Cover-Encodings of Fitness Landscapes

The traditional way of tackling discrete optimization problems is by using local search on suitably defined cost or fitness landscapes. Such approaches are however limited by the slowing down that occurs when the local minima that are a feature of the typically rugged landscapes encountered arrest the progress of the search process. Another way of tackling optimization problems is by the use of heuristic approximations to estimate a global cost minimum. Here we present a combination of these two approaches by using cover-encoding maps which map processes from a larger search space to subsets of the original search space. The key idea is to construct cover-encoding maps with the help of suitable heuristics that single out near-optimal solutions and result in landscapes on the larger search space that no longer exhibit trapping local minima. We present cover-encoding maps for the problems of the traveling salesman, number partitioning, maximum matching and maximum clique; the practical feasibility of our method is demonstrated by simulations of adaptive walks on the corresponding encoded landscapes which find the global minima for these problems.Comment: 15 pages, 4 figure

Pymrio – A Python Based Multi-Regional Input-Output Analysis Toolbox

Pymrio is an open source tool for Environmentally Extended Multi-Regional Input-Output (EE MRIO) analysis developed in Python. It provides a high-level abstraction layer for global EE MRIO databases in order to simplify common EE MRIO data tasks. Among others, Pymrio includes parsers for several openly available EE MRIO databases (EXIOBASE v1 – v3, WIOD, Eora26, OECD-ICIO) as well as methods for production and consumption based accounts calculation, aggregation, stressor origin estimation and visualization. The use of a consistent storage format including meta data and modification history for MRIOs allows to exchange data with other analysis tools, aiming for an increased interoperability of Industrial Ecology analysis software

Optimisation via encodings: a renormalisation group perspective

The traditional way of tackling discrete optimization problems is by using local search on suitably defined cost or fitness landscapes. Such approaches are however limited by the slowing down that occurs when local minima, that are a feature of the typically rugged landscapes encountered, arrest the progress of the search process. Another way of tackling optimization problems is by the use of heuristic approximations to estimate a global cost minimum. Here we present a combination of these two approaches by using cover-encoding maps which map processes from a larger search space to subsets of the original search space. The key idea is to construct cover-encoding maps with the help of suitable heuristics that single out near-optimal solutions and result in landscapes on the larger search space that no longer exhibit trapping local minima. The processes that are typically employed involve some form of coarse-graining, and we suggest here that they can be viewed as avatars of renormalisation group transformations.Comment: 17 pages, 2 figures. arXiv admin note: text overlap with arXiv:1806.0524

FRANz: reconstruction of wild multi-generation pedigrees

Summary: We present a software package for pedigree reconstruction in natural populations using co-dominant genomic markers such as microsatellites and single nucleotide polymorphisms (SNPs). If available, the algorithm makes use of prior information such as known relationships (sub-pedigrees) or the age and sex of individuals. Statistical confidence is estimated by Markov Chain Monte Carlo (MCMC) sampling. The accuracy of the algorithm is demonstrated for simulated data as well as an empirical dataset with known pedigree. The parentage inference is robust even in the presence of genotyping errors

Patterning the insect eye: from stochastic to deterministic mechanisms

While most processes in biology are highly deterministic, stochastic mechanisms are sometimes used to increase cellular diversity, such as in the specification of sensory receptors. In the human and Drosophila eye, photoreceptors sensitive to various wavelengths of light are distributed randomly across the retina. Mechanisms that underlie stochastic cell fate specification have been analysed in detail in the Drosophila retina. In contrast, the retinas of another group of dipteran flies exhibit highly ordered patterns. Species in the Dolichopodidae, the "long-legged" flies, have regular alternating columns of two types of ommatidia (unit eyes), each producing corneal lenses of different colours. Individual flies sometimes exhibit perturbations of this orderly pattern, with "mistakes" producing changes in pattern that can propagate across the entire eye, suggesting that the underlying developmental mechanisms follow local, cellular-automaton-like rules. We hypothesize that the regulatory circuitry patterning the eye is largely conserved among flies such that the difference between the Drosophila and Dolichopodidae eyes should be explicable in terms of relative interaction strengths, rather than requiring a rewiring of the regulatory network. We present a simple stochastic model which, among its other predictions, is capable of explaining both the random Drosophila eye and the ordered, striped pattern of Dolichopodidae.Comment: 24 pages, 4 figure

Connecting global emissions to fundamental human needs and their satisfaction

While quality of life (QOL) is the result of satisfying human needs, our current provision strategies result in global environmental degradation. To ensure sustainable QOL, we need to understand the environmental impact of human needs satisfaction. In this paper we deconstruct QOL, and apply the fundamental human needs framework developed by Max-Neef et al to calculate the carbon and energy footprints of subsistence, protection, creation, freedom, leisure, identity, understanding and participation. We find that half of global carbon emissions are driven by subsistence and protection. A similar amount are due to freedom, identity, creation and leisure together, whereas understanding and participation jointly account for less than 4% of global emissions. We use 35 objective and subjective indicators to evaluate human needs satisfaction and their associated carbon footprints across nations. We find that the relationship between QOL and environmental impact is more complex than previously identified through aggregated or single indicators. Satisfying needs such as protection, identity and leisure is generally not correlated with their corresponding footprints. In contrast, the likelihood of satisfying needs for understanding, creation, participation and freedom, increases steeply when moving from low to moderate emissions, and then stagnates. Most objective indicators show a threshold trend with respect to footprints, but most subjective indicators show no relationship, except for freedom and creation. Our study signals the importance of considering both subjective and objective satisfaction to assess QOL-impact relationships at the needs level. In this way, resources could be strategically invested where they strongly relate to social outcomes, and spared where non-consumption satisfiers could be more effective. Through this approach, decoupling human needs satisfaction from environmental damage becomes more attainable

Interferon-γ acutely augments inhibition of neocortical layer 5 pyramidal neurons

BACKGROUND: Interferon-γ (IFN-γ, a type II IFN) is present in the central nervous system (CNS) under various conditions. Evidence is emerging that, in addition to its immunological role, IFN-γ modulates neuronal morphology, function, and development in several brain regions. Previously, we have shown that raising levels of IFN-β (a type I IFN) lead to increased neuronal excitability of neocortical layer 5 pyramidal neurons. Because of shared non-canonical signaling pathways of both cytokines, we hypothesized a similar neocortical role of acutely applied IFN-γ. METHODS: We used semi-quantitative RT-PCR, immunoblotting, and immunohistochemistry to analyze neuronal expression of IFN-γ receptors and performed whole-cell patch-clamp recordings in layer 5 pyramidal neurons to investigate sub- and suprathreshold excitability, properties of hyperpolarization-activated cyclic nucleotide-gated current (Ih), and inhibitory neurotransmission under the influence of acutely applied IFN-γ. RESULTS: We show that IFN-γ receptors are present in the membrane of rat's neocortical layer 5 pyramidal neurons. As expected from this and the putative overlap in IFN type I and II alternative signaling pathways, IFN-γ diminished Ih, mirroring the effect of type I IFNs, suggesting a likewise activation of protein kinase C (PKC). In contrast, IFN-γ did neither alter subthreshold nor suprathreshold neuronal excitability, pointing to augmented inhibitory transmission by IFN-γ. Indeed, IFN-γ increased electrically evoked inhibitory postsynaptic currents (IPSCs) on neocortical layer 5 pyramidal neurons. Furthermore, amplitudes of spontaneous IPSCs and miniature IPSCs were elevated by IFN-γ, whereas their frequency remained unchanged. CONCLUSIONS: The expression of IFN-γ receptors on layer 5 neocortical pyramidal neurons together with the acute augmentation of inhibition in the neocortex by direct application of IFN-γ highlights an additional interaction between the CNS and immune system. Our results strengthen our understanding of the role of IFN-γ in neocortical neurotransmission and emphasize its impact beyond its immunological properties, particularly in the pathogenesis of neuropsychiatric disorders

A note on quasi-robust cycle bases

We investigate here some aspects of cycle bases of undirected graphs that allow the iterative construction of all elementary cycles. We introduce the concept of quasi-robust bases as a generalization of the notion of robust bases and demonstrate that a certain class of bases of the complete bipartite graphs K m,n with m,n _> 5 is quasi-robust but not robust. We furthermore disprove a conjecture for cycle bases of Cartesian product graphs

Colon cancer cell-derived 12(S)-HETE induces the retraction of cancer-associated fibroblast via MLC2, RHO/ROCK and Ca2+ signalling

Retraction of mesenchymal stromal cells supports the invasion of colorectal cancer cells (CRC) into the adjacent compartment. CRC-secreted 12(S)-HETE enhances the retraction of cancer-associated fibroblasts (CAFs) and therefore, 12(S)-HETE may enforce invasivity of CRC. Understanding the mechanisms of metastatic CRC is crucial for successful intervention. Therefore, we studied pro-invasive contributions of stromal cells in physiologically relevant three-dimensional in vitro assays consisting of CRC spheroids, CAFs, extracellular matrix and endothelial cells, as well as in reductionist models. In order to elucidate how CAFs support CRC invasion, tumour spheroid-induced CAF retraction and free intracellular Ca2+ levels were measured and pharmacological-or siRNA-based inhibition of selected signalling cascades was performed. CRC spheroids caused the retraction of CAFs, generating entry gates in the adjacent surrogate stroma. The responsible trigger factor 12(S)-HETE provoked a signal, which was transduced by PLC, IP3, free intracellular Ca2+, Ca(2+)calmodulin-kinase-II, RHO/ROCK and MYLK which led to the activation of myosin light chain 2, and subsequent CAF mobility. RHO activity was observed downstream as well as upstream of Ca2+ release. Thus, Ca2+ signalling served as central signal amplifier. Treatment with the FDA-approved drugs carbamazepine, cinnarizine, nifedipine and bepridil HCl, which reportedly interfere with cellular calcium availability, inhibited CAF-retraction. The elucidation of signalling pathways and identification of approved inhibitory drugs warrant development of intervention strategies targeting tumour-stroma interaction

8. 皮膚リーシュマニア症を疑った例(第434(B)回千葉医学会例会 第15回千葉皮膚科臨床談話会)

Additional file 3: Technical details on the compilation of the global material flow database