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Molecular quantum mechanical modeling, accelerated by machine learning, has opened the door to high‐throughput screening campaigns of complex properties, such as the activation energies of chemical reactions and absorption/emission spectra of materials and molecules; in silico. Here, we present an overview of the main principles, concepts, and design considerations involved in such hybrid computational quantum chemistry/machine learning screening workflows, with a special emphasis on some recent examples of their successful application. We end with a brief outlook of further advances that will benefit the field. [ABSTRACT FROM AUTHOR]

Binge drinking is a pattern of intermittent excessive alcohol consumption that is highly prevalent in young people. Neurocognitive dual-process models have described substance abuse and adolescence risk behaviours as the result of an imbalance between an overactivated affective-automatic system (related to motivational processing) and damaged and/or immature reflective system (related to cognitive control abilities). Previous studies have evaluated the reflective system of binge drinkers (BDs) through neutral response inhibition tasks and have reported anomalies in theta (4-8 Hz) and beta (12-30 Hz) bands. The present study aimed to investigate the influence of the motivational value of alcohol-related stimuli on brain functional networks devoted to response inhibition in young BDs. Sixty eight BDs and 78 control participants performed a beverage Go/NoGo task while undergoing electrophysiological recording. Whole cortical brain functional connectivity (FC) was evaluated during successful response inhibition trials (NoGo). BDs exhibited fast-beta and theta hyperconnectivity in regions related to cognitive control. These responses were modulated differently depending on the motivational content of the stimuli. The increased salience of alcohol-related stimuli may lead to overactivation of the affective-automatic system in BDs, and compensatory neural resources of the reflective system will thus be required during response inhibition. In BDs, inhibition of the response to alcohol stimuli may require higher theta FC to facilitate integration of information related to the task goal (withholding a response), while during inhibition of the response to no-alcoholic stimuli, higher fast-beta FC would allow to apply top-down inhibitory control of the information related to the prepotent response. [ABSTRACT FROM AUTHOR]

1,3‐Dipolar cycloadditions are the preferred method to generate five‐membered heterocyclic rings. Surprisingly, cycloadditions based on acyl‐isocyanide ylides have remained underexplored by the chemical community. Acyl‐isocyanide ylides readily react with dipolarophiles, such as substituted alkenes, to yield Δ1‐pyrroline derivatives. As an explanation for the observed reactivity of this reaction is lacking, extensive density functional theory calculations were performed to scrutinize the mechanistic features of the transformation. Herein we explain the experimental outcome of the reaction using a variety of reactivity theories and predict opposed regioselectivity for electron‐poor and electron‐rich dipolarophiles. With the insights obtained, we hope to incentivize the design of new cycloaddition reactions based on the acyl‐isocyanide ylides motif. [ABSTRACT FROM AUTHOR]

The incidence of age‐related dementia is growing with increased longevity, yet there are currently no disease‐modifying therapies for these devastating disorders. Studies over the last several years have led to an evolving awareness of the role of the immune system in supporting brain maintenance and repair, displaying a diverse repertoire of functions while orchestrating the crosstalk between the periphery and the brain. Here, we provide insights into the current understanding of therapeutic targets that could be adopted to modulate immune cell fate, either systemically or locally, to defeat brain aging and neurodegeneration. [ABSTRACT FROM AUTHOR]

Summary: Avocado seed was first washed, dehydrated, and pulverized, and thereafter, chemically modified with phosphoric acid in the presence of urea, to obtain a low density and sustainable fire retarding filler. Infrared spectroscopy, nuclear magnetic resonance, and X‐Ray photoelectron spectroscopy were used in order to determine the resulting chemical structure and confirm the presence of the proposed functional groups. In addition, scanning electron microscopy and elemental analysis were used to establish the resulting morphological changes, as well as the elements present on the modified material. Thermogravimetric analysis was also carried out in order to establish the thermal stability of the material and predict the effect on the flame retardancy due to the mentioned chemical modification. It was also determined that chemical modification greatly increased the thermal stability of the avocado seed. The flame‐retardant effect of the modified avocado seed was assessed in polyethylene/ethylene‐vinyl‐acetate (PE/EVA) composites via cone calorimeter tests. It was observed by DSC, that the incorporation of avocado seed, does not affect the melting temperature of the PE/EVA polymer blend. The results showed that the modified avocado seed decreased the peak of the heat release rate (pHRR) by 54% and the total heat released (THR) by 15%. The UL‐94 and LOI tests of the modified avocado biocomposites showed an improvement in the flame retardant properties, and reached a UL‐94 V‐1 classification. Tensile tests showed that the bio‐composites with unmodified and modified avocado seed exhibit similar tensile strength and modulus than the LDPE/EVA blend, but a lower elongation. These results suggest that phosphorylated avocado seed could be a good option as a renewable biofiller for polymer composites with enhanced flame‐retardant properties. [ABSTRACT FROM AUTHOR]

Background and objective: Andean lupin (Lupinus mutabilis Sweet) has health benefits with promising possibilities for food industry. The aim of this research was to determine the effect of processing (water debittering, extrusion, and spray‐drying) on chemical composition, heat damage and in vitro protein digestibility in Andean lupin. Findings: The processing treatment modified all the parameters while the genotype showed limited effect. The untreated lupins had high protein and lipid content (47.4 and 16.2 g/100 g dry matter). The extruded products showed higher protein content (55.7 g/100 g) and digestibility (68.1%) than the untreated lupins, along with limited heat damage (8.7 mg furosine/100 g protein). Spray‐drying led to the lowest protein content (31.8 g/100 g) and, when maltodextrin was used, the highest heat damage (54.1 ± 20.7 mg furosine/100 g protein; 0.60 mg hydroxymethylfurfural/kg; 0.58 mg glycosylisomaltol/kg), but also to the maximum protein digestibility (72.8%–74.0%). Conclusions: The chemical composition of Andean lupin was improved by the technological treatments (debittering, extrusion, and spray‐drying) applied. Processing enhanced nutritional value and digestibility, without inducing relevant heat damage. Significance and novelty: Extrusion and spray‐drying improve the in vitro protein digestibility of Andean lupin flour causing limited heat damage. [ABSTRACT FROM AUTHOR]

Background: The CNS constantly monitors the organism's internal state and orchestrates adaptive responses to perturbation of the body's homeostasis. Emerging evidence revealed that the brain can also instruct immune responses, which in turn can affect the condition of other organs, including the brain itself. Method: We used neuronal retrograde‐labelling, flow‐cytometry, mass cytometry, scRNAseq and cognitive tests in animal model of Alzheimer's disease (5xFAD) to study the relevance of the brain Brain‐Immune axis in the context of Alzheimer's Disease. Results: We found that catecholaminergic neurons are in direct communication with the spleen, the major secondary lymphoid organ of our body. This connection is impaired in an animal model of neurodegeneration (Alzheimer's Disease ‐ AD), and undermining this communication at early stage of the disease accelerated disease manifestation. We found that monocytes are the most sensitive cell type to noradrenaline released by the splenic nerve and halting neuronal inputs to the spleen impairs monocytes' migratory capacity. Monocytes are needed to cope with neurodegenerative diseases and acute CNS damage. Upon splenic denervation, we observed reduced number of monocytes in the brain of AD mice and impaired microglia maturation. Upon denervation of the spleen, reduced number of infiltrating monocytes was also observed in a model of retina excitotoxic damage. Conclusions: These results highlight a novel pathway through which the CNS can control immune function and therefore trigger tissue repairing processes. [ABSTRACT FROM AUTHOR]

A novel nanostructured architecture for the construction of electrochemical enzyme biosensors is here described. It implies the electrostatic layer-by-layer assembly of four-generation ethylenediamine core polyamidoamine G-4 dendrimers on glassy carbon electrodes coated with a graphene oxide-carboxymethylcellulose hybrid nanomaterial. This modified surface was further employed for the covalent immobilization of the model enzyme tyrosinase through a glutaraldehyde-mediated cross-linking. The prepared enzyme electrode allowed the amperometric detection of catechol in the 2-400 nM range. The biosensor showed excellent analytical performance with high sensitivity of 6.3 A/M and low detection limit of 0.9 nM. The enzyme electrode retained over 93 % of the initial activity after 40 days at 4 °C. [ABSTRACT FROM AUTHOR]

SUMMARY As an attempt to make network managers' life easier, we present M3Omon, a system architecture that helps to develop monitoring applications and perform network diagnosis. M3Omon behaves as an intermediate layer between the traffic and monitoring applications that provides advanced features, high performance and low cost. Such advanced features leverage a multi-granular and multi-purpose approach to the monitoring problem. Multi-granular monitoring provides answers to tasks that use traffic aggregates to identify an event, and requires either flow records or packet data or even both to understand it and, eventually, take convenient countermeasures. M3Omon provides a simple API to access traffic simultaneously at several different granularities, i.e. packet-level, flow-level and aggregate statistics. The multi-purposed design of M3Omon allows not only performing tasks in parallel that are specifically targeted to different traffic-related purposes (e.g. traffic classification and intrusion detection) but also sharing granularities between applications, e.g. several concurrent applications fed from flow records that are provided by M3Omon. Finally, the low-cost characteristic is brought by off-the-shelf systems (the combination of open-source software and commodity hardware) and the high performance is achieved thanks to modifications in the standard NIC driver, low-level hardware interaction, efficient memory management and programming optimization. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

SUMMARY Voice over IP (VoIP) is increasingly replacing the old public switched telephone network (PSTN) technology. In this new scenario, there are several challenges for VoIP providers. First, VoIP requires a detailed monitoring of both users' quality of service (QoS) and experience (QoE) to a greater extent than in traditional PSTNs. Second, such a monitoring process must be able to track VoIP traffic in high-speed networks, nowadays typically of multi-Gb/s rates. Third, recent government directives require that providers retain information from their users' calls. Similarly, the convergence of data and voice services allows operators to provide new services such as full-data retention, in which users' calls can be recorded for either quality assessment (call centers, QoE) or security purposes (lawful interception). This implies a significant investment in infrastructure, especially in large-scale networks which require multiple points of measurement and redundancy. This paper proposes a novel methodology, architecture and system to fulfill such challenges, called VoIPCallMon, as well as the data structures and necessary hardware-tuning knowledge for its development. As distinguishing features, VoIPCallMon provides very high performance, being able to process VoIP traffic on-the-fly at high bitrates, novel services and significant cost reduction by using commodity hardware with minimal interference with operational VoIP networks. The performance evaluation shows that the system copes with the VoIP load of real-world operators. We further evaluated the system performance at a fully saturated 10 Gb/s link and no packet loss was reported, therefore demonstrating the potential of commodity hardware solutions. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

ABSTRACT Nowadays, it is common to develop software development projects collaboratively among team members or organizations in different geographical locations. These teams, known as global software development (GSD) teams, allow organizations to save costs as well as have available highly qualified personnel. This kind of team is different from traditional teams, so it is necessary for team members to develop other essential competences to work efficiently in a global context. Unfortunately, there is no well-defined competence model that allows organizations to assess personnel competences and establish the relevant training program that allows them to work efficiently in such teams. This work defines and implements, in four GSD teams, a competence model specifically designed to address challenges that people face when they work in a GSD team. This competence model has been defined considering tasks a GSD team have to carry out, bodies of knowledge, and existing competence models for the software engineering profiles and the authors' experience working in such teams. As a result of the implementation process, it was confirmed that the competence model is a key factor for human capital improvement. When personnel have these competences, team and individual efficiency and product quality increase, and delays in delivering products decrease. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The heme of bacteria, plant and animal hemoglobins (Hbs) must be in the ferrous state to bind O2 and other physiological ligands. Here we have characterized the full set of non-symbiotic (class 1 and 2) and 'truncated' (class 3) Hbs of Lotus japonicus. Class 1 Hbs are hexacoordinate, but class 2 and 3 Hbs are pentacoordinate. Three of the globins, Glb1-1, Glb2 and Glb3-1, are nodule-enhanced proteins. The O2 affinity of Glb1-1 (50 p m) was the highest known for any Hb, and the protein may function as an O2 scavenger. The five globins were reduced by free flavins, which transfer electrons from NAD(P)H to the heme iron under aerobic and anaerobic conditions. Class 1 Hbs were reduced at very fast rates by FAD, class 2 Hbs at slower rates by both FMN and FAD, and class 3 Hbs at intermediate rates by FMN. The members of the three globin classes were immunolocalized predominantly in the nuclei. Flavins were quantified in legume nodules and nuclei, and their concentrations were sufficient to maintain Hbs in their functional state. All Hbs, except Glb1-1, were expressed in a flavohemoglobin-deficient yeast mutant and found to confer tolerance to oxidative stress induced by methyl viologen, copper or low temperature, indicating an anti-oxidative role for the hemes. However, only Glb1-2 and Glb2 afforded protection against nitrosative stress induced by S-nitrosoglutathione. Because this compound is specifically involved in transnitrosylation reactions with thiol groups, our results suggest a contribution of the single cysteine residues of both proteins in the stress response. [ABSTRACT FROM AUTHOR]

The one-pot preparation of azanucleotide analogues from proline derivatives has been achieved by a sequential radical decarboxylation/phosphorylation process. The process proceeded under mild conditions, giving high yields of the nucleotide analogues. Remarkably, the stereoselectivity of the reaction can be controlled by using different oxygen and nitrogen substituents at C-4 to give preferentially either the 2,4- cis or 2,4- trans products. In this way, the diastereomeric cis/ trans ratio can be shifted from 98:2 to 15:85. [ABSTRACT FROM AUTHOR]

Fms-like tyrosine kinase 3 ligand ( Flt3 L) is a major cytokine that drives development of dendritic cells ( DCs) under steady state, whereas GM- CSF becomes a prominent influence on differentiation during inflammation. The influence GM- CSF exerts on Flt3 L-induced DC development has not been thoroughly examined. Here, we report that GM- CSF alters Flt3 L-induced DC development. When BM cells were cultured with both Flt3 L and GM- CSF, few CD8+ equivalent DCs or plasmacytoid DCs developed compared to cultures supplemented with Flt3 L alone. The disappearance of these two cell subsets in GM- CSF + Flt3 L culture was not a result of simple inhibition of their development, but a diversion of the original differentiation trajectory to form a new cell population. As a consequence, both DC progeny and their functions were altered. The effect of GM- CSF on DC subset development was confirmed in vivo. First, the CD8+ DC numbers were increased under GM- CSF deficiency (when either GM- CSF or its receptor was ablated). Second, this population was decreased under GM- CSF hyperexpression (by transgenesis or by Listeria infection). Our finding that GM- CSF dominantly changes the regulation of DC development in vitro and in vivo has important implications for inflammatory diseases or GM- CSF therapy. [ABSTRACT FROM AUTHOR]

Serpinb9 (Sb9, also called Spi6) is an intracellular inhibitor of granzyme B (GrB) that protects activated cytotoxic lymphocytes from apoptosis. We show here that the CD8+ subset of splenic dendritic cells (DC), specialized in major histocompatibility complex class I (MHC I) presentation of exogenous antigens (cross-presentation), produce high levels of Sb9. Mice deficient in Sb9 are unable to generate a cytotoxic T-cell response against cell-associated antigen by cross-presentation, but maintain normal MHC-II presentation to helper T cells. This impaired cross-priming ability is autonomous to DC and is evident in animals deficient in both Sb9 and GrB, indicating that this role of Sb9 in DC is GrB-independent. In Sb9-deficient mice, CD8+ DC develop normally, survive as well as wild-type DC after antigenic challenge, and exhibit unimpaired capacity to take up antigen. Although the core processing machinery is unaffected, Sb9-deficient DC appear to process antigen faster. Our results point to a novel, GrB-independent role for Sb9 in DC cross-priming. [ABSTRACT FROM AUTHOR]

Mouse infection with intracellular bacteria induces a potent inflammatory response that requires protective mechanisms to avoid infection-induced immune pathology. CD69 is expressed in all leukocytes during activation after infection with a wide range of microbial pathogens. This study explores the way in which CD69 affects cell activation after Listeria monocytogenes (Lm) infection and its effects on host protection. We show that infectivity and bacterial clearance capability are unaltered in CD69−/− peritoneal macrophages, bone marrow-derived macrophages and dendritic cells. We found no major altered cell populations in splenocytes of Lm-infected CD69−/− mice. However, an increase in the expression of Th1 cytokines was observed after infection, with increased production of type I and II interferon (IFN). In addition, CD69−/− splenocytes showed increased apoptosis, consistent with IFN enhancement of lymphocyte apoptosis in response to Lm infection. CD69−/− mice showed liver and spleen damage, and greatly increased susceptibility to Lm infection, compared with wild-type controls. Lm-specific T cells were decreased in CD69−/− mice even if T-cell cross-presentation and T-cell intrinsic priming response were not compromised. As listeriosis was increased as early as day 1 post-infection but CD69−/−RAG2−/− mice were more efficient at controlling Listeria, we propose that CD69 controls the cross-talk between innate components and lymphocytes. These results highlight a role for CD69 in preventing infection-induced immunopathology. [ABSTRACT FROM AUTHOR]

• Despite the multiple roles played by antioxidants in rhizobia–legume symbioses, little is known about glutathione peroxidases (GPXs) in legumes. Here the characterization of six GPX genes of Lotus japonicus is reported. • Expression of GPX genes was analysed by quantitative reverse transcription–polymerase chain reaction in L. japonicus and Lotus corniculatus plants exposed to various treatments known to generate reactive oxygen and/or nitrogen species. • LjGPX1 and LjGPX3 were the most abundantly expressed genes in leaves, roots and nodules. Compared with roots, LjGPX1 and LjGPX6 were highly expressed in leaves and LjGPX3 and LjGPX6 in nodules. In roots, salinity decreased GPX4 expression, aluminium decreased expression of the six genes, and cadmium caused up-regulation of GPX3, GPX4 and GPX5 after 1 h and down-regulation of GPX1, GPX2, GPX4 and GPX6 after 3–24 h. Exposure of roots to sodium nitroprusside (a nitric oxide donor) for 1 h increased the mRNA levels of GPX4 and GPX6 by 3.3- and 30-fold, respectively. Thereafter, the GPX6 mRNA level remained consistently higher than that of the control. Immunogold labelling revealed the presence of GPX proteins in root and nodule amyloplasts and in leaf chloroplasts of L. japonicus and other legumes. Labelling was associated with starch grains. • These results underscore the differential regulation of GPX expression in response to cadmium, aluminium and nitric oxide, and strongly support a role for GPX6 and possibly other GPX genes in stress and/or metabolic signalling. [ABSTRACT FROM AUTHOR]

This work studies, from several cases, the implementation degree of TSP (Team Software Process) which exists in academic and business organizations. The analysis is made from different points of view, studying their weaknesses and strengths. Many of these cases studied show the improvement achieved after the implementation of TSP in an organization, but they do not explain exactly in which aspects the improvement is achieved. Moreover, data presented on the reports do not have sufficient formality, reliability or scientific rigour. So, this work has collected and analyzed published cases of study and it provides to the software engineering community, specially to the TSP community, a set of recommendations to improve the publication of cases of study in the future. Copyright © 2008 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The antioxidant composition and relative water stress tolerance of nodulated alfalfa plants (Medicago sativa L. × Sinorhizobium meliloti 102F78) of the elite genotype N4 and three derived transgenic lines have been studied in detail. These transgenic lines overproduced, respectively, Mn-containing superoxide dismutase (SOD) in the mitochondria of leaves and nodules, MnSOD in the chloroplasts, and FeSOD in the chloroplasts. In general for all lines, water stress caused moderate decreases in MnSOD and FeSOD activities in both leaves and nodules, but had distinct tissue-dependent effects on the activities of the peroxide-scavenging enzymes. During water stress, with a few exceptions, ascorbate peroxidase and catalase activities increased moderately in leaves but decreased in nodules. At mild water stress, transgenic lines showed, on average, 20% higher photosynthetic activity than the parental line, which suggests a superior tolerance of transgenic plants under these conditions. However, the untransformed and the transgenic plants performed similarly during moderate and severe water stress and recovery with respect to important markers of metabolic activity and of oxidative stress in leaves and nodules. We conclude that the base genotype used for transformation and the background SOD isozymic composition may have a profound effect on the relative tolerance of the transgenic lines to abiotic stress. [ABSTRACT FROM AUTHOR]

The thiol tripeptide glutathione (GSH; γGlu-Cys-Gly) is very abundant in legume nodules where it performs multiple functions that are critical for optimal nitrogen fixation. Some legume nodules contain another tripeptide, homoglutathione (hGSH; γGlu-Cys-β Ala), in addition to or instead of GSH. We have isolated from a pea (Pisum sativum L.) nodule library a cDNA, GSHS2, that is expressed in nodules but not in leaves. This cDNA was overexpressed in insect cells and its protein product was identified as a highly active and specific hGSH synthetase. The enzyme, the first of this type to be completely purified, is predicted to be a homodimeric cytosolic protein. It shows a specific activity of 3400 nmol hGSH min-1 mg-1 protein with a standard substrate concentration (5 mM β-alanine) and Km values of 1.9 mM for β-alanine and 104 mM for glycine. The specificity constant (Vmax/Km) shows that the pure enzyme is 57.3-fold more specific for β-alanine than for glycine. Southern blot analysis revealed that the gene is present as a single copy in the pea genome and that there are homologous genes in other legumes. We conclude that the synthesis of hGSH in pea nodules is catalysed by a specific hGSH synthetase and not by a GSH synthetase with broad substrate specificity. [ABSTRACT FROM AUTHOR]