To cite this article: Banfi C, Brioschi M, Lento S, Pirillo A, Galli S, Cosentino S, Tremoli E, Mussoni L. Statins prevent tissue factor induction by protease‐activated receptors 1 and 2 in human ...umbilical vein endothelial cells in vitro. J Thromb Haemost 2011; 9: 1608–19.
Summary. Background: Protease‐activated receptors (PARs) are G‐protein‐coupled receptors that function in hemostasis and thrombosis, as well as in the inflammatory and proliferative responses triggered by tissue injury. We have previously shown that PAR1 or PAR2 occupancy by specific PAR‐agonist peptides (PAR‐APs) induces tissue factor (TF) expression in human umbilical vein endothelial cells (HUVECs), where TF regulation by PAR1 (but not by PAR2) requires intact endothelial caveolin‐enriched membrane microdomains in which PAR1 and caveolin‐1 associate. Objectives: The aim of this study was to determine the effects of cholesterol‐lowering agents (statins) and cholesterol‐loading lipoprotein on PAR1‐AP‐mediated and PAR2‐AP‐mediated TF induction in HUVECs. Results: Statins completely prevented TF induction by PAR‐APs in an isoprenoid‐independent manner, induced the delocalization of PAR1 from caveolin‐enriched membrane microdomains without affecting PAR1 mRNA, and decreased PAR2 mRNA and protein levels. Statins also prevented PAR‐AP‐mediated extracellular signal‐related kinase 1/2 activation, which is crucial for TF induction. The redistribution of PAR1 is accompanied by the relocation of the membrane microdomain‐associated G‐protein α, caveolin‐1, and Src, which we previously showed to play a key role in signal transduction and TF induction. Conversely, cholesterol loading potently amplified PAR1‐AP‐induced TF, probably as a result of the increased abundance of PAR1 and the Src and G‐protein α signaling molecules in the caveolin‐1‐enriched fraction, without affecting PAR1 mRNA. Conclusions: As PARs have important functions in hemostasis, cancer, thrombosis, and inflammatory processes, our findings that statins prevent TF induction by PAR‐APs altering the membrane localization of PAR1 and the expression of PAR2 suggest that they may provide health benefits other than reducing atherosclerosis.
Organic matter balances of an ECF kraft mill fiberline were studied in three different operational conditions of the oxygen delignification stage by implementing mill measurements, collecting routine ...mill data and combining them in a modified PROCELL steady state model. Dissolved volatile solids was the basic measurement for organic matter in liquid streams. Normal operation of the O2D0E(O)D1E(OP)D2 fiberline was described successfully. It was also possible to describe exceptional operating situations in the oxygen delignification stage and their effects on other parts of the production process reasonably well in order to focus studies on aspects requiring further attention. The existence of organic matter lost through complete degradation and volatile organic compounds in unit processes as well as its sensitivity to yield and operational situations is shown. The different perspectives of pulp production and wastewater treatment can be brought closer to each other using the approach in this study. The variation in the fractions discharged to wastewater treatment, although a relatively small share of the overall organic matter balance, will continue to become more important also for pulp production when effluent streams are increasingly turned back to the production line through further closure. Studies like the one presented here, can contribute to the evaluation of this development.
Efficiency improvement in a pulp mill includes minimisation of environmental discharges simultaneously with the development of pulp quality and production economy. Material balances in production ...processes, including fate of sidestreams, are key in proceeding these matters. Different approaches of determining the material balances increase understanding of process behaviour. We have focused on measuring sidestream (carryovers, washing water, filtrate) dissolved organic matter (DOM) in fibreline unit process blocks of softwood ECF bleached kraft production. The DOM was analysed by traditional wastewater methods (volatile solids, organic carbon, chemical oxygen demand). The measured data was combined with primarily simulated water balances and routine operational mill data in a simulation model. From this balance, yield estimate included, lost organic matter through complete degradation (CD) and volatile organic compounds (VOC) can be calculated throughout the fibreline. The sensitivity of this considerable amount (23-35 kgDVS/adt in total) to various factors is discussed in this paper.
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Background: Post-diagnosis weight gain is common among women with early-stage breast cancer and is associated with increased risk of recurrence, breast cancer death, and all-cause mortality. ...Intentional weight loss following diagnosis is difficult to maintain. Targeted lifestyle interventions focusing on behavioral changes and education that can be implemented long-term are needed. Methods: This was a prospective single-arm pilot study in patients with history of early-stage breast cancer (NCT04753268). Key eligibility criteria included body mass index (BMI) ≥27.5 kg/m2, stage I-III breast cancer, and completion of active cancer treatment ≥6 months prior to study enrollment. Patients were recruited at the Dempsey Center in Lewiston, ME and via social media. Participants were given access to the Noom mobile application, which utilizes cognitive behavioral therapy, motivational interviewing, and self-determination theory to induce behavior change using an educational curriculum of daily articles, virtual health coaching, social networking, food records, and physical activity logs. The primary endpoint was change in self-reported weight from baseline to 26 weeks. Secondary endpoints included change in physical activity measured using step count and the Global Physical Activity Questionnaire (GPAQ), change in diet patterns analyzed using the Nutrition Data System for Research, patient-reported outcome (PRO) measures, and metrics for engagement with the mobile application. Results: 31 patients were enrolled; 24 at the Dempsey Center and 7 via social media. Mean age was 56.8 and mean baseline BMI was 33.5 kg/m2. Mean weight change was -4.8 kg (range +0.6 to -19.9 kg, p < 0.001) and mean percent weight change was -5.6%; 11/31 patients (35.5%) lost ≥5% of their initial weight. Average daily step count increased by 54.7% (p = 0.004). Mean GPAQ score for physical activity increased from 990 to 1773 (p = 0.01), and the proportion of patients who met physical activity guidelines increased from 45.1% to 74.2%. Mean energy intake did not change significantly over 26 weeks (p = 0.779). Improvements were observed in PROMIS-Physical Functioning T-scores and Body Image Scale scores (p = 0.04, p < 0.001 respectively). Metrics of engagement with Noom that were predictive of weight loss ≥5% included total articles read (p = 0.012), total weights logged (p = 0.006), total food records logged (p = 0.001), messages sent to coach (p = 0.001), and number of times the application was opened (p = 0.014). Conclusions: In this pilot study, breast cancer survivors lost weight and became more physically active using a commercially-available mobile application. This digital weight loss program is a scalable intervention, and these findings support future studies investigating impact on breast cancer outcomes. Clinical trial information: NCT04753268 .
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This data article is related to the research article entitled Proteomics of Tissue Factor silencing in cardiomyocytic cells reveals a new role for this coagulation factor in splicing machinery ...control by Lento et al 1.;
Tissue Factor (TF) is the key player in the coagulation cascade, but it has additional functions ranging from angiogenesis, tumor invasion and, in the heart, the maintenance of the integrity of cardiac cells. This article reports the nano-LC-MSE analysis of the cardiomyocytic HL-1 cell line proteome and describes the results obtained from a Gene Ontology analysis of those proteins affected by TF-gene silencing.
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It has long been known that Tissue Factor (TF) plays a role in blood coagulation and has a direct thrombotic action that is closely related to cardiovascular risk, but it is becoming increasingly ...clear that it has a much wider range of biological functions that range from inflammation to immunity. It is also involved in maintaining heart haemostasis and structure, and the observation that it is down-regulated in the myocardium of patients with dilated cardiomyopathy suggests that it influences cell-to-cell contact stability and contractility, and thus contributes to cardiac dysfunction. However, the molecular mechanisms underlying these coagulation-independent functions have not yet been fully elucidated.;
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In order to analyse the influence of TF on the cardiomyocitic proteome, we used functional biochemical approaches incorporating label-free quantitative proteomics and gene silencing, and found that this provided a powerful means of identifying a new role for TF in regulating splicing machinery together with the expression of several proteins of the spliceosome, and mRNA metabolism with a considerable impact on cell viability.
Without venture capital, many of the companies whose technical innovations sparked the digital revolution would not exist. Venture investments funded these firms to develop their bright ideas into ...commercial products that created new business models and established whole new markets. In Investing in Dynamic Markets, Henry Kressel, a partner at multi-billion-dollar global investing company Warburg Pincus, takes you behind the scenes of the private equity process. He draws on his extensive experience to show how venture capital works, why venture capitalists fund certain companies and not others, and what factors influence the success or failure of their high-risk, high-reward investments. He also discusses venture capital's future, now that the commercialization of technology requires larger investments and global market access. Written in clear, non-technical language, the book features informative case studies of venture capital funding in a wide range of industries, including telecommunications, software and services, semiconductors, and the internet.
This extensive selection of Tanikawa Shuntaro's poetry reflects the full depth and breadth of his work, from his appearance as a fresh new voice to the mastery of his later poetry. It traces his ...artistic development and his shift in focus from man's cosmic destiny to the pathos of everyday life and a more internalized struggle with the nature of human expression. Lovers of poetry will find the experience exhilarating. The only such collection in English, this volume will prove indispensable to students and scholars of Japanese literature, as it opens a valuable new perspective on postware Japanese literature. The Introduction clarifies the social and artistic background of Tanikawa's extraordinary work and career, illuminating major themes as his poetry evolves over time.
A
bstract
In this note, we explicitly compute the vacuum expectation value of the commutator of scalar fields in a
d
-dimensional conformal field theory on the cylinder. We find from explicit ...calculations that we need smearing not only in space but also in time to have finite commutators except for those of free scalar operators. Thus the equal time commutators of the scalar fields are not well-defined for a non-free conformal field theory, even if which is defined from the Lagrangian. We also have the commutator for a conformal field theory on Minkowski space, instead of the cylinder, by taking the small distance limit. For the conformal field theory on Minkowski space, the above statements are also applied.
PurposeThis paper explores who among the AACSB categorization of academics conducts the scholarship of teaching and learning (SoTL) research within business schools and how AACSB-accredited business ...schools capture SoTL research as part of their portfolio of intellectual contributions.Design/methodology/approachThis study adopts a qualitative-method research design by collecting primary data through surveys, semi-structured interviews and secondary data in policy documents focused on AACSB-accredited business schools in Canada and the United States.FindingsThe findings establish that scholarly and practice academics who possess rigorously acquired research skills due to their terminal degrees are most likely to conduct SoTL research. The results also reveal an even split among respondents regarding whether their AACSB-accredited business school captures SoTL with their journal ranking frameworks.Practical implicationsBased on the findings, two recommendations are offered to foster more SoTL research at AACSB-accredited schools. First, higher education leaders (e.g. business school deans) can further inculcate a culture of SoTL research at the department and institutional levels by creating communities of practice (CoPs). Second, AACSB-accredited business schools could adopt more inclusive journal ranking frameworks to capture better and incentivize SoTL research.Originality/valueThis is the first known study to explore how AACSB Standards 3 and 8 are implemented and operationalized regarding SoTL research. Understanding how these standards are adopted and implemented could help institutional leaders, standard setters and administrators better facilitate SoTL research.
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