Extended p_{3/2} Neutron Orbital and the N=32 Shell Closure in

The one-neutron knockout from ^{52}Ca in inverse kinematics onto a proton target was performed at ∼230 MeV/nucleon combined with prompt γ spectroscopy. Exclusive quasifree scattering cross sections to bound states in ^{51}Ca and the momentum distributions corresponding to the removal of 1f_{7/2} and 2p_{3/2} neutrons were measured. The cross sections, interpreted within the distorted-wave impulse approximation reaction framework, are consistent with a shell closure at the neutron number N=32, found as strong as at N=28 and N=34 in Ca isotopes from the same observables. The analysis of the momentum distributions leads to a difference of the root-mean-square radii of the neutron 1f_{7/2} and 2p_{3/2} orbitals of 0.61(23) fm, in agreement with the modified-shell-model prediction of 0.7 fm suggesting that the large root-mean-square radius of the 2p_{3/2} orbital in neutron-rich Ca isotopes is responsible for the unexpected linear increase of the charge radius with the neutron number.

Pairing Forces Govern Population of Doubly Magic

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.

Angular momentum generation in nuclear fission.

When a heavy atomic nucleus splits (fission), the resulting fragments are observed to emerge spinning1; this phenomenon has been a mystery in nuclear physics for over 40 years2,3. The internal generation of typically six or seven units of angular momentum in each fragment is particularly puzzling for systems that start with zero, or almost zero, spin. There are currently no experimental observations that enable decisive discrimination between the many competing theories for the mechanism that generates the angular momentum4-12. Nevertheless, the consensus is that excitation of collective vibrational modes generates the intrinsic spin before the nucleus splits (pre-scission). Here we show that there is no significant correlation between the spins of the fragment partners, which leads us to conclude that angular momentum in fission is actually generated after the nucleus splits (post-scission). We present comprehensive data showing that the average spin is strongly mass-dependent, varying in saw-tooth distributions. We observe no notable dependence of fragment spin on the mass or charge of the partner nucleus, confirming the uncorrelated post-scission nature of the spin mechanism. To explain these observations, we propose that the collective motion of nucleons in the ruptured neck of the fissioning system generates two independent torques, analogous to the snapping of an elastic band. A parameterization based on occupation of angular momentum states according to statistical theory describes the full range of experimental data well. This insight into the role of spin in nuclear fission is not only important for the fundamental understanding and theoretical description of fission, but also has consequences for the γ-ray heating problem in nuclear reactors13,14, for the study of the structure of neutron-rich isotopes15,16, and for the synthesis and stability of super-heavy elements17,18.

Sequential Nature of (p,3p) Two-Proton Knockout from Neutron-Rich Nuclei.

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.

Two-Neutron Halo is Unveiled in

We report the measurement of reaction cross sections (σ_{R}^{ex}) of ^{27,29}F with a carbon target at RIKEN. The unexpectedly large σ_{R}^{ex} and derived matter radius identify ^{29}F as the heaviest two-neutron Borromean halo to date. The halo is attributed to neutrons occupying the 2p_{3/2} orbital, thereby vanishing the shell closure associated with the neutron number N=20. The results are explained by state-of-the-art shell model calculations. Coupled-cluster computations based on effective field theories of the strong nuclear force describe the matter radius of ^{27}F but are challenged for ^{29}F.

Metastable States of

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 ß∼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.

Quasifree Neutron Knockout from

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.

Prominence of Pairing in Inclusive (p,2p) and (p,pn) Cross Sections from Neutron-Rich Nuclei.

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.

How Robust is the N=34 Subshell Closure? First Spectroscopy of

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.

First Spectroscopy of the Near Drip-line Nucleus

One of the most exotic light neutron-rich nuclei currently accessible for experimental study is ^{40}Mg, which lies at the intersection of the nucleon magic number N=28 and the neutron drip line. Low-lying excited states of ^{40}Mg have been studied for the first time following a one-proton removal reaction from ^{41}Al, performed at the Radioactive Isotope Beam Factory of RIKEN Nishina Center with the DALI2 γ-ray array and the ZeroDegree spectrometer. Two γ-ray transitions were observed, suggesting an excitation spectrum that shows unexpected properties as compared to both the systematics along the Z=12, N≥20 Mg isotopes and available state-of-the-art theoretical model predictions. A possible explanation for the observed structure involves weak-binding effects in the low-lying excitation spectrum.

Shape Evolution in Neutron-Rich Krypton Isotopes Beyond N=60: First Spectroscopy of

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.

Are There Signatures of Harmonic Oscillator Shells Far from Stability? First Spectroscopy of

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.

Role of the Δ Resonance in the Population of a Four-Nucleon State in the

The ^{54}Fe nucleus was populated from a ^{56}Fe beam impinging on a Be target with an energy of E/A=500 MeV. The internal decay via γ-ray emission of the 10^{+} metastable state was observed. As the structure of this isomeric state has to involve at least four unpaired nucleons, it cannot be populated in a simple two-neutron removal reaction from the ^{56}Fe ground state. The isomeric state was produced in the low-momentum (-energy) tail of the parallel momentum (energy) distribution of ^{54}Fe, suggesting that it was populated via the decay of the Δ^{0} resonance into a proton. This process allows the population of four-nucleon states, such as the observed isomer. Therefore, it is concluded that the observation of this 10^{+} metastable state in ^{54}Fe is a consequence of the quark structure of the nucleons.

Widespread blunting of hypothalamic and amygdala-septal activity and behavior in rats with long-term hyperglycemia.

Anxiety and depression in diabetic patients contributes to a poor prognosis, but possible causal relationships have been controversial. Anxiety, fear, and anhedonia are mediated by interactions between different deep structures of the temporal lobe (e.g., amygdala complex and hippocampus) and other forebrain-related structures (e.g., lateral septal nucleus). Connections between these structures and the hypothalamic orexinergic system are necessary for the maintenance of energy and wakefulness. However, few studies have explored the impact of long-term hyperglycemia in these structures on anxiety. We induced long-term hyperglycemia (glucose levels of ∼500mg/dl) in Wistar rats by injecting them with alloxan and simultaneously protecting them from hyperglycemia by injecting them daily with a low dose of insulin (i.e., just enough insulin to avoid death), thus maintaining hyperglycemia and ketonuria for as long as 6 weeks. Compared with controls, long-term hyperglycemic rats exhibited a significant reduction of Fos expression in the lateral septal nucleus and basolateral amygdala, but no differences were found in cerebellar regions. Orexin-A cells appeared to be inactive in the lateral hypothalamus. No differences were found in sucrose consumption or behavior in the elevated plus maze compared with the control group, but a decrease in general locomotion was observed. These data indicate a generalized blunting of the metabolic brain response, accompanied by a decrease in locomotion but no changes in hedonic- or anxiety-like behavior.

New isomers in the full seniority scheme of neutron-rich lead isotopes: the role of effective three-body forces.

The neutron-rich lead isotopes, up to (216)Pb, have been studied for the first time, exploiting the fragmentation of a primary uranium beam at the FRS-RISING setup at GSI. The observed isomeric states exhibit electromagnetic transition strengths which deviate from state-of-the-art shell-model calculations. It is shown that their complete description demands the introduction of effective three-body interactions and two-body transition operators in the conventional neutron valence space beyond (208)Pb.

Integration of active human beta-galactosidase gene (100 kb) into genome using HSV/AAV amplicon vector.

Vectors based on herpes simplex virus type-1 (HSV-1) permit delivery of transgenes of up to 150 kb, while the inverted terminal repeats and Rep of the adeno-associated virus (AAV) can confer site-specific integration into the AAVS1 site, which allows sustained expression of a transgene. In this study, combination of the viral elements in HSV/AAV hybrid vectors has been applied for the infectious transfer of the human lysosomal beta-galactosidase (BGAL) gene of 100 kb. Temporary expression and functional activity of beta-galactosidase (beta-gal) could be detected in human beta-gal-deficient patient and glioblastoma (Gli36) cells upon infection with the basic BGAL amplicon vector. Sustained expression of beta-gal was achieved in Gli36 cells infected with rep-plus, but not rep-minus, HSV/AAV hybrid vectors. None of five clones isolated after rep-minus hybrid vector infection showed elevated beta-gal activity or site-specific integration. In contrast, 80% of the rep-plus clones possessed beta-gal activity at least twofold greater than normal levels for up to 4 months of continuous growth, and 33% of the clones exhibited AAVS1-specific integration of the ITR-flanked transgene. One of the rep-plus clones displayed integration of the ITR cassette only at the AAVS1 site, with no sequences outside the cassette detectable and beta-gal activity fourfold above normal levels. These data demonstrate AAVS1-specific integration of an entire genomic locus and expression of the transgene from the endogenous promoter mediated by an HSV/AAV hybrid vector.

Expression of human ATM cDNA in Atm-deficient mouse brain mediated by HSV-1 amplicon vector.

Ataxia-telangiectasia (A-T) is an autosomal recessive disorder characterized by neurodegeneration, immunodeficiency, cancer predisposition, genome instability, and radiation sensitivity. Herpes simplex virus type 1 (HSV-1) amplicon vectors provide a means to deliver large genes to the nervous system efficiently and safely. We have generated an amplicon vector, carrying human FLAG-tagged A-T mutated (ATM), as well as an enhanced green fluorescent protein (EGFP) marker gene. Due to the lack of effective and reliable antibodies for ATM and FLAG appropriate for immunohistochemistry in mouse tissue sections, expression of the human FLAG-tagged ATM was confirmed in the mouse cerebellum at the RNA level by reverse transcription followed by quantitative PCR, and by radioactive in situ hybridization. In addition, we were able to immunoprecipitate the full-length human ATM protein from the cerebella of Atm -/- mice post-infection. This vector has been injected into the cerebella of Atm -/- mice with gene delivery to thousands of cells, including Purkinje cells, based on the EGFP marker gene. The expression of human FLAG-tagged ATM has been demonstrated in the cerebella of Atm-/- mice at the transcription and translational level three days post-infection. To our knowledge, this is the first report of vector-mediated delivery of the human ATM cDNA to an Atm -/- mouse. These vectors provide the groundwork to develop gene therapy approaches for A-T patients.

HSV-1 amplicon vector-mediated expression of ATM cDNA and correction of the ataxia-telangiectasia cellular phenotype.

Ataxia-telangiectasia (A-T) is an autosomal recessive disorder characterized by neurodegeneration, immunodeficiency, cancer predisposition, genome instability, and radiation sensitivity. Previous research has shown that it is possible to correct the hereditary deficiency A-T by DNA transfection in cell culture, but the large size of the ATM cDNA (9 kb) limits the use of many vector types for gene replacement. HSV-1 amplicon vectors provide a means to deliver large genes to cells efficiently and without toxicity. In this study, the FLAG-tagged cDNA for human ATM was inserted into an HSV-1 amplicon under control of the CMV promoter (designated as HGC-ATM). FLAG-ATM expression was confirmed in 293T/17 cells and human A-T fibroblasts (GM9607) after transduction, by immunoprecipitation, Western analysis, and immunocytochemistry. Functional recovery was assessed by two independent assays. First, in vitro kinase assay showed that vector-derived ATM in GM9607 cells could successfully phosphorylate wt p53 using recombinant GST-p53(1-101). Second, in A-T cells infected with the HGC-ATM vector, the extent of accumulation in G2/M phase at 24 h postirradiation was similar to that observed in cells with wild-type endogenous ATM and lower than that observed in A-T cells infected with a control vector. Thus, these vectors provide a tool to test the feasibility of HSV-amplicons as gene therapy vectors for A-T.

Cancer gene therapy by thyroid hormone-mediated expression of toxin genes.

Many of the strategies developed in the last few years to treat cancer by gene therapy are based on putative killer-suicide genes whose products convert a prodrug into a toxic compound. When the therapy is applied to humans, a vector carrying the killer gene is first inoculated into the tumor of the patient, who 1 week later receives the corresponding prodrug that will selectively kill the cells able to process it to its toxic derivative. A strategy that obviates the need for a prodrug to destroy the cancer cells would be preferable because the patient would only need one treatment instead of two consecutive ones. In the following study, we describe the construction of retroviral vectors in which a reporter or a toxin gene (either the Pseudomonas exotoxin or the Ricinus communis toxin, ricin) is placed under the control of the thyroid hormone (T3) regulatable promoter of the rat myelin basic protein (MBPp). We demonstrate that the expression of these genes under the control of MBPp is regulated by T3 in vitro and in vivo. In vitro, the MBPp is switched off when T3 is removed from the serum of the culture medium, allowing the production of retroviruses carrying the toxic gene. In vivo, the toxin gene bearing retroviruses is capable of eradicating experimentally induced brain tumors in Wistar rats. The gene therapy strategy described here does not require the use of a prodrug to destroy the neoplastic cells.