Proto-Adamastor ocean crust (920 Ma) described in Brasiliano Orogen from coetaneous zircon and tourmaline.

Proto-Adamastor ocean bathed Rodinia and successor continental fragments from 1.0e0.9 Ga up to 0.75 Ga, and evolved into world Adamastor Ocean at 0.75e0.60 Ga. Mesoproterozoic oceanic crust is poorly preserved on continents, only indirect evidence registered in Brasiliano Orogen. We report first evidence of ophiolite originated in proto-Adamastor. We use multi-technique U-Pb-Hf zircon and d11B tourmaline isotopic and elemental compositions. The host tourmalinite is enclosed in metaserpentinite, both belonging to the Bossoroca ophiolite. Zircon is 920 Ma-old, 3 Hf(920 Ma)??12, HfTDM ? 1.0 Ga and has ?oceanic? composition (e.g., U/Yb < 0.1). Tourmaline is dravite with d11B ? ?1.8& (Tur 1), 0& (Tur 2), 8.5& (Tur 3). These characteristics are a novel contribution to Rodinia and associated world ocean, because a fragment of proto-Adamastor oceanic crust and mantle evolved at the beginning of the Brasiliano Orogen

Feasibility and long-term results of focused radioguided parathyroidectomy using a "low" 37 MBq (1 mCi) (99m)Tc-sestamibi protocol

Aim of the present study was to investigate the feasibility and long-term results of focused radioguided parathyroidectomy using a "low" 37 MBq (1 mCi) (99m)Tc-sestamibi dose protocol compared to conventional "high 740 MBq (20 mCi) (99m)Tc-sestamibi dose protocol" in patients with primary hyperparathyroidism (PHPT). The data of focused radioguided surgery obtained in a group of 320 consecutive PHPT patients with high probability of the presence of a solitary parathyroid adenoma (PA) were studied. All patients underwent preoperative imaging work-up of double-tracer (99m)Tc-pertechnetate/(99m)Tc-sestamibi subtraction parathyroid scintigraphy (Sestamibi scintigraphy) and high resolution neck ultrasound (US). In 301/320 patients (96.6%) focused minimally invasive radioguided surgery was successfully performed by administering a "low" 37 MBq (1 mCi) (99m)Tc-sestamibi dose in the operating room 10 minutes before operation. No major intraoperative complications were recorded. Focused radioguided surgery required a mean time of 32 min and a mean hospital stay of 1.2 days. Local anesthesia was applied in 75 patients, 66 of whom (88%) were patients older than 65 years with comorbidities contraindicating general anesthesia. No case of persistent or recurrent PHPT was observed during post-surgical follow-up (range = 18–70 months; mean +/- SD = 15.3 +/- 9.1 months). Radiation exposure dose to the operating surgeon was 1.2 μSi/hour with the "low 37 MBq (1 mCi) (99m)Tc-sestamibi dose", and less than 1.0 μSi/hour for the other operating-room personnel. Focused low dose radioguided parathyroidectomy is a safe and effective means to localize parathyroid adenomas in patients affected by solitary PA thus reducing by 20 fold the radiation exposure dose to the patients and operating room personnel

Targeting Hypoxia in Cancer Cells by Restoring Homeodomain Interacting Protein-Kinase 2 and p53 Activity and Suppressing HIF-1α

BACKGROUND:The tumor suppressor homeodomain-interacting protein kinase-2 (HIPK2) by phosphorylating serine 46 (Ser46) is a crucial regulator of p53 apoptotic function. HIPK2 is also a transcriptional co-repressor of hypoxia-inducible factor-1alpha (HIF-1alpha) restraining tumor angiogenesis and chemoresistance. HIPK2 can be deregulated in tumors by several mechanisms including hypoxia. Here, we sought to target hypoxia by restoring HIPK2 function and suppressing HIF-1alpha, in order to provide evidence for the involvement of both HIPK2 and p53 in counteracting hypoxia-induced chemoresistance. METHODOLOGY/PRINCIPAL FINDINGS:Upon exposure of colon and lung cancer cells to hypoxia, by either low oxygen or cobalt, HIPK2 function was impaired allowing for increased HIF-1alpha expression and inhibiting the p53-apoptotic response to drug. Cobalt suppressed HIPK2 recruitment onto HIF-1alpha promoter. Hypoxia induced expression of the p53 target MDM2 that downregulates HIPK2, thus MDM2 inhibition by siRNA restored the HIPK2/p53Ser46 response to drug. Zinc supplementation to hypoxia-treated cells increased HIPK2 protein stability and nuclear accumulation, leading to restoration of HIPK2 binding to HIF-1alpha promoter, repression of MDR1, Bcl2, and VEGF genes, and activation of the p53 apoptotic response to drug. Combination of zinc and ADR strongly suppressed tumor growth in vivo by inhibiting HIF-1 pathway and upregulating p53 apoptotic target genes. CONCLUSIONS/SIGNIFICANCE:We show here for the first time that hypoxia-induced HIPK2 deregulation was counteracted by zinc that restored HIPK2 suppression of HIF-1 pathway and reactivated p53 apoptotic response to drug, underscoring the potential use of zinc supplementation in combination with chemotherapy to address hypoxia and improve tumor treatment

A DNA Vaccine Encoding Multiple HIV CD4 Epitopes Elicits Vigorous Polyfunctional, Long-Lived CD4+ and CD8+ T Cell Responses

T-cell based vaccines against HIV have the goal of limiting both transmission and disease progression by inducing broad and functionally relevant T cell responses. Moreover, polyfunctional and long-lived specific memory T cells have been associated to vaccine-induced protection. CD4+ T cells are important for the generation and maintenance of functional CD8+ cytotoxic T cells. We have recently developed a DNA vaccine encoding 18 conserved multiple HLA-DR-binding HIV-1 CD4 epitopes (HIVBr18), capable of eliciting broad CD4+ T cell responses in multiple HLA class II transgenic mice. Here, we evaluated the breadth and functional profile of HIVBr18-induced immune responses in BALB/c mice. Immunized mice displayed high-magnitude, broad CD4+/CD8+ T cell responses, and 8/18 vaccine-encoded peptides were recognized. In addition, HIVBr18 immunization was able to induce polyfunctional CD4+ and CD8+ T cells that proliferate and produce any two cytokines (IFNγ/TNFα, IFNγ/IL-2 or TNFα/IL-2) simultaneously in response to HIV-1 peptides. For CD4+ T cells exclusively, we also detected cells that proliferate and produce all three tested cytokines simultaneously (IFNγ/TNFα/IL-2). The vaccine also generated long-lived central and effector memory CD4+ T cells, a desirable feature for T-cell based vaccines. By virtue of inducing broad, polyfunctional and long-lived T cell responses against conserved CD4+ T cell epitopes, combined administration of this vaccine concept may provide sustained help for CD8+ T cells and antibody responses- elicited by other HIV immunogens

Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV

The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of √s = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pT≥20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60≤pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2≤{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal