Storing and Indexing Plan Derivations through Explanation-based Analysis of Retrieval Failures

Case-Based Planning (CBP) provides a way of scaling up domain-independent planning to solve large problems in complex domains. It replaces the detailed and lengthy search for a solution with the retrieval and adaptation of previous planning experiences. In general, CBP has been demonstrated to improve performance over generative (from-scratch) planning. However, the performance improvements it provides are dependent on adequate judgements as to problem similarity. In particular, although CBP may substantially reduce planning effort overall, it is subject to a mis-retrieval problem. The success of CBP depends on these retrieval errors being relatively rare. This paper describes the design and implementation of a replay framework for the case-based planner DERSNLP+EBL. DERSNLP+EBL extends current CBP methodology by incorporating explanation-based learning techniques that allow it to explain and learn from the retrieval failures it encounters. These techniques are used to refine judgements about case similarity in response to feedback when a wrong decision has been made. The same failure analysis is used in building the case library, through the addition of repairing cases. Large problems are split and stored as single goal subproblems. Multi-goal problems are stored only when these smaller cases fail to be merged into a full solution. An empirical evaluation of this approach demonstrates the advantage of learning from experienced retrieval failure.Comment: See http://www.jair.org/ for any accompanying file

On the Complexity of Case-Based Planning

We analyze the computational complexity of problems related to case-based planning: planning when a plan for a similar instance is known, and planning from a library of plans. We prove that planning from a single case has the same complexity than generative planning (i.e., planning "from scratch"); using an extended definition of cases, complexity is reduced if the domain stored in the case is similar to the one to search plans for. Planning from a library of cases is shown to have the same complexity. In both cases, the complexity of planning remains, in the worst case, PSPACE-complete

MAGE-A cancer/testis antigens inhibit MDM2 ubiquitylation function and promote increased levels of MDM4

Melanoma antigen A (MAGE-A) proteins comprise a structurally and biochemically similar sub-family of Cancer/Testis antigens that are expressed in many cancer types and are thought to contribute actively to malignancy. MAGE-A proteins are established regulators of certain cancer-associated transcription factors, including p53, and are activators of several RING finger-dependent ubiquitin E3 ligases. Here, we show that MAGE-A2 associates with MDM2, a ubiquitin E3 ligase that mediates ubiquitylation of more than 20 substrates including mainly p53, MDM2 itself, and MDM4, a potent p53 inhibitor and MDM2 partner that is structurally related to MDM2. We find that MAGE-A2 interacts with MDM2 via the N-terminal p53-binding pocket and the RING finger domain of MDM2 that is required for homo/hetero-dimerization and for E2 ligase interaction. Consistent with these data, we show that MAGE-A2 is a potent inhibitor of the E3 ubiquitin ligase activity of MDM2, yet it does not have any significant effect on p53 turnover mediated by MDM2. Strikingly, however, increased MAGE-A2 expression leads to reduced ubiquitylation and increased levels of MDM4. Similarly, silencing of endogenous MAGE-A expression diminishes MDM4 levels in a manner that can be rescued by the proteasomal inhibitor, bortezomid, and permits increased MDM2/MDM4 association. These data suggest that MAGE-A proteins can: (i) uncouple the ubiquitin ligase and degradation functions of MDM2; (ii) act as potent inhibitors of E3 ligase function; and (iii) regulate the turnover of MDM4. We also find an association between the presence of MAGE-A and increased MDM4 levels in primary breast cancer, suggesting that MAGE-A-dependent control of MDM4 levels has relevance to cancer clinically

Vector coherent state representations, induced representations, and geometric quantization: I. Scalar coherent state representations

Coherent state theory is shown to reproduce three categories of representations of the spectrum generating algebra for an algebraic model: (i) classical realizations which are the starting point for geometric quantization; (ii) induced unitary representations corresponding to prequantization; and (iii) irreducible unitary representations obtained in geometric quantization by choice of a polarization. These representations establish an intimate relation between coherent state theory and geometric quantization in the context of induced representations.Comment: 29 pages, part 1 of two papers, published versio

Shedding Light on the Photoisomerization Pathway of Donor-Acceptor Stenhouse Adducts

Donor-acceptor Stenhouse adducts (DASAs) are negative photochromes that hold great promise for a variety of applications. Key to optimizing their switching properties is a detailed understanding of the photoswitching mechanism, which, as yet, is absent. Here we characterize the actinic step of DASA-photoswitching and its key intermediate, which was studied using a combination of ultrafast visible and IR pump-probe spectroscopies and TD-DFT calculations. Comparison of the time-resolved IR spectra with DFT computations allowed to unambiguously identify the structure of the intermediate, confirming that light absorption induces a sequential reaction path in which a Z-E photoisomerization of C-2-C-3 is followed by a rotation around C-3-C-4 and a subsequent thermal cyclization step. First and second-generation DASAs share a common photoisomerization mechanism in chlorinated solvents with notable differences in kinetics and lifetimes of the excited states. The photogenerated intermediate of the second-generation DASA was photo-accumulated at low temperature and probed with time-resolved spectroscopy, demonstrating the photoreversibility of the isomerization process. Taken together, these results provide a detailed picture of the DASA isomerization pathway on a molecular level

The Role of the Yap5 Transcription Factor in Remodeling Gene Expression in Response to Fe Bioavailability

The budding yeast Saccharomyces cerevisiae has developed several mechanisms to avoid either the drastic consequences of iron deprivation or the toxic effects of iron excess. In this work, we analysed the global gene expression changes occurring in yeast cells undergoing iron overload. Several genes directly or indirectly involved in iron homeostasis showed altered expression and the relevance of these changes are discussed. Microarray analyses were also performed to identify new targets of the iron responsive factor Yap5. Besides the iron vacuolar transporter CCC1, Yap5 also controls the expression of glutaredoxin GRX4, previously known to be involved in the regulation of Aft1 nuclear localization. Consistently, we show that in the absence of Yap5 Aft1 nuclear exclusion is slightly impaired. These studies provide further evidence that cells control iron homeostasis by using multiple pathways

Using video modeling to teach complex social sequences to children with autism

This study comprised of two experiments was designed to teach complex social sequences to children with autism. Experimental control was achieved by collecting data using means of within-system design methodology. Across a number of conditions children were taken to a room to view one of the four short videos of two people engaging in a simple sequence of activities. Then, each child’s behavior was assessed in the same room. Results showed that this video modeling procedure enhanced the social initiation skills of all children. It also facilitated reciprocal play engagement and imitative responding of a sequence of behaviors, in which social initiation was not included. These behavior changes generalized across peers and maintained after a 1- and 2-month follow-up period