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A long-standing question in nuclear physics is whether chargeless nuclear systems can exist. To our knowledge, only neutron stars represent near-pure neutron systems, where neutrons are squeezed together by the gravitational force to very high densities. The experimental search for isolated multi-neutron systems has been an ongoing quest for several decades1, with a particular focus on the four-neutron system called the tetraneutron, resulting in only a few indications of its existence so far2–4, leaving the tetraneutron an elusive nuclear system for six decades. Here we report on the observation of a resonance-like structure near threshold in the four-neutron system that is consistent with a quasi-bound tetraneutron state existing for a very short time. The measured energy and width of this state provide a key benchmark for our understanding of the nuclear force. The use of an experimental approach based on a knockout reaction at large momentum transfer with a radioactive high-energy 8He beam was key.

The Fas/Fas ligand (Fas-L) system has been established as one of the regulatory pathways of apoptotic cell death. Fas is a type I membrane protein which belongs to the tumour [...]

Exotic nuclei are characterized by having a number of neutrons (or protons) in excess relative to stable nuclei. Their shell structure, which represents single-particle motion in a nucleus1,2, may vary due to nuclear force and excess neutrons3–6, in a phenomenon called shell evolution7. This effect could be counterbalanced by collective modes causing deformations of the nuclear surface8. Here, we study the interplay between shell evolution and shape deformation by focusing on the magnetic moment of an isomeric state of the neutron-rich nucleus 75Cu. We measure the magnetic moment using highly spin-controlled rare-isotope beams and achieve large spin alignment via a two-step reaction scheme9that incorporates an angular-momentum-selecting nucleon removal. By combining our experiments with numerical simulations of many-fermion correlations, we find that the low-lying states in 75Cu are, to a large extent, of single-particle nature on top of a correlated 74Ni core. We elucidate the crucial role of shell evolution even in the presence of the collective mode, and within the same framework we consider whether and how the double magicity of the 78Ni nucleus is restored, which is also of keen interest from the perspective of nucleosynthesis in explosive stellar processes.

Optimal pre-hospital care for out-of-hospital cardiac arrest (OHCA) caused by respiratory disease may differ from that for OHCA associated with other aetiologies, especially with respect to respiratory management. We aimed to investigate whether pre-hospital advanced airway management (AAM) was associated with favourable outcomes after OHCA caused by intrinsic respiratory disease. This nationwide, population-based, propensity score–matched study of adult patients in Japan with OHCA due to respiratory disease from 1 January 2005 to 31 December 2012 compared patients with and without pre-hospital AAM. The primary outcome was neurologically favourable survival at one month after the OHCA. Of 49,534 eligible patients, 20,458 received pre-hospital AAM and 29,076 did not. In a propensity score–matched cohort (18,483 versus 18,483 patients), the odds of neurologically favourable survival were significantly lower for patients receiving pre-hospital AAM (0.6% versus 1.5%; odds ratio [OR] 0.42 [95% confidence interval {CI} 0.34 to 0.52]). The results from multivariable logistic regression analysis also showed that pre-hospital AAM was significantly associated with a decreased chance of neurologically favourable survival (adjusted OR 0.43 [95% CI 0.35 to 0.52]). Similar findings were observed for one-month survival and pre-hospital return of spontaneous circulation. In subgroup analyses, pre-hospital AAM was associated with poor neurological outcomes, regardless of the type of airway device used (laryngeal mask airway, adjusted OR 0.35 [95% CI 0.19 to 0.57]; oesophageal obturator airway, adjusted OR 0.44 [95% CI 0.35 to 0.55]; and endotracheal tube, adjusted OR 0.47 [95% CI 0.30 to 0.69]). In conclusion, pre-hospital AAM was associated with poor neurological outcome among patients with OHCA caused by intrinsic respiratory disease.

Androgen receptor (AR) functions as a ligand-dependent transcription factor to regulate its downstream signaling for prostate cancer progression. AR complex formation by multiple transcription factors is important for enhancer activity and transcriptional regulation. However, the significance of such collaborative transcription factors has not been fully understood. In this study, we show that Oct1, an AR collaborative factor, coordinates genome-wide AR signaling for prostate cancer growth. Using global analysis by chromatin immunoprecipitation sequencing (ChIP-seq), we found that Oct1 is recruited to AR-binding enhancer/promoter regions and facilitates androgen signaling. Moreover, a major target of AR/Oct1 complex, acyl-CoA synthetase 3 (ACSL3), contributes to tumor growth in nude mice, and its high expression is associated with poor prognosis in prostate cancer patients. Next, we examined the therapeutic effects of pyrrole-imidazole polyamides that target the Oct1-binding sequence identified in the center of the ACSL3 AR-binding site. We observed that treatment with Oct1 polyamide severely blocked the Oct1 binding at the ACSL3 enhancer responsible for its transcriptional activity and ACSL3 induction. In addition, Oct1 polyamides suppressed castration-resistant tumor growth and specifically repressed global Oct1 chromatin association and androgen signaling in prostate cancer cells, with few nonspecific effects on basal promoter activity. Thus, targeting Oct1 binding could be a novel therapeutic strategy for AR-activated castration-resistant prostate cancer.

Tomato (Solanum lycopersicum L., Solanaceae) is an excellent model plant for genomic research of solanaceous plants, as well as for studying the development, ripening, and metabolism of fruit. In 2003, the International Solanaceae Project (SOL, www.sgn.cornell.edu) was initiated by members from more than 30 countries, and the tomato genome- sequencing project is currently underway. Genome sequence of tomato obtained by this project will provide a firm foundation for forthcoming genomic studies such as the comparative analysis of genes conserved among the Solanaceae species and the elucidation of the functions of unknown tomato genes. To exploit the wealth of the genome sequence information, there is an urgent need for novel resources and analytical tools for tomato functional genomics. Here, we present an overview of the development of genetic and genomic resources of tomato in the last decade, with a special focus on the activities of Japan SOL and the National Bio-Resource Project in the development of functional genomic resources of a model cultivar, Micro-Tom.

By taking advantage of the high efficiency of the Coulomb dissociation method, we studied the stellar 22Mg(p, γ)23Al reaction. The radiative width Γγ of the first excited state in 23Al was determined by measuring the intermediate-energy 23Al → 22Mg + p breakup process with a lead target.

Surface treatment using alkaline solutions was attempted to enhance the surface hydrophilicity and enzymatic hydrolyzability of hydrophobic poly(L-lactide) [ie poly(L-lactic acid) (PLLA) and poly(ɛ-caprolactone) (PCL). The alkaline treatment was performed by immersing the PLLA and PCL films in 0.01 and 4 N NaOH solutions, respectively, for various periods of time. The effects of the alkaline treatment on the hydrophilicity of the films were monitored by dynamic contact angle measurements, while the enzymatic hydrolyzability of the PLLA and PCL films after the alkaline treatment were evaluated by weight losses in the presence of proteinase K and Rhizopus arrhizus lipase, respectively. With the alkaline treatment the hydrophilicity of the PLLA and PCL films was controllable in the advancing contact angle (θ_a) ranges of 84-108° and of 69-93°, respectively, by varying the alkaline treatment time. The enzymatic hydrolysis rates of the PLLA films became higher with decrease of the θ_a, irrespective of the crystallinity, strongly suggesting that the surface hydrophilicity or the surface molecular weight is crucial to determine their enzymatic hydrolyzability. In contrast, the enzymatic hydrolyzability of the PCL films remained unchanged even when the θ_a decreased from 93° to 73° by alkaline treatment for 4 h. However, prolonged alkaline treatment for periods of time exceeding 4 h, which insignificantly altered the θ_a but caused the formation of pores and cracks on the PCL film surface, accelerated the enzymatic hydrolysis of the PCL films. This indicates that the enzymatic hydrolyzability of the PCL film depends on the surface area per unit weight rather than the surface hydrophilicity. Copyright © 2003 Society of Chemical Industry

Chronic renal failure patients usually develop secondary hyperparathyroidism and, as the disease progresses, there is a decrease in the number of vitamin D and calcium-sensing receptors (CaRs) in the parathyroid glands. Parathyroid cell function can be controlled if a functional gene is transferred into these cells using an adenovirus vector. Vitamin D or CaR genes transferred by the infected adenovirus vector induced a reduction in parathyroid hormone secretion. These results suggest that adenovirus-mediated gene transfer is a useful technique for control of parathyroid cell function.

The purpose of the present study is to evaluate the static strength of thick plate laser welded lap joints. The strength of thin sheet laser welded lap joints of thickness less than 1·6 mm has already been reported, but the strength of thick plate laser welded lap joints having a thickness greater than 10 mm is not known. It is the opinion of the present authors that application of such a thick laser welded lap joint to sandwich panel fabrication presents revolutionary opportunities for heavy industry. Mechanical tests have been conducted on 10 mm–6 mm thickness laser welded lap joints to determine their static strength. The measured nominal shear stress is found to be almost the same as the tensile strength of the weld metal. This result is significantly different to that for thin sheet laser welded lap joints. In the present report, the fracture criteria for thick plate laser welded lap joints are clarified.

This paper describes effective photocurrent generation based on a polymer Langmuir−Blodgett (LB) monolayer containing ruthenium complex on a silver electrode excited by surface plasmon resonance (SPR). It was found that photocurrent generation is greatly enhanced at an incident angle where the electromagnetic field was most enhanced by SPR. At this angle, the photocurrent is enhanced by a factor of 23.6 compared with that at the critical angle for total internal reflection. The incident monochromatic photon-to-current conversion efficiency was 9.53 × 10^-3%, higher than that of the corresponding polymer LB monolayer film on a transparent indium tin oxide electrode with conventional direct transmitted light (2.87 × 10^-3%). Furthermore, it was demonstrated that precoating with poly(N-dodecylacrylamide) homopolymer ensures adequate separation of the Ru(bpy)3²⁺ and silver surface, thereby suppressing the quenching of photoexcited Ru(bpy)3²⁺ by the silver. Controlling the distance between the Ru(bpy)3²⁺ layer and the silver using the Langmuir−Blodgett technique leads to effective photoexcitation of Ru(bpy)3²⁺ by SPR and suppression of quenching by the silver surface, resulting in efficient photocurrent generation.

Abstract:: Experimental studies on in-beam γ-ray spectroscopy using a 12Be radioactive beam are presented. Inelastic scattering of the neutron-rich 12Be nucleus on 208Pb, 12C, and (CH2)n targets has been studied by measuring de-excitation γ-rays in coincidence with scattered particles. The level schemes and transition probabilities are determined for low-lying excited states in 12Be. The present paper presents a brief review of the spectroscopic results, which may be associated with the N = 8 shell quenching near the drip line.

Abstract:: The electric quadrupole moment of 17B and the g-factor of 17C were measured by using the fragmentation-induced nuclear polarization technique combined with the β-NMR method. The experimental quadrupole moment of 17B is found strikingly close to that of the neutron closed-shell isotope 13B, indicating a strong quenching of the neutron E2 core-polarization charge. From the result obtained for the 17C g-factor, we can conclude that the ground-state spin-parity of 17C is 3/2+.

The highly neutron-rich nucleus 34Mg has been studied via Coulomb excitation using a radioactive 34Mg beam at 44.9 MeV/nucleon with a Pb target. The B(E2;0+g.s.→2+1) value for the previously proposed 2+1state in 34Mg was determined for the first time to be 631(126) e2fm4. This value corresponds to the quadrupole deformation parameter β2of 0.58(6), implying an anomalously large deformation of 34Mg.

An intramolecular enantiodivergent synthesis of both enantiomers of the ABCDE-ring analogue 22 of fredericamycin A is reported. Key steps involve an intramolecular [4 + 2] cycloaddition of 17 and an aromatic Pummerer-type reaction of 19. A lipase-catalyzed enantioselective desymmetrization of prochiral diol 2 using 1-ethoxyvinyl 2-furoate 3 led to the pivotal intermediate (R)-4.

Abstract: Magnetic dipole and electric quadrupole moments of nuclei in the light-mass neutron-rich region have been studied by taking advantage of spin-polarized radioactive nuclear beams that have been obtained from the projectile fragmentation reaction. Analyses of the results reveal a few interesting phenomena characteristic of nuclear structures in this region. In particular, we report in some detail the latest result on the magnetic moment of the 17C ground state. The distinctly small value of the g-factor obtained, |g(17C)|=0.50540.0025, clearly excludes a I π=1/2+ candidate for the spin-parity assignment of this marginally bound nucleus, providing a reasonable account of the non-halo nature reported in recent breakup reaction experiments. Finally, future plans at the upcoming radioactive beam facility presently under construction at RIKEN are briefly mentioned.

Abstract: Colloidal magnetite particles coated with chondroitin sulfate (abbreviated as Fe/CS) were prepared under conditions of varying Fe(II) fractions at a fixed Fe concentration and a given concentration of CS. The average size of the magnetite core region was estimated as 7 nm from transmittance electron microscopy measurements, while the size of the Fe/CS particles ranged 155–175 nm, as estimated using Rayleigh scattering measurements by reference to a control size derived from the dynamic light scattering. The reaction of various Fe/CS with NO−2 in aqueous solutions was determined by fluorometry using 2,3-diaminonaphthalene as a probe and by gas chromatography–mass spectrometry. The concentrations of NO−2 in the reaction mixtures decreased in the presence of Fe/CS to a greater extent under Ar compared with aerobic conditions. The reactivity of Fe/CS toward NO−2 under aerobic conditions increased with decreasing the size of Fe/CS particles or with increasing content of Fe(III) in the Fe/CS solutions, but was independent of the Fe(II) fraction in the preparation process. While CS molecules had no influence on the NO−2 decomposition, those coated with the magnetite core may prevent the diffusion of NO−2 to be adsorbed on the core surfaces. NO−2 was concluded to undergo redox reactions with Fe(II) and Fe(III) located on the core surface of magnetite crystalline structures of Fe/CS.

Measurements of CO(2) permeability in oocytes and liposomes containing water channel aquaporin-1 (AQP1) have suggested that AQP1 is able to transport both water and CO(2). We studied the physiological consequences of CO(2) transport by AQP1 by comparing CO(2) permeabilities in erythrocytes and intact lung of wild-type and AQP1 null mice. Erythrocytes from wild-type mice strongly expressed AQP1 protein and had 7-fold greater osmotic water permeability than did erythrocytes from null mice. CO(2) permeability was measured from the rate of intracellular acidification in response to addition of CO(2)/HCO(3)(-) in a stopped-flow fluorometer using 2',7'-bis-(2-carboxyethyl)-5-(and -6)-carboxyfluorescein (BCECF) as a cytoplasmic pH indicator. In erythrocytes from wild-type mice, acidification was rapid (t((1)/(2)), 7.3 +/- 0.4 ms, S.E., n = 11 mice) and blocked by acetazolamide and increasing external pH (to decrease CO(2)/HCO(3)(-) ratio). Apparent CO(2) permeability (P(CO(2))) was not different in erythrocytes from wild-type (0.012 +/- 0.0008 cm/s) versus null (0.011 +/- 0.001 cm/s) mice. Lung CO(2) transport was measured in anesthetized, ventilated mice subjected to a decrease in inspired CO(2) content from 5% to 0%, producing an average decrease in arterial blood pCO(2) from 77 +/- 4 to 39 +/- 3 mm Hg (14 mice) with a t((1)/(2)) of 1.4 min. The pCO(2) values and kinetics of decreasing pCO(2) were not different in wild-type versus null mice. Because AQP1 deletion did not affect CO(2) transport in erythrocytes and lung, we re-examined CO(2) permeability in AQP1-reconstituted liposomes containing carbonic anhydrase (CA) and a fluorescent pH indicator. Whereas osmotic water permeability in AQP1-reconstituted liposomes was >100-fold greater than that in control liposomes, apparent P(CO(2)) (approximately 10(-3) cm/s) did not differ. Measurements using different CA concentrations and HgCl(2) indicated that liposome P(CO(2)) is unstirred layer-limited and that HgCl(2) slows acidification because of inhibition of CA rather than AQP1. These results provide direct evidence against physiologically significant AQP1-mediated CO(2) transport and establish an upper limit to the CO(2) permeability through single AQP1 water channels.

The ion exchange of Pb2+and Cl−into calcium hydroxyapatite from aqueous solutions is studied at 293 K. Although the exchange of Cl−into CaHAp and PbHAp was not observed, in the presence of both Pb2+and Cl−in aqueous solution the exchange of both Pb2+and Cl−into CaHAp occurred, and, at least at intermediate concentrations of HCl, a proportionality between the sorbed quantities of these two ions was observed. The dissolution of CaHAp is shown to be dependent upon the pH, while the quantity of Pb2+exchanged into the solid is not a function of the proton content; consequently, the exchange is not primarily a dissolution–precipitation process.

An allene-doped liquid argon ionization chamber with 48mm×48mm×40mm sensitive volume has been constructed for precise energy measurement of heavy ions at around 100MeV/n. An energy resolution of 0.6%–0.7% (FWHM) was achieved for Ca and Ar ions both at 78MeV/n.

Our previous studies showed that mice during infancy are highly susceptible to the induction of several types of solid tumors. The present study was designed to elucidate the dose-response relationships for induction of solid tumors after exposure to 0.48-5.70 Gy of 137Cs gamma rays in the neonatal period in female mice. A total of 2988 mice were allowed to live out their life span under a specific pathogen free condition and lifetime incidences of liver, pituitary, ovarian, lung and bone tumors were recorded. The dose-response curves for liver, pituitary, ovarian and lung tumors were convex upward in the dose range examined, and were composed of three parts: an initial rapid increase of incidence at doses below 1 Gy, a gradual increase to the highest incidence, and a decrease in incidence with increasing dose in the higher dose range. The dose which induces neoplasm at the highest incidence seemed to be different for each type of solid tumor. The shape of the dose-response curve for induction of bone tumors was quite different from that for other solid tumors; the initial slope of the curve was concave upward. Dose-response relationships were analyzed using a model that allows for tumorigenic effect, inactivation of potentially tumorigenic cells and competing risks. The results showed that the tumorigenic effect was proportional to the dose of gamma rays for induction of liver, pituitary, ovarian and lung tumors; whereas the tumorigenic effect for bone tumors was proportional to the square of the dose. A significant increase in incidence was also found for gastrointestinal tumors, kidney tumors, adrenal tumors and hemangiomas of spleen, although dose-response relationships could not be analyzed.

In vivoeuterium MR imaging (2H MR) was investigated in rats after intraperitoneal administration of deuterated saline, and a dynamic study of the water movement in rat eyes was performed. Deuterium MR imaging was carried out by means of a gradient-echo (GRE) and a spin-echo (SE) pulse sequence. The rat eye was imaged in 2H MR more selectively by SE than by GRE, but a lower signal-to-noise ratio was obtained in 2H MR imaging using the SE sequence. The MR signal intensity of the rat eye was followed by a 3-compartment model, which enabled determination of the flow rate constant of the water in the eye (0.359/min). Deuterium MR imaging is useful to visualize the dynamic change of water in rat eyes using 2H MR at the same magnetic field (2 T) that can also be used for conventional MR imaging in humans.

Abstract: Selection of a cell line suitable for a hybrid artificial liver model employing cellulose porous beads (CPBs) was investigated. Hep G2 cells grown in a culture dish exhibited appreciably higher ureogenesis and gluconeogenesis activities than those grown in CPBs. SEM observation of CPBs revealed marked difference in the distribution of attached cells from one bead to another, and showed that almost all the cell-bearing micropores were completely packed with cells. With the aim of selecting a cell line not prone to excessive aggregation and which grows moderately so as not to fill up the micropores, cells of 6 cell lines, HLE, HLF, Hep 3B, PLC/PRF/5, Huh 7 and Hep G2, were cultivated in dishes. Hep G2, HLE, and HLF increased to 5 × 105 cells/cm2, whereas PLC/PRF/5 grew only to 5 × 104, and Hep 3B and Huh 7 up to 2 × 104 cells/cm2. The specific activities of ureogenesis and gluconeogenesis of Huh 7 were the highest among the lines tested - 42- and 7-fold those of Hep G2, respectively. When the 6 cell lines were grown in a submerged culture with 0.6 g/l of CPBs, Huh 7 had the lowest cell concentration of 0.54 × 106 cells/ml, and the highest activities of ammonia consumption and urea and glucose production (1.38 μ mol NH3, 99 nmol urea, and 14.5 nmol glucose/106cells/h). Consequently, Huh 7 is considered to be a suitable cell line for use in the development of an artificial liver model employing porous beads.

In vivo deuterium MR imaging (2H MR) was investigated in rats after intraperitoneal administration of deuterated saline, and a dynamic study of the water movement in rat eyes was performed. Deuterium MR imaging was carried out by means of a gradient-echo (GRE) and a spin-echo (SE) pulse sequence. The rat eye was imaged in 2H MR more selectively by SE than by GRE, but a lower signal-to-noise ratio was obtained in 2H MR imaging using the SE sequence. The MR signal intensity of the rat eye was followed by a 3-compartment model, which enabled determination of the flow rate constant of the water in the eye (0.359/min). Deuterium MR imaging is useful to visualize the dynamic change of water in rat eyes using 2H MR at the same magnetic field (2 T) that can also be used for conventional MR imaging in humans.

By means of magnetic resonance imaging (MRI), the proton spin-lattice relaxation times (T1 values) of the skeletal muscles were measured in Duchenne muscular dystrophy (DMD) carriers and normal controls. The bound water fraction (BWF) was calculated form the T1 values obtained, according to the fast proton diffusion model. In the DMD carriers, T1 values of the gluteus maximus and quadriceps femoris muscles were significantly higher, and BWFs of these muscles were significantly lower, than in normal control. Degenerative muscular changes accompanied by interstitial edema were presumed responsible for this abnormality. No correlation was observed between the muscle T1 and serum creatine kinase values. The present study showed that MRI could be a useful method for studying the dynamic state of water in both normal and pathological skeletal muscles. Its possible utility for DMD carrier detection was discussed briefly.