Tumor-derived exosomes confer antigen-specific immunosuppression in a murine delayed-type hypersensitivity model

Exosomes are endosome-derived small membrane vesicles that are secreted by most cell types including tumor cells. Tumor-derived exosomes usually contain tumor antigens and have been used as a source of tumor antigens to stimulate anti-tumor immune responses. However, many reports also suggest that tumor-derived exosomes can facilitate tumor immune evasion through different mechanisms, most of which are antigen-independent. In the present study we used a mouse model of delayed-type hypersensitivity (DTH) and demonstrated that local administration of tumor-derived exosomes carrying the model antigen chicken ovalbumin (OVA) resulted in the suppression of DTH response in an antigen-specific manner. Analysis of exosome trafficking demonstrated that following local injection, tumor-derived exosomes were internalized by CD11c+ cells and transported to the draining LN. Exosome-mediated DTH suppression is associated with increased mRNA levels of TGF-β1 and IL-4 in the draining LN. The tumor-derived exosomes examined were also found to inhibit DC maturation. Taken together, our results suggest a role for tumor-derived exosomes in inducing tumor antigen-specific immunosuppression, possibly by modulating the function of APCs. © 2011 Yang et al

Hadronization properties of b quarks compared to light quarks in e+e- -> q qbar from 183 to 200 GeV

The DELPHI detector at LEP has collected 54 pb^{-1} of data at a centre-of-mass energy around 183 GeV during 1997, 158 pb^{-1} around 189 GeV during 1998, and 187 pb^{-1} between 192 and 200 GeV during 1999. These data were used to measure the average charged particle multiplicity in e+e- -> b bbar events, _{bb}, and the difference delta_{bl} between _{bb} and the multiplicity, _{ll}, in generic light quark (u,d,s) events: delta_{bl}(183 GeV) = 4.55 +/- 1.31 (stat) +/- 0.73 (syst) delta_{bl}(189 GeV) = 4.43 +/- 0.85 (stat) +/- 0.61 (syst) delta_{bl}(200 GeV) = 3.39 +/- 0.89 (stat) +/- 1.01 (syst). This result is consistent with QCD predictions, while it is inconsistent with calculations assuming that the multiplicity accompanying the decay of a heavy quark is independent of the mass of the quark itself.Comment: 13 pages, 2 figure

Search for supersymmetric particles in scenarios with a gravitino LSP and stau NLSP

Sleptons, neutralinos and charginos were searched for in the context of scenarios where the lightest supersymmetric particle is the gravitino. It was assumed that the stau is the next-to-lightest supersymmetric particle. Data collected with the DELPHI detector at a centre-of-mass energy near 189 GeV were analysed combining the methods developed in previous searches at lower energies. No evidence for the production of these supersymmetric particles was found. Hence, limits were derived at 95% confidence level.Comment: 31 pages, 14 figure

The Beyond the Standard Model Working Group: Summary Report

Report of the "Beyond the Standard Model" working group for the Workshop `Physics at TeV Colliders', Les Houches, France, 21 May - 1 June 2001. It consists of 18 separate parts: 1. Preface; 2. Theoretical Discussion; 3. Numerical Calculation of the mSUGRA and Higgs Spectrum; 4. Theoretical Uncertainties in Sparticle Mass Predictions; 5. High Mass Supersymmetry with High Energy Hadron Colliders; 6. SUSY with Heavy Scalars at LHC; 7. Inclusive Study of MSSM in CMS; 8. Establishing a No-Lose Theorem for NMSSM Higgs Boson Discovery at the LHC; 9. Effects of Supersymmetric Phases on Higgs Production in Association with Squark Pairs in the Minimal Supersymmetric Standard Model; 10. Study of the Lepton Flavour Violating Decays of Charged Fermions in SUSY GUTs; 11. Interactions of the Goldstino Supermultiplet with Standard Model Fields; 12. Attempts at Explaining the NuTeV Observation of Di-Muon Events; 13. Kaluza-Klein States of the Standard Model Gauge Bosons: Constraints From High Energy Experiments; 14. Kaluza-Klein Excitations of Gauge Bosons in the ATLAS Detector; 15. Search for the Randall Sundrum Radion Using the ATLAS Detector; 16. Radion Mixing Effects on the Properties of the Standard Model Higgs Boson; 17. Probing Universal Extra Dimensions at Present and Future Colliders; 18. Black Hole Production at Future Colliders.Report of the Beyond the Standard Model working group for the Workshop `Physics at TeV Colliders', Les Houches, France, 21 May - 1 June 2001. It consists of 18 separate parts: 1. Preface: 2. Theoretical Discussion: 3. Numerical Calculation of the mSUGRA and Higgs Spectrum: 4. Theoretical Uncertainties in Sparticle Mass Predictions: 5. High Mass Supersymmetry with High Energy Hadron Colliders: 6. SUSY with Heavy Scalars at LHC: 7. Inclusive Study of MSSM in CMS: 8. Establishing a No-Lose Theorem for NMSSM Higgs Boson Discovery at the LHC: 9. Effects of Supersymmetric Phases on Higgs Production in Association with Squark Pairs in the Minimal Supersymmetric Standard Model: 10. Study of the Lepton Flavour Violating Decays of Charged Fermions in SUSY GUTs: 11. Interactions of the Goldstino Supermultiplet with Standard Model Fields: 12. Attempts at Explaining the NuTeV Observation of Di-Muon Events: 13. Kaluza-Klein States of the Standard Model Gauge Bosons: Constraints From High Energy Experiments: 14. Kaluza-Klein Excitations of Gauge Bosons in the ATLAS Detector: 15. Search for the Randall Sundrum Radion Using the ATLAS Detector: 16. Radion Mixing Effects on the Properties of the Standard Model Higgs Boson: 17. Probing Universal Extra Dimensions at Present and Future Colliders: 18. Black Hole Production at Future Colliders

IκBβ acts to inhibit and activate gene expression during the inflammatory response

The activation of pro-inflammatory gene programs by nuclear factor-κB (NF-κB) is primarily regulated through cytoplasmic sequestration of NF-κB by the inhibitor of κB (IκB) family of proteins1. IκBβ, a major isoform of IκB, can sequester NF-κB in the cytoplasm2, although its biological role remains unclear. Although cells lacking IκBβ have been reported3, 4, in vivo studies have been limited and suggested redundancy between IκBα and IκBβ5. Like IκBα, IκBβ is also inducibly degraded; however, upon stimulation by lipopolysaccharide (LPS), it is degraded slowly and re-synthesized as a hypophosphorylated form that can be detected in the nucleus6, 7, 8, 9, 10, 11. The crystal structure of IκBβ bound to p65 suggested this complex might bind DNA12. In vitro, hypophosphorylated IκBβ can bind DNA with p65 and c-Rel, and the DNA-bound NF-κB:IκBβ complexes are resistant to IκBα, suggesting hypophosphorylated, nuclear IκBβ may prolong the expression of certain genes9, 10, 11. Here we report that in vivo IκBβ serves both to inhibit and facilitate the inflammatory response. IκBβ degradation releases NF-κB dimers which upregulate pro-inflammatory target genes such as tumour necrosis factor-α (TNF-α). Surprisingly, absence of IκBβ results in a dramatic reduction of TNF-α in response to LPS even though activation of NF-κB is normal. The inhibition of TNF-α messenger RNA (mRNA) expression correlates with the absence of nuclear, hypophosphorylated-IκBβ bound to p65:c-Rel heterodimers at a specific κB site on the TNF-α promoter. Therefore IκBβ acts through p65:c-Rel dimers to maintain prolonged expression of TNF-α. As a result, IκBβ^(−/−) mice are resistant to LPS-induced septic shock and collagen-induced arthritis. Blocking IκBβ might be a promising new strategy for selectively inhibiting the chronic phase of TNF-α production during the inflammatory response

Measurement of pion and proton response and longitudinal shower profiles up to 20 nuclear interaction lengths with the ATLAS Tile calorimeter

The response of pions and protons in the energy range of 20 to 180 GeV produced at CERN's SPS H8 test beam line in the ATLAS iron-scintillator Tile hadron calorimeter has been measured. The test-beam configuration allowed to measure the longitudinal shower development for pions and protons up to 20 nuclear interaction lengths. It is found that pions penetrate deeper in the calorimeter than protons. However, protons induce showers that are wider laterally to the direction of the impinging particle. Including the measured total energy response, the pion to proton energy ratio and the resolution, all observations are consistent with a higher electromagnetic energy fraction in pion induced showers. The data are compared with GEANT4 simulations using several hadronic physics lists. The measured longitudinal shower profiles are described by an analytical shower parameterization within an accuracy of 5-10%. The amount of energy leaking out behind the calorimeter is determined and parameterised as a function of the beam energy and the calorimeter depth. This allows for a leakage correction of test-beam results in the standard projective geometry

Pro-apoptotic Bid is required for the resolution of the effector phase of inflammatory arthritis

Rheumatoid arthritis is an autoimmune disease characterized by hyperplasia of the synovial lining and destruction of cartilage and bone. Recent studies have suggested that a lack of apoptosis contributes to the hyperplasia of the synovial lining and to the failure in eliminating autoreactive cells. Mice lacking Fas or Bim, two pro-apoptotic proteins that mediate the extrinsic and intrinsic death cascades, respectively, develop enhanced K/BxN serum transfer-induced arthritis. Since the pro-apoptotic protein Bid functions as an intermediate between the extrinsic and intrinsic apoptotic pathways, we examined the role that it plays in inflammatory arthritis. Mice deficient in Bid (Bid-/-) show a delay in the resolution of K/BxN serum transfer-induced arthritis. Bid-/- mice display increased inflammation, bone destruction, and pannus formation compared to wild-type mice. Furthermore, Bid-/- mice have elevated levels of CXC chemokine and IL-1β in serum, which are associated with more inflammatory cells throughout the arthritic joint. In addition, there are fewer apoptotic cells in the synovium of Bid-/- compared to Wt mice. These data suggest that extrinsic and intrinsic apoptotic pathways cooperate through Bid to limit development of inflammatory arthritis

Mechanical construction and installation of the ATLAS tile calorimeter

This paper summarises the mechanical construction and installation of the Tile Calorimeter for the ATLAS experiment at the Large Hadron Collider in CERN, Switzerland. The Tile Calorimeter is a sampling calorimeter using scintillator as the sensitive detector and steel as the absorber and covers the central region of the ATLAS experiment up to pseudorapidities +/- 1.7. The mechanical construction of the Tile Calorimeter occurred over a period of about 10 years beginning in 1995 with the completion of the Technical Design Report and ending in 2006 with the installation of the final module in the ATLAS cavern. During this period approximately 2600 metric tons of steel were transformed into a laminated structure to form the absorber of the sampling calorimeter. Following instrumentation and testing, which is described elsewhere, the modules were installed in the ATLAS cavern with a remarkable accuracy for a structure of this size and weight

Search for narrow resonances in dilepton mass spectra in proton-proton collisions at root s=13 TeV and combination with 8 TeV data

Peer reviewe

Search for resonances in the mass spectrum of muon pairs produced in association with b quark jets in proton-proton collisions at root 8 and 13 TeV

A search for resonances in the mass range 12-70 GeV produced in association with a b quark jet and a second jet, and decaying to a muon pair, is reported. The analysis is based on data from proton-proton collisions at center-of-mass energies of 8 and 13 TeV, collected with the CMS detector at the LHC and corresponding to integrated luminosities of 19.7 and 35.9 fb(-1), respectively. The search is carried out in two mutually exclusive event categories. Events in the first category are required to have a b quark jet in the central region (|| 2.4) and at least one jet in the forward region (|| > 2.4). Events in the second category are required to have two jets in the central region, at least one of which is identified as a b quark jet, no jets in the forward region, and low missing transverse momentum. An excess of events above the background near a dimuon mass of 28 GeV is observed in the 8 TeV data, corresponding to local significances of 4.2 and 2.9 standard deviations for the first and second event categories, respectively. A similar analysis conducted with the 13 TeV data results in a mild excess over the background in the first event category corresponding to a local significance of 2.0 standard deviations, while the second category results in a 1.4 standard deviation deficit. The fiducial cross section measurements and 95% confidence level upper limits on those for a resonance consistent with the 8 TeV excess are provided at both collision energies