Feasibility studies for quarkonium production at a fixed-target experiment using the LHC proton and lead beams (AFTER@LHC)

Used in the fixed-target mode, the multi-TeV LHC proton and lead beams allow for studies of heavy-flavour hadroproduction with unprecedented precision at backward rapidities - far negative Feyman-x - using conventional detection techniques. At the nominal LHC energies, quarkonia can be studies in detail in p+p, p+d and p+A collisions at sqrt(s_NN) ~ 115 GeV as well as in Pb+p and Pb+A collisions at sqrt(s_NN) ~ 72 GeV with luminosities roughly equivalent to that of the collider mode, i.e. up to 20 fb-1 yr-1 in p+p and p+d collisions, up to 0.6 fb-1 yr-1 in p+A collisions and up to 10 nb-1 yr-1 in Pb+A collisions. In this paper, we assess the feasibility of such studies by performing fast simulations using the performance of a LHCb-like detector.Comment: 12 pages, 14 figure

Regulation of CYP17 gene expression in adrenocortical cells by transforming growth factor-β

W korze nadnerczy geny CYP, kodujące składniki kompleksów enzymatycznych hydroksylaz steroido-wych, są regulowane przez hormony i czynniki wzrostu. Cytochrom P450c17, składnik kompleksu 17α–hydroksylazy/17,20–liazy, konieczny do produkcji androgenów nadnerczowych, jest kodowany przez CYP17 i ekspresja tego genu, zarówno podstawowa, jak i stymulowana, wymagają steroidogennego czynnika 1 (SF-1). Nasze badania, prowadzone na komórkach kory nadnerczy ludzkich NCI-H295R, wskazują, że TGF-β, działając za pośrednictwem ścieżki sygnałowej białek Smad, hamuje zarówno podstawową, jak i stymulowaną przez cAMP transkrypcję CYP17 i wymaga fragmentu -485/-433 promotora CYP17, zawierającego potencjalny element odpowiedzi na SP-1. Aby wyjaśnić mechanizm zahamowania transkrypcji CYP17 przez TGF-β, badano także ekspresję SF-1. Wykazano, że aktywator cyklazy adenilanowej, for-skolina, która imituje działanie ACTH - wzmaga, podczas gdy TGF-β - obniża poziom transkryptu SF-1. Maksymalne obniżenie poziomu podstawowego mRNA dla SF-1 obserwowano po 48 godz. inkubacji komórek z TGF-β (60% zahamowania), podczas gdy w komórkach inkubowanych z forskoliną i TGF-β obserwowano 50% zahamowanie ekspresji już po 6 godz. inkubacji. W obu przypadkach efekt dotyczył transkrypcji genu i towarzyszyły mu równoległe zmiany stężenia produktu białkowego genu. Wnioskuje się, że ekspresja CYP17 jest regulowana negatywnie przez TGF-β na poziomie transkrypcji poprzez ścieżkę sygnałową białek Smad i ten efekt wymaga fragmentu -483/-433 promotora, zawierającego potencjalny element odpowiedzi na SP-1. Efekt TGF-β na ekspresję CYP17 jest specyficzny, ponieważ w tych samych warunkach ekspresja CYP11A1 pozostała niezmieniona i może przynajmniej w części być spowodowany zahamowaniem transkrypcji SF-1In the adrenal cortex, CYP genes encoding cytochromes P450 components of steroid hydroxylases are regulated by hormones and growth factors. Cytochrome P450c17, constituent of 17α-hydroxylase/17,20-lyase enzyme complex, essential for production of adrenal androgens, is encoded by CYP17 and the expression of this gene, both basal and ACTH-induced, requires steroidogenic factor-1 (SF-1).Our studies conducted in human adrenocortical NCI-H295R cells indicated that TGF-β acting through the Smad protein pathway, inhibited both basal and cAMP-stimulated transcription of CYP17, and that the –483/-433 fragment of CYP17 promoter, which contains a putative Sp1 response element, is the target for the inhibitory action of TGF-β. To elucidate the mechanism of inhibition of CYP17 transcription by TGF-β, the expression of SF-1 was also investigated. It was demonstrated that adenylyl cyclase activator, forskolin which mimicks the effect of ACTH, increased, while TGF-β decreased the level of SF-1 transcript. The maximal decrease of basal SF-1 mRNA level was observed after 48 h of incubation of the cells with TGF-β (60% inhibition), while in forskolin-treated cells TGF-β caused 50% decrease in Sf-1 transcript level, already after 6 h of treatment. In both cases the effect was transcriptional and was accompanied by parallel changes in the level of the protein product of the gene. It is concluded that CYP17 expression is negatively regulated by TGF-β at the transcriptional level via Smad protein pathway, and that this effect requires the –483/-433 fragment of CYP17 promoter containing a putative Sp1 response element. The effect of TGF-β on the expression of CYP17 is specific, since under the same conditions the expression of CYP11A1 is unaffected, and could be, at least in part, due to the inhibition of SF-1 transcription

Emergency department hyperoxia is associated with increased mortality in mechanically ventilated patients: A cohort study

Definitions of comorbid conditions. (DOCX 13 kb

Badania polimorfizmów genów CYP1A1, CYP1B1 i CYP3A4 u chorych z rakiem piersi

Abstract Background: The role of CYP1A1, CYP1B1 and CYP3A4 polymorphism in pathogenesis of breast cancer has not been fully elucidated. From three CYP1A1 polymorphisms *2A (3801T>C), *2C (2455A>G), and *2B variant, which harbors both polymorphisms, the *2A variant is potentially carcinogenic in African Americans and the Taiwanese, but not in Caucasians, and the CYP1B1*2 (355G>T) and CYP1B1*3 (4326C>G) variants might increase breast cancer risk. Although no association of any CYP3A4 polymorphisms and breast cancer has been documented, the CYP3A4*1B (392A>G) variant, correlates with earlier menarche and endometrial cancer secondary to tamoxifen therapy. Objective: The present study was designed to investigate the frequency of CYP1A1, CYP1B1 and CYP3A4 polymorphisms in a sample of breast cancer patients from the Polish population and to correlate the results with the clinical and laboratory findings. Material and methods: The frequencies of CYP1A1*2A; CYP1A1*2C; CYP1B1*3; CYP3A4*1B CYP3A4*2 polymorphisms were determined in 71 patients aged 36-87, with primary breast cancer and 100 healthy individuals. Genomic DNA was extracted from the tumor, and individual gene fragments were PCR-amplified. The polymorphisms were determined by RFLP and were correlated with the patients’ TNM stage, grade, estrogen and progesterone receptor status as well as the level of c-erbB-2 protein. Results: CYP1A1 polymorphisms were more frequent in younger patients and in the patients with high level of c erbB 2 protein. No correlation between these polymorphisms and the cancer stage or grade, as well as the receptor status was demonstrated. Conclusions: CYP1A1 polymorphisms probably predispose to an earlier onset of breast cancer and might be associated with higher c-erbB-2 protein level, but further studies on a much larger group are required to substantiate our findings.Streszczenie Wstęp: Rola polimorfizmów genów CYP1A1, CYP1B1 oraz CYP3A4 w patogenezie raka piersi nie została w pełni wyjaśniona. Spośród trzech polimorfizmów CYP1A1*2A (3801T>C), *2C (2455A>G), oraz *2B, który zawiera oba warianty, tylko wariant *2A jest potencjalnie rakotwórczy u afro-amerykanów i mieszkańców Tajwanu, ale nie u rasy kaukaskiej, natomiast polimorfizmy CYP1B1*2 (355G>T) i CYP1B1*3 (4326C>G) mogą zwiększać ryzyko rozwoju raka piersi. Chociaż nie stwierdzono związku żadnego z polimorfizmów CYP3A z rakiem piersi, dowiedziono, że wariant CYP3A4*1B (392A>G) współistnieje z wcześniejszym występowaniem miesiączki oraz rakiem endometrium w następstwie leczenia tamoksyfenem. Cel: Celem badań było oznaczenie częstości występowania polimorfizmów CYP1A1, CYP1B1 i CYP3A4 w grupie chorych z rakiem piersi z populacji polskiej oraz poszukiwanie korelacji z wynikami badań klinicznych i laboratoryjnych. Materiał i metody: Częstości polimorfizmów CYP1A1*2A; CYP1A1*2C; CYP1B1*3; CYP3A4*1B i CYP3A4*2 oznaczono u 71 chorych (w wieku 36-87 lat) oraz 100 zdrowych kobiet. Genomowy DNA wyekstrahowano z tkanki guza i fragmenty poszczególnych genów amplifikowano za pomocą PCR. Polimorfizmy wykrywano techniką RFLP i korelowano ich występowanie ze stopniem zaawansowania klinicznego i histologicznego nowotworu, obecnością receptorów estrogenów i progesteronu jak również poziomem białka c-erbB-2. Wyniki: Polimorfizmy CYP1A1 częściej występowały u młodszych chorych oraz u chorych z wysokim poziomem białka c-erbB-2. Nie wykazano korelacji pomiędzy obecnością polimorfizmów a stopniem zaawansowania nowotworu czy obecnością receptorów. Wnioski: Polimorfizmy CYP1A1 przypuszczalnie predysponują do wcześniejszego występowania raka piersi i mogą wiązać się z podwyższeniem poziomu białka c-erbB-2, lecz potwierdzenie tych spostrzeżeń wymaga dalszych badań w większych grupach pacjentów

Library Assessment: East, West and South

Conference theme: Library Leadership in the Asia Pacific CenturySession 8 Library Assessmentpublished_or_final_versio

Heavy-flavour and quarkonium production in the LHC era: from proton-proton to heavy-ion collisions

This report reviews the study of open heavy-flavour and quarkonium production in high-energy hadronic collisions, as tools to investigate fundamental aspects of Quantum Chromodynamics, from the proton and nucleus structure at high energy to deconfinement and the properties of the Quark-Gluon Plasma. Emphasis is given to the lessons learnt from LHC Run 1 results, which are reviewed in a global picture with the results from SPS and RHIC at lower energies, as well as to the questions to be addressed in the future. The report covers heavy flavour and quarkonium production in proton-proton, proton-nucleus and nucleus-nucleus collisions. This includes discussion of the effects of hot and cold strongly interacting matter, quarkonium photo-production in nucleus-nucleus collisions and perspectives on the study of heavy flavour and quarkonium with upgrades of existing experiments and new experiments. The report results from the activity of the SaporeGravis network of the I3 Hadron Physics programme of the European Union 7th Framework Programme

First measurement of Ξc0\Xi_{\rm c}^0 production in pp collisions at s\mathbf{\sqrt{s}} = 7 TeV

The production of the charm-strange baryon $\Xi_{\rm c}^0$ is measured for the first time at the LHC via its semileptonic decay into e$^+\Xi^-\nu_{\rm e}$ in pp collisions at $\sqrt{s}=7$ TeV with the ALICE detector. The transverse momentum ($p_{\rm T}$) differential cross section multiplied by the branching ratio is presented in the interval 1 $<$ $p_{\rm T}$ $<$ 8 GeV/$c$ at mid-rapidity, $|y|$ $<$ 0.5. The transverse momentum dependence of the $\Xi_{\rm c}^0$ baryon production relative to the D$^0$ meson production is compared to predictions of event generators with various tunes of the hadronisation mechanism, which are found to underestimate the measured cross-section ratio.Comment: 22 pages, 6 captioned figures, 1 table, authors from page 17, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/412

Constraining the magnitude of the Chiral Magnetic Effect with Event Shape Engineering in Pb-Pb collisions at sNN\sqrt{s_{\rm NN}} = 2.76$ TeV

In ultrarelativistic heavy-ion collisions, the event-by-event variation of the elliptic flow $v_2$ reflects fluctuations in the shape of the initial state of the system. This allows to select events with the same centrality but different initial geometry. This selection technique, Event Shape Engineering, has been used in the analysis of charge-dependent two- and three-particle correlations in Pb-Pb collisions at $\sqrt{s_{_{\rm NN}}} =2.76$ TeV. The two-particle correlator $\langle \cos(\varphi_\alpha - \varphi_\beta) \rangle$, calculated for different combinations of charges $\alpha$ and $\beta$, is almost independent of $v_2$ (for a given centrality), while the three-particle correlator $\langle \cos(\varphi_\alpha + \varphi_\beta - 2\Psi_2) \rangle$ scales almost linearly both with the event $v_2$ and charged-particle pseudorapidity density. The charge dependence of the three-particle correlator is often interpreted as evidence for the Chiral Magnetic Effect (CME), a parity violating effect of the strong interaction. However, its measured dependence on $v_2$ points to a large non-CME contribution to the correlator. Comparing the results with Monte Carlo calculations including a magnetic field due to the spectators, the upper limit of the CME signal contribution to the three-particle correlator in the 10-50% centrality interval is found to be 26-33% at 95% confidence level.Comment: 20 pages, 6 captioned figures, 1 tables, authors from page 15, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/382