169 research outputs found

    Improving DISPGB Algorithm Using the Discriminant Ideal

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    In 1992, V. Weispfenning proved the existence of Comprehensive Groebner Bases (CGB) and gave an algorithm to compute one. That algorithm was not very efficient and not canonical. Using his suggestions, A. Montes obtained in 2002 a more efficient algorithm (DISPGB) for Discussing Parametric Groebner Bases. Inspired in its philosophy, V. Weispfenning defined, in 2002, how to obtain a Canonical Comprehensive Groebner Basis (CCGB) for parametric polynomial ideals, and provided a constructive method. In this paper we use Weispfenning's CCGB ideas to make substantial improvements on Montes DISPGB algorithm. It now includes rewriting of the discussion tree using the Discriminant Ideal and provides a compact and effective discussion. We also describe the new algorithms in the DPGB library containing the improved DISPGB as well as new routines to check whether a given basis is a CGB or not, and to obtain a CGB. Examples and tests are also provided.Comment: 21 pages, see also http://www-ma2.upc.edu/~montes

    Suppression of endothelial miR-22 mediates non-small cell lung cancer cell-induced angiogenesis

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    MicroRNAs (miRNAs) expressed in endothelial cells (ECs) are powerful regulators of angiogenesis, which is essential for tumor growth and metastasis. Here, we demonstrated that miR-22 is preferentially and highly expressed in ECs, while its endothelial level is significantly downregulated in human non-small cell lung cancer (NSCLC) tissues when compared to matched nontumor lung tissues. This reduction of endothelial miR-22 is possibly induced by NSCLC cell-secreted interleukin-1b and subsequently activated transcription factor nuclear factor-kB. Endothelial miR-22 functions as a potent angiogenesis inhibitor that inhibits all of the key angiogenic activities of ECs and consequently NSCLC growth through directly targeting sirtuin 1 and fibroblast growth factor receptor 1 in ECs, leading to inactivation of AKT/mammalian target of rapamycin signaling. These findings provide insight into the molecular mechanisms of NSCLC angiogenesis and indicate that endothelial miR-22 represents a potential target for the future antiangiogenic treatment of NSCLC

    Exclusive Nightclubs and Lonely Hearts Columns: Non-Monotone Participation in Optional Intermediation

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    In many decentralised markets, the traders who benefit most from an exchange do not employ intermediaries even though they could easily afford them. At the same time, employing intermediaries is not worthwhile for traders who benefit little from trade. Together, these decisions amount to non-monotone participation choices in intermediation: only traders of middle ``type'' employ intermediaries, while the rest, the high and the low types, prefer to search for a trading partner directly. We provide a theoretical foundation for this, hitherto unexplained, phenomenon. We build a dynamic matching model, where a trader's equilibrium bargaining share is a convex increasing function of her type. We also show that this is indeed a necessary condition for the existence of non-monotone equilibria

    Proliferation and estrogen signaling can distinguish patients at risk for early versus late relapse among estrogen receptor positive breast cancers

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    Introduction: We examined if a combination of proliferation markers and estrogen receptor (ER) activity could predict early versus late relapses in ER-positive breast cancer and inform the choice and length of adjuvant endocrine therapy. Methods: Baseline affymetrix gene-expression profiles from ER-positive patients who received no systemic therapy (n = 559), adjuvant tamoxifen for 5 years (cohort-1: n = 683, cohort-2: n = 282) and from 58 patients treated with neoadjuvant letrozole for 3 months (gene-expression available at baseline, 14 and 90 days) were analyzed. A proliferation score based on the expression of mitotic kinases (MKS) and an ER-related score (ERS) adopted from Oncotype DX® were calculated. The same analysis was performed using the Genomic Grade Index as proliferation marker and the luminal gene score from the PAM50 classifier as measure of estrogen-related genes. Median values were used to define low and high marker groups and four combinations were created. Relapses were grouped into time cohorts of 0-2.5, 0-5, 5-10 years. Results: In the overall 10 years period, the proportional hazards assumption was violated for several biomarker groups indicating time-dependent effects. In tamoxifen-treated patients Low-MKS/Low-ERS cancers had continuously increasing risk of relapse that was higher after 5 years than Low-MKS/High-ERS cancers [0 to 10 year, HR 3.36; p = 0.013]. High-MKS/High-ERS cancers had low risk of early relapse [0-2.5 years HR 0.13; p = 0.0006], but high risk of late relapse which was higher than in the High-MKS/Low-ERS group [after 5 years HR 3.86; p = 0.007]. The High-MKS/Low-ERS subset had most of the early relapses [0 to 2.5 years, HR 6.53; p < 0.0001] especially in node negative tumors and showed minimal response to neoadjuvant letrozole. These findings were qualitatively confirmed in a smaller independent cohort of tamoxifen-treated patients. Using different biomarkers provided similar results. Conclusions: Early relapses are highest in highly proliferative/low-ERS cancers, in particular in node negative tumors. Relapses occurring after 5 years of adjuvant tamoxifen are highest among the highly-proliferative/high-ERS tumors although their risk of recurrence is modest in the first 5 years on tamoxifen. These tumors could be the best candidates for extended endocrine therapy

    Secondary malignant neoplasms, progression-free survival and overall survival in patients treated for Hodgkin lymphoma: A systematic review and meta-analysis of randomized clinical trials

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    Treatment intensification to maximize disease control and reduced intensity approaches to minimize the risk of late sequelae have been evaluated in newly diagnosed Hodgkin lymphoma. The influence of these interventions on the risk of secondary malignant neoplasms, progression-free survival and overall survival is reported in the meta-analysis herein, based on individual patient data from 9498 patients treated within 16 randomized controlled trials for newly diagnosed Hodgkin lymphoma between 1984 and 2007. Secondary malignant neoplasms were meta-analyzed using Peto\ue2\u80\u99s method as time-to-event outcomes. For progression-free and overall survival, hazard ratios derived from each trial using Cox regression were combined by inverse-variance weighting. Five study questions (combined-modality treatment vs. chemotherapy alone; more extended vs. involved-field radiotherapy; radiation at higher doses vs. radiation at 20 Gy; more vs. fewer cycles of the same chemotherapy protocol; standard-dose chemotherapy vs. intensified chemotherapy) were investigated. After a median follow-up of 7.4 years, dose-intensified chemotherapy resulted in better progression-free survival rates (P=0.007) as compared with standard-dose chemotherapy, but was associated with an increased risk of therapy-related acute myeloid leukemia/myelodysplastic syndromes (P=0.0028). No progression-free or overall survival differences were observed between combined-modality treatment and chemotherapy alone, but more secondary malignant neoplasms were seen after combined-modality treatment (P=0.010). For the remaining three study questions, outcomes and secondary malignancy rates did not differ significantly between treatment strategies. The results of this meta-analysis help to weigh up efficacy and secondary malignancy risk for the choice of first-line treatment for Hodgkin lymphoma patients. However, final conclusions regarding secondary solid tumors require longer follow-up

    Semidefinite Characterization and Computation of Real Radical Ideals

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    For an ideal IR[x]I\subseteq\mathbb{R}[x] given by a set of generators, a new semidefinite characterization of its real radical I(VR(I))I(V_\mathbb{R}(I)) is presented, provided it is zero-dimensional (even if II is not). Moreover we propose an algorithm using numerical linear algebra and semidefinite optimization techniques, to compute all (finitely many) points of the real variety VR(I)V_\mathbb{R}(I) as well as a set of generators of the real radical ideal. The latter is obtained in the form of a border or Gr\"obner basis. The algorithm is based on moment relaxations and, in contrast to other existing methods, it exploits the real algebraic nature of the problem right from the beginning and avoids the computation of complex components.Comment: 41 page

    Measurement of the cosmic ray spectrum above 4×10184{\times}10^{18} eV using inclined events detected with the Pierre Auger Observatory

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    A measurement of the cosmic-ray spectrum for energies exceeding 4×10184{\times}10^{18} eV is presented, which is based on the analysis of showers with zenith angles greater than 6060^{\circ} detected with the Pierre Auger Observatory between 1 January 2004 and 31 December 2013. The measured spectrum confirms a flux suppression at the highest energies. Above 5.3×10185.3{\times}10^{18} eV, the "ankle", the flux can be described by a power law EγE^{-\gamma} with index γ=2.70±0.02(stat)±0.1(sys)\gamma=2.70 \pm 0.02 \,\text{(stat)} \pm 0.1\,\text{(sys)} followed by a smooth suppression region. For the energy (EsE_\text{s}) at which the spectral flux has fallen to one-half of its extrapolated value in the absence of suppression, we find Es=(5.12±0.25(stat)1.2+1.0(sys))×1019E_\text{s}=(5.12\pm0.25\,\text{(stat)}^{+1.0}_{-1.2}\,\text{(sys)}){\times}10^{19} eV.Comment: Replaced with published version. Added journal reference and DO
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