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Methyl esters of gamma-linolenic acid, alpha-linolenic acid and stearidonic acid were epoxidised using m-chloroperbenzoic acid to achieve nine cis-monoepoxy-C18 fatty acid methyl esters (FAMEs), including novel methyl cis-monoepoxy derivatives of stearidonic acid and a cis-6,7-epoxy derivative of gamma-linolenic acid. These nine monoepoxy FAMEs were purified by normal-phase HPLC, identified by LC-MS, 1H and 13C NMR, and characterized by mass spectrometry and NMR spectroscopy. This study is focused on structural characterization of these C18 monoepoxy FAMEs using techniques in NMR spectroscopy including 1H, 13C, 1H-1H correlated spectroscopy (COSY) and 1H-13C heteronuclear correlation (HETCOR). The proton and carbon NMR chemical shifts of the epoxide, the double bonds, and the interrupted methylenes are assigned. Also discussed is an interpretation of the 1H and 13C NMR spectra of these monoepoxides including the changes in the 13C resonance of the olefinic carbons on the neighboring double bonds resulting from epoxide formation.

Many commercially important fish species use coastal marine environments such as mangroves, tidal flats and seagrass beds as nurseries or breeding grounds. The ecological importance of spatially connected habitats to conservation is well established for terrestrial environments. However, few studies have applied spatial metrics, including measures of structural connectivity to marine environments. We examined the relationship between catch-per-unit-effort for commercially caught species and the spatial patterning of mapped benthic habitat types along the coast of Queensland, Australia in their dominant fisheries (trawl, line, net or pot fisheries). We quantified the composition and spatial configuration of seascapes and calculated coastline length, number of estuaries, river length and geographical latitude using 12 metrics within ninety 30-nautical-mile grid cells, which supported inshore fish catch data from 21 species groups. Multiple regression analysis and non-metric multidimensional scaling plots indicated that ecological linkages may exist between geomorphic coastal features and nearshore fisheries production for a number of species groups. Connectivity indices for mangroves, salt marsh and channels explained the largest proportion (30–70%), suggesting the importance of connected tidal wetlands for fisheries. Barramundi (Lates calcarifer) catch-per-unit-effort was best explained by the number of wetland patches, mangrove connectivity and wetland connectivity (r2 = 0.38, n = 28). Catch-per-unit-effort for the Gulf of Carpentaria was highly correlated with wetland connectivity, the number of estuaries and seagrass patch density (r = 0.57, n = 29). The findings could guide the spatial design of marine protected area networks to maintain ecosystem services and avoid potential disruption to connectivity caused by habitat removal or modification. Application of the same approach to analyses of finer spatial scales would enable catch information to be related to particular estuarine habitats and provide better understanding of the importance of habitat connectivity for fisheries.

Objective This study examined predictive and mediated relationships among youth perception of critical parenting, Child Behavior Checklist Externalizing Subscale (CBCL) externalizing problem scores, adherence, and (hemoglobin A1c HbA1c), in youth with type 1 diabetes from low socioeconomic status families. Methods Caregiver/youth dyads (n ¼120) completed diabetes specific measures of family functioning regarding diabetes management and structured adherence interviews. Parents completed the CBCL, while assays of youth HbA1c were performed. Analyses were conducted using hierarchical linear regression. Results Combined measures predicted 44% of the variance in HbA1c. Adherence partially mediated critical parenting and HbA1c, while critical parenting and adherence mediated CBCL externalizing problem scores and HbA1c. CBCL externalizing problem scores did not mediate critical parenting and HbA1c. Conclusions The presence of youth perceptions of critical parenting and youth externalizing behavior problems may interfere with adherence, leading to increases in HbA1c.

Details are presented of the Whipple Observatory’s 10 m atmospheric Cherenkov telescope and camera, as it evolved during the period 1997 until 2006. The design of the telescope and camera’s optical and electronic systems is discussed together with a detailed description of the four-stage GRANITE (Gamma-RAy New Imaging TElescope) upgrade program, undertaken during the same time period. The objective of the upgrade was to improve the telescope’s sensitivity for the detection of very-high-energy gamma-rays. Results from the program are provided and are briefly discussed in the context of the design of VERITAS.

Thomas JJ, Shuford DM, Duke JC, Cipriani III DJ. Development and psychometric properties of the Self-Efficacy Scale for transfers for caregivers of children requiring transfer assistance. Objective To test the psychometric properties of a newly developed measure of caregiver self-efficacy, the Caregiver Self-Efficacy Scale for Transfers (CSEST), a 14-item questionnaire that measures the perceived self-efficacy of adult caregivers of dependent children and focuses on their perceived abilities and the challenges of assisting a child with restricted transfer ability. Design Reliability and validity study using survey data. Setting Community-based survey study. Participants Adult caregivers (eg, mother, father, grandparent) of dependent minors who require transfer assistance. Interventions Not applicable. Main Outcome Measure Using the Rasch measurement model, the CSEST was tested for reliability and separation, validity (hierarchical and content), and factor structure. Results The CSEST yields data with sufficient reliability (reliability indices of .96 and .94 for respondents and items, respectively) as well as sufficient separation of levels of self-efficacy (item separation index, 4.13; person separation index, 5.23). The CSEST has a stable hierarchical structure with adequate content validity (standardized χ 2 fit statistics Conclusions The CSEST yields reliable data and valid inferences of self-efficacy from adult caregivers of children requiring transfer assistance. The CSEST may identify areas of need and/or difficulty with transfers for parents caring for dependent children.

Objective: To examine the relative efficacy of intensive versus weekly cognitive-behavioral therapy (CBT) for children and adolescents with obsessive-compulsive disorder (OCD). Method: Forty children and adolescents with OCD (range 7-17 years) were randomized to receive 14 sessions of weekly or intensive (daily psychotherapy sessions) family-based CBT. Assessments were conducted at three time points: pretreatment, posttreatment, and 3-month follow-up. Raters were initially blind to randomization. Primary outcomes included scores on the Children's Yale-Brown Obsessive-Compulsive Scale, remission status, and ratings on the Clinical Global Impression-Severity and Clinical Global Improvement scales. Secondary outcomes included the Child Obsessive Compulsive Impact Scale-Parent Rated, Children's Depression Inventory, Multidimensional Anxiety Scale for Children, and Family Accommodation Scale. Adjunctive pharmacotherapy was not an exclusion criterion. Results: Intensive CBT was as effective as weekly treatment with some advantages present immediately after treatment. No group differences were found at follow-up, with gains being largely maintained over time. Although no group × time interaction was found for the Children's Yale-Brown Obsessive-Compulsive Scale ( F 1,38 = 2.2, p = .15), the intensive group was rated on the Clinical Global Impression-Severity as less ill relative to the weekly group ( F 1,38 = 9.4, p 2 1 = 3.6, p = .06). Conclusions: Both intensive and weekly CBT are efficacious treatments for pediatric OCD. Intensive treatment may have slight immediate advantages over weekly CBT, although both modalities have similar outcomes at 3-month follow-up.

VERITAS is a ground-based gamma-ray observatory covering energies between 100 GeV and 50 TeV and will start operating by January 2007. We give a brief report of the construction status and performance characteristics of the telescopes.

Control of primary infection with hepatitis C virus (HCV) is associated with robust and broad T cell immunity. In contrast, chronic infection is characterized by weak T cell responses suggesting that an approach that boosts these responses could be a therapeutic advance. Saccharomyces cerevisiae is an effective inducer of innate and adaptive cellular immunity and we have generated recombinant yeast cells (GI-5005) that produce an HCV NS3-Core fusion protein. Pre-clinical studies in mice showed that GI-5005 induced potent antigen-specific proliferative and cytotoxic T cell responses that were associated with Th1-type cytokine secretion. In studies in which GI-5005 was administered up to 13 times, no detectable vector neutralization or induction of tolerance was observed. Prophylactic as well as therapeutic administration of GI-5005 in mice led to eradication of tumor cells expressing HCV NS3 protein. Immunotherapy with GI-5005 is being evaluated in chronic HCV infected individuals in a Phase 1 clinical trial.

The identification of mutations that cause familial Parkinson's disease (PD) provides a framework for studies into pathways that may be perturbed also in the far more common, non-familial form of the disorder. Following this hypothesis, we have examined the gene regulatory network that links alpha-synuclein and parkin pathways with dopamine metabolism in neuropathologically verified cases of sporadic PD. By means of an in silico approach using a database of eukaryotic molecular interactions and a whole genome transcriptome dataset validated by qRT-PCR and histological methods, we found parkin and functionally associated genes to be up-regulated in the lateral substantia nigra (SN). In contrast, alpha-synuclein and ubiquitin carboxyl-terminal hydrolase L1 (UCHL1) gene expression levels were significantly reduced in both the lateral and medial SN in PD. Gene expression for Septin 4, a member of the GTP-binding protein family involved in alpha-synuclein metabolism was elevated in the lateral parkinsonian SN. Additionally, catalase and mitogen-activated protein kinase 8 and poly(ADP-ribose) polymerase family member 1 (PARP1) known to function in DNA repair and cell death induction, all members of the dopamine synthesis pathway, were up-regulated in the lateral SN. In contrast, two additional PD-linked genes, glucocerebrosidase and nuclear receptor subfamily 4, group A, member 2 (NR4A2) showed reduced expression. We show that in sporadic PD, parkin, alpha-synuclein and dopamine pathways are co-deregulated. Alpha-synuclein is a member of all three gene regulatory networks. Our analysis results support the view that alpha-synuclein has a central role in the familial as well as the non-familial form of the disease and provide steps towards a pathway definition of PD.

At the Structural Biology Center beamline 19BM, located at the Advanced Photon Source, the operational characteristics of the equipment are routinely checked to ensure they are in proper working order. After performing a partial flat-field calibration for the ADSC Quantum 210r CCD detector, it was confirmed that the detector operates within specifications. However, as a secondary check it was decided to scan a single reflection across one-half of a detector module to validate the accuracy of the calibration. The intensities from this single reflection varied by more than 30% from the module center to the corner of the module. Redistribution of light within bent fibers of the fiber-optic taper was identified to be a source of this variation. The degree to which the diffraction intensities are corrected to account for characteristics of the fiber-optic tapers depends primarily upon the experimental strategy of data collection, approximations made by the data processing software during scaling, and crystal symmetry.

Managing diabetes is known to be invasive, pervasive, and unrelenting, making adherence to the treatment regimen difficult to accomplish. Ongoing clinical and research efforts have attempted to address the struggles faced by youth and adults with diabetes. Recent research supports the integration of behavioral interventions into clinical practice to assist patients and families with the goal of improving health outcomes. Empirically supported and well-documented behavioral learning principles, particularly positive reinforcement, are often underutilized in modern diabetes care. We posit that most diabetes care providers are aware of these principles. However, the constraints of today’s medical systems have become significant barriers to purposefully and consistently applying them to promote improved diabetes care. We provide a brief overview of basic behavioral principles and common barriers to implementation, discuss relevant interventions, and present several examples of applications in clinical settings. We conclude with recommendations to raise awareness regarding the importance of consistently integrating relevant behavioral learning principles and interventions into diabetes care settings.

This chapter provides an overview of mangrove management, assessment, and monitoring. It addresses the need for integrated planning and management, based on sound legal principles. The central part of the chapter covers mangrove conservation and planting. Conserving existing mangrove forest is often more effective than planting new forests. When a decision for planting has been made, one has to differentiate between planting on degraded and non-degraded sites and distinguish between replanting, rehabilitation, restoration, and afforestation. Emphasis is put on the need for careful selection of appropriate sites and species and on an ecosystem-based approach to mangrove planting and management which uses and supports natural regeneration and other natural processes. Since the primary intention with any rehabilitation intervention works is for improved protection of existing seedlings and forests from degradation or destruction, then planting should be undertaken only if absolutely necessary. Involving local communities in mangrove management is an effective way of maintaining and enhancing the protection function of the mangrove forest while providing livelihood for local people and contributing to better assessment and governance of natural resources. Assessment of the status of mangrove forests is essential for better conservation planning and management. This includes research and economic assessment and valuation. The last section highlights the importance of applied/participatory as well as academic and long-term monitoring (see also chapter "Mangroves:​ Unusual Forests at the Seas Edge").

Mrk 501 is one of the brightest blazars at TeV energies and has been extensively studied since its first VHE detection in 1996. Our goal is to characterize in detail the source gamma-ray emission, together with the radio-to-X-ray emission, during the non-flaring (low) activity, which is less often studied than the occasional flaring (high) activity. We organized a multiwavelength (MW) campaign on Mrk 501 between March and May 2008. This multi-instrument effort included the most sensitive VHE gamma-ray instruments in the northern hemisphere, namely the imaging atmospheric Cherenkov telescopes MAGIC and VERITAS, as well as Swift, RXTE, the F-GAMMA, GASP-WEBT, and other collaborations and instruments. Mrk 501 was found to be in a low state of activity during the campaign, with a VHE flux in the range of 10%-20% of the Crab nebula flux. Nevertheless, significant flux variations were detected with various instruments, with a trend of increasing variability with energy. The broadband spectral energy distribution during the two different emission states of the campaign can be adequately described within the homogeneous one-zone synchrotron self-Compton model, with the (slightly) higher state described by an increase in the electron number density. This agrees with previous studies of the broadband emission of this source during flaring and non-flaring states. We report for the first time a tentative X-ray-to-VHE correlation during a low VHE activity. Although marginally significant, this positive correlation between X-ray and VHE, which has been reported many times during flaring activity, suggests that the mechanisms that dominate the X-ray/VHE emission during non-flaring-activity are not substantially different from those that are responsible for the emission during flaring activity., Comment: Accepted for publication in A&A

Mangroves form distinct sea-edge forested habitat of dense, undulating canopies in both wet and arid tropic regions of the world. These highly adapted, forest wetland ecosystems have many remarkable features, making them a constant source of wonder and inquiry. This chapter introduces mangrove forests, the factors that influence them, and some of their key benefits and functions. This knowledge is considered essential for those who propose to manage them sustainably. We describe key and currently recommended strategies in an accompanying article on mangrove forest management (Schmitt and Duke 2015).

In 2014, the Food and Drug Administration (FDA) launched its first tobacco-focused public education campaign, The Real Cost, aimed at reducing tobacco use among 12- to 17-year-olds in the United States. This study describes The Real Cost message strategy, implementation, and initial evaluation findings. The campaign was designed to encourage youth who had never smoked but are susceptible to trying cigarettes (susceptible nonsmokers) and youth who have previously experimented with smoking (experimenters) to reassess what they know about the "costs" of tobacco use to their body and mind. The Real Cost aired on national television, online, radio, and other media channels, resulting in high awareness levels. Overall, 89.0% of U.S. youth were aware of at least one advertisement 6 to 8 months after campaign launch, and high levels of awareness were attained within the campaign's two targeted audiences: susceptible nonsmokers (90.5%) and experimenters (94.6%). Most youth consider The Real Cost advertising to be effective, based on assessments of ad perceived effectiveness (mean = 4.0 on a scale from 1.0 to 5.0). High levels of awareness and positive ad reactions are requisite proximal indicators of health behavioral change. Additional research is being conducted to assess whether potential shifts in population-level cognitions and/or behaviors are attributable to this campaign. Current findings demonstrate that The Real Cost has attained high levels of ad awareness which is a critical first step in achieving positive changes in tobacco-related attitudes and behaviors. These data can also be used to inform ongoing message and media strategies for The Real Cost and other U.S. youth tobacco prevention campaigns.

Fretting fatigue is a structural damage mechanism observed when two contacting bodies are subjected to an oscillatory loading. A critical location for fretting fatigue induced damage has been identified at the blade/disk and blade/damper interfaces of gas turbine engine turbomachinery and space propulsion components. The high-temperature, high-frequency loading environment associated with such turbomachinery components can accelerate the fretting fatigue damage at these contact interfaces. The severe stress peaks and stress gradients that develop at the edge-of-contact can drive crack nucleation and propagation. These contact stresses are sensitive to the geometry of the contacting bodies, the contact loads, materials, temperature, and contact surface tribology (friction). To diagnose the threat that small and relatively undetectable fretting cracks pose to damage tolerance and structural integrity of in-service components, the objective of this work is to develop a well-characterized experimental fretting rig capable of investigating fretting behavior of advanced aerospace alloys subjected to load and temperature conditions representative of such turbomachinery components.

Literature indicates that herb-drug interaction of St. John's wort is largely due to increased metabolism of the co-administered drugs that are the substrates of cytochrome P450 (CYP) 3A4 enzyme, alteration of the activity and/or expression of the enzyme. The major St. John's wort constituents, acylphloroglucinols, were evaluated for their effects on CYP3A4 enzyme activity to investigate their roles in herb-drug interaction. Hyperforin and four oxidized analogues were isolated from the plant and fully characterized by mass spectral and NMR analysis. These acylphloroglucinols inhibited activity of CYP3A4 enzyme potently in the fluorometric assay using the recombinant enzyme. Furoadhyperforin (IC(50) 0.072 microM) was found to be the most potent inhibitor of CYP3A4 enzyme activity, followed by furohyperforin isomer 1 (IC(50) 0.079 microM), furohyperforin isomer 2 (IC(50) 0.23 microM), hyperforin (IC(50) 0.63 microM) and furohyperforin (IC(50) 1.3 microM). As the acylphloroglucinols are potent inhibitors of the CYP3A4 enzyme, their modulation of the enzyme activity is unlikely to be involved in increased drug metabolism by St. John's wort.

We analyzed a time series of aerial photographs and Landsat satellite imagery of the Pioneer River Estuary (near Mackay, Queensland, Australia) to document both natural and anthropogenic changes in the area of mangroves available to filter river runoff between 1948 and 2002. Over 54 years, there was a net loss of 137 ha (22%) of tidal mangroves during four successive periods that were characterized by different driving mechanisms: (1) little net change (1948–1962); (2) net gain from rapid mangrove expansion (1962–1972); (3) net loss from clearing and tidal isolation (1972–1991); and (4) net loss from a severe species-specific dieback affecting over 50% of remaining mangrove cover (1991–2002). Manual digitization of aerial photographs was accurate for mapping changes in the boundaries of mangrove distributions, but this technique underestimated the total loss due to dieback. Regions of mangrove dieback were identified and mapped more accurately and efficiently after applying the Normalized Difference Vegetation Index (NDVI) to Landsat Thematic Mapper satellite imagery, and then monitoring changes to the index over time. These remote sensing techniques to map and monitor mangrove changes are important for identifying habitat degradation, both spatially and temporally, in order to prioritize restoration for management of estuarine and adjacent marine ecosystems.

To establish Canadian guidelines for training in adult perioperative transesophageal echocardiography (TEE). Guidelines were established by the Canadian Perioperative Echocardiography Group with the support of the cardiovascular section of the Canadian Anesthesiologists’ Society (CAS) in conjunction with the Canadian Society of Echocardiography. Guidelines for training in echocardiography by the American Society of Echocardiography, the American College of Cardiology and the Society of Cardiovascular Anesthesiologists were reviewed, modified and expanded to produce the 2003 Quebec expert consensus for training in perioperative echocardiography. The Quebec expert consensus and the 2005 Guidelines for the provision of echocardiography in Canada formed the basis of the Canadian training guidelines in adult perioperative TEE. Basic, advanced and director levels of expertise were identified. The total number of echocardiographic examinations to achieve each level of expertise remains unchanged from the 2002 American Society of Echocardiography-Society of Cardiovascular Anesthesiologists guidelines. The increased proportion of examinations personally performed at basic and advanced levels, and the level of autonomy at the basic level suggested by the Quebec expert consensus are retained. These examinations can be performed in a perioperative setting and are not limited to intraoperative TEE. Training “on the job”, the role of the perioperative transesophageal echocardiography examination, requirements for maintenance of competence, and duration of training are also discussed for each level of training. The components of a TEE report and comprehensive TEE examination are also outlined. The Canadian guidelines for training in adult perioperative TEE reflect the unique Canadian practice profile in perioperative TEE and address the training requirements to obtain expertise in this field.

Purpose To establish Canadian guidelines for training in adult perioperative transesophageal echocardiography (TEE). Methods Guidelines were established by the Canadian Perioperative Echocardiography Group with the support of the cardiovascular section of the Canadian Anesthesiologists' Society in conjunction with the Canadian Society of Echocardiography. Guidelines for training in echocardiography by the American Society of Echocardiography, the American College of Cardiology and the Society of Cardiovascular Anesthesiologists were reviewed, modified and expanded to produce the 2003 Quebec expert consensus for training in perioperative echocardiography. The Quebec expert consensus and the 2005 guidelines for the provision of echocardiography in Canada formed the basis of the Canadian training guidelines in adult perioperative TEE. Results Basic, advanced and director levels of expertise were identified. The total number of echocardiographic examinations to achieve each level of expertise remains unchanged from the 2002 American Society of Echocardiography and the Society of Cardiovascular Anesthesiologists guidelines. The increased proportion of examinations personally performed at basic and advanced levels, as well as the level of autonomy at the basic level suggested by the Quebec expert consensus are retained. These examinations may be performed in a perioperative setting and are not limited to intraoperative TEE. Training ‘on-the-job', the role of the perioperative TEE examination, the requirements for maintenance of competence and the duration of training are also discussed for each level of training. The components of a TEE report and comprehensive TEE examination are also outlined. Conclusion The Canadian guidelines for training in adult perioperative TEE reflect the unique Canadian practice profile in perioperative TEE and address the training requirements to obtain expertise in this field.

The Very Energetic Radiation Imaging Telescope Array System (VERITAS) being constructed in Southern Arizona consists of an array of four Atmospheric Cherenkov 12m Telescopes designed to observe astrophysical gamma rays in the energy range from 100 GeV to tens of TeV. A first telescope has been in operation on a temporary site since the end of 2004 and meets all specifications. The second is being installed on the same site, 85m from the first, in order to test stereoscopic capabilities. The full system of four telescopes is expected to be installed on the definitive site by the end of 2006.

The speculation that climate change may impact on sustainable fish production suggests a need to understand how these effects influence fish catch on a broad scale. With a gross annual value of A$ 2.2 billion, the fishing industry is a significant primary industry in Australia. Many commercially important fish species use estuarine habitats such as mangroves, tidal flats and seagrass beds as nurseries or breeding grounds and have lifecycles correlated to rainfall and temperature patterns. Correlation of catches of mullet (e.g. Mugil cephalus) and barramundi (Lates calcarifer) with rainfall suggests that fisheries may be sensitive to effects of climate change. This work reviews key commercial fish and crustacean species and their link to estuaries and climate parameters. A conceptual model demonstrates ecological and biophysical links of estuarine habitats that influences capture fisheries production. The difficulty involved in explaining the effect of climate change on fisheries arising from the lack of ecological knowledge may be overcome by relating climate parameters with long-term fish catch data. Catch per unit effort (CPUE), rainfall, the Southern Oscillation Index (SOI) and catch time series for specific combinations of climate seasons and regions have been explored and surplus production models applied to Queensland's commercial fish catch data with the program CLIMPROD. Results indicate that up to 30% of Queensland's total fish catch and up to 80% of the barramundi catch variation for specific regions can be explained by rainfall often with a lagged response to rainfall events. Our approach allows an evaluation of the economic consequences of climate parameters on estuarine fisheries, thus highlighting the need to develop forecast models and manage estuaries for future climate change impact by adjusting the quota for climate change sensitive species. Different modelling approaches are discussed with respect to their forecast ability.

A new versatile synthetic route is described for the preparation of capsaicin-like molecules which contain an α-hydroxy ketone functional group mimicking the amide functional group in the capsaicin structure. The key reaction in this synthesis was the formation of α-(dimethylamino)alkanenitriles as intermediates. These nitriles were successfully prepared from both aliphatic and aromatic aldehydes by reaction with dimethylamine and aqueous sodium cyanide. Treatment of the nitriles with lithium diisopropylamide (LDA) followed by reaction with various aldehydes led to the formation of α-hydroxy ketone compounds, examples of which include 2-hydroxy-1-(4-hydroxy-3-methoxyphenyl)dodecan-3-one,(5R)- and (5S)-2-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-5,9-dimethyldec-8-en-3-one, representing novel capsaicin-like molecules. Formation of (4-benzyloxy-3-methoxyphenyl)acetaldehyde was also described from the Wittig reaction of 4-benzyloxy-3-methoxybenzadehyde with an ylide reagent (methoxymethyl)triphenylphosphonium bromide followed by acid hydrolysis to form the title compound. This aldehyde represents a useful precursor for the synthesis of capsaicin-like structures.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

We report on a multiwavelength campaign on the TeV gamma-ray blazar Mrk 421 performed during 2002 December and 2003 January. These target of opportunity observations were initiated by the detection of X-ray and TeV gamma-ray flares with the All Sky Monitor (ASM) on board the Rossi X-Ray Timing Explorer (RXTE) and the 10 m Whipple gamma-ray telescope. The campaign included observational coverage in the radio (University of Michigan Radio Astronomy Observatory), optical (Boltwood, La Palma KVA 0.6 m; WIYN 0.9 m), X-ray (RXTE pointed telescopes), and TeV gamma-ray (Whipple and HEGRA) bands. At TeV energies, the observations revealed several flares at intermediate flux levels, peaking between 1 and 1.5 times the flux from the Crab Nebula. While the time-averaged spectrum can be fitted with a single power law of photon index Gamma = 2.8 from dN gamma/dE proportional to E-Gamma, we find some evidence for spectral variability. Confirming earlier results, the campaign reveals a rather loose correlation between the X-ray and TeV gamma-ray fluxes. In one case, a very strong X-ray flare is not accompanied by a comparable TeV gamma-ray flare. Although the source flux was variable in the optical and radio bands, the sparse sampling of the optical and radio light curves does not allow us to study the correlation properties in detail. We present a simple analysis of the data with a synchrotron self-Compton model, emphasizing that models with very high Doppler factors and low magnetic fields can describe the data.

Nuclear factor (NF)-kappaB is important in the generation of inflammation. Besides regulating lipid metabolism, peroxisome proliferator-activated receptor (PPAR)-alpha activators also reduce NF-kappaB activation to terminate activation of inflammatory pathways. Gynostemma pentaphyllum (GP) has been used to treat various inflammatory diseases and hyperlipidemia. Here, we demonstrate that GP extract and one of its main components, Gypenoside XLIX (Gyp-XLIX) inhibited LPS-induced NF-kappaB activation in murine macrophages. Furthermore, Gyp-XLIX restored the LPS- and TNF-alpha-induced decrease in cytosolic I-kappaBalpha protein expression and inhibited the translocation of NF-kappaB(p65) to the nucleus in THP-1 monocyte and HUVEC cells. The inhibition of LPS- and TNF-alpha-induced NF-kappaB luciferase activity in macrophages was abolished by MK-886, a selective PPAR-alpha antagonist. GP extract and Gyp-XLIX (EC(50): 10.1 microM) enhanced PPAR-alpha luciferase activity in HEK293 cells transfected with the tK-PPREx3-Luc reporter plasmid and expression vectors for PPAR-alpha. Additionally, Gyp-XLIX specifically enhanced PPAR-alpha mRNA and protein expression in THP-1-derived macrophage cells. The selectivity of Gyp-XLIX for PPAR-alpha was demonstrated by the activation of only PPAR-alpha in HEK293 cells transfected with expression vectors for PPAR-alpha, PPAR-beta/delta or PPAR-gamma1 plasmids and in THP-1-derived macrophage naturally expressing all three PPAR isoforms. The present study demonstrates that Gyp-XLIX, a naturally occurring gynosaponin, inhibits NF-kappaB activation via a PPAR-alpha-dependent pathway.

Preparations of Harpagophytum procumbens, known as devil's claw, are used as an adjunctive therapy for the treatment of pain and osteoarthritis. Pharmacological evaluations have proven the effectiveness of this herbal drug as an anti-inflammatory and analgesic agent. The present study has investigated the mechanism of action of harpagoside, one of the major components of Harpagophytum procumbens, using human HepG2 hepatocarcinoma and RAW 264.7 macrophage cell lines. Harpagoside inhibited lipopolysaccharide-induced mRNA levels and protein expression of cyclooxygenase-2 and inducible nitric oxide in HepG2 cells. These inhibitions appeared to correlate with the suppression of NF-kappaB activation by harpagoside, as pre-treating cells with harpagoside blocked the translocation of NF-kappaB into the nuclear compartments and degradation of the inhibitory subunit IkappaB-alpha. Furthermore, harpagoside dose-dependently inhibited LPS-stimulated NF-kappaB promoter activity in a gene reporter assay in RAW 264.7 cells, indicating that harpagoside interfered with the activation of gene transcription. These results suggest that the inhibition of the expression of cyclooxygenase-2 and inducible nitric oxide by harpagoside involves suppression of NF-kappaB activation, thereby inhibiting downstream inflammation and subsequent pain events.

Obsessive-compulsive disorder (OCD) affects approximately 2-4% of the adult population. Despite the practical and emotional demands of having a family member with OCD, few systematic attempts have been made to assess the coping strategies used by relatives of individuals with such diagnoses. In this study we examined the relationships between hope, coping strategies, and depressive symptoms in a heterogeneous sample of 67 spouses/primary caregivers of individuals with a history of OCD. In support of our hypotheses, hope was negatively related to depressive symptoms, symptom severity, and denial disengagement coping strategies, and positively related to active reframing and social support coping strategies. Active, Reframing, Social Support, and Religiosity were negatively related to depressive symptoms. Denial/Disengagement was positively associated with depressive symptoms. Coping mediated the relationship between hope and depressive symptoms. Given the importance of family members in treatment, clinical implications of these findings are discussed.

Here's an important leasing strategy that CEOs, CFOs, and treasurers should know about. By applying constructive lease capitalization on the operating leases of several firms, the authors show that companies can hide many liabilities from financial reporting. And they can also enhance net income, retained earnings, and key financial ratios —all by reporting leases as operating leases instead of capital leases. © 2006 Wiley Periodicals, Inc.

Introduction Most US smokers do not use evidence-based interventions as part of their quit attempts. Quitlines and Web-based treatments may contribute to reductions in population-level tobacco use if successfully promoted. Currently, few states implement sustained media campaigns to promote services and increase adult smoking cessation. This study examines the effects of Florida’s tobacco cessation media campaign and a nationally funded media campaign on telephone quitline and Web-based registrations for cessation services from November 2010 through September 2013. Methods We conducted multivariable analyses of weekly media-market–level target rating points (TRPs) and weekly registrations for cessation services through the Florida Quitline (1-877-U-CAN-NOW) or its Web-based cessation service, Web Coach (www.quitnow.net/florida). Results During 35 months, 141,221 tobacco users registered for cessation services through the Florida Quitline, and 53,513 registered through Web Coach. An increase in 100 weekly TRPs was associated with an increase of 7 weekly Florida Quitline registrants (β = 6.8, P < .001) and 2 Web Coach registrants (β = 1.7, P = .003) in an average media market. An increase in TRPs affected registrants from multiple demographic subgroups similarly. When state and national media campaigns aired simultaneously, approximately one-fifth of Florida’s Quitline registrants came from the nationally advertised portal (1-800-QUIT-NOW). Conclusion Sustained, state-sponsored media can increase the number of registrants to telephone quitlines and Web-based cessation services. Federally funded media campaigns can further increase the reach of state-sponsored cessation services.

The 19ID undulator beamline of the Structure Biology Center has been designed and built to take full advantage of the high flux, brilliance and quality of X-ray beams delivered by the Advanced Photon Source. The beamline optics are capable of delivering monochromatic X-rays with photon energies from 3.5 to 20 keV (3.5-0.6 A wavelength) with fluxes up to 8-18 x 10(12) photons s(-1) (depending on photon energy) onto cryogenically cooled crystal samples. The size of the beam (full width at half-maximum) at the sample position can be varied from 2.2 mm x 1.0 mm (horizontal x vertical, unfocused) to 0.083 mm x 0.020 mm in its fully focused configuration. Specimen-to-detector distances of between 100 mm and 1500 mm can be used. The high flexibility, inherent in the design of the optics, coupled with a kappa-geometry goniometer and beamline control software allows optimal strategies to be adopted in protein crystallographic experiments, thus maximizing the chances of their success. A large-area mosaic 3 x 3 CCD detector allows high-quality diffraction data to be measured rapidly to the crystal diffraction limits. The beamline layout and the X-ray optical and endstation components are described in detail, and the results of representative crystallographic experiments are presented.

Purpose – Geotechnical fills are used for building roadway embankments, filling in behind retaining walls, and as backfill above buried pipelines. Lightweight fill reduces the load so structures can be built more economically. A new lightweight geo‐material made from recycled plastic bottles glued together in their original post‐consumer form was developed. The purpose of this work is to explore the use of this new material as a lightweight geotechnical fill.Design/methodology/approach – Through a preliminary laboratory and field study, aspects of the physical and mechanical characteristics of the recycled plastic bottle blocks were investigated. This new material is currently undergoing field trials behind a retaining wall on a bicycle path.Findings – It was found that the average density of this new material is very low, at 32.63 kg/m3 (2.04 lb/ft3), with 59.5 percent of a block made up of recycled plastic bottles. The plastic bottle waste stream obtained from a recycling plant is gap‐graded having appr...

The Diabetes Family Behavior Checklist (DFBC) assesses supportive and non-supportive parental behavior specific to diabetes management via parent and child reports. The DFBC was administered to 133 children with type 1 diabetes (T1D) and their caregivers. Subsequent analysis verified the two-factor structure of the DFBC corresponding to positive and negative support behaviors. Internal consistency was high for DFBC scores. Moderate to strong correlations with other measures of diabetes-specific familial behaviors, adherence, and metabolic control support the validity of the DFBC. Clinical application of the DFBC is discussed.

Liver X receptors (LXR) play an important role in cholesterol homeostasis by serving as regulatory sensors of cholesterol levels in tissues. The present study reports a novel LXR-alpha activator, (20S)-2alpha, 3beta, 12beta, 24(S)-pentahydroxydammar-25-ene 20-O-beta-d-glucopyranoside (TR1), a dammarane-type gynosaponin, isolated from the herbal medicine, Gynostemma pentaphyllum. Gynosaponin TR1 demonstrated greater selectivity toward activation of the LXR-alpha isoform than LXR-beta in HEK293 cells. TR1 selectively enhanced LXR-mediated transcriptional activation and protein expression of ABCA1 and apoE gene expression and secretion in THP-1-derived macrophages. The selectivity of TR1 for LXR-alpha was consistent with ligand docking studies, which showed favourable interaction of TR1 in the LXR-alpha-binding domain, whereas the presence of the sugar substituent interfered with binding to the LXR-beta site. Findings from the present study may provide insight into the development of pharmaceutical agents for treating atherosclerosis.

The trajectory of a primary γ-ray detected with an array of at least four atmospheric Cherenkov imaging telescopes can be reconstructed from the shower image centroid positions and geometrical considerations independent of the primary energy. Using only the image centroid positions some cosmic-ray discrimination is also possible. This minimal approach opens the possibility of pushing the analysis threshold to lower values, close to the hardware threshold.

In traditional Chinese medicine, Gynostemma pentaphyllum (Thunb.) Makino is a herbal drug of extreme versatility and has been extensively researched in China. The dammarane saponins isolated from Gynostemma pentaphyllum, namely gypenosides or gynosaponins, are believed to be the active components responsible for its various biological activities and reported clinical effects. This review attempts to encompass the available literature on Gynostemma pentaphyllum, from its cultivation to the isolation of its chemical entities and a summary of its diverse pharmacological properties attributed to its gypenoside content. Other aspects such as toxicology and pharmacokinetics are also discussed. In vitro and in vivo evidence suggests that Gynostemma pentaphyllum may complement the popular herbal medicine, Panax ginseng, as it also contains a high ginsenoside content and exhibits similar biological activities.

The Whipple Observatory 10 m γ-ray telescope has been used to survey the error boxes of EGRET unidentified sources in an attempt to find counterparts at energies of 350 GeV and above. Twenty-one unidentified sources detected by EGRET (more than 10% of the total number) have been included in this survey. In no case is a statistically significant signal found in the EGRET error box, which implies that, at least for this sample, the γ-ray spectra of these sources steepen between 100 MeV and 350 GeV. For each EGRET source location, we list candidate associations and derive upper limits on the integral γ-ray flux above 350 GeV.

The blazar 1ES 1959+650 was observed in a flaring state with the Whipple 10 m Imaging Atmospheric Cherenkov Telescope during May of 2002. A spectral analysis has been carried out on the data from that time period and the resulting very high energy gamma-ray spectrum ($E \geq 316$ GeV) can be well fit by a power-law of differential spectral index \alpha = 2.78 +/- 0.12_{stat.} +/- 0.21_{sys.}. On June 4th 2002, the source flared dramatically in the gamma-ray range without any coincident increase in the X-ray emission, providing the first unambiguous example of an `orphan' gamma-ray flare from a blazar. The gamma-ray spectrum for these data can also be described by a simple power-law fit with \alpha = 2.82 +/- 0.15_{stat.} +/- 0.30_{sys.}. There is no compelling evidence for spectral variability, or for any cut-off to the spectrum., Comment: 25 pages. Collaboration website at http://veritas.sao.arizona.edu/

Low concentrations of herbicides (up to 70 ng l(-1)), chiefly diuron (up to 50 ng l(-1)) were detected in surface waters associated with inter-tidal seagrass meadows of Zostera muelleri in Hervey Bay, south-east Queensland, Australia. Diuron and atrazine (up to 1.1 ng g(-1) dry weight of sediment) were detected in the sediments of these seagrass meadows. Concentration of the herbicides diuron, simazine and atrazine increased in surface waters associated with seagrass meadows during moderate river flow events indicating herbicides were washed from the catchment to the marine environment. Maximum herbicide concentration (sum of eight herbicides) in the Mary River during a moderate river flow event was 4260 ng l(-1). No photosynthetic stress was detected in seagrass in this study during low river flow. However, with moderate river flow events, nearshore seagrasses are at risk of being exposed to concentrations of herbicides that are known to inhibit photosynthesis.

Herbicides, particularly diuron, were correlated with severe and widespread dieback of the dominant mangrove, Avicennia marina (Forsk.) Vierh. var. eucalyptifolia (Val.) N.C. Duke (Avicenniaceae), its reduced canopy condition, and declines in seedling health within three neighbouring estuaries in the Mackay region of NE Australia. This unusual species-specific dieback, first observed in the early 1990s, had gotten notably worse by 2002 to affect30 km(2) of mangroves in at least five adjacent estuaries in the region. Over the past century, agricultural production has responded well to the demands of increasing population with improvements in farm efficiency assisted by significant increases in the use of agricultural chemicals. However, with regular and episodic river flow events, these chemicals have sometimes found their way into estuarine and nearshore water and sediments where their effects on marine habitats have been largely unquantified. Investigations over the last three years in the Mackay region provide compelling evidence of diuron, and possibly other agricultural herbicides, as the most likely cause of the severe and widespread mangrove dieback. The likely consequences of such dieback included declines in coastal water quality with increased turbidity, nutrients and sediment deposition, as well as further dispersal of the toxic chemicals. The implications of such findings are immense since they describe not only the serious deterioration of protected and beneficial mangrove habitat but also the potential for significant direct and indirect effects on other highly-valued estuarine and marine habitats in the region, including seagrass beds and coral reefs of the Great Barrier Reef lagoon. This article reviews all key findings and observations to date and describes the essential correlative and causative evidence.

Background Previous evidence from laboratory animal studies indicates that R-thiopental has a greater margin of safety than either the more potent S-thiopental or the clinically used rac-thiopental. Although thiopental can cause cardiovascular depression from direct myocardial effects as well as indirect central nervous system and peripheral effects, no studies have yet determined whether its myocardial effects are enantioselective. A lesser direct effect would provide further evidence supporting R-thiopental as a preferred single enantiomer replacement for rac-thiopental. Methods The direct myocardial effects of the thiopental enantiomers were compared to those of rac-thiopental and propofol, using a crossover design with small incremental doses infused over 3 min, on separate days, into the left coronary arteries of conscious sheep. Hemodynamic and electrocardiographic measurements were acquired, and serial blood samples were collected during the studies for drug analyses. Results All three forms of thiopental and propofol produced significant hemodynamic effects consisting of dose-related and rapid-onset decreases in left ventricular dP/dtmax and stroke volume, and increases in left coronary blood flow and heart rate. Cardiac output, mean arterial blood pressure, and central venous pressure remained unaltered. The effects did not differ significantly among rac-thiopental, enantiopure R- or S-thiopental, or propofol. Arterial blood drug concentrations were consistently less than those associated with systemic effects. Conclusions Although previous evidence indicates that R-thiopental could make a suitable single-enantiomer replacement for rac-thiopental, the current study did not find a significant difference in direct cardiac effects among the thiopental enantiomers, racemate, or propofol.

This study provides an expression signature of interferon-gamma (IFN-gamma)-activated microglia. Microglia are macrophage precursor cells residing in the brain and spinal cord. The microglial phenotype is highly plastic and changes in response to numerous pathological stimuli. IFN-gamma has been established as a strong immunological activator of microglial cells both in vitro and in vivo. Affymetrix RG_U34A microarrays were used to determine the effect of IFN-gamma stimulation on migroglia cells isolated from newborn Lewis rat brains. More than 8,000 gene sequences were examined, i.e., 7,000 known genes and 1,000 expressed sequence tag (EST) clusters. Under baseline conditions, microglia expressed 326 of 8,000 genes examined (approximately 4% of all genes, 182 known and 144 ESTs). Transcription of only 34 of 7,000 known genes and 8 of 1,000 ESTs was induced by IFN-gamma stimulation. The majority of the newly expressed genes encode pro-inflammatory cytokines and components of the MHC-mediated antigen presentation pathway. The expression of 60 of 182 identified genes and of 9 of 144 ESTs was increased by IFN-gamma, whereas 29 of 182 known genes and 7 of 144 ESTs were down-regulated or undetectable in IFN-gamma-stimulated cultures. Overall, the activating effect of IFN-gamma on the microglial transcriptome showed restriction to pathways involved in antigen presentation, protein degradation, actin binding, cell adhesion, apoptosis, and cell signaling. In comparison, down-regulatory effects of IFN-gamma stimulation appeared to be confined to pathways of growth regulation, remodeling of the extracellular matrix, lipid metabolism, and lysosomal processing. In addition, transcriptomic profiling revealed previously unknown microglial genes that were de novo expressed, such as calponin 3, or indicated differential regulatory responses, such as down-regulation of cathepsins that are up-regulated in response to other microglia stimulators.

The structure of a novel c(7)-type cytochrome domain that has two bishistidine coordinated hemes and one heme with histidine, methionine coordination (where the sixth ligand is a methionine residue) was determined at 1.7 A resolution. This domain is a representative of domains that form three polymers encoded by the Geobacter sulfurreducens genome. Two of these polymers consist of four and one protein of nine c(7)-type domains with a total of 12 and 27 hemes, respectively. Four individual domains (termed A, B, C, and D) from one such multiheme cytochrome c (ORF03300) were cloned and expressed in Escherichia coli. The domain C produced diffraction quality crystals from 2.4 M sodium malonate (pH 7). The structure was solved by MAD method and refined to an R-factor of 19.5% and R-free of 21.8%. Unlike the two c(7) molecules with known structures, one from G. sulfurreducens (PpcA) and one from Desulfuromonas acetoxidans where all three hemes are bishistidine coordinated, this domain contains a heme which is coordinated by a methionine and a histidine residue. As a result, the corresponding heme could have a higher potential than the other two hemes. The apparent midpoint reduction potential, E(app), of domain C is -105 mV, 50 mV higher than that of PpcA.

The increasing use of herbal medicinal products (HMPs) in the community where people are also receiving prescription medicines suggests that adverse herb-drug interactions may be of significant public health consequence. The evidence available to guide practitioners in decision making is complex and consists of a range of sources including adverse event database entries, spontaneous or case reports, in vivo and in vitro drug metabolism studies, and in vivo drug interaction studies in healthy subjects and patients. In the absence of further rigorous studies to assess the clinical significance of herb-drug interactions, an evidence-based appraisal of the current literature is essential to guide practitioners involved in patient care.

The Very Energetic Radiation Imaging Telescope Array System (VERITAS) is the major next generation imaging atmospheric Cherenkov γ-ray telescope in the western hemisphere and will be located in southern Arizona nearby Kitt Peak National Observatory. The VERITAS observatory will provide unprecedented sensitivity to photon energies between 50 GeV and 50 TeV. The first stage is an array of four telescopes to be fully operational in early 2006, with an expansion to seven telescopes envisioned for 2008. The construction of a prototype telescope is underway, for which first light is expected in Fall 2003. The technical concept is outlined and a progress report is given.

The structure of a cytochrome c(7) (PpcA) from Geobacter sulfurreducens was determined by X-ray diffraction at 1.45 A resolution; the R factor is 18.2%. The protein contains a three-heme core that is surrounded by 71 amino acid residues. An unusual feature of this cytochrome is that it has 17 lysine residues, but only nine hydrophobic residues that are larger than alanine. The details of the structure are described and compared with those of cytochrome c(7) from Desulfuromonas acetoxidans and with cytochromes c(3). The two cytochrome c(7) molecules have sequences that are 46% identical, but the arrangements of the hemes in the two structures differ; the rms deviation of all alpha-carbons is 2.5 A. These cytochromes can reduce various metal ions. The reduction site of the chromate ion in D. acetoxidans is occupied by a sulfate ion in the crystal structure of PpcA. We identified four additional homologues of cytochrome c(7) in the G. sulfurreducens genome and three polymers of c(7)-type domains. Of the polymers, two have four repeats and one has nine repeats. On the basis of sequence alignments, one of the hemes in each of the cytochrome c(7)-type domains does not have the bis-histidine coordination. The packing of themore » molecules in the crystal structure of PpcA suggests that the polymers have an elongated conformation and might form a 'nanowire'.« less