Search

Purpose: Ionoacoustics is one of the promising approaches to verify the beam range in proton therapy. However, the weakness of the wave signal remains a main hindrance to its application in clinics. Here we studied the potential use of a fixed-field alternating gradient accelerator (FFA), one of the accelerator candidates for future proton therapy. For such end, magnitude of the pressure wave and range accuracy achieved by the short-pulsed beam of FFA were assessed, using both simulation and experimental procedure., Methods: A 100 MeV proton beam from the FFA was applied on a water phantom, through the acrylic wall. The beam range measured by the Bragg peak (BP)-ionization chamber (BPC) was 77.6 mm, while the maximum dose at BP was estimated to be 0.35 Gy/pulse. A hydrophone was placed 20 mm downstream of the BP, and signals were amplified and stored by a digital oscilloscope, averaged, and low-pass filtered. Time-of-flight (TOF) and two relative TOF values were analyzed in order to determine the beam range. Furthermore, an acoustic wave transport simulation was conducted to estimate the amplitude of the pressure waves., Results: The range calculated when using two relative TOF was 78.16 ± 0.01 and 78.14 ± 0.01 mm, respectively, both values being coherent with the range measured by the BPC (the difference was 0.5-0.6 mm). In contrast, utilizing the direct TOF resulted in a range error of 1.8 mm. Fivefold and 50-fold averaging were required to suppress the range variation to below 1 mm for TOF and relative TOF measures, respectively. The simulation suggested the magnitude of pressure wave at the detector exceeded 7 Pascal., Conclusion: A submillimeter range accuracy was attained with a pulsed beam of about 21 ns from an FFA, at a clinical energy using relative TOF. To precisely quantify the range with a single TOF measurement, subsequent improvement in the measuring system is required., (© 2021 American Association of Physicists in Medicine.)

Direct proton-knockout reactions of ^{55}Sc at ∼220  MeV/nucleon were studied at the RIKEN Radioactive Isotope Beam Factory. Populated states of ^{54}Ca were investigated through γ-ray and invariant-mass spectroscopy. Level energies were calculated from the nuclear shell model employing a phenomenological internucleon interaction. Theoretical cross sections to states were calculated from distorted-wave impulse approximation estimates multiplied by the shell model spectroscopic factors, which describe the wave function overlap of the ^{55}Sc ground state with states in ^{54}Ca. Despite the calculations showing a significant amplitude of excited neutron configurations in the ground-state of ^{55}Sc, valence proton removals populated predominantly the ground state of ^{54}Ca. This counterintuitive result is attributed to pairing effects leading to a dominance of the ground-state spectroscopic factor. Owing to the ubiquity of the pairing interaction, this argument should be generally applicable to direct knockout reactions from odd-even to even-even nuclei.

Mutations of the gene encoding the RET tyrosine kinase causes Hirschsprung's disease (HSCR) and medullary thyroid carcinoma (MTC). Current consensus holds that HSCR and MTC are induced by inactivating and activating RET mutations, respectively. However, it remains unknown whether activating mutations in the RET gene have adverse effects on ENS development in vivo We addressed this issue by examining mice engineered to express RET51(C618F), an activating mutation identified in MTC patients. Although Ret 51(C618F)/51(C618F) mice displayed hyperganglionosis of the ENS, Ret 51(C618F)/- mice exhibited severe intestinal aganglionosis because of premature neuronal differentiation. Reduced levels of glial cell-derived neurotrophic factor (GDNF), a RET-activating neurotrophic factor, ameliorated the ENS phenotype of Ret 51(C618F)/- mice, demonstrating that GDNF-mediated activation of RET51(C618F) is responsible for severe aganglionic phenotype. The RET51(C618F) allele showed genetic interaction with Ednrb gene, one of modifier genes for HSCR. These data reveal that proliferation and differentiation of ENS precursors are exquisitely controlled by both the activation levels and total dose of RET. Increased RET activity coupled with a decreased gene dosage can cause intestinal aganglionosis, a finding that provides novel insight into HSCR pathogenesis., (Copyright © 2021 Okamoto et al.)

The spin-polarized triplet state generated by light irradiation has potential for applications such as triplet dynamic nuclear polarization (triplet-DNP). Recently, we have reported free-base porphyrins as versatile and biocompatible polarizing agents for triplet-DNP. However, the electron polarization of free-base porphyrins is not very high, and the dilemma is that the high polarization of metalloporphyrins is accompanied by a too short spin-lattice relaxation time to be used for triplet-DNP. We report here that the introduction of electron-withdrawing fluorine groups into Zn porphyrins enables a long enough spin-lattice relaxation time (>1 μs) while maintaining a high polarization ( P x : P y : P z = 0:0:1.0) at room temperature. Interestingly, the spin-lattice relaxation time of Zn porphyrin becomes much longer by introducing fluorine substituents, whereas the spin-lattice relaxation time of free-base porphyrin becomes shorter by the fluorine substitution. Theoretical calculations suggest that this is because the introduction of the electron-withdrawing fluorine substituents reduces the spin density on Zn atoms and weakens the spin-orbit interaction.

Triplet dynamic nuclear polarization (triplet-DNP) achieves nuclear spin polarization at moderate temperatures by using spin polarization of photoexcited triplet electrons. The applications of triplet-DNP for biomolecules have been hampered because acenes, the only polarizing agents used so far, tend to aggregate and lose their polarization in biomolecular matrices. Here, we report for the first time use of porphyrins as polarizing agents of triplet-DNP and propose a new concept of aggregation-tolerant polarizing agents. Sodium salts of tetrakis(4-carboxyphenyl)porphyrin (TCPPNa) can be dispersed in amorphous as well as crystalline biomolecular matrices, and importantly, it can generate polarized triplet electrons even in a slightly aggregated state. Triplet-DNP of crystalline erythritol containing slightly aggregated TCPPNa can achieve more than 120-fold signal enhancement. Because TCPPNa is also the first biocompatible triplet-DNP polarizing agent, this work provides a crucial step forward for the biological and medical applications of triplet-DNP.

A kinematically complete quasifree (p,pn) experiment in inverse kinematics was performed to study the structure of the Borromean nucleus ^{17}B, which had long been considered to have a neutron halo. By analyzing the momentum distributions and exclusive cross sections, we obtained the spectroscopic factors for 1s_{1/2} and 0d_{5/2} orbitals, and a surprisingly small percentage of 9(2)% was determined for 1s_{1/2}. Our finding of such a small 1s_{1/2} component and the halo features reported in prior experiments can be explained by the deformed relativistic Hartree-Bogoliubov theory in continuum, revealing a definite but not dominant neutron halo in ^{17}B. The present work gives the smallest s- or p-orbital component among known nuclei exhibiting halo features and implies that the dominant occupation of s or p orbitals is not a prerequisite for the occurrence of a neutron halo.

The surface of neutron-rich heavy nuclei, with a neutron skin created by excess neutrons, provides an important terrestrial model system to study dilute neutron-rich matter. By using quasi-free α cluster-knockout reactions, we obtained direct experimental evidence for the formation of α clusters at the surface of neutron-rich tin isotopes. The observed monotonous decrease of the reaction cross sections with increasing mass number, in excellent agreement with the theoretical prediction, implies a tight interplay between α-cluster formation and the neutron skin. This result, in turn, calls for a revision of the correlation between the neutron-skin thickness and the density dependence of the symmetry energy, which is essential for understanding neutron stars. Our result also provides a natural explanation for the origin of α particles in α decay., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

The formation of a dineutron in the ^{11}Li nucleus is found to be localized to the surface region. The experiment measured the intrinsic momentum of the struck neutron in ^{11}Li via the (p,pn) knockout reaction at 246  MeV/nucleon. The correlation angle between the two neutrons is, for the first time, measured as a function of the intrinsic neutron momentum. A comparison with reaction calculations reveals the localization of the dineutron at r∼3.6  fm. The results also support the density dependence of dineutron formation as deduced from Hartree-Fock-Bogoliubov calculations for nuclear matter.

In contrast to conventional X-ray therapy, proton beam therapy (PBT) can confine radiation doses to tumours because of the presence of the Bragg peak. However, the precision of the treatment is currently limited by the uncertainty in the beam range. Recently, a unique range verification methodology has been proposed based on simulation studies that exploit spherical ionoacoustic waves with resonant frequency (SPIREs). SPIREs are emitted from spherical gold markers in tumours initially introduced for accurate patient positioning when the proton beam is injected. These waves have a remarkable property: their amplitude is linearly correlated with the residual beam range at the marker position. Here, we present proof-of-principle experiments using short-pulsed proton beams at the clinical dose to demonstrate the feasibility of using SPIREs for beam-range verification with submillimetre accuracy. These results should substantially contribute to reducing the range uncertainty in future PBT applications.

We performed the first direct mass measurements of neutron-rich scandium, titanium, and vanadium isotopes around the neutron number 40 at the RIKEN RI Beam Factory using the time-of-flight magnetic-rigidity technique. The atomic mass excesses of ^{58-60}Sc, ^{60-62}Ti, and ^{62-64}V were measured for the first time. The experimental results show that the two-neutron separation energies in the vicinity of ^{62}Ti increase compared to neighboring nuclei. This shows that the masses of Ti isotopes near N=40 are affected by the Jahn-Teller effect. Therefore, a development of Jahn-Teller stabilization appears below the Cr isotopes, and the systematics in Sc, Ti, and V isotopes suggest that ^{62}Ti is located close to the peak of the Jahn-Teller effect.

Twenty-one two-proton knockout (p,3p) cross sections were measured from neutron-rich nuclei at ∼250  MeV/nucleon in inverse kinematics. The angular distribution of the three emitted protons was determined for the first time, demonstrating that the (p,3p) kinematics are consistent with two sequential proton-proton collisions within the projectile nucleus. Ratios of (p,3p) over (p,2p) inclusive cross sections follow the trend of other many-nucleon removal reactions, further reinforcing the sequential nature of (p,3p) in neutron-rich nuclei.

Dynamic nuclear polarization with photo-excited triplet electrons (triplet-DNP) has the potential to enhance the sensitivity of nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI) at a moderate temperature. While many efforts have been devoted to achieving a large nuclear polarization based on triplet-DNP, the application of triplet-DNP has been limited to nuclear physics experiments. The recent introduction of materials chemistry into the field of triplet-DNP has achieved air-stable and water-soluble polarizing agents as well as the hyperpolarization of nanomaterials with a large surface area such as nanoporous metal-organic frameworks (MOFs) and nanocrystal dispersion in water. This Feature Article overviews the recently-emerged materials chemistry of triplet-DNP that paves new paths towards unprecedented biological and medical applications.

Here we present new information on the shape evolution of the very neutron-rich ^{92,94}Se nuclei from an isomer-decay spectroscopy experiment at the Radioactive Isotope Beam Factory at RIKEN. High-resolution germanium detectors were used to identify delayed γ rays emitted following the decay of their isomers. New transitions are reported extending the previously known level schemes. The isomeric levels are interpreted as originating from high-K quasineutron states with an oblate deformation of β∼0.25, with the high-K state in ^{94}Se being metastable and K hindered. Following this, ^{94}Se is the lowest-mass neutron-rich nucleus known to date with such a substantial K hindrance. Furthermore, it is the first observation of an oblate K isomer in a deformed nucleus. This opens up the possibility for a new region of K isomers at low Z and at oblate deformation, involving the same neutron orbitals as the prolate orbitals within the classic Z∼72 deformed hafnium region. From an interpretation of the level scheme guided by theoretical calculations, an oblate deformation is also suggested for the ^{94}Se_{60} ground-state band.

The structure of a neutron-rich ^{25}F nucleus is investigated by a quasifree (p,2p) knockout reaction at 270A  MeV in inverse kinematics. The sum of spectroscopic factors of π0d_{5/2} orbital is found to be 1.0±0.3. However, the spectroscopic factor with residual ^{24}O nucleus being in the ground state is found to be only 0.36±0.13, while those in the excited state is 0.65±0.25. The result shows that the ^{24}O core of ^{25}F nucleus significantly differs from a free ^{24}O nucleus, and the core consists of ∼35% ^{24}O_{g.s.}. and ∼65% excited ^{24}O. The result may infer that the addition of the 0d_{5/2} proton considerably changes neutron structure in ^{25}F from that in ^{24}O, which could be a possible mechanism responsible for the oxygen dripline anomaly.

Missense mutations of the RET gene have been identified in both multiple endocrine neoplasia (MEN) type 2A/B and Hirschsprung disease (HSCR: congenital absence of the enteric nervous system, ENS). Current consensus holds that MEN2A/B and HSCR are caused by activating and inactivating RET mutations, respectively. However, the biological significance of RET missense mutations in vivo has not been fully elucidated. In the present study, we introduced one MEN2B-associated (M918T) and two HSCR-associated (N394K and Y791F) RET missense mutations into the corresponding regions of the mouse Ret gene by genome editing (Ret M919T , Ret N396K and Ret Y792F ) and performed histological examinations of Ret-expressing tissues to understand the pathogenetic impact of each mutant in vivo. Ret M919T/+ mice displayed MEN2B-related phenotypes, including C-cell hyperplasia and abnormal enlargement of the primary sympathetic ganglia. Similar sympathetic phenotype was observed in Ret M919T/- mice, demonstrating a strong pathogenetic effect of the Ret M918T by a single-allele expression. In contrast, no abnormality was found in the ENS of mice harboring the Ret N394K or Y791F mutation. Most surprisingly, single-allele expression of RET N394K or Y791F was sufficient for normal ENS development, indicating that these RET mutants exert largely physiological function in vivo. This study reveals contrasting pathogenetic effects between MEN2B- and HSCR-associated RET missense mutations, and suggests that some of HSCR-associated RET missense mutations are by themselves neither inactivating nor pathogenetic and require involvement of other gene mutations for disease expressivity., (© 2020 Japanese Society of Developmental Biologists.)

Detailed spectroscopy of the neutron-unbound nucleus ^{28}F has been performed for the first time following proton/neutron removal from ^{29}Ne/^{29}F beams at energies around 230  MeV/nucleon. The invariant-mass spectra were reconstructed for both the ^{27}F^{(*)}+n and ^{26}F^{(*)}+2n coincidences and revealed a series of well-defined resonances. A near-threshold state was observed in both reactions and is identified as the ^{28}F ground state, with S_{n}(^{28}F)=-199(6)  keV, while analysis of the 2n decay channel allowed a considerably improved S_{n}(^{27}F)=1620(60)  keV to be deduced. Comparison with shell-model predictions and eikonal-model reaction calculations have allowed spin-parity assignments to be proposed for some of the lower-lying levels of ^{28}F. Importantly, in the case of the ground state, the reconstructed ^{27}F+n momentum distribution following neutron removal from ^{29}F indicates that it arises mainly from the 1p_{3/2} neutron intruder configuration. This demonstrates that the island of inversion around N=20 includes ^{28}F, and most probably ^{29}F, and suggests that ^{28}O is not doubly magic.

Triplet dynamic nuclear polarization (triplet-DNP) allows hyperpolarization at a moderate temperature. While the triplet-DNP of water is strongly desired, water-soluble triplet polarizing agents have not yet been reported. Herein, the first example of triplet-DNP of crystalline ice is demonstrated by molecularly dispersing a novel water-soluble polarizing agent into ice.

Exclusive cross sections and momentum distributions have been measured for quasifree one-neutron knockout reactions from a ^{54}Ca beam striking on a liquid hydrogen target at ∼200  MeV/u. A significantly larger cross section to the p_{3/2} state compared to the f_{5/2} state observed in the excitation of ^{53}Ca provides direct evidence for the nature of the N=34 shell closure. This finding corroborates the arising of a new shell closure in neutron-rich calcium isotopes. The distorted-wave impulse approximation reaction formalism with shell model calculations using the effective GXPF1Bs interaction and ab initio calculations concur our experimental findings. Obtained transverse and parallel momentum distributions demonstrate the sensitivity of quasifree one-neutron knockout in inverse kinematics on a thick liquid hydrogen target with the reaction vertex reconstructed to final state spin-parity assignments.

Dynamic nuclear polarization with photo-excited triplet electrons (Triplet-DNP) is demonstrated using 6,13-diphenylpentacene (DPPentacene). DPPentacene is soluble in various organic solvents, while pentacene, which is used in most of the triplet-DNP experiments, has limited solubility. An enhancement factor of 81 is obtained for 1H spins in the glass of ethanol-d6 : water = 80 : 20 (w/w) doped with 0.1 mM DPPentacene at 90 K in 0.67 T.

While dynamic nuclear polarization using photo-excited triplet electrons (triplet-DNP) can improve the sensitivity of nuclear magnetic resonance at room temperature, it has not been carried out in water. Here, we report the first example of triplet-DNP in water by downsizing the conventional bulk crystals to nanocrystals.

Triplet dynamic nuclear polarization (triplet-DNP), a method to enhance nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI) sensitivity using photoexcited triplet electrons, has great potential to hyperpolarize nuclear spins at room temperature. Since the first report of room-temperature triplet-DNP in 1990, pentacene has been the only and best option of triplet polarizing agent. However, the poor air stability of pentacene has severely limited the applicability of triplet-DNP. We report the first example of polarizing agents with significant air stability as well as high polarizing ability comparable to pentacene. The introduction of electron-withdrawing diaza-substitution to pentacene and tetracene reduces the lowest unoccupied molecular orbital level and endows much improved stability under the ambient conditions. Importantly, the diaza-substituted pentacene and tetracene offer similar, or even slightly better, 1 H NMR signal enhancement compared with pentacene in the prototypical triplet-DNP test using p-terphenyl crystals. This work removes one of the largest obstacles toward the application of triplet-DNP for the hyperpolarization of biological molecules.

Nuclear magic numbers correspond to fully occupied energy shells of protons or neutrons inside atomic nuclei. Doubly magic nuclei, with magic numbers for both protons and neutrons, are spherical and extremely rare across the nuclear landscape. Although the sequence of magic numbers is well established for stable nuclei, experimental evidence has revealed modifications for nuclei with a large asymmetry between proton and neutron numbers. Here we provide a spectroscopic study of the doubly magic nucleus 78 Ni, which contains fourteen neutrons more than the heaviest stable nickel isotope. We provide direct evidence of its doubly magic nature, which is also predicted by ab initio calculations based on chiral effective-field theory interactions and the quasi-particle random-phase approximation. Our results also indicate the breakdown of the neutron magic number 50 and proton magic number 28 beyond this stronghold, caused by a competing deformed structure. State-of-the-art phenomenological shell-model calculations reproduce this shape coexistence, predicting a rapid transition from spherical to deformed ground states, with 78 Ni as the turning point.

Medullary thyroid carcinoma (MTC) develops from hyperplasia of thyroid C cells and represents one of the major causes of thyroid cancer mortality. Mutations in the cysteine-rich domain (CRD) of the RET gene are the most prevalent genetic cause of MTC. The current consensus holds that such cysteine mutations cause ligand-independent dimerization and constitutive activation of RET. However, given the number of the CRD mutations left uncharacterized, our understanding of the pathogenetic mechanisms by which CRD mutations lead to MTC remains incomplete. We report here that RET(C618F), a mutation identified in MTC patients, displays moderately high basal activity and requires the ligand for its full activation. To assess the biological significance of RET(C618F) in organogenesis, we generated a knock-in mouse line conditionally expressing RET(C618F) cDNA by the Ret promoter. The RET(C618F) allele can be made to be Ret-null and express mCherry by Cre-loxP recombination, which allows the assessment of the biological influence of RET(C618F) in vivo. Mice expressing RET(C618F) display mild C cell hyperplasia and increased numbers of enteric neurons, indicating that RET(C618F) confers gain-of-function phenotypes. This mouse line serves as a novel biological platform for investigating pathogenetic mechanisms involved in MTC and enteric hyperganglionosis., (© 2019 Wiley Periodicals, Inc.)

Fifty-five inclusive single nucleon-removal cross sections from medium mass neutron-rich nuclei impinging on a hydrogen target at ∼250  MeV/nucleon are measured at the RIKEN Radioactive Isotope Beam Factory. Systematically higher cross sections are found for proton removal from nuclei with an even number of protons as compared to odd-proton number projectiles for a given neutron separation energy. Neutron removal cross sections display no even-odd splitting, contrary to nuclear cascade model predictions. Both effects are understood through simple considerations of neutron separation energies and bound state level densities originating in pairing correlations in the daughter nuclei. These conclusions are supported by comparison with semimicroscopic model predictions, highlighting the enhanced role of low-lying level densities in nucleon-removal cross sections from loosely bound nuclei.

This study proposes a novel alternative range-verification method for proton beam with acoustic waves generated from spherical metal markers. When proton beam is incident on metal markers, most of the resulting pressure waves are confined in the markers because of the large difference in acoustic impedance between the metal and tissue. However, acoustic waves with frequency equal to marker's resonant frequency escape this confinement; the marker briefly acts as an acoustic transmitter. Herein, this phenomenon is exploited to measure the range of the proton beam. We test the proposed strategy in 3-D simulations, combining the dose calculations with modelling of acoustic-wave propagation. A spherical gold marker of 2.0 mm diameter was placed in water with a 60 MeV proton beam incident on it. We investigated the dependence of pressure waves on the width of beam pulse and marker position. At short beam pulse, specific high-frequency acoustic waves of 1.62 MHz originating from the marker were observed in wave simulations, whose amplitude correlated with the distance between the marker and Bragg peak. Results indicate that the Bragg peak position can be estimated by measuring the acoustic wave amplitudes from the marker, using a single detector properly designed for the resonance frequency.

The first γ-ray spectroscopy of ^{52}Ar, with the neutron number N=34, was measured using the ^{53}K(p,2p) one-proton removal reaction at ∼210  MeV/u at the RIBF facility. The 2_{1}^{+} excitation energy is found at 1656(18) keV, the highest among the Ar isotopes with N>20. This result is the first experimental signature of the persistence of the N=34 subshell closure beyond ^{54}Ca, i.e., below the magic proton number Z=20. Shell-model calculations with phenomenological and chiral-effective-field-theory interactions both reproduce the measured 2_{1}^{+} systematics of neutron-rich Ar isotopes, and support a N=34 subshell closure in ^{52}Ar.

While dynamic nuclear polarization based on photoexcited triplet electrons (triplet-DNP) has the potential to hyperpolarize nuclear spins of target substrates in the low magnetic field at room temperature, there has been no triplet-DNP system offering structural rigidity and substrate accessibility. Here, we report the first example of triplet-DNP of nanoporous metal-organic frameworks. Accommodation of a carboxylate-modified pentacene derivative in a partially deuterated ZIF-8 (D-ZIF-8) results in a clear 1 H NMR signal enhancement over thermal equilibrium.

The key parameter to discuss the possibility of the pion condensation in nuclear matter, i.e., the so-called Landau-Migdal parameter g^{'}, was extracted by measuring the double-differential cross sections for the (p,n) reaction at 216  MeV/u on a neutron-rich doubly magic unstable nucleus, ^{132}Sn with the quality comparable to data taken with stable nuclei. The extracted strengths for Gamow-Teller (GT) transitions from ^{132}Sn leading to ^{132}Sb exhibit the GT giant resonance (GTR) at the excitation energy of 16.3±0.4(stat)±0.4(syst)  MeV with the width of Γ=4.7±0.8  MeV. The integrated GT strength up to E_{x}=25  MeV is S_{GT}^{-}=53±5(stat)_{-10}^{+11}(syst), corresponding to 56% of Ikeda's sum rule of 3(N-Z)=96. The present result accurately constrains the Landau-Migdal parameter as g^{'}=0.68±0.07, thanks to the high sensitivity of the GTR energy to g^{'}. In combination with previous studies on the GTR for ^{90}Zr and ^{208}Pb, the result of this work shows the constancy of this parameter in the nuclear chart region with (N-Z)/A=0.11 to 0.24 and A=90 to 208.

This corrects the article DOI: 10.1103/PhysRevLett.119.192501.

We perform the first direct mass measurements of neutron-rich calcium isotopes beyond neutron number 34 at the RIKEN Radioactive Isotope Beam Factory by using the time-of-flight magnetic-rigidity technique. The atomic mass excesses of ^{55-57}Ca are determined for the first time to be -18650(160), -13510(250), and -7370(990)  keV, respectively. We examine the emergence of neutron magicity at N=34 based on the new atomic masses. The new masses provide experimental evidence for the appearance of a sizable energy gap between the neutron 2p_{1/2} and 1f_{5/2} orbitals in ^{54}Ca, comparable to the gap between the neutron 2p_{3/2} and 2p_{1/2} orbitals in ^{52}Ca. For the ^{56}Ca nucleus, an open-shell property in neutrons is suggested.

The (^{12}N, ^{12}C) charge-exchange reaction at 175  MeV/u was developed as a novel probe for studying the isovector spin giant monopole resonance (IVSMR), whose properties are important for better understanding the bulk properties of nuclei and asymmetric nuclear matter. This probe, now available through the production of ^{12}N as a secondary rare-isotope beam, is exothermic, is strongly absorbed at the surface of the target nucleus, and provides selectivity for spin-transfer excitations. All three properties enhance the excitation of the IVSMR compared to other, primarily light-ion, probes, which have been used to study the IVSMR thus far. The ^{90}Zr(^{12}N,^{12}C) reaction was measured and the excitation energy spectra up to about 70 MeV for both the spin-transfer and non-spin-transfer channels were deduced separately by tagging the decay by γ emission from the ^{12}C ejectile. Besides the well-known Gamow-Teller and isobaric analog transitions, a clear signature of the IVSMR was identified. By comparing with the results from light-ion reactions on the same target nucleus and theoretical predictions, the suitability of this new probe for studying the IVSMR was confirmed.

We observed the atomic 1s and 2p states of π^{-} bound to ^{121}Sn nuclei as distinct peak structures in the missing mass spectra of the ^{122}Sn(d,^{3}He) nuclear reaction. A very intense deuteron beam and a spectrometer with a large angular acceptance let us achieve a potential of discovery, which includes the capability of determining the angle-dependent cross sections with high statistics. The 2p state in a Sn nucleus was observed for the first time. The binding energies and widths of the pionic states are determined and found to be consistent with previous experimental results of other Sn isotopes. The spectrum is measured at finite reaction angles for the first time. The formation cross sections at the reaction angles between 0° and 2° are determined. The observed reaction-angle dependence of each state is reproduced by theoretical calculations. However, the quantitative comparison with our high-precision data reveals a significant discrepancy between the measured and calculated formation cross sections of the pionic 1s state.

In-beam γ-ray spectroscopy of ^{79}Cu is performed at the Radioactive Isotope Beam Factory of RIKEN. The nucleus of interest is produced through proton knockout from a ^{80}Zn beam at 270  MeV/nucleon. The level scheme up to 4.6 MeV is established for the first time and the results are compared to Monte Carlo shell-model calculations. We do not observe significant knockout feeding to the excited states below 2.2 MeV, which indicates that the Z=28 gap at N=50 remains large. The results show that the ^{79}Cu nucleus can be described in terms of a valence proton outside a ^{78}Ni core, implying the magic character of the latter.

We describe a case of deep cerebral venous sinus thrombosis(DCVST)that was successfully treated by oral administration of the Xa inhibitor edoxaban. A 53-year-old man was admitted to our hospital because of a headache and undifferentiated dizziness. Computed tomography(CT)demonstrated a low-density area in the bilateral thalamus and high-density lesions in the internal cerebral veins(ICVs)and vein of Galen. Magnetic resonance imaging with diffusion-weighted images detected areas of hyperintensity in the bilateral thalamus. Additionally, the inferior sagittal sinus, ICV, and vein of Galen were not detected by CT venography or cerebral angiography. We therefore diagnosed DCVST and started anticoagulation therapy with heparin(IV)and warfarin. A week after admission, lesions that showed hypointensity on T2 * images and high density on CT scans were detected in the bilateral thalamus. We thought that hemorrhagic infarction had occurred in association with DCVST, and changed the anticoagulation therapy to oral administration of edoxaban on day 9. The patient's symptoms gradually diminished, and CT venography indicated partial recanalization of the DCV from the ICV to the vein of Galen on day 72. We report our experience, and discuss the safety and usefulness of the Xa inhibitor for treating DCVST with hemorrhagic infarction.

We report on the first γ-ray spectroscopy of low-lying states in neutron-rich ^{98,100}Kr isotopes obtained from ^{99,101}Rb(p,2p) reactions at ∼220  MeV/nucleon. A reduction of the 2_{1}^{+} state energies beyond N=60 demonstrates a significant increase of deformation, shifted in neutron number compared to the sharper transition observed in strontium and zirconium isotopes. State-of-the-art beyond-mean-field calculations using the Gogny D1S interaction predict level energies in good agreement with experimental results. The identification of a low-lying (0_{2}^{+}, 2_{2}^{+}) state in ^{98}Kr provides the first experimental evidence of a competing configuration at low energy in neutron-rich krypton isotopes consistent with the oblate-prolate shape coexistence picture suggested by theory.

Materials often fail when subjected to stresses over a prolonged period. The time to failure, also called the lifetime, is known to exhibit large variability of many materials, particularly brittle and quasibrittle materials. For example, a coefficient of variation reaches 100% or even more. Its distribution shape is highly skewed toward zero lifetime, implying a large number of premature failures. This behavior contrasts with that of normal strength, which shows a variation of only 4%-10% and a nearly bell-shaped distribution. The fundamental cause of this large and unique variability of lifetime is not well understood because of the complex interplay between stochastic processes taking place on the molecular level and the hierarchical and disordered structure of the material. We have constructed fiber network models, both regular and random, as a paradigm for general material structures. With such networks, we have performed Monte Carlo simulations of creep failure to establish explicit relationships among fiber characteristics, network structures, system size, and lifetime distribution. We found that fiber characteristics have large, sometimes dominating, influences on the lifetime variability of a network. Among the factors investigated, geometrical disorders of the network were found to be essential to explain the large variability and highly skewed shape of the lifetime distribution. With increasing network size, the distribution asymptotically approaches a double-exponential form. The implication of this result is that, so-called "infant mortality," which is often predicted by the Weibull approximation of the lifetime distribution, may not exist for a large system.

The (^{10}Be,^{10}B^{*}[1.74  MeV]) charge-exchange reaction at 100  AMeV is presented as a new probe for isolating the isovector (ΔT=1) nonspin-transfer (ΔS=0) response of nuclei, with ^{28}Si being the first nucleus studied. By using a secondary ^{10}Be beam produced by fast fragmentation of ^{18}O nuclei at the NSCL Coupled Cyclotron Facility, applying the dispersion-matching technique with the S800 magnetic spectrometer to determine the excitation energy in ^{28}Al, and performing high-resolution γ-ray tracking with the Gamma-Ray Energy Tracking In-beam Nuclear Array (GRETINA) to identify the 1022-keV γ ray associated with the decay from the 1.74-MeV T=1 isobaric analog state in ^{10}B, a ΔS=0 excitation-energy spectrum in ^{28}Al was extracted. Monopole and dipole contributions were determined through a multipole-decomposition analysis, and the isovector giant dipole resonance and isovector giant monopole resonance (IVGMR) were identified. The results show that this probe is a powerful tool for studying the elusive IVGMR, which is of interest for performing stringent tests of modern density functional theories at high excitation energies and for constraining the bulk properties of nuclei and nuclear matter. The extracted distributions were compared with theoretical calculations based on the normal-modes formalism and the proton-neutron relativistic time-blocking approximation. Calculated cross sections based on these strengths underestimate the data by about a factor of 2, which likely indicates deficiencies in the reaction calculations based on the distorted wave Born approximation.

The first measurement of the low-lying states of the neutron-rich ^{110}Zr and ^{112}Mo was performed via in-beam γ-ray spectroscopy after one proton removal on hydrogen at ∼200  MeV/nucleon. The 2_{1}^{+} excitation energies were found at 185(11) keV in ^{110}Zr, and 235(7) keV in ^{112}Mo, while the R_{42}=E(4_{1}^{+})/E(2_{1}^{+}) ratios are 3.1(2), close to the rigid rotor value, and 2.7(1), respectively. These results are compared to modern energy density functional based configuration mixing models using Gogny and Skyrme effective interactions. We conclude that first levels of ^{110}Zr exhibit a rotational behavior, in agreement with previous observations of lighter zirconium isotopes as well as with the most advanced Monte Carlo shell model predictions. The data, therefore, do not support a harmonic oscillator shell stabilization scenario at Z=40 and N=70. The present data also invalidate predictions for a tetrahedral ground state symmetry in ^{110}Zr.

Masses of ^{52g,52m}Co were measured for the first time with an accuracy of ∼10  keV, an unprecedented precision reached for short-lived nuclei in the isochronous mass spectrometry. Combining our results with the previous β-γ measurements of ^{52}Ni, the T=2, J^{π}=0^{+} isobaric analog state (IAS) in ^{52}Co was newly assigned, questioning the conventional identification of IASs from the β-delayed proton emissions. Using our energy of the IAS in ^{52}Co, the masses of the T=2 multiplet fit well into the isobaric multiplet mass equation. We find that the IAS in ^{52}Co decays predominantly via γ transitions while the proton emission is negligibly small. According to our large-scale shell model calculations, this phenomenon has been interpreted to be due to very low isospin mixing in the IAS.

The gastrointestinal (GI) tract is innervated by intrinsic enteric neurons and by extrinsic efferent and afferent nerves. The enteric (intrinsic) nervous system (ENS) in most regions of the gut consists of two main ganglionated layers; myenteric and submucosal ganglia, containing numerous types of enteric neurons and glial cells. Axons arising from the ENS and from extrinsic neurons innervate most layers of the gut wall and regulate many gut functions. The majority of ENS cells are derived from vagal neural crest cells (NCCs), which proliferate, colonize the entire gut, and first populate the myenteric region. After gut colonization by vagal NCCs, the extrinsic nerve fibers reach the GI tract, and Schwann cell precursors (SCPs) enter the gut along the extrinsic nerves. Furthermore, a subpopulation of cells in myenteric ganglia undergoes a radial (inward) migration to form the submucosal plexus, and the intrinsic and extrinsic innervation to the mucosal region develops. Here, we focus on recent progress in understanding the developmental processes that occur after the gut is colonized by vagal ENS precursors, and provide an up-to-date overview of molecular mechanisms regulating the development of the intrinsic and extrinsic innervation of the GI tract., (Copyright © 2016 Elsevier Inc. All rights reserved.)

A candidate resonant tetraneutron state is found in the missing-mass spectrum obtained in the double-charge-exchange reaction ^{4}He(^{8}He,^{8}Be) at 186  MeV/u. The energy of the state is 0.83±0.65(stat)±1.25(syst)  MeV above the threshold of four-neutron decay with a significance level of 4.9σ. Utilizing the large positive Q value of the (^{8}He,^{8}Be) reaction, an almost recoilless condition of the four-neutron system was achieved so as to obtain a weakly interacting four-neutron system efficiently.

Introduction: Anorectal abscess is one of the most common anorectal conditions encountered in practice. However, such abscesses may rarely extend upward and cause life-threatening medical conditions., Presentation of Case: A 53-year-old woman presented with symptoms of anorectal abscess and evidence of severe inflammatory response and acute kidney injury. Computed tomography revealed a widespread abscess extending to the bilateral retroperitoneal spaces. Surgical drainage was performed via a totally extraperitoneal approach through a lower midline abdominal incision, and the patient had a rapid and uncomplicated recovery., Discussion: Although retroperitoneal abscesses originating from the anorectal region are rare, they are life-threating events that require immediate treatment. Percutaneous abscess drainage has been recently evolved; however, surgical drainage is required sometimes that may be challenging, particularly in the case of widespread abscesses, as in our case., Conclusion: The midline extraperitoneal approach reported here might be an effective surgical option for patients with bilateral widespread retroperitoneal abscesses., (Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)

We report on the measurement of the first 2(+) and 4(+) states of (66)Cr and (70,72)Fe via in-beam γ-ray spectroscopy. The nuclei of interest were produced by (p,2p) reactions at incident energies of 260  MeV/nucleon. The experiment was performed at the Radioactive Isotope Beam Factory, RIKEN, using the DALI 2γ-ray detector array and the novel MINOS device, a thick liquid hydrogen target combined with a vertex tracker. A low-energy plateau of 2(1)(+) and 4(1)(+) energies as a function of the neutron number was observed for N≥38 and N≥40 for even-even Cr and Fe isotopes, respectively. State-of-the-art shell model calculations with a modified Lenzi-Nowacki-Poves-Sieja (LNPS) interaction in the pfg(9/2)d(5/2) valence space reproduce the observations. Interpretation within the shell model shows an extension of the island of inversion at N=40 for more neutron-rich isotopes towards N=50.

Numerical simulations of time-dependent stochastic failure of fiber network have been performed by using a central-force, triangular lattice model. This two-dimensional (2D) network can be seen as the next level of structural hierarchy to fiber bundles, which have been investigated for many years both theoretically and numerically. Unlike fiber bundle models, the load sharing of the fiber network is determined by the network mechanics rather than a preassigned rule, and its failure is defined as the point of avalanche rather than the total fiber failure. We have assumed that the fiber in the network follows Coleman's probabilistic failure law [B. D. Coleman, J. Appl. Phys. 29, 968 (1958)] with the Weibull shape parameter β=1 (memory less fiber). Our interests are how the fiber-level probabilistic failure law is transformed into the one for the network and how the failure characteristics and disorders on the fiber level influence the network failure response. The simulation results showed that, with increasing the size of the network (N), weakest-link scaling (WLS) appeared and each lifetime distribution at a given size approximately followed Weibull distribution. However, the scaling behavior of the mean and the Weibull shape parameter clearly deviate from what we can predict from the WLS of Weibull distribution. We have found that a characteristic distribution function has, in fact, a double exponential form, not Weibull form. Accordingly, for the 2D network system, Coleman's probabilistic failure law holds but only approximately. Comparing the fiber and network failure properties, we found that the network structure induces an increase of the load sensitivity factor ρ (more brittle than fiber) and Weibull shape parameter β (less uncertainty of lifetime). Superimposed disorders on the fiber level reduce all these properties for the network.

Elucidation of the cellular identity of neuronal precursors provides mechanistic insights into the development and pathophysiology of the nervous system. In the enteric nervous system (ENS), neurogenesis persists from midgestation to the postnatal period. Cellular mechanism underlying the long-term neurogenesis in the ENS has remained unclear. Using genetic fate mapping in mice, we show here that a subset of Schwann cell precursors (SCPs), which invades the gut alongside the extrinsic nerves, adopts a neuronal fate in the postnatal period and contributes to the ENS. We found SCP-derived neurogenesis in the submucosal region of the small intestine in the absence of vagal neural crest-derived ENS precursors. Under physiological conditions, SCPs comprised up to 20% of enteric neurons in the large intestine and gave rise mainly to restricted neuronal subtypes, calretinin-expressing neurons. Genetic ablation of Ret, the signaling receptor for glial cell line-derived neurotrophic factor, in SCPs caused colonic oligoganglionosis, indicating that SCP-derived neurogenesis is essential to ENS integrity. Identification of Schwann cells as a physiological neurogenic source provides novel insight into the development and disorders of neural crest-derived tissues., Significance Statement: Elucidating the cellular identity of neuronal precursors provides novel insights into development and function of the nervous system. The enteric nervous system (ENS) is innervated richly by extrinsic nerve fibers, but little is known about the significance of extrinsic innervation to the structural integrity of the ENS. This report reveals that a subset of Schwann cell precursors (SCPs), which invades the gut alongside the extrinsic nerves, adopts a neuronal fate and differentiates into specific neuronal subtypes. SCP-specific ablation of the Ret gene leads to colonic oligoganglionosis, demonstrating a crucial role of SCP-derived neurogenesis in ENS development. Cross-lineage differentiation capacity in SCPs suggests their potential involvement in the development and pathology of a wide variety of neural crest-derived cell types., (Copyright © 2015 the authors 0270-6474/15/359879-10$15.00/0.)

We report a case of intraorbital varix. A 16-year-old girl showed sudden left-sided exophthalmos after vomiting. After several episodes of vomiting, she developed complete loss of vision in the left eye, followed by orbital pain, disruption of eye movement, and periorbital swelling. No change in symptoms or signs was observed after the Valsalva maneuver or jugular vein compression. Computed tomography (CT), magnetic resonance imaging (MRI), and angiography were inconclusive. Transcranial surgery revealed a large varix near the optic nerve. The lesion could not be completely resected because the orbital fat interfered with its complete visualization. We cauterized the lesion to reduce its volume. The patient's symptoms improved markedly after surgery and cauterization. Thus, cauterization appears to be an effective strategy to reduce the volume of an unresectable intraorbital varix.

A 33-year-old male presented with an extremely rare case of intraorbital fat necrosis. A magnetic resonance imaging scan showed a 10-mm mass lesion within the right lateral rectal muscle. Surgical removal was performed. Histological analysis showed diffuse adipose cells surrounded by macrophage cells. Fat necrosis was diagnosed.

Numerous approaches have been used to access aneurysms of the vertebral artery(VA)-posterior inferior cerebellar artery(PICA)complex for microsurgical clipping. Here, we report the case of a patient with an unruptured aneurysm of the left VA-PICA complex that was successfully treated using a contralateral suboccipital approach. Computed tomography angiography demonstrated a small saccular aneurysm arising from the lateral aspect of the left V4 segment just distal to the PICA origin. The aneurysm deviated to the right from the midline at the level of the jugular tubercle on angiographic evaluation, so we selected a contralateral suboccipital approach. The aneurysm was completely obliterated by neck clipping. After surgery, slight dysphagia and hoarseness appeared, but dysphagia disappeared within several days and hoarseness disappeared within 5 months. VA-PICA aneurysms can vary in their relationship to cranial nerves, brainstem, and bones of the skull base. Neurosurgeons should consider using a contralateral approach for certain aneurysms arising from a tortuous VA that has crossed the midline.

Patients with spinal degenerative diseases suffer not only neuropathy in the extremities but also lower urinary tract dysfunction(LUTD). Patients with cauda equina syndrome generally need emergency decompression to pelvic visceral function, especially that of the urinary bladder. However, less prominent voiding symptoms can be missed in clinical settings. There is a discrepancy between lower urinary tract symptoms and LUTD. Therefore, urodynamic studies are needed to screen of patients with spinal diseases. Cystometry and urethral sphincter electromyography are useful for increasing our understanding of LUTD but are too invasive for screening. Our protocol for the evaluation of LUTD consists of residual urine measurement and uroflowmetry(UFM). UFM is the simplest and noninvasive urodynamic technique;however, it has the disadvantage of being nonreproducible, which depends on bladder volume, diurnal variation, presence of obstructive disease, and mental stress. UFM was reportedly reproducible in normal individuals in 1979, but was not evaluated in patients with spinal disease. This study examined the reproducibility of UFM in patients with spinal disease. UFM was performed twice in 26 male patients with cervical or lumbar degenerative disease. Maximum urinary flow rate corrected with Siroky's nomogram was reproducible in 23(88.5%)of the 26 patients. A urinary flow curve was reproducible in 25(96.2%)of the 26 patients, and only 1 patient had excessive urination at the 1st UFM and normal urination at the 2nd UFM. The reproducibility of UFM was high in patients with spinal degenerative disease.

Pleiotropic growth factors play a number of critical roles in continuous processes of embryonic development; however, the mechanisms by which a single regulatory factor is able to orchestrate diverse developmental events remain imperfectly understood. In the development of the enteric nervous system (ENS), myenteric ganglia (MGs) form initially, after which the submucosal ganglia (SMGs) develop by radial inward migration of immature ENS precursors from the myenteric layer. Here, we demonstrate that glial cell line-derived neurotrophic factor (GDNF) is essential for the formation not only of the MGs, but the SMGs as well, establishing GDNF as a long-term acting neurotrophic factor for ENS development in a mouse model. GDNF promotes radial migration of SMG precursors. Interestingly, premigratory SMG precursors in the myenteric layer were distinguished from the surrounding neuronally differentiating cells by their lower activation of the GDNF-mediated MAPK pathway, suggesting that low activation of GDNF downstream pathways is required for the maintenance of the immature state. ENS precursors devoid of GDNF signaling during midgestation halt their migration, survive, and remain in an undifferentiated state over the long-term in vivo. Reactivation of GDNF signaling in these dormant precursors restores their migration and neuronal differentiation in gut organ culture. These findings suggest that pleiotropic function of GDNF is at least in part governed by modulating levels of intracellular activation of GDNF downstream pathways; high activation triggers neuronal differentiation, whereas low activation is crucial for the maintenance of progenitor state.