Joint Metabonomic and Instrumental Analysis for the Classification of Migraine Patients with 677-MTHFR Mutations

Migraine is a neurological disorder that correlates with an increased risk of cerebrovascular lesions. Genetic mutations of the MTHFR gene are correlated to migraine and to the increased risk of artery pathologies. Also, migraine patients show altered hematochemical parameters, linked to an impaired platelet aggregation mechanism. Hence, the vascular assessment of migraineurs is of primary importance

In vitro anticancer effects of a RAGE inhibitor discovered using a structure-based drug design system.

金沢大学医薬保健研究域医学系Receptor for advanced glycation end-products (RAGE) is a pattern recognition receptor implicated in the pathogenesis of certain types of cancer. In the present study, papaverine was identified as a RAGE inhibitor using the conversion to small molecules through optimized‑peptide strategy drug design system. Papaverine significantly inhibited RAGE‑dependent nuclear factor κ‑B activation driven by high mobility group box‑1, a RAGE ligand. Using RAGE‑ or dominant‑negative RAGE‑expressing HT1080 human fibrosarcoma cells, the present study revealed that papaverine suppressed RAGE‑dependent cell proliferation and migration dose‑dependently. Furthermore, papaverine significantly inhibited cell invasion. The results of the present study suggested that papaverine could inhibit RAGE, and provided novel insights into the field of RAGE biology, particularly anticancer therapies.Embargo Period 6 month

Precision Measurement of Cosmic-Ray Nitrogen and its Primary and Secondary Components with the Alpha Magnetic Spectrometer on the International Space Station

A precision measurement of the nitrogen flux with rigidity (momentum per unit charge) from 2.2 GV to 3.3 TV based on 2.2 x 10(6) events is presented. The detailed rigidity dependence of the nitrogen flux spectral index is presented for the first time. The spectral index rapidly hardens at high rigidities and becomes identical to the spectral indices of primary He, C, and O cosmic rays above similar to 700 GV. We observed that the nitrogen flux Phi(N) can be presented as the sum of its primary component Phi(P)(N) and secondary component Phi(S)(N), Phi(N) = Phi(P)(N) + Phi(S)(N), and we found Phi(N) is well described by the weighted sum of the oxygen flux Phi(O) (primary cosmic rays) and the boron flux Phi(B) (secondary cosmic rays), with Phi(P)(N) = (0.090 +/- 0.002) x Phi(O) and Phi(S)(N) = (0.62 +/- 0.02) x Phi(B) over the entire rigidity range. This corresponds to a change of the contribution of the secondary cosmic ray component in the nitrogen flux from 70% at a few GV to < 30% above 1 TV

Observation of Fine Time Structures in the Cosmic Proton and Helium Fluxes with the Alpha Magnetic Spectrometer on the International Space Station

We present the precision measurement from May 2011 to May 2017 (79 Bartels rotations) of the proton fluxes at rigidities from 1 to 60 GV and the helium fluxes from 1.9 to 60 GV based on a total of 1 x 109 events collected with the Alpha Magnetic Spectrometer aboard the International Space Station. This measurement is in solar cycle 24, which has the solar maximum in April 2014. We observed that, below 40 GV, the proton flux and the helium flux show nearly identical fine structures in both time and relative amplitude. The amplitudes of the flux structures decrease with increasing rigidity and vanish above 40 GV. The amplitudes of the structures are reduced during the time period, which started one year after solar maximum, when the proton and helium fluxes steadily increase. Above similar to 3 GV the p/He flux ratio is time independent. We observed that below similar to 3 GV the ratio has a long-term decrease coinciding with the period during which the fluxes start to rise

Observation of New Properties of Secondary Cosmic Rays Lithium, Beryllium, and Boron by the Alpha Magnetic Spectrometer on the International Space Station

We report on the observation of new properties of secondary cosmic rays Li, Be, and B measured in the rigidity (momentum per unit charge) range 1.9 GV to 3.3 TV with a total of 5.4 x 10(6) nuclei collected by AMS during the first five years of operation aboard the International Space Station. The Li and B fluxes have an identical rigidity dependence above 7 GV and all three fluxes have an identical rigidity dependence above 30 GV with the Li/Be flux ratio of 2.0 +/- 0.1. The three fluxes deviate from a single power law above 200 GV in an identical way. This behavior of secondary cosmic rays has also been observed in the AMS measurement of primary cosmic rays He, C, and O but the rigidity dependences of primary cosmic rays and of secondary cosmic rays are distinctly different. In particular, above 200 GV, the secondary cosmic rays harden more than the primary cosmic rays

Observation of the Identical Rigidity Dependence of He, C, and O Cosmic Rays at High Rigidities by the Alpha Magnetic Spectrometer on the International Space Station

We report the observation of new properties of primary cosmic rays He, C, and O measured in the rigidity (momentum/charge) range 2 GV to 3 TV with 90 x 10(6) helium, 8.4 x 10(6) carbon, and 7.0 x 10(6) oxygen nuclei collected by the Alpha Magnetic Spectrometer ( AMS) during the first five years of operation. Above 60 GV, these three spectra have identical rigidity dependence. They all deviate from a single power law above 200 GV and harden in an identical way

Antiproton Flux, Antiproton-to-Proton Flux Ratio, and Properties of Elementary Particle Fluxes in Primary Cosmic Rays Measured with the Alpha Magnetic Spectrometer on the International Space Station

A precision measurement by AMS of the antiproton flux and the antiproton-to-proton flux ratio in primary cosmic rays in the absolute rigidity range from 1 to 450 GV is presented based on 3.49 x 10(5) antiproton events and 2.42 x 10(9) proton events. The fluxes and flux ratios of charged elementary particles in cosmic rays are also presented. In the absolute rigidity range similar to 60 to similar to 500 GV, the antiproton (p) over bar, proton p, and positron e(+) fluxes are found to have nearly identical rigidity dependence and the electron e(-) flux exhibits a different rigidity dependence. Below 60 GV, the ((p) over bar /p), ((p) over bar /e(+)), and (p/e(+)) flux ratios each reaches a maximum. From similar to 60 to similar to 500 GV, the ((p) over bar /p), ((p) over bar /e(+)), and (p/e(+)) flux ratios show no rigidity dependence. These are new observations of the properties of elementary particles in the cosmos

Precision Measurement of the Helium Flux in Primary Cosmic Rays of Rigidities 1.9 GV to 3 TV with the Alpha Magnetic Spectrometer on the International Space Station

Knowledge of the precise rigidity dependence of the helium flux is important in understanding the origin, acceleration, and propagation of cosmic rays. A precise measurement of the helium flux in primary cosmic rays with rigidity (momentum/charge) from 1.9 GV to 3 TV based on 50 million events is presented and compared to the proton flux. The detailed variation with rigidity of the helium flux spectral index is presented for the first time. The spectral index progressively hardens at rigidities larger than 100 GV. The rigidity dependence of the helium flux spectral index is similar to that of the proton spectral index though the magnitudes are different. Remarkably, the spectral index of the proton to helium flux ratio increases with rigidity up to 45 GV and then becomes constant; the flux ratio above 45 GV is well described by a single power law.</p

Inferring specifications to detect errors in code

Abstract. A new technique is presented to statically check a given procedure against a user-provided property. The method requires no annotations; it automatically infers a context-dependent specification for each procedure call, so that only as much information about a procedure is used as is needed to analyze its caller. Specifications are inferred iteratively. Empty specifications are initially used to overapproximate the effects of all procedure calls; these are later refined in response to spurious counterexamples. When the analysis terminates, any remaining counterexample is guaranteed to be valid. However, since the heap is finitized, the absence of a counterexample does not guarantee the validity of the given property. 1

Genetic analysis of body weight in wild populations of medaka fish from different latitudes.

The genetic bases of growth and body weight are of economic and scientific interest, and teleost fish models have proven useful in such investigations. The Oryzias latipes species complex (medaka) is an abundant freshwater fish in Japan and suitable for genetic studies. We compared two wild medaka stocks originating from different latitudes. The Maizuru population from higher latitudes weighed more than the Ginoza population. We investigated the genetic basis of body weight, using quantitative trait locus (QTL) analysis of the F2 offspring of these populations. We detected one statistically significant QTL for body weight on medaka chromosome 4 and identified 12 candidate genes that might be associated with body weight or growth. Nine of these 12 genes had at least one single nucleotide polymorphism that caused amino acid substitutions in protein-coding regions, and we estimated the effects of these substitutions. The present findings might contribute to the marker-assisted selection of economically important aquaculture species