Particle-bombardment-mediated DNA vaccination with rotavirus VP4 or VP7 induces high levels of serum rotavirus IgG but fails to protect mice against challenge

We recently reported that epidermal immunization using the PowderJet particle delivery device with plasmid vector pcDNA1/EDIM6 encoding rotavirus VP6 of murine strain EDIM induced high levels of serum rotavirus IgG but failed to protect mice against EDIM infection (Choi, A. H., Knowlton, D. R., McNeal, M. M., and Ward, R. L. (1997) Virology 232, 129-138.). This was extended to determine whether pcDNA1/EDIM4 or pcDNA1/EDIM7, which encode either rotavirus VP4 or VP7, the rotavirus neutralization proteins, could also induce rotavirus-specific antibody responses and if these responses resulted in protection. Titers of rotavirus serum IgG increased with the first dose in mice immunized with pcDNA1/EDIM7, but little or no serum rotavirus IgG was detected in mice immunized with pcDNA1/EDIM4. In vitro assays with these plasmids in rabbit reticulocyte lysates showed that VP4 was expressed but the amount was considerably lower than VP6 or VP7. To improve expression of VP4 and induction of rotavirus-specific humoral responses, the coding region of VP4 was cloned into the high-expression plasmid WRG7054 as a fusion protein containing the 22-amino-acid secretory signal peptide of tissue plasminogen activator (tPA) at its N terminus. In vitro expression of tPA::VP4 was significantly higher than unmodified VP4, and mice inoculated with WRG7054/EDIM4 generated high titers of rotavirus IgG. The coding sequence of VP7 without the first 162 nucleotides was also cloned into WRG7054, but no difference was observed between titers of serum rotavirus IgG in mice immunized with this plasmid (WRG7054/EDIM7Delta1-162) and pcDNA1/EDIM7. The rotavirus-specific IgG titers in all immune sera were predominantly IgG1 indicating induction of Th 2-type responses. None of the mice immunized with any of the VP4 or VP7 plasmids developed serum or fecal rotavirus IgA or neutralizing antibody to EDIM. When immunized mice were challenged with EDIM virus, there was no significant reduction in viral shedding relative to unimmunized controls. Therefore epidermal immunization with VP4 or VP7 alone elicited rotavirus IgG responses but did not protect against homologous rotavirus challenge.     

The dusty atmosphere of the brown dwarf Gliese 229B

The brown dwarf Gliese 229B has an observable atmosphere too warm to contain ice clouds like those on Jupiter and too cool to contain silicate clouds like those on low-mass stars. These unique conditions permit visibility to higher pressures than possible in cool stars or planets. Gliese 229B's 0.85- to 1.0-micrometer spectrum indicates particulates deep in the atmosphere (10 to 50 bars) having optical properties of neither ice nor silicates. Their reddish color suggests an organic composition characteristic of aerosols in planetary stratospheres. The particles' mass fraction (10(-7)) agrees with a photochemical origin caused by incident radiation from the primary star and suggests the occurrence of processes native to planetary stratospheres.     

Agonist-induced calcium waves in oscillatory cells: a biological example of Burgers' equation

Oscillations in cytosolic Ca2+ concentrations in living cells are often a manifestation of propagating waves of Ca2+. Numerical simulations with a realistic model of inositol 1,4,5-trisphosphate (IP3)-induced Ca2+ wave trains lead to wave speeds that increase linearly at long times when (a) IP3 levels are in the range for Ca2+ oscillations, (b) a gradient of phase is established by either an initial ramp or pulse of IP3, and (c) IP3 concentrations asymptotically become uniform. We explore this phenomenon with analytical and numerical methods using a simple two-variable reduction of the De Young-Keizer model of the IP3 receptor that includes the influence of Ca2+ buffers. For concentrations of IP3 in the oscillatory regime, numerical solution of the resulting reaction diffusion equations produces nonlinear wave trains that shows the same asymptotic growth of wave speed. Due to buffering, diffusion of Ca2+ is quite slow and, as previously noted, these waves occur without appreciable bulk movement of Ca2+. Thus, following Neu and Murray, we explore the behavior of these waves using an asymptotic expansion based on the small size of the buffered diffusion constant for Ca2+. We find that the gradient in phase of the wave obeys Burgers' equation asymptotically in time. This result is used to explain the linear increase of the wave speed observed in the simulations.     

Solar/UV-induced photocatalytic degradation of three commercial textile dyes.

The photocatalytic degradation of three commercial textile dyes with different structure has been investigated using TiO(2) (Degussa P25) photocatalyst in aqueous solution under solar irradiation. Experiments were conducted to optimise various parameters viz. amount of catalyst, concentration of dye, pH and solar light intensity. Degradation of all the dyes were examined by using chemical oxygen demand (COD) method. The degradation efficiency of the three dyes is as follows: Reactive Yellow 17(RY17) > Reactive Red 2(RR2) > Reactive Blue 4 (RB4), respectively. The experimental results indicate that TiO(2) (Degussa P25) is the best catalyst in comparison with other commercial photocatalysts such as, TiO(2) (Merck), ZnO, ZrO(2), WO(3) and CdS. Though the UV irradiation can efficiently degrade the dyes, naturally abundant solar irradiation is also very effective in the mineralisation of dyes. The comparison between thin-film coating and aqueous slurry method reveals that slurry method is more efficient than coating but the problems of leaching and the requirement of separation can be avoided by using coating technique. These observations indicate that all the three dyes could be degraded completely at different time intervals. Hence, it may be a viable technique for the safe disposal of textile wastewater into the water streams.     

GD3/proteosome vaccines induce consistent IgM antibodies against the ganglioside GD3

The gangliosides of melanoma and other tumours of neuroectodermal origin are suitable targets for immune intervention with tumour vaccines. The optimal vaccines in current use contain ganglioside plus bacillus Calmette-Guérin and induce considerable morbidity. We have screened a variety of new adjuvants in the mouse, and describe one antigen-delivery system, proteosomes, which is especially effective. Highly hydrophobic Neisserial outer membrane proteins (OMP) form multimolecular liposome-like vesicular structures termed proteosomes which can readily incorporate amphiphilic molecules such as GD3 ganglioside. The optimal GD3/proteosome vaccine formulation for induction of GD3 antibodies in the mouse is determined. Interestingly, the use of potent immunological adjuvants in addition to proteosomes augments the IgM and IgG antibody titres against OMP in these vaccines but GD3 antibody titres are unaffected. The application of proteosomes to enhance the immune response to GD3 extends the concept of the proteosome immunopotentiating system from lipopeptides to amphipathic carbohydrate epitopes such as cell-surface gangliosides. The demonstrated safety of meningococcal OMP in humans and the data in mice presented here suggest that proteosome vaccines have potential for augmenting the immunogenicity of amphipathic tumour antigens in humans.     

Characterization of the cavity nucleation factor for life prediction under creep-fatigue interaction

It is understood that grain boundary cavitation is one of the detrimental processes for the degradation of materials that reduces the creep-fatigue life at high temperatures. In a previous investigation, a model for life prediction under creep-fatigue conditions was proposed in terms of cavity nucleation and growth. In that model, the cavity nucleation factor (P) was introduced to correlate between the number of cavities and the plastic strain range from which athermal vacancies are generated. It was considered to be a material specific constant which was independent of the experimental conditions. However, in this study, it is found that the cavity nucleation factor is a function of the plastic strain range but is independent of the testing temperature at near 0.5 T _m. In the light of this dependency, a new cavity nucleation factor (P'), is introduced. Using this new cavity nucleation factor (P'), a modified equation for life prediction is proposed, and it is shown that there is good agreement between predicted and experimental lives. Additionally, an interesting approach has been made to find the physical meaning of the new cavity nucleation factor (P'). According to this study, it is suggested that the new cavity nucleation factor, which is regarded as a material specific constant, is found to be strongly related to the density of the grain boundary precipitates with a linear relationship existing between them.     

Percutaneous transluminal angioplasty of an innominate artery occlusion

A middle-aged woman presented with recent-onset left hemiparesis and right subclavian steal syndrome. She was found to have an obstructed innominate artery. We successfully performed balloon angioplasty of the occluded innominate artery and encountered no complications during follow-up of currently 8 months.     

Improved performances of a S-SEED using extremely shallowquantum-wells and asymmetric Fabry-Perot cavity structure

The authors report significantly improved performances of a symmetric self-electrooptic-effect device (S-SEED), with high on-off contrast ratio (>30:l) and large optical bistability loop widths (ΔP=44%) at an applied bias of V_a=0 V, i.e., with no power supply. The S-SEED is made of extremely shallow quantum wells (ESQWs) in an asymmetric Fabry-Perot (AFP) cavity structure. At V_a =5 V ΔP increased by up to 95%, preserving the high contrast ratio. The reflectivity changes at V_a=0 and 5 V were about 15% and 30%, respectively. These are believed to be the largest values ever reported for such structures     

Essential contribution of caspase 3/CPP32 to apoptosis and its associated nuclear changes

Caspases are fundamental components of the mammalian apoptotic machinery, but the precise contribution of individual caspases is controversial. CPP32 (caspase 3) is a prototypical caspase that becomes activated during apoptosis. In this study, we took a comprehensive approach to examining the role of CPP32 in apoptosis using mice, embryonic stem (ES) cells, and mouse embryonic fibroblasts (MEFs) deficient for CPP32. CPP32(ex3-/-) mice have reduced viability and, consistent with an earlier report, display defective neuronal apoptosis and neurological defects. Inactivation of CPP32 dramatically reduces apoptosis in diverse settings, including activation-induced cell death (AICD) of peripheral T cells, as well as chemotherapy-induced apoptosis of oncogenically transformed CPP32(-/-) MEFs. As well, the requirement for CPP32 can be remarkably stimulus-dependent: In ES cells, CPP32 is necessary for efficient apoptosis following UV- but not gamma-irradiation. Conversely, the same stimulus can show a tissue-specific dependence on CPP32: Hence, TNFalpha treatment induces normal levels of apoptosis in CPP32 deficient thymocytes, but defective apoptosis in oncogenically transformed MEFs. Finally, in some settings, CPP32 is required for certain apoptotic events but not others: Select CPP32(ex3-/-) cell types undergoing cell death are incapable of chromatin condensation and DNA degradation, but display other hallmarks of apoptosis. Together, these results indicate that CPP32 is an essential component in apoptotic events that is remarkably system- and stimulus-dependent. Consequently, drugs that inhibit CPP32 may preferentially disrupt specific forms of cell death.     

Biochemical basis for increased susceptibility to Cidofovir of herpes simplex viruses with altered or deficient thymidine kinase activity

It has been observed that herpes simplex virus mutants with deficient or altered thymidine kinase activity are more susceptible to Cidofovir (CDV; 1-[(S)-3-hydroxy-2-(phosphonomethoxy)propyl]cytosine dihydrate) in tissue culture than are the parental strains. During infection of cells, the elevation of the dCTP pool by thymidine kinase mutant viruses is less than that induced by the wild-type virus. The competition between CDV diphosphate and dCTP at the viral polymerase is therefore changed in favor of CDV diphosphate, enhancing its activity.