Probabilistic inference for determining options in reinforcement learning

Tasks that require many sequential decisions or complex solutions are hard to solve using conventional reinforcement learning algorithms. Based on the semi Markov decision process setting (SMDP) and the option framework, we propose a model which aims to alleviate these concerns. Instead of learning a single monolithic policy, the agent learns a set of simpler sub-policies as well as the initiation and termination probabilities for each of those sub-policies. While existing option learning algorithms frequently require manual specification of components such as the sub-policies, we present an algorithm which infers all relevant components of the option framework from data. Furthermore, the proposed approach is based on parametric option representations and works well in combination with current policy search methods, which are particularly well suited for continuous real-world tasks. We present results on SMDPs with discrete as well as continuous state-action spaces. The results show that the presented algorithm can combine simple sub-policies to solve complex tasks and can improve learning performance on simpler tasks

Report on the 4th European Breast Cancer Conference, Hamburg, Germany, 16–20 March 2004

The 4th European Breast Cancer Conference, organized under the auspices of the European Organization for Research and Treatment of Cancer Breast Cancer Group, of the European Breast Cancer Coalition (Europa Donna) and of the European Society of Mastology (EUSOMA), was held in Hamburg, Germany on 16–20 March 2004. The leading theme of the conference was partnership among scientists, clinicians, carers, advocates and patients. The present article provides a brief description of the most important conference presentations on molecular biology, epidemiology, prevention, pathology, diagnosis and treatment at all stages of breast cancer

Wave vision

The basic applications of radio waves are communication an

Hypothesis: primary antiangiogenic method proposed to treat early stage breast cancer

<p>Abstract</p> <p>Background</p> <p>Women with Down syndrome very rarely develop breast cancer even though they now live to an age when it normally occurs. This may be related to the fact that Down syndrome persons have an additional copy of chromosome 21 where the gene that codes for the antiangiogenic protein Endostatin is located. Can this information lead to a primary antiangiogenic therapy for early stage breast cancer that indefinitely prolongs remission? A key question that arises is when is the initial angiogenic switch thrown in micrometastases? We have conjectured that avascular micrometastases are dormant and relatively stable if undisturbed but that for some patients angiogenesis is precipitated by surgery. We also proposed that angiogenesis of micrometastases very rarely occurs before surgical removal of the primary tumor. If that is so, it seems possible that we could suggest a primary antiangiogenic therapy but the problem then arises that starting a therapy before surgery would interfere with wound healing.</p> <p>Results</p> <p>The therapy must be initiated at least one day prior to surgical removal of the primary tumor and kept at a Down syndrome level perhaps indefinitely. That means the drug must have virtually no toxicity and not interfere meaningfully with wound healing. This specifically excludes drugs that significantly inhibit the VEGF pathway since that is important for wound healing and because these agents have some toxicity. Endostatin is apparently non-toxic and does not significantly interfere with wound healing since Down syndrome patients have no abnormal wound healing problems.</p> <p>Conclusion</p> <p>We propose a therapy for early stage breast cancer consisting of Endostatin at or above Down syndrome levels starting at least one day before surgery and continuing at that level. This should prevent micrometastatic angiogenesis resulting from surgery or at any time later. Adjuvant chemotherapy or hormone therapy should not be necessary. This can be continued indefinitely since there is no acquired resistance that develops, as happens in most cancer therapies.</p

A high throughput screen for next-generation leads targeting malaria parasite transmission

Spread of parasite resistance to artemisinin threatens current frontline antimalarial therapies, highlighting the need for new drugs with alternative modes of action. Since only 0.2–1% of asexual parasites differentiate into sexual, transmission-competent forms, targeting this natural bottleneck provides a tangible route to interrupt disease transmission and mitigate resistance selection. Here we present a high-throughput screen of gametogenesis against a ~70,000 compound diversity library, identifying seventeen drug-like molecules that target transmission. Hit molecules possess varied activity profiles including male-specific, dual acting male–female and dual-asexual-sexual, with one promising N-((4-hydroxychroman-4-yl)methyl)-sulphonamide scaffold found to have sub-micromolar activity in vitro and in vivo efficacy. Development of leads with modes of action focussed on the sexual stages of malaria parasite development provide a previously unexplored base from which future therapeutics can be developed, capable of preventing parasite transmission through the population

Regulation of Plasmodium falciparum Glideosome Associated Protein 45 (PfGAP45) Phosphorylation

The actomyosin motor complex of the glideosome provides the force needed by apicomplexan parasites such as Toxoplasma gondii (Tg) and Plasmodium falciparum (Pf) to invade their host cells and for gliding motility of their motile forms. Glideosome Associated Protein 45 (PfGAP45) is an essential component of the glideosome complex as it facilitates anchoring and effective functioning of the motor. Dissection of events that regulate PfGAP45 may provide insights into how the motor and the glideosome operate. We found that PfGAP45 is phosphorylated in response to Phospholipase C (PLC) and calcium signaling. It is phosphorylated by P. falciparum kinases Protein Kinase B (PfPKB) and Calcium Dependent Protein Kinase 1 (PfCDPK1), which are calcium dependent enzymes, at S89, S103 and S149. The Phospholipase C pathway influenced the phosphorylation of S103 and S149. The phosphorylation of PfGAP45 at these sites is differentially regulated during parasite development. The localization of PfGAP45 and its association may be independent of the phosphorylation of these sites. PfGAP45 regulation in response to calcium fits in well with the previously described role of calcium in host cell invasion by malaria parasite

On Schubert's Problem of Characteristics

The Schubert varieties on a flag manifold G/P give rise to a cell decomposition on G/P whose Kronecker duals, known as the Schubert classes on G/P, form an additive base of the integral cohomology of G/P. The Schubert's problem of characteristics asks to express a monomial in the Schubert classes as a linear combination in the Schubert basis. We present a unified formula expressing the characteristics of a flag manifold G/P as polynomials in the Cartan numbers of the group G. As application we develop a direct approach to our recent works on the Schubert presentation of the cohomology rings of flag manifolds G/P.Comment: 27page