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30 Doradus C is a superbubble which emits the brightest nonthermal X- and TeV gamma-rays in the Local Group. In order to explore detailed connection between the high energy radiation and the interstellar medium, we have carried out new CO and HI observations using the Atacama Large Millimeter$/$Submillimeter Array (ALMA), Atacama Submillimeter Telescope Experiment, and the Australia Telescope Compact Array with resolutions of up to 3 pc. The ALMA data of $^{12}$CO($J$ = 1-0) emission revealed 23 molecular clouds with the typical diameters of $\sim$6-12 pc and masses of $\sim$600-10000 $M_{\odot}$. The comparison with the X-rays of $XMM$-$Newton$ at $\sim$3 pc resolution shows that X-rays are enhanced toward these clouds. The CO data were combined with the HI to estimate the total interstellar protons. Comparison of the interstellar proton column density and the X-rays revealed that the X-rays are enhanced with the total proton. These are most likely due to the shock-cloud interaction modeled by the magnetohydrodynamical simulations (Inoue et al. 2012, ApJ, 744, 71). Further, we note a trend that the X-ray photon index varies with distance from the center of the high-mass star cluster, suggesting that the cosmic-ray electrons are accelerated by one or multiple supernovae in the cluster. Based on these results we discuss the role of the interstellar medium in cosmic-ray particle acceleration., Comment: 20 pages, 14 figures, 3 tables, accepted for publication in The Astrophysical Journal

30 Doradus C is a superbubble which emits the brightest nonthermal X- and TeV gamma-rays in the Local Group. In order to explore detailed connection between the high energy radiation and the interstellar medium, we have carried out new CO and HI observations using the Atacama Large Millimeter$/$Submillimeter Array (ALMA), Atacama Submillimeter Telescope Experiment, and the Australia Telescope Compact Array with resolutions of up to 3 pc. The ALMA data of $^{12}$CO($J$ = 1-0) emission revealed 23 molecular clouds with the typical diameters of $\sim$6-12 pc and masses of $\sim$600-10000 $M_{\odot}$. The comparison with the X-rays of $XMM$-$Newton$ at $\sim$3 pc resolution shows that X-rays are enhanced toward these clouds. The CO data were combined with the HI to estimate the total interstellar protons. Comparison of the interstellar proton column density and the X-rays revealed that the X-rays are enhanced with the total proton. These are most likely due to the shock-cloud interaction modeled by the magnetohydrodynamical simulations (Inoue et al. 2012, ApJ, 744, 71). Further, we note a trend that the X-ray photon index varies with distance from the center of the high-mass star cluster, suggesting that the cosmic-ray electrons are accelerated by one or multiple supernovae in the cluster. Based on these results we discuss the role of the interstellar medium in cosmic-ray particle acceleration., Comment: 20 pages, 14 figures, 3 tables, accepted for publication in The Astrophysical Journal

Karyotype is an important prognostic factor in childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL), but the underlying pharmacogenomics remain unknown. Asparaginase is an integral component in current chemotherapy for childhood BCP-ALL. Asparaginase therapy depletes serum asparagine. Normal hematopoietic cells can produce asparagine by asparagine synthetase (ASNS) activity, but ALL cells are unable to synthesize adequate amounts of asparagine. The ASNS gene has a typical CpG island in its promoter. Thus, methylation of the ASNS CpG island could be one of the epigenetic mechanisms for ASNS gene silencing in BCP-ALL. To gain deep insights into the pharmacogenomics of asparaginase therapy, we investigated the association of ASNS methylation status with asparaginase sensitivity. The ASNS CpG island is largely unmethylated in normal hematopoietic cells, but it is allele-specifically methylated in BCP-ALL cells. The ASNS gene is located at 7q21, an evolutionally conserved imprinted gene cluster. ASNS methylation in childhood BCP-ALL is associated with an aberrant methylation of the imprinted gene cluster at 7q21. Aberrant methylation of mouse Asns and a syntenic imprinted gene cluster is also confirmed in leukemic spleen samples from ETV6-RUNX1 knockin mice. In 3 childhood BCP-ALL cohorts, ASNS is highly methylated in BCP-ALL patients with favorable karyotypes but is mostly unmethylated in BCP-ALL patients with poor prognostic karyotypes. Higher ASNS methylation is associated with higher L-asparaginase sensitivity in BCP-ALL through lower ASNS gene and protein expression levels. These observations demonstrate that silencing of the ASNS gene as a result of aberrant imprinting is a pharmacogenetic mechanism for the leukemia-specific activity of asparaginase therapy in BCP-ALL.

We carried out $^{12}$CO($J$ = 1-0) observations of the Galactic gamma-ray supernova remnant (SNR) Kesteven 79 using the Nobeyama Radio Observatory 45 m radio telescope, which has an angular resolution of $\sim20$ arcsec. We identified molecular and atomic gas interacting with Kesteven 79 whose radial velocity is $\sim80$ km s$^{-1}$. The interacting molecular and atomic gases show good spatial correspondence with the X-ray and radio shells, which have an expanding motion with an expanding velocity of $\sim4$ km s$^{-1}$. The molecular gas associated with the radio and X-ray peaks also exhibits a high-intensity ratio of CO 3-2/1-0 $>$ 0.8, suggesting a kinematic temperature of $\sim24$ K, owing to heating by the supernova shock. We determined the kinematic distance to the SNR to be $\sim5.5$ kpc and the radius of the SNR to be $\sim8$ pc. The average interstellar proton density inside of the SNR is $\sim360$ cm$^{-3}$, of which atomic protons comprise only $\sim10$ $\%$. Assuming a hadronic origin for the gamma-ray emission, the total cosmic-ray proton energy above 1 GeV is estimated to be $\sim5 \times 10^{48}$ erg., Comment: 12 pages, 6 figures, 2 tables, accepted for publication in The Astrophysical Journal (ApJ)

We analyzed the 2.6-mm CO and 21-cm HI lines toward the Magellanic superbubble 30 Doradus C, in order to reveal the associated molecular and atomic gas. We uncovered five molecular clouds in a velocity range from 251 to 276 km s$^{-1}$ toward the western shell. The non-thermal X-rays are clearly enhanced around the molecular clouds on a pc scale, suggesting possible evidence for magnetic field amplification via shock-cloud interaction. The thermal X-rays are brighter in the eastern shell, where there are no dense molecular or atomic clouds, opposite to the western shell. The TeV $\gamma$-ray distribution may spatially match the total interstellar proton column density as well as the non-thermal X-rays. If the hadronic $\gamma$-ray is dominant, the total energy of the cosmic-ray protons is at least $\sim1.2 \times 10^{50}$ erg with the estimated mean interstellar proton density $\sim60$ cm$^{-3}$. In addition the $\gamma$-ray flux associated with the molecular cloud (e.g., MC3) could be detected and resolved by the Cherenkov Telescope Array (CTA). This should permit CTA to probe the diffusion of cosmic-rays into the associated dense ISM., Comment: 9 pages, 5 figures, 1 table, accepted for publication in The Astrophysical Journal (ApJ)

We carried out $^{12}$CO($J$ = 1-0) observations of the Galactic gamma-ray supernova remnant (SNR) Kesteven 79 using the Nobeyama Radio Observatory 45 m radio telescope, which has an angular resolution of $\sim20$ arcsec. We identified molecular and atomic gas interacting with Kesteven 79 whose radial velocity is $\sim80$ km s$^{-1}$. The interacting molecular and atomic gases show good spatial correspondence with the X-ray and radio shells, which have an expanding motion with an expanding velocity of $\sim4$ km s$^{-1}$. The molecular gas associated with the radio and X-ray peaks also exhibits a high-intensity ratio of CO 3-2/1-0 $>$ 0.8, suggesting a kinematic temperature of $\sim24$ K, owing to heating by the supernova shock. We determined the kinematic distance to the SNR to be $\sim5.5$ kpc and the radius of the SNR to be $\sim8$ pc. The average interstellar proton density inside of the SNR is $\sim360$ cm$^{-3}$, of which atomic protons comprise only $\sim10$ $\%$. Assuming a hadronic origin for the gamma-ray emission, the total cosmic-ray proton energy above 1 GeV is estimated to be $\sim5 \times 10^{48}$ erg., Comment: 12 pages, 6 figures, 2 tables, accepted for publication in The Astrophysical Journal (ApJ)

We analyzed the 2.6-mm CO and 21-cm HI lines toward the Magellanic superbubble 30 Doradus C, in order to reveal the associated molecular and atomic gas. We uncovered five molecular clouds in a velocity range from 251 to 276 km s$^{-1}$ toward the western shell. The non-thermal X-rays are clearly enhanced around the molecular clouds on a pc scale, suggesting possible evidence for magnetic field amplification via shock-cloud interaction. The thermal X-rays are brighter in the eastern shell, where there are no dense molecular or atomic clouds, opposite to the western shell. The TeV $\gamma$-ray distribution may spatially match the total interstellar proton column density as well as the non-thermal X-rays. If the hadronic $\gamma$-ray is dominant, the total energy of the cosmic-ray protons is at least $\sim1.2 \times 10^{50}$ erg with the estimated mean interstellar proton density $\sim60$ cm$^{-3}$. In addition the $\gamma$-ray flux associated with the molecular cloud (e.g., MC3) could be detected and resolved by the Cherenkov Telescope Array (CTA). This should permit CTA to probe the diffusion of cosmic-rays into the associated dense ISM., Comment: 9 pages, 5 figures, 1 table, accepted for publication in The Astrophysical Journal (ApJ)

Purpose: Although sympathetic reinnervation is accompanied by the improvement of exercise tolerability during several years after heart trans-plantation (HTx), little is known about parasympathetic reinnervation and its clinical impact. Methods: We enrolled 21 recipients (40 ± 16 years, 71% male) who had received successive cardiopulmonary exercise testing at 6 months, 1, and 2 years after HTx. They also received heart rate (HR) variability analy-ses at post-HTx 6 months, and Minnesota Living with Heart failure (HF) Questionnaire at post-HTx 6 months and 2 years. Results: Exercise parameters such as peak oxygen consumption or maximum load remained unchanged, whereas recovery parameters including HR recov-ery during 2 minutes and the delay of peak HR, both influened by parasym-pathetic activity, improved significantly during post-HTx 2 years (p<0.05 for both). Among 12 recipients who had also received HR variability analyses at 6 months after HTx, high frequency power, representing parasympathetic activity, was significantly associated with 2 recovery parameters (p<0.05 for all). Recipients with improved recovery parameters enjoyed a better HF-specific quality of life that was demonstrated by improved Minnesota Living with HF Questionnaire at post-HTx 2 years. Conclusion: Parasympathetic reinnervation emerges along with improved post-exercise recovery of HR and quality of life during post-HTx 2 years.

TBM jamming occurred frequently while driving the 4.2 km long S headrace tunnel, and the excavation was cancelled after 2.95 km. Primary site investigations based on uniaxial strength and seismic velocity tests had indicated that the ground was relatively hard slate and suitable for TBM excavation. A 2.8 m diameter double-shield type machine with 23 disc cutters was used. Seismic investigations and theoretical analyses carried out after tunnelling ended showed that the possibility of jamming was higher with increased tunnel cover, the TBM would be likely to jam if the cover was more than 360 m, and the loosened zone expanded to around 6-8 m where the jamming had occurred and squeezed more than expected., TBM jamming occurred frequently while driving the 4.2 km long S headrace tunnel, and the excavation was cancelled after 2.95 km. Primary site investigations based on uniaxial strength and seismic velocity tests had indicated that the ground was relatively hard slate and suitable for TBM excavation. A 2.8 m diameter double-shield type machine with 23 disc cutters was used. Seismic investigations and theoretical analyses carried out after tunnelling ended showed that the possibility of jamming was higher with increased tunnel cover, the TBM would be likely to jam if the cover was more than 360 m, and the loosened zone expanded to around 6-8 m where the jamming had occurred and squeezed more than expected.

A new kind of static rock splitter has been developed taking advantage of TiNi shape memory alloy which attains a maximum recovery force of about 600 MPa. The splitter consists of compressively prestrained TiNi rods and a pair of two-layered wedge type platens of steel, and requires no accessory equipment other than heating apparatus. To examine the performance of the splitter, theoretical analysis for crack initiation and laboratory tests using rocklike materials have been performed. The breaking time is much shorter than those of conventional breaking processes., A new kind of static rock splitter has been developed taking advantage of TiNi shape memory alloy which attains a maximum recovery force of about 600 MPa. The splitter consists of compressively prestrained TiNi rods and a pair of two-layered wedge type platens of steel, and requires no accessory equipment other than heating apparatus. To examine the performance of the splitter, theoretical analysis for crack initiation and laboratory tests using rocklike materials have been performed. The breaking time is much shorter than those of conventional breaking processes.

In a recently developed underground limestone mine the stress changes in the rock around the primary opening are being monitored by means of a pressure capsule. These stress changes were induced by excavation of the secondary openings above or below the primary opening. The floor displacements induced are also being measured by a special displacement meter coupling a laser beam and two solar batteries. Initial rock stress state and tangential stress state at the primary opening were measured using the double fracturing technique and stress compensation technique using lune-shaped flatjack, respectively. Furthermore, induced change of a pillar stress was predicted numerically. The paper outlines the excavation process, the measurement systems and the measured results which are compared with the predicted stress change with respect to excavation progress., In a recently developed underground limestone mine the stress changes in the rock around the primary opening are being monitored by means of a pressure capsule. These stress changes were induced by excavation of the secondary openings above or below the primary opening. The floor displacements induced are also being measured by a special displacement meter coupling a laser beam and two solar batteries. Initial rock stress state and tangential stress state at the primary opening were measured using the double fracturing technique and stress compensation technique using lune-shaped flatjack, respectively. Furthermore, induced change of a pillar stress was predicted numerically. The paper outlines the excavation process, the measurement systems and the measured results which are compared with the predicted stress change with respect to excavation progress.