Towards a design process for computer-aided biomimetics

Computer-Aided Biomimetics (CAB) tools aim to support the integration of relevant biological knowledge into biomimetic problem-solving processes. Specific steps of biomimetic processes that require support include the identification, selection and abstraction of relevant biological analogies. Existing CAB tools usually aim to support these steps by describing biological systems in terms of functions, although engineering functions do not map naturally to biological functions. Consequentially, the resulting static, functional view provides an incomplete understanding of biological processes, which are dynamic, cyclic and self-organizing. This paper proposes an alternative approach that revolves around the concept of trade-offs. The aim is to include the biological context, such as environmental characteristics, that may provide information crucial to the transfer of biological information to an engineering application. The proposed design process is exemplified by an illustrative case study

Nonparametric instrumental regression with non-convex constraints

This paper considers the nonparametric regression model with an additive error that is dependent on the explanatory variables. As is common in empirical studies in epidemiology and economics, it also supposes that valid instrumental variables are observed. A classical example in microeconomics considers the consumer demand function as a function of the price of goods and the income, both variables often considered as endogenous. In this framework, the economic theory also imposes shape restrictions on the demand function, like integrability conditions. Motivated by this illustration in microeconomics, we study an estimator of a nonparametric constrained regression function using instrumental variables by means of Tikhonov regularization. We derive rates of convergence for the regularized model both in a deterministic and stochastic setting under the assumption that the true regression function satisfies a projected source condition including, because of the non-convexity of the imposed constraints, an additional smallness condition

An instability criterion for nonlinear standing waves on nonzero backgrounds

A nonlinear Schr\"odinger equation with repulsive (defocusing) nonlinearity is considered. As an example, a system with a spatially varying coefficient of the nonlinear term is studied. The nonlinearity is chosen to be repelling except on a finite interval. Localized standing wave solutions on a non-zero background, e.g., dark solitons trapped by the inhomogeneity, are identified and studied. A novel instability criterion for such states is established through a topological argument. This allows instability to be determined quickly in many cases by considering simple geometric properties of the standing waves as viewed in the composite phase plane. Numerical calculations accompany the analytical results.Comment: 20 pages, 11 figure

ADI splitting schemes for a fourth-order nonlinear partial differential equation from image processing

We present directional operator splitting schemes for the numerical solution of a fourth-order, nonlinear partial differential evolution equation which arises in image processing. This equation constitutes the H−1-gradient flow of the total variation and represents a prototype of higher-order equations of similar type which are popular in imaging for denoising, deblurring and inpainting problems. The efficient numerical solution of this equation is very challenging due to the stiffness of most numerical schemes. We show that the combination of directional splitting schemes with implicit time-stepping provides a stable and computationally cheap numerical realisation of the equation

Spontaneous creation of Kibble-Zurek solitons in a Bose-Einstein condensate

When a system crosses a second-order phase transition on a finite timescale, spontaneous symmetry breaking can cause the development of domains with independent order parameters, which then grow and approach each other creating boundary defects. This is known as Kibble-Zurek mechanism. Originally introduced in cosmology, it applies both to classical and quantum phase transitions, in a wide variety of physical systems. Here we report on the spontaneous creation of solitons in Bose-Einstein condensates via the Kibble-Zurek mechanism. We measure the power-law dependence of defects number with the quench time, and provide a check of the Kibble-Zurek scaling with the sonic horizon. These results provide a promising test bed for the determination of critical exponents in Bose-Einstein condensates.Comment: 7 pages, 4 figure

Angular momenta creation in relativistic electron-positron plasma

Creation of angular momentum in a relativistic electron-positron plasma is explored. It is shown that a chain of angular momentum carrying vortices is a robust asymptotic state sustained by the generalized nonlinear Schrodinger equation characteristic to the system. The results may suggest a possible electromagnetic origin of angular momenta when it is applied to the MeV epoch of the early Universe.Comment: 20 pages, 6 figure

Allele-specific miRNA-binding analysis identifies candidate target genes for breast cancer risk

Most breast cancer (BC) risk-associated single-nucleotide polymorphisms (raSNPs) identified in genome-wide association studies (GWAS) are believed to cis-regulate the expression of genes. We hypothesise that cis-regulatory variants contributing to disease risk may be affecting microRNA (miRNA) genes and/or miRNA binding. To test this, we adapted two miRNA-binding prediction algorithms-TargetScan and miRanda-to perform allele-specific queries, and integrated differential allelic expression (DAE) and expression quantitative trait loci (eQTL) data, to query 150 genome-wide significant ( P≤5×10-8 ) raSNPs, plus proxies. We found that no raSNP mapped to a miRNA gene, suggesting that altered miRNA targeting is an unlikely mechanism involved in BC risk. Also, 11.5% (6 out of 52) raSNPs located in 3'-untranslated regions of putative miRNA target genes were predicted to alter miRNA::mRNA (messenger RNA) pair binding stability in five candidate target genes. Of these, we propose RNF115, at locus 1q21.1, as a strong novel target gene associated with BC risk, and reinforce the role of miRNA-mediated cis-regulation at locus 19p13.11. We believe that integrating allele-specific querying in miRNA-binding prediction, and data supporting cis-regulation of expression, improves the identification of candidate target genes in BC risk, as well as in other common cancers and complex diseases.Funding Agency Portuguese Foundation for Science and Technology CRESC ALGARVE 2020 European Union (EU) 303745 Maratona da Saude Award DL 57/2016/CP1361/CT0042 SFRH/BPD/99502/2014 CBMR-UID/BIM/04773/2013 POCI-01-0145-FEDER-022184info:eu-repo/semantics/publishedVersio

O(N) methods in electronic structure calculations

Linear scaling methods, or O(N) methods, have computational and memory requirements which scale linearly with the number of atoms in the system, N, in contrast to standard approaches which scale with the cube of the number of atoms. These methods, which rely on the short-ranged nature of electronic structure, will allow accurate, ab initio simulations of systems of unprecedented size. The theory behind the locality of electronic structure is described and related to physical properties of systems to be modelled, along with a survey of recent developments in real-space methods which are important for efficient use of high performance computers. The linear scaling methods proposed to date can be divided into seven different areas, and the applicability, efficiency and advantages of the methods proposed in these areas is then discussed. The applications of linear scaling methods, as well as the implementations available as computer programs, are considered. Finally, the prospects for and the challenges facing linear scaling methods are discussed.Comment: 85 pages, 15 figures, 488 references. Resubmitted to Rep. Prog. Phys (small changes

SLAMF6 as a Regulator of Exhausted CD8+ T Cells in Cancer

The tumor microenvironment in leukemia and solid tumors induces a shift of activated CD8+ cytotoxic T cells to an exhausted state, characterized by loss of proliferative capacity and impaired immunologic synapse formation. Efficient strategies and targets need to be identified to overcome T-cell exhaustion and further improve overall responses in the clinic. Here, we took advantage of the Eμ-TCL1 chronic lymphocytic leukemia (CLL) and B16 melanoma mouse models to assess the role of the homophilic cell-surface receptor SLAMF6 as an immune-checkpoint regulator. The transfer of SLAMF6+ Eμ-TCL1 cells into SLAMF6−/− recipients, in contrast to wild-type (WT) recipients, significantly induced expansion of a PD-1+ subpopulation among CD3+CD44+CD8+ T cells, which had impaired cytotoxic functions. Conversely, administering anti-SLAMF6 significantly reduced the leukemic burden in Eμ-TCL1 recipient WT mice concomitantly with a loss of PD-1+CD3+CD44+CD8+ T cells with significantly increased effector functions. Anti-SLAMF6 significantly reduced leukemic burden in the peritoneal cavity, a niche where antibody-dependent cellular cytotoxicity (ADCC) is impaired, possibly through activation of CD8+ T cells. Targeting of SLAMF6 affected tumor growth not only in B cell–related leukemia and lymphomas but also in nonhematopoietic tumors such as B16 melanoma, where SLAMF6 is not expressed. In vitro exhausted CD8+ T cells showed increased degranulation when anti-human SLAMF6 was added in culture. Taken together, anti-SLAMF6 both effectively corrected CD8+ T-cell dysfunction and had a direct effect on tumor progression. The outcomes of our studies suggest that targeting SLAMF6 is a potential therapeutic strategy