Free search in multidimensional space

One of the challenges for modern search methods is resolving multidimensional tasks where optimization parameters are hundreds, thousands and more. Many evolutionary, swarm and adaptive methods, which perform well on numerical test with up to 10 dimensions are suffering insuperable stagnation when are applied to the same tests extended to 50, 100 and more dimensions. This article presents an original investigation on Free Search, Differential Evolution and Particle Swarm Optimization applied to multidimensional versions of several heterogeneous real-value numerical tests. The aim is to identify how dimensionality reflects on the search space complexity, in particular to evaluate relation between tasks’ dimensions’ number and corresponding iterations’ number required by used methods for reaching acceptable solution with non-zero probability. Experimental results are presented and analyzed

GNAQ (guanine nucleotide binding protein (G protein), q polypeptide)

Review on GNAQ (guanine nucleotide binding protein (G protein), q polypeptide), with data on DNA, on the protein encoded, and where the gene is implicated

Static solitons with non-zero Hopf number

We investigate a generalized non-linear O(3) $\sigma$-model in three space dimensions where the fields are maps $S^3 \mapsto S^2$. Such maps are classified by a homotopy invariant called the Hopf number which takes integer values. The model exhibits soliton solutions of closed vortex type which have a lower topological bound on their energies. We explicitly compute the fields for topological charge 1 and 2 and discuss their shapes and binding energies. The effect of an additional potential term is considered and an approximation is given for the spectrum of slowly rotating solitons.Comment: 13 pages, RevTeX, 7 Postscript figures, minor changes have been made, a reference has been corrected and a figure replace

Nonlocal Automated Comparative Static Analysis

This paper reviews work on the development of a program Nasa for the automated comparative static analysis of parameterized nonlinear systems over parameter intervals. Nasa incorporates a fast and efficient algorithm Feed for the automatic evaluation of higher-order partial derivatives, as well as an adaptive homotopy continuation algorithm for obtaining all required initial conditions. Applications are envisioned for fields such as economics where models tend to be complex and closed-form solutions are difficult to obtain

Derivative based global sensitivity measures

The method of derivative based global sensitivity measures (DGSM) has recently become popular among practitioners. It has a strong link with the Morris screening method and Sobol' sensitivity indices and has several advantages over them. DGSM are very easy to implement and evaluate numerically. The computational time required for numerical evaluation of DGSM is generally much lower than that for estimation of Sobol' sensitivity indices. This paper presents a survey of recent advances in DGSM concerning lower and upper bounds on the values of Sobol' total sensitivity indices $S\_{i}^{tot}$. Using these bounds it is possible in most cases to get a good practical estimation of the values of $S\_{i}^{tot}$. Several examples are used to illustrate an application of DGSM

The boundary Riemann solver coming from the real vanishing viscosity approximation

We study a family of initial boundary value problems associated to mixed hyperbolic-parabolic systems: v^{\epsilon} _t + A (v^{\epsilon}, \epsilon v^{\epsilon}_x ) v^{\epsilon}_x = \epsilon B (v^{\epsilon} ) v^{\epsilon}_{xx} The conservative case is, in particular, included in the previous formulation. We suppose that the solutions $v^{\epsilon}$ to these problems converge to a unique limit. Also, it is assumed smallness of the total variation and other technical hypotheses and it is provided a complete characterization of the limit. The most interesting points are the following two. First, the boundary characteristic case is considered, i.e. one eigenvalue of $A$ can be $0$. Second, we take into account the possibility that $B$ is not invertible. To deal with this case, we take as hypotheses conditions that were introduced by Kawashima and Shizuta relying on physically meaningful examples. We also introduce a new condition of block linear degeneracy. We prove that, if it is not satisfied, then pathological behaviours may occur.Comment: 84 pages, 6 figures. Text changes in Sections 1 and 3.2.3. Added Section 3.1.2. Minor changes in other section

Differential influence of vemurafenib and dabrafenib on patients' lymphocytes despite similar clinical efficacy in melanoma

In this study, we demonstrate that vemurafenib but not dabrafenib reduces peripheral lymphocyte counts in melanoma patients while both agents show similar clinical efficacy. Within the lymphocyte compartment, vemurafenib selectively decreases circulating CD4+ T cells and changes their phenotype and function. This indicates that selective BRAFi need to be assessed individually for immunomodulatory effects, especially, when planning combinations with immunotherapie

Application of circulating cell-free tumor DNA profiles for therapeutic monitoring and outcome prediction in genetically heterogeneous metastatic melanoma

PURPOSE Circulating cell-free tumor DNA (ctDNA) reflects the heterogeneousspectrum of tumor-specific mutations, especially in systemic disease. We validated plasma-based assays that allow the dynamic quantitative detection of ctDNA as a prognostic biomarker for tumor load and prediction of therapy response in melanoma. MATERIALS and METHODS We analyzed plasma-derived ctDNA from a large training cohort (n = 96) of patients with advanced-stage melanoma, with assays for the BRAFV600E and NRASQ61 driver mutations as well as TERTC250T and TERTC228T promoter mutations. An independent patient cohort (n = 35) was used to validate the utility of ctDNA monitoring under mitogen-activated protein kinase–targeted or immune checkpoint therapies. RESULTS Elevated plasma ctDNA level at baseline was an independent prognostic factor of disease progression when compared with serum S100 and lactate dehydrogenase levels in multivariable analyses (hazard ratio [HR], 7.43; 95% CI, 1.01 to 55.19; P = .05). The change in ctDNA levels during therapy correlated with treatment response, where increasing ctDNA was predictive for shorter progression-free survival (eg, for BRAFV600EctDNA, HR, 3.70; 95% CI, 1.86 to 7.34; P < .001). Increasing ctDNA levels predicted disease progression significantly earlier than did routine radiologic scans (P < .05), with a mean lead time of 3.5 months. NRAS-mutant ctDNA was detected in a significant proportion of patients with BRAF-mutant tumors under therapy, but unexpectedly also at baseline. In vitro sensitivity studies suggested that this represents higher-than-expected intratumoral heterogeneity. The detection of NRASQ61 ctDNA in baseline samples of patients with BRAFV600E mutation who were treated with mitogen-activated protein kinase inhibitors significantly correlated with shorter progression-free survival (HR, 3.18; 95% CI, 1.31 to 7.68; P = .03) and shorter overall survival (HR, 4.08; 95% CI, 1.57 to 10.58; P = .01). CONCLUSION Our results show the potential role of ctDNA measurement as a sensitive monitoring and prediction tool for the early assessment of disease progression and therapeutic response in patients with metastaticmelanoma

PLZF induces an intravascular surveillance program mediated by long-lived LFA-1–ICAM-1 interactions

PLZF-expressing NKT cells establish residence at intravascular locations, failing to enter the circulation because of constitutive interactions with LFA-1 and ICAM-1