Transcriptomic Resources for the Medicinal Legume \u3ci\u3eMucuna pruriens\u3c/i\u3e: \u3ci\u3ede novo\u3c/i\u3e Transcriptome Assembly, Annotation, Identification and Validation of EST-SSR Markers

Background: The medicinal legume Mucuna pruriens (L.) DC. has attracted attention worldwide as a source of the anti-Parkinson’s drug L-Dopa. It is also a popular green manure cover crop that offers many agronomic benefits including high protein content, nitrogen fixation and soil nutrients. The plant currently lacks genomic resources and there is limited knowledge on gene expression, metabolic pathways, and genetics of secondary metabolite production. Here, we present transcriptomic resources for M. pruriens, including a de novo transcriptome assembly and annotation, as well as differential transcript expression analyses between root, leaf, and pod tissues. We also develop microsatellite markers and analyze genetic diversity and population structure within a set of Indian germplasm accessions. Results: One-hundred ninety-one million two hundred thirty-three thousand two hundred forty-two bp cleaned reads were assembled into 67,561 transcripts with mean length of 626 bp and N50 of 987 bp. Assembled sequences were annotated using BLASTX against public databases with over 80% of transcripts annotated. We identified 7,493 simple sequence repeat (SSR) motifs, including 787 polymorphic repeats between the parents of a mapping population. 134 SSRs from expressed sequenced tags (ESTs) were screened against 23 M. pruriens accessions from India, with 52 EST-SSRs retained after quality control. Population structure analysis using a Bayesian framework implemented in fastSTRUCTURE showed nearly similar groupings as with distance-based (neighbor-joining) and principal component analyses, with most of the accessions clustering per geographical origins. Pair-wise comparison of transcript expression in leaves, roots and pods identified 4,387 differentially expressed transcripts with the highest number occurring between roots and leaves. Differentially expressed transcripts were enriched with transcription factors and transcripts annotated as belonging to secondary metabolite pathways. Conclusions: The M. pruriens transcriptomic resources generated in this study provide foundational resources for gene discovery and development of molecular markers. Polymorphic SSRs identified can be used for genetic diversity, marker-trait analyses, and development of functional markers for crop improvement. The results of differential expression studies can be used to investigate genes involved in L-Dopa synthesis and other key metabolic pathways in M. pruriens

Cationic distribution, exchange interactions, and relaxation dynamics in Zn-diluted MnCo 2 O 4 nanostructures

We report an experimental investigation of the electronic structure and magnetic properties of bulk and nanosized MnCo 2 O 4 diluted with Zn. The cationic distribution for tetrahedral A-site dilution is (Co 1-y A2 +Zn yA 2+ ) A Mn 3+ Co 3+ B O 4 ± δ, whereas B-site dilution results in (Co 2+ ) A Mn 1-xB 3+ Zn xB 2+ Co 3+ B O 4-δ . The strength of exchange interaction J ij between the magnetic ions in a bulk spinel lattice decreases by � 15 % for A-site dilution relative to the undiluted compound; however, B-site dilution results in an enhancement in J ij by 17%. The frequency and temperature dependence of dynamic-susceptibility � ac (f,T) studies of nanostructured compounds reveals the existence of spin-glass like behavior below the freezing temperature T F � 125.7K (for x B = 0.2) and 154.3 K (y A = 0.1). Relaxation time � follows the Power-Law variation with a dynamical critical exponent z ν = 6.17 and microscopic spin relaxation time � 0 = 4.4 � 10 -15 s for x B = 0.2 (for y A = 0.1, z ν = 5.2 and � o = 5.4 � 10 -13 s ). The amplitude and peak position in � ac (T) decreases with an increase in the DC bias field, which indicates that the spin-glass phase can survive in the presence of low fields forming a critical line with an exponent 2/3. This behavior is similar to the de Almeida-Thouless (AT-line) analysis in the T-H phase diagram which supports the existence of spin-glass like behavior below T F in these Zn diluted spinels. © 2019 Author(s)

DRL-FORCH: A Scalable Deep Reinforcement Learning-based Fog Computing Orchestrator

We consider the problem of designing and training a neural network-based orchestrator for fog computing service deployment. Our goal is to train an orchestrator able to optimize diversified and competing QoS requirements, such as blocking probability and service delay, while potentially supporting thousands of fog nodes. To cope with said challenges, we implement our neural orchestrator as a Deep Set (DS) network operating on sets of fog nodes, and we leverage Deep Reinforcement Learning (DRL) with invalid action masking to find an optimal trade-off between competing objectives. Illustrative numerical results show that our Deep Set-based policy generalizes well to problem sizes (i.e., in terms of numbers of fog nodes) up to two orders of magnitude larger than the ones seen during the training phase, outperforming both greedy heuristics and traditional Multi-Layer Perceptron (MLP)-based DRL. In addition, inference times of our DS-based policy are up to an order of magnitude faster than an MLP, allowing for excellent scalability and near real-Time online decision-making

Transcriptomic resources for the medicinal legume Mucuna pruriens: de novo transcriptome assembly, annotation, identification and validation of EST-SSR markers

Abstract Background The medicinal legume Mucuna pruriens (L.) DC. has attracted attention worldwide as a source of the anti-Parkinson’s drug L-Dopa. It is also a popular green manure cover crop that offers many agronomic benefits including high protein content, nitrogen fixation and soil nutrients. The plant currently lacks genomic resources and there is limited knowledge on gene expression, metabolic pathways, and genetics of secondary metabolite production. Here, we present transcriptomic resources for M. pruriens, including a de novo transcriptome assembly and annotation, as well as differential transcript expression analyses between root, leaf, and pod tissues. We also develop microsatellite markers and analyze genetic diversity and population structure within a set of Indian germplasm accessions. Results One-hundred ninety-one million two hundred thirty-three thousand two hundred forty-two bp cleaned reads were assembled into 67,561 transcripts with mean length of 626 bp and N50 of 987 bp. Assembled sequences were annotated using BLASTX against public databases with over 80% of transcripts annotated. We identified 7,493 simple sequence repeat (SSR) motifs, including 787 polymorphic repeats between the parents of a mapping population. 134 SSRs from expressed sequenced tags (ESTs) were screened against 23 M. pruriens accessions from India, with 52 EST-SSRs retained after quality control. Population structure analysis using a Bayesian framework implemented in fastSTRUCTURE showed nearly similar groupings as with distance-based (neighbor-joining) and principal component analyses, with most of the accessions clustering per geographical origins. Pair-wise comparison of transcript expression in leaves, roots and pods identified 4,387 differentially expressed transcripts with the highest number occurring between roots and leaves. Differentially expressed transcripts were enriched with transcription factors and transcripts annotated as belonging to secondary metabolite pathways. Conclusions The M. pruriens transcriptomic resources generated in this study provide foundational resources for gene discovery and development of molecular markers. Polymorphic SSRs identified can be used for genetic diversity, marker-trait analyses, and development of functional markers for crop improvement. The results of differential expression studies can be used to investigate genes involved in L-Dopa synthesis and other key metabolic pathways in M. pruriens

Characterization of Carnosine Effect on Human Microglial Cells under Basal Conditions

The activity of microglia is fundamental for the regulation of numerous physiological processes including brain development, synaptic plasticity, and neurogenesis, and its deviation from homeostasis can lead to pathological conditions, including numerous neurodegenerative disorders. Carnosine is a naturally occurring molecule with well-characterized antioxidant and anti-inflammatory activities, able to modulate the response and polarization of immune cells and ameliorate their cellular energy metabolism. The better understanding of microglia characteristics under basal physiological conditions, as well as the possible modulation of the mechanisms related to its response to environmental challenges and/or pro-inflammatory/pro-oxidant stimuli, are of utmost importance for the development of therapeutic strategies. In the present study, we assessed the activity of carnosine on human HMC3 microglial cells, first investigating the effects of increasing concentrations of carnosine on cell viability. When used at a concentration of 20 mM, carnosine led to a decrease of cell viability, paralleled by gene expression increase and decrease, respectively, of interleukin 6 and heme oxygenase 1. When using the maximal non-toxic concentration (10 mM), carnosine decreased nitric oxide bioavailability, with no changes in the intracellular levels of superoxide ion. The characterization of energy metabolism of HMC3 microglial cells under basal conditions, never reported before, demonstrated that it is mainly based on mitochondrial oxidative metabolism, paralleled by a high rate of biosynthetic reactions. The exposure of HMC3 cells to carnosine seems to ameliorate microglia energy state, as indicated by the increase in the adenosine triphosphate/adenosine diphosphate (ATP/ADP) ratio and energy charge potential. The improvement of cell energy metabolism mediated by 10 mM carnosine could represent a useful protective weapon in the case of human microglia undergoing stressing conditions

Assessing social and distributional impacts of transportation policies for optimizing sustainability

Los intentos de integrar la sostenibilidad en el proceso de toma de decisiones de las políticas de transporte continúan ganando impulso. En este sentido, existe un consenso general sobre la necesidad de implementar de manera conjunta los objetivos de eficiencia y equidad en las decisiones relativas a la planificación de transporte. En consecuencia, los planificadores del transporte suelen verse en la necesidad de diseñar, implementar y evaluar políticas que contribuyan a favorecer el desarrollo económico y a satisfacer las necesidades de transporte de la sociedad, en consonancia con las leyes naturales y con los valores humanos. En este contexto, la equidad social ha ganado importancia como requisito para el desarrollo sostenible, que comprende las dimensiones social, económica y ambiental con una perspectiva de largo plazo. Sin embargo, la mayoría de las evaluaciones sociales en el ámbito de la planificación del transporte siguen siendo puramente cualitativas y, a menudo, muy superficiales, ya que en la práctica existen pocas directrices para su análisis exhaustivo. A pesar de que las políticas de transporte a menudo producen impactos significativos y diversos sobre la sociedad en su conjunto, la evaluación de sus implicaciones en términos de equidad e incidencia distributiva es por el momento muy limitada. En este sentido, a pesar de la amplia implementación de políticas de transporte en zonas urbanas, se han llevado a cabo muy pocos análisis cuantitativos para evaluar si realmente responden a las necesidades de los estratos sociales más desfavorecidos. Sin este tipo de análisis, no es posible determinar con certeza el alcance real de estas medidas en la promoción de la inclusión social. Sobre la base de estas consideraciones, el objetivo general de esta Tesis es revisar y evaluar los impactos sociales de diversas políticas de transporte existentes, así como y sus posibles consecuencias en términos de equidad desde el punto de vista de la sostenibilidad. Para ello, se evalúa la incidencia de diferentes intervenciones reales de planificación sobre la inclusión social –particularmente sobre la distribución del ingreso– aplicando técnicas econométricas y estadísticas, como los modelos de regresión y de elección discreta. En particular, la investigación analiza el impacto de políticas de transporte comúnmente asumidas como progresivas (subsidios y beneficios al transporte) y regresivas (tarificación vial), tomando como casos de estudio la ciudad de Madrid, la región de Nueva York-Nueva Jersey y la red de autopistas de peaje de España. Asimismo, la Tesis proporciona un marco general sobre la evaluación de las intervenciones de transporte con el fin de comprender el papel de los impactos sociales y distributivos en las evaluaciones ex−ante. La investigación también propone un esquema de ponderación alternativo para integrar las cuestiones de equidad social en el proceso de toma de decisiones. Finalmente, la Tesis obtiene conclusiones relevantes tanto para los responsables de la formulación de políticas como para los profesionales del sector, con el objetivo de promover políticas de transporte más eficientes y socialmente incluyentes. Attempts to integrate sustainability in the decision-making process for transport policies continue to gain momentum. At this point, there is a general consensus on the need to achieve the dual goals of efficiency and equity when implementing transport planning decisions. Therefore, transport planners are usually involved in designing, implementing and evaluating policies that contribute to favour economic development and to accomplish transportation needs of society in a manner consistent with natural laws and human values. In this context, social equity has been gaining importance as a requirement for sustainable development, which comprises social, economic and environmental dimensions with a long-term perspective. However, most social assessments of transport planning decisions remain purely qualitative and often very superficial since, in practice, there is little guidance for its comprehensive analysis. Despite the fact that transportation policies and planning practices often have significant and diverse impacts, there is still only a limited evaluation of the equity implications and the distributional incidence of these policies. As a result, regardless of the widespread implementation of transport policies in many cities and urban areas, few quantitative assessments have been carried out to evaluate whether they meet social needs of the disadvantaged people. Without this kind of analyses, the extent to which they promote social inclusion cannot be determined with certainty. On the basis of these considerations, the overarching objective of this Thesis is to review, assess and evaluate the social impacts of existing transportation policies and their potential equity consequences from the sustainability viewpoint. To that end, the research evaluates the incidence of different real transportation planning decisions on social inclusion —particularly on income distribution— by applying econometric methodologies and statistical techniques such as regression and discrete choice models. Particularly, the research involves analyses on commonly assumed progressive (transport subsidies and transport benefits) and regressive (road pricing) policy alternatives, taking the city of Madrid, the region of New York-New Jersey and the Spanish interurban toll network as case studies. Furthermore, a comprehensive framework on the topic of transport evaluation is provided aimed at understanding the role of social and distributional impacts in exante assessments. The research also gives insight for an alternative weighting scheme to embed social equity issues into the existing appraisal process. Finally, the Thesis yielded some interesting conclusions for both policy-makers and practicing planners with regard to the promotion of more efficient and socially inclusive transport policies

Synthesis and receptor binding of new thieno[2,3-d]pyrimidines as selective ligands of 5-HT3 receptors

With the aim to develop new potent and selective ligands of 5-HT3-type serotonin receptors and to acquire more information on their structure-affinity relationships, new thieno[2,3-d]pyrimidine derivatives 32-39 were synthesized and their binding to 5-HT3 versus 5-HT4 receptors was studied. Some of these new compounds exhibit good affinity for cortical 5-HT3 receptors, but not for 5-HT4 receptors. Among these derivatives, 6-ethyl-4-(4-methyl-l-piperazinyl)-2-(methylthio)thieno[2,3-d]pyrimidine 32 is the most potent ligand (K-i = 67 nM); it behaves as a competitive antagonist of the 5-HT3 receptor function in the guinea pig colon. Its binding interactions with 5-HT3A receptors were analysed by using receptor modelling and comparative docking