MicroRNAs Modulate Pathogenesis Resulting from Chlamydial Infection in Mice

Not all women infected with chlamydiae develop upper genital tract disease, but the reason(s) for this remains undefined. Host genetics and hormonal changes associated with the menstrual cycle are possible explanations for variable infection outcomes. It is also possible that disease severity depends on the virulence of the chlamydial inoculum. It is likely that the inoculum contains multiple genetic variants, differing in virulence. If the virulent variants dominate, then the individual is more likely to develop severe disease. Based on our previous studies, we hypothesized that the relative degree of virulence of a chlamydial population dictates the microRNA (miRNA) expression profile of the host, which, in turn, through regulation of the host inflammatory response, determines disease severity. Thus, we infected C57BL/6 mice with two populations of Chlamydia muridarum, each comprised of multiple genetic variants and differing in virulence: an attenuated strain (NiggA) and a virulent strain (NiggV). NiggA and NiggV elicited upper tract pathology in 54% and 91% of mice, respectively. miRNA expression analysis in NiggV-infected mice showed significant downregulation of miRNAs involved in dampening fibrosis (miR-200b, miR-200b-5p, and 200b-3p miR-200a-3p) and in transcriptional regulation of cytokine responses (miR-148a-3p, miR-152-3p, miR-132, and miR-212) and upregulation of profibrotic miRNAs (miR-142, and miR-147). Downregulated miRNAs were associated with increased expression of interleukin 8 (IL-8), CXCL2, IL-1β, tumor necrosis factor alpha (TNF-α), and IL-6. Infection with NiggV but not NiggA led to decreased expression of Dicer and Ago 2, suggesting that NiggV interaction with host cells inhibits expression of the miRNA biogenesis machinery, leading to increased cytokine expression and pathology

Effects of hyperlinks on navigation in virtual environments

Hyperlinks introduce discontinuities of movement to 3-D virtual environments (VEs). Nine independent attributes of hyperlinks are defined and their likely effects on navigation in VEs are discussed. Four experiments are described in which participants repeatedly navigated VEs that were either conventional (i.e. obeyed the laws of Euclidean space), or contained hyperlinks. Participants learned spatial knowledge slowly in both types of environment, echoing the findings of previous studies that used conventional VEs. The detrimental effects on participants' spatial knowledge of using hyperlinks for movement were reduced when a time-delay was introduced, but participants still developed less accurate knowledge than they did in the conventional VEs. Visual continuity had a greater influence on participants' rate of learning than continuity of movement, and participants were able to exploit hyperlinks that connected together disparate regions of a VE to reduce travel time

ROCs in Eyewitness Identification: Instructions vs. Confidence Ratings

From the perspective of signal-detection theory, different lineup instructions may induce different levels of response bias (Clark, 2005). If so, then collecting correct and false identification rates across different instructional conditions will trace out the ROC – the same ROC that, theoretically, could also be traced out from a single instruction condition in which each eyewitness decision is accompanied by a confidence rating. We tested whether the two approaches do in fact yield the same ROC. Participants were assigned to a confidence rating condition or to an instructional biasing condition (liberal, neutral, unbiased, or conservative). After watching a video of a mock crime, participants were presented with instructions followed by a 6-person simultaneous photo lineup. The ROCs from both methods were similar, but they were not exactly the same. These findings have potentially important policy implications for how the legal system should go about controlling eyewitness response bias

SPE 116226 Next-Generation Perforating System Enhances the Testing and Treatment of Fracture Stimulated Wells in Canada

Abstract Ineffective perforation can adversely affect the completion of fracture stimulated wells in several ways. If the interval is to be tested prior to fracturing, a clean connection to the formation is required to facilitate meaningful data acquisition. Excessive perforation damage can mask true formation potential and lead to incorrect diagnosis and decision making. Inadequate perforations can result in significant fracture tortuosity, increasing formation breakdown pressure -occasionally beyond the capacity of surface equipment or design rating of the well. Finally, limited entry perforation -a common technique for diverting a treatment across multiple fracture initiation points -demands that as many perforations as possible are open and can accept treatment fluids. Low perforating efficiency and variations in perforation cleanup associated with heterogeneous formations can cause uneven treatment distribution and suboptimal completion. Traditional methods for achieving clean perforations depend on creating a pressure gradient between formation and wellbore to induce flow and remove debris from the perforation tunnels -this can be difficult to accomplish, especially in low-pressure reservoirs. Underbalance cleanup favors intervals with higher flow potential -typically those with greater permeability -and may result in low perforation efficiency in poor or variable quality zones. Operators of wells requiring fracture stimulation are therefore faced with a significant challenge to find reliable, cost-effective perforating methods. A new class of reactive shaped charges has recently been introduced that generates a powerful secondary effect within each perforation tunnel immediately after it is formed. The reaction supercharges each tunnel, causing a surge of flow into the wellbore that removes all compacted debris and the near-tunnel crushed zone that would otherwise impair flow performance. Since this effect is independent of rock properties and wellbore conditions, a very high percentage of clean tunnels can be obtained across the entire interval without necessarily perforating in an underbalanced condition. This paper describes the new charge technology in greater detail and reports on its successful deployment in more than a dozen wells for different operators in Canada. Specific examples are used to illustrate how the system facilitates pre-frac evaluation, fracture initiation and limited entry fracture stimulation. Introduction Shaped charge perforators are the dominant method used to create a flow path between formations of interest and the wellbore in a cased and perforated completion. The vast majority of perforated completions depend on the use of shaped charges because of the relative speed and simplicity of their deployment compared to alternatives, such as mechanical penetrators or hydro-abrasive jetting tools. However, despite these advantages shaped charges provide an imperfect solution. Shaped charges are formed by compressing high explosive powder within a metal case using a conical or parabolic metal liner, as depicted i

Global survey of the omega-3 fatty acids, docosahexaenoic acid and eicosapentaenoic acid in the blood stream of healthy adults

Published by Elsevier, and Made available in open-access under the CC-BY-4.0 International license http://creativecommons.org/licenses/by/4.0/. http:/dx.doi.org/10.1016/j.plipres.2016.05.001Studies reporting blood levels of the omega-3 polyunsaturated fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), were systematically identified in order to create a global map identifying countries and regions with different blood levels. Included studies were those of healthy adults, published in 1980 or later. A total of 298 studies met all inclusion criteria. Studies reported fatty acids in various blood fractions including plasma total lipids (33%), plasma phospholipid (32%), erythrocytes (32%) and whole blood (3.0%). Fatty acid data from each blood fraction were converted to relative weight percentages (wt.%) and then assigned to one of four discrete ranges (high, moderate, low, very low) corresponding to wt.% EPA + DHA in erythrocyte equivalents. Regions with high EPA + DHA blood levels (>8%) included the Sea of Japan, Scandinavia, and areas with indigenous populations or populations not fully adapted to Westernized food habits. Very low blood levels (<= 4%) were observed in North America, Central and South America, Europe, the Middle East, Southeast Asia, and Africa. The present review reveals considerable variability in blood levels of EPA + DHA and the very low to low range of blood EPA + DHA for most of the world may increase global risk for chronic disease. (C) 2016 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license.DSM Nutritional Product

Guidance for Evidence-Informed Policies about Health Systems: Linking Guidance Development to Policy Development

In the second paper in a three-part series on health systems guidance, John Lavis and colleagues explore the challenge of linking guidance development and policy development at global and national levels

Evaluation of bottom-up and top-down strategies for aggregated forecasts: state space models and arima applications

Abstract. In this research, we consider monthly series from the M4 competition to study the relative performance of top-down and bottom-up strategies by means of implementing forecast automation of state space and ARIMA models. For the bottomup strategy, the forecast for each series is developed individually and then these are combined to produce a cumulative forecast of the aggregated series. For the top-down strategy, the series or components values are first combined and then a single forecast is determined for the aggregated series. Based on our implementation, state space models showed a higher forecast performance when a top-down strategy is applied. ARIMA models had a higher forecast performance for the bottom-up strategy. For state space models the top-down strategy reduced the overall error significantly. ARIMA models showed to be more accurate when forecasts are first determined individually. As part of the development we also proposed an approach to improve the forecasting procedure of aggregation strategies

Convergent Evolution of Escape from Hepaciviral Antagonism in Primates

Escape from antagonism by hepatitis C and related viruses has repeatedly evolved in antiviral factor MAVS via convergent evolution, revealing an ancient history of previous viral encounters in primates