Dialogue to address the roots of resource competition: Lessons for policy and practice

Conflict management is an intrinsic element of natural resource management, and becomes increasingly important amid growing pressure on natural resources from local uses, as well as from external drivers such as climate change and international investment. If policymakers and practitioners aim to truly improve livelihood resilience and reduce vulnerabilities of poor rural households, issues of resource competition and conflict management cannot be ignored. This synthesis report summarizes outcomes and lessons from three ecoregions: Lake Victoria, with a focus on Uganda; Lake Kariba, with a focus on Zambia; and Tonle Sap Lake in Cambodia. Partners used a common approach to stakeholder engagement and action research that we call “Collaborating for Resilience”. In each region, partners assisted local stakeholders in developing a shared understanding of risks and opportunities, weighing alternative actions, developing action plans, and evaluating and learning from the outcomes. These experiences demonstrate that investing in capacities for conflict management is practical and can contribute to broader improvements in resource governance

Measurement of the cross-section and charge asymmetry of WW bosons produced in proton-proton collisions at s=8\sqrt{s}=8 TeV with the ATLAS detector

This paper presents measurements of the $W^+ \rightarrow \mu^+\nu$ and $W^- \rightarrow \mu^-\nu$ cross-sections and the associated charge asymmetry as a function of the absolute pseudorapidity of the decay muon. The data were collected in proton--proton collisions at a centre-of-mass energy of 8 TeV with the ATLAS experiment at the LHC and correspond to a total integrated luminosity of 20.2~\mbox{fb^{-1}}. The precision of the cross-section measurements varies between 0.8% to 1.5% as a function of the pseudorapidity, excluding the 1.9% uncertainty on the integrated luminosity. The charge asymmetry is measured with an uncertainty between 0.002 and 0.003. The results are compared with predictions based on next-to-next-to-leading-order calculations with various parton distribution functions and have the sensitivity to discriminate between them.Comment: 38 pages in total, author list starting page 22, 5 figures, 4 tables, submitted to EPJC. All figures including auxiliary figures are available at https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2017-13

Highly Efficient Elimination of Colorectal Tumor-Initiating Cells by an EpCAM/CD3-Bispecific Antibody Engaging Human T Cells

With their resistance to genotoxic and anti-proliferative drugs and potential to grow tumors and metastases from very few cells, cancer stem or tumor-initiating cells (TICs) are a severe limitation for the treatment of cancer by conventional therapies. Here, we explored whether human T cells that are redirected via an EpCAM/CD3-bispecific antibody called MT110 can lyse colorectal TICs and prevent tumor growth from TICs. MT110 recognizes EpCAM, a cell adhesion molecule expressed on TICs from diverse human carcinoma, which was recently shown to promote tumor growth through engagement of elements of the wnt pathway. MT110 was highly potent in mediating complete redirected lysis of KRAS-, PI3 kinase- and BRAF-mutated colorectal TICs, as demonstrated in a soft agar assay. In immunodeficient mice, MT110 prevented growth of tumors from a 5,000-fold excess of a minimally tumorigenic TIC dose. T cells engaged by MT110 may provide a potent therapeutic means to eradicate TICs and bulk tumor cells derived thereof

Therapeutic T cells induce tumor-directed chemotaxis of innate immune cells through tumor-specific secretion of chemokines and stimulation of B16BL6 melanoma to secrete chemokines

Background: The mechanisms by which tumor-specific T cells induce regression of established metastases are not fully characterized. In using the poorly immunogenic B16BL6-D5 (D5) melanoma model we reported that T cell-mediated tumor regression can occur independently of perforin, IFN-gamma or the combination of both. Characterization of regressing pulmonary metastases identified macrophages as a major component of the cells infiltrating the tumor after adoptive transfer of effector T cells. This led us to hypothesize that macrophages played a central role in tumor regression following T-cell transfer. Here, we sought to determine the factors responsible for the infiltration of macrophages at the tumor site. Methods: These studies used the poorly immunogenic D5 melanoma model. Tumor-specific effector T cells, generated from tumor vaccine-draining lymph nodes (TVDLN), were used for adoptive immunotherapy and in vitro analysis of chemokine expression. Cellular infiltrates into pulmonary metastases were determined by immunohistochemistry. Chemokine expression by the D5 melanoma following co-culture with T cells, IFN-gamma or TNF-alpha was determined by RT-PCR and ELISA. Functional activity of chemokines was confirmed using a macrophage migration assay. T cell activation of macrophages to release nitric oxide (NO) was determined using GRIES reagent. Results: We observed that tumor-specific T cells with a type 1 cytokine profile also expressed message for and secreted RANTES, MIP-1 alpha and MIP-1 beta following stimulation with specific tumor. Unexpectedly, D5 melanoma cells cultured with IFN-gamma or TNF-alpha, two type 1 cytokines expressed by therapeutic T cells, secreted Keratinocyte Chemoattractant (KC), MCP-1, IP-10 and RANTES and expressed mRNA for MIG. The chemokines released by T cells and cytokine-stimulated tumor cells were functional and induced migration of the DJ2PM macrophage cell line. Additionally, tumor-specific stimulation of wt or perforin-deficient (PKO) effector T cells induced macrophages to secrete nitric oxide (NO), providing an additional effector mechanism for T cell-mediated tumor regression. Conclusion: These data suggest two possible sources for chemokine secretion that stimulates macrophage recruitment to the site of tumor metastases. Both appear to be initiated by T cell recognition of specific antigen, but one is dependent on the tumor cells to produce the chemokines that recruit macrophages

Combination immunotherapy and active-specific tumor cell vaccination augments anti-cancer immunity in a mouse model of gastric cancer

<p>Abstract</p> <p>Background</p> <p>Active-specific immunotherapy used as an adjuvant therapeutic strategy is rather unexplored for cancers with poorly characterized tumor antigens like gastric cancer. The aim of this study was to augment a therapeutic immune response to a low immunogenic tumor cell line derived from a spontaneous gastric tumor of a CEA424-SV40 large T antigen (CEA424-SV40 TAg) transgenic mouse.</p> <p>Methods</p> <p>Mice were treated with a lymphodepleting dose of cyclophosphamide prior to reconstitution with syngeneic spleen cells and vaccination with a whole tumor cell vaccine combined with GM-CSF (a treatment strategy abbreviated as LRAST). Anti-tumor activity to subcutaneous tumor challenge was examined in a prophylactic as well as a therapeutic setting and compared to corresponding controls.</p> <p>Results</p> <p>LRAST enhances tumor-specific T cell responses and efficiently inhibits growth of subsequent transplanted tumor cells. In addition, LRAST tended to slow down growth of established tumors. The improved anti-tumor immune response was accompanied by a transient decrease in the frequency and absolute number of CD4⁺CD25⁺FoxP3⁺T cells (Tregs).</p> <p>Conclusions</p> <p>Our data support the concept that whole tumor cell vaccination in a lymphodepleted and reconstituted host in combination with GM-CSF induces therapeutic tumor-specific T cells. However, the long-term efficacy of the treatment may be dampened by the recurrence of Tregs. Strategies to counteract suppressive immune mechanisms are required to further evaluate this therapeutic vaccination protocol.</p

Search for heavy particles decaying into a top-quark pair in the fully hadronic final state in pp collisions at √s=13 TeV with the ATLAS detector

A search for new particles decaying into a pair of top quarks is performed using proton-proton collision data recorded with the ATLAS detector at the Large Hadron Collider at a center-of-mass energy of √s=13  TeV corresponding to an integrated luminosity of 36.1  fb−1. Events consistent with top-quark pair production and the fully hadronic decay mode of the top quarks are selected by requiring multiple high transverse momentum jets including those containing b-hadrons. Two analysis techniques, exploiting dedicated top-quark pair reconstruction in different kinematic regimes, are used to optimize the search sensitivity to new hypothetical particles over a wide mass range. The invariant mass distribution of the two reconstructed top-quark candidates is examined for resonant production of new particles with various spins and decay widths. No significant deviation from the Standard Model prediction is observed and limits are set on the production cross-section times branching fraction for new hypothetical Z′ bosons, dark-matter mediators, Kaluza-Klein gravitons and Kaluza-Klein gluons. By comparing with the predicted production cross sections, the Z′ boson in the topcolor-assisted-technicolor model is excluded for masses up to 3.1–3.6 TeV, the dark-matter mediators in a simplified framework are excluded in the mass ranges from 0.8 to 0.9 TeV and from 2.0 to 2.2 TeV, and the Kaluza-Klein gluon is excluded for masses up to 3.4 TeV, depending on the decay widths of the particles

Search for heavy charged long-lived particles in the ATLAS detector in 36.1 fb− 1 of proton-proton collision data at √s =13 TeV

A search for heavy charged long-lived particles is performed using a data sample of 36.1 fb−1 of proton-proton collisions at √s =13 TeV collected by the ATLAS experiment at the Large Hadron Collider. The search is based on observables related to ionization energy loss and time of flight, which are sensitive to the velocity of heavy charged particles traveling significantly slower than the speed of light. Multiple search strategies for a wide range of lifetimes, corresponding to path lengths of a few meters, are defined as model independently as possible, by referencing several representative physics cases that yield long-lived particles within supersymmetric models, such as gluinos/squarks (R-hadrons), charginos and staus. No significant deviations from the expected Standard Model background are observed. Upper limits at 95% confidence level are provided on the production cross sections of long-lived R-hadrons as well as directly pair produced staus and charginos. These results translate into lower limits on the masses of long-lived gluino, sbottom and stop R-hadrons, as well as staus and charginos of 2000, 1250, 1340, 430, and 1090 GeV, respectively

Searches for exclusive Higgs and Z boson decays into J/ψγ,ψ(2S)γ,and Υ(nS)γ at √s=13 TeV with the ATLAS detector

Searches for the exclusive decays of the Higgs and Z bosons into a J/ψ,ψ(2S), or Υ(nS)(n=1,2,3) meson and a photon are performed with a pp collision data sample corresponding to an integrated luminosity of 36.1 fb −1 collected at √s =13 TeV with the ATLAS detector at the CERN Large Hadron Collider. No significant excess of events is observed above the expected backgrounds, and 95% confidence-level upper limits on the branching fractions of the Higgs boson decays to J/ψγ, ψ(2S)γ,and Υ(nS)γ of 3.5×10 −4, 2.0×10−3,and(4.9,5.9,5.7)×10 −4,respectively, are obtained assuming Standard Model production. The corresponding 95% confidence-level upper limits for the branching fractions of the Z boson decays are 2.3×10 −6, 4.5×10 −6 and (2.8,1.7,4.8)×10 −6, respectively

Measurements of inclusive and differential fiducial cross-sections of tt production with additional heavy-flavour jets in proton-proton collisions at √ s= 13 TeV with the ATLAS detector

This paper presents measurements of tt production in association with additional b-jets in pp collisions at the LHC at a centre-of-mass energy of 13 TeV. The data were recorded with the ATLAS detector and correspond to an integrated luminosity of 36.1 fb−1. Fiducial cross-section measurements are performed in the dilepton and lepton-plus-jets tt decay channels. Results are presented at particle level in the form of inclusive cross-sections of tt final states with three and four b-jets as well as differential cross-sections as a function of global event properties and properties of b-jet pairs. The measured inclusive fiducial cross-sections generally exceed the ttbb predictions from various next-to-leading-order matrix element calculations matched to a parton shower but are compatible within the total uncertainties. The experimental uncertainties are smaller than the uncertainties in the predictions. Comparisons of state-of-the-art theoretical predictions with the differential measurements are shown and good agreement with data is found for most of them