235 research outputs found

    Cruise Report for cruise Kilo Moana KM1811 in the U.S. Gulf of Alaska continental margin

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    Cruise report of RV Kilo Moana cruise 1811 on the U.S. margin in the Gulf of Alaska, north Pacific Ocean. The National Oceanic and Atmospheric Administration (NOAA), on behalf of the United States Government, has a requirement to carry out mapping surveys of specific regions on the margins in the Gulf of Alaska, north Pacific Ocean in order to determine the detailed bathymetry of the margins. The data are required to support any potential claim for extended jurisdiction by the United States under United Nations Convention on the Law of the Sea (UNCLOS) Article 76. The requirement is for the collection and processing of full-coverage multibeam sonar data in water depths of approximately 1000 to 5500 m in order to precisely define the location of potential natural prolongations to the continent as defined under UNCLOS Article 76. As part of the NOAA-funded research program, University of Hawaii researchers oversaw data acquisition, and University of New Hampshire (UNH) researchers performed the cruise planning and oversaw processing and archiving of the data collected during the cruise. A full patch test was conducted in deep water in the immediate area prior to commencement of mapping. New sound-speed profiles were collected by 139 XBT casts whenever the sound speed at the transducer differed by more than 0.5 m/s. All soundings are within 0.5% (2 sigma) of water depth, based on cross-line checks. Positions were determined by corrected differential GPS-aided inertial navigation. Sound-speed profiles were calculated from an XBT cast calibrated to an XSV cast during a patch test performed on the cruise prior to data collection. Horizontal_Positional_Accuracy_Report: Horizontal positioning of the vessel was determined using Applanix POS/MV inertial motion unit (IMU) version 5 which was provided with wide-area satellite-based differential positioning using the built-in Fugro Marinestar service as well as GNSS G2 service. Positioning is accurate to better than 0.5 meters (at 95% confidence) during all surveying. All positioning is referenced to the WGS84 Datum. Vertical_Positional_Accuracy_Report: Depth errors are within +/-0.5% of water depth. Process_Description: Raw data are as recorded by Kongsberg Maritime SIS data acquisition system. Depth units: meters Reference ellipsoid: WGS-84 Projection: unprojected geographic longitude, latitude Vertical reference: instantaneous sea level

    Patterning in Placental 11-B Hydroxysteroid Dehydrogenase Methylation According to Prenatal Socioeconomic Adversity

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    Background: Prenatal socioeconomic adversity as an intrauterine exposure is associated with a range of perinatal outcomes although the explanatory mechanisms are not well understood. The development of the fetus can be shaped by the intrauterine environment through alterations in the function of the placenta. In the placenta, the HSD11B2 gene encodes the 11-beta hydroxysteroid dehydrogenase enzyme, which is responsible for the inactivation of maternal cortisol thereby protecting the developing fetus from this exposure. This gene is regulated by DNA methylation, and this methylation and the expression it controls has been shown to be susceptible to a variety of stressors from the maternal environment. The association of prenatal socioeconomic adversity and placental HSD11B2 methylation has not been examined. Following a developmental origins of disease framework, prenatal socioeconomic adversity may alter fetal response to the postnatal environment through functional epigenetic alterations in the placenta. Therefore, we hypothesized that prenatal socioeconomic adversity would be associated with less HSD11B2 methylation. Methods and Findings: We examined the association between DNA methylation of the HSD11B2 promoter region in the placenta of 444 healthy term newborn infants and several markers of prenatal socioeconomic adversity: maternal education, poverty, dwelling crowding, tobacco use and cumulative risk. We also examined whether such associations were sex-specific. We found that infants whose mothers experienced the greatest levels of socioeconomic adversity during pregnancy had the lowest extent of placental HSD11B2 methylation, particularly for males. Associations were maintained for maternal education when adjusting for confounders (p\u3c0.05). Conclusions: Patterns of HSD11B2 methylation suggest that environmental cues transmitted from the mother during gestation may program the developing fetus’s response to an adverse postnatal environment, potentially via less exposure to cortisol during development. Less methylation of placental HSD11B2 may therefore be adaptive and promote the effective management of stress associated with social adversity in a postnatal environment

    Toric G_2 and Spin(7) holonomy spaces from gravitational instantons and other examples

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    Non-compact G_2 holonomy metrics that arise from a T^2 bundle over a hyper-Kahler space are discussed. These are one parameter deformations of the metrics studied by Gibbons, Lu, Pope and Stelle in hep-th/0108191. Seven-dimensional spaces with G_2 holonomy fibered over the Taub-Nut and the Eguchi-Hanson gravitational instantons are found, together with other examples. By considering the Apostolov-Salamon theorem math.DG/0303197, we construct a new example that, still being a T^2 bundle over hyper-Kahler, represents a non trivial two parameter deformation of the metrics studied in hep-th/0108191. We then review the Spin(7) metrics arising from a T^3 bundle over a hyper-Kahler and we find two parameter deformation of such spaces as well. We show that if the hyper-Kahler base satisfies certain properties, a non trivial three parameter deformations is also possible. The relation between these spaces with the half-flat structures and almost G_2 holonomy spaces is briefly discussed.Comment: 27 pages. Typos corrected. Accepted for publication in Commun.Math.Phy

    The leadership component of Kelly’s Mobilisation Theory : contribution, tensions, limitations and further development

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    This reassessment of Kelly’s analysis of the relationship of activist leadership to collective action within the overall jigsaw of mobilisation theory draws on social movement literature, studies by industrial relations scholars utilising aspects of Kelly’s approach – including this author’s own work – and related research on union leadership within collective mobilisation. In the process, it identifies and celebrates how Kelly’s work, whilst contributing a distinct and substantive actor-related approach, recognised that leadership is one ingredient amongst other factors, including important structural opportunities and constraints. It considers three potential ambiguities/tensions within Kelly’s conceptualisation of leadership related to the social construction of workers’ interests, spontaneity of workers’ action and the ‘leader/follower’ interplay. The review also identifies two important limitations, related to the union member/bureaucracy dynamic and the role of left-wing political leadership, and concludes by signalling different forms of leadership relationships on which further refinement and development would be fruitful

    Interactions of Shiga-like toxin with human peripheral blood monocytes

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    The cytotoxic effect of Shiga-like toxin (Stx; produced by certain Escherichia coli strains) plays a central role in typical hemolytic uremic syndrome (HUS). It damages the renal endothelium by inhibiting the cellular protein synthesis. Also, the monocyte has a specific receptor for Stx but is not sensitive for the cytotoxic effect. In this work, monocytes were studied as a potential transporter for Stx to the renal endothelium. Coincubation of isolated human monocytes loaded with Stx and target cells (vero cells and human umbilical vascular endothelial cells) were performed. Transfer was determined by measuring the protein synthesis of target cells and by flow cytometry. Furthermore, the effect of a temperature shift on loaded monocytes was investigated. Stx-loaded monocytes reduced the protein synthesis of target cells. After adding an antibody against Stx, incomplete recovery occurred. Also, adding only the supernatant of coincubation was followed by protein synthesis inhibition. Stx detached from its receptor on the monocyte after a change in temperature, and no release was detected without this temperature shift. Although the monocyte plays an important role in the pathogenesis of HUS, it has no role in the transfer of Stx

    Revisiting Folk Moral Realism

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    Moral realists believe that there are objective moral truths. According to one of the most prominent arguments in favour of this view, ordinary people experience morality as realist-seeming, and we have therefore prima facie reason to believe that realism is true. Some proponents of this argument have claimed that the hypothesis that ordinary people experience morality as realist-seeming is supported by psychological research on folk metaethics. While most recent research has been thought to contradict this claim, four prominent earlier studies (by Goodwin and Darley, Wainryb et al., Nichols, and Nichols and Folds-Bennett) indeed seem to suggest a tendency towards realism. My aim in this paper is to provide a detailed internal critique of these four studies. I argue that, once interpreted properly, all of them turn out in line with recent research. They suggest that most ordinary people experience morality as “pluralist-” rather than realist-seeming, i.e., that ordinary people have the intuition that realism is true with regard to some moral issues, but variants of anti-realism are true with regard to others. This result means that moral realism may be less well justified than commonly assumed

    Structure–activity study of N-((trans)-4-(2-(7-cyano-3,4-dihydroisoquinolin-2(1H)-yl)ethyl)cyclohexyl)-1H-indole-2-carboxamide (SB269652), a bitopic ligand that acts as a negative allosteric modulator of the dopamine D2 receptor

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    We recently demonstrated that SB269652 (1) engages one protomer of a dopamine D2 receptor (D2R) dimer in a bitopic mode to allosterically inhibit the binding of dopamine at the other protomer. Herein, we investigate structural deter- minants for allostery, focusing on modifications to three moieties within 1. We find that orthosteric “head” groups with small 7-substituents were important to maintain the limited negative cooperativity of analogues of 1, and replacement of the tetrahydroisoquinoline head group with other D2R “privileged structures” generated orthosteric antagonists. Additionally, replacement of the cyclohexylene linker with polymethylene chains conferred linker length dependency in allosteric pharma- cology. We validated the importance of the indolic NH as a hydrogen bond donor moiety for maintaining allostery. Replacement of the indole ring with azaindole conferred a 30-fold increase in affinity while maintaining negative cooperativity. Combined, these results provide novel SAR insight for bitopic ligands that act as negative allosteric modulators of the D2R

    Development and validation of an ultra?performance liquid chromatography quadrupole time of flight mass spectrometry method for rapid quantification of free amino acids in human urine

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    An ultra-performance liquid chromatography quadrupole time of flight mass spectrometry (UPLC-qTOFMS)method using hydrophilic interaction liquid chromatography was developed and validated for simultaneous quantification of 18 free amino acids in urine with a total acquisition time including the column re-equilibration of less than 18 min per sample. This method involves simple sample preparation steps which consisted of 15 times dilution with acetonitrile to give a final composition of 25 % aqueous and 75 % acetonitrile without the need of any derivatization. The dynamic range for our calibration curve is approximately two orders of magnitude (120-fold from the lowest calibration curve point) with good linearity (r2 ? 0.995 for all amino acids). Good separation of all amino acids as well as good intra- and inter-day accuracy (<15 %) and precision (<15 %) were observed using three quality control samples at a concentration of low, medium and high range of the calibration curve. The limits of detection (LOD) and lower limit of quantification of our method were ranging from approximately 1–300 nM and 0.01–0.5 ”M, respectively. The stability of amino acids in the prepared urine samples was found to be stable for 72 h at 4 °C, after one freeze thaw cycle and for up to 4 weeks at ?80 °C. We have applied this method to quantify the content of 18 free amino acids in 646 urine samples from a dietary intervention study. We were able to quantify all 18 free amino acids in these urine samples, if they were present at a level above the LOD. We found our method to be reproducible (accuracy and precision were typically <10 % for QCL, QCM and QCH) and the relatively high sample throughput nature of this method potentially makes it a suitable alternative for the analysis of urine samples in clinical setting
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