IDENTIFYING EFFECTIVE POLICIES IN APPROXIMATE DYNAMIC PROGRAMMING: BEYOND REGRESSION

ABSTRACT Dynamic programming formulations may be used to solve for optimal policies in Markov decision processes. Due to computational complexity dynamic programs must often be solved approximately. We consider the case of a tunable approximation architecture used in lieu of computing true value functions. The standard methodology advocates tuning the approximation architecture via sample path information and regression to get a good fit to the true value function. We provide an example which shows that this approach may unnecessarily lead to poorly performing policies and suggest direct search methods to find better performing value function approximations. We illustrate this concept with an application from ambulance redeployment

Distinct Pathways Mediate the Sorting of Tail-Anchored Proteins to the Plastid Outer Envelope

Background: Tail-anchored (TA) proteins are a distinct class of membrane proteins that are sorted post-translationally to various organelles and function in a number of important cellular processes, including redox reactions, vesicular trafficking and protein translocation. While the molecular targeting signals and pathways responsible for sorting TA proteins to their correct intracellular destinations in yeasts and mammals have begun to be characterized, relatively little is known about TA protein biogenesis in plant cells, especially for those sorted to the plastid outer envelope. Methodology/Principal Findings: Here we investigated the biogenesis of three plastid TA proteins, including the 33-kDa and 34-kDa GTPases of the translocon at the outer envelope of chloroplasts (Toc33 and Toc34) and a novel 9-kDa protein of unknown function that we define here as an outer envelope TA protein (OEP9). Using a combination of in vivo and in vitro assays we show that OEP9 utilizes a different sorting pathway than that used by Toc33 and Toc34. For instance, while all three TA proteins interact with the cytosolic OEP chaperone/receptor, AKR2A, the plastid targeting information within OEP9 is distinct from that within Toc33 and Toc34. Toc33 and Toc34 also appear to differ from OEP9 in that their insertion is dependent on themselves and the unique lipid composition of the plastid outer envelope. By contrast, the insertion of OEP9 into the plastid outer envelope occurs in a proteinaceous-dependent, but Toc33/34-independent manner and membrane lipids appear to serve primarily to facilitate normal thermodynamic integration of this TA protein. Conclusions/Significance: Collectively, the results provide evidence in support of at least two sorting pathways for plastid TA outer envelope proteins and shed light on not only the complex diversity of pathways involved in the targeting and insertion of proteins into plastids, but also the molecular mechanisms that underlie the delivery of TA proteins to their proper intracellular locations in general

KMT-2016-BLG-2052L: Microlensing Binary Composed of M Dwarfs Revealed from a Very Long Time-scale Event

We present the analysis of a binary microlensing event KMT-2016-BLG-2052, for which the lensing-induced brightening of the source star lasted for 2 seasons. We determine the lens mass from the combined measurements of the microlens parallax \pie and angular Einstein radius \thetae. The measured mass indicates that the lens is a binary composed of M dwarfs with masses of $M_1\sim 0.34~M_\odot$ and $M_2\sim 0.17~M_\odot$. The measured relative lens-source proper motion of $\mu\sim 3.9~{\rm mas}~{\rm yr}^{-1}$ is smaller than $\sim 5~{\rm mas}~{\rm yr}^{-1}$ of typical Galactic lensing events, while the estimated angular Einstein radius of \thetae\sim 1.2~{\rm mas} is substantially greater than the typical value of $\sim 0.5~{\rm mas}$. Therefore, it turns out that the long time scale of the event is caused by the combination of the slow $\mu$ and large \thetae rather than the heavy mass of the lens. From the simulation of Galactic lensing events with very long time scales ($t_{\rm E}\gtrsim 100$ days), we find that the probabilities that long time-scale events are produced by lenses with masses $\geq 1.0~M_\odot$ and $\geq 3.0~M_\odot$ are $\sim 19\%$ and 2.6\%, respectively, indicating that events produced by heavy lenses comprise a minor fraction of long time-scale events. The results indicate that it is essential to determine lens masses by measuring both \pie and \thetae in order to firmly identify heavy stellar remnants such as neutron stars and black holes.Comment: 9 pages, 11 figure

Developing and enhancing biodiversity monitoring programmes: a collaborative assessment of priorities

1.Biodiversity is changing at unprecedented rates, and it is increasingly important that these changes are quantified through monitoring programmes. Previous recommendations for developing or enhancing these programmes focus either on the end goals, that is the intended use of the data, or on how these goals are achieved, for example through volunteer involvement in citizen science, but not both. These recommendations are rarely prioritized. 2.We used a collaborative approach, involving 52 experts in biodiversity monitoring in the UK, to develop a list of attributes of relevance to any biodiversity monitoring programme and to order these attributes by their priority. We also ranked the attributes according to their importance in monitoring biodiversity in the UK. Experts involved included data users, funders, programme organizers and participants in data collection. They covered expertise in a wide range of taxa. 3.We developed a final list of 25 attributes of biodiversity monitoring schemes, ordered from the most elemental (those essential for monitoring schemes; e.g. articulate the objectives and gain sufficient participants) to the most aspirational (e.g. electronic data capture in the field, reporting change annually). This ordered list is a practical framework which can be used to support the development of monitoring programmes. 4.People's ranking of attributes revealed a difference between those who considered attributes with benefits to end users to be most important (e.g. people from governmental organizations) and those who considered attributes with greatest benefit to participants to be most important (e.g. people involved with volunteer biological recording schemes). This reveals a distinction between focussing on aims and the pragmatism in achieving those aims. 5.Synthesis and applications. The ordered list of attributes developed in this study will assist in prioritizing resources to develop biodiversity monitoring programmes (including citizen science). The potential conflict between end users of data and participants in data collection that we discovered should be addressed by involving the diversity of stakeholders at all stages of programme development. This will maximize the chance of successfully achieving the goals of biodiversity monitoring programmes

Excretory-secretory products from adult helminth <i>Nippostrongylus brasiliensis</i> have <i>in vitro</i> bactericidal activity

Introduction. Intestinal helminths and microbiota share the same anatomical niche during infection and are likely to interact either directly or indirectly. Whether intestinal helminths employ bactericidal strategies that influence their microbial environment is not completely understood.Hypothesis. In the present study, the hypothesis that the adult hookworm Nippostrongylus brasiliensis produces molecules that impair bacterial growth in vitro, is tested.Aim. To investigate the in vitro bactericidal activity of Nippostrongylus brasiliensis against commensal and pathogenic bacteria.Methodology. The bactericidal effect of somatic extract and excretory-secretory products of adult Nippostrongylus brasiliensis on Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli, Salmonella enterica serovar Typhimurium, and Klebsiella pneumoniae) bacteria was assessed using growth assays. Minimum inhibitory concentration and minimum bactericidal concentration assays were performed using excretory-secretory products released from the pathogen.Results. Broad-spectrum in vitro bactericidal activity in excretory-secretory products, but not somatic extract of adult Nippostrongylus brasiliensis was detected. The bactericidal activity of excretory-secretory products was concentration-dependent, maintained after heat treatment, and preserved after repeated freezing and thawing.Conclusion. The results of this study demonstrate that helminths such as Nippostrongylus brasiliensis release molecules via their excretory-secretory pathway that have broad-spectrum bactericidal activity. The mechanisms responsible for this bactericidal activity remain to be determined and further studies aimed at isolating and identifying active bactericidal molecules are needed

Job Strain, Health and Sickness Absence: Results from the Hordaland Health Study

MW and SBH are funded by NSW Health. M. Henderson and M. Hotopf were supported by the NIHR Biomedical Research Centre for Mental Health at the South London and Maudsley NHS Foundation Trust and Institute of Psychiatry, King’s College London. AM and SO were funded by the Norwegian Research Council

Complex interactions of HIV-1 nucleocapsid protein with oligonucleotides

The HIV-1 nucleocapsid (NC) protein is a small, basic protein containing two retroviral zinc fingers. It is a highly active nucleic acid chaperone; because of this activity, it plays a crucial role in virus replication as a cofactor during reverse transcription, and is probably important in other steps of the replication cycle as well. We previously reported that NC binds with high-affinity to the repeating sequence d(TG)(n). We have now analyzed the interaction between NC and d(TG)(4) in considerable detail, using surface plasmon resonance (SPR), tryptophan fluorescence quenching (TFQ), fluorescence anisotropy (FA), isothermal titration calorimetry (ITC) and electrospray ionization Fourier transform mass spectrometry (ESI-FTMS). Our results show that the interactions between these two molecules are surprisngly complex: while the K(d) for binding of a single d(TG)(4) molecule to NC is only ∼5 nM in 150 mM NaCl, a single NC molecule is capable of interacting with more than one d(TG)(4) molecule, and conversely, more than one NC molecule can bind to a single d(TG)(4) molecule. The strengths of these additional binding reactions are quantitated. The implications of this multivalency for the functions of NC in virus replication are discussed

Planet Sensitivity from Combined Ground- and Space-based Microlensing Observations

To move one step forward toward a Galactic distribution of planets, we present the first planet sensitivity analysis for microlensing events with simultaneous observations from space and the ground. We present this analysis for two such events, OGLE-2014-BLG-0939 and OGLE-2014-BLG-0124, which both show substantial planet sensitivity even though neither of them reached high magnification. This suggests that an ensemble of low to moderate magnification events can also yield significant planet sensitivity and therefore probability to detect planets. The implications of our results to the ongoing and future space-based microlensing experiments to measure the Galactic distribution of planets are discussed.Comment: 10 pages, 5 figures, 1 table; ApJ in pres