Nelinearno upravljanje s unutarnjim modelom za pogon s prekidačkim reluktantnim motorom bez oscilacija momenta

Based on the nonlinear internal-model control (IMC), associated with the suitable commutation strategy, a novel control solution for switched reluctance motor (SRM) is formulated and designed. The commutation strategy uses a definite critical rotor position as commutation point, which reduces the computational burden. The nonlinear IMC-based voltage control scheme for SRM extracts the simplicity of the feedback linearization control and the robustness of IMC structure, which ensures the torque ripple-free and the drive\u27s robustness in spite of the plant-model mismatch disturbances. Some important properties are presented. Simulation results show that the high-performance control for SRM has been achieved.Predloženo je i razrađeno novo rješenje za upravljanje sklopnim reluktantnim motorom (SRM) zasnovano na nelinearnom upravljanju s unutarnjim modelom (IMC) i prikladnoj strategiji komutacije. Strategija komutacije koristi definiranu kritičnu poziciju rotora kao točku komutacije što doprinosi smanjenju računskih zahtjevnosti. Shema za upravljanje naponom SRM-a zasnovana na nelinearnom IMC-u osigurava linearizaciju zatvorenog sustava i robusnost IMC strukture što rezultira ukupnom robusnošću pogona bez oscilacija momenta unatoč nepodudaranju modela smetnji sa stvarnim smetnjama. Opisana su neka važna svojstva ovoga načina upravljanja. Simulacijskim se rezultatima pokazuje visoka kvaliteta upravljanja SRM-a

Rotavirus antigen, cytokine, and neutralising antibody profiles in sera of children with and without HIV infection in Blantyre, Malawi

Background: Rotavirus and HIV infection are major causes of death among children in sub-Saharan Africa. A previous study reported no association between concomitant HIV infection and rotavirus disease severity among hospitalised children in Malawi. This study examined rotavirus antigenaemia and broader immune responses among HIV-infected and uninfected children.Methods: Stored (−80°C), paired sera from acute and convalescent phases of Malawian children less than 5 years old, hospitalised for acute gastroenteritis in the primary study, collected from July 1997 to June 1999, were utilised. Among children older than 15 months, HIV infection was defined as the presence of HIV antibody in the blood, when confirmed by at least 2 established methods. For those younger than 15 months, nested polymerase chain reaction (PCR) amplification of proviral DNA was used for verification. All were followed for up to 4 weeks after hospital discharge. Rotavirus antigen levels in sera were measured with Premier™ Rotaclone® rotavirus enzyme immunoassay (EIA) kit. Acute-phase sera were examined for 17 cytokines, using Luminex fluorescent bead human cytokine immunoassay kit. Rotavirus-specific IgA and neutralising activity were determined by EIA and microneutralisation (MN) assay, respectively. Human strains and bovine–human reassortants were propagated in MA104 cells with serum-free Iscove’s Modified Dulbecco’s Medium (IMDM). Differences in results, from specimens with and without HIV infection, were analysed for statistical significance using the chi-square test.Results: We detected rotavirus antigen in 30% of the HIV-infected and 21% HIV-uninfected, in the acute-phase sera. HIV-infected children developed slightly prolonged rotavirus antigenaemia compared to HIV-uninfected children.Conclusions: Rotavirus-specific IgA seroconversion rates and neutralising titres were similar in HIV-infected and HIV-uninfected children, thus, HIV infection had no major effect on immune responses to rotavirus infection

Association of Maternal Immunity with Rotavirus Vaccine Immunogenicity in Zambian Infants

IntroductionLive attenuated oral vaccines against rotavirus (RV) have been shown to be less efficacious in children from developing countries. Reasons for this disparity are not fully understood. We assessed the role of maternal factors including breast milk RV-specific IgA, transplacentally acquired infant serum RV-specific IgG and maternal HIV status in seroconversion among Zambian infants routinely immunized with Rotarix™ (RV1).Methods420 mother-child pairs were recruited at infant age 6–12 weeks in Lusaka. Clinical information and samples were collected at baseline and at one month following the second dose of RV1. Determination of breast milk RV-specific IgA and serum RV-specific IgA and IgG was done using standardized ELISA. Seroconversion was defined as a ≥ 4 fold rise in serum IgA titre from baseline to one-month post RV1 dose 2, while seropositivity of IgA was defined as serum titre ≥ 40 and antibody variables were modelled on log-base 2. Logistic regression was used to identify predictors of the odds of seroconversion.ResultsBaseline infant seropositivity was 25.5% (91/357). The seroconversion frequency was 60.2% (130/216). Infants who were IgA seropositive at baseline were less likely to seroconvert compared to their seronegative counterparts (P = 0.04). There was no evidence of an association between maternal HIV status and seroconversion (P = 0.25). Higher titres of breast milk rotavirus-specific IgA were associated with a lower frequency of seroconverson (Nonparametric test for trend Z = -2.84; P<0.01): a two-fold increase in breast milk RV-specific IgA titres was associated with a 22% lower odds of seroconversion (OR = 0.80; 95% CI = 0.68–0.94; P = 0.01). There was seasonal variation in baseline breast milk rotavirus-specific IgA titres, with significantly higher GMTs during the cold dry months (P = 0.01).ConclusionLow immunogenicity of RV1 vaccine could be explained in part by exposure to high antibody titres in breast milk and early exposure to wild-type rotavirus infections. Potential interference of anti-RV specific IgA in breast milk and pre-vaccination serum RV specific-IgA and IgG titres with RV1 seroconversion and effectiveness requires further research

Novel G9 rotavirus strains co-circulate in children and pigs, Taiwan

Molecular epidemiologic studies collecting information of the spatiotemporal distribution of rotavirus VP7 (G) and VP4 (P) genotypes have shown evidence for the increasing global importance of genotype G9 rotaviruses in humans and pigs. Sequence comparison of the VP7 gene of G9 strains identified different lineages to prevail in the respective host species although some of these lineages appear to be shared among heterologous hosts providing evidence of interspecies transmission events. The majority of these events indicates the pig-to-human spillover, although a reverse route of transmission cannot be excluded either. In this study, new variants of G9 rotaviruses were identified in two children with diarrhea and numerous pigs in Taiwan. Whole genome sequence and phylogenetic analyses of selected strains showed close genetic relationship among porcine and human strains suggesting zoonotic origin of Taiwanese human G9 strains detected in 2014–2015. Although the identified human G9P[19] and G9P[13] rotaviruses represented minority strains, the repeated detection of porcine-like rotavirus strains in Taiwanese children over time justifies the continuation of synchronized strain surveillance in humans and domestic animals

Isolation and characterization of a new simian rotavirus, YK-1

BACKGROUND: To effectively analyze the requirements for protection to rotavirus infection, a reliable animal model that reasonably mimics infection and disease in humans is needed. A requirement for an effective animal model is the availability of appropriate rotavirus stocks for challenge. RESULTS: A new simian rotavirus, designated YK-1, was isolated from a 2-year-old immunodeficient pigtailed macaque with chronic diarrhea. YK-1 was distinguishable by electropherotype from the other simian rotavirus strains, SA11 and RRV. One variant of YK-1, clone 311, which was isolated after adaptation and plaque purification in cell cultures, displayed an unusual RNA electropherotype with an abnormally migrating gene 11 segment. Sequence analysis demonstrated a genetic rearrangement that involved a partial duplication of the gene 11 ORF encoding NSP5. YK-1 was identified as a Group A rotavirus belonging to subgroup 1. To further characterize the YK-1 strain, the genes encoding VP4, VP7, and NSP4 were sequenced. Analysis of VP4 and VP7 gene fragments suggests that this strain is a G3P[3] rotavirus and is closely related to the simian rotavirus strain RRV. Serotype analysis also identified YK-1 as a G3 rotavirus. The NSP4 genotype of YK-1 is C, the same genotype as RRV. CONCLUSION: This newly isolated rotavirus, YK-1, is being used to establish a nonhuman primate model for studying the infectivity, immunity, and pathogenesis of rotavirus and for evaluating candidate rotavirus vaccines

Innate Immune Factors in Mothers' Breast Milk and Their Lack of Association With Rotavirus Vaccine Immunogenicity in Nicaraguan Infants

To better understand underlying causes of lower rotavirus vaccine effectiveness in low-middle income countries (LMICs), we measured innate antiviral factors in Nicaraguan mothers' milk and immune response to the first dose of the pentavalent rotavirus vaccine in corresponding infants. No relationship was found between concentrations of innate factors and rotavirus vaccine response

Mutant Ahi1 Affects Retinal Axon Projection in Zebrafish via Toxic Gain of Function

Joubert syndrome (JBTS) is an inherited autosomal recessive disorder associated with cerebellum and brainstem malformation and can be caused by mutations in the Abelson helper integration site-1 (AHI1) gene. Although AHI1 mutations in humans cause abnormal cerebellar development and impaired axonal decussation in JBTS, these phenotypes are not robust or are absent in various mouse models with Ahi1 mutations. AHI1 contains an N-terminal coiled-coil domain, multiple WD40 repeats, and a C-terminal Src homology 3 (SH3) domain, suggesting that AHI1 functions as a signaling or scaffolding protein. Since most AHI1 mutations in humans can result in truncated AHI1 proteins lacking WD40 repeats and the SH3 domain, it remains unclear whether mutant AHI1 elicits toxicity via a gain-of-function mechanism by the truncated AHI1. Because Ahi1 in zebrafish and humans share a similar N-terminal region with a coiled-coil domain that is absent in mouse Ahi1, we used zebrafish as a model to investigate whether Ahi1 mutations could affect axonal decussation. Using in situ hybridization, we found that ahi1 is highly expressed in zebrafish ocular tissues, especially in retina, allowing us to examine its effect on retinal ganglion cell (RGC) projection and eye morphology. We injected a morpholino to zebrafish embryos, which can generate mutant Ahi1 lacking the intact WD40 repeats, and found RGC axon misprojection and ocular dysplasia in 4 dpf (days post-fertilization) larvae after the injection. However, ahi1 null zebrafish showed normal RGC axon projection and ocular morphology. We then used CRISPR/Cas9 to generate truncated ahi1 and also found similar defects in the RGC axon projection as seen in those injected with ahi1 morpholino. Thus, the aberrant retinal axon projection in zebrafish is caused by the presence of mutant ahi1 rather than the loss of ahi1, suggesting that mutant Ahi1 may affect axonal decussation via toxic gain of function

Impact of withholding breastfeeding at the time of vaccination on the immunogenicity of oral rotavirus vaccine--a randomized trial

Background: Breast milk contains anti-rotavirus IgA antibodies and other innate immune factors that inhibit rotavirus replication in vitro. These factors could diminish the immunogenicity of oral rotavirus vaccines, particularly if breastfeeding occurs close to the time of vaccine administration.Methods: Between April 2011 and November 2012, we conducted an open label, randomized trial to compare the immunogenicity of Rotarix (RV1) in infants whose breastfeeding was withheld one hour before through one hour after vaccination with that in infants breastfed at the time of vaccination. The trial was conducted in the peri-urban area of Ibrahim Hyderi in Karachi, Pakistan. Both groups received three doses of RV1 at 6, 10 and 14 weeks of age. Seroconversion (anti-rotavirus IgA antibodies ≥ 20 U/mL in subjects seronegative at 6 weeks of age) following three vaccine doses (6, 10 and 14 weeks) was determined at 18 weeks of age (primary objective) and seroconversion following two doses (6 and 10 weeks) was determined at 14 weeks of age (secondary objective).Results: Four hundred eligible infants were randomly assigned in a 1:1 ratio between the withholding breastfeeding and immediate breastfeeding arms. Overall, 353 (88.3%) infants completed the study according to protocol; 181 in the withholding breastfeeding group and 172 in the immediate breastfeeding group. After three RV1 doses, anti-rotavirus IgA antibody seroconversion was 28.2% (95% CI: 22.1; 35.1) in the withholding arm and 37.8% (95% CI: 30.9; 45.2) in the immediate breastfeeding arm (difference: -9.6% [95% CI: -19.2; 0.2] p = 0.07). After two doses of RV1, seroconversion was 16.6% (95% CI: 11.9; 22.7) in the withholding arm and 29.1% (95% CI: 22.8, 36.3) in the immediate breastfeeding arm (difference: -12.5% [95% CI: -21.2,-3.8] p = 0.005).Conclusions: Withholding breastfeeding around the time of RV1 vaccine administration did not lead to increased anti-rotavirus IgA seroconversion compared with that seen with a breastfeed at the time of vaccination. On the contrary, IgA seroconversion in infants immediately breastfed tended to be higher than in those withheld from a feeding. Our findings suggest that breastfeeding should be continued adlib around the time of rotavirus vaccination and withholding breastfeeding at that time is unlikely to improve the vaccine immunogenicity