Corrosion of the International Simple Glass under acidic to hyperalkaline conditions

Assessment of glass dissolution kinetics, under disposal relevant temperature and pH environments, is required to credibly estimate radionuclide release rates from vitrified radioactive waste. Leaching of the International Simple Glass (ISG) under acidic to hyperalkaline conditions was examined. Forward rate measurements have been obtained using the dynamic leaching SPFT protocol and rate parameters for B, Na and Si in the basic regime; errors in rates predicted using these parameters at high pH and temperature are significant because the fitting uses logarithmic data. Longer term behaviour under hyperalkaline conditions, representative of some disposal environments, was investigated using the PCT and MCC-1 static leaching protocols with Ca(OH)2 solutions for up to 120 days (PCT) and 720 days (MCC-1). In hyperalkaline conditions dissolution was incongruent for all elements and the presence of alternating zirconia-rich and zirconia-poor alteration layers was observed on all leached monoliths, indicating the occurrence of a self-organisation phenomenon during leaching

Characterization and Utilization of the Flexor Digitorum Brevis for Assessing Skeletal Muscle Function

Abstract Background The ability to assess skeletal muscle function and delineate regulatory mechanisms is essential to uncovering therapeutic approaches that preserve functional independence in a disease state. Skeletal muscle provides distinct experimental challenges due to inherent differences across muscle groups, including fiber type and size that may limit experimental approaches. The flexor digitorum brevis (FDB) possesses numerous properties that offer the investigator a high degree of experimental flexibility to address specific hypotheses. To date, surprisingly few studies have taken advantage of the FDB to investigate mechanisms regulating skeletal muscle function. The purpose of this study was to characterize and experimentally demonstrate the value of the FDB muscle for scientific investigations. Methods First, we characterized the FDB phenotype and provide reference comparisons to skeletal muscles commonly used in the field. We developed approaches allowing for experimental assessment of force production, in vitro and in vivo microscopy, and mitochondrial respiration to demonstrate the versatility of the FDB. As proof-of principle, we performed experiments to alter force production or mitochondrial respiration to validate the flexibility the FDB affords the investigator. Results The FDB is made up of small predominantly type IIa and IIx fibers that collectively produce less peak isometric force than the extensor digitorum longus (EDL) or soleus muscles, but demonstrates a greater fatigue resistance than the EDL. Unlike the other muscles, inherent properties of the FDB muscle make it amenable to multiple in vitro- and in vivo-based microscopy methods. Due to its anatomical location, the FDB can be used in cardiotoxin-induced muscle injury protocols and is amenable to electroporation of cDNA with a high degree of efficiency allowing for an effective means of genetic manipulation. Using a novel approach, we also demonstrate methods for assessing mitochondrial respiration in the FDB, which are comparable to the commonly used gastrocnemius muscle. As proof of principle, short-term overexpression of Pgc1α in the FDB increased mitochondrial respiration rates. Conclusion The results highlight the experimental flexibility afforded the investigator by using the FDB muscle to assess mechanisms that regulate skeletal muscle function

Impact of short-term dietary modification on postprandial oxidative stress

<p>Abstract</p> <p>Background</p> <p>We have recently reported that short-term (21-day) dietary modification in accordance with a stringent vegan diet (i.e., a Daniel Fast) lowers blood lipids as well as biomarkers of oxidative stress. However, this work only involved measurements obtained in a fasted state. In the present study, we determined the postprandial response to a high-fat milkshake with regards to blood triglycerides (TAG), biomarkers of oxidative stress, and hemodynamic variables before and following a 21-day Daniel Fast.</p> <p>Methods</p> <p>Twenty-two subjects (10 men and 12 women; aged 35 ± 3 years) completed a 21-day Daniel Fast. To induce oxidative stress, a milkshake (fat = 0.8 g·kg^-1; carbohydrate = 1.0 g·kg^-1; protein = 0.25 g·kg^-1) was consumed by subjects on day one and day 22 in a rested and 12-hour fasted state. Before and at 2 and 4 h after consumption of the milkshake, heart rate (HR) and blood pressure were measured. Blood samples were also collected at these times and analyzed for TAG, malondialdehyde (MDA), hydrogen peroxide (H₂O₂), advanced oxidation protein products (AOPP), nitrate/nitrite (NOx), and Trolox Equivalent Antioxidant Capacity (TEAC).</p> <p>Results</p> <p>A time effect was noted for HR (<it>p </it>= 0.006), with values higher at 2 hr post intake of the milkshake as compared to pre intake (<it>p </it>< 0.05). Diastolic blood pressure was lower post fast as compared to pre fast (<it>p </it>= 0.02), and a trend for lower systolic blood pressure was noted (<it>p </it>= 0.07). Time effects were noted for TAG (<it>p </it>= 0.001), MDA (<it>p </it>< 0.0001), H₂O₂(<it>p </it>< 0.0001), AOPP (<it>p </it>< 0.0001), and TEAC (<it>p </it>< 0.0001); all concentrations were higher at 2 h and 4 h post intake compared to pre intake, except for TEAC, which was lower at these times (<it>p </it>< 0.05). A condition effect was noted for NOx (<it>p </it>= 0.02), which was higher post fast as compared to pre fast. No pre/post fast × time interactions were noted (<it>p </it>> 0.05), with the area under the curve from pre to post fast reduced only slightly for TAG (11%), MDA (11%), H₂O₂(8%), and AOPP (12%), with a 37% increase noted for NOx.</p> <p>Conclusion</p> <p>Partaking in a 21-day Daniel Fast does not result in a statistically significant reduction in postprandial oxidative stress. It is possible that a longer time course of adherence to the Daniel Fast eating plan may be needed to observe significant findings.</p

Conceptualising and historicising the US foreign policy establishment in a racialised class structure

In recent years critical scholars of U.S. foreign policy have challenged the mainstream paradigm that fails to account for the racial dimensions of international relations. This article introduces a conceptual and historical analysis of the US foreign policy establishment that posits race and racism at its centre. While alluding to conventional theories of American power such as pluralism and statism, the article also highlights classical Marxism’s failure to acknowledge that US exceptionalism and racism conjoined in a manner that conferred a racial dimension to class politics. The article argues that the U.S. foreign policy establishment has been presided over by an elite or ruling elite; and irrespective of challenges from below, increasing diversity, or the insistence that America is a meritocratic classless society, the U.S establishment is at heart, elitist, racialised and generally Anglo-centric. The article identifies links between the racial dimensions of U.S. foreign policy and the identity profile of the power elite. The paper extends and critiques C. Wright Mills’ definition of the power elite by mapping its racial dimension. Finally the article argues that although the election of Obama represented a more inclusive and cosmopolitan version of the establishment, Obama’s presence has helped to consolidate the status quo as the structural constraints on the executive branch and symbolism associated with the election of the first African-American president has generally silenced the Left and quietly fostered the suggestion that an unconventional identity profile will not necessarily result in the change we can believe in

Protein kinase A-mediated CREB phosphorylation is an oxidant-induced survival pathway in alveolar type II cells

Oxidant stress plays a role in the pathogenesis of pulmonary diseases, including fibrotic lung disease and cancer. We previously found that hydrogen peroxide (H2O2) initiates an increase in Ca2+/cAMP-response element binding protein (CREB) phosphorylation in C10 alveolar type II cells that requires activation of extracellular regulated kinases 1/2 (ERK1/2). Here, we investigated the role of crosstalk between protein kinase A (PKA) and epidermal growth factor receptor (EGFR) in oxidant-induced signaling to ERK1/2 and CREB in C10 cells. Application of H2O2 increased nuclear accumulation of PKA, and inhibition of PKA with H89 reduced oxidant-mediated phosphorylation of both CREB and ERK1/2. Single cell measurements of cAMP and redox status, using a FRET-based biosensor and a redox-sensitive GFP, respectively, indicated that H2O2 increases production of cAMP that correlates with redox state. Inhibition of EGFR activity decreased both H2O2-induced CREB phosphorylation and translocation of PKA to the nucleus, suggesting that crosstalk between PKA and EGFR underlies the oxidant-induced CREB response. Furthermore, knockdown of CREB expression using siRNA led to a decrease in bcl-2 and an increase in oxidant-induced apoptosis. Together these data reveal a novel role for crosstalk between PKA, ERK1/2 and CREB that mediates cell survival during oxidant stress

Lmo4 in the Basolateral Complex of the Amygdala Modulates Fear Learning

Pavlovian fear conditioning is an associative learning paradigm in which mice learn to associate a neutral conditioned stimulus with an aversive unconditioned stimulus. In this study, we demonstrate a novel role for the transcriptional regulator Lmo4 in fear learning. LMO4 is predominantly expressed in pyramidal projection neurons of the basolateral complex of the amygdala (BLC). Mice heterozygous for a genetrap insertion in the Lmo4 locus (Lmo4gt/+), which express 50% less Lmo4 than their wild type (WT) counterparts display enhanced freezing to both the context and the cue in which they received the aversive stimulus. Small-hairpin RNA-mediated knockdown of Lmo4 in the BLC, but not the dentate gyrus region of the hippocampus recapitulated this enhanced conditioning phenotype, suggesting an adult- and brain region-specific role for Lmo4 in fear learning. Immunohistochemical analyses revealed an increase in the number of c-Fos positive puncta in the BLC of Lmo4gt/+ mice in comparison to their WT counterparts after fear conditioning. Lastly, we measured anxiety-like behavior in Lmo4gt/+ mice and in mice with BLC-specific downregulation of Lmo4 using the elevated plus maze, open field, and light/dark box tests. Global or BLC-specific knockdown of Lmo4 did not significantly affect anxiety-like behavior. These results suggest a selective role for LMO4 in the BLC in modulating learned but not unlearned fear

Progesterone reduces erectile dysfunction in sleep-deprived spontaneously hypertensive rats

BACKGROUND: Paradoxical sleep deprivation (PSD) associated with cocaine has been shown to enhance genital reflexes (penile erection-PE and ejaculation-EJ) in Wistar rats. Since hypertension predisposes males to erectile dysfunction, the aim of the present study was to investigate the effects of PSD on genital reflexes in the spontaneously hypertensive rat (SHR) compared to the Wistar strain. We also extended our study to examine how PSD affect steroid hormone concentrations involved in genital events in both experimental models. METHODS: The first experiment investigated the effects of PSD on genital reflexes of Wistar and SHR rats challenged by saline and cocaine (n = 10/group). To further examine the impact of the PSD on concentrations of sexual hormones, we performed a hormonal analysis of testosterone and progesterone in the Wistar and in SHR strains. Since after PSD progesterone concentrations decreased in the SHR compared to the Wistar PSD group we extended our study by investigating whether progesterone (25 mg/kg or 50 mg/kg) or testosterone (0.5 mg/kg or 1.0 mg/kg) administration during PSD would have a facilitator effect on the occurrence of genital reflexes in this hypertensive strain. RESULTS: A 4-day period of PSD induced PE in 50% of the Wistar rats against 10% for the SHR. These genital reflexes was potentiated by cocaine in Wistar rats whereas this scenario did not promote significant enhancement in PE and EJ in hypertensive rats, and the percentage of SHR displaying genital reflexes still figured significantly lower than that of the Wistar strain. As for hormone concentrations, both sleep-deprived Wistar and SHR showed lower testosterone concentrations than their respective controls. Sleep deprivation promoted an increase in concentrations of progesterone in Wistar rats, whereas no significant alterations were found after PSD in the SHR strain, which did not present enhancement in erectile responses. In order to explore the role of progesterone in the occurrence of genital reflexes, SHR were treated daily during the sleep deprivation period with progesterone; after the administration of this hormone and challenge with cocaine, we observed a significant increase in erectile events compared with the vehicle PSD SHR+cocaine group. CONCLUSION: Our data showed that the low frequency of genital reflexes found in SHR sleep deprived rats may be attributed to the lower concentrations of progesterone in these rats, based on the observation that progesterone replacement increased genital reflexes in this strain

Comparison of yoga versus stretching for chronic low back pain: protocol for the Yoga Exercise Self-care (YES) trial

<p>Abstract</p> <p>Background</p> <p>Back pain, one of the most prevalent conditions afflicting American adults, is the leading reason for using complementary and alternative medicine (CAM) therapies. Yoga is an increasingly popular "mind-body" CAM therapy often used for relieving back pain and several small studies have found yoga effective for this condition. This study will assess whether yoga is effective for treating chronic low back pain compared with self care and exercise and will explore the mechanisms responsible for any observed benefits.</p> <p>Methods/Design</p> <p>A total of 210 participants with low back pain lasting at least 3 months will be recruited from primary care clinics of a large healthcare system based in Seattle. They will be randomized in a 2:2:1 ratio to receive 12 weekly yoga classes, 12 weekly conventional therapeutic exercise classes of comparable physical exertion, or a self-care book. Interviewers masked to participants' treatment group will assess outcomes at baseline and 6, 12 and 26 weeks after randomization. Primary outcomes will be back-related dysfunction and symptom bothersomeness. In addition, data will be collected on physical measurements (e.g., flexion) at baseline and 12 weeks and saliva samples will be obtained at baseline, 6 and 12 weeks. Information will be collected on specific physical, psychological, and physiological factors to allow exploration of possible mechanisms of action through which yoga could relieve back pain and dysfunction. The effectiveness of yoga will be assessed using analysis of covariance (using general estimating equations - GEE) within an intention-to-treat context. If yoga is found effective, further analyses will explore whether yoga's benefits are attributable to physical, psychological and/or physiological factors.</p> <p>Conclusions</p> <p>This study will provide the clearest evidence to date about the value of yoga as a therapeutic option for treating chronic back pain, and if the results are positive, will help focus future, more in-depth, research on the most promising potential mechanisms of action identified by this study.</p> <p>Trial registration</p> <p>This trial is registered in ClinicalTrials.gov, with the ID number of <it>NCT00447668</it>.</p

Balancing, Proportionality, and Constitutional Rights

In the theory and practice of constitutional adjudication, proportionality review plays a crucial role. At a theoretical level, it lies at core of the debate on rights adjudication; in judicial practice, it is a widespread decision-making model characterizing the action of constitutional, supra-national and international courts. Despite its circulation and centrality in contemporary legal discourse, proportionality in rights-adjudication is still extremely controversial. It raises normative questions—concerning its justification and limits—and descriptive questions—regarding its nature and distinctive features. The chapter addresses both orders of questions. Part I centres on the justification of proportionality review, the connection between proportionality, balancing and theories of rights and the critical aspects of this connection. Part II identifies and analyses the different forms of proportionality both in review, as a template for rights-adjudication, and of review, as a way of defining the scope and limits of adjudication

Variability in Avian Eggshell Colour: A Comparative Study of Museum Eggshells

Background: The exceptional diversity of coloration found in avian eggshells has long fascinated biologists and inspired a broad range of adaptive hypotheses to explain its evolution. Three main impediments to understanding the variability of eggshell appearance are: (1) the reliable quantification of the variation in eggshell colours; (2) its perception by birds themselves, and (3) its relation to avian phylogeny. Here we use an extensive museum collection to address these problems directly, and to test how diversity in eggshell coloration is distributed among different phylogenetic levels of the class Aves. Methodology and Results: Spectrophotometric data on eggshell coloration were collected from a taxonomically representative sample of 251 bird species to determine the change in reflectance across different wavelengths and the taxonomic level where the variation resides. As many hypotheses for the evolution of eggshell coloration assume that egg colours provide a communication signal for an avian receiver, we also modelled reflectance spectra of shell coloration for the avian visual system. We found that a majority of species have eggs with similar background colour (long wavelengths) but that striking differences are just as likely to occur between congeners as between members of different families. The region of greatest variability in eggshell colour among closely related species coincided with the medium-wavelength sensitive region around 500 nm. Conclusions: The majority of bird species share similar background eggshell colours, while the greatest variability among species aligns with differences along a red-brown to blue axis that most likely corresponds with variation in the presence and concentration of two tetrapyrrole pigments responsible for eggshell coloration. Additionally, our results confirm previous findings of temporal changes in museum collections, and this will be of particular concern for studies testing intraspecific hypotheses relating temporal patterns to adaptation of eggshell colour. We suggest that future studies investigating the phylogenetic association between the composition and concentration of eggshell pigments, and between the evolutionary drivers and functional impacts of eggshell colour variability will be most rewarding.Phillip Cassey, Steven J. Portugal, Golo Maurer, John G. Ewen, Rebecca L. Boulton, Mark E. Hauber and Tim M. Blackbur