Analysis of the potential of cancer cell lines to release tissue factor-containing microvesicles: correlation with tissue factor and PAR2 expression

BackgroundDespite the association of cancer-derived circulating tissue factor (TF)-containing microvesicles and hypercoagulable state, correlations with the incidence of thrombosis remain unclear.MethodsIn this study the upregulation of TF release upon activation of various cancer cell lines, and the correlation with TF and PAR2 expression and/or activity was examined. Microvesicle release was induced by PAR2 activation in seventeen cell lines and released microvesicle density, microvesicle-associated TF activity, and phoshpatidylserine-mediated activity were measured. The time-course for TF release was monitored over 90 min in each cell line. In addition, TF mRNA expression, cellular TF protein and cell-surface TF activities were quantified. Moreover, the relative expression of PAR2 mRNA and cellular protein were analysed. Any correlations between the above parameters were examined by determining the Pearson’s correlation coefficients.ResultsTF release as microvesicles peaked between 30–60 min post-activation in the majority of cell lines tested. The magnitude of the maximal TF release positively correlated with TF mRNA (c = 0.717; p

Building up or out? Disparate sequence architectures along an active rift margin—Corinth rift, Greece

Early Pleistocene synrift deltas developed along the southern Corinth rift margin were deposited in a single, dominantly lacustrine depocenter and were subject to the same climate-related base-level and sediment supply cyclicity. Two synrift deltas, just 50 km apart, show markedly different sequence geometry and evolution related to their location along the evolving border fault. In the west, strongly aggradational fan deltas (>600 m thick; 2–4 km radius) deposited in the immediate hanging wall of the active border fault comprise stacked 30–100-m-thick stratal units bounded by flooding surfaces. Each unit evolves from aggradational to progradational with no evidence for abrupt subaerial exposure or fluvial incision. In contrast, in the central rift, the border fault propagated upward into an already deep lacustrine environment, locating rift-margin deltas 15 km into the footwall. The deltas here have a radius of >9 km and comprise northward downstepping and offlapping units, 50–200 m thick, that unconformably overlie older synrift sediments and are themselves incised. The key factors driving the marked variation in sequence stratigraphic architecture are: (1) differential uplift and subsidence related to position with respect to the border fault system, and (2) inherited topography that influenced shoreline position and offshore bathymetry. Our work illustrates that stratal units and their bounding surfaces may have only local (<10 km) extent, highlighting the uncertainty involved in assigning chronostratigraphic significance to systems tracts and in calculating base-level changes from stratigraphy where marked spatial variations in uplift and subsidence occur

Effects of serum proteins on corrosion behavior of ISO 5832–9 alloy modified by titania coatings

Stainless steel ISO 5832–9 type is often used to perform implants which operate in protein-containing physiological environments. The interaction between proteins and surface of the implant may affect its corrosive properties. The aim of this work was to study the effect of selected serum proteins (albumin and γ-globulins) on the corrosion of ISO 5832–9 alloy (trade name M30NW) which surface was modified by titania coatings. These coatings were obtained by sol– gel method and heated at temperatures of 400 and 800 °C. To evaluate the effect of the proteins, the corrosion tests were performed with and without the addition of proteins with concentration of 1 g L−1 to the physiological saline solution (0.9 % NaCl, pH 7.4) at 37 °C. The tests were carried out within 7 days. The following electrochemical methods were used: open circuit potential, linear polarization resistance, and electrochemical impedance spectroscopy. In addition, surface analysis by optical microscopy and X-ray photoelectron spectroscopy (XPS) method was done at the end of weekly corrosion tests. The results of corrosion tests showed that M30NW alloy both uncoated and modified with titania coatings exhibits a very good corrosion resistance during weekly exposition to corrosion medium. The best corrosion resistance in 0.9 % NaCl solution is shown by alloy samples modified by titania coating annealed at 400 °C. The serumproteins have no significant effect onto corrosion of investigated biomedical steel. The XPS results confirmed the presence of proteins on the alloy surface after 7 days of immersion in proteincontaining solutions.The investigations were supported by the National Science Centre project No. N N507 501339. The authors gratefully acknowledge Dr. Janusz Sobczak and Dr. hab. Wojciech Lisowski from Institute of Physical Chemistry of PAS for XPS surface analyses

SPECULOOS exoplanet search and its prototype on TRAPPIST

One of the most significant goals of modern science is establishing whether life exists around other suns. The most direct path towards its achievement is the detection and atmospheric characterization of terrestrial exoplanets with potentially habitable surface conditions. The nearest ultracool dwarfs (UCDs), i.e. very-low-mass stars and brown dwarfs with effective temperatures lower than 2700 K, represent a unique opportunity to reach this goal within the next decade. The potential of the transit method for detecting potentially habitable Earth-sized planets around these objects is drastically increased compared to Earth-Sun analogs. Furthermore, only a terrestrial planet transiting a nearby UCD would be amenable for a thorough atmospheric characterization, including the search for possible biosignatures, with near-future facilities such as the James Webb Space Telescope. In this chapter, we first describe the physical properties of UCDs as well as the unique potential they offer for the detection of potentially habitable Earth-sized planets suitable for atmospheric characterization. Then, we present the SPECULOOS ground-based transit survey, that will search for Earth-sized planets transiting the nearest UCDs, as well as its prototype survey on the TRAPPIST telescopes. We conclude by discussing the prospects offered by the recent detection by this prototype survey of a system of seven temperate Earth-sized planets transiting a nearby UCD, TRAPPIST-1.Comment: Submitted as a chapter in the "Handbook of Exoplanets" (editors: H. Deeg & J.A. Belmonte; Section Editor: N. Narita). 16 pages, 4 figure

Violent video games and morality: a meta-ethical approach

This paper considers what it is about violent video games that leads one reasonably minded person to declare "That is immoral" while another denies it. Three interpretations of video game content a re discussed: reductionist, narrow, and broad. It is argued that a broad interpretation is required for a moral objection to be justified. It is further argued that understanding the meaning of moral utterances – like "x is immoral" – is important to an understanding of why there is a lack of moral consensus when it comes to the content of violent video games. Constructive ecumenical expressivism is presented as a means of explaining what it is that we are doing when we make moral pronouncements and why, when it comes to video game content, differing moral attitudes abound. Constructive ecumenical expressivism is also presented as a means of illuminating what would be required for moral consensus to be achieved

"I am your mother and your father!": In vitro derived gametes and the ethics of solo reproduction

In this paper, we will discuss the prospect of human reproduction achieved with gametes originating from only one person. According to statements by a minority of scientists working on the generation of gametes in vitro, it may become possible to create eggs from men’s non-reproductive cells and sperm from women’s. This would enable, at least in principle, the creation of an embryo from cells obtained from only one individual: ‘solo reproduction’. We will consider what might motivate people to reproduce in this way, and the implications that solo reproduction might have for ethics and policy. We suggest that such an innovation is unlikely to revolutionise reproduction and parenting. Indeed, in some respects it is less revolutionary than in vitro fertilisation as a whole. Furthermore, we show that solo reproduction with in vitro created gametes is not necessarily any more ethically problematic than gamete donation—and probably less so. Where appropriate, we draw parallels with the debate surrounding reproductive cloning. We note that solo reproduction may serve to perpetuate reductive geneticised accounts of reproduction, and that this may indeed be ethically questionable. However, in this it is not unique among other technologies of assisted reproduction, many of which focus on genetic transmission. It is for this reason that a ban on solo reproduction might be inconsistent with continuing to permit other kinds of reproduction that also bear the potential to strengthen attachment to a geneticised account of reproduction. Our claim is that there are at least as good reasons to pursue research towards enabling solo reproduction, and eventually to introduce solo reproduction as an option for fertility treatment, as there are to do so for other infertility related purposes

Selective Inhibition of Type III Secretion Activated Signaling by the Salmonella Effector AvrA

Salmonella enterica utilizes a type III secretion system (TTSS) encoded in its pathogenicity island 1 to mediate its initial interactions with intestinal epithelial cells, which are characterized by the stimulation of actin cytoskeleton reorganization and a profound reprogramming of gene expression. These responses result from the stimulation of Rho-family GTPases and downstream signaling pathways by specific effector proteins delivered by this TTSS. We show here that AvrA, an effector protein of this TTSS, specifically inhibits the Salmonella-induced activation of the JNK pathway through its interaction with MKK7, although it does not interfere with the bacterial infection-induced NF-κB activation. We also show that AvrA is phosphorylated at evolutionary conserved residues by a TTSS-effector-activated ERK pathway. This interplay between effector proteins delivered by the same TTSS highlights the remarkable complexity of these systems

A mid year comparison study of career satisfaction and emotional states between residents and faculty at one academic medical center

BACKGROUND: The Accreditation Council for Graduate Medical Education's (ACGME) new requirements raise multiple challenges for academic medical centers. We sought to evaluate career satisfaction, emotional states, positive and negative experiences, work hours and sleep among residents and faculty simultaneously in one academic medical center after implementation of the ACGME duty hour requirements. METHODS: Residents and faculty (1330) in the academic health center were asked to participate in a confidential survey; 72% of the residents and 66% of the faculty completed the survey. RESULTS: Compared to residents, faculty had higher levels of satisfaction with career choice, competence, importance and usefulness; lower levels of anxiousness and depression. The most positive experiences for both groups corresponded to strong interpersonal relationships and educational value; most negative experiences to poor interpersonal relationships and issues perceived outside of the physician's control. Approximately 13% of the residents and 14% of the faculty were out of compliance with duty hour requirements. Nearly 5% of faculty reported working more than 100 hours per week. For faculty who worked 24 hour shifts, nearly 60% were out of compliance with the duty-hour requirements. CONCLUSION: Reasons for increased satisfaction with career choice, positive emotional states and experiences for faculty compared to residents are unexplained. Earlier studies from this institution identified similar positive findings among advanced residents compared to more junior residents. Faculty are more frequently at risk for duty-hour violations. If patient safety is of prime importance, faculty, in particular, should be compliant with the duty hour requirements. Perhaps the ACGME should contain faculty work hours as part of its regulatory function

Industry-supported meta-analyses compared with meta-analyses with non-profit or no support: Differences in methodological quality and conclusions

<p>Abstract</p> <p>Background</p> <p>Studies have shown that industry-sponsored meta-analyses of drugs lack scientific rigour and have biased conclusions. However, these studies have been restricted to certain medical specialities. We compared all industry-supported meta-analyses of drug-drug comparisons with those without industry support.</p> <p>Methods</p> <p>We searched PubMed for all meta-analyses that compared different drugs or classes of drugs published in 2004. Two authors assessed the meta-analyses and independently extracted data. We used a validated scale for judging the methodological quality and a binary scale for judging conclusions. We divided the meta-analyses according to the type of support in 3 categories: industry-supported, non-profit support or no support, and undeclared support.</p> <p>Results</p> <p>We included 39 meta-analyses. Ten had industry support, 18 non-profit or no support, and 11 undeclared support. On a 0–7 scale, the median quality score was 6 for meta-analyses with non-profit or no support and 2.5 for the industry-supported meta-analyses (P < 0.01). Compared with industry-supported meta-analyses, more meta-analyses with non-profit or no support avoided bias in the selection of studies (P = 0.01), more often stated the search methods used to find studies (P = 0.02), searched comprehensively (P < 0.01), reported criteria for assessing the validity of the studies (P = 0.02), used appropriate criteria (P = 0.04), described methods of allocation concealment (P = 0.05), described methods of blinding (P = 0.05), and described excluded patients (P = 0.08) and studies (P = 0.15). Forty percent of the industry-supported meta-analyses recommended the experimental drug without reservations, compared with 22% of the meta-analyses with non-profit or no support (P = 0.57).</p> <p>In a sensitivity analysis, we contacted the authors of the meta-analyses with undeclared support. Eight who replied that they had not received industry funding were added to those with non-profit or no support, and 3 who did not reply were added to those with industry support. This analysis did not change the results much.</p> <p>Conclusion</p> <p>Transparency is essential for readers to make their own judgment about medical interventions guided by the results of meta-analyses. We found that industry-supported meta-analyses are less transparent than meta-analyses with non-profit support or no support.</p