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Articles 1 - 11 of 11
Full-Text Articles in Operations Research, Systems Engineering and Industrial Engineering
Genetically Attenuated Plasmodium Berghei Liver Stages Induce Sterile Protracted Protection That Is Mediated By Major Histocompatibility Complex Class I–Dependent Interferon-Y–Producing Cd8+ T Cells, Ousman Jobe, Joanne Lumsden, Ann-Kristin Mueller, Jackie Williams, Hilda Silva-Rivera, Stefan H. I. Kappe, Robert J. Schwenk, Kai Matuschewski, Urszula Krzych
Genetically Attenuated Plasmodium Berghei Liver Stages Induce Sterile Protracted Protection That Is Mediated By Major Histocompatibility Complex Class I–Dependent Interferon-Y–Producing Cd8+ T Cells, Ousman Jobe, Joanne Lumsden, Ann-Kristin Mueller, Jackie Williams, Hilda Silva-Rivera, Stefan H. I. Kappe, Robert J. Schwenk, Kai Matuschewski, Urszula Krzych
US Army Research
At present, radiation-attenuated plasmodia sporozoites (y-spz) is the only vaccine that induces sterile and lasting protection in malaria-naive humans and laboratory rodents. However, g-spz are not without risks. For example, the heterogeneity of the y-spz could explain occasional breakthrough infections. To avoid this possibility, we constructed a double-knockout P. berghei parasite by removing 2 genes, UIS3 and UIS4, that are up-regulated in infective spz.We evaluated the double-knockout Pbuis3(-)/4(-) parasites for protective efficacy and the contribution of CD8+ T cells to protection. Pbuis3(-)/4(-) spz induced sterile and protracted protection in C57BL/6 mice. Protection was linked to CD8+ …
A Dendroclimatic Record Of Paleoclimate Of The Last 10,000 Years, Glacier Bay National Park And Preserve: Progress Understanding Climate Change In Southeast Alaska, Daniel Lawson, Greg Wiles, David Finnegan
A Dendroclimatic Record Of Paleoclimate Of The Last 10,000 Years, Glacier Bay National Park And Preserve: Progress Understanding Climate Change In Southeast Alaska, Daniel Lawson, Greg Wiles, David Finnegan
US Army Research
Our investigations in 2007 focused on continuing collection and analyses of tree rings from living trees and building a long ring-width series from interstadial wood. These interstadial forests were extensive and their preservation, although discontinuous and fragmented, is remarkable. In situ stumps, still rooted in growth position, and logs held within sediments remain from forests that existed at various times between glaciations over approximately the last 10,000 years.
We have analyzed previous and new collections of ring-width tree-ring series, including a multiple species collection from near Excursion Ridge in the southeast portion of the Park. These tree-ring series have a …
Weak Base Dispiro-1,2,4-Trioxolanes: Potent Antimalarial Ozonides, Yuanqing Tang, Yuxiang Dong, Sergio Wittlin, Susan A. Charman, Jacques Chollet, Francis C. K. Chiu, William N. Charman, Hugues Matile, Heinrich Urwyler, Arnulf Dorn, Saroj Bajpai, Xiaofang Wang, Maniyan Padmanilayam, Jean M. Karle, Reto Brun, Jonathan L. Vennerstrom
Weak Base Dispiro-1,2,4-Trioxolanes: Potent Antimalarial Ozonides, Yuanqing Tang, Yuxiang Dong, Sergio Wittlin, Susan A. Charman, Jacques Chollet, Francis C. K. Chiu, William N. Charman, Hugues Matile, Heinrich Urwyler, Arnulf Dorn, Saroj Bajpai, Xiaofang Wang, Maniyan Padmanilayam, Jean M. Karle, Reto Brun, Jonathan L. Vennerstrom
US Army Research
Thirty weak base 1,2,4-dispiro trioxolanes (secondary ozonides) were synthesized. Amino amide trioxolanes had the best combination of antimalarial and biopharmaceutical properties. Guanidine, aminoxy, and amino acid trioxolanes had poor antimalarial activity. Lipophilic trioxolanes were less stable metabolically than their more polar counterparts.
Phase I Dose Escalation Safety And Immunogenicity Trial Of Plasmodium Falciparum Apical Membrane Protein (Ama-1) Fmp2.1, Adjuvanted With As02a, In Malaria-Naive Adults At The Walter Reed Army Institute Of Research, Mark E. Polhemus, Alan J. Magill, James F. Cummings, Kent E. Kester, Chris F. Ockenhouse, David E. Lanar, Sheetij Dutta, Arnoldo Barbosa, Lorraine Soisson, Carter L. Diggs, Sally A. Robinson, John D. Haynes, V. Ann Stewart, Lisa A. Ware, Clara Brando, Urszula Krzych, Robert A. Bowden, Joe D. Cohen, Marie-Claude Dubois, Opokua Ofori-Anyinam, Els De-Kock, W. Ripley Ballou, D. Gray Heppner Jr.
Phase I Dose Escalation Safety And Immunogenicity Trial Of Plasmodium Falciparum Apical Membrane Protein (Ama-1) Fmp2.1, Adjuvanted With As02a, In Malaria-Naive Adults At The Walter Reed Army Institute Of Research, Mark E. Polhemus, Alan J. Magill, James F. Cummings, Kent E. Kester, Chris F. Ockenhouse, David E. Lanar, Sheetij Dutta, Arnoldo Barbosa, Lorraine Soisson, Carter L. Diggs, Sally A. Robinson, John D. Haynes, V. Ann Stewart, Lisa A. Ware, Clara Brando, Urszula Krzych, Robert A. Bowden, Joe D. Cohen, Marie-Claude Dubois, Opokua Ofori-Anyinam, Els De-Kock, W. Ripley Ballou, D. Gray Heppner Jr.
US Army Research
We report the first safety and immunogenicity trial of the Plasmodium falciparum vaccine candidate FMP2.1/AS02A, a recombinant E. coli-expressed protein based upon the apical membrane antigen-1 (AMA-1) of the 3D7 clone formulated with the AS02A adjuvant. We conducted an open-label, staggered-start, dose-escalating Phase I trial in 23 malaria-naıve volunteers who received 8, 20 or 40 _g of FMP2.1 in a fixed volume of 0.5mL of AS02A on a 0, 1, and 2 month schedule. Nineteen of 23 volunteers received all three scheduled immunizations. The most frequent solicited local and systemic adverse events associated with immunization were injection site pain (68%) …
An In Vitro Comparative Study On The Reactivation Of Nerve Agent-Inhibited Guinea Pig And Human Acetylcholinesterases By Oximes, Chunyuan Luo, Min Tong, Nageswararao Chilukuri, Karen Brecht, Donald M. Maxwell, Ashima Saxena
An In Vitro Comparative Study On The Reactivation Of Nerve Agent-Inhibited Guinea Pig And Human Acetylcholinesterases By Oximes, Chunyuan Luo, Min Tong, Nageswararao Chilukuri, Karen Brecht, Donald M. Maxwell, Ashima Saxena
US Army Research
The reactivation of nerve agent-inhibited acetylcholinesterase (AChE) by oxime is the most important step in the treatment of nerve agent poisoning. Since the evaluation of nerve agent antidotes cannot be conducted in humans, results from animal experiments are extrapolated to humans. Guinea pig is one of the animal models that is frequently used for conducting nerve agent antidote evaluations. Several investigations have demonstrated that the efficacy of an oxime primarily depends on its ability to reactivate nerve agent-inhibited AChE. If the in Vitro oxime reactivation of nerve agent-inhibited animal AChE is similar to that of human AChE, it is likely …
Synthesis And Antimalarial Activity Of New Isotebuquine Analogues, Olga V. Miroshnikova, Thomas H. Hudson, Lucia Gerena, Dennis E. Kyle, Ai J. Lin
Synthesis And Antimalarial Activity Of New Isotebuquine Analogues, Olga V. Miroshnikova, Thomas H. Hudson, Lucia Gerena, Dennis E. Kyle, Ai J. Lin
US Army Research
Amodiaquine (AQ) and tebuquine are 4-aminoquinoline antimalarials with Mannich base side chain and are highly effective against chloroquine (CQ)-resistant strains of Plasmodium falciparum. Clinical use of AQ has been severely restricted due to hepatoxicity and agranulocytosis side effects associated with its long term use. Lysosomal accumulation and bioactivation to generate reactive quinoneimine metabolite are implicated to be the cause of the observed AQ toxicities. To avoid the quinoneimine formation and thus the toxicity, a series of isotebuquine analogues and their Nω-oxides with hydroxy group meta to the amino rather than in para position of the aniline moiety …
Remediation Of Rdx- And Hmx-Contaminated Groundwater Using Organic Mulch Permeable Reactive Barriers, Farrukh Ahmad, Stephen P. Schnitker, Charles J. Newell
Remediation Of Rdx- And Hmx-Contaminated Groundwater Using Organic Mulch Permeable Reactive Barriers, Farrukh Ahmad, Stephen P. Schnitker, Charles J. Newell
US Army Research
Organic mulch is a complex organic material that is typically populated with its own consortium of microorganisms. The organisms in mulch breakdown complex organics to soluble carbon, which can then be used by these and other microorganisms as an electron donor for treating RDX and HMX via reductive pathways. A bench-scale treatability study with organic mulch was conducted for the treatment of RDX- and HMX-contaminated groundwater obtained from a plume at the Pueblo Chemical Depot (PCD) in Pueblo, Colorado. The site-specific cleanup criteria of 0.55 ppb RDX and 602 ppb HMX were used as the logical goals of the study. …
Army Research Needs For Automated Neuropsychological Tests: Monitoring Soldier Health And Performance Status, Karl E. Friedl, Stephen J. Grate, Susan P. Proctor, James W. Ness, Brian J. Lukey, Robert L. Kane
Army Research Needs For Automated Neuropsychological Tests: Monitoring Soldier Health And Performance Status, Karl E. Friedl, Stephen J. Grate, Susan P. Proctor, James W. Ness, Brian J. Lukey, Robert L. Kane
US Army Research
Information on the mental status of soldiers operating at the limits of human tolerance will be vital to their management in future deployments; it may also allow earlier intervention for conditions such as undiagnosed Gulf War illnesses and Parkinson’s Disease. The Army needs a parsimonious set of neuropsychological tests that reliably identify subtle changes for: (1) early detection of individual health and military performance impairments and (2) management of occupational and deployment health risks. Testing must characterize cognitive lapses in healthy individuals faced with relevant operational stressors (i.e., anxiety, information overload, thermal strain, hypoxia, fatigue, head impact, chemical or radiation …
Thermally Driven Assembly Of Nanoparticles In Polymer Matrices, Philip J. Costanzo, Frederick L. Beyer
Thermally Driven Assembly Of Nanoparticles In Polymer Matrices, Philip J. Costanzo, Frederick L. Beyer
US Army Research
Thermally responsive bulk polymer films utilizing reversible Diels-Alder chemistry have been developed. Gold nanoparticles (AuNPs) were passivated with thiol-terminated poly(styrene)-b-poly(ethylene glycol) (PS-b-PEG) copolymer ligand, where the PS and PEG blocks are joined via a Diels-Alder (DA) linkage. The ligand-functionalized nanoparticles were dispersed within a microphase-separated PS-b-poly(methyl methacrylate) (PS-b-PMMA) block copolymer. Nanoparticle location was dictated by the compatibility of the external shell with the block copolymer matrix. As cast, the PEG shell compatibilized the nanoparticles with the PMMA domains. Subsequent thermal treatment caused the Diels-Alder linkages between the polymer blocks to dissociate, leaving the AuNPs functionalized by PS ligands. Immiscibility within …
Improved Formulation Of A Recombinant Ricin A-Chain Vaccine Iincreases Its Stability And Effective Antigenicity, John H. Carra, Robert W. Wannemacher, Ralph F. Tammariello, Changhong Y. Lindsey, Richard E. Dinterman, Rowena D. Schokman, Leonard A. Smith
Improved Formulation Of A Recombinant Ricin A-Chain Vaccine Iincreases Its Stability And Effective Antigenicity, John H. Carra, Robert W. Wannemacher, Ralph F. Tammariello, Changhong Y. Lindsey, Richard E. Dinterman, Rowena D. Schokman, Leonard A. Smith
US Army Research
Ricin is a potent toxin associated with bioterrorism for which no vaccine or specific countermeasures are currently available. A stable, non-toxic and immunogenic recombinant ricin A-chain vaccine (RTA 1-33/44-198) has been developed by protein engineering. We identified optimal formulation conditions for this vaccine under which it remained stable and potent in storage for up to 18 months, and resisted multiple rounds of freeze–thawing without stabilizing co-solvents. Reformulation from phosphate buffer to succinate buffer increased adherence of the protein to aluminum hydroxide adjuvant from 15 to 91%, with a concomitant increase of nearly threefold in effective antigenicity in a mouse model. …
A Refined Pharmacophore Identifies Potent 4-Amino-7-Chloroquinoline-Based Inhibitors Of The Botulinum Neurotoxin Serotype A Metalloprotease, James C. Burnett, Dejan Opsenica, Kamaraj Sriraghavan, Rekha G. Panchal, Gordon Ruthel, Ann R. Hermone, Tam L. Nguyen, Tara A. Kenny, Douglas J. Lane, Connor F. Mcgrath, James J. Schmidt, Jonathan L. Vennerstrom, Rick Gussio, Bogdan A. Solaja, Sina Bavari
A Refined Pharmacophore Identifies Potent 4-Amino-7-Chloroquinoline-Based Inhibitors Of The Botulinum Neurotoxin Serotype A Metalloprotease, James C. Burnett, Dejan Opsenica, Kamaraj Sriraghavan, Rekha G. Panchal, Gordon Ruthel, Ann R. Hermone, Tam L. Nguyen, Tara A. Kenny, Douglas J. Lane, Connor F. Mcgrath, James J. Schmidt, Jonathan L. Vennerstrom, Rick Gussio, Bogdan A. Solaja, Sina Bavari
US Army Research
We previously identified structurally diverse small molecule (non-peptidic) inhibitors (SMNPIs) of the botulinum neurotoxin serotype A (BoNT/A) light chain (LC). Of these, several (including antimalarial drugs) contained a 4-amino-7-chloroquinoline (ACQ) substructure and a separate positive ionizable amine component. The same antimalarials have also been found to interfere with BoNT/A translocation into neurons, via pH elevation of the toxin-mediated endosome. Thus, this structural class of small molecules may serve as dual-function BoNT/A inhibitors. In this study, we used a refined pharmacophore for BoNT/A LC inhibition to identify four new, potent inhibitors of this structural class (IC50’s ranged from 3.2 to 17 …