32 results on '"Williams, Daniel M."'
Search Results
2. Establishing SARS-CoV-2 membrane protein-specific antibodies as a valuable serological target via high-content microscopy
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Williams, Daniel M., Hornsby, Hailey R., Shehata, Ola M., Brown, Rebecca, Gallis, Marta, Meardon, Naomi, Newman, Thomas A.H., Plowright, Megan, Zafred, Domen, Shun-Shion, Amber S.M., Hodder, Anthony J., Bliss, Deepa, Metcalfe, Andrew, Edgar, James R., Gordon, David E., Sayers, Jon R., Nicklin, Martin J., Carroll, Miles, Collini, Paul J., Brown, Stephen, de Silva, Thushan I., and Peden, Andrew A.
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- 2023
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3. Perioperative and safety outcomes following tissue-sparing posterior cervical fusion to revise a pseudarthrosis: A multicenter retrospective review of 150 cases.
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LEMONS, ALEXANDER C., HAGLUND, MICHAEL M., MCCORMACK, BRUCE M., WILLIAMS, DANIEL M., BOHR, ADAM D., and SUMMERSIDE, ERIK M.
- Abstract
Background: Posterior cervical fusion (PCF) with lateral mass screws is a favorable treatment option to revise a symptomatic pseudarthrosis due to reliable rates of arthrodesis; however, this technique introduces elevated risk for wound infection and hospital readmission. A tissue-sparing PCF approach involving facet fixation instrumentation reduces the rates of postoperative complications while stabilizing the symptomatic level to achieve arthrodesis; however, these outcomes have been limited to small study cohorts from individual surgeons commonly with mixed indications for treatment. Materials and Methods: One hundred and fifty cases were identified from a retrospective chart review performed by seven surgeons across six sites in the United States. All cases involved PCF revision for a pseudarthrosis at one or more levels from C3 to C7 following anterior cervical discectomy and fusion (ACDF). PCF was performed using a tissue-sparing technique with facet instrumentation. Cases involving additional supplemental fixation such as lateral mass screws, rods, wires, or other hardware were excluded. Demographics, operative notes, postoperative complications, hospital readmission, and subsequent surgical interventions were summarized as an entire cohort and according to the following risk factors: age, sex, number of levels revised, body mass index (BMI), and history of nicotine use. Results: The average age of patients at the time of PCF revision was 55 ± 11 years and 63% were female. The average BMI was 29 ± 6 kg/m2 and 19% reported a history of nicotine use. Postoperative follow-up visits were available with a median of 68 days (interquartile range = 41-209 days) from revision PCF. There were 91 1-level, 49 2-level, 8 3-level, and 2 4±-level PCF revision cases. The mean operative duration was 52 ± 3 min with an estimated blood loss of 14 ± 1.5cc. Participants were discharged an average of 1 ± 0.05 days following surgery. Multilevel treatment resulted in longer procedure times (single = 45 min, multi = 59 min, P = 0.01) but did not impact estimated blood loss (P = 0.94). Total nights in the hospital increased by 0.2 nights with multilevel treatment (P = 0.01). Sex, age, nicotine history, and BMI had no effect on recorded perioperative outcomes. There was one instance of rehospitalization due to deep-vein thrombosis, one instance of persistent pseudarthrosis at the revised level treated with ACDF, and four instances of adjacent segment disease. In patients initially treated with multilevel ACDF, revisions occurred most commonly on the caudal level (48% of revised levels), followed by the cranial (43%), and least often in the middle level (9%). Conclusions: This chart review of perioperative and safety outcomes provides evidence in support of tissue-sparing PCF with facet instrumentation as a treatment for symptomatic pseudarthrosis after ACDF. The most common locations requiring revision were the caudal and cranial levels. Operative duration and estimated blood loss were favorable when compared to open alternatives. There were no instances of postoperative wound infection, and the majority of patients were discharged the day following surgery. [ABSTRACT FROM AUTHOR]
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- 2024
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4. Disruptions in endocytic traffic contribute to the activation of the NLRP3 inflammasome.
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Lee, Bali, Hoyle, Christopher, Wellens, Rose, Green, Jack P., Martin-Sanchez, Fatima, Williams, Daniel M., Matchett, Billie J., Seoane, Paula I., Bennett, Hayley, Adamson, Antony, Lopez-Castejon, Gloria, Lowe, Martin, and Brough, David
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NLRP3 protein ,INFLAMMASOMES ,TRAFFIC congestion ,ENDOCYTOSIS ,CELLULAR signal transduction ,LYSOSOMES ,INOSITOL - Abstract
Inflammation driven by the NLRP3 inflammasome is coordinated through multiple signaling pathways and is regulated by subcellular organelles. Here, we tested the hypothesis that NLRP3 senses disrupted endosome trafficking to trigger inflammasome formation and inflammatory cytokine secretion. NLRP3-activating stimuli disrupted endosome trafficking and triggered localization of NLRP3 to vesicles positive for endolysosomal markers and for the inositol lipid PI4P. Chemical disruption of endosome trafficking sensitized macrophages to the NLRP3 activator imiquimod, driving enhanced inflammasome activation and cytokine secretion. Together, these data suggest that NLRP3 can sense disruptions in the trafficking of endosomal cargoes, which may explain in part the spatial activation of the NLRP3 inflammasome. These data highlight mechanisms that could be exploited in the therapeutic targeting of NLRP3. Inflammation-inducing traffic jams: The NLRP3 inflammasome assembles and is activated by diverse cellular stresses to produce proinflammatory cytokines. Lee et al. investigated whether the NLRP3 inflammasome was activated by disruptions in endosomal trafficking. By analyzing various cell types, including bone marrow-derived macrophages, the authors found that NLRP3-activating stimuli resulted in perturbations in endosomal trafficking and conversely, that chemical interference with endosomal trafficking potentiated NLRP3 activation, although it was insufficient to activate NLRP3 by itself. Activated NLRP3 was recruited to endolysosomal vesicles, where it colocalized with the lipid PI4P, which the authors speculated may be the additional stimulus required for NLRP3 activation. Thus, NLRP3 senses and is activated by cellular stress resulting from disordered endosomal trafficking. —WW [ABSTRACT FROM AUTHOR]
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- 2023
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5. Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms
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Gordon, David E., Hiatt, Joseph, Bouhaddou, Mehdi, Rezelj, Veronica V., Ulferts, Svenja, Braberg, Hannes, Jureka, Alexander S., Obernier, Kirsten, Guo, Jeffrey Z., Batra, Jyoti, Kaake, Robyn M., Weckstein, Andrew R., Owens, Tristan W., Gupta, Meghna, Pourmal, Sergei, Titus, Erron W., Cakir, Merve, Soucheray, Margaret, McGregor, Michael, Cakir, Zeynep, Jang, Gwendolyn, O’Meara, Matthew J., Tummino, Tia A., Zhang, Ziyang, Foussard, Helene, Rojc, Ajda, Zhou, Yuan, Kuchenov, Dmitry, Hüttenhain, Ruth, Xu, Jiewei, Eckhardt, Manon, Swaney, Danielle L., Fabius, Jacqueline M., Ummadi, Manisha, Tutuncuoglu, Beril, Rathore, Ujjwal, Modak, Maya, Haas, Paige, Haas, Kelsey M., Naing, Zun Zar Chi, Pulido, Ernst H., Shi, Ying, Barrio-Hernandez, Inigo, Memon, Danish, Petsalaki, Eirini, Dunham, Alistair, Marrero, Miguel Correa, Burke, David, Koh, Cassandra, Vallet, Thomas, Silvas, Jesus A., Azumaya, Caleigh M., Billesbølle, Christian, Brilot, Axel F., Campbell, Melody G., Diallo, Amy, Dickinson, Miles Sasha, Diwanji, Devan, Herrera, Nadia, Hoppe, Nick, Kratochvil, Huong T., Liu, Yanxin, Merz, Gregory E., Moritz, Michelle, Nguyen, Henry C., Nowotny, Carlos, Puchades, Cristina, Rizo, Alexandrea N., Schulze-Gahmen, Ursula, Smith, Amber M., Sun, Ming, Young, Iris D., Zhao, Jianhua, Asarnow, Daniel, Biel, Justin, Bowen, Alisa, Braxton, Julian R., Chen, Jen, Chio, Cynthia M., Chio, Un Seng, Deshpande, Ishan, Doan, Loan, Faust, Bryan, Flores, Sebastian, Jin, Mingliang, Kim, Kate, Lam, Victor L., Li, Fei, Li, Junrui, Li, Yen-Li, Li, Yang, Liu, Xi, Lo, Megan, Lopez, Kyle E., Melo, Arthur A., Moss, Frank R., Nguyen, Phuong, Paulino, Joana, Pawar, Komal Ishwar, Peters, Jessica K., Pospiech, Thomas H., Safari, Maliheh, Sangwan, Smriti, Schaefer, Kaitlin, Thomas, Paul V., Thwin, Aye C., Trenker, Raphael, Tse, Eric, Tsui, Tsz Kin Martin, Wang, Feng, Whitis, Natalie, Yu, Zanlin, Zhang, Kaihua, Zhang, Yang, Zhou, Fengbo, Saltzberg, Daniel, Hodder, Anthony J., Shun-Shion, Amber S., Williams, Daniel M., White, Kris M., Rosales, Romel, Kehrer, Thomas, Miorin, Lisa, Moreno, Elena, Patel, Arvind H., Rihn, Suzannah, Khalid, Mir M., Vallejo-Gracia, Albert, Fozouni, Parinaz, Simoneau, Camille R., Roth, Theodore L., Wu, David, Karim, Mohd Anisul, Ghoussaini, Maya, Dunham, Ian, Berardi, Francesco, Weigang, Sebastian, Chazal, Maxime, Park, Jisoo, Logue, James, McGrath, Marisa, Weston, Stuart, Haupt, Robert, Hastie, C. James, Elliott, Matthew, Brown, Fiona, Burness, Kerry A., Reid, Elaine, Dorward, Mark, Johnson, Clare, Wilkinson, Stuart G., Geyer, Anna, Giesel, Daniel M., Baillie, Carla, Raggett, Samantha, Leech, Hannah, Toth, Rachel, Goodman, Nicola, Keough, Kathleen C., Lind, Abigail L., Klesh, Reyna J., Hemphill, Kafi R., Carlson-Stevermer, Jared, Oki, Jennifer, Holden, Kevin, Maures, Travis, Pollard, Katherine S., Sali, Andrej, Agard, David A., Cheng, Yifan, Fraser, James S., Frost, Adam, Jura, Natalia, Kortemme, Tanja, Manglik, Aashish, Southworth, Daniel R., Stroud, Robert M., Alessi, Dario R., Davies, Paul, Frieman, Matthew B., Ideker, Trey, Abate, Carmen, Jouvenet, Nolwenn, Kochs, Georg, Shoichet, Brian, Ott, Melanie, Palmarini, Massimo, Shokat, Kevan M., García-Sastre, Adolfo, Rassen, Jeremy A., Grosse, Robert, Rosenberg, Oren S., Verba, Kliment A., Basler, Christopher F., Vignuzzi, Marco, Peden, Andrew A., Beltrao, Pedro, Krogan, Nevan J., Trinidad, Donovan, Damas, Joana, Hughes, Graham M., Painter, Corrie A., Persky, Nicole S., Corbo, Marco, Kirilenko, Bodgan, Hiller, Michael, Koepfli, Klaus-Peter, Kaplow, Irene, Wirthlin, Morgan, Pfenning, Andreas R., Zhao, Huabin, Genereux, Diane P., Swofford, Ross, Lind, Abigail, Ryderq, Oliver A., Nweeia, Martin T., Meadows, Jennifer, Dong, Michael, Wallerman, Ola, Marinescu, Vikki, Lindblad-Toh, Kerstin, Ray, David A., Power, Sarahjane, Teeling, Emma C., Chauhan, Gaurav, Li, Shirley Xue, Karlsson, Elinor K., Lewin, Harris A., Centre National de la Recherche Scientifique (CNRS), Quantitative Biosciences Institute [UC San Francisco, USA] (QBI), University of California [San Francisco] (UC San Francisco), University of California (UC)-University of California (UC), Populations virales et Pathogenèse - Viral Populations and Pathogenesis, and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)
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Infectious Medicine ,Middle East respiratory syndrome coronavirus ,Viral protein ,viruses ,[SDV]Life Sciences [q-bio] ,Infektionsmedicin ,medicine.disease_cause ,Conserved sequence ,Microbiology in the medical area ,03 medical and health sciences ,Mitochondrial membrane transport protein ,0302 clinical medicine ,Protein structure ,Pandemic ,medicine ,Mikrobiologi inom det medicinska området ,ComputingMilieux_MISCELLANEOUS ,030304 developmental biology ,Coronavirus ,0303 health sciences ,Multidisciplinary ,biology ,virus diseases ,Virology ,3. Good health ,biology.protein ,Viral disease ,030217 neurology & neurosurgery - Abstract
INTRODUCTION The emergence of three lethal coronaviruses in Jennifer Meadows, Michael Dong, Ola Wallerman, Vikki Marinescu & Kerstin Lindblad-Toh ingår i gruppen Zoonomia Consortium
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- 2020
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6. Concept validation experiment for small aircraft transportation system higher-volume operations
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Consiglio, Maria C., Williams, Daniel M., Murdoch, Jennifer L., and Adams, Catherine A.
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Transportation industry ,Flying-machines ,Aerospace and defense industries ,Business ,Science and technology - Abstract
DOI: 10.2514/1.20588 A human-in-the-loop simulation experiment was conducted at the NASA Langley Research Center's Air Traffic Operations Laboratory in an effort to comprehensively validate tools and procedures intended to enable the small aircraft transportation system higher-volume-operations concept of operations. These procedures were developed with the goal of increasing the rate of operations at nontowered, nonradar airports in near all-weather conditions. A key element of the new design is the establishment of a volume of airspace around designated airports at which pilots accept responsibility for self-separation. Flights operating at these airports are given approach-sequencing information computed by a ground-based automated system. The validation experiment was conducted to determine if a pilot could safely and proficiently fly an airplane while performing the newly developed procedures. Comparative measures of flight path error, perceived workload, and situation awareness were obtained for two types of simulated scenarios. Baseline scenarios were representative of today's system using procedure separation, in which air traffic control grants one approach or departure clearance at a time. Test scenarios represented the newly developed approach and departure procedures. Results from the experiment indicate that low-time pilots were able to fly the test procedures in a simulation environment and maintain self-separation as safely and proficiently as flying today's procedures.
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- 2008
7. Conflict prevention and separation assurance in small aircraft transportation systems
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Consiglio, Maria C., Carreno, Victor, Williams, Daniel M., and Munoz, Cesar
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Algorithms ,Transportation industry ,Flying-machines ,Algorithm ,Aerospace and defense industries ,Business ,Science and technology - Abstract
DOI: 10.2514/1.20586 A multilayer approach to the prevention of conflicts due to the loss of aircraft-to-aircraft separation that relies on procedures and onboard automation was implemented as part of the Small Aircraft Transportation Systems Higher-Volume-Operations concept. The multilayer system gives pilots support and guidance during the execution of normal operations and advance warning for procedure deviations or off-nominal operations. This paper describes the major concept elements of this multilayer approach to separation assurance and conflict prevention and provides the rationale for its design. All the algorithms and functionality described in this paper were implemented in an aircraft simulation in the Air Traffic Operations Laboratory at NASA Langley Research Center and on the NASA Cirrus SR22 research aircraft.
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- 2008
8. Incorporating data link messaging into a multi-function display to support the Small Aircraft Transportation System (SATS) and the self-separation of general aviation aircraft
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Adams, Catherine A., Murdoch, Jennifer L., Consiglio, Maria C., and Williams, Daniel M.
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Transportation industry -- Equipment and supplies ,Transportation industry -- Technology application ,Aeronautics -- Technology application ,Aeronautics -- Information management ,Ergonomic aid ,Ergonomics ,Technology application ,Company systems management ,Engineering and manufacturing industries ,Health ,Human resources and labor relations - Abstract
One objective of the Small Aircraft Transportation System (SATS) Project is to increase the capacity and utilization of small non-towered, non-radar equipped airports by transferring traffic management activities to an automated system and separation responsibilities to general aviation (GA) pilots. This paper describes the development of a research multi-function display (MED) to support the interaction between pilots and an automated Airport Management Module (AMM). Preliminary results of simulation and flight tests indicate that adding the responsibility of monitoring other traffic for self-separation does not increase pilots' subjective workload levels. Pilots preferred using the enhanced MFD to execute flight procedures, reporting improved situation awareness (SA) over conventional instrument flight rules (IFR) procedures. Keywords: Small Aircraft Transportation System; SATS Higher Volume Operations; MFD and SATS; Data link and general aviation; Data link messaging
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- 2007
9. Small Aircraft Transportation System Higher Volume Operations Flight Experiment
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Williams, Daniel M., Murdoch, Jennifer L., and Adams, Catherine H.
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Air traffic control -- Technology application ,Air traffic control -- Methods ,Air traffic control -- Testing ,Technology application ,Aerospace and defense industries ,Business ,Science and technology - Abstract
This paper summarizes findings from the Small Aircraft Transportation System Higher Volume Operations Flight Experiment. The higher volume operations concept improves efficiency at nontowered, nonradar airports in instrument meteorological conditions. The success of the higher volume operations concept is based on pilot acceptability as determined through objective and subjective assessments when compared with the procedural control operations in use today at nontowered, nonradar-controlled airfields in instrument meteorological conditions. Flight experiment data indicate that the concept is viable. The experiment, flown on a general aviation aircraft, used a subset of the Higher Volume Operations Simulation Experiment scenarios and evaluation pilots to validate the simulation experiment results. Results reveal that all 12 low-time instrument-rated pilots preferred Small Aircraft Transportation System Higher Volume Operations when compared with current procedural separation operations. These pilots also flew the higher volume operations procedures safely and proficiently without additional workload in comparison to today's system. Detailed results of pilot flight technical error and their subjective assessments of workload and situation awareness are presented. DOI: 10.2514/1.20403
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- 2006
10. A new class of small molecule RNA polymerase inhibitors with activity against Rifampicin-resistant Staphylococcus aureus
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Arhin, Francis, Bélanger, Odette, Ciblat, Stéphane, Dehbi, Mohammed, Delorme, Daniel, Dietrich, Evelyne, Dixit, Dilip, Lafontaine, Yanick, Lehoux, Dario, Liu, Jing, McKay, Geoffrey A., Moeck, Greg, Reddy, Ranga, Rose, Yannick, Srikumar, Ramakrishnan, Tanaka, Kelly S.E., Williams, Daniel M., Gros, Philippe, Pelletier, Jerry, Parr, Thomas R., Jr., and Far, Adel Rafai
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- 2006
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11. Current Practices in Runway Configuration Management (RCM) and Arrival/Departure Runway Balancing (ADRB)
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Lohr, Gary W and Williams, Daniel M
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Aircraft Communications And Navigation - Abstract
Significant air traffic increases are anticipated for the future of the National Airspace System (NAS). To cope with future traffic increases, fundamental changes are required in many aspects of the air traffic management process including the planning and use of NAS resources. Two critical elements of this process are the selection of airport runway configurations, and the effective management of active runways. Two specific research areas in NASA's Airspace Systems Program (ASP) have been identified to address efficient runway management: Runway Configuration Management (RCM) and Arrival/Departure Runway Balancing (ADRB). This report documents efforts in assessing past as well as current work in these two areas.
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- 2008
12. Information Requirements for Supervisory Air Traffic Controllers in Support of a Wake Vortex Departure System
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Lohr, Gary W, Williams, Daniel M, and Trujillo, Anna C
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Air Transportation And Safety - Abstract
Closely Space Parallel Runway (CSPR) configurations are capacity limited for departures due to the requirement to apply wake vortex separation standards from traffic departing on the adjacent parallel runway. To mitigate the effects of this constraint, a concept focusing on wind dependent departure operations has been developed, known as the Wake Turbulence Mitigation for Departures (WTMD). This concept takes advantage of the fact that crosswinds of sufficient velocity blow wakes generated by aircraft departing from the downwind runway away from the upwind runway. Consequently, under certain conditions, wake separations on the upwind runway would not be required based on wakes generated by aircraft on the downwind runway, as is currently the case. It follows that information requirements, and sources for this information, would need to be determined for airport traffic control tower (ATCT) supervisory personnel who would be charged with decisions regarding use of the procedure. To determine the information requirements, data were collected from ATCT supervisors and controller-in-charge qualified individuals at Lambert-St. Louis International Airport (STL) and George Bush Houston Intercontinental Airport (IAH). STL and IAH were chosen as data collection sites based on the implementation of a WTMD prototype system, operating in shadow mode, at these locations. The 17 total subjects (STL: 5, IAH: 12) represented a broad-base of air traffic experience. Results indicated that the following information was required to support the conduct of WTMD operations: current and forecast weather information, current and forecast traffic demand and traffic flow restrictions, and WTMD System status information and alerting. Subjects further indicated that the requisite information is currently available in the tower cab with the exception of the WTMD status and alerting. Subjects were given a demonstration of a display supporting the prototype systems and unanimously stated that the WTMD status information they felt important was represented. Overwhelmingly, subjects felt that approving, monitoring and terminating the WTMD procedure could be integrated into their supervisory workload.
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- 2008
13. Wake Turbulence Mitigation for Arrivals (WTMA)
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Williams, Daniel M, Lohr, Gary W, and Trujillo, Anna C
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Air Transportation And Safety - Abstract
The preliminary Wake Turbulence Mitigation for Arrivals (WTMA) concept of operations is described in this paper. The WTMA concept provides further detail to work initiated by the Wake Vortex Avoidance System Concept Evaluation Team and is an evolution of the Wake Turbulence Mitigation for Departure concept. Anticipated benefits about reducing wake turbulence separation standards in crosswind conditions, and candidate WTMA system considerations are discussed.
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- 2008
14. Information Requirements for Supervisory Air Traffic Controllers in Support of a Mid-Term Wake Vortex Departure System
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Lohr, Gary W, Williams, Daniel M, Trujillo, Anna C, Johnson, Edward J, and Domino, David A
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Air Transportation And Safety - Abstract
A concept focusing on wind dependent departure operations has been developed the current version of this concept is called the Wake Turbulence Mitigation for Departures (WTMD). This concept takes advantage the fact that cross winds of sufficient velocity blow wakes generated by "heavy" and B757 category aircraft on the downwind runway away from the upwind runway. Supervisory Air Traffic Controllers would be responsible for authorization of the Procedure. An investigation of the information requirements necessary to for Supervisors to approve monitor and terminate the Procedure was conducted. Results clearly indicated that the requisite information is currently available in air traffic control towers and that additional information was not required.
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- 2008
15. Small Aircraft Transportation System Higher Volume Operations Concept
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Abbott, Terence S, Consiglio, Maria C, Baxley, Brian T, Williams, Daniel M, Jones, Kenneth M, and Adams, Catherine A
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Air Transportation And Safety - Abstract
This document defines the Small Aircraft Transportation System (SATS) Higher Volume Operations concept. The general philosophy underlying this concept is the establishment of a newly defined area of flight operations called a Self-Controlled Area (SCA). Within the SCA, pilots would take responsibility for separation assurance between their aircraft and other similarly equipped aircraft. This document also provides details for a number of off-nominal and emergency procedures which address situations that could be expected to occur in a future SCA. The details for this operational concept along with a description of candidate aircraft systems to support this concept are provided.
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- 2006
16. Point-to-Point! Validation of the Small Aircraft Transportation System Higher Volume Operations Concept
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Williams, Daniel M
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Air Transportation And Safety - Abstract
Described is the research process that NASA researchers used to validate the Small Aircraft Transportation System (SATS) Higher Volume Operations (HVO) concept. The four phase building-block validation and verification process included multiple elements ranging from formal analysis of HVO procedures to flight test, to full-system architecture prototype that was successfully shown to the public at the June 2005 SATS Technical Demonstration in Danville, VA. Presented are significant results of each of the four research phases that extend early results presented at ICAS 2004. HVO study results have been incorporated into the development of the Next Generation Air Transportation System (NGATS) vision and offer a validated concept to provide a significant portion of the 3X capacity improvement sought after in the United States National Airspace System (NAS).
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- 2006
17. Conflict Prevention and Separation Assurance Method in the Small Aircraft Transportation System
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Consiglio, Maria C, Carreno, Victor A, Williams, Daniel M, and Munoz, Cesar
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Air Transportation And Safety - Abstract
A multilayer approach to the prevention of conflicts due to the loss of aircraft-to-aircraft separation which relies on procedures and on-board automation was implemented as part of the SATS HVO Concept of Operations. The multilayer system gives pilots support and guidance during the execution of normal operations and advance warning for procedure deviations or off-nominal operations. This paper describes the major concept elements of this multilayer approach to separation assurance and conflict prevention and provides the rationale for its design. All the algorithms and functionality described in this paper have been implemented in an aircraft simulation in the NASA Langley Research Center s Air Traffic Operation Lab and on the NASA Cirrus SR22 research aircraft.
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- 2005
18. Small Aircraft Transportation System, Higher Volume Operations Concept: Off-Nominal Operations
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Abbott, Terence S, Consiglio, Maria C, Baxley, Brian T, Williams, Daniel M, and Conway, Sheila R
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Air Transportation And Safety - Abstract
This document expands the Small Aircraft Transportation System, (SATS) Higher Volume Operations (HVO) concept to include off-nominal conditions. The general philosophy underlying the HVO concept is the establishment of a newly defined area of flight operations called a Self-Controlled Area (SCA). During periods of poor weather, a block of airspace would be established around designated non-towered, non-radar airports. Aircraft flying enroute to a SATS airport would be on a standard instrument flight rules flight clearance with Air Traffic Control providing separation services. Within the SCA, pilots would take responsibility for separation assurance between their aircraft and other similarly equipped aircraft. Previous work developed the procedures for normal HVO operations. This document provides details for off-nominal and emergency procedures for situations that could be expected to occur in a future SCA.
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- 2005
19. Incorporating Data Link Features into a Multi-Function Display to Support Self-Separation and Spacing Tasks for General Aviation Pilots
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Adams, Catherine A, Murdoch, Jennifer L, Consiglio, Maria C, and WIlliams, Daniel M
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Air Transportation And Safety - Abstract
One objective of the Small Aircraft Transportation System (SATS) Higher Volume Operations (HVO) project is to increase the capacity and utilization of small non-towered, non-radar equipped airports by transferring traffic management activities to an automated Airport Management Module (AMM) and separation responsibilities to general aviation (GA) pilots. Implementation of this concept required the development of a research Multi-Function Display (MFD) to support the interactive communications between pilots and the AMM. The interface also had to accommodate traffic awareness, self-separation, and spacing tasks through dynamic messaging and symbology for flight path conformance and conflict detection and alerting (CDA). The display served as the mechanism to support the examination of the viability of executing instrument operations designed for SATS designated airports. Results of simulation and flight experiments conducted at the National Aeronautics and Space Administration's (NASA) Langley Research Center indicate that the concept, as facilitated by the research MFD, did not increase pilots subjective workload levels or reduce their situation awareness (SA). Post-test usability assessments revealed that pilots preferred using the enhanced MFD to execute flight procedures, reporting improved SA over conventional instrument flight rules (IFR) procedures.
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- 2005
20. The Small Aircraft Transportation System Higher Volume Operations (SATS HVO) Flight Experiment
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Williams, Daniel M, Murdoch, Jennifer L, and Adams, Catherine H
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Air Transportation And Safety - Abstract
This paper provides a summary of conclusions from the Small Aircraft Transportation System (SATS) Higher Volume Operations (HVO) Flight Experiment which NASA conducted to determine pilot acceptability of the HVO concept for normal conditions. The SATS HVO concept improves efficiency at non-towered, non-radar airports in Instrument Meteorological Conditions (IMC) while achieving a level of safety equal to today s system. Reported are results from flight experiment data that indicate that the SATS HVO concept is viable. The success of the SATS HVO concept is based on acceptable pilot workload, performance, and subjective criteria when compared to the procedural control operations in use today at non-towered, non-radar controlled airfields in IMC. The HVO Flight Experiment, flown on NASA's Cirrus SR22, used a subset of the HVO Simulation Experiment scenarios and evaluation pilots in order to validate the simulation experiment results. HVO and Baseline (today s system) scenarios flown included: single aircraft arriving for a GPS non-precision approach; aircraft arriving for the approach with multiple traffic aircraft; and aircraft arriving for the approach with multiple traffic aircraft and then conducting a missed approach. Results reveal that all twelve low-time instrument-rated pilots preferred SATS HVO when compared to current procedural separation operations. These pilots also flew the HVO procedures safely and proficiently without additional workload in comparison to today s system (Baseline). Detailed results of pilot flight technical error, and their subjective assessments of workload and situation awareness are presented in this paper.
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- 2005
21. Flight Technical Error Analysis of the SATS Higher Volume Operations Simulation and Flight Experiments
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Williams, Daniel M, Consiglio, Maria C, Murdoch, Jennifer L, and Adams, Catherine H
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Air Transportation And Safety - Abstract
This paper provides an analysis of Flight Technical Error (FTE) from recent SATS experiments, called the Higher Volume Operations (HVO) Simulation and Flight experiments, which NASA conducted to determine pilot acceptability of the HVO concept for normal operating conditions. Reported are FTE results from simulation and flight experiment data indicating the SATS HVO concept is viable and acceptable to low-time instrument rated pilots when compared with today s system (baseline). Described is the comparative FTE analysis of lateral, vertical, and airspeed deviations from the baseline and SATS HVO experimental flight procedures. Based on FTE analysis, all evaluation subjects, low-time instrument-rated pilots, flew the HVO procedures safely and proficiently in comparison to today s system. In all cases, the results of the flight experiment validated the results of the simulation experiment and confirm the utility of the simulation platform for comparative Human in the Loop (HITL) studies of SATS HVO and Baseline operations.
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- 2005
22. Small Aircraft Transportation System, Higher Volume Operations Concept: Normal Operations
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Abbott, Terence S, Jones, Kenneth M, Consiglio, Maria C, Williams, Daniel M, and Adams, Catherine A
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Air Transportation And Safety - Abstract
This document defines the Small Aircraft Transportation System (SATS), Higher Volume Operations (HVO) concept for normal conditions. In this concept, a block of airspace would be established around designated non-towered, non-radar airports during periods of poor weather. Within this new airspace, pilots would take responsibility for separation assurance between their aircraft and other similarly equipped aircraft. Using onboard equipment and procedures, they would then approach and land at the airport. Departures would be handled in a similar fashion. The details for this operational concept are provided in this document.
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- 2004
23. Concept of Operations for Commercial and Business Aircraft Synthetic Vision Systems
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Williams Daniel M, Waller, Marvin C, Koelling, John H, Burdette, Daniel W, Capron, William R, Barry, John S, Gifford, Richard B, and Doyle, Thomas M
- Subjects
Air Transportation And Safety - Abstract
A concept of operations (CONOPS) for the Commercial and Business (CaB) aircraft synthetic vision systems (SVS) is described. The CaB SVS is expected to provide increased safety and operational benefits in normal and low visibility conditions. Providing operational benefits will promote SVS implementation in the Net, improve aviation safety, and assist in meeting the national aviation safety goal. SVS will enhance safety and enable consistent gate-to-gate aircraft operations in normal and low visibility conditions. The goal for developing SVS is to support operational minima as low as Category 3b in a variety of environments. For departure and ground operations, the SVS goal is to enable operations with a runway visual range of 300 feet. The system is an integrated display concept that provides a virtual visual environment. The SVS virtual visual environment is composed of three components: an enhanced intuitive view of the flight environment, hazard and obstacle defection and display, and precision navigation guidance. The virtual visual environment will support enhanced operations procedures during all phases of flight - ground operations, departure, en route, and arrival. The applications selected for emphasis in this document include low visibility departures and arrivals including parallel runway operations, and low visibility airport surface operations. These particular applications were selected because of significant potential benefits afforded by SVS.
- Published
- 2001
24. Proton demand inversion in a mutant protein tyrosine kinase reaction
- Author
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Williams, Daniel M. and Cole, Philip A.
- Subjects
Phosphorylation -- Research ,Mutagenesis -- Research ,Tyrosine -- Research ,Tyrosine -- Chemical properties ,Chemistry - Abstract
The complementarity of site-directed mutagenesis and synthetic substrate analogues are used to investigate the dissociative mechanistic model for protein tyrosine kinase-catalyzed reaction and use of substrate neutral phenol in phosphorylation reaction, instead of chemically more reactive phenoxide anion.
- Published
- 2002
25. Paroxysmal Hypnogenic Dyskinesia Responsive to Doxylamine: A Case Report
- Author
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Williams, Daniel M.
- Subjects
Article Subject ,otorhinolaryngologic diseases - Abstract
Paroxysmal hypnogenic dyskinesia is a rare clinical entity characterized by intermittent dystonia and choreoathetoid movements that begin exclusively during sleep, often with consciousness preserved once the patient is awakened during the episodes. They occur almost every night and are often misdiagnosed as sleeping disorders. Paroxysmal hypnogenic dyskinesia is currently known to be a form of frontal lobe epilepsy, but not in all cases. We present a 19-year-old male patient with paroxysmal hypnogenic dyskinesia who responded to antihistamines. This supports an alternative theory from 1977 (before the cases had been adequately described) that the disorder lies in dysregulation in the basal ganglia. This description now appears similar to acute dystonic reactions such as extrapyramidal symptoms from antipsychotic medications, which also respond to antihistamines.
- Published
- 2012
- Full Text
- View/download PDF
26. Hip arthroscopy for osteochondral loose body removal after a posterior hip dislocation
- Author
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Svoboda, Steven J, Williams, Daniel M, and Murphy, Kevin P
- Published
- 2003
- Full Text
- View/download PDF
27. Kinase chips hit the proteomics era.
- Author
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Williams, Daniel M. and Cole, Philip A.
- Subjects
- *
PROTEIN kinases , *YEAST , *PHOSPHORYLATION , *GENETICS - Abstract
Deals with the use of protein kinase chips to evaluate the protein kinases encoded by the yeast genome. Examination of kinases ability to phosphorylate using the chips; Processes involved in the assays of protein kinase activity; Information on how the protein chip technology works; Discussion on other techniques to assess protein kinase function.
- Published
- 2001
- Full Text
- View/download PDF
28. Chemical Approaches to Reversible Protein Phosphorylation.
- Author
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Cole, Philip A., Courtney, Aliya D., Shen, Kui, Zhang, Zhongsen, Qiao, Yingfeng, Lu, Wei, and Williams, Daniel M.
- Published
- 2003
- Full Text
- View/download PDF
29. Csk, a Critical Link of G Protein Signals to Actin Cytoskeletal Reorganization.
- Author
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Lowry, William E., Huang, Jianyun, Ma, Yong-Chao, Ali, Shariq, Wang, Dongxia, Williams, Daniel M., Okada, Masato, Cole, Philip A., and Huang, Xin-Yun
- Subjects
- *
G proteins , *ACTIN , *CYTOSKELETON - Abstract
Heterotrimeric G proteins can signal to reorganize the actin cytoskeleton, but the mechanism is unclear. Here we report that, in tyrosine kinase Csk-deficient mouse embryonic fibroblast cells, G protein (Gβγ, Gα12, Gα13, and Gαq)-induced, and G protein-coupled receptor-induced, actin stress fiber formation was completely blocked. Reintroduction of Csk into Csk-deficent cells restored the G protein-induced actin stress fiber formation. Chemical rescue experiments with catalytic mutants of Csk demonstrated that the catalytic activity of Csk was required for this process. Furthermore, we uncovered that Gβγ can both translocate Csk to the plasma membrane and directly increase Csk kinase activity. Our genetic and biochemical studies demonstrate that Csk plays a critical role in mediating G protein signals to actin cytoskeletal reorganization. [Copyright &y& Elsevier]
- Published
- 2002
- Full Text
- View/download PDF
30. Assessment of endocytic traffic and Ocrl function in the developing zebrafish neuroepithelium.
- Author
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Williams DM, Gungordu L, Jackson-Crawford A, and Lowe M
- Subjects
- Animals, Carrier Proteins metabolism, Endocytosis, Ligands, Lipoproteins, LDL metabolism, Zebrafish metabolism, Oculocerebrorenal Syndrome, Phosphoric Monoester Hydrolases metabolism, Zebrafish Proteins metabolism
- Abstract
Endocytosis allows cells to internalise a wide range of molecules from their environment and to maintain their plasma membrane composition. It is vital during development and for maintenance of tissue homeostasis. The ability to visualise endocytosis in vivo requires suitable assays to monitor the process. Here, we describe imaging-based assays to visualise endocytosis in the neuroepithelium of living zebrafish embryos. Injection of fluorescent tracers into the brain ventricles followed by live imaging was used to study fluid-phase or receptor-mediated endocytosis, for which we used receptor-associated protein (RAP, encoded by Lrpap1) as a ligand for low-density lipoprotein receptor-related protein (LRP) receptors. Using dual-colour imaging combined with expression of endocytic markers, it is possible to track the progression of endocytosed tracers and to monitor trafficking dynamics. Using these assays, we reveal a role for the Lowe syndrome protein Ocrl in endocytic trafficking within the neuroepithelium. We also found that the RAP-binding receptor Lrp2 (encoded by lrp2a) appears to contribute only partially to neuroepithelial RAP endocytosis. Altogether, our results provide a basis to track endocytosis within the neuroepithelium in vivo and support a role for Ocrl in this process. This article has an associated First Person interview with the first author of the paper., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2022. Published by The Company of Biologists Ltd.)
- Published
- 2022
- Full Text
- View/download PDF
31. Bacillus anthracis lethal toxin reduces human alveolar epithelial barrier function.
- Author
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Langer M, Duggan ES, Booth JL, Patel VI, Zander RA, Silasi-Mansat R, Ramani V, Veres TZ, Prenzler F, Sewald K, Williams DM, Coggeshall KM, Awasthi S, Lupu F, Burian D, Ballard JD, Braun A, and Metcalf JP
- Subjects
- Actins metabolism, Alveolar Epithelial Cells cytology, Alveolar Epithelial Cells metabolism, Alveolar Epithelial Cells microbiology, Animals, Anthrax microbiology, Antigens, Bacterial genetics, Bacillus anthracis genetics, Bacillus anthracis metabolism, Bacterial Toxins genetics, Calcium-Binding Proteins genetics, Calcium-Binding Proteins metabolism, Cells, Cultured, Humans, Membrane Proteins genetics, Membrane Proteins metabolism, Mice, Mixed Function Oxygenases genetics, Mixed Function Oxygenases metabolism, Muscle Proteins genetics, Muscle Proteins metabolism, Receptors, Peptide genetics, Receptors, Peptide metabolism, Respiratory Tract Infections microbiology, Virulence, Alveolar Epithelial Cells drug effects, Anthrax pathology, Antigens, Bacterial toxicity, Bacillus anthracis pathogenicity, Bacterial Toxins toxicity, Respiratory Tract Infections pathology
- Abstract
The lung is the site of entry for Bacillus anthracis in inhalation anthrax, the deadliest form of the disease. Bacillus anthracis produces virulence toxins required for disease. Alveolar macrophages were considered the primary target of the Bacillus anthracis virulence factor lethal toxin because lethal toxin inhibits mouse macrophages through cleavage of MEK signaling pathway components, but we have reported that human alveolar macrophages are not a target of lethal toxin. Our current results suggest that, unlike human alveolar macrophages, the cells lining the respiratory units of the lung, alveolar epithelial cells, are a target of lethal toxin in humans. Alveolar epithelial cells expressed lethal toxin receptor protein, bound the protective antigen component of lethal toxin, and were subject to lethal-toxin-induced cleavage of multiple MEKs. These findings suggest that human alveolar epithelial cells are a target of Bacillus anthracis lethal toxin. Further, no reduction in alveolar epithelial cell viability was observed, but lethal toxin caused actin rearrangement and impaired desmosome formation, consistent with impaired barrier function as well as reduced surfactant production. Therefore, by compromising epithelial barrier function, lethal toxin may play a role in the pathogenesis of inhalation anthrax by facilitating the dissemination of Bacillus anthracis from the lung in early disease and promoting edema in late stages of the illness.
- Published
- 2012
- Full Text
- View/download PDF
32. Chemical approaches to reversible protein phosphorylation.
- Author
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Cole PA, Courtney AD, Shen K, Zhang Z, Qiao Y, Lu W, and Williams DM
- Subjects
- Amino Acid Sequence, Drug Design, Enzyme Inhibitors chemistry, Enzyme Inhibitors pharmacology, Phosphorylation drug effects, Protein Kinase Inhibitors, Protein Kinases genetics, Signal Transduction drug effects, Protein Kinases metabolism, Proteins chemistry, Proteins metabolism
- Abstract
Protein phosphorylation catalyzed by protein kinases plays a critical role in cellular signaling. Here we review several chemical approaches to understanding protein kinases and the consequences of protein phosphorylation. We discuss the design of bisubstrate analogue inhibitors based on a dissociative transition state, the development of reagents for cross-linking protein kinases with their substrates, the chemical rescue of mutant protein tyrosine kinases, and the application of expressed protein ligation to understanding protein phosphorylation.
- Published
- 2003
- Full Text
- View/download PDF
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