Tumor cell α3β1 integrin and vascular laminin-5 mediate pulmonary arrest and metastasis

Arrest of circulating tumor cells in distant organs is required for hematogenous metastasis, but the tumor cell surface molecules responsible have not been identified. Here, we show that the tumor cell α3β1 integrin makes an important contribution to arrest in the lung and to early colony formation. These analyses indicated that pulmonary arrest does not occur merely due to size restriction, and raised the question of how the tumor cell α3β1 integrin contacts its best-defined ligand, laminin (LN)-5, a basement membrane (BM) component. Further analyses revealed that LN-5 is available to the tumor cell in preexisting patches of exposed BM in the pulmonary vasculature. The early arrest of tumor cells in the pulmonary vasculature through interaction of α3β1 integrin with LN-5 in exposed BM provides both a molecular and a structural basis for cell arrest during pulmonary metastasis

Prognostic Factors Associated with Survival in Patients with Primary Duodenal Adenocarcinoma

Background/Aims: The prognostic factors in primary duodenal adenocarcinoma remain controversial. This study evaluated the prognostic factors associated with survival in patients with primary duodenal adenocarcinoma. Methods: From March 1996 to June 2008, the medical records of 30 patients with a final diagnosis of primary duodenal epithelial malignancy seen at two referral centers were reviewed retrospectively. The prognostic factors for survival were evaluated 6 months and 1, 2, and 5 years after the diagnosis. Results: The median survival was 5.7 months. The survival rate was 46.7 % (14/30), 16.7 % (5/30), 10 % (3/30), and 6.7 % (2/30) at 6 months and 1, 2, and 5 years, respectively. Multivariate analysis showed that cancer-direct-ed treatment, including curative surgery or chemotherapy, was a common independent risk factor at all follow-up times. Total bilirubin, cytology, and TNM stage were independent risk factors for survival at 1, 2, and 5 years. The white blood cell count was an independent risk factor at 1 year only. The actuarial probability of survival in patients undergoing cancer-directed treatment was significantly higher than in those without treatment at 6 months (71.4 vs. 25.0%, p < 0.01), 1 year (28.6 vs. 6.3%, p < 0.01), 2 years (21.4 vs. 0%, p < 0.01), and 5 years (14.3 vs. 0%, p < 0.01). Conclusions: The prognostic factors in patients with primary duodenal adenocarcinoma were total bilirubin, TNM stage, cytology, and cancer-directed treatments until the 5-year follow-up. Especially, cancer-directed treat-ments improved patient survival. (Korean J Intern Med 2011;26:34-40

Enhancing quantum efficiency of thin-film silicon solar cells by Pareto optimality

We present a composite design methodology for the simulation and optimization of the solar cell performance. Our method is based on the synergy of different computational techniques and it is especially designed for the thin-film cell technology. In particular, we aim to efficiently simulate light trapping and plasmonic effects to enhance the light harvesting of the cell. The methodology is based on the sequential application of a hierarchy of approaches: (a) full Maxwell simulations are applied to derive the photon’s scattering probability in systems presenting textured interfaces; (b) calibrated Photonic Monte Carlo is used in junction with the scattering matrices method to evaluate coherent and scattered photon absorption in the full cell architectures; (c) the results of these advanced optical simulations are used as the pair generation terms in model implemented in an effective Technology Computer Aided Design tool for the derivation of the cell performance; (d) the models are investigated by qualitative and quantitative sensitivity analysis algorithms, to evaluate the importance of the design parameters considered on the models output and to get a first order descriptions of the objective space; (e) sensitivity analysis results are used to guide and simplify the optimization of the model achieved through both Single Objective Optimization (in order to fully maximize devices efficiency) and Multi Objective Optimization (in order to balance efficiency and cost); (f) Local, Global and “Glocal” robustness of optimal solutions found by the optimization algorithms are statistically evaluated; (g) data-based Identifiability Analysis is used to study the relationship between parameters. The results obtained show a noteworthy improvement with respect to the quantum efficiency of the reference cell demonstrating that the methodology presented is suitable for effective optimization of solar cell devices

mTORC1 signalling and eIF4E/4E-BP1 translation initiation factor stoichiometry influence recombinant protein productivity from GS-CHOK1 cells

Many protein-based biotherapeutics are produced in cultured Chinese hamster ovary (CHO) cell lines. Recent reports have demonstrated that translation of recombinant mRNAs and global control of the translation machinery via mammalian target of rapamycin (mTOR) signalling are important determinants of the amount and quality of recombinant protein such cells can produce. mTOR complex 1 (mTORC1) is a master regulator of cell growth/division, ribosome biogenesis and protein synthesis, but the relationship between mTORC1 signalling, cell growth and proliferation and recombinant protein yields from mammalian cells, and whether this master regulating signalling pathway can be manipulated to enhance cell biomass and recombinant protein production (rPP) are not well explored. We have investigated mTORC1 signalling and activity throughout batch culture of a panel of sister recombinant glutamine synthetase-CHO cell lines expressing different amounts of a model monoclonal IgG4, to evaluate the links between mTORC1 signalling and cell proliferation, autophagy, recombinant protein expression, global protein synthesis and mRNA translation initiation. We find that the expression of the mTORC1 substrate 4E-binding protein 1 (4E-BP1) fluctuates throughout the course of cell culture and, as expected, that the 4E-BP1 phosphorylation profiles change across the culture. Importantly, we find that the eIF4E/4E-BP1 stoichiometry positively correlates with cell productivity. Furthermore, eIF4E amounts appear to be co-regulated with 4E-BP1 amounts. This may reflect a sensing of either change at the mRNA level as opposed to the protein level or the fact that the phosphorylation status, as well as the amount of 4E-BP1 present, is important in the co-regulation of eIF4E and 4E-BP1

Evidence for an excess of B -> D(*) Tau Nu decays

Based on the full BaBar data sample, we report improved measurements of the ratios R(D(*)) = B(B -> D(*) Tau Nu)/B(B -> D(*) l Nu), where l is either e or mu. These ratios are sensitive to new physics contributions in the form of a charged Higgs boson. We measure R(D) = 0.440 +- 0.058 +- 0.042 and R(D*) = 0.332 +- 0.024 +- 0.018, which exceed the Standard Model expectations by 2.0 sigma and 2.7 sigma, respectively. Taken together, our results disagree with these expectations at the 3.4 sigma level. This excess cannot be explained by a charged Higgs boson in the type II two-Higgs-doublet model. We also report the observation of the decay B -> D Tau Nu, with a significance of 6.8 sigma.Comment: Expanded section on systematics, text corrections, improved the format of Figure 2 and included the effect of the change of the Tau polarization due to the charged Higg

A search for the decay modes B+/- to h+/- tau l

We present a search for the lepton flavor violating decay modes B+/- to h+/- tau l (h= K,pi; l= e,mu) using the BaBar data sample, which corresponds to 472 million BBbar pairs. The search uses events where one B meson is fully reconstructed in one of several hadronic final states. Using the momenta of the reconstructed B, h, and l candidates, we are able to fully determine the tau four-momentum. The resulting tau candidate mass is our main discriminant against combinatorial background. We see no evidence for B+/- to h+/- tau l decays and set a 90% confidence level upper limit on each branching fraction at the level of a few times 10^-5.Comment: 15 pages, 7 figures, submitted to Phys. Rev.

Search for the decay modes D^0 → e^+e^-, D^0 → μ^+μ^-, and D^0 → e^±μ∓

We present searches for the rare decay modes D^0→e^+e^-, D^0→μ^+μ^-, and D^0→e^±μ^∓ in continuum e^+e^-→cc events recorded by the BABAR detector in a data sample that corresponds to an integrated luminosity of 468  fb^(-1). These decays are highly Glashow–Iliopoulos–Maiani suppressed but may be enhanced in several extensions of the standard model. Our observed event yields are consistent with the expected backgrounds. An excess is seen in the D^0→μ^+μ^- channel, although the observed yield is consistent with an upward background fluctuation at the 5% level. Using the Feldman–Cousins method, we set the following 90% confidence level intervals on the branching fractions: B(D^0→e^+e^-)<1.7×10^(-7), B(D^0→μ^+μ^-) within [0.6,8.1]×10^(-7), and B(D^0→e^±μ^∓)<3.3×10^(-7)