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The proposed investigation deals with the assessment of several models for the prediction of the dynamic behaviour of turbomachinery supported by Active Magnetic Bearing when drop events occur leading the rotor to drop onto its Touch-Down Bearings (TDBs), which are emergency rolling element bearings in series with a ribbon damper. The rotor exhibits a non-linear transient motion where the amount of damping provided by the ribbon damper is a key parameter for avoiding dangerous behaviours. The ribbon damper is modelled successively with the Masing, the generalized Dahl and the Kelvin-Voigt models. Usually, the TDB is modelled as a viscous damper, used here as reference for comparisons. The originality of this work lies in the new modellings of that ribbon, based on dry-friction theory, where parameters are benchmarked to experimental results. The three models presented are successively integrated in the TDB model followed by rotor drop simulations. Comparisons are done in terms of rotor drop dynamics and show that the transient responses predicted with the Masing and generalized Dahl models are similar.

Background The primary genetic risk factor for heritable pulmonary arterial hypertension is the presence of monoallelic mutations in the BMPR2 gene. The incomplete penetrance of BMPR2 mutations implies that additional triggers are necessary for pulmonary arterial hypertension occurrence. Pulmonary artery stenosis directly raises pulmonary artery pressure, and the redirection of blood flow to unobstructed arteries leads to endothelial dysfunction and vascular remodeling. We hypothesized that right pulmonary artery occlusion (RPAO) triggers pulmonary hypertension (PH) in rats with Bmpr2 mutations. Methods and Results Male and female rats with a 71 bp monoallelic deletion in exon 1 of Bmpr2 and their wild‐type siblings underwent acute and chronic RPAO. They were subjected to full high‐fidelity hemodynamic characterization. We also examined how chronic RPAO can mimic the pulmonary gene expression pattern associated with installed PH in unobstructed territories. RPAO induced precapillary PH in male and female rats, both acutely and chronically. Bmpr2 mutant and male rats manifested more severe PH compared with their counterparts. Although wild‐type rats adapted to RPAO, Bmpr2 mutant rats experienced heightened mortality. RPAO induced a decline in cardiac contractility index, particularly pronounced in male Bmpr2 rats. Chronic RPAO resulted in elevated pulmonary IL‐6 (interleukin‐6) expression and decreased Gdf2 expression (corrected P value1). In this context, male rats expressed higher pulmonary levels of endothelin‐1 and IL‐6 than females. Conclusions Our novel 2‐hit rat model presents a promising avenue to explore the adaptation of the right ventricle and pulmonary vasculature to PH, shedding light on pertinent sex‐ and gene‐related effects.

The contribution of two basal energy sources – detrital organic matter and primary producers – as part of aquatic food webs varies typically along river continua. A host of barriers to river flow increase the water residence time and sediment and nutrient retention in reservoirs worldwide, and potentially alter the balance between detritus-based and algae-based energy pathways in the downstream food webs. We explored this issue on the Sélune River (Normandy, France), a small coastal stream that drains an agricultural catchment with high sediment runoff. Seasonal measurements of the following parameters were compared upstream and downstream of the reservoirs of two large dams (16 m and 36 m high): sediment fluxes, nutrient and chlorophyll a concentrations, algal communities in the epilithic biofilm (taxonomic composition, biomass and growth), and benthic invertebrate communities (abundance and trophic guild structure). As anticipated, annual sediment fluxes were much lower downstream of the reservoirs, where significant decreases in water turbidity, phosphate and silicate concentrations were recorded. A higher chlorophyll a concentration in water and a higher contribution of pelagic algae taxa to the photosynthetic biofilm suggested drifting and deposition of reservoir-borne phytoplankton downriver. Photosynthetic biofilm growth was higher downstream of the reservoirs in spring and fall, and so was the abundance of herbivores in the invertebrate community, notably scrapers and algae eaters. Energy pathways within riverine food webs were traced using stable isotope analyses of carbon (C) and nitrogen in the tissues of aquatic consumers (invertebrates and fish). Mixing models revealed a discontinuity in the origin of the C entering the food webs along the river continuum, confirming a greater contribution of algal C to aquatic consumers downstream of the reservoirs. These results illustrate mechanisms whereby large reservoirs can modulate C flow in food webs along a small coastal river with high sediment loads, and make it possible to anticipate the effects of dam removal on the future river ecosystem.

The cartography and quantification of irrigated fields in the context of decreasing rainfall constitute a key element for water resources management. Therefore, in this context, the use of remote sensing methods applied to Landsat-type images with a high spatial resolution for monitoring the changes in land use in general and irrigated crops, in particular, is highly relevant. This paper aims to present a method for mapping spatial and temporal changes in irrigated parcels in the Guigou Plain, located in the central Middle Atlas, based on Landsat images and fieldwork. For the years 1985, 1998, 2010 and 2018, the use of a supervised classification method based on the principle of machine learning, fed by precise field surveys, has made it possible to highlight a significant extension of irrigated areas to the expense of pastureland and rainfed crops. Over the entire period under consideration, the results obtained with good precision (98.5% overall accuracy) showed that the area under irrigated crops has increased from approximately 699 ha to 3988 ha, i.e. an increase of 570%. The corollary of this increase is strong pressure on the water resource, especially groundwater. This information on the total extension of irrigated plots can be taken as a reference in the perspective of reasoned management of water resources in the sector.

Monitoring the structural and functional dimensions of natural vegetation is a critical issue to ensure effective management of biodiversity. While coarse-resolution satellite image time-series have been used extensively to monitor vegetation physiognomies, their potential to describe plant species composition remains understudied. The objective of this study is to assess the potential of annual time-series of MODIS images to discriminate combinations of plant communities, called “vegetation series,” and characterize their structural and functional dimensions at the landscape scale. Twelve vegetation series were mapped in a 16 574 ha study area in a Mediterranean context located in Corsica (France). First, the structural dimension of vegetation series was examined using a random forest (RF) model calibrated with a reference field map to (i) measure the importance of each MODIS image in discriminating vegetation series; (ii) quantify the influence of the number of dates on model accuracy; and (iii) map the vegetation series with the optimal subset of MODIS images. Second, the functional dimension of vegetation series was analyzed by ordinating three functional indices through principal component analysis. These indices were the annual sum of normalized difference vegetation index (NDVI), the annual amplitude of NDVI, and the date of maximum NDVI, considered as a proxy for annual primary production, seasonality of carbon fluxes, and vegetation phenology, respectively. Results showed that (i) vegetation series were mapped accurately (median Kappa index 0.70, median overall accuracy 0.76), preferably using images acquired from February to August; (ii) at least 10 MODIS images were required to achieve sufficient accuracy; and (iii) a functional gradient was detected, ranging from high annual net primary production with low seasonality of carbon fluxes and early phenology in Mediterranean vegetation series to low annual net primary production with high seasonality of carbon fluxes and late phenology in alpine vegetation series.

Abstract A striking feature of the human pulmonary circulation is that mean (mPAP) and systolic (sPAP) pulmonary artery pressures (PAPs) are strongly related and, thus, are essentially redundant. According to the empirical formula documented under normotensive and hypertensive conditions (mPAP = 0.61 sPAP + 2 mmHg), sPAP matches ~160%mPAP on average. This attests to the high pulsatility of PAP, as also witnessed by the near equality of PA pulse pressure and mPAP. Our prospective study tested if pressure redundancy and high pulsatility also apply in a piglet model of chronic thromboembolic pulmonary hypertension (CTEPH). At baseline (Week‐0, W0), Sham (n = 8) and CTEPH (n = 27) had similar mPAP and stroke volume. At W6, mPAP increased in CTEPH only, with a two‐ to three‐fold increase in PA stiffness and total pulmonary resistance. Seven CTEPH piglets were also studied at W16 at baseline, after volume loading, and after acute pulmonary embolism associated with dobutamine infusion. There was a strong linear relationship between sPAP and mPAP (1) at W0 and W6 (n = 70 data points, r² = 0.95); (2) in the subgroup studied at W16 (n = 21, r² = 0.97); and (3) when all data were pooled (n = 91, r² = 0.97, sPAP range 9–112 mmHg). The PA pulsatility was lower than that expected based on observations in humans: sPAP matched ~120%mPAP only and PA pulse pressure was markedly lower than mPAP. In conclusion, the redundancy between mPAP and sPAP seems a characteristic of the pulmonary circulation independent of the species. However, it is suggested that the sPAP thresholds used to define PH in animals are species‐ and/or model‐dependent and thus must be validated.

Abstract The atmosphere is an important route for transporting and disseminating microorganisms over short and long distances. Understanding how microorganisms are distributed in the atmosphere is critical due to their role in public health, meteorology and atmospheric chemistry. In order to determine the dominant processes that structure airborne microbial communities, we investigated the diversity and abundance of both bacteria and fungi from the PM10 particle size (particulate matter of 10 micrometers or less in diameter) as well as particulate matter chemistry and local meteorological characteristics over time at nine different meteorological stations around the world. The bacterial genera Bacillus and Sphingomonas as well as the fungal species Pseudotaeniolina globaosa and Cladophialophora proteae were the most abundant taxa of the dataset, although their relative abundances varied greatly based on sampling site. Bacterial and fungal concentration was the highest at the high-altitude and semi-arid plateau of Namco (China; 3.56 × 106 ± 3.01 × 106 cells/m3) and at the high-altitude and vegetated mountain peak Storm-Peak (Colorado, USA; 8.78 × 104 ± 6.49 × 104 cells/m3), respectively. Surrounding ecosystems, especially within a 50 km perimeter of our sampling stations, were the main contributors to the composition of airborne microbial communities. Temporal stability in the composition of airborne microbial communities was mainly explained by the diversity and evenness of the surrounding landscapes and the wind direction variability over time. Airborne microbial communities appear to be the result of large inputs from nearby sources with possible low and diluted inputs from distant sources.

The interplay between microbes and atmospheric physical and chemical conditions is an open field of research that can only be fully addressed using multidisciplinary approaches. The lack of coordinated efforts to gather data at representative temporal and spatial scales limits aerobiology to help understand large scale patterns of global microbial biodiversity and its causal relationships with the environmental context. This paper presents the sampling strategy and analytical protocols developed in order to integrate different fields of research such as microbiology, –omics biology, atmospheric chemistry, physics and meteorology to characterize atmospheric microbial life. These include control of chemical and microbial contaminations from sampling to analysis and identification of experimental procedures for characterizing airborne microbial biodiversity and its functioning from the atmospheric samples collected at remote sites from low cell density environments. We used high-volume sampling strategy to address both chemical and microbial composition of the atmosphere, because it can help overcome low aerosol and microbial cell concentrations. To account for contaminations, exposed and unexposed control filters were processed along with the samples. We present a method that allows for the extraction of chemical and biological data from the same quartz filters. We tested different sampling times, extraction kits and methods to optimize DNA yield from filters. Based on our results, we recommend supplementary sterilization steps to reduce filter contamination induced by handling and transport. These include manipulation under laminar flow hoods and UV sterilization. In terms of DNA extraction, we recommend a vortex step and a heating step to reduce binding to the quartz fibers of the filters. These steps have led to a 10-fold increase in DNA yield, allowing for downstream omics analysis of air samples. Based on our results, our method can be integrated into pre-existing long-term monitoring field protocols for the atmosphere both in terms of atmospheric chemistry and biology. We recommend using standardized air volumes and to develop standard operating protocols for field users to better control the operational quality.

This research aims to assess the capabilities of Very High Spatial Resolution (VHSR) hyperspectral satellite data in order to discriminate urban tree diversity. Four dimension reduction methods and two classifiers are tested, using two learning methods and applied with four in situ sample datasets. An airborne HySpex image (408 bands/2 m) was acquired in July 2015 from which prototypal spaceborne hyperspectral images (named HYPXIM) at 4 m and 8 m and a multispectral Sentinel2 image at 10 m have been simulated for the purpose of this study. A comparison is made using these methods and datasets. The influence of dimension reduction methods is assessed on hyperspectral (HySpex and HYPXIM) and Sentinel2 datasets. The influence of conventional classifiers (Support Vector Machine −SVM− and Random Forest −RF−) and learning methods is evaluated on all image datasets (reduced and non-reduced hyperspectral and Sentinel2 datasets). Results show that HYPXIM 4 m and HySpex 2 m reduced by Minimum Noise Fraction (MNF) provide the greatest classification of 14 species using the SVM with an overall accuracy of 78.4% (±1.5) and a kappa index of agreement of 0.7. More generally, the learning methods have a stronger influence than classifiers, or even than dimensional reduction methods, on urban tree diversity classification. Prototypal HYPXIM images appear to present a great compromise (192 spectral bands/4 m resolution) for urban vegetation applications compared to HySpex or Sentinel2 images.

One of the main strategies to control the spread of infectious animal diseases is the implementation of movement restrictions. This paper shows a loss in efficiency of the movement restriction policy (MRP) when behavioral responses of farmers are taken into account. Incorporating the strategic behavior of farmers in an epidemiologic model reveals that the MRP can trigger premature animal sales by farms at high risk of becoming infected that significantly reduce the efficacy of the policy. The results are validated in a parameterized network via Monte Carlo simulations and measures to mitigate the loss of efficiency of the MRP are discussed. Financial aid to farmers can be justified by public health concerns, not only for equity. This paper contributes to developing an interdisciplinary analytical framework regarding the expansion of infectious diseases combining economic and epidemiologic dimensions.

Immune checkpoint blockade is a promising approach to activate antitumor immunity and improve the survival of patients with cancer. V-domain immunoglobulin suppressor of T cell activation (VISTA) is an immune checkpoint target; however, the downstream signaling mechanisms are elusive. Here, we identify leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) as a VISTA binding partner, which acts as an inhibitory receptor by engaging VISTA and suppressing T cell receptor signaling pathways. Mice with T cell-specific LRIG1 deletion developed superior antitumor responses because of expansion of tumor-specific cytotoxic T lymphocytes (CTLs) with increased effector function and survival. Sustained tumor control was associated with a reduction of quiescent CTLs (TCF1 + CD62L hi PD-1 low ) and a reciprocal increase in progenitor and memory-like CTLs (TCF1 + PD-1 + ). In patients with melanoma, elevated LRIG1 expression on tumor-infiltrating CD8 + CTLs correlated with resistance to immunotherapies. These results delineate the role of LRIG1 as an inhibitory immune checkpoint receptor and propose a rationale for targeting the VISTA/LRIG1 axis for cancer immunotherapy.

Myeloid-derived suppressor cells (MDSCs) impair antitumor immune responses. Identifying regulatory circuits during MDSC development may bring new opportunities for therapeutic interventions. We report that the V-domain suppressor of T cell activation (VISTA) functions as a key enabler of MDSC differentiation. VISTA deficiency reduced STAT3 activation and STAT3-dependent production of polyamines, which causally impaired mitochondrial respiration and MDSC expansion. In both mixed bone marrow (BM) chimera mice and myeloid-specific VISTA conditional knockout mice, VISTA deficiency significantly reduced tumor-associated MDSCs but expanded monocyte-derived dendritic cells (DCs) and enhanced T cell-mediated tumor control. Correlated expression of VISTA and arginase-1 (ARG1), a key enzyme supporting polyamine biosynthesis, was observed in multiple human cancer types. In human endometrial cancer, co-expression of VISTA and ARG1 on tumor-associated myeloid cells is associated with poor survival. Taken together, these findings unveil the VISTA/polyamine axis as a central regulator of MDSC differentiation and warrant therapeutically targeting this axis for cancer immunotherapy., Competing Interests: Declaration of interests L.L.W is an inventor involved with the commercial development of VISTA with ImmuNext Inc. Corporation (Lebanon, NH, USA)., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: A single arm, phase II trial of carboplatin, nab-paclitaxel, and pembrolizumab (CNP) in metastatic triple-negative breast cancer (mTNBC) was designed to evaluate overall response rate (ORR), progression-free survival (PFS), duration of response (DOR), safety/tolerability, overall survival (OS), and identify pathologic and transcriptomic correlates of response to therapy., Patients and Methods: Patients with ≤2 prior therapies for metastatic disease were treated with CNP regardless of tumor programmed cell death-ligand 1 status. Core tissue biopsies were obtained prior to treatment initiation. ORR was assessed using a binomial distribution. Survival was analyzed via the Kaplan-Meier method. Bulk RNA sequencing was employed for correlative studies., Results: Thirty patients were enrolled. The ORR was 48.0%: 2 (7%) complete responses (CR), 11 (41%) partial responses (PR), and 8 (30%) stable disease (SD). The median DOR for patients with CR or PR was 6.4 months [95% confidence interval (CI), 4-8.5 months]. For patients with CR, DOR was >24 months. Overall median PFS and OS were 5.8 (95% CI, 4.7-8.5 months) and 13.4 months (8.9-17.3 months), respectively. We identified unique transcriptomic landscapes associated with each RECIST category of radiographic treatment response. In CR and durable PR, IGHG1 expression was enriched. IGHG1high tumors were associated with improved OS (P = 0.045) and were concurrently enriched with B cells and follicular helper T cells, indicating IGHG1 as a promising marker for lymphocytic infiltration and robust response to chemo-immunotherapy., Conclusions: Pretreatment tissue sampling in mTNBC treated with CNP reveals transcriptomic signatures that may predict radiographic responses to chemo-immunotherapy., (©2023 The Authors; Published by the American Association for Cancer Research.)

Objective: We sought to develop screening criteria predicting the lack of poor neurologic outcomes in patients presenting with traumatic subarachnoid hemorrhage (tSAH) and to evaluate their potential to improve resource allocation in these cases., Methods: We retrospectively reviewed patients presenting with tSAH to the emergency department (ED) of a tertiary-care institution from 2016 to 2018. We defined good neurologic outcomes as patients with stable/improving neurologic status, who did not require neurosurgical intervention, had no expanding bleed, and needed no hospital readmission. Univariate and multivariate models were generated to predict risk factors inversely associated with good neurologic outcome., Results: A total of 167 patients presented with tSAH from 2016 to 2018. The presence of depressed skull fracture, concomitant spinal fracture, low Glasgow Coma Scale (GCS) score, cranial nerve palsies, disorientation, concomitant hemorrhages, midline shift, increased international normalized ratio (INR), and emergent medical intervention were inversely correlated with likelihood of good neurologic outcome on univariate analysis. Multivariate regression showed that midline shift (odds ratio [OR], 0.22; 95% confidence interval [CI], 0.05-0.89; P = 0.04), GCS score <13 (OR, 0.22; 95% CI, 0.05-0.99; P = 0.05), increased INR (OR, 0.18; 95% CI, 0.03-0.85; P = 0.04), and emergent medical intervention (OR, 0.18; 95% CI, 0.04-0.63; P = 0.01) were independently associated with lower likelihood of good neurologic outcome. Forty-six patients without any factors had good outcomes but were held in the ED or admitted to the hospital. These patients (if instead discharged directly) meant a potential cost savings of $179,172., Conclusions: In our study, we found multiple risk factors inversely associated with good neurologic outcome, namely low GCS score, midline shift, emergent medical intervention, and INR ≥1.4. Our findings may aid clinicians in determining which tSAH patients are candidates for safe early discharge., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Glioblastoma (GBM) is the most prevalent primary malignant brain tumor and is associated with extensive tumor cell infiltration into the adjacent brain parenchyma. However, there are limited targeted therapies that address this disease hallmark. While the invasive capacity of self-renewing cancer stem cells (CSCs) and their non-CSC progeny has been investigated, the mode(s) of migration used by CSCs during invasion is currently unknown. Here we used time-lapse microscopy to evaluate the migratory behavior of CSCs, with a focus on identifying key regulators of migration. A head-to-head migration assay demonstrated that CSCs are more invasive than non-CSCs. Time-lapse live cell imaging further revealed that GBM patient-derived CSC models either migrate in a collective manner or in a single cell fashion. To uncover conserved molecular regulators responsible for collective cell invasion, we utilized the genetically tractable Drosophila border cell collective migration model. Candidates for functional studies were generated using results from a targeted Drosophila genetic screen followed by gene expression analysis of the human homologs in GBM tumors and associated GBM patient prognosis. This strategy identified the highly conserved small GTPase, Rap1a, as a potential regulator of cell invasion. Alteration of Rap1a activity impaired the forward progress of Drosophila border cells during development. Rap1a expression was elevated in GBM and associated with higher tumor grade. Functionally, the levels of activated Rap1a impacted CSC migration speed out of spheres onto extracellular matrix. The data presented here demonstrate that CSCs are more invasive than non-CSCs, are capable of both collective and single cell migration, and express conserved genes that are required for migration and invasion. Using this integrated approach, we identified a new role for Rap1a in the migration of GBM CSCs.

The proteoglycan versican is implicated in growth and metastases of several cancers. Here we investigated a potential contribution of stromal versican to tumor growth and angiogenesis. We initially determined versican expression by several cancer cell lines. Among these, MDA-MB231 and B16F10 had none to minimal expression in contrast to Lewis lung carcinoma (LLC). Notably, tumors arising from these cell lines had higher versican levels than the cell lines themselves suggesting a contribution from the host-derived tumor stroma. In LLC-derived tumors, both the tumor and stroma expressed versican at high levels. Thus, tumor stroma can make a significant contribution to tumor versican content. Versican localized preferentially to the vicinity of tumor vasculature and macrophages in the tumor. However, an ADAMTS protease-generated versican fragment uniquely localized to vascular endothelium. To specifically determine the impact of host/stroma-derived versican we therefore compared growth of tumors from B16F10 cells, which produced littleversican, in Vcan hdf/+ mice and wild-type littermates. Tumors in Vcan hdf/+ mice had reduced growth with a lower capillary density and accumulation of capillaries at the tumor periphery. These findings illustrate the variability of tumor cell line expression of versican, and demonstrate that versican is consistently contributed by the stromal tissue, where it contributes to tumor angiogenesis.

The location and extent of an abnormal signal on MRI of the optic nerve affected by optic neuritis are said to correlate with the severity of initial visual loss and recovery. We used gadolinium-enhanced fat-suppressed MRI to show abnormal enhancement of the optic nerve to determine the sensitivity of this modality in acute optic neuritis and whether the abnormal enhancement correlates with presenting visual deficits or recovery. A total of 107 patients, 93 with follow-up (68 steroid treated), were included; 101 patients had enhancement of the affected optic nerve and no unaffected nerve enhanced. The baseline visual performance was similar between nerves with and without enhancement. Optic nerves with enhancement in the optic canal had poorer colour vision (P = 0.04) and nerves with all segments involved had worse threshold perimetry (P = 0.001) and colour vision (P = 0.008). Nerves with enhancement >10 mm had worse threshold perimetry (P = 0.004), while nerves with enhancing segments >17 mm had poorer baseline visual acuity (P = 0.02), threshold perimetry (P = 0.009) and colour vision (P = 0.01). For all parameters of vision, recovery was similar regardless of location or length of abnormal enhancement. Abnormal contrast enhancement of the optic nerve is a sensitive (94%) finding in acute optic neuritis and is absent in unaffected or previously affected optic nerves. Although lesions involving the canal or longer segments of optic nerve have worse starting vision, the location and length of enhancement are not predictive of recovery.

The authors describe an innovative continuing medical education (CME) program they developed to improve the ability of community practitioners to manage common cardiology problems. The program includes an objective structured clinical examination (OSCE) with nine standardized patient (SP) stations. The SPs are trained to use checklists to assess the examinees' clinical skills, and to enter the checklist data directly into computers located within each of the examining rooms. Checklists cover the participants' knowledge of cardiology, and their interviewing, physical-examination, and counseling skills. The computer immediately generates detailed individual reports, which include a skills report, reflecting performance of core skills across all nine stations with group means for comparison, and an omissions report, listing items missed in each case for each participant and, again, comparing the results with group means. Participants review and discuss their performances and then discuss identified learning issues with a cardiologist. The cardiologist also reviews state-of-the-art diagnosis and treatment for the cases presented in the OSCE. Participants have reported having a high regard for the program and have indicated that the program has left them better prepared to deal with clinical cardiology issues.