Towards building a trustworthy pipeline integrating Neuroscience Gateway and Open Science Chain.

When the scientific dataset evolves or is reused in workflows creating derived datasets, the integrity of the dataset with its metadata information, including provenance, needs to be securely preserved while providing assurances that they are not accidentally or maliciously altered during the process. Providing a secure method to efficiently share and verify the data as well as metadata is essential for the reuse of the scientific data. The National Science Foundation (NSF) funded Open Science Chain (OSC) utilizes consortium blockchain to provide a cyberinfrastructure solution to maintain integrity of the provenance metadata for published datasets and provides a way to perform independent verification of the dataset while promoting reuse and reproducibility. The NSF- and National Institutes of Health (NIH)-funded Neuroscience Gateway (NSG) provides a freely available web portal that allows neuroscience researchers to execute computational data analysis pipeline on high performance computing resources. Combined, the OSC and NSG platforms form an efficient, integrated framework to automatically and securely preserve and verify the integrity of the artifacts used in research workflows while using the NSG platform. This paper presents the results of the first study that integrates OSC-NSG frameworks to track the provenance of neurophysiological signal data analysis to study brain network dynamics using the Neuro-Integrative Connectivity tool, which is deployed in the NSG platform. Database URL: https://www.opensciencechain.org.

Intraspecific variation in morphology of spiny pollen grains along an altitudinal gradient in an insect-pollinated shrub.

Intraspecific variations in pollen morphological traits are poorly studied. Interspecific variations are often associated with pollination systems and pollinator types. Altitudinal environmental changes, which can influence local pollinator assemblages, provide opportunities to explore differentiation in pollen traits of a single species over short distances. The aim of this study is to examine intraspecific variations in pollen traits of an insect-pollinated shrub, Weigela hortensis (Caprifoliaceae), along an altitudinal gradient. Pollen spine phenotypes (length, number and density), pollen diameter, lipid mass (pollenkitt) around pollen grains, pollen production per flower and pollinator assemblages were compared at four sites at different altitudes. Spine length and the spine length/diameter ratio of pollen grains were greater at higher altitudes but not correlated with flower or plant size. Spine number and density increased as flower size increased, and pollen lipid mass decreased as plant size increased. Bees were the predominant pollinators at low-altitude sites whereas flies, specifically Oligoneura spp. (Acroceridae), increased in relative abundance with increasing altitude. The results of this study suggest that the increase in spine length with altitude was the result of selection favouring longer spines at higher-altitude sites and/or shorter spines at lower-altitude sites. The altitudinal variation in selection pressure on spine length could reflect changes in local pollinator assemblages with altitude.

Adaptive Capon beamforming for lensless electron cyclotron emission imaging with high spatial resolution.

Electron cyclotron emission (ECE) imaging diagnostics incorporating a lensless approach have been developed for measurements involving active spatial selectivity and direction-of-arrival estimation. The Capon method for adaptive-array analysis was proposed to improve the spatial resolution of the two-dimensional ECE imaging technique. Broadband noise source emissions were used to simulate the ECE to verify the practical effectiveness of the Capon method in the ECE imaging. Multiple noise source emission positions were properly estimated with a high spatial resolution using the Capon method.

Continuous partially hydrolyzed guar gum intake reduces cold-like symptoms: a randomized, placebo-controlled, double-blinded trial in healthy adults.

OBJECTIVE: Partially hydrolyzed guar gum (PHGG), a water-soluble dietary fiber produced by the controlled partial enzymatic hydrolysis of guar gum beans, has various physiological roles. PHGG is expected to influence the immune function and prevent infections. The objective of this study was to examine the effect of continuous ingestion of PHGG for 12 weeks on the development of cold-like symptoms. PATIENTS AND METHODS: A placebo-controlled, double blind, randomized, parallel-group comparative study was conducted. 96 healthy Japanese adults received 5.2 g PHGG or placebo daily for 12 weeks. Cold-like symptoms were assessed based on patient diary, and the levels of short-chain fatty acids (SCFAs) in stool and blood immune markers at baseline and at weeks 6 and 12. RESULTS: The cumulative number of "no symptoms" days for all symptoms was significantly larger in the PHGG than in the placebo group. The result of the analysis by severity of cold-like symptoms also showed significant differences, with the PHGG group having a lower severity of cold-like symptoms. Propionic acid at weeks 6 and 12 and n-butyric acid and total SCFAs at week 12 were significantly higher in the PHGG than in the placebo group. The Interferon-γ level was significantly lower at week 6 in the PHGG than in the placebo group. CONCLUSIONS: PHGG intake may affect immune function and suppress cold-like symptoms through the production of SCFAs in healthy adults.

Magnetic structures and electronic properties of cubic-pyrochlore ruthenates from first principles.

The magnetic ground states ofR2Ru2O7andA2Ru2O7withR= Pr, Gd, Ho, and Er, as well asA= Ca, Cd are predicted devising a combination of the cluster-multipole (CMP) theory and spin-density-functional theory (SDFT). The strong electronic correlation effects are estimated by the constrained-random-phase approximation (cRPA) and taken into account within the dynamical-mean-field theory (DMFT). The target compounds feature d-orbital magnetism on Ru4+and Ru5+ions forRandA, respectively, as well as f-orbital magnetism on theRsite, which leads to an intriguing interplay of magnetic interactions in a strongly correlated system. We find CMP + SDFT is capable of describing the magnetic ground states in these compounds. The cRPA captures a difference in the screening strength betweenR2Ru2O7andA2Ru2O7compounds, which leads to a qualitative and quantitative understanding of the electronic properties within DMFT.

Spin-Polarized Positronium Time-of-Flight Spectroscopy for Probing Spin-Polarized Surface Electronic States.

The energy spectrum of positronium atoms generated at a solid surface reflects the electron density of states (DOS) associated solely with the first surface layer. Using spin-polarized positrons, the spin-dependent surface DOS can be studied. For this purpose, we have developed a spin-polarized positronium time-of-flight spectroscopy apparatus based on a ^{22}Na positron source and an electrostatic beam transportation system, which enables the sampling of topmost surface electrons around the Γ point and near the Fermi level. We applied this technique to nonmagnetic Pt(111) and W(001), ferromagnetic Ni(111), Co(0001) and graphene on them, Co_{2}FeGa_{0.5}Ge_{0.5} (CFGG) and Co_{2}MnSi (CMS). The results showed that the electrons of Ni(111) and Co(0001) surfaces have characteristic negative spin polarizations, while these spin polarizations vanished upon graphene deposition, suggesting that the spin polarizations of graphene on Ni(111) and Co(0001) were mainly induced at the Dirac points that were out of range in the present measurement. The CFGG and CMS surfaces also exhibited only weak spin polarizations suggesting that the half-metallicity expected for these bulk states was not maintained at the surfaces.

Magnetic Friedel Oscillation at the Fe(001) Surface: Direct Observation by Atomic-Layer-Resolved Synchrotron Radiation

The surface magnetism of Fe(001) was studied in an atomic layer-by-layer fashion by using the in situ iron-57 probe layer method with a synchrotron Mössbauer source. The observed internal hyperfine field H_{int} exhibits a marked decrease at the surface and an oscillatory behavior with increasing depth in the individual upper four layers below the surface. The calculated layer-depth dependencies of the effective hyperfine field |H_{eff}|, isomer shift δ, and quadrupole shift 2ϵ agree well with the observed experimental parameters. These results provide the first experimental evidence for the magnetic Friedel oscillations, which penetrate several layers from the Fe(001) surface.

Silk fibroin nanofibers: a promising ink additive for extrusion three-dimensional bioprinting.

Here, we investigated the usefulness of silk fibroin nanofibers obtained via mechanical grinding of degummed silkworm silk fibers as an additive in bioinks for extrusion three-dimensional (3D) bioprinting of cell-laden constructs. The nanofibers could be sterilized by autoclaving, and addition of the nanofibers improved the shear thinning of polymeric aqueous solutions, independent of electric charge and the content of cross-linkable moieties in the polymers. The addition of nanofibers to bioinks resulted in the fabrication of hydrogel constructs with higher fidelity to blueprints. Mammalian cells in the constructs showed >85% viability independent of the presence of nanofibers. The nanofibers did not affect the morphologies of enclosed cells. These results demonstrate the great potential of silk fibroin nanofibers obtained via mechanical grinding of degummed silkworm silk fibers as an additive in bioinks for extrusion 3D bioprinting.

Search for a Variation of the Fine Structure Constant around the Supermassive Black Hole in Our Galactic Center.

Searching for space-time variations of the constants of Nature is a promising way to search for new physics beyond general relativity and the standard model motivated by unification theories and models of dark matter and dark energy. We propose a new way to search for a variation of the fine-structure constant using measurements of late-type evolved giant stars from the S star cluster orbiting the supermassive black hole in our Galactic Center. A measurement of the difference between distinct absorption lines (with different sensitivity to the fine structure constant) from a star leads to a direct estimate of a variation of the fine structure constant between the star's location and Earth. Using spectroscopic measurements of five stars, we obtain a constraint on the relative variation of the fine structure constant below 10^{-5}. This is the first time a varying constant of nature is searched for around a black hole and in a high gravitational potential. This analysis shows new ways the monitoring of stars in the Galactic Center can be used to probe fundamental physics.

Large Variation of Dirac Semimetal State in Perovskite CaIrO_{3} with Pressure-Tuning of Electron Correlation.

The impact of electron correlation on the Dirac semimetal state is investigated for perovskite CaIrO_{3} in terms of the magnetotransport properties under varying pressures. The reduction of electron correlation with a pressure of 1 GPa enhances the Fermi velocity as much as 40%, but it reduces the mobility by an order of magnitude by detuning the Dirac node from the Fermi energy. Moreover, the giant magnetoresistance at the quantum limit due to the one-dimensional confinement of Dirac electrons is critically suppressed under pressure. These results indicate that the electron correlation is a crucial knob for controlling the transport of a correlated Dirac semimetal.

Lactobacillus delbrueckii ssp. bulgaricus OLL1073R-1 feeding enhances humoral immune responses, which are suppressed by the antiviral neuraminidase inhibitor oseltamivir in influenza A virus-infected mice.

Antiviral neuraminidase inhibitors, such as oseltamivir, zanamivir, and peramivir, are widely used for treatment of influenza virus infection. We reported previously that oseltamivir inhibits the viral growth cycle, ameliorates symptoms, and reduces viral antigen quantities. Suppressed viral antigen production, however, induces a reduction of acquired antiviral humoral immunity, and increases the incidence of re-infection rate in the following year. To achieve effective treatment of influenza virus infection, it is necessary to overcome these adverse effects of antiviral neuraminidase inhibitors. Feeding of yogurt fermented with Lactobacillus delbrueckii ssp. bulgaricus (L. bulgaricus) OLL1073R-1 is reported to have immune-stimulatory effects on influenza virus infection in mice and humans. In the present study, we assessed the effect of feeding L. bulgaricus OLL1073R-1 yogurt cultures (YC) on local and systemic humoral immune responses, which were suppressed by oseltamivir treatment, in mice infected with influenza A virus. Yogurt culture (1.14 × 108 cfu/0.4 mL per mouse per day) or sterile water (vehicle) was administered by intragastric gavage for 35 d. At d 22, influenza A virus/Puerto Rico/8/34 (H1N1) (PR8; 0.5 pfu/15 µL per mouse) was instilled intranasally, followed immediately by oral administration of oseltamivir (50 µg/100 µL per mouse, twice daily) or 5% methylcellulose (100 µL/mouse) as a vehicle for 13 d. Titers of anti-PR8-specific IgG and IgA in serum and mucosal secretory IgA (S-IgA) and IgG in bronchoalveolar lavage fluid (BALF) were analyzed by ELISA at 14 d after infection. Oseltamivir significantly suppressed the induction of anti-PR8-specific IgG and IgA in serum and S-IgA and IgG in BALF after infection. Feeding YC mildly but significantly stimulated production of PR8-specific IgA in serum, S-IgA in BALF, and IgG in serum without changing the IgG2a:IgG1 ratio. We analyzed the neutralizing activities against PR8 in serum and BALF and found that oseltamivir also reduced protective immunity, and YC feeding abrogated this effect. The immune-stimulatory tendency of YC on anti-PR8-specific IgA and IgG titers in serum and BALF was also detected in mice re-infected with PR8, but the effect was insignificant, unlike the effect of YC in the initial infection.

Strong-correlation induced high-mobility electrons in Dirac semimetal of perovskite oxide.

Electrons in conventional metals become less mobile under the influence of electron correlation. Contrary to this empirical knowledge, we report here that electrons with the highest mobility ever found in known bulk oxide semiconductors emerge in the strong-correlation regime of the Dirac semimetal of perovskite CaIrO3. The transport measurements reveal that the high mobility exceeding 60,000 cm2V-1s-1 originates from the proximity of the Fermi energy to the Dirac node (ΔE < 10 meV). The calculation based on the density functional theory and the dynamical mean field theory reveals that the energy difference becomes smaller as the system approaches the Mott transition, highlighting a crucial role of correlation effects cooperating with the spin-orbit coupling. The correlation-induced self-tuning of Dirac node enables the quantum limit at a modest magnetic field with a giant magnetoresistance, thus providing an ideal platform to study the novel phenomena of correlated Dirac electron.

Effects of resistance training on arterial compliance and plasma endothelin-1 levels in healthy men.

Arterial compliance (AC) is an index of the elasticity of large arteries. Endothelial dysfunction has been reported to result in reduced arterial compliance, which represents increased arterial stiffness. A reduction in AC is elicited by high-intensity resistance training, however the mechanisms are obscure. Because a single bout of resistance exercise causes a transient increase in circulating plasma endothelin-1 in humans, some vasoconstrictors may play a role in the mechanisms. The present study aimed to investigate whether resistance training-induced decrease in AC is associated with changes in circulating vasoconstrictors levels in young men. Young sedentary men were assigned to control (n=5) or training (n=9) groups. The training group performed four-week high-intensity resistance training (weight training exercise; three sessions/week). We measured AC and plasma levels of endothelin-1, angiotensin II, and norepinephrine before and after intervention. Resistance training significantly decreased AC, whereas the changes in plasma levels of neither endothelin-1, nor angiotensin II, nor norepinephrine were significantly different between the control and the training groups. Moreover, we found no significant correlations between changes in circulating plasma levels (endothelin-1, angiotensin II, and norepinephrine) and in the AC. Despite of no alteration of the resting circulating plasma levels (endothelin-1, etc.), we cannot exclude a possibility that the tissue/local concentrations of vasoconstrictors (endothelin-1, etc.) around the vessels might be increased and also involved in a reduction of AC in the training group. Taken together, the present results suggest that circulating vasoconstrictors (endothelin-1, etc.) in plasma are not involved in a reduction in AC by the resistance training.

The glucagon-like peptide-1 receptor agonist liraglutide improves hypoxia-induced pulmonary hypertension in mice partly via normalization of reduced ET(B) receptor expression.

The glucagon-like peptide-1 receptor (GLP-1R) agonist liraglutide is an incretin hormone mimetic used in the treatment of diabetes. However, the effects of liraglutide on pulmonary hypertension (PH) and pulmonary endothelin (ET) system are unknown. Eight-week-old C57BL6/J mice were injected liraglutide or vehicle for 5 weeks. One week after injection, the mice were exposed to either room air (normoxia) or chronic hypoxia (10 % O(2)) for 4 weeks. The right ventricular systolic pressure (RVSP) was significantly higher in hypoxia + vehicle group than in normoxia + vehicle group. ET-1 mRNA expression in the lungs was comparable among all the groups. ET(B) mRNA and protein expression in the lungs was significantly lower in hypoxia + vehicle group than in normoxia + vehicle group. The above changes were normalized by liraglutide treatment. The expression of phospho-eNOS and phospho-AMPK proteins in the lungs was significantly higher in hypoxia + liraglutide group than in normoxia + vehicle group. We demonstrated for the first time that liraglutide effectively improved RVSP and RV hypertrophy in hypoxia-induced PH mice by activating eNOS through normalization of impaired ET(B) pathway and augmentation of AMPK pathway. Therefore, GLP-1R agonists can be promising therapeutic agents for PH.

Relationship of hyaluronan and HYBID (KIAA1199) expression with roughness parameters of photoaged skin in Caucasian women.

BACKGROUND: Hyaluronan (HA) is an important constituent of extracellular matrix (ECM) in the skin, and HA degradation mediated by HYBID (KIAA1199) is suggested to be implicated in facial skin wrinkling in Japanese women. Ethnic difference in skin wrinkle formation is known between Caucasian and Japanese women, but no information is available for the relations of HA and HYBID expression levels with skin wrinkling in Caucasian women. METHODS: The skin surface roughness at the eye corner of the Caucasian female subjects was measured, and the skin specimens biopsied from the same areas were subjected to microarray gene analysis, HA staining, and immunohistochemistry for HYBID. RESULTS: Among the ECM genes and those related to ECM metabolism, only HYBID expression levels positively correlated with the skin roughness parameters. When the skin sample groups with high expression of HYBID or low expression of HYBID were compared, the HA staining intensity and the ratio of HYBID-immunoreactive cells to total cells in the superficial dermis were significantly reduced and increased in the high-HYBID-expression group compared with the low-HYBID-expression group, respectively. CONCLUSION: Our data suggest that like Japanese women, HYBID-mediated reduction of HA in the superficial dermis is involved in the formation of wrinkles in Caucasian women.

Defective positioning in granulomas but not lung-homing limits CD4 T-cell interactions with Mycobacterium tuberculosis-infected macrophages in rhesus macaques.

Protection against Mycobacterium tuberculosis (Mtb) infection requires CD4 T cells to migrate into the lung and interact with infected macrophages. In mice, less-differentiated CXCR3+ CD4 T cells migrate into the lung and suppress growth of Mtb, whereas CX3CR1+ terminally differentiated Th1 cells accumulate in the blood vasculature and do not control pulmonary infection. Here we examine CD4 T-cell differentiation and lung homing during primary Mtb infection of rhesus macaques. Mtb-specific CD4 T cells simultaneously appeared in the airways and blood ∼21-28 days post exposure, indicating that recently primed effectors are quickly recruited into the lungs after entering circulation. Mtb-specific CD4 T cells in granulomas display a tissue-parenchymal CXCR3+CX3CR1-PD-1hiCTLA-4+ phenotype. However, most granuloma CD4 T cells are found within the outer lymphocyte cuff and few localize to the myeloid cell core containing the bacilli. Using the intravascular stain approach, we find essentially all Mtb-specific CD4 T cells in granulomas have extravasated across the vascular endothelium into the parenchyma. Therefore, it is unlikely to be that lung-homing defects introduced by terminal differentiation limit the migration of CD4 T cells into granulomas following primary Mtb infection of macaques. However, intralesional positioning defects within the granuloma may pose a major barrier to T-cell-mediated immunity during tuberculosis.

RNA-binding motif protein 47 inhibits Nrf2 activity to suppress tumor growth in lung adenocarcinoma.

This corrects the article DOI: 10.1038/onc.2016.35.

Testing General Relativity with Stellar Orbits around the Supermassive Black Hole in Our Galactic Center.

We demonstrate that short-period stars orbiting around the supermassive black hole in our Galactic center can successfully be used to probe the gravitational theory in a strong regime. We use 19 years of observations of the two best measured short-period stars orbiting our Galactic center to constrain a hypothetical fifth force that arises in various scenarios motivated by the development of a unification theory or in some models of dark matter and dark energy. No deviation from general relativity is reported and the fifth force strength is restricted to an upper 95% confidence limit of |α|<0.016 at a length scale of λ=150 astronomical units. We also derive a 95% confidence upper limit on a linear drift of the argument of periastron of the short-period star S0-2 of |ω[over ˙]_{S0-2}|<1.6×10^{-3} rad/yr, which can be used to constrain various gravitational and astrophysical theories. This analysis provides the first fully self-consistent test of the gravitational theory using orbital dynamic in a strong gravitational regime, that of a supermassive black hole. A sensitivity analysis for future measurements is also presented.

Von Willebrand Factor Deposition and ADAMTS-13 Consumption in Allograft Tissue of Thrombotic Microangiopathy-like Disorder After Living Donor Liver Transplantation: A Case Report.

BACKGROUND: Thrombotic microangiopathy (TMA) pathogenesis after living donor liver transplantation (LDLT) is thought to be caused by release of unusually large von Willebrand factor multimers (UL-vWFMs) resulting from sinusoidal endothelial cell damage and induction of platelet adhesion and aggregation. A decrease in a disintegrin-like and metalloproteinase with thrombospondin type 1 motifs-13 (ADAMTS-13) that cleave UL-vWFMs might cause excessive UL-vWFMs activity and result in platelet thrombus formation. However, this phenomenon has not undergone a full pathologic assessment. PROCEDURES: A 60-year-old man was diagnosed with hepatitis C-related end-stage cirrhosis. His son was the donor, and he underwent LDLT. On postoperative day 44, his laboratory findings met most TMA diagnostic criteria, and he was diagnosed with TMA-like disorder (TMALD). Localization of CD42b as a platelet marker, vWF, and ADAMTS-13 in allograft tissue of this patient were evaluated using immunohistochemistry. RESULTS: CD42b expression was observed as platelet aggregates attached to hepatocytes or within the hepatocyte cytoplasm, a morphology called extravasated platelet aggregation (EPA). vWF expression was observed mainly as deposited compact clusters, and ADAMTS-13 expression resembled distinct dots throughout the liver tissue. CONCLUSION: These findings suggest that EPA indicated sinusoidal endothelial cell damage followed by detachment, and vWF deposition resulted from UL-vWFM oversynthesis. ADAMTS-13 might be consumed in the allograft tissue to cleave UL-vWFMs, but ADAMTS-13 levels might be insufficient to cleave all the deposited UL-vWFMs. We present the case of an LDLT recipient diagnosed with TMALD using blood tests, which showed the presence of TMA pathogenesis in the allograft.

Bone morphogenetic protein signaling mediated by ALK-2 and DLX2 regulates apoptosis in glioma-initiating cells.

Bone morphogenetic protein (BMP) signaling exerts antitumor activities in glioblastoma; however, its precise mechanisms remain to be elucidated. Here, we demonstrated that the BMP type I receptor ALK-2 (encoded by the ACVR1 gene) has crucial roles in apoptosis induction of patient-derived glioma-initiating cells (GICs), TGS-01 and TGS-04. We also characterized a BMP target gene, Distal-less homeobox 2 (DLX2), and found that DLX2 promoted apoptosis and neural differentiation of GICs. The tumor-suppressive effects of ALK-2 and DLX2 were further confirmed in a mouse orthotopic transplantation model. Interestingly, valproic acid (VPA), an anti-epileptic compound, induced BMP2, BMP4, ACVR1 and DLX2 mRNA expression with a concomitant increase in phosphorylation of Smad1/5. Consistently, we showed that treatment with VPA induced apoptosis of GICs, whereas silencing of ALK-2 or DLX2 expression partially suppressed it. Our study thus reveals BMP-mediated inhibitory mechanisms for glioblastoma, which explains, at least in part, the therapeutic effects of VPA.