Ligation of protease-activated receptor 1 enhances alpha(v)beta(6) integrin-dependent TGF-beta activation and promotes acute lung injury

Activation of latent TGF-beta by the alpha(v)beta(6) integrin is a critical step in the development of acute lung injury. However, the mechanism by which a alpha(v)beta(6)-mediated TGF-beta activation is regulated has not been identified. We show that thrombin, and other agonists of protease-activated receptor 1(PAR1), activate TGF-beta in an alpha(v)beta(6) integrin-specific manner. This effect is PART specific and is mediated by RhoA and Rho kinase. Intratracheal instillation of the PART-specific peptide TFLLRN increases lung edema during high-tidal-volume ventilation, and this effect is completely inhibited by a blocking antibody against the alpha(v)beta(6) integrin. Instillation of TFLLRN during high-tidal-volume ventilation is associated with increased pulmonary TGF-beta activation; however, this is not observed in Itgb6(-/-) mice. Furthermore, Itgb6(-/-) mice are also protected from ventilator-induced lung edema. We also demonstrate that pulmonary edema and TGF-beta activity are similarly reduced in Par1(-/-) mice following bleomycin-induced lung injury. These results suggest that PART-mediated enhancement of a alpha(v)beta(6)-dependent TGF-beta activation could be one mechanism by which activation of the coagulation cascade contributes to the development of acute lung injury, and they identify PART and the alpha(v)beta(6) integrin as potential therapeutic targets in this condition

Flavor-symmetry Breaking with Charged Probes

We discuss the recombination of brane/anti-brane pairs carrying $D3$ brane charge in $AdS_5 \times S^5$. These configurations are dual to co-dimension one defects in the ${\cal N}=4$ super-Yang-Mills description. Due to their $D3$ charge, these defects are actually domain walls in the dual gauge theory, interpolating between vacua of different gauge symmetry. A pair of unjoined defects each carry localized $(2+1)$ dimensional fermions and possess a global $U(N)\times U(N)$ flavor symmetry while the recombined brane/anti-brane pairs exhibit only a diagonal U(N). We study the thermodynamics of this flavor-symmetry breaking under the influence of external magnetic field.Comment: 21 pages, 10 figure

Validating two-dimensional leadership models on three-dimensionally structured fish schools

Identifying leader–follower interactions is crucial for understanding how a group decides where or when to move, and how this information is transferred between members. Although many animal groups have a three-dimensional structure, previous studies investigating leader–follower interactions have often ignored vertical information. This raises the question of whether commonly used two-dimensional leader–follower analyses can be used justifiably on groups that interact in three dimensions. To address this, we quantified the individual movements of banded tetra fish (Astyanax mexicanus) within shoals by computing the three-dimensional trajectories of all individuals using a stereo-camera technique. We used these data firstly to identify and compare leader–follower interactions in two and three dimensions, and secondly to analyse leadership with respect to an individual's spatial position in three dimensions. We show that for 95% of all pairwise interactions leadership identified through two-dimensional analysis matches that identified through three-dimensional analysis, and we reveal that fish attend to the same shoalmates for vertical information as they do for horizontal information. Our results therefore highlight that three-dimensional analyses are not always required to identify leader–follower relationships in species that move freely in three dimensions. We discuss our results in terms of the importance of taking species' sensory capacities into account when studying interaction networks within groups

Enabling three-dimensional densitometric measurements using laboratory source X-ray micro-computed tomography

We present new software allowing significantly improved quantitative mapping of the three-dimensional density distribution of objects using laboratory source polychromatic X-rays via a beam characterisation approach (c.f. filtering or comparison to phantoms). One key advantage is that a precise representation of the specimen material is not required. The method exploits well-established, widely available, non-destructive and increasingly accessible laboratory-source X-ray tomography. Beam characterisation is performed in two stages: (1) projection data are collected through a range of known materials utilising a novel hardware design integrated into the rotation stage; and (2) a Python code optimises a spectral response model of the system. We provide hardware designs for use with a rotation stage able to be tilted, yet the concept is easily adaptable to virtually any laboratory system and sample, and implicitly corrects the image artefact known as beam hardening

Magnetic effects in a holographic Fermi-like liquid

We explore the magnetic properties of the Fermi-like liquid represented by the D3-D7' system. The system exhibits interesting magnetic properties such as ferromagnetism and an anomalous Hall effect, which are due to the Chern-Simons term in the effective gravitational action. We investigate the spectrum of quasi-normal modes in the presence of a magnetic field and show that the magnetic field mitigates the instability towards a striped phase. In addition, we find a critical magnetic field above which the zero sound mode becomes massive.Comment: 18 pages, 15 figure

Characteristics of temporal patterns of cortisol and luteinizing hormone in primiparous, postpartum, anovular, suckled, beef cows exposed acutely to bulls

BACKGROUND: The physiological mechanism by which bulls stimulate resumption of ovarian cycling activity in postpartum, anovular, suckled cows after calving may involve the concurrent activation of the hypothalamic-hypophyseal-ovarian (HPO) axis and hypothalamic-hypophyseal-adrenal (HPA) axis. Thus, the objectives of this experiment were to determine if characteristics of temporal patterns of cortisol and luteinizing hormone (LH) in postpartum, anovular, beef cows are influenced by acute exposure to bulls. The null hypotheses were that daily, temporal characteristics of cortisol and LH concentration patterns do not differ between cows exposed acutely to bulls or steers. METHODS: Sixteen cows were assigned randomly 67 +/- 4 (+/- SE) after calving to be exposed to bulls (EB, n = 8) or steers (ES, n = 8) 5 h daily for 9 d (D 0 to 8). Blood samples were collected daily from each cow via jugular catheters at 15-min intervals for 6 h from 1000 to 1600 h each day. The 5-h exposure period began 1 h after the start of the intensive bleeding period. Characteristics of cortisol and LH concentration patterns (mean, baseline, pulse frequency, pulse amplitude, and pulse duration) were identified by PULSAR analyses. RESULTS: Mean cortisol concentrations decreased (P < 0.05) in cows in both treatments from D 0 to D 2. Thereafter, mean cortisol concentrations stabilized and did not differ (P > 0.10) between EB and ES cows. The decrease in mean cortisol concentrations in EB and ES cows from D 0 to D 2 was attributed to cows acclimatizing to intensive blood sampling and handling procedures. Consequently, analyses for characteristics of cortisol and LH concentration patterns included D 2 through 8 only. Cortisol mean and baseline concentrations, and pulse amplitude did not differ (P > 0.10) between EB and ES cows. However, cortisol pulse duration tended to be longer (P = 0.09) and pulse frequency was lower (P = 0.05) in EB than ES cows. LH pulse frequency was greater (P = 0.06) in EB than ES cows. All other characteristics of LH concentration patterns did not differ (P > 0.10) between EB and ES cows. Characteristics of cortisol concentration patterns were not related to characteristics of LH concentration patterns for ES cows (P > 0.10). However, as cortisol pulse amplitude increased, LH pulse amplitude decreased (b1 = -0.04; P < 0.05) for EB cows. CONCLUSIONS: In conclusion, exposing primiparous, postpartum, anovular, suckled cows to bulls for 5-h daily over a 9-d period did not alter mean concentrations of cortisol or LH compared to mean concentrations of cortisol and LH in cows exposed to steers. However, exposing cows to bull in this manner altered characteristics of temporal patterns of both LH and cortisol by increasing LH pulse frequency and decreasing cortisol pulse frequency. Interestingly, in cows exposed to bulls, as amplitude and frequency of cortisol pulses decreased, amplitudes of LH pulses increased and frequency of LH pulses tended to increase. Thus, the physiological mechanism of the biostimulatory effect of bulls may initially involve modification of the HPA axis and these changes may facilitate activation of the HPO axis and resumption of ovulatory cycles in postpartum, anovular, suckled cows

Chiral primary one-point functions in the D3-D7 defect conformal field theory

JHEP is an open-access journal funded by SCOAP3 and licensed under CC BY 4.0archiveprefix: arXiv primaryclass: hep-th reportnumber: NORDITA-2012-81 slaccitation: %%CITATION = ARXIV:1210.7015;%%archiveprefix: arXiv primaryclass: hep-th reportnumber: NORDITA-2012-81 slaccitation: %%CITATION = ARXIV:1210.7015;%%C.F.K. and D.Y. were supported in part by FNU through grant number 272-08-0329. G.W.S. is supported by NSERC of Canada and by the Villum foundation through their Velux Visiting Professor program

Transitions of care from child and adolescent mental health services to adult mental health services (TRACK Study) : a study of protocols in Greater London

Background: Although young people's transition from Child and Adolescent Mental Health Services (CAMHS) to Adult Mental Health Services (AMHS) in England is a significant health issue for service users, commissioners and providers, there is little evidence available to guide service development. The TRACK study aims to identify factors which facilitate or impede effective transition from CAHMS to AMHS. This paper presents findings from a survey of transition protocols in Greater London. Methods: A questionnaire survey (Jan-April 2005) of Greater London CAMHS to identify transition protocols and collect data on team size, structure, transition protocols, population served and referral rates to AMHS. Identified transition protocols were subjected to content analysis. Results: Forty two of the 65 teams contacted (65%) responded to the survey. Teams varied in type (generic/targeted/in-patient), catchment area (locality-based, wider or national) and transition boundaries with AMHS. Estimated annual average number of cases considered suitable for transfer to AMHS, per CAMHS team (mean 12.3, range 0–70, SD 14.5, n = 37) was greater than the annual average number of cases actually accepted by AMHS (mean 8.3, range 0–50, SD 9.5, n = 33). In April 2005, there were 13 active and 2 draft protocols in Greater London. Protocols were largely similar in stated aims and policies, but differed in key procedural details, such as joint working between CAHMS and AMHS and whether protocols were shared at Trust or locality level. While the centrality of service users' involvement in the transition process was identified, no protocol specified how users should be prepared for transition. A major omission from protocols was procedures to ensure continuity of care for patients not accepted by AMHS. Conclusion: At least 13 transition protocols were in operation in Greater London in April 2005. Not all protocols meet all requirements set by government policy. Variation in protocol-sharing organisational units and transition process suggest that practice may vary. There is discontinuity of care provision for some patients who 'graduate' from CAMHS services but are not accepted by adult services