4,290 results on '"Weigt, A."'
Search Results
2. Fluctuations and the limit of predictability in protein evolution
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Rossi, Saverio, Di Bari, Leonardo, Weigt, Martin, and Zamponi, Francesco
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Quantitative Biology - Biomolecules ,Condensed Matter - Disordered Systems and Neural Networks ,Quantitative Biology - Populations and Evolution - Abstract
Protein evolution involves mutations occurring across a wide range of time scales. In analogy with other disordered systems, this dynamical heterogeneity suggests strong correlations between mutations happening at distinct sites and times. To quantify these correlations, we examine the role of various fluctuation sources in protein evolution, simulated using a data-driven epistatic landscape. By applying spatio-temporal correlation functions inspired by statistical physics, we disentangle fluctuations originating from the ancestral protein sequence from those driven by stochastic mutations along independent evolutionary paths. Our analysis shows that, in diverse protein families, fluctuations from the ancestral sequence predominate at shorter time scales. This allows us to identify a time scale over which ancestral sequence information persists, enabling its reconstruction. We link this persistence to the strength of epistatic interactions: ancestral sequences with stronger epistatic signatures impact evolutionary trajectories over extended periods. At longer time scales, however, ancestral influence fades as epistatically constrained sites evolve collectively. To confirm this idea, we apply a standard ancestral sequence reconstruction algorithm and verify that the time-dependent recovery error is influenced by the properties of the ancestor itself.
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- 2024
3. Sobolev bounds and counterexamples for the second derivative of the maximal function in one dimension
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Weigt, Julian
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Mathematics - Classical Analysis and ODEs ,42B25, 26A45 - Abstract
We investigate the question whether the $L^1(\mathbb R)$-norm of the second derivative of the uncentered Hardy-Littlewood maximal function can be bounded by a constant times the $L^1(\mathbb R)$-norm of the function itself. We give a positive answer for a class of functions that contains Sobolev functions on the real line which are decreasing away from the origin and even, and we provide a counterexample which is also decreasing away from the origin but not even., Comment: 26 pages
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- 2024
4. Triple-Organ Transplantation: Dual Heart-Kidney Transplantation After Lung Transplantation.
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Webb, Martine, Wilson, James, Weigt, S, Sayah, David, Nassiri, Nima, Ardehali, Abbas, Cruz, Daniel, Nsair, Ali, and Kamath, Megan
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advanced heart failure ,heart transplantation ,multiorgan transplantation ,transplant medicine - Abstract
We present a patient with a history of lung transplantation who subsequently underwent dual heart-kidney transplantation for nonischemic cardiomyopathy and chronic kidney disease, becoming one of the rare cases of triple-organ transplantation. This case underscores the evolving challenges and successes in managing complex transplant recipients.
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- 2024
5. Emergent time scales of epistasis in protein evolution
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Di Bari, Leonardo, Bisardi, Matteo, Cotogno, Sabrina, Weigt, Martin, and Zamponi, Francesco
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Quantitative Biology - Biomolecules ,Condensed Matter - Disordered Systems and Neural Networks ,Quantitative Biology - Populations and Evolution - Abstract
We introduce a data-driven epistatic model of protein evolution, capable of generating evolutionary trajectories spanning very different time scales reaching from individual mutations to diverged homologs. Our in silico evolution encompasses random nucleotide mutations, insertions and deletions, and models selection using a fitness landscape, which is inferred via a generative probabilistic model for protein families. We show that the proposed framework accurately reproduces the sequence statistics of both short-time (experimental) and long-time (natural) protein evolution, suggesting applicability also to relatively data-poor intermediate evolutionary time scales, which are currently inaccessible to evolution experiments. Our model uncovers a highly collective nature of epistasis, gradually changing the fitness effect of mutations in a diverging sequence context, rather than acting via strong interactions between individual mutations. This collective nature triggers the emergence of a long evolutionary time scale, separating fast mutational processes inside a given sequence context, from the slow evolution of the context itself. The model quantitatively reproduces epistatic phenomena such as contingency and entrenchment, as well as the loss of predictability in protein evolution observed in deep mutational scanning experiments of distant homologs. It thereby deepens our understanding of the interplay between mutation and selection in shaping protein diversity and novel functions, allows one to statistically forecast evolution, and challenges the prevailing independent-site models of protein evolution, which are unable to capture the fundamental importance of epistasis., Comment: 31 pages, 16 figures - final version
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- 2024
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6. Tracking solar radio bursts using Bayesian multilateration
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Cañizares, L. A., Badman, S. T., Maloney, S. A., Owens, M. J., Weigt, D. M., Carley, E. P., and Gallagher, P. T.
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Astrophysics - Solar and Stellar Astrophysics ,Physics - Space Physics - Abstract
Solar radio bursts (SRBs), are emitted by electrons propagating through the corona and interplanetary space. Tracking such bursts is key to understanding the properties of accelerated electrons and radio wave propagation as well as the local plasma environment that they propagate through. Here, we present a novel multilateration algorithm called BayEsian LocaLisation Algorithm (BELLA). In addition, apparent SRB positions from BELLA are compared with comparable localisation methods and the predictions of solar wind models. BELLA uses Bayesian inference to create probabilistic distributions of source positions and their uncertainties. This facilitates the estimation of algorithmic, instrumental, and physical uncertainties in a quantitative manner. We validated BELLA using simulations and a Type III SRB observed by STEREO A/B and Wind. BELLA tracked the Type III source from $\sim$ 10--150 $R_{sun}$ (2-0.15 MHz) along a spiral trajectory. This allowed for an estimate of an apparent solar wind speed of $v_{sw} \sim$ 400 km s$^{-1}$ and a source longitude of $\phi_0 \sim$ 30deg. We compared these results with well-established methods of positioning: Goniopolarimetric (GP), analytical time-difference-of-arrival (TDOA), and Solar radio burst Electron Motion Tracker (SEMP). We found them to be in agreement with the results obtained by BELLA. Additionally, the results aligned with solar wind properties assimilated by the Heliospheric Upwind Extrapolation with time dependence (HUXt) model. We have validated BELLA and used it to identify apparent source positions as well as velocities and densities of the solar wind. Furthermore, we identified higher than expected electron densities, suggesting that the true emission sources were at lower altitudes than those identified by BELLA, an effect that may be due to appreciable scattering of electromagnetic waves by electrons in interplanetary space., Comment: 13 pages, 12 figures, in press, accepted by Astronomy and Astrophysics for publication
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- 2024
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7. Author Correction: Understanding epistatic networks in the B1 β-lactamases through coevolutionary statistical modeling and deep mutational scanning
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Chen, J. Z., Bisardi, M., Lee, D., Cotogno, S., Zamponi, F., Weigt, M., and Tokuriki, N.
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- 2024
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8. Understanding epistatic networks in the B1 β-lactamases through coevolutionary statistical modeling and deep mutational scanning
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Chen, J. Z., Bisardi, M., Lee, D., Cotogno, S., Zamponi, F., Weigt, M., and Tokuriki, N.
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- 2024
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9. Weighted fractional Poincaré inequalities via isoperimetric inequalities
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Myyryläinen, Kim, Pérez, Carlos, and Weigt, Julian
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- 2024
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10. Revolutionary Solar System Science Enabled by the Line Emission Mapper X-ray Probe
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Dunn, William R., Koutroumpa, Dimitra, Carter, Jennifer A., Kuntz, Kip D., McEntee, Sean, Deskins, Thomas, Parry, Bryn, Wolk, Scott, Lisse, Carey, Dennerl, Konrad, Jackman, Caitriona M., Weigt, Dale M., Porter, F. Scott, Branduardi-Raymont, Graziella, Bodewits, Dennis, Leppard, Fenn, Foster, Adam, Gladstone, G. Randall, Parmar, Vatsal, Brophy-Lee, Stephenie, Feldman, Charly, Ness, Jan-Uwe, Cumbee, Renata, Markevitch, Maxim, Kraft, Ralph, Bogdan, Akos, Bhardwaj, Anil, Wibisono, Affelia, Mernier, Francois, and Ogorzalek, Anna
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Astrophysics - Instrumentation and Methods for Astrophysics ,Astrophysics - Earth and Planetary Astrophysics ,Astrophysics - High Energy Astrophysical Phenomena ,Astrophysics - Solar and Stellar Astrophysics - Abstract
The Line Emission Mapper's (LEM's) exquisite spectral resolution and effective area will open new research domains in Astrophysics, Planetary Science and Heliophysics. LEM will provide step-change capabilities for the fluorescence, solar wind charge exchange (SWCX) and auroral precipitation processes that dominate X-ray emissions in our Solar System. The observatory will enable novel X-ray measurements of historically inaccessible line species, thermal broadening, characteristic line ratios and Doppler shifts - a universally valuable new astrophysics diagnostic toolkit. These measurements will identify the underlying compositions, conditions and physical processes from km-scale ultra-cold comets to the MK solar wind in the heliopause at 120 AU. Here, we focus on the paradigm-shifts LEM will provide for understanding the nature of the interaction between a star and its planets, especially the fundamental processes that govern the transfer of mass and energy within our Solar System, and the distribution of elements throughout the heliosphere. In this White Paper we show how LEM will enable a treasure trove of new scientific contributions that directly address key questions from the National Academies' 2023-2032 Planetary Science and 2013-2022 Heliophysics Decadal Strategies. The topics we highlight include: 1. The richest global trace element maps of the Lunar Surface ever produced; insights that address Solar System and planetary formation, and provide invaluable context ahead of Artemis and the Lunar Gateway. 2. Global maps of our Heliosphere through Solar Wind Charge Exchange (SWCX) that trace the interstellar neutral distributions in interplanetary space and measure system-wide solar wind ion abundances and velocities; a key new understanding of our local astrosphere and a synergistic complement to NASA IMAP observations of heliospheric interactions..., Comment: White Paper for the Line Emission Mapper Astrophysics APEX X-ray Probe
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- 2023
11. Towards Parsimonious Generative Modeling of RNA Families
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Calvanese, Francesco, Lambert, Camille N., Nghe, Philippe, Zamponi, Francesco, and Weigt, Martin
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Quantitative Biology - Biomolecules ,Condensed Matter - Statistical Mechanics ,Quantitative Biology - Genomics ,Quantitative Biology - Quantitative Methods - Abstract
Generative probabilistic models emerge as a new paradigm in data-driven, evolution-informed design of biomolecular sequences. This paper introduces a novel approach, called Edge Activation Direct Coupling Analysis (eaDCA), tailored to the characteristics of RNA sequences, with a strong emphasis on simplicity, efficiency, and interpretability. eaDCA explicitly constructs sparse coevolutionary models for RNA families, achieving performance levels comparable to more complex methods while utilizing a significantly lower number of parameters. Our approach demonstrates efficiency in generating artificial RNA sequences that closely resemble their natural counterparts in both statistical analyses and SHAPE-MaP experiments, and in predicting the effect of mutations. Notably, eaDCA provides a unique feature: estimating the number of potential functional sequences within a given RNA family. For example, in the case of cyclic di-AMP riboswitches (RF00379), our analysis suggests the existence of approximately $\mathbf{10^{39}}$ functional nucleotide sequences. While huge compared to the known $< \mathbf{4,000}$ natural sequences, this number represents only a tiny fraction of the vast pool of nearly $\mathbf{10^{82}}$ possible nucleotide sequences of the same length (136 nucleotides). These results underscore the promise of sparse and interpretable generative models, such as eaDCA, in enhancing our understanding of the expansive RNA sequence space., Comment: 33 pages (including SI)
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- 2023
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12. The science behind SURROUND: a constellation of CubeSats around the Sun
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Weigt, D. M., Cañizares, L. A., Maloney, S. A., Murray, S. A., Carley, E. P., Gallagher, P. T., Macario-Rojas, A., Crisp, N., and McGrath, C.
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Astrophysics - Solar and Stellar Astrophysics ,Astrophysics - Instrumentation and Methods for Astrophysics ,Physics - Space Physics - Abstract
One of the greatest challenge facing current space weather monitoring operations is forecasting the arrival of coronal mass ejections (CMEs) and Solar Energetic Particles (SEPs) within their Earth-Sun propagation timescales. Current campaigns mainly rely on extreme ultra-violet and white light observations to create forecasts, missing out many potential events that may be hazardous to Earth's infrastructure undetectable at these wavelengths. Here we introduce the SURROUND mission, a constellation of CubeSats each with identical radio spectrometers, and the results of the initial Phase-0 study for the concept. The main goal of SURROUND is to monitor and track solar radio bursts (SRBs), widely utilised as a useful diagnostic for space weather activity, and revolutionise current forecasting capabilities. The Phase-0 study concludes that SURROUND can achieve its mission objectives using 3 - 5 spacecraft using current technologies with feasible SEP and CME forecasting potential: a first for heliospheric monitors., Comment: 12 pages, 3 figures, 2 tables, submitted to Planetary, Solar and Heliospheric Radio Emissions IX, held 26-28 September, 2022 [ACCEPTED]; Edited by: C. K. Louis, C. M. Jackman, G. Fischer, A. H. Sulaiman, P. Zucca, Publishers: Dublin Institute for Advanced Studies and Trinity College Dublin. (these authors contributed equally to this work: D. M. Weigt, L. A. Ca\~nizares)
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- 2023
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13. CCR5 drives NK cell-associated airway damage in pulmonary ischemia-reperfusion injury.
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Santos, Jesse, Wang, Ping, Shemesh, Avishai, Liu, Fengchun, Tsao, Tasha, Aguilar, Oscar, Cleary, Simon, Singer, Jonathan, Gao, Ying, Hays, Steven, Golden, Jeffrey, Leard, Lorriana, Kleinhenz, Mary, Kolaitis, Nicholas, Shah, Rupal, Venado, Aida, Weigt, S, Belperio, John, Looney, Mark, Calabrese, Daniel, Kukreja, Jasleen, Lanier, Lewis, and Greenland, John
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Chemokines ,Innate immunity ,NK cells ,Pulmonology ,Transplantation ,Animals ,Humans ,Mice ,Killer Cells ,Natural ,Ligands ,Lung ,Lung Injury ,Receptors ,CCR5 ,Reperfusion Injury - Abstract
Primary graft dysfunction (PGD) limits clinical benefit after lung transplantation, a life-prolonging therapy for patients with end-stage disease. PGD is the clinical syndrome resulting from pulmonary ischemia-reperfusion injury (IRI), driven by innate immune inflammation. We recently demonstrated a key role for NK cells in the airways of mouse models and human tissue samples of IRI. Here, we used 2 mouse models paired with human lung transplant samples to investigate the mechanisms whereby NK cells migrate to the airways to mediate lung injury. We demonstrate that chemokine receptor ligand transcripts and proteins are increased in mouse and human disease. CCR5 ligand transcripts were correlated with NK cell gene signatures independently of NK cell CCR5 ligand secretion. NK cells expressing CCR5 were increased in the lung and airways during IRI and had increased markers of tissue residency and maturation. Allosteric CCR5 drug blockade reduced the migration of NK cells to the site of injury. CCR5 blockade also blunted quantitative measures of experimental IRI. Additionally, in human lung transplant bronchoalveolar lavage samples, we found that CCR5 ligand was associated with increased patient morbidity and that the CCR5 receptor was increased in expression on human NK cells following PGD. These data support a potential mechanism for NK cell migration during lung injury and identify a plausible preventative treatment for PGD.
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- 2023
14. Molecular selection of soybean towards adaptation to Central European agroclimatic conditions
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Rychel-Bielska, Sandra, Książkiewicz, Michał, Kurasiak-Popowska, Danuta, Tomkowiak, Agnieszka, Bielski, Wojciech, Weigt, Dorota, Niemann, Janetta, Surma, Anna, Kozak, Bartosz, and Nawracała, Jerzy
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- 2024
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15. Understanding epistatic networks in the B1 β-lactamases through coevolutionary statistical modeling and deep mutational scanning
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J. Z. Chen, M. Bisardi, D. Lee, S. Cotogno, F. Zamponi, M. Weigt, and N. Tokuriki
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Science - Abstract
Abstract Throughout evolution, protein families undergo substantial sequence divergence while preserving structure and function. Although most mutations are deleterious, evolution can explore sequence space via epistatic networks of intramolecular interactions that alleviate the harmful mutations. However, comprehensive analysis of such epistatic networks across protein families remains limited. Thus, we conduct a family wide analysis of the B1 metallo-β-lactamases, combining experiments (deep mutational scanning, DMS) on two distant homologs (NDM-1 and VIM-2) and computational analyses (in silico DMS based on Direct Coupling Analysis, DCA) of 100 homologs. The methods jointly reveal and quantify prevalent epistasis, as ~1/3rd of equivalent mutations are epistatic in DMS. From DCA, half of the positions have a >6.5 fold difference in effective number of tolerated mutations across the entire family. Notably, both methods locate residues with the strongest epistasis in regions of intermediate residue burial, suggesting a balance of residue packing and mutational freedom in forming epistatic networks. We identify entrenched WT residues between NDM-1 and VIM-2 in DMS, which display statistically distinct behaviors in DCA from non-entrenched residues. Entrenched residues are not easily compensated by changes in single nearby interactions, reinforcing existing findings where a complex epistatic network compounds smaller effects from many interacting residues.
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- 2024
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16. Weighted fractional Poincar\'e inequalities via isoperimetric inequalities
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Myyryläinen, Kim, Pérez, Carlos, and Weigt, Julian
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Mathematics - Classical Analysis and ODEs ,Mathematics - Analysis of PDEs ,46E35, 42B25 - Abstract
Our main result is a weighted fractional Poincar\'e-Sobolev inequality improving the celebrated estimate by Bourgain-Brezis-Mironescu. This also yields an improvement of the classical Meyers-Ziemer theorem in several ways. The proof is based on a fractional isoperimetric inequality and is new even in the non-weighted setting. We also extend the celebrated Poincar\'e-Sobolev estimate with $A_p$ weights of Fabes-Kenig-Serapioni by means of a fractional type result in the spirit of Bourgain-Brezis-Mironescu. Examples are given to show that the corresponding $L^p$-versions of weighted Poincar\'e inequalities do not hold for $p>1$., Comment: 26 pages, 2 figure. Added Figure 2 and Remark 3.4
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- 2023
17. Exploring Fundamental Particle Acceleration and Loss Processes in Heliophysics through an Orbiting X-ray Instrument in the Jovian System
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Dunn, W., Berland, G., Roussos, E., Clark, G., Kollmann, P., Turner, D., Feldman, C., Stallard, T., Branduardi-Raymont, G., Woodfield, E. E., Rae, I. J., Ray, L. C., Carter, J. A., Lindsay, S. T., Yao, Z., Marshall, R., A., A. N. Jaynes, Ezoe, Y., Numazawa, M., Hospodarsky, G. B., Wu, X., Weigt, D. M., Jackman, C. M., Mori, K., Nénon, Q., Desai, R. T, Blum, L. W., Nordheim, T. A., Ness, J. U., Bodewits, D., Kimura, T., Li, W., Smith, H. T., Millas, D., Wibisono, A. D., Achilleos, N., Koutroumpa, D., McEntee, S. C., Collier, H., Bhardwaj, A., Martindale, A., Wolk, S. J., Badman, S. V., and Kraft, R. P.
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Astrophysics - Instrumentation and Methods for Astrophysics ,Astrophysics - Earth and Planetary Astrophysics ,Astrophysics - High Energy Astrophysical Phenomena ,Physics - Space Physics - Abstract
Jupiter's magnetosphere is considered to be the most powerful particle accelerator in the Solar System, accelerating electrons from eV to 70 MeV and ions to GeV energies. How electromagnetic processes drive energy and particle flows, producing and removing energetic particles, is at the heart of Heliophysics. Particularly, the 2013 Decadal Strategy for Solar and Space Physics was to "Discover and characterize fundamental processes that occur both within the heliosphere and throughout the universe". The Jovian system offers an ideal natural laboratory to investigate all of the universal processes highlighted in the previous Decadal. The X-ray waveband has been widely used to remotely study plasma across astrophysical systems. The majority of astrophysical emissions can be grouped into 5 X-ray processes: fluorescence, thermal/coronal, scattering, charge exchange and particle acceleration. The Jovian system offers perhaps the only system that presents a rich catalog of all of these X-ray emission processes and can also be visited in-situ, affording the special possibility to directly link fundamental plasma processes with their resulting X-ray signatures. This offers invaluable ground-truths for astrophysical objects beyond the reach of in-situ exploration (e.g. brown dwarfs, magnetars or galaxy clusters that map the cosmos). Here, we show how coupling in-situ measurements with in-orbit X-ray observations of Jupiter's radiation belts, Galilean satellites, Io Torus, and atmosphere addresses fundamental heliophysics questions with wide-reaching impact across helio- and astrophysics. New developments like miniaturized X-ray optics and radiation-tolerant detectors, provide compact, lightweight, wide-field X-ray instruments perfectly suited to the Jupiter system, enabling this exciting new possibility., Comment: A White Paper for the 2024-2033 Solar and Space Physics (Heliophysics) Decadal Survey
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- 2023
18. ‘You grow with the allergy’: a grounded theory study of families’ experiences with food allergy risk or diagnosis in early childhood
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Christian Apfelbacher, Susanne Brandstetter, Julia Weigt, Madlen Hörold, Katharina Gerhardinger, Mara König, and Magdalena Rohr
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Medicine - Abstract
Objective Childhood food allergy is increasing in western societies. Preventing and managing food allergies is therefore essential for both parents and children. Given the limited previous research on parents’ experiences of food allergy prevention in early childhood, this study aimed to develop a grounded theory to understand the experiences and interactions of families whose children are at risk of, or have been diagnosed with, food allergy.Design Using a constructivist grounded theory approach, we used initial, focused and theoretical coding, as well as constant comparative analysis and memoing to interpret our data.Setting Thematic interviews were conducted in Germany between March and September 2022.Participant We included 28 carers (25 mothers and 3 fathers) of children aged 0–3 years diagnosed with food allergy or at risk of food allergy. We recruited participants using snowball and theoretical sampling.Results We developed a theory that we named ‘negotiating uncertainty in childhood food allergy’. This theory describes the experiences and interactions of families with a child at risk or diagnosed with food allergy with the central phenomena of negotiation uncertainty. Negotiation is used to transform perceived challenges of uncertainty into feelings of competence in relation to (the prevention of) food allergy. Core themes included ‘parental roles’, ‘healthcare’, ‘childcare’, ‘informal support’ and ‘family routines’. To cope with the challenges, parents relied on two main resources: self-efficacy and health literacy.Conclusion The study highlights the dynamic process of negotiation within families at risk of or coping with paediatric food allergy. Furthermore, our findings highlight the need to promote parental health literacy.
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- 2024
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19. Effect of a magnetosphere compression on Jovian radio emissions: in situ case study using Juno data
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Louis, C. K., Jackman, C. M., Hospodarsky, G., Hackett, A. O'Kane, Devon-Hurley, E., Zarka, P., Kurth, W. S., Ebert, R. W., Weigt, D. M., Fogg, A. R., Waters, J. E., Entee, S. Mc, Connerney, J. E. P., Louarn, P., Levin, S., and Bolton, S. J.
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Astrophysics - Earth and Planetary Astrophysics ,Physics - Space Physics - Abstract
During its 53-day polar orbit around Jupiter, Juno often crosses the boundaries of the Jovian magnetosphere (namely the magnetopause and bow shock). From the boundary locations, the upstream solar wind dynamic pressure can be inferred, which in turn illustrates the state of compression or relaxation of the system. The aim of this study is to examine Jovian radio emissions during magnetospheric compressions, in order to determine the relationship between the solar wind and Jovian radio emissions. In this paper, we give a complete list of bow shock and magnetopause crossings (from June 2016 to August 2022), along with some extra informations (e.g. solar wind dynamic pressure and position of the standoff distances inferred from Joy et al. (2002)). We then select two compression events that occur in succession (inferred from magnetopause crossings) and we present a case study of the response of the Jovian radio emissions. We demonstrate that magnetospheric compressions lead to the activation of new radio sources. Newly activated broadband kilometric emissions are observed almost simultaneously to compression of the magnetosphere, with sources covering a large range of longitudes. Decametric emission sources are seen to be activated more than one rotation later only at specific longitudes and dusk local times. Finally, the activation of narrowband kilometric radiation is not observed during the compression phase, but when the magnetosphere is in its expansion phase.
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- 2022
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20. Line Emission Mapper (LEM): Probing the physics of cosmic ecosystems
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Kraft, Ralph, Markevitch, Maxim, Kilbourne, Caroline, Adams, Joseph S., Akamatsu, Hiroki, Ayromlou, Mohammadreza, Bandler, Simon R., Barbera, Marco, Bennett, Douglas A., Bhardwaj, Anil, Biffi, Veronica, Bodewits, Dennis, Bogdan, Akos, Bonamente, Massimiliano, Borgani, Stefano, Branduardi-Raymont, Graziella, Bregman, Joel N., Burchett, Joseph N., Cann, Jenna, Carter, Jenny, Chakraborty, Priyanka, Churazov, Eugene, Crain, Robert A., Cumbee, Renata, Dave, Romeel, DiPirro, Michael, Dolag, Klaus, Doriese, W. Bertrand, Drake, Jeremy, Dunn, William, Eckart, Megan, Eckert, Dominique, Ettori, Stefano, Forman, William, Galeazzi, Massimiliano, Gall, Amy, Gatuzz, Efrain, Hell, Natalie, Hodges-Kluck, Edmund, Jackman, Caitriona, Jahromi, Amir, Jennings, Fred, Jones, Christine, Kaaret, Philip, Kavanagh, Patrick J., Kelley, Richard L., Khabibullin, Ildar, Kim, Chang-Goo, Koutroumpa, Dimitra, Kovacs, Orsolya, Kuntz, K. D., Lau, Erwin, Lee, Shiu-Hang, Leutenegger, Maurice, Lin, Sheng-Chieh, Lisse, Carey, Cicero, Ugo Lo, Lovisari, Lorenzo, McCammon, Dan, McEntee, Sean, Mernier, Francois, Miller, Eric D., Nagai, Daisuke, Negro, Michela, Nelson, Dylan, Ness, Jan-Uwe, Nulsen, Paul, Ogorzalek, Anna, Oppenheimer, Benjamin D., Oskinova, Lidia, Patnaude, Daniel, Pfeifle, Ryan W., Pillepich, Annalisa, Plucinsky, Paul, Pooley, David, Porter, Frederick S., Randall, Scott, Rasia, Elena, Raymond, John, Ruszkowski, Mateusz, Sakai, Kazuhiro, Sarkar, Arnab, Sasaki, Manami, Sato, Kosuke, Schellenberger, Gerrit, Schaye, Joop, Simionescu, Aurora, Smith, Stephen J., Steiner, James F., Stern, Jonathan, Su, Yuanyuan, Sun, Ming, Tremblay, Grant, Truong, Nhut, Tutt, James, Ursino, Eugenio, Veilleux, Sylvain, Vikhlinin, Alexey, Vladutescu-Zopp, Stephan, Vogelsberger, Mark, Walker, Stephen A., Weaver, Kimberly, Weigt, Dale M., Werk, Jessica, Werner, Norbert, Wolk, Scott J., Zhang, Congyao, Zhang, William W., Zhuravleva, Irina, and ZuHone, John
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Astrophysics - Instrumentation and Methods for Astrophysics ,Astrophysics - Astrophysics of Galaxies ,Astrophysics - High Energy Astrophysical Phenomena - Abstract
The Line Emission Mapper (LEM) is an X-ray Probe for the 2030s that will answer the outstanding questions of the Universe's structure formation. It will also provide transformative new observing capabilities for every area of astrophysics, and to heliophysics and planetary physics as well. LEM's main goal is a comprehensive look at the physics of galaxy formation, including stellar and black-hole feedback and flows of baryonic matter into and out of galaxies. These processes are best studied in X-rays, and emission-line mapping is the pressing need in this area. LEM will use a large microcalorimeter array/IFU, covering a 30x30' field with 10" angular resolution, to map the soft X-ray line emission from objects that constitute galactic ecosystems. These include supernova remnants, star-forming regions, superbubbles, galactic outflows (such as the Fermi/eROSITA bubbles in the Milky Way and their analogs in other galaxies), the Circumgalactic Medium in the Milky Way and other galaxies, and the Intergalactic Medium at the outskirts and beyond the confines of galaxies and clusters. LEM's 1-2 eV spectral resolution in the 0.2-2 keV band will make it possible to disentangle the faintest emission lines in those objects from the bright Milky Way foreground, providing groundbreaking measurements of the physics of these plasmas, from temperatures, densities, chemical composition to gas dynamics. While LEM's main focus is on galaxy formation, it will provide transformative capability for all classes of astrophysical objects, from the Earth's magnetosphere, planets and comets to the interstellar medium and X-ray binaries in nearby galaxies, AGN, and cooling gas in galaxy clusters. In addition to pointed observations, LEM will perform a shallow all-sky survey that will dramatically expand the discovery space., Comment: 18 pages. White paper for a mission concept to be submitted for the 2023 NASA Astrophysics Probes opportunity. v2: All-sky survey figure expanded, references fixed. v3: Added energy resolution measurements for prototype detector array. v4: Author list and reference fixes
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- 2022
21. Machine-learning-assisted Monte Carlo fails at sampling computationally hard problems
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Ciarella, Simone, Trinquier, Jeanne, Weigt, Martin, and Zamponi, Francesco
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Condensed Matter - Disordered Systems and Neural Networks - Abstract
Several strategies have been recently proposed in order to improve Monte Carlo sampling efficiency using machine learning tools. Here, we challenge these methods by considering a class of problems that are known to be exponentially hard to sample using conventional local Monte Carlo at low enough temperatures. In particular, we study the antiferromagnetic Potts model on a random graph, which reduces to the coloring of random graphs at zero temperature. We test several machine-learning-assisted Monte Carlo approaches, and we find that they all fail. Our work thus provides good benchmarks for future proposals for smart sampling algorithms.
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- 2022
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22. Combining phylogeny and coevolution improves the inference of interaction partners among paralogous proteins
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Gandarilla-Perez, Carlos A., Pinilla, Sergio, Bitbol, Anne-Florence, and Weigt, Martin
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Quantitative Biology - Biomolecules ,Condensed Matter - Statistical Mechanics ,Quantitative Biology - Molecular Networks - Abstract
Predicting protein-protein interactions from sequences is an important goal of computational biology. Various sources of information can be used to this end. Starting from the sequences of two interacting protein families, one can use phylogeny or residue coevolution to infer which paralogs are specific interaction partners within each species. We show that these two signals can be combined to improve the performance of the inference of interaction partners among paralogs. For this, we first align the sequence-similarity graphs of the two families through simulated annealing, yielding a robust partial pairing. We next use this partial pairing to seed a coevolution-based iterative pairing algorithm. This combined method improves performance over either separate method. The improvement obtained is striking in the difficult cases where the average number of paralogs per species is large or where the total number of sequences is modest., Comment: 19 pages
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- 2022
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23. Author Correction: Understanding epistatic networks in the B1 β-lactamases through coevolutionary statistical modeling and deep mutational scanning
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J. Z. Chen, M. Bisardi, D. Lee, S. Cotogno, F. Zamponi, M. Weigt, and N. Tokuriki
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Science - Published
- 2024
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24. ‘3D Printed Breast Phantoms Materials for X-ray Imaging Techniques’
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Dermitzakis, Aris, Pichotka, Martin, Petrai, Antzela, Weigt, Moritz, Pallikarakis, Nicolas, Magjarević, Ratko, Series Editor, Ładyżyński, Piotr, Associate Editor, Ibrahim, Fatimah, Associate Editor, Lackovic, Igor, Associate Editor, Rock, Emilio Sacristan, Associate Editor, Badnjević, Almir, editor, and Gurbeta Pokvić, Lejla, editor
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- 2024
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25. Statistical-physics approaches to RNA molecules, families and networks
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Cocco, Simona, De Martino, Andrea, Pagnani, Andrea, and Weigt, Martin
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Condensed Matter - Statistical Mechanics ,Condensed Matter - Disordered Systems and Neural Networks ,Physics - Biological Physics ,Quantitative Biology - Biomolecules ,Quantitative Biology - Molecular Networks - Abstract
This contribution focuses on the fascinating RNA molecule, its sequence-dependent folding driven by base-pairing interactions, the interplay between these interactions and natural evolution, and its multiple regulatory roles. The four of us have dug into these topics using the tools and the spirit of the statistical physics of disordered systems, and in particular the concept of a disordered (energy/fitness) landscape. After an introduction to RNA molecules and the perspectives they open not only in evolutionary and synthetic biology but also in medicine, we will introduce the important notions of energy and fitness landscapes for these molecules. In Section III we will review some models and algorithms for RNA sequence-to-secondary-structure mapping. Section IV discusses how the secondary-structure energy landscape can be derived from unzipping data. Section V deals with the inference of RNA structure from evolutionary sequence data sampled in different organisms. This will shift the focus from the `sequence-to-structure' mapping described in Section III to a `sequence-to-function' landscape that can be inferred from laboratory evolutionary data on DNA aptamers. Finally, in Section VI, we shall discuss the rich theoretical picture linking networks of interacting RNA molecules to the organization of robust, systemic regulatory programs. Along this path, we will therefore explore phenomena across multiple scales in space, number of molecules and time, showing how the biological complexity of the RNA world can be captured by the unifying concepts of statistical physics., Comment: 19 pages, 6 figures, to appear in "Spin Glass Theory and Far Beyond - Replica Symmetry Breaking after 40 years" (edited by P Charbonneau, E Marinari, G Parisi, F Ricci Tersenghi, G Sicuro and F Zamponi)
- Published
- 2022
26. NKG2D receptor activation drives primary graft dysfunction severity and poor lung transplantation outcomes
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Calabrese, Daniel R, Tsao, Tasha, Magnen, Mélia, Valet, Colin, Gao, Ying, Mallavia, Beñat, Tian, Jennifer J, Aminian, Emily A, Wang, Kristin M, Shemesh, Avishai, Punzalan, Elman B, Sarma, Aartik, Calfee, Carolyn S, Christenson, Stephanie A, Langelier, Charles R, Hays, Steven R, Golden, Jeff A, Leard, Lorriana E, Kleinhenz, Mary E, Kolaitis, Nicholas A, Shah, Rupal J, Venado, Aida, Lanier, Lewis L, Greenland, John R, Sayah, David M, Ardehali, Abbas, Kukreja, Jasleen, Weigt, S Sam, Belperio, John A, Singer, Jonathan P, and Looney, Mark R
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Transplantation ,Lung ,Acute Respiratory Distress Syndrome ,Genetics ,Rare Diseases ,Clinical Research ,Aetiology ,2.1 Biological and endogenous factors ,Inflammatory and immune system ,Respiratory ,Humans ,NK Cell Lectin-Like Receptor Subfamily K ,Primary Graft Dysfunction ,Tumor Necrosis Factor-alpha ,Lung Transplantation ,Immunology ,NK cells ,Neutrophils ,Organ transplantation ,Pulmonology - Abstract
Clinical outcomes after lung transplantation, a life-saving therapy for patients with end-stage lung diseases, are limited by primary graft dysfunction (PGD). PGD is an early form of acute lung injury with no specific pharmacologic therapies. Here, we present a large multicenter study of plasma and bronchoalveolar lavage (BAL) samples collected on the first posttransplant day, a critical time for investigations of immune pathways related to PGD. We demonstrated that ligands for NKG2D receptors were increased in the BAL from participants who developed severe PGD and were associated with increased time to extubation, prolonged intensive care unit length of stay, and poor peak lung function. Neutrophil extracellular traps (NETs) were increased in PGD and correlated with BAL TNF-α and IFN-γ cytokines. Mechanistically, we found that airway epithelial cell NKG2D ligands were increased following hypoxic challenge. NK cell killing of hypoxic airway epithelial cells was abrogated with NKG2D receptor blockade, and TNF-α and IFN-γ provoked neutrophils to release NETs in culture. These data support an aberrant NK cell/neutrophil axis in human PGD pathogenesis. Early measurement of stress ligands and blockade of the NKG2D receptor hold promise for risk stratification and management of PGD.
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- 2022
27. Alterations in circulating measures of Th2 immune responses pre-lung transplant associates with reduced primary graft dysfunction
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Schaenman, Joanna M., Weigt, Stephen Samuel, Pan, Mengtong, Lee, Joshua J., Zhou, Xinkai, Elashoff, David, Shino, Michael Y., Reynolds, John M., Budev, Marie, Shah, Pali, Singer, Lianne G., Todd, Jamie L., Snyder, Laurie D., Palmer, Scott, and Belperio, John
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- 2024
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28. Recent human-induced atmospheric drying across Europe unprecedented in the last 400 years
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Treydte, Kerstin, Liu, Laibao, Padrón, Ryan S., Martínez-Sancho, Elisabet, Babst, Flurin, Frank, David C., Gessler, Arthur, Kahmen, Ansgar, Poulter, Benjamin, Seneviratne, Sonia I., Stegehuis, Annemiek I., Wilson, Rob, Andreu-Hayles, Laia, Bale, Roderick, Bednarz, Zdzislaw, Boettger, Tatjana, Berninger, Frank, Büntgen, Ulf, Daux, Valerie, Dorado-Liñán, Isabel, Esper, Jan, Friedrich, Michael, Gagen, Mary, Grabner, Michael, Grudd, Håkan, Gunnarsson, Björn E., Gutiérrez, Emilia, Hafner, Polona, Haupt, Marika, Hilasvuori, Emmi, Heinrich, Ingo, Helle, Gerhard, Jalkanen, Risto, Jungner, Högne, Kalela-Brundin, Maarit, Kessler, Andreas, Kirchhefer, Andreas, Klesse, Stephan, Krapiec, Marek, Levanič, Tom, Leuenberger, Markus, Linderholm, Hans W., McCarroll, Danny, Masson-Delmotte, Valérie, Pawelczyk, Slawomira, Pazdur, Anna, Planells, Octavi, Pukiene, Rutile, Rinne-Garmston, Katja T., Robertson, Iain, Saracino, Antonio, Saurer, Matthias, Schleser, Gerhard H., Seftigen, Kristina, Siegwolf, Rolf T. W., Sonninen, Eloni, Stievenard, Michel, Szychowska-Krapiec, Elzbieta, Szymaszek, Malgorzata, Todaro, Luigi, Waterhouse, John S., Weigl-Kuska, Martin, Weigt, Rosemarie B., Wimmer, Rupert, Woodley, Ewan J., Vitas, Adomas, Young, Giles, and Loader, Neil J.
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- 2024
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29. Plasma CXCL9 and CXCL10 at allograft injury predict chronic lung allograft dysfunction.
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Shino, Michael, Todd, Jamie, Neely, Megan, Kirchner, Jerry, Frankel, Courtney, Snyder, Laurie, Pavlisko, Elizabeth, Schaenman, Joanna, Mason, Kristen, Kesler, Karen, Martinu, Tereza, Singer, Lianne, Tsuang, Wayne, Budev, Marie, Shah, Pali, Reynolds, John, Williams, Nikki, Robien, Mark, Palmer, Scott, Weigt, S, Belperio, John, and Fishbein, Gregory
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cytokines/cytokine receptors ,immunobiology ,lung (allograft) function/dysfunction ,lung failure/injury ,lung transplantation/pulmonology ,lung transplantation: living donor ,pathology/histopathology ,rejection: acute ,translational research/science ,Allografts ,Biomarkers ,Chemokine CXCL10 ,Chemokine CXCL9 ,Graft Rejection ,Graft vs Host Disease ,Humans ,Lung ,Lung Transplantation ,Prospective Studies - Abstract
Histopathologic lung allograft injuries are putative harbingers for chronic lung allograft dysfunction (CLAD). However, the mechanisms responsible are not well understood. CXCL9 and CXCL10 are potent chemoattractants of mononuclear cells and potential propagators of allograft injury. We hypothesized that these chemokines would be quantifiable in plasma, and would associate with subsequent CLAD development. In this prospective multicenter study, we evaluated 721 plasma samples for CXCL9/CXCL10 levels from 184 participants at the time of transbronchial biopsies during their first-year post-transplantation. We determined the association between plasma chemokines, histopathologic injury, and CLAD risk using Cox proportional hazards models. We also evaluated CXCL9/CXCL10 levels in bronchoalveolar lavage (BAL) fluid and compared plasma to BAL with respect to CLAD risk. Plasma CXCL9/CXCL10 levels were elevated during the injury patterns associated with CLAD, acute rejection, and acute lung injury, with a dose-response relationship between chemokine levels and CLAD risk. Importantly, there were strong interactions between injury and plasma CXCL9/CXCL10, where histopathologic injury associated with CLAD only in the presence of elevated plasma chemokines. We observed similar associations and interactions with BAL CXCL9/CXCL10 levels. Elevated plasma CXCL9/CXCL10 during allograft injury may contribute to CLAD pathogenesis and has potential as a minimally invasive immune monitoring biomarker.
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- 2022
30. The safety profile of a protocolized transbronchial cryobiopsy program utilizing a 2.4 mm cryoprobe for interstitial lung disease.
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Oh, Scott, Ronaghi, Reza, He, Tao, Oberg, Catherine, Channick, Colleen, Susanto, Irawan, Carroll, Mathew, Weigt, S Sam, Sayah, David, Dolinay, Tamas, Chung, Augustine, Fishbein, Gregory, Lynch, Joseph P, and Belperio, John A
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Lung ,Humans ,Lung Diseases ,Interstitial ,Bronchoscopy ,Biopsy ,Prospective Studies ,Rare Diseases ,Clinical Research ,Cancer ,Lung Cancer ,Good Health and Well Being ,Cardiorespiratory Medicine and Haematology ,Clinical Sciences ,Respiratory System - Abstract
IntroductionTransbronchial lung cryobiopsy (TBLC) has emerged as a promising alternative to surgical lung biopsy for the diagnosis of interstitial lung disease. However, uncertainty remains regarding its overall complications due to a lack of procedural standardization including the size of cryoprobe utilized.MethodsThis is a prospective cohort study of a protocolized transbronchial cryobiopsy program utilizing a 2.4 mm cryoprobe. 201 consecutive subjects were enrolled at a single academic center.ResultsThe average biopsy size was 106.2 ± 39.3 mm2. Complications included a total pneumothorax rate of 4.9% with 3.5% undergoing chest tube placement. Severe bleeding defined by the Nashville Working Group occurred in 0.5% of cases. There were no deaths at 30-days.DiscussionA protocolized transbronchial cryobiopsy program utilizing a 2.4 mm cryoprobe in can achieve a high diagnostic yield with a favorable safety profile.
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- 2022
31. Epistatic models predict mutable sites in SARS-CoV-2 proteins and epitopes
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Rodriguez-Rivas, Juan, Croce, Giancarlo, Muscat, Maureen, and Weigt, Martin
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Quantitative Biology - Genomics ,Quantitative Biology - Populations and Evolution - Abstract
The emergence of new variants of SARS-CoV-2 is a major concern given their potential impact on the transmissibility and pathogenicity of the virus as well as the efficacy of therapeutic interventions. Here, we predict the mutability of all positions in SARS-CoV-2 protein domains to forecast the appearance of unseen variants. Using sequence data from other coronaviruses, pre-existing to SARS-CoV-2, we build statistical models that do not only capture amino-acid conservation but more complex patterns resulting from epistasis. We show that these models are notably superior to conservation profiles in estimating the already observable SARS-CoV-2 variability. In the receptor binding domain of the spike protein, we observe that the predicted mutability correlates well with experimental measures of protein stability and that both are reliable mutability predictors (ROC AUC ~0.8). Most interestingly, we observe an increasing agreement between our model and the observed variability as more data become available over time, proving the anticipatory capacity of our model. When combined with data concerning the immune response, our approach identifies positions where current variants of concern are highly overrepresented. These results could assist studies on viral evolution, future viral outbreaks and, in particular, guide the exploration and anticipation of potentially harmful future SARS-CoV-2 variants., Comment: 21 pages + supplementary information
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- 2021
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32. Emicizumab versus immunosuppressive therapy for the management of acquired hemophilia A
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Hart, Christina, Klamroth, Robert, Sachs, Ulrich J., Greil, Richard, Knoebl, Paul, Oldenburg, Johannes, Miesbach, Wolfgang, Pfrepper, Christian, Trautmann-Grill, Karolin, Pekrul, Isabell, Holstein, Katharina, Eichler, Hermann, Weigt, Carmen, Schipp, Dorothea, Werwitzke, Sonja, and Tiede, Andreas
- Published
- 2024
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33. Decommissioning of commercial nuclear power plants: Insights from a multiple-case study
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Bärenbold, Rebekka, Bah, Muhammad Maladoh, Lordan-Perret, Rebecca, Steigerwald, Björn, von Hirschhausen, Christian, Wealer, Ben, Weigt, Hannes, and Wimmers, Alexander
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- 2024
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34. Quantitative Image Analysis at Chronic Lung Allograft Dysfunction Onset Predicts Mortality
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Weigt, S Samuel, Kim, Grace-Hyun J, Jones, Heather D, Ramsey, Allison L, Amubieya, Olawale, Abtin, Fereidoun, Pourzand, Lila, Lee, Jihey, Shino, Michael Y, DerHovanessian, Ariss, Stripp, Barry, Noble, Paul W, Sayah, David M, Saggar, Rajan, Britton, Ian, Lynch, Joseph P, Belperio, John A, and Goldin, Jonathan
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Biomedical and Clinical Sciences ,Clinical Sciences ,Organ Transplantation ,Rare Diseases ,Lung ,Biomedical Imaging ,Clinical Research ,Infectious Diseases ,Transplantation ,Good Health and Well Being ,Allografts ,Bronchiolitis Obliterans ,Chronic Disease ,Follow-Up Studies ,Humans ,Lung Transplantation ,Primary Graft Dysfunction ,Retrospective Studies ,Risk Factors ,Syndrome ,Medical and Health Sciences ,Surgery ,Clinical sciences ,Immunology - Abstract
BackgroundChronic lung allograft dysfunction (CLAD) phenotype determines prognosis and may have therapeutic implications. Despite the clarity achieved by recent consensus statement definitions, their reliance on radiologic interpretation introduces subjectivity. The Center for Computer Vision and Imaging Biomarkers at the University of California, Los Angeles (UCLA) has established protocols for chest high-resolution computed tomography (HRCT)-based computer-aided quantification of both interstitial disease and air-trapping. We applied quantitative image analysis (QIA) at CLAD onset to demonstrate radiographic phenotypes with clinical implications.MethodsWe studied 47 first bilateral lung transplant recipients at UCLA with chest HRCT performed within 90 d of CLAD onset and 47 no-CLAD control HRCTs. QIA determined the proportion of lung volume affected by interstitial disease and air-trapping in total lung capacity and residual volume images, respectively. We compared QIA scores between no-CLAD and CLAD, and between phenotypes. We also assigned radiographic phenotypes based solely on QIA, and compared their survival outcomes.ResultsCLAD onset HRCTs had more lung affected by the interstitial disease (P = 0.003) than no-CLAD controls. Bronchiolitis obliterans syndrome (BOS) cases had lower scores for interstitial disease as compared with probable restrictive allograft syndrome (RAS) (P < 0.0001) and mixed CLAD (P = 0.02) phenotypes. BOS cases had more air-trapping than probable RAS (P < 0.0001). Among phenotypes assigned by QIA, the relative risk of death was greatest for mixed (relative risk [RR] 11.81), followed by RAS (RR 6.27) and BOS (RR 3.15).ConclusionsChest HRCT QIA at CLAD onset appears promising as a method for precise determination of CLAD phenotypes with survival implications.
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- 2022
35. The Variation of the Uncentered Maximal Operator with respect to Cubes
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Weigt, Julian
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Mathematics - Classical Analysis and ODEs ,Mathematics - Analysis of PDEs ,42B25, 26B30 - Abstract
We consider the maximal operator with respect to uncentered cubes on Euclidean space with arbitrary dimension. We prove that for any function with bounded variation, the variation of its maximal function is bounded by the variation of the function times a dimensional constant. We also prove the corresponding result for maximal operators with respect to collections of more general sets than cubes. The sets are required to satisfy a certain inner cone star condition and in addition the collection must enjoy a tiling property which for example the collection of all cubes does enjoy and the collection of all Euclidean balls does not., Comment: The results are generalized from cubes to \(L\)-complete \(\Lambda\)-stars. Formulations and minor corrections of proofs
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- 2021
36. adabmDCA: Adaptive Boltzmann machine learning for biological sequences
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Muntoni, Anna Paola, Pagnani, Andrea, Weigt, Martin, and Zamponi, Francesco
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Quantitative Biology - Quantitative Methods ,Condensed Matter - Disordered Systems and Neural Networks ,Quantitative Biology - Biomolecules - Abstract
Boltzmann machines are energy-based models that have been shown to provide an accurate statistical description of domains of evolutionary-related protein and RNA families. They are parametrized in terms of local biases accounting for residue conservation, and pairwise terms to model epistatic coevolution between residues. From the model parameters, it is possible to extract an accurate prediction of the three-dimensional contact map of the target domain. More recently, the accuracy of these models has been also assessed in terms of their ability in predicting mutational effects and generating in silico functional sequences. Our adaptive implementation of Boltzmann machine learning, adabmDCA, can be generally applied to both protein and RNA families and accomplishes several learning set-ups, depending on the complexity of the input data and on the user requirements. The code is fully available at https://github.com/anna-pa-m/adabmDCA. As an example, we have performed the learning of three Boltzmann machines modeling the Kunitz and Beta-lactamase2 protein domains and TPP-riboswitch RNA domain. The models learned by adabmDCA are comparable to those obtained by state-of-the-art techniques for this task, in terms of the quality of the inferred contact map as well as of the synthetically generated sequences. In addition, the code implements both equilibrium and out-of-equilibrium learning, which allows for an accurate and lossless training when the equilibrium one is prohibitive in terms of computational time, and allows for pruning irrelevant parameters using an information-based criterion.
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- 2021
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37. Posaconazole and risk of cutaneous squamous cell carcinoma after lung transplantation: a single institution, retrospective cohort study
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Kuklinski, Lawrence F., Klomhaus, Alexandra M., Shen, Amy, Achamallah, Natalie, Soriano, Teresa T., Saggar, Rajan, and Weigt, Stephen S.
- Published
- 2023
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38. Auroral X-ray emissions from the gas giant planets : remote sensing and in situ magnetospheric diagnostics
- Author
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Weigt, Dale Michael and Altamirano, Diego
- Abstract
The thesis begins by introducing the reader to the fundamental concepts used throughout the field of space physics today (Chapter 1) and then applies them to the the jovian magnetosphere, the largest coherent object (or fully unified structure if visible to the naked eye) within our Solar System (Chapter 2). This chapter focuses on the structure and internal dynamics of the jovian magnetosphere observed throughout the literature, with particular emphasis of the complex X-ray auroral emissions at the poles. This chapter concludes by analysing previous literature and the ongoing effort to search for the complicated magnetospheric driver, or drivers, responsible for these complex emissions at the gas giant planets - the largest open question in our field, which this thesis aims to answer. The studies that are contained within this thesis focus on constraining the magnetospheric driver, or drivers, responsible for the X-ray auroral emissions at the gas giants, in particular at Jupiter. The research throughout focuses on observations performed by the Chandra X-ray telescope (CXO), using the onboard high resolution camera (HRC), combined with by other remote sensing data, such as ultraviolet observations form the Hubble Space Telescope (HST), and in situ spacecraft data from Juno , when available to provide vital magnetospheric context (Chapter 3). The first work chapter (Chapter 4) is a case studying analysing a Chandra observation during a compression event while Juno was near its apojove position, the furthest point from Jupiter in its orbit. The mapping analysis of the X-ray auroral emissions was carried on using a newly developed and freely available Python pipeline (Weigt, 2021), utilising the high spatial resolution of Chandra. This mapping algorithm is used throughout this thesis. Chapter 5 then applies these analytical methods, techniques and definitions to the full ∼ 20-year Chandra dataset of the northern auroral emissions to determine the more extreme and typical behaviour of the northern X-ray emissions. This case study eludes to the possibility of numerous magnetospheric drivers likely located in the noon and dusk flank of the jovian magnetosphere, based on the Grodent Anomaly Magnetic field model (Grodent et al., 2008), with a statistically significant region at noon. Comparisons of the timing and mapping analysis with previous literature highlight that the X-ray emissions may be associated with ultra-low frequency wave activity in the form of Shear Alfven waves. ´ Chapter 6 expands on the the idea of multiple drivers through the creation of physics-informed auroral families during the Juno-era, allowing us to associate morphological features with magnetospheric drivers located throughout the jovian system. The X-ray auroral morphologies identified in this case study may also be a useful monitor of magnetospheric conditions at Jupiter. The penultimate chapter (Chapter 7) changes focus to the exploration of kronian X-rays, analysing Chandra observations aimed to monitor Saturn's magnetospheric response during a rare planetary alignment with Jupiter. Due to the orbits of the planets, this event occurs once in every ∼ 19-20 years, analysing this unique parameter space for the first time. This case study predicts the flux and power of the emissions and compares with solar flux data from Geostationary Operational Environmental Satellites (GOES) to find any correlations between solar activity and the counts detected from Saturn's disk emissions. The thesis concludes with an exploration into future work, further utilising the Chandra data as much as possible and comparing with other datasets to provide more coherent catalogues of the temporal and spatial behaviour of the auroral emissions that can be used for future studies.
- Published
- 2022
39. The allograft injury marker CXCL9 determines prognosis of anti-HLA antibodies after lung transplantation.
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Shino, Michael, Zhang, Qiuheng, Li, Ning, Derhovanessian, Ariss, Ramsey, Allison, Saggar, Rajan, Britton, Ian, Amubieya, Olawale, Lari, Shahrzad, Hickey, Michelle, Reed, Elaine, Noble, Paul, Stripp, Barry, Fishbein, Gregory, Lynch, Joseph, Ardehali, Abbas, Sayah, David, Weigt, S, and Belperio, John
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alloantibody ,biomarker ,bronchoalveolar lavage (BAL) ,cytokine receptors ,cytokines ,dysfunction ,immunobiology ,lung (allograft) function ,lung transplantation / pulmonology ,translational research / science ,Allografts ,Biomarkers ,Chemokine CXCL9 ,Cohort Studies ,Graft Rejection ,Graft Survival ,HLA Antigens ,Humans ,Isoantibodies ,Lung Transplantation ,Prognosis ,Retrospective Studies ,Tissue Donors - Abstract
Despite the common detection of non-donor specific anti-HLA antibodies (non-DSAs) after lung transplantation, their clinical significance remains unclear. In this retrospective single-center cohort study of 325 lung transplant recipients, we evaluated the association between donor-specific HLA antibodies (DSAs) and non-DSAs with subsequent CLAD development. DSAs were detected in 30% of recipients and were associated with increased CLAD risk, with higher HRs for both de novo and high MFI (>5000) DSAs. Non-DSAs were detected in 56% of recipients, and 85% of DSA positive tests had concurrent non-DSAs. In general, non-DSAs did not increase CLAD risk in multivariable models accounting for DSAs. However, non-DSAs in conjunction with high BAL CXCL9 levels were associated with increased CLAD risk. Multivariable proportional hazards models demonstrate the importance of the HLA antibody-CXCL9 interaction: CLAD risk increases when HLA antibodies (both DSAs and non-DSAs) are detected in conjunction with high CXCL9. Conversely, CLAD risk is not increased when HLA antibodies are detected with low CXCL9. This study supports the potential utility of BAL CXCL9 measurement as a biomarker to risk stratify HLA antibodies for future CLAD. The ability to discriminate between high versus low-risk HLA antibodies may improve management by allowing for guided treatment decisions.
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- 2022
40. The one-dimensional centred maximal function diminishes the variation of indicator functions
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Bilz, Constantin and Weigt, Julian
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Mathematics - Classical Analysis and ODEs ,42B25 (Primary) 26A45 (Secondary) - Abstract
We prove sharp local and global variation bounds for the centred Hardy--Littlewood maximal functions of indicator functions in one dimension. We characterise maximisers, treat both the continuous and discrete settings and extend our results to a larger class of functions., Comment: 18 pages, 3 figures
- Published
- 2021
41. Searching for Saturn's X-rays during a rare Jupiter Magnetotail Crossing using Chandra
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Weigt, D. M., Dunn, W. R., Jackman, C. M., Kraft, R., Branduardi-Raymont, G., Nichols, J. D., Wibisono, A. D., Vogt, M. F., and Gladstone, G. R.
- Subjects
Astrophysics - Earth and Planetary Astrophysics ,Physics - Space Physics - Abstract
Every 19 years, Saturn passes through Jupiter's 'flapping' magnetotail. Here, we report Chandra X-ray observations of Saturn planned to coincide with this rare planetary alignment and to analyse Saturn's magnetospheric response when transitioning to this unique parameter space. We analyse three Director's Discretionary Time (DDT) observations from the High Resolution Camera (HRC-I) on-board Chandra, taken on November 19, 21 and 23 2020 with the aim to find auroral and/or disk emissions. We infer the conditions in the kronian system by looking at coincident soft X-ray solar flux data from the Geostationary Operational Environmental Satellite (GOES) and Hubble Space Telescope (HST) observations of Saturn's ultraviolet (UV) auroral emissions. The large Saturn-Sun-Earth angle during this time would mean that most flares from the Earth-facing side of the Sun would not have impacted Saturn. We find no significant detection of Saturn's disk or auroral emissions in any of our observations. We calculate the 3$\sigma$ upper band energy flux of Saturn during this time to be 0.9 - 3.04 $\times$ 10$^{14}$ erg cm$^{-2}$ s$^{-1}$ which agrees with fluxes found from previous modelled spectra of the disk emissions. We conclude by discussing the implications of this non-detection and how it is imperative that the next fleet of X-ray telescope (such as Athena and the Lynx mission concept) continue to observe Saturn with their improved spatial and spectral resolution and very enhanced sensitivity to help us finally solve the mysteries behind Saturn's apparently elusive X-ray aurora., Comment: 8 pages, 3 figures, accepted for publication in MNRAS
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- 2021
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42. Modeling sequence-space exploration and emergence of epistatic signals in protein evolution
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Bisardi, Matteo, Rodriguez-Rivas, Juan, Zamponi, Francesco, and Weigt, Martin
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Quantitative Biology - Biomolecules ,Condensed Matter - Disordered Systems and Neural Networks ,Quantitative Biology - Populations and Evolution ,Quantitative Biology - Quantitative Methods - Abstract
During their evolution, proteins explore sequence space via an interplay between random mutations and phenotypic selection. Here we build upon recent progress in reconstructing data-driven fitness landscapes for families of homologous proteins, to propose stochastic models of experimental protein evolution. These models predict quantitatively important features of experimentally evolved sequence libraries, like fitness distributions and position-specific mutational spectra. They also allow us to efficiently simulate sequence libraries for a vast array of combinations of experimental parameters like sequence divergence, selection strength and library size. We showcase the potential of the approach in re-analyzing two recent experiments to determine protein structure from signals of epistasis emerging in experimental sequence libraries. To be detectable, these signals require sufficiently large and sufficiently diverged libraries. Our modeling framework offers a quantitative explanation for the variable success of recently published experiments. Furthermore, we can forecast the outcome of time- and resource-intensive evolution experiments, opening thereby a way to computationally optimize experimental protocols., Comment: 16 pages, 14 figures
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- 2021
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43. Efficient generative modeling of protein sequences using simple autoregressive models
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Trinquier, Jeanne, Uguzzoni, Guido, Pagnani, Andrea, Zamponi, Francesco, and Weigt, Martin
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Quantitative Biology - Biomolecules ,Condensed Matter - Disordered Systems and Neural Networks ,Condensed Matter - Statistical Mechanics ,Quantitative Biology - Quantitative Methods - Abstract
Generative models emerge as promising candidates for novel sequence-data driven approaches to protein design, and for the extraction of structural and functional information about proteins deeply hidden in rapidly growing sequence databases. Here we propose simple autoregressive models as highly accurate but computationally efficient generative sequence models. We show that they perform similarly to existing approaches based on Boltzmann machines or deep generative models, but at a substantially lower computational cost (by a factor between $10^2$ and $10^3$). Furthermore, the simple structure of our models has distinctive mathematical advantages, which translate into an improved applicability in sequence generation and evaluation. Within these models, we can easily estimate both the probability of a given sequence, and, using the model's entropy, the size of the functional sequence space related to a specific protein family. In the example of response regulators, we find a huge number of ca. $10^{68}$ possible sequences, which nevertheless constitute only the astronomically small fraction $10^{-80}$ of all amino-acid sequences of the same length. These findings illustrate the potential and the difficulty in exploring sequence space via generative sequence models., Comment: 12 pages, 4 Figures + Supplementary Material
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- 2021
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44. Continuity of the gradient of the fractional maximal operator on $W^{1,1}(\mathbb{R}^d)$
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Beltran, David, González-Riquelme, Cristian, Madrid, José, and Weigt, Julian
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Mathematics - Classical Analysis and ODEs ,42B25, 46E35 - Abstract
We establish that the map $f\mapsto |\nabla \mathcal{M}_{\alpha}f|$ is continuous from $W^{1,1}(\mathbb{R}^d)$ to $L^{q}(\mathbb{R}^d)$, where $\alpha\in (0,d)$, $q=\frac{d}{d-\alpha}$ and $\mathcal{M}_{\alpha}$ denotes either the centered or non-centered fractional Hardy--Littlewood maximal operator. In particular, we cover the cases $d >1$ and $\alpha \in (0,1)$ in full generality, for which results were only known for radial functions., Comment: 12 pages, 1 figure
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- 2021
45. Global multivariate model learning from hierarchically correlated data
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Horta, Edwin Rodriguez, Lage, Alejandro, Weigt, Martin, and Barrat-Charlaix, Pierre
- Subjects
Condensed Matter - Disordered Systems and Neural Networks ,Condensed Matter - Statistical Mechanics ,Quantitative Biology - Quantitative Methods - Abstract
Inverse statistical physics aims at inferring models compatible with a set of empirical averages estimated from a high-dimensional dataset of independently distributed equilibrium configurations of a given system. However, in several applications such as biology, data result from stochastic evolutionary processes, and configurations are related through a hierarchical structure, typically represented by a tree, and therefore not independent. In turn, empirical averages of observables superpose intrinsic signal related to the equilibrium distribution of the studied system and spurious historical (or phylogenetic) signal resulting from the structure underlying the data-generating process. The naive application of inverse statistical physics techniques therefore leads to systematic biases and an effective reduction of the sample size. To advance on the currently open task of extracting intrinsic signals from correlated data, we study a system described by a multivariate Ornstein-Uhlenbeck process defined on a finite tree. Using a Bayesian framework, we can disentangle covariances in the data corresponding to their multivariate Gaussian equilibrium distribution from those resulting from the historical correlations. Our approach leads to a clear gain in accuracy in the inferred equilibrium distribution, which corresponds to an effective two- to fourfold increase in sample size., Comment: 34 pages 10 figures
- Published
- 2021
46. Review and Assessment of Decarbonized Future Electricity Markets
- Author
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Ali Darudi and Hannes Weigt
- Subjects
renewable energy ,electricity market ,investment ,renewable support ,Technology - Abstract
The electricity sector plays a key role in achieving zero emissions targets. The required transition will lead to substantial changes in the supply, demand, and distribution of electricity, as well as in stakeholder roles. Future market designs may change substantially to accommodate these changes, address challenges, and take advantage of new opportunities. This paper reviews the characteristics of future carbon-neutral electricity systems and electricity market design options. To provide a guiding framework for the literature review, we transfer the complexity of electricity systems into a three-layer structure: Firstly, we analyze papers that rely on techno-economic modeling of the physical electricity system. As a case study, we analyze various studies focusing on a decarbonized European electricity system in 2050. Secondly, we review papers that investigate the economic behavior and effects of self-interest-seeking stakeholders such as producers, network operators, and consumers. Finally, we review papers focusing on policy and market design questions that guide policymakers in achieving a target physical asset combination while considering the behavior of stakeholders. We highlight common trends and disagreements in the literature, review the main drivers of future markets, and finally provide a mapping between those drivers, challenges, and opportunities. The review concludes that the most promising next step toward a fully comprehensive assessment approach is to combine existing approaches across topical and disciplinary boundaries.
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- 2024
- Full Text
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47. Serum markers of cardiac complications in a systemic sclerosis cohort
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Tennøe, Anders H, Murbræch, Klaus, Didriksen, Henriette, Ueland, Thor, Palchevskiy, Vyacheslav, Weigt, Stephen S, Fretheim, Håvard, Midtvedt, Øyvind, Garen, Torhild, Brunborg, Cathrine, Aukrust, Pål, Molberg, Øyvind, Belperio, John A, and Hoffmann-Vold, Anna-Maria
- Subjects
Biomedical and Clinical Sciences ,Cardiovascular Medicine and Haematology ,Clinical Sciences ,Rare Diseases ,Clinical Research ,Autoimmune Disease ,Neurosciences ,Scleroderma ,Heart Disease ,Cardiovascular ,2.1 Biological and endogenous factors ,Aetiology ,Biomarkers ,Cardiomyopathies ,Echocardiography ,Female ,Heart Diseases ,Humans ,Hypertension ,Pulmonary ,Middle Aged ,Scleroderma ,Systemic ,Ventricular Dysfunction ,Left ,Ventricular Dysfunction ,Right - Abstract
Primary cardiac involvement is one of the leading causes of mortality in systemic sclerosis (SSc), but little is known regarding circulating biomarkers for cardiac SSc. Here, we aimed to investigate potential associations between cardiac SSc and candidate serum markers. Serum samples from patients of the Oslo University SSc cohort and 100 healthy controls were screened against two custom-made candidate marker panels containing molecules deemed relevant for cardiopulmonary and/or fibrotic diseases. Left (LV) and right ventricular (RV) dysfunction was assessed by protocol echocardiography, performed within three years from serum sampling. Patients suspected of pulmonary hypertension underwent right heart catheterization. Vital status at study end was available for all patients. Descriptive analyses, logistic and Cox regressions were conducted to assess associations between cardiac SSc and candidate serum markers. The 371 patients presented an average age of 57.2 (± 13.9) years. Female sex (84%) and limited cutaneous SSc (73%) were predominant. Association between LV diastolic dysfunction and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) (OR 0.41, 95% CI 0.21-0.78, p = 0.007) was identified. LV systolic dysfunction defined by global longitudinal strain was associated with angiopoietin 2 (ANGPT2) (OR 3.42, 95% CI 1.52-7.71, p = 0.003) and osteopontin (OPN) (OR 1.95, 95% CI 1.08-3.52, p = 0.026). RV systolic dysfunction, measured by tricuspid annular plane systolic excursion, was associated to markers of LV dysfunction (ANGPT2, OPN, and TRAIL) (OR 1.67, 95% CI 1.11-2.50, p = 0.014, OR 1.86, 95% CI 1.25-2.77, p = 0.002, OR 0.32, 95% CI 0.15-0.66, p = 0.002, respectively) and endostatin (OR 1.86, 95% CI 1.22-2.84, p = 0.004). In conclusion, ANGPT2, OPN and TRAIL seem to be circulating biomarkers associated with both LV and RV dysfunction in SSc.
- Published
- 2022
48. The 2022 Banff Meeting Lung Report
- Author
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Pavlisko, Elizabeth N., Adam, Benjamin A., Berry, Gerald J., Calabrese, Fiorella, Cortes-Santiago, Nahir, Glass, Carolyn H., Goddard, Martin, Greenland, John R., Kreisel, Daniel, Levine, Deborah J., Martinu, Tereza, Verleden, Stijn E., Weigt, S. Sam, and Roux, Antoine
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- 2024
- Full Text
- View/download PDF
49. Statistical Physics of Biological Molecules
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Cocco, Simona, primary, De Martino, Andrea, additional, Pagnani, Andrea, additional, Weigt, Martin, additional, and Ritort, Felix, additional
- Published
- 2023
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50. Preoperative hemoglobin thresholds for survival equity in women and men
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Florian Rumpf, Lotta Hof, Oliver Old, Patrick Friederich, Jens Friedrich, Josef Thoma, Maria Wittmann, Kai Zacharowski, Suma Choorapoikayil, Patrick Meybohm, German Patient Blood Management Network Collaborators, Olaf Baumhove, Samuel de Leeuw van Weenen, Markus Velten, Claudia Neumann, Andrea Kirfel, Nadine Straßberger-Nerschbach, Heidi Ehrentraut, Daniel Grigutsch, Vera Guttenthaler, Alma Puskarevic, Ghaith Mohssen, Jan Görtzen, Diana Narita, Lighvani Barbara, Michael Josef Huber, Valeska Lea Blum, Sabine Isik, Vanessa Neef, Florian Piekarski, Thomas Walther, Harald Keller, Andreas Schnitzbauer, Thomas Schmitz-Rixen, Kyriakos Oikonomou, Bjoern Steffen, Stefan Zeuzem, Marcus Czabanka, Felix Chun, Ingo Marzi, Timo Stöver, Shahram Ghanaati, Frank Louwen, M. Markus Mueller, Christoph Geisen, Erhard Seyfried, Eva Herrmann, Alexandra Bayer, Henry Weigt, Björn Lange, Ansgar Raadts, Christoph Haas, Johannes Duemmler, Ulf Lorenzen, Matthias Pagel, Thomas Puehler, Julius Pochhammer, Tim Klueter, Hajrullah Ahmeti, Dirk Bauerschlag, Henning Wieker, René Rusch, Gerd Molter, München Klinik, Janina Dana Jenke, Kira Kieserling, Dennie Scholle, U. Andrea Steinbicker, Alexander Zarbock, Sven Martens, Andres Schrader, G. R. Geissler, H. Hillmann, Georg Lenz, Klaus Schwendner, Viola Weber, Philipp Helmer, Sebastian Hottenrott, Peter Kranke, Daniel Roeder, Tobias Schlesinger, Magdalena Sitter, and Jan Stumpner
- Subjects
hemoglobin ,equitable health care ,anemia ,perioperative management ,perioperative medicine ,Medicine (General) ,R5-920 - Abstract
Anemia affects humans throughout life, and is linked to higher morbidity and mortality. Unclear is whether hemoglobin values are equivalent between women and men. This study evaluates the association of preoperative hemoglobin levels with in-hospital mortality and estimates thresholds for survival equity between men and women. All adult patients undergoing surgery between 2010 and 2019 from 14 German hospitals were included in the study. Thresholds for survival equity were determined with generalized additive models. In total, 842,130 patients with a median in-hospital follow-up time of 7 days were analyzed. During follow-up 20,370 deaths occurred. Preoperative hemoglobin stratified in-hospital mortality (log-rank test p
- Published
- 2024
- Full Text
- View/download PDF
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