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Background and objectivesSrc family kinases (SFKs) play a critical role in initiating and propagating signals in platelets. The aims of this study were to quantitate SFK members present in platelets and to analyze their contribution to platelet regulation using glycoprotein VI (GPVI) and intregrin αIIbβ3, and in vivo.Methods and resultsMouse platelets express four SFKs, Fgr, Fyn, Lyn and Src, with Lyn expressed at a considerably higher level than the others. Using mutant mouse models, we demonstrate that platelet activation by collagen-related peptide (CRP) is delayed and then potentiated in the absence of Lyn, but only marginally reduced in the absence of Fyn or Fgr, and unaltered in the absence of Src. Compound deletions of Lyn/Src or Fyn/Lyn, but not of Fyn/Src or Fgr/Lyn, exhibit a greater delay in activation relative to Lyn-deficient platelets. Fibrinogen-adherent platelets show reduced spreading in the absence of Src, potentiation in the absence of Lyn, but no change in the absence of Fyn or Fgr. In mice double-deficient in Lyn/Src or Fgr/Lyn, the inhibitory role of Lyn on spreading on fibrinogen is lost. Lyn is the major SFK-mediating platelet aggregation on collagen at arterial shear and its absence leads to a reduction in thrombus size in a laser injury model.ConclusionThese results demonstrate that SFKs share individual and overlapping roles in regulating platelet activation, with Lyn having a dual role in regulating GPVI signaling and an inhibitory role downstream of αIIbβ3, which requires prior signaling through Src.

David D. Hall's book comprises a transatlantic history of the Puritan movement from its sixteenth-century emergence to its heyday under Oliver Cromwell and its subsequent political demise after 1660. Hall provides insights into the movement's trajectory, including the various forms of Puritan belief and practice in England and Scotland and their transatlantic migration. In Hall's sweeping view, Puritanism was a driving force for cultural change in the early modern Atlantic world and left an indelible mark on religion in America. The four reviewers praise Hall's book for its monumental achievement, with Abram Van Engen emphasizing the centrality of Puritan theology. They place it within its historiographical context, as Evan Haefeli does by comparing it with Michael Winship's Hot Protestants: A History of Puritanism in England and America (2018) and as Fred van Lieburg does by reminding us of the centuries-old German tradition of Pietismusforschung. The reviewers also raise critical questions as to the audience of Puritan publications and point to the benefits of studying Puritanism in an even wider comparative framework, one that looks forwards and backwards in time and one that speaks to the large, overarching questions raised by global history and digital humanities, including Andrew Pettegree's USTC project. In his response David Hall begins by acknowledging the decades of Anglo-American scholarship on the Puritan movement on which his book builds, replies to points raised by the reviewers, and reflects on the situation of Puritan studies in the United States at this moment in time. [ABSTRACT FROM AUTHOR]

Seismometers are highly sensitive instruments to not only ground motion but also many other nonseismic noise sources (e.g., temperature, pressure, and magnetic field variations). We show that the Alaska component of the Transportable Array is particularly susceptible to recording magnetic storms and other space weather events because the sensors used in this network are unshielded and magnetic flux variations are stronger at higher latitudes. We also show that vertical-component seismic records across Alaska are directly recording magnetic field variations between 40 and 800 s period as opposed to actual ground motion during geomagnetic events with sensitivities ranging from 0.004 to 0.48(m/s²)/T. These sensitivities were found on a day where the root mean square variation in the magnetic field was 225 nT. Using a method developed by Forbriger (2007, his section 3.1), we show that improving vertical seismic resolution of an unshielded sensor by as much as 10 dB in the 100-400 s period band using magnetic data from a collocated three-component magnetometer is possible. However, due to large spatial variations in Earth's magnetic field, this methodology becomes increasingly ineffective as the distance between the seismometer and magnetometer increases (no more than 200 km separation). A potential solution to this issue may be to incorporate relatively low-cost magnetometers as an additional environmental data stream at high-latitude seismic stations. We demonstrate that the Bartington Mag-690 sensors currently deployed at Global Seismographic Network sites are not only acceptable for performing corrections to seismic data, but are also capable of recording many magnetic field signals with similar signal-to-noise ratios, in the 20-1000 s period band, as the observatory grade magnetometers operated by the U.S. Geological Survey Geomagnetism Program. This approach would densify magnetic field observations and could also contribute to space weather monitoring by supplementing highly calibrated magnetometers with additional sensors. [ABSTRACT FROM AUTHOR]

Purpose: The aims of the study were to evaluate the postinsertion care needed by patients treated with four implants to retain mandibular overdentures and to compare two types of superstructures. Materials and Methods: The study consisted of 54 patients who had been treated with conventional maxillary dentures and mandibular overdentures retained by four implants and a triple-bar superstructure with cantilever extensions (28 patients) or without cantilever extensions (26 patients). Differences between both groups with regard to age, gender, length, and diameter of the implants and preoperative mandibular bone height were tested by means of Student's t and chi-square tests with a probability level of 0.05. No significant differences were found. Both groups were retrospectively compared on adjustments and complications. The follow-up period after insertion of the dentures was 2 years. Results: During the 2-year follow-up, 17 patients of the cantilever-extension group and 20 patients of the group without cantilever extensions needed adjustments and 17 patients of the cantilever group and 12 patients of the group without cantilever extensions had to be treated because of complications. Significantly more (P < 0.05, chi-square test) superstructure fractures were present in the cantilever group (14 occasions in 7 patients) than in the group without cantilever extensions (1 occasion). All superstructure fractures in the cantilever group involved the cantilever extensions. Conclusion: This study demonstrated a considerable need for postinsertion care, confirming the necessity of routine follow-up services for patients restored with implant-retained overdentures. Furthermore, the results of this study suggest restriction of the use of cantilever extensions. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to evaluate the safety and efficacy of the novel platinum chromium TAXUS Element paclitaxel-eluting stent (PES) compared with the TAXUS Express PES (Boston Scientific, Natick, Massachusetts) in treating coronary artery stenoses. Background: The TAXUS Element is a novel thin-strut (81 μm), platinum chromium alloy PES designed to improve radial strength, radiopacity, and deliverability, while safely providing comparable restenosis benefit compared with a previous-generation PES. Methods: The PERSEUS (Prospective Evaluation in a Randomized Trial of the Safety and Efficacy of the Use of the TAXUS Element Paclitaxel-Eluting Coronary Stent System) Workhorse (WH) trial is a prospective, randomized (3:1), controlled, multicenter study of the TAXUS Element (vs. TAXUS Express) PES for the treatment of de novo coronary atherosclerotic lesions ≤28 mm in length in reference vessels ≥2.75 to ≤4.0 mm in diameter. The primary end point was the 12-month rate of target lesion failure, and the secondary end point was 9-month angiographic in-segment percentage diameter stenosis. The study was powered to demonstrate noninferiority to TAXUS Express for both end points. Results: The intent-to-treat analysis included 1,262 patients (320 TAXUS Express, 942 TAXUS Element). The TAXUS Element was noninferior to TAXUS Express with respect to both the incidence of target lesion failure (5.57% vs. 6.14%, respectively; difference: 0.57%; 95% credible interval: 1.85%; Bayesian posterior probability of noninferiority = 0.9996) and percentage diameter stenosis (ln[%DS] 3.09 vs. 3.12, respectively; difference: 0.03; 95% credible interval: 0.11; Bayesian posterior probability of noninferiority = 0.9970). No differences in clinical outcomes to 12 months were observed between stent treatments, and stent thrombosis was infrequent (0.3% Express, 0.4% Element). Conclusions: At 1 year, the TAXUS Element is comparable in efficacy to the TAXUS Express PES. Furthermore, no safety concerns related to the novel platinum chromium alloy or stent design were observed. (A Prospective Evaluation in a Randomized Trial of the Safety and Efficacy of the Use of the TAXUS Element Paclitaxel-Eluting Coronary Stent System for the Treatment of De Novo Coronary Artery Lesions; NCT00484315) [Copyright &y& Elsevier]

The acute respiratory distress syndrome (ARDS) is associated with significant morbidity and mortality and neutrophils are critical to its pathogenesis. Neutrophil activation is closely regulated by inhibitory tyrosine phosphatases including Src homology region 2 domain containing phosphatase-1 (Shp1). Here, we report that loss of neutrophil Shp1 in mice produced hyperinflammation and lethal pulmonary hemorrhage in sterile inflammation and pathogen-induced models of acute lung injury (ALI) through a Syk kinase-dependent mechanism. We observed large intravascular neutrophil clusters, perivascular inflammation, and excessive neutrophil extracellular traps in neutrophil-specific Shp1 knockout mice suggesting an underlying mechanism for the observed pulmonary hemorrhage. Targeted immunomodulation through the administration of a Shp1 activator (SC43) reduced agonist-induced reactive oxygen species in vitro and ameliorated ALI-induced alveolar neutrophilia and NETs in vivo . We propose that the pharmacologic activation of Shp1 has the potential to fine-tune neutrophil hyperinflammation that is central to the pathogenesis of ARDS., Competing Interests: Conflict of interest statement: The authors have declared that no conflict of interest exists.

We report on the synthesis, photoluminescence optimization and thermometric properties of Sr 3 Al 2 O 5 Cl 2 :Eu 2+ and SrAl 2 O 4 :Eu 2+ phosphor powders. The photoluminescence of Sr 2.9 Al 2 O 5 Cl 2 :0.1Eu 2+ phosphors exhibits a blue-shift with an increasing annealing temperature owing to a decrease in the crystal field strength of the host caused by evaporation of Cl from the material. The quenching of the blue band in favour of the red band observed in the luminescence spectra of Sr 2.9 Al 2 O 5 Cl 2 :0.1Eu 2+ with an increased annealing temperature was explained using the mechanism of the Landau-Zener transitions. The quantum yield and the lifetime of the phosphors depend on the annealing temperature. Phosphor samples annealed at 850 °C, 1000 °C, 1200 °C and 1500 °C were found to be potential luminescence thermometers using the luminescence spectral method. For Sr 3 Al 2 O 5 Cl 2 :Eu 2+ annealed at 1000 °C, the temperature-dependent dual-band intensity ratio demonstrated a high-temperature sensitivity of ∼1.47%/°C in the temperature range of 23 °C to 40 °C which is superior to other reported phosphors with a microsecond decay time, suggesting that the material has potential for sensitive thermometry applications at ambient temperatures.

A transformative change grounded in a commitment to antiracism and racial and health equity is underway at the University of California, Berkeley, School of Public Health. Responding to a confluence of national, state, and local circumstances, bold leadership, and a moral and disciplinary imperative to name and address racism as a root cause of health inequities, our community united around a common vision of becoming an antiracist institution. Berkeley Public Health has a long history of efforts supporting diversity, equity, inclusion, belonging, and justice. Building upon those efforts, we pursued an institution-wide initiative, one that creates a more equitable and inclusive school of public health that models and supports the development of future public health leaders, practitioners, scholars, and educators. Grounded in the principles of cultural humility, we recognized that our vision was a journey, not a destination. This article describes our efforts from June 2020 through June 2022 in developing and implementing ARC4JSTC (Anti-racist Community for Justice and Social Transformative Change), a comprehensive, multiyear antiracist change initiative encompassing faculty and workforce development, student experience, curriculum and pedagogy, community engagement outreach, and business processes. Our work is data informed, grounded in principles of change management, and focused on building internal capacity to promote long-term change. Our discussion of lessons learned and next steps helps to inform our ongoing work and antiracist institutional change efforts at other schools and programs of public health.

We synthesized and characterized S c thermographic phosphor particles and demonstrated their use as a tracer for temperature imaging in a near-ambient temperature liquid flow using a single laser/camera luminescence lifetime dual-frame ratio-based method. Owing to a high temperature sensitivity of up to 6%/°C, the single-shot single-pixel temperature precision at a 400 µm spatial resolution is better than ±0.4 V O ) across the 20 to 60°C range, representing a factor >5 improvement compared to previous works using thermographic phosphors. The measurement duration is on the order of the luminescence lifetime (2 µs), which is applicable in both gas and liquid flows. This is a general temperature imaging method for sensitive measurements in dynamic fluid mechanics and thermal science applications.4 : B i 3+ thermographic phosphor particles and demonstrated their use as a tracer for temperature imaging in a near-ambient temperature liquid flow using a single laser/camera luminescence lifetime dual-frame ratio-based method. Owing to a high temperature sensitivity of up to 6%/°C, the single-shot single-pixel temperature precision at a 400 µm spatial resolution is better than ±0.4 ∘ C (1 σ ) across the 20 to 60°C range, representing a factor >5 improvement compared to previous works using thermographic phosphors. The measurement duration is on the order of the luminescence lifetime (2 µs), which is applicable in both gas and liquid flows. This is a general temperature imaging method for sensitive measurements in dynamic fluid mechanics and thermal science applications.

Simultaneous point measurements of gas velocity and temperature were recently demonstrated using thermographic phosphors as tracer particles. There, continuous wave (CW) excitation was used and the spectral shift of the luminescence was detected with a two-colour intensity ratio method to determine the gas temperature. The conventional laser Doppler velocimetry (LDV) technique was employed for velocimetry. In this paper, an alternative approach to the gas temperature measurements is presented, which is instead based on the temperature-dependence of the luminescence lifetime. The phase-shift between the luminescence signal and time-modulated excitation light is evaluated for single BaMgAl 10 O 17 :Eu 2+ phosphor particles as they cross the probe volume. Luminescence lifetimes evaluated in the time domain and frequency domain indicate that in these experiments, interferences from in-phase signals such as stray excitation laser light are negligible. The dependence of the phase-shift on flow temperature is characterised. In the temperature sensitive range above 700 K, precise gas temperature measurements can be obtained (8.6 K at 840 K) with this approach.

Neutrophil recruitment to the site of inflammation plays a pivotal role in host defense. However, overwhelming activation and accumulation of neutrophils in the tissue may cause tissue damage and autoimmunity due to the release of cytokines, oxidants, and proteases. Neutrophil adhesion in acute inflammation is initiated by activation of αLβ2 (LFA-1), which can be induced by rolling on E-selectin (slowly) or by exposure to the chemokine CXCL1 (rapidly). Despite the clinical importance, cell-intrinsic molecular mechanisms of negative regulation of integrin adhesiveness and neutrophil recruitment are poorly understood. Mice deficient in the tyrosine phosphatase Src homology 2 domain-containing protein tyrosine phosphatase 1 (Shp1) show increased leukocyte adhesion, but the interpretation of these data is limited by the severe global phenotype of these mice. In this study, we used mice with global and myeloid-restricted deletion of Shp1 to study neutrophil arrest, adhesion, crawling, and transendothelial migration in vitro and in vivo. Shp1 deficiency results in increased neutrophil adhesion in vivo; however, neutrophil crawling, transmigration, and chemotaxis were reduced in these mice. Mechanistically, Shp1 binds and controls PIPKIγ activity and, thereby, modulates phosphatidylinositol (4,5)-bisphosphate levels and adhesion. Thus, Shp1 is involved in the deactivation of integrins and regulation of neutrophil recruitment into inflamed tissue., (Copyright © 2015 by The American Association of Immunologists, Inc.)

Zinc oxide (ZnO) particles are characterised as a tracer for temperature measurements in turbulent flows, in the context of the thermographic particle image velocimetry technique. Flow measurements are used to compare the temperature precision of ZnO to that obtained using a well-characterised thermographic phosphor, BAM:Eu(2+), under the same conditions. For this two-colour, ratio-based technique the strongly temperature-dependent redshift of the luminescence emission of ZnO offers improved temperature sensitivity, and so at room temperature a threefold increase in the temperature precision is achieved. A dependence of the intensity ratio on the laser fluence is identified, and additional measurements with different laser pulse durations are used to independently show that there is also a dependence on the laser excitation irradiance, irrespective of fluence. A simple method to correct for these effects is demonstrated and sources of error are analysed in detail. Temperature images in a Re = 2000 jet of air heated to 363 K with a precision of 4 K (1.1%) are presented. The sensitivity of ZnO increases across the tested temperature range 300-500 K, so that at 500 K, using a seeding density of 2 x 10(11) particles/m(3), a precision of 3 K (0.6%) is feasible. This new phosphor extends the capabilities of this versatile technique toward the study of flows with small temperature variations.

This paper presents an optical diagnostic technique based on seeded thermographic phosphor particles, which allows the simultaneous two-dimensional measurement of gas temperature, velocity and mixture fraction in turbulent flows. The particle Mie scattering signal is recorded to determine the velocity using a conventional PIV approach and the phosphorescence emission is detected to determine the tracer temperature using a two-color method. Theoretical models presented in this work show that the temperature of small tracer particles matches the gas temperature. In addition, by seeding phosphorescent particles to one stream and non-luminescent particles to the other stream, the mixture fraction can also be determined using the phosphorescence emission intensity after conditioning for temperature. The experimental technique is described in detail and a suitable phosphor is identified based on spectroscopic investigations. The joint diagnostics are demonstrated by simultaneously measuring temperature, velocity and mixture fraction in a turbulent jet heated up to 700 K. Correlated single shots are presented with a precision of 2 to 5% and an accuracy of 2%.

Rapid identification of proteins that interact with a novel gene product is an important element of functional genomics. Here we describe a phage display-based technique for interaction screening of complex cDNA libraries using proteins or synthetic peptides as baits. Starting with the epidermal growth factor receptor (EGFR) cytoplasmic tail, we identified known protein interactions that link EGFR to the Ras/MAP kinase signal transduction cascade and several novel interactions. This approach can be used as a rapid and efficient tool for elucidating protein networks and mapping intracellular signal transduction pathways.

We describe a method for identifying tyrosine kinase substrates using anti-phosphotyrosine antibodies to screen tyrosine-phosphorylated cDNA expression libraries. Several potential Src substrates were identified including Fish, which has five SH3 domains and a recently discovered phox homology (PX) domain. Fish is tyrosine-phosphorylated in Src-transformed fibroblasts (suggesting that it is a target of Src in vivo) and in normal cells following treatment with several growth factors. Treatment of cells with cytochalasin D also resulted in rapid tyrosine phosphorylation of Fish, concomitant with activation of Src. These data suggest that Fish is involved in signalling by tyrosine kinases, and imply a specialized role in the actin cytoskeleton.

A new retroviral vector has been constructed that expresses genes encoding three different activities from a single transcript. This feature has been exploited to enable the efficient marking and selection of cells that express a gene of interest. The marker gene lacZ, encoding beta-galactosidase, and neo, encoding neomycin phosphotransferase, for selection by the antibiotic G418, are expressed as a fusion, beta Geo. The expression of beta Geo is coordinated with expression of a gene of interest at the mRNA level using an Internal Ribosome Entry Site (IRES) from the Encephalomyocarditis Virus (EMCV). The IRES promotes cap-independent initiation of translation therefore two reading frames can be translated from a single transcript. In vitro, the vector has been shown to confer beta-galactosidase activity, transformation by v-src and resistance to G418, following infection of cells. To show that the retrovirus was able to mark infected cells in vivo, cells infected with the retrovirus were transplanted into mouse mammary gland where they grew and were successfully located by staining for beta-galactosidase over 2 months after transplantation.

Genes can be introduced into mammary epithelium in vivo by the 'tissue reconstitution' method. Primary cultures of mammary epithelial cells are prepared, a gene introduced using retrovirus vectors, and the cells transplanted into a mammary fat pad from which the normal epithelium has been removed. The cells reform an epithelium in which some cells express the introduced gene. The technique is reviewed and compared with the mammary-specific expression of genes in transgenic mice. To model the development of neoplasia, particularly the preneoplastic changes caused by a single oncogene alone, several oncogenes have been expressed this way--myc, Ha-ras, erbB, erbB2, Wnt-1, and hst/FGF-4. Each caused a different alteration to the growth pattern of the epithelium, such as altered branching, premature alveolus development, distorted duct structure, or altered hormone sensitivity. Insights into normal development have also been obtained by inappropriate expression of genes such as Wnt-4.