3,388 research outputs found

    Forecast Rationality and Monetary Policy Frameworks: Evidence from UK Interest Rate Forecasts

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    This paper explores the heterogeneity and rationality of professional forecasts at both short and long forecast horizons. We employ disaggregated survey data for forecasts of three-month inter-bank rates and ten-year gilt yields for the period 1989-2006. We find evidence of heterogeneity among forecasters. Moreover, forecasts violate both the unbiasedness and orthogonality conditions of the rational expectations hypothesis. The majority of biased forecasts underestimate the future spot rate. The rationality of forecasts varies across maturities and forecast horizons with short horizon and short maturity forecasts exhibiting more rationality. It also varies across sub-periods corresponding to different monetary policy frameworks. We produce evidence indicating that both monetary policy actions and elements of communication policy have information content regarding the rationality of forecasts. Changes in official bank rates and disagreement, as recorded in the minutes of the Monetary Policy Committee, influence the rationality of forecasts. The publication of inflation reports has no effect

    Using Intelligent Prefetching to Reduce the Energy Consumption of a Large-scale Storage System

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    Many high performance large-scale storage systems will experience significant workload increases as their user base and content availability grow over time. The U.S. Geological Survey (USGS) Earth Resources Observation and Science (EROS) center hosts one such system that has recently undergone a period of rapid growth as its user population grew nearly 400% in just about three years. When administrators of these massive storage systems face the challenge of meeting the demands of an ever increasing number of requests, the easiest solution is to integrate more advanced hardware to existing systems. However, additional investment in hardware may significantly increase the system cost as well as daily power consumption. In this paper, we present evidence that well-selected software level optimization is capable of achieving comparable levels of performance without the cost and power consumption overhead caused by physically expanding the system. Specifically, we develop intelligent prefetching algorithms that are suitable for the unique workloads and user behaviors of the world\u27s largest satellite images distribution system managed by USGS EROS. Our experimental results, derived from real-world traces with over five million requests sent by users around the globe, show that the EROS hybrid storage system could maintain the same performance with over 30% of energy savings by utilizing our proposed prefetching algorithms, compared to the alternative solution of doubling the size of the current FTP server farm

    Adjuvant and post-surgical treatment in high-grade epithelial ovarian cancer

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    Cytoreductive surgery is the mainstay of treatment for high-grade epithelial ovarian cancer. Although for early stage disease outcomes following surgery alone are good, the risk of recurrence necessitates adjuvant chemotherapy for the majority of patients. Post-operative chemotherapy in advanced-stage disease, or neoadjuvant chemotherapy followed by surgery has improved progression-free survival (PFS) and overall survival (OS). However, despite the use of chemotherapy, the rate of recurrence remains high. In recent years, there has been considerable increase in knowledge regarding the biology of ovarian cancer, which has led to a journey of drug discovery, facilitating the use of novel targeted agents such as VEGF inhibitors and, more recently, PARP inhibitors in the first-line treatment of ovarian cancer. Here, we outline the current evidence-based guidance for systemic therapies in ovarian cancer and highlight the ongoing research to improve patient outcome

    Forecasting Player Behavioral Data and Simulating in-Game Events

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    Understanding player behavior is fundamental in game data science. Video games evolve as players interact with the game, so being able to foresee player experience would help to ensure a successful game development. In particular, game developers need to evaluate beforehand the impact of in-game events. Simulation optimization of these events is crucial to increase player engagement and maximize monetization. We present an experimental analysis of several methods to forecast game-related variables, with two main aims: to obtain accurate predictions of in-app purchases and playtime in an operational production environment, and to perform simulations of in-game events in order to maximize sales and playtime. Our ultimate purpose is to take a step towards the data-driven development of games. The results suggest that, even though the performance of traditional approaches such as ARIMA is still better, the outcomes of state-of-the-art techniques like deep learning are promising. Deep learning comes up as a well-suited general model that could be used to forecast a variety of time series with different dynamic behaviors

    CometChip: A High-throughput 96-Well Platform for Measuring DNA Damage in Microarrayed Human Cells

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    DNA damaging agents can promote aging, disease and cancer and they are ubiquitous in the environment and produced within human cells as normal cellular metabolites. Ironically, at high doses DNA damaging agents are also used to treat cancer. The ability to quantify DNA damage responses is thus critical in the public health, pharmaceutical and clinical domains. Here, we describe a novel platform that exploits microfabrication techniques to pattern cells in a fixed microarray The ‘CometChip’ is based upon the well-established single cell gel electrophoresis assay (a.k.a. the comet assay), which estimates the level of DNA damage by evaluating the extent of DNA migration through a matrix in an electrical field. The type of damage measured by this assay includes abasic sites, crosslinks, and strand breaks. Instead of being randomly dispersed in agarose in the traditional assay, cells are captured into an agarose microwell array by gravity. The platform also expands from the size of a standard microscope slide to a 96-well format, enabling parallel processing. Here we describe the protocols of using the chip to evaluate DNA damage caused by known genotoxic agents and the cellular repair response followed after exposure. Through the integration of biological and engineering principles, this method potentiates robust and sensitive measurements of DNA damage in human cells and provides the necessary throughput for genotoxicity testing, drug development, epidemiological studies and clinical assays.National Institute of Environmental Health Sciences (Training Grant in Environmental Toxicology T32-ES007020)Massachusetts Institute of Technology. Center for Environmental Health Sciences (P30-ES002109)National Institute of Environmental Health Sciences (5-UO1-ES016045)National Institute of Environmental Health Sciences (1-R21-ES019498)National Institute of Environmental Health Sciences (R44-ES021116

    Metagenomic study of the viruses of African straw-coloured fruit bats: detection of a chiropteran poxvirus and isolation of a novel adenovirus

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    Viral emergence as a result of zoonotic transmission constitutes a continuous public health threat. Emerging viruses such as SARS coronavirus, hantaviruses and henipaviruses have wildlife reservoirs. Characterising the viruses of candidate reservoir species in geographical hot spots for viral emergence is a sensible approach to develop tools to predict, prevent, or contain emergence events. Here, we explore the viruses of Eidolon helvum, an Old World fruit bat species widely distributed in Africa that lives in close proximity to humans. We identified a great abundance and diversity of novel herpes and papillomaviruses, described the isolation of a novel adenovirus, and detected, for the first time, sequences of a chiropteran poxvirus closely related with Molluscum contagiosum. In sum, E. helvum display a wide variety of mammalian viruses, some of them genetically similar to known human pathogens, highlighting the possibility of zoonotic transmission

    Efficiencies of recovery and extraction of trace DNA from non-porous surfaces

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    DNA recovery and extraction efficiencies are key considerations for trace DNA interpretation in casework, but prior studies have tended to focus on assessing these for body fluids rather than trace DNA. This study therefore examined the recovery and extraction of trace DNA using different collection methods from a range of non-porous surfaces relevant to crimes including homicides, terror attacks, and wildlife poaching. Direct extraction of DNA from solutions of a known concentration revealed absolute extraction efficiencies of ∼82%. When DNA was extracted from swabs seeded with the DNA solution, a similarly high efficiency of ∼85% was achieved from nylon-flocked swabs, with a lower efficiency of ∼55% from cotton swabs. However, when DNA was recovered from non-porous surfaces with swabs, ∼55% of DNA was still recovered from plastic knife handles, but lower efficiencies were achieved from the other substrates, particularly metal cable. Varied and poor recovery was observed using mini-tapes and requires further investigation. These results demonstrate that > 50% recovery efficiency of trace DNA is achievable with both swab types, although recovery rates may be affected by surface type and/or practitioner experience

    The effective expression of xylanase gene in Candida utilis by 18S rDNA targeted homologous recombination in pGLR9K

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    In order to test whether 18S rDNA can influence positively xylanase gene effective expression in the yeast of Candida utilis, a targeting vector pGLR9K-XA was constructed by adding an interested gene xynA from Streptomyces olivaceoviridis into the vector pGLR9K which is constructed by ourselves. pGLR9K contains the 18S rDNA, GAP promoter and CYH resistance gene sequence, all of which is from C. utilis. Then the vector pGLR9K-XA was transformed into C. utilis. To test the vector and transformed system, PCR, Southern blot and DNS methods were used. The results showed that xylanase gene can be detected in the chromosome DNA of recombinant C. utilis and the enzyme activity of xylanase is up to 60 IU ml(-1) in the study. It is suggested that this system can be used to express exogenous genes in C. utilis as a bioreactors. This is the first report that xylanase gene was expressed in C. utilis

    Reconstructing the three-dimensional GABAergic microcircuit of the striatum

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    A system's wiring constrains its dynamics, yet modelling of neural structures often overlooks the specific networks formed by their neurons. We developed an approach for constructing anatomically realistic networks and reconstructed the GABAergic microcircuit formed by the medium spiny neurons (MSNs) and fast-spiking interneurons (FSIs) of the adult rat striatum. We grew dendrite and axon models for these neurons and extracted probabilities for the presence of these neurites as a function of distance from the soma. From these, we found the probabilities of intersection between the neurites of two neurons given their inter-somatic distance, and used these to construct three-dimensional striatal networks. The MSN dendrite models predicted that half of all dendritic spines are within 100 mu m of the soma. The constructed networks predict distributions of gap junctions between FSI dendrites, synaptic contacts between MSNs, and synaptic inputs from FSIs to MSNs that are consistent with current estimates. The models predict that to achieve this, FSIs should be at most 1% of the striatal population. They also show that the striatum is sparsely connected: FSI-MSN and MSN-MSN contacts respectively form 7% and 1.7% of all possible connections. The models predict two striking network properties: the dominant GABAergic input to a MSN arises from neurons with somas at the edge of its dendritic field; and FSIs are interconnected on two different spatial scales: locally by gap junctions and distally by synapses. We show that both properties influence striatal dynamics: the most potent inhibition of a MSN arises from a region of striatum at the edge of its dendritic field; and the combination of local gap junction and distal synaptic networks between FSIs sets a robust input-output regime for the MSN population. Our models thus intimately link striatal micro-anatomy to its dynamics, providing a biologically grounded platform for further study

    The Role of Citrullinated Proteins Suggests a Novel Mechanism in the Pathogenesis of Multiple Sclerosis

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    The pathogenesis of MS is unknown. In our studies, we have demonstrated an important role for citrullinated myelin basic protein (MBP). The accompanying loss of positive charge compromises the ability of MBP to interact with the lipid bilayer. The conversion of arginine to citrulline in brain is carried out by an enzyme peptidyl arginine deiminase (PAD) 2. The amount of PAD 2 in brain was increased in MS normal-appearing white matter. The mechanism responsible for this increase involved hypomethylation of the promoter region in the PAD 2 gene in MS, but no change (compared to normal) was found in thymus tissue DNA from the same MS patients. In addition, no change was observed in other neurological diseases, including Alzheimer’s, Parkinson’s, and Huntington’s. We propose that citrullinated MBP, resulting from elevated levels of PAD 2 represents an important biochemical pathway in the pathogenesis of MS
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