Asymptotes in SU(2) Recoupling Theory: Wigner Matrices, 3j3j Symbols, and Character Localization

In this paper we employ a novel technique combining the Euler Maclaurin formula with the saddle point approximation method to obtain the asymptotic behavior (in the limit of large representation index $J$) of generic Wigner matrix elements $D^{J}_{MM'}(g)$. We use this result to derive asymptotic formulae for the character $\chi^J(g)$ of an SU(2) group element and for Wigner's $3j$ symbol. Surprisingly, given that we perform five successive layers of approximations, the asymptotic formula we obtain for $\chi^J(g)$ is in fact exact. This result provides a non trivial example of a Duistermaat-Heckman like localization property for discrete sums.Comment: 36 pages, 3 figure

Large-space shell-model calculations for light nuclei

An effective two-body interaction is constructed from a new Reid-like $NN$ potential for a large no-core space consisting of six major shells and is used to generate the shell-model properties for light nuclei from $A$=2 to 6. (For practical reasons, the model space is partially truncated for $A$=6.) Binding energies and other physical observables are calculated and compare favorably with experiment.Comment: prepared using LaTex, 21 manuscript pages, no figure

Thyroid hormone and vitamin D regulate VGF expression and promoter activity

The Siberian hamster (Phodopus sungorus) survives winter by decreasing food intake and catabolizing abdominal fat reserves, resulting in a sustained, profound loss of body weight. Hypothalamic tanycytes are pivotal for this process. In these cells, short-winter photoperiods upregulate deiodinase 3, an enzyme that regulates thyroid hormone availability, and downregulate genes encoding components of retinoic acid (RA) uptake and signaling. The aim of the current studies was to identify mechanisms by which seasonal changes in thyroid hormone and RA signaling from tanycytes might ultimately regulate appetite and energy expenditure. proVGF is one of the most abundant peptides in the mammalian brain, and studies have suggested a role for VGF-derived peptides in the photoperiodic regulation of body weight in the Siberian hamster. In silico studies identified possible thyroid and vitamin D response elements in the VGF promoter. Using the human neuroblastoma SH-SY5Y cell line, we demonstrate that RA increases endogenous VG expression (P!0.05) and VGF promoter activity (P!0.0001). Similarly, treatment with 1,25-ihydroxyvitamin D3 increased endogenous VGF mRNA expression (P!0.05) and VGF promoter activity (P!0.0001),whereas triiodothyronine (T3) decreased both (P!0.01 and P!0.0001). Finally, intrahypothalamic administration of T3 blocked the short day-induced increase in VGF expression in the dorsomedial posterior arcuate nucleus of Siberian hamsters. Thus, we conclude that VGF expression is a likely target of photoperiod-induced changes in tanycyte-derived signals and is potentially a regulator of seasonal changes in appetite and energy expenditure

Ovarian hormones induce de novo DNA methyltransferase expression in the Siberian hamster suprachiasmatic nucleus

Experiments investigated neuroanatomically localized changes in de novo DNA methyltransferase expression in the female Siberian hamster (Phodopus sungorus). The objectives were to identify the neuroendocrine substrates that exhibit rhythmic Dnmt3a and Dnmt3b expression across the oestrous cycle and examine the role of ovarian steroids. Hypothalamic Dnmt3a expression was observed to significantly increase during the transition from proestrous to oestrous. A single bolus injection of diethylstilbestrol (DES) and progesterone was sufficient to increase Dnmt3a cell numbers and Dnmt3b immunoreactive intensity in the suprachiasmatic nucleus (SCN). In vitro analyses using an embryonic rodent cell line revealed that DES was sufficient to induce Dnmt3b expression. Upregulating DNA methylation in vitro reduced expression of vasoactive intestinal polypeptide, Vip, and the circadian clock gene, Bmal1. Together, these data indicate that ovarian steroids drive de novo DNA methyltransferase expression in the mammalian suprachiasmatic nucleus and increased methylation may regulate genes involved in the circadian timing of oestrous: Vip and Bmal1. Overall, epigenetically mediated neuroendocrine reproductive events may reflect an evolutionarily ancient process involved in the timing of female fertility

Theoretical description of deformed proton emitters: nonadiabatic coupled-channel method

The newly developed nonadiabatic method based on the coupled-channel Schroedinger equation with Gamow states is used to study the phenomenon of proton radioactivity. The new method, adopting the weak coupling regime of the particle-plus-rotor model, allows for the inclusion of excitations in the daughter nucleus. This can lead to rather different predictions for lifetimes and branching ratios as compared to the standard adiabatic approximation corresponding to the strong coupling scheme. Calculations are performed for several experimentally seen, non-spherical nuclei beyond the proton dripline. By comparing theory and experiment, we are able to characterize the angular momentum content of the observed narrow resonance.Comment: 12 pages including 10 figure

The use of viral 2A sequence for the simultaneous over-expression of both the vgf gene and enhanced green fluorescent protein eGFP

Introduction: The viral 2A sequence has become an attractive alternative to the traditional internal ribosomal entry site (IRES) for simultaneous over-expression of two genes and in combination with recombinant adeno-associated viruses (rAAV) has been used to manipulate gene expression in vitro.New Method: To develop a rAAV construct in combination with the viral 2A sequence to allow long-term over-expression of the vgf gene and fluorescent marker gene for tracking of the transfected neurones in vivo.Results: Transient transfection of the AAV plasmid containing the vgf gene, viral 2A sequence and eGFP into SH-SY5Y cells resulted in eGFP fluorescence comparable to a commercially available reporter construct. This increase in fluorescent cells was accompanied by an increase in VGF mRNA expression. Infusion of the rAAV vector containing VGF, viral 2A sequence and eGFP resulted in eGFP fluorescence in the hypothalamus of both mice and Siberian hamsters, 32 weeks post infusion. In-situ hybridisation confirmed that the location of VGF mRNA expression in the hypothalamus corresponded to the eGFP pattern of fluorescence.Comparison with old method: The viral 2A sequence is much smaller than the traditional IRES and therefore allowed over-expression of vgf with fluorescent tracking without compromising viral capacity. Conclusion: The use of the viral 2A sequence in the AAV plasmid allowed the simultaneous expression of both genes in vitro. When used in combination with rAAV it resulted in long-term over-expression of both genes at equivalent locations in the hypothalamus of both Siberian hamsters and mice, without any adverse effects

Darkness visible: reflections on underground ecology

1 Soil science and ecology have developed independently, making it difficult for ecologists to contribute to urgent current debates on the destruction of the global soil resource and its key role in the global carbon cycle. Soils are believed to be exceptionally biodiverse parts of ecosystems, a view confirmed by recent data from the UK Soil Biodiversity Programme at Sourhope, Scotland, where high diversity was a characteristic of small organisms, but not of larger ones. Explaining this difference requires knowledge that we currently lack about the basic biology and biogeography of micro-organisms. 2 It seems inherently plausible that the high levels of biological diversity in soil play some part in determining the ability of soils to undertake ecosystem-level processes, such as carbon and mineral cycling. However, we lack conceptual models to address this issue, and debate about the role of biodiversity in ecosystem processes has centred around the concept of functional redundancy, and has consequently been largely semantic. More precise construction of our experimental questions is needed to advance understanding. 3 These issues are well illustrated by the fungi that form arbuscular mycorrhizas, the Glomeromycota. This ancient symbiosis of plants and fungi is responsible for phosphate uptake in most land plants, and the phylum is generally held to be species-poor and non-specific, with most members readily colonizing any plant species. Molecular techniques have shown both those assumptions to be unsafe, raising questions about what factors have promoted diversification in these fungi. One source of this genetic diversity may be functional diversity. 4 Specificity of the mycorrhizal interaction between plants and fungi would have important ecosystem consequences. One example would be in the control of invasiveness in introduced plant species: surprisingly, naturalized plant species in Britain are disproportionately from mycorrhizal families, suggesting that these fungi may play a role in assisting invasion. 5 What emerges from an attempt to relate biodiversity and ecosystem processes in soil is our extraordinary ignorance about the organisms involved. There are fundamental questions that are now answerable with new techniques and sufficient will, such as how biodiverse are natural soils? Do microbes have biogeography? Are there rare or even endangered microbes

Search for the Proton Decay Mode proton to neutrino K+ in Soudan 2

We have searched for the proton decay mode proton to neutrino K+ using the one-kiloton Soudan 2 high resolution calorimeter. Contained events obtained from a 3.56 kiloton-year fiducial exposure through June 1997 are examined for occurrence of a visible K+ track which decays at rest into mu+ nu or pi+ pi0. We found one candidate event consistent with background, yielding a limit, tau/B > 4.3 10^{31} years at 90% CL with no background subtraction.Comment: 13 pages, Latex, 3 tables and 3 figures, Accepted by Physics Letters

IL-7 Receptor Mutations and Steroid Resistance in Pediatric T cell Acute Lymphoblastic Leukemia: A Genome Sequencing Study

Background: Pediatric acute lymphoblastic leukemia (ALL) is the most common childhood cancer and the leading cause of cancer-related mortality in children. T cell ALL (T-ALL) represents about 15% of pediatric ALL cases and is considered a high-risk disease. T-ALL is often associated with resistance to treatment, including steroids, which are currently the cornerstone for treating ALL; moreover, initial steroid response strongly predicts survival and cure. However, the cellular mechanisms underlying steroid resistance in T-ALL patients are poorly understood. In this study, we combined various genomic datasets in order to identify candidate genetic mechanisms underlying steroid resistance in children undergoing T-ALL treatment. Methods and Findings: We performed whole genome sequencing on paired pre-treatment (diagnostic) and post-treatment (remission) samples from 13 patients, and targeted exome sequencing of pre-treatment samples from 69 additional T-ALL patients. We then integrated mutation data with copy number data for 151 mutated genes, and this integrated dataset was tested for associations of mutations with clinical outcomes and in vitro drug response. Our analysis revealed that mutations in JAK1 and KRAS, two genes encoding components of the interleukin 7 receptor (IL7R) signaling pathway, were associated with steroid resistance and poor outcome. We then sequenced JAK1, KRAS, and other genes in this pathway, including IL7R, JAK3, NF1, NRAS, and AKT, in these 69 T-ALL patients and a further 77 T-ALL patients. We identified mutations in 32% (47/146) of patients, the majority of whom had a specific T-ALL subtype (early thymic progenitor ALL or TLX). Based on the outcomes of these patients and their prednisolone responsiveness measured in vitro, we then confirmed that these mutations were associated with both steroid resistance and poor outcome. To explore how these mutations in IL7R signaling pathway genes cause steroid resistance and subsequent poor outcome, we expressed wild-type and mutant IL7R signaling molecules in two steroid-sensitive T-ALL cell lines (SUPT1 and P12 Ichikawa cells) using inducible lentiviral expression constructs. We found that expressing mutant IL7R, JAK1, or NRAS, or wild-type NRAS or AKT, specifically induced steroid resistance without affecting sensitivity to vincristine or L-asparaginase. In contrast, wild-type IL7R, JAK1, and JAK3, as well as mutant JAK3 and mutant AKT, had no effect. We then performed a functional study to examine the mechanisms underlying steroid resistance and found that, rather than changing the steroid receptor’s ability to activate downstream targets, steroid resistance was associated with strong activation of MEK-ERK and AKT, downstream components of the IL7R signaling pathway, thereby inducing a robust antiapoptotic response by upregulating MCL1 and BCLXL expression. Both the MEK-ERK and AKT pathways also inactivate BIM, an essential molecule for steroid-induced cell death, and inhibit GSK3B, an important regulator of proapoptotic BIM. Importantly, treating our cell lines with IL7R signaling inhibitors restored steroid sensitivity. To address clinical relevance, we treated primary T-ALL cells obtained from 11 patients with steroids either alone or in combination with IL7R signaling inhibitors; we found that including a MEK, AKT, mTOR, or dual PI3K/mTOR inhibitor strongly increased steroid-induced cell death. Therefore, combining these inhibitors with steroid treatment may enhance steroid sensitivity in pat