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Search Results: 1 - 10 of 17271 matches for " Andrew Geall "
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Enhanced Delivery and Potency of Self-Amplifying mRNA Vaccines by Electroporation in Situ
Yen Cu,Kate E. Broderick,Kaustuv Banerjee,Julie Hickman,Gillis Otten,Susan Barnett,Gleb Kichaev,Niranjan Y. Sardesai,Jeffrey B. Ulmer,Andrew Geall
Vaccines , 2013, DOI: 10.3390/vaccines1030367
Abstract: Nucleic acid-based vaccines such as viral vectors, plasmid DNA (pDNA), and mRNA are being developed as a means to address limitations of both live-attenuated and subunit vaccines. DNA vaccines have been shown to be potent in a wide variety of animal species and several products are now licensed for commercial veterinary but not human use. Electroporation delivery technologies have been shown to improve the generation of T and B cell responses from synthetic DNA vaccines in many animal species and now in humans. However, parallel RNA approaches have lagged due to potential issues of potency and production. Many of the obstacles to mRNA vaccine development have recently been addressed, resulting in a revival in the use of non-amplifying and self-amplifying mRNA for vaccine and gene therapy applications. In this paper, we explore the utility of EP for the in vivo delivery of large, self-amplifying mRNA, as measured by reporter gene expression and immunogenicity of genes encoding HIV envelope protein. These studies demonstrated that EP delivery of self-amplifying mRNA elicited strong and broad immune responses in mice, which were comparable to those induced by EP delivery of pDNA.
Induction of multi-antigen multi-stage immune responses against Plasmodium falciparum in rhesus monkeys, in the absence of antigen interference, with heterologous DNA prime/poxvirus boost immunization
George Jiang, Yupin Charoenvit, Alberto Moreno, Maria F Baraceros, Glenna Banania, Nancy Richie, Steve Abot, Harini Ganeshan, Victoria Fallarme, Noelle B Patterson, Andrew Geall, Walter R Weiss, Elizabeth Strobert, Ivette Caro-Aquilar, David E Lanar, Allan Saul, Laura B Martin, Kalpana Gowda, Craig R Morrissette, David C Kaslow, Daniel J Carucci, Mary R Galinski, Denise L Doolan
Malaria Journal , 2007, DOI: 10.1186/1475-2875-6-135
Abstract: Despite intense research efforts, malaria remains a significant public health problem [1] and is associated with significant constraints on economic progress and productivity [2] in the developing world. Especially with the spread of drug-resistant Plasmodium parasites and insecticide-resistant Anopheles vectors, development of an effective malaria vaccine is considered a public health priority [3]. Two human models demonstrate the feasibility of developing a malaria vaccine. Immunization with radiation-attenuated Plasmodium spp. parasites has been shown to confer sterile protection against sporozoite challenge in humans [4,5] as well as rodent [6] and non-human primate [7] models, and natural long-term exposure to the parasite is associated with an age-related decrease in the incidence, prevalence, and density of infection [8]. The critical effector mechanism in the radiation-attenuated sporozoite model is thought to be CD8+ T-cell responses directed against parasite antigens expressed in the liver stage [9-11]. In the naturally acquired immunity model, antibodies directed against blood-stage parasite antigens are thought to be responsible for protective immunity [12-14].Based on these two models, a multi-stage multi-immune response vaccine against malaria comprising antigens expressed in the liver stage and targeted by T-cell responses, as well as antigens expressed in the blood-stage and targeted by antibody responses, is being developed [15]. The hypothesis is that by reducing the numbers of parasites emerging from the liver (T-cell immune responses directed against those antigens expressed by irradiated sporozoites in hepatocytes) and priming the immune system to erythrocytic stage antigens that will be boosted by infection from natural exposure (antibody responses directed against parasite proteins expressed on the surface of merozoites or infected erythrocytes or in apical organelles), one will reduce the severity and mortality due to Plasmodium falciparum ma
ATP-Dependent Infra-Slow (<0.1 Hz) Oscillations in Thalamic Networks
Magor L. L?rincz, Freya Geall, Ying Bao, Vincenzo Crunelli, Stuart W. Hughes
PLOS ONE , 2009, DOI: 10.1371/journal.pone.0004447
Abstract: An increasing number of EEG and resting state fMRI studies in both humans and animals indicate that spontaneous low frequency fluctuations in cerebral activity at <0.1 Hz (infra-slow oscillations, ISOs) represent a fundamental component of brain functioning, being known to correlate with faster neuronal ensemble oscillations, regulate behavioural performance and influence seizure susceptibility. Although these oscillations have been commonly indicated to involve the thalamus their basic cellular mechanisms remain poorly understood. Here we show that various nuclei in the dorsal thalamus in vitro can express a robust ISO at ~0.005–0.1 Hz that is greatly facilitated by activating metabotropic glutamate receptors (mGluRs) and/or Ach receptors (AchRs). This ISO is a neuronal population phenomenon which modulates faster gap junction (GJ)-dependent network oscillations, and can underlie epileptic activity when AchRs or mGluRs are stimulated excessively. In individual thalamocortical neurons the ISO is primarily shaped by rhythmic, long-lasting hyperpolarizing potentials which reflect the activation of A1 receptors, by ATP-derived adenosine, and subsequent opening of Ba2+-sensitive K+ channels. We argue that this ISO has a likely non-neuronal origin and may contribute to shaping ISOs in the intact brain.
Can a Massive Graviton be a Stable Particle  [PDF]
Andrew Beckwith
Journal of Modern Physics (JMP) , 2011, DOI: 10.4236/jmp.2011.25043
Abstract: This document is based on a question asked in the Dark Side of the Universe 2010 conference in Leon, Mexico, when a researcher from India asked the author about how to obtain a stability analysis of massive gravitons. The answer to this question involves an extension of the usual Pauli_Fiertz Langrangian as written by Ortin, with non- zero graviton mass contributing to a relationship between the trace of a revised GR stress-energy tensor (assuming non- zero graviton mass), and the trace of a revised symmetric tensor times a tiny mass for a 4 dimensional graviton. The resulting analysis makes use of Visser’s treatment of a stress en-ergy tensor, with experimental applications discussed in the resulting analysis. If the square of frequency of a massive graviton is real valued and greater than zero, stability can be possibly confirmed experimentally.
Octonionic Gravity Formation, Its Connections to Micro Physics  [PDF]
Andrew Beckwith
Open Journal of Microphysics (OJM) , 2011, DOI: 10.4236/ojm.2011.11002
Abstract: We ask if Octonionic quantum gravity is a relevant consideration near the Planck scale. Furthermore, we examine whether gravitational waves would be generated during the initial phase, , of the universe when triggered by changes in spacetime geometry; i.e. what role would an increase in degrees of freedom have in setting the conditions during , so that the result of these conditions can be observed and analyzed by a gravitational detector. The micro physics interaction is due to the formation of a pre Planckian to Planckian space time transition in spatial dimensions at and near the Planck dimensional values, i.e. 10–33 centimeters in spatial dimensions. This transition would be abrupt and arising in micro physics regimes of space time.
Detailing Coherent, Minimum Uncertainty States of Gravitons, as Semi Classical Components of Gravity Waves, and How Squeezed States Affect Upper Limits To Graviton Mass  [PDF]
Andrew Beckwith
Journal of Modern Physics (JMP) , 2011, DOI: 10.4236/jmp.2011.27086
Abstract: We present what is relevant to squeezed states of initial space time and how that affects both the composition of relic GW, and also gravitons. A side issue to consider is if gravitons can be configured as semi classical "particles", which is akin to the Pilot model of Quantum Mechanics as embedded in a larger non linear "deterministic" background.
What the Null Energy Condition (and When It May Be Violated) Tells Us about Gravitational Wave Frequencies in/for Relic Cosmology?  [PDF]
Andrew Beckwith
Journal of Modern Physics (JMP) , 2011, DOI: 10.4236/jmp.2011.29118
Abstract: We introduce a criterion as to the range of HFGW generated by early universe conditions. The 1 to 10 Giga Hertz range is constructed initially starting with what Grupen writes as far as what to expect of GW frequencies which can be detected assuming a sensitivity of 7×h~10-27 . From there we examine the implications of an earlier Hubble parameter at the start of inflation, and a phase transition treatment of pre to post Planckian inflation physics via use of inflatons. We close with an analysis of how gravitational constant G may vary with time, the tie in with the NEC condition and how to select a range of relic GW frequencies. The gravitational frequencies in turn may enable resolving a mis match between the datum that the entropy of the center of the galaxy black hole is greater than the entropy of the present four dimensional universe as we can infer and measure.
Result-Based Management in the Public Sector: A Decade of Experience for the Tanzanian Executive Agencies  [PDF]
Andrew Sulle
Journal of Service Science and Management (JSSM) , 2011, DOI: 10.4236/jssm.2011.44057
Abstract: One element of the NPM-inspired reforms is the adoption of result-based management in the Tanzanian public sector. This paper examines the implementation of this type of reform by focusing on executive agencies. Executive agencies were especially created to be result-oriented public organizations. Our empirical question is whether or not and to what extent the management of executive agencies has shifted to result-based approach as promised by NPM-reform doctrine. Our findings indicate that result-based approach has only been partially implemented in the Tanzanian public sector. There is less emphasis on managing for results and management processes have continued to be predominantly based on inputs and processes.
Can We Form Gravitinos by Something Other Than a Higgs Boson in the Electro-Weak Era?  [PDF]
Andrew Beckwith
Journal of Modern Physics (JMP) , 2012, DOI: 10.4236/jmp.2012.329162
Abstract: What is the physical nature of gravitinos? As asked before, this question was the template of how to introduce Machian Physics as a way to link gravitinos in the electro weak era and gravitons as of the present. What we wish to do now is to ask how a flaw in the Higgs equation as brought up by Comay shows a branch off from orthodox quantum physics, leading to, with the Machs principle application done earlier a way to embed the beginning of the universe as a semi classical superstructure of which Quantum Mechanics is a subset of. We argue that this will necessitate a review of the Higgs equation of state for reasons stated in the manuscript. We also finally review a proprosal for another form of mass formation mechanism as a replacement for the Higgs mass as introduced by Glinka and Beckwith, 2012, with commentary as to how suitable it may be to get a gravitino mass in fidelity to the Machian proposal introduced by Beckwith previously, to get linkage between electroweak era gravitinos and present day gravitons.
Variation of Vacuum Energy if Scale Factor Becomes Infinitely Small, with Fixed Entropy Due to a Non Pathological Big Bang Singularity Accessible to Modified Einstein Equations  [PDF]
Andrew Beckwith
Journal of Modern Physics (JMP) , 2012, DOI: 10.4236/jmp.2012.329171
Abstract: When initial radius Rinitial 0 if Stoica actually derived Einstein equations in a formalism which remove the big bang singularity pathology, then the reason for Planck length no longer holds. The implications of Rinitial 0 are the first part of this manuscript. Then the resolution is alluded to by work from Muller and Lousto, as to implications of entanglement entropy. We present entanglement entropy in the early universe with a steadily shrinking scale factor, due to work from Muller and Lousto, and show that there are consequences due to initial entanged Sentropy=0.3rH2/a2 for a time dependent horizon radius rH in cosmology, with for flat space conditions rH= for conformal time. In the case of a curved, but not flat space version of entropy, we look at vacuum energy as proportional to the inverse of scale factor squared times the inverse of initial entropy, effectively when there is no initial time in line with ~H2/G H≈a-1. The consequences for this initial entropy being entangled are elaborated in this manuscript. No matter how small the length gets, Sentropy if it is entanglement entropy, will not go to zero. The requirement is that the smallest length of time, t, re scaled does not go to zero. Even if the length goes to zero. This preserves a minimum non zero vacuum energy, and in doing so keep the bits, for computational bits cosmological evolution even if Rinitial 0.
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