18,128 results on '"Jacob, S"'
Search Results
2. Flight Demonstration and Model Validation of a Prototype Variable-Altitude Venus Aerobot
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Izraelevitz, Jacob S., Krishnamoorthy, Siddharth, Goel, Ashish, Turner, Caleb, Aiazzi, Carolina, Pauken, Michael, Carlson, Kevin, Walsh, Gerald, Leake, Carl, Quintana, Carlos, Lim, Christopher, Jain, Abhi, Dorsky, Leonard, Baines, Kevin, Cutts, James, Byrne, Paul K., Lachenmeier, Tim, and Hall, Jeffery L.
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Computer Science - Robotics - Abstract
This paper details a significant milestone towards maturing a buoyant aerial robotic platform, or aerobot, for flight in the Venus clouds. We describe two flights of our subscale altitude-controlled aerobot, fabricated from the materials necessary to survive Venus conditions. During these flights over the Nevada Black Rock desert, the prototype flew at the identical atmospheric densities as 54 to 55 km cloud layer altitudes on Venus. We further describe a first-principle aerobot dynamics model which we validate against the Nevada flight data and subsequently employ to predict the performance of future aerobots on Venus. The aerobot discussed in this paper is under JPL development for an in-situ mission flying multiple circumnavigations of Venus, sampling the chemical and physical properties of the planet's atmosphere and also remotely sensing surface properties., Comment: Preprint submitted to AIAA Journal of Aircraft
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- 2024
3. Curiosity-Driven Science: The in Situ Jungle Biomechanics Lab in the Amazon Rainforest
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Stupski, S. David, Ferrer, Laura Casas, Harrison, Jacob S., Jackson, Justina, Mansilla, Carolina Paucarhuanca, Livano, Loribeth Maricielo Bolo, Narla, Avaneesh, Chai, Chew, Clark, Elizabeth, Ha, Nami, Nina, Jaime Quispe, Wold, Ethan, Reyes-Quinteros, Johana, Gallice, Geoffrey, and Bhamla, Saad
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Quantitative Biology - Other Quantitative Biology - Abstract
Field work is an essential component not just for organismal biology, but also for the expanding umbrella of disciplines which have turned their attention towards living systems. Observing organisms in naturalistic contexts is a critical component of discovery; however, conducting field research can be a massive barrier for scientists who do not have experience working with organisms in a naturalistic context under challenging field conditions. Here we propose 8 critical steps for organizing and executing interdisciplinary curiosity-driven field research, drawing on the insights from The in Situ Jungle Biomechanics Lab (JBL). The JBL program is a field research course that helps early-career scientists gain experience in organizing and conducting interdisciplinary field research. JBL uses a curiosity-driven approach to field science education by encouraging early-career researchers to explore scientific questions in the Peruvian Amazon with a non-prescriptive approach to research output. We achieve an inclusive research space by bringing scientists from across disciplines together, with local communities to collaborate and spark new questions and ideas. To stoke curiosity, the JBL imparts a naturalist tradition set forth by organismal biologists of the 20th century who have extolled the merits of observing the natural world as a form of scientific exploration.
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- 2024
4. $^{229}\mathrm{ThF}_4$ thin films for solid-state nuclear clocks
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Zhang, Chuankun, von der Wense, Lars, Doyle, Jack F., Higgins, Jacob S., Ooi, Tian, Friebel, Hans U., Ye, Jun, Elwell, R., Terhune, J. E. S., Morgan, H. W. T., Alexandrova, A. N., Tan, H. B. Tran, Derevianko, Andrei, and Hudson, Eric R.
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Physics - Atomic Physics ,Nuclear Experiment ,Physics - Optics ,Quantum Physics - Abstract
After nearly fifty years of searching, the vacuum ultraviolet $^{229}$Th nuclear isomeric transition has recently been directly laser excited [1,2] and measured with high spectroscopic precision [3]. Nuclear clocks based on this transition are expected to be more robust [4,5] than and may outperform [6,7] current optical atomic clocks. They also promise sensitive tests for new physics beyond the standard model [5,8,9]. In light of these important advances and applications, a dramatic increase in the need for $^{229}$Th spectroscopy targets in a variety of platforms is anticipated. However, the growth and handling of high-concentration $^{229}$Th-doped crystals [5] used in previous measurements [1-3,10] are challenging due to the scarcity and radioactivity of the $^{229}$Th material. Here, we demonstrate a potentially scalable solution to these problems by demonstrating laser excitation of the nuclear transition in $^{229}$ThF$_4$ thin films grown with a physical vapor deposition process, consuming only micrograms of $^{229}$Th material. The $^{229}$ThF$_4$ thin films are intrinsically compatible with photonics platforms and nanofabrication tools for integration with laser sources and detectors, paving the way for an integrated and field-deployable solid-state nuclear clock with radioactivity up to three orders of magnitude smaller than typical \thor-doped crystals [1-3,10]. The high nuclear emitter density in $^{229}$ThF$_4$ also potentially enables quantum optics studies in a new regime. Finally, we describe the operation and present the estimation of the performance of a nuclear clock based on a defect-free ThF$_4$ crystal., Comment: 15 pages, 3 figures
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- 2024
5. Temperature sensitivity of a Thorium-229 solid-state nuclear clock
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Higgins, Jacob S., Ooi, Tian, Doyle, Jack F., Zhang, Chuankun, Ye, Jun, Beeks, Kjeld, Sikorsky, Tomas, and Schumm, Thorsten
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Physics - Atomic Physics - Abstract
Quantum state-resolved spectroscopy of the low energy thorium-229 nuclear transition was recently achieved. The five allowed transitions within the electric quadrupole splitting structure were measured to the kilohertz level in a calcium fluoride host crystal, opening the field of nuclear-based optical clocks. Central to the performance of solid-state clock operation is an understanding of systematic shifts such as the temperature dependence of the clock transitions. In this work, we measure the four strongest transitions of thorium-229 in the same crystal at three temperature values: 150 K, 229 K, and 293 K. We find shifts of the unsplit frequency and the electric quadrupole splittings, corresponding to decreases in the electron density, electric field gradient, and field gradient asymmetry at the nucleus as temperature increases. The $\textit{m}$ = $\pm 5/2 \rightarrow \pm 3/2$ line shifts only 62(6) kHz over the temperature range, i.e., approximately 0.4 kHz/K, representing a promising candidate for a future solid-state optical clock. Achieving 10$^{-18}$ precision requires crystal temperature stability of 5$\mu$K., Comment: 7 pages, 3 figures, 2 tables
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- 2024
6. Chebyshev polynomials related to Jacobi weights
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Christiansen, Jacob S. and Rubin, Olof
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Mathematics - Classical Analysis and ODEs ,Mathematics - Complex Variables ,41A50, 30C10, 33C45 - Abstract
We investigate Chebyshev polynomials corresponding to Jacobi weights and determine monotonicity properties of their related Widom factors. This complements work by Bernstein from 1930-31 where the asymptotical behavior of the related Chebyshev norms was established. As a part of the proof, we analyze a Bernstein-type inequality for Jacobi polynomials due to Chow et al. Our findings shed new light on the asymptotical uniform bounds of Jacobi polynomials. We also show a relation between weighted Chebyshev polynomials on the unit circle and Jacobi weighted Chebyshev polynomials on [-1,1]. This generalizes work by Lachance et al. In order to complete the picture we provide numerical experiments on the remaining cases that our proof does not cover.
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- 2024
7. Is Native Mass Spectrometry in Ammonium Acetate Really Native? Protein Stability Differences in Biochemically Relevant Salt Solutions
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Lee, Katherine J, Jordan, Jacob S, and Williams, Evan R
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Analytical Chemistry ,Chemical Sciences ,Physical Chemistry ,Other Chemical Sciences ,Medical biochemistry and metabolomics ,Analytical chemistry ,Chemical engineering - Abstract
Ammonium acetate is widely used in native mass spectrometry to provide adequate ionic strength without adducting to protein ions, but different ions can preferentially stabilize or destabilize the native form of proteins in solution. The stability of bovine serum albumin (BSA) was investigated in 50 mM solutions of a variety of salts using electrospray emitters with submicron tips to desalt protein ions. The charge-state distribution of BSA is narrow (+14 to +18) in ammonium acetate (AmmAc), whereas it is much broader (+13 to +42) in solutions containing sodium acetate (NaAc), ammonium chloride (AmmCl), potassium chloride (KCl), and sodium chloride (NaCl). The average charge state and percent of unfolded protein increase in these respective solutions, indicating greater extents of protein destabilization and conformational changes. In contrast, no high charge states of either bovine carbonic anhydrase II or IgG1 were formed in AmmAc or NaCl despite their similar melting temperatures to BSA, indicating that the presence of unfolded BSA in some of these solutions is not an artifact of the electrospray ionization process. The charge states formed from the nonvolatile salt solutions do not change significantly for up to 7 min of electrospray, but higher charging occurs after 10 min, consistent with solution acidification. Formation of unfolded BSA in NaAc but not in AmmAc indicates that the cation identity, not acidification, is responsible for structural differences in these two solutions. Temperature-dependent measurements show both increased charging and aggregation at lower temperatures in NaCl:Tris than in AmmAc, consistent with lower protein stability in the former solution. These results are consistent with the order of these ions in the Hofmeister series and indicate that data on protein stability in AmmAc may not be representative of solutions containing nonvolatile salts that are directly relevant to biology.
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- 2024
8. High-Throughput Single-Particle Characterization of Aggregation Pathways and the Effects of Inhibitors for Large (Megadalton) Protein Oligomers
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Jordan, Jacob S, Harper, Conner C, and Williams, Evan R
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Analytical Chemistry ,Chemical Sciences ,Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) ,Neurosciences ,Alzheimer's Disease ,Neurodegenerative ,Brain Disorders ,Acquired Cognitive Impairment ,Dementia ,Aging ,1.1 Normal biological development and functioning ,Other Chemical Sciences ,Medical biochemistry and metabolomics ,Analytical chemistry ,Chemical engineering - Abstract
Protein aggregation is involved in many human diseases, but characterizing the sizes and shapes of intermediate oligomers (∼10-100 nm) that are important to the formation of macroscale aggregates like amyloid fibrils is a significant analytical challenge. Here, charge detection mass spectrometry (CDMS) is used to characterize individual conformational states of bovine serum albumin oligomers with up to ∼225 molecules (15 MDa). Elongated, partially folded, and globular conformational families for each oligomer can be readily distinguished based on the extent of charging. The abundances of individual conformers vary with changes in the monomer concentration or by adding aggregation inhibitors, such as SDS, heparin, or MgCl2. These results show the potential of CDMS for investigating intermediate oligomers in protein aggregation processes that are important for understanding aggregate formation and inhibition mechanisms and could accelerate formulation buffer development to prevent the aggregation of biotherapeutics.
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- 2024
9. Asymmetric gas diffusion layers for improved water management in PGM-free electrodes
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Arman, Tanvir Alam, Babu, Siddharth Komini, Sabharwal, Mayank, Weber, Adam Z, Pasaogullari, Ugur, and Spendelow, Jacob S
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Engineering ,Materials Engineering - Abstract
Proton-exchange-membrane fuel cells (PEMFCs) offer a long-term, carbon-emission free solution to the energy needs of the transportation sector. However, high cost continues to limit PEMFC commercialization. Replacing expensive platinum group metal (PGM) catalysts with PGM-free catalysts could reduce cost, but the low active site density of PGM-free catalysts necessitates the use of thick electrodes that suffer from substantial mass transport losses. In these thick PGM-free electrodes, effective water management and oxygen transport are crucial to achieve high performance. In this work, we investigate the role of anode and cathode gas diffusion layer (GDL) configurations in controlling water management. Asymmetric GDL configurations, in which the anode GDL exhibits higher permeability than the cathode GDL, showed higher performance compared to conventional symmetric configurations. Computational modeling showed that the improved performance is mainly due to improved water management, resulting in lower liquid water saturation and faster oxygen transport in the cathode.
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- 2024
10. 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
11. Fine-structure constant sensitivity of the Th-229 nuclear clock transition
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Beeks, Kjeld, Kazakov, Georgy A., Schaden, Fabian, Morawetz, Ira, de Col, Luca Toscani, Riebner, Thomas, Bartokos, Michael, Sikorsky, Tomas, Schumm, Thorsten, Zhang, Chuankun, Ooi, Tian, Higgins, Jacob S., Doyle, Jack F., Ye, Jun, and Safronova, Marianna S.
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Nuclear Theory ,Nuclear Experiment ,Physics - Atomic Physics - Abstract
State-resolved laser spectroscopy at the 10$^{-12}$ precision level recently reported in $arXiv$:2406.18719 determined the fractional change in nuclear quadrupole moment between the ground and isomeric state of $^{229}\rm{Th}$, $\Delta Q_0/Q_0$=1.791(2) %. Assuming a prolate spheroid nucleus, this allows to quantify the sensitivity of the nuclear transition frequency to variations of the fine-structure constant $\alpha$ to $K=5900(2300)$, with the uncertainty dominated by the experimentally measured charge radius difference $\Delta \langle r^2 \rangle$ between the ground and isomeric state. This result indicates a three orders of magnitude enhancement over atomic clock schemes based on electron shell transitions. We find that $\Delta Q_0$ is highly sensitive to tiny changes in the nuclear volume, thus the constant volume approximation cannot be used to accurately relate changes in $\langle r^2 \rangle$ and $Q_0$. The difference between the experimental and estimated values in $\Delta Q_0/Q_0$ raises a further question on the octupole contribution to the alpha-sensitivity., Comment: 10 pages, 2 figures
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- 2024
12. Frequency ratio of the $^{229\mathrm{m}}$Th nuclear isomeric transition and the $^{87}$Sr atomic clock
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Zhang, Chuankun, Ooi, Tian, Higgins, Jacob S., Doyle, Jack F., von der Wense, Lars, Beeks, Kjeld, Leitner, Adrian, Kazakov, Georgy, Li, Peng, Thirolf, Peter G., Schumm, Thorsten, and Ye, Jun
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Physics - Atomic Physics ,Nuclear Experiment ,Physics - Optics ,Quantum Physics - Abstract
Optical atomic clocks$^{1,2}$ use electronic energy levels to precisely keep track of time. A clock based on nuclear energy levels promises a next-generation platform for precision metrology and fundamental physics studies. Thorium-229 nuclei exhibit a uniquely low energy nuclear transition within reach of state-of-the-art vacuum ultraviolet (VUV) laser light sources and have therefore been proposed for construction of the first nuclear clock$^{3,4}$. However, quantum state-resolved spectroscopy of the $^{229m}$Th isomer to determine the underlying nuclear structure and establish a direct frequency connection with existing atomic clocks has yet to be performed. Here, we use a VUV frequency comb to directly excite the narrow $^{229}$Th nuclear clock transition in a solid-state CaF$_2$ host material and determine the absolute transition frequency. We stabilize the fundamental frequency comb to the JILA $^{87}$Sr clock$^2$ and coherently upconvert the fundamental to its 7th harmonic in the VUV range using a femtosecond enhancement cavity. This VUV comb establishes a frequency link between nuclear and electronic energy levels and allows us to directly measure the frequency ratio of the $^{229}$Th nuclear clock transition and the $^{87}$Sr atomic clock. We also precisely measure the nuclear quadrupole splittings and extract intrinsic properties of the isomer. These results mark the start of nuclear-based solid-state optical clock and demonstrate the first comparison of nuclear and atomic clocks for fundamental physics studies. This work represents a confluence of precision metrology, ultrafast strong field physics, nuclear physics, and fundamental physics., Comment: 22 pages, 5 figures, 1 extended data figure
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- 2024
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13. WISDOM project XX -- Strong shear tearing molecular clouds apart in NGC 524
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Lu, Anan, Haggard, Daryl, Bureau, Martin, Gensior, Jindra, Jeffreson, Sarah, Robert, Carmelle, Williams, Thomas G., Liang, Fu-Heng, Choi, Woorak, Davis, Timothy A., Babic, Sara, Boyce, Hope, Cheung, Benjamin, Drissen, Laurent, Elford, Jacob S., Liu, Lijie, Martin, Thomas, Rhea, Carter, Rousseau-Nepton, Laurie, and Ruffa, Ilaria
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Astrophysics - Astrophysics of Galaxies - Abstract
Early-type galaxies (ETGs) are known to harbour dense spheroids of stars but scarce star formation (SF). Approximately a quarter of these galaxies have rich molecular gas reservoirs yet do not form stars efficiently. We study here the ETG NGC~524, with strong shear suspected to result in a smooth molecular gas disc and low star-formation efficiency (SFE). We present new spatially-resolved observations of the \textsuperscript{12}CO(2-1)-emitting cold molecular gas from the Atacama Large Millimeter/sub-millimeter Array (ALMA) and of the warm ionised-gas emission lines from SITELLE at the Canada-France-Hawaii Telescope. Although constrained by the resolution of the ALMA observations ($\approx37$~pc), we identify only $52$ GMCs with radii ranging from $30$ to $140$~pc, a low mean molecular gas mass surface density $\langle\Sigma_{\rm gas}\rangle\approx125$~M$_\odot$~pc$^{-2}$ and a high mean virial parameter $\langle\alpha_{\rm obs,vir}\rangle\approx5.3$. We measure spatially-resolved molecular gas depletion times ($\tau_{\rm dep}\equiv1/{\rm SFE}$) with a spatial resolution of $\approx100$~pc within a galactocentric distance of $1.5$~kpc. The global depletion time is $\approx2.0$~Gyr but $\tau_{\rm dep}$ increases toward the galaxy centre, with a maximum $\tau_{\rm dep,max}\approx5.2$~Gyr. However, no pure \ion{H}{II} region is identified in NGC~524 using ionised-gas emission-line ratio diagnostics, so the $\tau_{\rm dep}$ inferred are in fact lower limits. Measuring the GMC properties and dynamical states, we conclude that shear is the dominant mechanism shaping the molecular gas properties and regulating SF in NGC~524. This is supported by analogous analyses of the GMCs in a simulated ETG similar to NGC~524., Comment: 17 pages, 10 figures. To be published in MNRAS, accepted on May 27
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- 2024
14. Charge Detection Mass Spectrometry Reveals Conformational Heterogeneity in Megadalton-Sized Monoclonal Antibody Aggregates
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Jordan, Jacob S, Harper, Conner C, Zhang, Fan, Kofman, Esther, Li, Mandy, Sathiyamoorthy, Karthik, Zaragoza, Jan Paulo, Fayadat-Dilman, Laurence, and Williams, Evan R
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Analytical Chemistry ,Chemical Sciences ,Physical Chemistry ,Biotechnology ,1.1 Normal biological development and functioning ,Antibodies ,Monoclonal ,Chromatography ,Gel ,Electrophoresis ,Capillary ,Protein Conformation ,Mass Spectrometry ,Protein Aggregates ,General Chemistry ,Chemical sciences ,Engineering - Abstract
Aggregation of protein-based therapeutics can occur during development, production, or storage and can lead to loss of efficacy and potential toxicity. Native mass spectrometry of a covalently linked pentameric monoclonal antibody complex with a mass of ∼800 kDa reveals several distinct conformations, smaller complexes, and abundant higher-order aggregates of the pentameric species. Charge detection mass spectrometry (CDMS) reveals individual oligomers up to the pentamer mAb trimer (15 individual mAb molecules; ∼2.4 MDa) whereas intermediate aggregates composed of 6-9 mAb molecules and aggregates larger than the pentameric dimer (1.6 MDa) were not detected/resolved by standard mass spectrometry, size exclusion chromatography (SEC), capillary electrophoresis (CE-SDS), or by mass photometry. Conventional quadrupole time-of-flight mass spectrometry (QTOF MS), mass photometry, SEC, and CE-SDS did not resolve partially or more fully unfolded conformations of each oligomer that were readily identified using CDMS by their significantly higher extents of charging. Trends in the charge-state distributions of individual oligomers provides detailed insight into how the structures of compact and elongated mAb aggregates change as a function of aggregate size. These results demonstrate the advantages of CDMS for obtaining accurate masses and information about the conformations of large antibody aggregates despite extensive overlapping m/z values. These results open up the ability to investigate structural changes that occur in small, soluble oligomers during the earliest stages of aggregation for antibodies or other proteins.
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- 2024
15. Characterization of Mass, Diameter, Density, and Surface Properties of Colloidal Nanoparticles Enabled by Charge Detection Mass Spectrometry
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Harper, Conner C, Jordan, Jacob S, Papanu, Steven, and Williams, Evan R
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Analytical Chemistry ,Biomedical and Clinical Sciences ,Chemical Sciences ,Physical Chemistry ,Engineering ,Medical Biotechnology ,Nanotechnology ,Bioengineering ,mass ,charge ,characterization ,nanoparticle ,density ,precision ,surface ,Nanoscience & Nanotechnology - Abstract
A variety of scattering-based, microscopy-based, and mobility-based methods are frequently used to probe the size distributions of colloidal nanoparticles with transmission electron microscopy (TEM) often considered to be the "gold standard". Charge detection mass spectrometry (CDMS) is an alternative method for nanoparticle characterization that can rapidly measure the mass and charge of individual nanoparticle ions with high accuracy. Two low polydispersity, ∼100 nm diameter nanoparticle size standards with different compositions (polymethyl methacrylate/polystyrene copolymer and 100% polystyrene) were characterized using both TEM and CDMS to explore the merits and complementary aspects of both methods. Mass and diameter distributions are rapidly obtained from CDMS measurements of thousands of individual ions of known spherical shape, requiring less time than TEM sample preparation and image analysis. TEM image-to-image variations resulted in a ∼1-2 nm range in the determined mean diameters whereas the CDMS mass precision of ∼1% in these experiments leads to a diameter uncertainty of just 0.3 nm. For the 100% polystyrene nanoparticles with known density, the CDMS and TEM particle diameter distributions were in excellent agreement. For the copolymer nanoparticles with unknown density, the diameter from TEM measurements combined with the mass from CDMS measurements enabled an accurate measurement of nanoparticle density. Differing extents of charging for the two nanoparticle standards measured by CDMS show that charging is sensitive to nanoparticle surface properties. A mixture of the two samples was separated based on their different extents of charging despite having overlapping mass distributions centered at 341.5 and 331.0 MDa.
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- 2024
16. “De novo replication repair deficient glioblastoma, IDH-wildtype” is a distinct glioblastoma subtype in adults that may benefit from immune checkpoint blockade
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Hadad, Sara, Gupta, Rohit, Oberheim Bush, Nancy Ann, Taylor, Jennie W, Villanueva-Meyer, Javier E, Young, Jacob S, Wu, Jasper, Ravindranathan, Ajay, Zhang, Yalan, Warrier, Gayathri, McCoy, Lucie, Shai, Anny, Pekmezci, Melike, Perry, Arie, Bollen, Andrew W, Phillips, Joanna J, Braunstein, Steve E, Raleigh, David R, Theodosopoulos, Philip, Aghi, Manish K, Chang, Edward F, Hervey-Jumper, Shawn L, Costello, Joseph F, de Groot, John, Butowski, Nicholas A, Clarke, Jennifer L, Chang, Susan M, Berger, Mitchel S, Molinaro, Annette M, and Solomon, David A
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Biomedical and Clinical Sciences ,Clinical Sciences ,Oncology and Carcinogenesis ,Brain Cancer ,Cancer ,Precision Medicine ,Brain Disorders ,Genetics ,Human Genome ,Clinical Research ,Cancer Genomics ,Neurosciences ,Immunotherapy ,Orphan Drug ,Rare Diseases ,2.1 Biological and endogenous factors ,Good Health and Well Being ,Adult ,Humans ,Child ,Middle Aged ,Aged ,Glioblastoma ,Immune Checkpoint Inhibitors ,Homozygote ,Prospective Studies ,Brain Neoplasms ,Sequence Deletion ,Mutation ,Isocitrate Dehydrogenase ,Giant cell glioblastoma ,Hypermutation ,Ultrahypermutation ,Mismatch repair deficiency ,POLE ,Lynch syndrome ,Immune checkpoint blockade ,Molecular neuropathology ,Molecular neuro-oncology ,Neurology & Neurosurgery - Abstract
Glioblastoma is a clinically and molecularly heterogeneous disease, and new predictive biomarkers are needed to identify those patients most likely to respond to specific treatments. Through prospective genomic profiling of 459 consecutive primary treatment-naïve IDH-wildtype glioblastomas in adults, we identified a unique subgroup (2%, 9/459) defined by somatic hypermutation and DNA replication repair deficiency due to biallelic inactivation of a canonical mismatch repair gene. The deleterious mutations in mismatch repair genes were often present in the germline in the heterozygous state with somatic inactivation of the remaining allele, consistent with glioblastomas arising due to underlying Lynch syndrome. A subset of tumors had accompanying proofreading domain mutations in the DNA polymerase POLE and resultant "ultrahypermutation". The median age at diagnosis was 50 years (range 27-78), compared with 63 years for the other 450 patients with conventional glioblastoma (p
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- 2024
17. WISDOM Project -- XIX. Figures of merit for supermassive black hole mass measurements using molecular gas and/or megamaser kinematics
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Zhang, Hengyue, Bureau, Martin, Smith, Mark D., Cappellari, Michele, Davis, Timothy A., Dominiak, Pandora, Elford, Jacob S., Liang, Fu-Heng, Ruffa, Ilaria, and Williams, Thomas G.
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Astrophysics - Astrophysics of Galaxies - Abstract
The mass ($M_\mathrm{BH}$) of a supermassive black hole (SMBH) can be measured using spatially-resolved kinematics of the region where the SMBH dominates gravitationally. The most reliable measurements are those that resolve the smallest physical scales around the SMBHs. We consider here three metrics to compare the physical scales probed by kinematic tracers dominated by rotation: the radius of the innermost detected kinematic tracer $R_\mathrm{min}$ normalised by respectively the SMBH's Schwarzschild radius ($R_\mathrm{Schw}\equiv 2GM_\mathrm{BH}/c^2$, where $G$ is the gravitational constant and $c$ the speed of light), sphere-of-influence (SOI) radius ($R_\mathrm{SOI}\equiv GM_\mathrm{BH}/\sigma_\mathrm{e}^2$, where $\sigma_\mathrm{e}$ is the stellar velocity dispersion within the galaxy's effective radius) and equality radius [the radius $R_\mathrm{eq}$ at which the SMBH mass equals the enclosed stellar mass, $M_\mathrm{BH}=M_*(R_\mathrm{eq})$, where $M_*(R)$ is the stellar mass enclosed within the radius $R$]. All metrics lead to analogous simple relations between $R_\mathrm{min}$ and the highest circular velocity probed $V_\mathrm{c}$. Adopting these metrics to compare the SMBH mass measurements using molecular gas kinematics to those using megamaser kinematics, we demonstrate that the best molecular gas measurements resolve material that is physically closer to the SMBHs in terms of $R_\mathrm{Schw}$ but is slightly farther in terms of $R_\mathrm{SOI}$ and $R_\mathrm{eq}$. However, molecular gas observations of nearby galaxies using the most extended configurations of the Atacama Large Millimeter/sub-millimeter Array can resolve the SOI comparably well and thus enable SMBH mass measurements as precise as the best megamaser measurements., Comment: 13 pages, 9 figures. Accepted by MNRAS
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- 2024
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18. A Physics Preserving Neural Network Based Approach for Constitutive Modeling of Isotropic Fibrous Materials
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Parvez, Nishan and Merson, Jacob S.
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Physics - Biological Physics ,Condensed Matter - Soft Condensed Matter ,Computer Science - Computational Engineering, Finance, and Science - Abstract
We develop a new neural network architecture that strictly enforces constitutive constraints such as polyconvexity, frame-indifference, and the symmetry of the stress and material stiffness. Additionally, we show that the accuracy of the stress and material stiffness predictions is significantly improved for this neural network by using a Sobolev minimization strategy that includes derivative terms. Using our neural network, we model the constitutive behavior of fibrous-type discrete network material. With Sobolev minimization, we obtain a normalized mean square error of 0.15% for the strain energy density, 0.815% averaged across the components of the stress, and 5.4% averaged across the components of the stiffness tensor. This machine-learned constitutive model was deployed in a finite element simulation of a facet capsular ligament. The displacement fields and stress-strain curves were compared to a multiscale simulation that required running on a GPU-based supercomputer. The new approach maintained upward of 85% accuracy in stress up to 70% strain while reducing the computation cost by orders of magnitude., Comment: Data and code can be found at https://zenodo.org/doi/10.5281/zenodo.11205879 and https://github.com/LACES-LAB/ML-biotissues
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- 2024
19. General Multipoles and Their Implications for Dark Matter Inference
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Cohen, Jacob S., Fassnacht, Christopher D., O'Riordan, Conor M., and Vegetti, Simona
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Astrophysics - Cosmology and Nongalactic Astrophysics - Abstract
The flux ratios of strongly lensed quasars have previously been used to infer the properties of dark matter. In these analyses it is crucial to separate the effect of the main lensing galaxy and the low-mass dark matter halo population. In this work, we investigate flux-ratio perturbations resulting from general third- and fourth-order multipole perturbations to the main lensing galaxy's mass profile. We simulate four lens systems, each with a different lensing configuration, without multipoles. The simulated flux ratios are perturbed by 10-40 per cent by a population of low-mass haloes consistent with CDM and, in one case, also a satellite galaxy. This level of perturbation is comparable to the magnitude of flux-ratio anomalies in real data that has been previously analyzed. We then attempt to fit the simulated systems using multipoles instead of low-mass haloes. We find that multipoles with amplitudes of 0.01 or less can produce flux-ratio perturbations in excess of 40 per cent. In all cases, third- or fourth-order multipoles can individually reduce the magnitude of, if not eliminate, flux-ratio anomalies. When both multipole orders are jointly included, all simulated flux ratios can be fit to within the observational uncertainty. Our results indicate that low-mass haloes and multipoles are highly degenerate when modelling quadruply-imaged quasars based just on image positions and flux ratios. In the presence of this degeneracy, flux-ratio anomalies in lensed quasars alone cannot be used to place strong constraints on the properties of dark matter without additional information that can inform our priors., Comment: 13 pages, 9 figures, to be submitted to MNRAS; figures 2-7 updated for clarity
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- 2024
20. The impact of intraoperative mapping during re-resection in recurrent gliomas: a systematic review
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van Opijnen, Mark P., Sadigh, Yasmin, Dijkstra, Miles E., Young, Jacob S., Krieg, Sandro M., Ille, Sebastian, Sanai, Nader, Rincon-Torroella, Jordina, Maruyama, Takashi, Schucht, Philippe, Smith, Timothy R., Nahed, Brian V., Broekman, Marike L. D., De Vleeschouwer, Steven, Berger, Mitchel S., Vincent, Arnaud J. P. E., and Gerritsen, Jasper K. W.
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- 2024
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21. Antinociceptive and anti-inflammatory activities of Ayapana triplinervis essential oil rich in thymohydroquinone dimethyl ether from Brazil
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de Sousa P. Barros, Luana, de Jesus, Ellen Nayara Silva, da L. Froz, Maria Juliana, Silva, Renata Cunha, da Silva, Pedro Iuri C., de Lima, Anderson B., Freitas, Jofre Jacob S., Mourão, Rosa Helena V., Setzer, William N., da Silva, Joyce Kelly R., Negrão, José Nazareno C., and Figueiredo, Pablo Luis B.
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- 2024
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22. Extremal Polynomials and Sets of Minimal Capacity
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Christiansen, Jacob S., Eichinger, Benjamin, and Rubin, Olof
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- 2024
- Full Text
- View/download PDF
23. HTS based 400 mm level sensor for liquid nitrogen
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Gour, Abhay S., Sagar, Pankaj, Sudharshan, H., Karunanithi, R., and Jacob, S.
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- 2018
- Full Text
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24. An assessment of quantum phase estimation protocols for early fault-tolerant quantum computers
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Nelson, Jacob S. and Baczewski, Andrew D.
- Subjects
Quantum Physics - Abstract
We compare several quantum phase estimation (QPE) protocols intended for early fault-tolerant quantum computers (EFTQCs) in the context of models of their implementations on a surface code architecture. We estimate the logical and physical resources required to use these protocols to calculate the ground state energy of molecular hydrogen in a minimal basis with error below $10^{-3}$ atomic units in the presence of depolarizing logical errors. Accounting for the overhead of rotation synthesis and magic state distillation, we find that the total $T$-gate counts do not vary significantly among the EFT QPE protocols at fixed state overlap. In addition to reducing the number of ancilla qubits and circuit depth, the noise robustness of the EFT protocols can be leveraged to reduce resource requirements below those of textbook QPE, realizing approximately a 300-fold reduction in computational volume in some cases. Even so, our estimates are well beyond the scale of existing early fault-tolerance demonstrations., Comment: 14 pages, 15 figures
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- 2024
25. The Early Universe as an Open Quantum System: Complexity and Decoherence
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Bhattacharyya, Arpan, Brahma, Suddhasattwa, Haque, S. Shajidul, Lund, Jacob S., and Paul, Arpon
- Subjects
High Energy Physics - Theory ,General Relativity and Quantum Cosmology ,Quantum Physics - Abstract
In this work, we extend previous results, demonstrating how complexity in an open quantum system can identify decoherence between two fields, even in the presence of an accelerating background. Using the curved-space Caldeira-Leggett two-field model in de Sitter as our toy model, we discover a distinctive feature in the growth of complexity of purification, providing an alternative diagnostic for studying decoherence when the adiabatic perturbation is coupled to a heavy field. This paper initiates a new pathway to explore the features of quantum complexity in an accelerating background, thereby expanding our understanding of the evolution of primordial cosmological perturbations in the early universe., Comment: 24 pages, 8 figures
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- 2024
- Full Text
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26. Development of the Squaramide Scaffold for High Potential and Multielectron Catholytes for Use in Redox Flow Batteries
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Tracy, Jacob S, Broderick, Conor H, and Toste, F Dean
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Engineering ,Materials Engineering ,Chemical Sciences ,Physical Chemistry ,Affordable and Clean Energy ,General Chemistry ,Chemical sciences - Abstract
Nonaqueous organic redox flow batteries (N-ORFBs) are a promising technology for grid-scale storage of energy generated from intermittent renewable sources. Their primary benefit over traditional aqueous RFBs is the wide electrochemical stability window of organic solvents, but the design of catholyte materials, which can exploit the upper range of this window, has proven challenging. We report herein a new class of N-ORFB catholytes in the form of squaric acid quinoxaline (SQX) and squaric acid amide (SQA) materials. Mechanistic investigation of decomposition in battery-relevant conditions via NMR, HRMS, and electrochemical methods enabled a rational design approach to optimizing these scaffolds. Three lead compounds were developed: a highly stable one-electron SQX material with an oxidation potential of 0.51 V vs Fc/Fc+ that maintained 99% of peak capacity after 102 cycles (51 h) when incorporated into a 1.58 V flow battery; a high-potential one-electron SQA material with an oxidation potential of 0.81 V vs Fc/Fc+ that demonstrated negligible loss of redox active material as measured by pre- and postcycling CV peak currents when incorporated in a 1.63 V flow battery for 110 cycles over 29 h; and a proof-of-concept two-electron SQA catholyte material with oxidation potentials of 0.48 and 0.85 V vs Fc/Fc+ that demonstrated a capacity fade of just 0.56% per hour during static H-cell cycling. These findings expand the previously reported space of high-potential catholyte materials and showcase the power of mechanistically informed synthetic design for N-ORFB materials development.
- Published
- 2024
27. Overcoming aggregation with laser heated nanoelectrospray mass spectrometry: thermal stability and pathways for loss of bicarbonate from carbonic anhydrase II
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Jordan, Jacob S, Lee, Katherine J, and Williams, Evan R
- Subjects
Analytical Chemistry ,Chemical Sciences ,Physical Chemistry ,Biotechnology ,Other Chemical Sciences ,Analytical chemistry - Abstract
Variable temperature electrospray mass spectrometry is useful for multiplexed measurements of the thermal stabilities of biomolecules, but the ionization process can be disrupted by aggregation-prone proteins/complexes that have irreversible unfolding transitions. Resistively heating solutions containing a mixture of bovine carbonic anhydrase II (BCAII), a CO2 fixing enzyme involved in many biochemical pathways, and cytochrome c leads to complete loss of carbonic anhydrase signal and a significant reduction in cytochrome c signal above ∼72 °C due to aggregation. In contrast, when the tips of borosilicate glass nanoelectrospray emitters are heated with a laser, complete thermal denaturation curves for both proteins are obtained in
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- 2024
28. Extremal polynomials and polynomial preimages
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Christiansen, Jacob S., Eichinger, Benjamin, and Rubin, Olof
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Mathematics - Classical Analysis and ODEs ,Mathematics - Complex Variables ,41A50, 30C10, 26D05 - Abstract
This article examines the asymptotic behavior of the Widom factors, denoted $\mathcal{W}_n$, for Chebyshev polynomials of finite unions of Jordan arcs. We prove that, in contrast to Widom's proposal, when dealing with a single smooth Jordan arc, $\mathcal{W}_n$ converges to 2 exclusively when the arc is a straight line segment. Our main focus is on analysing polynomial preimages of the interval $[-2,2]$, and we provide a complete description of the asymptotic behavior of $\mathcal{W}_n$ for symmetric star graphs and quadratic preimages of $[-2,2]$. We observe that in the case of star graphs, the Chebyshev polynomials and the polynomials orthogonal with respect to equilibrium measure share the same norm asymptotics, suggesting a potential extension of a conjecture posed by Christiansen, Simon and Zinchenko. Lastly, we propose a possible connection between the $S$-property and Widom factors converging to $2$.
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- 2023
29. Design and development of experimental setup to measure the RRR values of a thin film coated superconducting sample
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Sagar, Pankaj, Krishna, Vignesh, Gour, Abhay S., Gowthaman, M, Sudharshan, H, Srinivasan, S. Sai Guru, Karunanithi, R., and Jacob, S.
- Published
- 2017
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30. Unwinding of a eukaryotic origin of replication visualized by cryo-EM
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Henrikus, Sarah S., Gross, Marta H., Willhoft, Oliver, Pühringer, Thomas, Lewis, Jacob S., McClure, Allison W., Greiwe, Julia F., Palm, Giacomo, Nans, Andrea, Diffley, John F. X., and Costa, Alessandro
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- 2024
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31. Psychedelic-assisted psychotherapy: where is the psychotherapy research?
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Aday, Jacob S., Horton, David, Fernandes-Osterhold, Gisele, O’Donovan, Aoife, Bradley, Ellen R., Rosen, Raymond C., and Woolley, Joshua D.
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- 2024
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32. Rapid automatized naming: what it is, what it is not, and why it matters
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Gray, Jacob S. and Powell-Smith, Kelly A.
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- 2024
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33. Stereoretentive enantioconvergent reactions
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Bennett, Steven H., Bestwick, Jacob S., Demertzidou, Vera P., Jones, David J., Jones, Helen E., Richard, François, Homer, Joshua A., Street-Jeakings, Rosie, Tiberia, Andrew F., and Lawrence, Andrew L.
- Published
- 2024
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34. Violent Riots and South African Satisfaction with Democracy
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Lewis, Jacob S.
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- 2024
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35. A new open-source framework for multiscale modeling of fibrous materials on heterogeneous supercomputers
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Merson, Jacob S., Picu, Catalin R., and Shephard, Mark S.
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- 2024
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36. WISDOM Project -- XVI. The link between circumnuclear molecular gas reservoirs and active galactic nucleus fuelling
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Elford, Jacob S., Davis, Timothy A., Ruffa, Ilaria, Bureau, Martin, Cappellari, Michele, Gensior, Jindra, Iguchi, Satoru, Liang, Fu-Heng, Liu, Lijie, Lu, Anan, and Williams, Thomas G.
- Subjects
Astrophysics - Astrophysics of Galaxies - Abstract
We use high-resolution data from the millimetre-Wave Interferometric Survey of Dark Object Masses (WISDOM) project to investigate the connection between circumnuclear gas reservoirs and nuclear activity in a sample of nearby galaxies. Our sample spans a wide range of nuclear activity types including radio galaxies, Seyfert galaxies, low-luminosity active galactic nuclei (AGN) and inactive galaxies. We use measurements of nuclear millimetre continuum emission along with other archival tracers of AGN accretion/activity to investigate previous claims that at, circumnuclear scales (<100 pc), these should correlate with the mass of the cold molecular gas. We find that the molecular gas mass does not correlate with any tracer of nuclear activity. This suggests the level of nuclear activity cannot solely be regulated by the amount of cold gas around the supermassive black hole (SMBH). This indicates that AGN fuelling, that drives gas from the large scale galaxy to the nuclear regions, is not a ubiquitous process and may vary between AGN type, with timescale variations likely to be very important. By studying the structure of the central molecular gas reservoirs, we find our galaxies have a range of nuclear molecular gas concentrations. This could indicate that some of our galaxies may have had their circumnuclear regions impacted by AGN feedback, even though they currently have low nuclear activity. On the other hand, the nuclear molecular gas concentrations in our galaxies could instead be set by secular processes., Comment: 15 pages plus 3 in the appendix, 8 figures plus 1 in the appendix, 3 tables plus 4 in the appendix
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- 2023
37. WISDOM project -- XVIII. Molecular gas distributions and kinematics of three megamaser galaxies
- Author
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Liang, Fu-Heng, Smith, Mark D., Bureau, Martin, Gao, Feng, Davis, Timothy A., Cappellari, Michele, Elford, Jacob S., Greene, Jenny E., Iguchi, Satoru, Lelli, Federico, Lu, Anan, Ruffa, Ilaria, Williams, Thomas G., and Zhang, Hengyue
- Subjects
Astrophysics - Astrophysics of Galaxies - Abstract
The co-evolution of galaxies and supermassive black holes (SMBHs) underpins our understanding of galaxy evolution, but different methods to measure SMBH masses have only infrequently been cross-checked. We attempt to identify targets to cross-check two of the most accurate methods, megamaser and cold molecular gas dynamics. Three promising galaxies are selected from all those with existing megamaser SMBH mass measurements. We present Atacama Large Millimeter/sub-millimeter Array (ALMA) 12CO(2-1) and 230-GHz continuum observations with angular resolutions of about 0.5". Every galaxy has an extended rotating molecular gas disc and 230-GHz continuum source(s), but all also have irregularities and/or non-axisymmetric features: NGC1194 is highly inclined and has disturbed and lopsided central 12CO(2-1) emission; NGC3393 has a nuclear disc with fairly regular but patchy 12CO(2-1) emission with little gas near the kinematic major axis, faint emission in the very centre and two brighter structures reminiscent of a nuclear ring and/or spiral; NGC5765B has a strong bar and very bright 12CO(2-1) emission concentrated along two bisymmetric offset dust lanes and two bisymmetric nuclear spiral arms. 12CO(2-1) and 12CO(3-2) observations with the James Clerk Maxwell Telescope are compared with the ALMA observations. Because of the disturbed gas kinematics and the impractically long integration times required for higher angular resolution observations, none of the three galaxies is suitable for a future SMBH mass measurement. Nonetheless, increasing the number of molecular gas observations of megamaser galaxies is valuable, and the ubiquitous disturbances suggest a link between large-scale gas properties and the existence of megamasers., Comment: 17 pages, 5 figures, accepted by MNRAS
- Published
- 2023
38. Effect of Engineered Cracks in Catalyst Layers on PEMFC Catalyst Layer Durability
- Author
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Lee, ChungHyuk, Babu, Siddharth Komini, Patterson, Brian M, Reeves, Kimberly S, Yu, Haoran, Cullen, David A, Mukundan, Rangachary, Borup, Rod L, and Spendelow, Jacob S
- Subjects
Engineering ,Materials Engineering ,Affordable and Clean Energy ,fuel cells - PEM ,electrode ,catalyst layer ,durability ,cracks ,carbon corrosion ,Macromolecular and Materials Chemistry ,Physical Chemistry (incl. Structural) ,Energy ,Physical chemistry ,Materials engineering - Abstract
Proton exchange membrane fuel cells (PEMFCs) are expected to play a pivotal role in decarbonizing the transportation sector, and particularly heavy-duty vehicles (HDVs). However, improvements in durability are needed for PEMFCs to compete with state-of-the-art power sources for HDVs. Here, we examine how catalyst layer (CL) cracks that are engineered affect the CL durability by using patterned silicon templates to control the CL crack density at the micrometer scale. Electrochemical analyses show that the initial PEMFC performance is relatively unaffected by crack density, but the performance after durability testing was strongly affected. Specifically, CLs with high crack density showed higher performance relative to CLs without cracks after application of a carbon corrosion accelerated stress test. Electrochemical analyses coupled with X-ray computed tomography and scanning transmission electron microscopy with energy dispersive X-ray spectroscopy showed that the cracks provide shorter oxygen diffusion pathways to reaction sites, leading to decreased oxygen transport resistance. Additionally, we observed that the catalyst durability is unaffected by cracks. Our results provide a mechanistic explanation of the role of cracks in CL durability.
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- 2024
39. Effect of different solvents on ZnO thin films for gas sensing application by nebulizer spray pyrolysis method
- Author
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Sebastian, S., Raj, CSA, Jacob, S. Santhosh Kumar, Diana, P., and Ganesh, V.
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- 2024
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40. (Invited) Fuel Cell Component Durability for Million Mile Fuel Cell Trucks
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Borup, Rod L, Weber, Adam Z, Myers, Deborah J, Neyerlin, KC, Kusoglu, Ahmet, Ahluwalia, Rajesh, Mukundan, Rangachary, Cullen, David A, Spendelow, Jacob S, and Kleen, Gregory
- Subjects
Transportation ,Logistics and Supply Chains ,Engineering ,Civil Engineering ,Commerce ,Management ,Tourism and Services ,Affordable and Clean Energy - Abstract
While significant advances have been made and early commercial fuel cell light-duty vehicles (LDVs) are starting to be produced, fuel cells in the heavy-duty-vehicle (HDV) transportation sector (including trucks, long-haul semitrailers, maritime, trains, etc.) are nascent, despite the fact that advantages of fuel cells compared to both diesel and electric powertrains are very compelling in terms of emissions, charging time, efficiency, power-to-weight ratio, among others. However, the fuel-cell technology for HDVs requires a paradigm shift in fuel-cell research and development compared to LDVs, where the emphasis becomes efficiency and improvements in durability instead of a focus on increased power densities and lower cell costs. Heavy-duty applications require significantly longer vehicle lifetimes (>25,000 hours/1,000,000 miles for heavy-duty trucks), and therefore require improved fuel cell durability compared to light-duty vehicles. In 2020, HFTO formed the Million Mile Fuel Cell Truck Consortium (M2FCT) that includes a core team of five national laboratories to overcome durability and efficiency challenges in PEMFCs for heavy-duty applications with an initial focus on long-haul trucks. While targets and testing protocols have been developed for light-duty vehicles, the same level of targets and testing protocols have not been established for heavy-duty transportation. With operational times of greater than > 25,000 hours required, the need for well-developed accelerated stress tests (ASTs) is amplified. Results from these ASTs demonstrate the need for more durable electrode layers and well-controlled potential variations. This presentation will provide an overview of the DOE’s Fuel Cell R&D approach, highlighting past and current activities, as well as strategies to enable fuel cell competiveness for heavy-duty applications. Acknowledgments This work was funded through the DOE M2FCT Consortium with thanks to DOE EERE HFTO, Fuel Cell Technologies Office. Team Leader: Dimitrios Papageoropoulos and Technical Development Manager: Greg Kleen.
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- 2023
41. Targeted gene expression profiling predicts meningioma outcomes and radiotherapy responses
- Author
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Chen, William C, Choudhury, Abrar, Youngblood, Mark W, Polley, Mei-Yin C, Lucas, Calixto-Hope G, Mirchia, Kanish, Maas, Sybren LN, Suwala, Abigail K, Won, Minhee, Bayley, James C, Harmanci, Akdes S, Harmanci, Arif O, Klisch, Tiemo J, Nguyen, Minh P, Vasudevan, Harish N, McCortney, Kathleen, Yu, Theresa J, Bhave, Varun, Lam, Tai-Chung, Pu, Jenny Kan-Suen, Li, Lai-Fung, Leung, Gilberto Ka-Kit, Chan, Jason W, Perlow, Haley K, Palmer, Joshua D, Haberler, Christine, Berghoff, Anna S, Preusser, Matthias, Nicolaides, Theodore P, Mawrin, Christian, Agnihotri, Sameer, Resnick, Adam, Rood, Brian R, Chew, Jessica, Young, Jacob S, Boreta, Lauren, Braunstein, Steve E, Schulte, Jessica, Butowski, Nicholas, Santagata, Sandro, Spetzler, David, Bush, Nancy Ann Oberheim, Villanueva-Meyer, Javier E, Chandler, James P, Solomon, David A, Rogers, C Leland, Pugh, Stephanie L, Mehta, Minesh P, Sneed, Penny K, Berger, Mitchel S, Horbinski, Craig M, McDermott, Michael W, Perry, Arie, Bi, Wenya Linda, Patel, Akash J, Sahm, Felix, Magill, Stephen T, and Raleigh, David R
- Subjects
Biomedical and Clinical Sciences ,Clinical Sciences ,Oncology and Carcinogenesis ,Cancer ,Clinical Research ,Brain Disorders ,Brain Cancer ,Rare Diseases ,4.2 Evaluation of markers and technologies ,Detection ,screening and diagnosis ,Humans ,Biomarkers ,Gene Expression Profiling ,Meningeal Neoplasms ,Meningioma ,Neoplasm Recurrence ,Local ,Prospective Studies ,Medical and Health Sciences ,Immunology ,Biomedical and clinical sciences ,Health sciences - Abstract
Surgery is the mainstay of treatment for meningioma, the most common primary intracranial tumor, but improvements in meningioma risk stratification are needed and indications for postoperative radiotherapy are controversial. Here we develop a targeted gene expression biomarker that predicts meningioma outcomes and radiotherapy responses. Using a discovery cohort of 173 meningiomas, we developed a 34-gene expression risk score and performed clinical and analytical validation of this biomarker on independent meningiomas from 12 institutions across 3 continents (N = 1,856), including 103 meningiomas from a prospective clinical trial. The gene expression biomarker improved discrimination of outcomes compared with all other systems tested (N = 9) in the clinical validation cohort for local recurrence (5-year area under the curve (AUC) 0.81) and overall survival (5-year AUC 0.80). The increase in AUC compared with the standard of care, World Health Organization 2021 grade, was 0.11 for local recurrence (95% confidence interval 0.07 to 0.17, P
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- 2023
42. Assessing the predictive role of platelet-lymphocyte ratio in EGFR-mutated non-small cell lung cancer patients treated with tyrosine kinase inhibitors: an analysis across TKI generations
- Author
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Ryan Cooper, Dhruv Ramaswami, Jacob S. Thomas, Jorge J. Nieva, and Robert Hsu
- Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Introduction The predictive utility of laboratory markers in patients with non-small cell lung cancer (NSCLC) harboring EGFR mutations treated with tyrosine kinase inhibitors (TKIs) is an ongoing area of research. The predictability of the platelet-lymphocyte ratio (PLR) on survival outcomes depending on the generation of EGFR TKI is undetermined. Methods 151 patients treated with EGFR TKIs in Los Angeles were grouped according to generation of TKI. Differences in progression free survival (PFS) by stratification by PLR was determined using Kaplan–Meier analysis. Differences in median change in laboratory markers by generation of TKI was analyzed using Mann–Whitney tests. Cox Hazard Regression was used to perform multivariate analysis. Results Median PFS of those managed with 1st or 2nd generation TKIs was significantly lower in patients with a PLR ≥ 180 (10.5 months) compared to those with PLR
- Published
- 2024
- Full Text
- View/download PDF
43. WISDOM Project -- XVII. Beam-by-beam Properties of the Molecular Gas in Early-type Galaxies
- Author
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Williams, Thomas G., Bureau, Martin, Davis, Timothy A., Cappellari, Michele, Choi, Woorak, Elford, Jacob S., Iguchi, Satoru, Gensior, Jindra, Liang, Fu-Heng, Lu, Anan, Ruffa, Ilaria, and Zhang, Hengyue
- Subjects
Astrophysics - Astrophysics of Galaxies - Abstract
We present a study of the molecular gas of seven early-type galaxies with high angular resolution data obtained as part of the mm-Wave Interferometric Survey of Dark Object Masses (WISDOM) project with the Atacama Large Millimeter/submillimeter Array. Using a fixed spatial scale approach, we study the mass surface density ($\Sigma$) and velocity dispersion ($\sigma$) of the molecular gas on spatial scales ranging from $60$ to $120$pc. Given the spatial resolution of our data ($20$ - $70$pc), we characterise these properties across many thousands of individual sight lines ($\approx50,000$ at our highest physical resolution). The molecular gas along these sight lines has a large range ($\approx2$dex) of mass surface densities and velocity dispersions $\approx40\%$ higher than those of star-forming spiral galaxies. It has virial parameters $\alpha_\mathrm{vir}$ that depend weakly on the physical scale observed, likely due to beam smearing of the bulk galactic rotation, and is generally super-virial. Comparing the internal turbulent pressure ($P_\mathrm{turb}$) to the pressure required for dynamic equilibrium ($P_\mathrm{DE}$), the ratio $P_\mathrm{turb}$/$P_\mathrm{DE}$ is significantly less than unity in all galaxies, indicating that the gas is not in dynamic equilibrium and is strongly compressed, in apparent contradiction to the virial parameters. This may be due to our neglect of shear and tidal forces, and/or the combination of three-dimensional and vertical diagnostics. Both $\alpha_\mathrm{vir}$ and $P_\mathrm{turb}$ anti-correlate with the global star-formation rate of our galaxies. We therefore conclude that the molecular gas in early-type galaxies is likely unbound, and that large-scale dynamics likely plays a critical role in its regulation. This contrasts to the giant molecular clouds in the discs of late-type galaxies, that are much closer to dynamical equilibrium., Comment: 32 pages (16 of Appendices), 39 Figures (27 in Appendices). Accepted for publication in MNRAS
- Published
- 2023
44. A geometric approach to approximating the limit set of eigenvalues for banded Toeplitz matrices
- Author
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Bucht, Teodor and Christiansen, Jacob S.
- Subjects
Mathematics - Numerical Analysis ,Mathematics - Spectral Theory ,15B05, 47B06, 47B35, 65F15 - Abstract
This article is about finding the limit set for banded Toeplitz matrices. Our main result is a new approach to approximate the limit set $\Lambda(b)$ where $b$ is the symbol of the banded Toeplitz matrix. The new approach is geometrical and based on the formula $\Lambda(b) = \cap_{\rho \in (0, \infty)} \text{sp } T(b_\rho)$, where $\rho$ is a scaling factor, i.e. $b_\rho(t) := b(\rho t)$, and $\text{sp }(\cdot)$ denotes the spectrum. We show that the full intersection can be approximated by the intersection for a finite number of $\rho$'s, and that the intersection of polygon approximations for $\text{sp } T(b_\rho)$ yields an approximating polygon for $\Lambda(b)$ that converges to $\Lambda(b)$ in the Hausdorff metric. Further, we show that one can slightly expand the polygon approximations for $\text{sp } T(b_\rho)$ to ensure that they contain $\text{sp } T(b_\rho)$. Then, taking the intersection yields an approximating superset of $\Lambda(b)$ which converges to $\Lambda(b)$ in the Hausdorff metric, and is guaranteed to contain $\Lambda(b)$. Combining the established algebraic (root-finding) method with our approximating superset, we are able to give an explicit bound on the Hausdorff distance to the true limit set. We implement the algorithm in Python and test it. It performs on par to and better in some cases than existing algorithms. We argue, but do not prove, that the average time complexity of the algorithm is $O(n^2 + mn\log m)$, where $n$ is the number of $\rho$'s and $m$ is the number of vertices for the polygons approximating $\text{sp } T(b_\rho)$. Further, we argue that the distance from $\Lambda(b)$ to both the approximating polygon and the approximating superset decreases as $O(1/\sqrt{k})$ for most of $\Lambda(b)$, where $k$ is the number of elementary operations required by the algorithm., Comment: 25 pages, 9 figures. Revised version, Algorithm 2 and Example 4.1 added, final version
- Published
- 2023
- Full Text
- View/download PDF
45. A fundamental plane of black hole accretion at millimetre wavelengths
- Author
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Ruffa, Ilaria, Davis, Timothy A., Elford, Jacob S., Bureau, Martin, Cappellari, Michele, Gensior, Jindra, Haggard, Daryl, Iguchi, Satoru, Lelli, Federico, Liang, Fu-Heng, Liu, Lijie, Sarzi, Marc, Williams, Thomas G., and Zhang, Hengyue
- Subjects
Astrophysics - Astrophysics of Galaxies - Abstract
We report the discovery of the ``mm fundamental plane of black-hole accretion'', which is a tight correlation between the nuclear 1 mm luminosity ($L_{\rm \nu, mm}$), the intrinsic $2$ -- $10$~keV X-ray luminosity ($L_{\rm X,2-10}$) and the supermassive black hole (SMBH) mass ($M_{\rm BH}$) with an intrinsic scatter ($\sigma_{\rm int}$) of $0.40$ dex. The plane is found for a sample of 48 nearby galaxies, most of which are low-luminosity active galactic nuclei (LLAGN). Combining these sources with a sample of high-luminosity (quasar-like) nearby AGN, we find that the plane still holds. We also find that $M_{\rm BH}$ correlates with $L_{\rm \nu, mm}$ at a highly significant level, although such correlation is less tight than the mm fundamental plane ($\sigma_{\rm int}=0.51$ dex). Crucially, we show that spectral energy distribution (SED) models for both advection-dominated accretion flows (ADAFs) and compact jets can explain the existence of these relations, which are not reproduced by the standard torus-thin accretion disc models usually associated to quasar-like AGN. The ADAF models reproduces the observed relations somewhat better than those for compact jets, although neither provides a perfect prediction. Our findings thus suggest that radiatively-inefficient accretion processes such as those in ADAFs or compact (and thus possibly young) jets may play a key role in both low- and high-luminosity AGN. This mm fundamental plane also offers a new, rapid method to (indirectly) estimate SMBH masses., Comment: 9 pages, 5 figures
- Published
- 2023
46. Enhanced weathering in the U.S. Corn Belt delivers carbon removal with agronomic benefits
- Author
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Beerling, David J., Epihov, Dimitar Z., Kantola, Ilsa B., Masters, Michael D., Reershemius, Tom, Planavsky, Noah J., Reinhard, Christopher T., Jordan, Jacob S., Thorne, Sarah J., Weber, James, Martin, Maria Val, Freckleton, Robert P., Hartley, Sue E., James, Rachael H., Pearce, Christopher R., DeLucia, Evan H., and Banwart, Steven A.
- Subjects
Physics - Physics and Society - Abstract
Enhanced weathering (EW) with crushed basalt on farmlands is a promising scalable atmospheric carbon dioxide removal strategy that urgently requires performance assessment with commercial farming practices. Our large-scale replicated EW field trial in the heart of the U.S. Corn Belt shows cumulative time-integrated carbon sequestration of 15.4 +/- 4.1 t CO2 ha-1 over four years, with additional emissions mitigation of ~0.1 - 0.4 t CO2,e ha-1 yr-1 for soil nitrous oxide, a potent long-lived greenhouse gas. Maize and soybean yields increased 12-16% with EW following improved soil fertility, decreased soil acidification, and upregulation of root nutrient transport genes. Our findings suggest that widespread adoption of EW across farming sectors has the potential to contribute significantly to net-zero greenhouse gas emissions goals and global food and soil security.
- Published
- 2023
47. Comment on: Assessing ChatGPT’s ability to answer questions pertaining to erectile dysfunction
- Author
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Hershenhouse, Jacob S. and Cacciamani, Giovanni E.
- Published
- 2024
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48. Author Correction: Grooved electrodes for high-power-density fuel cells
- Author
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Lee, ChungHyuk, Kort-Kamp, Wilton JM, Yu, Haoran, Cullen, David A, Patterson, Brian M, Arman, Tanvir Alam, Komini Babu, Siddharth, Mukundan, Rangachary, Borup, Rod L, and Spendelow, Jacob S
- Subjects
Engineering ,Electrical Engineering ,Mechanical Engineering ,Electrical and Electronic Engineering ,Environmental Engineering ,Electrical engineering ,Mechanical engineering - Abstract
Correction to: Nature Energy. Published online 25 May 2023. This paper was originally published under a standard Springer Nature license (© The Author(s), under exclusive licence to Springer Nature Limited). It is now available as an open-access paper under a Creative Commons Attribution 4.0 International license, © The Author(s). The error has been corrected in the online version of the article.
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- 2023
49. A framework for standardised tissue sampling and processing during resection of diffuse intracranial glioma: joint recommendations from four RANO groups
- Author
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Karschnia, Philipp, Smits, Marion, Reifenberger, Guido, Le Rhun, Emilie, Ellingson, Benjamin M, Galldiks, Norbert, Kim, Michelle M, Huse, Jason T, Schnell, Oliver, Harter, Patrick N, Mohme, Malte, Panel, Rater, Aldape, Kenneth, Baehring, Joachim M, Bello, Lorenzo, Brat, Daniel J, Cahill, Daniel P, Chung, Caroline, Colman, Howard, Dietrich, Jorg, Drummond, Katharine, Esquenazi, Yoshua, Gerstner, Elizabeth R, Furtner, Julia, Garibotto, Valentina, Kaufmann, Timothy J, Komori, Takashi, Kotecha, Rupesh, Liau, Linda M, Lupo, Janine M, Minniti, Giuseppe, Narita, Yoshitaka, Niyazi, Maximilian, Perry, Arie, Preusser, Matthias, Rudà, Roberta, Sanai, Nader, Schmidt, Nils-Ole, Steinbach, Joachim P, Thust, Stefanie C, Tolboom, Nelleke, van der Hoorn, Anouk, van der Vaart, Thijs, Verger, Antoine, Vik-Mo, Einar Osland, Watts, Colin, Westphal, Manfred, Wesseling, Pieter, Young, Jacob S, von Baumgarten, Louisa, Albert, Nathalie L, Huang, Raymond Y, Mehta, Minesh P, van den Bent, Martin, Weller, Michael, Vogelbaum, Michael A, Chang, Susan M, Berger, Mitchel S, and Tonn, Joerg-Christian
- Subjects
Biomedical and Clinical Sciences ,Clinical Sciences ,Oncology and Carcinogenesis ,Brain Cancer ,Brain Disorders ,Rare Diseases ,Neurosciences ,Cancer ,Humans ,Brain Neoplasms ,Prospective Studies ,Biological Specimen Banks ,Neoplasm Recurrence ,Local ,Glioma ,Expert Rater Panel ,Oncology & Carcinogenesis ,Oncology and carcinogenesis - Abstract
Surgical resection represents the standard of care for people with newly diagnosed diffuse gliomas, and the neuropathological and molecular profile of the resected tissue guides clinical management and forms the basis for research. The Response Assessment in Neuro-Oncology (RANO) consortium is an international, multidisciplinary effort that aims to standardise research practice in neuro-oncology. These recommendations represent a multidisciplinary consensus from the four RANO groups: RANO resect, RANO recurrent glioblastoma, RANO radiotherapy, and RANO/PET for a standardised workflow to achieve a representative tumour evaluation in a disease characterised by intratumoural heterogeneity, including recommendations on which tumour regions should be surgically sampled, how to define those regions on the basis of preoperative imaging, and the optimal sample volume. Practical recommendations for tissue sampling are given for people with low-grade and high-grade gliomas, as well as for people with newly diagnosed and recurrent disease. Sampling of liquid biopsies is also addressed. A standardised workflow for subsequent handling of the resected tissue is proposed to avoid information loss due to decreasing tissue quality or insufficient clinical information. The recommendations offer a framework for prospective biobanking studies.
- Published
- 2023
50. Coaxial Nanowire Electrodes Enable Exceptional Fuel Cell Durability
- Author
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Yang, Gaoqiang, Babu, Siddharth Komini, Liyanage, Wipula PR, Martinez, Ulises, Routkevitch, Dmitri, Mukundan, Rangachary, Borup, Rodney L, Cullen, David A, and Spendelow, Jacob S
- Subjects
Engineering ,Materials Engineering ,Chemical Sciences ,Physical Chemistry ,Bioengineering ,Nanotechnology ,Affordable and Clean Energy ,catalyst layers ,fuel cells ,ionomer nanowires ,structured electrodes ,thin-film catalysts ,Physical Sciences ,Nanoscience & Nanotechnology ,Chemical sciences ,Physical sciences - Abstract
Polymer-electrolyte-membrane fuel cells (PEMFCs) hold great promise for applications in clean energy conversion, but cost and durability continue to limit commercialization. This work presents a new class of catalyst/electrode architecture that does not rely on Pt particles or carbon supports, eliminating the primary degradation mechanisms in conventional electrodes, and thereby enabling transformative durability improvements. The coaxial nanowire electrode (CANE) architecture consists of an array of vertically aligned nanowires, each comprising an ionomer core encapsulated by a nanoscale Pt film. This unique design eliminates the triple-phase boundary and replaces it with two double-phase boundaries, increasing Pt utilization. It also eliminates the need for carbon support and ionomer binder, enabling improved durability and faster mass transport. Fuel cell membrane electrode assemblies based on CANEs demonstrate extraordinary durability in accelerated stress tests (ASTs), with only 2% and 5% loss in performance after 5000 support AST cycles and 30000 catalysts AST cycles, respectively. The high power density and extremely high durability provided by CANEs can enable a paradigm shift from random electrodes based on unstable platinum nanoparticles dispersed on carbon to ordered electrodes based on durable Pt nanofilms, facilitating rapid deployment of fuel cells in transportation and other clean energy applications.
- Published
- 2023
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