Induction of chronic migraine phenotypes in a rat model after environmental irritant exposure

Air pollution is linked to increased emergency department visits for headache and migraine patients frequently cite chemicals or odors as headache triggers, but the association between air pollutants and headache is not well understood. We previously reported that chronic environmental irritant exposure sensitizes the trigeminovascular system response to nasal administration of environmental irritants. Here, we examine whether chronic environmental irritant exposure induces migraine behavioral phenotypes. Male rats were exposed to acrolein, a transient receptor potential channel ankyrin-1 (TRPA1) agonist, or room air by inhalation for 4 days before meningeal blood flow measurements, periorbital cutaneous sensory testing, or other behavioral testing. Touch-induced c-Fos expression in trigeminal nucleus caudalis was compared in animals exposed to room air or acrolein. Spontaneous behavior and olfactory discrimination was examined in open-field testing. Acrolein inhalation exposure produced long-lasting potentiation of blood flow responses to a subsequent TRPA1 agonist and sensitized cutaneous responses to mechanical stimulation. C-Fos expression in response to touch was increased in trigeminal nucleus caudalis in animals exposed to acrolein compared with room air. Spontaneous activity in an open-field and scent preference behavior was different in acrolein-exposed compared with room air-exposed animals. Sumatriptan, an acute migraine treatment blocked acute blood flow changes in response to TRPA1 or transient receptor potential vanilloid receptor-1 agonists. Pretreatment with valproic acid, a prophylactic migraine treatment, attenuated the enhanced blood flow responses observed after acrolein inhalation exposures. Environmental irritant exposure yields an animal model of chronic migraine in which to study mechanisms for enhanced headache susceptibility after chemical exposure

On The Nature of Variations in the Measured Star Formation Efficiency of Molecular Clouds

Measurements of the star formation efficiency (SFE) of giant molecular clouds (GMCs) in the Milky Way generally show a large scatter, which could be intrinsic or observational. We use magnetohydrodynamic simulations of GMCs (including feedback) to forward-model the relationship between the true GMC SFE and observational proxies. We show that individual GMCs trace broad ranges of observed SFE throughout collapse, star formation, and disruption. Low measured SFEs (<<1%) are "real" but correspond to early stages, the true "per-freefall" SFE where most stars actually form can be much larger. Very high (>>10%) values are often artificially enhanced by rapid gas dispersal. Simulations including stellar feedback reproduce observed GMC-scale SFEs, but simulations without feedback produce 20x larger SFEs. Radiative feedback dominates among mechanisms simulated. An anticorrelation of SFE with cloud mass is shown to be an observational artifact. We also explore individual dense "clumps" within GMCs and show that (with feedback) their bulk properties agree well with observations. Predicted SFEs within the dense clumps are ~2x larger than observed, possibly indicating physics other than feedback from massive (main sequence) stars is needed to regulate their collapse.Comment: Fixed typo in the arXiv abstrac

Determination of Allergen Levels, Isoforms, and Their Hydroxyproline Modifications Among Peanut Genotypes by Mass Spectrometry

The recently published reference genome of peanuts enables a detailed molecular description of the allergenic proteins of the seed. We used LC-MS/MS to investigate peanuts of different genotypes to assess variability and to better describe naturally occurring allergens and isoforms. Using relative quantification by mass spectrometry, minor variation of some allergenic proteins was observed, but total levels of Ara h 1, 2, 3, and 6 were relatively consistent among 20 genotypes. Previously published RPHPLC methodology was used for comparison. The abundance of three Ara h 3 isoforms were variable among the genotypes and contributed to a large proportion of total Ara h 3 where present. Previously unpublished hydroxyproline sites were identified in Ara h 1 and 3. Hydroxylation did not vary significantly where sites were present. Peanut allergen composition was largely stable, with only some isoforms displaying differences between genotypes. The resulting differences in allergenicity are of unknown clinical significance but are likely to be minor. The data presented herein allow for the design of targeted MS methodology to allow the quantitation and therefore control of peanut allergens of clinical relevance and observed variability

Wave propagation in stereo-lithographical (STL) bone replicas at oblique incidence

Comparisons between predictions of a Biot-Allard model allowing for angle-dependent elasticity and angle-and-porosity dependent tortuosity and transmission data obtained at normal incidence on water-saturated replica bones are extended to oblique incidence. The model includes two parameters which are adjusted for best fit at normal incidence. Using the same parameter values, it is found that predictions of the variation of transmitted waveforms with angle through two types of bone replica are in reasonable agreement with data despite the fact that scattering is not included in the theory

Production of nanoparticles-in-microparticles by a double emulsion method : a comprehensive study

AbstractA method based on a double emulsion system (solid-in-water-in-oil-in-water) has been developed for the production of nanoparticles-in-microparticles (NIMs). The distribution of nanoparticles within the NIMs was explored using light and electron microscopy and through assessment of drug loading and release profiles. The extent of nanoparticle entrapment within the NIMs was found to be dependent on the state (wet vs. dry) in which the nanoparticles were introduced to the formulation. The technique was readily adaptable to produce NIMs of different morphologies. It is proposed that NIMs and this method to produce them have broad application in drug delivery research

Comprehensive Solution to the Cosmological Constant, Zero-Point Energy, and Quantum Gravity Problems

We present a solution to the cosmological constant, the zero-point energy, and the quantum gravity problems within a single comprehensive framework. We show that in quantum theories of gravity in which the zero-point energy density of the gravitational field is well-defined, the cosmological constant and zero-point energy problems solve each other by mutual cancellation between the cosmological constant and the matter and gravitational field zero-point energy densities. Because of this cancellation, regulation of the matter field zero-point energy density is not needed, and thus does not cause any trace anomaly to arise. We exhibit our results in two theories of gravity that are well-defined quantum-mechanically. Both of these theories are locally conformal invariant, quantum Einstein gravity in two dimensions and Weyl-tensor-based quantum conformal gravity in four dimensions (a fourth-order derivative quantum theory of the type that Bender and Mannheim have recently shown to be ghost-free and unitary). Central to our approach is the requirement that any and all departures of the geometry from Minkowski are to be brought about by quantum mechanics alone. Consequently, there have to be no fundamental classical fields, and all mass scales have to be generated by dynamical condensates. In such a situation the trace of the matter field energy-momentum tensor is zero, a constraint that obliges its cosmological constant and zero-point contributions to cancel each other identically, no matter how large they might be. Quantization of the gravitational field is caused by its coupling to quantized matter fields, with the gravitational field not needing any independent quantization of its own. With there being no a priori classical curvature, one does not have to make it compatible with quantization.Comment: Final version, to appear in General Relativity and Gravitation (the final publication is available at http://www.springerlink.com). 58 pages, revtex4, some additions to text and some added reference

ISEP: A Joint SRAG/CCMC Collaboration to Improve Mitigation of Space Weather Effects on Crew Health in the Exo-LEO Era

The Space Radiation Analysis Group (SRAG) at Johnson Space Center (JSC) is tasked with monitoring changes to space weather and mitigating any resultant impacts to crew health and safety. As human spaceflight goals extend from Low-Earth Orbit (LEO) missions like the International Space Station (ISS) to the moon, Mars and beyond, SRAG will need to update their current approach for crew monitoring of and protection from radiation exposure due to energetic Solar Particle Events (ESPEs). Challenges faced in planning exo-LEO missions include the lack of protection from the Earths geomagnetic field employed by the ISS in addition to limited communication capability between the crew and the ground. In the event of an ESPE, the current ISS trajectory ensures that the vehicle is only traveling through fields of higher radiation exposure for a brief period of time; the Earths geomagnetic field prevents the penetration of the high-energy particles of concern throughout the majority of the orbit. Exo-LEO missions, on the other hand, require that the vehicle travel through free space, exposing vehicle and crew to the full impact of the ESPE. NASA has combined multiple approaches to resolve this radiation exposure issue. New vehicles are designed to take advantage of advances in particle transport modeling capabilities and shielding technology, allowing redistribution of mass throughout the vehicle to areas of thinner shielding when the energetic particle flux has increased to levels of concern. Although vehicle shielding is an important aspect of radiation exposure protection, there is a continued requirement to monitor and predict the space weather environment. To this end, SRAG maintains a console position in Mission Control with 24/7 mission support capability. In the event of increased solar activity, SRAG collaborates with the Flight Control Team (FCT) to determine if crew action (i.e., shelter) is required. During any increase in solar activity, the FCT needs three pieces of information to effectively decide the crew response in light of other required mission tasks: if an event (ESPE) will occur, how intense an observed event will be, and how long will an observed event will last. An ideal alert system limits false alarms, therefore causing the crew to take action unnecessarily, without ignoring events that pose a hazard to the crew. SRAGs current operational concept for ISS missions focuses on short-term forecasts, best described as now-casting. Console operators are in daily communication with the Space Weather Prediction Center (SWPC) for situational awareness purposes. When conditions exist that may lead to increased solar activity, operators receive notifications from SWPC. In the case of a well-connected ESPE, the console operator may only have on the order of minutes to several hours to notify the FCT of the event and provide a recommendation for crew action. As NASA shifts to exo-LEO missions, the increased time in free space as well as the reduced ability to communicate with the crew will force a transition in crew protection strategy that emphasizes improvments to both the accuracy and the lead time in forecasting capabilities

The positive association of infant weight gain with adulthood body mass index has strengthened over time in the Fels Longitudinal Study

Background Infant weight gain is positively related to adulthood body mass index (BMI), but it is unknown whether or not this association is stronger for individuals born during (compared to before) the obesity epidemic. Objectives To examine how the infant weight gain–adulthood BMI association might have changed across successive birth year cohorts spanning most of the 20th century. Methods The sample comprised 346 participants in the Fels Longitudinal Study. Confounder-adjusted regression models were used to test the associations of conditional weight-for-length Z-score (WLZ), capturing weight change between ages 0-2 years, with young adulthood BMI and blood pressure, including cohort (1933-1949 (N=137), 1950-1969 (N=108), 1970-1997 (N=101)) as an effect modifier. Results Conditional WLZ was positively related to adulthood BMI, but there was significant effect modification by birth year cohort such that the association was over two times stronger in the 1970-1997 cohort (β 2.31; 95% confidence interval 1.59, 3.03) compared to the 1933-1949 (0.98; 0.31, 1.65) and 1950-1969 (0.87; 0.21, 1.54) cohorts. A similar pattern was found for systolic blood pressure. Conclusions The infant weight gain–adulthood BMI association was over two times stronger among a cohort born during the obesity epidemic era compared to cohorts born earlier in the 20th century