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.

Association between Sarcopenia, Its Defining Indices, and Driving Cessation in Older Adults.

OBJECTIVES: Driving a car is essential for older adults to support their activities of daily living and maintain their quality of life. However, physical function - which often declines with age - is a key factor to determine whether older adults can continue driving safely. As such, we sought to examine the association between sarcopenia and driving cessation in older adults. DESIGN: A prospective study. SETTING: A community setting. PARTICIPANTS: We conducted a study including 2,874 older adult participants from the community (mean age: 71.0 ± 4.7 years [range: 65-93 years], women: 36.3%). MEASUREMENTS: We assessed whether they were still driving at baseline examination as well as their degree of sarcopenia. Sarcopenia was assessed according to the clinical definition provided by the EWGSOP2 by measuring muscle mass, muscle strength, and physical performance represented by gait speed. Driving cessation was determined based on driving status at the initial visit and at a follow-up examination approximately 15 months later. RESULTS: At the baseline assessment, there were 62 participants (2.2%) with confirmed sarcopenia and 23 participants (0.8%) with severe sarcopenia. Participants were classified into either the ongoing driving (n = 2816) or driving cessation (n = 58) group. Low muscle strength and low muscle mass were associated with driving cessation (low muscle strength: odds ratio [OR] 2.09, 95% confidence interval [CI] 1.13-3.87; low muscle mass: OR 2.00, 95% CI 1.04-3.85). Slow gait was not associated with driving cessation (OR 1.35, 95% CI 0.68-2.69). Significantly, sarcopenia was associated with driving cessation (confirmed sarcopenia: OR 4.48, 95% CI 1.63-12.29; severe sarcopenia: OR 4.46, 95% CI 1.21-16.41). CONCLUSIONS: Sarcopenia is associated with an increased likelihood of driving cessation in community-dwelling older adults. Evaluation of physical function related to sarcopenia would be useful for judgment of the ability to drive safely among older adults.

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.

Cognitive Frailty as a Risk Factor for Incident Disability During Late Life: A 24-Month Follow-Up Longitudinal Study.

OBJECTIVES: Association between cognitive frailty as identified by a new operational definition and incident disability in the community setting remains unclear. This will be the catalyst for preventive interventions designed to treat adverse health problems among elderlies. DESIGN: A 24-month follow-up longitudinal study on a community-based cohort. SETTING: Community-setting. PARTICIPANTS: Participants included a total of 9,936 older adults aged 65 years or older. MEASUREMENTS: Frailty was characterized as slow walking speed or/and muscle weakness represented by grip strength. Cognitive function was assessed according to several tests. Cognitive impairment was defined below the age-education reference threshold. Participants were categorized into the four groups: robust, cognitive impairment alone, frailty alone, and cognitive frailty (both frail and cognitive impairment). Incident disability data was extracted from the Japanese Long-Term Care system. RESULTS: The prevalence of cognitive frailty was 11.2%. The cumulative incidence rates of incident disability in each group were also estimated (robust, 9.6/1,000 person-years (95% CI 7.9 to 11.7); cognitive impairment, 21.3/1,000 person years (95% CI 16.3 to 27.7); frailty, 45.4/1,000 person years (95% CI 39.5 to 52.3); and cognitive frailty, 79.9/1,000 person years (95% CI 68.6 to 93.1)). Adjusted Cox proportional hazard model revealed that the cognitive frailty group had the highest hazard ratio (HR 3.86, 95%CI 2.95 - 5.05, P < 0.001). CONCLUSIONS: A proper operational definition was developed to determine cognitive frailty among elderlies. Cognitive frailty is more associated with incident disability in community-setting than cognitive impairment or physical frailty alone.

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.

Canine squamous cell carcinoma cell lines with high expression of survivin are sensitive to survivin inhibitor YM155.

Treatment of unresectable canine squamous cell carcinoma (SCC) remains challenging and new therapeutic strategies are needed. Survivin is a member of the inhibitor of apoptosis protein family and its inhibitor, YM155, is a potential anti-tumour agent. In the present study, 10 canine tumour cell lines (representing eight different tumour types) were screened for sensitivity to YM155; the drug potently inhibited the growth of the HAPPY SCC cell line. The growth inhibitory properties of YM155 were then examined in more detail using a panel of seven SCC cell lines. YM155 inhibited the growth of the cell lines HAPPY and SQ4; in contrast to the other lines in the panel, these two cell lines had high levels of expression of survivin. In HAPPY cells, YM155 inhibited expression of the survivin gene at the transcriptional level. In contrast, YM155 down-regulated survivin at the post-transcriptional level in SQ4 cells. YM155 suppressed cell growth in HAPPY cells, mostly via induction of apoptosis, but this was not the case in SQ4 cells. Two canine SCC cell lines with high cellular expression of survivin were sensitive to YM155. The possible underlying mechanisms of the cytotoxic effect of YM155 in these cell lines were different. One cell line had down-regulation of survivin mRNA and protein expression, associated with induction of apoptotic cell death. The other cell line had post-transcriptional down-regulation of survivin expression and subsequent induction of non-apoptotic cell death. Targeting survivin with YM155 is a potential approach for the treatment of canine SCCs with high expression of survivin.

Pulsating aurora from electron scattering by chorus waves.

Auroral substorms, dynamic phenomena that occur in the upper atmosphere at night, are caused by global reconfiguration of the magnetosphere, which releases stored solar wind energy. These storms are characterized by auroral brightening from dusk to midnight, followed by violent motions of distinct auroral arcs that suddenly break up, and the subsequent emergence of diffuse, pulsating auroral patches at dawn. Pulsating aurorae, which are quasiperiodic, blinking patches of light tens to hundreds of kilometres across, appear at altitudes of about 100 kilometres in the high-latitude regions of both hemispheres, and multiple patches often cover the entire sky. This auroral pulsation, with periods of several to tens of seconds, is generated by the intermittent precipitation of energetic electrons (several to tens of kiloelectronvolts) arriving from the magnetosphere and colliding with the atoms and molecules of the upper atmosphere. A possible cause of this precipitation is the interaction between magnetospheric electrons and electromagnetic waves called whistler-mode chorus waves. However, no direct observational evidence of this interaction has been obtained so far. Here we report that energetic electrons are scattered by chorus waves, resulting in their precipitation. Our observations were made in March 2017 with a magnetospheric spacecraft equipped with a high-angular-resolution electron sensor and electromagnetic field instruments. The measured quasiperiodic precipitating electron flux was sufficiently intense to generate a pulsating aurora, which was indeed simultaneously observed by a ground auroral imager.

Effect of dasatinib in a xenograft mouse model of canine histiocytic sarcoma and in vitro expression status of its potential target EPHA2.

Canine histiocytic sarcoma (HS) is an aggressive and highly metastatic tumor. Previously, the kinase inhibitor dasatinib was shown to have potent growth inhibitory activity against HS cells in vitro, possibly via targeting the EPHA2 receptor. Here, the in vivo effect of dasatinib in HS cells was investigated using a xenograft mouse model. Moreover, the expression status of EPHA2 was examined in six HS cell lines, ranging from insensitive to highly sensitive to dasatinib. In the HS xenograft mouse model, dasatinib significantly suppressed tumor growth, as illustrated by a decrease in mitotic and Ki67 indices and an increase in apoptotic index in tumor tissues. On Western blot analysis, EPHA2 was only weakly detected in all HS cell lines, regardless of sensitivity to dasatinib. Dasatinib likely results in the inhibition of xenograft tumor growth via a mechanism other than targeting EPHA2. The findings of this study suggest that dasatinib is a targeted therapy drug worthy of further exploration for the treatment of canine HS.

Selective growth inhibition by suppression of F1Fo ATPase in canine malignant melanoma cell lines.

Canine malignant melanoma (CMM) is a highly aggressive and fatal neoplasm. To identify potential therapeutic compounds and/or targets, 320 compounds were screened for their growth inhibitory activity in a CMM line (CMM-1) using a chemical library known to target specific signaling pathways/cell growth-related molecules. Among the compounds screened, the F1Fo ATPase inhibitor oligomycin showed potent growth inhibitory effects in CMM-1 cells, while exhibiting less toxic effects in a non-neoplastic control cell line (MDCK cells). The growth inhibitory effect of oligomycin A was then examined using six CMM lines and MDCK cells. Three CMM lines were highly sensitive to oligomycin A, with around 3000-20 000 times lower IC50 compared with oligomycin A-resistant CMM lines and MDCK cells. Oligomycin A-sensitive CMM-1 cells exhibited much greater oligomycin A-induced decreases in cellular ATP compared to oligomycin A-resistant cell lines. Although the oligomycins are clinically unsuitable because of its in vivo toxicity, these findings implicate the potential of F1Fo ATPase as a therapeutic target in a subset of CMM.

GLI3-dependent repression of DR4 mediates hedgehog antagonism of TRAIL-induced apoptosis.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis through its cognate receptors death receptor 4 (DR4) and death receptor 5 (DR5), preferentially in malignant cells. However, many malignant cells remain resistant to TRAIL cytotoxicity by poorly characterized mechanisms. Here, using cholangiocarcinoma cells, as a model for TRAIL resistance, we identified a role for the oncogenic Hedgehog (Hh)-GLI pathway in the regulation of TRAIL cytotoxicity. Blockade of Hh using pharmacological and genetic tools sensitizes the cells to TRAIL cytotoxicity. Restoration of apoptosis sensitivity coincided with upregulation of DR4 expression, while expression of other death effector proteins remained unaltered. Knockdown of DR4 mimics Hh-mediated resistance to TRAIL cytotoxicity. Hh regulates the expression of DR4 by modulating the activity of its promoter. Luciferase, chromatin immunoprecipitation and expression assays show that the transcription factor GLI3 binds to the DR4 promoter and Hh requires an intact GLI3-repression activity to silence DR4 expression. Finally, small interfering RNA (siRNA)-targeted knockdown of GLI3, but not GLI1 or GLI2, restores DR4 expression and TRAIL sensitivity, indicating that the Hh effect is exclusively mediated by this transcription factor. In conclusion, these data provide evidence of a regulatory mechanism, which modulates TRAIL signaling in cancer cells and suggest new therapeutic approaches for TRAIL-resistant neoplasms.

Heart rate to arterial pressure impulse response during one lung ventilation.

BACKGROUND: Although one lung ventilation (OLV) is commonly used, little is known about the modulation of the autonomic nervous system with OLV while under general anesthesia. As the frequency domain and time domain analyses are powerful analytic tools, we investigated their modulation during OLV. METHODS: Patients undergoing thoracic surgery were classified into two groups: those who did (group A, n=8) and those who did not (group N, n=8) receive atropine. After a double lumen tube was placed endotracheally, mechanical ventilation of both lungs (BLV) was established at 18 min(-1) while under isoflurane anesthesia. Electrocardiogram, systolic arterial pressure (SAP), and inspiratory flow (Finsp) were digitally recorded as follows: awake before anesthesia; BLV after anesthesia; BLV after intravenous 10 microg kg(-1) of atropine (group A) or not (group N); left OLV; and right OLV. Power spectral analyses of heart rate (HR) and SAP were computed by determining low-(LF, 0.04-0.15 Hz) and high-frequency (HF, 0.15-0.40 Hz) components, and impulse response analysis was executed among HR, SAP, and Finsp. Impulse responses were assessed by the maximum values in the time domain. RESULTS: In frequency domain analysis, atropine depressed LF and LF/HF but not HF in HR variability, while no difference was observed between right OLV and left OLV. The heart rate to SAP impulse response was maintained at a significantly higher level in group A than in group N (905+/-360 vs. 425+/-375 mmHg beats(-1)min(-1)) at right OLV. A significant difference was also observed between left and right OLV within group N. CONCLUSION: Impulse response analysis demonstrated that there is a greater effect on autonomic nervous system modulation during right OLV than in left OLV, which mainly results from a parasympathetic neural linkage origin.

Superior mesenteric vein thrombosis presented transient false positivity for lupus anticoagulant under heparin treatment.

A 24-year-old Japanese man was admitted because of massive haematemesis and melaena with persistent abdominal pain. Markedly bloody ascites and severely oedematous small intestine were recognized, and angiography then revealed superior mesenteric vein thrombosis. After resection of the necrotic small intestine, continuous intravenous infusion of heparin and urokinase was performed. This patient had no familial or personal history of thrombosis. On the 15th day after operation, an initial search for lupus anticoagulant revealed that the prothrombin time (PT) ratio and dilute activated partial thromboplastin time (aPTT) were positive under heparin treatment, without evidence of rheumatic or connective tissue disease. Thrombocytopenia was observed with a nearly normocellular bone marrow. A follow-up examination 1 year later still revealed an increased aPTT. However, all tests for antiphospholipid antibodies had been negative including dilute aPTT for about 2 years since the 15th day after operation. These findings suggest that, in this patient, superior mesenteric vein thrombosis has not been associated with primary antiphospholipid syndrome but is probably idiopathic. Positive tests for lupus anticoagulant in the initial period may be unreliable due to heparin treatment.

Plasma procalcitonin in sepsis and organ failure.

INTRODUCTION: Because the use of procalcitonin (PCT) as a marker of bacterial infection has been advocated, this study was carried out to determine the usefulness of plasma PCT in the early diagnosis and differentiation of patients with non-infectious systemic inflammatory response syndrome (SIRS) from those with sepsis, and the relationship between plasma PCT level and severity of organ failure. MATERIALS AND METHODS: Thirty-five patients with non-septic SIRS (n = 16), sepsis (n = 7) or septic shock (n = 12) were included in this study. PCT and C-reactive protein (CRP) levels were measured and sepsis-related organ failure assessment (SOFA) score was calculated for these patients. Plasma PCT was measured by immunoluminometric assay. RESULTS: The median (minimum, maximum) plasma PCT levels were 0.6 (0.1, 3.4) ng/mL in non-septic SIRS, 5.4 (0.9, 47.7) ng/mL in sepsis and 73.4 (9.6, 824.1) ng/mL in septic shock, and significant differences existed in plasma PCT levels among the three groups. The median (minimum, maximum) CRP levels were 13.8 (0.3, 48.8) mg/dL in non-septic SIRS, 23.3 (1.4, 26.6) mg/dL in sepsis and 17.4 (2.2, 34.1) mg/dL in septic shock, without significant differences among the three groups. A good correlation was found between plasma PCT level and SOFA score (rs = 0.766, P < 0.0001), although no correlation was found between CRP level and SOFA score. CONCLUSIONS: CRP is increased by inflammatory disease as well as infection and is therefore not a good indicator of infection in patients with severe SIRS. On the other hand, PCT is a good indicator of severity of sepsis and organ failure in patients with severe SIRS since PCT levels correlated with sepsis and SOFA scores. PCT level is useful for diagnosis of sepsis and as an indicator of severity of organ failure in patients with SIRS.

Interferon regulatory factor 1 promoter polymorphism and response to type 1 interferon.

The clinical success of interferon-treatment has been found to vary in different individuals. To explain this, we hypothesized that responses to type 1 interferons could be partly determined by interferon regulatory factor-1 gene transcription, because the latter is an important transcription factor in the interferon system. We demonstrated that the antiproliferative effect of type 1 interferons on human liver cancer cells correlates with levels of transcription of the interferon regulatory factor-1 gene in parallel with those of p21(WAF-1) expression. Here, we investigated whether mutations in the interferon regulatory factor-1 gene cause different responses to type 1 interferons. DNA from several human liver cancer cell lines and peripheral blood mononuclear cells was investigated. Nucleotide sequences of the interferon regulatory factor-1 gene and polymerase chain reaction products of its upstream region were determined directly and after cloning. The promoter activity of the upstream region of this gene was measured by the luciferase reporter assay. We found 4 point mutations in the upstream (- 1 approximately - 495) region, and the luciferase promoter assay demonstrated that these mutations did modify promoter activity. Analysis of DNA from healthy volunteers showed that these mutations are single nucleotide polymorphisms. These results suggest that single nucleotide polymorphisms of the interferon regulatory factor-1 promoter contribute, at least in part, to determining responses to type 1 interferons. J. Cell. Biochem. Suppl. 36: 191-200, 2001.

Synthesis and properties of optically active 1,1':5',1":5",1"'-hexol (QUANOL).

Optically active (R,R,R)- and (R,S,R)-1,1':5',1":5",1'"-quatemaphthalene-2,2',6',2",6",2"'-hexol (QUANOL) were prepared from (R)-BINOL in five steps. The CD spectrum of (R,R,R)-QUANOL showed a larger A value than those of (R)-BINOL and (R,S,R)-QUANOL, but additivity of the axial chiralities in the A value was not observed. Other basic properties for the use of QUANOL as a chiral ligand are also reported.

Pheochromocytoma of the urinary bladder: a case report.

We present a 66-year old female patient with pheochromocytoma of the urinary bladder. We performed transabdominal needle biopsy of the tumor without suspicion of pheochromocytoma because of her well-controlled blood pressure and no characteristic symptoms following administration of antihypertensive medication. Hypertensive crisis (260/130 mmHg) occurred just after the needle insertion. The diagnosis was pheochromocytoma. The norepinephrine level in the serum and her blood pressure normalized without antihypertensive medication after partial cystectomy. Pheochromocytoma should be suspected in cases of intramural bladder tumors, especially in a normotensive patients receiving antihypertensive medication.

Echocardiographic diagnosis of extrapericardial tamponade due to dilated gastric roll following oesophagectomy.

A complication of lower thoracic oesophagectomy for oesophageal carcinoma is reported. Extrapericardial tamponade was caused by a dilated retrosternal gastric roll. Echocardiography was useful for diagnosis. Diagnosis, investigation and management of this unusual but life-threatening complication are discussed. Transthoracic echocardiography is a useful and practical investigation for the evaluation of complications of oesophagectomy.

Phylogeny of the lady fern group, tribe Physematieae (Dryopteridaceae), based on chloroplast rbcL gene sequences.

Nucleotide sequences of the chloroplast gene rbcL from 42 species of the fern tribe Physematieae (Dryopteridaceae) were analyzed to gain insights into the inter- and intrageneric relationships and the generic circumscriptions in the tribe. The phylogenetic relationships were inferred using the neighbor-joining and maximum-parsimony methods, and both methods produced largely congruent trees. These trees reveal that: (1) Athyrium, Cornopteris, Pseudocystopteris, and Anisocampium form a clade and Athyrium is polyphyletic; (2) Deparia sensu lato is monophyletic and Dictyodroma formosana is included in the Deparia clade; (3) Diplaziopsis forms a clade with Homalosorus, which is isolated from the other genera of the Physematieae; (4) Monomelangium is included in the monophyletic Diplazium clade; and (5) Rhachidosorus is not closely related to either Athyrium or Diplazium.

[The clinical statistics of the operations at the Department of Urology, Tokatsu Hospital: from 1994 to 1999].

We investigated the clinical statistics of the operations and inpatients since the establishment of the department in June 1994 up to May 1999. The total number of inpatients was 1,269 (1,047 males and 222 females), and a total of 1,098 operations were performed. Extracorporeal shock wave lithotriopy (ESWL) was also introduced in 1997, and in addition, it seemed that the number of operations and inpatients would be increasing in future.