Time series prediction via aggregation : an oracle bound including numerical cost

We address the problem of forecasting a time series meeting the Causal Bernoulli Shift model, using a parametric set of predictors. The aggregation technique provides a predictor with well established and quite satisfying theoretical properties expressed by an oracle inequality for the prediction risk. The numerical computation of the aggregated predictor usually relies on a Markov chain Monte Carlo method whose convergence should be evaluated. In particular, it is crucial to bound the number of simulations needed to achieve a numerical precision of the same order as the prediction risk. In this direction we present a fairly general result which can be seen as an oracle inequality including the numerical cost of the predictor computation. The numerical cost appears by letting the oracle inequality depend on the number of simulations required in the Monte Carlo approximation. Some numerical experiments are then carried out to support our findings

Managerial Work in a Practice-Embodying Institution - The role of calling, the virtue of constancy

What can be learned from a small scale study of managerial work in a highly marginal and under-researched working community? This paper uses the ‘goods-virtues-practices-institutions’ framework to examine the managerial work of owner-directors of traditional circuses. Inspired by MacIntyre’s arguments for the necessity of a narrative understanding of the virtues, interviews explored how British and Irish circus directors accounted for their working lives. A purposive sample was used to select subjects who had owned and managed traditional touring circuses for at least 15 years, a period in which the economic and reputational fortunes of traditional circuses have suffered badly. This sample enabled the research to examine the self-understanding of people who had, at least on the face of it, exhibited the virtue of constancy. The research contributes to our understanding of the role of the virtues in organizations by presenting evidence of an intimate relationship between the virtue of constancy and a ‘calling’ work orientation. This enhances our understanding of the virtues that are required if management is exercised as a domain-related practice

Design of the AGS Booster Beam Position Monitor electronics

The operational requirements of the AGS Booster Beam Position Monitor system necessitate the use of electronics with wide dynamic range and broad instantaneous bandwidth. Bunch synchronization is provided by a remote timing sequencer coupled to the local ring electronics via digital fiber-optic links. The Sequencer and local ring circuitry work together to provide single turn trajectory or average orbit and intensity information, integrated over 1 to 225 bunches. Test capabilities are built in for the purpose of enhancing BPM system accuracy. This paper describes the design of the Booster Beam Position Monitor electronics, and presents performance details of the front end processing, acquisition and timing circuitry

Outbreak of influenza in highly vaccinated crew of U.S. Navy ship.

An outbreak of influenza A (H3N2) occurred aboard a U.S. Navy ship in February 1996, despite 95% of the crew's having been appropriately vaccinated. Virus isolated from ill crew members was antigenically distinct from the vaccination strain. With an attack rate of 42%, this outbreak demonstrates the potential for rapid spread of influenza in a confined population and the impact subsequent illness may have upon the workplace

Plug-in Plan Tool v3.0.3.1

The role of PLUTO (Plug-in Port UTilization Officer) and the growth of the International Space Station (ISS) have exceeded the capabilities of the current tool PiP (Plug-in Plan). Its users (crew and flight controllers) have expressed an interest in a new, easy-to-use tool with a higher level of interactivity and functionality that is not bound by the limitations of Excel. The PiP Tool assists crewmembers and ground controllers in making real-time decisions concerning the safety and compatibility of hardware plugged into the UOPs (Utility Outlet Panels) onboard the ISS. The PiP Tool also provides a reference to the current configuration of the hardware plugged in to the UOPs, and enables the PLUTO and crew to test Plug-in locations for constraint violations (such as cable connector mismatches or amp limit violations), to see the amps and volts for an end item, to see whether or not the end item uses 1553 data, and the cable length between the outlet and the end item. As new equipment is flown or returned, the database can be updated appropriately as needed. The current tool is a macroheavy Excel spreadsheet with its own database and reporting functionality. The new tool captures the capabilities of the original tool, ports them to new software, defines a new dataset, and compensates for ever-growing unique constraints associated with the Plug-in Plan. New constraints were designed into the tool, and updates to existing constraints were added to provide more flexibility and customizability. In addition, there is an option to associate a "Flag" with each device that will let the user know there is a unique constraint associated with it when they use it. This helps improve the safety and efficiency of real-time calls by limiting the amount of "corporate knowledge" overhead that has to be trained and learned through use. The tool helps save time by automating previous manual processes, such as calculating connector types and deciding which cables are required and in what order

Unravelling the molecular determinants of bee sensitivity to neonicotinoid insecticides

This is the final version of the article. Available from the publisher via the DOI in this record.The impact of neonicotinoid insecticides on the health of bee pollinators is a topic of intensive research and considerable current debate [1]. As insecticides, certain neonicotinoids, i.e., N-nitroguanidine compounds such as imidacloprid and thiamethoxam, are as intrinsically toxic to bees as to the insect pests they target. However, this is not the case for all neonicotinoids, with honeybees orders of magnitude less sensitive to N-cyanoamidine compounds such as thiacloprid [2]. Although previous work has suggested that this is due to rapid metabolism of these compounds [2, 3, 4, 5], the specific gene(s) or enzyme(s) involved remain unknown. Here, we show that the sensitivity of the two most economically important bee species to neonicotinoids is determined by cytochrome P450s of the CYP9Q subfamily. Radioligand binding and inhibitor assays showed that variation in honeybee sensitivity to N-nitroguanidine and N-cyanoamidine neonicotinoids does not reside in differences in their affinity for the receptor but rather in divergent metabolism by P450s. Functional expression of the entire CYP3 clade of P450s from honeybees identified a single P450, CYP9Q3, that metabolizes thiacloprid with high efficiency but has little activity against imidacloprid. We demonstrate that bumble bees also exhibit profound differences in their sensitivity to different neonicotinoids, and we identify CYP9Q4 as a functional ortholog of honeybee CYP9Q3 and a key metabolic determinant of neonicotinoid sensitivity in this species. Our results demonstrate that bee pollinators are equipped with biochemical defense systems that define their sensitivity to insecticides and this knowledge can be leveraged to safeguard bee health.his study received funding from Bayer AG. C.B. received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement no. 646625 ). C.B. and K.B. received funding from Biotechnology and Biological Sciences Research Council (BBSRC, award number 15076182 ). The work at Rothamsted forms part of the Smart Crop Protection (SCP) strategic programme ( BBS/OS/CP/000001 ) funded through the Biotechnology and Biological Sciences Research Council’s Industrial Strategy Challenge Fund

Genomic insights into neonicotinoid sensitivity in the solitary bee Osmia bicornis

This is the final version. Available from the publisher via the DOI in this record.The Osmia bicornis whole genome shotgun project has been deposited at DDBJ/ENA/GenBank under the accession MPJT00000000. The RNAseq data generated in this study has been deposited in the Sequence Read Archive (SRA) under accession SRP065762. Accession numbers of the bee P450 genes manually curated in this study are shown in S5 Table. All other relevant data are within the paper and its Supporting Information files.The impact of pesticides on the health of bee pollinators is determined in part by the capacity of bee detoxification systems to convert these compounds to less toxic forms. For example, recent work has shown that cytochrome P450s of the CYP9Q subfamily are critically important in defining the sensitivity of honey bees and bumblebees to pesticides, including neonicotinoid insecticides. However, it is currently unclear if solitary bees have functional equivalents of these enzymes with potentially serious implications in relation to their capacity to metabolise certain insecticides. To address this question, we sequenced the genome of the red mason bee, Osmia bicornis, the most abundant and economically important solitary bee species in Central Europe. We show that O. bicornis lacks the CYP9Q subfamily of P450s but, despite this, exhibits low acute toxicity to the N-cyanoamidine neonicotinoid thiacloprid. Functional studies revealed that variation in the sensitivity of O. bicornis to N-cyanoamidine and N-nitroguanidine neonicotinoids does not reside in differences in their affinity for the nicotinic acetylcholine receptor or speed of cuticular penetration. Rather, a P450 within the CYP9BU subfamily, with recent shared ancestry to the Apidae CYP9Q subfamily, metabolises thiacloprid in vitro and confers tolerance in vivo. Our data reveal conserved detoxification pathways in model solitary and eusocial bees despite key differences in the evolution of specific pesticide-metabolising enzymes in the two species groups. The discovery that P450 enzymes of solitary bees can act as metabolic defence systems against certain pesticides can be leveraged to avoid negative pesticide impacts on these important pollinators.Biotechnology and Biological Science Research Council (BBSRC)Bayer AGEuropean Research Council (ERC

Rescue of DNA damage after constricted migration reveals a mechano-regulated threshold for cell cycle.

Migration through 3D constrictions can cause nuclear rupture and mislocalization of nuclear proteins, but damage to DNA remains uncertain, as does any effect on cell cycle. Here, myosin II inhibition rescues rupture and partially rescues the DNA damage marker γH2AX, but an apparent block in cell cycle appears unaffected. Co-overexpression of multiple DNA repair factors or antioxidant inhibition of break formation also exert partial effects, independently of rupture. Combined treatments completely rescue cell cycle suppression by DNA damage, revealing a sigmoidal dependence of cell cycle on excess DNA damage. Migration through custom-etched pores yields the same damage threshold, with ∼4-µm pores causing intermediate levels of both damage and cell cycle suppression. High curvature imposed rapidly by pores or probes or else by small micronuclei consistently associates nuclear rupture with dilution of stiff lamin-B filaments, loss of repair factors, and entry from cytoplasm of chromatin-binding cGAS (cyclic GMP-AMP synthase). The cell cycle block caused by constricted migration is nonetheless reversible, with a potential for DNA misrepair and genome variation