3,651 research outputs found

    Role of (p)ppGpp in Viability and Biofilm Formation of Actinobacillus pleuropneumoniae S8.

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    Actinobacillus pleuropneumoniae is a Gram-negative bacterium and the cause of porcine pleuropneumonia. When the bacterium encounters nutritional starvation, the relA-dependent (p)ppGpp-mediated stringent response is activated. The modified nucleotides guanosine 5'-diphosphate 3'-diphosphate (ppGpp) and guanosine 5'-triphosphate 3'-diphosphate (pppGpp) are known to be signaling molecules in other prokaryotes. Here, to investigate the role of (p)ppGpp in A. pleuropneumoniae, we created a mutant A. pleuropneumoniae strain, S8ΔrelA, which lacks the (p)ppGpp-synthesizing enzyme RelA, and investigated its phenotype in vitro. S8ΔrelA did not survive after stationary phase (starvation condition) and grew exclusively as non-extended cells. Compared to the wild-type (WT) strain, the S8ΔrelA mutant had an increased ability to form a biofilm. Transcriptional profiles of early stationary phase cultures revealed that a total of 405 bacterial genes were differentially expressed (including 380 up-regulated and 25 down-regulated genes) in S8ΔrelA as compared with the WT strain. Most of the up-regulated genes are involved in ribosomal structure and biogenesis, amino acid transport and metabolism, translation cell wall/membrane/envelope biogenesis. The data indicate that (p)ppGpp coordinates the growth, viability, morphology, biofilm formation and metabolic ability of A. pleuropneumoniae in starvation conditions. Furthermore, S8ΔrelA could not use certain sugars nor produce urease which has been associated with the virulence of A. pleuropneumoniae, suggesting that (p)ppGpp may directly or indirectly affect the pathogenesis of A. pleuropneumoniae during the infection process. In summary, (p)ppGpp signaling represents an essential component of the regulatory network governing stress adaptation and virulence in A. pleuropneumoniae

    Balson: Bayesian least squares optimization with nonnegative L1-Norm constraint

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    © 2018 IEEE. A Bayesian approach termed the BAyesian Least Squares Optimization with Nonnegative L1-norm constraint (BALSON) is proposed. The error distribution of data fitting is described by Gaussian likelihood. The parameter distribution is assumed to be a Dirichlet distribution. With the Bayes rule, searching for the optimal parameters is equivalent to finding the mode of the posterior distribution. In order to explicitly characterize the nonnegative L1-norm constraint of the parameters, we further approximate the true posterior distribution by a Dirichlet distribution. We estimate the moments of the approximated Dirichlet posterior distribution by sampling methods. Four sampling methods have been introduced and implemented. With the estimated posterior distributions, the original parameters can be effectively reconstructed in polynomial fitting problems, and the BALSON framework is found to perform better than conventional methods

    In vivo testing of novel vaccine prototypes against Actinobacillus pleuropneumoniae

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    Actinobacillus pleuropneumoniae (A. pleuropneumoniae) is a Gram-negative bacterium that represents the main cause of porcine pleuropneumonia in pigs, causing significant economic losses to the livestock industry worldwide. A. pleuropneumoniae, as the majority of Gram-negative bacteria, excrete vesicles from its outer membrane (OM), accordingly defined as outer membrane vesicles (OMVs). Thanks to their antigenic similarity to the OM, OMVs have emerged as a promising tool in vaccinology. In this study we describe the in vivo testing of several vaccine prototypes for the prevention of infection by all known A. pleuropneumoniae serotypes. Previously identified vaccine candidates, the recombinant proteins ApfA and VacJ, administered individually or in various combinations with the OMVs, were employed as vaccination strategies. Our data show that the addition of the OMVs in the vaccine formulations significantly increased the specific IgG titer against both ApfA and VacJ in the immunized animals, confirming the previously postulated potential of the OMVs as adjuvant. Unfortunately, the antibody response raised did not translate into an effective protection against A. pleuropneumoniae infection, as none of the immunized groups following challenge showed a significantly lower degree of lesions than the controls. Interestingly, quite the opposite was true, as the animals with the highest IgG titers were also the ones bearing the most extensive lesions in their lungs. These results shed new light on A. pleuropneumoniae pathogenicity, suggesting that antibody-mediated cytotoxicity from the host immune response may play a central role in the development of the lesions typically associated with A. pleuropneumoniae infections

    A novel COMP mutation in a pseudoachondroplasia family of Chinese origin

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    <p>Abstract</p> <p>Background</p> <p>Pseudoachondroplasia (PSACH) is caused exclusively by mutations in the gene for cartilage oligomeric matrix protein (<it>COMP</it>). Only a small number of studies have documented the clinical phenotype and genetic basis in Chinese PSACH patients.</p> <p>Case presentation</p> <p>We investigated a four-generation PSACH pedigree of Chinese Han origin. Two patients and two unaffected individuals were recruited for clinical evaluation and molecular genetic analysis. The genomic DNA was extracted from peripheral blood leukocytes. Polymerase chain reaction (PCR) was adopted to amplify the 8-19 exons of <it>COMP </it>gene. Then the products were sequenced bi-directionally for screening mutation. Clinical evaluation revealed that PSACH patients in this pedigree had a severe disproportionate short stature (-10SD). A heterozygous TGTCCCTGG insertion in exon 13, between nucleotide 1352T and 1353G, were identified in the patients except the unaffected individuals, which resulted in a three-amino-acid insertion (451V_452P ins VPG) in the sixth calmodulin-like repeat of the <it>COMP </it>protein.</p> <p>Conclusion</p> <p>This c. 1352_1353ins TGTCCCTGG is a novel mutation responsible for severe familial PSACH.</p

    Transparency in health economic modeling : options, issues and potential solutions

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    Economic models are increasingly being used by health economists to assess the value of health technologies and inform healthcare decision making. However, most published economic models represent a kind of black box, with known inputs and outputs but undisclosed internal calculations and assumptions. This lack of transparency makes the evaluation of the model results challenging, complicates comparisons between models, and limits the reproducibility of the models. Here, we aim to provide an overview of the possible steps that could be undertaken to make economic models more transparent and encourage model developers to share more detailed calculations and assumptions with their peers. Scenarios with different levels of transparency (i.e., how much information is disclosed) and reach of transparency (i.e., who has access to the disclosed information) are discussed, and five key concerns (copyrights, model misuse, confidential data, software, and time/resources) pertaining to model transparency are presented, along with possible solutions. While a shift toward open-source models is underway in health economics, as has happened before in other research fields, the challenges ahead should not be underestimated. Importantly, there is a pressing need to find an acceptable trade-off between the added value of model transparency and the time and resources needed to achieve such transparency. To this end, it will be crucial to set incentives at different stakeholder levels. Despite the many challenges, the many benefits of publicly sharing economic models make increased transparency a goal worth pursuing

    Simulation of InP-based monolithically integrated PIN-HEMT front-end optical receiver

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    Model is developed for the dc I-V characteristics and microwave small-signal parameters of the InP-based In(0.52)Al(0.28)As/In(0.65)Ga(0.35)As HEMT's based on physical principles, and the effect of the extrinsic source and drain resistances has also been included. Using the parameters obtained by this model and the small-signal model of PIN detector, we simulated the transimpedance configurations with an inverter and a cascode input circuit of monolithically integrated PIN-HEMT front-end optical receiver. The results indicate that the cascode input stage can realize a smaller input capacitance than the inverter-type, so it has a wider bandwidth. In order to operate in 2.5Gb/s transmission system, the cascode input stage is applied and the parameters are optimized. The simulations reveal that the transimpedance gain is larger than 63.2dB Omega and the sensitivity is 30dBm when the bit rate is 2.5Gb/s. The results obtained in this paper provide a guideline for the fabrication of PIN-HEMT optical receiver

    Impact of Community-Based Larviciding on the Prevalence of Malaria Infection in Dar es Salaam, Tanzania.

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    The use of larval source management is not prioritized by contemporary malaria control programs in sub-Saharan Africa despite historical success. Larviciding, in particular, could be effective in urban areas where transmission is focal and accessibility to Anopheles breeding habitats is generally easier than in rural settings. The objective of this study is to assess the effectiveness of a community-based microbial larviciding intervention to reduce the prevalence of malaria infection in Dar es Salaam, United Republic of Tanzania. Larviciding was implemented in 3 out of 15 targeted wards of Dar es Salaam in 2006 after two years of baseline data collection. This intervention was subsequently scaled up to 9 wards a year later, and to all 15 targeted wards in 2008. Continuous randomized cluster sampling of malaria prevalence and socio-demographic characteristics was carried out during 6 survey rounds (2004-2008), which included both cross-sectional and longitudinal data (N = 64,537). Bayesian random effects logistic regression models were used to quantify the effect of the intervention on malaria prevalence at the individual level. Effect size estimates suggest a significant protective effect of the larviciding intervention. After adjustment for confounders, the odds of individuals living in areas treated with larviciding being infected with malaria were 21% lower (Odds Ratio = 0.79; 95% Credible Intervals: 0.66-0.93) than those who lived in areas not treated. The larviciding intervention was most effective during dry seasons and had synergistic effects with other protective measures such as use of insecticide-treated bed nets and house proofing (i.e., complete ceiling or window screens). A large-scale community-based larviciding intervention significantly reduced the prevalence of malaria infection in urban Dar es Salaam

    AUTO3D: Novel view synthesis through unsupervisely learned variational viewpoint and global 3D representation

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    This paper targets on learning-based novel view synthesis from a single or limited 2D images without the pose supervision. In the viewer-centered coordinates, we construct an end-to-end trainable conditional variational framework to disentangle the unsupervisely learned relative-pose/rotation and implicit global 3D representation (shape, texture and the origin of viewer-centered coordinates, etc.). The global appearance of the 3D object is given by several appearance-describing images taken from any number of viewpoints. Our spatial correlation module extracts a global 3D representation from the appearance-describing images in a permutation invariant manner. Our system can achieve implicitly 3D understanding without explicitly 3D reconstruction. With an unsupervisely learned viewer-centered relative-pose/rotation code, the decoder can hallucinate the novel view continuously by sampling the relative-pose in a prior distribution. In various applications, we demonstrate that our model can achieve comparable or even better results than pose/3D model-supervised learning-based novel view synthesis (NVS) methods with any number of input views.Comment: ECCV 202
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