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.

The Space Physics Environment Data Analysis System (SPEDAS).

With the advent of the Heliophysics/Geospace System Observatory (H/GSO), a complement of multi-spacecraft missions and ground-based observatories to study the space environment, data retrieval, analysis, and visualization of space physics data can be daunting. The Space Physics Environment Data Analysis System (SPEDAS), a grass-roots software development platform (www.spedas.org), is now officially supported by NASA Heliophysics as part of its data environment infrastructure. It serves more than a dozen space missions and ground observatories and can integrate the full complement of past and upcoming space physics missions with minimal resources, following clear, simple, and well-proven guidelines. Free, modular and configurable to the needs of individual missions, it works in both command-line (ideal for experienced users) and Graphical User Interface (GUI) mode (reducing the learning curve for first-time users). Both options have "crib-sheets," user-command sequences in ASCII format that can facilitate record-and-repeat actions, especially for complex operations and plotting. Crib-sheets enhance scientific interactions, as users can move rapidly and accurately from exchanges of technical information on data processing to efficient discussions regarding data interpretation and science. SPEDAS can readily query and ingest all International Solar Terrestrial Physics (ISTP)-compatible products from the Space Physics Data Facility (SPDF), enabling access to a vast collection of historic and current mission data. The planned incorporation of Heliophysics Application Programmer's Interface (HAPI) standards will facilitate data ingestion from distributed datasets that adhere to these standards. Although SPEDAS is currently Interactive Data Language (IDL)-based (and interfaces to Java-based tools such as Autoplot), efforts are under-way to expand it further to work with python (first as an interface tool and potentially even receiving an under-the-hood replacement). We review the SPEDAS development history, goals, and current implementation. We explain its "modes of use" with examples geared for users and outline its technical implementation and requirements with software developers in mind. We also describe SPEDAS personnel and software management, interfaces with other organizations, resources and support structure available to the community, and future development plans. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11214-018-0576-4) contains supplementary material, which is available to authorized users.

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.

The use of repetitive DNA in cytogenetic studies of plant sex chromosomes.

The structure of sex chromosomes in plants was analyzed by fluorescent in situ hybridization (FISH) with repetitive DNAs. FISH probes were successfully obtained from DNA libraries that were amplified from microdissected sex chromosomes. Some probes hybridized to the subtelomeric regions, where many kinds of repetitive DNAs are located with intrachromosomal similarity of their repeat units rather than interchromosomal similarity. For example, FISH with the subtelomeric repetitive sequence can easily show the location of the pseudoautosomal region (PAR) on the X chromosome of Silene latifolia. The other probes were localized on the interstitial region of the sex chromosomes. The interstitial region contains chloroplast DNAs or neighboring sequences of the internal telomeres, suggesting insertion or translocation occurred during differentiation of the sex chromosome. These data are very informative for understanding the structure of the plant sex chromosomes and their evolutionary process.

Chromosome 18q deletion and Smad4 protein inactivation correlate with liver metastasis: A study matched for T- and N- classification.

Smad4 protein, whose gene is coded at chromosome 18q21.1, is an important tumour suppressor that mediates transforming growth factor-beta. It has been reported that inactivation of the Smad4 gene and allelic loss of chromosome 18q correlate with liver metastasis and poorer prognosis in colorectal cancers. Utilising a recently developed method of immunohistochemical staining for Smad4 protein, we focused on the specific impact of Smad4 protein expression on liver metastasis in colorectal cancer. We also evaluated the association between chromosome18q deletion and liver metastasis. We selected 20 colorectal cancers with liver metastasis for the experimental group, and 20 cases without liver metastasis for the control. In order to exclude the influence of lymph node metastasis, all cases were lymph node negative. In addition, the two groups were matched for tumour depth, tumour differentiation and tumour location. We compared the expression level of Smad4 protein immunohistochemically in these 20 matched pairs. We also compared the loss of heterozygosity status at chromosome 18q in these 20 matched pairs. Immunohistochemical staining revealed a significant difference (P = 0.024) in the level of Smad4 protein between the two groups. We also observed a significantly different (P=0.0054) ratio of allelic deletion at chromosome 18q21. Smad4 protein expression level and allelic loss at 18q21 are associated with the process of liver metastasis in colorectal cancers evaluated when excluding clinical and pathological features except for liver metastasis.

Uso de substancias classificadas como "proscritas" no receituario homeopatico / Homeopathic use of substances classified as "proscript"

O uso, em homeopatia, de substancias classificadas como proscritas tm sido, nos ultimos anos, um problema tanto para prescritores como para mnipuladores. O medicamento homeopatico, quando prescrito pela lei dos semelhantes... (AU)

Brain metastases of malignant melanoma showing unbalanced whole arm chromosomal translocations der (8; 14) (q10; q10) and der (11; 15) (q10; q10) in a Japanese patient.

Since malignant melanoma is a rare malignancy in Japan, little is known about the cytogenetic abnormalities in Japanese patients. We report a case of malignant melanoma showing complex chromosomal abnormalities. A 70-year-old woman was admitted to our hospital because of anorexia, delirium, and right hemiplegia. Cranial CT disclosed several metastatic brain tumors. Multiple subcutaneous and intra-abdominal metastases were also found. A diagnosis of metastatic malignant melanoma was made by biopsy of a subcutaneous tumor. Chromosomal analysis of the tumor cells disclosed complex karyotypic abnormalities including novel unbalanced whole arm translocations der (8; 14) (q10; q10) and der (11; 15) (q10; q10).

Myelodysplastic syndrome progresses rapidly into erythroleukemia associated with synchronous double cancers of the stomach and the papilla of Vater.

Patients with myelodysplastic syndrome (MDS) show a relatively high incidence of developing cancers. However, it is extremely rare that synchronous double cancers develop in an MDS patient. We report a case of MDS that progressed rapidly into erythroleukemia (M6 by French-American-British classification) complicated by gastric cancer and carcinoma of the papilla of Vater. A 66-year-old man was admitted because of pancytopenia with peripheral blasts. A diagnosis of MDS (with refractory anemia with excess of blasts in transformation [RAEB-T]) was made by bone marrow examination. Chromosome analysis revealed 46,XY. An early gastric cancer was also diagnosed by endoscopic examination. The peripheral blasts gradually proliferated and the disease progressed to M6. A chromosome abnormality 46,XY,del(1)(q42) was detected at the leukemic transformation. A CAG (low-dose cytarabine and aclarubicin in combination with granulocyte colony-stimulating factor) regimen was started as a remission-induction therapy. However, obstructive jaundice developed and a marked dilatation of bile ducts was observed by abdominal computed tomography (CT). A carcinoma of the papilla of Vater was detected by endoscopy. As remission was achieved and the pancytopenia improved, the patient subsequently underwent a surgical jejuno-choledochostomy to manage the jaundice. However, the leukemia relapsed thereafter and additional chromosome abnormalities including der(5)t(5;10)(p15:q11) were observed.

[Association of idiopathic thrombocytopenic purpura and type 1 diabetes mellitus in a patient with sarcoidosis].

Occurrence of autoimmune diseases with sarcoidosis is well known. However, a case in which more than one of these diseases coexist with sarcoidosis is rare. We present a young man with suspected sarcoidosis, complicated by idiopathic thrombocytopenic purpura (ITP) and type 1 A diabetes mellitus (DM). A 21-year-old man was admitted to our hospital because of thrombocytopenia, hyperglycemia, and bilateral hilar lymphadenopathy (BHL). Although a histological proof could not be obtained, the patient was considered to have sarcoidosis because 67-gallium scintigraphy disclosed "Lambda" and "Panda" signs which are highly specific for sarcoidosis. Type 1 A DM was also diagnosed as the patient had antiglutamic acid decarboxylase antibodies. The patient disclosed no hepatosplenomegaly or no lymphadenopathy and diagnosis of ITP was confirmed by bone marrow examination. High dose steroid was started as the thrombocytopenia progressed. The platelet number increased satisfactorily and shrinkage of BHL was also observed with the therapy.

Genomic structure and promoter activity of the human tissue factor pathway inhibitor-2 gene.

Human type-2 tissue factor pathway inhibitor (TFPI-2), also known as placental protein 5, is a 32 kDa serine proteinase inhibitor consisting of three tandemly arranged Kunitz-type inhibitor domains homologous to tissue factor pathway inhibitor. TFPI-2 strongly inhibits a wide variety of serine proteinases including trypsin, chymotrypsin, plasmin, kallikrein and blood coagulation factor XIa. In this study, we have isolated and characterized a genomic clone from an artificial chromosome genomic library that encodes the entire human TFPI-2 gene. The human TFPI-2 gene spans approximately 7 kb and consists of five exons and four introns. Each Kunitz-type domain is encoded by a single exon, similar to that observed for murine TFPI-2 and other Kunitz-type proteinase inhibitors. A total of 535 bp of the 3'-flanking region contain two probable polyadenylation sites (AATAAA) at +4297 and +4314. A single transcription initiation site was identified by oligo-capping and reverse transcription-PCR analysis. Transient transfection of reporter plasmids containing segments of the 5'-flanking region into human transformed bone marrow endothelial cells and glioblastoma cells identified an 85 bp region (-224 to -139) sufficient for transcription of the human TFPI-2 gene.

Nucleotide sequence of the gene encoding murine tissue factor pathway inhibitor-2.

Tissue factor pathway inhibitor-2 (TFPI-2), also known as placental protein 5, is a 32 kDa extracellular matrix-associated serine proteinase inhibitor consisting of three tandemly-arranged Kunitz-type domains. Two overlapping genomic clones containing sequences encoding murine TFPI-2 were isolated from a lambda FIXII 129 SVJ mouse genomic library, and the complete nucleotide sequence of the gene was determined. The murine TFPI-2 gene spans approximately 9.3 kilobases and consists of five exons and four introns. The nucleotide sequences surrounding all the exon-intron boundaries are highly conserved and obey the GT-AG rule. Each Kunitz-type domain is encoded by a single exon, similar to that observed for other Kunitz-type proteinase inhibitors. A total of 1,577 bp of the 3'-flanking region contains a probable polyadenylation site (ATTAAA) at +5,759 and an apparent cleavage or termination site (CATTG) at +6,170. The 5'-flanking region of the murine TFPI-2 gene contains a prototypical TATA box, a GC box and two CAAT boxes. In addition, several candidate transcription factor binding sites responsible for placenta-, endothelial cell-, and smooth muscle cell-specific expression of the TFPI-2 gene were also identified.

Correlates of problem drinking among young Japanese women: personality and early experiences.

Problem drinking patterns were measured by the CAGE questionnaire among 90 currently drinking young Japanese women who were recently recruited by a Japanese company. Problem drinking was examined in terms of personality (temperament and character as defined by Cloninger) and early life experiences (perceived parental behavior, parental abusive behavior, being bullied at school, and positive and negative life events experienced before the age of 16). Multiple regression analysis revealed that problem drinking could be predicted by a set of personality scores, early death of a close friend, and the interaction of the death of a close friend and low explorative excitability (novelty-seeking component 1). This suggests that problem drinking in young women is partly determined by both personality and negative life events during childhood.

Relationship between MLR blocking antibodies and the outcome of the third pregnancy in patients with two consecutive spontaneous abortions.

To determine the relationship between mixed lymphocyte culture reaction (MLR) blocking antibodies (BAbs), immunological humoral factors, which generated in pregnant women and the outcome of pregnancy, the natural outcome of the third pregnancy in fifty-five patients with primary twice consecutive abortion was evaluated, and MLR-BAbs in sera were examined during their third pregnancy. The third pregnancy in 39 of 55 patients (70.9%) continued successfully, and remaining 16 patients (29.1%) experienced repeated abortion at the first trimester. Out of these 55 patients, MLR-BAbs were examined in 27 (17 with successful outcome and 10 with repeated abortion). The positive rate of MLR-BAbs was 82.4% in patients with successful outcome (15 of 17 cases), and that in patients with repeated abortion was 10% (one of 10 cases). The positive rate of MLR-BAbs was significantly higher in the successful pregnancy group compared with that in the repeated abortion group (p < 0.001). The blocking effect on MLR significantly increased along with the prenatal course in patients with successful outcome. Thus, MLR-BAbs are strongly associated with the outcome of pregnancy in patients with primary twice consecutive spontaneous abortions.

The importance of the binding of factor Xa to phospholipids in the inhibitory mechanism of tissue factor pathway inhibitor: the transmembrane and cytoplasmic domains of tissue factor are not essential for the inhibitory action of tissue factor pathway inhibitor.

To investigate the inhibitory mechanism of tissue factor pathway inhibitor (TFPI), an attempt was made to examine the inhibitory activity of TFPI toward the factor VIIa-truncated tissue factor (TF1-219) complex, which lacks its transmembrane and cytoplasmic domains. Factor VIIa-TF1-219 activity was significantly inhibited by TFPI-factor Xa complex in the presence of phospholipids, but was not in the absence of phospholipids. In addition, TFPI did not inhibit factor VIIa-TF1-219 activity in the presence of gamma-carboxyglutamic acid-domainless factor Xa. The ability of TFPI-factor Xa complex to inhibit factor VIIa-TF1-219 activity was totally dependent on the presence of phospholipids and was neutralized by prothrombin fragment 1 in a dose-dependent manner. These results indicate that the transmembrane and cytoplasmic domains of tissue factor are not essential for the inhibitory mechanism of TFPI and confirm that the binding of factor Xa to phospholipids through its gamma-carboxyglutamic acid domain is essential for this reaction.

Hepsin, a putative membrane-associated serine protease, activates human factor VII and initiates a pathway of blood coagulation on the cell surface leading to thrombin formation.

Previous studies have shown that hepsin is a putative membrane-associated serine protease that is required for cell growth (Torres-Rosado, A., O'Shea, K. S., Tsuji, A., Chou, S.-H., and Kurachi, K. (1993) Proc. Natl. Acad. Sci. U.S. A. 90, 7181 7185). In the present study, we have transfected baby hamster kidney (BHK) cells with a plasmid containing the cDNA for human hepsin and examined these cells for their ability to activate several blood coagulation factors including factors X, IX, VII, prothrombin, and protein C. Little, if any, proteolytic activation of factors X, IX, prothrombin, or protein C was observed when these clotting factors were incubated with hepsin-transfected cells. On the other hand, hepsin-transfected cells proteolytically activated significant concentrations of human factor VII in a time- and calcium-dependent manner, whereas essentially no activation of factor VII was observed in BHK cells transfected with plasmid lacking the cDNA for hepsin. The factor VII activating activity in the hepsin-transfected BHK cell line was confined exclusively to the total membrane fraction and was inhibited > 95% by antibody raised against a fusion protein consisting of maltose-binding protein and the extracellular domain of human hepsin. An active site factor VII mutant, S344A factor VII, was cleaved as readily as plasma-derived factor VII by hepsin-transfected cells, indicating that factor VII was not converted to factor VIIa autocatalytically on the cell surface. In contrast, an activation cleavage site factor VII mutant, R152E factor VII, was not cleaved by hepsin-transfected cells, suggesting that factor VII and S344A factor VII were activated on these cells by cleavage of the Arg152-Ile153 peptide bond. In the copresence of factor VII and factor X, hepsin-transfected BHK cells supported the formation of factor Xa. In addition, in the copresence of factor VII, factor X, and prothrombin, hepsin-transfected BHK cells supported the formation of thrombin. These results strongly suggest that membrane-associated hepsin converts zymogen factor VII to factor VIIa, which in turn, is capable of initiating a coagulation pathway on the cell surface that ultimately leads to thrombin formation.