5,745 results on '"Rubin, M."'
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2. A Strain Energy Function for Planar Response of a Constrained Cosserat Extensible Elastica with a General Reference Planar Shape
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Rubin, M. B.
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- 2024
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3. An Approximate Stress Distribution in a Conical Heap of Jammed Dry Granular Material
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Rubin, M. B.
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- 2024
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4. A Generalized Model for Large Deformations of an Elastically Isotropic Material with Elastic-Inelastic Response
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Rubin, M. B.
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- 2024
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5. A Simplified Eulerian Formulation of a Multi-Phase Soft Tissue Model with Homeostasis and Phase Transformation
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Rubin, M. B.
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- 2024
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6. Oxygen-bearing organic molecules in comet 67P's dusty coma: first evidence for abundant heterocycles
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Hänni, N., Altwegg, K., Baklouti, D., Combi, M., Fuselier, S. A., De Keyser, J., Müller, D. R., Rubin, M., and Wampfler, S. F.
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Astrophysics - Earth and Planetary Astrophysics - Abstract
The puzzling complexity of terrestrial biomolecules is driving the search for complex organic molecules in the Interstellar Medium (ISM) and serves as a motivation for many in situ studies of reservoirs of extraterrestrial organics from meteorites and interplanetary dust particles (IDPs) to comets and asteroids. Comet 67P/Churyumov-Gerasimenko (67P) -- the best-studied comet to date -- has been visited and accompanied for two years by the European Space Agency's Rosetta spacecraft. Around 67P's perihelion and under dusty conditions, the high-resolution mass spectrometer on board provided a spectacular glimpse into this comet's chemical complexity. For this work, we analyzed in unprecedented detail the O-bearing organic volatiles. In a comparison of 67P's inventory to molecules detected in the ISM, in other comets, and in Soluble Organic Matter (SOM) extracted from the Murchison meteorite, we also highlight the (pre)biotic relevance of different chemical groups of species. We report first evidence for abundant extraterrestrial O-bearing heterocycles (with abundances relative to methanol often on the order of 10% with a relative error margin of 30-50%) and various representatives of other molecule classes such as carboxylic acids and esters, aldehydes, ketones, and alcohols. Like with the pure hydrocarbons, some hydrogenated forms seem to be dominant over their dehydrogenated counterparts. An interesting example is tetrahydrofuran (THF) as it might be a more promising candidate for searches in the ISM than the long-sought furan itself. Our findings not only support and guide future efforts to investigate the origins of chemical complexity in space, but also they strongly encourage studies of, e.g., the ratios of unbranched vs. branched and hydrogenated vs. dehydrogenated species in astrophysical ice analogs in the laboratory as well as by modeling., Comment: Reproduced with permission from Astronomy & Astrophysics, copyright ESO
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- 2023
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7. The source of electrons at comet 67P
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Stephenson, P., Beth, A., Deca, J., Galand, M., Goetz, C., Henri, P., Heritier, K., Lewis, Z., Moeslinger, A., Nilsson, H., and Rubin, M.
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Astrophysics - Earth and Planetary Astrophysics ,Physics - Space Physics - Abstract
We examine the origin of electrons in a weakly outgassing comet, using Rosetta mission data and a 3D collisional model of electrons at a comet. We have calculated a new dataset of electron-impact ionization (EII) frequency throughout the Rosetta escort phase, with measurements of the Rosetta Plasma Consortium's Ion and Electron Sensor (RPC/IES). The EII frequency is evaluated in 15-minute intervals and compared to other Rosetta datasets. Electron-impact ionization is the dominant source of electrons at 67P away from perihelion and is highly variable (by up to three orders of magnitude). Around perihelion, EII is much less variable and less efficient than photoionization at Rosetta. Several drivers of the EII frequency are identified, including magnetic field strength and the outgassing rate. Energetic electrons are correlated to the Rosetta-upstream solar wind potential difference, confirming that the ionizing electrons are solar wind electrons accelerated by an ambipolar field. The collisional test particle model incorporates a spherically symmetric, pure water coma and all the relevant electron-neutral collision processes. Electric and magnetic fields are stationary model inputs, and are computed using a fully-kinetic, collisionless Particle-in-Cell simulation. Collisional electrons are modelled at outgassing rates of $Q=10^{26}$ s$^{-1}$ and $Q=1.5\times10^{27}$ s$^{-1}$. Secondary electrons are the dominant population within a weakly outgassing comet. These are produced by collisions of solar wind electrons with the neutral coma. The implications of large ion flow speed estimates at Rosetta, away from perihelion, are discussed in relation to multi-instrument studies and the new results of the EII frequency obtained in the present study., Comment: 27 Pages including Appendices, 24 Figures
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- 2023
8. Pathogenesis of Pulmonary Arterial Hypertension
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Ponticos, Markella, Lee, Michael H., Holmes, Alan M., Tuder, Rubin M., Allanore, Yannick, editor, Varga, John, editor, Denton, Christopher P., editor, Kuwana, Masataka, editor, Chung, Lorinda, editor, and Shah, Ami A., editor
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- 2024
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9. Repetitive schistosoma exposure causes perivascular lung fibrosis and persistent pulmonary hypertension
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Kumar, Rahul, Lee, Michael H, Kassa, Biruk, Balladares, Dara C Fonseca, Mickael, Claudia, Sanders, Linda, Andruska, Adam, Kumar, Maya, Spiekerkoetter, Edda, Bandeira, Angela, Stenmark, Kurt R, Tuder, Rubin M, and Graham, Brian B
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Digestive Diseases ,Lung ,Rare Diseases ,Vector-Borne Diseases ,2.1 Biological and endogenous factors ,Aetiology ,Good Health and Well Being ,Humans ,Animals ,Mice ,Hypertension ,Pulmonary ,Pulmonary Fibrosis ,Schistosoma mansoni ,Schistosomiasis ,Fibrosis ,Inflammation ,Pulmonary hypertension ,Vascular remodeling ,Medical and Health Sciences ,Cardiovascular System & Hematology - Abstract
BackgroundPulmonary hypertension (PH) can occur as a complication of schistosomiasis. In humans, schistosomiasis-PH persists despite antihelminthic therapy and parasite eradication. We hypothesized that persistent disease arises as a consequence of exposure repetition.MethodsFollowing intraperitoneal sensitization, mice were experimentally exposed to Schistosoma eggs by intravenous injection, either once or three times repeatedly. The phenotype was characterized by right heart catheterization and tissue analysis.ResultsFollowing intraperitoneal sensitization, a single intravenous Schistosoma egg exposure resulted in a PH phenotype that peaked at 7-14 days, followed by spontaneous resolution. Three sequential exposures resulted in a persistent PH phenotype. Inflammatory cytokines were not significantly different between mice exposed to one or three egg doses, but there was an increase in perivascular fibrosis in those who received three egg doses. Significant perivascular fibrosis was also observed in autopsy specimens from patients who died of this condition.ConclusionsRepeatedly exposing mice to schistosomiasis causes a persistent PH phenotype, accompanied by perivascular fibrosis. Perivascular fibrosis may contribute to the persistent schistosomiasis-PH observed in humans with this disease.
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- 2023
10. Abundant ammonium hydrosulphide embedded in cometary dust grains
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Altwegg, K., Combi, M., Fuselier, S. A., Hänni, N., De Keyser, J., Mahjoub, A., Müller, D. R., Pestoni, B., Rubin, M., and Wampfler, S. F.
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Astrophysics - Earth and Planetary Astrophysics - Abstract
Ammonium hydrosulphide has long since been postulated to exist at least in certain layers of the giant planets. Its radiation products may be the reason for the red colour seen on Jupiter. Several ammonium salts, the products of NH3 and an acid, have previously been detected at comet 67P/Churyumov-Gerasimenko. The acid H2S is the fifth most abundant molecule in the coma of 67P followed by NH3. In order to look for the salt NH4+SH-, we analysed in situ measurements from the Rosetta/ROSINA Double Focusing Mass Spectrometer during the Rosetta mission. NH3 and H2S appear to be independent of each other when sublimating directly from the nucleus. However, we observe a strong correlation between the two species during dust impacts, clearly pointing to the salt. We find that NH4+SH- is by far the most abundant salt, more abundant in the dust impacts than even water. We also find all previously detected ammonium salts and for the first time ammonium fluoride. The amount of ammonia and acids balance each other, confirming that ammonia is mostly in the form of salt embedded into dust grains. Allotropes S2 and S3 are strongly enhanced in the impacts, while H2S2 and its fragment HS2 are not detected, which is most probably the result of radiolysis of NH4+SH-. This makes a prestellar origin of the salt likely. Our findings may explain the apparent depletion of nitrogen in comets and maybe help to solve the riddle of the missing sulphur in star forming regions., Comment: accepted by MNRAS
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- 2022
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11. Integrative Multiomics in the Lung Reveals a Protective Role of Asporin in Pulmonary Arterial Hypertension
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Hong, Jason, Medzikovic, Lejla, Sun, Wasila, Wong, Brenda, Ruffenach, Grégoire, Rhodes, Christopher J., Brownstein, Adam, Liang, Lloyd L., Aryan, Laila, Li, Min, Vadgama, Arjun, Kurt, Zeyneb, Schwantes-An, Tae-Hwi, Mickler, Elizabeth A., Gräf, Stefan, Eyries, Mélanie, Lutz, Katie A., Pauciulo, Michael W., Trembath, Richard C., Perros, Frédéric, Montani, David, Morrell, Nicholas W., Soubrier, Florent, Wilkins, Martin R., Nichols, William C., Aldred, Micheala A., Desai, Ankit A., Trégouët, David-Alexandre, Umar, Soban, Saggar, Rajan, Channick, Richard, Tuder, Rubin M., Geraci, Mark W., Stearman, Robert S., Yang, Xia, and Eghbali, Mansoureh
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- 2024
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12. Crossing the border between epileptic and vascular pathology: a report of CACNA1A-related treatment-resistant hemiplegic migraine
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Rubin, M., Cutillo, G., Zanandrea, L., Montini, F., Zanetta, C., Bellini, A., Cecchetti, G., Fanelli, G. F., Falini, A., Scotti, R., Calloni, S. F., Di Bella, D., Filippi, M., and Colombo, B.
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- 2023
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13. An Eulerian Formulation of a Growing Constrained Elastic-Viscoplastic Generalized Membrane
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Rubin, M. B.
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- 2023
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14. Ozanimod: A Practical Review for Nurses and Advanced Practice Providers
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Rubin M and Kutz C
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ulcerative colitis ,ozanimod ,sphingosine 1-phosphate ,safety ,Nursing ,RT1-120 - Abstract
Michele Rubin,1 Christen Kutz2 1Department of Colorectal Surgery, University of Chicago IBD Center, Joliet, IL, USA; 2Colorado Springs Neurological Associates, Colorado Springs, CO, USACorrespondence: Michele Rubin, Associate Director of IBD Center, University of Chicago IBD Center, 2914 Hintze Court, Joliet, IL, 60435, USA, Tel +1-815-347-8307, Fax +1-773-834-1995, Email michele.rubin@uchospitals.eduAbstract: Ozanimod is the first sphingosine 1-phosphate (S1P) receptor modulator approved for the treatment of moderately to severely active ulcerative colitis (UC). In clinical trials, participants with moderately to severely active UC who received once-daily oral ozanimod demonstrated significantly improved rates of clinical, endoscopic, and histologic outcomes than participants receiving placebo. Ozanimod is also approved for the treatment of relapsing forms of multiple sclerosis (MS). This review summarizes safety data from UC and MS clinical trials and discusses treatment considerations when using ozanimod in clinical practice. Ozanimod is an oral, small molecule agent with a novel mechaism of action that differentiates it from other UC therapies. Ozanimod was generally well tolerated in clinical trials, and the incidence of adverse events of special interest based on prior associations with S1P receptor modulation was low overall. Of note, the risk for clinically significant bradycardia upon treatment initiation was mitigated by gradual dose titration, few patients experienced lymphopenia or serious infections, macular edema and malignancy occurred infrequently, and most hepatic events were transient and did not require treatment discontinuation. Given the safety and efficacy profile of ozanimod, it may be an early treatment option in patients with moderate disease or in those hesitant to use biologics, and it could also be beneficial after other treatments have failed. Further investigation is needed to determine the positioning of ozanimod within the UC treatment armamentarium.Plain Language Summary: This article provides information about the use of ozanimod in treating patients with moderately to severely active ulcerative colitis (UC) and offers practical guidance for nurses, nurse practitioners, and other healthcare providers to help address questions that may come up in clinical practice. Ozanimod is an oral medication that improves UC symptoms as well as current biologics, while also reducing the need for corticosteroids, a key aspect in treating UC. Ozanimod may be used either after a patient has failed a biologic or as an early treatment option before starting a biologic in patients with moderate UC who may be hesitant to start biologics. This article includes tools to help guide clinical practice decision-making, educate on possible adverse events, and provide the monitoring necessary to ensure patient safety and best practices in the use of ozanimod.Keywords: ulcerative colitis, ozanimod, sphingosine 1-phosphate, safety
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- 2024
15. Interstitial macrophage phenotypes in Schistosoma-induced pulmonary hypertension
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Rahul Kumar, Sushil Kumar, Claudia Mickael, Dara Fonseca Balladares, Kevin Nolan, Michael H. Lee, Linda Sanders, Julia Nilsson, Ari B. Molofsky, Rubin M. Tuder, Kurt R. Stenmark, and Brian B. Graham
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macrophages ,inflammation ,schistosomiasis ,pulmonary hypertension ,type 2 inflammation ,Immunologic diseases. Allergy ,RC581-607 - Abstract
BackgroundSchistosomiasis is a common cause of pulmonary hypertension (PH) worldwide. Type 2 inflammation contributes to the development of Schistosoma-induced PH. Specifically, interstitial macrophages (IMs) derived from monocytes play a pivotal role by producing thrombospondin-1 (TSP-1), which in turn activates TGF-β, thereby driving the pathology of PH. Resident and recruited IM subpopulations have recently been identified. We hypothesized that in Schistosoma-PH, one IM subpopulation expresses monocyte recruitment factors, whereas recruited monocytes become a separate IM subpopulation that expresses TSP-1.MethodsMice were intraperitoneally sensitized and then intravenously challenged with S. mansoni eggs. Flow cytometry on lungs and blood was performed on wildtype and reporter mice to identify IM subpopulations and protein expression. Single-cell RNA sequencing (scRNAseq) was performed on flow-sorted IMs from unexposed and at day 1, 3 and 7 following Schistosoma exposure to complement flow cytometry based IM characterization and identify gene expression.ResultsFlow cytometry and scRNAseq both identified 3 IM subpopulations, characterized by CCR2, MHCII, and FOLR2 expression. Following Schistosoma exposure, the CCR2+ IM subpopulation expanded, suggestive of circulating monocyte recruitment. Schistosoma exposure caused increased monocyte-recruitment ligand CCL2 expression in the resident FOLR2+ IM subpopulation. In contrast, the vascular pathology-driving protein TSP-1 was greatest in the CCR2+ IM subpopulation.ConclusionSchistosoma-induced PH involves crosstalk between IM subpopulations, with increased expression of monocyte recruitment ligands by resident FOLR2+ IMs, and the recruitment of CCR2+ IMs which express TSP-1 that activates TGF-β and causes PH.
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- 2024
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16. Mass calibration of Rosetta’s ROSINA/DFMS mass spectrometer
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De Keyser, J., Dhooghe, F., Altwegg, K., Rubin, M., Hänni, N., Fuselier, S.A., Berthelier, J.-J., and Neefs, E.
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- 2024
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17. The role of macrophages in right ventricular remodeling in experimental pulmonary hypertension
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Gu, Sue, Mickael, Claudia, Kumar, Rahul, Lee, Michael H, Sanders, Linda, Kassa, Biruk, Harral, Julie, Williams, Jason, Hansen, Kirk C, Stenmark, Kurt R, Tuder, Rubin M, and Graham, Brian B
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Biomedical and Clinical Sciences ,Medical Physiology ,Cardiovascular Medicine and Haematology ,Lung ,Heart Disease ,Cardiovascular ,Aetiology ,2.1 Biological and endogenous factors ,Good Health and Well Being ,adaptation ,hypoxia ,inflammation ,right heart ,Schistosoma ,Cardiorespiratory Medicine and Haematology ,Cardiovascular medicine and haematology - Abstract
Right ventricular (RV) failure is the primary cause of death in pulmonary hypertension (PH), but the mechanisms of RV failure are not well understood. We hypothesized macrophages in the RV contribute to the RV response in PH. We induced PH in mice with hypoxia (FiO2 10%) and Schistosoma mansoni exposure, and in rats with SU5416-hypoxia. We quantified cardiac macrophages in mice using flow cytometry. Parabiosis between congenic CD45.1/.2 mice or Cx3cr1-green fluorescent protein and wild-type mice was used to quantify circulation-derived macrophages in experimental PH conditions. We administered clodronate liposomes to Sugen hypoxia (SU-Hx) exposed rats to deplete macrophages and evaluated the effect on the extracellular matrix (ECM) and capillary network in the RV. In hypoxia exposed mice, the overall number of macrophages did not significantly change but two macrophage subpopulations increased. Parabiosis identified populations of RV macrophages that at steady state is derived from the circulation, with one subpopulation that significantly increased with PH stimuli. Clodronate treatment of SU-Hx rats resulted in a change in the RV ECM, without altering the RV vasculature, and correlated with improved RV function. Populations of RV macrophages increase and contribute to RV remodeling in PH, including through regulation of the RV ECM.
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- 2022
18. In situ plasma and neutral gas observation time windows during a comet flyby: Application to the Comet Interceptor mission
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De Keyser, J., Edberg, N.J.T., Henri, P., Auster, H.-U., Galand, M., Rubin, M., Nilsson, H., Soucek, J., André, N., Corte, V. Della, Rothkaehl, H., Funase, R., Kasahara, S., and Van Damme, C. Corral
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- 2024
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19. Numerical algorithm for quaternion integration based on three independent parameters with no need for re-normalization
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Rubin, M. B. and Weiss, H.
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- 2023
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20. Experimental Schistosoma japonicum-induced pulmonary hypertension
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Kassa, Biruk, Lee, Michael H, Kumar, Rahul, Mickael, Claudia, Sanders, Linda, Tuder, Rubin M, Mentink-Kane, Margaret, and Graham, Brian B
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Biomedical and Clinical Sciences ,Clinical Sciences ,Digestive Diseases ,Lung ,Infectious Diseases ,Rare Diseases ,Vector-Borne Diseases ,Cardiovascular ,Good Health and Well Being ,Animals ,Hypertension ,Pulmonary ,Inflammation ,Mice ,Schistosoma japonicum ,Schistosoma mansoni ,Schistosomiasis ,Biological Sciences ,Medical and Health Sciences ,Tropical Medicine ,Biological sciences ,Biomedical and clinical sciences ,Health sciences - Abstract
BackgroundSchistosomiasis, a major cause of pulmonary arterial hypertension (PAH) worldwide, is most clearly described complicating infection by one species, Schistosoma mansoni. Controlled exposure of mice can be used to induce Type 2 inflammation-dependent S. mansoni pulmonary hypertension (PH). We sought to determine if another common species, S. japonicum, can also cause experimental PH.MethodsSchistosome eggs were obtained from infected mice, and administered by intraperitoneal sensitization followed by intravenous challenge to experimental mice, which underwent right heart catheterization and tissue analysis.ResultsS. japonicum sensitized and challenged mice developed PH, which was milder than that following S. mansoni sensitization and challenge. The degree of pulmonary vascular remodeling and Type 2 inflammation in the lungs was similarly proportionate. Cross-sensitization revealed that antigens from either species are sufficient to sensitize for intravenous challenge with either egg, and the degree of PH severity depended on primarily the species used for intravenous challenge. Compared to a relatively uniform distribution of S. mansoni eggs, S. japonicum eggs were observed in clusters in the lungs.ConclusionsS. japonicum can induce experimental PH, which is milder than that resulting from comparable S. mansoni exposure. This difference may result from the distribution of eggs in the lungs, and is independent of which species is used for sensitization. This result is consistent with the clearer association between S. mansoni infection and the development of schistosomiasis-associated PAH in humans.
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- 2022
21. Cyanogen, cyanoacetylene, and acetonitrile in comet 67P and their relationship to the cyano radical
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Hänni, N., Altwegg, K., Balsiger, H., Combi, M., Fuselier, S. A., De Keyser, J., Pestoni, B., Rubin, M., and Wampfler, S. F.
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Astrophysics - Earth and Planetary Astrophysics - Abstract
The cyano radical (CN) is one of the most frequently remotely observed species in space, also in comets. Data from the high-resolution Double Focusing Mass Spectrometer (DFMS) on board the Rosetta orbiter, collected in the inner coma of comet 67P/Churyumov-Gerasimenko, revealed an unexpected chemical complexity, and, recently, also more CN than expected from photodissociation of its most likely parent hydrogen cyanide (HCN). This work is dedicated to the derivation of abundances relative to HCN of three cometary nitriles (including structural isomers) from DFMS data. Mass spectrometry of complex mixtures does not always allow distinction of structural isomers. We assumed the most stable and most abundant (in similar environments) structure in our analysis, that is HCN for CHN, CH3CN for C2H3N, HC3N for C3HN, and NCCN for C2N2. For cyanoacetylene (HC3N) and acetonitrile (CH3CN) the complete mission timeline was evaluated, while cyanogen (NCCN) often was below detection limit. By carefully selecting periods where cyanogen was above detection limit, we were able to follow the abundance ratio between NCCN and HCN from 3.16 au inbound to 3.42 au outbound. These are the first measurements of NCCN in a comet.We find that neither NCCN, nor any of the other two nitriles, is sufficiently abundant to be a relevant alternative parent to CN.
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- 2021
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22. Multi-instrument analysis of far-ultraviolet aurora in the southern hemisphere of comet 67P/Churyumov-Gerasimenko
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Stephenson, P., Galand, M., Feldman, P. D., Beth, A., Rubin, M., Bockelée-Morvan, D., Biver, N., Cheng, Y. -C, Parker, J., Burch, J., Johansson, F. L., and Eriksson, A.
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Astrophysics - Earth and Planetary Astrophysics ,Physics - Space Physics - Abstract
Aims. We aim to determine whether dissociative excitation of cometary neutrals by electron impact is the major source of far-ultraviolet (FUV) emissions at comet 67P/Churyumov-Gerasimenko in the southern hemisphere at large heliocentric distances, both during quiet conditions and impacts of corotating interaction regions observed in the summer of 2016. Methods. We combined multiple datasets from the Rosetta mission through a multi-instrument analysis to complete the first forward modelling of FUV emissions in the southern hemisphere of comet 67P and compared modelled brightnesses to observations with the Alice FUV imaging spectrograph. We modelled the brightness of OI1356, OI1304, Lyman-$\beta$, CI1657, and CII1335 emissions, which are associated with the dissociation products of the four major neutral species in the coma: CO$_2$, H$_2$O, CO, and O$_2$. The suprathermal electron population was probed by RPC/IES and the neutral column density was constrained by several instruments: ROSINA, MIRO and VIRTIS. Results. The modelled and observed brightnesses of the FUV emission lines agree closely when viewing nadir and dissociative excitation by electron impact is shown to be the dominant source of emissions away from perihelion. The CII1335 emissions are shown to be consistent with the volume mixing ratio of CO derived from ROSINA. When viewing the limb during the impacts of corotating interaction regions, the model reproduces brightnesses of OI1356 and CI1657 well, but resonance scattering in the extended coma may contribute significantly to the observed Lyman-$\beta$ and OI1304 emissions. The correlation between variations in the suprathermal electron flux and the observed FUV line brightnesses when viewing the comet's limb suggests electrons are accelerated on large scales and that they originate in the solar wind. This means that the FUV emissions are auroral in nature., Comment: 20 pages, 13 figures. Accepted for publication in Astronomy & Astrophysics
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- 2021
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23. Molecule dependent oxygen isotopic ratios in the coma of comet 67P/Churyumov-Gerasimenko
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Altwegg, K., Balsiger, H., Combi, M., De Keyser, J., Drozdovskaya, M. N., Fuselier, S. A., Gombosi, T. I., Hänni, N., Rubin, M., Schuhmann, M., Schroeder, I., and Wampfler, S.
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Astrophysics - Earth and Planetary Astrophysics - Abstract
The ratios of the three stable oxygen isotopes 16O, 17O and 18O on Earth and, as far as we know in the solar system, show variations on the order of a few percent at most, with a few outliers in meteorites. However, in the interstellar medium there are some highly fractionated oxygen isotopic ratios in some specific molecules. The goal of this work is to investigate the oxygen isotopic ratios in different volatile molecules found in the coma of comet 67P/Churyumov-Gerasimenko and compare them with findings from interstellar clouds in order to assess commonalities and differences. To accomplish this goal, we analyzed data from the ROSINA instrument on Rosetta during its mission around the comet. 16O/18O ratios could be determined for O2, methanol, formaldehyde, carbonyl sulfide and sulfur monoxide/dioxide. For O2 the 16O/17O ratio is also available. Some ratios are strongly enriched in the heavy isotopes, especially for sulfur bearing molecules and formaldehyde, whereas for methanol the ratios are compatible with the ones in the solar system. O2 falls in-between, but its oxygen isotopic ratios clearly differ from water, which likely rules out an origin of O2 from water, be it by radiolysis, dismutation during sublimation or the Eley-Rideal process from water ions hitting the nucleus as postulated in the literature.
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- 2020
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24. The Effect of Cosmic Rays on Cometary Nuclei: I Dose deposition
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Gronoff, G., Maggiolo, R., Cessateur, G., Moore, W. B., Airapetian, V., De Keyser, J., Dhooghe, F., Gibbons, A., Gunell, H., Mertens, C. J., Rubin, M., and Hosseini, S.
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Astrophysics - Earth and Planetary Astrophysics ,Astrophysics - High Energy Astrophysical Phenomena ,Physics - Space Physics - Abstract
Comets are small bodies thought to contain the most pristine material in the solar system. However, since their formation 4.5 Gy ago, they have been altered by different processes. While not exposed to much electromagnetic radiation, they experience intense particle radiation. Galactic cosmic rays and solar energetic particles have a broad spectrum of energies and interact with the cometary surface and subsurface; they are the main source of space weathering for a comet in the Kuiper Belt or in the Oort cloud; and also affect the ice prior to the comet agglomeration. While low energy particles interact only with the cometary surface, the most energetic ones deposit a significant amount of energy down to tens of meters. This interaction can modify the isotopic ratios in cometary ices and create secondary compounds through radiolysis, such as O2 and H2O2 (paper II: Maggiolo et al., 2020). In this paper, we model the energy deposition of energetic particles as a function of depth using a Geant4 application modified to account for the isotope creation process. We quantify the energy deposited in cometary nucleus by galactic cosmic rays and solar energetic particles. The consequences of the energy deposition on the isotopic and chemical composition of cometary ices and their implication on the interpretation of cometary observations, notably of 67P/Churyumov Gerasimenko by the ESA/Rosetta spacecraft, will be discussed in Paper II.
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- 2020
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25. A Generalized Ogden-Type Elastically Isotropic Hyperelastic Model Including Elastic-Viscoplastic Response
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Rubin, M. B. and Heiduschke, K.
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- 2023
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26. ROSINA ion zoo at Comet 67P
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Beth, A., Altwegg, K., Balsiger, H., Berthelier, J. -J., Combi, M. R., De Keyser, J., Fiethe, B., Fuselier, S. A., Galand, M., Gombosi, T. I., Rubin, M., and Sémon, T.
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Astrophysics - Earth and Planetary Astrophysics ,Astrophysics - Instrumentation and Methods for Astrophysics - Abstract
The Rosetta spacecraft escorted Comet 67P/Churyumov-Gerasimenko for 2 years along its journey through the Solar System between 3.8 and 1.24~au. Thanks to the high resolution mass spectrometer on board Rosetta, the detailed ion composition within a coma has been accurately assessed in situ for the very first time. Previous cometary missions, such as $\text{Giotto}$, did not have the instrumental capabilities to identify the exact nature of the plasma in a coma because the mass resolution of the spectrometers onboard was too low to separate ion species with similar masses. In contrast, the Double Focusing Mass Spectrometer (DFMS), part of the Rosetta Orbiter Spectrometer for Ion and Neutral Analysis on board Rosetta (ROSINA), with its high mass resolution mode, outperformed all of them, revealing the diversity of cometary ions. We calibrated and analysed the set of spectra acquired by DFMS in ion mode from October 2014 to April 2016. In particular, we focused on the range from 13-39 u$\cdot$q$^{-1}$. The high mass resolution of DFMS allows for accurate identifications of ions with quasi-similar masses, separating $^{13}$C$^+$ from CH$^+$, for instance. We confirm the presence in situ of predicted cations at comets, such as CH$_m^+$ ($m=1-4$), H$_n$O$^+$ ($n=1-3$), O$^+$, Na$^+$, and several ionised and protonated molecules. Prior to Rosetta, only a fraction of them had been confirmed from Earth-based observations. In addition, we report for the first time the unambiguous presence of a molecular dication in the gas envelope of a Solar System body, namely CO$_2^{++}$., Comment: Accepted for publication in A&A
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- 2020
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27. Electron Dynamics near Diamagnetic Regions of Comet 67P/Churyumov-Gerasimenko
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Madanian, H., Burch, J. L., Eriksson, A. I., Cravens, T. E., Galand, M., Vigren, E., Goldstein, R., Nemeth, Z., Mokashi, P., Richter, I., and Rubin, M.
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Physics - Space Physics ,Physics - Plasma Physics - Abstract
The Rosetta spacecraft detected transient and sporadic diamagnetic regions around comet 67P/Churyumov-Gerasimenko. In this paper we present a statistical analysis of bulk and suprathermal electron dynamics, as well as a case study of suprathermal electron pitch angle distributions (PADs) near a diamagnetic region. Bulk electron densities are correlated with the local neutral density and we find a distinct enhancement in electron densities measured over the southern latitudes of the comet. Flux of suprathermal electrons with energies between tens of eV to a couple of hundred eV decreases each time the spacecraft enters a diamagnetic region. We propose a mechanism in which this reduction can be explained by solar wind electrons that are tied to the magnetic field and after having been transported adiabatically in a decaying magnetic field environment, have limited access to the diamagnetic regions. Our analysis shows that suprathermal electron PADs evolve from an almost isotropic outside the diamagnetic cavity to a field-aligned distribution near the boundary. Electron transport becomes chaotic and non-adiabatic when electron gyroradius becomes comparable to the size of the magnetic field line curvature, which determines the upper energy limit of the flux variation. This study is based on Rosetta observations at around 200 km cometocentric distance when the comet was at 1.24 AU from the Sun and during the southern summer cometary season.
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- 2020
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28. Evidence of ammonium salts in comet 67P as explanation for the nitrogen depletion in cometary comae
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Altwegg, K., Balsiger, H., Berthelier, J. -J., Briois, C., Combi, M., Cottin, H., De Keyser, J., Dhooghe, F., Fiethe, B., Fuselier, S. A., Gombosi, T. I., Hänni, N., Rubin, M., Schuhmann, M., Schroeder, I., Sémon, T., and Wampfler, S.
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Astrophysics - Earth and Planetary Astrophysics - Abstract
Cometary comae are generally depleted in nitrogen. The main carriers for volatile nitrogen in comets are NH3 and HCN. It is known that ammonia readily combines with many acids like e.g. HCN, HNCO, HCOOH, etc. encountered in the interstellar medium as well as in cometary ice to form ammonium salts (NH4+X-) at low temperatures. Ammonium salts, which can play a significant role in prebiotic chemistry, are hard to detect in space as they are unstable in the gas phase and their infrared signature is often hidden by thermal radiation or by e.g. OH in minerals. Here we report the presence of all possible sublimation products of five different ammonium salts at comet 67P/Churyumov-Gerasimenko measured by the ROSINA instrument on Rosetta. The relatively high sublimation temperatures of the salts leads to an apparent lack of volatile nitrogen in the coma. This then also explains the observed trend of higher NH3/H2O ratios with decreasing perihelion distances in comets.
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- 2019
29. ALMA and ROSINA detections of phosphorus-bearing molecules: the interstellar thread between star-forming regions and comets
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Rivilla, V. M., Drozdovskaya, M. N., Altwegg, K., Caselli, P., Beltrán, M. T., Fontani, F., van der Tak, F. F. S., Cesaroni, R., Vasyunin, A., Rubin, M., Lique, F., Marinakis, S., Testi, L., and team, the ROSINA
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Astrophysics - Astrophysics of Galaxies ,Astrophysics - Solar and Stellar Astrophysics - Abstract
To understand how Phosphorus-bearing molecules are formed in star-forming regions, we have analysed ALMA observations of PN and PO towards the massive star-forming region AFGL 5142, combined with a new analysis of the data of the comet 67P/Churyumov-Gerasimenko taken with the ROSINA instrument onboard Rosetta. The ALMA maps show that the emission of PN and PO arises from several spots associated with low-velocity gas with narrow linewidths in the cavity walls of a bipolar outflow. PO is more abundant than PN in most of the spots, with the PO/PN ratio increasing as a function of the distance to the protostar. Our data favor a formation scenario in which shocks sputter phosphorus from the surface of dust grains, and gas-phase photochemistry induced by UV photons from the protostar allows efficient formation of the two species in the cavity walls. Our analysis of the ROSINA data has revealed that PO is the main carrier of P in the comet, with PO/PN>10. Since comets may have delivered a significant amount of prebiotic material to the early Earth, this finding suggests that PO could contribute significantly to the phosphorus reservoir during the dawn of our planet. There is evidence that PO was already in the cometary ices prior to the birth of the Sun, so the chemical budget of the comet might be inherited from the natal environment of the Solar System, which is thought to be a stellar cluster including also massive stars., Comment: Accepted in MNRAS (20 pages, 12 figures)
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- 2019
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30. A nanolander for a space mission to an active asteroid in the main belt
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Ho, T.M., Kührt, E., Zhang, X.J., Auster, U., Biele, J., Grott, M., Grundmann, J.T., He, H., Hördt, A., Huang, J.C., Ma, T., Mottola, S., Otto, K., Plettemeier, D., Qin, L., Rubin, M., Schmitz, N., Ulamec, S., and Vincent, J.B.
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- 2023
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31. Cometary plasma science: Open science questions for future space missions
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Goetz, C., Gunell, H., Volwerk, M., Beth, A., Eriksson, A., Galand, M., Henri, P., Nilsson, H., Wedlund, C. Simon, Alho, M., Andersson, L., Andre, N., De Keyser, J., Deca, J., Ge, Y., Glassmeier, K.-H., Hajra, R., Karlsson, T., Kasahara, S., Kolmasova, I., LLera, K., Madanian, H., Mann, I., Mazelle, C., Odelstad, E., Plaschke, F., Rubin, M., Sanchez-Cano, B., Snodgrass, C., and Vigren, E.
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- 2022
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32. Sample return of primitive matter from the outer Solar System
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Vernazza, P., Beck, P., Ruesch, O., Bischoff, A., Bonal, L., Brennecka, G., Brunetto, R., Busemann, H., Carter, J., Carli, C., Cartier, C., Ciarniello, M., Debaille, V., Delsanti, A., D’Hendecourt, L., Füri, E., Groussin, O., Guilbert-Lepoutre, A., Helbert, J., Hoppe, P., Jehin, E., Jorda, L., King, A., Kleine, T., Lamy, P., Lasue, J., Le Guillou, C., Leroux, H., Leya, I., Magna, T., Marrocchi, Y., Morlok, A., Mousis, O., Palomba, E., Piani, L., Quirico, E., Remusat, L., Roskosz, M., Rubin, M., Russell, S., Schönbächler, M., Thomas, N., Villeneuve, J., Vinogradoff, V., Wurz, P., and Zanda, B.
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- 2022
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33. Interstitial macrophage-derived thrombospondin-1 contributes to hypoxia-induced pulmonary hypertension
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Kumar, Rahul, Mickael, Claudia, Kassa, Biruk, Sanders, Linda, Hernandez-Saavedra, Daniel, Koyanagi, Daniel E, Kumar, Sushil, Pugliese, Steve C, Thomas, Stacey, McClendon, Jazalle, Maloney, James P, Janssen, William J, Stenmark, Kurt R, Tuder, Rubin M, and Graham, Brian B
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Lung ,Clinical Research ,Stem Cell Research ,Stem Cell Research - Nonembryonic - Non-Human ,2.1 Biological and endogenous factors ,Aetiology ,Cardiovascular ,Animals ,Basic Helix-Loop-Helix Transcription Factors ,Blood Pressure ,Disease Models ,Animal ,Hypertension ,Pulmonary ,Hypoxia ,Macrophages ,Mice ,Inbred C57BL ,Mice ,Knockout ,Parabiosis ,Signal Transduction ,Thrombospondin 1 ,Transforming Growth Factor beta1 ,Vasoconstriction ,rho-Associated Kinases ,Pulmonary hypertension ,Interstitial macrophages ,Inflammation - Abstract
AimsTransforming growth factor-β (TGF-β) signalling is required for chronic hypoxia-induced pulmonary hypertension (PH). The activation of TGF-β by thrombospondin-1 (TSP-1) contributes to the pathogenesis of hypoxia-induced PH. However, neither the cellular source of pathologic TSP-1 nor the downstream signalling pathway that link activated TGF-β to PH have been determined. In this study, we hypothesized that circulating monocytes, which are recruited to become interstitial macrophages (IMs), are the major source of TSP-1 in hypoxia-exposed mice, and TSP-1 activates TGF-β with increased Rho-kinase signalling, causing vasoconstriction.Methods and resultsFlow cytometry revealed that a specific subset of IMs is the major source of pathologic TSP-1 in hypoxia. Intravenous depletion and parabiosis experiments demonstrated that these cells are circulating prior to recruitment into the interstitium. Rho-kinase-mediated vasoconstriction was a major downstream target of active TGF-β. Thbs1 deficient bone marrow (BM) protected against hypoxic-PH by blocking TGF-β activation and Rho-kinase-mediated vasoconstriction.ConclusionIn hypoxia-challenged mice, BM derived and circulating monocytes are recruited to become IMs which express TSP-1, resulting in TGF-β activation and Rho-kinase-mediated vasoconstriction.
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- 2020
34. Publisher Correction: Stable isotope metabolomics of pulmonary artery smooth muscle and endothelial cells in pulmonary hypertension and with TGF-beta treatment.
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Hernandez-Saavedra, Daniel, Sanders, Linda, Freeman, Scott, Reisz, Julie A, Lee, Michael H, Mickael, Claudia, Kumar, Rahul, Kassa, Biruk, Gu, Sue, D' Alessandro, Angelo, Stenmark, Kurt R, Tuder, Rubin M, and Graham, Brian B
- Abstract
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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- 2020
35. Stable isotope metabolomics of pulmonary artery smooth muscle and endothelial cells in pulmonary hypertension and with TGF-beta treatment.
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Hernandez-Saavedra, Daniel, Sanders, Linda, Freeman, Scott, Reisz, Julie A, Lee, Michael H, Mickael, Claudia, Kumar, Rahul, Kassa, Biruk, Gu, Sue, D' Alessandro, Angelo, Stenmark, Kurt R, Tuder, Rubin M, and Graham, Brian B
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Muscle ,Smooth ,Vascular ,Pulmonary Artery ,Endothelium ,Vascular ,Cells ,Cultured ,Humans ,Hypertension ,Pulmonary ,Transforming Growth Factor beta ,Case-Control Studies ,Isotope Labeling ,Signal Transduction ,Cell Proliferation ,Citric Acid Cycle ,Glycolysis ,Adolescent ,Adult ,Middle Aged ,Female ,Male ,Pentose Phosphate Pathway ,Metabolome - Abstract
Altered metabolism in pulmonary artery smooth muscle cells (PASMCs) and endothelial cells (PAECs) contributes to the pathology of pulmonary hypertension (PH), but changes in substrate uptake and how substrates are utilized have not been fully characterized. We hypothesized stable isotope metabolomics would identify increased glucose, glutamine and fatty acid uptake and utilization in human PASMCs and PAECs from PH versus control specimens, and that TGF-β treatment would phenocopy these metabolic changes. We used 13C-labeled glucose, glutamine or a long-chain fatty acid mixture added to cell culture media, and mass spectrometry-based metabolomics to detect and quantify 13C-labeled metabolites. We found PH PASMCs had increased glucose uptake and utilization by glycolysis and the pentose shunt, but no changes in glutamine or fatty acid uptake or utilization. Diseased PAECs had increased proximate glycolysis pathway intermediates, less pentose shunt flux, increased anaplerosis from glutamine, and decreased fatty acid β-oxidation. TGF-β treatment increased glycolysis in PASMCs, but did not recapitulate the PAEC disease phenotype. In TGF-β-treated PASMCs, glucose, glutamine and fatty acids all contributed carbons to the TCA cycle. In conclusion, PASMCs and PAECs collected from PH subjects have significant changes in metabolite uptake and utilization, partially recapitulated by TGF-β treatment.
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- 2020
36. Descending Aortic Distensibility and Cardiovascular Outcomes: A Cardiac Magnetic Resonance Imaging Study
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Sood MR, Abdelmoneim SS, Dontineni N, Ivanov A, Lee E, Rubin M, Vittoria M, Meykler M, Ramachandran V, Sacchi T, Brener S, Klem I, and Heitner JF
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cardiovascular magnetic resonance ,aortic distensibility ,descending aorta ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Michael R Sood,1,2 Sahar S Abdelmoneim,1 Nripen Dontineni,1 Alexander Ivanov,1 Ernest Lee,1 Michael Rubin,1 Michael Vittoria,1 Marcella Meykler,1 Vidhya Ramachandran,1 Terrence Sacchi,1 Sorin Brener,1 Igor Klem,3 John F Heitner1,4 1Division of Cardiology, New York-Presbyterian Hospital, Brooklyn, NY, USA; 2Division of Cardiology, Mount Sinai South Nassau, Oceanside, NY, USA; 3Duke University, Raleigh Durham, NC, USA; 4Division of Cardiology, New York University-Langone Health, Brooklyn, NY, USACorrespondence: Michael R Sood, Division of Cardiology, Mount Sinai South Nassau, Oceanside, NY, USA, Email mike.sood@gmail.comBackground: Aortic distensibility (AD) is an important determinant of cardiovascular (CV) morbidity and mortality. There is scant data on the association between AD measured within the descending thoracic aorta and CV outcomes.Objective: We evaluated the association of AD at the descending thoracic aorta (AD desc) with the primary outcome of all-cause mortality, myocardial infarction (MI), stroke or coronary revascularization in patients referred for a cardiovascular magnetic resonance (CMR) study.Methods: 928 consecutive patients [(mean age 60 ± 17; 33% with prior cardiovascular disease (CVD))] were evaluated. AD desc was measured at the cross-section of the descending thoracic aorta in the 4-chamber view (via steady-state free precession [SSFP] cine sequences) and was grouped into quintiles (with the 1st quintile corresponding to the least AD, i.e., the stiffest aorta). Cox proportional-hazards regression analysis were performed for the primary outcome.Results: A total of 315 patients (34%) experienced the primary outcome during a median (25% IQR, 75% IQR) follow-up of 5.0 (0.56, 9.3) years. A decreased AD was significantly associated with hypertension, diabetes, renal disease, and dyslipidemia (p < 0.0001). A primary outcome occurred in 43% of patients with AD desc ≤ median compared to 25% with AD desc > median, p < 0.0001, and in 44% of patients with AD desc in the 1st quintile compared to 31% with AD desc in the other quintiles (p = 0.0004). Event free survival was incrementally reduced amongst quintiles (p < 0.0001). However, AD desc ≤ median was not an independent predictor of the primary endpoint after multivariable adjustment in the overall population [adjusted HR 1.09 (95% CI:0.82– 1.45), p = 0.518] or in the subgroup analysis of patients with or without prior CVD.Conclusion: In this real-world cohort of 928 patients referred for CMR, AD desc is not an independent predictor of CV outcomes.Keywords: cardiovascular magnetic resonance, aortic distensibility, descending aorta, AD, CMR
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- 2022
37. Interstitial macrophage phenotypes in Schistosoma-induced pulmonary hypertension
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Kumar, Rahul, primary, Kumar, Sushil, additional, Mickael, Claudia, additional, Fonseca Balladares, Dara, additional, Nolan, Kevin, additional, Lee, Michael H., additional, Sanders, Linda, additional, Nilsson, Julia, additional, Molofsky, Ari B., additional, Tuder, Rubin M., additional, Stenmark, Kurt R., additional, and Graham, Brian B., additional
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- 2024
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38. Spanning latent and observable factors
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Andreou, E., primary, Gagliardini, P., additional, Ghysels, E., additional, and Rubin, M., additional
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- 2024
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39. Plasma Density Structures at Comet 67P/Churyumov-Gerasimenko
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Engelhardt, I. A. D., Eriksson, A. I., Wieser, G. Stenberg, Goetz, C., Rubin, M., Henri, P., Nilsson, H., Odelstad, E., Hajra, R., and Vallières, X.
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Physics - Space Physics ,Astrophysics - Earth and Planetary Astrophysics - Abstract
We present Rosetta RPC case study from four events at various radial distance, phase angle and local time from autumn 2015, just after perihelion of comet 67P/Churyumov-Gerasimenko. Pulse like (high amplitude, up to minutes in time) signatures are seen with several RPC instruments in the plasma density (LAP, MIP), ion energy and flux (ICA) as well as magnetic field intensity (MAG). Furthermore the cometocentric distance relative to the electron exobase is seen to be a good organizing parameter for the measured plasma variations. The closer Rosetta is to this boundary, the more pulses are measured. This is consistent with the pulses being filaments of plasma originating from the diamagnetic cavity boundary as predicted by simulations., Comment: This article has been accepted for publication in Monthly Notices of the Royal Astronomical Society, Published by Oxford University Press on behalf of the Royal Astronomical Society
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- 2018
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40. Hall Effect in the coma of 67P/Churyumov-Gerasimenko
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Huang, Z., Toth, G., Gombosi, T. I., Jia, X., Combi, M. R., Hansen, K. C., Fougere, N., Shou, Y., Tenishev, V., Altwegg, K., and Rubin, M.
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Astrophysics - Earth and Planetary Astrophysics ,Physics - Space Physics - Abstract
Magnetohydrodynamics simulations have been carried out in studying the solar wind and cometary plasma interactions for decades. Various plasma boundaries have been simulated and compared well with observations for comet 1P/Halley. The Rosetta mission, which studies comet 67P/Churyumov-Gerasimenko, challenges our understanding of the solar wind and comet interactions. The Rosetta Plasma Consortium observed regions of very weak magnetic field outside the predicted diamagnetic cavity. In this paper, we simulate the inner coma with the Hall magnetohydrodynamics equations and show that the Hall effect is important in the inner coma environment. The magnetic field topology becomes complex and magnetic reconnection occurs on the dayside when the Hall effect is taken into account. The magnetic reconnection on the dayside can generate weak magnetic filed regions outside the global diamagnetic cavity, which may explain the Rosetta Plasma Consortium observations. We conclude that the substantial change in the inner coma environment is due to the fact that the ion inertial length (or gyro radius) is not much smaller than the size of the diamagnetic cavity., Comment: 23 pages, 6 figurs
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- 2018
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41. Th2 CD4+ T Cells Are Necessary and Sufficient for Schistosoma‐Pulmonary Hypertension
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Kumar, Rahul, Mickael, Claudia, Kassa, Biruk, Sanders, Linda, Koyanagi, Dan, Hernandez‐Saavedra, Daniel, Freeman, Scott, Morales‐Cano, Daniel, Cogolludo, Angel, McKee, Amy S, Fontenot, Andrew P, Butrous, Ghazwan, Tuder, Rubin M, and Graham, Brian B
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Rare Diseases ,Digestive Diseases ,Lung ,Vector-Borne Diseases ,2.1 Biological and endogenous factors ,Aetiology ,Good Health and Well Being ,Animals ,CD4-Positive T-Lymphocytes ,Disease Models ,Animal ,Female ,Hypertension ,Pulmonary ,Mice ,Mice ,Inbred C57BL ,Pneumonia ,Schistosomiasis ,Th2 Cells ,CD4 T cell ,pulmonary hypertension ,schistosomiasis ,type 2 immunity ,Cardiorespiratory Medicine and Haematology - Abstract
Background Inflammation underlies many forms of pulmonary hypertension (PH), including that resulting from Schistosoma infection, a major cause of PH worldwide. Schistosomiasis-associated PH is proximately triggered by embolization of parasite eggs into the lungs, resulting in localized type 2 inflammation. However, the role of CD4+ T cells in this disease is not well defined. Methods and Results We used a mouse model of schistosomiasis-associated PH, induced by intraperitoneal egg sensitization followed by intravenous egg challenge, with outcomes including right ventricle systolic pressure measured by cardiac catheterization, and cell density and phenotype assessed by flow cytometry. We identified that embolization of Schistosoma eggs into lungs of egg-sensitized mice increased the perivascular density of T-helper 2 (Th2) CD4+ T cells by recruitment of cells from the circulation and triggered type 2 inflammation. Parabiosis confirmed that egg embolization is required for localized type 2 immunity. We found Th2 CD4+ T cells were necessary for Schistosoma-induced PH, given that deletion of CD4+ T cells or inhibiting their Th2 function protected against type 2 inflammation and PH following Schistosoma exposure. We also observed that adoptive transfer of Schistosoma-sensitized CD4+ Th2 cells was sufficient to drive type 2 inflammation and PH. Conclusions Th2 CD4+ T cells are a necessary and sufficient component for the type 2 inflammation-induced PH following Schistosoma exposure.
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- 2019
42. Systems Analysis of the Human Pulmonary Arterial Hypertension Lung Transcriptome
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Stearman, Robert S, Bui, Quan M, Speyer, Gil, Handen, Adam, Cornelius, Amber R, Graham, Brian B, Kim, Seungchan, Mickler, Elizabeth A, Tuder, Rubin M, Chan, Stephen Y, and Geraci, Mark W
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Lung ,Rare Diseases ,Biotechnology ,Cardiovascular ,Heart Disease ,Genetics ,2.1 Biological and endogenous factors ,Aetiology ,Adolescent ,Adult ,Aged ,Child ,Child ,Preschool ,Female ,Gene Expression Regulation ,Gene Ontology ,Humans ,Infant ,Male ,Middle Aged ,Pulmonary Arterial Hypertension ,Sex Characteristics ,Signal Transduction ,Systems Analysis ,Transcriptome ,Young Adult ,pulmonary arterial hypertension ,lung transcriptomics ,bioinformatics ,Cardiorespiratory Medicine and Haematology ,Respiratory System - Abstract
Pulmonary arterial hypertension (PAH) is characterized by increased pulmonary artery pressure and vascular resistance, typically leading to right heart failure and death. Current therapies improve quality of life of the patients but have a modest effect on long-term survival. A detailed transcriptomics and systems biology view of the PAH lung is expected to provide new testable hypotheses for exploring novel treatments. We completed transcriptomics analysis of PAH and control lung tissue to develop disease-specific and clinical data/tissue pathology gene expression classifiers from expression datasets. Gene expression data were integrated into pathway analyses. Gene expression microarray data were collected from 58 PAH and 25 control lung tissues. The strength of the dataset and its derived disease classifier was validated using multiple approaches. Pathways and upstream regulators analyses was completed with standard and novel graphical approaches. The PAH lung dataset identified expression patterns specific to PAH subtypes, clinical parameters, and lung pathology variables. Pathway analyses indicate the important global role of TNF and transforming growth factor signaling pathways. In addition, novel upstream regulators and insight into the cellular and innate immune responses driving PAH were identified. Finally, WNT-signaling pathways may be a major determinant underlying the observed sex differences in PAH. This study provides a transcriptional framework for the PAH-diseased lung, supported by previously reported findings, and will be a valuable resource to the PAH research community. Our investigation revealed novel potential targets and pathways amenable to further study in a variety of experimental systems.
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- 2019
43. Paclitaxel blocks Th2‐mediated TGF‐β activation in Schistosoma mansoni‐induced pulmonary hypertension
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Kassa, Biruk, Mickael, Claudia, Kumar, Rahul, Sanders, Linda, Koyanagi, Dan, Hernandez‐Saavedra, Daniel, Tuder, Rubin M, and Graham, Brian B
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Biomedical and Clinical Sciences ,Clinical Sciences ,Lung ,Rare Diseases ,Digestive Diseases ,Vector-Borne Diseases ,Aetiology ,2.1 Biological and endogenous factors ,Cardiovascular ,Good Health and Well Being ,parasitic infections ,pulmonary hypertension experimental ,inflammation ,Cardiorespiratory Medicine and Haematology ,Cardiovascular medicine and haematology - Abstract
Schistosomiasis is a leading cause of pulmonary hypertension (PH) worldwide. Recent studies reveal that the type-2 immune cytokines IL-4 and IL-13, as well as consequent activation of TGF-β, are key factors in the pathogenesis of Schistosoma-PH. Paclitaxel has been reported to act as an adjuvant for Th2 inflammation while downregulating TGF-β activation. Moreover, paclitaxel blocks PH in monocrotaline and SU5416-hypoxia models. We hypothesized that paclitaxel would augment Th2 inflammation while blocking TGF-β activation and PH after schistosomiasis exposure. Wild-type mice (C57BL6/J; 6/group) were intraperitoneally (IP) sensitized and then intravenously (IV) challenged with Schistosoma mansoni eggs. One day after IV egg challenge, the mice were treated with a single IP dose of 25 mg/kg paclitaxel or vehicle. Right ventricular (RV) catheterization was performed and granuloma volumes and vascular remodeling were quantified. Lung cytokines were quantified by ELISA and reverse transcription polymerase chain reaction, and the quantity of active TGF-β was determined using a cell reporter line. We also investigated hypoxia-induced PH. Paclitaxel treatment significantly protected mice from Schistosoma-PH, with decreased RV systolic pressure ( P = 0.005) and pulmonary vascular media thickness. Inflammation was significantly suppressed, contrary to our hypothesis, with decreased IL-4 and IL-13 levels, smaller granulomas, and less active TGF-β following paclitaxel treatment. There was no change in IFN-γ or FoxO1 or FoxO3 expression. Paclitaxel did not suppress chronic hypoxia-induced PH, which is also TGF-β-driven but independent of type-2 immunity. Paclitaxel protects against Schistosoma-induced PH in mice, although by blocking proximate Th2 inflammation rather than suppressing distal TGF-β activation.
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- 2019
44. Identification and characterization of a new ensemble of cometary organic molecules
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Hänni, N., Altwegg, K., Combi, M., Fuselier, S. A., De Keyser, J., Rubin, M., and Wampfler, S. F.
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- 2022
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45. Anisotropy of a discrete fiber icosahedron model for fibrous tissues exhibited for large deformations
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Rubin, M. B.
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- 2022
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46. The Castalia Mission to Main Belt Comet 133P/Elst-Pizarro
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Snodgrass, C., Jones, G. H., Boehnhardt, H., Gibbings, A., Homeister, M., Andre, N., Beck, P., Bentley, M. S., Bertini, I., Bowles, N., Capria, M. T., Carr, C., Ceriotti, M., Coates, A. J., Della Corte, V., Hanna, K. L. Donaldson, Fitzsimmons, A., Gutierrez, P. J., Hainaut, O. R., Herique, A., Hilchenbach, M., Hsieh, H. H., Jehin, E., Karatekin, O., Kofman, W., Lara, L. M., Laudan, K., Licandro, J., Lowry, S. C., Marzari, F., Masters, A., Meech, K. J., Moreno, F., Morse, A., Orosei, R., Pack, A., Plettemeier, D., Prialnik, D., Rotundi, A., Rubin, M., Sanchez, J. P., Sheridan, S., Trieloff, M., and Winterboer, A.
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Astrophysics - Earth and Planetary Astrophysics - Abstract
We describe Castalia, a proposed mission to rendezvous with a Main Belt Comet (MBC), 133P/Elst-Pizarro. MBCs are a recently discovered population of apparently icy bodies within the main asteroid belt between Mars and Jupiter, which may represent the remnants of the population which supplied the early Earth with water. Castalia will perform the first exploration of this population by characterising 133P in detail, solving the puzzle of the MBC's activity, and making the first in situ measurements of water in the asteroid belt. In many ways a successor to ESA's highly successful Rosetta mission, Castalia will allow direct comparison between very different classes of comet, including measuring critical isotope ratios, plasma and dust properties. It will also feature the first radar system to visit a minor body, mapping the ice in the interior. Castalia was proposed, in slightly different versions, to the ESA M4 and M5 calls within the Cosmic Vision programme. We describe the science motivation for the mission, the measurements required to achieve the scientific goals, and the proposed instrument payload and spacecraft to achieve these., Comment: Accepted for publication in Advances in Space Research (special issue on Small Body Exploration). 30 pages
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- 2017
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47. Evidence for depletion of heavy silicon isotopes at comet 67P/Churyumov-Gerasimenko
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Rubin, M., Altwegg, K., Balsiger, H., Berthelier, J. -J., Bieler, A., Calmonte, U., Combi, M., De Keyser, J., Engrand, C., Fiethe, B., Fuselier, S. A., Gasc, S., Gombosi, T. I., Hansen, K. C., Hässig, M., Roy, L. Le, Mezger, K., Tzou, C. -Y., Wampfler, S. F., and Wurz, P.
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Astrophysics - Earth and Planetary Astrophysics ,Astrophysics - Solar and Stellar Astrophysics - Abstract
Context. The Rosetta Orbiter Spectrometer for Ion and Neutral Analysis (ROSINA) was designed to measure the composition of the gas in the coma of comet 67P/Churyumov-Gerasimenko, the target of the European Space Agency's Rosetta mission. In addition to the volatiles, ROSINA measured refractories sputtered off the comet by the interaction of solar wind protons with the surface of the comet. Aims. The origin of different solar system materials is still heavily debated. Isotopic ratios can be used to distinguish between different reservoirs and investigate processes occurring during the formation of the solar system. Methods. ROSINA consisted of two mass spectrometers and a pressure sensor. In the ROSINA Double Focusing Mass Spectrometer (DFMS), the neutral gas of cometary origin was ionized and then deflected in an electric and a magnetic field that separated the ions based on their mass-to-charge ratio. The DFMS had a high mass resolution, dynamic range, and sensitivity that allowed detection of rare species and the known major volatiles. Results. We measured the relative abundance of all three stable silicon isotopes with the ROSINA instrument on board the Rosetta spacecraft. Furthermore, we measured $^{13}$C/$^{12}$C in C$_2$H$_4$, C$_2$H$_5$, and CO. The DFMS in situ measurements indicate that the average silicon isotopic composition shows depletion in the heavy isotopes $^{29}$Si and $^{30}$Si with respect to $^{28}$Si and solar abundances, while $^{13}$C to $^{12}$C is analytically indistinguishable from bulk planetary and meteorite compositions. Although the origin of the deficiency of the heavy silicon isotopes cannot be explained unambiguously, we discuss mechanisms that could have contributed to the measured depletion of the isotopes $^{29}$Si and $^{30}$Si., Comment: Accepted for publication in Astronomy & Astrophysics
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- 2017
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48. Impact of radiogenic heating on the formation conditions of comet 67P/Churyumov-Gerasimenko
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Mousis, O., Drouard, A., Vernazza, P., Lunine, J. I., Monnereau, M., Maggiolo, R., Altwegg, K., Balsiger, H., Berthelier, J. -J., Cessateur, G., De Keyser, J., Fuselier, S. A., Gasc, S., Korth, A., Deun, T. Le, Mall, U., Marty, B., Rème, H., Rubin, M., Tzou, C. -Y., Waite, J. H., and Wurz, P.
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Astrophysics - Earth and Planetary Astrophysics - Abstract
Because of the high fraction of refractory material present in comets, the heat produced by the radiogenic decay of elements such as aluminium and iron can be high enough to induce the loss of ultravolatile species such as nitrogen, argon or carbon monoxide during their accretion phase in the protosolar nebula. Here, we investigate how heat generated by the radioactive decay of 26Al and 60Fe influences the formation of comet 67P/Churyumov-Gerasimenko, as a function of its accretion time and size of parent body. We use an existing thermal evolution model that includes various phase transitions, heat transfer in the ice-dust matrix, and gas diffusion throughout the porous material, based on thermodynamic parameters derived from Rosetta observations. Two possibilities are considered: either, to account for its bilobate shape, 67P/Churyumov-Gerasimenko was assembled from two primordial ~2 kilometer-sized planetesimals, or it resulted from the disruption of a larger parent body with a size corresponding to that of comet Hale-Bopp (~70 km). To fully preserve its volatile content, we find that either 67P/Churyumov-Gerasimenko's formation was delayed between ~2.2 and 7.7 Myr after that of Ca-Al-rich Inclusions in the protosolar nebula or the comet's accretion phase took place over the entire time interval, depending on the primordial size of its parent body and the composition of the icy material considered. Our calculations suggest that the formation of 67P/Churyumov-Gerasimenko is consistent with both its accretion from primordial building blocks formed in the nebula or from debris issued from the disruption of a Hale-Bopp-like body., Comment: Accepted for publication in The Astrophysical Journal Letters
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- 2017
- Full Text
- View/download PDF
49. Classical dendritic cells contribute to hypoxia‐induced pulmonary hypertension.
- Author
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Mickael, Claudia, Sanders, Linda A., Lee, Michael H., Kumar, Rahul, Fonseca‐Balladares, Dara, Gandjeva, Aneta, Cautivo‐Reyes, Kelly, Kassa, Biruk, Kumar, Sushil, Irwin, David, Swindle, Delaney, Phang, Tzu, Stearman, Robert S., Molofsky, Ari B., McKee, Amy S., Stenmark, Kurt R., Graham, Brian B., and Tuder, Rubin M.
- Published
- 2024
- Full Text
- View/download PDF
50. Digital Spatial Profiling Identifies Distinct Molecular Signatures of Vascular Lesions in Pulmonary Arterial Hypertension.
- Author
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Tuder, Rubin M., Gandjeva, Aneta, Williams, Sarah, Kumar, Sushil, Kheyfets, Vitaly O., Hatton-Jones, Kyle Matthew, Starr, Jacqueline R., Yun, Jeong, Hong, Jason, West, Nicholas P., and Stenmark, Kurt R.
- Subjects
PULMONARY arterial hypertension ,VASCULAR remodeling ,TRANSFORMING growth factors ,PULMONARY artery ,GENETIC disorders ,PULMONARY hypertension ,ENDOTHELIUM diseases - Abstract
Rationale: Idiopathic pulmonary arterial hypertension (IPAH) is characterized by extensive pulmonary vascular remodeling caused by plexiform and obliterative lesions, media hypertrophy, inflammatory cell infiltration, and alterations of the adventitia. Objective: We sought to test the hypothesis that microscopic IPAH vascular lesions express unique molecular profiles, which collectively are different from control pulmonary arteries. Methods: We used digital spatial transcriptomics to profile the genomewide differential transcriptomic signature of key pathological lesions (plexiform, obliterative, intima+media hypertrophy, and adventitia) in IPAH lungs (n = 11) and compared these data with the intima+media hypertrophy and adventitia of control pulmonary artery (n = 5). Measurements and Main Results: We detected 8,273 transcripts in the IPAH lesions and control lung pulmonary arteries. Plexiform lesions and IPAH adventitia exhibited the greatest number of differentially expressed genes when compared with intima+media hypertrophy and obliterative lesions. Plexiform lesions in IPAH showed enrichment for 1) genes associated with transforming growth factor β signaling and 2) mutated genes affecting the extracellular matrix and endothelial-mesenchymal transformation. Plexiform lesions and IPAH adventitia showed upregulation of genes involved in immune and IFN signaling, coagulation, and complement pathways. Cellular deconvolution indicated variability in the number of vascular and inflammatory cells between IPAH lesions, which underlies the differential transcript profiling. Conclusions: IPAH lesions express unique molecular transcript profiles enriched for pathways involving pathogenetic pathways, including genetic disease drivers, innate and acquired immunity, hypoxia sensing, and angiogenesis signaling. These data provide a rich molecular-structural framework in IPAH vascular lesions that inform novel biomarkers and therapeutic targets in this highly morbid disease. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
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