Evidence for bimodal fission in the heaviest elements

We have measured the mass and kinetic-energy partitioning in the spontaneous fission of five heavy nuclides: /sup 258/Fm, /sup 259/Md, /sup 260/Md /sup 258/No, and /sup 260/(104). Each was produced by heavy-ion reactions with either /sup 248/Cm, /sup 249/Bk, or /sup 254/Es targets. Energies of correlated fragments from the isotopes with millisecond half lives, /sup 258/No and /sup 260/(104), were measured on-line by a special rotating-wheel instrument, while the others were determined off-line after mass separation. All fissioned with mass distributions that were symmetric. Total-kinetic-energy distributions peaked near either 200 or 235 MeV. Surprisingly, because only a single Gaussian energy distribution had been observed previously in actinide fission, these energy distributions were skewed upward or downward from the peak in each case, except for /sup 260/(104), indicating a composite of two energy distributions. We were able to fit accurately two Gaussian curves to the gross energy distributions from the four remaining nuclides. From the multiple TKE distributions and the shapes of the mass distributions, we conclude that there is a low-energy fission component with liquid-drop characteristics which is admixed with a much higher-energy component due to closed fragment shells. We now have further evidence for this conclusion from measurements of the neutron multiplicity in the spontaneous fission of /sup 260/Md. 25 refs., 9 figs

New Fragment Separation Technology for Superheavy Element Research

This project consisted of three major research areas: (1) development of a solid Pu ceramic target for the MASHA separator, (2) chemical separation of nuclear decay products, and (3) production of new isotopes and elements through nuclear reactions. There have been 16 publications as a result of this project, and this collection of papers summarizes our accomplishments in each of the three areas of research listed above. The MASHA (Mass Analyzer for Super-Heavy Atoms) separator is being constructed at the U400 Cyclotron at the Flerov Laboratory of Nuclear Reactions in Dubna, Russia. The purpose of the separator is to physically separate the products from nuclear reactions based on their isotopic masses rather than their decay characteristics. The separator was designed to have a separation between isotopic masses of {+-}0.25 amu, which would enable the mass of element 114 isotopes to be measured with outstanding resolution, thereby confirming their discovery. In order to increase the production rate of element 114 nuclides produced via the {sup 244}Pu+{sup 48}Ca reaction, a new target technology was required. Instead of a traditional thin actinide target, the MASHA separator required a thick, ceramic-based Pu target that was thick enough to increase element 114 production while still being porous enough to allow reaction products to migrate out of the target and travel through the separator to the detector array located at the back end. In collaboration with UNLV, we began work on development of the Pu target for MASHA. Using waste-form synthesis technology, we began by creating zirconia-based matrices that would form a ceramic with plutonium oxide. We used samarium oxide as a surrogate for Pu and created ceramics that had varying amounts of the starting materials in order to establish trends in material density and porosity. The results from this work are described in more detail in Refs. [1,4,10]. Unfortunately, work on MASHA was delayed in Russia because it was found that the efficiency of transporting products from the target chamber to the detector array was much too low for applications in heavy element experiments where production rates are on the order of one atom per day or less. Work continues on the MASHA separator, and once the efficiency has been improved, we plan to continue our work on the Pu target for future element 114 experiments. Due to the delays of the MASHA separator, work on establishing the identity of heavy element species produced through nuclear reactions focused instead on chemical separations. In particular, element 115 decays through a series of alpha decays, terminating with an element 105 isotope with a long half-life ({approx} 1 day). By chemically separating the element 105 daughter and observing its subsequent fission decay, the identity of the original parent nucleus can be established through the genetic correlation of the initial series of alpha decays. Chemical separations of element 105 were developed in Switzerland, Russia, and at LLNL. Over the course of two experiments, reaction products from the {sup 243}Am+{sup 48}Ca reaction were collected in a copper block and subsequently processed for chemical separation of the Group Five elements [8,9,13,15]. The Group Five elements were initially separated from the Group Four species, and then the samples were sub-divided into tantalum and niobium fractions. All of the fission events were observed in the tantalum fractions, which implied that element 105 behaved more like tantalum under the chemical conditions of these experiments. These experiments were very successful, and not only demonstrated that chemical separation could be performed on single atoms of interest, but also lent proof to the identity of the parent nucleus as element 115. Subsequent analysis of the alpha spectra taken during the experiment further prove that the fission events observed during the two experiments came from element 105 as the decay daughter of element 115 and could not attributed to interference from other background species [16]. The final aspect of this project was the production of new isotopes and elements. All of the experiments were performed in Dubna at the U400 Cyclotron and the results are described in more detail in Refs. [2,3,5-8,11,12,14]. The first experiments were designed to establish the decay properties of isotopes of elements 112, 114, and 116 [5]. Because these isotopic signatures were established through these initial experiments, the discovery of element 118 [11] was possible, since the 118 nuclides decayed into these previously studied isotopes. This was the first successful report of the discovery of element 118, which was reported by the media to a large extent. The last experiment that was performed for this project was the production and detection of a new isotope of element 113 [14]

Ceramic Plutonium Target Development for the MASHA Separator for the Synthesis of Element 114

We are currently developing a Pu ceramic target for the MASHA mass separator. MASHA will use a Pu ceramic target capable of tolerating temperatures up to 2000 C. Reaction products will diffuse out of the target into an ion source, and transported through the separator to a position-sensitive focal-plane detector array for mass identification. Experiments on MASHA will allow us to make measurements that will cement our identification of element 114 and provide data for future experiments on chemical properties of the heaviest elements. In this study (Sm,Zr)O{sub 2-x} ceramics are produced and evaluated for studies on the production of Pb (homolog of element 114) by the reaction of Ca on Sm. This work will provide an initial analysis on the feasibility of using a ZrO{sub 2}-PuO{sub 2} as a target for the production of element 114

Constitutively active GSK3 beta as a means to bolster dendritic cell functionality in the face of tumor-mediated immune suppression

In patients with cancer, the functionality of Dendritic Cells (DC) is hampered by high levels of tumor-derived suppressive cytokines, which interfere with DC development and maturation. Poor DC development can limit the efficacy of immune checkpoint blockade and in vivo vaccination approaches. Interference in intracellular signaling cascades downstream from the receptors of major tumor-associated suppressive cytokines like IL-10 and IL-6, might improve DC development and activation, and thus enhance immunotherapy efficacy. We performed exploratory functional screens on arrays consisting of >1000 human kinase peptide substrates to identify pathways involved in DC development and its inhibition by IL-10 or IL-6. The resulting alterations in phosphorylation of the kinome substrate profile pointed to glycogen-synthase kinase-3 beta (GSK3 beta) as a pivotal kinase in both DC development and suppression. GSK3 beta inhibition blocked human DC differentiation in vitro, which was accompanied by decreased levels of IL-12p70 secretion, and a reduced capacity for T cell priming. More importantly, adenoviral transduction of monocytes with a constitutively active form of GSK3 beta induced resistance to the suppressive effects of IL-10 and melanoma-derived supernatants alike, resulting in improved DC development, accompanied by up-regulation of co-stimulatory markers, an increase in CD83 expression levels in mature DC, and diminished release of IL-10. Moreover, adenovirus-mediated intratumoral manipulation of this pathway in an in vivo melanoma model resulted in DC activation and recruitment, and in improved immune surveillance and tumor control. We propose the induction of constitutive GSK3 beta activity as a novel therapeutic means to bolster DC functionality in the tumor microenvironment.Peer reviewe

Adrenal suppression: A practical guide to the screening and management of this under-recognized complication of inhaled corticosteroid therapy

Inhaled corticosteroids (ICSs) are the most effective anti-inflammatory agents available for the treatment of asthma and represent the mainstay of therapy for most patients with the disease. Although these medications are considered safe at low-to-moderate doses, safety concerns with prolonged use of high ICS doses remain; among these concerns is the risk of adrenal suppression (AS). AS is a condition characterized by the inability to produce adequate amounts of the glucocorticoid, cortisol, which is critical during periods of physiological stress. It is a proven, yet under-recognized, complication of most forms of glucocorticoid therapy that can persist for up to 1 year after cessation of corticosteroid treatment. If left unnoticed, AS can lead to significant morbidity and even mortality. More than 60 recent cases of AS have been described in the literature and almost all cases have involved children being treated with ≥500 μg/day of fluticasone

Membrane Potential Controls Adipogenic and Osteogenic Differentiation of Mesenchymal Stem Cells

Background: Control of stem cell behavior is a crucial aspect of developmental biology and regenerative medicine. While the functional role of electrophysiology in stem cell biology is poorly understood, it has become clear that endogenous ion flows represent a powerful set of signals by means of which cell proliferation, differentiation, and migration can be controlled in regeneration and embryonic morphogenesis. Methodology/Principal Findings: We examined the membrane potential (Vmem) changes exhibited by human mesenchymal stem cells (hMSCs) undergoing adipogenic (AD) and osteogenic (OS) differentiation, and uncovered a characteristic hyperpolarization of differentiated cells versus undifferentiated cells. Reversal of the progressive polarization via pharmacological modulation of transmembrane potential revealed that depolarization of hMSCs prevents differentiation. In contrast, treatment with hyperpolarizing reagents upregulated osteogenic markers. Conclusions/Significance: Taken together, these data suggest that the endogenous hyperpolarization is a functiona

Multi-decadal changes in tundra environments and ecosystems: Synthesis of the International Polar Year-Back to the Future Project (IPY-BTF).

Understanding the responses of tundra systems to global change has global implications. Most tundra regions lack sustained environmental monitoring and one of the only ways to document multi-decadal change is to resample historic research sites. The International Polar Year (IPY) provided a unique opportunity for such research through the Back to the Future (BTF) project (IPY project #512). This article synthesizes the results from 13 papers within this Ambio Special Issue. Abiotic changes include glacial recession in the Altai Mountains, Russia; increased snow depth and hardness, permafrost warming, and increased growing season length in sub-arctic Sweden; drying of ponds in Greenland; increased nutrient availability in Alaskan tundra ponds, and warming at most locations studied. Biotic changes ranged from relatively minor plant community change at two sites in Greenland to moderate change in the Yukon, and to dramatic increases in shrub and tree density on Herschel Island, and in sub-arctic Sweden. The population of geese tripled at one site in northeast Greenland where biomass in non-grazed plots doubled. A model parameterized using results from a BTF study forecasts substantial declines in all snowbeds and increases in shrub tundra on Niwot Ridge, Colorado over the next century. In general, results support and provide improved capacities for validating experimental manipulation, remote sensing, and modeling studies

Common Genetic Variants Contribute to Risk of Transposition of the Great Arteries.

RATIONALE: Dextro-transposition of the great arteries (D-TGA) is a severe congenital heart defect which affects approximately 1 in 4,000 live births. While there are several reports of D-TGA patients with rare variants in individual genes, the majority of D-TGA cases remain genetically elusive. Familial recurrence patterns and the observation that most cases with D-TGA are sporadic suggest a polygenic inheritance for the disorder, yet this remains unexplored. OBJECTIVE: We sought to study the role of common single nucleotide polymorphisms (SNPs) in risk for D-TGA. METHODS AND RESULTS: We conducted a genome-wide association study in an international set of 1,237 patients with D-TGA and identified a genome-wide significant susceptibility locus on chromosome 3p14.3, which was subsequently replicated in an independent case-control set (rs56219800, meta-analysis P=8.6x10 CONCLUSIONS: This work provides support for a polygenic architecture in D-TGA and identifies a susceptibility locus on chromosome 3p14.3 nea

Chemical Identification of a Long-Lived Isotope of Dubnium, a Descendant of Element 115

The recognition criterion for discovery of a new chemical element includes two aspects, the characterization properties and the assignment properties. In this paper, we will discuss the status of element 115 experiments that have been performed in Dubna, Russia, highlighting the characterization and assignment properties as they specifically relate to a recent experiment. After discussing the status of what is known about the decay properties of element 115 [1], observed previously using the Dubna Gas-Filled Recoil Separator, we will discuss the prior chemical studies that have been performed on the Db descendant of element 115 [2]. Following the success of that experiment, some additional chemical information was desired. Two separation chemistries were then developed at LLNL and JINR. LLNL utilized reversed phase chromatography and JINR utilized anion exchange chromatography to perform not only +4/+5 separations, but also intra-group separations, where Nb-like and Ta-like fractions were eluted. The results from an experiment using these chemistries for the first time during December 2005 in Dubna, Russia, will be compared with prior chemical results. We will conclude with a discussion of possible enhancements to the work already performed and the current status of the future experimental plans