1,639 results on '"W. Cross"'
Search Results
2. Sub-THz and THz Cherenkov radiation source with two-dimensional periodic surface lattice and multistage depressed collector
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Amy J. MacLachlan, Liang Zhang, Ivan V. Konoplev, Alan D. R. Phelps, Craig W. Robertson, Philip MacInnes, Colin G. Whyte, Kevin Ronald, Adrian W. Cross, and Mark A. Henderson
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Medicine ,Science - Abstract
Abstract We present the theory, concept and design of an efficient, megawatt coherent Cherenkov radiation source based on a two-dimensional periodic surface lattice (2D-PSL) cavity combined with a novel energy recovery system for the generation of highly efficient (> 50%) single-frequency radiation. We demonstrate the scalability of the transverse dimension of the 2D-PSL cavity of the Cherenkov source and thus the potential for efficient, continuous-wave, high-power (> 1 MW) operation; fundamental to the eventual realization of clean, fusion energy. These new sources, with the capacity to operate in the 0.1-10THz range, hold strong promise to address the long-standing “Terahertz gap”. By combining a Cherenkov oscillator driven by a non-gyrating beam with an innovative four-stage depressed collector energy recovery system, the overall device efficiency can be increased to be competitive with gyrotrons in the requirements for heating and current drive in fusion plasma. In these Cherenkov devices, the frequency independence of the magnetic guide field enables advantageous frequency scaling without deployment constraints, making them especially attractive for high-impact applications in fusion science, turbulence diagnostics, non-destructive testing and biochemical spectroscopy. The novel energy recovery techniques presented in this paper have broad applicability to many electron-beam driven devices, bringing revolutionary potential to future THz source technologies.
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- 2024
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3. Monoclonal antibody therapy demonstrates increased virulence of a lineage VII strain of Lassa virus in nonhuman primates
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Courtney Woolsey, Robert W. Cross, Abhishek N. Prasad, Krystle N. Agans, Viktoriya Borisevich, Daniel J. Deer, Natalie S. Dobias, Alyssa C. Fears, Mack B. Harrison, Megan L. Heinrich, Karla A. Fenton, Robert F. Garry, Luis M. Branco, and Thomas W. Geisbert
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Lassa virus ,arenavirus ,monoclonal antibodies ,haemorrhagic fever ,nonhuman primates ,Infectious and parasitic diseases ,RC109-216 ,Microbiology ,QR1-502 - Abstract
ABSTRACTLassa virus (LASV) is a World Health Organization (WHO) priority pathogen that causes high morbidity and mortality. Recently, we showed that a combination of three broadly neutralizing human monoclonal antibodies known as Arevirumab-3 (8.9F, 12.1F, 37.2D) based on the lineage IV Josiah strain protected 100% of cynomolgus macaques against heterologous challenge with lineage II and III strains of LASV when therapy was initiated beginning at day 8 after challenge. LASV strains from Benin and Togo represent a new lineage VII that are more genetically diverse from lineage IV than strains from lineages II and III. Here, we tested the ability of Arevirumab-3 to protect macaques against a LASV lineage VII Togo isolate when treatment was administered beginning 8 days after exposure. Unexpectedly, only 40% of treated animals survived challenge. In a subsequent study we showed that Arevirumab-3 protected 100% of macaques from lethal challenge when treatment was initiated 7 days after LASV Togo exposure. Based on our transcriptomics data, successful Arevirumab-3 treatment correlated with diminished neutrophil signatures and the predicted development of T cell responses. As the in vitro antiviral activity of Arevirumab-3 against LASV Togo was equivalent to lineage II and III strains, the reduced protection in macaques against Togo likely reflects the faster disease course of LASV Togo in macaques than other strains. This data causes concern regarding the ability of heterologous vaccines and treatments to provide cross protection against lineage VII LASV isolates.
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- 2024
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4. High-threshold and low-overhead fault-tolerant quantum memory.
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Sergey Bravyi 0001, Andrew W. Cross, Jay M. Gambetta, Dmitri Maslov, Patrick Rall, and Theodore J. Yoder
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- 2024
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5. Aberrant stem cell and developmental programs in pediatric leukemia
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Rebecca E. Ling, Joe W. Cross, and Anindita Roy
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leukemia ,stem cells ,development genes ,gene regulation ,fetal oncogenes ,Biology (General) ,QH301-705.5 - Abstract
Hematopoiesis is a finely orchestrated process, whereby hematopoietic stem cells give rise to all mature blood cells. Crucially, they maintain the ability to self-renew and/or differentiate to replenish downstream progeny. This process starts at an embryonic stage and continues throughout the human lifespan. Blood cancers such as leukemia occur when normal hematopoiesis is disrupted, leading to uncontrolled proliferation and a block in differentiation of progenitors of a particular lineage (myeloid or lymphoid). Although normal stem cell programs are crucial for tissue homeostasis, these can be co-opted in many cancers, including leukemia. Myeloid or lymphoid leukemias often display stem cell-like properties that not only allow proliferation and survival of leukemic blasts but also enable them to escape treatments currently employed to treat patients. In addition, some leukemias, especially in children, have a fetal stem cell profile, which may reflect the developmental origins of the disease. Aberrant fetal stem cell programs necessary for leukemia maintenance are particularly attractive therapeutic targets. Understanding how hijacked stem cell programs lead to aberrant gene expression in place and time, and drive the biology of leukemia, will help us develop the best treatment strategies for patients.
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- 2024
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6. Quantum computing with Qiskit.
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Ali Javadi-Abhari, Matthew Treinish, Kevin Krsulich, Christopher J. Wood, Jake Lishman, Julien Gacon, Simon Martiel, Paul D. Nation, Lev S. Bishop, Andrew W. Cross, Blake R. Johnson, and Jay M. Gambetta
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- 2024
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7. Defining Best Practices for Quantum Benchmarks.
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Mirko Amico, Helena Zhang, Petar Jurcevic, Lev S. Bishop, Paul D. Nation, Andrew W. Cross, and David C. McKay
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- 2023
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8. Natural history of Sudan ebolavirus infection in rhesus and cynomolgus macaques
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Courtney Woolsey, Alyssa C. Fears, Viktoriya Borisevich, Krystle N. Agans, Natalie S. Dobias, Abhishek N. Prasad, Daniel J. Deer, Joan B. Geisbert, Karla A. Fenton, Thomas W. Geisbert, and Robert W. Cross
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Sudan ebolavirus ,Sudan virus ,filovirus ,Ebola virus ,natural history ,nonhuman primates ,Infectious and parasitic diseases ,RC109-216 ,Microbiology ,QR1-502 - Abstract
Due to its high mortality rate and continued re-emergence, Ebolavirus disease (EVD) continues to pose a serious threat to global health. A group of viruses within the genus Ebolavirus causes this severe hemorrhagic disease in humans: Ebola virus (EBOV; species Zaire ebolavirus), Sudan virus (SUDV; species Sudan ebolavirus), Bundibugyo virus, and Taï Forest virus. EBOV and SUDV are associated with the highest case fatality rates. While the host response to EBOV has been comprehensively examined, limited data exists for SUDV infection. For medical countermeasure testing, well-characterized SUDV nonhuman primate (NHP) models are thus needed. Here, we describe a natural history study in which rhesus (N = 11) and cynomolgus macaques (N = 14) were intramuscularly exposed to a 1000 plaque-forming unit dose of SUDV (Gulu variant). Time-course analyses of various hematological, pathological, serological, coagulation, and transcriptomic findings are reported. SUDV infection was uniformly lethal in cynomolgus macaques (100% mortality), whereas a single rhesus macaque subject (91% mortality) survived to the study endpoint (median time-to-death of ∼8.0 and ∼8.5 days in cynomolgus and rhesus macaques, respectively). Infected macaques exhibited hallmark features of human EVD. The early stage was typified by viremia, granulocytosis, lymphopenia, albuminemia, thrombocytopenia, and decreased expression of HLA-class transcripts. At mid-to-late disease, animals developed fever and petechial rashes, and expressed high levels of pro-inflammatory mediators, pro-thrombotic factors, and markers indicative of liver and kidney injury. End-stage disease was characterized by shock and multi-organ failure. In summary, macaques recapitulate human SUDV disease, supporting these models for use in the development of vaccines and therapeutics.
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- 2022
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9. Giallar: push-button verification for the qiskit Quantum compiler.
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Runzhou Tao, Yunong Shi, Jianan Yao, Xupeng Li, Ali Javadi-Abhari, Andrew W. Cross, Frederic T. Chong, and Ronghui Gu
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- 2022
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10. The Therapeutic Monoclonal Antibody Bamlanivimab Does Not Enhance SARS-CoV-2 Infection by FcR-Mediated Mechanisms
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Robert W. Cross, Christopher M. Wiethoff, Patricia Brown-Augsburger, Shawn Berens, Jamie Blackbourne, Ling Liu, Xiaohua Wu, Jonathan Tetreault, Carter Dodd, Ramtin Sina, Derrick R. Witcher, Deanna Newcomb, Denzil Frost, Angela Wilcox, Viktoriya Borisevich, Krystle N. Agans, Courtney Woolsey, Abhishek N. Prasad, Daniel J. Deer, Joan B. Geisbert, Natalie S. Dobias, Karla A. Fenton, Beth Strifler, Philip Ebert, Richard Higgs, Anne Beall, Sumit Chanda, Laura Riva, Xin Yin, and Thomas W. Geisbert
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bamlanivimab ,antibody-dependent enhancement ,SARS-CoV-2 ,COVID-19 ,monoclonal antibodies ,Medicine - Abstract
As part of the non-clinical safety package characterizing bamlanivimab (SARS-CoV-2 neutralizing monoclonal antibody), the risk profile for antibody-dependent enhancement of infection (ADE) was evaluated in vitro and in an African green monkey (AGM) model of COVID-19. In vitro ADE assays in primary human macrophage, Raji, or THP-1 cells were used to evaluate enhancement of viral infection. Bamlanivimab binding to C1q, FcR, and cell-based effector activity was also assessed. In AGMs, the impact of bamlanivimab pretreatment on viral loads and clinical and histological pathology was assessed to evaluate enhanced SARS-CoV-2 replication or pathology. Bamlanivimab did not increase viral replication in vitro, despite a demonstrated effector function. In vivo, no significant differences were found among the AGM groups for weight, temperature, or food intake. Treatment with bamlanivimab reduced viral loads in nasal and oral swabs and BAL fluid relative to control groups. Viral antigen was not detected in lung tissue from animals treated with the highest dose of bamlanivimab. Bamlanivimab did not induce ADE of SARS-CoV-2 infection in vitro or in an AGM model of infection at any dose evaluated. The findings suggest that high-affinity monoclonal antibodies pose a low risk of mediating ADE in patients and support their safety profile as a treatment of COVID-19 disease.
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- 2023
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11. Non-Clifford and parallelizable fault-tolerant logical gates on constant and almost-constant rate homological quantum LDPC codes via higher symmetries.
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Guanyu Zhu, Shehryar Sikander, Elia Portnoy, Andrew W. Cross, and Benjamin J. Brown
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- 2023
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12. High-threshold and low-overhead fault-tolerant quantum memory.
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Sergey Bravyi 0001, Andrew W. Cross, Jay M. Gambetta, Dmitri Maslov, Patrick Rall, and Theodore J. Yoder
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- 2023
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13. Global and Local Agendas of Computing Ethics Education.
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Janet M. Hughes, Ethan R. Plaut, Feng Wang, Elizabeth von Briesen, Cheryl Brown, Gerry W. Cross, Viraj Kumar, and Paul Myers
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- 2020
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14. Critical faults of leakage errors on the surface code.
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Natalie C. Brown, Andrew W. Cross, and Kenneth R. Brown
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- 2020
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15. Single dose rVSVΔG-JUNVGP vaccine protects guinea pigs against lethal Junin virus challenge
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Teresa E. Sorvillo, Robert W. Cross, Dylan M. Johnson, Natalie S. Dobias, Karla A. Fenton, Chad E. Mire, and Thomas W. Geisbert
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Immunologic diseases. Allergy ,RC581-607 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Junin virus (JUNV) is a pathogen of biodefense importance due to its potential for aerosol transmission and mortality rates reaching 30%. Currently, there are no JUNV vaccines licensed by the United States Food and Drug Administration (FDA) for at-risk individuals. A vaccine based on recombinant vesicular stomatitis virus (rVSV) has been effectively used to prevent Ebola virus disease in humans. Here, we evaluated the protective efficacy of a rVSV expressing the JUNV glycoprotein (rVSVΔG-JUNVGP) in a guinea pig model of lethal JUNV disease. Two groups of guinea pigs, one prime and one prime-boost, were vaccinated with rVSVΔG-JUNVGP; six control animals remained unvaccinated. Survival for prime and prime-boost vaccinated animals was 100% while the challenge virus was uniformly lethal in all control animals. Animals in both vaccine groups developed robust, high avidity IgG antibody titers post-vaccination as well as detectable neutralizing antibodies while control animals failed to develop detectable antibody responses. This study demonstrates for the first time that rVSV expressing the JUNV GP fully protects guinea pigs from lethal JUNV challenge with a single injection vaccine.
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- 2021
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16. Simulations of the Self-Focused Pseudospark-Sourced Electron Beam in a Background Ion Channel.
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Liang Zhang, Alan D. R. Phelps, Kevin Ronald, and Adrian W. Cross
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- 2021
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17. A highly attenuated Vesiculovax vaccine rapidly protects nonhuman primates against lethal Marburg virus challenge.
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Courtney Woolsey, Robert W Cross, Krystle N Agans, Viktoriya Borisevich, Daniel J Deer, Joan B Geisbert, Cheryl Gerardi, Theresa E Latham, Karla A Fenton, Michael A Egan, John H Eldridge, Thomas W Geisbert, and Demetrius Matassov
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Arctic medicine. Tropical medicine ,RC955-962 ,Public aspects of medicine ,RA1-1270 - Abstract
BackgroundMarburg virus (MARV), an Ebola-like virus, remains an eminent threat to public health as demonstrated by its high associated mortality rate (23-90%) and recent emergence in West Africa for the first time. Although a recombinant vesicular stomatitis virus (rVSV)-based vaccine (Ervebo) is licensed for Ebola virus disease (EVD), no approved countermeasures exist against MARV. Results from clinical trials indicate Ervebo prevents EVD in 97.5-100% of vaccinees 10 days onwards post-immunization.Methodology/findingsGiven the rapid immunogenicity of the Ervebo platform against EVD, we tested whether a similar, but highly attenuated, rVSV-based Vesiculovax vector expressing the glycoprotein (GP) of MARV (rVSV-N4CT1-MARV-GP) could provide swift protection against Marburg virus disease (MVD). Here, groups of cynomolgus monkeys were vaccinated 7, 5, or 3 days before exposure to a lethal dose of MARV (Angola variant). All subjects (100%) immunized one week prior to challenge survived; 80% and 20% of subjects survived when vaccinated 5- and 3-days pre-exposure, respectively. Lethality was associated with higher viral load and sustained innate immunity transcriptional signatures, whereas survival correlated with development of MARV GP-specific antibodies and early expression of predicted NK cell-, B-cell-, and cytotoxic T-cell-type quantities.Conclusions/significanceThese results emphasize the utility of Vesiculovax vaccines for MVD outbreak management. The highly attenuated nature of rVSV-N4CT1 vaccines, which are clinically safe in humans, may be preferable to vaccines based on the same platform as Ervebo (rVSV "delta G" platform), which in some trial participants induced vaccine-related adverse events in association with viral replication including arthralgia/arthritis, dermatitis, and cutaneous vasculitis.
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- 2022
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18. LY-CoV1404 (bebtelovimab) potently neutralizes SARS-CoV-2 variants
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Kathryn Westendorf, Stefanie Žentelis, Lingshu Wang, Denisa Foster, Peter Vaillancourt, Matthew Wiggin, Erica Lovett, Robin van der Lee, Jörg Hendle, Anna Pustilnik, J. Michael Sauder, Lucas Kraft, Yuri Hwang, Robert W. Siegel, Jinbiao Chen, Beverly A. Heinz, Richard E. Higgs, Nicole L. Kallewaard, Kevin Jepson, Rodrigo Goya, Maia A. Smith, David W. Collins, Davide Pellacani, Ping Xiang, Valentine de Puyraimond, Marketa Ricicova, Lindsay Devorkin, Caitlin Pritchard, Aoise O’Neill, Kush Dalal, Pankaj Panwar, Harveer Dhupar, Fabian A. Garces, Courtney A. Cohen, John M. Dye, Kathleen E. Huie, Catherine V. Badger, Darwyn Kobasa, Jonathan Audet, Joshua J. Freitas, Saleema Hassanali, Ina Hughes, Luis Munoz, Holly C. Palma, Bharathi Ramamurthy, Robert W. Cross, Thomas W. Geisbert, Vineet Menachery, Kumari Lokugamage, Viktoriya Borisevich, Iliana Lanz, Lisa Anderson, Payal Sipahimalani, Kizzmekia S. Corbett, Eun Sung Yang, Yi Zhang, Wei Shi, Tongqing Zhou, Misook Choe, John Misasi, Peter D. Kwong, Nancy J. Sullivan, Barney S. Graham, Tara L. Fernandez, Carl L. Hansen, Ester Falconer, John R. Mascola, Bryan E. Jones, and Bryan C. Barnhart
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CP: Microbiology ,Biology (General) ,QH301-705.5 - Abstract
Summary: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-neutralizing monoclonal antibodies (mAbs) can reduce the risk of hospitalization from coronavirus disease 2019 (COVID-19) when administered early. However, SARS-CoV-2 variants of concern (VOCs) have negatively affected therapeutic use of some authorized mAbs. Using a high-throughput B cell screening pipeline, we isolated LY-CoV1404 (bebtelovimab), a highly potent SARS-CoV-2 spike glycoprotein receptor binding domain (RBD)-specific antibody. LY-CoV1404 potently neutralizes authentic SARS-CoV-2, B.1.1.7, B.1.351, and B.1.617.2. In pseudovirus neutralization studies, LY-CoV1404 potently neutralizes variants, including B.1.1.7, B.1.351, B.1.617.2, B.1.427/B.1.429, P.1, B.1.526, B.1.1.529, and the BA.2 subvariant. Structural analysis reveals that the contact residues of the LY-CoV1404 epitope are highly conserved, except for N439 and N501. The binding and neutralizing activity of LY-CoV1404 is unaffected by the most common mutations at these positions (N439K and N501Y). The broad and potent neutralization activity and the relatively conserved epitope suggest that LY-CoV1404 has the potential to be an effective therapeutic agent to treat all known variants.
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- 2022
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19. Combination therapy protects macaques against advanced Marburg virus disease
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Robert W. Cross, Zachary A. Bornholdt, Abhishek N. Prasad, Viktoriya Borisevich, Krystle N. Agans, Daniel J. Deer, Dafna M. Abelson, Do H. Kim, William S. Shestowsky, Lioudmila A. Campbell, Elaine Bunyan, Joan B. Geisbert, Karla A. Fenton, Larry Zeitlin, Danielle P. Porter, and Thomas W. Geisbert
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Science - Abstract
Extending the therapeutic window for acute viral infections could save lives. Here, the authors show that combination treatment with a human monoclonal antibody and remdesivir initiated at 6 days post infection with Marburg virus provides 80% protection in non-human primates.
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- 2021
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20. A single dose investigational subunit vaccine for human use against Nipah virus and Hendra virus
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Thomas W. Geisbert, Kathryn Bobb, Viktoriya Borisevich, Joan B. Geisbert, Krystle N. Agans, Robert W. Cross, Abhishek N. Prasad, Karla A. Fenton, Hao Yu, Timothy R. Fouts, Christopher C. Broder, and Antony S. Dimitrov
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Immunologic diseases. Allergy ,RC581-607 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Nipah and Hendra viruses are highly pathogenic bat-borne paramyxoviruses recently included in the WHO Blueprint priority diseases list. A fully registered horse anti-Hendra virus subunit vaccine has been in use in Australia since 2012. Based on the same immunogen, the Hendra virus attachment glycoprotein ectodomain, a subunit vaccine formulation for use in people is now in a Phase I clinical trial. We report that a single dose vaccination regimen of this human vaccine formulation protects against otherwise lethal challenges of either Hendra or Nipah virus in a nonhuman primate model. The protection against the Nipah Bangladesh strain begins as soon as 7 days post immunization with low dose of 0.1 mg protein subunit. Our data suggest this human vaccine could be utilized as efficient emergency vaccine to disrupt potential spreading of Nipah disease in an outbreak setting.
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- 2021
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21. Quantum circuit compilers using gate commutation rules.
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Toshinari Itoko, Rudy Raymond, Takashi Imamichi, Atsushi Matsuo, and Andrew W. Cross
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- 2019
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22. Resource-Efficient Quantum Computing by Breaking Abstractions.
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Yunong Shi, Pranav Gokhale, Prakash Murali, Jonathan M. Baker, Casey Duckering, Yongshan Ding 0001, Natalie C. Brown, Christopher Chamberland, Ali Javadi-Abhari, Andrew W. Cross, David I. Schuster, Kenneth R. Brown, Margaret Martonosi, and Frederic T. Chong
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- 2020
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23. Challenges and Opportunities of Near-Term Quantum Computing Systems.
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Antonio D. Córcoles, Abhinav Kandala, Ali Javadi-Abhari, Douglas T. McClure, Andrew W. Cross, Kristan Temme, Paul D. Nation, Matthias Steffen, and Jay M. Gambetta
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- 2020
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24. Endotheliopathy and Platelet Dysfunction as Hallmarks of Fatal Lassa Fever
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Lucy E. Horton, Robert W. Cross, Jessica N. Hartnett, Emily J. Engel, Saori Sakabe, Augustine Goba, Mambu Momoh, John Demby Sandi, Thomas W. Geisbert, Robert F. Garry, John S. Schieffelin, Donald S. Grant, and Brian M. Sullivan
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Lassa fever ,hemostasis ,platelet ,protein C ,coagulation ,fibrinolysis ,Medicine ,Infectious and parasitic diseases ,RC109-216 - Abstract
Lassa fever (LF) causes multisystem disease and has a fatality rate
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- 2020
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25. Quantum Locally Testable Code with Exotic Parameters.
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Andrew W. Cross, Zhiyang He, Anand Natarajan, Mario Szegedy, and Guanyu Zhu
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- 2022
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26. Intranasal exposure of African green monkeys to SARS-CoV-2 results in acute phase pneumonia with shedding and lung injury still present in the early convalescence phase
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Robert W. Cross, Krystle N. Agans, Abhishek N. Prasad, Viktoriya Borisevich, Courtney Woolsey, Daniel J. Deer, Natalie S. Dobias, Joan B. Geisbert, Karla A. Fenton, and Thomas W. Geisbert
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Coronavirus ,SARS-CoV-2 ,COVID-19 ,Nonhuman primate ,Animal models ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract We recently reported the development of the first African green monkey (AGM) model for COVID-19 based on a combined liquid intranasal (i.n.) and intratracheal (i.t.) exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we followed up on this work by assessing an i.n. particle only route of exposure using the LMA mucosal atomization device (MAD). Six AGMs were infected with SARS-CoV-2; three animals were euthanized near the peak stage of virus replication (day 5) and three animals were euthanized during the early convalescence period (day 34). All six AGMs supported robust SARS-CoV-2 replication and developed respiratory disease. Evidence of coagulation dysfunction as noted by a transient increases in aPTT and circulating levels of fibrinogen was observed in all AGMs. The level of SARS-CoV-2 replication and lung pathology was not quite as pronounced as previously reported with AGMs exposed by the combined i.n. and i.t. routes; however, SARS-CoV-2 RNA was detected in nasal swabs of some animals as late as day 15 and rectal swabs as late as day 28 after virus challenge. Of particular importance to this study, all three AGMs that were followed until the early convalescence stage of COVID-19 showed substantial lung pathology at necropsy as evidenced by multifocal chronic interstitial pneumonia and increased collagen deposition in alveolar walls despite the absence of detectable SARS-CoV-2 in any of the lungs of these animals. These findings are consistent with human COVID-19 further demonstrating that the AGM faithfully reproduces the human condition.
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- 2020
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27. Prior vaccination with rVSV-ZEBOV does not interfere with but improves efficacy of postexposure antibody treatment
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Robert W. Cross, Zachary A. Bornholdt, Abhishek N. Prasad, Joan B. Geisbert, Viktoriya Borisevich, Krystle N. Agans, Daniel J. Deer, Kevin Melody, Karla A. Fenton, Heinz Feldmann, Armand Sprecher, Larry Zeitlin, and Thomas W. Geisbert
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Science - Abstract
During an ongoing Ebola virus outbreak, infection before onset of protective immunity from vaccination is a possible scenario. Here the authors show in non-human primates that vaccination shortly before treatment with a monoclonal antibody does not negatively affect effectiveness of the antibody therapy.
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- 2020
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28. Rational design of universal immunotherapy for TfR1-tropic arenaviruses
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Hadas Cohen-Dvashi, Ron Amon, Krystle N. Agans, Robert W. Cross, Aliza Borenstein-Katz, Mathieu Mateo, Sylvain Baize, Vered Padler-Karavani, Thomas W. Geisbert, and Ron Diskin
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Science - Abstract
New World arenaviruses utilize the cellular transferrin receptor 1 (TfR1) to enter host cells. Here, the authors develop a TfR1-mimetic immunoadhesin, Arenacept, that targets viral spike complexes and exerts effective pan-reactive neutralization against pathogenic mammarenaviruses.
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- 2020
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29. Dual-mode terahertz extended interaction oscillator driven by a pseudospark-sourced sheet electron beam
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Jie Xie, Xue-Song Yuan, Liang Zhang, Adrian W. Cross, Hua-Bi Yin, Qing-Yun Chen, Tong-Bin Yang, Xiao-Tao Xu, Yang Yan, and Lin Meng
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Dual-mode operation ,Extended interaction oscillator (EIO) ,High-power radiation ,Pseudospark-sourced electron beam ,Sheet electron beam (SEB) ,Terahertz ,Electronic computers. Computer science ,QA75.5-76.95 ,Electrical engineering. Electronics. Nuclear engineering ,TK1-9971 - Abstract
A terahertz dual-mode extended interaction oscillator (EIO) driven by a pseudospark-sourced sheet electron beam (SEB) was presented. The major advantages of the newly developed circuit include 1) high-density SEB interacting with the TM11 and TM31 modes, respectively, and 2) high output power of over 1 kW at the sub-terahertz frequency range. Two different types of 2π modes and their output characteristics were studied, and the circuit was optimized to ensure efficient outputs of two standing-wave modes. The three-dimensional (3D) particle-in-cell (PIC) simulation predicts the maximum output power of 1.3 kW with a 3-dB bandwidth of ~0.5 GHz at 303 GHz when operating at the TM11 mode, and 3.18 kW, 3-dB bandwidth of ~0.85 GHz at 364 GHz when operating at the TM31 mode.
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- 2021
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30. Bundibugyo ebolavirus Survival Is Associated with Early Activation of Adaptive Immunity and Reduced Myeloid-Derived Suppressor Cell Signaling
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Courtney Woolsey, Viktoriya Borisevich, Krystle N. Agans, Karla A. Fenton, Robert W. Cross, and Thomas W. Geisbert
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coagulation ,Ebola virus ,filovirus ,immunology ,myeloid-derived suppressor cell ,nonhuman primate ,Microbiology ,QR1-502 - Abstract
ABSTRACT Ebolaviruses Bundibugyo virus (BDBV) and Ebola virus (EBOV) cause fatal hemorrhagic disease in humans and nonhuman primates. While the host response to EBOV is well characterized, less is known about BDBV infection. Moreover, immune signatures that mediate natural protection against all ebolaviruses remain poorly defined. To explore these knowledge gaps, we transcriptionally profiled BDBV-infected rhesus macaques, a disease model that results in incomplete lethality. This approach enabled us to identify prognostic indicators. As expected, survival (∼60%) correlated with reduced clinical pathology and circulating infectious virus, although peak viral RNA loads were not significantly different between surviving and nonsurviving macaques. Survivors had higher anti-BDBV antibody titers and transcriptionally derived cytotoxic T cell-, memory B cell-, and plasma cell-type quantities, demonstrating activation of adaptive immunity. Conversely, a poor prognosis was associated with lack of an appropriate adaptive response, sustained innate immune signaling, and higher expression of myeloid-derived suppressor cell (MDSC)-related transcripts (S100A8, S100A9, CEBPB, PTGS2, CXCR1, and LILRA3). MDSCs are potent immunosuppressors of cellular and humoral immunity, and therefore, they represent a potential therapeutic target. Circulating plasminogen activator inhibitor 1 (PAI-1) and tissue plasminogen activator (tPA) levels were also elevated in nonsurvivors and in survivors exhibiting severe illness, emphasizing the importance of maintaining coagulation homeostasis to control disease progression. IMPORTANCE Bundibugyo virus (BDBV) and Ebola virus (EBOV) are ebolaviruses endemic to Africa that cause severe, often fatal hemorrhagic disease. BDBV is considered a less pathogenic ebolavirus due to its reduced lethality during human outbreaks, as well as in experimentally infected nonhuman primates. The reduced mortality of BDBV in NHP models, resulting in a pool of survivors, afforded us the unique opportunity of identifying immune correlates that confer protection against ebolaviruses. In this study, we discovered that the survival of BDBV-infected nonhuman primates (NHPs) was dependent on early development of adaptive (memory) immune responses and reduced myeloid-derived suppressor cell (MDSC)-related signaling. MDSCs are a heterogenous group of immune cells implicated in a number of diseases that are powerful immunosuppressors of cellular and humoral immunity. Thus, MDSCs represent a novel therapeutic target to prevent ebolavirus disease. To our knowledge, this is the first study to link increased morbidity with recruitment of these potent immunosuppressive cells.
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- 2021
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31. The Effects of Electron Cyclotron Absorption in Powerful Narrow-Band Sub-THz Oscillators Exploiting Volume and Surface Modes
- Author
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A. J. MacLachlan, C. W. Robertson, Adrian W. Cross, and A. D. R. Phelps
- Subjects
Electrical and Electronic Engineering ,Electronic, Optical and Magnetic Materials - Published
- 2023
32. The impact of heterotopic ossification prophylaxis after surgical fixation of acetabular fractures: national treatment patterns and related outcomes
- Author
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Adam Boissonneault, Nathan O Hara, David Pogorzelski, Lucas Marchand, Thomas Higgins, Leah Gitajn, Mark J. Gage, Roman M. Natoli, Ishani Sharma, Sarah Pierrie, Robert V O’Toole, Sheila Sprague, Gerard Slobogean, Gerard P. Slobogean, Jeffrey Wells, Mohit Bhandari, Anthony D. Harris, C. Daniel Mullins, Lehana Thabane, Amber Wood, Gregory J. Della Rocca, Joan Hebden, Kyle J. Jeray, Lucas S. Marchand, Lyndsay M. O'Hara, Robert Zura, Christopher Lee, Joseph Patterson, Michael J. Gardner, Jenna Blasman, Jonah Davies, Stephen Liang, Monica Taljaard, PJ Devereaux, Gordon H. Guyatt, Diane Heels-Ansdell, Debra Marvel, Jana Palmer Jeffrey Wells, Jeff Friedrich, Nathan N. O'Hara, Frances Grissom, I. Leah Gitajn, Saam Morshed, Robert V. O'Toole, Bradley A. Petrisor, Franca Mossuto, Manjari G. Joshi, Jean-Claude D'Alleyrand, Justin Fowler, Jessica Rivera, Max Talbot, Shannon Dodds, Silvia Li, Alejandra Rojas, Gina Del Fabbro, Olivia Paige Szasz, Paula McKay, Alexandra Minea, Andrea Howe, Haley Demyanovich, Michelle Medeiros, Genevieve Polk, Eric Kettering, Nirmen Mahal, Andrew Eglseder, Aaron Johnson, Christopher Langhammer, Christopher Lebrun, Jason Nascone, Raymond Pensy, Andrew Pollak, Marcus Sciadini, Yasmin Degani, Haley K. Demyanovich, Heather Phipps, Eric Hempen, Christine Holler, Brad A. Petrisor, Herman Johal, Bill Ristevski, Dale Williams, Matthew Denkers, Krishan Rajaratnam, Jamal Al-Asiri, Jodi Gallant, Kaitlyn Pusztai, Sarah MacRae, Sara Renaud, John D. Adams, Michael L. Beckish, Christopher C. Bray, Timothy R. Brown, Andrew W. Cross, Timothy Dew, Gregory K. Faucher, Richard W. Gurich, David E. Lazarus, S. John Millon, M. Christian Moody, M. Jason Palmer, Scott E. Porter, Thomas M. Schaller, Michael S. Sridhar, John L. Sanders, L. Edwin Rudisill, Michael J. Garitty, Andrew S. Poole, Michael L. Sims, Clark M. Walker, Robert Carlisle, Erin A. Hofer, Brandon Huggins, Michael Hunter, William Marshall, Shea B. Ray, Cory Smith, Kyle M. Altman, Erin Pichiotino, Julia C. Quirion, Markus F. Loeffler, Erin R. Pichiotino, Austin A. Cole, Ethan J. Maltz, Wesley Parker, T. Bennett Ramsey, Alex Burnikel, Michael Colello, Russell Stewart, Jeremy Wise, Matthew Anderson, Joshua Eskew, Benjamin Judkins, James M. Miller, Stephanie L. Tanner, Rebecca G. Snider, Christine E. Townsend, Kayla H. Pham, Abigail Martin, Emily Robertson, Emily Bray, J. Wilson Sykes, Krystina Yoder, Kelsey Conner, Harper Abbott, Todd O. McKinley, Walter W. Virkus, Anthony T. Sorkin, Jan P. Szatkowski, Brian H. Mullis, Yohan Jang, Luke A. Lopas, Lauren C. Hill, Courteney L. Fentz, Maricela M. Diaz, Krista Brown, Katelyn M. Garst, Emma W. Denari, Patrick Osborn, Maria Herrera, Theodore Miclau, Meir Marmor, Amir Matityahu, R. Trigg McClellan, David Shearer, Paul Toogood, Anthony Ding, Jothi Murali, Ashraf El Naga, Jennifer Tangtiphaiboontana, Tigist Belaye, Eleni Berhaneselase, Dmitry Pokhvashchev, William T Obremskey, Amir Alex Jahangir, Manish Sethi, Robert Boyce, Daniel J. Stinner, Phillip Mitchell, Karen Trochez, Elsa Rodriguez, Charles Pritchett, Natalie Hogan, A. Fidel Moreno, Jennifer E. Hagen, Matthew Patrick, Richard Vlasak, Thomas Krupko, Michael Talerico, Marybeth Horodyski, Marissa Pazik, Elizabeth Lossada-Soto, Joshua L. Gary, Stephen J Warner, John W. Munz, Andrew M. Choo, Timothy S. Achor, Milton L. 'Chip' Routt, Michael Kutzler, Sterling Boutte, Ryan J. Warth, Michael Prayson, Indresh Venkatarayappa, Brandon Horne, Jennifer Jerele, Linda Clark, Christina Boulton, Jason Lowe, John T. Ruth, Brad Askam, Andrea Seach, Alejandro Cruz, Breanna Featherston, Robin Carlson, Iliana Romero, Isaac Zarif, Niloofar Dehghan, Michael McKee, Clifford B Jones, Debra L Sietsema, Alyse Williams, Tayler Dykes, Ernesto Guerra-Farfan, Jordi Tomas-Hernandez, Jordi Teixidor-Serra, Vicente Molero-Garcia, Jordi Selga-Marsa, Juan Antonio Porcel-Vazquez, Jose Vicente Andres-Peiro, Ignacio Esteban-Feliu, Nuria Vidal-Tarrason, Jordi Serracanta, Jorge Nuñez-Camarena, Maria del Mar Villar-Casares, Jaume Mestre-Torres, Pilar Lalueza-Broto, Felipe Moreira-Borim, Yaiza Garcia-Sanchez, Francesc Marcano-Fernández, Laia Martínez-Carreres, David Martí-Garín, Jorge Serrano-Sanz, Joel Sánchez-Fernández, Matsuyama Sanz-Molero, Alejandro Carballo, Xavier Pelfort, Francesc Acerboni-Flores, Anna Alavedra-Massana, Neus Anglada-Torres, Alexandre Berenguer, Jaume Cámara-Cabrera, Ariadna Caparros-García, Ferran Fillat-Gomà, Ruben Fuentes-López, Ramona Garcia-Rodriguez, Nuria Gimeno-Calavia, Marta Martínez-Álvarez, Patricia Martínez-Grau, Raúl Pellejero-García, Ona Ràfols-Perramon, Juan Manuel Peñalver, Mònica Salomó Domènech, Albert Soler-Cano, Aldo Velasco-Barrera, Christian Yela-Verdú, Mercedes Bueno-Ruiz, Estrella Sánchez-Palomino, Vito Andriola, Matilde Molina-Corbacho, Yeray Maldonado-Sotoca, Alfons Gasset-Teixidor, Jorge Blasco-Moreu, Núria Fernández-Poch, Josep Rodoreda-Puigdemasa, Arnau Verdaguer-Figuerola, Heber Enrique Cueva-Sevieri, Santiago Garcia-Gimenez, Darius G. Viskontas, Kelly L. Apostle, Dory S. Boyer, Farhad O. Moola, Bertrand H. Perey, Trevor B. Stone, H. Michael Lemke, Ella Spicer, Kyrsten Payne, Robert A. Hymes, Cary C. Schwartzbach, Jeff E. Schulman, A. Stephen Malekzadeh, Michael A. Holzman, Greg E. Gaski, Jonathan Wills, Holly Pilson, Eben A. Carroll, Jason J. Halvorson, Sharon Babcock, J. Brett Goodman, Martha B. Holden, Wendy Williams, Taylor Hill, Ariel Brotherton, Nicholas M. Romeo, Heather A Vallier, Anna Vergon, Thomas F. Higgins, Justin M. Haller, David L. Rothberg, Zachary M. Olsen, Abby V. McGowan, Sophia Hill, Morgan K. Dauk, Patrick F. Bergin, George V. Russell, Matthew L. Graves, John Morellato, Sheketha L. McGee, Eldrin L. Bhanat, Ugur Yener, Rajinder Khanna, Priyanka Nehete, Dr. David Potter, Dr. Robert VanDemark, Kyle Seabold, Nicholas Staudenmier, Marcus Coe, Kevin Dwyer, Devin S. Mullin, Theresa A. Chockbengboun, Peter A. DePalo, Kevin Phelps, Michael Bosse, Madhav Karunakar, Laurence Kempton, Stephen Sims, Joseph Hsu, Rachel Seymour, Christine Churchill, Ada Mayfield, Juliette Sweeney, Todd Jaeblon, Robert Beer, Brent Bauer, Sean Meredith, Sneh Talwar, Christopher M. Domes, Rachel M. Reilly, Ariana Paniagua, JaNell Dupree, Michael J. Weaver, Arvind G. von Keudell, Abigail E. Sagona, Samir Mehta, Derek Donegan, Annamarie Horan, Mary Dooley, Marilyn Heng, Mitchel B. Harris, David W. Lhowe, John G. Esposito, Ahmad Alnasser, Steven F. Shannon, Alesha N. Scott, Bobbi Clinch, Becky Weber, Michael J. Beltran, Michael T. Archdeacon, Henry Claude Sagi, John D. Wyrick, Theodore Toan Le, Richard T. Laughlin, Cameron G. Thomson, Kimberly Hasselfeld, Carol A. Lin, Mark S. Vrahas, Charles N. Moon, Milton T. Little, Geoffrey S. Marecek, Denice M. Dubuclet, John A. Scolaro, James R. Learned, Philip K. Lim, Susan Demas, Arya Amirhekmat, and Yan Marco Dela Cruz
- Subjects
General Earth and Planetary Sciences ,General Environmental Science - Published
- 2023
33. Vesicular Stomatitis Virus-Based Vaccine Protects Mice against Crimean-Congo Hemorrhagic Fever
- Author
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Sergio E. Rodriguez, Robert W. Cross, Karla A. Fenton, Dennis A. Bente, Chad E. Mire, and Thomas W. Geisbert
- Subjects
Medicine ,Science - Abstract
Abstract Crimean-Congo hemorrhagic fever virus (CCHFV), a tick-borne bunyavirus, can cause a life-threatening hemorrhagic syndrome in humans but not in its animal host. The virus is widely distributed throughout southeastern Europe, the Middle East, Africa, and Asia. Disease management has proven difficult and there are no broadly licensed vaccines or therapeutics. Recombinant vesicular stomatitis viruses (rVSV) expressing foreign glycoproteins (GP) have shown promise as experimental vaccines for several viral hemorrhagic fevers. Here, we developed and assessed a replication competent rVSV vector expressing the CCHFV glycoprotein precursor (GPC), which encodes CCHFV structural glycoproteins. This construct drives strong expression of CCHFV-GP, in vitro. Using these vectors, we vaccinated STAT-1 knock-out mice, an animal model for CCHFV. The vector was tolerated and 100% efficacious against challenge from a clinical strain of CCHFV. Anti-CCHFV-GP IgG and neutralizing antibody titers were observed in surviving animals. This study demonstrates that a rVSV expressing only the CCHFV-GP has the potential to serve as a replication competent vaccine platform against CCHF infections.
- Published
- 2019
- Full Text
- View/download PDF
34. Reversion of Ebolavirus Disease from a Single Intramuscular Injection of a Pan-Ebolavirus Immunotherapeutic
- Author
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Erin Kuang, Robert W. Cross, Maria McCavitt-Malvido, Dafna M. Abelson, Viktoriya Borisevich, Lauren Stuart, Krystle N. Agans, Neil Mlakar, Arumugapradeep Marimuthu, Daniel J. Deer, William S. Shestowsky, Do Kim, Joan B. Geisbert, Larry Zeitlin, Crystal L. Moyer, Chad J. Roy, Thomas W. Geisbert, and Zachary A. Bornholdt
- Subjects
pan-ebolavirus ,MBP134 ,immunotherapeutic ,Sudan ,SUDV ,EBOV ,Medicine - Abstract
Intravenous (IV) administration of antiviral monoclonal antibodies (mAbs) can be challenging, particularly during an ongoing epidemic, due to the considerable resources required for performing infusions. An ebolavirus therapeutic administered via intramuscular (IM) injection would reduce the burdens associated with IV infusion and allow rapid treatment of exposed individuals during an outbreak. Here, we demonstrate how MBP134, a cocktail of two pan-ebolavirus mAbs, reverses the course of Sudan ebolavirus disease (Gulu variant) with a single IV or IM dose in non-human primates (NHPs) as late as five days post-exposure. We also investigate the utility of adding half-life extension mutations to the MBP134 mAbs, ultimately creating a half-life extended cocktail designated MBP431. When delivered as a post-exposure prophylactic or therapeutic, a single IM dose of MBP431 offered complete or significant protection in NHPs challenged with Zaire ebolavirus. In conjunction with previous studies, these results support the use of MBP431 as a rapidly deployable IM medical countermeasure against every known species of ebolavirus.
- Published
- 2022
- Full Text
- View/download PDF
35. Lead-Free Solid State Mechanochemical Synthesis of Cs2NaBi1–xFexCl6 Double Perovskite: Reduces Band Gap and Enhances Optical Properties
- Author
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Rohini Udavant, Sachin Thawarkar, Sachin Rondiya, Ankita Shelke, Rahul Aher, Thalasseril G. Ajithkumar, Russell W. Cross, Nelson Y. Dzade, and Sandesh Jadkar
- Subjects
Inorganic Chemistry ,Physical and Theoretical Chemistry - Published
- 2023
36. Understanding International Benchmarks on Student Engagement: Awareness and Research Alignment from a Computer Science Perspective.
- Author
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Michael Morgan, Jane E. Sinclair, Matthew Butler 0002, Neena Thota, Janet Fraser, Gerry W. Cross, and Jana Jacková
- Published
- 2017
- Full Text
- View/download PDF
37. Combination treatment of mannose and GalNAc conjugated small interfering RNA protects against lethal Marburg virus infection
- Author
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Xin Ye, Richard Holland, Mark Wood, Chris Pasetka, Lorne Palmer, Eleni Samaridou, Kevin McClintock, Viktoriya Borisevich, Thomas W. Geisbert, Robert W. Cross, and James Heyes
- Subjects
Pharmacology ,Drug Discovery ,Genetics ,Molecular Medicine ,Molecular Biology - Abstract
Marburg virus (MARV) infection results in severe viral hemorrhagic fever with mortalities up to 90%, and there is a pressing need for effective therapies. Here, we established a small interfering RNA (siRNA) conjugate platform that enabled successful subcutaneous delivery of siRNAs targeting the MARV nucleoprotein. We identified a hexavalent mannose ligand with high affinity to macrophages and dendritic cells, which are key cellular targets of MARV infection. This ligand enabled successful siRNA conjugate delivery to macrophages both in vitro and in vivo. The delivered hexa-mannose-siRNA conjugates rendered substantial target gene silencing in macrophages when supported by a mannose functionalized endosome release polymer. This hexa-mannose-siRNA conjugate was further evaluated alongside our hepatocyte-targeting GalNAc-siRNA conjugate, to expand targeting of infected liver cells. In MARV-Angola-infected guinea pigs, these platforms offered limited survival benefit when used as individual agents. However, in combination, they achieved up to 100% protection when dosed 24 h post infection. This novel approach, using two different ligands to simultaneously deliver siRNA to multiple cell types relevant to infection, provides a convenient subcutaneous route of administration for treating infection by these dangerous pathogens. The mannose conjugate platform has potential application to other diseases involving macrophages and dendritic cells.
- Published
- 2023
38. Efficient, 0.35-THz Overmoded Oscillator Based on a Two-Dimensional Periodic Surface Lattice
- Author
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A. J. MacLachlan, C. W. Robertson, A. W. Cross, and A. D. R. Phelps
- Subjects
Electrical and Electronic Engineering ,Electronic, Optical and Magnetic Materials - Published
- 2022
39. RuO2 Nanorods as an Electrocatalyst for Proton Exchange Membrane Water Electrolysis
- Author
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Michael W. Cross, Richard P. Smith, and Walter J. Varhue
- Subjects
electrolyzer ,electrocatalyst ,nanorods ,hydrogen production ,Mechanical engineering and machinery ,TJ1-1570 - Abstract
A custom-built PEM electrolyzer cell was assembled using 6” stainless-steel ConFlat flanges which were fitted with a RuO2 nanorod-decorated, mixed metal oxide (MMO) ribbon mesh anode catalyst. The current density–voltage characteristics were measured for the RuO2 nanorod electrocatalyst while under constant water feed operation. The electrocatalytic behavior was investigated by making a series of physical modifications to the anode catalyst material. These experiments showed an improved activity due to the RuO2 nanorod electrocatalyst, resulting in a corresponding decrease in the electrochemical overpotential. These overpotentials were identified by collecting experimental data from various electrolyzer cell configurations, resulting in an improved understanding of the enhanced catalytic behavior. The micro-to-nano surface structure of the anode electrocatalyst layer is a critical factor determining the overall operation of the PEM electrolyzer. The improvement was determined to be due to the lowering of the potential barrier to electron escape in an electric field generated in the vicinity of a nanorod.
- Published
- 2021
- Full Text
- View/download PDF
40. Development of a SARS-CoV-2 Vaccine Candidate Using Plant-Based Manufacturing and a Tobacco Mosaic Virus-like Nano-Particle
- Author
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Joshua M. Royal, Carrie A. Simpson, Alison A. McCormick, Amanda Phillips, Steve Hume, Josh Morton, John Shepherd, Youngjun Oh, Kelsi Swope, Jennifer L. DeBeauchamp, Richard J. Webby, Robert W. Cross, Viktoriya Borisevich, Thomas W. Geisbert, Jennifer K. Demarco, Barry Bratcher, Hugh Haydon, and Gregory P. Pogue
- Subjects
SARS-CoV-2 vaccine ,nanoparticle ,receptor-binding domain ,plant-based manufacturing ,Medicine - Abstract
Stable, effective, easy-to-manufacture vaccines are critical to stopping the COVID-19 pandemic resulting from the coronavirus SARS-CoV-2. We constructed a vaccine candidate CoV-RBD121-NP, which is comprised of the SARS-CoV-2 receptor-binding domain (RBD) of the spike glycoprotein (S) fused to a human IgG1 Fc domain (CoV-RBD121) and conjugated to a modified tobacco mosaic virus (TMV) nanoparticle. In vitro, CoV-RBD121 bound to the host virus receptor ACE2 and to the monoclonal antibody CR3022, a neutralizing antibody that blocks S binding to ACE2. The CoV-RBD121-NP vaccine candidate retained key SARS-CoV-2 spike protein epitopes, had consistent manufacturing release properties of safety, identity, and strength, and displayed stable potency when stored for 12 months at 2–8 °C or 22–28 °C. Immunogenicity studies revealed strong antibody responses in C57BL/6 mice with non-adjuvanted or adjuvanted (7909 CpG) formulations. The non-adjuvanted vaccine induced a balanced Th1/Th2 response and antibodies that recognized both the S1 domain and full S protein from SARS2-CoV-2, whereas the adjuvanted vaccine induced a Th1-biased response. Both adjuvanted and non-adjuvanted vaccines induced virus neutralizing titers as measured by three different assays. Collectively, these data showed the production of a stable candidate vaccine for COVID-19 through the association of the SARS-CoV-2 RBD with the TMV-like nanoparticle.
- Published
- 2021
- Full Text
- View/download PDF
41. Negotiating the Maze of Academic Integrity in Computing Education.
- Author
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Simon, Judy Sheard, Michael Morgan, Andrew Petersen 0001, Amber Settle, Jane E. Sinclair, Gerry W. Cross, and Charles Riedesel
- Published
- 2016
- Full Text
- View/download PDF
42. Design, Simulation, and Cold Test of a W-Band Double Nonparallel Staggered Grating Backward Wave Oscillator
- Author
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Jin Zhang, Yasir Alfadhl, Xiaodong Chen, Liang Zhang, and Adrian W. Cross
- Subjects
Electrical and Electronic Engineering ,QC ,Electronic, Optical and Magnetic Materials - Abstract
A novel double nonparallel staggered grating (DNPSG) slow wave structure (SWS) is proposed to enhance the coupling impedance in a W-band backward wave oscillator (BWO) driven by a pseudosparksourced sheet electron beam. The DNPSG SWS has been shown a broadband of 72–125 GHz and a higher coupling impedance compared with the traditional double staggered grating (DSG) SWS in simulation. The DNPSG BWO structure consisting of ten SWS units and a broadband output structure is designed and fabricated. In the cold test of the DNPSG BWO, the measured S11 (double of the losses in the DNPSG BWO) is above −10 dB in most of the band, which is satisfactory in the pseudospark-driven high-power device. The hot-test performance of the DNPSG BWO is analyzed by particle-in-cell (PIC) simulation in a beam voltage range of 14–90 kV and a current density range of 1.5–5 × 107 A/m2, obtaining a high output power (max. 190 kW) over an ultrawide tuning band of 38 GHz (75–113 GHz) due to enhanced coupling impedance.
- Published
- 2022
43. RADICALS-HD: Reflections before the Results are Known
- Author
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C C, Parker, N W, Clarke, C, Catton, H, Kynaston, A, Cook, W, Cross, C, Davidson, C, Goldstein, J, Logue, C, Maniatis, P M, Petersen, P, Neville, H, Payne, R, Persad, C, Pugh, A, Stirling, F, Saad, W R, Parulekar, M K B, Parmar, and M R, Sydes
- Subjects
Oncology ,Radiology, Nuclear Medicine and imaging - Published
- 2022
44. Demonstrating multi-round subsystem quantum error correction using matching and maximum likelihood decoders
- Author
-
Neereja Sundaresan, Theodore J. Yoder, Youngseok Kim, Muyuan Li, Edward H. Chen, Grace Harper, Ted Thorbeck, Andrew W. Cross, Antonio D. Córcoles, and Maika Takita
- Subjects
Multidisciplinary ,General Physics and Astronomy ,General Chemistry ,General Biochemistry, Genetics and Molecular Biology - Abstract
Quantum error correction offers a promising path for performing high fidelity quantum computations. Although fully fault-tolerant executions of algorithms remain unrealized, recent improvements in control electronics and quantum hardware enable increasingly advanced demonstrations of the necessary operations for error correction. Here, we perform quantum error correction on superconducting qubits connected in a heavy-hexagon lattice. We encode a logical qubit with distance three and perform several rounds of fault-tolerant syndrome measurements that allow for the correction of any single fault in the circuitry. Using real-time feedback, we reset syndrome and flag qubits conditionally after each syndrome extraction cycle. We report decoder dependent logical error, with average logical error per syndrome measurement in Z(X)-basis of ~0.040 (~0.088) and ~0.037 (~0.087) for matching and maximum likelihood decoders, respectively, on leakage post-selected data.
- Published
- 2023
45. A highly attenuated pan-filovirus VesiculoVax vaccine rapidly protects nonhuman primates against Marburg virus and three species of Ebolavirus
- Author
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Courtney Woolsey, Viktoriya Borisevich, Krystle N Agans, Rachel O’Toole, Karla A Fenton, Mack B Harrison, Abhishek N Prasad, Daniel J Deer, Cheryl Gerardi, Nneka Morrison, Robert W Cross, John H Eldridge, Demetrius Matassov, and Thomas W Geisbert
- Subjects
Infectious Diseases ,Immunology and Allergy - Abstract
Background The family Filoviridae consists of several virus members known to cause significant mortality and disease in humans. Among these, Ebola virus (EBOV), Marburg virus (MARV), Sudan virus (SUDV), and Bundibugyo virus (BDBV) are considered the deadliest. The sole US FDA approved filovirus vaccine, Ervebo®, is indicated only for EBOV infections with limited heterologous protection against other filoviruses. In clinical trials, Ervebo® was shown to rapidly protect humans against Ebola disease ten days plus post immunization. Whether multivalent formulations of similar recombinant vesicular stomatitis virus (rVSV)-based vaccines could likewise confer rapid protection is unclear. Methodology/Findings Here, we tested the ability of a highly attenuated, quadrivalent pan-filovirus Vesiculovax vaccine (rVSV-Filo) to elicit fast-acting protection against MARV, EBOV, SUDV, and BDBV. Groups of cynomolgus monkeys were vaccinated seven days before exposure to each of the four viral pathogens. All subjects (100%) immunized one-week prior survived MARV, SUDV, and BDBV challenge; 80% of subjects survived EBOV challenge. Survival correlated with lower viral load, higher glycoprotein-specific IgG titers, and the expression of B cell-, cytotoxic cell-, and antigen presentation-associated transcripts. Conclusions/Significance These results demonstrate multivalent Vesiculovax vaccines are suitable for filovirus outbreak management. The highly attenuated nature of the rVSV-Filo vaccine may be preferable to the Ervebo® “delta G” platform, which induced arthralgia, cutaneous vasculitis, and dermatitis in a subset of recipients.
- Published
- 2023
46. Pathogenesis of aerosolized Ebola virus variant Makona in nonhuman primates
- Author
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Abhishek N Prasad, Karla A Fenton, Krystle N Agans, Viktoriya Borisevich, Courtney Woolsey, Jason E Comer, Natalie S Dobias, Jennifer E Peel, Daniel J Deer, Joan B Geisbert, William S Lawrence, Robert W Cross, and Thomas W Geisbert
- Subjects
Infectious Diseases ,Immunology and Allergy - Abstract
Background The primary route of infection by Ebola virus (EBOV) and other pathogenic filoviruses in humans is through contact of contaminated body fluids with mucosal surfaces. Despite this, filoviruses hold capacity for delivery by both large and small particle artificial aerosols, and thus present potential for intentional misuse. Previous studies have shown that high doses of EBOV (≥ 1000 PFU) delivered by small particle aerosol cause uniform lethality in nonhuman primates (NHP) while only a few small studies have assessed lower doses in NHPs. Methods To further characterize the pathogenesis of EBOV infection via the small particle aerosol route, we challenged cohorts of cynomolgus monkeys with low doses (10 PFU, 1 PFU, 0.1 PFU) of EBOV variant Makona, which may help to define risks associated with small particle aerosol exposures. Results Despite using challenge doses several orders of magnitude lower than previously published studies, infection via this route was uniformly lethal across all cohorts; however, the time to death was delayed in a dose-dependent manner between aerosol-challenged cohorts, as well as in comparison to animals challenged via the intramuscular route. Here, we describe the observed clinical and pathological details including serum biomarkers, viral burden, and histopathological changes leading to death. Conclusions Our observations in this model highlight the striking susceptibility of NHPs, and by extension, likely humans, via small particle aerosol exposure to EBOV and emphasize the need for further development of rapid diagnostics and potent postexposure prophylactics in the event of intentional release via deployment of an aerosol-producing device.
- Published
- 2023
47. Contract-based verification of a realistic quantum compiler.
- Author
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Yunong Shi, Xupeng Li, Runzhou Tao, Ali Javadi-Abhari, Andrew W. Cross, Frederic T. Chong, and Ronghui Gu
- Published
- 2019
48. What's in a Name?: International Interpretations of Computing Education Terminology.
- Author
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Simon, Alison Clear, Janet Carter, Gerry W. Cross, Atanas Radenski, Liviana Tudor, and Eno Tõnisson
- Published
- 2015
- Full Text
- View/download PDF
49. Leakage suppression in the toric code.
- Author
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Martin Suchara, Andrew W. Cross, and Jay M. Gambetta
- Published
- 2015
- Full Text
- View/download PDF
50. Demonstration of quantum advantage in machine learning
- Author
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Diego Ristè, Marcus P. da Silva, Colm A. Ryan, Andrew W. Cross, Antonio D. Córcoles, John A. Smolin, Jay M. Gambetta, Jerry M. Chow, and Blake R. Johnson
- Subjects
Physics ,QC1-999 ,Electronic computers. Computer science ,QA75.5-76.95 - Abstract
Large advantage in small quantum computers Quantum computing promises to revolutionize all fields of science by solving problems that are too complex for conventional computers. However, the realization of a full-fledged, universal quantum computer is still far ahead, requiring millions of quantum bits and very low error rates. Despite this, D. Ristè and colleagues at Raytheon BBN Technologies, with collaborators at IBM, have demonstrated that a quantum advantage already appears with only a few quantum bits and a highly noisy system. The team solved a particular problem, known as learning parity with noise, using a five-qubit superconducting quantum processor. Counting the number of times that the processor runs, they demonstrate that the implemented quantum algorithm finds the solution much faster than by classical methods
- Published
- 2017
- Full Text
- View/download PDF
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