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Search Results: 1 - 10 of 183008 matches for " Mark E. Polhemus "
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Antigen-Displaying Lipid-Enveloped PLGA Nanoparticles as Delivery Agents for a Plasmodium vivax Malaria Vaccine
James J. Moon, Heikyung Suh, Mark E. Polhemus, Christian F. Ockenhouse, Anjali Yadava, Darrell J. Irvine
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0031472
Abstract: The parasite Plasmodium vivax is the most frequent cause of malaria outside of sub-Saharan Africa, but efforts to develop viable vaccines against P. vivax so far have been inadequate. We recently developed pathogen-mimicking polymeric vaccine nanoparticles composed of the FDA-approved biodegradable polymer poly(lactide-co-glycolide) acid (PLGA) “enveloped” by a lipid membrane. In this study, we sought to determine whether this vaccine delivery platform could be applied to enhance the immune response against P. vivax sporozoites. A candidate malaria antigen, VMP001, was conjugated to the lipid membrane of the particles, and an immunostimulatory molecule, monophosphoryl lipid A (MPLA), was incorporated into the lipid membranes, creating pathogen-mimicking nanoparticle vaccines (VMP001-NPs). Vaccination with VMP001-NPs promoted germinal center formation and elicited durable antigen-specific antibodies with significantly higher titers and more balanced Th1/Th2 responses in vivo, compared with vaccines composed of soluble protein mixed with MPLA. Antibodies raised by NP vaccinations also exhibited enhanced avidity and affinity toward the domains within the circumsporozoite protein implicated in protection and were able to agglutinate live P. vivax sporozoites. These results demonstrate that these VMP001-NPs are promising vaccines candidates that may elicit protective immunity against P. vivax sporozoites.
A Global Map of Suitability for Coastal Vibrio cholerae Under Current and Future Climate Conditions
Luis E. Escobar,Sadie J. Ryan,Anna M. Stewart-Ibarra,Julia L. Finkelstein,Christine A. King,Huijie Qiao,Mark E. Polhemus
Quantitative Biology , 2015, DOI: 10.1016/j.actatropica.2015.05.028
Abstract: Vibrio cholerae is a globally distributed water-borne pathogen that causes severe diarrheal disease and mortality, with current outbreaks as part of the seventh pandemic. Further understanding of the role of environmental factors in potential pathogen distribution and corresponding V. cholerae disease transmission over time and space is urgently needed to target surveillance of cholera and other climate and water-sensitive diseases. We used an ecological niche model (ENM) to identify environmental variables associated with V. cholerae presence in marine environments, to project a global model of V. cholerae distribution in ocean waters under current and future climate scenarios. We generated an ENM using published reports of V. cholerae in seawater and freely available remotely sensed imagery. Models indicated that factors associated with V. cholerae presence included chlorophyll-a, pH, and sea surface temperature (SST), with chlorophyll-a demonstrating the greatest explanatory power from variables selected for model calibration. We identified specific geographic areas for potential V. cholerae distribution. Coastal Bangladesh, where cholera is endemic, was found to be environmentally similar to coastal areas in Latin America. In a conservative climate change scenario, we observed a predicted increase in areas with environmental conditions suitable for V. cholerae. Findings highlight the potential for vulnerability maps to inform cholera surveillance, early warning systems, and disease prevention and control.
A Randomized Controlled Trial of Local Heat Therapy Versus Intravenous Sodium Stibogluconate for the Treatment of Cutaneous Leishmania major Infection
Naomi E. Aronson ,Glenn W. Wortmann,William R. Byrne,Robin S. Howard,Wendy B. Bernstein,Mary A. Marovich,Mark E. Polhemus,In-Kyu Yoon,Kelly A. Hummer,Robert A. Gasser Jr,Charles N. Oster,Paul M. Benson
PLOS Neglected Tropical Diseases , 2010, DOI: 10.1371/journal.pntd.0000628
Abstract: Background Cutaneous Leishmania major has affected many travelers including military personnel in Iraq and Afghanistan. Optimal treatment for this localized infection has not been defined, but interestingly the parasite is thermosensitive. Methodology/Principal Findings Participants with parasitologically confirmed L. major infection were randomized to receive intravenous sodium stibogluconate (SSG) 20mg/kg/day for ten doses or localized ThermoMed (TM) device heat treatment (applied at 50°C for 30 seconds) in one session. Those with facial lesions, infection with other species of Leishmania, or more than 20 lesions were excluded. Primary outcome was complete re-epithelialization or visual healing at two months without relapse over 12 months. Fifty-four/56 enrolled participants received intervention, 27 SSG and 27 TM. In an intent to treat analysis the per subject efficacy at two months with 12 months follow-up was 54% SSG and 48% TM (p = 0.78), and the per lesion efficacy was 59% SSG and 73% TM (p = 0.053). Reversible abdominal pain/pancreatitis, arthralgias, myalgias, headache, fatigue, mild cytopenias, and elevated transaminases were more commonly present in the SSG treated participants, whereas blistering, oozing, and erythema were more common in the TM arm. Conclusions/Significance Skin lesions due to L. major treated with heat delivered by the ThermoMed device healed at a similar rate and with less associated systemic toxicity than lesions treated with intravenous SSG. Clinical Trial Registration ClinicalTrials.gov NCT 00884377
Impact of RTS,S/AS02A and RTS,S/AS01B on Genotypes of P. falciparum in Adults Participating in a Malaria Vaccine Clinical Trial
John N. Waitumbi,Samuel B. Anyona,Carol W. Hunja,Carolyne M. Kifude,Mark E. Polhemus,Douglas S. Walsh,Chris F. Ockenhouse,D. Gray Heppner Jr,Amanda Leach,Marc Lievens,W. Ripley Ballou,Joe D. Cohen,Colin J. Sutherland
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0007849
Abstract: RTS,S, a candidate vaccine for malaria, is a recombinant protein expressed in yeast containing part of the circumsporozoite protein (CSP) sequence of 3D7 strain of Plasmodium falciparum linked to the hepatitis B surface antigen in a hybrid protein. The RTS,S antigen is formulated with GSK Biologicals' proprietary Adjuvant Systems AS02A or AS01B. A recent trial of the RTS,S/AS02A and RTS,S/AS01B vaccines evaluated safety, immunogenicity and impact on the development of parasitemia of the two formulations. Parasite isolates from this study were used to determine the molecular impact of RTS,S/AS02A and RTS,S/AS01B on the multiplicity of infection (MOI) and the csp allelic characteristics of subsequent parasitemias.
Evaluation of RTS,S/AS02A and RTS,S/AS01B in Adults in a High Malaria Transmission Area
Mark E. Polhemus, Shon A. Remich, Bernhards R. Ogutu, John N. Waitumbi, Lucas Otieno, Stella Apollo, James F. Cummings, Kent E. Kester, Christian F. Ockenhouse, Ann Stewart, Opokua Ofori-Anyinam, Isabelle Ramboer, Conor P. Cahill, Marc Lievens, Marie-Claude Dubois, Marie-Ange Demoitie, Amanda Leach, Joe Cohen, W. Ripley Ballou, D. Gray Heppner
PLOS ONE , 2009, DOI: 10.1371/journal.pone.0006465
Abstract: Background This study advances the clinical development of the RTS,S/AS01B candidate malaria vaccine to malaria endemic populations. As a primary objective it compares the safety and reactogenicity of RTS,S/AS01B to the more extensively evaluated RTS,S/AS02A vaccine. Methodology A Phase IIb, single centre, double-blind, controlled trial of 6 months duration with a subsequent 6 month single-blind follow-up conducted in Kisumu West District, Kenya between August 2005 and August 2006. 255 healthy adults aged 18 to 35 years were randomized (1:1:1) to receive 3 doses of RTS,S/AS02A, RTS,S/AS01B or rabies vaccine (Rabipur?; Chiron Behring GmbH) at months 0, 1, 2. The primary objective was the occurrence of severe (grade 3) solicited or unsolicited general (i.e. systemic) adverse events (AEs) during 7 days follow up after each vaccination. Principal Findings Both candidate vaccines had a good safety profile and were well tolerated. One grade 3 systemic AE occurred within 7 days of vaccination (RTS,S/AS01B group). No unsolicited AEs or SAEs were related to vaccine. A marked increase in anti-CS antibody GMTs was observed post Dose 2 of both RTS,S/AS01B (31.6 EU/mL [95% CI: 23.9 to 41.6]) and RTS,S/AS02A (16.7 EU/mL [95% CI: 12.9 to 21.7]). A further increase was observed post Dose 3 in both the RTS,S/AS01B (41.4 EU/mL [95% CI: 31.7 to 54.2]) and RTS,S/AS02A (21.4 EU/mL [95% CI: 16.0 to 28.7]) groups. Anti-CS antibody GMTs were significantly greater with RTS,S/AS01B compared to RTS,S/AS02A at all time points post Dose 2 and Dose 3. Both candidate vaccines produced strong anti-HBs responses. Vaccine efficacy in the RTS,S/AS01B group was 29.5% (95% CI: ?15.4 to 56.9, p = 0.164) and in the RTS,S/AS02A group 31.7% (95% CI: ?11.6 to 58.2, p = 0.128). Conclusions Both candidate malaria vaccines were well tolerated over a 12 month surveillance period. A more favorable immunogenicity profile was observed with RTS,S/AS01B than with RTS,S/AS02A. Trial Registration Clinicaltrials.gov NCT00197054
Eigenvalue Repulsion and Matrix Black Holes
Gavin Polhemus
Physics , 1999,
Abstract: Eigenvalue repulsion can explain the holographic growth of black holes in Matrix theory. The resulting picture is essentially the same as the Boltzman gas picture but avoids any assumption about the effective potential between the D0 branes. Further, eigenvalue repulsion extends the Boltzman gas picture past the BFKS point to N >> S. The use of Boltzman statistics is natural in this picture.
Statistical Mechanics of Multiply Wound D-Branes
Gavin Polhemus
Physics , 1996, DOI: 10.1103/PhysRevD.56.2202
Abstract: The D-brane counting of black hole entropy is commonly understood in terms of excitations carrying fractional charges living on long, multiply-wound branes (e.g. open strings with fractional Kaluza-Klein momentum). This paper addresses why the branes become multiply wound. Since multiply wound branes are T-dual to branes evenly spaced around the compact dimension, this tendency for branes to become multiply wound can be seen as an effective repulsion between branes in the T-dual picture. We also discuss how the fractional charges on multiply wound branes conspire to always form configurations with integer charge.
Immunization with Pre-Erythrocytic Antigen CelTOS from Plasmodium falciparum Elicits Cross-Species Protection against Heterologous Challenge with Plasmodium berghei
Elke S. Bergmann-Leitner,Ryan M. Mease,Patricia De La Vega,Tatyana Savranskaya,Mark Polhemus,Christian Ockenhouse,Evelina Angov
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0012294
Abstract: The Plasmodium protein Cell-traversal protein for ookinetes and sporozoites (CelTOS) plays an important role in cell traversal of host cells in both, mosquito and vertebrates, and is required for successful malaria infections. CelTOS is highly conserved among the Plasmodium species, suggesting an important functional role across all species. Therefore, targeting the immune response to this highly conserved protein and thus potentially interfering with its biological function may result in protection against infection even by heterologous species of Plasmodium.
Understanding the individual with Alzheimer’s disease: Can socioemotional selectivity theory guide us?  [PDF]
Ruth E. Mark
Advances in Alzheimer's Disease (AAD) , 2012, DOI: 10.4236/aad.2012.13010
Abstract: Individuals often get lost behind the diagnosis of Alzheimer’s disease (AD) while widespread differences between these patients are morecommon than similarities. Socioemotional Selectivity Theory (SST) suggests that as we age our goals change from future-oriented (acquiringnew information) to present-oriented (enhancing the emotional, especially positive, meaning of encounters). The goal of the current article is to examine whether the principles of SST might also apply for people with AD. Some aspects of SST are found especially in the early stages of AD when awareness is often intact and cognitive impairment is relatively limited. This review has clinical significance for the treatment of AD because it focuses on what is important to the individual rather than treating patients as a homogenous group. It also highlights the importance of social networks and emphasizes the role of the proxy in AD care. Lastly, it suggests that if those with AD (like the healthy elderly) have a positivity bias then positive emotional stimuli/wording/instructions could usefully be employed in their daily treatment. I suggest that SST may be a useful starting point when attempting to address what matters to individuals with AD and conclude by providing a few suggestions for future studies.
DNA Prime/Adenovirus Boost Malaria Vaccine Encoding P. falciparum CSP and AMA1 Induces Sterile Protection Associated with Cell-Mediated Immunity
Ilin Chuang, Martha Sedegah, Susan Cicatelli, Michele Spring, Mark Polhemus, Cindy Tamminga, Noelle Patterson, Melanie Guerrero, Jason W. Bennett, Shannon McGrath, Harini Ganeshan, Maria Belmonte, Fouzia Farooq, Esteban Abot, Jo Glenna Banania, Jun Huang, Rhonda Newcomer, Lisa Rein, Dianne Litilit, Nancy O. Richie, Chloe Wood, Jittawadee Murphy, Robert Sauerwein, Cornelus C. Hermsen, Andrea J. McCoy, Edwin Kamau, James Cummings, Jack Komisar, Awalludin Sutamihardja, Meng Shi, Judith E. Epstein, Santina Maiolatesi, Donna Tosh, Keith Limbach, Evelina Angov, Elke Bergmann-Leitner, Joseph T. Bruder, Denise L. Doolan, C. Richter King, Daniel Carucci, Sheetij Dutta, Lorraine Soisson, Carter Diggs, Michael R. Hollingdale, Christian F. Ockenhouse, Thomas L. Richie
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0055571
Abstract: Background Gene-based vaccination using prime/boost regimens protects animals and humans against malaria, inducing cell-mediated responses that in animal models target liver stage malaria parasites. We tested a DNA prime/adenovirus boost malaria vaccine in a Phase 1 clinical trial with controlled human malaria infection. Methodology/Principal Findings The vaccine regimen was three monthly doses of two DNA plasmids (DNA) followed four months later by a single boost with two non-replicating human serotype 5 adenovirus vectors (Ad). The constructs encoded genes expressing P. falciparum circumsporozoite protein (CSP) and apical membrane antigen-1 (AMA1). The regimen was safe and well-tolerated, with mostly mild adverse events that occurred at the site of injection. Only one AE (diarrhea), possibly related to immunization, was severe (Grade 3), preventing daily activities. Four weeks after the Ad boost, 15 study subjects were challenged with P. falciparum sporozoites by mosquito bite, and four (27%) were sterilely protected. Antibody responses by ELISA rose after Ad boost but were low (CSP geometric mean titer 210, range 44–817; AMA1 geometric mean micrograms/milliliter 11.9, range 1.5–102) and were not associated with protection. Ex vivo IFN-γ ELISpot responses after Ad boost were modest (CSP geometric mean spot forming cells/million peripheral blood mononuclear cells 86, range 13–408; AMA1 348, range 88–1270) and were highest in three protected subjects. ELISpot responses to AMA1 were significantly associated with protection (p = 0.019). Flow cytometry identified predominant IFN-γ mono-secreting CD8+ T cell responses in three protected subjects. No subjects with high pre-existing anti-Ad5 neutralizing antibodies were protected but the association was not statistically significant. Significance The DNA/Ad regimen provided the highest sterile immunity achieved against malaria following immunization with a gene-based subunit vaccine (27%). Protection was associated with cell-mediated immunity to AMA1, with CSP probably contributing. Substituting a low seroprevalence vector for Ad5 and supplementing CSP/AMA1 with additional antigens may improve protection. Trial Registration ClinicalTrials.govNCT00870987.
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