2,268 research outputs found
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
Revenue vs expenditure based fiscal consolidation: the pass-through from federal cuts to local taxes
A growing literature emphasizes that the output effect of fiscal consolidation hinges on its composition, as the choice of increasing revenues vs cutting expenditure is not neutral. Existing studies, however, underscore the role of local governments in a federal setting. Indeed, transfer cuts at the central level might translate into higher local taxes, changing the effective composition of the fiscal adjustment. We evaluate this transmission mechanism in Italy, where municipalities below the threshold of 5,000 inhabitants were exempted from (large) transfer cuts in 2012. This allows us to implement a difference-in-discontinuities design in order to estimate the causal impact of transfer cuts on the composition of fiscal adjustment, also because tight fiscal rules impose a balanced budget on Italian municipalities. We find a pass-through mechanism by which local governments react to the contraction of intergovernmental grants by mainly increasing taxes rather than reducing spending. From a political economy perspective, this revenue based fiscal consolidation is driven by local governments with low electoral competition and low party fragmentation
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)
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