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For the first time, the (d,^{2}He) reaction was successfully used in inverse kinematics to extract the Gamow-Teller transition strength in the ß^{+} direction from an unstable nucleus. The new technique was made possible by the use of an active-target time-projection chamber and a magnetic spectrometer, and opens a path to addressing a range of scientific challenges, including in astrophysics and neutrino physics. In this Letter, the nucleus studied was ^{14}O, and the Gamow-Teller transition strength to ^{14}N was extracted up to an excitation energy of 22 MeV. The data were compared to shell-model and state-of-the-art coupled-cluster calculations. Shell-model calculations reproduce the measured Gamow-Teller strength distribution up to about 15 MeV reasonably well, after the application of a phenomenological quenching factor. In a significant step forward to better understand this quenching, the coupled-cluster calculation reproduces the full strength distribution well without such quenching, owing to the large model space, the inclusion of strong correlations, and the coupling of the weak interaction to two nucleons through two-body currents.

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The discrepancy between observations from γ-ray astronomy of the ^{60}Fe/^{26}Al γ-ray flux ratio and recent calculations is an unresolved puzzle in nuclear astrophysics. The stellar ß-decay rate of ^{59}Fe is one of the major nuclear uncertainties impeding us from a precise prediction. The important Gamow-Teller strengths from the low-lying states in ^{59}Fe to the ^{59}Co ground state are measured for the first time using the exclusive measurement of the ^{59}Co(t,^{3}He+γ)^{59}Fe charge-exchange reaction. The new stellar decay rate of ^{59}Fe is a factor of 3.5±1.1 larger than the currently adopted rate at T=1.2 GK. Stellar evolution calculations show that the ^{60}Fe production yield of an 18 solar mass star is decreased significantly by 40% when using the new rate. Our result eliminates one of the major nuclear uncertainties in the predicted yield of ^{60}Fe and alleviates the existing discrepancy of the ^{60}Fe/^{26}Al ratio.

Excitation of the Isovector Spin Monopole Resonance via the Exothermic

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.

Spectroscopy of Pionic Atoms in

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.

Observation of the Isovector Giant Monopole Resonance via the

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.

Prognostic value of tumor-infiltrating lymphocytes differs depending on histological type and smoking habit in completely resected non-small-cell lung cancer.

BACKGROUND: T-cell infiltration in tumors has been used as a prognostic tool in non-small-cell lung cancer (NSCLC). However, the influence of smoking habit and histological type on tumor-infiltrating lymphocytes (TILs) in NSCLC remains unclear. PATIENTS AND METHODS: We evaluated the prognostic significance of TILs (CD4+, CD8+, CD20+, and FOXP3+) according to histological type and smoking habit using automatic immunohistochemical staining and cell counting in 218 patients with NSCLC. RESULTS: In multivariate survival analyses of clinical, pathological, and immunological factors, a high ratio of FOXP3+ to CD4+ T cells (FOXP3/CD4) [hazard ratio (HR): 4.46, P < 0.01 for overall survival (OS); HR: 1.96, P < 0.05 for recurrence-free survival (RFS)] and a low accumulation of CD20+ B cells (HR: 2.45, P = 0.09 for OS; HR: 2.86, P < 0.01 for RFS) were identified as worse prognostic factors in patients with adenocarcinoma (AD). In non-AD, a low number of CD8+ T cells were correlated with an unfavorable outcome (HR: 7.69, P < 0.01 for OS; HR: 3.57, P < 0.02 for RFS). Regarding smoking habit in AD, a high FOXP3/CD4 ratio was poorly prognostic with a smoking history (HR: 5.21, P < 0.01 for OS; HR: 2.38, P < 0.03 for RFS), whereas a low accumulation of CD20+ B cells (HR: 4.54, P = 0.03 for OS; HR: 2.94, P < 0.01 for RFS) was confirmed as an unfavorable factor in non-smokers with AD. CONCLUSIONS: A low number of CD8+ T cells in non-AD, a high FOXP3/CD4 ratio in smokers with AD, and a low number of CD20+ B cells in non-smokers with AD were identified as independent unfavorable prognostic factors in resected NSCLC. Evaluating the influence of histological type and smoking habit on the immunological environment may lead to the establishment of immunological diagnosis and appropriate individualized immunotherapy for NSCLC.

Candidate Resonant Tetraneutron State Populated by the

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.

Determining the rp-process flow through 56Ni: resonances in 57Cu(p,γ)58Zn identified with GRETINA.

An approach is presented to experimentally constrain previously unreachable (p, γ) reaction rates on nuclei far from stability in the astrophysical rp process. Energies of all critical resonances in the (57)Cu(p,γ)(58)Zn reaction are deduced by populating states in (58)Zn with a (d, n) reaction in inverse kinematics at 75 MeV/u, and detecting γ-ray-recoil coincidences with the state-of-the-art γ-ray tracking array GRETINA and the S800 spectrograph at the National Superconducting Cyclotron Laboratory. The results reduce the uncertainty in the (57)Cu(p,γ) reaction rate by several orders of magnitude. The effective lifetime of (56)Ni, an important waiting point in the rp process in x-ray bursts, can now be determined entirely from experimentally constrained reaction rates.

ß+ Gamow-Teller transition strengths from 46Ti and stellar electron-capture rates.

The Gamow-Teller strength in the ß(+) direction to (46)Sc was extracted via the (46)Ti(t,(3)He + γ) reaction at 115 MeV/u. The γ-ray coincidences served to precisely measure the very weak Gamow-Teller transition to a final state at 991 keV. Although this transition is weak, it is crucial for accurately estimating electron-capture rates in astrophysical scenarios with relatively low stellar densities and temperatures, such as presupernova stellar evolution. Shell-model calculations with different effective interactions in the pf shell-model space do not reproduce the experimental Gamow-Teller strengths, which is likely due to sd-shell admixtures. Calculations in the quasiparticle random phase approximation that are often used in astrophysical simulations also fail to reproduce the experimental Gamow-Teller strength distribution, leading to strongly overestimated electron-capture rates. Because reliable theoretical predictions of Gamow-Teller strengths are important for providing astrophysical electron-capture reaction rates for a broad set of nuclei in the lower pf shell, we conclude that further theoretical improvements are required to match astrophysical needs.

A mutation in the Pax-6 gene in rat small eye is associated with impaired migration of midbrain crest cells.

The rat small eye strain (rSey) lacks eyes and nose in the homozygote, and is similar to the mouse Sey strain with mutations in the Pax-6 gene. We isolated Pax-6 cDNA clones from an rSey homozygote library, and found an internal deletion of about 600 basepairs in the serine/threonine-rich domain. At the genomic level, a single base (G) insertion in an exon generates an abnormal 5' donor splice site, thereby producing the truncated mRNA. Anterior midbrain crest cells in the homozygous rSey embryos reached the eye rudiments but did not migrate any further to the nasal rudiments, suggesting that the Pax-6 gene is involved in conducting migration of neural crest cells from the anterior midbrain.

Identification of the ß+ isovector spin monopole resonance via the 208Pb and 90Zr(t,3He) reactions at 300 MeV/u.

The double-differential cross sections for the (208)Pb and (90)Zr(t,(3)He) reactions at 300 MeV/u have been measured at the RI Beam Factory at RIKEN. This was the first physics experiment with the SHARAQ magnetic spectrometer. The combined analysis of the present (t,(3)He) data and previous (n,p) data provides the clearest identification for the ß(+) isovector spin monopole resonance both in the (208)Tl and (90)Y nuclei, and puts the observations of this giant resonance on a firm foundation. The measured distributions of the (t,(3)He) monopole cross sections were well reproduced by the distorted-wave Born approximation calculation, where the target transition density was calculated with the self-consistent Hartree-Fock plus random-phase approximation using the T43 Skyrme interaction. A major part of the expected ß(+) isovector spin monopole strength was found in the measured cross section spectra.

34P(7Li,7Be+γ) reaction at 100A MeV in inverse kinematics.

We report on the first successful extraction of a ß+ Gamow-Teller strength distribution from a radioactive isotope in an intermediate-energy charge-exchange experiment in inverse kinematics. The (7Li,7Be+γ(429 keV)) reaction at 100A MeV was used to measure Gamow-Teller transition strengths from 34P to states in 34Si. The results show that little mixing occurs between sd and pf shell configurations for the low-lying 0+ and 2+ states even though 34Si neighbors the island of inversion and low-lying 2ℏω intruder states exist. Shell-model calculations in the sdpf model space are consistent with these findings.

Bone morphogenetic protein signaling is required for maintenance of differentiated phenotype, control of proliferation, and hypertrophy in chondrocytes.

To examine the role of bone morphogenetic protein (BMP) signaling in chondrocytes during endochondral ossification, the dominant negative (DN) forms of BMP receptors were introduced into immature and mature chondrocytes isolated from lower and upper portions of chick embryo sternum, respectively. We found that control sternal chondrocyte populations expressed type IA, IB, and II BMP receptors as well as BMP-4 and -7. Expression of a DN-type II BMP receptor (termed DN-BMPR-II) in immature lower sternal (LS) chondrocytes led to a loss of differentiated functions; compared with control cells, the DN-BMPR- II-expressing LS chondrocytes proliferated more rapidly, acquired a fibroblastic morphology, showed little expression of type II collagen and aggrecan genes, and upregulated type I collagen gene expression. Expression of DN-BMPR-II in mature hypertrophic upper sternal (US) chondrocytes caused similar effects. In addition, the DN-BMPR-II-expressing US cells exhibited little alkaline phosphatase activity and type X collagen gene expression, while the control US cells produced both alkaline phosphatase and type X collagen. Both DN-BMPR-II-expressing US and LS chondrocytes failed to respond to treatment with BMP-2 . When we examined the effects of DN forms of types IA and IB BMP receptors, we found that DN-BMPR-IA had little effect, while DN-BMPR-IB had similar but weaker effects compared with those of DN-BMPR-II. We conclude that BMP signaling, particularly that mediated by the type II BMP receptor, is required for maintenance of the differentiated phenotype, control of cell proliferation, and expression of hypertrophic phenotype.

Identification of alpha-fodrin as a candidate autoantigen in primary Sjögren's syndrome.

It is unclear whether organ-specific autoantigens are critical for the development of primary Sjögren's syndrome (SS). A 120-kilodalton organ-specific autoantigen was purified from salivary gland tissues of an NFS/sld mouse model of human SS. The amino-terminal residues were identical to those of the human cytoskeletal protein alpha-fodrin. The purified antigen induced proliferative T cell responses and production of interleukin-2 and interferon-gamma in vitro. Neonatal immunization with the 120-kilodalton antigen prevented the disease in mice. Sera from patients with SS reacted positively with purified antigen and recombinant human alpha-fodrin protein, whereas those from patients with systemic lupus erythematosus and rheumatoid arthritis did not. Thus, the immune response to 120-kilodalton alpha-fodrin could be important in the initial development of primary SS.

[Successful treatment of ruptured descending thoracic aortic aneurysm associated with right tension hemothorax during operation].

A 59-year-old man was admitted to the hospital, suspected of the rupture of descending thoracic aortic aneurysm due to sudden back pain. Enhanced computed tomography revealed a ruptured descending thoracic aortic aneurysm with huge hematoma and abdominal aortic aneurysm. Based on the above diagnosis, we performed urgent operation through left thoracotomy under unilateral lung ventilation. While dissecting the aneurysm, sudden hemodynamics deterioration occurred. Although cardiopulmonary bypass was introduced immediately through femoral artery and femoral vein cannulations, hemodynamics was not improved and unilateral lung ventilation got more unmanageable. We diagnosed right tension hemothorax due to the extension of aneurysm rupture into the right thoracic cavity. After placing a cannula at the distal arch for a central perfusion, we clamped the descending thoracic aorta at both the proximal and distal sites of the aneurysm. Thereafter we opened the aneurysm and drained the right thorax through the aneursym's tear. The aneurysm was replaced with a prosthetic woven-Dacron vascular graft. The patient's postoperative condition had been stable with no significant unfavorable event. The abdominal aortic aneurysm was replaced with a bifurcated graft on 51st postoperative day. He was discharged in good condition on the 69th postoperative day.

Atelocollagen-mediated local and systemic applications of myostatin-targeting siRNA increase skeletal muscle mass.

RNA interference (RNAi) offers a novel therapeutic strategy based on the highly specific and efficient silencing of a target gene. Since it relies on small interfering RNAs (siRNAs), a major issue is the delivery of therapeutically active siRNAs into the target tissue/target cells in vivo. For safety reasons, strategies based on vector delivery may be of only limited clinical use. The more desirable approach is to directly apply active siRNAs in vivo. Here, we report the effectiveness of in vivo siRNA delivery into skeletal muscles of normal or diseased mice through nanoparticle formation of chemically unmodified siRNAs with atelocollagen (ATCOL). ATCOL-mediated local application of siRNA targeting myostatin, a negative regulator of skeletal muscle growth, in mouse skeletal muscles or intravenously, caused a marked increase in the muscle mass within a few weeks after application. These results imply that ATCOL-mediated application of siRNAs is a powerful tool for future therapeutic use for diseases including muscular atrophy.

Caveolin-3 regulates myostatin signaling. Mini-review.

Caveolins, components of the uncoated invaginations of plasma membrane, regulate signal transduction and vesicular trafflicking. Loss of caveolin-3, resulting from dominant negative mutations of caveolin-3 causes autosomal dominant limb-girdle muscular dystrophy (LGMD) 1C and autosomal dominant rippling muscle disease (AD-RMD). Myostatin, a member of the muscle-specific transforming growth factor (TGF)-beta superfamily, negatively regulates skeletal muscle volume. Herein we review caveolin-3 suppressing of activation of type I myostatin receptor, thereby inhibiting subsequent intracellular signaling. In addition, a mouse model of LGMD1C has shown atrophic myopathy with enhanced myostatin signaling. Myostatin inhibition ameliorates muscular phenotype in the model mouse, accompanied by normalized myostatin signaling. Enhanced myostatin signaling by caveolin-3 mutation in human may contribute to the pathogenesis of LGMD1C. Therefore, myostatin inhibition therapy may be a promising treatment for patients with LGMD1C. More recent studies concerning regulation of TGF-beta superfamily signaling by caveolins have provided new insights into the pathogenesis of several human diseases.

[Successful surgical treatment of acute pulmonary thromboembolism caused by giant intra-pervic tumor; report of a case].

A 40-year-old woman was admitted to our hospital because of operation for giant intra-pervic tumor. She had a history of deep vein thrombosis. Suddenly she complained severe dyspnea while having a bath, and subsequently cardiogenic shock occurred. Immediately we set up percutaneous cardiopulmonary support (PCPS) for acute pulmonary thromboembolism. Despite thrombolytic therapy including the administration of urokinase and rt-PA, hemodinamics were not improved. Emergent pulmonary embolectomy was performed on-pump beating. Postoperative course was uneventful. The intra-pervic tumor was removed on the 24th postoperative day. She was discharged in good condition on the 38th postoperative day. Quick diagnosis and appropriate therapy are essential in patient with acute massive pulmonary thromboembolism.

Hypoplasia of pancreatic islets in transgenic mice expressing activin receptor mutants.

Activin, a member of the TGF-beta superfamily, regulates the growth and differentiation of a variety of cell types. Based on the expression of activin in pancreatic rudiments of rat embryos and stimulation of insulin secretion from adult rat pancreatic islets by activin, activin is implicated in the development and function of islets. To examine the significance of activin signaling in the fetal and postnatal development of islets, transgenic mice expressing a dominant negative form of activin receptor (dn-ActR) or a constitutively active form of activin receptor (ActR-T206D) in islets were generated together with the transgenic mice expressing intact activin receptor (intact ActR) as a negative control. Transgenic mice with both dn-ActR and ActR-T206D showed lower survival rates, smaller islet area, and lower insulin content in the whole pancreas with impaired glucose tolerance when compared with transgenic mice with intact ActR or littermates, but they showed the same alpha cell/beta cell ratios as their littermates. In addition to islet hypoplasia, the insulin response to glucose was severely impaired in dn-ActR transgenic mice. It is suggested that a precisely regulated intensity of activin signaling is necessary for the normal development of islets at the stage before differentiation into alpha and beta cells, and that activin plays a role in the postnatal functional maturation of islet beta cells.

The characteristics of karyotype and telomeric satellite DNA sequences in the cricket, Gryllus bimaculatus (Orthoptera, Gryllidae).

The chromosomes derived from the Japanese population of Gryllus bimaculatus were characterized by C-banding and Ag-NOR staining. The chromosome number, 2n = 28 + XX (female)/XO (male), corresponded with that of other populations of G. bimaculatus, but the chromosome configuration in idiograms varied between the populations. NORs were carried on one pair of autosomes and appeared polymorphous. The positive C-bands located at the centromere of all chromosomes and the distal regions of many chromosome pairs, and the size and the distribution pattern of the distal C-heterochromatin showed differences among the chromosomes. In addition, this paper reports on the characteristics of HindIII satellite DNA isolated from the genome of G. bimaculatus. The HindIII repetitive fragments were about 0.54 kb long, and localized at the distal C-bands of the autosomes and the interstitial C-bands of the X chromosome. Molecular analysis showed two distinct satellite DNA sequences, named the GBH535 and GBH542 families, with high AT contents of about 67 and 66%, respectively. The two repetitive families seem to be derived from a common ancestral sequence, and both families possessed the same 13-bp palindrome sequence. The results of Southern blot hybridization suggest that the sequence of the GBH535 family is conserved in the genomic DNAs of Gryllus species, whereas the GBH542 family is a species-specific sequence.