A Foldable Tightly Coupled Crossed Rings Antenna Array of Ultrawide Bandwidth and Dual Polarization

Low-profile foldable array antennas are becoming increasingly more important for a wide range of applications such as satellite communications and wearable electronic devices. The conventional arrays formed by patch-like antennas have been extensively studied on surfaces with a curvature but they have exhibited limited bandwidth and polarization performance. This study investigates a coupling enhanced crossed rings antenna array with two typical configurations for dual polarization, which inherently produces ultrawide bandwidth, dipole-like polarization characteristics and a fully curved array (FCA) eventually. The fractional bandwidth of the array is over 100% on a planar surface and expanded to approximately 140% on the curved surface. For the bent array of slant polarization, the beamwidth increases by over 20° compared to the planar array and cross polarization discrimination (XPD) maintains above 15 dB. The effects of curvature on the impedance matching and polarized radiation patterns for such arrays are investigated by measuring the performance of the fabricated prototype arrays. The results revealed that the tightly coupled crossed rings antenna array on a curved surface has a potential to form multiple beams on a limited aperture size through smaller subarrays which can yield ultrawide bandwidth due to concentrated mutual coupling mechanism. This characteristic is promising in applications where traditional flat panel arrays are difficult to implement such as in mobile stations, moving platforms and for satellite communication on-the-move

Protective Immunity Induced by Incorporating Multiple Antigenic Proteins of Toxoplasma gondii Into Influenza Virus-Like Particles

Virus-like particle (VLP) as a highly efficient vaccine platform has been used to present single or multiple antigenic proteins. In this study, we generated VLPs (multi-antigen VLPs, TG146) in insect cells co-infected with recombinant baculoviruses presenting IMC, ROP18, and MIC8 of Toxoplasma gondii together with influenza matrix protein 1 (M1) as a core protein. We also generated three VLPs expressing IMC, ROP18, or MIC8 together with M1 for combination VLPs (TG1/TG4/TG6). A total of four kinds of VLPs generated were characterized by TEM. Higher number of VLPs particles per μm2 were observed in multi-antigen VLPs compared to combination VLPs. Mice (BALB/c) were intranasually immunized with multi-antigen VLPs or combination VLPs and challenged with T. gondii tachyzoites (GT1) intraperitoneally. Compared to combination VLPs, multi-antigen VLPs showed significantly higher levels of CD4+ T cell, and germinal center B cell responses with reduced apoptosis responses, resulting in significant reduction on parasite burden. These results indicate that higher efficacy of VLPs generated by multi-antigen VLPs can induce significant reduction of parasite burden and better survival of mice than that by combination VLPs, providing important insights into vaccine design strategy for VLPs vaccine expressing multiple antigenic proteins

Virus-Like Particle Vaccine Protects against 2009 H1N1 Pandemic Influenza Virus in Mice

Background: The 2009 influenza pandemic and shortages in vaccine supplies worldwide underscore the need for new approaches to develop more effective vaccines. Methodology/Principal Findings: We generated influenza virus-like particles (VLPs) containing proteins derived from the A/ California/04/2009 virus, and tested their efficacy as a vaccine in mice. A single intramuscular vaccination with VLPs provided complete protection against lethal challenge with the A/California/04/2009 virus and partial protection against A/ PR/8/1934 virus, an antigenically distant human isolate. VLP vaccination induced predominant IgG2a antibody responses, high hemagglutination inhibition (HAI) titers, and recall IgG and IgA antibody responses. HAI titers after VLP vaccination were equivalent to those observed after live virus infection. VLP immune sera also showed HAI responses against diverse geographic pandemic isolates. Notably, a low dose of VLPs could provide protection against lethal infection. Conclusion/Significance: This study demonstrates that VLP vaccination provides highly effective protection against the 2009 pandemic influenza virus. The results indicate that VLPs can be developed into an effective vaccine, which can b

Antenna array calibration methods based on simultaneous perturbation

Antenna arrays have gained significant interest in millimetre-wave communication systems as an enabling technology to achieve higher capacity and mitigate the high propagation loss. Such arrays with a large bandwidth need to be efficiently calibrated to maximise their performance. An antenna array calibration method based on a stochastic approximation algorithm and simultaneous perturbation has been developed and the procedures to implement it in both frequency and time domains have been presented. The approaches to define objective functions and establish gradient approximations to fulfill a successful convergence for acquiring calibration coefficients in both domains have been explored. In the time domain implementation, only a fraction of the measurement time was required to calibrate an antenna array of ultrawide bandwidth compared with other methods using a perturbation technique. The effectiveness of the proposed method has been validated via numerical experiments in both domains

The Plasmodium knowlesi Pk41 surface protein diversity, natural selection, sub population and geographical clustering: a 6-cysteine protein family member

Introduction The zoonotic malaria parasite Plasmodium knowlesi has currently become the most dominant form of infection in humans in Malaysia and is an emerging infectious disease in most Southeast Asian countries. The P41 is a merozoite surface protein belonging to the 6-cysteine family and is a well-characterized vaccine candidate in P. vivax and P. falciparum; however, no study has been done in the orthologous gene of P. knowlesi. This study investigates the level of polymorphism, haplotypes and natural selection of pk41 genes in clinical isolates from Malaysia. Method Thirty-five full-length pk41 sequences from clinical isolates of Malaysia along with four laboratory lines (along with H-strain) were downloaded from public databases. For comparative analysis between species, orthologous P41 genes from P. falciparum, P. vivax, P. coatneyi and P. cynomolgi were also downloaded. Genetic diversity, polymorphism, haplotype and natural selection were determined using DnaSP 5.10 software. Phylogenetic relationships between Pk41 genes were determined using MEGA 5.0 software. Results Analysis of 39 full-length pk41 sequences along with the H-strain identified 36 SNPs (20 non-synonymous and 16 synonymous substitutions) resulting in 31 haplotypes. Nucleotide diversity across the full-length gene was low and was similar to its ortholog in P. vivax; pv41. Domain-wise amino acid analysis of the two s48/45 domains indicated low level of polymorphisms for both the domains, and the glutamic acid rich region had extensive size variations. In the central domain, upstream to the glutamate rich region, a unique two to six (K-E)n repeat region was identified within the clinical isolates. Overall, the pk41 genes were indicative of negative/purifying selection due to functional constraints. Domain-wise analysis of the s48/45 domains also indicated purifying selection. However, analysis of Tajima’s D across the genes identified non-synonymous SNPs in the s48/45 domain II with high positive values indicating possible epitope binding regions. All the 6-cysteine residues within the s48/45 domains were conserved within the clinical isolates indicating functional conservation of these regions. Phylogenetic analysis of full-length pk41 genes indicated geographical clustering and identified three subpopulations of P. knowlesi; one originating in the laboratory lines and two originating from Sarawak, Malaysian Borneo. Conclusion This is the first study to report on the polymorphism and natural selection of pk41 genes from clinical isolates of Malaysia. The results reveal that there is low level of polymorphism in both s48/45 domains, indicating that this antigen could be a potential vaccine target. However, genetic and molecular immunology studies involving higher number of samples from various parts of Malaysia would be necessary to validate this antigen’s candidacy as a vaccine target for P. knowlesi

Modified HIV envelope proteins with enhanced binding to neutralizing monoclonal antibodies

AbstractThe target for neutralizing antibodies against human immunodeficiency virus (HIV) is the trimeric Env protein on the native virion. Conserved neutralizing epitopes of receptor binding sites are located in the recessed core of the Env protein, partially masked by glycosylations and variable loops. In this study, we have investigated the effects of modifications of the HIV Env protein by glycosylation site mutations, deletions of variable loops, or combinations of both types of mutations on their protein functions and reactivities with neutralizing antibodies. Modified Env proteins were expressed in insect or mammalian cells, and their reactivity with epitope-specific broadly neutralizing monoclonal antibodies (Mabs) was determined by flow cytometry. A unique mutant designated 3G with mutations in three glycosylation motifs within the V3/C3 domains surrounding the CD4 binding site showed higher levels of binding to most broadly neutralizing Mabs (b12 and 2F5) in both insect and mammalian expression systems. Mutants with a deletion of both V1 and V2 loop domains or with a unique combination of both types of mutations also bound to most neutralizing Mabs at higher levels compared to the wild-type control. Most mutants maintained the ability to bind CD4 and to induce syncytium formation at similar or higher levels as compared to that of the wild-type Env protein, except for a mutant with a combination of variable loop deletions and deglycosylation mutations. Our study suggests that modified HIV Env proteins with reduced glycosylation in domains surrounding the CD4 binding site or variable loop-deleted mutants expose important neutralizing epitopes at higher levels than wild type and may provide novel vaccine immunogens

Alendronate prevents angiotensin II-induced collagen I production through geranylgeranylation-dependent RhoA/Rho kinase activation in cardiac fibroblasts

AbstractCollagen I is the main component of extracellular matrix in cardiac fibrosis. Our previous studies have reported inhibition of farnesylpyrophosphate synthase prevents angiotensin II-induced cardiac fibrosis, while the exact molecular mechanism was still unclear. This paper was designed to investigate the effect of alendronate, a farnesylpyrophosphate synthase inhibitor, on regulating angiotensin II-induced collagen I expression in cultured cardiac fibroblasts and to explore the underlying mechanism. By measuring the mRNA and protein levels of collagen I, we found that alendronate prevented angiotensin II-induced collagen I production in a dose-dependent manner. The inhibitory effect on collagen I expression was reversed by geranylgeraniol, and mimicked by inhibitors of RhoA/Rho kinase pathway including C3 exoenzyme and GGTI-286. Thus we suggested geranylgeranylation-dependent RhoA/Rho kinase activation was involved in alendronate-mediated anti-collagen I synthetic effect. Furthermore, we accessed the activation status of RhoA in alendronate-, geranylgeraniol- and GGTI-286-treated cardiac fibroblasts and gave an indirect evidence for RhoA activation via geranylgeranylation. Then we came to the conclusion that in cardiac fibroblasts, alendronate could protect against angiotensin II-induced collagen I synthesis through inhibition of geranylgeranylation and inactivation of RhoA/Rho kinase signaling. Targeting geranylgeranylation and RhoA/Rho kinase signaling will hopefully serve as therapeutic strategies to reduce fibrosis in heart remodeling

A role of brassinosteroids in early fruit development in cucumber

Brassinosteroids (BRs) are essential for many biological processes in plants, however, little is known about their roles in early fruit development. To address this, BR levels were manipulated through the application of exogenous BRs (24-epibrassinolide, EBR) or a BR biosynthesis inhibitor (brassinazole, Brz) and their effects on early fruit development, cell division, and expression of cyclin and cyclin-dependent kinases (CDKs) genes were examined in two cucumber cultivars that differ in parthenocarpic capacity. The application of EBR induced parthenocarpic growth accompanied by active cell division in Jinchun No. 4, a cultivar without parthenocarpic capacity, whereas Brz treatment inhibited fruit set and, subsequently, fruit growth in Jinchun No. 2, a cultivar with natural parthenocarpic capacity, and this inhibitory effect could be rescued by the application of EBR. RT-PCR analysis showed both pollination and EBR induced expression of cell cycle-related genes (CycA, CycB, CycD3;1, CycD3;2, and CDKB) after anthesis. cDNA sequences for CsCycD3;1 and CsCycD3;2 were isolated through PCR amplification. Both CsCycD3;1 and CsCycD3;2 transcripts were up-regulated by EBR treatment and pollination but strongly repressed by Brz treatment. Meanwhile, BR6ox1 and SMT transcripts, two genes involved in BR synthesis, exhibited feedback regulation. These results strongly suggest that BRs play an important role during early fruit development in cucumber

Dynamic expression of cytokine and transcription factor genes during experimental Fasciola gigantica infection in buffaloes

Background Determining the mechanisms involved in the immune-pathogenesis of the tropical liver fluke, Fasciola gigantica, is crucial to the development of any effective therapeutic intervention. Here, we examined the differential gene expression of cytokines and transcription factors in the liver of F. gigantica-infected buffaloes, over the course of infection. Methods Water buffaloes (swamp type) were infected orally with 500 F. gigantica encysted metacercariae. Liver tissue samples were collected 3, 10, 28, 42, 70 and 98 days post-infection (dpi). Levels of gene expression of nine cytokines (IFN-γ, TGF-β, IL-1β, IL-4, IL-6, IL-10, IL-12B, IL-13 and IL-17A) and four transcription factors (T-bet, GATA-3, Foxp3 and ROR-γτ) were determined using quantitative real-time PCR (qRT-PCR). We evaluated any correlation between gene expression of these immune-regulatory factors and the severity of liver pathology. Results Histopathological examination revealed that cellular infiltration, hemorrhage and fibrosis without calcification in the liver parenchyma of infected buffaloes, increased over the course of infection. This progressive pathology was attributed to dysregulated and excessive inflammatory responses induced by infection. The early infection phase (3–10 dpi) was marked by a generalized immunosuppression and elevated TGF-β expression in order to facilitate parasite colonization. A mixed Th1/Th2 immune response was dominant from 28 to 70 dpi, to promote parasite survival while minimizing host tissue damage. During late infection (98 dpi), the response was biased towards Th1/Treg in order to inhibit the host’s Th2 protective response and promote chronic infection. Both IL-10 and IL-17A and the Th17/Treg balance, played key roles in mediating the inflammatory and immunoregulatory mechanisms in the liver during chronic fasciolosis. Conclusions Our data showed distinct CD4+ T helper (Th) polarization and cytokine dysregulation in response to F. gigantica infection in water buffaloes over the course of infection. Characterizing the temporal expression profiles for host immune genes during infection should provide important information for defining how F. gigantica adapts and survives in the liver of buffaloes and how host immune responses influence F. gigantica pathogenicity

In vitro drug release behavior from a novel thermosensitive composite hydrogel based on Pluronic f127 and poly(ethylene glycol)-poly(ε-caprolactone)-poly(ethylene glycol) copolymer

<p>Abstract</p> <p>Background</p> <p>Most conventional methods for delivering chemotherapeutic agents fail to achieve therapeutic concentrations of drugs, despite reaching toxic systemic levels. Novel controlled drug delivery systems are designed to deliver drugs at predetermined rates for predefined periods at the target organ and overcome the shortcomings of conventional drug formulations therefore could diminish the side effects and improve the life quality of the patients. Thus, a suitable controlled drug delivery system is extremely important for chemotherapy.</p> <p>Results</p> <p>A novel biodegradable thermosensitive composite hydrogel, based on poly(ethylene glycol)-poly(ε-caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG, PECE) and Pluronic F127 copolymer, was successfully prepared in this work, which underwent thermosensitive sol-gel-sol transition. And it was flowing sol at ambient temperature but became non-flowing gel at body temperature. By varying the composition, sol-gel-sol transition and <it>in vitro </it>drug release behavior of the composite hydrogel could be adjusted. Cytotoxicity of the composite hydrogel was conducted by cell viability assay using human HEK293 cells. The 293 cell viability of composite hydrogel copolymers were yet higher than 71.4%, even when the input copolymers were 500 μg per well. Vitamin B₁₂(VB₁₂), honokiol (HK), and bovine serum albumin (BSA) were used as model drugs to investigate the <it>in vitro </it>release behavior of hydrophilic small molecular drug, hydrophobic small molecular drug, and protein drug from the composite hydrogel respectively. All the above-mentioned drugs in this work could be released slowly from composite hydrogel in an extended period. Chemical composition of composite hydrogel, initial drug loading, and hydrogel concentration substantially affected the drug release behavior. The higher Pluronic F127 content, lower initial drug loading amount, or lower hydrogel concentration resulted in higher cumulative release rate.</p> <p>Conclusion</p> <p>The results showed that composite hydrogel prepared in this paper were biocompatible with low cell cytotoxicity, and the drugs in this work could be released slowly from composite hydrogel in an extended period, which suggested that the composite hydrogel might have great potential applications in biomedical fields.</p