waves and 26 representative electron distributions that are examined in detail. Two were narrow; 17 were clearly broadened, and 8 were very broad. The two with narrow strahl occurred when there were either no whistlers or very intermittent low amplitude waves. Six of the eight broadest distributions were associated with intense, long duration waves. Approximately half of the observed electron distributions have features consistent with an energy dependent scattering mechanism, as would be expected from interactions with narrowband waves. A comparison of the wave power in the whistler-mode frequency band to pitch angle width and a measure of anisotropy provides additional evidence for the electron scattering by whistler-mode waves. The pitch angle broadening occurs in over an energy range comparable to that obtained for the n=1 (co-streaming) resonance for the observed wave and plasma parameters. The additional observation that the heat flux is lower in the interval with multiple switchbacks may provide clues to the nature of switchbacks. These results provide strong evidence that the heat flux is reduced by narroweband whistler-mode waves scattering of strahl-energy electrons., 19 pages, 4 figures, 1 table

Aims.Large amplitude narrowband obliquely propagating whistler-mode waves at frequencies of ~0.2fce(electron cyclotron frequency) are commonly observed at 1 AU, and they are most consistent with the whistler heat flux fan instability. We want to determine whether similar whistler-mode waves occur inside 0.3 AU and how their properties compare to those at 1 AU.Methods.We utilized the waveform capture data from the Parker Solar Probe Fields instrument from Encounters 1 through 4 to develop a data base of narrowband whistler waves. The Solar Wind Electrons Alphas and Protons Investigation (SWEAP) instrument, in conjunction with the quasi-thermal noise measurement from Fields, provides the electron heat flux, beta, and other electron parameters.Results.Parker Solar Probe observations inside ~0.3 AU show that the waves are often more intermittent than at 1 AU, and they are interspersed with electrostatic whistler-Bernstein waves at higher-frequencies. This is likely due to the more variable solar wind observed closer to the Sun. The whistlers usually occur within regions when the magnetic field is more variable and often with small increases in the solar wind speed. The near-Sun whistler-mode waves are also narrowband and large amplitude, and they are associated with beta greater than 1. The association with heat flux and beta is generally consistent with the whistler fan instability. Strong scattering of strahl energy electrons is seen in association with the waves, providing evidence that the waves regulate the electron heat flux.

Display Omitted We introduce a semantic delta methodology for analyzing change in SNOMED CT.Two change analysis techniques are combined into one comprehensive methodology.Changes to sets of concepts are summarized and visualized.Changes in SNOMED CT's Bacterial infectious disease subhierarchy are analyzed. Thousands of changes are applied to SNOMED CTs concepts during each release cycle. These changes are the result of efforts to improve or expand the coverage of health domains in the terminology. Understanding which concepts changed, how they changed, and the overall impact of a set of changes is important for editors and end users. Each SNOMED CT release comes with delta files, which identify all of the individual additions and removals of concepts and relationships. These files typically contain tens of thousands of individual entries, overwhelming users. They also do not identify the editorial processes that were applied to individual concepts and they do not capture the overall impact of a set of changes on a subhierarchy of concepts.In this paper we introduce a methodology and accompanying software tool called a SNOMED CT Visual Semantic Delta (semantic delta for short) to enable a comprehensive review of changes in SNOMED CT. The semantic delta displays a graphical list of editing operations that provides semantics and context to the additions and removals in the delta files. However, there may still be thousands of editing operations applied to a set of concepts. To address this issue, a semantic delta includes a visual summary of changes that affected sets of structurally and semantically similar concepts. The software tool for creating semantic deltas offers views of various granularities, allowing a user to control how much change information they view. In this tool a user can select a set of structurally and semantically similar concepts and review the editing operations that affected their modeling. The semantic delta methodology is demonstrated on SNOMED CTs Bacterial infectious disease subhierarchy, which has undergone a significant remodeling effort over the last two years.

Objective: Quality assurance of large ontological systems such as SNOMED CT is an indispensable part of the terminology management lifecycle. We introduce a hybrid structural-lexical method for scalable and systematic discovery of missing hierarchical relations and concepts in SNOMED CT. Material and Methods: All non-lattice subgraphs (the structural part) in SNOMED CT are exhaustively extracted using a scalable MapReduce algorithm. Four lexical patterns (the lexical part) are identified among the extracted non-lattice subgraphs. Non-lattice subgraphs exhibiting such lexical patterns are often indicative of missing hierarchical relations or concepts. Each lexical pattern is associated with a potential specific type of error. Results: Applying the structural-lexical method to SNOMED CT (September 2015 US edition), we found 6801 non-lattice subgraphs that matched these lexical patterns, of which 2046 were amenable to visual inspection. We evaluated a random sample of 100 small subgraphs, of which 59 were reviewed in detail by domain experts. All the subgraphs reviewed contained errors confirmed by the experts. The most frequent type of error was missing is-a relations due to incomplete or inconsistent modeling of the concepts. Conclusions: Our hybrid structural-lexical method is innovative and proved effective not only in detecting errors in SNOMED CT, but also in suggesting remediation for these errors.

A miniaturized antipodal Vivaldi antenna to operate from 1 to 30 GHz is designed for nondestructive testing and evaluation of construction materials, such as concrete, polymers, and dielectric composites. A step-by-step procedure has been employed to design and optimize performance of the proposed antenna. First, a conventional antipodal Vivaldi antenna (CAVA) is designed as a reference. Second, the CAVA is shortened to have a small size of the CAVA. Third, to extend the low end of frequency band, the inner edges of the top and bottom radiators of the shortened CAVA have been bent. To enhance gain at lower frequencies, regular slit edge technique is employed. Finally, a half elliptical-shaped dielectric lens as an extension of the antenna substrate is added to the antenna to feature high gain and front-to-back ratio. A prototype of the antenna is employed as a part of the microwave imaging system to detect voids inside concrete specimen. High-range resolution images of voids are achieved by applying synthetic aperture radar algorithm.

A small antipodal Vivaldi antenna with rectangular slits at sun-shaped configuration and a half elliptical-shaped dielectric lens is designed for microwave and millimeter-wave imaging applications. The slits are developed to extend low end of frequency band and increase antenna gain at lower frequencies, while the lens is applied to this antenna to feature high gain at higher frequencies, high front-to-back ratio, low sidelobe and cross-polarization levels, narrow half-power beamwidth, and modification on E-plane tilt of beam. A prototype of the antenna with small size of 30 × 55 × 0.508 mm3 is fabricated and employed as a part of microwave and millimeter-wave imaging system. Applicability of the proposed antenna for 3-D and 2-D images of targets such as rubber discs and metal rods at different depths inside construction materials including foam and plasterboard sheet-layered structures is demonstrated. High-range resolution images are achieved by applying synthetic aperture radar algorithm.

SNOMED CT is a large, complex and widely-used terminology. Auditing is part of the life cycle of terminologies. A review of terminologies’ content can identify two error categories: commission errors, such as an incorrect parent or attribute relationship, indicating errors in a concept’s modeling, and omission errors, such as missing a parent or attribute relationship, representing incomplete modeling of a concept. According to our experience, terminology curators are mostly interested in commission errors. In recent years, a long-term remodeling project has addressed modeling issues in SNOMED CT’s Infectious disease and Congenital disease subhierarchies. In this longitudinal study, we investigated a posteriori the efficacy of complex concepts, called overlapping concepts, to identify commission errors during intensive auditing periods and during maintenance periods over several releases. The algorithmic implication is that when auditing resources are scarce, a methodology of auditing first, or only, the overlapping concepts will obtain a higher auditing yield.