3,369,813 results on '"Were, Stephen"'
Search Results
202. Climate, food and humans predict communities of mammals in the United States
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Kays, Roland, Snider, Matthew H., Hess, George, Cove, Michael V., Jensen, Alex, Shamon, Hila, McShea, William J., Rooney, Brigit, Allen, Maximilian L., Pekins, Charles E., Wilmers, Christopher C., Pendergast, Mary E., Green, Austin M., Suraci, Justin, Leslie, Matthew S., Nasrallah, Sophie, Farkas, Dan, Jordan, Mark, Grigione, Melissa, LaScaleia, Michael C., Davis, Miranda L., Hansen, Chris, Millspaugh, Josh, Lewis, Jesse S., Havrda, Michael, Long, Robert, Remine, Kathryn R., Jaspers, Kodi J., Lafferty, Diana J. R., Hubbard, Tru, Studds, Colin E., Barthelmess, Erika L., Andy, Katherine, Romero, Andrea, O'Neill, Brian J., Hawkins, Melissa T. R., Lombardi, Jason V., Sergeyev, Maksim, Fisher-Reid, M. Caitlin, Rentz, Michael S., Nagy, Christopher, Davenport, Jon M., Rega-Brodsky, Christine C., Appel, Cara L., Lesmeister, Damon B., Giery, Sean T., Whittier, Christopher A., Alston, Jesse M., Sutherland, Chris, Rota, Christopher, Murphy, Thomas, Lee, Thomas E., Mortelliti, Alessio, Bergman, Dylan L., Compton, Justin A., Gerber, Brian D., Burr, Jess, Rezendes, Kylie, DeGregorio, Brett A., Wehr, Nathaniel H., Benson, John F., O’Mara, M. Teague, Jachowski, David S., Gray, Morgan, Beyer, Dean E., Belant, Jerrold L., Horan, Robert V., Lonsinger, Robert C., Kuhn, Kellie M., Hasstedt, Steven C. M., Zimova, Marketa, Moore, Sophie M., Herrera, Daniel J., Fritts, Sarah, Edelman, Andrew J., Flaherty, Elizabeth A., Petroelje, Tyler R., Neiswenter, Sean A., Risch, Derek R., Iannarilli, Fabiola, van der Merwe, Marius, Maher, Sean P., Farris, Zach J., Webb, Stephen L., Mason, David S., Lashley, Marcus A., Wilson, Andrew M., Vanek, John P., Wehr, Samuel R., Conner, L. Mike, Beasley, James C., Bontrager, Helen L., Baruzzi, Carolina, Ellis-Felege, Susan N., Proctor, Mike D., Schipper, Jan, Weiss, Katherine C. B., Darracq, Andrea K., Barr, Evan G., Alexander, Peter D., Şekercioğlu, Çağan H., Bogan, Daniel A., Schalk, Christopher M., Fantle-Lepczyk, Jean E., Lepczyk, Christopher A., LaPoint, Scott, Whipple, Laura S., Rowe, Helen Ivy, Mullen, Kayleigh, Bird, Tori, Zorn, Adam, Brandt, LaRoy, Lathrop, Richard G., McCain, Craig, Crupi, Anthony P., Clark, James, and Parsons, Arielle
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- 2024
203. Is it time to start moving soil microbial fuel cell research out of the lab and into the field?
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Taylor, Stephen, Jaliff, Laura, Wells, George, and Josephson, Colleen
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Biological Sciences ,Industrial Biotechnology ,Affordable and Clean Energy ,Microbial fuel cell ,Soil ,Soil microbial fuel cell ,Environmental Sciences - Abstract
Soil microbial fuel cells (SMFCs) function as bioelectrochemical energy harvesters that convert electrons stored in soil organic matter into useful electrical energy. Broadly, an SMFC comprises three essential components: an anode buried in the soil (the negative terminal), a colony of exoelectrogenic microorganisms residing on this anode, and a cathode (the positive terminal). As the exoelectrogens respire, they release electrons to the anode, which acts as an external receptor. These released electrons then flow through a load (e.g. a resistor), connecting the anode and cathode. Though minuscule, the electrical power produced by SMFCs has a number of potential applications such as sustaining low-power embedded electronics, pollutant remediation, or as a bio-sensing proxy for soil qualities and microbial activity. This discussion aims to emphasize the potential of SMFCs in addressing real-world environmental issues and to generate interest in the larger scientific community for broad interdisciplinary research efforts, particularly in field deployments.
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- 2024
204. Targeting Cholesterol Biosynthesis with Statins Synergizes with AKT Inhibitors in Triple-Negative Breast Cancer.
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Hillis, Alissandra, Martin, Timothy, Manchester, Haley, Högström, Jenny, Zhang, Na, Lecky, Emmalyn, Kozlova, Nina, Lee, Jonah, Persky, Nicole, Root, David, Brown, Myles, Cichowski, Karen, Elledge, Stephen, Muranen, Taru, Fruman, David, Barry, Simon, Clohessy, John, Madsen, Ralitsa, and Toker, Alex
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Triple Negative Breast Neoplasms ,Humans ,Animals ,Mice ,Cholesterol ,Female ,Proto-Oncogene Proteins c-akt ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,Quinolines ,Xenograft Model Antitumor Assays ,Drug Synergism ,Cell Line ,Tumor ,Sterol Regulatory Element Binding Protein 2 ,Cell Proliferation - Abstract
Triple-negative breast cancer (TNBC) is responsible for a disproportionate number of breast cancer patient deaths due to extensive molecular heterogeneity, high recurrence rates, and lack of targeted therapies. Dysregulation of the phosphoinositide 3-kinase (PI3K)/AKT pathway occurs in approximately 50% of TNBC patients. Here, we performed a genome-wide CRISPR/Cas9 screen with PI3Kα and AKT inhibitors to find targetable synthetic lethalities in TNBC. Cholesterol homeostasis was identified as a collateral vulnerability with AKT inhibition. Disruption of cholesterol homeostasis with pitavastatin synergized with AKT inhibition to induce TNBC cytotoxicity in vitro in mouse TNBC xenografts and in patient-derived estrogen receptor (ER)-negative breast cancer organoids. Neither ER-positive breast cancer cell lines nor ER-positive organoids were sensitive to combined AKT inhibitor and pitavastatin. Mechanistically, TNBC cells showed impaired sterol regulatory element-binding protein 2 (SREBP-2) activation in response to single-agent or combination treatment with AKT inhibitor and pitavastatin, which was rescued by inhibition of the cholesterol-trafficking protein Niemann-Pick C1 (NPC1). NPC1 loss caused lysosomal cholesterol accumulation, decreased endoplasmic reticulum cholesterol levels, and promoted SREBP-2 activation. Taken together, these data identify a TNBC-specific vulnerability to the combination of AKT inhibitors and pitavastatin mediated by dysregulated cholesterol trafficking. These findings support combining AKT inhibitors with pitavastatin as a therapeutic modality in TNBC. Significance: Two FDA-approved compounds, AKT inhibitors and pitavastatin, synergize to induce cell death in triple-negative breast cancer, motivating evaluation of the efficacy of this combination in clinical trials.
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- 2024
205. Epidemiology and characteristics of coral snake bites reported to the National Poison Data System (2006‒2022).
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Velagapudi, Mary, Navarro, Juliana, Hill, Alexander, Darracq, Michael, and Thornton, Stephen
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antivenom ,coral snake ,elapidae - Abstract
OBJECTIVES: North American coral snake envenomations can result in life-threatening neurotoxicity. Their bites are relatively rare, making large studies difficult. Using the National Poison Data System (NPDS), we sought to investigate the epidemiological trends and clinical outcomes associated with North American coral snake bites over a 17-year period. METHODS: NPDS cases involving coral snakes from January 1, 2006, to December 31, 2022, were analyzed. Data collected included patient age, date, geographic location, clinical effects, treatments administered, and medical outcomes including incidence of dry bites (non-envenomation) and death. RESULTS: During the 17-year period, a total of 1374 cases were reported and analyzed. Cases included adults (≥ 20 years), accounting for 80% (n = 1107), and pediatric patients (≤19 years), accounting for 20% (n = 267) of total cases. Out of 50 US states and District of Columbia, 20 states reported cases. Florida and Texas accounted for 90.5% of all bites (n = 1243) with April being the month with the most reported cases (n = 184). The most bites (n = 96) were reported in 2008 and the fewest (n = 69) in 2016. Male patients predominated for both pediatric (75.7%, n = 202) and adult cases (75.3%, n = 834). Moderate to major clinical outcomes were documented in approximately 30% of total cases; with no reported deaths. Moderate effect is defined as the patient exhibited symptoms as a result of the exposure that were more pronounced, more prolonged, or more of a systemic nature than minor symptoms. Major effect was defined as the patient exhibited symptoms as a result of the exposure that were life threatening or resulted in significant residual disability or disfigurement. The three most reported clinical effects were wound/sting, dermal irritation/pain, and edema. Antivenom was administered in 21% (n = 286) of total cases and 37% (n = 511) of patients were admitted to a critical care unit. Dry bites occurred in 7% (n = 100) of total cases. CONCLUSION: Coral snake bites were rare, but consistently reported. While bites were associated with significant morbidity in adult and pediatric patients, there were no deaths reported. Antivenom use declined over the study period but was not associated with an increase in morbidity. An increased incidence of intubations was seen in association with decreased antivenom use.
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- 2024
206. Multi-site EEG studies in early infancy: Methods to enhance data quality.
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Dickinson, Abigail, Booth, Madison, Daniel, Manjari, Campbell, Alana, Miller, Neely, Lau, Bonnie, Zempel, John, Webb, Sara, Elison, Jed, Lee, Adrian, Estes, Annette, Dager, Stephen, Hazlett, Heather, Wolff, Jason, Schultz, Robert, Marrus, Natasha, Evans, Alan, Piven, Joseph, Pruett, John, and Jeste, Shafali
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Autism ,Early identification ,Electrophysiology ,Multi-site ,Multimodal ,Humans ,Electroencephalography ,Infant ,Male ,Female ,Autism Spectrum Disorder ,Brain ,Magnetic Resonance Imaging ,Data Accuracy ,Longitudinal Studies ,Feasibility Studies ,Artifacts - Abstract
Brain differences linked to autism spectrum disorder (ASD) can manifest before observable symptoms. Studying these early neural precursors in larger and more diverse cohorts is crucial for advancing our understanding of developmental pathways and potentially facilitating earlier identification. EEG is an ideal tool for investigating early neural differences in ASD, given its scalability and high tolerability in infant populations. In this context, we integrated EEG into an existing multi-site MRI study of infants with a higher familial likelihood of developing ASD. This paper describes the comprehensive protocol established to collect longitudinal, high-density EEG data from infants across five sites as part of the Infant Brain Imaging Study (IBIS) Network and reports interim feasibility and data quality results. We evaluated feasibility by measuring the percentage of infants from whom we successfully collected each EEG paradigm. The quality of task-free data was assessed based on the duration of EEG recordings remaining after artifact removal. Preliminary analyses revealed low data loss, with average in-session loss rates at 4.16 % and quality control loss rates at 11.66 %. Overall, the task-free data retention rate, accounting for both in-session issues and quality control, was 84.16 %, with high consistency across sites. The insights gained from this preliminary analysis highlight key sources of data attrition and provide practical considerations to guide similar research endeavors.
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- 2024
207. Challenges and Future Directions in Quantifying Terrestrial Evapotranspiration
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Yi, Koong, Senay, Gabriel B, Fisher, Joshua B, Wang, Lixin, Suvočarev, Kosana, Chu, Housen, Moore, Georgianne W, Novick, Kimberly A, Barnes, Mallory L, Keenan, Trevor F, Mallick, Kanishka, Luo, Xiangzhong, Missik, Justine EC, Delwiche, Kyle B, Nelson, Jacob A, Good, Stephen P, Xiao, Xiangming, Kannenberg, Steven A, Ahmadi, Arman, Wang, Tianxin, Bohrer, Gil, Litvak, Marcy E, Reed, David E, Oishi, A Christopher, Torn, Margaret S, and Baldocchi, Dennis
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Physical Geography and Environmental Geoscience ,Civil Engineering ,Environmental Engineering ,Hydrology ,Civil engineering ,Environmental engineering - Abstract
Abstract: Terrestrial evapotranspiration is the second‐largest component of the land water cycle, linking the water, energy, and carbon cycles and influencing the productivity and health of ecosystems. The dynamics of ET across a spectrum of spatiotemporal scales and their controls remain an active focus of research across different science disciplines. Here, we provide an overview of the current state of ET science across in situ measurements, partitioning of ET, and remote sensing, and discuss how different approaches complement one another based on their advantages and shortcomings. We aim to facilitate collaboration among a cross‐disciplinary group of ET scientists to overcome the challenges identified in this paper and ultimately advance our integrated understanding of ET.
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- 2024
208. The Role of Spin–Orbit Coupling in the Linear Absorption Spectrum and Intersystem Crossing Rate Coefficients of Ruthenium Polypyridyl Dyes
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Talbot, Justin J, Cheshire, Thomas P, Cotton, Stephen J, Houle, Frances A, and Head-Gordon, Martin
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Physical Sciences ,Chemical Sciences ,Physical Chemistry ,Theoretical and Computational Chemistry ,1.1 Normal biological development and functioning ,Atomic ,Molecular ,Nuclear ,Particle and Plasma Physics ,Physical Chemistry (incl. Structural) ,Physical chemistry ,Theoretical and computational chemistry ,Atomic ,molecular and optical physics - Abstract
The successful use of molecular dyes for solar energy conversion requires efficient charge injection, which in turn requires the formation of states with sufficiently long lifetimes (e.g., triplets). The molecular structure elements that confer this property can be found empirically, however computational predictions using ab initio electronic structure methods are invaluable to identify structure-property relations for dye sensitizers. The primary challenge for simulations to elucidate the electronic and nuclear origins of these properties is a spin-orbit interaction which drives transitions between electronic states. In this work, we present a computational analysis of the spin-orbit corrected linear absorption cross sections and intersystem crossing rate coefficients for a derivative set of phosphonated tris(2,2'-bipyridine)ruthenium(2+) dye molecules. After sampling the ground state vibrational distributions, the predicted linear absorption cross sections indicate that the mixture between singlet and triplet states plays a crucial role in defining the line shape of the metal-to-ligand charge transfer bands in these derivatives. Additionally, an analysis of the intersystem crossing rate coefficients suggests that transitions from the singlet into the triplet manifolds are ultrafast with rate coefficients on the order of 1013 s-1 for each dye molecule.
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- 2024
209. fSCIG 10% in pediatric primary immunodeficiency diseases: a European post-authorization safety study.
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Čižnár, Peter, Roderick, Marion, Schneiderova, Helen, Jeseňák, Miloš, Kriván, Gergely, Brodszki, Nicholas, Jolles, Stephen, Atisso, Charles, Fielhauer, Katharina, Saeed-Khawaja, Shumyla, McCoy, Barbara, and Yel, Leman
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Hyaluronidase ,Immunoglobulins ,Inborn errors of immunity (IEI) ,Patient safety ,Pediatrics ,Primary immunodeficiency diseases ,Subcutaneous - Abstract
BACKGROUND: The safety, tolerability, and immunogenicity of hyaluronidase-facilitated subcutaneous immunoglobulin (fSCIG) 10% (dual-vial unit of human immunoglobulin 10% and recombinant human hyaluronidase [rHuPH20]) were assessed in children with primary immunodeficiency diseases (PIDs). METHODS: This phase 4, post-authorization, prospective, interventional, multicenter study (NCT03116347) conducted in the European Economic Area, enrolled patients aged 2 to < 18 years with a documented PID diagnosis who had received immunoglobulin therapy for ≥ 3 months before enrollment. New fSCIG 10% starters underwent fSCIG 10% dose ramp-up for ≤ 6 weeks (epoch 1) before receiving fSCIG 10% for ≤ 3 years (epoch 2); patients pretreated with fSCIG 10% entered epoch 2 directly. The primary outcome was the number and rate (per infusion) of all noninfectious treatment-related serious and severe adverse events (AEs). RESULTS: In total, 42 patients were enrolled and dosed (median [range] age: 11.5 [3-17] years; 81% male; 23 new starters; 19 pretreated). Overall, 49 related noninfectious, treatment-emergent AEs (TEAEs) were reported in 15 patients; most were mild in severity (87.8%). No treatment-related serious TEAEs were reported. Two TEAEs (infusion site pain and emotional distress) were reported as severe and treatment-related in a single new fSCIG 10% starter. The rate of local TEAEs was lower in pretreated patients (0.1 event/patient-year) versus new starters (1.3 events/patient-year). No patients tested positive for binding anti-rHuPH20 antibodies (titer of ≥ 1:160). CONCLUSIONS: No safety signals were identified, and the incidence of local AEs declined over the duration of fSCIG 10% treatment. This study supports fSCIG 10% long-term safety in children with PIDs. TRIAL REGISTRATION NUMBER (CLINICALTRIALS.GOV): NCT03116347.
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- 2024
210. Mammals show faster recovery from capture and tagging in human-disturbed landscapes.
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Stiegler, Jonas, Gallagher, Cara, Hering, Robert, Müller, Thomas, Tucker, Marlee, Apollonio, Marco, Arnold, Janosch, Barker, Nancy, Barthel, Leon, Bassano, Bruno, Beest, Floris, Belant, Jerrold, Berger, Anne, Beyer, Dean, Bidner, Laura, Blake, Stephen, Börner, Konstantin, Brivio, Francesca, Brogi, Rudy, Buuveibaatar, Bayarbaatar, Cagnacci, Francesca, Dekker, Jasja, Dentinger, Jane, Duľa, Martin, Duquette, Jarred, Eccard, Jana, Evans, Meaghan, Ferguson, Adam, Fichtel, Claudia, Ford, Adam, Fowler, Nicholas, Gehr, Benedikt, Getz, Wayne, Goheen, Jacob, Goossens, Benoit, Grignolio, Stefano, Haugaard, Lars, Hauptfleisch, Morgan, Heim, Morten, Heurich, Marco, Hewison, Mark, Isbell, Lynne, Janssen, René, Jarnemo, Anders, Jeltsch, Florian, Miloš, Jezek, Kaczensky, Petra, Kamiński, Tomasz, Kappeler, Peter, Kasper, Katharina, Kautz, Todd, Kimmig, Sophia, Kjellander, Petter, Kowalczyk, Rafał, Kramer-Schadt, Stephanie, Kröschel, Max, Krop-Benesch, Anette, Linderoth, Peter, Lobas, Christoph, Lokeny, Peter, Lührs, Mia-Lana, Matsushima, Stephanie, McDonough, Molly, Melzheimer, Jörg, Morellet, Nicolas, Ngatia, Dedan, Obermair, Leopold, Olson, Kirk, Patanant, Kidan, Payne, John, Petroelje, Tyler, Pina, Manuel, Piqué, Josep, Premier, Joseph, Pufelski, Jan, Pyritz, Lennart, Ramanzin, Maurizio, Roeleke, Manuel, Rolandsen, Christer, Saïd, Sonia, Sandfort, Robin, Schmidt, Krzysztof, Schmidt, Niels, Scholz, Carolin, Schubert, Nadine, Selva, Nuria, Sergiel, Agnieszka, Serieys, Laurel, Silovský, Václav, Slotow, Rob, Sönnichsen, Leif, Solberg, Erling, Stelvig, Mikkel, Street, Garrett, Sunde, Peter, Svoboda, Nathan, Thaker, Maria, Tomowski, Maxi, Ullmann, Wiebke, and Vanak, Abi
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Animals ,Humans ,Mammals ,Ecosystem ,Male ,Female ,Locomotion ,Herbivory ,Animals ,Wild ,Behavior ,Animal ,Species Specificity - Abstract
Wildlife tagging provides critical insights into animal movement ecology, physiology, and behavior amid global ecosystem changes. However, the stress induced by capture, handling, and tagging can impact post-release locomotion and activity and, consequently, the interpretation of study results. Here, we analyze post-tagging effects on 1585 individuals of 42 terrestrial mammal species using collar-collected GPS and accelerometer data. Species-specific displacements and overall dynamic body acceleration, as a proxy for activity, were assessed over 20 days post-release to quantify disturbance intensity, recovery duration, and speed. Differences were evaluated, considering species-specific traits and the human footprint of the study region. Over 70% of the analyzed species exhibited significant behavioral changes following collaring events. Herbivores traveled farther with variable activity reactions, while omnivores and carnivores were initially less active and mobile. Recovery duration proved brief, with alterations diminishing within 4-7 tracking days for most species. Herbivores, particularly males, showed quicker displacement recovery (4 days) but slower activity recovery (7 days). Individuals in high human footprint areas displayed faster recovery, indicating adaptation to human disturbance. Our findings emphasize the necessity of extending tracking periods beyond 1 week and particular caution in remote study areas or herbivore-focused research, specifically in smaller mammals.
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- 2024
211. An Insert Goniometer Can Help Select the Optimal Insert Thickness When Performing Kinematically Aligned Total Knee Arthroplasty with a Medial 1:1 Ball-in-Socket and Lateral Flat Surface Insert and Posterior Cruciate Ligament Retention.
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Sanghavi, Sahil, Nedopil, Alexander, Howell, Stephen, and Hull, Maury
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external tibial rotation ,internal tibial rotation ,quadriceps line of force ,screw home mechanism ,tibiofemoral kinematics ,total knee replacement - Abstract
Current surgical practices in total knee arthroplasty (TKA) have advanced and include significant changes and improvements in alignment philosophies, femorotibial implant conformities, and ligament management to replicate in vivo knee kinematics. While corrective measures have emphasized sagittal plane alignment to restore normal flexion-extension (F-E) motion and coronal plane ligament balance, internal-external (I-E) rotation kinematics in the axial plane have been largely neglected. Recent in vivo evidence indicates that the combination of factors necessary to closely restore native tibial rotation as the knee flexes and extends is kinematic alignment (KA), which resurfaces the patients pre-arthritic knee without releasing ligaments, an insert with medial 1:1 ball-in-socket conformity and a lateral flat surface, and posterior cruciate ligament (PCL) retention. However, the inherent anterior-posterior (A-P) stability provided by the medial 1:1 ball-in-socket limits the surgeons ability to select the correct insert thickness using manual laxity testing. Accordingly, this review presents the design and validation of an instrument called an insert goniometer that measures I-E tibial rotation for inserts that differ in thickness by 1 mm and uses rotation limits at extension and 90° flexion to select the optimal insert thickness. The optimal thickness is the one that provides the greatest external tibial orientation in extension and internal tibial orientation at 90° flexion without lift-off of the insert.
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- 2024
212. Dynamic allostery drives autocrine and paracrine TGF-β signaling
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Jin, Mingliang, Seed, Robert I, Cai, Guoqing, Shing, Tiffany, Wang, Li, Ito, Saburo, Cormier, Anthony, Wankowicz, Stephanie A, Jespersen, Jillian M, Baron, Jody L, Carey, Nicholas D, Campbell, Melody G, Yu, Zanlin, Tang, Phu K, Cossio, Pilar, Wen, Weihua, Lou, Jianlong, Marks, James, Nishimura, Stephen L, and Cheng, Yifan
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Biochemistry and Cell Biology ,Biomedical and Clinical Sciences ,Biological Sciences ,1.1 Normal biological development and functioning ,2.1 Biological and endogenous factors ,TGF-b signaling ,TGF-b1 ,TGF-b3 ,activation ,autocrine signaling ,avb8 integrin ,dynamic allostery ,entropy redistribution ,furin ,latency ,paracrine signaling ,regulatory T cells ,single-particle cryo-EM ,Medical and Health Sciences ,Developmental Biology ,Biological sciences ,Biomedical and clinical sciences - Abstract
TGF-β, essential for development and immunity, is expressed as a latent complex (L-TGF-β) non-covalently associated with its prodomain and presented on immune cell surfaces by covalent association with GARP. Binding to integrin αvβ8 activates L-TGF-β1/GARP. The dogma is that mature TGF-β must physically dissociate from L-TGF-β1 for signaling to occur. Our previous studies discovered that αvβ8-mediated TGF-β autocrine signaling can occur without TGF-β1 release from its latent form. Here, we show that mice engineered to express TGF-β1 that cannot release from L-TGF-β1 survive without early lethal tissue inflammation, unlike those with TGF-β1 deficiency. Combining cryogenic electron microscopy with cell-based assays, we reveal a dynamic allosteric mechanism of autocrine TGF-β1 signaling without release where αvβ8 binding redistributes the intrinsic flexibility of L-TGF-β1 to expose TGF-β1 to its receptors. Dynamic allostery explains the TGF-β3 latency/activation mechanism and why TGF-β3 functions distinctly from TGF-β1, suggesting that it broadly applies to other flexible cell surface receptor/ligand systems.
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- 2024
213. Neoadjuvant Osimertinib for the Treatment of Stage I-IIIA Epidermal Growth Factor Receptor–Mutated Non–Small Cell Lung Cancer: A Phase II Multicenter Study
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Blakely, Collin M, Urisman, Anatoly, Gubens, Matthew A, Mulvey, Claire K, Allen, Greg M, Shiboski, Stephen C, Rotow, Julia K, Chakrabarti, Turja, Kerr, D Lucas, Aredo, Jacqueline V, Bacaltos, Bianca, Gee, Megan, Tan, Lisa, Jones, Kirk D, Devine, W Patrick, Doebele, Robert C, Aisner, Dara L, Patil, Tejas, Schenk, Erin L, Bivona, Trever G, Riess, Jonathan W, Coleman, Melissa, Kratz, Johannes R, and Jablons, David M
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Biomedical and Clinical Sciences ,Clinical Sciences ,Oncology and Carcinogenesis ,Lung ,Women's Health ,Clinical Research ,Clinical Trials and Supportive Activities ,Cancer ,Minority Health ,Lung Cancer ,Patient Safety ,6.4 Surgery ,6.1 Pharmaceuticals ,Humans ,Acrylamides ,Female ,Carcinoma ,Non-Small-Cell Lung ,Aniline Compounds ,Male ,Lung Neoplasms ,Middle Aged ,ErbB Receptors ,Aged ,Neoadjuvant Therapy ,Mutation ,Neoplasm Staging ,Adult ,Protein Kinase Inhibitors ,Antineoplastic Agents ,Indoles ,Pyrimidines ,Oncology & Carcinogenesis ,Oncology and carcinogenesis - Abstract
PurposeTo assess the safety and efficacy of the third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor osimertinib as neoadjuvant therapy in patients with surgically resectable stage I-IIIA EGFR-mutated non-small cell lung cancer (NSCLC).Patients and methodsThis was a multi-institutional phase II trial of neoadjuvant osimertinib for patients with surgically resectable stage I-IIIA (American Joint Committee on Cancer [AJCC] V7) EGFR-mutated (L858R or exon 19 deletion) NSCLC (ClinicalTrials.gov identifier: NCT03433469). Patients received osimertinib 80 mg orally once daily for up to two 28-day cycles before surgical resection. The primary end point was major pathological response (MPR) rate. Secondary safety and efficacy end points were also assessed. Exploratory end points included pretreatment and post-treatment tumor mutation profiling.ResultsA total of 27 patients were enrolled and treated with neoadjuvant osimertinib for a median 56 days before surgical resection. Twenty-four (89%) patients underwent subsequent surgery; three (11%) patients were converted to definitive chemoradiotherapy. The MPR rate was 14.8% (95% CI, 4.2 to 33.7). No pathological complete responses were observed. The ORR was 52%, and the median DFS was 40.9 months. One treatment-related serious adverse event (AE) occurred (3.7%). No patients were unable to undergo surgical resection or had surgery delayed because of an AE. The most common co-occurring tumor genomic alterations were in TP53 (42%) and RBM10 (21%).ConclusionTreatment with neoadjuvant osimertinib in surgically resectable (stage IA-IIIA, AJCC V7) EGFR-mutated NSCLC did not meet its primary end point for MPR rate. However, neoadjuvant osimertinib did not lead to unanticipated AEs, surgical delays, nor result in a significant unresectability rate.
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- 2024
214. Moon Shadows (Nocturnes)
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White, Stephen A
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TenorSax ,Piano ,Nocturnes - Abstract
This music score was submitted for Resonate 2024: An Open Access Call for Scores by the UCLA Music Library with Bent Frequency and Jan Berry Baker.
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- 2024
215. Sonata #2 Inner Dance for Soprano Saxophone and Piano
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Kleiman, Stephen
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This music score was submitted for Resonate 2024: An Open Access Call for Scores by the UCLA Music Library with Bent Frequency and Jan Berry Baker.
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- 2024
216. A Multiscale Model to Understand the Interface Chemistry, Contacts, and Dynamics During Lithium Stripping
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Feng, Min, Liu, Xing, Harris, Stephen J, Sheldon, Brian W, and Qi, Yue
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Engineering ,Materials Engineering ,Mathematical Sciences ,Physical Sciences ,Mechanical Engineering & Transports ,Mathematical sciences ,Physical sciences - Abstract
A reversible Li-metal electrode, paired with a solid electrolyte, is critical for attaining higher energy density and safer batteries beyond the current lithium-ion cells. A stable stripping process may be even harder to attain as the stripping process will remove Li-atoms from the surface, and naturally reduce surface contact area, if not self-corrected by other mechanisms, such as diffusion and plastic deformation under an applied external stack pressure. Here, we capture these mechanisms occurring at multiple length- and time- scales, i.e., interface interactions, vacancy hopping, and plastic deformation, by integrating density functional theory (DFT) simulations, kinetic Monte Carlo (KMC), and continuum finite element method (FEM). By assuming the self-affine nature of multiscale contacts, we predict the steady-state contact area as a function of stripping current density, interface wettability, and stack pressure. We further estimate the exponential increase of overpotential due to contact area loss to maintain the same stripping current density. We demonstrate that a lithiophilic interface requires less stack pressure to reach the same steady-state contact area fraction than a lithiophobic interface. A “tolerable steady-state” contact area loss for maintaining stable stripping is estimated at 20 %, corresponding to a 10 % increase in overpotential. To constrain contact loss within the tolerance, the required stack pressure is 0.1, 0.5, and 2 times the yield strength of lithium metal for three distinct interfaces, lithiophilic Li/lithium oxide(Li2O), Li/lithium lanthanum zirconium oxide(LLZO), and lithiophoblic Li/lithium fluoride(LiF), respectively. The modeling results agree with experiments on the impact of the stack pressure quantitatively, while the discrepancy in stripping rate sensitivity is attributed to the simplifying interface interaction in our simulations. Overall, this multiscale simulation framework demonstrates the importance of electrochemical-mechanical coupling in understanding the dynamics of the Li/SE interface during stripping.
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- 2024
217. Emerging multiscale insights on microbial carbon use efficiency in the land carbon cycle
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He, Xianjin, Abs, Elsa, Allison, Steven D, Tao, Feng, Huang, Yuanyuan, Manzoni, Stefano, Abramoff, Rose, Bruni, Elisa, Bowring, Simon PK, Chakrawal, Arjun, Ciais, Philippe, Elsgaard, Lars, Friedlingstein, Pierre, Georgiou, Katerina, Hugelius, Gustaf, Holm, Lasse Busk, Li, Wei, Luo, Yiqi, Marmasse, Gaëlle, Nunan, Naoise, Qiu, Chunjing, Sitch, Stephen, Wang, Ying-Ping, and Goll, Daniel S
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Agricultural ,Veterinary and Food Sciences ,Biological Sciences ,Forestry Sciences ,Life on Land ,Carbon Cycle ,Soil Microbiology ,Carbon ,Soil ,Ecosystem ,Bacteria - Abstract
Microbial carbon use efficiency (CUE) affects the fate and storage of carbon in terrestrial ecosystems, but its global importance remains uncertain. Accurately modeling and predicting CUE on a global scale is challenging due to inconsistencies in measurement techniques and the complex interactions of climatic, edaphic, and biological factors across scales. The link between microbial CUE and soil organic carbon relies on the stabilization of microbial necromass within soil aggregates or its association with minerals, necessitating an integration of microbial and stabilization processes in modeling approaches. In this perspective, we propose a comprehensive framework that integrates diverse data sources, ranging from genomic information to traditional soil carbon assessments, to refine carbon cycle models by incorporating variations in CUE, thereby enhancing our understanding of the microbial contribution to carbon cycling.
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- 2024
218. Unveiling the Distant Universe: Characterizing z ≥ 9 Galaxies in the First Epoch of COSMOS-Web
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Franco, Maximilien, Akins, Hollis B, Casey, Caitlin M, Finkelstein, Steven L, Shuntov, Marko, Chworowsky, Katherine, Faisst, Andreas L, Fujimoto, Seiji, Ilbert, Olivier, Koekemoer, Anton M, Liu, Daizhong, Lovell, Christopher C, Maraston, Claudia, McCracken, Henry Joy, McKinney, Jed, Robertson, Brant E, Bagley, Micaela B, Champagne, Jaclyn B, Cooper, Olivia R, Ding, Xuheng, Drakos, Nicole E, Enia, Andrea, Gillman, Steven, Gozaliasl, Ghassem, Harish, Santosh, Hayward, Christopher C, Hirschmann, Michaela, Jin, Shuowen, Kartaltepe, Jeyhan S, Kokorev, Vasily, Laigle, Clotilde, Long, Arianna S, Magdis, Georgios, Mahler, Guillaume, Martin, Crystal L, Massey, Richard, Mobasher, Bahram, Paquereau, Louise, Renzini, Alvio, Rhodes, Jason, Rich, R Michael, Sheth, Kartik, Silverman, John D, Sparre, Martin, Talia, Margherita, Trakhtenbrot, Benny, Valentino, Francesco, Vijayan, Aswin P, Wilkins, Stephen M, Yang, Lilan, and Zavala, Jorge A
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Astronomical Sciences ,Physical Sciences ,Astronomical and Space Sciences ,Atomic ,Molecular ,Nuclear ,Particle and Plasma Physics ,Physical Chemistry (incl. Structural) ,Astronomy & Astrophysics ,Astronomical sciences ,Particle and high energy physics ,Space sciences - Abstract
We report the identification of 15 galaxy candidates at z ≥ 9 using the initial COSMOS-Web JWST observations over 77 arcmin2 through four Near Infrared Camera filters (F115W, F150W, F277W, and F444W) with an overlap with the Mid-Infrared Imager (F770W) of 8.7 arcmin2. We fit the sample using several publicly available spectral energy distribution (SED) fitting and photometric redshift codes and determine their redshifts between z = 9.3 and z = 10.9 (〈z〉 = 10.0), UV magnitudes between M UV = −21.2 and −19.5 (with 〈M UV〉 = −20.2), and rest-frame UV slopes (〈β〉 = −2.4). These galaxies are, on average, more luminous than most z ≥ 9 candidates discovered by JWST so far in the literature, while exhibiting similar blue colors in their rest-frame UV. The rest-frame UV slopes derived from SED fitting are blue (β ∼ [−2.0, −2.7]) without reaching extremely blue values as reported in other recent studies at these redshifts. The blue color is consistent with models that suggest the underlying stellar population is not yet fully enriched in metals like similarly luminous galaxies in the lower-redshift Universe. The derived stellar masses with 〈 log 10 ( M ⋆/M ⊙)〉 ≈ 8-9 are not in tension with the standard Lambda cold dark matter (ΛCDM) model, and our measurement of the volume density of such UV-luminous galaxies aligns well with previously measured values presented in the literature at z ∼ 9-10. Our sample of galaxies, although compact, is significantly resolved.
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- 2024
219. IHMCIF: An Extension of the PDBx/mmCIF Data Standard for Integrative Structure Determination Methods.
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Vallat, Brinda, Webb, Benjamin, Westbrook, John, Goddard, Thomas, Hanke, Christian, Graziadei, Andrea, Peisach, Ezra, Zalevsky, Arthur, Sagendorf, Jared, Tangmunarunkit, Hongsuda, Voinea, Serban, Sekharan, Monica, Yu, Jian, Bonvin, Alexander, DiMaio, Frank, Hummer, Gerhard, Meiler, Jens, Tajkhorshid, Emad, Ferrin, Thomas, Lawson, Catherine, Leitner, Alexander, Rappsilber, Juri, Seidel, Claus, Jeffries, Cy, Burley, Stephen, Hoch, Jeffrey, Kurisu, Genji, Morris, Kyle, Patwardhan, Ardan, Velankar, Sameer, Schwede, Torsten, Trewhella, Jill, Kesselman, Carl, Berman, Helen, and Sali, Andrej
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Data Standard ,IHMCIF ,PDB-Dev ,PDBx/mmCIF ,Worldwide Protein Data Bank ,Databases ,Protein ,Proteins ,Protein Conformation ,Models ,Molecular ,Software ,Crystallography ,X-Ray ,Macromolecular Substances ,Computational Biology ,Ligands - Abstract
IHMCIF (github.com/ihmwg/IHMCIF) is a data information framework that supports archiving and disseminating macromolecular structures determined by integrative or hybrid modeling (IHM), and making them Findable, Accessible, Interoperable, and Reusable (FAIR). IHMCIF is an extension of the Protein Data Bank Exchange/macromolecular Crystallographic Information Framework (PDBx/mmCIF) that serves as the framework for the Protein Data Bank (PDB) to archive experimentally determined atomic structures of biological macromolecules and their complexes with one another and small molecule ligands (e.g., enzyme cofactors and drugs). IHMCIF serves as the foundational data standard for the PDB-Dev prototype system, developed for archiving and disseminating integrative structures. It utilizes a flexible data representation to describe integrative structures that span multiple spatiotemporal scales and structural states with definitions for restraints from a variety of experimental methods contributing to integrative structural biology. The IHMCIF extension was created with the benefit of considerable community input and recommendations gathered by the Worldwide Protein Data Bank (wwPDB) Task Force for Integrative or Hybrid Methods (wwpdb.org/task/hybrid). Herein, we describe the development of IHMCIF to support evolving methodologies and ongoing advancements in integrative structural biology. Ultimately, IHMCIF will facilitate the unification of PDB-Dev data and tools with the PDB archive so that integrative structures can be archived and disseminated through PDB.
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- 2024
220. MerlinS13 phosphorylation regulates meningioma Wnt signaling and magnetic resonance imaging features
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Eaton, Charlotte D, Avalos, Lauro, Liu, S John, Chen, Zhenhong, Zakimi, Naomi, Casey-Clyde, Tim, Bisignano, Paola, Lucas, Calixto-Hope G, Stevenson, Erica, Choudhury, Abrar, Vasudevan, Harish N, Magill, Stephen T, Young, Jacob S, Krogan, Nevan J, Villanueva-Meyer, Javier E, Swaney, Danielle L, and Raleigh, David R
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Biomedical and Clinical Sciences ,Clinical Sciences ,Biomedical Imaging ,Clinical Trials and Supportive Activities ,Rare Diseases ,Cancer ,Clinical Research ,Brain Disorders ,Brain Cancer ,Neurosciences ,Meningioma ,Humans ,Phosphorylation ,Wnt Signaling Pathway ,Neurofibromin 2 ,Animals ,Magnetic Resonance Imaging ,Meningeal Neoplasms ,Mice ,Cell Line ,Tumor ,beta Catenin ,Female ,Serine ,Male ,Proteomics ,Biomarkers ,Tumor - Abstract
Meningiomas are associated with inactivation of NF2/Merlin, but approximately one-third of meningiomas with favorable clinical outcomes retain Merlin expression. Biochemical mechanisms underlying Merlin-intact meningioma growth are incompletely understood, and non-invasive biomarkers that may be used to guide treatment de-escalation or imaging surveillance are lacking. Here, we use single-cell RNA sequencing, proximity-labeling proteomic mass spectrometry, mechanistic and functional approaches, and magnetic resonance imaging (MRI) across meningioma xenografts and patients to define biochemical mechanisms and an imaging biomarker that underlie Merlin-intact meningiomas. We find Merlin serine 13 (S13) dephosphorylation drives meningioma Wnt signaling and tumor growth by attenuating inhibitory interactions with β-catenin and activating the Wnt pathway. MRI analyses show Merlin-intact meningiomas with S13 phosphorylation and favorable clinical outcomes are associated with high apparent diffusion coefficient (ADC). These results define mechanisms underlying a potential imaging biomarker that could be used to guide treatment de-escalation or imaging surveillance for patients with Merlin-intact meningiomas.
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- 2024
221. Archetype-based Redshift Estimation for the Dark Energy Spectroscopic Instrument Survey
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Anand, Abhijeet, Guy, Julien, Bailey, Stephen, Moustakas, John, Aguilar, J, Ahlen, S, Bolton, AS, Brodzeller, A, Brooks, D, Claybaugh, T, Cole, S, de la Macorra, A, Dey, Biprateep, Fanning, K, Forero-Romero, JE, Gaztañaga, E, Gontcho, S Gontcho A, Gutierrez, G, Honscheid, K, Howlett, C, Juneau, S, Kirkby, D, Kisner, T, Kremin, A, Lambert, A, Landriau, M, Le Guillou, L, Manera, M, Meisner, A, Miquel, R, Mueller, E, Niz, G, Palanque-Delabrouille, N, Percival, WJ, Poppett, C, Prada, F, Raichoor, A, Rezaie, M, Rossi, G, Sanchez, E, Schlafly, EF, Schlegel, D, Schubnell, M, Sprayberry, D, Tarlé, G, Warner, C, Weaver, BA, Zhou, R, and Zou, H
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Particle and High Energy Physics ,Astronomical Sciences ,Physical Sciences ,Affordable and Clean Energy ,Astronomical and Space Sciences ,Astronomy & Astrophysics ,Astronomical sciences ,Particle and high energy physics - Abstract
We present a computationally efficient galaxy archetype-based redshift estimation and spectral classification method for the Dark Energy Survey Instrument (DESI) survey. The DESI survey currently relies on a redshift fitter and spectral classifier using a linear combination of principal component analysis-derived templates, which is very efficient in processing large volumes of DESI spectra within a short time frame. However, this method occasionally yields unphysical model fits for galaxies and fails to adequately absorb calibration errors that may still be occasionally visible in the reduced spectra. Our proposed approach improves upon this existing method by refitting the spectra with carefully generated physical galaxy archetypes combined with additional terms designed to absorb data reduction defects and provide more physical models to the DESI spectra. We test our method on an extensive data set derived from the survey validation (SV) and Year 1 (Y1) data of DESI. Our findings indicate that the new method delivers marginally better redshift success for SV tiles while reducing catastrophic redshift failure by 10%-30%. At the same time, results from millions of targets from the main survey show that our model has relatively higher redshift success and purity rates (0.5%-0.8% higher) for galaxy targets while having similar success for QSOs. These improvements also demonstrate that the main DESI redshift pipeline is generally robust. Additionally, it reduces the false-positive redshift estimation by 5%−40% for sky fibers. We also discuss the generic nature of our method and how it can be extended to other large spectroscopic surveys, along with possible future improvements.
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- 2024
222. The TESS-Keck Survey. XXII. A Sub-Neptune Orbiting TOI-1437
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Pidhorodetska, Daria, Gilbert, Emily A, Kane, Stephen R, Barclay, Thomas, Polanski, Alex S, Hill, Michelle L, Stassun, Keivan G, Giacalone, Steven, Ciardi, David R, Boyle, Andrew W, Howell, Steve B, Lillo-Box, Jorge, MacDougall, Mason G, Fetherolf, Tara, Batalha, Natalie M, Crossfield, Ian JM, Dressing, Courtney, Fulton, Benjamin, Howard, Andrew W, Huber, Daniel, Isaacson, Howard, Petigura, Erik A, Robertson, Paul, Weiss, Lauren M, Angelo, Isabel, Beard, Corey, Behmard, Aida, Blunt, Sarah, Brinkman, Casey L, Chontos, Ashley, Dai, Fei, Dalba, Paul A, Holcomb, Rae, Lubin, Jack, Mayo, Andrew W, Murphy, Joseph M Akana, Rice, Malena, Rubenzahl, Ryan, Scarsdale, Nicholas, Turtelboom, Emma V, Tyler, Dakotah, Van Zandt, Judah, and Schwieterman, Edward W
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Space Sciences ,Physical Sciences ,Astronomical Sciences ,Astronomical and Space Sciences ,Astronomy & Astrophysics ,Astronomical sciences ,Particle and high energy physics - Abstract
Exoplanet discoveries have revealed a dramatic diversity of planet sizes across a vast array of orbital architectures. Sub-Neptunes are of particular interest; due to their absence in our own solar system, we rely on demographics of exoplanets to better understand their bulk composition and formation scenarios. Here, we present the discovery and characterization of TOI-1437 b, a sub-Neptune with a 18.84 day orbit around a near-solar analog (M⋆ = 1.10 ± 0.10 M☉, R⋆=1.17 ± 0.12 R☉). The planet was detected using photometric data from the Transiting Exoplanet Survey Satellite (TESS) mission and radial velocity (RV) follow-up observations were carried out as a part of the TESS-Keck Survey using both the HIRES instrument at Keck Observatory and the Levy Spectrograph on the Automated Planet Finder telescope. A combined analysis of these data reveal a planet radius of Rp = 2.24 ± 0.23 R⊕ and a mass measurement of Mp = 9.6 ± 3.9 M⊕). TOI-1437 b is one of few (∼50) known transiting sub-Neptunes orbiting a solar-mass star that has a RV mass measurement. As the formation pathway of these worlds remains an unanswered question, the precise mass characterization of TOI-1437 b may provide further insight into this class of planet.
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- 2024
223. Improving impact assessments to reduce impacts of deep-sea fisheries on vulnerable marine ecosystems
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Kaikkonen, Laura, Amaro, Teresa, Auster, Peter J, Bailey, David M, Bell, James B, Brandt, Angelika, Clark, Malcolm R, Drazen, Jeffrey C, Du Preez, Cherisse, Escobar-Briones, Elva, Giacomello, Eva, Gianni, Matthew, Johnson, Andrew F, Levin, Lisa A, Milligan, Rosanna J, Oduware, Stephen, Pearman, Tabitha RR, Pham, Christopher K, Ramalho, Sofia P, Rowden, Ashley A, Sutton, Tracey T, Taylor, Michelle L, Watling, Les, and Victorero, Lissette
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Environmental Sciences ,Environmental Management ,Life Below Water ,Environmental Science and Management ,Political Science ,Law ,Fisheries ,Environmental management ,Policy and administration ,Political science - Published
- 2024
224. C. elegans LIN-66 mediates EIF-3/eIF3-dependent protein translation via a cold-shock domain.
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Blazie, Stephen, Fortunati, Daniel, Zhao, Yan, and Jin, Yishi
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Animals ,Caenorhabditis elegans ,Caenorhabditis elegans Proteins ,Eukaryotic Initiation Factor-3 ,Protein Biosynthesis ,Motor Neurons ,Mutation ,RNA ,Messenger ,Amino Acid Sequence ,Cold-Shock Response ,Protein Domains - Abstract
Protein translation initiation is a conserved process involving many proteins acting in concert. The 13 subunit eukaryotic initiation factor 3 (eIF3) complex is essential for assembly of the pre-initiation complex that scans mRNA and positions ribosome at the initiation codon. We previously reported that a gain-of-function (gf) mutation affecting the G subunit of the Caenorhabditis elegans eIF3 complex, eif-3.g(gf), selectively modulates protein translation in the ventral cord cholinergic motor neurons. Here, through unbiased genetic suppressor screening, we identified that the gene lin-66 mediates eif-3.g(gf)-dependent protein translation in motor neurons. LIN-66 is composed largely of low-complexity amino acid sequences with unknown functional domains. We combined bioinformatics analysis with in vivo functional dissection and identified a cold-shock domain in LIN-66 critical for its function. In cholinergic motor neurons, LIN-66 shows a close association with EIF-3.G in the cytoplasm. The low-complexity amino acid sequences of LIN-66 modulate its subcellular pattern. As cold-shock domains function broadly in RNA regulation, we propose that LIN-66 mediates stimulus-dependent protein translation by facilitating the interaction of mRNAs with EIF-3.G.
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- 2024
225. Genetic Signatures of Positive Selection in Human Populations Adapted to High Altitude in Papua New Guinea.
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González-Buenfil, Ram, Vieyra-Sánchez, Sofía, Quinto-Cortés, Consuelo, Oppenheimer, Stephen, Pomat, William, Laman, Moses, Cervantes-Hernández, Mayté, Barberena-Jonas, Carmina, Auckland, Kathryn, Allen, Angela, Allen, Stephen, Phipps, Maude, Huerta-Sanchez, Emilia, Ioannidis, Alexander, Mentzer, Alexander, and Moreno-Estrada, Andrés
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Papua New Guinea ,archaic introgression. population genomics ,high altitude ,human adaptation ,positive selection ,Humans ,Selection ,Genetic ,Altitude ,Papua New Guinea ,Adaptation ,Physiological ,Genome ,Human ,Altitude Sickness - Abstract
Papua New Guinea (PNG) hosts distinct environments mainly represented by the ecoregions of the Highlands and Lowlands that display increased altitude and a predominance of pathogens, respectively. Since its initial peopling approximately 50,000 years ago, inhabitants of these ecoregions might have differentially adapted to the environmental pressures exerted by each of them. However, the genetic basis of adaptation in populations from these areas remains understudied. Here, we investigated signals of positive selection in 62 highlanders and 43 lowlanders across 14 locations in the main island of PNG using whole-genome genotype data from the Oceanian Genome Variation Project (OGVP) and searched for signals of positive selection through population differentiation and haplotype-based selection scans. Additionally, we performed archaic ancestry estimation to detect selection signals in highlanders within introgressed regions of the genome. Among highland populations we identified candidate genes representing known biomarkers for mountain sickness (SAA4, SAA1, PRDX1, LDHA) as well as candidate genes of the Notch signaling pathway (PSEN1, NUMB, RBPJ, MAML3), a novel proposed pathway for high altitude adaptation in multiple organisms. We also identified candidate genes involved in oxidative stress, inflammation, and angiogenesis, processes inducible by hypoxia, as well as in components of the eye lens and the immune response. In contrast, candidate genes in the lowlands are mainly related to the immune response (HLA-DQB1, HLA-DQA2, TAAR6, TAAR9, TAAR8, RNASE4, RNASE6, ANG). Moreover, we find two candidate regions to be also enriched with archaic introgressed segments, suggesting that archaic admixture has played a role in the local adaptation of PNG populations.
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- 2024
226. Transcriptome-wide association analysis identifies candidate susceptibility genes for prostate-specific antigen levels in men without prostate cancer.
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Chen, Dorothy, Dong, Ruocheng, Kachuri, Linda, Hoffmann, Thomas, Jiang, Yu, Berndt, Sonja, Shelley, John, Schaffer, Kerry, Machiela, Mitchell, Freedman, Neal, Huang, Wen-Yi, Li, Shengchao, Lilja, Hans, Justice, Amy, Madduri, Ravi, Rodriguez, Alex, Van Den Eeden, Stephen, Chanock, Stephen, Haiman, Christopher, Conti, David, Klein, Robert, Mosley, Jonathan, Witte, John, and Graff, Rebecca
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gene expression ,genetics ,prostate cancer ,prostate-specific antigen ,screening ,transcriptome-wide association study ,Humans ,Male ,Prostate-Specific Antigen ,Genome-Wide Association Study ,Prostatic Neoplasms ,Genetic Predisposition to Disease ,Transcriptome ,Gene Expression Profiling ,Polymorphism ,Single Nucleotide - Abstract
Deciphering the genetic basis of prostate-specific antigen (PSA) levels may improve their utility for prostate cancer (PCa) screening. Using genome-wide association study (GWAS) summary statistics from 95,768 PCa-free men, we conducted a transcriptome-wide association study (TWAS) to examine impacts of genetically predicted gene expression on PSA. Analyses identified 41 statistically significant (p 0.5: CCNA2 and HIST1H2BN. Six of the 20 identified genes are not known to impact PCa risk. Fine-mapping based on whole blood and prostate tissue revealed five protein-coding genes with evidence of causal relationships with PSA levels. Of these five genes, four exhibited evidence of colocalization and one was conditionally independent of previous GWAS findings. These results yield hypotheses that should be further explored to improve understanding of genetic factors underlying PSA levels.
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- 2024
227. Monte Carlo calculations of cryogenic photodetector readout of scintillating GaAs for dark matter detection
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Derenzo, Stephen E.
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Physics - Instrumentation and Detectors ,Astrophysics - Instrumentation and Methods for Astrophysics ,High Energy Physics - Experiment ,78M31 ,D.1 - Abstract
The recent discovery that GaAs(Si,B) is a bright cryogenic scintillator with no apparent afterglow offers new opportunities for detecting rare, low-energy, electronic excitations from interacting dark matter. This paper presents Monte Carlo calculations of the scintillation photon detection efficiencies of optical cavities using three current cryogenic photodetector technologies. In order of photon detection efficiency these are: (1) Ge/TES: germanium absorbers that convert interacting photons to athermal phonons that are readout by transition edge sensors, (2) KID: kinetic induction detectors that respond to the breaking of cooper pairs by a change in resonance frequency, and (3) SNSPD: superconducting nanowire single photon detectors, where a photon briefly transitions a thin wire from superconducting to normal. The detection efficiencies depend strongly on the n-type GaAs absolute absorption coefficient KA, which is a part of the narrow beam absorption that has never been directly measured. However, the high cryogenic scintillation luminosity of GaAs(Si,B) sets an upper limit on KA of 0.03/cm. Using that value and properties published for Ge/TES, KID, and SNSPD photodetectors, this work calculates that those photodetectors attached to opposing faces of a 1 cm3 cubic GaAs(Si,B) crystal in an optical cavity with gold mirrors would have scintillation photon detection efficiencies of 35%, 25%, and 8%, respectively. Larger values would be expected for lower values of KA., Comment: 15 pages, 6 figures, 5 tables
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- 2024
228. RenDetNet: Weakly-supervised Shadow Detection with Shadow Caster Verification
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Kubiak, Nikolina, Wortman, Elliot, Mustafa, Armin, Phillipson, Graeme, Jolly, Stephen, and Hadfield, Simon
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Computer Science - Computer Vision and Pattern Recognition ,Computer Science - Graphics - Abstract
Existing shadow detection models struggle to differentiate dark image areas from shadows. In this paper, we tackle this issue by verifying that all detected shadows are real, i.e. they have paired shadow casters. We perform this step in a physically-accurate manner by differentiably re-rendering the scene and observing the changes stemming from carving out estimated shadow casters. Thanks to this approach, the RenDetNet proposed in this paper is the first learning-based shadow detection model whose supervisory signals can be computed in a self-supervised manner. The developed system compares favourably against recent models trained on our data. As part of this publication, we release our code on github., Comment: AIM @ ECCV 2024 / code available at https://github.com/n-kubiak/RenDetNet
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- 2024
229. Revisiting collisional broadening of $^{85}$Rb Rydberg levels: conclusions for vapor cell manufacture
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Lei, Mingxin, Eckel, Stephen P., Norrgard, Eric B., Prajapati, Nikunjkumar, Artusio-Glimpse, Alexandra B., Simons, Matthew T., and Holloway, Christopher L.
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Physics - Atomic Physics - Abstract
Electrometry based on electromagnetically induced transparency (EIT) in alkali Rydberg vapor cells may suffer reduced sensitivity due to spurious line broadening effects, caused by surface charges, contaminant gases, or other manufacturing defects. In order to draw conclusions about the deleterious effects of potential contaminant gases inside Rydberg electrometry vapor cells, we revisit collisional broadening and shifts of both the D$_2$ line and Rydberg levels of rubidium. Specifically, we measure the broadening and shifts of the $5{\rm S}_{1/2}\rightarrow 5{\rm P}_{3/2}$ (i.e., the D$_2$ line) and $5{\rm S}_{1/2}\rightarrow 5{\rm P}_{3/2}\rightarrow (25{\rm D},27{\rm S},30{\rm D},32{\rm S},35{\rm D},37{\rm S})$ transitions of $^{85}$Rb due to He, Ne, N$_2$ and Ar. By combining these measurements with observations of velocity changing collisions in the sub-Doppler spectrum of the D$_2$ line, we conclude the following: (1) that contaminant gases are most likely not the cause of irregular line shapes or shifts of Rydberg transitions due to the high pressures required, and (2) the sub-Doppler spectrum of the D$_2$ line, through its accompanying loss of contrast at high pressures, can validate that a vapor cell is sufficiently free of contaminant gas for EIT electrometry. We use the theory of Omont, J. Phys. France 38, 1343 (1977), to extend our results to a wide variety of possible contaminant gases and further derive scaling laws applicable to all gases., Comment: 10 pages, 6 figures, 3 tables
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- 2024
230. The MIRI Exoplanets Orbiting White Dwarfs (MEOW) Survey: Mid-Infrared Excess Reveals a Giant Planet Candidate around a Nearby White Dwarf
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Limbach, Mary Anne, Vanderburg, Andrew, Venner, Alexander, Blouin, Simon, Stevenson, Kevin B., MacDonald, Ryan J., Jenkins, Sydney, Bowens-Rubin, Rachel, Soares-Furtado, Melinda, Morley, Caroline, Janson, Markus, Debes, John, Xu, Siyi, Kleisioti, Evangelia, Kenworthy, Matthew, Butler, Paul, Crane, Jeffrey D., Osip, Dave, Shectman, Stephen, and Teske, Johanna
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Astrophysics - Earth and Planetary Astrophysics ,Astrophysics - Solar and Stellar Astrophysics - Abstract
The MIRI Exoplanets Orbiting White dwarfs (MEOW) Survey is a cycle 2 JWST program to search for exoplanets around dozens of nearby white dwarfs via infrared excess and direct imaging. In this paper, we present the detection of mid-infrared excess at 18 and 21 microns towards the bright (V = 11.4) metal-polluted white dwarf WD 0310-688. The source of the IR excess is almost certainly within the system; the probability of background contamination is $<0.1\%$. While the IR excess could be due to an unprecedentedly small and cold debris disk, it is best explained by a $3.0^{+5.5}_{-1.9}$ M$_{\rm Jup}$ cold (248$^{+84}_{-61}$ K) giant planet orbiting the white dwarf within the forbidden zone (the region where planets are expected to be destroyed during the star's red giant phase). We constrain the source of the IR excess to an orbital separation of 0.1-2 AU, marking the first discovery of a white dwarf planet candidate within this range of separations. WD 0310-688 is a young remnant of an A or late B-type star, and at just 10.4 pc it is now the closest white dwarf with a known planet candidate. Future JWST observations could distinguish the two scenarios by either detecting or ruling out spectral features indicative of a planet atmosphere., Comment: Accepted for publication to ApJL
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- 2024
231. Winning Lights Out with Fibonacci
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Arangala, Crista, Bailey, Stephen, and Mazur, Kristen
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Mathematics - History and Overview - Abstract
Lights Out is a single-player electronic handheld game from the 1990s that features a 5 by 5 grid of light-up buttons. The game begins with some lights on and others off. The goal is to turn off all lights but pressing a button changes its state and changes the states of the buttons above and below and to the left and right of the button. We examine a cylindrical Lights Out game in which the left side of the board is connected to the right. Moreover, instead of just on and off we let the lights have $k$ states for $k \ge 2$. We then apply a modified light chasing strategy in which we try to systematically turn off all lights in a row by pressing the buttons in the row below. We ask if the game begins with all lights starting at the same state, how many rows must the board have in order for all lights to be turned off using this type of modified light chasing after we press the last row of lights. We connect this light chasing strategy to the Fibonacci numbers and are able to provide answer to our question by studying the Fibonacci numbers (mod $k$).
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- 2024
232. Spin Excitation Continuum in the Exactly Solvable Triangular-Lattice Spin Liquid CeMgAl11O19
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Gao, Bin, Chen, Tong, Liu, Chunxiao, Klemm, Mason L., Zhang, Shu, Ma, Zhen, Xu, Xianghan, Won, Choongjae, McCandless, Gregory T., Murai, Naoki, Ohira-Kawamura, Seiko, Moxim, Stephen J., Ryan, Jason T., Huang, Xiaozhou, Wang, Xiaoping, Chan, Julia Y., Cheong, Sang-Wook, Tchernyshyov, Oleg, Balents, Leon, and Dai, Pengcheng
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Condensed Matter - Strongly Correlated Electrons - Abstract
In magnetically ordered insulators, elementary quasiparticles manifest as spin waves - collective motions of localized magnetic moments propagating through the lattice - observed via inelastic neutron scattering. In effective spin-1/2 systems where geometric frustrations suppress static magnetic order, spin excitation continua can emerge, either from degenerate classical spin ground states or from entangled quantum spins characterized by emergent gauge fields and deconfined fractionalized excitations. Comparing the spin Hamiltonian with theoretical models can unveil the microscopic origins of these zero-field spin excitation continua. Here, we use neutron scattering to study spin excitations of the two-dimensional (2D) triangular-lattice effective spin-1/2 antiferromagnet CeMgAl11O19. Analyzing the spin waves in the field-polarized ferromagnetic state, we find that the spin Hamiltonian is close to an exactly solvable 2D triangular-lattice XXZ model, where degenerate 120$^\circ$ ordered ground states - umbrella states - develop in the zero temperature limit. We then find that the observed zero-field spin excitation continuum matches the calculated ensemble of spin waves from the umbrella state manifold, and thus conclude that CeMgAl11O19 is the first example of an exactly solvable spin liquid on a triangular lattice where the spin excitation continuum arises from the ground state degeneracy., Comment: 11 pages, 5 figures
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- 2024
233. Narrow Linewidth Distributed Feedback Lasers Utilizing Distributed Phase Shift
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Sun, Yiming, Yuan, Bocheng, Sun, Xiao, Zhu, Simeng, Fan, Yizhe, Al-Rubaiee, Mohanad, Marsh, John H., Sweeney, Stephen J., and Hou, Lianping
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Physics - Optics ,78 - Abstract
This study proposes and experimentally demonstrates a distributed feedback (DFB) laser with a distributed phase shift (DPS) region at the center of the DFB cavity. By modeling the field intensity distribution in the cavity and the output spectrum, the DPS region length and phase shift values have been optimized. Experimental comparisons with lasers using traditional {\pi}-phase shifts confirm that DFB lasers with optimized DPS lengths and larger phase shifts (up to 15{\pi}) achieve stable single longitudinal mode operation over a broader current range, with lower threshold current, higher power slope efficiency, and a higher side mode suppression ratio (SMSR). Furthermore, the minimum optical linewidth is reduced significantly, from 1.3 MHz to 220 kHz., Comment: 5 pages, 5 figures
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- 2024
234. Atmospheric retrievals suggest the presence of a secondary atmosphere and possible sulfur species on L 98-59 d from JWST NIRSpec G395H transmission spectroscopy
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Banerjee, Agnibha, Barstow, Joanna K., Gressier, Amélie, Espinoza, Néstor, Sing, David K., Allen, Natalie H., Birkmann, Stephan M., Challener, Ryan C., Crouzet, Nicolas, Haswell, Carole A., Lewis, Nikole K., Lewis, Stephen R., and Yang, Jingxuan
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Astrophysics - Earth and Planetary Astrophysics - Abstract
L 98-59 d is a Super-Earth planet orbiting an M-type star. We performed retrievals on the transmission spectrum of L 98-59 d obtained using NIRSpec G395H during a single transit, from JWST Cycle 1 GTO 1224. The wavelength range of this spectrum allows us to detect the presence of several atmospheric species. We found that the spectrum is consistent with a high mean molecular weight atmosphere. The atmospheric spectrum indicates the possible presence of the sulfur-bearing species H$_2$S and SO$_2$, which could hint at active volcanism on this planet if verified by future observations. We also tested for signs of stellar contamination in the spectrum, and found signs of unocculted faculae on the star. The tentative signs of an atmosphere on L 98-59 d presented in this work from just one transit bodes well for possible molecular detections in the future, particularly as it is one of the best targets among small exoplanets for atmospheric characterization using JWST., Comment: Accepted for publication to ApJL
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- 2024
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235. Massive star cluster formation III. Early mass segregation during cluster assembly
- Author
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Polak, Brooke, Mac Low, Mordecai-Mark, Klessen, Ralf S., Zwart, Simon Portegies, Andersson, Eric P., Appel, Sabrina M., Cloutier, Claude Cournoyer, Glover, Simon C. O., and McMillan, Stephen L. W.
- Subjects
Astrophysics - Astrophysics of Galaxies - Abstract
Mass segregation is seen in many star clusters, but whether massive stars form in the center of a cluster or migrate there dynamically is still debated. N-body simulations have shown that early dynamical mass segregation is possible when sub-clusters merge to form a dense core with a small crossing time. However, the effect of gas dynamics on both the formation and dynamics of the stars could inhibit the formation of the dense core. We aim to study the dynamical mass segregation of star cluster models that include gas dynamics and self-consistently form stars from the dense substructure in the gas. Our models use the Torch framework, which is based on AMUSE and includes stellar and magnetized gas dynamics, as well as stellar evolution and feedback from radiation, stellar winds, and supernovae. Our models consist of three star clusters forming from initial turbulent spherical clouds of mass $10^{4,5,6}\rm~M_\odot$ and radius $11.7\rm~pc$ that have final stellar masses of $3.6\times10^3\rm~M_\odot$, $6.5\times10^4\rm~M_\odot$, and $8.9\times10^5\rm~M_\odot$, respectively. There is no primordial mass segregation in the model by construction. All three clusters become dynamically mass segregated at early times via collapse confirming that this mechanism occurs within sub-clusters forming directly out of the dense substructure in the gas. The dynamics of the embedded gas and stellar feedback do not inhibit the collapse of the cluster. We find that each model cluster becomes mass segregated within $2~$Myr of the onset of star formation, reaching the levels observed in young clusters in the Milky Way. However, we note that the exact values are highly time-variable during these early phases of evolution. Massive stars that segregate to the center during core collapse are likely to be dynamically ejected, a process that can decrease the overall level of mass segregation again., Comment: Submitted to A&A. 8 pages, 4 figures
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- 2024
236. WIP: Identifying Tutorial Affordances for Interdisciplinary Learning Environments
- Author
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Kim, Hannah, Pond, Sergei L. Kosakovsky, and MacNeil, Stephen
- Subjects
Computer Science - Computers and Society ,Computer Science - Human-Computer Interaction ,D.2.2 ,J.3 ,K.3.2 - Abstract
This work-in-progress research paper explores the effectiveness of tutorials in interdisciplinary learning environments, specifically focusing on bioinformatics. Tutorials are typically designed for a single audience, but our study aims to uncover how they function in contexts where learners have diverse backgrounds. With the rise of interdisciplinary learning, the importance of learning materials that accommodate diverse learner needs has become evident. We chose bioinformatics as our context because it involves at least two distinct user groups: those with computational backgrounds and those with biological backgrounds. The goal of our research is to better understand current bioinformatics software tutorial designs and assess them in the conceptual framework of interdisciplinarity. We conducted a content analysis of 22 representative bioinformatics software tutorials to identify design patterns and understand their strengths and limitations. We found common codes in the representative tutorials and synthesized them into ten themes. Our assessment shows degrees to which current bioinformatics software tutorials fulfill interdisciplinarity., Comment: 5 pages, 1 table, 2024 ASEE/IEEE Frontiers in Education (FIE) Conference preprint
- Published
- 2024
237. Making Formulog Fast: An Argument for Unconventional Datalog Evaluation (Extended Version)
- Author
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Bembenek, Aaron, Greenberg, Michael, and Chong, Stephen
- Subjects
Computer Science - Programming Languages - Abstract
By combining Datalog, SMT solving, and functional programming, the language Formulog provides an appealing mix of features for implementing SMT-based static analyses (e.g., refinement type checking, symbolic execution) in a natural, declarative way. At the same time, the performance of its custom Datalog solver can be an impediment to using Formulog beyond prototyping -- a common problem for Datalog variants that aspire to solve large problem instances. In this work we speed up Formulog evaluation, with surprising results: while 2.2x speedups are obtained by using the conventional techniques for high-performance Datalog (e.g., compilation, specialized data structures), the big wins come by abandoning the central assumption in modern performant Datalog engines, semi-naive Datalog evaluation. In its place, we develop eager evaluation, a concurrent Datalog evaluation algorithm that explores the logical inference space via a depth-first traversal order. In practice, eager evaluation leads to an advantageous distribution of Formulog's SMT workload to external SMT solvers and improved SMT solving times: our eager evaluation extensions to the Formulog interpreter and Souffl\'e's code generator achieve mean 5.2x and 7.6x speedups, respectively, over the optimized code generated by off-the-shelf Souffl\'e on SMT-heavy Formulog benchmarks. Using compilation and eager evaluation, Formulog implementations of refinement type checking, bottom-up pointer analysis, and symbolic execution achieve speedups on 20 out of 23 benchmarks over previously published, hand-tuned analyses written in F#, Java, and C++, providing strong evidence that Formulog can be the basis of a realistic platform for SMT-based static analysis. Moreover, our experience adds nuance to the conventional wisdom that semi-naive evaluation is the one-size-fits-all best Datalog evaluation algorithm for static analysis workloads., Comment: Please cite the official PACMPL version of this article, available at https://doi.org/10.1145/3689754. The second version fixes minor typos in the formalism of the first arXiv version; the third version clarifies some language discussing the results of the scaling experiments
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- 2024
238. Preparing angular momentum eigenstates using engineered quantum walks
- Author
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Shi, Yuan, Beck, Kristin M., Kruse, Veronika Anneliese, and Libby, Stephen B.
- Subjects
Quantum Physics ,Mathematical Physics - Abstract
Coupled angular momentum eigenstates are widely used in atomic and nuclear physics calculations, and are building blocks for spin networks and the Schur transform. To combine two angular momenta $\mathbf{J}_1$ and $\mathbf{J}_2$, forming eigenstates of their total angular momentum $\mathbf{J}=\mathbf{J}_1+\mathbf{J}_2$, we develop a quantum-walk scheme that does not require inputting $O(j^3)$ nonzero Clebsch-Gordan (CG) coefficients classically. In fact, our scheme may be regarded as a unitary method for computing CG coefficients on quantum computers with a typical complexity of $O(j)$ and a worst-case complexity of $O(j^3)$. Equivalently, our scheme provides decompositions of the dense CG unitary into sparser unitary operations. Our scheme prepares angular momentum eigenstates using a sequence of Hamiltonians to move an initial state deterministically to desired final states, which are usually highly entangled states in the computational basis. In contrast to usual quantum walks, whose Hamiltonians are prescribed, we engineer the Hamiltonians in $\mathfrak{su}(2)\times \mathfrak{su}(2)$, which are inspired by, but different from, Hamiltonians that govern magnetic resonances and dipole interactions. To achieve a deterministic preparation of both ket and bra states, we use projection and destructive interference to double pinch the quantum walks, such that each step is a unit-probability population transfer within a two-level system. We test our state preparation scheme on classical computers, reproducing CG coefficients. We also implement small test problems on current quantum hardware., Comment: 26 pages total, 17 pages main text, 8 figures
- Published
- 2024
239. Modeling Spitzer 3.6 and 4.5 $\mu$m Eclipse Depths for the Inflated Hot Jupiter in the Evolved Binary System HD 202772
- Author
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Adams, Arthur D., Bott, Kimberly, Dalba, Paul A., Fetherolf, Tara, Kane, Stephen R., Crossfield, Ian, Deming, Drake, Dragomir, Diana, Gorjian, Varoujan, Kreidberg, Laura, Morales, Farisa Y., and Werner, Michael W.
- Subjects
Astrophysics - Earth and Planetary Astrophysics - Abstract
As an inflated Hot Jupiter orbiting an early-type primary star in the evolved binary HD 202772 system, HD 202772 A b's presence invites a study of how such a planet forms and evolves. As a prelude to potential atmospheric characterization with the latest generation of observatories, we present a reduction and analysis of eclipse light curve observations of HD 202772 A b acquired with the Spitzer Space Telescope using the 3.6 and 4.5 $\mu$m channels. We find eclipse depths of $680\pm68$ and $1081^{+54}_{-53}$ ppm, respectively, corresponding to day-side effective temperatures of $2130^{+102}_{-91}$ and $2611^{+46}_{-49}$ K. The corresponding Bond albedos are consistent with the distribution of albedos for Hot Jupiters observed with both Spitzer and TESS. The heat redistribution efficiencies consistent with the Bond albedo range predicted by 1-D atmospheric models in radiative-convective equilibrium are $0.71\pm0.10$ and $0.03^{+0.03}_{-0.02}$, respectively, indicating a weak day-night contrast for the former and a strong contrast for the latter. Given this, and the unique environment in which this planet resides, we recommend follow-up observations with JWST to more precisely constrain its atmospheric composition and structure, as well as its host stellar environment, to elucidate if and how the atmospheres of these close-in giants evolve with host stars in binaries past the main sequence., Comment: 17 pages, 7 figures, accepted for publication in AAS Journals
- Published
- 2024
240. Influence of selection criteria on the interpretation of rotational behaviour of wide-binary star systems
- Author
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Cookson, Stephen
- Subjects
Astrophysics - Astrophysics of Galaxies - Abstract
Binary star systems are expected to follow Newtonian dynamics similarly to planetary systems. However, reports have been made of wide binary systems with separations around 0.01 pc and larger, showing potential deviations from standard Newtonian motion. This phenomenon, suggestive of the flattening of galactic rotation curves, calls for closer inspection. This study presents an analysis of wide binary stars using data from Gaia Data Release 3 (DR3), a space-based astrometry mission funded by the European Space Agency. The study compares different choices of selection criteria to examine the nature of these apparent anomalous kinematics within the solar neighbourhood. The Gaia data set furnishes detailed parameters, including radial velocity, mass, age, and binary probability in addition to standard parameters. A custom Python tool named BYNARY facilitated both data processing and analysis. This report reveals that the signs of any anomalous signals systematically diminish as the initial selection criteria are relaxed for degrouping while subsequent filtering remains stringent, leading to the complete elimination of any apparent non-Newtonian motion for binary separations within 0.5 pc. The study shows that an y observ ed anomalous behaviour in solar neighbourhood wide binaries within 130 pc must be produced either by faint companion stars orbiting primary or secondary stars, or by flyby stars. The findings emphasize the importance of the choice of selection criteria in disentangling genuine binary dynamics from external influences. The conclusions align with the predictions of Newtonian mechanics and general relativity, though they do not exclude other phenomena at larger scales., Comment: 10 pages, 6 figures
- Published
- 2024
- Full Text
- View/download PDF
241. Perturbations in $\mathbf{O}(D,D)$ string cosmology from double field theory
- Author
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Angus, Stephen and Mukohyama, Shinji
- Subjects
High Energy Physics - Theory ,Astrophysics - Cosmology and Nongalactic Astrophysics ,General Relativity and Quantum Cosmology - Abstract
The low-energy limit of string theory contains additional gravitational degrees of freedom, a skew-symmetric tensor $B$-field and a scalar dilaton, that are not present in general relativity. Together with the metric, these three fields are naturally embedded in the $\mathbf{O}(D,D)$-symmetric framework of double field theory. The $\mathbf{O}(D,D)$ symmetry uniquely prescribes the interactions between the extended gravitational sector and other matter, leading to novel features beyond conventional string cosmology. In this work we present the equations of motion for linear perturbations around $\mathbf{O}(D,D)$ string cosmological backgrounds in $D=4$ under a scalar-vector-tensor decomposition. We obtain analytic solutions in the superhorizon limit for scalar perturbations around various homogeneous and isotropic background solutions, including some candidate models for bouncing cosmologies. The generalized energy-momentum tensor includes source terms for the $B$-field and dilaton, and we show how the resulting generalized conservation laws modify the conditions for conservation of curvature perturbations., Comment: 41 + 16 pages (main body + title, appendices, and references)
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- 2024
242. Q-ball collisions and their Gravitational Waves
- Author
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Hong, Deog Ki and Lonsdale, Stephen J.
- Subjects
High Energy Physics - Phenomenology ,General Relativity and Quantum Cosmology - Abstract
Sydney Coleman's Q-ball remains a compelling instance of localised object formation within classical field theory, independently of the quantum evolution. The theoretical possibility of such objects forming and colliding in the early universe from models such as Affleck-Dine fragmentation, or from a number of mechanisms where they are produced copiously with various size and charges to be dark matter candidates, makes it important to study in detail Q-ball collision phenomenology. In this work we present results from a study of Q-ball collisions and their gravitational waves, using a new general code package for scalar fields coupled to gravity. We then comment on the possibility of future gravitational wave detectors searching for signals of Q-ball collisions., Comment: 11 pages, 13 figures
- Published
- 2024
243. Examining the Commitments and Difficulties Inherent in Multimodal Foundation Models for Street View Imagery
- Author
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Yang, Zhenyuan, Lin, Xuhui, He, Qinyi, Huang, Ziye, Liu, Zhengliang, Jiang, Hanqi, Shu, Peng, Wu, Zihao, Li, Yiwei, Law, Stephen, Mai, Gengchen, Liu, Tianming, and Yang, Tao
- Subjects
Computer Science - Computer Vision and Pattern Recognition ,Computer Science - Artificial Intelligence - Abstract
The emergence of Large Language Models (LLMs) and multimodal foundation models (FMs) has generated heightened interest in their applications that integrate vision and language. This paper investigates the capabilities of ChatGPT-4V and Gemini Pro for Street View Imagery, Built Environment, and Interior by evaluating their performance across various tasks. The assessments include street furniture identification, pedestrian and car counts, and road width measurement in Street View Imagery; building function classification, building age analysis, building height analysis, and building structure classification in the Built Environment; and interior room classification, interior design style analysis, interior furniture counts, and interior length measurement in Interior. The results reveal proficiency in length measurement, style analysis, question answering, and basic image understanding, but highlight limitations in detailed recognition and counting tasks. While zero-shot learning shows potential, performance varies depending on the problem domains and image complexities. This study provides new insights into the strengths and weaknesses of multimodal foundation models for practical challenges in Street View Imagery, Built Environment, and Interior. Overall, the findings demonstrate foundational multimodal intelligence, emphasizing the potential of FMs to drive forward interdisciplinary applications at the intersection of computer vision and language.
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- 2024
244. Multilevel Interpretability Of Artificial Neural Networks: Leveraging Framework And Methods From Neuroscience
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He, Zhonghao, Achterberg, Jascha, Collins, Katie, Nejad, Kevin, Akarca, Danyal, Yang, Yinzhu, Gurnee, Wes, Sucholutsky, Ilia, Tang, Yuhan, Ianov, Rebeca, Ogden, George, Li, Chole, Sandbrink, Kai, Casper, Stephen, Ivanova, Anna, and Lindsay, Grace W.
- Subjects
Computer Science - Artificial Intelligence ,Quantitative Biology - Neurons and Cognition - Abstract
As deep learning systems are scaled up to many billions of parameters, relating their internal structure to external behaviors becomes very challenging. Although daunting, this problem is not new: Neuroscientists and cognitive scientists have accumulated decades of experience analyzing a particularly complex system - the brain. In this work, we argue that interpreting both biological and artificial neural systems requires analyzing those systems at multiple levels of analysis, with different analytic tools for each level. We first lay out a joint grand challenge among scientists who study the brain and who study artificial neural networks: understanding how distributed neural mechanisms give rise to complex cognition and behavior. We then present a series of analytical tools that can be used to analyze biological and artificial neural systems, organizing those tools according to Marr's three levels of analysis: computation/behavior, algorithm/representation, and implementation. Overall, the multilevel interpretability framework provides a principled way to tackle neural system complexity; links structure, computation, and behavior; clarifies assumptions and research priorities at each level; and paves the way toward a unified effort for understanding intelligent systems, may they be biological or artificial.
- Published
- 2024
245. biorecap: an R package for summarizing bioRxiv preprints with a local LLM
- Author
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Turner, Stephen D.
- Subjects
Quantitative Biology - Other Quantitative Biology - Abstract
The establishment of bioRxiv facilitated the rapid adoption of preprints in the life sciences, accelerating the dissemination of new research findings. However, the sheer volume of preprints published daily can be overwhelming, making it challenging for researchers to stay updated on the latest developments. Here, I introduce biorecap, an R package that retrieves and summarizes bioRxiv preprints using a large language model (LLM) running locally on nearly any commodity laptop. biorecap leverages the ollamar package to interface with the Ollama server and API endpoints, allowing users to prompt any local LLM available through Ollama. The package follows tidyverse conventions, enabling users to pipe the output of one function as input to another. Additionally, biorecap provides a single wrapper function that generates a timestamped CSV file and HTML report containing short summaries of recent preprints published in user-configurable subject areas. By combining the strengths of LLMs with the flexibility and security of local execution, biorecap represents an advancement in the tools available for managing the information overload in modern scientific research. The biorecap R package is available on GitHub at https://github.com/stephenturner/biorecap under an open-source (MIT) license., Comment: 5 pages, 1 figure
- Published
- 2024
246. Zeitlin's model for axisymmetric 3-D Euler equations
- Author
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Modin, Klas and Preston, Stephen C.
- Subjects
Mathematics - Differential Geometry ,Mathematical Physics ,Mathematics - Numerical Analysis ,35Q31, 53D50, 76M60, 76B47, 53D25 - Abstract
Zeitlin's model is a spatial discretization for the 2-D Euler equations on the flat 2-torus or the 2-sphere. Contrary to other discretizations, it preserves the underlying geometric structure, namely that the Euler equations describe Riemannian geodesics on a Lie group. Here we show how to extend Zeitlin's approach to the axisymmetric Euler equations on the 3-sphere. It is the first discretization of the 3-D Euler equations that fully preserves the geometric structure. Thus, this finite-dimensional model admits Riemannian curvature and Jacobi equations, which are discussed., Comment: 24 pages, 4 figures
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- 2024
247. Unirationality is the Same as Rational Connectedness in Characteristic Zero
- Author
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Maguire, Stephen
- Subjects
Mathematics - Algebraic Geometry ,14E08 - Abstract
In this paper we describe a fibration for a smooth, projective variety $ X $ over a field of characteristic zero. This fibration is similar to the MRC fibration, and we call it the MU fibration of $ X $. The MU fibration $ \pi: X \dashrightarrow MU(X) $ is characterized by the following properties: i) The very general fibres of $ \pi $ are unirational, ii) if $ Z $ is a unirational sub-variety of $ X $, $ z $ is a very general point of $ MU(X) $ (i.e., a point in the complement of a countable union of Zariski closed sub-sets of $ MU(X) $), and $ Z $ intersects $ \pi^{-1}(z) $ non-trivially, then $ Z $ is contained in $ \pi^{-1}(z) $, iii) The variety $ MU(X) $ is unique up to birational equivalence. If we call $ MU(X) $ a maximal unirational quotient, then $ X $ is unirational if and only if the dimension of any maximal unirational quotient is equal to zero. We use this work to show that unirationality, rational connectedness, and rational chain connectedness are equivalent for smooth varieties over a field of characteristic zero, and that the MRC quotient of a smooth, projective variety over a field of characteristic zero is not uniruled., Comment: 11 pages
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- 2024
248. Predictive Anchoring: A Novel Interaction to Support Contextualized Suggestions for Grid Displays
- Author
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Zastudil, Cynthia, Holyfield, Christine, Smith, June A., Nguyen, Hannah Vy, and MacNeil, Stephen
- Subjects
Computer Science - Human-Computer Interaction - Abstract
Grid displays are the most common form of augmentative and alternative communication device recommended by speech-language pathologists for children. Grid displays present a large variety of vocabulary which can be beneficial for a users' language development. However, the extensive navigation and cognitive overhead required of users of grid displays can negatively impact users' ability to actively participate in social interactions, which is an important factor of their language development. We present a novel interaction technique for grid displays, Predictive Anchoring, based on user interaction theory and language development theory. Our design is informed by existing literature in AAC research, presented in the form of a set of design goals and a preliminary design sketch. Future work in user studies and interaction design are also discussed.
- Published
- 2024
249. Exploring the use of Generative AI to Support Automated Just-in-Time Programming for Visual Scene Displays
- Author
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Zastudil, Cynthia, Holyfield, Christine, Kapp, Christine, Crosland, Xandria, Lorah, Elizabeth, Zimmerman, Tara, and MacNeil, Stephen
- Subjects
Computer Science - Human-Computer Interaction - Abstract
Millions of people worldwide rely on alternative and augmentative communication devices to communicate. Visual scene displays (VSDs) can enhance communication for these individuals by embedding communication options within contextualized images. However, existing VSDs often present default images that may lack relevance or require manual configuration, placing a significant burden on communication partners. In this study, we assess the feasibility of leveraging large multimodal models (LMM), such as GPT-4V, to automatically create communication options for VSDs. Communication options were sourced from a LMM and speech-language pathologists (SLPs) and AAC researchers (N=13) for evaluation through an expert assessment conducted by the SLPs and AAC researchers. We present the study's findings, supplemented by insights from semi-structured interviews (N=5) about SLP's and AAC researchers' opinions on the use of generative AI in augmentative and alternative communication devices. Our results indicate that the communication options generated by the LMM were contextually relevant and often resembled those created by humans. However, vital questions remain that must be addressed before LMMs can be confidently implemented in AAC devices.
- Published
- 2024
250. Detection of the large-scale tidal field with galaxy multiplet alignment in the DESI Y1 spectroscopic survey
- Author
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Lamman, Claire, Eisenstein, Daniel, Forero-Romero, Jaime E., Aguilar, Jessica Nicole, Ahlen, Steven, Bailey, Stephen, Bianchi, Davide, Brooks, David, Claybaugh, Todd, de la Macorra, Axel, Doel, Peter, Ferraro, Simone, Font-Ribera, Andreu, Gaztañaga, Enrique, Gontcho, Satya Gontcho A, Gutierrez, Gaston, Honscheid, Klaus, Howlett, Cullan, Kremin, Anthony, Lambert, Andrew, Landriau, Martin, Guillou, Laurent Le, Levi, Michael E., Meisner, Aaron, Miquel, Ramon, Moustakas, John, Newman, Jeffrey A., Niz, Gustavo, Prada, Francisco, Pérez-Ràfols, Ignasi, Ross, Ashley J., Rossi, Graziano, Sanchez, Eusebio, Schubnell, Michael, Sprayberry, David, Tarlé, Gregory, Vargas-Magaña, Mariana, Weaver, Benjamin Alan, and Zou, Hu
- Subjects
Astrophysics - Cosmology and Nongalactic Astrophysics - Abstract
We explore correlations between the orientations of small galaxy groups, or "multiplets", and the large-scale gravitational tidal field. Using data from the Dark Energy Spectroscopic Instrument (DESI) Y1 survey, we detect the intrinsic alignment (IA) of multiplets to the galaxy-traced matter field out to separations of 100 Mpc/h. Unlike traditional IA measurements of individual galaxies, this estimator is not limited by imaging of galaxy shapes and allows for direct IA detection beyond redshift z = 1. Multiplet alignment is a form of higher-order clustering, for which the scale-dependence traces the underlying tidal field and amplitude is a result of small-scale (< 1 Mpc/h) dynamics. Within samples of bright galaxies (BGS), luminous red galaxies (LRG) and emission-line galaxies (ELG), we find similar scale-dependence regardless of intrinsic luminosity or colour. This is promising for measuring tidal alignment in galaxy samples that typically display no intrinsic alignment. DESI's LRG mock galaxy catalogues created from the AbacusSummit N-body simulations produce a similar alignment signal, though with a 33% lower amplitude at all scales. An analytic model using a non-linear power spectrum (NLA) only matches the signal down to 20 Mpc/h. Our detection demonstrates that galaxy clustering in the non-linear regime of structure formation preserves an interpretable memory of the large-scale tidal field. Multiplet alignment complements traditional two-point measurements by retaining directional information imprinted by tidal forces, and contains additional line-of-sight information compared to weak lensing. This is a more effective estimator than the alignment of individual galaxies in dense, blue, or faint galaxy samples., Comment: For an accessible summary of this paper, see https://cmlamman.github.io/doc/multipletIA_summary.pdf
- Published
- 2024
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