Global Monitoring for Environment and Security (GMES) is the European programme to establish a European capacity for Earth Observation. GMES is designed to provide European policy makers and public ...authorities with accurate and timely information to better manage the environment, understand and mitigate the effects of climate change and ensure civil security. Sentinel-3 is an Earth observation satellite mission specifically designed for GMES to ensure the long-term collection and operational delivery of high-quality measurements to GMES ocean, land, and atmospheric services, while contributing to the GMES, emergency and security services. Key Sentinel-3 measurement requirements, corresponding to identified GMES user needs, have been derived as follows:•Sea surface topography (SSH), significant wave height (Hs) and surface wind speed derived over the global ocean to an equivalent accuracy and precision as that presently achieved by ENVISAT Radar Altimeter-2 (RA-2) but with enhanced surface topography measurements in the coastal zone, sea ice regions and over inland rivers, their tributaries and lakes.•Sea surface temperature (SST) determined for oceanic and coastal waters globally to an equivalent accuracy and precision as that presently achieved by the ENVISAT Advanced Along Track Scanning Radiometer (AATSR) over the ocean (i.e. <0.3K), at a spatial resolution of 1km.•Visible, and Short-Wave Infrared radiances for oceanic, inland and coastal waters at a spatial resolution of 0.3km (simultaneously and co-registered with SST measurements), determined to an equivalent level of accuracy and precision as ENVISAT Medium Resolution Imaging Spectrometer with complete ocean coverage in 2–3days.•Visible and infrared radiances over global land-surfaces in 1–2days, sea-ice and ice-sheets equivalent to those currently provided from ENVISAT MERIS, AATSR and Système Probatoire d'Observation de la Terre (SPOT) Vegetation.
The Sentinel-3 mission addresses these requirements by implementing and operating:•A dual frequency, Synthetic Aperture Radar Altimeter (SRAL) instrument supported by a dual frequency passive microwave radiometer (MWR) for wet-tropospheric correction, a Precise Orbit Determination package including a GPS receiver, a DORIS instrument and a laser retro-reflector.•A highly sensitive Ocean and Land Colour Imager (OLCI) delivering multi-channel wide-swath optical measurements for ocean and land surfaces.•A dual-view Sea and Land Surface Temperature Radiometer (SLSTR) delivering accurate surface ocean, land, and ice temperature.•A collaborative ground segment providing management of the mission, management, development, production and access to core data products in an operational near real time delivery context.
The mission foresees a series of satellites, each having 7-year lifetime, over a 20-year period starting with the launch of Sentinel-3A in late 2013 and of Sentinel-3B in late 2014. During full operations two identical satellites will be maintained in the same orbit with a phase delay of 180°.
This paper provides an overview of the GMES Sentinel-3 mission including the mission background and user requirements, a technical description of the space segment, a brief overview of the ground segment concept, and a summary description of Sentinel-3 data products and their anticipated performance.
► A new satellite mission called Sentinel-3 dedicated to oceanography is described. ► A technical overview of the Sentinel-3 instrument payload is presented. ► A summary of the Sentinel-3 ground segment and operations concept is presented. ► A summary of products derived from Sentinel-3 payload instruments is presented.
We previously demonstrated that beta II protein kinase C (βIIPKC) activity is elevated in failing hearts and contributes to this pathology. Here we report that βIIPKC accumulates on the mitochondrial ...outer membrane and phosphorylates mitofusin 1 (Mfn1) at serine 86. Mfn1 phosphorylation results in partial loss of its GTPase activity and in a buildup of fragmented and dysfunctional mitochondria in heart failure. βIIPKC siRNA or a βIIPKC inhibitor mitigates mitochondrial fragmentation and cell death. We confirm that Mfn1-βIIPKC interaction alone is critical in inhibiting mitochondrial function and cardiac myocyte viability using SAMβA, a rationally-designed peptide that selectively antagonizes Mfn1-βIIPKC association. SAMβA treatment protects cultured neonatal and adult cardiac myocytes, but not Mfn1 knockout cells, from stress-induced death. Importantly, SAMβA treatment re-establishes mitochondrial morphology and function and improves cardiac contractility in rats with heart failure, suggesting that SAMβA may be a potential treatment for patients with heart failure.
Acetylcholinesterase (AChE) enzymes play an essential role in the development of Alzheimer's disease (AD). Its excessive activity causes several neuronal problems, particularly psychopathies and ...neuronal cell death. A bioactive pose on the
AChE B site of the human acetylcholinesterase (
AChE) enzyme employed in this investigation, which was obtained from the Protein Data Bank (PDB ID 4EY6), allowed for the prediction of the binding affinity and free binding energy between the protein and the ligand. Virtual screening was performed to obtain structures similar to Galantamine (GNT) with potential
AChE activity. The top 200 hit compounds were prioritized through the use of filters in ZincPharmer, with special features related to the pharmacophore. Critical analyses were carried out, such as hierarchical clustering analysis (HCA), ADME/Tox predictions, molecular docking, molecular simulation studies, synthetic accessibility (SA), lipophilicity, water solubility, and hot spots to confirm the stable binding of the two promising molecules (ZINC16951574-LMQC2, and ZINC08342556-LMQC5). The metabolism prediction, with metabolites M3-2, which is formed by Glutathionation reaction (Phase II), M1-2, and M2-2 formed from the reaction of S-oxidation and Aliphatic hydroxylation (Phase I), were both reactive but with no side effects. Theoretical synthetic routes and prediction of synthetic accessibility for the most promising compounds are also proposed. In conclusion, this study shows that in silico modeling can be used to create new drug candidate inhibitors for
AChE. The compounds ZINC16951574-LMQC2, and ZINC08342556-LMQC5 are particularly promising for oral administration because they have a favorable drug-likeness profile, excellent lipid solubility, high bioavailability, and adequate pharmacokinetics.
Raman Signature of Graphene Superlattices Carozo, Victor; Almeida, Clara M; Ferreira, Erlon H. M ...
Nano letters,
11/2011, Letnik:
11, Številka:
11
Journal Article
Recenzirano
When two identical two-dimensional periodic structures are superposed, a mismatch rotation angle between the structures generates a superlattice. This effect is commonly observed in graphite, where ...the rotation between graphene layers generates Moiré patterns in scanning tunneling microscopy images. Here, a study of intravalley and intervalley double-resonance Raman processes mediated by static potentials in rotationally stacked bilayer graphene is presented. The peak properties depend on the mismatch rotation angle and can be used as an optical signature for superlattices in bilayer graphene. An atomic force microscopy system is used to produce and identify specific rotationally stacked bilayer graphenes that demonstrate the validity of our model.
Iron deficiency is one of the main causes of chlorosis in plants, which leads to losses in field crops quality and yield. The use of synthetic chelates to prevent or correct iron-deficiency is not ...satisfactory mainly due to their poor biodegradability. The present work aimed to search suitable microorganisms to produce alternative, environment-friendly iron-chelating agents (siderophores). For this purpose, the performance of five bacteria (
Azotobacter vinelandii
,
Bacillus megaterium
,
Bacillus subtilis
,
Pantoea allii
and
Rhizobium radiobacter
) was evaluated, regarding siderophore production kinetics, level of siderophore production (determined by chrome azurol S, CAS method), type of siderophore produced (using Arnow and Csaky’s tests) and iron-chelating capacity at pH 9.0. All bacteria were in stationary phase at 24 h, except
A. vinelandii
(at 72 h) and produced the maximum siderophore amount (80–140 µmol L
−1
) between 24 and 48 h, with the exception of
A. vinelandii
(at 72 h). The analysis of culture filtrates revealed the presence of catechol-type siderophores for
B. subtilis
and
R. radiobacter
and hydroxamate-type siderophores for
B. megaterium
and
P. allii
. In the case of
A. vinelandii
, both siderophore-types (catechol and hydroxamates) were detected. The highest iron-chelating capacity, at pH 9.0, was obtained by
B. megaterium
followed by
B. subtilis
and
A. vinelandii.
Therefore, these three bacteria strains are the most promising bacteria for siderophore production and chlorosis correction under alkaline conditions.
In order to address the ever-increasing problem of the world's population food needs, the optimization of farming crops yield, the combat of iron deficiency in plants (chlorosis) and the ...elimination/reduction of crop pathogens are of key challenges to solve. Traditional ways of solving these problems are either unpractical on a large scale (e.g. use of manure) or are not environmental friendly (e.g. application of iron-synthetic fertilizers or indiscriminate use of pesticides). Therefore, the search for greener substitutes, such as the application of siderophores of bacterial source or the use of plant-growth promoting bacteria (PGPB), is presented as a very promising alternative to enhance yield of crops and performance. However, the use of microorganisms is not a risk-free solution and the potential biohazards associated with the utilization of bacteria in agriculture should be considered. The present work gives a current overview of the main mechanisms associated with the use of bacteria in the promotion of plant growth. The potentiality of several bacterial genera (Azotobacter, Azospirillum, Bacillus, Pantoea, Pseudomonas and Rhizobium) regarding to siderophore production capacity and other plant growth-promoting properties are presented. In addition, the field performance of these bacteria genera as well as the biosafety aspects related with their use for agricultural proposes are reviewed and discussed.
Display omitted
•The usefulness of bacteria for solving main agriculture problems is critically reviewed.•Biosafety aspects linked with the use of PGPB in agriculture practices are discussed.•An up to date overview of the main mechanisms associated with the use of PGPB is presented.•The potentialities of several bacterial genera regarding their PGP properties are reviewed.•Applied studies (field performance) of PGPB are presented.
The design, synthesis, and evaluation of novel non-steroidal anti-inflammatory drugs (NSAIDs) with better activity and lower side effects are big challenges today. In this work, two ...5-acetamido-2-hydroxy benzoic acid derivatives were proposed, increasing the alkyl position (methyl) in an acetamide moiety, and synthesized, and their structural elucidation was performed using 1H NMR and 13C NMR. The changes in methyl in larger groups such as phenyl and benzyl aim to increase their selectivity over cyclooxygenase 2 (COX-2). These 5-acetamido-2-hydroxy benzoic acid derivatives were prepared using classic methods of acylation reactions with anhydride or acyl chloride. Pharmacokinetics and toxicological properties were predicted using computational tools, and their binding affinity (kcal/mol) with COX-2 receptors (Mus musculus and Homo sapiens) was analyzed using docking studies (PDB ID 4PH9, 5KIR, 1PXX and 5F1A). An in-silico study showed that 5-acetamido-2-hydroxy benzoic acid derivates have a better bioavailability and binding affinity with the COX-2 receptor, and in-vivo anti-nociceptive activity was investigated by means of a writhing test induced by acetic acid and a hot plate. PS3, at doses of 20 and 50 mg/kg, reduced painful activity by 74% and 75%, respectively, when compared to the control group (20 mg/kg). Regarding the anti-nociceptive activity, the benzyl showed reductions in painful activity when compared to acetaminophen and 5-acetamido-2-hydroxy benzoic acid. However, the proposed derivatives are potentially more active than 5-acetamido-2-hydroxy benzoic acid and they support the design of novel and safer derivative candidates. Consequently, more studies need to be conducted to evaluate the different pharmacological actions, the toxicity of possible metabolites that can be generated, and their potential use in inflammation and pain therapy.
We previously reported that facilitating the clearance of damaged mitochondria through macroautophagy/autophagy protects against acute myocardial infarction. Here we characterize the impact of ...exercise, a safe strategy against cardiovascular disease, on cardiac autophagy and its contribution to mitochondrial quality control, bioenergetics and oxidative damage in a post-myocardial infarction-induced heart failure animal model. We found that failing hearts displayed reduced autophagic flux depicted by accumulation of autophagy-related markers and loss of responsiveness to chloroquine treatment at 4 and 12 wk after myocardial infarction. These changes were accompanied by accumulation of fragmented mitochondria with reduced O
2
consumption, elevated H
2
O
2
release and increased Ca
2+
-induced mitochondrial permeability transition pore opening. Of interest, disruption of autophagic flux was sufficient to decrease cardiac mitochondrial function in sham-treated animals and increase cardiomyocyte toxicity upon mitochondrial stress. Importantly, 8 wk of exercise training, starting 4 wk after myocardial infarction at a time when autophagy and mitochondrial oxidative capacity were already impaired, improved cardiac autophagic flux. These changes were followed by reduced mitochondrial number:size ratio, increased mitochondrial bioenergetics and better cardiac function. Moreover, exercise training increased cardiac mitochondrial number, size and oxidative capacity without affecting autophagic flux in sham-treated animals. Further supporting an autophagy mechanism for exercise-induced improvements of mitochondrial bioenergetics in heart failure, acute in vivo inhibition of autophagic flux was sufficient to mitigate the increased mitochondrial oxidative capacity triggered by exercise in failing hearts. Collectively, our findings uncover the potential contribution of exercise in restoring cardiac autophagy flux in heart failure, which is associated with better mitochondrial quality control, bioenergetics and cardiac function.
Postpartum hemorrhage is the most common cause of maternal death. Oxytocin is the standard therapy for the prevention of postpartum hemorrhage, but it requires cold storage, which is not available in ...many countries. In a large trial, we compared a novel formulation of heat-stable carbetocin with oxytocin.
We enrolled women across 23 sites in 10 countries in a randomized, double-blind, noninferiority trial comparing intramuscular injections of heat-stable carbetocin (at a dose of 100 μg) with oxytocin (at a dose of 10 IU) administered immediately after vaginal birth. Both drugs were kept in cold storage (2 to 8°C) to maintain double-blinding. There were two primary outcomes: the proportion of women with blood loss of at least 500 ml or the use of additional uterotonic agents, and the proportion of women with blood loss of at least 1000 ml. The noninferiority margins for the relative risks of these outcomes were 1.16 and 1.23, respectively.
A total of 29,645 women underwent randomization. The frequency of blood loss of at least 500 ml or the use of additional uterotonic agents was 14.5% in the carbetocin group and 14.4% in the oxytocin group (relative risk, 1.01; 95% confidence interval CI, 0.95 to 1.06), a finding that was consistent with noninferiority. The frequency of blood loss of at least 1000 ml was 1.51% in the carbetocin group and 1.45% in the oxytocin group (relative risk, 1.04; 95% CI, 0.87 to 1.25), with the confidence interval crossing the margin of noninferiority. The use of additional uterotonic agents, interventions to stop bleeding, and adverse effects did not differ significantly between the two groups.
Heat-stable carbetocin was noninferior to oxytocin for the prevention of blood loss of at least 500 ml or the use of additional uterotonic agents. Noninferiority was not shown for the outcome of blood loss of at least 1000 ml; low event rates for this outcome reduced the power of the trial. (Funded by Merck Sharpe & Dohme; CHAMPION Australian New Zealand Clinical Trials Registry number, ACTRN12614000870651 ; EudraCT number, 2014-004445-26 ; and Clinical Trials Registry-India number, CTRI/2016/05/006969 .).
T-cell prolymphocytic leukemia (T-PLL) is a rare and poor-prognostic mature T-cell malignancy. Here we integrated large-scale profiling data of alterations in gene expression, allelic copy number ...(CN), and nucleotide sequences in 111 well-characterized patients. Besides prominent signatures of T-cell activation and prevalent clonal variants, we also identify novel hot-spots for CN variability, fusion molecules, alternative transcripts, and progression-associated dynamics. The overall lesional spectrum of T-PLL is mainly annotated to axes of DNA damage responses, T-cell receptor/cytokine signaling, and histone modulation. We formulate a multi-dimensional model of T-PLL pathogenesis centered around a unique combination of TCL1 overexpression with damaging ATM aberrations as initiating core lesions. The effects imposed by TCL1 cooperate with compromised ATM toward a leukemogenic phenotype of impaired DNA damage processing. Dysfunctional ATM appears inefficient in alleviating elevated redox burdens and telomere attrition and in evoking a p53-dependent apoptotic response to genotoxic insults. As non-genotoxic strategies, synergistic combinations of p53 reactivators and deacetylase inhibitors reinstate such cell death execution.
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