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Phys.Rev.Lett. 88 (2002) 012301 New data are presented on the p(e,e'p)\pi^0 reaction at threshold at a
four-momentum transfer of Q^2=0.05 GeV^2/c^2. The data were taken with the
three-spectrometer ...setup of the A1 Collaboration at the Mainz Microtron MAMI.
The complete center of mass solid angle was covered up to a center of mass
energy of 4 MeV above threshold. Combined with measurements at three different
values of the virtual photon polarization \epsilon, the structure functions
\sigma_T, \sigma_L, \sigma_{TT}, and \sigma_{TL} are determined. The results
are compared with calculations in Heavy Baryon Chiral Perturbation Theory and
with a phenomenological model. The measured cross section is significantly
smaller than both predictions.
New data are presented on the p(e,e'p)\pi^0 reaction at threshold at a four-momentum transfer of Q^2=0.05 GeV^2/c^2. The data were taken with the three-spectrometer setup of the A1 Collaboration at ...the Mainz Microtron MAMI. The complete center of mass solid angle was covered up to a center of mass energy of 4 MeV above threshold. Combined with measurements at three different values of the virtual photon polarization \epsilon, the structure functions \sigma_T, \sigma_L, \sigma_{TT}, and \sigma_{TL} are determined. The results are compared with calculations in Heavy Baryon Chiral Perturbation Theory and with a phenomenological model. The measured cross section is significantly smaller than both predictions.
The rate of protein synthesis in the adult heart is one of the lowest in mammalian tissues, but it increases substantially in response to stress and hypertrophic stimuli through largely obscure ...mechanisms. Here, we demonstrate that regulated expression of cytosolic poly(A)-binding protein 1 (PABPC1) modulates protein synthetic capacity of the mammalian heart. We uncover a poly(A) tail-based regulatory mechanism that dynamically controls PABPC1 protein synthesis in cardiomyocytes and thereby titrates cellular translation in response to developmental and hypertrophic cues. Our findings identify PABPC1 as a direct regulator of cardiac hypertrophy and define a new paradigm of gene regulation in the heart, where controlled changes in poly(A) tail length influence mRNA translation.
The trifunctional antibody catumaxomab is a targeted immunotherapy for the intraperitoneal treatment of malignant ascites. In a Phase II/III trial in cancer patients (n = 258) with malignant ascites, ...catumaxomab showed a clear clinical benefit vs. paracentesis and had an acceptable safety profile. Human antimouse antibodies (HAMAs), which could be associated with beneficial humoral effects and prolonged survival, may develop against catumaxomab as it is a mouse/rat antibody. This post hoc analysis investigated whether there was a correlation between the detection of HAMAs 8 days after the fourth catumaxomab infusion and clinical outcome. HAMA‐positive and HAMA‐negative patients in the catumaxomab group and patients in the control group were analyzed separately for all three clinical outcome measures (puncture‐free survival, time to next puncture and overall survival) and compared to each other. There was a strong correlation between humoral response and clinical outcome: patients who developed HAMAs after catumaxomab showed significant improvement in all three clinical outcome measures vs. HAMA‐negative patients. In the overall population in HAMA‐positive vs. HAMA‐negative patients, median puncture‐free survival was 64 vs. 27 days (p < 0.0001; HR 0.330), median time to next therapeutic puncture was 104 vs. 46 days (p = 0.0002; HR 0.307) and median overall survival was 129 vs. 64 days (p = 0.0003; HR 0.433). Similar differences between HAMA‐positive and HAMA‐negative patients were seen in the ovarian, nonovarian and gastric cancer subgroups. In conclusion, HAMA development may be a biomarker for catumaxomab response and patients who developed HAMAs sooner derived greater benefit from catumaxomab treatment.
We report the role of relative lymphocyte count (RLC) as a potential biomarker with prognostic impact for catumaxomab efficacy and overall survival (OS) based on a post hoc analysis of the pivotal ...phase II/III study of intraperitoneal catumaxomab treatment of malignant ascites.
The impact of treatment and RLC on OS was evaluated using multivariate Cox models. Kaplan-Meier and log-rank tests were used for group comparisons. Survival analyses were performed on the safety population patients with paracentesis plus ≥ 1 dose of catumaxomab (n = 157) and paracentesis alone (n = 88). Determination of the optimal cutoff value for RLC was based on five optimality criteria.
OS was significantly longer with catumaxomab versus paracentesis alone (P = 0.0219). The 6-month OS rate with catumaxomab was 28.9% versus 6.7% with paracentesis alone. RLC had a positive impact on OS and was an independent prognostic factor (P < 0.0001). In patients with RLC > 13% (n = 159: catumaxomab, 100 and control, 59), catumaxomab was associated with a favorable effect on OS versus paracentesis alone (P = 0.0072), with a median/mean OS benefit of 41/131 days and an increased 6-month survival rate of 37.0% versus 5.2%, respectively. In patients with RLC ≤ 13% at screening (n = 74: catumaxomab, 50 and control, 24), the median (mean) OS difference between the catumaxomab and the control group was 3 (16) days, respectively (P = 0.2561).
OS was significantly improved after catumaxomab treatment in patients with malignant ascites. An RLC > 13% at baseline was a significant prognostic biomarker.
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