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.

NIR electrochemical fluorescence switching from polymethine dyes

Seo, S.,Pascal, S.,Park, C.,Shin, K.,Yang, X.,Maury, O.,Sarwade, B.,Andraud, C.,Kim, E. THE ROYAL SOCIETY OF CHEMISTRY 2014 Chemical Science Vol.5 No.4

A polymethine dye was used as a fluorophore and an electroactive modulator in order to achieve reversible electrochemical fluorescence switching in the near infrared (NIR) region. An NIR emissive polymethine dye, 3H-indolium, 2-[2-[2-chloro-3-[2-[1,3-dihydro-3,3-dimethyl-1-(phenylmethyl)-2H-indol-2-ylidene]-ethylidene]-5-(1,1-dimethylethyl)-1-cyclohexen-1-yl]ethenyl]-3,3-dimethyl-1-(phenylmethyl)-bromide (PM1), displayed high absorption and emission in the NIR region. In addition, it showed a relatively reversible electrochemical reaction between -0.5 and 1.1 V vs. Ag wire. In contrast, a keto group (C=O) bridged polymethine analogue, 2,6-bis[2-(1,3-dihydro-1-hexyl-3,3-dimethyl-2H-indol-2-ylidene)ethylidene]-4-(1,1-dimethylethyl)cyclohexanone (PM2), showed an irreversible electrochemical reaction, possibly due to the keto group interrupting the full conjugation of the entire molecule in PM2. The reversible redox reaction of PM1 allowed electrochemical fluorescence switching in the NIR region for the first time. The NIR fluorescence switching was visually observable through a visible light cut-off filter with a cyclability of over 100.

A model-based Technique for Early and Robust Detection of Oscillatory Failure Case in A380 Actuators

Loïc Lavigne,Ali Zolghadri,Philippe Goupil,Pascal Simon 제어·로봇·시스템학회 2011 International Journal of Control, Automation, and Vol.9 No.1

This paper addresses the problem of Oscillatory Failure Cases (OFC) detection in the Electrical Flight Control System (EFCS) of the Airbus airplanes. OFC can lead to strong interactions with loads and aero-elasticity and consequently are to be detected very early in time. The work describes the status of on going research activity undertaken within a collaborative project between Bordeaux University (France) and Airbus. An hydraulic actuator model is currently used as the basis for a robust analytical redundancy-based technique implemented in A380 Flight Control Computer (FCC) for detecting unauthorized oscillatory events. For upcoming and future generation aircraft (A/C), it could be re-quired to detect OFC earlier with less important amplitude. The method presented here is based on nonlinear state space modeling, associated with the same decision test as used by in-service Airbus A/C. It is shown that the model quality could be improved significantly by reliable estimating of some physical parameters. The fault indicating signals are compared on data set obtained from A380 com-puters during flight tests.

High removal of emerging contaminants from wastewater by activated carbons derived from the shell of cashew of Para

Pascal S. Thue,Diana R. Lima,Mu Naushad,Eder C. Lima,Ytallo R. T. de Albuquerque,Silvio L. P. Dias,Mariene R. Cunha,Guilherme L. Dotto,Irineu A. S. de Brum 한국탄소학회 2021 Carbon Letters Vol.31 No.1

Abstract Activated carbon from the shell of the cashew of Para (SCP) was produced by chemical activation with ZnCl using the ratio of SCP: ZnCl2 1.0:1.5 at 700 °C. The prepared activated carbon (SCP700) was used for the removal of two emerging contaminants, 4-bromophenol (4-BrPhOH) and 4-chloroaniline (4-ClPhNH2) that are primarily employed in the industry. Different analytical techniques were used to characterize the activated carbon. From the N2 adsorption–desorption isotherms were obtained the specific surface area of 1520 m2 g? 1 and total pore volume of 0.492 cm3 g?1. The functional groups were identified by the FTIR technique and quantified by modified Boehm titration. The results revealed the bearing of several functional groups on the SCP700 surface, which may utterly influence the removal of the emerging contaminants. The equilibrium experiments showed that the maximum uptaken capacities (Qmax) achieved at 45 °C were 488.2 (4-BrPhOH) and 552.5 mg g?1 (4-ClPhNH2). The thermodynamic parameters demonstrated that the processes of 4-BrPhOH and 4-ClPhNH2 adsorption are exothermic, spontaneous, energetically suitable, and the magnitude of ΔH° is compatible with physisorption. The mechanism of the adsorption of the emerging contaminants onto the carbon surface is dominated by microporous filling, hydrogen bonds, π-stacking interactions, and other Van der Waals interactions. The use of activated carbon for the treatment of industrial synthetic wastewater with several inorganic and organic molecules commonly found in industrial effluents showed a very high percentage of uptaking (up to 98.64%).

Comprehensive phenolic composition analysis and evaluation of Yak-Kong soybean (<i>Glycine max</i>) for the prevention of atherosclerosis

Lee, Charles C.,Dudonné,, Sté,phanie,Dubé,, Pascal,Desjardins, Yves,Kim, Jong Hun,Kim, Ji Seung,Kim, Jong-Eun,Park, Jung Han Yoon,Lee, Ki Won,Lee, Chang Yong Elsevier 2017 Food chemistry Vol.234 No.-

<P><B>Abstract</B></P> <P>Yak-Kong (YK) (<I>Glycine max</I>), a small black soybean cultivar with a green embryo, was evaluated for functional constituents with a focus on atherosclerosis prevention. In comparison to common yellow and black soybean cultivars, YK contains significantly higher concentrations of antioxidants, particularly in its seed coat. A comprehensive phenolic composition analysis revealed that proanthocyanidins were the major phenolic group in YK. In contrast to other proanthocyanidin-rich foods, YK was rich in bioavailable proanthocyanidins (with a degree of polymerization ≤3) specifically with A-type dimers. Significant concentrations of phloridzin and coumestrol were also exclusively found in YK seed coat and the embryo, respectively. Extracts of both the proanthocyanidin-rich seed coat and isoflavonoid-rich embryo of YK attenuated adhesion of THP-1 to LPS-stimulated human umbilical vascular endothelial cells, suggesting that they are important sources of coronary heart disease-preventive phenolics. YK has promising potential for further development as a functional food source targeted at atherosclerosis prevention.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Yak-Kong, a small black soybean with a green embryo, is rich in proanthocyanidins. </LI> <LI> Procyanidin A dimers and phloridzin are newly found in soybean seed coat. </LI> <LI> Significant amount of coumestrol is found in Yak-Kong soybean embryo. </LI> <LI> Both Yak-Kong seed coat and embryo attenuated monocyte-endothelial cell adhesion. </LI> </UL> </P>

A major daidzin metabolite 7,8,4′-trihydroxyisoflavone found in the plasma of soybean extract-fed rats attenuates monocyte-endothelial cell adhesion

Lee, Charles C.,Dudonné,, Sté,phanie,Kim, Jong Hun,Kim, Ji Seung,Dubé,, Pascal,Kim, Jong-Eun,Desjardins, Yves,Park, Jung Han Yoon,Lee, Ki Won,Lee, Chang Yong Applied Science Publishers 2018 Food chemistry Vol.240 No.-

<P><B>Abstract</B></P> <P>Among many functional foods and their phytochemicals, ingestion of soybean (<I>Glycine max</I>) is highly correlated to reduced risk of cardiovascular diseases. Validation of potential health benefits of functional foods requires information about the bioavailability and metabolism of bioactive compounds. In this context, several phase I and II metabolites of isoflavones were target-analyzed in the plasma of rats acutely supplemented with soybean embryo extract. A daidzein metabolite, 7,8,4′-trihydroxyisoflavone (7,8,4′-THI), was found to have the highest average area under curve value (574.3±112.8). Therefore, its potential prevention effect on atherosclerosis was investigated using monocyte-endothelial cell adhesion assay. Different from its precursor daidzein or daidzin, 7,8,4′-THI attenuated adhesion of THP-1 monocytes to tumor necrosis factor-alpha (TNF-α) stimulated human umbilical vein endothelial cells (HUVECs). In addition, 7,8,4′-THI significantly downregulated TNF-α stimulated the expression of vascular cell adhesion molecule-1 and monocyte chemotactic protein-1 and phosphorylation of IκB kinase and IκBα involved in the initiation of atherosclerosis in HUVECs. Therefore, 7,8,4′-THI, a highly bioavailable hydroxylated isoflavone metabolite, has potential anti-atherosclerotic effect via inhibiting monocyte-endothelial adhesion.</P> <P><B>Highlights</B></P> <P> <UL> <LI> 7,8,4′-Trihydroxyisoflavone was found in the rat plasma after soybean intake. </LI> <LI> The highest average AUC of 7,8,4′-THI was 10 times higher than its precursor daidzein. </LI> <LI> 7,8,4′-THI inhibited TNF-α stimulated monocyte-endothelial cell adhesion. </LI> </UL> </P>

Phase-coherent microwave-to-optical link with a self-referenced microcomb

Del'Haye, Pascal,Coillet, Auré,lien,Fortier, Tara,Beha, Katja,Cole, Daniel C.,Yang, Ki Youl,Lee, Hansuek,Vahala, Kerry J.,Papp, Scott B.,Diddams, Scott A. Nature Publishing Group 2016 Nature photonics Vol.10 No.8

<P>Precise measurements of the frequencies of light waves have become common with mode-locked laser frequency combs(1). Despite their huge success, optical frequency combs currently remain bulky and expensive laboratory devices. Integrated photonic microresonators are promising candidates for comb generators in out-of-the-lab applications, with the potential for reductions in cost, power consumption and size(2). Such advances will significantly impact fields ranging from spectroscopy and trace gas sensing(3) to astronomy(4), communications(5) and atomic time-keeping(6,7). Yet, in spite of the remarkable progress shown over recent years(8-10), microresonator frequency combs ('microcombs') have been without the key function of direct f-2f self-referencing(1), which enables precise determination of the absolute frequency of each comb line. Here, we realize this missing element using a 16.4 GHz microcomb that is coherently broadened to an octave-spanning spectrum and subsequently fully phase-stabilized to an atomic clock. We show phase-coherent control of the comb and demonstrate its low-noise operation.</P>

Broadband dispersion-engineered microresonator on a chip

Yang, Ki Youl,Beha, Katja,Cole, Daniel C.,Yi, Xu,Del'Haye, Pascal,Lee, Hansuek,Li, Jiang,Oh, Dong Yoon,Diddams, Scott A.,Papp, Scott B.,Vahala, Kerry J. Nature Publishing Group 2016 Nature photonics Vol.10 No.5

The control of dispersion in fibre optical waveguides is of critical importance to optical fibre communications systems and more recently for continuum generation from the ultraviolet to the mid-infrared. The wavelength at which the group velocity dispersion crosses zero can be set by varying the fibre core diameter or index step. Moreover, sophisticated methods to manipulate higher-order dispersion so as to shape and even flatten the dispersion over wide bandwidths are possible using multi-cladding fibres. Here we introduce design and fabrication techniques that allow analogous dispersion control in chip-integrated optical microresonators, and thereby demonstrate higher-order, wide-bandwidth dispersion control over an octave of spectrum. Importantly, the fabrication method we employ for dispersion control simultaneously permits optical Q factors above 100 million, which is critical for the efficient operation of nonlinear optical oscillators. Dispersion control in high-Q systems has become of great importance in recent years with increased interest in chip-integrable optical frequency combs.

Tungsten/Copper Functionally Graded Materials : Possible Applications and Processing through the Powder Metallurgy Route

Ozer O.,Missiaen J.M.,Pascal C.,Lay S.,Chaix J.M.,Mitteau R. 한국분말야금학회 2006 한국분말야금학회 학술대회논문집 Vol.2006 No.1

Processing of W-Cu graded materials from attritor-milled W-CuO mixtures is described. The powder reduction steps are investigated by TG and XRD analyses and by microstructural observations (SEM, TEM). Sintering of reduced powder with different compositions is analysed by dilatometry. Sintering behaviour of the graded component processed by co-compaction of a 10/20/30wt%Cu multi-layer material is briefly discussed. Liquid Cu migration is observed and smooths the composition gradient. Perspectives to control this migration are discussed.

The PMIP4 contribution to CMIP6 - Part 3: The last millennium, scientific objective, and experimental design for the PMIP4 <i>past1000</i> simulations

Jungclaus, Johann H.,Bard, Edouard,Baroni, Mé,lanie,Braconnot, Pascale,Cao, Jian,Chini, Louise P.,Egorova, Tania,Evans, Michael,Gonzá,lez-Rouco, J. Fidel,Goosse, Hugues,Hurtt, George C.,Jo Copernicus GmbH 2017 Geoscientific model development Vol.10 No.11

<P><p><strong>Abstract.</strong> The pre-industrial millennium is among the periods selected by the Paleoclimate Model Intercomparison Project (PMIP) for experiments contributing to the sixth phase of the Coupled Model Intercomparison Project (CMIP6) and the fourth phase of the PMIP (PMIP4). The <i>past1000</i> transient simulations serve to investigate the response to (mainly) natural forcing under background conditions not too different from today, and to discriminate between forced and internally generated variability on interannual to centennial timescales. This paper describes the motivation and the experimental set-ups for the PMIP4-CMIP6 <i>past1000</i> simulations, and discusses the forcing agents orbital, solar, volcanic, and land use/land cover changes, and variations in greenhouse gas concentrations. The <i>past1000</i> simulations covering the pre-industrial millennium from 850 Common Era (CE) to 1849<span class='thinspace'></span>CE have to be complemented by <i>historical</i> simulations (1850 to 2014<span class='thinspace'></span>CE) following the CMIP6 protocol. The external forcings for the <i>past1000</i> experiments have been adapted to provide a seamless transition across these time periods. Protocols for the <i>past1000</i> simulations have been divided into three tiers. A default forcing data set has been defined for the Tier 1 (the CMIP6 <i>past1000</i>) experiment. However, the PMIP community has maintained the flexibility to conduct coordinated sensitivity experiments to explore uncertainty in forcing reconstructions as well as parameter uncertainty in dedicated Tier 2 simulations. Additional experiments (Tier 3) are defined to foster collaborative model experiments focusing on the early instrumental period and to extend the temporal range and the scope of the simulations. This paper outlines current and future research foci and common analyses for collaborative work between the PMIP and the observational communities (reconstructions, instrumental data).</p> </P>