Local cytokine transcription in naïve and previously infected sheep and lambs following challenge with Teladorsagia circumcincta

<b>Background</b><p></p> The abomasal helminth Teladorsagia circumcincta is one of the most economically important parasites affecting sheep in temperate regions. Infection is particularly detrimental to lambs, in which it can cause pronounced morbidity and severe production losses. Due to the spreading resistance of this parasite to all classes of anthelmintic drugs, teladorsagiosis is having an increasingly severe impact on the sheep industry with significant implications for sheep welfare. Protective immunity develops slowly, wanes rapidly and does not appear to be as effective in young lambs. To investigate the development of immunity to T. circumcincta in sheep and lambs, we used cytokine transcript profiling to examine differences in the abomasal mucosa and gastric lymph node of naïve and previously infected sheep and lambs following challenge.<p></p> <b>Results</b><p></p> The results of these experiments demonstrated that the abomasal mucosa is a major source of cytokines during abomasal helminth infection. A local Th2-type cytokine response was observed in the abomasal mucosa and gastric lymph node of the previously infected sheep and lambs when compared with those of the naïve during the early stages of infection. In contrast, a pro-inflammatory component more was evident in the abomasal mucosa and gastric lymph node of the naïve sheep when compared with those of the previously infected, which was not observed in the lambs.<p></p> <b>Conclusions</b><p></p> The greater levels of Th2-type cytokine transcripts in both the abomasum and gastric lymph node of the previously infected compared with naïve sheep and lambs emphasises the importance of these mechanisms in the immune response to T. circumcincta infection. Younger lambs appear to be able to generate similar Th2-type responses in the abomasum suggesting that the increased morbidity and apparent lack of resistance in younger lambs following continuous or repeated exposure to T. circumcincta is unlikely to be due to a lack of appropriate Th2-type cytokine production

A Quarter-Century of Observations of Comet 10P/Tempel 2 at Lowell Observatory: Continued Spin-Down, Coma Morphology, Production Rates, and Numerical Modeling

We report on photometry and imaging of Comet 10P/Tempel 2 obtained at Lowell Observatory from 1983 through 2011. We measured a nucleus rotation period of 8.950 +/- 0.002 hr from 2010 September to 2011 January. This rotation period is longer than the period we previously measured in 1999, which was itself longer than the period measured in 1988. A nearly linear jet was observed which varied little during a rotation cycle in both R and CN images acquired during the 1999 and 2010 apparitions. We measured the projected direction of this jet throughout the two apparitions and, under the assumption that the source region of the jet was near the comet's pole, determined a rotational pole direction of RA/Dec = 151deg/+59deg from CN measurements and RA/Dec = 173deg/+57deg from dust measurements (we estimate a circular uncertainty of 3deg for CN and 4deg for dust). Different combinations of effects likely bias both gas and dust solutions and we elected to average these solutions for a final pole of RA/Dec = 162 +/- 11deg/+58 +/- 1deg. Photoelectric photometry was acquired in 1983, 1988, 1999/2000, and 2010/2011. The activity exhibited a steep turn-on ~3 months prior to perihelion (the exact timing of which varies) and a relatively smooth decline after perihelion. The activity during the 1999 and 2010 apparitions was similar; limited data in 1983 and 1988 were systematically higher and the difference cannot be explained entirely by the smaller perihelion distance. We measured a "typical" composition, in agreement with previous investigators. Monte Carlo numerical modeling with our pole solution best replicated the observed coma morphology for a source region located near a comet latitude of +80deg and having a radius of ~10deg. Our model reproduced the seasonal changes in activity, suggesting that the majority of Tempel 2's activity originates from a small active region located near the pole.Comment: Accepted by AJ; 29 pages of text (preprint style), 8 tables, 7 figure

The Increasing Rotation Period of Comet 10P/Tempel 2

We imaged comet 10P/Tempel 2 on 32 nights from 1999 April through 2000 March. R-band lightcurves were obtained on 11 of these nights from 1999 April through 1999 June, prior to both the onset of significant coma activity and perihelion. Phasing of the data yields a double-peaked lightcurve and indicates a nucleus rotational period of 8.941 +/- 0.002 hr with a peak-to-peak amplitude of ~0.75 mag. Our data are sufficient to rule out all other possible double-peaked solutions as well as the single- and triple- peaked solutions. This rotation period agrees with one of five possible solutions found in post-perihelion data from 1994 by Mueller and Ferrin (1996, Icarus, 123, 463-477), and unambiguously eliminates their remaining four solutions. We applied our same techniques to published lightcurves from 1988 which were obtained at an equivalent orbital position and viewing geometry as in 1999. We found a rotation period of 8.932 +/- 0.001 hr in 1988, consistent with the findings of previous authors and incompatible with our 1999 solution. This reveals that Tempel 2 spun-down by ~32 s between 1988 and 1999 (two intervening perihelion passages). If the spin-down is due to a systematic torque, then the rotation period prior to perihelion during the 2010 apparition is expected to be an additional 32 s longer than in 1999.Comment: Accepted by The Astronomical Journal; 22 pages of text, 3 tables, 6 figure

Bubble-Driven Inertial Micropump

The fundamental action of the bubble-driven inertial micropump is investigated. The pump has no moving parts and consists of a thermal resistor placed asymmetrically within a straight channel connecting two reservoirs. Using numerical simulations, the net flow is studied as a function of channel geometry, resistor location, vapor bubble strength, fluid viscosity, and surface tension. Two major regimes of behavior are identified: axial and non-axial. In the axial regime, the drive bubble either remains inside the channel or continues to grow axially when it reaches the reservoir. In the non-axial regime the bubble grows out of the channel and in all three dimensions while inside the reservoir. The net flow in the axial regime is parabolic with respect to the hydraulic diameter of the channel cross-section but in the non-axial regime it is not. From numerical modeling, it is determined that the net flow is maximal when the axial regime crosses over to the non-axial regime. To elucidate the basic physical principles of the pump, a phenomenological one-dimensional model is developed and solved. A linear array of micropumps has been built using silicon-SU8 fabrication technology, and semi-continuous pumping across a 2 mm-wide channel has been demonstrated experimentally. Measured variation of the net flow with fluid viscosity is in excellent agreement with simulation results.Comment: 18 pages, 18 figures, single colum

Population-level impact of shorter-course regimens for tuberculosis: a model-based analysis.

Despite current control efforts, global tuberculosis (TB) incidence is decreasing slowly. New regimens that can shorten treatment hold promise for improving treatment completion and success, but their impact on population-level transmission remains unclear. Earlier models projected that a four-month regimen could reduce TB incidence by 10% but assumed that an entire course of therapy must be completed to derive any benefit. We constructed a dynamic transmission model of TB disease calibrated to global estimates of incidence, prevalence, mortality, and treatment success. To account for the efficacy of partial treatment, we used data from clinical trials of early short-course regimens to estimate relapse rates among TB patients who completed one-third, one-half, two-thirds, and all of their first-line treatment regimens. We projected population-level incidence and mortality over 10 years, comparing standard six-month therapy to hypothetical shorter-course regimens with equivalent treatment success but fewer defaults. The impact of hypothetical four-month regimens on TB incidence after 10 years was smaller than estimated in previous modeling analyses (1.9% [95% uncertainty range 0.6-3.1%] vs. 10%). Impact on TB mortality was larger (3.5% at 10 years) but still modest. Transmission impact was most sensitive to the proportion of patients completing therapy: four-month therapy led to greater incidence reductions in settings where 25% of patients leave care ("default") over six months. Our findings remained robust under one-way variation of model parameters. These findings suggest that novel regimens that shorten treatment duration may have only a modest effect on TB transmission except in settings of very low treatment completion

Drivers and trajectories of resistance to new first-line drug regimens for tuberculosis.

BACKGROUND: New first-line drug regimens for treatment of tuberculosis (TB) are in clinical trials: emergence of resistance is a key concern. Because population-level data on resistance cannot be collected in advance, epidemiological models are important tools for understanding the drivers and dynamics of resistance before novel drug regimens are launched. METHODS: We developed a transmission model of TB after launch of a new drug regimen, defining drug-resistant TB (DR-TB) as resistance to the new regimen. The model is characterized by (1) the probability of acquiring resistance during treatment, (2) the transmission fitness of DR-TB relative to drug-susceptible TB (DS-TB), and (3) the probability of treatment success for DR-TB versus DS-TB. We evaluate the effect of each factor on future DR-TB prevalence, defined as the proportion of incident TB that is drug-resistant. RESULTS: Probability of acquired resistance was the strongest predictor of the DR-TB proportion in the first 5 years after the launch of a new drug regimen. Over a longer term, however, the DR-TB proportion was driven by the resistant population's transmission fitness and treatment success rates. Regardless of uncertainty in acquisition probability and transmission fitness, high levels (>10%) of drug resistance were unlikely to emerge within 50 years if, among all cases of TB that were detected, 85% of those with DR-TB could be appropriately diagnosed as such and then successfully treated. CONCLUSIONS: Short-term surveillance cannot predict long-term drug resistance trends after launch of novel first-line TB regimens. Ensuring high treatment success of drug-resistant TB through early diagnosis and appropriate second-line therapy can mitigate many epidemiological uncertainties and may substantially slow the emergence of drug-resistant TB

Tuning graphitic oxide for initiator- and metal-free aerobic epoxidation of linear alkenes

Graphitic oxide has potential as a carbocatalyst for a wide range of reactions. Interest in this material has risen enormously due to it being a precursor to graphene via the chemical oxidation of graphite. Despite some studies suggesting that the chosen method of graphite oxidation can influence the physical properties of the graphitic oxide, the preparation method and extent of oxidation remain unresolved for catalytic applications. Here we show that tuning the graphitic oxide surface can be achieved by varying the amount and type of oxidant. The resulting materials differ in level of oxidation, surface oxygen content and functionality. Most importantly, we show that these graphitic oxide materials are active as unique carbocatalysts for low-temperature aerobic epoxidation of linear alkenes in the absence of initiator or metal. An optimum level of oxidation is necessary and materials produced via conventional permanganate-based methods are far from optimal