Development of miracle medicines from sialic acids

Sialic acids are electronegatively charged C9-sugars and are considered to play important roles in higher animals and some microorganisms. Denoting their significance, understanding and exploiting the complexity of the sialic acids has been referred to as the “the third language of life”. In essence, “sialic acid derivatives possess a harmonious shape and good balance between two opposing hydrophilic and hydrophobic parts, meaning that they should display various kinds of potentially unique and possibly conflicting physiological activities (glycolipoids)”. Consequently, there are good omens that unprecedented ‘miracle’ medicines could be developed from sialic acid derivatives. In this review, the first problem, the preparation of sialic acids, is covered, the synthesis of sialic acid derivatives and confirmation of their structures obviously being of critical significance. In addition we needed to confirm their precise stereochemistry and a hydrolysis method has been developed for confirmation of the anomeric position. Several of the compounds have already demonstrated interesting bioactivity

EFHC1 variants in juvenile myoclonic epilepsy: reanalysis according to NHGRI and ACMG guidelines for assigning disease causality

Peer reviewe

Search for Anisotropy of Ultra-High Energy Cosmic Rays with the Telescope Array Experiment

We study the anisotropy of Ultra-High Energy Cosmic Ray (UHECR) events collected by the Telescope Array (TA) detector in the first 40 months of operation. Following earlier studies, we examine event sets with energy thresholds of 10 EeV, 40 EeV, and 57 EeV. We find that the distributions of the events in right ascension and declination are compatible with an isotropic distribution in all three sets. We then compare with previously reported clustering of the UHECR events at small angular scales. No significant clustering is found in the TA data. We then check the events with E>57 EeV for correlations with nearby active galactic nuclei. No significant correlation is found. Finally, we examine all three sets for correlations with the large-scale structure of the Universe. We find that the two higher-energy sets are compatible with both an isotropic distribution and the hypothesis that UHECR sources follow the matter distribution of the Universe (the LSS hypothesis), while the event set with E>10 EeV is compatible with isotropy and is not compatible with the LSS hypothesis at 95% CL unless large deflection angles are also assumed. We show that accounting for UHECR deflections in a realistic model of the Galactic magnetic field can make this set compatible with the LSS hypothesis.Comment: 10 pages, 9 figure

Critical Exponents, Hyperscaling and Universal Amplitude Ratios for Two- and Three-Dimensional Self-Avoiding Walks

We make a high-precision Monte Carlo study of two- and three-dimensional self-avoiding walks (SAWs) of length up to 80000 steps, using the pivot algorithm and the Karp-Luby algorithm. We study the critical exponents $\nu$ and $2\Delta_4 -\gamma$ as well as several universal amplitude ratios; in particular, we make an extremely sensitive test of the hyperscaling relation $d\nu = 2\Delta_4 -\gamma$. In two dimensions, we confirm the predicted exponent $\nu = 3/4$ and the hyperscaling relation; we estimate the universal ratios $\ / \ = 0.14026 \pm 0.00007$, $\ / \ = 0.43961 \pm 0.00034$ and $\Psi^* = 0.66296 \pm 0.00043$ (68\% confidence limits). In three dimensions, we estimate $\nu = 0.5877 \pm 0.0006$ with a correction-to-scaling exponent $\Delta_1 = 0.56 \pm 0.03$ (subjective 68\% confidence limits). This value for $\nu$ agrees excellently with the field-theoretic renormalization-group prediction, but there is some discrepancy for $\Delta_1$. Earlier Monte Carlo estimates of $\nu$, which were $\approx\! 0.592$, are now seen to be biased by corrections to scaling. We estimate the universal ratios $\ / \ = 0.1599 \pm 0.0002$ and $\Psi^* = 0.2471 \pm 0.0003$; since $\Psi^* > 0$, hyperscaling holds. The approach to $\Psi^*$ is from above, contrary to the prediction of the two-parameter renormalization-group theory. We critically reexamine this theory, and explain where the error lies.Comment: 87 pages including 12 figures, 1029558 bytes Postscript (NYU-TH-94/09/01

The 2L1S/1L2S Degeneracy for Two Microlensing Planet Candidates Discovered by the KMTNet Survey in 2017

We report two microlensing planet candidates discovered by the KMTNet survey in $2017$. However, both events have the 2L1S/1L2S degeneracy, which is an obstacle to claiming the discovery of the planets with certainty unless the degeneracy can be resolved. For KMT-2017-BLG-0962, the degeneracy cannot be resolved. If the 2L1S solution is correct, KMT-2017-BLG-0962 might be produced by a super Jupiter-mass planet orbiting a mid-M dwarf host star. For KMT-2017-BLG-1119, the light curve modeling favors the 2L1S solution but higher-resolution observations of the baseline object tend to support the 1L2S interpretation rather than the planetary interpretation. This degeneracy might be resolved by a future measurement of the lens-source relative proper motion. This study shows the problem of resolving 2L1S/1L2S degeneracy exists over a much wider range of conditions than those considered by the theoretical study of Gaudi (1998).Comment: 15 pages, 12 figures, 4 tables, accepted in A

OGLE-2015-BLG-1649Lb:A gas giant planet around a low-mass dwarf

We report the discovery of an exoplanet from the analysis of the gravitational microlensing event OGLE-2015-BLG-1649 that challenges the core accretion model of planet formation and appears to support the disk instability model. The planet/host-star mass ratio is q = 7.2 × 10−3 and the projected separation normalized to the angular Einstein radius is s = 0.9. We conducted high-resolution follow-up observations using the Infrared Camera and Spectrograph (IRCS) camera on the Subaru telescope and are able to place an upper limit on the lens flux. From these measurements we are able to exclude all host stars greater than or equal in mass to a G-type dwarf. We conducted a Bayesian analysis with these new flux constraints included as priors resulting in estimates of the masses of the host star and planet. These are M L = 0.34 ± 0.19 M ⊙ and M p =2.5+1.5 -1.4 M jup, respectively. The distance to the system is D L = 4.23 +1.51-1.64 kpc. The projected star–planet separation is a ⊥ = 2.07+0.65-0.77 au. The estimated relative lens-source proper motion, ~7.1 mas yr−1, is fairly high and thus the lens can be better constrained if additional follow-up observations are conducted several years after the event.PostprintPeer reviewe

MEK–ERK-dependent multiple caspase activation by mitochondrial proapoptotic Bcl-2 family proteins is essential for heavy ion irradiation-induced glioma cell death

Recently developed heavy ion irradiation therapy using a carbon beam (CB) against systemic malignancy has numerous advantages. However, the clinical results of CB therapy against glioblastoma still have room for improvement. Therefore, we tried to clarify the molecular mechanism of CB-induced glioma cell death. T98G and U251 human glioblastoma cell lines were irradiated by CB, and caspase-dependent apoptosis was induced in both cell lines in a dose-dependent manner. Knockdown of Bax (BCL-2-associated X protein) and Bak (BCL-2-associated killer) and overexpression of Bcl-2 or Bcl-xl (B-cell lymphoma-extra large) showed the involvement of Bcl-2 family proteins upstream of caspase activation, including caspase-8, in CB-induced glioma cell death. We also detected the activation of extracellular signal-regulated kinase (ERK) and the knockdown of ERK regulator mitogen-activated protein kinase kinase (MEK)1/2 or overexpression of a dominant-negative (DN) ERK inhibited CB-induced glioma cell death upstream of the mitochondria. In addition, application of MEK-specific inhibitors for defined periods showed that the recovery of activation of ERK between 2 and 36 h after irradiation is essential for CB-induced glioma cell death. Furthermore, MEK inhibitors or overexpression of a DN ERK failed to significantly inhibit X-ray-induced T98G and U251 cell death. These results suggested that the MEK–ERK cascade has a crucial role in CB-induced glioma cell death, which is known to have a limited contribution to X-ray-induced glioma cell death

DECIGO pathfinder

DECIGO pathfinder (DPF) is a milestone satellite mission for DECIGO (DECi-hertz Interferometer Gravitational wave Observatory), which is a future space gravitational wave antenna. DECIGO is expected to provide fruitful insights into the universe, particularly about dark energy, the formation mechanism of supermassive black holes and the inflation of the universe. Since DECIGO will be an extremely challenging mission, which will be formed by three drag-free spacecraft with 1000 km separation, it is important to increase the technical feasibility of DECIGO before its planned launch in 2024. Thus, we are planning to launch two milestone missions: DPF and pre-DECIGO. In this paper, we review the conceptual design and current status of the first milestone mission, DPF