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In 2014, germline signal transducer and activator of transcription (STAT) 3 gain-of-function (GOF) mutations were first described to cause a novel multisystem disease of early-onset lymphoproliferation and autoimmunity. This pivotal cohort study defines the scope, natural history, treatment, and overall survival of a large global cohort of patients with pathogenic STAT3 GOF variants. We identified 191 patients from 33 countries with 72 unique mutations. Inclusion criteria included symptoms of immune dysregulation and a biochemically confirmed germline heterozygous GOF variant in STAT3. Overall survival was 88%, median age at onset of symptoms was 2.3 years, and median age at diagnosis was 12 years. Immune dysregulatory features were present in all patients: lymphoproliferation was the most common manifestation (73%); increased frequencies of double-negative (CD4 − CD8 −) T cells were found in 83% of patients tested. Autoimmune cytopenias were the second most common clinical manifestation (67%), followed by growth delay, enteropathy, skin disease, pulmonary disease, endocrinopathy, arthritis, autoimmune hepatitis, neurologic disease, vasculopathy, renal disease, and malignancy. Infections were reported in 72% of the cohort. A cellular and humoral immunodeficiency was observed in 37% and 51% of patients, respectively. Clinical symptoms dramatically improved in patients treated with JAK inhibitors, while a variety of other immunomodulatory treatment modalities were less efficacious. Thus far, 23 patients have undergone bone marrow transplantation, with a 62% survival rate. : STAT3 GOF patients present with a wide array of immune-mediated disease including lymphoproliferation, autoimmune cytopenias, and multisystem autoimmunity. Patient care tends to be siloed, without a clear treatment strategy. Thus, early identification and prompt treatment implementation are lifesaving for STAT3 GOF syndrome. [ABSTRACT FROM AUTHOR]

• Trajectory analysis could be used to determine the deviation of aircraft trajectories. • Predicting deviation patterns in the airspace helps to improve air traffic control. • Determining where/when are conflicts produced help to release the airspace. • London's terminal airspace contains high-adherence and low-adherence routes. This paper proposes a methodology to characterize and evaluate the performance of the aircraft operation in complex systemized terminal manoeuvring area based on the study of its standard routes structure and their actual traffic. The methodology is composed of two main components. The first component identifies recurrent patterns by calculating the 4D adherence to the standard routes and flight plan. This process is based on the comparison of the Spatio-Temporal (S-T) differences between the actual and planned trajectories. The second component identifies and characterizes concurrence events based on the analysis of the standard routes and the along-track deviation derived from the first component to analyze the causes that produce recurrent patterns in the terminal airspace. The developed framework is applied to a study case of a representative Multi-Airport System (MAS). The quantitative effectiveness of the framework is derived by simulations using historical traffic data samples of the London Terminal Manoeuvring Area (LTMA). [ABSTRACT FROM AUTHOR]

• New departure synchronization mechanism in a Multi-Airport system to reduce the probability of separation minima infringement. • Airspace digitalization for efficient potential concurrence event detection and mitigation. • New interdependency metrics for reducing downstream domino effects in ATM. • Rolling horizon methodology for detecting concurrence events, analysing their trajectory interdependencies and applying a strategic mitigation measure that shifts the Estimated Take-Off Time (ETOT) within the assigned Calculated Take-Off Time (CTOT) window. • Use Constraint Programming models supporting optimal mitigation measures. • Experimental work showing the potential benefits of such a STAM procedures by applying the methodology to distribute the demand of a sector located in the London Terminal Manoeuvring Area (LTMA). Pre-tactically managing the imbalances of the network and organizing the resources of the airspace is one of the main objectives of Dynamic Demand & Capacity Balancing (dDCB). Introducing Short-term Air Traffic Flow and Capacity Management (STAM) measures such as minor ground delays or slight speed adjustments applied to a selected number of flights on the day of operations, supports the dDCB process by reducing the traffic complexity and the probability of Air Traffic Controllers interventions. This paper introduces a rolling horizon methodology for detecting concurrence events, analysing their trajectory interdependencies and applying a strategic mitigation measure that shifts the Estimated Take-Off Time (ETOT) within the assigned Calculated Take-Off Time (CTOT) window. The methodology proposes a collaborative decision-making process for a better coordination of departures from airports feeding airspace volumes with high air traffic demand. The experimental part of this paper aims at showing the potential benefits of such a STAM procedure by applying the methodology to distribute the demand of a sector located in the London Terminal Manoeuvring Area (LTMA). Experiments have considered regulated traffic scenarios where ETOT were allocated in order to reduce departure time uncertainties. Lastly, it is analysed the impact of the parameters used by the methodology to calculate the mitigation measures: safe separation criteria, look-ahead time and number of coordinated airports. [ABSTRACT FROM AUTHOR]

The economic sustainability of guayule (Parthenium argentatum A. Gray) cultivation will largely depend on its profitability, which drives strategies for the integral utilization of its biomass. Because guayule resin has been proposed as a broad-spectrum biopesticide, the aim of the present study was to test and compare its bioactivity against the agricultural pest Labidostomis lusitanica (Coleoptera: Chrysomelidae) Germar, with essential oils (EOs) from thyme (Thymus vulgaris L.), savory (Satureja montana L.), and oregano (Origanum vulgare L.). Repellency, oviposition and feeding inhibition activity were measured using free choice assays under controlled conditions, and minimal inhibitory concentrations of guayule resin fractions and isolated compounds were determined. Finally, guayule resin was tested under simulated field conditions. Results showed that the solvent used to dissolve and apply the resin had a great impact on its performance. Guayule crude resin was more active than tested EOs, particularly as an antifeedant. However, its activity did not seem to be concentration dependent, and was effective within a narrow range. In contrast to low molecular-weight rubber (LMWR), which acted as attractant, the refined resin was repellent. Nevertheless, the two different enriched resin fractions, with sesquiterpene bioactive compounds acted as attractants and feeding stimulants, as well as the isolated compounds. In the semi-field trial, crude guayule resin again showed repellency and feeding deterrence, with no mortality, overall suggesting that while guayule resin is active against L. lusitanica , the compounds responsible for this activity are likely not the sesquiterpenes. • Guayule resin does not cause mortality on Labidostomis lusitanica. • Guayule resin shows antifeedant activity against Labidostomis lusitanica. • The activity is due to the synergistic effect between compounds. • The solvent used to dissolve the resin has a great impact on its bioactivity. [ABSTRACT FROM AUTHOR]

The genomic features of Azoarcus sp. CIB reflect its most distinguishing phenotypes as a diazotroph, facultative anaerobe, capable of degrading either aerobically and/or anaerobically a wide range of aromatic compounds, including some toxic hydrocarbons such as toluene and m -xylene, as well as its endophytic lifestyle. The analyses of its genome have expanded the catabolic potential of strain CIB toward common natural compounds, such as certain diterpenes, that were not anticipated as carbon sources. The high number of predicted solvent efflux pumps and heavy metal resistance gene clusters has provided the first evidence for two environmentally relevant features of this bacterium that remained unknown. Genome mining has revealed several gene clusters likely involved in the endophytic lifestyle of strain CIB, opening the door to the molecular characterization of some plant growth promoting traits. Horizontal gene transfer and mobile genetic elements appear to have played a major role as a mechanism of adaptation of this bacterium to different lifestyles. This work paves the way for a systems biology-based understanding of the abilities of Azoarcus sp. CIB to integrate aerobic and anaerobic metabolism of aromatic compounds, tolerate stress conditions, and interact with plants as an endophyte of great potential for phytostimulation and phytoremediation strategies. Comparative genomics provides an Azoarcus pan genome that confirms the global metabolic flexibility of this genus, and suggests that its phylogeny should be revisited. [ABSTRACT FROM AUTHOR]

Abstract: Different dehydrated waste grape skins from the juice industry were added into aged and young red wines as an innovative way of compensating for colour loss before bottling. After addition of grape skins, colour intensity of wines increased a mean 11% and a maximum of 31% with predominance of the red component. Total polyphenols mean increase was 10% with a maximum value of 20%. Analysis of low molecular weight phenolic compounds by HPLC–DAD showed a significant (p <0.05) content increase of the bioactive compounds gallic acid, (+)-catechin, (−)-epicatechin, and (E)-resveratrol. Anthocyanins content also increased at an average of 50mg/l. The volatile profile of wines analysed by SBSE–GC–MS was only moderately influenced by the treatments. Mixtures of dehydrated waste grape skins were useful to improve the colour and polyphenol profile of red wines, considering them a useful tool for correcting colour loss before bottling. [Copyright &y& Elsevier]

Abstract: A preliminary study of the bulk hydrogen, carbon and nitrogen stable isotope composition of 28 authentic saffron samples produced from Crocus sativus L. cultivated in the typical production areas of Western Macedonia in Greece (8), Khorasan Province in Iran (7), Sardinia in Italy (6) and Castilla-La Mancha in Spain (7) is described. A chemical characterisation of 16 key quality parameters was also completed on the same samples by UV–Vis, HPLC and GC analyses. Multivariate analysis of the data revealed that 60.7% of saffron samples could be correctly assigned to their respective production countries using the chemical parameters. However, the combined bio-element stable isotope data reliably classified 100% of the saffron samples according to their respective geographical origins using posterior cross validation. Further work is required to establish the long-term stability of these models with respect to different years of production and other major producers such as India and Morocco. [Copyright &y& Elsevier]

Abstract: Seventy-three saffron samples belonging to three different storage time (<1year, 3–4 and 8–9years) were analysed using ultrasound assisted extraction-gas chromatography–mass spectrometry and ultrasound assisted extraction-gas chromatography–olfactometry. Nineteen volatile compounds were identified and their aromatic notes were assigned. In addition to safranal, the main compound found, (30.14–43.94% in mass of total volatiles), other major compounds were 4-hydroxy-2,6,6-trimethyl-1-cyclohexen-1-carboxaldehyde and 3,5,5-trimethyl-2-cyclohexene-1-one. These compounds were significantly different for less than 1year storage when compared with the 3–4 and 8–9years of storage, although the minor constituents 2-hydroxy-3,5,5-trimethylcyclohex-2-en-1,4-dione and isomer of 4-hydroxy-3,5,5-trimethyl-2-cyclohex-1-one varied significantly for all three harvests. Positive and negative aroma descriptors were related with the overall saffron chemical volatile composition. Saffron with less than 1year storage contained a higher proportion of saffron, flower and spicy descriptors, while the oldest saffrons (3–4 and 8–9years of storage) contained volatiles with vegetal, caramel and citrus notes. The aromatic notes that contributed most to saffron storage differentiation are spicy, freshly cut grass and vegetable. [Copyright &y& Elsevier]

Abstract: The application of solid phase extraction (SPE) in the determination of picrocrocin by UV–vis spectrophotometry has been studied in order to develop a rapid and low cost method that can be used in the industry for routine quality control of saffron spice. Parameters influencing the SPE procedure, such as concentration of the initial extract, sample size and eluents, were studied and optimized. Twenty different saffron spice samples from Greece, Iran, Italy and Spain were used in the intra-laboratory validation of the SPE method. The results indicated the selectivity, trueness, linearity, precision (repeatability: RSD<6%, intermediate precision: RSD<10%), good recovery (about 90%) and sensitivity (LOD=0.30mgL−1; LOQ=0.63mgL−1). The method also proved valid for overcoming the limitations of 257nm due to crocetin esters in the determination of picrocrocin. [Copyright &y& Elsevier]

A microbiological study of saffron spice was undertaken in the context of a European research project (Methodologies for Implementing International Standards for Saffron Purity and Quality, the acronym for which is SAFFIC), analyzing 79 samples obtained from the main producer countries, namely Greece, Iran, Italy, Morocco, and Spain. Current microbiological quality criteria are the same as for other spices, but saffron is added in minute quantities during the cooking process, so the health risk associated with microbial contamination might be lower. We did not detect Salmonella either by culture or by PCR methods in any sample, and Escherichia coli was only found in five samples. Enterobacteriaceae were frequently found (70.9% of the samples), but most of them belonged to species of probable environmental origin. Aerobic sporulated bacteria were also common, but only three samples contained Bacillus cereus at low levels (<200 CFU g-1). Clostridium perfringens counts were also very low, with only one sample reaching > 100 CFU g-1, an acceptable value. Overall, microbial contamination in saffron was markedly lower than it was in other spices. [ABSTRACT FROM AUTHOR]

Abstract: The flavonoid fraction in saffron spice has been analysed, for the first time, by LC-DAD-MS/MS ESI and five kaempferol derivatives have been found. Compounds such as kaempferol-3-sophoroside, kaempferol-3-sophoroside-7-glucoside and kaempferol-3,7,4′-triglucoside were tentatively identified, whereas other compounds, such as kaempferol tetrahexoside and kaempferol-3-dihexoside were detected. Saffron samples from different geographical origins were clearly separated by their kaempferol 3-sophoroside contents that were able to explain 100% of the variance when a discriminant test was carried out. [Copyright &y& Elsevier]

Abstract: A simple model has been developed to predict the removal of hydrocarbon fractions from wastewater using sacrificial Al anodes. The model was successfully applied to the interpretation of experimental data obtained in a laboratory electrochemical cell operated in a batchwise manner. The adsorption equilibrium of organic matter on Al hydroxide was modelled using three equations, with the best results obtained using a Langmuir-type equation. The model was able to describe the effects of current density and pollutant concentration on the efficiency of wastewater treatment. Different values were obtained for the parameters depending on the nature of the hydrocarbon suspension. Aluminium hydroxide showed a far higher affinity for the oil/kerosene suspension but exhibited a higher capacity to remove heavy oil suspensions. The removal rates of pollutants were found to depend on the initial concentration and the current density. When the current density was sufficient to destabilise the emulsion, the zeta potential of the clear fraction measured at pH 7.0 became positive. This change was also characterised by a significant reduction in turbidity. Furthermore, the application of higher current densities did not allow further treatment of the water. However, the efficiency of emulsion destabilisation was found to depend on the concentration and current densities that were too low were ineffective. [Copyright &y& Elsevier]

• A time-based horizontal interdependency metric is defined and validated. • The location of the TOD was shown to be statistically dependent on the interdependency measure. • The runway configuration was a key hidden variable impacting on the position of the TOD. • ANN flow-based trajectory predictors demonstrated to maintain their performance on the testing dataset. Air Traffic Management is evolving towards a Trajectory-Based Operations paradigm. Trajectory prediction will hold a key role supporting its deployment, but it is limited by a lack of understanding of air traffic associated uncertainties, specifically contextual factors. Trajectory predictors are usually based on modelling aircraft dynamics based on intrinsic aircraft features. These aircraft operate within a known air route structure and under given meteorological conditions. However, actual aircraft trajectories are modified by the air traffic control depending on potential conflicts with other traffics. This paper introduces surrounding air traffic as a feature for ground-based trajectory prediction. The introduction of air traffic as a contextual factor is addressed by identifying aircraft which are likely to lose the horizontal separation. For doing so, this paper develops a probabilistic horizontal interdependency measure between aircraft supported by machine learning algorithms, addressing time separations at crossing points. Then, vertical profiles of flight trajectories are characterised depending on this factor and other intrinsic features. The paper has focused on the descent phase of the trajectories, using datasets corresponding to an en-route Spanish airspace volume. The proposed interdependency measure demonstrates to identify in advance conflicting situations between pairs of aircraft for this use case. This is validated by identifying associated air traffic control actions upon them and their impact on the vertical profile of the trajectories. Finally, a trajectory predictor for the vertical profile of the trajectory is developed, considering the interdependency measure and other operational factors. The paper concludes that the air traffic can be included as a factor for the trajectory prediction, impacting on the location of the top of descent for the specific case which has been studied. [ABSTRACT FROM AUTHOR]

Quince (Cydonia oblonga Miller) is a seasonal fruit that is commonly processed by the food industry to produce marmalades, jellies and wines, resulting in a large amount of by-products. The filmogenic capacity of quince seeds has been well studied in the literature, but not that of the entire by-product generated in the industry. This work addresses the study of the filmogenic capacity of these by-products, at two formulation levels (QW1 and QW2), and compares them with that of only seeds (QS) in terms of physicochemical, optical, mechanical, morphological, antioxidant and thermal properties. The yield of mucilage obtained from both by-product formulations doubled the obtained from isolated seed (22–27 % vs. 10.9 %) and showed higher tensile strength (106–107 % vs. 85.3 %) and elongation at break values (2–3 vs. 1.9 MPa). The three types of films showed excellent protection properties against UV radiation, attractive optical properties and good DPPH radical scavenging capacity (34–37 %). Microstructural changes over time in the morphology of the three films were also observed by scanning electron microscopy between 24 and 48 h. [Display omitted] • Edible films can be developed from by-products of quince processing. • The obtaining of mucilage from quince by-products is easier than those from seeds. • The quince by-product provides better yields than the seeds. • The quince by-products films have better mechanical properties than those from seeds. [ABSTRACT FROM AUTHOR]

Here we characterized the first known transcriptional regulator that accounts for carbon catabolite repression (CCR) control of the anaerobic catabolism of aromatic compounds in bacteria. The AccR response regulator of Azoarcus sp. CIB controls succinate-responsive CCR of the central pathways for the anaerobic catabolism of aromatics by this strain. Phosphorylation of AccR to AccR-P triggers a monomer-to-dimer transition as well as the ability to bind to the target promoter and causes repression both in vivo and in vitro. Substitution of the Asp60 phosphorylation target residue of the N-terminal receiver motif of AccR to a phosphomimic Glu residue generates a constitutively active derivative that behaves as a superrepressor of the target genes. AccR-P binds in vitro to a conserved inverted repeat (ATGCAN6-TGCAT) present at two different locations within the PN promoter of the bzd genes for anaerobic benzoate degradation. Because the DNA binding-proficient C-terminal domain of AccR is monomeric, we propose an activation mechanism in which phosphorylation of Asp60 of AccR alleviates interdomain repression mediated by the N-terminal domain. The presence of AccR-like proteins encoded in the genomes of other β-proteobacteria of the Azoarcus/Thauera group further suggests that AccR constitutes a master regulator that controls anaerobic CCR in these bacteria. [ABSTRACT FROM AUTHOR]

Abstract: A new sulfonated material from styrene–divinylbenzene copolymer, P(St–DVB), containing di(2-ethylhexyl)phosphoric acid (DEHPA) that combines the advantages and capabilities of the ion exchange and the solvent extraction technologies has been developed. Microcapsules with a DEHPA content of 34.86wt.%, an average particle size of 340.83μm and an equivalent thickness shell of 22.4μm were prepared by suspension-like polymerization technique and further sulfonated. The influence of the chemical nature and properties of the suspending agent on the microcapsules characteristics were studied. The polluting potential of the wastewater generated in the encapsulation process with the different suspending agents was also evaluated. Arabic gum:PVA showed to be the best combination of suspending agent for the process. The incorporation of sulfonic groups to the polymeric network turn the hydrophobic nature of the particle into another with hydrophilic character. The increase of the sulfonation time from 10 to 30min promoted the cracking of the microcapsules (from 24.49 to 75.36wt.%). A total ion exchange capacity of 3.56meqg−1 was achieved. The large ion exchange rate and capacity observed confirm that the sulfonation of the shell makes easier the mobility of the metallic ions from the liquid phase to the extractant agent phase through the shell. It was also observed that the presence of DEHPA into the microcapsules makes them more selective than a conventional ion exchange material. [Copyright &y& Elsevier]

Abstract: A method to determine safranal content based on non-polar solvent extraction followed by UV–Vis analysis available in the industry for quality control of saffron spice has been studied. Ultrasound-assisted extraction of safranal was carried out and optimised with respect to the solvent: diethyl ether, hexane and chloroform; the time of extraction; and the concentration of saffron in each organic solvent. Best extraction conditions were obtained when 20gL−1 of saffron was extracted with chloroform for 15min. Intra-laboratory validation of the optimised conditions and analysis by UV–Vis spectrophotometry showed satisfactory results in linearity, repeatability, intermediate precision and recovery. The limit of detection was 1mg safranal kg−1 saffron and the limit of quantification was 3mg safranal kg−1 saffron. [Copyright &y& Elsevier]

Abstract: A transport mathematical model to describe the performance of ion exchange processes in fixed beds, to use the regeneration curves as a tool to optimize the regeneration process was developed. The model is based on both the Nernst–Planck equation and the mass action law. This model allowed to obtain the optimum amount of regenerant agent to be used, regardless the system considered. Therefore, it would be possible to minimize the final waste volume and maximize the recovered bed capacity without any additional consumption of regenerant agent. The results obtained allowed to conclude that the sodium chloride is better regenerant agent than chlorhydric acid for strong acid resins, because it requires a lower amount of equivalents to reach the same regeneration level and is cheaper. Finally, the concentration of regenerant agent required for copper elution is less than that required for the other ions (Cd2+ and Zn2+). These results were found to agree with the affinity of the resin. [Copyright &y& Elsevier]

Abstract: A generalized theoretical model for the measurement of effective diffusion coefficients of heterovalent ions in macroporous ion-exchange resins by the zero-length column method was developed. The model includes the resistance to mass transfer both in the particle and in the film and described ion fluxes with Nernst–Planck equations. Equilibrium was described using the Langmuir type empirical equation. The values of intraparticle diffusivity of , , , and on commercial Lewatit TP-207 were obtained by non-linear regression, these values agree fairly well with data reported previously in literature. The following trend was observed: . [Copyright &y& Elsevier]

A generalized theoretical model for the measurement of effective diffusion coefficients of heterovalent ions in ion exchange resins by the zero-length column method was developed. The model included the resistance to mass transfer both in the particle and in the film and described ion fluxes with Nernst–Planck equations. Equilibria were described using a model based on the mass action law. The values of intraparticle diffusivity of Cu2+, Cd2+, Zn2+, and H+ on commercial Amberlite IR-120 were obtained by non-linear regression, these values agree fairly well with data reported previously in literature. The following trend was observed: DCu>DZn>DCd. [Copyright &y& Elsevier]