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Development of HPV16 mouse and dog models for more accurate prediction of human vaccine efficacy
Emmanuelle Totain,Loïc Lindner,Nicolas Martin,Yolande Misseri,Alexandra Iché,Marie-Christine Birling,Tania Sorg,Yann Herault,Alain Bousquet-Melou,Pascale Bouillé,Christine Duthoit,Guillaume Pavlovic,S 한국실험동물학회 2023 Laboratory Animal Research Vol.39 No.2
Background: Animal models are essential to understand the physiopathology of human diseases but also to evaluate new therapies. However, for several diseases there is no appropriate animal model, which complicates the development of effective therapies. HPV infections, responsible for carcinoma cancers, are among these. So far, the lack of relevant animal models has hampered the development of therapeutic vaccines. In this study, we used a candidate therapeutic vaccine named C216, similar to the ProCervix candidate therapeutic vaccine, to validate new mouse and dog HPV preclinical models. ProCervix has shown promising results with classical subcutaneous murine TC-1 cell tumor isografts but has failed in a phase II study. Results: We first generated E7/HPV16 syngeneic transgenic mice in which the expression of the E7 antigen could be switched on through the use of Cre–lox recombination. Non-integrative LentiFlash® viral particles were used to locally deliver Cre mRNA, resulting in E7/HPV16 expression and GFP reporter fluorescence. The expression of E7/HPV16 was monitored by in vivo fluorescence using Cellvizio imaging and by local mRNA expression quantification. In the experimental conditions used, we observed no differences in E7 expression between C216 vaccinated and control groups. To mimic the MHC diversity of humans, E7/HPV16 transgenes were locally delivered by injection of lentiviral particles in the muscle of dogs. Vaccination with C216, tested with two different adjuvants, induced a strong immune response in dogs. However, we detected no relationship between the level of cellular response against E7/HPV16 and the elimination of E7-expressing cells, either by fluorescence or by RT-ddPCR analysis. Conclusions: In this study, we have developed two animal models, with a genetic design that is easily transposable to different antigens, to validate the efficacy of candidate vaccines. Our results indicate that, despite being immunogenic, the C216 candidate vaccine did not induce a sufficiently strong immune response to eliminate infected cells. Our results are in line with the failure of the ProCervix vaccine that was observed at the end of the phase II clinical trial, reinforcing the relevance of appropriate animal models.
Numerical Investigation of Free Surface Vortices Formed around Intake Pipe in Pump Sump
Ich Long Ngo,Byeong Rog Shin 대한기계학회 2013 대한기계학회 춘추학술대회 Vol.2013 No.12
A numerical study on the influence of the variation of water flow rate and water level on free surface vortices formed around an intake pipe in a pump sump was carried out. Free surface turbulent flow in a single intake channel was solved by using finite volume method with RANS equations with k-ω Shear Stress Transport turbulence model. A VOF multiphase model and typical open channel model are used to solve the problem of 3-D multiphase flow in the sump. The multi-blocked structure grid system which is verified for the grid dependency using the GCI was used to capture the behavior and interaction of flow between two fluid phases with higher accuracy. The numerical results showed that the depth of free surface vortex is proportional to the flow rate at the same water level. When the flow rate is high enough, the air bubble may create after separating from free surface vortex and the variation of vortices are no longer stable. By monitoring the minimum elevation of the air-water interface in time, the mechanism of formation of free surface vortex in term of changing water level was found out. It is stated that the lower water level is, the more the free surface vortex appears. A relatively common phenomenon in experimental pump sump models, in which the very high perturbation of turbulent fluid flow caused by air-entrained free and submerged vortices, was also reproduced. The detailed investigation of surface vortex behavior with respect to water flow rate as well as water level is made and discussed.
Ich-Long Ngo,변찬 대한기계학회 2015 JOURNAL OF MECHANICAL SCIENCE AND TECHNOLOGY Vol.29 No.7
Finite element method was used to investigate the effects of heater location and heater size on the natural convection heat transfer in a2D square cavity heated partially or fully from below and cooled from above. Rayleigh number (5Í102 ≤ Ra ≤ 5Í105), heater size (0.1≤ D/L ≤ 1.0), and heater location (0.1 ≤ xh/L ≤ 0.5) were considered. Numerical results indicated that the average Nusselt number (Num)increases as the heater size decreases. In addition, when xh/L is less than 0.4, Num increases as xh/L increases, and Num decreases againfor a larger value of xh/L. However, this trend changes when Ra is less than 104, suggesting that Num attains its maximum value at theregion close to the bottom surface center. This study aims to gain insight into the behaviors of natural convection in order to potentiallyimprove internal natural convection heat transfer.
Sen-Ich Oda,이계주,Tatsuo Arii,Keiji Imoto,현병화,박인성,김현,유임주 대한해부학회 2010 Anatomy & Cell Biology Vol.43 No.3
Voltage dependent calcium channels (VDCC) participate in regulation of neuronal Ca2+. The Rolling mouse Nagoya (Cacna1atg-rol) is a spontaneous P/Q type VDCC mutant, which has been suggested as an animal model for some human neurological diseases such as autosomal dominant cerebellar ataxia (SCA6), familial hemiplegic migraine and episodic ataxia type-2. Morphology of Purkinje cell (PC) dendritic spine is suggested to be regulated by signal molecules such as Ca2+ and by interactions with afferent inputs. The amplitude of excitatory postsynaptic current was decreased in parallel fiber (PF) to PC synapses, whereas apparently increased in climbing fiber (CF) to PC synapses in rolling mice Nagoya. We have studied synaptic morphology changes in cerebella of this mutant strain. We previously found altered synapses between PF varicosity and PC dendritic spines. To study dendritic spine plasticity of PC in the condition of insufficient P/Q type VDCC function, we used high voltage electron microscopy (HVEM). We measured the density and length of PC dendritic spines at tertiary braches. We observed statistically a significant decrease in spine density as well as shorter spine length in rolling mice compared to wild type mice at tertiary dendritic braches. In proximal PC dendrites, however, there were more numerous dendritic spines in rolling mice Nagoya. The differential regulation of rolling PC spines at tertiary and proximal dendrites in rolling mice Nagoya suggests that two major excitatory afferent systems may be regulated reciprocally in the cerebellum of rolling mouse Nagoya.
Ngo, Ich-Long,Prabhakar Vattikuti, S.V.,Byon, Chan Pergamon Press 2017 International journal of heat and mass transfer Vol. No.
<P><B>Abstract</B></P> <P>This paper describes an extensive study on thermal conductivity (TC) of polymer composites with randomly distributed hybrid fillers. Finite element method in combination with user-defined code is used to predict accurately the TC of these composites under many effects and effective parameters such as volume fractions (VFs) and TC ratios of fillers to that of the matrix. A literature review on the TC prediction models of hybrid-filler polymer composites is studied and discussed. The effects of particle distribution and particle size of hybrid filler are also taken into account and analyzed. It was found that these effects become important and affect significantly to the effective TC, particularly at high VF, high TC, and large particle size. Remarkably, a modified Hashin-Shtrikman model is first proposed based on an extensively numerical results. It can be widely utilized for predicting the TC of polymer composites with randomly distributed hybrid fillers accurately and effectively, regardless of non-spherical filler shape.</P> <P><B>Highlights</B></P> <P> <UL> <LI> A literature review on the prediction models of thermal conductivity (TC) of hybrid-filler polymer composites is first studied and discussed. </LI> <LI> Effects of particle distribution and particle size of hybrid filler affect significantly to the effective TC, particularly at high volume fraction, high TC, and large particle size. </LI> <LI> A modified Hashin-Shtrikman model is first proposed for predicting the TC of polymer composites with randomly distributed hybrid fillers accurately and effectively. </LI> </UL> </P>