136 research outputs found

    Spatial Evolution of Resonant Harmonic Mode Triads in a Blasius Boundary Layer

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    Blasius boundary layer evolution is studied by means of bicoherence calculations. The layer is acoustically excited at the T-S frequency to provide a controlled transition. Measurements are made using a smooth surface as well as various roughness patterns

    Factors involved in soil organic matter stabilization in Peruvian Amazonian soils (Ucayali region) and the molecular composition of extractable lipids

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    Poster E1012b presentado en el 27th International Meeting on Organic Geochemistry September 13–18, 2015, Prague, Czech RepublicAmazonian ecosystems are considered important sinks for atmospheric CO2 on Earth. It is therefore desirable to preserve their biodiversity and productivity. In this communication an assessment of the influence of different agro-forestry practices on soil C storage in representative ecosystems from the Peruvian Ucayali region is approached by analyzing the soil lipid fraction. In fact, this organic matter fraction is an important source of analytical surrogates of soil C stabilization and accumulation processes (Naafs at al., 2004; Poulenard et al., 2004; Rumpel et al., 2004). Top (0–20 cm) and subsoil (20–40 cm) samples were taken from the Amazonian Ucayali region (Pucallpa, Perú), ranging from recent alluvial soils in muddy zones of riverside areas (wetlands referred to as ‘mud’, ‘beach’ and low ‘restinga’ soils) to more developed soils located in medium and higher riverine terraces, as well as in hills. The lipid fraction was Soxhlet extracted with a mixture of ichloromethane:methanol (2:1 by vol.), saponified and divided into neutral and acid subfractions. The acid fractions were then sequentially methylated and silylated prior to the chromatographic analysis (González-Vila et al., 2003). Neutral and acid sub-fractions were separated and the major compounds were identified by gas chromatography-mass spectrometry using an HP G1800A GCD System (electron impact detector at 70 eV) equipped with a DB-5 fused silica capillary column (30 m × 0.32 mm i.d., film thickness 0.25 µm) and using He as carrier gas at a flow rate of 1.5 mL min-1. The chromatographic oven temperature was programmed to increase from 40 to 100 ºC at 30 ºC min-1 and then to 300 ºC at 6 ºC min -1. The values of soil organic matter and lipids ranged from 25.8 to 5.8 g kg-1, and from 5.2 to 0.2 g kg-1, respectively. This variability as well as the differences in lipid molecular composition could suggest differences in the soils’ use and management practices (Van Bergen et al.,1996). The main families of signature lipids detected in the soil extracts were n-alkanes, linear isoprenoids, cyclic alkanes, n-fatty acids, branched fatty acids, unsaturated fatty acids, hydroxyacids, n-alcohols, ketones, polycyclic hydrocarbons and sterols. Very significant differences in qualitative and quantitative lipid composition were found in terms of soil depth. This effect was more pronounced in the soils from the riverine high terraces devoted to agro-forestry practices (Figs. 1 and 2). In addition, lipidic compounds of high molecular weight (i.e., di- and triterpenes) were detected as regular components of the free lipid fractions from the different ecosystems (wetlands, terraces and hills) reflecting specific vegetation and soil-use influences. Xenobiotic compounds (naphthenic acids) detected within the unresolved chromatographic ‘hump’ (highly unresolved mixture of cyclic or branched hydrocarbons) were also observed, indicating anthropogenic contamination by mineral oils. Likewise, dialkyl phthalates (Phth) from plasticizers were also detected.Projects CGL2012-38655-C04-01 and CGL2008-04296 and fellowship BES-2013-062573 given to N.T.J.M by the Spanish Ministry of Economy and Competitiveness. Dr. J.M.R. is the recipient of a fellowship from the JAE-Doc subprogram financed by the CSIC and the European Social Fund.Peer Reviewe

    Dissecting the role of TP53 alterations in del(11q) chronic lymphocytic leukemia

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    © 2021 The Authors.[Background]: Several genetic alterations have been identified as driver events in chronic lymphocytic leukemia (CLL) pathogenesis and oncogenic evolution. Concurrent driver alterations usually coexist within the same tumoral clone, but how the cooperation of multiple genomic abnormalities contributes to disease progression remains poorly understood. Specifically, the biological and clinical consequences of concurrent high-risk alterations such as del(11q)/ATM-mutations and del(17p)/TP53-mutations have not been established.[Methods]: We integrated next-generation sequencing (NGS) and clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 techniques to characterize the in vitro and in vivo effects of concurrent monoallelic or biallelic ATM and/or TP53 alterations in CLL prognosis, clonal evolution, and therapy response.[Results]: Targeted sequencing analysis of the co-occurrence of high-risk alterations in 271 CLLs revealed that biallelic inactivation of both ATM and TP53 was mutually exclusive, whereas monoallelic del(11q) and TP53 alterations significantly co-occurred in a subset of CLL patients with a highly adverse clinical outcome. We determined the biological effects of combined del(11q), ATM and/or TP53 mutations in CRISPR/Cas9-edited CLL cell lines. Our results showed that the combination of monoallelic del(11q) and TP53 mutations in CLL cells led to a clonal advantage in vitro and in in vivo clonal competition experiments, whereas CLL cells harboring biallelic ATM and TP53 loss failed to compete in in vivo xenotransplants. Furthermore, we demonstrated that CLL cell lines harboring del(11q) and TP53 mutations show only partial responses to B cell receptor signaling inhibitors, but may potentially benefit from ATR inhibition.[Conclusions]: Our work highlights that combined monoallelic del(11q) and TP53 alterations coordinately contribute to clonal advantage and shorter overall survival in CLL.Spanish Fondo de Investigaciones Sanitarias, Grant/Award Numbers: PI15/01471, PI18/01500); Fundación Memoria Don Samuel Solórzano Barruso, Grant/Award Number: RD12/0036/006

    Flavonoid-enriched plant-extract-loaded emulsion: a novel phytocosmetic sunscreen formulation with antioxidant properties

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    The aim of this study was to develop a phytocosmetic sunscreen emulsion with antioxidant effect, containing a blend of flavonoid-enriched plant extracts. In vitro sun protection factor, antioxidant activity, skin irritation, photostability, cutaneous permeation, and retention of flavonoids were evaluated. Thermodynamically stable emulsions were obtained and tested for sensorial analysis after loading the blend of extracts. The selected emulsion was stable when stored at low temperatures (5 C), for which after 120 days the concentration of quercetin and rutin were above their limit of quantification, i.e., 2.8 ± 0.39 µg/mL and 30.39 ± 0.39 µg/mL, respectively. Spreadability, low rupture strength and adhesiveness were shown to be similar to a conventional topical product. Higher brittleness, pseudo-plastic, and viscoelastic behaviors were also recorded for the developed phytocosmetic sunscreen. The product presented a critical wavelength of 387.0 nm and ultraviolet rays A and B (UVA/UVB) rate of 0.78, confirming that the developed formulation shows capacity for UVA/UVB protection, protecting skin against damages caused by Ultraviolet (UV) radiation. Rutin was shown to permeate the skin barrier and was also quantified in the stratum corneum (3.27 ± 1.92 µg/mL) by tape stripping and retention test (114.68 ± 8.70 µg/mL). The developed flavonoid-enriched phytocosmetic was shown to be non-irritant to skin by an in vitro assay. Our results confirm the antioxidant activity, sun protection, and physical properties of the developed phytocosmetic for topical application.This research was funded by FAPESP (grant number 2015/25533‐7 and 2017/14757‐7), CAPES and CNPq. The authors also received support from the Portuguese Science and Technology Foundation (FCT/MCT) and from European Funds (PRODER/COMPETE) under the project reference M‐ERA‐NET/0004/2015‐PAIRED, co‐financed by FEDER, under the Partnership Agreement PT2020, and PhD scholarship (SFRH/BD/130555/2017).info:eu-repo/semantics/publishedVersio

    Pembrolizumab as consolidation strategy in patients with multiple myeloma: Results of the GEM-Pembresid clinical trial

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    PD1 expression in CD4+ and CD8+ T cells is increased after treatment in multiple myeloma patients with persistent disease. The GEM-Pembresid trial analyzed the efficacy and safety of pembrolizumab as consolidation in patients achieving at least very good partial response but with persistent measurable disease after first- or second-line treatment. Moreover, the characteristics of the immune system were investigated to identify potential biomarkers of response to pembrolizumab. One out of the 17 evaluable patients showed a decrease in the amount of M-protein, although a potential late effect of high-dose melphalan could not be ruled out. Fourteen adverse events were considered related to pembrolizumab, two of which (G3 diarrhea and G2 pneumonitis) prompted treatment discontinuation and all resolving without sequelae. Interestingly, pembrolizumab induced a decrease in the percentage of NK cells at cycle 3, due to the reduction of the circulating and adaptive subsets (0.615 vs. 0.43, p = 0.007; 1.12 vs. 0.86, p = 0.02). In the early progressors, a significantly lower expression of PD1 in CD8+ effector memory T cells (MFI 1327 vs. 926, p = 0.03) was observed. In conclusion, pembrolizumab used as consolidation monotherapy shows an acceptable toxicity profile but did not improve responses in this MM patient population. The trial was registered at clinicaltrials.gov with identifier NCT02636010 and with EUDRACT number 2015-003359-23

    Natural Course of the Diffusing Capacity of the Lungs for Carbon Monoxide in COPD: Importance of Sex

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    [Background] The value of the single-breath diffusing capacity of the lungs for carbon monoxide (Dlco) relates to outcomes for patients with COPD. However, little is known about the natural course of Dlco over time, intersubject variability, and factors that may influence Dlco progression.[Research Question] What is the natural course of Dlco in patients with COPD over time, and which other factors, including sex differences, could influence this progression?[Study Design and Methods] We phenotyped 602 smokers (women, 33%), of whom 506 (84%) had COPD and 96 (16%) had no airflow limitation. Lung function, including Dlco, was monitored annually over 5 years. A random coefficients model was used to evaluate Dlco changes over time.[Results] The mean (± SE) yearly decline in Dlco % in patients with COPD was 1.34% ± 0.015%/y. This was steeper compared with non-COPD control subjects (0.04% ± 0.032%/y; P = .004). Sixteen percent of the patients with COPD, vs 4.3% of the control subjects, had a statistically significant Dlco % slope annual decline (4.14%/y). At baseline, women with COPD had lower Dlco values (11.37% ± 2.27%; P < .001) in spite of a higher FEV1 % than men. Compared with men, women with COPD had a steeper Dlco annual decline of 0.89% ± 0.42%/y (P = .039).[Interpretation] Patients with COPD have an accelerated decline in Dlco compared with smokers without the disease. However, the decline is slow, and a testing interval of 3 to 4 years may be clinically informative. The lower and more rapid decline in Dlco values in women, compared with men, suggests a differential impact of sex in gas exchange function.[Trial Registry] ClinicalTrials.gov; No.: NCT01122758; URL: www.clinicaltrials.govThis study was funded in part by an unrestricted grant from AstraZeneca, and also by the COPD Research Program of the Spanish Respiratory Society (PII de EPOC of SEPAR).Peer reviewe

    Reaction rate reconstruction from biomass concentration measurement in bioreactors using modified second-order sliding mode algorithms

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    This paper deals with the estimation of unknown signals in bioreactors using sliding observers. Particular attention is drawn to estimate the specific growth rate of microorganisms from measurement of biomass concentration. In a recent article, notions of high-order sliding modes have been used to derive a growth rate observer for batch processes. In this paper we generalize and refine these preliminary results. We develop a new observer with a different error structure to cope with other types of processes. Furthermore, we show that these observers are equivalent, under coordinate transformations and time scaling, to the classical super-twisting differentiator algorithm, thus inheriting all its distinctive features. The new observers’ family achieves convergence to timevarying unknown signals in finite time, and presents the best attainable estimation error order in the presence of noise. In addition, the observers are robust to modeling and parameter uncertainties since they are based on minimal assumptions on bioprocess dynamics. In addition, they have interesting applications in fault detection and monitoring. The observers performance in batch, fed-batch and continuous bioreactors is assessed by experimental data obtained from the fermentation of Saccharomyces Cerevisiae on glucose.This work was supported by the National University of La Plata (Project 2012-2015), the Agency for the Promotion of Science and Technology ANPCyT (PICT2007-00535) and the National Research Council CONICET (PIP112-200801-01052) of Argentina; the Technical University of Valencia (PAID-02-09), the CICYT (DPI2005-01180) and AECID (A/024186/09) of Spain; and by the project FEDER of the European Union.De Battista, H.; Picó Marco, JA.; Garelli, F.; Navarro Herrero, JL. (2012). 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