Exploiting problem structure in derivative free optimization

A structured version of derivative-free random pattern search optimization algorithms is introduced which is able to exploit coordinate partially separable structure (typically associated with sparsity) often present in unconstrained and bound-constrained optimization problems. This technique improves performance by orders of magnitude and makes it possible to solve large problems that otherwise are totally intractable by other derivative-free methods. A library of interpolation-based modelling tools is also described, which can be associated to the structured or unstructured versions of the initial pattern search algorithm. The use of the library further enhances performance, especially when associated with structure. The significant gains in performance associated with these two techniques are illustrated using a new freely-available release of the BFO (Brute Force Optimizer) package firstly introduced in [Porcelli,Toint, ACM TOMS, 2017], which incorporates them. An interesting conclusion of the numerical results presented is that providing global structural information on a problem can result in significantly less evaluations of the objective function than attempting to building local Taylor-like models

Metastatic melanoma cells with BRAF G469A mutation: nab‑paclitaxel better than vemurafenib?

Purpose BRAF G469A is a missense mutation within exon 11 of the BRAF gene resulting in a constitutively activated enzyme frequently associated with MAP kinase cascade signaling activation. No evidence currently exists about its role in determining sensitivity/resistance to BRAF inhibitors, utilized in the treatment of patients carrying BRAF V600 mutations, and to chemotherapy. The newly established metastatic melanoma (MM) cell line MO-1 was characterized for its sensitivity to vemurafenib and nabpaclitaxel, both already utilized for the treatment of MM. Methods All analyses were carried out by comparing results with those found in MM cells wild type for BRAF or mutated in V600. In addition, cellular effectors were investigated by ELISA kits, western blotting and flow cytometry. Results The exposure to vemurafenib inhibited MO-1 cell proliferation at concentrations similar to those obtained in vemurafenib-resistant melanoma models, and an explanation of this sensitivity is the strong activation of Erk1/2 . and the low expression of MITF. Nab-paclitaxel strongly reduced proliferation of MO-1 cells perhaps for the very low expression level of PMEL17, transcriptionally regulated by MITF and negatively involved in determining sensitivity to taxanes. Conclusions Thus, the mutation BRAF G469A in MM might be related to a weak effectiveness of therapy with BRAF inhibitors and a promising therapeutic approach may be with nab-paclitaxel

The third KV62 radar scan: Searching for hidden chambers adjacent to Tutankhamun's tomb

The existence of hidden chambers and corridors adjacent to Tutankhamun’s tomb (code name KV62) hasbeen long debated. In 2015 it was suggested that these chambers may host the as yet undiscovered burialof Nefertiti. In order to test this hypothesis, two Ground Penetrating Radar (GPR) surveys, conductedin 2015 and 2016 from inside KV62, were carried out, but gave contradictory results. To solve theseuncertainties and obtain a more confident and conclusive response, a third GPR survey was conductedby our team in February 2018. The results of this third radar scan are reported in this article. Three GPRsystems with multiple frequency bands (from 150 MHz to 3000 MHz) and very dense spatial samplingwere adopted. After careful data processing, no evidence of marked discontinuities due to the passagefrom natural rock to artificial blocking walls were found in the radargrams. It is therefore concluded thatthere are no hidden chambers immediately adjacent to the Tomb of Tutankhamun

Editorial: Building and delivering real-world, integrated sustainability solutions: Insights, methods and case-study applications

This Research Topic aims to showcase research, development and technology (RDT) work toward devising and delivering integrated solutions that support and enhance the climate smart landscape (CSL)-based approach. This Research Topic comprises 13 articles, including 10 Original Research articles,1 Review, 1 Hypothesis and Theory article, and 1 Technology Report. State-of-the-art modeling approaches and sampling technologies are showcased. Contributed papers present new methodological/technological innovation, findings, and/or insights across four themes: (1) landscape productivity and crop suitability, (2) variable crop requirements for water and nutrients,(3) crop health status, phenology and phenotyping, (4)crop disease assessment and prediction under integrated pest management (IPM) and the CSL approach

Tracing U mobility in deep groundwater using Ra isotopes

The mobility of natural U is compared among four boreholes in a fractured granite using Ra isotopes and geochemical modelling. Rn-222/Ra-226 activity ratios (ARs) spanning an order of magnitude underline differences in reactive surface area. (Ra-224/Ra-228)(ARs) up to 9 indicate recent changes in hydrogeochemistry, and (Ra-226/Ra-228)(ARs) 0.6-30 indicate variable deposition of U. Dissolved U is related to dissolution of a solid U(VI) phase by groundwater with HCO3- > 20 mg.L-1. U reduction is hindered by Ca2UO2(CO3)(3)(0)