Collaborative Research Activities of the Arase and Van Allen Probes.

This paper presents the highlights of joint observations of the inner magnetosphere by the Arase spacecraft, the Van Allen Probes spacecraft, and ground-based experiments integrated into spacecraft programs. The concurrent operation of the two missions in 2017-2019 facilitated the separation of the spatial and temporal structures of dynamic phenomena occurring in the inner magnetosphere. Because the orbital inclination angle of Arase is larger than that of Van Allen Probes, Arase collected observations at higher L -shells up to L ∼ 10 . After March 2017, similar variations in plasma and waves were detected by Van Allen Probes and Arase. We describe plasma wave observations at longitudinally separated locations in space and geomagnetically-conjugate locations in space and on the ground. The results of instrument intercalibrations between the two missions are also presented. Arase continued its normal operation after the scientific operation of Van Allen Probes completed in October 2019. The combined Van Allen Probes (2012-2019) and Arase (2017-present) observations will cover a full solar cycle. This will be the first comprehensive long-term observation of the inner magnetosphere and radiation belts.

Penetration of MeV electrons into the mesosphere accompanying pulsating aurorae.

Pulsating aurorae (PsA) are caused by the intermittent precipitations of magnetospheric electrons (energies of a few keV to a few tens of keV) through wave-particle interactions, thereby depositing most of their energy at altitudes ~ 100 km. However, the maximum energy of precipitated electrons and its impacts on the atmosphere are unknown. Herein, we report unique observations by the European Incoherent Scatter (EISCAT) radar showing electron precipitations ranging from a few hundred keV to a few MeV during a PsA associated with a weak geomagnetic storm. Simultaneously, the Arase spacecraft has observed intense whistler-mode chorus waves at the conjugate location along magnetic field lines. A computer simulation based on the EISCAT observations shows immediate catalytic ozone depletion at the mesospheric altitudes. Since PsA occurs frequently, often in daily basis, and extends its impact over large MLT areas, we anticipate that the PsA possesses a significant forcing to the mesospheric ozone chemistry in high latitudes through high energy electron precipitations. Therefore, the generation of PsA results in the depletion of mesospheric ozone through high-energy electron precipitations caused by whistler-mode chorus waves, which are similar to the well-known effect due to solar energetic protons triggered by solar flares.

Oxygen torus and its coincidence with EMIC wave in the deep inner magnetosphere: Van Allen Probe B and Arase observations.

We investigate the longitudinal structure of the oxygen torus in the inner magnetosphere for a specific event found on 12 September 2017, using simultaneous observations from the Van Allen Probe B and Arase satellites. It is found that Probe B observed a clear enhancement in the average plasma mass (M) up to 3-4 amu at L = 3.3-3.6 and magnetic local time (MLT) = 9.0 h. In the afternoon sector at MLT ~ 16.0 h, both Probe B and Arase found no clear enhancements in M. This result suggests that the oxygen torus does not extend over all MLT but is skewed toward the dawn. Since a similar result has been reported for another event of the oxygen torus in a previous study, a crescent-shaped torus or a pinched torus centered around dawn may be a general feature of the O+ density enhancement in the inner magnetosphere. We newly find that an electromagnetic ion cyclotron (EMIC) wave in the H+ band appeared coincidently with the oxygen torus. From the lower cutoff frequency of the EMIC wave, the ion composition of the oxygen torus is estimated to be 80.6% H+, 3.4% He+, and 16.0% O+. According to the linearized dispersion relation for EMIC waves, both He+ and O+ ions inhibit EMIC wave growth and the stabilizing effect is stronger for He+ than O+. Therefore, when the H+ fraction or M is constant, the denser O+ ions are naturally accompanied by the more tenuous He+ ions, resulting in a weaker stabilizing effect (i.e., larger growth rate). From the Probe B observations, we find that the growth rate becomes larger in the oxygen torus than in the adjacent regions in the plasma trough and the plasmasphere.

Multiple time-scale beats in aurora: precise orchestration via magnetospheric chorus waves.

The brightness of aurorae in Earth's polar region often beats with periods ranging from sub-second to a few tens of a second. Past observations showed that the beat of the aurora is composed of a superposition of two independent periodicities that co-exist hierarchically. However, the origin of such multiple time-scale beats in aurora remains poorly understood due to a lack of measurements with sufficiently high temporal resolution. By coordinating experiments using ultrafast auroral imagers deployed in the Arctic with the newly-launched magnetospheric satellite Arase, we succeeded in identifying an excellent agreement between the beats in aurorae and intensity modulations of natural electromagnetic waves in space called "chorus". In particular, sub-second scintillations of aurorae are precisely controlled by fine-scale chirping rhythms in chorus. The observation of this striking correlation demonstrates that resonant interaction between energetic electrons and chorus waves in magnetospheres orchestrates the complex behavior of aurora on Earth and other magnetized planets.

Evidence for global electron transportation into the jovian inner magnetosphere.

Jupiter's magnetosphere is a strong particle accelerator that contains ultrarelativistic electrons in its inner part. They are thought to be accelerated by whistler-mode waves excited by anisotropic hot electrons (>10 kiloelectron volts) injected from the outer magnetosphere. However, electron transportation in the inner magnetosphere is not well understood. By analyzing the extreme ultraviolet line emission from the inner magnetosphere, we show evidence for global inward transport of flux tubes containing hot plasma. High-spectral-resolution scanning observations of the Io plasma torus in the inner magnetosphere enable us to generate radial profiles of the hot electron fraction. It gradually decreases with decreasing radial distance, despite the short collisional time scale that should thermalize them rapidly. This indicates a fast and continuous resupply of hot electrons responsible for exciting the whistler-mode waves.

Study of the relationship between acetaminophen and asthma in Mexican children aged 6 to 7 years in 3 Mexican cities using ISAAC methodology.

OBJECTIVE: To establish the relationship between the use of acetaminophen and the frequency of asthma in Mexican children in 3 Mexican cities. METHODS: Ours was a multicenter, observational, descriptive, cross-sectional study. Patients from 6 to 7 years of age participating in Phase Three B of the ISAAC (International Study of Asthma and Allergies in Children) living in the north of Mexico City, Victoria City, and Merida were included. After adjusting for confounders, we calculated the odds ratios (OR) for the presence of wheezing ever, wheezing in the last 12 months, asthma ever, and the use of acetaminophen in the first year of life and during the last 12 months. RESULTS: The ORs for wheezing ever, wheezing in the last year, and asthma ever with respect to use of acetaminophen in the first year of life were not statistically significant (P > .05) in Mexico City, but they were significant in Victoria City (P < .05) and Merida (P < .05). The ORs (95% confidence intervals) for wheezing ever, wheezing in the last year, and asthma ever with respect to use of acetaminophen in the last year were 3.44 (2.96-4.0), 7.97 (5.89-10.78), and 6.10 (3.30-8.81) (P < .05) in Mexico City. Values forVictoria City were 1.36 (1.13-1.63), 3.80 (2.88-5.05), and 2.18(1.57-3.01) (P < .05). Those for Merida were 1.61 (1.40-1.85), 2.07 (1.73-2.48), and 1.53 (1.29-1.82) (P < .05). CONCLUSION: The use of acetaminophen is associated with the presence of wheezing and asthma in 3 different cities in Mexico.

[Adverse reactions to vaccines]. / Reacciones adversas a vacunas.

Vaccination is one of the medicine's achievements to control and/or eradicate certain infectious diseases. Vaccines contain antigenic doses derived from microorganisms and/or its toxins, besides they are composed of other substances such as aluminum, gelatin, egg proteins, mercury components (as thimerosal), and antibiotics; therefore, these substances can produce hypersensitivity reactions. The above-mentioned reactions can be evidenced with itch, edema, hives, asthmatic crisis, hypotension and even anaphylactic shock. Due to the importance of vaccination, especially in childhood, it is essential to know the benefits of vaccines, their impact in morbidity and mortality decrease of certain infected-contagious diseases, as well as the adverse effects and the allergic reactions to their application. As immunizations prevent natural infections, they might contribute to a free infectious environment that would allow atopic response. This paper reviews the allergic reactions to vaccines and their influence on the development of atopic disease.

Preliminary evaluation of fungicidal and termiticidal activities of filtrates from biomass slurry fuel production.

Biomass slurry fuel (BSF) production has recently been developed as a natural energy for the conversion of solid biomass into fuel. In addition to using fuel, filtrates from BSF production may also serve a chemical source with several organic compounds. There is an increasing interest in the research and application of biomass-based filtrates. In this study, fungicidal and termiticidal properties of filtrates from BSF production using sugi (Cryptomeria japonica) and acacia (Acacia mangium) wood were evaluated in laboratory decay and termite resistance tests. Wood blocks treated with the filtrates showed increased resistance against brown-rot fungus, Fomitopsis palustris. However the filtrates from sugi wood processed at 270 degrees C which contained less phenolic compounds than the other filtrates were effective against white-rot fungus, Trametes versicolor. Phenolic compounds of filtrates seemed to play a role in the decay resistance tests however the filtrates did not increase the durability of the wood blocks against subterranean termites Coptotermes formosanus. Despite high acetic and lactic acid content of the filtrates, vanillin content of the filtrates may have served as an additional food source and promoted termite attack. It can be concluded that filtrates with phenolic compounds from lignin degradation during BSF production can be considered for targeted inhibition of brown-rot.

EBAG9/RCAS1 in human breast carcinoma: a possible factor in endocrine-immune interactions.

EBAG9 has been recently identified as an oestrogen responsive gene in MCF-7 human breast carcinoma cells. EBAG9 is identical to RCAS1, a cancer cell surface antigen possibly involved in immune escape. In this study, we examined the expression of EBAG9/RCAS1 in human breast carcinomas using immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR). EBAG9 immunoreactivity was also associated with various clinicopathological parameters, including intratumoural infiltration of inflammatory cells, to examine the biological significance of EBAG9 in human breast carcinomas. EBAG9 immunoreactivity was detected in the entire surface and cytoplasm of carcinoma cells in 82 out of 91 invasive ductal carcinomas (90.1%). In non-neoplastic mammary glands, EBAG9 immunoreactivity was weakly present on the luminal surface of epithelial cells. Results from RT-PCR (n = 7) were consistent with those of immunohistochemistry. EBAG9 immunoreactivity was significantly associated with estrogen receptor (ER) alpha labelling index (P = 0.0081), and inversely associated with the degree of intratumoural infiltration of mononuclear cells (P = 0.0020), or CD3(+) T lymphocytes (P = 0.0025). This study suggests that EBAG9 is produced via ER in carcinoma cells and inhibits the intratumoural infiltration of T lymphocytes in the context of a possible endocrine-immune interaction in human breast carcinomas.

Pharmacokinetic and pharmacodynamic analysis of the antihypercalcemic effect of incadronate disodium in rats.

Incadronate concentrates into the bone as a target organ after intravenous administration of incadronate disodium. Mature osteoclasts has take up incadronate from the bone surface and convert it from an active to an inactive form. As a result, incadronate decreases the plasma calcium concentration by suppressing bone resorption. In this study, the pharmacokinetic and pharmacodynamic (PK/PD) analysis model for ascertaining the antihypercalcemic effects of incadronate disodium was developed in rats. Data on both the concentration of incadronate in bone and that of free calcium in blood after intravenous administration from our previous study were used for analysis. To estimate the concentration in the surface layer of bone, data on the concentration of incadronate in bone after single intravenous administration were analyzed based on the PK model considering three-compartments. The estimated concentrations in the surface layer in bone were applied to the PD model as an input function. The PD model was developed to analyze the changes in the plasma calcium concentration after a single intravenous administration considering an irreversible inhibition of osteoclast activity. The obtained fitted curves were in good agreement with the observed data. The model could explain the long duration of the antihypercalcemic effect of incadronate disodium and should be useful for planning rational dose regimens for effective antihypercalcemic therapy.

Molecular cloning and characterization of mouse EBAG9, homolog of a human cancer associated surface antigen: expression and regulation by estrogen.

We previously identified a human estrogen-responsive gene, EBAG9 (ER-binding fragment-associated antigen9) (Watanabe, T. et al., Mol. Cell. Biol. 18, 442-449, 1998). It was later reported as RCAS1 (receptor-binding cancer antigen expressed on SiSo cells) that induced apoptosis and suppressed the growth of several cells such as activated T cells (Nakashima, M. et al., Nat. Med. 5, 938-942, 1999). Here, we have isolated both cDNA and genomic DNA of mouse EBAG9/RCAS1. Mouse EBAG9 gene spans about 30 kb in genomic DNA and consists of 7 exons. Mouse EBAG9 cDNA encodes a protein that contains the transmenbrane segment and coiled-coil domain. An alignment between the predicted mouse and human EBAG9 shows a high degree of homology at the amino acid level (98%). Northern and Western blot analyses demonstrate that EBAG9 is expressed in several tissues including the heart, brain, spleen, liver, kidney, and testis, and also in developing embryo. In the uterus, a target organ for estrogen, the EBAG9 was shown to be upregulated in vivo by 17beta-estradiol. To determine the biological action of mouse EBAG9, NIH3T3 fibroblastic cells were incubated with recombinant EBAG9 protein, resulting in suppression of cell growth. These findings suggest that EBAG9 is an in vivo estrogen-responsive gene that inhibits the cell growth.

[A survey of radical surgery without neoadjuvant therapy for patients with stage B and C prostatic carcinoma].

There has been much controversy regarding radical surgery for both localized and locally extensive carcinoma of the prostate. We analyzed the outcome of radical prostatectomy and the preoperative evaluation in order to assess the indication of radical prostatectomy. Fifty-six patients with clinical stage B or C prostate cancer were treated by radical prostatectomy without neoadjuvant therapy. Endocrine therapy was added to the non-curative cases postoperatively. Preoperative evaluation was compared with pathological results and survival, and furthermore the usefulness of the preoperative PSA and PSA half-life were investigated. The mean follow-up period was 44.5 months. The accuracy of the grade and the clinical stage were 58.9% and 23.2%, respectively. Organ-confined disease was seen in patients with an initial PSA level less than 30 ng/ml. Postoperative PSA half-life is significantly prolonged in cases with poorly differentiated adenocarcinoma or lymph node involvement and may be a predictor of PSA failure. The cause-specific 5-year survival rates were 92.7% on the whole, 92.9% for well differentiated, 96.7% for moderately differentiated, 85.7% for poorly differentiated, 100% for stage B1, 95.0% for stage B2 and 86.8% for stage C. These results indicated that patients with an initial PSA level of less than 30 ng/ml will benefit from radical prostatectomy.

Time dependence of aggregation in crystallizing lysozyme solutions probed using NMR self-diffusion measurements.

The time dependence of aggregation in supersaturated lysozyme solutions was studied using pulsed-gradient spin-echo NMR diffusion measurements as a function of lysozyme concentration at pH 6.0 and 298 K in the presence of 0.5 M NaCl. The measurements provide estimates of the weight-averaged diffusion coefficient of the monomeric to intermediate molecular weight lysozyme species present in the solution (very large aggregates and crystals are excluded from the average due to the NMR relaxation-weighting effects inherent in the method). The results show that the average molecular weight of the various lysozyme aggregates changed with sigmoidal kinetics and that these kinetics were strongly influenced by the initial lysozyme concentration. The visualization of the time dependence of the protein aggregation afforded by this method provides a deeper understanding of how the crystallizing conditions (especially the initial protein concentration) are related to the resulting crystals.

[A case of bladder tumor producing granulocyte-colony stimulation factor and parathyroid hormone-related protein].

A 68-year-old woman presented with urinary pain and frequency. Cystoscopy, intravenous pyelography and magnetic resonance imaging showed a huge bladder mass and hydronephrosis of the left kidney. Transurethral resection of bladder tumor (TUR-Bt) was done. Histopathological findings of TUR-biopsy was high grade transitional cell carcinoma. Post operatively, the laboratory examination showed marked leukocytosis with a maximum of 99,600/mm3 in the peripheral blood and a high level of granulocyte colony stimulating factor (G-CSF), 70 pg/ml in the serum (normal: less than 9.8 pg/ml). Serum calcium level increased gradually and parathyroid hormone-related protein (PTH-rP) revealed high, 8.4 pMol/l (normal: less than 0.6 pMol/l). The tumor cells were positive for G-CSF and PTH-rP immunohistochemical staining. She died of the disease 46 days after the operation. This is the third case of G-CSF and PTH-rP producing bladder tumor in the literature.

Serum-free coculture of stromal and epithelial cells from benign prostatic hyperplasia with keratinocyte growth factor.

We developed a serum-free coculture model of benign prostatic hyperplasia (BPH) to clarify whether stromal cells stimulate growth of epithelial cells from BPH tissues. Epithelial and stromal cells from freshly isolated BPH tissue were cultured separately in defined serum-free WAJC 404/RPMI 1640 medium supplemented with insulin, transferrin, selenium, hydrocortisone, bovine serum albumin, epidermal growth factor, basic fibroblast growth factor and keratinocyte growth factor. (3)H-Tdr incorporation into epithelial cells and stromal cells was used as a measure of proliferation. When epithelial cells were cocultured with stromal cells, (3)H-Tdr incorporation into epithelial cells was increased in comparison to that in epithelial cells cultured alone. Dihydrotestosterone significantly increased this effect. It is likely that the in vitro coculture model reported here will be useful for isolating and understanding stromal cell-derived paracrine growth factor(s).

Promoter analysis and chromosomal mapping of human EBAG9 gene.

The human EBAG9 was previously identified as an estrogen responsive gene using CpG-genomic binding site cloning (Watanate et al., (1998) Mol. Cell. Biol. 18: 442-449). Recently it was revealed that the EBAG9 is identical with RCAS1 which is a cancer cell surface antigen implicated in immune escape. Here, we isolated and analyzed the 5'-flanking region of human EBAG9 gene. We determined transcription initiation site, which has a homology with an initiator element YYCAYYYY, and found that TATA motif was absent. Deletion analysis of the 5'-flanking region using MCF-7 breast cancer cells indicated that the sequences -86 to -36 containing the ERE had the basal level of promoter activity and the upstream GC-rich region positively regulated the activity. EBAG9 promoter luciferase reporters containing the ERE could respond to estrogen, and electrophoretic mobility shift assay showed that ERalpha bound to the ERE. Moreover, fluorescent in situ hybridization analysis has shown that the human EBAG9 gene is located at chromosome 8q23 which is frequently amplified in tumors. These findings suggest that the human EBAG9 might be involved in carcinogenesis as an estrogen responsive gene.

An electrospray-ionization mass spectrometry analysis of the pH-dependent dissociation and denaturation processes of a heterodimeric protein.

Electrospray ionization mass spectrometry (ESI-MS) was applied to the analysis of the dissociation and denaturation processes of a heterodimeric yeast killer toxin SMKT. The two distinct subunits of SMKT noncovalently associate under acidic conditions, but become dissociated and denatured under neutral and basic conditions. In order to understand the unique pH-dependent denaturation mechanism of this protein, a pH titration was performed by utilizing ESI-MS. The molecular ions of the heterodimer which possesses the highly ordered structure, were mainly observed below pH 4.6. However, the two subunits immediately dissociated at this pH. The spectra measured with various settings of the mass spectrometer indirectly demonstrated that the pH-dependent dissociation occurs in the liquid phase. The current result as well as the three-dimensional structure of SMKT suggest that the deprotonation of a specific carboxyl group triggers a cooperative dissociation process of this protein. In conclusion, the pH titration of a protein by ESI-MS is particularly effective, when the unfolding process or the biological function of the protein is related to the interaction with other molecules.

Equilibrium studies on complexation in water and solvent extraction of zinc(II) and cadmium(II) with benzo-18-crown-6.

The formation constants (K(ML)) in water of 1:1 complexes of benzo-18-crown-6 (B18C6) and 18-crown-6 (18C6) with Zn(2+) and Cd(2+), the sizes of which are much smaller than the ligand cavities, were determined at 25 degrees C by conductometry. Compared with Cd(2+), the crown ethers form more stable complexes with Zn(2+) although the size of Zn(2+) is less suited for the cavities. B18C6 forms a more stable complex with each metal ion than 18C6. Moreover, the extraction equilibria of these metal ions (M(2+)) with B18C6 (L) for the benzene/water system in the presence of picric acid (HA) were investigated at 25 degrees C. The association between L and HA in benzene was examined for evaluating the intrinsic extraction equilibria of M(2+) with B18C6. The extracted species were found to be MLA(2) and ML(2)A(2), and the overall extraction constants (K(ex,1) and K(ex,2), respectively) were obtained. The values of K(ex,1) for these metal ions are almost the same, but the K(ex,2) is larger for Zn(2+) than for Cd(2+). The extraction selectivity was interpreted quantitatively by the constituent equilibrium constants, i.e. K(ML), the ion-pair extraction constant of ML(2+) with A(-), and the adduct formation constant of MLA(2) with L in benzene.

Stage-specific expression of estrogen receptor subtypes and estrogen responsive finger protein in preimplantational mouse embryos.

In hope of understanding possible roles of estrogen during early embryogenesis, we examined the expression of both estrogen receptor alpha (ER alpha) and ER beta, a recently cloned novel subtype, in mouse oocytes and preimplantation embryos by means of reverse transcription polymerase chain reaction (RT-PCR). To investigate whether estrogen actually exerts its action, we further determined the expression of efp (estrogen-responsive finger protein), a newly characterized estrogen responsive gene belonging to the RING finger family. ER alpha mRNA was detected in whole ovaries, cumulus-oocyte complexes, denuded oocytes, 2-cell and 4-cell embryos, whereas it was undetected in 8-cell embryos. Interestingly it reappeared in morulae and blastocysts. ER beta mRNA was detected similarly to ER alpha except for the absence of ER beta mRNA in morulae. The efp mRNA was detected in whole ovaries, cumulus-oocyte complexes, 4-cell embryos, morulae and blastocysts. The stage specific expression of ER alpha and ER beta along with detection of the product of the estrogen responsive gene in early preimplantation embryos may indicate the possible physiological roles of estrogen in early embryogenesis.

Characterization of the solution properties of Pichia farinosa killer toxin using PGSE NMR diffusion measurements.

The solution behaviour with respect to pH and NaCl concentration of the tertiary structure and propensity for aggregation of salt- mediated killer toxin (SMKT) from Pichia farinosa was examined using pulsed-gradient spin-echo NMR diffusion measurements. It was found that in 0.15m NaCl the tertiary structure of SMKT was constant below pH 5.0, with the native SMKT existing as an unaggregated heterodimer containing the beta-subunit in a compactly folded form. However, above pH 5.0 the beta-subunit dissociated and lost its compact structure, becoming a random coil with an approximately 37% increase in effective hydrodynamic radius. To determine the effects of NaCl concentration on the tertiary structure of SMKT, diffusion measurements were performed at pH 3.5 and NaCl concentrations up to 2M. Both the tertiary structure and aggregation state of SMKT were found to be insensitive to the salt concentration which indicates that the activity of the toxin is not a direct result of salt-protein interactions.