The effect of bovine milk lactoferrin on human breast cancer cell lines

The evidence that biologically active food components are key environmental factors affecting the incidence of many chronic diseases is overwhelming. However, the full extent of such components in our diet is unknown, as well as our understanding of their mechanisms of action. Beyond their interaction with the gut and intestinal immune functions, more benefits are being tested for whey proteins such as lactoferrin, namely as anti-cancer agents. Lactoferrin is an iron-binding protein that has been reported to inhibit several types of cancer. In the present work, the effects of bovine milk lactoferrin on human breast cancer HS578T and T47D cells were studied. The cells were either untreated or submitted to lactoferrin concentrations ranging from 0. 125 to 125 μM. Lactoferrin decreased 47% and 54% the cell viability of HS578T and T47D, respectively, and increased apoptosis about twofold for both cell lines. Proliferation rates decreased between 40.3 and 63.9% for HS578T and T47D, respectively. T47D cell migration decreased in the presence of the protein. Although the mechanisms of action have still not been unrevealed, the results gathered in this work suggest that lactoferrin interferes with some of the most important steps involved in cancer development.(undefined

Study of radial heat transport in W7-X using the transfer entropy

Autor colectivo: W7-X TeamIn this work, we analyze data obtained using the electron cyclotron emission radiometer at the Wendelstein 7-X stellarator using a relatively new technique: the transfer entropy. Thus, we detect the propagation of information and find that it occurs in a stepwise fashion: we observe both 'trapping zones' and radial 'jumps', when the information is apparently skipping over intermediate positions. Using scans of the rotational transform, we observe that the 'trapping zones' appear to be associated with rational surfaces. Power scan experiments show that these 'jumps' increase in importance when power is increased, thus enhancing the effective diffusivity. The observations are interpreted in terms of a resistive magneto-hydrodynamic model, which displays behavior similar to the experimental results. The 'trapping zones' are explained in terms of zonal flows associated with rational surfaces, while the 'jumps' are ascribed to mode coupling effects, i.e. the transmission of turbulent energy via the magnetic field

Population Pharmacokinetics and Safety of Ceftolozane-Tazobactam in Adult Cystic Fibrosis Patients Admitted with Acute Pulmonary Exacerbation

ABSTRACT Ceftolozane-tazobactam has potent activity against Pseudomonas aeruginosa , a pathogen associated with cystic fibrosis (CF) acute pulmonary exacerbations (APE). Due to the rapid elimination of many antibiotics, CF patients frequently have altered pharmacokinetics. In this multicenter, open-label study, we described the population pharmacokinetics and safety of ceftolozane-tazobactam at 3 g every 8 h (q8h) in 20 adult CF patients admitted with APE. Population pharmacokinetics were determined using the nonparametric adaptive grid program in Pmetrics for R. A 5,000-patient Monte Carlo simulation was performed to determine the probability of target attainment (PTA) for the ceftolozane component at 1.5 g and 3 g of ceftolozane-tazobactam q8h across a range of MICs using a primary threshold exposure of 60% free time above the MIC ( fT >MIC). In these 20 adult CF patients, ceftolozane and tazobactam concentration data were best described by 2-compartment models, and ceftolozane clearance (CL) was significantly correlated with creatinine clearance ( r = 0.71, P MIC, ceftolozane-tazobactam regimens of 1.5 g and 3 g q8h should achieve PTAs of ≥90% at MICs up to 4 and 8 μg/ml, respectively. Ceftolozane-tazobactam at 3 g q8h was well tolerated. These observations support additional studies of ceftolozane-tazobactam for Pseudomonas aeruginosa APE in CF patients. (This study has been registered at ClinicalTrials.gov under identifier NCT02421120.

Effects of Topography and Surface Soil Cover on Erosion for Mining Reclamation: The Experimental Spoil Heap at El Machorro Mine (Central Spain)

Mining reclamation tries to reduce environmental impacts, including accelerated runoff, erosion and sediment load in the nearby fluvial networks and their ecosystems. This study compares the effects of topography and surface soil cover on erosion on man-made slopes coming from surface mining reclamation in Central Spain. Two topographic profiles, linear and concave, with two surface soil covers, subsoil and topsoil, were monitored for two hydrologic years. Sediment load, rill development and plant colonization from the four profiles were measured under field conditions. The results show that, in the case of this experiment, a thick and non-compacted topsoil cover on a linear slope yielded less sediment than carbonate colluvium or topsoil cover on a concave slope. This study also shows that vegetation establishment, which plays an important role in erosion control, depends on topography. Plant cover was more widespread and more homogeneous on linear profiles with topsoil cover. On concave slopes, plant establishment was severely limited on the steepest upper part and favoured in the bottom. This study suggests that management of topography and surface soil cover should be approached systematically, taking three outcomes into consideration: (i) topsoil can lead to a successful mining reclamation regardless of topography, (ii) created concave slopes can lead to a successful mining reclamation and (iii) topography determines the vegetation colonization pattern.The experiment was funded by a research contract between the Spanish mining company 602 CAOBAR S.A. and the Department of Geodynamics of the Complutense University of Madrid 603 (research contract numbers 234/2007, 290/2008 261/2009). The data analyses and manuscript 604 production were developed within two Research Projects, CGL2009-14508-C02-01 and 605 CGL2010-21754-C02, of the Spanish Ministry of Science and Technology and by the 606 Ecological Restoration network REMEDINAL-2 (S2009/AMB-1783).Peer reviewe

A conceptual model for sheet-flow drawn from rapid granular flow theories

33rd IAHR Congress: Water Engineering for a Sustainable EnvironmentThis paper is aimed at presenting i) a simple, yet sound, conceptual model applicable to the simulation of erosion, deposition and transport of cohesionless sediment in stratified flows under high shear stresses and ii) numerical solutions in idealized unsteady flow non-equilibrium transport situations. The conceptual model for the granular phase comprises 2DV mass and momentum and energy equations and constitutive equations, all derived within the dense limit of the Chapman-Enskog kinetic theory. 1D shallow-flow conservation and closure equations are derived for the fluid-granular mixture. Formulas for the average velocity in the transport layers, the vertical net flux of sediment mass and the thickness of the transport layer are thus obtained. Numerical solutions for dam-break flows over cohesionless mobile beds in prismatic and non-prismatic channels are obtained and discussed

Interpolation and harmonic majorants in big Hardy-Orlicz spaces

Free interpolation in Hardy spaces is caracterized by the well-known Carleson condition. The result extends to Hardy-Orlicz spaces contained in the scale of classical Hardy spaces $H^p$, $p>0$. For the Smirnov and the Nevanlinna classes, interpolating sequences have been characterized in a recent paper in terms of the existence of harmonic majorants (quasi-bounded in the case of the Smirnov class). Since the Smirnov class can be regarded as the union over all Hardy-Orlicz spaces associated with a so-called strongly convex function, it is natural to ask how the condition changes from the Carleson condition in classical Hardy spaces to harmonic majorants in the Smirnov class. The aim of this paper is to narrow down this gap from the Smirnov class to ``big'' Hardy-Orlicz spaces. More precisely, we characterize interpolating sequences for a class of Hardy-Orlicz spaces that carry an algebraic structure and that are strictly bigger than $\bigcup_{p>0} H^p$. It turns out that the interpolating sequences are again characterized by the existence of quasi-bounded majorants, but now the weights of the majorants have to be in suitable Orlicz spaces. The existence of harmonic majorants in such Orlicz spaces will also be discussed in the general situation. We finish the paper with an example of a separated Blaschke sequence that is interpolating for certain Hardy-Orlicz spaces without being interpolating for slightly smaller ones.Comment: 19 pages, 2 figure

HI Narrow Line Absorption in Dark Clouds

We have used the Arecibo telescope to carry out an survey of 31 dark clouds in the Taurus/Perseus region for narrow absorption features in HI ($\lambda$ 21cm) and OH (1667 and 1665 MHz) emission. We detected HI narrow self--absorption (HINSA) in 77% of the clouds that we observed. HINSA and OH emission, observed simultaneously are remarkably well correlated. Spectrally, they have the same nonthermal line width and the same line centroid velocity. Spatially, they both peak at the optically--selected central position of each cloud, and both fall off toward the cloud edges. Sources with clear HINSA feature have also been observed in transitions of CO, \13co, \c18o, and CI. HINSA exhibits better correlation with molecular tracers than with CI. The line width of the absorption feature, together with analyses of the relevant radiative transfer provide upper limits to the kinetic temperature of the gas producing the HINSA. Some sources must have a temperature close to or lower than 10 K. The correlation of column densities and line widths of HINSA with those characteristics of molecular tracers suggest that a significant fraction of the atomic hydrogen is located in the cold, well--shielded portions of molecular clouds, and is mixed with the molecular gas. The average number density ratio [HI]/[\h2] is $1.5\times10^{-3}$. The inferred HI density appears consistent with but is slightly higher than the value expected in steady state equilibrium between formation of HI via cosmic ray destruction of H$_2$ and destruction via formation of H$_2$ on grain surfaces. The distribution and abundance of atomic hydrogen in molecular clouds is a critical test of dark cloud chemistry and structure, including the issues of grain surface reaction rates, PDRs, circulation, and turbulent diffusion.Comment: 40 pages, 10 figures, accepted by Ap

Sudden cardiac death in patients with ischemic heart failure undergoing coronary artery bypass grafting results from the STICH randomized clinical trial (Surgical Treatment for Ischemic Heart Failure)

Background—The risk of sudden cardiac death (SCD) in patients with heart failure following CABG has not been examined in a contemporary clinical trial of surgical revascularization. This analysis describes the incidence, timing and clinical predictors of SCD after CABG. Methods—Patients enrolled in the Surgical Treatment of Ischemic Heart Failure (STICH) trial who underwent CABG with or without surgical ventricular reconstruction (SVR) were included. We excluded patients with prior ICD and those randomized only to medical therapy. The primary outcome was SCD as adjudicated by a blinded committee. A Cox model was used to examine and identify predictors of SCD. The Fine and Gray method was used to estimate the incidence of SCD accounting for the competing risk of other deaths. Results—Over a median follow-up of 46 months, 113 patients of 1411 patients who received CABG without (n = 934) or with SVR (n = 477) had SCD; 311 died of other causes. The mean LVEF at enrollment was 28±9%. The 5-year cumulative incidence of SCD was 8.5%. Patients who had SCD and those who did not die were younger and had fewer comorbid conditions than those who died for reasons other than SCD. In the first 30 days after CABG, SCD (n=5) accounted for 7% of all deaths. The numerically greatest monthly rate of SCD was in the 31-90 day time period. In a multivariable analysis including baseline demographics, risk factors, coronary anatomy and LV function, ESVI and BNP were most strongly associated with SCD. Conclusions—The monthly risk of SCD shortly after CABG among patients with a low LVEF is highest between the first and third month, suggesting that risk stratification for SCD should occur early in the postoperative period, particularly in patients with increased preoperative ESVI and/or BNP

Population pharmacokinetics of meropenem administered as a prolonged infusion in children with cystic fibrosis

OBJECTIVES: Meropenem is frequently used to treat pulmonary exacerbations in children with cystic fibrosis (CF) in the USA. Prolonged-infusion meropenem improves the time that free drug concentrations remain above the MIC (fT> MIC) in adults, but data in CF children are sparse. We describe the population pharmacokinetics, tolerability and treatment burden of prolonged-infusion meropenem in CF children. METHODS: Thirty children aged 6-17 years with a pulmonary exacerbation received 40 mg/kg meropenem every 8 h; each dose was administered as a 3 h infusion. Pharmacokinetics were determined using population methods in Pmetrics. Monte Carlo simulation was employed to compare 0.5 with 3 h infusions to estimate the probability of pharmacodynamic target attainment (PTA) at 40% fT> MIC. NCT#01429259. RESULTS: A two-compartment model fitted the data best with clearance and volume predicted by body weight. Clearance and volume of the central compartment were 0.41 ± 0.23 L/h/kg and 0.30 ± 0.17 L/kg, respectively. Half-life was 1.11 ± 0.38 h. At MICs of 1, 2 and 4 mg/L, PTAs for the 0.5 h infusion were 87.6%, 70.1% and 35.4%, respectively. The prolonged infusion increased PTAs to >99% for these MICs and achieved 82.8% at 8 mg/L. Of the 30 children, 18 (60%) completed treatment with prolonged infusion; 5 did so at home without any reported burden. Nine patients were changed to a 0.5 h infusion when discharged home. CONCLUSIONS: In these CF children, meropenem clearance was greater compared with published values from non-CF children. Prolonged infusion provided an exposure benefit against pathogens with MICs ≥1 mg/L, was well tolerated and was feasible to administer in the hospital and home settings, the latter depending on perception and family schedule