Secondary flow in contour currents controls the formation of moat-drift contourite systems

Ocean currents control seafloor morphology and the transport of sediments, organic carbon, nutrients, and pollutants in deep-water environments. A better connection between sedimentary deposits formed by bottom currents (contourites) and hydrodynamics is necessary to improve reconstructions of paleocurrent and sediment transport pathways. Here we use physical modeling in a three-dimensional flume tank to analyse the morphology and hydrodynamics of a self-emerging contourite system. The sedimentary features that developed on a flat surface parallel to a slope are an elongated depression (moat) and an associated sediment accumulation (drift). The moat-drift system can only form in the presence of a secondary flow near the seafloor that transports sediment from the slope toward the drift. The secondary flow increases with higher speeds and steeper slopes, leading to steeper adjacent drifts. This study shows how bottom currents shape the morphology of the moat-drift system and highlights their potential to estimate paleo-ocean current strength

The equilibrium flow and mass balance of the Taku Glacier, Alaska 1950?2006

International audienceThe Taku Glacier, Alaska has advanced 7.5 km since the late nineteenth century, while all other primary outlet glaciers of the Juneau Icefield are in retreat. The Juneau Icefield Research Program has completed field work on the Taku Glacier annually since 1946. The collected observations of surface mass balance, glacier velocity and glacier thickness at Profile IV 29 km above the terminus and 4 km above the equilibrium line provide a means to assess the equilibrium nature of the Taku Glacier. Velocity measured over a twelve month span and annual summer velocity measurements completed at a Profile IV from 1950?2006 indicate insignificant variations in velocity seasonally or from year to year. The consistency of velocity over the 56-year period indicates that in the vicinity of the equilibrium line, the flow of the Taku Glacier has been in an equilibrium state. Surface mass balance was positive from 1946?1988 averaging +0.42 m a?1. This led to glacier thickening. From 1988?2006 an important change has occurred and annual balance has been ?0.14 m a?1, and the glacier thickness has ceased increasing along Profile IV. Field measurements of ice depth and surface velocity allow calculation of the volume flux at Profile IV. Volume flux is then compared with the surface balance flux from the region of the glacier above Profile IV, determined annually in the field. Above Profile IV the observed mean surface flux is 5.50×108 m3/a (±5%), while the calculated volume flux range flowing through profile IV is 5.00?5.47×108 m3/a. The mean surface flux has been greater than the volume flux, which has led to slow thickening of the Taku Glacier up to 1988. The thickening has not led to a change in the flow of Taku Glacier at Profile IV

Comparison of the Conceptual Map and Traditional Lecture Methods on Students’ Learning Based on the VARK Learning Style Model: A Randomized Controlled Trial

Developing skills and knowledge in nursing education remains a considerable challenge. Nurse instructors need to be aware of students' learning styles so as to meet students' individual learning preferences and optimize knowledge and understanding. The aim of this study was to compare the effects of the conceptual map and the traditional lecture methods on students' learning based on the VARK learning styles model. In this randomized controlled trial, 160 students from nursing, nurse anesthetics, and midwifery disciplines with four different learning styles of visual, auditory, reading/writing, and kinesthetic were selected using the convenience sampling method. Participants were randomly assigned to the intervention (conceptual map method) or control (traditional lecture method) groups. A medical-surgical nursing course was taught to the students in both groups over 6 weeks. Data collection tools consisted of the VARK questionnaire and pre-and postassessments. Data were analyzed using descriptive and inferential statistics via the SPSS software. Teaching using the conceptual map method had different effects on the students' learning outcomes based on their learning styles. The conceptual map method had a statistically significant impact on the students' learning in the intervention group compared with the control group in the students with a visual learning style (p ¼ .036). No statistically significant differences were reported between the groups in other three learning styles. Nurse instructors should assess students' learning styles based on the VARK model before the application of a particular teaching method to improve the quality of nursing education and facilitate deeper learning

Antiproliferative activity, mechanism of action and oral antitumor activity of CP-4126, a fatty acid derivative of gemcitabine, in in vitro and in vivo tumor models

Gemcitabine is a deoxycytidine (dCyd) analog with activity in leukemia and solid tumors, which requires phosphorylation by deoxycytidine kinase (dCK). Decreased membrane transport is a mechanism of resistance to gemcitabine. In order to facilitate gemcitabine uptake and prolong retention in the cell, a lipophilic pro-drug was synthesized (CP-4126), with an elaidic fatty acid esterified at the 5'position. CP-4126 was tested in cell lines resistant to cytarabine, another dCyd analog or gemcitabine. Activity of gemcitabine and the derivative was comparable in the parent cell lines, while in dCK deficient cells all compounds were inactive. However, inhibition of nucleoside transport increased the IC(50) for gemcitabine up to 200-fold, but not for CP-4126, underlining the independence of a nucleoside transporter. For in vivo evaluation, nude mice bearing a human xenograft were treated intraperitoneally every third day for five doses at the maximal tolerated dose. In melanoma, sarcoma, lung, prostate, pancreatic and breast cancer xenografts, gemcitabine and CP-4126 were equally and highly effective; in four other xenografts moderately but equally active. In contrast to gemcitabine, CP-4126 could be administered orally, with a schedule and dose dependent toxicity and antitumor activity. In a colon cancer xenograft, antitumor activity of orally administered CP-4126 was equal to the intraperitoneally administered drug. In conclusion, CP-4126 is membrane transporter independent. Intraperitoneally administered CP-4126 was as effective as gemcitabine in several xenografts and CP-4126 is tolerated when orally administered. CP-4126 seems to be a promising new anticancer drug

Route of Administration of the TLR9 Agonist CpG Critically Determines the Efficacy of Cancer Immunotherapy in Mice

Contains fulltext : 81648.pdf (publisher's version ) (Open Access)BACKGROUND: The TLR9 agonist CpG is increasingly applied in preclinical and clinical studies as a therapeutic modality to enhance tumor immunity. The clinical application of CpG appears, however, less successful than would be predicted from animal studies. One reason might be the different administration routes applied in most mouse studies and clinical trials. We studied whether the efficacy of CpG as an adjuvant in cancer immunotherapy is dependent on the route of CpG administration, in particular when the tumor is destructed in situ. METHODOLOGY/PRINCIPAL FINDINGS: In situ tumor destruction techniques are minimally invasive therapeutic alternatives for the treatment of (nonresectable) solid tumors. In contrast to surgical resection, tumor destruction leads to the induction of weak but tumor-specific immunity that can be enhanced by coapplication of CpG. As in situ tumor destruction by cryosurgery creates an instant local release of antigens, we applied this model to study the efficacy of CpG to enhance antitumor immunity when administrated via different routes: peritumoral, intravenous, and subcutaneous but distant from the tumor. We show that peritumoral administration is superior in the activation of dendritic cells, induction of tumor-specific CTL, and long-lasting tumor protection. Although the intravenous and subcutaneous (at distant site) exposures are commonly used in clinical trials, they only provided partial protection or even failed to enhance antitumor responses as induced by cryosurgery alone. CONCLUSIONS/SIGNIFICANCE: CpG administration greatly enhances the efficacy of in situ tumor destruction techniques, provided that CpG is administered in close proximity of the released antigens. Hence, this study helps to provide directions to fully benefit from CpG as immune stimulant in a clinical setting

Improving poverty reduction in Europe: what works best where?

This article examines how income poverty is affected by changes to the scale of tax-benefit policies and which are the most cost-effective policies in reducing poverty or limiting its increase in seven diverse EU countries. We do that by measuring the implications of increasing/reducing the scale of each policy instrument, using microsimulation methods while holding constant the policy design and national context. We consider commonly applied policy instruments with a direct effect on household income: child benefits, social assistance, income tax lower thresholds and a benchmark case of rescaling the whole tax-benefit system. We find that the assessment of the most cost-effective instrument may depend on the measure of poverty used and the direction and scale of the change. Nevertheless, our results indicate that the options that reduce poverty most cost-effectively in most countries are increasing child benefits and social assistance, while reducing the former is a particularly poverty-increasing way of making budgetary cuts

Novel insights in the regulation of CCL18 secretion by monocytes and dendritic cells via cytokines, Toll-like receptors and rheumatoid synovial fluid

BACKGROUND: The T cell attracting chemokine CCL18 is produced by antigen presenting cells and a role for CCL18 has been suggested in the pathogenesis of a variety of diseases. Rheumatoid arthritis (RA) is one of these conditions, in which abundant CCL18 production is present. Although Th2 cytokines and IL-10 are known to have an effect on CCL18 production, there are several gaps in our knowledge regarding the exact regulation of CCL18 secretion, both in general and in RA. In this study we provide new insights in the regulation of CCL18 secretion by monocytes and dendritic cells. RESULTS: In contrast to a large panel of pro-inflammatory stimuli (IL-1β, TNF-α, IL-10, IL-13, IL-15, IL-17, IL-18, IFN-γ), T cell mimicking molecules (RANKL, CD40L) or TLR driven maturation, the anti-inflammatory IL-10 strongly stimulated DC to secrete CCL18. On freshly isolated monocytes, CCL18 secretion was induced by IL-4 and IL-13, in strong synergy with IL-10. This synergistic effect could already be observed after only 24 hours, indicating that not only macrophages and dendritic cells, but also monocytes secrete CCL18 under these stimulatory conditions. A high CCL18 expression was detected in RA synovial tissue and incubation of monocytes with synovial fluid from RA patients clearly enhanced the effects of IL-4, IL-13 and IL-10. Surprisingly, the effect of synovial fluid was not driven by IL-10 of IL-13, suggesting the presence of another CCL18 inducing factor in synovial fluid. CONCLUSION: In summary, IL-10 synergistically induces CCL18 secretion in combination with IL-4 of IL-13 on monocytes and monocyte derived cells. The effects of IL-14, IL-13 and IL-10 are strongly enhanced by synovial fluid. This synergy may contribute to the high CCL18 expression in RA