53,190 research outputs found
Negative selection during the peripheral immune response to antigen
No full textThymic selection depends on positive and negative selective mechanisms based on the avidity of T cell interaction with antigen-major histocompatibility Complex complexes. However, peripheral mechanisms for the recruitment and clonal expansion of the responding T cell repertoire remain obscure. Here we provide evidence for an avidity-based model of peripheral T cell clonal expansion in response to antigenic challenge. We have used the encephalitogenic, H-2 Au-restricted, acetylated NH2-terminal nonameric peptide (Ac1-9) epitope from myelin basic protein as our model antigen. Peptide analogues were generated that varied in antigenic strength (as assessed by in vitro assay) based on differences in their binding affinity for Au. In vivo, these analogues elicited distinct repertoires of T cells that displayed marked differences in antigen sensitivity. Immunization with the weakest (wild-type) antigen expanded the high affinity T cells required to induce encephalomyelitis. In contrast, immunization with strongly antigenic analogues led to the elimination of T cells bearing high affinity T cell receptors by apoptosis, thereby preventing disease development. Moreover, the T cell repertoire was consistently tuned to respond to the immunizing antigen with the same activation threshold. This tuning mechanism provides a peripheral control against the expansion of autoreactive T cells and has implications for immunotherapy and vaccine design.</p
"Closing the R&D Gap, Evaluating the Sources of R&D Spending"
No full textBoth spending and tax policies have been implemented in the United States with the goal of stimulating private sector research and development (R&D). Karier questions whether current R&D policy, especially the research and experimentation tax credit, can contribute to closing the gap between nondefense expenditures on R&D in the United States and such expenditures in other countries, such as Japan and Germany. He also explores possible changes to our current R&D policy to make it more effective.
Letter from C. D. Dawson, Tusayan Copper Mining and Smelting, to Carl Hayden
No full textLetter from C. D. Dawson to Carl Hayden urging him to consider the rights of miners and farmers when drawing up the boundaries for the proposed park
Measurement of the D+/- production asymmetry in 7 TeV pp collisions
No full textThe asymmetry in the production cross-section \sigma of D+/- mesons, A_P = (\sigma(D+) - \sigma(D-))/(\sigma(D+) + \sigma(D-)), is measured in bins of pseudorapidity \eta and transverse momentum p_T within the acceptance of the LHCb detector. The result is obtained with a sample of D+ -> K_S pi+ decays corresponding to an integrated luminosity of 1.0 fb^-1, collected in pp collisions at a centre of mass energy of 7 TeV at the Large Hadron Collider. When integrated over the kinematic range 2.0 K_S pi+ decay is negligible. No significant dependence on \eta or p_T is observed
D* (D)over-bar* molecule interpretation of Z(c)(4025)
No full textWe have used QCD sum rules to study the newly observed charged state Z(c)(4025) as a hidden-charm D*(D) over bar* molecular state with the quantum numbers I-G(J(P)) =1(+)(1(+)). Using a D*(D) over bar* molecular interpolating current, we have calculated the two-point correlation function and the spectral density up to dimension eight at leading order in alpha(s). The extracted mass is m(X) = (4.04 +/- 0.24) GeV. This result is compatible with the observed mass of Z(c)(4025) within the errors, which implies a possible molecule interpretation of this new resonance. We also predict the mass of the corresponding hidden-bottom B*(B) over bar* molecular state: m(Zb) = (9.98 +/- 0.21) GeV.Physics, Particles & FieldsSCI(E)[email protected]; [email protected]; [email protected]; [email protected]
Prompt charm production in pp collisions at √<span style="text-decoration:overline">s</span>=7 TeV
No full textCharm production at the LHC in pp collisions at s√=7 TeV is studied with the LHCb detector. The decays D0→K−π+, D+→K−π+π+, D⁎+→D0(K−π+)π+, D+s→ϕ(K−K+)π+, Λ+c→pK−π+, and their charge conjugates are analysed in a data set corresponding to an integrated luminosity of 15 nb−1. Differential cross-sections dσ/dpT are measured for prompt production of the five charmed hadron species in bins of transverse momentum and rapidity in the region 0<pT<8 GeV/c and 2.0<y<4.5. Theoretical predictions are compared to the measured differential cross-sections. The integrated cross-sections of the charm hadrons are computed in the above pT-y range, and their ratios are reported. A combination of the five integrated cross-section measurements gives
σ(cc¯)pT<8 GeV/c,2.0<y<4.5=1419±12(stat)±116(syst)±65(frag) μb,
where the uncertainties are statistical, systematic, and due to the fragmentation functions
Z(c)(3900) as a (D)over-barD* molecule from the pole counting rule
No full textA comprehensive study on the nature of the Zc(3900) resonant structure is carried out in this work. By constructing the pertinent effective Lagrangians and considering the important final-state-interaction effects, we first give a unified description to all the relevant experimental data available, including the J/psi pi and pi invariant mass distributions from the e(+)e(-) -> J/psi pi process, the h(c)pi distribution from e(+)e(-) -> h(c)pi pi, and also the D (D) over bar* spectrum in the e(+)e(-) -> D (D) over bar*pi process. After fitting the unknown parameters to the previous data, we search the pole in the complex energy plane and find only one pole in the nearby energy region in different Riemann sheets. Therefore, we conclude that Z(c)(3900) is of D (D) over bar* molecular nature, according to the pole counting rule method [Nucl. Phys. A543, 632 (1992); Phys. Rev. D 35, 1633 (1987)]. We emphasize that the conclusion based upon the pole counting method is not trivial, since both the D (D) over bar* contact interactions and the explicit Z(c) exchanges are introduced in our analyses andNational Nature Science Foundations of China (NSFC) [10925522, 11021092, 11575052, 11105038]; Natural Science Foundation of Hebei Province [A2015205205]; inoGerman Collaborative Research Center "Symmetries and the Emergence of Structure in QCD" [CRC 110]; DFG; NSFCSCI(E)ARTICLE119
Long-term follow-up of endurance and safety outcomes during enzyme replacement therapy for mucopolysaccharidosis VI: Final results of three clinical studies of recombinant human N-acetylgalactosamine 4-sulfatase
No full textCopyright © 2008 Elsevier Inc. All rights reserved.UnlabelledThe objective of this study was to evaluate the long-term clinical benefits and safety of recombinant human arylsulfatase B (rhASB) treatment of mucopolysaccharidosis type VI (MPS VI: Maroteaux-Lamy syndrome), a lysosomal storage disease. Fifty-six patients derived from 3 clinical studies were followed in open-label extension studies for a total period of 97-260 Weeks. All patients received weekly infusions of rhASB at 1 mg/kg. Efficacy was evaluated by (1) distance walked in a 12-minute walk test (12MWT) or 6-minute walk test (6MWT), (2) stairs climbed in the 3-minute stair climb (3MSC), and (3) reduction in urinary glycosaminoglycans (GAG). Safety was evaluated by compliance, adverse event (AE) reporting and adherence to treatment.ResultsA significant reduction in urinary GAG (71-79%) was sustained. For the 12MWT, subjects in Phase 2 showed improvement of 255+/-191 m (mean+/-SD) at Week 144; those in Phase 3 Extension demonstrated improvement from study baseline of 183+/-26 m (mean+/- SE) in the rhASB/rhASB group at Week 96 and from treatment baseline (Week 24) of 117+/-25 m in the placebo/rhASB group. The Phase 1/2 6MWT and the 3MSC from Phase 2 and 3 also showed sustained improvements through the final study measurements. Compliance was 98% overall. Only 560 of 4121 reported AEs (14%) were related to treatment with only 10 of 560 (2%) described as severe.ConclusionrhASB treatment up to 5 years results in sustained improvements in endurance and has an acceptable safety profile.Paul Harmatz, Roberto Giugliani, Ida Vanessa D. Schwartz, Nathalie Guffon, Elisa Leão Teles, M. Clara Sá Miranda, J. Edmond Wraith, Michael Beck, Laila Arash, Maurizio Scarpa, David Ketteridge, John J. Hopwood, Barbara Plecko, Robert Steiner, Chester B. Whitley, Paige Kaplan, Zi-Fan Yu, Stuart J. Swiedler, Celeste Decker and for the MPS VI Study Grouphttp://www.elsevier.com/wps/find/journaldescription.cws_home/622920/description#descriptio
Numerical analysis of a 3-D printed porous trailing edge for broadband noise reduction
No full textLattice Boltzmann simulations were carried out to investigate the noise mitigation mechanisms of a 3-D printed porous trailing-edge insert, elucidating the link between noise reduction and material permeability. The porous insert is based on a unit cell resembling a lattice of diamond atoms. It replaces the last 20 % chord of a NACA 0018 at zero angle-of-attack. A partially blocked insert is considered by adding a solid partition between 84 % and 96 % of the aerofoil chord. The regular porous insert achieves a substantial noise reduction at low frequencies, although a slight noise increase is found at high frequencies. The partially blocked porous insert exhibits a lower noise reduction level, but the noise emission at mid-to-high frequency is slightly affected. The segment of the porous insert near the tip plays a dominant role in promoting noise mitigation, whereas the solid-porous junction contributes, in addition to the rough surface, towards the high-frequency excess noise. The current study demonstrates the existence of an entrance length associated with the porous material geometry, which is linked to the pressure release process that is responsible for promoting noise mitigation. This process is characterised by the aerodynamic interaction between pressure fluctuations across the porous medium, which is found at locations where the porous insert thickness is less than twice the entrance length. Present results also suggest that the noise attenuation level is related to both the chordwise extent of the porous insert and the streamwise turbulent length scale. The porous inserts also cause a slight drag increase compared to their solid counterpart. Wind Energ
Going Beyond Counting First Authors in Author Co-citation Analysis
No full textThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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