Large-size redox flow battery stacks require flow channels for uniform flow circulation of electrolyte over the electrode without incurring too high a pressure drop penalty. In the present work, the ...use of thin graphite sheets in a flow-through mode, i.e., with the electrolyte being pumped directly into the electrode is explored. In order to reduce the pressure drop when such designs are scaled to large size cells, use of relatively thick polypropylene frames to hold carbon felt electrodes is studied. Experiments have been conducted in cells of nominal electrode areas of 120 and 440 cm2 having a 0.6 mm thick graphite sheet as the bipolar plate. Pressure drop and electrochemical characterization studies show that sufficient convection velocities of electrolyte in the carbon felt, in the range of 3–5 mm s−1, are needed to obtain high round-trip energy efficiency as well as discharge energy density. This observation is supported by estimates of mass transport limited current density for the cell. Under these conditions, use of thin graphite sheets yields a weight reduction of over 75% when compared to cells with thick graphite plates while giving comparable hydrodynamic and electrochemical performance.
•Novel cell architecture proposed for vanadium redox flow batteries.•New cell design features thin bipolar plates and thick electrode.•Low pressure drop and high electrochemical efficiency demonstrated in two cell sizes.•Analytical model for estimation of limiting current density proposed and validated.
Maize lethal necrosis (MLN) disease is a significant constraint for maize producers in sub-Saharan Africa (SSA). The disease decimates the maize crop, in some cases, causing total crop failure with ...far-reaching impacts on regional food security. In this review, we analyze the impacts of MLN in Africa, finding that resource-poor farmers and consumers are the most vulnerable populations. We examine the molecular mechanism of MLN virus transmission, role of vectors and host plant resistance identifying a range of potential opportunities for genetic and phytosanitary interventions to control MLN. We discuss the likely exacerbating effects of climate change on the MLN menace and describe a sobering example of negative genetic association between tolerance to heat/drought and susceptibility to viral infection. We also review role of microRNAs in host plant response to MLN causing viruses as well as heat/drought stress that can be carefully engineered to develop resistant varieties using novel molecular techniques. With the dual drivers of increased crop loss due to MLN and increased demand of maize for food, the development and deployment of simple and safe technologies, like resistant cultivars developed through accelerated breeding or emerging gene editing technologies, will have substantial positive impact on livelihoods in the region. We have summarized the available genetic resources and identified a few large-effect QTLs that can be further exploited to accelerate conversion of existing farmer-preferred varieties into resistant cultivars.
Tar spot complex (TSC) is a major fungal disease of maize in Mexico and several Central and South American countries. The causal agents of the disease are Phyllachora maydis and Monographella maydis. ...Yield losses of up to 58% associated with this disease have been reported previously. The majority of commercial maize germplasm in the United States is considered highly susceptible to TSC. In order to accelerate the disease resistance improvement process, genes for resistance to TSC and molecular markers linked to these genes, need to be identified and characterized. Here, we used an association mapping technique to detect quantitative trait loci (QTLs) for TSC resistance using genome‐wide association study (GWAS)‐based genotyping‐by‐sequencing (GBS) and Diversity Arrays Technology Sequencing (DArTseq) single‐nucleotide polymorphisms. An association mapping panel of 228 CIMMYT maize lines was used for the GWAS. One major QTL explaining 27.66% of the phenotypic variance and four minor QTLs explaining 10.18%, 12.72%, 10.14% and 13.38% of the phenotypic variance, respectively, were identified by the GBS‐based association mapping. Two QTLs were identified by DArTseq‐based association mapping explaining 1.07% and 18.29% of the phenotypic variance, respectively. These QTLs are expected to facilitate subsequent maize improvement using marker‐assisted selection.
With a limited global supply of vaccines and an increasing vaccine hesitancy, improving vaccination coverage has become a priority. Current vaccination regimes require multiple doses to be ...administered in a defined schedule where missed doses may lead to incomplete vaccine coverage and failure of immunization programmes. As such, there is an ever-increasing demand to convert multi-dose injectable vaccines into single-dose formats, often called single administration vaccines (SAVs).
This review summarizes recent developments in the field of SAVs, with a focus on pulsatile or controlled-release formulations. It will identify the technical challenges, translational as well as commercial barriers to SAVs development. Furthermore, the progress of SAV formulations for hepatitis B and polio vaccines will be reviewed thoroughly as case studies, with a focus on the development challenges and the preclinical immunogenicity/reactogenicity data.
Despite the efforts to develop SAVs, few attempts have advanced to Phase-I trials. Considering the SAV development journey and bottlenecks, including commercial barriers from the early stages, may overcome some of the hurdles around the technology. The renewed global focus on vaccines since the COVID-19 pandemic could facilitate development of a new generation of technologies for pandemic preparedness including strategies for SAVs.
Virus-Like Particles (VLPs) have been used as immunogenic molecules in numerous recombinant vaccines. VLPs can also serve as vaccine platform to exogenous antigens, usually peptides incorporated ...within the protein sequences which compose the VLPs or conjugated to them. We herein described the conjugation of a synthetic tetrasaccharide mimicking the
Streptococcus pneumoniae
serotype 14 capsular polysaccharide to recombinant adenoviral type 3 dodecahedron, formed by the self-assembling of twelve penton bases and investigated the induced immune response when administered subcutaneously (
s.c
.). Whether formulated in the form of a dodecahedron or disassembled, the glycoconjugate induced an anti-protein response after two and three immunizations equivalent to that observed when the native dodecahedron was administered. On the other hand, the glycoconjugate induced a weak anti-IgM response which diminishes after two doses but no IgM-to-IgG switch was observed in mice against the serotype 14 capsular polysaccharide. In definitive, the whole conjugation process preserved both particulate nature and immunogenicity of the adenoviral dodecahedron. Further studies are needed to fully exploit adenoviral dodecahedron potential in terms of plasticity towards sequence engineering and of its capacity to stimulate the immune system via the intranasal route of administration as well as to shift the response to the carbohydrate antigen by playing both with the carbohydrate to protein ratio and the length of the synthetic carbohydrate antigen.
The fall armyworm (FAW), Spodoptera frugiperda, a pest of maize native to the Americas first reported in West and Central Africa in 2016, severely threatens maize production and food security in ...Sub-Saharan Africa. Native genetic resistance is one of the best methods of control of insect pests as it is contained in the seed making it more amenable for use by farmers compared to other interventions and it is also compatible with other integrated pest management (IPM) options. An intensive screening against FAW was carried out by artificial infestation in greenhouse conditions in Kenya between 2017 and 2018 on about 3000 inbred lines available in the germplasm collection of the International Maize and Wheat Improvement Center (CIMMYT). Among these lines, only four showed to be resistant to FAW, but the mechanisms of resistance are not yet known. The objective of this study was to determine the resistance mechanisms specifically non-preference and antibiosis to S. frugiperda in these four selected resistant inbred lines. The studies were conducted under laboratory and net house conditions in Kenya from April 2020 to November 2021. Non-preference was assessed estimating the feeding preference by counting the number of FAW neonates found on each leaf portion, silk portion and grain using binary and multiple choice methods under laboratory conditions, while antibiosis was assessed through the relative growth rate (RGR) and developmental time of FAW larvae on leaves, silks and grains under both laboratory and net house conditions. Among the four resistant maize inbred lines tested, two, namely CML71 and CKSBL10008, exhibited the highest level of antibiosis resistance on leaves. Under laboratory conditions, the larval RGR reduced from 13 mg/d on the most susceptible line to 8 mg/d on CML71. CML71 also showed a good non-preference on leaves compared to other tested lines. Only 6% of neonates choose to feed on CML71 whereas more than 10% choose to feed on the other lines (and 15% on the most susceptible) in multiple choice tests. The non-preference for feeding and lower RGR of larvae on CML71 suggest a biochemical involvement resistance to FAW. Through this study, CML71 is revealed as a highly promising line for use in breeding for native genetic resistance to FAW in tropical maize.
Tar spot complex (TSC), caused by at least two fungal pathogens,
and
, is one of the major foliar diseases of maize in Central and South America.
was also detected in the United States of America in ...2015 and since then the pathogen has spread in the maize growing regions of the country. Although remote sensing (RS) techniques are increasingly being used for plant phenotyping, they have not been applied to phenotyping TSC resistance in maize. In this study, several multispectral vegetation indices (VIs) and thermal imaging of maize plots under disease pressure and disease-free conditions were tested using an unmanned aerial vehicle (UAV) over two crop seasons. A strong relationship between grain yield, a vegetative index (MCARI2), and canopy temperature was observed under disease pressure. A strong relationship was also observed between the area under the disease progress curve of TSC and three vegetative indices (RDVI, MCARI1, and MCARI2). In addition, we demonstrated that TSC could cause up to 58% yield loss in the most susceptible maize hybrids. Our results suggest that the RS techniques tested in this study could be used for high throughput phenotyping of TSC resistance and potentially for other foliar diseases of maize. This may help reduce the cost and time required for the development of improved maize germplasm. Challenges and opportunities in the use of RS technologies for disease resistance phenotyping are discussed.
Globally, downy mildews are among the important foliar diseases of maize that cause significant yield losses. We conducted a genome-wide association study for sorghum downy mildew (SDM; ...Peronosclerospora sorghi) resistance in a panel of 368 inbred lines adapted to the Asian tropics. High density SNPs from Genotyping-by-sequencing were used in GWAS after controlling for population structure and kinship in the panel using a single locus mixed model. The study identified a set of 26 SNPs that were significantly associated with SDM resistance, with Bonferroni corrected P values ≤ 0.05. Among all the identified SNPs, the minor alleles were found to be favorable to SDM resistance in the mapping panel. Trend regression analysis with 16 independent genetic variants including 12 SNPs and four haplotype blocks identified SNP S2_6154311 on chromosome 2 with P value 2.61E-24 and contributing 26.7% of the phenotypic variation. Six of the SNPs/haplotypes were within the same chromosomal bins as the QTLs for SDM resistance mapped in previous studies. Apart from this, eight novel genomic regions for SDM resistance were identified in this study; they need further validation before being applied in the breeding pipeline. Ten SNPs identified in this study were co-located in reported mildew resistance genes.
Glycoconjugate vaccines are formed by covalently link a carbohydrate antigen to a carrier protein whose role is to achieve a long lasting immune response directed against the carbohydrate antigen. ...The nature of the sugar antigen, its length, its ratio per carrier protein and the conjugation chemistry impact on both structure and the immune response of a glycoconjugate vaccine. In addition it has long been assumed that the sites at which the carbohydrate antigen is attached can also have an impact. These important issue can now be addressed owing to the development of novel chemoselective ligation reactions as well as techniques such as site-selective mutagenesis, glycoengineering, or extension of the genetic code. The preparation and characterization of homogeneous bivalent pneumococcal vaccines is reported. The preparation and characterization of homogeneous bivalent pneumococcal vaccines is reported. A synthetic tetrasaccharide representative of the serotype 14 capsular polysaccharide of
Streptococcus pneumoniae
has been linked using the thiol/maleimide coupling chemistry to four different Pneumococcal surface adhesin A (PsaA) mutants, each harboring a single cysteine mutation at a defined position. Humoral response of these 1 to 1 carbohydrate antigen/PsaA conjugates have been assessed in mice. Our results showed that the carbohydrate antigen-PsaA connectivity impacts the anti-carrier response and raise questions about the design of glycoconjugate vaccine whereby the protein plays the dual role of immunogen and carrier.
Core–shell nanostructures are promising platforms for combination drug delivery. However, their complicated synthesis process, poor stability, surface engineering, and low biocompatibility are major ...hurdles. Herein, a carboxymethyl chitosan-coated poly(lactide-co-glycolide) (cmcPLGA) core–shell nanostructure is prepared via a simple one-step nanoprecipitation self-assembly process. Engineered core–shell nanostructures are tested for combination delivery of loaded docetaxel and doxorubicin in a cancer-mimicked environment. The drugs are compartmentalized in a shell (doxorubicin, Dox) and a core (docetaxel, Dtxl) with loading contents of ∼1.2 and ∼2.06%, respectively. Carboxymethyl chitosan with both amine and carboxyl groups act as a polyampholyte in diminishing ζ-potential of nanoparticles from fairly negative (−13 mV) to near neutral (−2 mV) while moving from a physiological pH (7.4) to an acidic tumor pH (6) that can help the nanoparticles to accumulate and release the drug on-site. The dual-drug formulation was found to carry a clinically comparable 1.7:1 weight ratio of Dtxl/Dox, nanoengineered for the sequential release of Dox followed by Dtxl. Single and engineered combinatorial nanoformulations show better growth inhibition toward three different cancer cells compared to free drug treatment. Importantly, Dox–Dtxl cmcPLGA nanoparticles scored synergism with combination index values between 0.2 and 0.3 in BT549 (breast ductal carcinoma), PC3 (prostate cancer), and A549 (lung adenocarcinoma) cell lines, demonstrating significant cell growth inhibition at lower drug concentrations as compared to single-drug control groups. The observed promising performance of dual-drug formulation is due to the G2/M phase arrest and apoptosis.