Planning When Goals Change: A Moving Target Search Approach

International audienceDevising intelligent robots or agents that interact with humans is a major challenge for artificial intelligence. In such contexts, agents must constantly adapt their decisions according to human activities and modify their goals. In this paper, we tackle this problem by introducing a novel planning approach, called Moving Goal Planning (MGP), to adapt plans to goal evolutions. This planning algorithm draws inspiration from Moving Target Search (MTS) algorithms. In order to limit the number of search iterations and to improve its efficiency, MGP delays as much as possible triggering new searches when the goal changes over time. To this purpose, MGP uses two strategies: Open Check (OC) that checks if the new goal is still in the current search tree and Plan Follow (PF) that estimates whether executing actions of the current plan brings MGP closer to the new goal. Moreover, MGP uses a parsimonious strategy to update incrementally the search tree at each new search that reduces the number of calls to the heuristic function and speeds up the search. Finally, we show evaluation results that demonstrate the effectiveness of our approach

Local variations of HER2 dimerization in breast cancer cells discovered by correlative fluorescence and liquid electron microscopy

The formation of HER2 homodimers plays an important role in breast cancer aggressiveness and progression; however, little is known about its localization. We have studied the intra- and intercellular variation of HER2 at the single-molecule level in intact SKBR3 breast cancer cells. Whole cells were visualized in hydrated state with correlative fluorescence microscopy and environmental scanning electron microscopy (ESEM). The locations of individual HER2 receptors were detected using an anti-HER2 affibody in combination with a quantum dot (QD), a fluorescent nanoparticle. Fluorescence microscopy revealed considerable differences of HER2 membrane expression between individual cells and between different membrane regions of the same cell (that is, membrane ruffles and flat areas). Subsequent ESEM of the corresponding cellular regions provided images of individually labeled HER2 receptors. The high spatial resolution of 3 nm and the close proximity between the QD and the receptor allowed quantifying the stoichiometry of HER2 complexes, distinguishing between monomers, dimers, and higher-order clusters. Downstream data analysis based on calculating the pair correlation function from receptor positions showed that cellular regions exhibiting membrane ruffles contained a substantial fraction of HER2 in homodimeric state. Larger-order clusters were also present. Membrane areas with homogeneous membrane topography, on the contrary, displayed HER2 in random distribution. Second, HER2 homodimers appeared to be absent from a small subpopulation of cells exhibiting a flat membrane topography, possibly resting cells. Local differences in homodimer presence may point toward functional differences with possible relevance for studying metastasis and drug response

Evidence for a DNA-Based Mechanism of Intron-Mediated Enhancement

Many introns significantly increase gene expression through a process termed intron-mediated enhancement (IME). Introns exist in the transcribed DNA and the nascent RNA, and could affect expression from either location. To determine which is more relevant to IME, hybrid introns were constructed that contain sequences from stimulating Arabidopsis thaliana introns either in their normal orientation or as the reverse complement. Both ends of each intron are from the non-stimulatory COR15a intron in their normal orientation to allow splicing. The inversions create major alterations to the sequence of the transcribed RNA with relatively minor changes to the DNA structure. Introns containing portions of either the UBQ10 or ATPK1 intron increased expression to a similar degree regardless of orientation. Also, computational predictions of IME improve when both intron strands are considered. These findings are more consistent with models of IME that act at the level of DNA rather than RNA

Neural progenitor cell implants modulate vascular endothelial growth factor and brain-derived neurotrophic factor expression in rat axotomized neurons

Axotomy of central neurons leads to functional and structural alterations which largely revert when neural progenitor cells (NPCs) are implanted in the lesion site. The new microenvironment created by NPCs in the host tissue might modulate in the damaged neurons the expression of a high variety of molecules with relevant roles in the repair mechanisms, including neurotrophic factors. In the present work, we aimed to analyze changes in neurotrophic factor expression in axotomized neurons induced by NPC implants. For this purpose, we performed immunofluorescence followed by confocal microscopy analysis for the detection of vascular endothelial growth factor (VEGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and nerve growth factor (NGF) on brainstem sections from rats with axotomy of abducens internuclear neurons that received NPC implants (implanted group) or vehicle injections (axotomized group) in the lesion site. Control abducens internuclear neurons were strongly immunoreactive to VEGF and BDNF but showed a weak staining for NT-3 and NGF. Comparisons between groups revealed that lesioned neurons from animals that received NPC implants showed a significant increase in VEGF content with respect to animals receiving vehicle injections. However, the immunoreactivity for BDNF, which was increased in the axotomized group as compared to control, was not modified in the implanted group. The modifications induced by NPC implants on VEGF and BDNF content were specific for the population of axotomized abducens internuclear neurons since the neighboring abducens motoneurons were not affected. Similar levels of NT-3 and NGF immunolabeling were obtained in injured neurons from axotomized and implanted animals. Among all the analyzed neurotrophic factors, only VEGF was expressed by the implanted cells in the lesion site. Our results point to a role of NPC implants in the modulation of neurotrophic factor expression by lesioned central neurons, which might contribute to the restorative effects of these implants

Liquid-phase electron microscopy of molecular drug response in breast cancer cells reveals irresponsive cell subpopulations related to lack of HER2 homodimers

The development of drug resistance in cancer poses a major clinical problem. An example is human epidermal growth factor receptor 2 (HER2) overexpressing breast cancer often treated with anti-HER2 antibody therapies, such as trastuzumab. Because drug resistance is rooted mainly in tumor cell heterogeneity, we examined the drug effect in different subpopulations of SKBR3 breast cancer cells and compared the results with those of a drugresistant cell line, HCC1954. Correlative light microscopy and liquid-phase scanning transmission electron microscopy were used to quantitatively analyze HER2 responses upon drug binding, whereby many tens of whole cells were imaged. Trastuzumab was found to selectively cross-link and down-regulate HER2 homodimers from the plasma membranes of bulk cancer cells. In contrast, HER2 resided mainly as monomers in rare subpopulations of resting and cancer stem cells (CSCs), and these monomers were not internalized after drug binding. The HER2 distribution was hardly influenced by trastuzumab for the HCC1954 cells. These findings show that resting cells and CSCs are irresponsive to the drug and thus point toward a molecular explanation behind the origin of drug resistance. This analytical method is broadly applicable to study membrane protein interactions in the intact plasma membrane, while accounting for cell heterogeneity

The predicament of pastoral sovereignty

This is the final version. Available from Elsevier via the DOI in this record. This paper seeks to understand the conditions of possibility of “sanctuary” – the claiming of a “sacred” space of (humanitarian) exception - in the midst of civil war. Sanctuary codifies an exceptional space where sovereign and pastoral registers of power converge into a form of “pastoral sovereignty” that can temporarily “interrupt” the law of violence of sovereign power. In civil war this can enable civilians to be saved and protected from killings and suffering. However, this pastoral sovereignty is precarious as it depends on the belligerents' good will and tacit authorization: this is what we call the predicament of pastoral sovereignty. Using the case study of Church sanctuary in Sri Lanka's civil war, this paper explores how this predicament of pastoral sovereignty comes into effect in moments of acute crisis. Throughout Sri Lanka's brutal civil war, Catholic priests provided “sanctuary” to Tamil civilians in the form of territorial sanctuary (Church compounds), bodily sanctuary (the priests' bodies providing protection), and numerous other humanitarian activities. Our ethnographic material illustrates the force and fragility of the Church's claims to pastoral sovereignty and its sanctuary practices and provides detailed accounts of numerous constellations. The paper thereby raises fundamental questions about the ontology of sovereignty and its operability in moments of humanitarian crisis.Economic and Social Research Council (ESRC)Swiss National Science Foundation (SNF)Swiss National Science Foundation (SNF)Swiss National Science Foundation (SNF

Phase Transition in the Number Partitioning Problem

Number partitioning is an NP-complete problem of combinatorial optimization. A statistical mechanics analysis reveals the existence of a phase transition that separates the easy from the hard to solve instances and that reflects the pseudo-polynomiality of number partitioning. The phase diagram and the value of the typical ground state energy are calculated.Comment: minor changes (references, typos and discussion of results

Random Costs in Combinatorial Optimization

The random cost problem is the problem of finding the minimum in an exponentially long list of random numbers. By definition, this problem cannot be solved faster than by exhaustive search. It is shown that a classical NP-hard optimization problem, number partitioning, is essentially equivalent to the random cost problem. This explains the bad performance of heuristic approaches to the number partitioning problem and allows us to calculate the probability distributions of the optimum and sub-optimum costs.Comment: 4 pages, Revtex, 2 figures (eps), submitted to PR