260 research outputs found

    Bonn Potential and Shell-Model Calculations for 206,205,204Pb

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    The structure of the nuclei 206,205,204Pb is studied interms of shell model employing a realistic effective interaction derived from the Bonn A nucleon-nucleon potential. The energy spectra, binding energies and electromagnetic properties are calculated and compared with experiment. A very good overall agreement is obtained. This evidences the reliability of our realistic effective interaction and encourages use of modern realistic potentials in shell-model calculations for heavy-mass nuclei.Comment: 4 pages, 4 figures, submitted to Physical Review

    HPV sensitizes OPSCC cells to cisplatin-induced apoptosis by inhibiting autophagy through E7-mediated degradation of AMBRA1

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    Oropharyngeal squamous cell carcinoma (OPSCC) is an increasing world health problem with a more favorable prognosis for patients with human papillomavirus (HPV)-positive tumors compared to those with HPV-negative OPSCC. How HPV confers a less aggressive phenotype, however, remains undefined. We demonstrated that HPV-positive OPSCC cells display reduced macroautophagy/autophagy activity, mediated by the ability of HPV-E7 to interact with AMBRA1, to compete with its binding to BECN1 and to trigger its calpain-dependent degradation. Moreover, we have shown that AMBRA1 downregulation and pharmacological inhibition of autophagy sensitized HPV-negative OPSCC cells to the cytotoxic effects of cisplatin. Importantly, semi-quantitative immunohistochemical analysis in primary OPSCCs confirmed that AMBRA1 expression is reduced in HPV-positive compared to HPV-negative tumors. Collectively, these data identify AMBRA1 as a key target of HPV to impair autophagy and propose the targeting of autophagy as a viable therapeutic strategy to improve treatment response of HPV-negative OPSCC. Abbreviations: AMBRA1: autophagy and beclin 1 regulator 1; CDDP: cisplatin (CDDP); FFPE: formalin-fixed paraffin-embedded (FFPE); HNC: head and neck cancers (HNC); HPV: human papillomavirus (HPV); hrHPV: high risk human papillomavirus (hrHPV); OCSCC: oral cavity squamous carcinomas (OCSSC); OPSCC: oropharyngeal squamous cell carcinoma (OPSCC); OS: overall survival (OS); qPCR: quantitative polymerase chain reaction; RB1: RB transcriptional corepressor 1; ROC: receiver operating characteristic curve (ROC)

    Particle-hole excited states in 133 Te

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    Excited states in neutron-rich 133Te{}^{133}\mathrm{Te} have been identified with the Gamma sphere array by measuring three- and higher-fold prompt coincidence events following spontaneous fission of 252Cf.{}^{252}\mathrm{Cf}. Four types of particle-hole bands built on the known 334.3 keV isomer in 133Te{}^{133}\mathrm{Te} are identified. The yrast and near yrast particle-hole states observed up to 6.2 MeV in 133Te{}^{133}\mathrm{Te} have characteristics quite similar to those in 134Te.{}^{134}\mathrm{Te}. These states are interpreted as a result of coupling a neutron \ensuremath{\nu}{h}_{11/2} hole to the 134Te{}^{134}\mathrm{Te} core. The group of states observed above 5.214 MeV is the result of a neutron particle-hole excitation of the double magic core nucleus 132Sn,{}^{132}\mathrm{Sn}, and is a candidate for a tilted rotor band. Shell-model calculations considering 132Sn{}^{132}\mathrm{Sn} as a closed core have been performed and have provided guidance to the interpretation of the levels below 4.3 MeV. Very good agreement between theory and experiment is obtained for these states

    Identification and shell model calculation of high spin states in 137,138Cs nuclei

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    High spin states of 137,138Cs^{137,138}\mathrm{Cs} have been studied by measuring \ensuremath{\gamma}\text{\ensuremath{-}}\ensuremath{\gamma}\text{\ensuremath{-}}\ensuremath{\gamma} coincidences from the spontaneous fission of 252Cf^{252}\mathrm{Cf} with the LBNL Gammasphere detector array. The high spin level scheme of the N=83N=83 neutron-rich Cs (Z=55Z=55) isotope, 138Cs^{138}\mathrm{Cs}, built on the {6}^{\ensuremath{-}} isomeric state, has been established for the first time up to a 4626 keV level, assigned (16+{16}^{+}). The level scheme of 137Cs^{137}\mathrm{Cs} has been expanded up to a 5495 keV level, assigned (31/{2}^{\ensuremath{-}}). Spins, parities, and configurations are assigned based on the agreement between experimental level energies and shell model calculations and level systematics. Similarities are observed in the N=82N=82 isotones, 137Cs^{137}\mathrm{Cs} and 135I^{135}\mathrm{I}, up to 17/2+17/{2}^{+} as well as in the N=83N=83 isotones, 138Cs^{138}\mathrm{Cs} and 136I^{136}\mathrm{I}, up to {12}^{\ensuremath{-}}. The shell model calculations indicate the important role played by interactions between the excitation of the valence protons outside the Z=50Z=50 major shell and the f7/2{f}_{7/2} valence neutron outside the N=82N=82 major shell

    Signatures of three-nucleon interactions in few-nucleon systems

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    Recent experimental results in three-body systems have unambiguously shown that calculations based only on nucleon-nucleon forces fail to accurately describe many experimental observables and one needs to include effects which are beyond the realm of the two-body potentials. This conclusion owes its significance to the fact that experiments and calculations can both be performed with a high accuracy. In this review, both theoretical and experimental achievements of the past decade will be underlined. Selected results will be presented. The discussion on the effects of the three-nucleon forces is, however, limited to the hadronic sector. It will be shown that despite the major successes in describing these seemingly simple systems, there are still clear discrepancies between data and the state-of-the-art calculations.Comment: accepted for publication in Rep. Prog. Phy

    Public responses to CO2 storage sites: Lessons from five European cases

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    Studies of the factors involved in public perceptions of CO2 storage projects reveal a level of complexity and diversity that arguably confounds a comprehensive theoretical account. To some extent, a conceptual approach that simply organises the relevant social scientific knowledge thematically, rather than seeking an integrated explanation, is as useful as any single account that fails to do justice to the contingencies involved. This paper reviews and assembles such knowledge in terms of six themes and applies these themes to five European cases of carbon capture and storage (CCS) implementation. We identify the main factors involved in community responses to CCS as relating to: the characteristics of the project; the engagement process; risk perceptions; the actions of the stakeholders; the characteristics of the community, and the socio-political context

    Hypoxia-inducible factor-2α regulates the expression of TRAIL receptor DR5 in renal cancer cells

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    To understand the role of hypoxia-inducible factor (HIF)-2α in regulating sensitivity of renal cancer cells to tumor necrosis factor-related apoptosis inducing ligand (TRAIL)-induced apoptosis, we transfected wild-type and mutant von Hippel Lindau (VHL) proteins into TRAIL-sensitive, VHL-negative A498 cells. We find that wild-type VHL, but not the VHL mutants S65W and C162F that do not degrade HIF proteins, cause TRAIL resistance. Knock down of the HIF-2α protein by RNA interference (short hairpin RNA) blocked TRAIL-induced apoptosis, decreased the level of TRAIL receptor (DR5) protein and inhibited the transcription of DR5 messenger RNA. By using luciferase constructs containing the upstream region of the DR5 promoter, we demonstrate that HIF-2α stimulates the transcription of the DR5 gene by activating the upstream region between −448 and −1188. Because HIF-2α is thought to exert its effect on gene transcription by interacting with the Max protein partner of Myc in the Myc/Max dimer, small interfering RNAs to Myc were used to lower the levels of this protein. In multiple renal cancer cell lines decreasing the levels of Myc blocked the ability of HIF-2α to stimulate DR5 transcription. PS-341 (VELCADE, bortezomib), a proteasome inhibitor used to treat human cancer, increases the levels of both HIF-2α and c-Myc and elevates the level of DR5 in renal cancer, sensitizing renal cancer cells to TRAIL therapy. Similarly, increasing HIF-2α in prostate and lung cancer cell lines increased the levels of DR5. Thus, in renal cancer cell lines expressing HIF-2α, this protein plays a role in regulating the levels of the TRAIL receptor DR5

    Community responses to communication campaigns for influenza A (H1N1): a focus group study

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    <p>Abstract</p> <p>Background</p> <p>This research was a part of a contestable rapid response initiative launched by the Health Research Council of New Zealand and the Ministry of Health in response to the 2009 influenza A pandemic. The aim was to provide health authorities in New Zealand with evidence-based practical information to guide the development and delivery of effective health messages for H1N1 and other health campaigns. This study contributed to the initiative by providing qualitative data about community responses to key health messages in the 2009 and 2010 H1N1 campaigns, the impact of messages on behavioural change and the differential impact on vulnerable groups in New Zealand.</p> <p>Methods</p> <p>Qualitative data were collected on community responses to key health messages in the 2009 and 2010 Ministry of Health H1N1 campaigns, the impact of messages on behaviour and the differential impact on vulnerable groups. Eight focus groups were held in the winter of 2010 with 80 participants from groups identified by the Ministry of Health as vulnerable to the H1N1 virus, such as people with chronic health conditions, pregnant women, children, Pacific Peoples and Māori. Because this study was part of a rapid response initiative, focus groups were selected as the most efficient means of data collection in the time available. For Māori, focus group discussion (hui) is a culturally appropriate methodology.</p> <p>Results</p> <p>Thematic analysis of data identified four major themes: personal and community risk, building community strategies, responsibility and information sources. People wanted messages about specific actions that they could take to protect themselves and their families and to mitigate any consequences. They wanted transparent and factual communication where both good and bad news is conveyed by people who they could trust.</p> <p>Conclusions</p> <p>The responses from all groups endorsed the need for community based risk management including information dissemination. Engaging with communities will be essential to facilitate preparedness and build community resilience to future pandemic events. This research provides an illustration of the complexities of how people understand and respond to health messages related to the H1N1 pandemic. The importance of the differences identified in the analysis is not the differences per se but highlight problems with a "one size fits all" pandemic warning strategy.</p

    Human embryonic stem cell neural differentiation and enhanced cell survival promoted by hypoxic preconditioning

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    Transplantation of neural progenitors derived from human embryonic stem cells (hESCs) provides a potential therapy for ischemic stroke. However, poor graft survival within the host environment has hampered the benefits and applications of cell-based therapies. The present investigation tested a preconditioning strategy to enhance hESC tolerance, thereby improving graft survival and the therapeutic potential of hESC transplantation. UC06 hESCs underwent neural induction and terminal differentiation for up to 30 days, becoming neural lineage cells, exhibiting extensive neurites and axonal projections, generating synapses and action potentials. To induce a cytoprotective phenotype, hESC-derived neurospheres were cultured at 0.1% oxygen for 12 h, dissociated and plated for terminal differentiation under 21% oxygen. Immunocytochemistry and electrophysiology demonstrated the ‘hypoxic preconditioning' promoted neuronal differentiation. Western blotting revealed significantly upregulated oxygen-sensitive transcription factors hypoxia-inducible factor (HIF)-1α and HIF-2α, while producing a biphasic response within HIF targets, including erythropoietin, vascular endothelial growth factor and Bcl-2 family members, during hypoxia and subsequent reoxygenation. This cytoprotective phenotype resulted in a 50% increase in both total and neural precursor cell survival after either hydrogen peroxide insult or oxygen–glucose deprivation. Cellular protection was maintained for at least 5 days and corresponded to upregulation of neuroprotective proteins. These results suggest that hypoxic preconditioning could be used to improve the effectiveness of human neural precursor transplantation therapies

    The Mitochondrial Genome of the Legume Vigna radiata and the Analysis of Recombination across Short Mitochondrial Repeats

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    The mitochondrial genomes of seed plants are exceptionally fluid in size, structure, and sequence content, with the accumulation and activity of repetitive sequences underlying much of this variation. We report the first fully sequenced mitochondrial genome of a legume, Vigna radiata (mung bean), and show that despite its unexceptional size (401,262 nt), the genome is unusually depauperate in repetitive DNA and "promiscuous" sequences from the chloroplast and nuclear genomes. Although Vigna lacks the large, recombinationally active repeats typical of most other seed plants, a PCR survey of its modest repertoire of short (38–297 nt) repeats nevertheless revealed evidence for recombination across all of them. A set of novel control assays showed, however, that these results could instead reflect, in part or entirely, artifacts of PCR-mediated recombination. Consequently, we recommend that other methods, especially high-depth genome sequencing, be used instead of PCR to infer patterns of plant mitochondrial recombination. The average-sized but repeat- and feature-poor mitochondrial genome of Vigna makes it ever more difficult to generalize about the factors shaping the size and sequence content of plant mitochondrial genomes
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