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Safety,immunogenicity,and protection provided by unadjuvanted and adjuvanted formulations of a recombinant plant-derived virus-like particle vaccine candidate for COvID-19 in nonhuman primates

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Cellular & Molecular Immunology 2022年第2期19卷 222-233页

作者： Stéphane Pillet Prabhu SArunachalam Guadalupe Andreani Nadia Golden Jane Fontenot Pyone Pyone Aye Katharina Röltgen Gabrielle Lehmicke Philipe Gobeil Charlotte Dubé Sonia Trépanier Nathalie Charland Marc-AndréD’Aoust Kasi Russell-Lodrigue Christopher Monjure robert v.blair Scott D.Boyd Rudolf P.Bohm Jay Rappaport François villinger Nathalie Landry Bali Pulendran Brian J.Ward Medicago Inc. QuébecQCCanada. Institute for Immunity Transplantation and InfectionStanford University School of MedicineStanford UniversityStanfordCAUSA. Tulane National Primate Research Center CovingtonLAUSA. New Iberia Research Center University of Louisiana at LafayetteNew IberiaLAUSA. Department of Pathology Stanford University School of MedicineStanford UniversityStanfordCAUSA. Department of Microbiology and Immunology Tulane University School of MedicineNew OrleansLAUSA. Department of Microbiology and Immunology Stanford University School of MedicineStanford UniversityStanfordCAUSA. Institute for Immunity Transplantation&InfectionStanford University School of MedicineStanford UniversityStanfordCAUSA Research Institute of the McGill University Health Centre MontrealQCCanada.

Although antivirals are important tools to control severe acute respiratory syndrome coronavirus 2(SARS-Cov-2)infection,effective vaccines are essential to control the current coronavirus disease 2019(COvID-19)***-derived virus-like particle(vLP)vaccine candidates have previously demonstrated immunogenicity and efficacy against ***,we report the immunogenicity and protection induced in rhesus macaques by intramuscular injections of a vLP bearing a SARS-Cov-2 spike protein(CovLP)vaccine candidate formulated with or without Adjuvant System 03(AS03)or cytidine-phospho-guanosine(CpG)*** a single dose of the unadjuvanted CovLP vaccine candidate stimulated humoral and cell-mediated immune responses,booster immunization(at 28 days after priming)and adjuvant administration significantly improved both responses,with higher immunogenicity and protection provided by the AS03-adjuvanted *** micrograms of CovLP adjuvanted with AS03 induced a polyfunctional interleukin-2(IL-2)-driven response and IL-4 expression in CD4 T *** were challenged by multiple routes(i.e.,intratracheal,intranasal,and ocular)with a total viral dose of 106 plaque-forming units of *** viral replication in nasal swabs and bronchoalveolar lavage fluid(BALF)as well as fewer SARS-Cov-2-infected cells and immune cell infiltrates in the lungs concomitant with reduced levels of proinflammatory cytokines and chemotactic factors in the BALF were observed in animals immunized with the CovLP adjuvanted with *** clinical,pathologic,or virologic evidence of vaccineassociated enhanced disease was observed in vaccinated *** CovLP adjuvanted with AS03 was therefore selected for vaccine development and clinical trials.

关键词： SARS-Cov-2 virus-like particles Non-humane primates AS03 CpG1018

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A radical reinterpretation of the growth and form of the stromatolite Conophyton lituus(Maslov)from evidence of syngenetic biofilm mineralisation

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Journal of Palaeogeography 2022年第1期11卷 69-84页

作者： robert v.Burne Research School of Earth Sciences The Australian National University CanberraACT 0200Australia School of Earth and Environmental Sciences The University of QueenslandBrisbaneQLD 4072Australia

Conophyton(Maslov)is a cylindroidal stromatolite form-genus characterized by nested conical ***-preserved Conophyton,up to 4 m tall and with basal diameters of up to 50 cm,are exposed in the Proterozoic Atar Formation of Mauritania,where many occur together,in growth position,as fields of individual columns spaced between 5 and 70 cm *** uniformity of these forms and their regular distribution suggest that they grew in quiet-water environments below wave *** for their penecontemporaneous organomineralization is indicated by nearby toppled examples of undeformed Conophyton forms alongside eroded lithified Conophyton fragments in carbonate *** characteristics of Conophyton have been used to classify the structures-the form of the lamination and the nature of its axial structure.A mathematical/physical model provides an explanation for the growth pattern of *** predicts that coniform structures with thickened axial zones form when upward organic growth of a biofilm moderately exceeds the rate of its *** varying characteristics of these features between different forms of Conophyton are thought to reflect biomineralization of the decaying biofilm rather than differences in the composition of microbial communities.A modern example of a syngenetic mineralization process capable of producing similar structures has been observed in the contemporary sediments of Lake Preston,Western Australia,where benthic microbial mats are being transformed into coniform lithified *** initial biomineralization of the coniform mat forms magnesium silicate that first coats and permineralizes web-like microbial extracellular polymeric substances(EPS)and then coalesces into a uniform mass that provides mechanical strength to the *** a later stage,massive carbonate crystal growth occurs that over-prints much of this texture,leaving only small,remnant areas of the magnesium silicate *** fossil Conophyton are composed o

关键词： Conophyton Morphogenesis Proterozoic Stromatolite Microbialite Mineralisation Biofilm Lake Clifton Lake Preston Maslov

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Reducing intrathecal pressure after traumatic spinal cord injury: a potential clinical target to promote tissue survival

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Neural Regeneration Research 2015年第3期10卷 380-382页

作者： Anna v Leonard robert vink School of Medical Sciences University of Adelaide Division of Health Sciences University of South Australia

Spinal cord injury （SCI） is an unexpected event that is both devastating and debilitating, resulting in not just motor and sensory loss, but also autonomic dysfunction of the bladder, bowel and sexual organs. Currently, there are no treatments available to improve outcome follow- ing SCI, leaving individuals with permanent and lifelong physical disability. Worldwide it is estimated that more than 500,000 people sustain a SCI each year, with average lifetime cost of paraplegia and quadriplegia estimated at $5 million and $9.5 million respectively. We therefore urgently need effective therapies to improve quality of life following SCI, and this requires a greater understanding of how cell and axonal injury develops after the traumatic event.

关键词： ITP TBI a potential clinical target to promote tissue survival Reducing intrathecal pressure after traumatic spinal cord injury SCI

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A micromechanical model for efective conductivity in granular electrode structures

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Acta Mechanica Sinica 2013年第5期29卷 682-698页

作者： Julia Ott Benjamin vlker Yixiang Gan robert M.Mc Meeking Marc Kamlah Institute of Applied Materials Karlsruhe Institute of Technology76131 Karlsruhe Germany Department of Mechanical Engineering University of CaliforniaSanta BarbaraCA 93106 USA School of Civil Engineering The University of SydneyNSW 2006 Australia Materials Department University of CaliforniaSanta BarbaraCA 93106 USA School of Engineering University of AberdeenKing’s CollegeAberdeenAB24 3UE Scotland UK INM-Leibniz Institute for New Materials Campus D22 66123 Saarbrücken Germany

Optimization of composition and microstructure is important to enhance performance of solid oxide fuel cells （SOFC） and lithium-ion batteries （LIB）. For this, the porous electrode structures of both SOFC and LIB are modeled as a binary mixture of electronic and ionic conducting particles to estimate effective transport properties. Particle packings of 10000 spherical, binary sized and randomly positioned particles are created numerically and densified considering the different manufacturing processes in SOFC and LIB： the sintering of SOFC electrodes is approximated geometrically, whereas the calendering process and volume change due to intercalation in LIB are modeled physically by a discrete el- ement approach. A combination of a tracking algorithm and a resistor network approach is developed to predict the con- nectivity and effective conductivity for the various densified structures. For SOFC, a systematic study of the influence of morphology on connectivity and conductivity is performed on a large number of assemblies with different compositions and particle size ratios between 1 and 10. In comparison to percolation theory, an enlarged percolation area is found, es- pecially for large size ratios. It is shown that in contrast to former studies the percolation threshold correlates to varying coordination numbers. The effective conductivity shows not only an increase with volume fraction as expected but also with size ratio. For LIB, a general increase of conductivity during the intercalation process was observed in correlation with increasing contact forces. The positive influence of cal- endering on the percolation threshold and the effective conductivity of carbon black is shown. The anisotropy caused by the calendering process does not influence the carbon black phase.

关键词： Granular electrode structures Effective conductivity - Percolation

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Systemic RNAi in western corn rootworm, Diabrotica virgifera virgifera, does not involve transitive pathways

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Insect Science 2018年第1期25卷 45-56页

作者： Huarong Li Andrew J. Bowling Premchand Gandra Murugesan Rangasamy Heather E. Pence robert E. McEwan Chitvan Khajuria blair D. Siegfried Kenneth E. Narva Dow AgroSciences LLC 9330 Zionsville Rd. Indianapolis Indiana USA Department of Entomology University of Nebraska Lincoln Nebraska USA Monsanto Company Chesterfield Missouri USA Entomology and Nematology Department University of Florida Gainesville Florida USA

Western corn rootworm （WCR, Diabrotica virgifera virgifera LeConte） is highly sensitive to orally delivered double-stranded RNA （dsRNA）. RNAi in WCR is systemic and spreads throughout the insect body. This raises the question whether transitive RNAi is a mechanism that functions in WCR to amplify the RNAi response via production of secondary siRNA. Secondary siRNA production is achieved through RNA-dependent RNA polymerase （RdRP） activity in other eukaryotic organisms, but RdRP has not been identified in WCR and any other insects. This study visualized the spread of the RNAi- mediated knockdown of Dr v-ATPase C mRNA throughout the WCR gut and other tissues using high-sensitivity branched DNA in situ hybridization. Furthermore, we did not detect either secondary siRNA production or transitive RNAi in WCR through siRNA sequence profile analysis. Nucleotide mismatched sequences introduced into either the sense or antisense strand of v-ATPase C dsRNAs were maintained in siRNAs derived from WCR fed with the mismatched dsRNAs in a strand specific manner. The distribution of all siRNAs was restricted to within the original target sequence regions, which may indicate the lack of new dsRNA synthesis leading to production of secondary siRNA. Thus, the systemic spread of RNAi in WCR may be derived from the original dsRNA molecules taken up from the gut lumen. These results indicate that the initial dsRNA dose is important for a lethal systemic RNAi response in WCR and have implications in developing effective dsRNA traits to control WCR and in resistance management to prolong the durability of RNAi trait technology.

关键词： corn rootworm Diabrotica secondary siRNA production systemic RNAi transitive RNAi

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A tunable diode laser absorption spectrometer for formaldehyde atmospheric measurements validated by simulation chamber instrumentation

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Journal of Environmental Sciences 2012年第1期24卷 22-33页

作者： v.Catoire F.Bernard Y.Mbarki A.Mellouki G.Eyglunent v.Daёle C.robert Laboratoire de Physique et Chimie de l'Environnement et de l'Espace (LPC2E) CNRS-Universit d'Orlans (UMR 6115)Observatoire des Sciences de l'Univers en rgion Centre (OSUC)3A Avenue de la Recherche Scientifique45071 Orlans Cedex 2France Institut de Combustion ArothermiqueRactivit et Environnement (ICARE)CNRS (UPR 3021)Observatoire des Sciences de l'Univers en rgion Centre (OSUC)1C Avenue de la Recherche Scientifique45071 Orlans Cedex 2France

A tunable diode laser absorption spectrometer （TDLAS） for formaldehyde atmospheric measurements has been set up and validated through comparison experiments with a Fourier transform infrared spectrometer （FT-IR） in a simulation *** was generated in situ in the chamber from reaction of ethene with *** HCHO ro-vibrational line intensities （at 2909.71,2912.09 and 2914.46 cm-1） possibly used by TDLAS were calibrated by FT-IR spectra simultaneously recorded in the 1600–3200 cm-1 domain during ethene ozonolysis,enabling the on-line deduction of the varying concentration for HCHO in *** experimental line intensities values inferred confirmed the calculated ones from the updated HITRAN *** addition,the feasibility of stratospheric in situ HCHO measurements using the 2912.09 cm-1 line was *** TDLAS performances were also assessed,leading to a 2σ detection limit of 88 ppt in volume mixing ratio with a response time of 60 sec at 30 Torr and 294 K for 112 m optical *** part of this work,the room-temperature rate constant of this reaction and the HCHO formation yield were found to be in excellent agreement with the compiled literature data.

关键词： formaldehyde ethene ozonolysis in situ measurements stratosphere simulation chamber TDLAS FT-IR

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Plant Carbonic Anhydrases： Structures, Locations, Evolution, and Physiological Roles

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Molecular Plant 2017年第1期10卷 30-46页

作者： robert J. DiMario Harmony Clayton Ananya Mukhedee Martha Ludwig James v. Moroney Department of Biological Sciences Louisiana State University Baton Rouge LA 70803 USA School of Chemistry and Biochemistry University of Western Australia Perth WA 6009 Australia

Carbonic anhydrases （CAs） are zinc metalloenzymes that catalyze the interconversion of CO2 and HCO3- and are ubiquitous in nature. Higher plants contain three evolutionarily distinct CA families, αCAs, 13CAs, and γCAs, where each family is represented by multiple isoforms in all species. Alternative splicing of CA transcripts appears common; consequently, the number of functional CA isoforms in a species may exceed the number of genes. CAs are expressed in numerous plant tissues and in different cellular locations. The most prevalent CAs are those in the chloroplast, cytosol, and mitochondria. This diversity in location is paralleled in the many physiological and biochemical roles that CAs play in plants. In this review, the number and types of CAs in C3, C4, and crassulacean acid metabolism （CAM） plants are considered, and the roles of the α and yCAs are briefly discussed. The remainder of the review focuses on plant βCAs and includes the identification of homologs between species using phylogenetic approaches, a consideration of the inter- and intracellular localization of the proteins, along with the evidence for alternative splice forms. Current understanding of βCA tissue-specific expression patterns and what controls them are reviewed, and the physiological roles for which βCAs have been implicated are presented.

关键词： carbonic anhydrase regulation alternative splicing physiological role

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Bone morphogenetic protein signaling：a promising target for white matter protection in perinatal brain injury

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Neural Regeneration Research 2018年第7期13卷 1183-1184页

作者： Jill Chang robert W.Dettman Maria L.v.Dizon Department of Pediatrics Feinberg School of Medicine Northwestern University Chicago IL USA Stanley Manne Research Institute Chicago IL USA

Prematurely born newborns,as well as those born at term,may suffer from several types of brain injury including hypoxic-ischemic injury,intracranial hemorrhage,both intraventricular and parenchymal,and injury that is the consequence of intrauterine growth restriction（IUGR）.Injury of all types can impact the motor and cognitive abilities of *** mechanisms leading to disability are not completely understood.

关键词： In Bone morphogenetic protein signaling:a promising target for white matter protection in perinatal brain injury

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Crustal thickness beneath Atlas region from gravity,topographic,sediment and seismic data

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Geodesy and Geodynamics 2020年第1期11卷 18-30页

作者： Franck Eitel Kemgang Ghomsi robert Tenzer Sévérin Nguiya Animesh Mandal robert Nouayou Department of Physics The University of YaoundeⅠYaoundeCameroon Department of Land Surveying and Geo-Informatics Hong Kong Polytechnic UniversityHong KongChina Faculty of Industrial Engineering University of DoualaDoualaCameroon Department of Earth Sciences Indian Institute of TechnologyKanpurIndia

The Atlas region in northwest Africa is characterized by the Quaternary volcanism and elevated topography with past complex tectonic mitigation between the African and European *** of this atypical region has left indubitably imprints in crustal architectonics,mainly regarding the crustal thickness as well as the crustal density *** knowledge of crustal thickness variations is of a significant interest,since it provides a crucial constraint to geodynamic and geophysical modelling of this *** this study,we use gravity,topographic,bathymetric and sediment data together with results of seismic surveys to image the Moho topography beneath the Atlas *** Bouguer gravity anomalies used for a gravimetric Moho recovery are obtained from the free-air gravity anomalies after subtracting the gravitational contributions of topography,bathymetry and *** regional gravimetric Moho inversion constrained on seismic data is carried out by applying a regularized inversion technique based on Gauss-Newton’s formulation of improved Bott’s method,while adopting Earth’s spherical *** numerical result reveals relatively significant Moho depth variations in the Moroccan Atlas,with minima of approximately 24 km along continental margins of the Mediterranean Sea and maxima exceeding 51 km beneath the Rif *** Moho depth beneath the West African Craton varies from 32 km in its southern margin to 45 km beneath the Middle *** Tell Atlas is characterized by the shallow Moho depth of approximately 22 km and further deepening to 42 km towards the northern edge of the Aures *** findings indicate a limited tectonic shortening of the High Atlas with the crustal thickness mostly within 36-42 *** discrepancies between the Rif Cordillera and the Atlas Mountains suggest that the hypothesis of isostatic compensation cannot be fully established.

关键词： Atlas Gravity Inversion Moho Seismic data

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Outcomes and patients' perspectives of transition from paediatric to adult care in inflammatory bowel disease

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World Journal of Gastroenterology 2016年第8期22卷 2611-2620页

作者： Alice L Bennett David Moore Peter A Bampton robert v Bryant Jane M Andrews Department of Gastroenterology Royal Adelaide Hospital North Terrace Adelaide SA 5000 Australia Department of Gastroenterology Flinders Medical Centre Flinders Drive Bedford Park SA 5042 Australia School of Medicine University of Adelaide Adelaide SA 5000 Australia Department of Gastroenterology Women's and Children's Hospital Adelaide SA 5006 Australia School of Medicine Flinders University Adelaide SA 5001 Australia

AIM: To describe the disease and psychosocial outcomes of an inflammatory bowel disease (IBD) transition cohort and their ***: Patients with IBD, aged > 18 years, who had moved from paediatric to adult care within 10 years were identified through IBD databases at three tertiary hospitals. Participants were surveyed regarding demographic and disease specific data and their perspectives on the transition process. Survey response data were compared to contemporaneously recorded information in paediatric service case notes. Data were compared to a similar age cohort who had never received paediatric IBD care and therefore who had not undergone a transition ***: There were 81 returned surveys from 46 transition and 35 non-transition patients. No statistically significant differences were found in disease burden, disease outcomes or adult roles and responsibilities between cohorts. Despite a high prevalence of mood disturbance (35%), there was a very low usage (5%) of psychological services in both cohorts. In the transition cohort, knowledge of their transition plan was reported by only 25/46 patients and the majority (54%) felt they were not strongly prepared. A high rate (78%) of discussion about work/study plans was recorded prior to transition, but a near complete absence of discussion regarding sex (8%), and other adult issues was recorded. Both cohorts agreed that their preferred method of future transition practices (of the options offered) was a shared clinic appointment with all key ***: Transition did not appear to adversely affect disease or psychosocial outcomes. Current transition care processes could be optimised, with better psychosocial preparation and agreed transition plans.

关键词： Transition care Crohn’ s disease Ulcerative colitis Chronic illness Inflammatory bowel disease Patient perspectives Disease outcomes

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