1,175 research outputs found
Development and optimization of animal origin-free, serum-free media for human treg manufacturing
Regulatory T cells (Treg) constitute a small subset of immunosuppressive CD4+ T cells. Studies have shown that imbalanced or aberrant Treg function can result in autoimmune disorders. The importance of Tregs in dampening immune responses has been described in multiple studies and Treg immunotherapies are being explored to develop personalized therapies for various autoimmune diseases. Scalable commercial development of Treg therapies suffers similar challenges as other T cell immunotherapies: biosafety and supply chain concerns of human serum and limitations regarding bioprocess development due to serum variability. Additionally, there a challenges regarding Treg isolation for both magnetically isolated (blockade of CD25+ epitope may affect function and low purity) and flow cytometry sorted Tregs (low numbers and viability). In addition, the starting population and purity (measured by FOXP3 expression) can be low, resulting in small cell numbers post expansion which can impact dose escalation studies. To address these challenges, we are developing a serum-free, animal origin component â free, defined medium and Treg optimized Dynabeadsâą. Our strategy was to exploit metabolic differences between Tregs and conventional Tcells as well as optimizing the level of activation ligands to develop a defined Treg manufacturing system. Using design of experiment (DOE) approaches we explored factors described in the literature to be associated with Treg development. DOE studies were followed by testing in combination with Treg Dynabeadsâą in development. Feasibility was evaluated with positively selected Tregs (CD4+CD25+CD127lo, n=5). Tregs cultured in our system achieve higher FOXP3+ frequencies (\u3e60% FOXP3+) outperforming control containing 10% human serum (~30% FOXP3+). In summary, our results suggest that serum can be eliminated from Treg workflows to generate highly suppressive enriched FOXP3+ Treg immunotherapy product. We believe that our defined serum-free medium and Dynabeadsâą Treg system will enable the development of better immunotherapies for autoimmunity
Gaining further insight into photo-Fenton treatment of phenolic compounds commonly found in food processing industry
A mixture of eight phenolic compounds, namely 2,4-dinitrophenol, tannic, ellagic, gallic, protocatechuic, vanillic, syringic and sinapic acids, have been treated by means of a photo-Fenton process under simulated and real sunlight. An experimental design methodology, based in Doehlert matrixes, was employed to check the effect of the concentration of Fe(II) and H2O2, as well as pH. Response surfaces show that photo-Fenton can be extended to pH values clearly above 2.8, probably due to complexation of iron with the phenolic substances. Experiments performed under solar irradiation at pH = 3.9 showed that complete removal of the monitored pollutants was achieved in less than 3 min; mineralisation was also efficient, although some organics remained in the solution. Toxicity was monitored according to Pseudokirchneriella subcapitata and Daphnia magna bioassays; Recombinant Yeast Assay (RYA) was employed to assess estrogenic and dioxin-like activities. 2,4-Dinitrophenol was demonstrated to be the major concern and, in general, photo-Fenton resulted in a detoxification of the solution. Finally, excitation emission matrix (EEM) fluorimetry was employed to obtain complementary information on the behaviour of organic matter. Most peaks associated with the parent pollutants disappeared after short irradiation periods and, at 12 min of irradiation chromophores were destroyed, what can be associated with the removal of complex molecules. (C) 2015 Elsevier B.V. All rights reserved.The authors want to thank the financial support of the Spanish Ministerio de Education y Ciencia (CTQ2012-38754-C03-02) and Generalitat Valenciana (GV/2015/074). Sara Garcia-Ballesteros would like to thank Spanish Ministerio de Economia y Competitividad for her fellowship (BES-2013-066201).GarcĂa Ballesteros, S.; Mora Carbonell, M.; Vicente Candela, R.; Sabater Marco, C.; Castillo LĂłpez, MĂ.; Arques Sanz, A.; Amat PayĂĄ, AM. (2016). Gaining further insight into photo-Fenton treatment of phenolic compounds commonly found in food processing industry. Chemical Engineering Journal. 288:126-136. https://doi.org/10.1016/j.cej.2015.11.031S12613628
Mortality prediction in chronic obstructive pulmonary disease comparing the GOLD 2015 and GOLD 2019 staging: a pooled analysis of individual patient data
In 2019, The Global Initiative for Chronic Obstructive Lung Disease (GOLD) modified the grading system for patients with COPD, creating 16 subgroups (1A-4D). As part of the COPD Cohorts Collaborative International Assessment (3CIA) initiative, we aim to compare the mortality prediction of the 2015 and 2019 COPD GOLD staging systems. We studied 17 139 COPD patients from the 3CIA study, selecting those with complete data. Patients were classified by the 2015 and 2019 GOLD ABCD systems, and we compared the predictive ability for 5-year mortality of both classifications. In total, 17139 patients with COPD were enrolled in 22 cohorts from 11 countries between 2003 and 2017; 8823 of them had complete data and were analysed. Mean +/- SD age was 63.9 +/- 9.8 years and 62.9% were male. GOLD 2019 classified the patients in milder degrees of COPD. For both classifications, group D had higher mortality. 5-year mortality did not differ between groups B and C in GOLD 2015; in GOLD 2019, mortality was greater for group B than C. Patients classified as group A and B had better sensitivity and positive predictive value with the GOLD 2019 classification than GOLD 2015. GOLD 2015 had better sensitivity for group C and D than GOLD 2019. The area under the curve values for 5-year mortality were only 0.67 (95% CI 0.66-0.68) for GOLD 2015 and 0.65 (95% CI 0.63-0.66) for GOLD 2019. The new GOLD 2019 classification does not predict mortality better than the previous GOLD 2015 system
Sex differences between women and men with COPD: A new analysis of the 3CIA study
Background: There is partial evidence that COPD is expressed differently in women than in men, namely on symptoms, pulmonary function, exacerbations, comorbidities or prognosis. There is a need to improve the characterization of COPD in females.
Methods: We obtained and pooled data of 17 139 patients from 22 COPD cohorts and analysed the clinical differences by sex, establishing the relationship between these characteristics in women and the prognosis and severity of the disease. Comparisons were established with standard statistics and survival analysis, including crude and multivariate Cox-regression analysis.
Results: Overall, 5355 (31.2%) women were compared with men with COPD. Women were younger, had lower pack-years, greater FEV1%, lower BMI and a greater number of exacerbations (all p < 0.05). On symptoms, women reported more dyspnea, equal cough but less expectoration (p < 0.001). There were no differences in the BODE index score in women (2.4) versus men (2.4) (p = 0.5), but the distribution of all BODE components was highly variable by sex within different thresholds of BODE. On prognosis, 5-year survival was higher in COPD females (86.9%) than in males (76.3%), p < 0.001, in all patients and within each of the specific comorbidities that we assessed. The crude and adjusted RR and 95% C.I. for death in males was 1.82 (1.69â1.96) and 1.73 (1.50â2.00), respectively.
Conclusions: COPD in women has some characteristic traits expressed differently than compared to men, mainly with more dyspnea and COPD exacerbations and less phlegm, among others, although long-term survival appears better in female COPD patients
Centrality dependence of charged particle production at large transverse momentum in Pb-Pb collisions at TeV
The inclusive transverse momentum () distributions of primary
charged particles are measured in the pseudo-rapidity range as a
function of event centrality in Pb-Pb collisions at
TeV with ALICE at the LHC. The data are presented in the range
GeV/ for nine centrality intervals from 70-80% to 0-5%.
The Pb-Pb spectra are presented in terms of the nuclear modification factor
using a pp reference spectrum measured at the same collision
energy. We observe that the suppression of high- particles strongly
depends on event centrality. In central collisions (0-5%) the yield is most
suppressed with at -7 GeV/. Above
GeV/, there is a significant rise in the nuclear modification
factor, which reaches for GeV/. In
peripheral collisions (70-80%), the suppression is weaker with almost independently of . The measured nuclear
modification factors are compared to other measurements and model calculations.Comment: 17 pages, 4 captioned figures, 2 tables, authors from page 12,
published version, figures at
http://aliceinfo.cern.ch/ArtSubmission/node/284
Evidence for a mixed mass composition at the `ankle' in the cosmic-ray spectrum
We report a first measurement for ultra-high energy cosmic rays of the
correlation between the depth of shower maximum and the signal in the water
Cherenkov stations of air-showers registered simultaneously by the fluorescence
and the surface detectors of the Pierre Auger Observatory. Such a correlation
measurement is a unique feature of a hybrid air-shower observatory with
sensitivity to both the electromagnetic and muonic components. It allows an
accurate determination of the spread of primary masses in the cosmic-ray flux.
Up till now, constraints on the spread of primary masses have been dominated by
systematic uncertainties. The present correlation measurement is not affected
by systematics in the measurement of the depth of shower maximum or the signal
in the water Cherenkov stations. The analysis relies on general characteristics
of air showers and is thus robust also with respect to uncertainties in
hadronic event generators. The observed correlation in the energy range around
the `ankle' at differs significantly from
expectations for pure primary cosmic-ray compositions. A light composition made
up of proton and helium only is equally inconsistent with observations. The
data are explained well by a mixed composition including nuclei with mass . Scenarios such as the proton dip model, with almost pure compositions, are
thus disfavoured as the sole explanation of the ultrahigh-energy cosmic-ray
flux at Earth.Comment: Published version. Added journal reference and DOI. Added Report
Numbe
Anisotropic flow of charged hadrons, pions and (anti-)protons measured at high transverse momentum in Pb-Pb collisions at TeV
The elliptic, , triangular, , and quadrangular, , azimuthal
anisotropic flow coefficients are measured for unidentified charged particles,
pions and (anti-)protons in Pb-Pb collisions at TeV
with the ALICE detector at the Large Hadron Collider. Results obtained with the
event plane and four-particle cumulant methods are reported for the
pseudo-rapidity range at different collision centralities and as a
function of transverse momentum, , out to GeV/.
The observed non-zero elliptic and triangular flow depends only weakly on
transverse momentum for GeV/. The small dependence
of the difference between elliptic flow results obtained from the event plane
and four-particle cumulant methods suggests a common origin of flow
fluctuations up to GeV/. The magnitude of the (anti-)proton
elliptic and triangular flow is larger than that of pions out to at least
GeV/ indicating that the particle type dependence persists out
to high .Comment: 16 pages, 5 captioned figures, authors from page 11, published
version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/186
Measurement of charm production at central rapidity in proton-proton collisions at TeV
The -differential production cross sections of the prompt (B
feed-down subtracted) charmed mesons D, D, and D in the rapidity
range , and for transverse momentum GeV/, were
measured in proton-proton collisions at TeV with the ALICE
detector at the Large Hadron Collider. The analysis exploited the hadronic
decays DK, DK, DD, and their charge conjugates, and was performed on a
nb event sample collected in 2011 with a
minimum-bias trigger. The total charm production cross section at TeV and at 7 TeV was evaluated by extrapolating to the full phase space
the -differential production cross sections at TeV
and our previous measurements at TeV. The results were compared
to existing measurements and to perturbative-QCD calculations. The fraction of
cdbar D mesons produced in a vector state was also determined.Comment: 20 pages, 5 captioned figures, 4 tables, authors from page 15,
published version, figures at
http://aliceinfo.cern.ch/ArtSubmission/node/307
Particle-yield modification in jet-like azimuthal di-hadron correlations in Pb-Pb collisions at = 2.76 TeV
The yield of charged particles associated with high- trigger
particles ( GeV/) is measured with the ALICE detector in
Pb-Pb collisions at = 2.76 TeV relative to proton-proton
collisions at the same energy. The conditional per-trigger yields are extracted
from the narrow jet-like correlation peaks in azimuthal di-hadron correlations.
In the 5% most central collisions, we observe that the yield of associated
charged particles with transverse momenta GeV/ on the
away-side drops to about 60% of that observed in pp collisions, while on the
near-side a moderate enhancement of 20-30% is found.Comment: 15 pages, 2 captioned figures, 1 table, authors from page 10,
published version, figures at
http://aliceinfo.cern.ch/ArtSubmission/node/350
Measurement of the polarisation of W bosons produced with large transverse momentum in pp collisions at sqrt(s) = 7 TeV with the ATLAS experiment
This paper describes an analysis of the angular distribution of W->enu and
W->munu decays, using data from pp collisions at sqrt(s) = 7 TeV recorded with
the ATLAS detector at the LHC in 2010, corresponding to an integrated
luminosity of about 35 pb^-1. Using the decay lepton transverse momentum and
the missing transverse energy, the W decay angular distribution projected onto
the transverse plane is obtained and analysed in terms of helicity fractions
f0, fL and fR over two ranges of W transverse momentum (ptw): 35 < ptw < 50 GeV
and ptw > 50 GeV. Good agreement is found with theoretical predictions. For ptw
> 50 GeV, the values of f0 and fL-fR, averaged over charge and lepton flavour,
are measured to be : f0 = 0.127 +/- 0.030 +/- 0.108 and fL-fR = 0.252 +/- 0.017
+/- 0.030, where the first uncertainties are statistical, and the second
include all systematic effects.Comment: 19 pages plus author list (34 pages total), 9 figures, 11 tables,
revised author list, matches European Journal of Physics C versio
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