Influence-Optimistic Local Values for Multiagent Planning --- Extended Version

Recent years have seen the development of methods for multiagent planning under uncertainty that scale to tens or even hundreds of agents. However, most of these methods either make restrictive assumptions on the problem domain, or provide approximate solutions without any guarantees on quality. Methods in the former category typically build on heuristic search using upper bounds on the value function. Unfortunately, no techniques exist to compute such upper bounds for problems with non-factored value functions. To allow for meaningful benchmarking through measurable quality guarantees on a very general class of problems, this paper introduces a family of influence-optimistic upper bounds for factored decentralized partially observable Markov decision processes (Dec-POMDPs) that do not have factored value functions. Intuitively, we derive bounds on very large multiagent planning problems by subdividing them in sub-problems, and at each of these sub-problems making optimistic assumptions with respect to the influence that will be exerted by the rest of the system. We numerically compare the different upper bounds and demonstrate how we can achieve a non-trivial guarantee that a heuristic solution for problems with hundreds of agents is close to optimal. Furthermore, we provide evidence that the upper bounds may improve the effectiveness of heuristic influence search, and discuss further potential applications to multiagent planning.Comment: Long version of IJCAI 2015 paper (and extended abstract at AAMAS 2015

Theoretical Guidance on the Determinants of Success in Agricultural Marketing and Production Clubs

Institutional and Behavioral Economics, Marketing,

Identification and removal of low-complexity sites in allele-specific analysis of ChIP-seq data

Motivation: High-throughput sequencing technologies enable the genome-wide analysis of the impact of genetic variation on molecular phenotypes at unprecedented resolution. However, although powerful, these technologies can also introduce unexpected artifacts. Results: We investigated the impact of library amplification bias on the identification of allele-specific (AS) molecular events from high-throughput sequencing data derived from chromatin immunoprecipitation assays (ChIP-seq). Putative AS DNA binding activity for RNA polymerase II was determined using ChIP-seq data derived from lymphoblastoid cell lines of two parent-daughter trios. We found that, at high-sequencing depth, many significant AS binding sites suffered from an amplification bias, as evidenced by a larger number of clonal reads representing one of the two alleles. To alleviate this bias, we devised an amplification bias detection strategy, which filters out sites with low read complexity and sites featuring a significant excess of clonal reads. This method will be useful for AS analyses involving ChIP-seq and other functional sequencing assays. Availability: The R package absfilter for library clonality simulations and detection of amplification-biased sites is available from http://updepla1srv1.epfl.ch/waszaks/absfilter Contact: [email protected] or [email protected] Supplementary information: Supplementary data are available at Bioinformatics onlin

Coordinated effects of sequence variation on DNA binding, chromatin structure, and transcription.

DNA sequence variation has been associated with quantitative changes in molecular phenotypes such as gene expression, but its impact on chromatin states is poorly characterized. To understand the interplay between chromatin and genetic control of gene regulation, we quantified allelic variability in transcription factor binding, histone modifications, and gene expression within humans. We found abundant allelic specificity in chromatin and extensive local, short-range, and long-range allelic coordination among the studied molecular phenotypes. We observed genetic influence on most of these phenotypes, with histone modifications exhibiting strong context-dependent behavior. Our results implicate transcription factors as primary mediators of sequence-specific regulation of gene expression programs, with histone modifications frequently reflecting the primary regulatory event

Response and resistance to BET bromodomain inhibitors in triple-negative breast cancer

Triple-negative breast cancer (TNBC) is a heterogeneous and clinically aggressive disease for which there is no targeted therapy. BET bromodomain inhibitors, which have shown efficacy in several models of cancer have not been evaluated in TNBC. These inhibitors displace BET bromodomain proteins such as BRD4 from chromatin by competing with their acetyl-lysine recognition modules, leading to inhibition of oncogenic transcriptional programs. Here we report the preferential sensitivity of TNBCs to BET bromodomain inhibition in vitro and in vivo, establishing a rationale for clinical investigation and further motivation to understand mechanisms of resistance. In paired cell lines selected for acquired resistance to BET inhibition from previously sensitive TNBCs, we failed to identify gatekeeper mutations, new driver events or drug pump activation. BET-resistant TNBC cells remain dependent on wild-type BRD4, which supports transcription and cell proliferation in a bromodomain-independent manner. Proteomic studies of resistant TNBC identify strong association with MED1 and hyper-phosphorylation of BRD4 attributable to decreased activity of PP2A, identified here as a principal BRD4 serine phosphatase. Together, these studies provide a rationale for BET inhibition in TNBC and present mechanism-based combination strategies to anticipate clinical drug resistance

Rhizosphere-mediated effects of the invasive grass Bromus tectorum L. and native Elymus elymoides on nitrogen cycling in Great Basin Desert soils

Background and aims: There is evidence that the invasive grass Bromus tectorum can affect soil nitrogen (N) cycling, possibly leading to a positive plant-soil feedback. Rhizosphere priming of N mineralization could provide a mechanistic explanation for such a feedback. Methods: We conducted a greenhouse study to isolate rhizosphere effects on N cycling by the invasive annual grass, Bromus tectorum L., and the native perennial grass, Elymus elymoides (Raf.) Swezey, in invaded and uninvaded soils. We compared the rhizosphere priming effect (RPE) on N mineralization by species and the distribution of N in various pools by planting treatment and soil type. Results: B. tectorum had a negative RPE (−23 and −22 % in invaded and uninvaded soils, respectively), while E. elymoides had no significant RPE. B. tectorum was more competitive over E. elymoides in invaded compared to uninvaded soil. Conclusions: B. tectorum had a negative effect on soil N availability via root-mediated processes, even though its growth and competitiveness increased in invaded soils. Positive plant-soil feedback effects of B. tectorum may be mediated by aboveground inputs rather than belowground and/or depend on site-specific conditions