Abstract Measurements of the production cross sections of prompt D0, D+, D*+, D s + $$ {\textrm{D}}_{\textrm{s}}^{+} $$ , Λ c + $$ {\Lambda}_{\textrm{c}}^{+} $$ , and Ξ c + $$ {\Xi}_{\textrm{c}}^{+} ...$$ charm hadrons at midrapidity in proton-proton collisions at s $$ \sqrt{s} $$ = 13 TeV with the ALICE detector are presented. The D-meson cross sections as a function of transverse momentum (p T) are provided with improved precision and granularity. The ratios of p T-differential meson production cross sections based on this publication and on measurements at different rapidity and collision energy provide a constraint on gluon parton distribution functions at low values of Bjorken-x (10 −5–10 −4). The measurements of Λ c + $$ {\Lambda}_{\textrm{c}}^{+} $$ ( Ξ c + $$ {\Xi}_{\textrm{c}}^{+} $$ ) baryon production extend the measured p T intervals down to p T = 0(3) GeV/c. These measurements are used to determine the charm-quark fragmentation fractions and the c c ¯ $$ \textrm{c}\overline{\textrm{c}} $$ production cross section at midrapidity (|y| < 0.5) based on the sum of the cross sections of the weakly-decaying ground-state charm hadrons D0, D+, D s + $$ {\textrm{D}}_{\textrm{s}}^{+} $$ , Λ c + $$ {\Lambda}_{\textrm{c}}^{+} $$ , Ξ c 0 $$ {\Xi}_{\textrm{c}}^0 $$ and, for the first time, Ξ c + $$ {\Xi}_{\textrm{c}}^{+} $$ , and of the strongly-decaying J/ψ mesons. The first measurements of Ξ c + $$ {\Xi}_{\textrm{c}}^{+} $$ and Σ c 0 , + + $$ {\Sigma}_{\textrm{c}}^{0,++} $$ fragmentation fractions at midrapidity are also reported. A significantly larger fraction of charm quarks hadronising to baryons is found compared to e+e − and ep collisions. The c c ¯ $$ \textrm{c}\overline{\textrm{c}} $$ production cross section at midrapidity is found to be at the upper bound of state-of-the-art perturbative QCD calculations.
Abstract The fractions of non-prompt (i.e. originating from beauty-hadron decays) D0 and D+ mesons with respect to the inclusive yield are measured as a function of the charged-particle multiplicity ...in proton-proton collisions at a centre-of-mass energy of s $$ \sqrt{s} $$ = 13 TeV with the ALICE detector at the LHC. The results are reported in intervals of transverse momentum (p T) and integrated in the range 1 < p T < 24 GeV/c. The fraction of non-prompt D0 and D+ mesons is found to increase slightly as a function of p T in all the measured multiplicity intervals, while no significant dependence on the charged-particle multiplicity is observed. In order to investigate the production and hadronisation mechanisms of charm and beauty quarks, the results are compared to PYTHIA 8 as well as EPOS 3 and EPOS 4 Monte Carlo simulations, and to calculations based on the colour glass condensate including three-pomeron fusion.
We designed hybrid molecules between propamidine and benzimidazole in order to retain the antiprotozoal action, but decreasing the toxic effect of the molecule.
Design and prepare 12 hybrids for ...testing their antiparasitic effect over three protozoa: Giardia intestinalis, Trichomonas vaginalis and Leishmania mexicana, as well as conduct several in silico simulations such as toxicological profile, molecular docking and molecular dynamics in order to understand their potential mode of action.
Hybrids 1-3, 6-9 and 12 were obtained using a chemical pathway previously reported. Compounds 4, 5, 10 and 11 were prepared using a one-pot reduction-cyclization reaction. The in vitro antiparasitic and cytotoxic activities of these compounds were conducted. It was calculated several properties such as toxicity, PK behavior, as well as docking studies and molecular dynamics of the most active compound performed in a DNA sequence dodecamer in comparison with propamidine.
Compound 2 was 183, 127 and 202 times more active against G. intestinalis than metronidazole, pentamidine and propamidine. It was eleven times more active than pentamidine against L. mexicana. This compound showed low in vitro mammalian cytotoxicity. Molecular simulations showed a stable complex 2-DNA that occurred in the minor groove, analogous to propamidine-DNA complex.
Compound 2, exhibited the higher bioactivity, especially towards G. intestinalis and L. mexicana. This study demonstrated that the replacement of benzimidazole scaffold instead of toxic amidine group in propamidine, results in an enhancement of antiprotozoal bioactivity. The preliminary molecular dynamics simulation suggests that the ligand-DNA complex is stable.
The present work reports the synthesis and characterization of a bisquinoline (BQT) with very attractive aggregation-induced emission (AIE) and optical nonlinear response. BQT was characterized by ...FTIR spectroscopy and mass spectrometry to confirm the product obtained. Linear optical characterization was performed using UV-Vis and fluorescence spectrophotometry. Maximum absorption and emission wavelengths of 408 nm and 539 nm, respectively, were determined in solution; the optical band gap on the film is 1.95 eV. BQT exhibits aggregation-induced emission (AIE), a property exhibited by some fluorescent molecules that broaden the range of applications in which they can be used. BQT exhibits two-photon absorption with a negative nonlinear refractive index. This response is associated with the charge transfer processes that favour the A-D-A architecture of the molecule. Their HOMO and LUMO energy levels (-5.39 eV and -3.67 eV, respectively) and electrochemical band gap (-1.72 eV) were determined by cyclic voltammetry; these values indicate that BQT is an attractive organic semiconductor which energy levels could match those required for photovoltaic applications. The results suggest that BQT is an attractive material for its application in optoelectronic devices such as OLEDs and nonlinear optical applications.
There is growing evidence that exposure to titanium dioxide nanoparticles (TiO2 NPs) could be harmful. Previously, we have shown that TiO2 NPs induces endothelial cell dysfunction and damage in glial ...cells. Considering that inhaled particles can induce systemic effects and the evidence that nanoparticles may translocate out of the lungs, we evaluated whether different types of TiO2 NPs can induce the expression of receptors for adhesion molecules on monocytes (U937 cell line). We evaluated the role of reactive oxygen spices (ROS) on these effects.
The expression of receptors for early (sLe(x) and PSGL-1) and late (LFA-1, VLA-4 and αVβ3) adhesion molecules was evaluated in U937 cells on a time course (3-24 h) using a wide range of concentrations (0.001-100 μg/mL) of three types of TiO2 NPs (<25 nm anatase, 50 nm anatase-rutile or < 100 nm anatase). Cells exposed to TNFα were considered positive controls, and unexposed cells, negative controls. In some experiments we added 10 μmolar of N-acetylcysteine (NAC) to evaluate the role of ROS.
All tested particles, starting at a concentration of 0.03 μg/mL, induced the expression of receptors for early and late adhesion molecules. The largest increases were induced by the different molecules after 3 h of exposure for sLe(x) and PSGL-1 (up to 3-fold of the positive controls) and after 18 h of exposure for LFA-1, VLA-4 and αVβ3 (up to 2.5-fold of the positive controls). Oxidative stress was observed as early as 10 min after exposure, but the maximum peak was found after 4 h of exposure. Adhesion of exposed or unexposed monocytes to unexposed or exposed endothelial cells was tested, and we observed that monocytes cells adhere in similar amounts to endothelial cells if one of the two cell types, or both were exposed. When NAC was added, the expression of the receptors was inhibited.
These results show that small concentrations of particles may activate monocytes that attach to endothelial cells. These results suggest that distal effects can be induced by small amounts of particles that may translocate from the lungs. ROS play a central role in the induction of the expression of these receptors.
Ra223 is a life-prolonging alpha-emitter bone targeted therapy for mCRPC patients with bone metastases. However, evidence on biomarkers that may help us in patient selection are lacking. Total ALP ...(tALP) appeared to be a potential marker of Ra223 effect in early studies (Sartor, Ann Oncol, 2017). Other bone-related markers, as bone-specific ALP (BALP), have demonstrated its prognostic value in mCRPC patients with bone metastases (Fizazi K, Eur Urol, 2015; Lara PN, J Natl Cancer Inst, 2014).
PRORADIUM (NCT022925702) is a prospective multicentre cohort study in mCRPC patients treated with Ra223. The primary aim was to assess the impact of baseline serum biomarkers of bone formation (BALP and C-terminal of type 1 collagen propeptide CICP) on overall survival (OS). Secondary aims include the correlation of progression-free survival (PFS), time to PSA progression (TTPP) and skeletal-related events free-survival (SRE-FS) with serum bone markers.
142 out of 168 pts enrolled in the study were included in this preliminary analysis. Median age was 74 yrs, 85.5% pts had ECOG 0-1, 52% pts completed 5-6 cycles of Ra223. Higher baseline levels of BALP and CICP were associated to number of metastases in bone-scan (p=0.007 and p=0.016, respectively) and baseline pain (p=0.014 and p=0.050, respectively). After a median follow-up of 18 months, 91 deaths were observed, with a median OS of 11.5 months (95%CI: 9.1-13.9). Patients with baseline BALP and CICP values above the median showed a trend to shorter TTPP (BALP: 2.8 vs 3.1 m, p=0.016; CICP: 2.8 vs 3.0 m, p=0.091) and PFS (BALP: 4.4 vs 5.1 m, p=0.070; CICP: 4.2 vs 5.5 m, p=0.281), respectively. The elevation of bone markers above the median was significantly associated with worse OS (BALP: 8.8 vs 17.9 m, p<0.001; CICP: 9.4 vs 16.8 m, p=0.001). There were not associations found with SRE-FS.
Our results suggest that baseline serum markers of bone formation may serve as biomarkers for prognosis in mCRPC patients treated with Ra233.
NCT022925702.
IBIMA and CNIO.
Bayer, CRIS Cancer Foundation, Grant from Instituto de Salud Carlos III (PI16/01565).
N. Romero Laorden: Honoraria (self), Travel / Accommodation / Expenses: Bayer, Astellas Pharma, Janssen-Cilag, Sanofi-Aventis, PharmaMar, MSD, Roche. R. Lozano Mejorada: Honoraria (self): Roche, Janssen-Cilag, Bayer; Research grant / Funding (institution): Bayer, Janssen-Cilag; Travel / Accommodation / Expenses: Roche, Janssen-Cilag, Astellas Pharma. E. Almagro Casado: Honoraria (self): MSD; Travel / Accommodation / Expenses: BMS. E. Gonzalez Billalabeitia: Travel / Accommodation / Expenses: BMS, Pfizer, Janssen-Cilag, Astellas Pharma, Sanofi. A. Montesa: Advisory / Consultancy: Janssen-Cilag, Pfizer, Sanofi, Astellas Pharma; Travel / Accommodation / Expenses: Pfizer. G.A. De Velasco Oria de Rueda: Honoraria (self), Advisory / Consultancy: Pfizer, Novartis, Ipsen, Astellas Pharma, BMS, Bayer, MSD, Roche. R. Morales Barrera: Honoraria (self): MSD, Sanofi, AstraZeneca, Janssen, Roche/Genentech; Advisory / Consultancy: MSD, Sanofi, AstraZeneca, Janssen, Roche/Genentech; Speaker Bureau / Expert testimony: MSD, Sanofi, AstraZeneca, Asofarma, Janssen; Research grant / Funding (institution): AB Science, Aragon Pharmaceuticals, INC, Astellas Pharma, AstraZeneca, Aveo Pharmaceuticals, Bayer, Blueprint Medicines Corporation, BN Immunotherapeutics, Boehringer Ingelheim España, BMS, Clovis Oncology, Cougar Technology, Deciphera Pharmaceuticals LL; Travel / Accommodation / Expenses: MSD, Roche, Lilly, Clovis Oncology, Bayer, Janssen-Cilag, Astellas Pharma, AstraZeneca. D. Lorente: Honoraria (self): Janssen-Cilag, Bayer, Astellas Pharma, Sanofi; Advisory / Consultancy: Janssen-Cilag, Bayer, Sanofi; Travel / Accommodation / Expenses: Sanofi, Astellas, Janssen-Cilag, Celgene. E. Castro: Honoraria (self): Astellas Pharma, Janssen-Cilag, AstraZeneca, Bayer, Pfizer; Advisory / Consultancy: Bayer, Janssen-Cilag; Research grant / Funding (institution): Janssen-Cilag, AstraZeneca, Bayer, Genentech, Roche, Pfizer, Astellas Medivation, Tokai Pharmaceuticals; Travel / Accommodation / Expenses: Bayer, Janssen-Cilag, Roche, Astellas Pharma. D. Olmos Hidalgo: Honoraria (self): Janssen-Cilag, Bayer, Sanofi; Advisory / Consultancy: Bayer, Janssen-Cilag, AstraZeneca, Clovis Oncology; Research grant / Funding (institution): Bayer, Janssen, AstraZeneca, Roche/Genentech, Medivation/Pfizer, Astellas, Tokai, MSD, GSK; Travel / Accommodation / Expenses: Bayer, Janssen-Cilag, Ipsen. All other authors have declared no conflicts of interest.
Context.
Teegarden’s Star is the brightest and one of the nearest ultra-cool dwarfs in the solar neighbourhood. For its late spectral type (M7.0 V), the star shows relatively little activity and is a ...prime target for near-infrared radial velocity surveys such as CARMENES.
Aims.
As part of the CARMENES search for exoplanets around M dwarfs, we obtained more than 200 radial-velocity measurements of Teegarden’s Star and analysed them for planetary signals.
Methods.
We find periodic variability in the radial velocities of Teegarden’s Star. We also studied photometric measurements to rule out stellar brightness variations mimicking planetary signals.
Results.
We find evidence for two planet candidates, each with 1.1
M
⊕
minimum mass, orbiting at periods of 4.91 and 11.4 d, respectively. No evidence for planetary transits could be found in archival and follow-up photometry. Small photometric variability is suggestive of slow rotation and old age.
Conclusions.
The two planets are among the lowest-mass planets discovered so far, and they are the first Earth-mass planets around an ultra-cool dwarf for which the masses have been determined using radial velocities.
A number of PCR-based techniques can be used to detect polymorphisms in plants. For their wide-scale usage in germplasm characterisation and breeding it is important that these marker technologies ...can be exchanged between laboratories, which in turn requires that they can be standardised to yield reproducible results, so that direct collation and comparison of the data are possible. This article describes a network experiment involving several European laboratories, in which the reproducibility of three popular molecular marker techniques was examined: random-amplified fragment length polymorphism (RAPD), amplified fragment length polymorphism (AFLP) and sequence-tagged microsatellites (SSR). For each technique, an optimal system was chosen, which had been standardised and routinely used by one laboratory. This system (genetic screening package) was distributed to different participating laboratories in the network and the results obtained compared with those of the original sender. Different experiences were gained in this exchange experiment with the different techniques. RAPDs proved difficult to reproduce. For AFLPs, a single-band difference was observed in one track, whilst SSR alleles were amplified by all laboratories, but small differences in their sizing were obtained.
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