On the Runtime Analysis of the Clearing Diversity-Preserving Mechanism

Clearing is a niching method inspired by the principle of assigning the available resources among a niche to a single individual. The clearing procedure supplies these resources only to the best individual of each niche: the winner. So far, its analysis has been focused on experimental approaches that have shown that clearing is a powerful diversity-preserving mechanism. Using rigorous runtime analysis to explain how and why it is a powerful method, we prove that a mutation-based evolutionary algorithm with a large enough population size, and a phenotypic distance function always succeeds in optimising all functions of unitation for small niches in polynomial time, while a genotypic distance function requires exponential time. Finally, we prove that with phenotypic and genotypic distances clearing is able to find both optima for Twomax and several general classes of bimodal functions in polynomial expected time. We use empirical analysis to highlight some of the characteristics that makes it a useful mechanism and to support the theoretical results

Discovery and Preliminary Characterization of Translational Modulators that Impair the Binding of eIF6 to 60S Ribosomal Subunits

Eukaryotic initiation factor 6 (eIF6) is necessary for the nucleolar biogenesis of 60S ribosomes. However, most of eIF6 resides in the cytoplasm, where it acts as an initiation factor. eIF6 is necessary for maximal protein synthesis downstream of growth factor stimulation. eIF6 is an antiassociation factor that binds 60S subunits, in turn preventing premature 40S joining and thus the formation of inactive 80S subunits. It is widely thought that eIF6 antiassociation activity is critical for its function. Here, we exploited and improved our assay for eIF6 binding to ribosomes (iRIA) in order to screen for modulators of eIF6 binding to the 60S. Three compounds, eIFsixty-1 (clofazimine), eIFsixty-4, and eIFsixty-6 were identified and characterized. All three inhibit the binding of eIF6 to the 60S in the micromolar range. eIFsixty-4 robustly inhibits cell growth, whereas eIFsixty-1 and eIFsixty-6 might have dose- and cell-specific effects. Puromycin labeling shows that eIF6ixty-4 is a strong global translational inhibitor, whereas the other two are mild modulators. Polysome profiling and RT-qPCR show that all three inhibitors reduce the specific translation of well-known eIF6 targets. In contrast, none of them affect the nucleolar localization of eIF6. These data provide proof of principle that the generation of eIF6 translational modulators is feasible

Retrofit of existing railway bridges of short to medium spans for high-speed traffic using viscoelastic dampers

This paper presents a study on the energy-absorbing capacities of viscoelastic dampers (VEDs) for reducing the resonant vibrations of simply supported high-speed railway bridges of short to medium span. The proposed solution is based on retrofitting the bridge with a set of discrete VEDs connected to the slab and to an auxiliary structure, placed underneath the bridge deck and resting on the abutments. In this investigation attention is focused on mitigating flexural vibrations; therefore, both the bridge and the auxiliary structure are modelled as simply supported beams with Bernoulli-Euler (B-E) behavior, whereas a discrete fractional derivative model simulates the behavior of the damping material. Firstly, a parametric study of this planar model is carried out, which has led to a dimensioning procedure of the dissipative system. The technical feasibility of this particular retrofit design is numerically evaluated by applying it to a numerical model of a simply supported railway bridge with inadmissible vertical accelerations. Numerical results show that the dynamic response of the structure can be significantly reduced in resonance with the proposed damping system. © 2012 Elsevier Ltd.The authors wish to express their gratitude to the Spanish Ministry of Public Works for the financial support received in the framework of Research Project number 80021/A04.Moliner Cabedo, E.; Museros Romero, P.; Martínez Rodrigo, MDLD. (2012). Retrofit of existing railway bridges of short to medium spans for high-speed traffic using viscoelastic dampers. Engineering Structures. 40:519-528. doi:10.1016/j.engstruct.2012.03.016S5195284

Role of MRI in staging and follow-up of endometrial and cervical cancer:pitfalls and mimickers

Abstract MRI plays important roles in endometrial and cervical cancer assessment, from detection to recurrent disease evaluation. Endometrial cancer (EC) is the most common malignant tumor of the female genital tract in Western countries. EC patients are divided into risk categories based on histopathological tumor type, grade, and myometrial invasion depth. EC is surgically staged using the International Federation of Gynecology and Obstetrics (FIGO) system. Since FIGO (2009) stage correlates with prognosis, preoperative staging is essential for tailored treatment. MRI reveals myometrial invasion depth, which correlates with tumor grade and lymph node metastases, and thus correlates with prognosis. Cervical cancer (CC) is the second most common cancer, and the third leading cause of cancer-related death among females in developing countries. The FIGO Gynecologic Oncology Committee recently revised its CC staging guidelines, allowing staging based on imaging and pathological findings when available. The revised FIGO (2018) staging includes node involvement and thus enables both therapy selection and evaluation, prognosis estimation, and calculation of end results. MRI can accurately assess prognostic indicators, e.g., tumor size, parametrial invasion, pelvic sidewall, and lymph node invasion. Despite these important roles of MRI, radiologists still face challenges due to the technical and interpretation pitfalls of MRI during all phases of endometrial and cervical cancer evaluation. Awareness of mimics that can simulate both cancers is critical. With careful application, functional MRI with DWI and DCE sequences can help establish a correct diagnosis, although it is sometimes necessary to perform biopsy and histopathological analysis