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Infection with SARS-CoV-2 causes COVID-19 and has a well-established set of clinical symptoms. Olfactory and gustatory dysfunction are among the non-life threatening sequalae observed with both acute and chronic SARS-CoV-2 infection. This can lead to the loss of taste and smell and has been observed in large subsets of COVID-19 patients. Although non-life threatening, loss of taste and smell can contribute to decreased quality of life and prevent sufficient nutrient intake, which may negatively affect prognosis and recovery. Despite progress in the treatment of other symptoms caused by COVID-19, there are currently no standardized treatment protocols to mitigate loss of taste and smell caused by SARS-CoV-2 infection and most approaches thus far have evaluated sensory training and regimen-based treatment strategies independently. In this retrospective case series, we demonstrate the effectiveness of a comprehensive, combined treatment protocol for COVID-19-induced taste and smell dysfunction using olfactory and gustatory training in combination with vitamins and supplements, nasal irrigations, nerve stimulation exercises, and anti-inflammatory prophylaxis. Acutely infected patients with COVID-19-related loss of taste and smell were given a daily regimen of zinc, vitamin A, B-complex, vitamin D, and alpha lipoic acid in addition to saline nasal irrigation, fluticasone spray, nerve stimulation exercises, and repeated olfactory-gustatory training. Triamcinalone paste, theophylline, and prednisone were included daily with the observation of partial recovery. At two timepoints over approximately 20–37 days of treatment, taste and smell scores were quantified based on detection of agents included on each sensory training panel. Following this novel and comprehensive “Training ‘N’ Treatment” (TNT) protocol, every patient exhibited a complete recovery of taste and smell. Given the potential to provide relief to the many people with olfactory and gustatory dysfunction following SARS-CoV-2 infection, the effectiveness of this protocol warrants validation in a larger study.

Background/PurposeDistinct, disease-associated intracellular miRNA (miR) expression profiles have been identified from peripheral blood mononuclear cells (PBMCs) of systemic lupus erythematous (SLE) patients. We have previously demonstrated novel estrogenic responses in PBMCs from SLE patients and discovered that estrogen lowers the threshold of immune cell activation to a greater extent in females, including significant upregulation of toll-like receptor (TLR)7 and TLR8 expression. TLR7 and TLR8 bind viral-derived single-stranded RNA to stimulate innate inflammatory responses, but recent studies have shown that miR-21, mir-29a, and miR-29b can also bind and activate these receptors when packaged and secreted in extracellular vesicles (EVs).ObjectiveThe objective of this study was to characterize the estrogen-mediated immunomodulatory effects of distinct EV-encapsulated miR profiles in SLE and evaluate the potential therapeutic approach of miR inhibition in a humanized mouse model.MethodsSLE patients meeting revised ACR guidelines and age/sex-matched healthy controls provided informed consent to participate in this IRB-approved study. Plasma-derived EVs were isolated by differential ultracentrifugation and quantified. PBMCs were isolated from whole blood and cultured in hormone free conditions before stimulation with 17β-estradiol (estrogen; E2). RNA was isolated following E2 stimulation or EV isolation and bulk RNA-sequencing (RNAseq) reads were analyzed. Additionally, PBMCs from active SLE patients were injected into immunodeficient mice to produce chimeras. Prior to transfer, the PBMCs were incubated with liposomal EVs containing complementary locked nucleic acid (LNA) antagonists to miR-21, mir-29a, and miR-29b. After three weeks, blood was collected for both immunophenotyping and cytokine analysis and tissue was harvested for histopathological examination.ResultsEVs were found to be increased in the plasma of SLE patients and differentially expressed EV-derived miR profiles were detected compared to healthy controls, including miR-21, mir-29a, and miR-29b. E2 stimulation of PBMCs identified upregulated pathways involved in miR transcription/processing. Specifically, small RNA binding proteins and synthesis enzymes demonstrated significant signaling pathway association and upregulation with E2 treatment. Human immune cell subtypes were successfully recovered from whole blood of chimeric mice at similar levels with and without miR inhibition, but levels of human IL-6, IL-1β, IL-4, and TNF-α were significantly reduced by the LNA antagonists. Moreover, miR antagonists significantly reduced histopathological infiltrates in the small intestine, liver, and kidney, as demonstrated by H&E-stained tissue sections and immunohistochemistry measuring human CD3.ConclusionThese data suggest E2-mediated regulation of miR synthesis and demonstrate distinct EV-derived small RNA signatures representing SLE-associated biomarkers. Targeting upregulated EV-encapsulated miR signaling by antagonizing miRs that may bind to TLR7 and TLR8 reveals a novel therapeutic opportunity to suppress autoimmune-mediated inflammation and pathogenesis in SLE.

Antiviral therapeutics to treat SARS-CoV-2 are much desired for the on-going pandemic. A well-precedented viral enzyme is the main protease (MPro), which is now targeted by an approved drug and by several investigational drugs. With the inevitable liabilities of these new drugs, and facing viral resistance, there remains a call for new chemical scaffolds against MPro. We virtually docked 1.2 billion non-covalent and a new library of 6.5 million electrophilic molecules against the enzyme structure. From these, 29 non-covalent and 11 covalent inhibitors were identified in 37 series, the most potent having an IC50 of 29 μM and 20 μM, respectively. Several series were optimized, resulting in inhibitors active in the low micromolar range. Subsequent crystallography confirmed the docking predicted binding modes and may template further optimization. Together, these compounds reveal new chemotypes to aid in further discovery of MPro inhibitors for SARS-CoV-2 and other future coronaviruses.

The biophysical processes occurring in the unsaturated zone have a direct impact on the water table dynamics. Representing these processes through the application of unsaturated zone models of different complexity has an impact on the estimates of the volumes of water flowing between the unsaturated zone and the aquifer. These fluxes, known as net recharge, are often used as the shared variable that couples unsaturated to groundwater models. However, as recharge estimates are always affected by a degree of uncertainty, model–data fusion methods, such as data assimilation, can be used to inform these coupled models and reduce uncertainty. This study assesses the effect of unsaturated zone models complexity (conceptual versus physically based) to update groundwater model outputs, through the assimilation of actual evapotranspiration rates, for a water-limited site in South Australia. Actual evapotranspiration rates are assimilated because they have been shown to be related to the water table dynamics and thus form the link between remote sensing data and the deeper parts of the soil profile. Results have been quantified using standard metrics, such as the root mean square error and Pearson correlation coefficient, and reinforced by calculating the continuous ranked probability score, which is specifically designed to determine a more representative error in stochastic models. It has been found that, once properly calibrated to reproduce the actual evapotranspiration–water table dynamics, a simple conceptual model may be sufficient for this purpose; thus using one configuration over the other should be motivated by the specific purpose of the simulation and the information available.

This paper presents new results to fractional boundary value problems in relation to the existence of solutions and providing a priori bounds on all possible solutions subject to a differential inequality. This provides the scope of these results to be applicable to a vast range of problems that may have unrestricted growth to prove the existence of solutions. This contributes to the practically of these results through their application in modelling real world phenomena. Refereed/Peer-reviewed

Multiple wavelength devices are now available for photobiomodulation (PBM) treatments, but their dosimetry for individual or combinatorial use remains unclear. The present work investigated the effects of 447, 532, 658, 810, 980 and 1064 nm wavelengths on odontoblast differentiation at 10 mW/cm

Participatory approaches, such as community photography, can engage the public in questions of societal and scientific interest while helping advance understanding of ecological patterns and processes. We combined data extracted from community‐sourced, spatially explicit photographs with research findings from 2018 fieldwork in the Yukon, Canada, to evaluate winter coat molt patterns and phenology in mountain goats (Oreamnos americanus), a cold‐adapted, alpine mammal. Leveraging the community science portals iNaturalist and CitSci, in less than a year we amassed a database of almost seven hundred unique photographs spanning some 4,500 km between latitudes 37.6°N and 61.1°N from 0 to 4,333 m elevation. Using statistical methods accounting for incomplete data, a common issue in community science datasets, we identified the effects of intrinsic (sex and presence of offspring) and broad environmental (latitude and elevation) factors on molt onset and rate and compared our findings with published data. Shedding occurred over a 3‐month period between 29 May and 6 September. Effects of sex and offspring on the timing of molt were consistent between the community‐sourced and our Yukon data and with findings on wild mountain goats at a long‐term research site in west‐central Alberta, Canada. Males molted first, followed by females without offspring (4.4 days later in the coarse‐grained, geographically wide community science sample; 29.2 days later in our fine‐grained Yukon sample) and lastly females with new kids (6.2; 21.2 days later, respectively). Shedding was later at higher elevations and faster at northern latitudes. Our findings establish a basis for employing community photography to examine broad‐scale questions about the timing of ecological events, as well as sex differences in response to possible climate drivers. In addition, community photography can help inspire public participation in environmental and outdoor activities specifically with reference to iconic wildlife., We combined data extracted from community‐sourced, spatially explicit photographs with research findings from fieldwork in the Yukon, Canada, to evaluate winter coat molt patterns and phenology in mountain goats (Oreamnos americanus). Using statistical methods accounting for incomplete data—a common issue in community science datasets—we evaluated the effects of intrinsic and environmental factors on molt. Our findings that males molt first and before females and that females with offspring molt last were consistent between our focal research data in the Yukon and community‐sourced data, which, being more geographically broad, enabled us to also find that molt occurs later at higher elevations and is faster at northern latitudes.

We report a simple but detailed solution 13C nuclear magnetic resonance spectroscopic study of atomically precise neutral Au25(SR)180 (SR = alkyl thiolate) clusters. The paramagnetic 13C Knight shi...

Prior studies have shown that trifluoromethylarenes can be labeled in high molar activities (Am > 200 GBq/μmol) with positron-emitting carbon-11 (t1/2 = 20.4 min) by the reaction of the copper(I) derivative of [11C]fluoroform [11C]CuCF3, with several types of precursors, such as aryl iodides, arylboronic acids, and aryldiazonium salts. Nonetheless, these precursors can be challenging to synthesize, and in the case of diazonium salts, are unstable. Methods that reduce challenges in precursor preparation for the synthesis of [11C]trifluoromethylarenes are desirable to enhance possibilities for developing biologically relevant 11C-labeled compounds as radiotracers for biomedical imaging with positron emission tomography (PET). Here, we explored the production of no-carrier-added [11C]trifluoromethylarenes from commercially available primary aromatic amines through reactions of [11C]CuCF3 with diazonium salts that were generated in situ. Moderate to high isolated decay-corrected radiochemical yields (RCY) (32-84%) were obtained rapidly (within 2 min) for many para-substituted and meta-substituted primary aromatic amines bearing a halo, methoxy, thiomethyl, hydroxy, nitro, nitrile, carboxyl, ethylcarboxy, or trifluoromethyl substituent. Null to low RCYs (0-13%) were observed only for ortho bromo-, nitro-, or nitrile-substituted precursors. This new radiosynthetic method usefully expands options for producing PET radiotracers bearing a [11C]trifluoromethyl group, especially from aryl amine precursors.

As systematic inequities in higher education and society have been brought to the forefront, graduate programs are interested in increasing the diversity of their applicants and enrollees. Yet, structures in place to evaluate applicants may not support such aims. One potential solution to support those aims is rubric-based holistic review. Starting in 2018, our physics department implemented a rubric-based holistic review process for all applicants to our graduate program. The rubric assessed applicants on 18 metrics covering their grades, test scores, research experiences, noncognitive competencies, and fit with the program. We then compared faculty's ratings of applicants by admission status, sex, and undergraduate program over a three-year period. We find that the rubric scores show statistically significant differences between admitted and non-admitted students as hoped and that statistically significant differences based on sex or undergraduate program aligned with known disparities in GRE scores and service work expectations. Our results then suggest rubric-based holistic review as a possible route to making graduate admissions in physics more equitable., 21 pages, 8 figures

Rubric-based admissions are claimed to help make the graduate admissions process more equitable, possibly helping to address the historical and ongoing inequities in the U.S. physics graduate school admissions process that have often excluded applicants from minoritized races, ethnicities, genders, and backgrounds. Yet, no studies have examined whether rubric-based admissions methods represent a fundamental change of the admissions process or simply represent a new tool that achieves the same outcome. To address that, we developed supervised machine learning models of graduate admissions data collected from our department over a seven-year period. During the first four years, our department used a traditional admissions process and switched to a rubric-based process for the following three years, allowing us to compare which parts of the applications were used to drive admissions decisions. We find that faculty focused on applicants' physics GRE scores and grade point averages when making admissions decisions before the implementation of the rubric. While we were able to develop a sufficiently good model whose results we could trust for the data before the implementation of the rubric, we were unable to do so for the data collected after the implementation of the rubric, despite multiple modifications to the algorithms and data such as implementing Tomek Links. Our inability to model the second data set despite being able to model the first combined with model comparison analyses suggests that rubric-based admissions does change the underlying process. These results suggest that rubric-based holistic review is a method that could make the graduate admissions process in physics more equitable., Follow up to arXiv:2110.04329; Parts of manuscript originally published as a conference paper (arXiv:1907.01570)

In the southwestern United States, non-native grass invasions have increased wildfire occurrence in deserts and the likelihood of fire spread to and from other biomes with disparate fire regimes. The elevational transition between desertscrub and montane grasslands, woodlands, and forests generally occurs at ∼1,200 masl and has experienced fast suburbanization and an expanding wildland-urban interface (WUI). In summer 2020, the Bighorn Fire in the Santa Catalina Mountains burned 486 km2and prompted alerts and evacuations along a 40-km stretch of WUI below 1,200 masl on the outskirts of Tucson, Arizona, a metropolitan area of >1M people. To better understand the changing nature of the WUI here and elsewhere in the region, we took a multidimensional and timely approach to assess fire dynamics along the Desertscrub-Semi-desert Grassland ecotone in the Catalina foothills, which is in various stages of non-native grass invasion. The Bighorn Fire was principally a forest fire driven by a long-history of fire suppression, accumulation of fine fuels following a wet winter and spring, and two decades of hotter droughts, culminating in the hottest and second driest summer in the 125-yr Tucson weather record. Saguaro (Carnegia gigantea), a giant columnar cactus, experienced high mortality. Resprouting by several desert shrub species may confer some post-fire resiliency in desertscrub. Buffelgrass and other non-native species played a minor role in carrying the fire due to the patchiness of infestation at the upper edge of the Desertscrub biome. Coupled state-and-transition fire-spread simulation models suggest a marked increase in both burned area and fire frequency if buffelgrass patches continue to expand and coalesce at the Desertscrub/Semi-desert Grassland interface. A survey of area residents six months after the fire showed awareness of buffelgrass was significantly higher among residents that were evacuated or lost recreation access, with higher awareness of fire risk, saguaro loss and declining property values, in that order. Sustained and timely efforts to document and assess fast-evolving fire connectivity due to grass invasions, and social awareness and perceptions, are needed to understand and motivate mitigation of an increasingly fire-prone future in the region.

One argument for keeping the physics Graduate Record Exam (GRE) is that it can help applicants who might otherwise be missed in the admissions process stand out. In this work, we evaluate whether this claim is supported by physics graduate school admissions decisions. We used admissions data from five Ph.D.-granting physics departments over a 2-year period (N=2537) to see how the fraction of applicants admitted varied based on their physics GRE scores. We compared applicants with low GPAs to applicants with higher GPAs, applicants from large undergraduate universities to applicants from smaller undergraduate universities, and applicants from selective undergraduate institutions to applicants from less selective undergraduate institutions. We also performed a mediation and moderation analysis to provide statistical rigor and to better understand the previous relationships. We find that for applicants who might otherwise have been missed (e.g., have a low GPA or attended a small or less selective school), having a high physics GRE score did not seem to increase the applicant’s chances of being admitted to the schools. However, having a low physics GRE score seemed to penalize otherwise competitive applicants (i.e., applicants with mid to high GPAs). Thus, our work suggests that the physics GRE does not, in fact, help applicants who might otherwise be missed stand out.

We compared children's gains in oral reading fluency after applying a standard fluency-building intervention to three training passages that differed in word overlap (high, low, and multiple exemplar) with an untrained generalization passage. Participants were 132 White and Hispanic third-grade children from two schools in the northeast and mountain west. Children were randomly assigned within classrooms to the three word overlap conditions, pre-tested on their assigned training and a common generalization passage, received a fluency-building intervention on their assigned training passage, and then post-tested on the same two passages. Regression analyses were conducted to examine the effects of word overlap condition on the children's fluency gains after controlling for pre-test fluency and classroom. Results revealed significantly larger priming and generalization effects for the multiple exemplar versus both the low- and high-word overlap conditions. Survival curves showed that a significantly larger proportion of children in the multiple exemplar condition survived as generalized responders at all generalization levels relative to the other two conditions. Implications for assessing and promoting generalized oral reading fluency in response-to-intervention models and directions for future research are discussed.

Much like finding a needle in a haystack, the effort required to detect a rare and endangered species increases inversely with limited taxa distribution. The infrequency of detections combined with limited fiscal resources often leaves scientists with knowledge gaps about the ecological niche and habitat requirements necessary for conserving rare species. The Arsapnia arapahoe snowfly (A. arapahoe), was thought to be a rare and cryptic aquatic invertebrate for which only 13 individuals from two locations were known to exist in Colorado. In response to potential listing by the US Fish and Wildlife Service as a threatened species, we sought to implement an improved sampling protocol and tested an iterative predictive modeling approach. Species distribution models successively employed annual presence data collected from 2015 to 2017 and detections improved. Although now understood to be a hybrid taxa, the model predicted the locations of seven additional localities while concurrently narrowing the search area and expanding the known geographic range of A. arapahoe. Given our results, we recommend an iterative species distribution modeling and sampling strategy to refine search areas and improve detection rates for rare and endangered species.

The Bale Mountains of Ethiopia contain the largest contiguous area of alpine habitat in Africa. The region provides critical water resources and other essential environmental services to highland communities, endemic wildlife, and millions of downstream people in East Africa. Increasing land use change has created concern over degradation to headwater wetlands and potential impacts on hydrologic regimes. Baseline understanding of wetland dynamics is lacking, however, and little is known about their function in the regional hydrologic system. We used remote sensing, machine learning, and field surveys to map the distribution of Afroalpine wetlands in the Bale Mountains. We developed a wetland typology based on hydrogeomorphic characteristics and a conceptual model of surface-groundwater flow. Our results show that wetland extent more than doubles between wet and dry seasons and that only 4 percent of the Afroalpine zone is saturated year-round. We also found evidence of a hydrologic continuum based on volc...

Narrowing the communication and knowledge gap between producers and users of scientific data is a longstanding problem in ecological conservation and land management. Decision support tools (DSTs), including websites or interactive web applications, provide platforms that can help bridge this gap. DSTs can most effectively disseminate and translate research results when producers and users collaboratively and iteratively design content and features. One data resource seldom incorporated into DSTs are species distribution models (SDMs), which can produce spatial predictions of habitat suitability. Outputs from SDMs can inform management decisions, but their complexity and inaccessibility can limit their use by resource managers or policy makers. To overcome these limitations, we present the Invasive Species Habitat Tool (INHABIT), a novel, web-based DST built with R Shiny to display spatial predictions and tabular summaries of habitat suitability from SDMs for invasive plants across the contiguous United States. INHABIT provides actionable science to support the prevention and management of invasive species. Two case studies demonstrate the important role of end user feedback in confirming INHABIT’s credibility, utility, and relevance.

To identify the anthocyanin content in tart cherry juice concentrate (TCJC) and establish the anti-inflammatory effect of in a murine acute gout model.The main anthocyanins in the TCJC were identified by liquid chromatography mass spectroscopy (LCMS). TCJC or phosphate-buffered saline (PBS) as control were administered daily by oral gavage to BALB/C-Tg(NFκB-RE-luc)-Xen mice that harbour a firefly luciferase cDNA reporter under the regulation of 3 Nuclear factor-κB (NF-κB) response elements. After 14 days, gouty inflammation was induced by intra-articular injection of monosodium urate (MSU) crystals into the tibio-tarsal joint (ankle). NF-κB activity was measured locally in the injected ankle using the Xenogen in vivo imaging system (IVIS), and decalcified feet/ankles were paraffin-embedded and analysed histopathologically.The major anthocyanin compound present in TCJC was cyanidin 3-glucosylrutinoside followed by cyanidin 3-rutinoside. In the murine acute gout model, MSU injection increased NF-κB activity and oral administration of TCJC significantly reduced NF-κB activity in mouse foot, and ankle joints as assessed by IVIS analysis. Bioluminescent imaging detection of NF-κB activation was inhibited approximately 2-fold relative to control mice receiving PBS. Histopathologic examination showed suppression of infiltrates into the tibio-tarsal joint space of the mice receiving TCJC compared to PBS-treated control counterparts.The major anthocyanin in TCJC was cyanidin 3-glucosylrutinoside. Clinically relevant doses of TCJC significantly inhibit inflammation and NF-κB activation induced by MSU crystals.

Despite limiting access to applicants from underrepresented racial and ethnic groups, the practice of using hard or soft Graduate Record Examination (GRE) cutoff scores in physics graduate program admissions is still a popular method for reducing the pool of applicants. The present study considers whether the undergraduate institutions of applicants have any influence on the admissions process by modeling a physics GRE cutoff score with application data from admissions offices of five universities. Two distinct approaches based on inferential and predictive modeling are conducted. While there is some disagreement regarding the relative importance between features, the two approaches largely agree that including institutional information significantly aids the analysis. Both models identify cases where the institutional effects are comparable to factors of known importance such as gender and undergraduate GPA. As the results are stable across many cutoff scores, we advocate against the practice of employing physics GRE cutoff scores in admissions.

Objective Since enhanced cardiac magnetic resonance imaging (cMRI) signals have been associated with lupus disease activity in humans prior to renal failure and novel, cardiac-focused therapeutic strategies could be investigated with an associated animal model, autoimmune myocarditis was characterized in murine lupus nephritis (NZM2410). Methods Weekly blood urea nitrogen (BUN) levels and weights were recorded. Cardiac function was assessed by echocardiogram. Myocardial edema was measured with quantitative T2 cMRI mapping. Endpoint serum and cardiac tissue were collected for histopathological analysis and cytokine measurements. Results Despite showing no signs of significant renal disease, mice displayed evidence of myocarditis and fibrosis histologically at 30–35 weeks. Moreover, T2 cMRI mapping displayed robust signals and analysis of sagittal heart sections showed significant myocardium thickening. Cytokine expression levels of IL-2, IL-10, TNF-α, CXCL1, and IL-6 were significantly enhanced in serum. Echocardiograms demonstrated significantly increased ventricular diameters and reduced ejection fractions, while immunohistochemical staining identified CD4+ and CD8+ T cells, and IL-17 in cardiac infiltrates. Human lupus cardiac tissue showed similar histopathology with enhanced infiltrates by H&E, fibrosis, and CD4+ detection. Conclusions Histopathology, functional abnormalities, and enhanced cMRI signals indicative of myocarditis are detected in NZM2410 mice without glomerulonephritis, which supports the primary pathological role of autoimmune-mediated, cardiac-targeted inflammation in lupus.

γ-Tilmanocept (99m Tc-tilmanocept) is a receptor-directed, radiolabeled tracer that is FDA-approved for guiding sentinel lymph node biopsy. Tilmanocept binds the C-type lectin mannose receptor (MR, CD206) on macrophages. In this study, nonradioactive, fluorescently-labeled Cy3-tilmanocept was used to detect CD206+ mononuclear cells in the cartilage of mice with antibody-induced arthritis and in the synovial fluid and tissue of human subjects with rheumatoid arthritis (RA) for comparison with osteoarthritis (OA), and healthy volunteer (HV) controls. Murine arthritis was induced by injection of monoclonal anti-cartilage antibody followed by injection of Escherichia coli lipopolysaccharide. Post-arthritis development (7-11 days), the mice were injected intravenously with Cy3-tilmanocept followed by in vivo and ex vivo epifluorescence imaging. Two-photon imaging, immunofluorescence, and immunohistochemistry were used to identify articular and synovial macrophages (CD206, F4/80, and Cy3-tilmanocept binding) in murine tissues. Cy3-tilmanocept epifluorescence was present in arthritic knees and elbows of murine tissues; no radiographic changes were noted in the skeletons. However, inflammatory arthritic changes were apparent by histopathology and immunohistochemistry (F4/80), immunofluorescence (CD206) and Cy3-tilmanocept binding. In human RA synovial fluid, Cy3-tilmanocept staining correlated with CD206+ /CD16+ cells; negligible labeling was observed in OA samples. Cy3-tilmanocept colocalized with CD206 and staining was significantly higher in RA synovial tissue compared to OA or HV. Our results demonstrate that imaging with Cy3-tilmanocept can detect in vivo inflammatory, CD206+ macrophages in an early arthritis animal model and in human RA patients. These data establish a novel tool for preclinical research of early arthritis and have implications for early RA detection and monitoring of therapeutic efficacy in humans.

Declining populations of Zizania palustris L. (northern wildrice, or wildrice) during the last century drives the demand for new and innovative techniques to support monitoring of this culturally and ecologically significant crop wild relative. We trained three wildrice detection models in R and Google Earth Engine using data from annual aquatic vegetation surveys in northern Minnesota. Three different training datasets, varying in the definition of wildrice presence, were combined with Landsat 8 Operational Land Imager (OLI) and Sentinel-1 C-band synthetic aperture radar (SAR) imagery to map wildrice in 2015 using random forests. Spectral predictors were derived from phenologically important time periods of emergence (June–July) and peak harvest (August–September). The range of the Vertical Vertical (VV) polarization between the two time periods was consistently the top predictor. Model outputs were evaluated using both point and area-based validation (polygon). While all models performed well in the point validation with percent correctly classified ranging from 83.8% to 91.1%, we found polygon validation necessary to comprehensively assess wildrice detection accuracy. Our practical approach highlights a variety of applications that can be applied to guide field excursions and estimate the extent of occurrence at landscape scales. Further testing and validation of the methods we present may support multiyear monitoring which is foundational for the preservation of wildrice for future generations.

We report a simple but detailed solution

Idiopathic inflammatory myopathies (IIM) involve chronic inflammation of skeletal muscle and subsequent muscle degeneration due to an uncontrolled autoimmune response; however, the mechanisms leading to pathogenesis are not well understood. A compromised sarcolemmal repair process could promote an aberrant exposure of intramuscular antigens with the subsequent initiation of an inflammatory response that contributes to IIM. Using an adoptive transfer mouse model of IIM, we show that sarcolemmal repair is significantly compromised in distal skeletal muscle in the absence of inflammation. We identified autoantibodies against TRIM72 (also known as MG53), a muscle-enriched membrane repair protein, in IIM patient sera and in our mouse model of IIM by ELISA. We found that patient sera with elevated levels of TRIM72 autoantibodies suppress sarcolemmal resealing in healthy skeletal muscle, and depletion of TRIM72 antibodies from these same serum samples rescues sarcolemmal repair capacity. Autoantibodies targeting TRIM72 lead to skeletal muscle fibers with compromised membrane barrier function, providing a continuous source of autoantigens to promote autoimmunity and further amplifying humoral responses. These findings reveal a potential pathogenic mechanism that acts as a feedback loop contributing to the progression of IIM.

Purpose Although more than 18,000,000 fractures occur each year in the US, methods to promote fracture healing still rely primarily on fracture stabilization, with use of bone anabolic agents to accelerate fracture repair limited to rare occasions when the agent can be applied to the fracture surface. Because management of broken bones could be improved if bone anabolic agents could be continuously applied to a fracture over the entire course of the healing process, we undertook to identify strategies that would allow selective concentration of bone anabolic agents on a fracture surface following systemic administration. Moreover, because hydroxyapatite is uniquely exposed on a broken bone, we searched for molecules that would bind with high affinity and specificity for hydroxyapatite. We envisioned that by conjugating such osteotropic ligands to a bone anabolic agent, we could acquire the ability to continuously stimulate fracture healing. Results Although bisphosphonates and tetracyclines were capable of localizing small amounts of peptidic payloads to fracture surfaces 2-fold over healthy bone, their specificities and capacities for drug delivery were significantly inferior to subsequent other ligands, and were therefore considered no further. In contrast, short oligopeptides of acidic amino acids were found to localize a peptide payload to a bone fracture 91.9 times more than the control untargeted peptide payload. Furthermore acidic oligopeptides were observed to be capable of targeting all classes of peptides, including hydrophobic, neutral, cationic, anionic, short oligopeptides, and long polypeptides. We further found that highly specific bone fracture targeting of multiple peptidic cargoes can be achieved by subcutaneous injection of the construct. Conclusions Using similar constructs, we anticipate that healing of bone fractures in humans that have relied on immobilization alone can be greately enhanced by continuous stimulation of bone growth using systemic administration of fracture-targeted bone anabolic agents.

Ecological forecasts of the extent and impacts of invasive species can inform conservation management decisions. Such forecasts are hampered by ecological uncertainties associated with non-analog conditions resulting from the introduction of an invader to an ecosystem. We developed a state-and-transition simulation model tied to a fire behavior model to simulate the spread of buffelgrass (Cenchrus ciliaris) in Saguaro National Park, AZ, USA over a 30-year period. The simulation models forecast the potential extent and impact of a buffelgrass invasion including size and frequency of fire events and displacement of saguaro cacti and other native species. Using simulation models allowed us to evaluate how model uncertainties affected forecasted landscape outcomes. We compared scenarios covering a range of parameter uncertainties including model initialization (landscape susceptibility to invasion) and expert-identified ecological uncertainties (buffelgrass patch infill rates and precipitation). Our simulations showed substantial differences in the amount of buffelgrass on the landscape and the size and frequency of fires for dry years with slow patch infill scenarios compared to wet years with fast patch infill scenarios. We identified uncertainty in buffelgrass patch infill rates as a key area for research to improve forecasts. Our approach could be used to investigate novel processes in other invaded systems.

Predictions of habitat suitability for invasive plant species can guide risk assessments at regional and national scales and inform early detection and rapid-response strategies at local scales. We present a general approach to invasive species modeling and mapping that meets objectives at multiple scales. Our methodology is designed to balance trade-offs between developing highly customized models for few species versus fitting non-specific and generic models for numerous species. We developed a national library of environmental variables known to physiologically limit plant distributions and relied on human input based on natural history knowledge to further narrow the variable set for each species before developing habitat suitability models. To ensure efficiency, we used largely automated modeling approaches and human input only at key junctures. We explore and present uncertainty by using two alternative sources of background samples, including five statistical algorithms, and constructing model ensembles. We demonstrate the use and efficiency of the Software for Assisted Habitat Modeling [SAHM 2.1.2], a package in VisTrails, which performs the majority of the modeling analyses. Our workflow includes solicitation of expert feedback on model outputs such as spatial prediction results and variable response curves, and iterative improvement based on new data availability and directed field validation of initial model results. We highlight the utility of the models for decision-making at regional and local scales with case studies of two plant species that invade natural areas: fountain grass (Pennisetum setaceum) and goutweed (Aegopodium podagraria). By balancing model automation with human intervention, we can efficiently provide land managers with mapped predicted distributions for multiple invasive species to inform decisions across spatial scales.

Aquatic non-native invasive species are commonly traded in the worldwide water garden and aquarium markets, and some of these species pose major threats to the economy, the environment, and human health. Understanding the potential suitable habitat for these species at a global scale and at regional scales can inform risk assessments and predict future potential establishment. Typically, global habitat suitability models are fit for freshwater species with only climate variables, which provides little information about suitable terrestrial conditions for aquatic species. Remotely sensed data including topography and land cover data have the potential to improve our understanding of suitable habitat for aquatic species. In this study, we fit species distribution models using five different model algorithms for three non-native aquatic invasive species with bioclimatic, topographic, and remotely sensed covariates to evaluate potential suitable habitat beyond simple climate matches. The species examined included a frog (Xenopus laevis), toad (Bombina orientalis), and snail (Pomacea spp.). Using a unique modeling approach for each species including background point selection based on known established populations resulted in robust ensemble habitat suitability models. All models for all species had test area under the receiver operating characteristic curve values greater than 0.70 and percent correctly classified values greater than 0.65. Importantly, we employed multivariate environmental similarity surface maps to evaluate potential extrapolation beyond observed conditions when applying models globally. These global models provide necessary forecasts of where these aquatic invasive species have the potential for establishment outside their native range, a key component in risk analyses.

The purpose of this article is to discuss contemporary educational pedagogy for the 21 st century adult student (commonly called andragogy) with attention to current learning styles theory. As the roles and responsibilities of current faculty continue to develop it is important to also focus on how learning styles theory and adult learning theory can be used to enhance andragogy in universities and colleges. This article will also address research on andragogy and its practical application to teaching, as well as student strategies for success. As the role of faculty continues to evolve, higher education needs to be responsible and responsive in preparing to address the diverse, contemporary and future challenges of the 21 st teacher and student. Article DOI: https://dx.doi.org/10.20319/pijtel.2017.11.8696 This work is licensed under the Creative Commons Attribution-Non-commercial 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc/4.0/ or send a letter to Creative Commons, PO Box 1866, Mountain View, CA 94042, USA.

A musician would not take a multiple choice test to join a band Yet such tests are how many physics and astronomy graduate programs select students As a result, departments unintentionally limit the talent that enters the field With testing centers closed because of the coronavirus and with concerns about the fairness or the lack of online alternatives, physics and astronomy graduate programs have temporarily stopped using entrance exams to make admissions decisions Here, Young suggests that become a permanent change Many faculty members and students believe that the physics Graduate Record Examination (GRE) is one of the most important aspects of graduate admissions Many programs require a certain score for admission In theory, a standardized test provides an objective measure for comparing applicants Everyone takes the same test, so it allows candidates the ability to distinguish themselves by scoring well, or so the argument goes

Accurate maps of wetlands and riparian areas are critical for targeting conservation and monitoring efforts. However, detailed inventories in mountain regions are largely non-existent, as conventional mapping approaches are hindered by high costs, remoteness, and landscape variability. Contemporary modeling techniques can circumvent many of these issues, but are often difficult to interpret and tend to rely on specialized datasets that prevent their wider application. In this study, we used machine learning, Landsat 8 imagery and geomorphometric indices to map the distribution of wetlands and riparian areas in the Cache la Poudre River watershed, Colorado, USA. We used a presence-background approach to develop and compare predictions from three popular algorithms: boosted regression trees, MaxEnt and random forests. In addition, we developed the models within three elevation-based life zones to account for altitudinal changes in ecohydrology and land use. Our results showed strong predictive performance, with top-performing models achieving area under the curve values as high as 0.98 and correctly classifying up to 95% of test data. Model performance varied by elevation zone, and no algorithm consistently outperformed the others. The boosted regression trees approach was uniquely able to differentiate wetlands from irrigated agriculture and residential areas in lower elevations. Multi-seasonal greenness and wetness indices were highly influential predictors in all models, underscoring the importance of capturing local phenological characteristics and hydrological regimes. Dissection and roughness terrain metrics were key predictors for identifying valley bottom meadows and emergent wetlands in high-elevation forests. We demonstrate how integrating ecological interpretation into the modeling workflow can inform conventional accuracy statistics and help bridge field-based and remote sensing perspectives. We also show how continuous model outputs can facilitate this process by depicting nuances of the wetland-upland continuum. Our approach requires only public data that are widely available, and can be easily adapted to other heterogeneous mountain settings.

Recent studies implicate innate immunity to systemic lupus erythematosus (SLE) pathogenesis. Toll-like receptor (TLR)8 is estrogen-regulated and binds viral ssRNA to stimulate innate immune responses, but recent work indicates that microRNA (miR)-21 within extracellular vesicles (EVs) can also trigger this receptor. Our objective was to examine TLR8 expression/activation to better understand sex-biased responses involving TLR8 in SLE. Our data identify an estrogen response element that promotes STAT1 expression and demonstrate STAT1-dependent transcriptional activation of TLR8 with estrogen stimulation. In lieu of viral ssRNA activation, we explored EV-encapsulated miR-21 as an endogenous ligand and observed induction of both TLR8 and cytokine expression in vitro. Moreover, extracellular miR detection was found predominantly within EVs. Thus, just as a cytokine or chemokine, EV-encapsulated miR-21 can act as an inflammatory signaling molecule, or miRokine, by virtue of being an endogenous ligand of TLR8. Collectively, our data elucidates a novel innate inflammatory pathway in SLE.

The greatest extent of Afromontane environments in the world is found in Ethiopia. These areas support exceptional biodiversity, but forest cover and ecological integrity have declined sharply in recent decades. Conservation and management efforts are hampered in part by an inadequate understanding of the basic ecology of major tree species. We investigated population structure and inferred population dynamics from size frequency distributions of 22 forest tree species encountered in montane forests of Ethiopia. We collected new empirical data from four sites in the Bale Mountains, where some of the country's most extensive and least disturbed forests remain, and conducted a systematic review and analysis of all such studies that reported population structure for one or more of these species in Ethiopia. Thirteen widespread montane tree species showed a reverse-J size distribution, indicating a relatively stable population structure. Six other species had size-frequency distributions that indicate episodic recruitment and/or removal of certain size classes. Specific causes of these patterns are uncertain: they may involve timber harvesting, herbivory, fire, or natural disturbances, but patterns were inconsistent and locality dependent. For three other tree species, existing data are inadequate for any interpretation of population structure and dynamics. A species of particular conservation concern that emerged from this analysis was Hagenia abyssinica, which was found in all areas to consist only of larger individuals with no recent recruitment. For management and conservation purposes, the species in most urgent need of new research are those with inadequate or inconsistent data, and H. abyssinica.

Gout is characterized by attacks of arthritis with hyperuricemia and monosodium urate (MSU) crystal-induced inflammation within joints. Innate immune responses are the primary drivers for tissue destruction and inflammation in gout. MSU crystals engage the Nlrp3 inflammasome, leading to the activation of caspase-1 and production of IL-1β and IL-18 within gout-affected joints, promoting the influx of neutrophils and monocytes. Here, we show that caspase-11 -/- mice and their derived macrophages produce significantly reduced levels of gout-specific cytokines including IL-1β, TNFα, IL-6, and KC, while others like IFNγ and IL-12p70 are not altered. IL-1β induces the expression of caspase-11 in an IL-1 receptor-dependent manner in macrophages contributing to the priming of macrophages during sterile inflammation. The absence of caspase-11 reduced the ability of macrophages and neutrophils to migrate in response to exogenously injected KC in vivo. Notably, in vitro, caspase-11 -/- neutrophils displayed random migration in response to a KC gradient when compared to their WT counterparts. This phenotype was associated with altered cofilin phosphorylation. Unlike their wild-type counterparts, caspase-11 -/- neutrophils also failed to produce neutrophil extracellular traps (NETs) when treated with MSU. Together, this is the first report demonstrating that caspase-11 promotes neutrophil directional trafficking and function in an acute model of gout. Caspase-11 also governs the production of inflammasome-dependent and -independent cytokines from macrophages. Our results offer new, previously unrecognized functions for caspase-11 in macrophages and neutrophils that may apply to other neutrophil-mediated disease conditions besides gout.

Gadolinium (Gd) is a rare earth element used in magnetic resonance imaging (MRI) contrast agents that has recently been identified as an emerging contaminant of concern due to its possible toxic effects and accumulation in the environment. The objectives of this preliminary study were to determine the occurrence and fate of Gd in surface water and sediment of a constructed wetland that receives effluent from a wastewater treatment plant. The rate of anthropogenic Gd entering the wetland was determined to be approximately 25 g Gd day−1, with surface water concentrations in the parts per trillion. Anthropogenic Gd concentrations in surface waters decreased as a function of distance from the inlet site to near the outfall, and were three orders of magnitude higher in sediment than in surface water suggesting that the wetland was providing a sink for Gd possibly through plant uptake and incorporation in organic biomass. An anthropogenic Gd anomaly was observed with an average GdAnt/GdGeo ratio of 5.34. Sediment with higher total organic carbon (TOC) tended to be higher in anthropogenic Gd, suggesting that Gd sequestration may occur through uptake by plants and/or through flocculation and deposition of natural organic matter.

Among all of the first-year graduate students enrolled in doctoral-granting physics departments, the percentage of female and racial minority students has remained unchanged for the past 20 years. The current graduate program admissions process can create challenges for achieving diversity goals in physics. In this paper, we will investigate how the various aspects of a prospective student's application to a physics doctoral program affect the likelihood the applicant will be admitted. Admissions data was collected from a large, Midwestern public research university that has a decentralized admissions process and included applicants' undergraduate GPAs and institutions, research interests, and GRE scores. Because the collected data varied in scale, we used supervised machine learning algorithms to create models that predict who was admitted into the PhD program. We find that using only the applicant's undergraduate GPA and physics GRE score, we are able to predict with 75% accuracy who will be admitted to the program., Comment: 6 pages, 2 figures, submitted to the 2019 PERC proceedings

Invasive species can alter ecosystem properties and cause state shifts in landscapes. Resource managers charged with maintaining landscapes require tools to understand implications of alternative actions (or inactions) on landscape structure and function. Simulation models can serve as a virtual laboratory to explore these alternatives and their potential impacts on a landscape. To be useful, however, managers need to participate in model development to ensure that model structure can evaluate the response of key resources to plausible actions. Here, we detail development of a state‐and‐transition simulation model (STSM) to evaluate buffelgrass (Cenchrus ciliaris L. syn Pennisetum ciliare (L.) Link) in Saguaro National Park (SNP), Arizona, USA, through collaboration between managers and researchers. We integrate expert knowledge and research to create and parameterize a stochastic, spatially explicit STSM to evaluate specific management objectives. We also develop a dynamic link between the STSM and a fire behavior model to allow exploration of potential novel processes introduced to the ecosystem by buffelgrass invasion. Our projections show that buffelgrass can be expected to increase on the landscape and that the integration of fire into the model accelerates the projected rate of invasion and increases degradation of resources of management concern. We highlight the benefit of engaging end users in the modeling process so that the model is targeted to evaluate management objectives, in this case retention of saguaro cacti (Carnegiea gigantea (Engelm.) Britton & Rose) on the landscape. Being able to integrate an external model that can help address the unique characteristics of a problem such as the introduction of fire into the SNP desert ecosystem increases the ability of simulations to address complex ecological and management questions.