A
bstract
The NA48/2 experiment at CERN reports the first observation of the
K
±
→
π
0
π
0
μ
±
ν
decay based on a sample of 2437 candidates with 15% background contamination collected in 2003–2004. ...The decay branching ratio in the kinematic region of the squared dilepton mass above 0.03 GeV
2
/
c
4
is measured to be (0.65 ± 0.03) × 10
−
6
. The extrapolation to the full kinematic space, using a specific model, is found to be (3.45 ± 0.16) × 10
−
6
, in agreement with chiral perturbation theory predictions.
BACKGROUND AND PURPOSE Haem oxygenase 1 (HO‐1) is an inducible protein that plays a major protective role in conditions such as ischaemia‐reperfusion injury and inflammation. In this study, we have ...investigated the role of haem arginate (HA) in human male subjects in the modulation of HO‐1 expression and its correlation with the GT length polymorphism (GTn) in the promoter of the HO‐1 gene.
EXPERIMENTAL APPROACH In a dose‐escalation, randomized, placebo‐controlled trial, seven healthy male subjects with a homozygous short (S/S) and eight with a long (L/L) GTn genotype received intravenous HA. HO‐1 protein expression and mRNA levels in peripheral blood monocytes, bilirubin, haptoglobin, haemopexin and haem levels were analysed over a 48 h observation period.
KEY RESULTS We found that the baseline mRNA levels of HO‐1 were higher in L/L subjects, while protein levels were higher in S/S subjects. HA induced a dose‐dependent increase in the baseline corrected area under the curve values of HO‐1 mRNA and protein over 48 h. The response of HO‐1 mRNA was more pronounced in L/L subjects but the protein level was similar across the groups.
CONCLUSIONS AND IMPLICATION HA is an effective inducer of HO‐1 in humans irrespective of the GTn genotype. The potential therapeutic application of HA needs to be evaluated in clinical trials.
Breast cancer is the leading cause of cancer death in women living in the western hemisphere. Despite major advances in first-line endocrine therapy of advanced oestrogen receptor (ER)-positive ...breast cancer, the frequent recurrence of resistant cancer cells represents a serious obstacle to successful treatment. Understanding the mechanisms leading to acquired resistance, therefore, could pave the way to the development of second-line therapeutics. To this end, we generated an ER-positive breast cancer cell line (MCF-7) with resistance to the therapeutic anti-oestrogen fulvestrant (FUL) and studied the molecular changes involved in resistance.
Naive MCF-7 cells were treated with increasing FUL concentrations and the gene expression profile of the resulting FUL-resistant strain (FR.MCF-7) was compared with that of naive cells using GeneChip arrays. After validation by real-time PCR and/or western blotting, selected resistance-associated genes were functionally studied by siRNA-mediated silencing or pharmacological inhibition. Furthermore, general mechanisms causing aberrant gene expression were investigated.
Fulvestrant resistance was associated with repression of GPER and the overexpression of CDK6, whereas ERBB2, ABCG2, ER and ER-related genes (GREB1, RERG) or genes expressed in resistant breast cancer (BCAR1, BCAR3) did not contribute to resistance. Aberrant GPER and CDK6 expression was most likely caused by modification of DNA methylation and histone acetylation, respectively. Therefore, part of the resistance mechanism was loss of RB1 control. The hSWI/SNF (human SWItch/Sucrose NonFermentable) chromatin remodelling complex, which is tightly linked to nucleosome acetylation and repositioning, was also affected, because as a stress response to FUL treatment-naive cells altered the expression of five subunits within a few hours (BRG1, BAF250A, BAF170, BAF155, BAF47). The aberrant constitutive expression of BAF250A, BAF170 and BAF155 and a deviant stress response of BRG1, BAF170 and BAF47 in FR.MCF-7 cells to FUL treatment accompanied acquired FUL resistance. The regular and aberrant expression profiles of BAF155 correlated directly with that of CDK6 in naive and in FR.MCF-7 cells corroborating the finding that CDK6 overexpression was due to nucleosome alterations.
The study revealed that FUL resistance is associated with the dysregulation of GPER and CDK6. A mechanism leading to aberrant gene expression was most likely unscheduled chromatin remodelling by hSWI/SNF. Hence, three targets should be conceptually addressed in a second-line adjuvant therapy: the catalytic centre of SWI/SNF (BRG1) to delay the development of FUL resistance, GPER to increase sensitivity to FUL and the reconstitution of the RB1 pathway to overcome resistance.
A sample of 7253 K±→π±e+e−(γ) decay candidates with 1.0% background contamination has been collected by the NA48/2 experiment at the CERN SPS, which allowed a precise measurement of the decay ...properties. The branching ratio in the full kinematic range was measured to be BR=(3.11±0.12)×10−7, where the uncertainty includes also the model dependence. The shape of the form factor W(z), where z=(Mee/MK)2, was parameterized according to several models, and, in particular, the slope δ of the linear form factor W(z)=W0(1+δz) was determined to be δ=2.32±0.18. A possible CP violating asymmetry of K+ and K− decay widths was investigated, and a conservative upper limit of 2.1×10−2 at 90% CL was established.
We report results from a new measurement of the K
e4
decay K
±
→π
+
π
-
e
±
ν by the NA48/2 collaboration at the CERN SPS, based on a partial sample of more than 670 000 K
e4
decays in both charged ...modes collected in 2003. The form factors of the hadronic current (F,G,H) and ππ phase difference (δ=δ
s
-δ
p
) have been measured in ten independent bins of the ππ mass spectrum to investigate their variation. A sizeable acceptance at large ππ mass, a low background and a very good resolution contribute to an improved experimental accuracy, a factor two better than in the previous measurement, when extracting the ππ scattering lengths a
0
0
and a
0
2
. Under the assumption of isospin symmetry and using numerical solutions of the Roy equations, the following values are obtained in the plane (a
0
0
,a
0
2
): a
0
0
=0.233±0.016stat±0.007syst,a
0
2
=-0.0471±0.011stat±0.004syst. The presence of potentially large isospin effects is also considered and will allow comparison with precise predictions from Chiral Perturbation Theory.
New measurement of the K±→π±μ+μ− decay Kalmus, G.; Lazzeroni, C.; Munday, D.J. ...
Physics letters. B,
02/2011, Letnik:
697, Številka:
2
Journal Article
Recenzirano
Odprti dostop
A sample of 3120 K±→π±μ+μ− decay candidates with (3.3±0.7)% background contamination has been collected by the NA48/2 experiment at the CERN SPS, allowing a detailed study of the decay properties. ...The branching ratio was measured to be BR=(9.62±0.25)×10−8. The form factor W(z), where z=(Mμμ/MK)2, was parameterized according to several models. In particular, the slope of the linear form factor W(z)=W0(1+δz) was measured to be δ=3.11±0.57. Upper limits of 2.9×10−2 and 2.3×10−2 on possible charge asymmetry and forward–backward asymmetry were established at 90% CL. An upper limit BR(K±→π∓μ±μ±)<1.1×10−9 was established at 90% CL for the rate of the lepton number violating decay.
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