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The Match method for the quantification of polar chemical ozone loss is investigated mainly with respect to the impact of the transport of air masses across the vortex edge. For the winter 2002/03, we show that significant transport across the vortex edge occurred and was simulated by the Chemical Lagrangian Model of the Stratosphere. In-situ observations of inert tracers and ozone from HAGAR on the Geophysica aircraft and balloon-borne sondes, and remote observations from MIPAS on the ENVISAT satellite were reproduced well by CLaMS. The model even reproduced a small vortex remnant that remained a distinct feature until June 2003 and was also observed in-situ by a balloon-borne whole air sampler. We use this CLaMS simulation to quantify the impact of transport across the vortex edge on ozone loss estimates from the Match method. We show that a time integration of the determined vortex average ozone loss rates, as performed in Match, results in a larger ozone loss than the polar vortex average ozone loss in CLaMS. The determination of the Match ozone loss rates is also influenced by the transport of air across the vortex edge. We use the model to investigate how the sampling of the ozone sondes on which Match is based represents the vortex average ozone loss rate. Both the time integration of ozone loss and the determination of ozone loss rates for Match are evaluated using the winter 2002/2003 CLaMS simulation. These impacts can explain the majority of the differences between CLaMS and Match column ozone loss. While the investigated effects somewhat reduce the apparent discrepancy in January ozone loss rates reported earlier, a distinct discrepancy between simulations and Match remains. However, its contribution to the accumulated ozone loss over the winter is not large.
The Match method for quantification of polar chemical ozone loss is investigated mainly with respect to the impact of mixing across the vortex edge onto this estimate. We show for the winter 2002/03 that significant mixing across the vortex edge occurred and was accurately modeled by the Chemical Lagrangian Model of the Stratosphere. Observations of inert tracers and ozone in-situ from HAGAR on the Geophysica aircraft and sondes and also remote from MIPAS on ENVISAT were reproduced well. The model even reproduced a small vortex remnant that was isolated until June 2003 and was observed in-situ by a balloon-borne whole air sampler. We use this CLaMS simulation to quantify the impact of cross vortex edge mixing on the results of the Match method. It is shown that a time integration of the determined vortex average ozone loss rates as performed in Match results in larger ozone loss than the polar vortex average ozone loss in CLaMS. Also, the determination of the Match ozone loss rates can be influenced by mixing. This is especially important below 430 K, where ozone outside the vortex is lower than inside and the vortex boundary is not a strong transport barrier. This effect and further sampling effects cause an offset between vortex average ozone loss rates derived from Match and deduced from CLaMS with an even sampling for the entire vortex. Both, the time-integration of ozone loss and the determination of ozone loss rates for Match are evaluated using the winter 2002/03 CLaMS simulation. These impacts can explain the differences between CLaMS and Match column ozone loss. While the investigated effects somewhat reduce the apparent discrepancy in January ozone loss rates, a discrepancy between simulations and Match remains. However, its contribution to the accumulated ozone loss over the winter is not large.
Biogenic organic precursors play an important role in atmospheric new particle formation (NPF). One of the major precursor species is α-pinene, which upon oxidation can form a suite of products covering a wide range of volatilities. Highly oxygenated organic molecules (HOMs) comprise a fraction of the oxidation products formed. While it is known that HOMs contribute to secondary organic aerosol (SOA) formation, including NPF, they have not been well studied in newly formed particles due to their very low mass concentrations. Here we present gas- and particle-phase chemical composition data from experimental studies of α-pinene oxidation, including in the presence of isoprene, at temperatures (−50 and −30 ∘C) and relative humidities (20 % and 60 %) relevant in the upper free troposphere. The measurements took place at the CERN Cosmics Leaving Outdoor Droplets (CLOUD) chamber. The particle chemical composition was analyzed by a thermal desorption differential mobility analyzer (TD-DMA) coupled to a nitrate chemical ionization–atmospheric pressure interface–time-of-flight (CI-APi-TOF) mass spectrometer. CI-APi-TOF was used for particle- and gas-phase measurements, applying the same ionization and detection scheme. Our measurements revealed the presence of C8−10 monomers and C18−20 dimers as the major compounds in the particles (diameter up to ∼ 100 nm). Particularly, for the system with isoprene added, C5 (C5H10O5−7) and C15 compounds (C15H24O5−10) were detected. This observation is consistent with the previously observed formation of such compounds in the gas phase. However, although the C5 and C15 compounds do not easily nucleate, our measurements indicate that they can still contribute to the particle growth at free tropospheric conditions. For the experiments reported here, most likely isoprene oxidation products enhance the growth of particles larger than 15 nm. Additionally, we report on the nucleation rates measured at 1.7 nm (J1.7 nm) and compared with previous studies, we found lower J1.7 nm values, very likely due to the higher α-pinene and ozone mixing ratios used in the present study.
Biogenic organic precursors play an important role in atmospheric new particle formation (NPF). One of the major precursor species is α-pinene, which upon oxidation can form a suite of products covering a wide range of volatilities. Highly oxygenated organic molecules (HOMs) comprise a fraction of the oxidation products formed. While it is known that HOMs contribute to secondary organic aerosol (SOA) formation, including NPF, they have not been well studied in newly formed particles due to their very low mass concentrations. Here we present gas- and particle-phase chemical composition data from experimental studies of α-pinene oxidation, including in the presence of isoprene, at temperatures (−50 and −30 ∘C) and relative humidities (20 % and 60 %) relevant in the upper free troposphere. The measurements took place at the CERN Cosmics Leaving Outdoor Droplets (CLOUD) chamber. The particle chemical composition was analyzed by a thermal desorption differential mobility analyzer (TD-DMA) coupled to a nitrate chemical ionization–atmospheric pressure interface–time-of-flight (CI-APi-TOF) mass spectrometer. CI-APi-TOF was used for particle- and gas-phase measurements, applying the same ionization and detection scheme. Our measurements revealed the presence of C8−10 monomers and C18−20 dimers as the major compounds in the particles (diameter up to ∼ 100 nm). Particularly, for the system with isoprene added, C5 (C5H10O5−7) and C15 compounds (C15H24O5−10) were detected. This observation is consistent with the previously observed formation of such compounds in the gas phase. However, although the C5 and C15 compounds do not easily nucleate, our measurements indicate that they can still contribute to the particle growth at free tropospheric conditions. For the experiments reported here, most likely isoprene oxidation products enhance the growth of particles larger than 15 nm. Additionally, we report on the nucleation rates measured at 1.7 nm (J1.7 nm) and compared with previous studies, we found lower J1.7 nm values, very likely due to the higher α-pinene and ozone mixing ratios used in the present study.
Erratum for: Cyclic AMP induces transactivation of the receptors for epidermal growth factor and nerve growth factor, thereby modulating activation of MAP kinase, Akt, and neurite outgrowth in PC12 cells.Journal of biological chemistry, 2002 Nov 15;277(46):43623-30. doi: 10.1074/jbc.M203926200. Epub 2002 Sep 5.
Purpose: The PELICAN trial evaluates for the first time efficacy and safety of pegylated liposomal doxorubicin (PLD) versus capecitabine as first-line treatment of metastatic breast cancer (MBC).
Methods: This randomized, phase III, open-label, multicenter trial enrolled first-line MBC patients who were ineligible for endocrine or trastuzumab therapy. Cumulative adjuvant anthracyclines of 360 mg/m2 doxorubicin or equivalent were allowed. Left ventricular ejection fraction of >50 % was required. Patients received PLD 50 mg/m2 every 28 days or capecitabine 1250 mg/m2 twice daily for 14 days every 21 days. The primary endpoint was time-to-disease progression (TTP).
Results: 210 patients were randomized (n = 105, PLD and n = 105, capecitabine). Adjuvant anthracyclines were given to 37 % (PLD) and 36 % (capecitabine) of patients. No significant difference was observed in TTP [HR = 1.21 (95 % confidence interval, 0.838–1.750)]. Median TTP was 6.0 months for both PLD and capecitabine. Comparing patients with or without prior anthracyclines, no significant difference in TTP was observed in the PLD arm (log-rank P = 0.64). For PLD versus capecitabine, respectively, overall survival (median, 23.3 months vs. 26.8 months) and time-to-treatment failure (median, 4.6 months vs. 3.7 months) were not statistically significantly different. Compared to PLD, patients on capecitabine experienced more serious adverse events (P = 0.015) and more cardiac events among patients who had prior anthracycline exposure (18 vs. 8 %; P = 0.31).
Conclusion: Both PLD and capecitabine are effective first-line agents for MBC.
In PC12 cells, a well studied model for neuronal differentiation, an elevation in the intracellular cAMP level increases cell survival, stimulates neurite outgrowth, and causes activation of extracellular signal-regulated protein kinase 1 and 2 (ERK1/2). Here we show that an increase in the intracellular cAMP concentration induces tyrosine phosphorylation of two receptor tyrosine kinases, i.e. the epidermal growth factor (EGF) receptor and the high affinity receptor for nerve growth factor (NGF), also termed Trk(A). cAMP-induced tyrosine phosphorylation of the EGF receptor is rapid and correlates with ERK1/2 activation. It occurs also in Panc-1, but not in human mesangial cells. cAMP-induced tyrosine phosphorylation of the NGF receptor is slower and correlates with Akt activation. Inhibition of EGF receptor tyrosine phosphorylation, but not of the NGF receptor, reduces cAMP-induced neurite outgrowth. Expression of dominant-negative Akt does not abolish cAMP-induced survival in serum-free media, but increases cAMP-induced ERK1/2 activation and neurite outgrowth. Together, our results demonstrate that cAMP induces dual signaling in PC12 cells: transactivation of the EGF receptor triggering the ERK1/2 pathway and neurite outgrowth; and transactivation of the NGF receptor promoting Akt activation and thereby modulating ERK1/2 activation and neurite outgrowth.
Erratum in: Correction: Cyclic AMP induces transactivation of the receptors for epidermal growth factor and nerve growth factor, thereby modulating activation of MAP kinase, Akt, and neurite outgrowth in PC12 cells. Journal of biological chemistry 2020 Oct 23;295(43):14792. doi: 10.1074/jbc.AAC120.016177.
The first measurement of two-pion Bose–Einstein correlations in central Pb–Pb collisions at √sNN=2.76 TeV at the Large Hadron Collider is presented. We observe a growing trend with energy now not only for the longitudinal and the outward but also for the sideward pion source radius. The pion homogeneity volume and the decoupling time are significantly larger than those measured at RHIC.
Inclusive transverse momentum spectra of primary charged particles in Pb–Pb collisions at √sNN=2.76 TeV have been measured by the ALICE Collaboration at the LHC. The data are presented for central and peripheral collisions, corresponding to 0–5% and 70–80% of the hadronic Pb–Pb cross section. The measured charged particle spectra in |η|<0.8 and 0.3<pT<20 GeV/c are compared to the expectation in pp collisions at the same sNN, scaled by the number of underlying nucleon–nucleon collisions. The comparison is expressed in terms of the nuclear modification factor RAA. The result indicates only weak medium effects (RAA≈0.7) in peripheral collisions. In central collisions, RAA reaches a minimum of about 0.14 at pT=6–7 GeV/c and increases significantly at larger pT. The measured suppression of high-pT particles is stronger than that observed at lower collision energies, indicating that a very dense medium is formed in central Pb–Pb collisions at the LHC.
The inclusive charged particle transverse momentum distribution is measured in proton–proton collisions at s=900 GeV at the LHC using the ALICE detector. The measurement is performed in the central pseudorapidity region (|η|<0.8) over the transverse momentum range 0.15<pT<10 GeV/c. The correlation between transverse momentum and particle multiplicity is also studied. Results are presented for inelastic (INEL) and non-single-diffractive (NSD) events. The average transverse momentum for |η|<0.8 is 〈pT〉INEL=0.483±0.001 (stat.)±0.007 (syst.) GeV/c and 〈pT〉NSD=0.489±0.001 (stat.)±0.007 (syst.) GeV/c, respectively. The data exhibit a slightly larger 〈pT〉 than measurements in wider pseudorapidity intervals. The results are compared to simulations with the Monte Carlo event generators PYTHIA and PHOJET.