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Using a three-dimensional fluid dynamic model for eruption cloud dynamics, we present numerical simulations of the development of a volcanic eruption column and umbrella cloud formed during the 13 February 2014 eruptions of Mount Kelud, Indonesia. The model used in this study quantitatively reproduces the observed data and, in particular, the plume height and the horizontal expansion level and rate of the umbrella cloud. The simulation results suggest that on the basis of the plume height and structures and the horizontal expansion level of the umbrella cloud the mass eruption rate (MER) for the 2014 Kelud eruptions was 3 × 107 to 4 × 107 kg s− 1. On the basis of the horizontal expansion rate of the umbrella cloud, on the other hand, the estimated MER was 1 × 108 kg s− 1. The difference between these two estimates implies the strong diffusion in the umbrella cloud or the efficient entrainment of ambient air by eruption column.

We have developed a new two-layer pyroclastic density current (PDC) model that considers the effects of the entrainment and thermal expansion of ambient air in the upper dilute layer in order to investigate the dominant factors controlling the run-out distance of large-scale PDCs. Numerical simulations show a dilute current spreading radially from the collapsing eruption column edge and forming a thin, dense, basal current through particle settling; i.e., a two-layer PDC forms. Forward propagation of the two-layer PDC stops owing to lift-off of the dilute current and/or deposition of the dense current, and eventually the two-layer PDC converges to a steady state. Our parametric study classifies the flow patterns of steady-state two-layer PDCs into one of two flow regimes according to the relative magnitude of the run-out distances of the dilute and dense currents. This relative magnitude critically depends on the ratio of the deposition speed at the base of the dense current (D) to the speed of particles settling from the dilute current to the dense current (Ws). The run-out distance of the whole two-layer PDC is determined by that of the dilute current when D/Ws is large (≳4 × 10−3). Otherwise, when D/Ws is small (≲4 × 10−3), the run-out distance of the dense basal current exceeds that of the dilute current; the former increases as D/Ws decreases. The run-out distance of the dilute current is too short to explain some of the long run-out distances of PDCs observed in the field (e.g., the 1991 Pinatubo and 2014 Kelud eruptions). It is suggested that the dense current traveling beyond the lift-off point of the parent dilute current plays a significant role in the emplacement of PDCs with such long run-out distances.

Height of plumes generated during explosive volcanic eruptions is commonly used to estimate the associated eruption intensity (i.e., mass eruption rate; MER). In order to quantify the relationship between plume height and MER, we performed a parametric study using a three-dimensional (3D) numerical model of volcanic plumes for different vent sizes. The results of five simulations indicate that the flow pattern in the lower region of the plume systematically changes with vent size, and hence, with MER. For MERs 7 kg s − 1 , the flow in the lower region has a jet-like structure (the jet-like regime). For MERs > 10 8 kg s − 1 , the flow shows a fountain-like structure (the fountain-like regime). The flow pattern of plumes with 4 × 10 7 kg s − 1 8 kg s − 1 shows transitional features between the two flow regimes. Within each of the two flow regimes, the plume height increases as the MER increases, whereas plume heights remain almost constant or even decrease as MER increases in the transitional regime; as a result, the jet-like and fountain-like regimes show distinct relationships of plume height and MER. The different relationships between the two regimes reflect the fact that the efficiency of entrainment of ambient air in the jet-like regime is substantially lower than that in the fountain-like regime. It is suggested that, in order to estimate eruption intensity from the observed plume heights, it is necessary to take the different flow regimes depending on MER into account.

We performed an inter-comparison study of three-dimensional models of volcanic plumes. A set of common volcanological input parameters and meteorological conditions were provided for two kinds of eruptions, representing a weak and a strong eruption column. From the different models, we compared the maximum plume height, neutral buoyancy level (where plume density equals that of the atmosphere), and level of maximum radial spreading of the umbrella cloud. We also compared the vertical profiles of eruption column properties, integrated across cross-sections of the plume (integral variables). Although the models use different numerical procedures and treatments of subgrid turbulence and particle dynamics, the inter-comparison shows qualitatively consistent results. In the weak plume case (mass eruption rate 1.5 × 106 kg s− 1), the vertical profiles of plume properties (e.g., vertical velocity, temperature) are similar among models, especially in the buoyant plume region. Variability among the simulated maximum heights is ~ 20%, whereas neutral buoyancy level and level of maximum radial spreading vary by ~ 10%. Time-averaging of the three-dimensional (3D) flow fields indicates an effective entrainment coefficient around 0.1 in the buoyant plume region, with much lower values in the jet region, which is consistent with findings of small-scale laboratory experiments. On the other hand, the strong plume case (mass eruption rate 1.5 × 109 kg s− 1) shows greater variability in the vertical plume profiles predicted by the different models. Our analysis suggests that the unstable flow dynamics in the strong plume enhances differences in the formulation and numerical solution of the models. This is especially evident in the overshooting top of the plume, which extends a significant portion (~ 1/8) of the maximum plume height. Nonetheless, overall variability in the spreading level and neutral buoyancy level is ~ 20%, whereas that of maximum height is ~ 10%. This inter-comparison study has highlighted the different capabilities of 3D volcanic plume models, and identified key features of weak and strong plumes, including the roles of jet stability, entrainment efficiency, and particle non-equilibrium, which deserve future investigation in field, laboratory, and numerical studies.

The injection of HCl into the stratosphere by large volcanic eruptions has long been considered to be of minor importance. This is due to the widespread assumption that any HCl will be efficiently taken up by hydrometeors in the cooling plume. However, this assumption does not account for the possibility that prior scavenging processes can act within the high temperature core of the eruption plume. The adsorption of HCl onto ash surfaces to form soluble –Cl salts is a hitherto unconstrained scavenging mechanism, and their fate within the atmosphere and environment is uncertain. Here, we investigate the capacity of volcanic glasses of tephrite, phonolite, dacite and rhyolite composition to adsorb HCl. The experiments are conducted in the presence of He–SO 2 –CO 2 mixtures at temperatures of 200–800 °C. Our experimental findings show that only the tephrite and phonolite glasses exhibit significant reactivity to HCl, which show optimal efficiency of uptake at 400–600 °C. The primary reaction product formed during adsorption is halite (NaCl), in addition to minor quantities of Ca-, K-, Al- and Fe-bearing chlorides. Uptake of HCl by glass surfaces is sustained by the outward diffusion of Na + and other Cl-reactive cations via exchange with H + . Simple mathematical models can be used to yield Na diffusion coefficients for the four experimental glasses, and suggest that a varying structural role for Na within the glass network governs the capacity for HCl retention. The uptake of HCl under experimental conditions is limited above 500 °C by a Cl-induced dehydroxylation process, but the presence of H 2 O in the hydrous plume may sustain or even enhance adsorption. The present experimental data, combined with cooling gradients obtained from established plume evolution models, lead us to conclude that HCl adsorption within the eruption plume core can be a more significant scavenging mechanism in large explosive eruptions than previously considered. We additionally highlight the importance of magma composition in dictating volatile adsorption, and suggest that HCl adsorption by peralkaline ash may be highly effective as an HCl sink. The fate of adsorbed HCl is variable; some may be removed from the plume within pyroclastic flows, whereas any chloride-coated ash ejected into the stratosphere could promote the formation of reactive Cl species. Our study also suggests that HCl adsorption could emplace Fe- and Cl-bearing salts on ash surfaces within the plume cores of large explosive eruptions. The ocean fertilising potential of such eruptions could therefore be greater than that inferred from ash from smaller, compositionally similar events.

We propose a simple method for estimating the exit velocities of volcanic eruptions from the observation of volcanic plumes. For this purpose, we used a model of a vortex ring of an experimental jet, which was developed in the engineering field. To validate the model for the vortex structures of volcanic plumes, we applied it to plumes generated in 3-D numerical simulations. In 11 cases where exit velocity (66.8–200.5 m/s) is given as a boundary condition, we successfully estimated it with 7% underestimation by analyzing the size and motion of the leading vortex ring that forms at the plume front. Using the same procedure, we could also estimate the exit velocity by analyzing the trailing vortices that develop behind the vortex ring (14% underestimation). From these results, we conclude that: (i) the model of the vortex ring proposed by the jet engineering studies is appropriate for the vortex ring at the front of simulated volcanic plumes, and (ii) the model is also applicable to the trailing vortices of the plumes. These conclusions indicate that we can estimate the time evolution of the exit velocity for a series of eruptions from observations of the vortex structures of the actual volcanic plumes. By applying that method to an eruption of Sakurajima volcano on February 15, 2011, we found that following an increase during the first 10 s of the eruption, the exit velocity remained constant at >40 m/s up to 80 s after the onset of the eruption. Our method will be useful in understanding the time evolution of eruptive events, such as the transitional behavior from stable column to column collapse, from observations of volcanic plumes.

Buoyant columns or pyroclastic flows form during explosive volcanic eruptions. In the transition-state, these two eruption styles can develop simultaneously. We investigated the critical condition that separates the two eruption styles (referred to as “the column collapse condition”) by performing a series of three-dimensional numerical simulations. In the simulation results, we identify two types of flow regime: a turbulent jet that efficiently entrains ambient air (jet-type) and a fountain with a high-concentration of the ejected material (fountain-type). Hence, there are two types of column collapse (jet-type and fountain-type). Which type of collapse occurs at the column collapse condition depends on whether the critical mass discharge rate for column collapse (MDR CC ) is larger or smaller than that for the generation of a fountain (MDR JF ) for a given exit velocity. Temperature controls the relative magnitude of MDR CC relative to MDR JF , and hence the type of collapse. For given magma properties (e.g., temperature and water content), the column collapse condition is expressed by a critical value of the Richardson number (Ri CC ≡ g′ 0 L 0 / w 0 2 , where g′ 0 is the source buoyancy, L 0 is the vent radius, and w 0 is the exit velocity). When the jet-type collapse occurs at the column collapse condition, Ri CC is independent of the exit velocity. When the fountain type collapse occurs at the column collapse condition, on the other hand, Ri CC decreases as the exit velocity increases. As the exit velocity exceeds the sound velocity, a robust flow structure with a series of standing shock waves develops in the fountain, which suppresses entrainment of ambient air and enhances column collapse.

The distribution of pituitary adenylatecyclase-activating polypeptide-immunoreactive (PACAP-IR) nerve fibers was studied in the rat epiglottis and pharynx. PACAP-IR nerve fibers were located beneath the mucous epithelium, and occasionally penetrated the epithelium. These nerve fibers were abundant on the laryngeal side of the epiglottis and in the dorsal and lateral border region between naso-oral and laryngeal parts of the pharynx. PACAP-IR nerve fibers were also detected in taste buds within the epiglottis and pharynx. In addition, many PACAP-IR nerve fibers were found around acinar cells and blood vessels. The double immunofluorescence method demonstrated that distribution of PACAP-IR nerve fibers was similar to that in CGRP-IR nerve fibers in the epithelium and taste bud. However, distributions of PACAP-IR and CGRP-IR nerve fibers innervating mucous glands and blood vessels were different. The retrograde tracing method also demonstrated that PACAP and CGRP were co-expressed by vagal and glossopharyngeal sensory neurons innervating the pharynx. These findings suggest that PACAP-IR nerve fibers in the epithelium and taste bud of the epiglottis and pharynx which originate from the vagal and glossopharyngeal sensory ganglia include nociceptors and chemoreceptors. The origin of PACAP-IR nerve fibers which innervate mucous glands and blood vessels may be the autonomic ganglion.

During an explosive volcanic eruption, tephra fall out from the umbrella region of the eruption cloud to the ground surface. We investigated the effect of the intensity of turbulence in the umbrella cloud on dispersion and sedimentation of tephra by performing a series of laboratory experiments and three dimensional (3-D) numerical simulations. In the laboratory experiments, spherical glass-bead particles are mixed in stirred water with various intensities of turbulence, and the spatial distribution and the temporal evolution of the particle concentration are measured. The experimental results show that, when the root-mean-square of velocity fluctuation in the fluid ( W rms ) is much greater than the particle terminal velocity ( v t ), the particles are homogeneously distributed in the fluid, and settle at their terminal velocities at the base of the fluid where turbulence diminishes. On the other hand, when W rms is as small as or smaller than v t , the particle concentration increases toward the base of the fluid during settling, which substantially increases the rate of particle settling. The results of the 3-D simulations of eruption cloud indicate that W rms is up to 40 m/s in most of the umbrella cloud even during a large scale plinian eruption with a magma discharge rate of 10 9 kg/s. These results suggest that relatively coarse pyroclasts (more than a few mm in diameter) tend to concentrate around the base of the umbrella cloud, whereas fine pyroclasts (less than 1/8 mm in diameter) may be distributed homogeneously throughout the umbrella cloud during tephra dispersion. The effect of the gradient of particle concentration in the umbrella cloud explains the granulometric data of the Pinatubo 1991 plinian deposits.

Anti-influenza hemagglutinin (HA) Fabs were isolated from a phage display library using purified HA of influenza virus A/Puerto Rico/8/34 (PR8; H1N1) as an antigen. Four Fab clones displaying a 25-50-fold higher binding signal to PR8 HA than the control were selected for further analysis and comparison with anti-PR8 monoclonal antibody (mAb). All four Fabs and mAb recognized the PR8 HA under non-reducing conditions but rarely bound to reduced PR8 HA. Inhibition of influenza virus infection on MDCK cells was observed with Fab1 and mAb in a dose-dependent manner while Fab3 and 4 exhibited only a partial inhibitory effect. Moreover, Fab1 clone and mAb exhibited cross-reactivity with the A/Peking/262/95 (A/Peking; H1N1) strain. The inhibitory effects of mAb on both influenza strains were more potent than Fab1, which is likely attributed to its higher affinity for the antigen. SPR analyses, in fact, revealed that Fab1 and mAb have K(D) of 1.5 x 10(-8) and 3.2 x 10(-9)M, respectively. These results strongly suggest that phage library-derived Fabs can be readily prepared and that such HA-specific Fabs with inhibitory action on influenza infection may be used to treat influenza patients.

A 60-year-old woman presented with a dry cough without dyspnea or wheezing. Chest CT showed an image of mucoid impactions, which were identified as mucoid impactions by bronchofiberscopy. Aspergillus niger was cultured from her mucus. Her serum total IgE was 5150 IU/ml. Precipitins and IgE specific for Aspergillus were positive. She had no history of asthma and no evidence of bronchoconstriction by pulmonary function tests. Thus, a diagnosis was made of allergic bronchopulmonary aspergillosis without asthma. She refused to take oral corticosteroids, although she improved spontaneously. However, her dry cough persisted. Her cough was relieved by administering an inhaled β-2 agonist; therefore, cough variant asthma was diagnosed. She was treated with an inhaled corticosteroid and her cough resolved completely.

The effectiveness and safety of mutant Escherichia coli heat-labile enterotoxin, LT H44A (His to Arg substitution at position 44 from the N-terminus of the A1 fragment of the A subunit) as an adjuvant for nasal influenza vaccine were examined. (1) When 0.2 microg of LT H44A, together with 0.2 microg of influenza A/PR/8/34 virus (PR8, H1N1) vaccine, was administered intranasally into BALB/c mice (twice, 4 weeks apart), anti-PR8 hemagglutinin (HA) IgA and IgG antibody (Ab) responses were induced at levels that were sufficient to provide either complete protection against infection with a small volume of PR8 virus suspension or partial protection against infection with a lethal dose of the suspension. The dose of the mutant LT and vaccine used here (0.2 microg/ 20 g doses mouse) corresponded to the estimated dose per person, i.e. 0.1 mg/10 kg body weight. (2) Using these vaccination conditions, no additional total IgE Ab responses were induced. (3) The mutant was confirmed to be less toxic than the native LT when the toxicity was analyzed either using Y1 adrenal cells in vitro (1/483 EC(50)) or by an ileal loop test. (4) One hundred micrograms of the mutant, administered intranasally or intraperitoneally into guinea-pigs (Heartley strain, 0.3-0.4 kg), caused no body-weight changes 7 days after administration, although 100 microg of the native LT administered intraperitoneally caused death in all guinea-pigs due to diarrhea within 2 days. The intranasal administration of 100 microg of the mutant resulted in almost no pathological changes in the nasal mucosa 3 days after administration. These results suggest that LT H44A, which can be produced in high yields in an E. coli culture (about 5 mg/l), could be used as one of the effective and safe adjuvants for nasal influenza vaccine in humans.

We evaluated the potential application of ion-exchange resins for the enhancement of intranasal immune response to influenza HA vaccine in mice. Female Balb/c mice were intranasally immunized with inactivated influenza HA vaccine with one of four kinds of resin microparticles: sodium polystyrene sulfonate, calcium polystyrene sulfonate, polystyrene benzyltrimetylammonium chloride, or polystyrene divinylbenzene. Haemagglutinin-inhibiting antibodies were measured in the serum and IgA antibodies in the nasal wash after 4 weeks. The results demonstrated that intranasal administration of influenza HA vaccine in combination with the 20-45 microns sized particles of sodium polystyrene sulfonate resin induced the highest levels of mucosal IgA, and enhanced systemic haemagglutinin-inhibiting antibodies. While the Th2-type cytokine IL-4 was detected in the sera after intranasal immunization with HA vaccine and sodium polystyrene sulfonate, neither IFN-gamma nor IL-2 could be detected. Furthermore, mice intranasally immunized with HA vaccine together with sodium polystyrene sulfonate resin showed higher protection against viral challenge than those that received HA vaccine alone. Intranasal administration of influenza HA vaccine with sodium polystyrene sulfonate resin might be both a safe and an effective means of immunization.

The effectiveness and safety of known mutants of Escherichia coli heat-labile enterotoxin (LT) as an adjuvant for nasal influenza vaccine were examined. Six mutants, called LT7K (Arg to Lys), LT61F (Ser to Phe), LT112K (Glu to Lys), LT118E (Gly to Glu), LT146E (Arg to Glu) and LT192G (Arg to Gly) were constructed by the replacement of one amino acid at one position of the A1 subunit to another using site-directed mutagenesis. All mutants were confirmed to be less toxic than wild-type LT when analyzed using Y-1 adrenal cells in vitro. When influenza vaccine was administered intranasally with LT7K and LT192G, BALBc mice developed high levels of serum and local antibodies to the HA molecules. The adjuvant activity of these mutant LTs corresponded to that of wild-type LT when 1 μg of these mutant LTs (or wild-type LT) was coadministered with the vaccine. From the point of view of safety, LT7K was considered to be the most potent mucosal adjuvant and was examined in more detail. The adjuvant activity of the mutant was lowered more rapidly with a decrease in dose than was that of wild-type LT. The low level of adjuvant activity of a relatively small amount of LT7K was heightened by adding LTB to the mutant LT. These results suggest that LT7K supplemented with LTB can be used as a less toxic, effective adjuvant for nasal influenza vaccine.

In previous papers, we have shown that Escherichia coli heat-labile enterotoxin B subunit, supplemented with a trace amount of the holotoxin (LTB ∗ ) could be used as a potent adjuvant for a nasal influenza HA (haemagglutinin) vaccine in humans 1,2 . The present study was designed to determine whether the effectiveness of a combined LTB ∗ -HA vaccine could be limited by preexisting immunity to LTB and how many times the adjuvant-combined vaccine could be administered intranasally without reducing its protective efficacy in BALB/c, C3H and B10 mice. The magnitude of both nasal and serum Ab responses to HA vaccine was correlated with the degree of protection against virus infection. Higher doses of LTB ∗ -combined vaccine were required for inducing high enough levels of anti-HA Ab responses to provide complete protection in low responder mice. Repeated pretreatments with LTB ∗ alone (more than six times), which provided high levels of preexisting Abs to LTB, inhibited the induction of anti-HA Ab responses and reduced the protective efficacy of the adjuvant-combined vaccine. However, the LTB ∗ -combined vaccine could be given repeatedly (about ten times) to mice without reducing the effectiveness of the adjuvant-combined vaccine. These results suggest that the LTB ∗ -combined nasal influenza vaccine can be given to humans once every few years when an epidemic of influenza may occur.

Evaluation of the efficacy of nasal influenza vaccine combined with Escherichia coli heat-labile enterotoxin B subunit (LTB) containing a trace amount of the holotoxin (LT) in inducing antibody responses among volunteers, which was conducted during the winter season of 1993-1994, is reported. A trivalent inactivated vaccine, composed of A/Yamagata/32/89 (H1N1), A/Kitakyusyu/159/93 (H3N2) and B/Bangkok/163/90 influenza virus strains, was used alone or together with the adjuvant, recombinant LTB supplemented with 0.5% recombinant LT (LTB*). The volunteers were divided into two groups: 73 volunteers (mean age 35.0 +/- 12.0 years) inoculated intranasally (i.n.) with LTB*-combined vaccine and 49 volunteers (37.9 +/- 11.3) inoculated i.n. with the vaccine alone. Vaccination was done twice 4 weeks apart. Salivary secretory IgA and serum hemagglutination-inhibiting (HI) antibodies were measured before and 8 weeks after the primary vaccination. For the sake of convenience, more than a 1.4-fold rise in IgA antibody response (units of specific IgA antibody per microgram of total IgA) and a fourfold or greater rise in HI antibody titer after vaccination were regarded as a positive antibody response. Thirty-seven (50.3%) and 36 (49.3%) of the 73 vaccinees, respectively, given the nasal LTB*-combined vaccine showed positive IgA and HI antibody responses to one or more of the three vaccine strains. In comparison, positive antibody responses in the group given vaccine alone were 32.7% for IgA and 30.6% for HI antibody. There was a significant difference between these two groups. These results suggest that the nasal LTB*-combined vaccine could enhance the production of higher levels not only of serum HI antibody but IgA antibodies in the respiratory tract than do the nasal vaccine alone.

When mouse-adapted influenza virus A/PR/8/34 (A/PR8) (10 PFU/cell) was adsorbed to Madin-Darby canine kidney (MDCK) cells at 4 degrees C for 1 h and incubated at 37 degrees C, release of the virus from the cells was detected in the medium from 4 h after incubation and reached to plateau at 8 h. However, 5,7,4'-trihydroxy-8-methoxyflavone (F36) from the roots of Scutellaria baicalensis significantly reduced this single-cycle replication of A/PR8 from 4 h to 12 h after incubation by dose-dependent manner and the dose which decrease the virus titer one tenth was 11 microM. F36 (50 microM) did not inhibit the adsorption of A/PR8 to MDCK cells, but reduced release of the virus in the medium, when it was added at 0 or 2 h after the incubation. The cell-associated virus determined by sialidase activity was also reduced by F36 treatment at 0 or 2 h. F36 also inhibited the fusion of A/PR8 with liposomes containing bovine brain mixed gangliosides at pH 5.0. However, F36 little affected on the elongation activity of the viral RNA-dependent RNA polymerase in vitro. These results suggest that F36 reduces the replication of A/PR8 by inhibiting the fusion of the virus with endosome/lysosome membrane which occurs at early stage of virus infection cycle. Whereas, when F36 was added to the MDCK cells infected with A/PR8 at 3 or 4 h after incubation, release of the virus in the medium was reduced but the cell-associated virus was increased in comparison with control.(ABSTRACT TRUNCATED AT 250 WORDS)

Isoscutellarein (5,7,8,4'-tetrahydroxyflavone) from the leaf of Scutellaria baicalensis non-competitively inhibited (IC50, 20 microM) the hydrolysis of sodium p-nitrophenyl-N-acetyl-alpha-D-neuraminate by influenza virus sialidase with an apparent Ki value of 41 microM. Negligible inhibitory activity was observed for mouse liver sialidase at a concentration of 79 microM. Isoscutellarein also inhibited the replication of influenza virus A/WSN/33 in Madin-Darby bovine kidney cells with 50% virus inhibitory dose at 16 nmol/well and influenza virus A/PR/8/34 in the allantoic sac of embryonated egg with little toxic effects. The flavone showed significant anti-influenza virus activity in vitro similar to isoscutellarein-8-methylether (F36) (Nagai, T., Miyaichi, Y., Tomimori, T., Suzuki, Y. and Yamada H., 1990, Chem. Pharm. Bull. 38, 1329-1332), and more potent virucidal activity in ovo than F36. However, F36 completely prevented proliferation of mouse-adapted influenza virus A/PR/8/34 in mouse lung by the intranasal (0.5 mg/kg) and intraperitoneal (4 mg/kg) administrations, and it was more potent than the known anti-influenza virus substance, amantadine. Intranasal administration of F36 (0.5 mg/kg) also protected mice against a lethal influenza virus A/PR/8/34 infection. Isoscutellarein significantly inhibited lung virus proliferation when administered intranasally or orally to mice. F36 and isoscutellarein showed negligible toxic effect against mice. These results suggested that flavones, which have potent influenza virus sialidase inhibitory activity, have anti-influenza virus activity in vivo.