Global analysis of gene expression reveals mRNA superinduction is required for the inducible immune response to a bacterial pathogen.

The inducible innate immune response to infection requires a concerted process of gene expression that is regulated at multiple levels. Most global analyses of the innate immune response have focused on transcription induced by defined immunostimulatory ligands, such as lipopolysaccharide. However, the response to pathogens involves additional complexity, as pathogens interfere with virtually every step of gene expression. How cells respond to pathogen-mediated disruption of gene expression to nevertheless initiate protective responses remains unclear. We previously discovered that a pathogen-mediated blockade of host protein synthesis provokes the production of specific pro-inflammatory cytokines. It remains unclear how these cytokines are produced despite the global pathogen-induced block of translation. We addressed this question by using parallel RNAseq and ribosome profiling to characterize the response of macrophages to infection with the intracellular bacterial pathogen Legionella pneumophila. Our results reveal that mRNA superinduction is required for the inducible immune response to a bacterial pathogen

Modeling Acreage Response and US Farm Policy In a New Market Environment

Replaced with revised version of poster 9/2/11.Agricultural and Food Policy,

Warming winters and New Hampshire’s lost ski areas: An integrated case study

New Hampshire’s mountains and winter climate support a ski industry that contributes substantially to the state economy. Through more than 70 years of history, this industry has adapted and changed with its host society. The climate itself has changed during this period too, in ways that influenced the ski industry’s development. During the 20th century, New Hampshire’s mean winter temperature warmed about 2.1° C (3.8° F). Much of that change occurred since 1970. The mult‐decadal variations in New Hampshire winters follow global temperature trends. Snowfall exhibits a downward trend, strongest in southern New Hampshire, and also correlates with the North Atlantic Oscillation. Many small ski areas opened during the early years while winters were cold and snowy. As winters warmed, areas in southern or lowelevation locations faced a critical disadvantage. Under pressure from both climate and competition, the number of small ski areas leveled off and then fell steeply after 1970. The number of larger, chairliftoperating ski areas began falling too after 1980. Aprolonged warming period increased the importance of geographic advantages, and also of capital investment in snowmaking, grooming and economic diversification. The consolidation trend continues today. Most of the surviving ski areas are located in the northern mountains. Elsewhere around the state, one can find the remains of “lost” ski areas in places that now rarely have snow suitable for downhill skiing. This case study demonstrates a general approach for conducting integrated empirical research on the human dimensions of climate change

A Puzzle of Enforceability: Why do Moral Duties Differ in their Enforceability?

When someone is poised to fail to fulfil a moral duty, we can respond in a variety of ways. We might remind them of their duty, or seek to persuade them through argument. Or we might intervene forcibly to ensure that they act in accordance with their duty. Some duties appear to be such that the duty-bearer can be liable to forcible interference when this is necessary to ensure that they comply with them. We’ll call duties that carry such liabilities enforcement-apt. Not all duties seem to be enforcement-apt. Some, for example, accept that a person in a monogamous marriage has a moral duty to refrain from infidelity, but deny that a spouse can be compelled to comply with their duty to be faithful without transgressing her rights. More controversially, some think that our duties to assist others in severe need are not enforcement-apt. What could explain the contrast between duties that are enforcement-apt while and those that are not? We’ll call this the puzzle of enforceability and our paper considers three broad strategies for responding to it. The first strategy takes the form of identifying some substantive feature or features that are necessary and/or sufficient for a duty to possess some enforcement status. We consider a range of candidate explanations of this sort but find that none are plausible. The second strategy rejects the idea that there are genuinely enforcement-inapt duties and instead seeks to explain why there can nonetheless be marked differences amongst duties concerning how they can be enforced and who can enforce them. We find that this strategy too is largely unsuccessful. The third strategy offered seeks an explanation of differences in enforcement status by appeal to the broader social costs of enforcing certain kinds of duties. We find that this approach holds some promise but note that it requires adopting a controversial set of moral commitments. We conclude by considering our options in the absence of a solution to our puzzle

The cost of systemic corticosteroid-induced morbidity in severe asthma : a health economic analysis

The study data-set was supported by the Respiratory Effectiveness Group through their academic partnership with Optimum Patient Care. Ciaran O'Neill was funded under a HRB Research Leader Award (RL/13/16).Peer reviewedPublisher PD

Forecasting Inflation: the Relevance of Higher Moments

We provide evidence that higher moments of the relative price distribution improve out-of-sample forecasts of inflation. Further, we show how theoretically consistent higher moments can be calculated by expanding the seminal work by Theil (1967). Results presented here are of direct relevance to monetary authorities, policy analysts and academic economistsrelative price distribution, higher moments, out-of-sample inflation forecasting

Pilots' use of a traffic alert and collision-avoidance system (TCAS 2) in simulated air carrier operations. Volume 1: Methodology, summary and conclusions

Pilots' use of and responses to a traffic alert and collision-avoidance system (TCAS 2) in simulated air carrier line operations are described in Volume 1. TCAS 2 monitors the positions of nearby aircraft by means of transponder interrogation, and it commands a climb or descent when conflicting aircraft are projected to reach an unsafe closest point-of-approach within 20 to 25 seconds. A different level of information about the location of other air traffic was presented to each of three groups of flight crews during their execution of eight simulated air carrier flights. A fourth group of pilots flew the same segments without TCAS 2 equipment. Traffic conflicts were generated at intervals during the flights; many of the conflict aircraft were visible to the flight crews. The TCAS equipment successfully ameliorated the seriousness of all conflicts; three of four non-TCAS crews had hazardous encounters. Response times to TCAS maneuver commands did not differ as a function of the amount of information provided, nor did response accuracy. Differences in flight experience did not appear to contribute to the small performance differences observed. Pilots used the displays of conflicting traffic to maneuver to avoid unseen traffic before maneuver advisories were issued by the TCAS equipment. The results indicate: (1) that pilots utilize TCAS effectively within the response times allocated by the TCAS logic, and (2) that TCAS 2 is an effective collision avoidance device. Volume II contains the appendices referenced in Volume I, providing details of the experiment and the results, and the text of two reports written in support of the program

Pilots' use of a traffic alert and collision-avoidance system (TCAS 2) in simulated air carrier operations. Volume 2: Appendices

Pilots' use of and responses to a traffic alert and collision-avoidance system (TCAS 2) in simulated air carrier line operations are discribed in Volume 1. TCAS 2 monitors the positions of nearby aircraft by means of transponder interrogation, and it commands a climb or descent which conflicting aircraft are projected to reach an unsafe closest point-of-approach within 20 to 25 seconds. A different level of information about the location of other air traffic was presented to each of three groups of flight crews during their execution of eight simulated air carrier flights. A fourth group of pilots flew the same segments without TCAS 2 equipment. Traffic conflicts were generated at intervals during the flights; many of the conflict aircraft were visible to the flight crews. The TCAS equipment successfully ameliorated the seriousness of all conflicts; three of four non-TCAS crews had hazardous encounters. Response times to TCAS maneuver commands did not differ as a function of the amount of information provided, nor did response accuracy. Differences in flight experience did not appear to contribute to the small performance differences observed. Pilots used the displays of conflicting traffic to maneuver to avoid unseen traffic before maneuver advisories were issued by the TCAS equipment. The results indicate: (1) that pilots utilize TCAS effectively within the response times allocated by the TCAS logic, and (2) that TCAS 2 is an effective collision avoidance device. Volume 2 contains the appendices referenced in Volume 1, providing details of the experiment and the results, and the text of two reports written in support of the program