Live Attenuated S. Typhimurium Vaccine with Improved Safety in Immuno-Compromised Mice

Live attenuated vaccines are of great value for preventing infectious diseases. They represent a delicate compromise between sufficient colonization-mediated adaptive immunity and minimizing the risk for infection by the vaccine strain itself. Immune defects can predispose to vaccine strain infections. It has remained unclear whether vaccine safety could be improved via mutations attenuating a vaccine in immune-deficient individuals without compromising the vaccine's performance in the normal host. We have addressed this hypothesis using a mouse model for Salmonella diarrhea and a live attenuated Salmonella Typhimurium strain (ssaV). Vaccination with this strain elicited protective immunity in wild type mice, but a fatal systemic infection in immune-deficient cybb-/-nos2-/- animals lacking NADPH oxidase and inducible NO synthase. In cybb-/-nos2-/- mice, we analyzed the attenuation of 35 ssaV strains carrying one additional mutation each. One strain, Z234 (ssaV SL1344_3093), was >1000-fold attenuated in cybb-/-nos2-/- mice and ≈100 fold attenuated in tnfr1-/- animals. However, in wt mice, Z234 was as efficient as ssaV with respect to host colonization and the elicitation of a protective, O-antigen specific mucosal secretory IgA (sIgA) response. These data suggest that it is possible to engineer live attenuated vaccines which are specifically attenuated in immuno-compromised hosts. This might help to improve vaccine safety. © 2012 Periaswamy et al.

Generation of picosecond pulses with a repetition frequency of 100 GHz by a multicomponent injection laser

A mode for generating a sequence of spectrally limited pulses with a duration of 2 nsec and a repetition frequency of approximately 100 GHz in AlGaAs/GaAs by an injection heterolaser, which has amplifying and absorbing parts combined in a common resonator, is discussed.

Discrete multicomponent model for biodiesel spray combustion simulation

An important first step in spray combustion simulation is an accurate determination of the fuel properties which affects the modelling of spray formation and reaction. In a practical combustion simulation, the implementation of a multicomponent model is important in capturing the relative volatility of different fuel components. A Discrete Multicomponent (DM) model is deemed to be an appropriate candidate to model a composite fuel like biodiesel which consists of four components of fatty acid methyl esters (FAME). In this paper, the DM model is compared with the traditional Continuous Thermodynamics (CTM) model for both diesel and biodiesel. The CTM model is formulated based on mixing rules that incorporate the physical and thermophysical properties of pure components into a single continuous surrogate for the composite fuel. The models are implemented within the open-source CFD code OpenFOAM, and a semi-quantitative comparison is made between the predicted spray-combustion characteristics and optical measurements of a swirl-stabilised flame of diesel and biodiesel. The DM model performs better than the CTM model in predicting a higher magnitude of heat release rate in the top flame brush region of the biodiesel flame compared to that of the diesel flame. Using both the DM and CTM models, the simulation successfully reproduces the droplet size, volume flux, and droplet density profiles of diesel and biodiesel. The DM model predicts a longer spray penetration length for biodiesel compared to that of diesel, as seen in the experimental data. Also, the DM model reproduces a segregated biodiesel fuel vapour field and spray in which the most abundant FAME component has the longest vapour penetration. In the biodiesel flame, the relative abundance of each fuel component is found to dominate over the relative volatility in terms of the vapour species distribution and vice versa in the liquid species distribution. © 2014 Elsevier Ltd. All rights reserved.

Optimization by orthogonal array design and humoral immunity of the bivalent vaccine against Aeromonas hydrophila and Vibrio fluvialis infection in crucian carp (Carassius auratus L.)

Aeromonas hydrophila and Vibrio fluvialis are the causative agents of a serious haemorrhagic septicaemia that affects a wide range of freshwater fish in China. In order to develop a bivalent anti-A. hydrophila and anti-V. fluvialis formalin-killed vaccine to prevent this disease, an orthogonal array design (OAD) method was used to optimize the production conditions, using three factors, each having three levels. The effects of these factors and levels on the relative per cent survival for crucian carp were quantitatively evaluated by analysis of variance. The final optimized formulation was established. The data showed that inactivation temperature had a significant effect on the potency of vaccine, but formalin concentration did not. The bivalent vaccine could elicit a strong humoral response in crucian carp (Carassius auratus L.) against both A. hydrophila and V. fluvialis simultaneously, which peaked at 3 or 5 weeks respectively. Antibody titres remained high until week 12, the end of the experiment, after a single intraperitoneal injection. The verification experiment confirmed that an optimized preparation could provide protection for fish at least against A. hydrophila infection, and did perform better than the non-optimized vaccine judged by the antibody levels and protection rate, suggesting that OAD is of value in the development of improved vaccine formulations.

Electrospinning of multicomponent ultrathin fibrous nonwovens for semi-occlusive wound dressings

This work describes the design and assembly of multifunctional and cost-efficient composite fiber nonwovens as semi-occlusive wound dressings using a simple electrospinning process to incorporate a variety Of functional components into an Ultrathin fiber. These components include non-hydrophilic poly(L-lactide) (PLLA) as fibrous backbone, hydrophilic poly(vinyl pyrrolidone)iodine (PVP-I), TiO2 nanoparticles, zinc chloride as antimicrobial, odor-controlling, and antiphlogistic agents, respectively. The process of synthesis starts with a multicomponent solution Of PLLA, PVP, TiO2 nanoparticles plus zinc chloride, in which TiO2 nanoparticles are synthesized by in situ hydrolysis of TiO2 precursors in a PVP Solution for the sake of obtaining the particle-uniformly dispersive solution. Subsequent electrospinning generates the corresponding composite fibers. A further iodine vapor treatment to the composite fibers combines iodine with PVP to produce the PVP-I complexes. Experiments indicate that the assembled composite fibers (300-400 nm) possess the ointment-releasing characteristic and the phase-separate, core-sheath structures in which PVP-I residing in fiber Surface layer becomes the sheath, and PLLA distributing inside the fiber acts as the core.

Role of Lithium in Multicomponent Oxide Catalysts for Oxidative Coupling of Methane

The effect of Li content in a series of multicomponent oxides LixLa0.5Ti0.5 For methane oxidative coupling has been studied. The catalytic activities of LiLa0.5Ti0.5 catalyst before and after washing with boiling water have been compared. The surface and

ON THE SIGNIFICANCE OF WAVELENGTH POSITIONING ACCURACY IN MULTICOMPONENT ANALYSIS TECHNIQUES FOR THE CORRECTION OF LINE INTERFERENCES IN INDUCTIVELY COUPLED PLASMA ATOMIC EMISSION-SPECTROMETRY

The present paper reports some definite evidence for the significance of wavelength positioning accuracy in multicomponent analysis techniques for the correction of line interferences in inductively coupled plasma atomic emission spectrometry (ICP-AES). Using scanning spectrometers commercially available today, a large relative error, DELTA(A) may occur in the estimated analyte concentration, owing to wavelength positioning errors, unless a procedure for data processing can eliminate the problem of optical instability. The emphasis is on the effect of the positioning error (deltalambda) in a model scan, which is evaluated theoretically and determined experimentally. A quantitative relation between DELTA(A) and deltalambda, the peak distance, and the effective widths of the analysis and interfering lines is established under the assumption of Gaussian line profiles. The agreement between calculated and experimental DELTA(A) is also illustrated. The DELTA(A) originating from deltalambda is independent of the net analyte/interferent signal ratio; this contrasts with the situation for the positioning error (dlambda) in a sample scan, where DELTA(A) decreases with an increase in the ratio. Compared with dlambda, the effect of deltalambda is generally less significant.

WAVELENGTH POSITIONING ERRORS AND TRUE DETECTION LIMIT IN RELATION TO MULTICOMPONENT ANALYSIS TECHNIQUES FOR THE CORRECTION OF LINE INTERFERENCES IN INDUCTIVELY COUPLED PLASMA ATOMIC EMISSION-SPECTROMETRY

The present paper deals with the evaluation of the relative error (DELTA(A)) in estimated analyte concentrations originating from the wavelength positioning error in a sample scan when multicomponent analysis (MCA) techniques are used for correcting line interferences in inductively coupled plasma atomic emission spectrometry. In the theoretical part, a quantitative relation of DELTA(A) with the extent of line overlap, bandwidth and the magnitude of the positioning error is developed under the assumption of Gaussian line profiles. The measurements of eleven samples covering various typical line interferences showed that the calculated DELTA(A) generally agrees well with the experimental one. An expression of the true detection limit associated with MCA techniques was thus formulated. With MCA techniques, the determination of the analyte and interferent concentrations depend on each other while with conventional correction techniques, such as the three-point method, the estimate of interfering signals is independent of the analyte signals. Therefore. a given positioning error results in a larger DELTA(A) and hence a higher true detection limit in the case of MCA techniques than that in the case of conventional correction methods. although the latter could be a reasonable approximation of the former when the peak distance expressed in the effective width of the interfering line is larger than 0.4. In the light of the effect of wavelength positioning errors, MCA techniques have no advantages over conventional correction methods unless the former can bring an essential reduction ot the positioning error.

STUDIED ON THE SIMULTANEOUS SPECTROPHOTOMETRIC DETERMINATION OF INORGANIC MULTICOMPONENT SYSTEMS .3. DETERMINATION OF MICROAMOUNTS OF TUNGSTEN, MOLYBDENUM AND TITANIUM

The absorption spectra of W, Mo and Ti-phenylfluorone cetyltrimethylammonium bromide complexes and the optimum conditions for the simultaneous spectrophotometric determination of microamounts of W, Mo and Ti were studied. In order to examine the effect of the errors of calibration matrix on the analytical resulte, the approach of selecting the analytical wavelengths was investigated and the comparison of computation results between AKC method (the matrix representation of Beer-Lambert's Law) and ...

Immunoprotective analysis of VhhP2, a Vibrio harveyi vaccine candidate

VhhP2 is an Outer membrane protein identified in a pathogenic Vibrio harveyi strain, T4, isolated from diseased fish. When used as a Subunit Vaccine, purified recombinant VhhP2 affords high level of protection upon Japanese flounder against V harveyi challenge. Vaccination with VhhP2 induced the expression of a number of immune-related genes, especially those encoding immunoglobulin M (IgM) and major histocompatibility complex (MHC) II alpha. A VhhP2 surface display system, in the form of the fish commensal strain FIR harboring the vhhP2-expressing plasmid pJVP, was constructed. PF3/pJVP is able to produce and present recombinant VhhP2 on cell surface. Vaccination of fish with live PF3/pJVP via intraperitoneal injection elicited Strong immunoprotection. Vaccination of fish orally with live PF3/pJVP embedded in alginate microspheres also induced effective immunoprotection. In addition, a VhhP2-based surface display system was created, in which VhhP2 serves as a carrier for the Surface delivery of a heterologous Edwardsiella tarda immunogen, Et18, that is fused in-frame to VhhP2. DH5 alpha/pJVP18, which expresses and surface-displays the VhhP2-Et18 chimera, proved to be an effective vaccine that call protect fish against infections by V. harveyi and E. tarda to the extents comparable to those produced by vaccination with purified recombinant VhhP2 and Et18, respectively. These data suggest that VhhP2 may be applied as a vaccine and a vaccine carrier against infections by V. harveyi and other pathogens such as F. tarda. (C) 2009 Elsevier Ltd. All rights reserved.

Construction of an attenuated Pseudomonas fluorescens strain and evaluation of its potential as a cross-protective vaccine

Ferric uptake regulator (Fur) is a global transcription regulator that is ubiquitous to Gram-negative bacteria and regulates diverse biological processes, including iron uptake, cellular metabolism, stress response, and production of virulence determinants. As a result, for many pathogenic bacteria, Fur plays a crucial role in the course of infection and disease development. In this study, the fur gene was cloned from a pathogenic Pseudomonas fluorescens strain, TSS, isolated from diseased Japanese flounder cultured in a local farm. TSS Fur can partially complement the defective phenotype of an Escherichia coli fur mutant. A TSS fur null mutant, TFM, was constructed. Compared to TSS, TFM exhibits reduced growth ability, aberrant production of outer membrane proteins, decreased resistance against host serum bactericidal activity, impaired ability to disseminate in host blood and tissues, and drastic attenuation in overall bacterial virulence in a Japanese flounder infection model. When used as a live vaccine administered via the injection, immersion, and oral routes, TFM affords high levels of protection upon Japanese flounder against not only P.fluorescens infection but also Aeromonas hydrophila infection. Furthermore, a plasmid, pJAQ, was constructed, which expresses the coding element of the Vibrio harveyi antigen AgaV-DegQ. TFM harboring pJAQ can secret AgaV-DegQ into the extracellular milieu. Vaccination of Japanese flounder with live TFM/pJAQ elicited strong immunoprotection against both V. harveyi and A. hydrophila infections. (C) 2009 Elsevier Ltd. All rights reserved.