The influence of μ-opioid and noradrenaline reuptake inhibition in the modulation of pain responsive neurones in the central amygdala by tapentadol in rats with neuropathy

Treatments for neuropathic pain are either not fully effective or have problematic side effects. Combinations of drugs are often used. Tapentadol is a newer molecule that produces analgesia in various pain models through two inhibitory mechanisms, namely central μ-opioid receptor (MOR) agonism and noradrenaline reuptake inhibition. These two components interact synergistically, resulting in levels of analgesia similar to opioid analgesics such as oxycodone and morphine, but with more tolerable side effects. The right central nucleus of the amygdala (CeA) is critical for the lateral spinal ascending pain pathway, regulates descending pain pathways and is key in the emotional-affective components of pain. Few studies have investigated the pharmacology of limbic brain areas in pain models. Here we determined the actions of systemic tapentadol on right CeA neurones of animals with neuropathy and which component of tapentadol contributes to its effect. Neuronal responses to multimodal peripheral stimulation of animals with spinal nerve ligation or sham surgery were recorded before and after two doses of tapentadol. After the higher dose of tapentadol either naloxone or yohimbine were administered. Systemic tapentadol resulted in dose-dependent decrease in right CeA neuronal activity only in neuropathy. Both naloxone and yohimbine reversed this effect to an extent that was modality selective. The interactions of the components of tapentadol are not limited to the synergy between the MOR and α2-adrenoceptors seen at spinal levels, but are seen at this supraspinal site where suppression of responses may relate to the ability of the drug to alter affective components of pain

The nature of operating flight loads and their effect on propulsion system structures

Past diagnostics studies revealed the primary causes of performance deterioration of high by-pass turbofan engines to be flight loads, erosion, and thermal distortion. The various types of airplane loads that are imposed on the engine throughout the lifetime of an airplane are examined. These include flight loads from gusts and maneuvers and ground loads from takeoff, landing, and taxi conditions. Clarification is made in definitions of the airframer's limit and ultimate design loads and the engine manufacturer's operating design loads. Finally, the influence of these loads on the propulsion system structures is discussed

Does Fact-Finding Promote Settlement? Theory and a Test

Some labor negotiations include a break in which a non-binding recommendation is made by a fact-finder as an intermediate dispute resolution procedure. There is some uncertainty, however, as to whether this fact-finding increases or reduces the likelihood of settlement. Inasmuch as fact-finding reduces uncertainty about the outcome, it may chill bargaining and increase the need for additional dispute resolution procedures. On the other hand, the fact-finder\u27s recommendation may give the parties a focal point around which they are able to craft an agreement, thus reducing the incidence of disputes. Which of these effects dominates is a question that we consider using both a theoretical model and data from a controlled experimental bargaining environment

Oil and gas in Kent and southern Lambton counties, Ontario, Canada

Master of ScienceGeology and MineralogyUniversity of Michiganhttp://deepblue.lib.umich.edu/bitstream/2027.42/115418/2/39015003269233.pd

Willingness-to-Pay For Information: Experimental Evidence on Product Traceability From the U.S.A., Canada, the U.K., and Japan

Traceable product systems provide a tool to track the inputs of a final good throughout the entire production chain. This tool can provide valuable information to consumers on verifiable characteristics of the product, can improve the speed of product recall, and can help identify areas of inefficiency in the product chain. Recent examples of traceable systems include those used in the diamond, lumber, and food industries. This article reports results from a case study on traceability using Vickrey auctions to generate willingness-to-pay (WTP) data for traceability and related product characteristics. Specifically, we examine WTP for traceable meat, which is a timely topic given that major customers and competitors in the multi-billion dollar red-meat market are all implementing traceable meat systems. However, the largest player in world red-meat markets, the U.S., is lagging in the development of these systems. We conduct comparable auctions in the U.S., Canada, the U.K., and Japan and find that subjects are willing to pay a nontrivial premium for traceability, but the same subjects show even higher WTP for traceability-provided characteristics like additional meat safety and humane animal treatment guarantees. The implication is that producers can likely implement such a traceable meat system profitably by tailoring the verifiable characteristics of the product to consumer preferences. For other types of traceable products, these results highlight the importance of full exploitation of traceable systems by providing consumers with the additional product information that only a traceable system can verify

Stability of diurnal cortisol measures across days, weeks, and years across middle childhood and early adolescence: Exploring the role of age, pubertal development, and sex.

Effective regulation of the hypothalamic-pituitary-adrenal axis (HPA-axis) has been linked to numerous health outcomes. Within-person variation in diurnal measures of HPA-axis regulation assessed over days, months, and years can range between 50-73% of total variation. In this study of 59 youth (ages 8-13), we quantified the stability of the cortisol awakening response (CAR), the diurnal slope, and tonic cortisol concentrations at waking and bedtime across 8 days (2 sets of 4 consecutive days separated by 3 weeks), 3 weeks, and 3 years. We then compared the stability of these indices across three key developmental factors: age, pubertal status, and sex. Youth provided 4 saliva samples per day (waking, 30 min post-waking, before dinner, and before bedtime) for 4 consecutive days during the 3rd week of an ongoing 8-week daily diary study. Youth repeated this same sampling procedure 3 weeks and 3 years later. Using multi-level modeling, we computed the amount of variance in diurnal HPA-axis regulation that was accounted for by nesting an individual's diurnal cortisol indices within days, weeks, or years. Across days, diurnal slope was the most stable index, whereas waking cortisol and CAR were the least stable. All indices except bedtime cortisol were similarly stable when measured across weeks, and all indices were uniformly stable when measured across 3 years. Boys, younger participants, and youth earlier in their pubertal development at study enrollment exhibited greater HPA-axis stability overall compared with females and older, more physically mature participants. We conclude that important within- and between-subjects questions can be answered about health and human development by studying HPA-axis regulation, and selection of the index of interest should be determined in part by its psychometric characteristics. To this end, we propose a decision tree to guide study design for research in pediatric samples by longitudinal timeframe and sample characteristics

The lady vanishes: what's missing from the stem cell debate

Most opponents of somatic cell nuclear transfer and embryonic stem cell technologies base their arguments on the twin assertions that the embryo is either a human being or a potential human being, and that it is wrong to destroy a human being or potential human being in order to produce stem cell lines. Proponents’ justifications of stem cell research are more varied, but not enough to escape the charge of obsession with the status of the embryo. What unites the two warring sides in ‘the stem cell wars’ is that women are equally invisible to both: ‘the lady vanishes’. Yet the only legitimate property in the body is that which women possess in their reproductive tissue and the products of their reproductive labour. By drawing on the accepted characterisation in law of property as a bundle of rights, and on a Hegelian model of contract as mutual recognition, we can lessen the impact of the tendency to regard women and their eggs as merely receptacles and women’s reproductive labour as unimportant

Chutzpadik advertising and its effectiveness: Four studies of agencies and audiences

publishedVersio

Spa47 is an oligomerization-activated type three secretion system (T3SS) ATPase from \u3cem\u3eShigella flexneri\u3c/em\u3e

Gram-negative pathogens often use conserved type three secretion systems (T3SS) for virulence. The Shigella type three secretion apparatus (T3SA) penetrates the host cell membrane and provides a unidirectional conduit for injection of effectors into host cells. The protein Spa47 localizes to the base of the apparatus and is speculated to be an ATPase that provides the energy for T3SA formation and secretion. Here, we developed an expression and purification protocol, producing active Spa47 and providing the first direct evidence that Spa47 is a bona fide ATPase. Additionally, size exclusion chromatography and analytical ultracentrifugation identified multiple oligomeric species of Spa47 with the largest greater than 8 fold more active for ATP hydrolysis than the monomer. An ATPase inactive Spa47 point mutant was then engineered by targeting a conserved Lysine within the predicted Walker A motif of Spa47. Interestingly, the mutant maintained a similar oligomerization pattern as active Spa47, but was unable to restore invasion phenotype when used to complement a spa47 null S. flexneri strain. Together, these results identify Spa47 as a Shigella T3SS ATPase and suggest that its activity is linked to oligomerization, perhaps as a regulatory mechanism as seen in some related pathogens. Additionally, Spa47 catalyzed ATP hydrolysis appears to be essential for host cell invasion, providing a strong platform for additional studies dissecting its role in virulence and providing an attractive target for anti-infective agents

EVA Glove Research Team

The goal of the basic research portion of the extravehicular activity (EVA) glove research program is to gain a greater understanding of the kinematics of the hand, the characteristics of the pressurized EVA glove, and the interaction of the two. Examination of the literature showed that there existed no acceptable, non-invasive method of obtaining accurate biomechanical data on the hand. For this reason a project was initiated to develop magnetic resonance imaging as a tool for biomechanical data acquisition and visualization. Literature reviews also revealed a lack of practical modeling methods for fabric structures, so a basic science research program was also initiated in this area