Desarrollo de frameworks con .NET

La expansión experimentada por la informática, las nuevas tecnologías e internet en los últimos años, no solo viene dada por la evolución del hardware subyacente, sino por la evolución del desarrollo de software y del crecimiento del número de desarrolladores. Este incremento ha hecho evolucionar el software de unos sistemas de gestión basados en ficheros, prácticamente sin interfaz gráfico y de unos pocos miles de líneas a grandes sistemas distribuidos multiplataforma. El desarrollo de estos grandes sistemas, requiere gran cantidad de personas involucradas en el desarrollo, y que las herramientas de desarrollo hayan crecido también para facilitar su análisis, diseño, codificación, pruebas, implantación y mantenimiento. La base de estas herramientas software las proveen las propias plataformas de desarrollo, pero la experiencia de los desarrolladores puede aportar un sinfín de utilidades y de técnicas que agilicen los desarrollos y cumplan los requisitos del software en base a la reutilización de soluciones lo suficientemente probadas y optimizadas. Dichas herramientas se agrupan ordenadamente, creando así frameworks personalizados, con herramientas de todo tipo, clases, controles, interfaces, patrones de diseño, de tal manera que se dan soluciones personalizadas a un amplio número de problemas para emplearlas cuantas veces se quiera, bien marcando directrices de desarrollo mediante el uso de patrones, bien con la encapsulación de complejidades de tal modo que los desarrolladores ya dispongan de componentes que asuman cierta lógica o cierta complejidad aliviando así la fase de construcción. En este trabajo se abordan temas sobre las tecnologías base y plataformas de desarrollo para poder acometer la creación de un framework personalizado, necesidades a evaluar antes de acometerlo, y técnicas a emplear para la consecución del mismo, orientadas a la documentación, mantenimiento y extensión del framework. La exposición teórica consiste en mostrar y evaluar los requisitos para crear un framework, requisitos de la plataforma de desarrollo, y explicar cómo funcionan las grandes plataformas de desarrollo actuales, que elementos los componen y su funcionamiento, así como marcar ciertas pautas de estructuración y nomenclatura que el desarrollo de un framework debe contemplar para su mantenimiento y extensión. En la parte metodológica se ha usado un subconjunto de Métrica V3, ya que para el desarrollo de controles no aplica dicha metodología en su totalidad, pero contempla el catálogo de requisitos, los casos de uso, diagramas de clase, diagramas de secuencia, etc… Aparte de los conceptos teóricos, se presenta un caso práctico con fines didácticos de cómo parametrizar y configurar el desarrollo bajo la plataforma .NET. Dicho caso práctico consiste en la extensión de un control de usuario genérico de la plataforma .NET, de tal modo que se aplican conceptos más allá del hecho de crear funciones como las funcionalidades que puede brindar un API. Conceptos sobre como extender y modificar controles ya existentes, que interactúan por medio de eventos con otros controles, con vistas a que ese nuevo control forme parte de una biblioteca de controles de usuario personalizados ampliamente divulgada. Los controles de usuario son algo que no solo tienen una parte funcional, sino que también tienen una parte visual, y definiciones funcionales distintas de las típicas del software de gestión, puesto que han de controlar eventos, visualizaciones mientras se dan estos eventos y requisitos no funcionales de optimización de rendimiento, etc… Para el caso práctico se toma como herramienta la plataforma de desarrollo .Net Framework, en todas sus versiones, ya que el control a extender es el control ListView y hacerlo editable. Este control está presente en todas las versiones de .NET framework y con un alto grado de reutilización. Esta extensión muestra además como se puede migrar fácilmente este tipo de extensiones sobre todos los frameworks. Los entornos de desarrollo usados son varias versiones de Visual Studio para el mostrar dicha compatibilidad, aunque el desarrollo que acompaña este documento esté realizado sobre Visual Studio 2013. ABSTRACT The expansion in computer science, new technologies and the Internet in recent years, not only is given by the evolution of the underlying hardware, but for the evolution of software development and the growing number of developers. This increase has evolved software from management systems based on files almost without graphical interface and a few thousand of code lines, to large multiplatform distributed systems. The development of these large systems, require lots of people involved in development, and development tools have also grown to facilitate analysis, design, coding, testing, deployment and maintenance. The basis of these software tools are providing by their own development platforms, but the experience of the developers can bring a lot of utilities and techniques to speed up developments and meet the requirements of software reuse based on sufficiently proven solutions and optimized. These tools are grouped neatly, creating in this way custom frameworks, with tools of all types, classes, controls, interfaces, design patterns,… in such a way that they provide customized solutions to a wide range of problems to use them many times as you want to occur, either by dialing development guidelines by using patterns or along with the encapsulation of complexities, so that developers already have components that take some logic or some complexity relieving the construction phase. This paper cover matters based on technologies and development platforms to undertake the creation of a custom framework, needs to evaluate before rush it and techniques to use in order to achieve it, a part from techniques oriented to documentation, maintenance and framework extension. The theoretical explanation consists in to demonstrate and to evaluate the requirements for creating a framework, development platform requirements, and explain how large current development platforms work, which elements compose them and their operation work, as well as mark certain patterns of structure and nomenclature that the development of a framework should include for its maintenance and extension. In the methodological part, a subset of Métrica V3 has been used, because of, for the development of custom controls this methodology does not apply in its entirety, but provides a catalogue of requirements, use cases, class diagrams, sequence diagrams, etc ... Apart from the theoretical concepts, a study case for teaching purposes about how to parameterize and configure the development under the .NET platform is presented. This study case involves the extension of a generic user control of the .NET platform, so that concepts apply beyond the fact of creating functions as the functionalities that can provide an API. Concepts on how to extend and modify existing controls that interact through events with other controls, overlooking that new control as a part of a custom user controls library widely publicized. User controls are something that not only have a functional part, but also have a visual part, and various functional definitions of typical management software, since that they have to control events, visualizations while these events are given and not functional of performance optimization requirements, etc ... For the study case the development platform .Net Framework is taken as tool, in all its versions, considering that control to extend is the ListView control and make it editable. This control is present in all versions of .NET framework and with a high degree of reuse. This extension also shows how you can easily migrate these extensions on all frameworks. The used development environments are several versions of Visual Studio to show that compatibility, although the development that accompanies this document is done on Visual Studio 2013.

Intermittent pluri-sink model and the emergence of complex heterogeneity patterns: a simple paradigm for explaining complexity in soil chemical distributions

The spatial complexity of the distribution of organic matter, chemicals, nutrients, pollutants has been demonstrated to have multifractal nature (Kravchenco et al. [1]). This fact supports the possibility of existence of some emergent heterogeneity structure built under the evolution of the system. The aim of this note is providing a consistent explanation to the mentioned results via an extremely simple model.

Horizontal gene transfer among genomes: The complexity hypothesis

Increasingly, studies of genes and genomes are indicating that considerable horizontal transfer has occurred between prokaryotes. Extensive horizontal transfer has occurred for operational genes (those involved in housekeeping), whereas informational genes (those involved in transcription, translation, and related processes) are seldomly horizontally transferred. Through phylogenetic analysis of six complete prokaryotic genomes and the identification of 312 sets of orthologous genes present in all six genomes, we tested two theories describing the temporal flow of horizontal transfer. We show that operational genes have been horizontally transferred continuously since the divergence of the prokaryotes, rather than having been exchanged in one, or a few, massive events that occurred early in the evolution of prokaryotes. In agreement with earlier studies, we found that differences in rates of evolution between operational and informational genes are minimal, suggesting that factors other than rate of evolution are responsible for the observed differences in horizontal transfer. We propose that a major factor in the more frequent horizontal transfer of operational genes is that informational genes are typically members of large, complex systems, whereas operational genes are not, thereby making horizontal transfer of informational gene products less probable (the complexity hypothesis).

Gene number in an invertebrate chordate, Ciona intestinalis

Gene number can be considered a pragmatic measure of biological complexity, but reliable data is scarce. Estimates for vertebrates are 50-100,000 genes per haploid genome, whereas invertebrate estimates fall below 25,000. We wished to test the hypothesis that the origin of vertebrates coincided with extensive gene creation. A prediction is that gene number will differ sharply between invertebrate and vertebrate members of the chordate phylum. A gene number estimation method requiring limited sequence sampling of genomic DNA was developed and validated by using data for Caenorhabditis elegans. Using the method, we estimated that the invertebrate chordate Ciona intestinalis has 15,500 protein-coding genes (±3,700). This number is significantly lower than gene numbers of vertebrate chordates, but similar to those of invertebrates in distantly related phyla. The data indicate that evolution of vertebrates was accompanied by a dramatic increase in protein-coding capacity of the genome.

The U5 RNA of trypanosomes deviates from the canonical U5 RNA: The Leptomonas collosoma U5 RNA and its coding gene

Fractionation of the abundant small ribonucleoproteins (RNPs) of the trypanosomatid Leptomonas collosoma revealed the existence of a group of unidentified small RNPs that were shown to fractionate differently than the well-characterized trans-spliceosomal RNPs. One of these RNAs, an 80-nt RNA, did not possess a trimethylguanosine (TMG) cap structure but did possess a 5′ phosphate terminus and an invariant consensus U5 snRNA loop 1. The gene coding for the RNA was cloned, and the coding region showed 55% sequence identity to the recently described U5 homologue of Trypanosoma brucei [Dungan, J. D., Watkins, K. P. & Agabian, N. (1996) EMBO J. 15, 4016–4029]. The L. collosoma U5 homologue exists in multiple forms of RNP complexes, a 10S monoparticle, and two subgroups of 18S particles that either contain or lack the U4 and U6 small nuclear RNAs, suggesting the existence of a U4/U6⋅U5 tri-small nuclear RNP complex. In contrast to T. brucei U5 RNA (62 nt), the L. collosoma homologue is longer (80 nt) and possesses a second stem–loop. Like the trypanosome U3, U6, and 7SL RNA genes, a tRNA gene coding for tRNACys was found 98 nt upstream to the U5 gene. A potential for base pair interaction between U5 and SL RNA in the 5′ splice site region (positions −1 and +1) and downstream from it is proposed. The presence of a U5-like RNA in trypanosomes suggests that the most essential small nuclear RNPs are ubiquitous for both cis- and trans-splicing, yet even among the trypanosomatids the U5 RNA is highly divergent.

Interleaved concatenated codes: New perspectives on approaching the Shannon limit

The last few years have witnessed a significant decrease in the gap between the Shannon channel capacity limit and what is practically achievable. Progress has resulted from novel extensions of previously known coding techniques involving interleaved concatenated codes. A considerable body of simulation results is now available, supported by an important but limited theoretical basis. This paper presents a computational technique which further ties simulation results to the known theory and reveals a considerable reduction in the complexity required to approach the Shannon limit.

In silico identification and characterisation of 17 polymorphic anonymous non-coding sequence markers (ANMs) for red grouse (Lagopus lagopus scotica)

Peer reviewed

Exome-wide analysis of rare coding variation identifies novel associations with COPD and airflow limitation in MOCS3, IFIT3 and SERPINA12

Funding: British Women’s Heart and Health Study is funded by the Department of Health grant no. 90049 and the British Heart Foundation grant no. PG/09/022. British Regional Heart Study is supported by the British Heart Foundation (grant RG/ 13/16/30528). CB (COPDBEAT) received funding from the Medical Research Council UK (grant no. G0601369), CB (COPDBEAT) and AJW (UKCOPD) were supported by the National Institute for Health Research (NIHR Leicester Biomedical Research Unit). MB (COPDBEAT) received funding from the NIHR (grant no. PDF-2013-06-052). Hertfordshire Cohort Study received support from the Medical Research Council, Arthritis Research UK, the International Osteoporosis Foundation and the British Heart Foundation; NIHR Biomedical Research Centre in Nutrition, University of Southampton; NIHR Musculoskeletal Biomedical Research Unit, University of Oxford. Generation Scotland: Scottish Family Health Study is funded by the Chief Scientist Office, Scottish Government Health Directorates, grant number CZD/16/6 and the Scottish Funding Council grant HR03006. EU COPD Gene Scan is funded by the European Union, grant no. QLG1-CT-2001-01012. English Longitudinal Study of Aging is funded by the Institute of Aging, NIH grant No. AG1764406S1. GoDARTs is funded by the Wellcome Trust grants 072960, 084726 and 104970. MDT has been supported by MRC fellowship G0902313. UK Biobank Lung Exome Variant Evaluation study was funded by a Medical Research Council strategic award to MDT, IPH, DPS and LVW (MC_PC_12010)

New lower bounds for the topological complexity of aspherical spaces

Date of Acceptance: 5/04/2015 15 pages, 4 figures

Hypoxic Regulation of Vascular Endothelial Growth Factor mRNA Stability Requires the Cooperation of Multiple RNA Elements

Vascular endothelial growth factor (VEGF) is a key regulator of developmental, physiological, and tumor angiogenesis. Upregulation of VEGF expression by hypoxia appears to be a critical step in the neovascularization of solid cancers. The VEGF mRNA is intrinsically labile, but in response to hypoxia the mRNA is stabilized. We have systematically analyzed the regions in the VEGF mRNA that are responsible for its lability under normoxic conditions and for stabilization in response to hypoxia. We find that the VEGF mRNA not only contains destabilizing elements in its 3′ untranslated region (3′UTR), but also contains destabilizing elements in the 5′UTR and coding region. Each region can independently promote mRNA degradation, and together they act additively to effect rapid degradation under normoxic conditions. Stabilization of the mRNA in response to hypoxia is completely dependent on the cooperation of elements in each of the 5′UTR, coding region, and 3′UTR. Combinations of any of two of these three regions were completely ineffective in responding to hypoxia, whereas combining all three regions allowed recapitulation of the hypoxic stabilization seen with the endogenous VEGF mRNA. We conclude that multiple regions in the VEGF mRNA cooperate both to ensure the rapid degradation of the mRNA under normoxic conditions and to allow stabilization of the mRNA in response to hypoxia. Our findings highlight the complexity of VEGF gene expression and also reveal a mechanism of gene regulation that could become the target for strategies of therapeutic intervention.

A herpes simplex virus 1 recombinant lacking the glycoprotein G coding sequences is defective in entry through apical surfaces of polarized epithelial cells in culture and in vivo

During infection of a new host, the first surfaces encountered by herpes simplex viruses are the apical membranes of epithelial cells of mucosal surfaces. These cells are highly polarized, and the protein composition of their apical and basolateral membranes are very different, so that different viral entry pathways have evolved for each surface. To determine whether the viral glycoprotein G (gG) is specifically required for efficient infection of a particular surface of polarized cells, apical and basal surfaces were infected with wild-type virus or a gG deletion mutant. After infection of polarized cells in culture, the gG− virus was deficient in infection of apical surfaces but was able to infect cells through basal membranes, replicate, and spread into surrounding cells. The gG-dependent step in apical infection was a stage beyond attachment. After in vivo infection of apical surfaces of epithelial cells of nonscarified mouse corneas, infection by glycoprotein C− or gG− virus was considerably reduced as compared with that observed after infection with wild-type virus. In contrast, when corneas were scarified, allowing virus access to other cell surfaces, the gG and glycoprotein C deletion mutants infected eyes as efficiently as wild-type viruses. A secondary mutation allowing infection of apical surfaces by gG− virus arose readily during passage of the virus in nonpolarized cells, indicating that either the gG-dependent step of apical infection can be bypassed or that another viral protein can acquire the same function.

Fundamental patterns underlying gene expression profiles: Simplicity from complexity

Analysis of previously published sets of DNA microarray gene expression data by singular value decomposition has uncovered underlying patterns or “characteristic modes” in their temporal profiles. These patterns contribute unequally to the structure of the expression profiles. Moreover, the essential features of a given set of expression profiles are captured using just a small number of characteristic modes. This leads to the striking conclusion that the transcriptional response of a genome is orchestrated in a few fundamental patterns of gene expression change. These patterns are both simple and robust, dominating the alterations in expression of genes throughout the genome. Moreover, the characteristic modes of gene expression change in response to environmental perturbations are similar in such distant organisms as yeast and human cells. This analysis reveals simple regularities in the seemingly complex transcriptional transitions of diverse cells to new states, and these provide insights into the operation of the underlying genetic networks.

Complex promoter and coding region β2-adrenergic receptor haplotypes alter receptor expression and predict in vivo responsiveness

The human β2-adrenergic receptor gene has multiple single-nucleotide polymorphisms (SNPs), but the relevance of chromosomally phased SNPs (haplotypes) is not known. The phylogeny and the in vitro and in vivo consequences of variations in the 5′ upstream and ORF were delineated in a multiethnic reference population and an asthmatic cohort. Thirteen SNPs were found organized into 12 haplotypes out of the theoretically possible 8,192 combinations. Deep divergence in the distribution of some haplotypes was noted in Caucasian, African-American, Asian, and Hispanic-Latino ethnic groups with >20-fold differences among the frequencies of the four major haplotypes. The relevance of the five most common β2-adrenergic receptor haplotype pairs was determined in vivo by assessing the bronchodilator response to β agonist in asthmatics. Mean responses by haplotype pair varied by >2-fold, and response was significantly related to the haplotype pair (P = 0.007) but not to individual SNPs. Expression vectors representing two of the haplotypes differing at eight of the SNP loci and associated with divergent in vivo responsiveness to agonist were used to transfect HEK293 cells. β2-adrenergic receptor mRNA levels and receptor density in cells transfected with the haplotype associated with the greater physiologic response were ≈50% greater than those transfected with the lower response haplotype. The results indicate that the unique interactions of multiple SNPs within a haplotype ultimately can affect biologic and therapeutic phenotype and that individual SNPs may have poor predictive power as pharmacogenetic loci.

How the owl resolves auditory coding ambiguity

The barn owl (Tyto alba) uses interaural time difference (ITD) cues to localize sounds in the horizontal plane. Low-order binaural auditory neurons with sharp frequency tuning act as narrow-band coincidence detectors; such neurons respond equally well to sounds with a particular ITD and its phase equivalents and are said to be phase ambiguous. Higher-order neurons with broad frequency tuning are unambiguously selective for single ITDs in response to broad-band sounds and show little or no response to phase equivalents. Selectivity for single ITDs is thought to arise from the convergence of parallel, narrow-band frequency channels that originate in the cochlea. ITD tuning to variable bandwidth stimuli was measured in higher-order neurons of the owl’s inferior colliculus to examine the rules that govern the relationship between frequency channel convergence and the resolution of phase ambiguity. Ambiguity decreased as stimulus bandwidth increased, reaching a minimum at 2–3 kHz. Two independent mechanisms appear to contribute to the elimination of ambiguity: one suppressive and one facilitative. The integration of information carried by parallel, distributed processing channels is a common theme of sensory processing that spans both modality and species boundaries. The principles underlying the resolution of phase ambiguity and frequency channel convergence in the owl may have implications for other sensory systems, such as electrolocation in electric fish and the computation of binocular disparity in the avian and mammalian visual systems.

Bidirectional imprinting of a single gene: GNAS1 encodes maternally, paternally, and biallelically derived proteins

The GNAS1 gene encodes the α subunit of the guanine nucleotide-binding protein Gs, which couples signaling through peptide hormone receptors to cAMP generation. GNAS1 mutations underlie the hormone resistance syndrome pseudohypoparathyroidism type Ia (PHP-Ia), so the maternal inheritance displayed by PHP-Ia has raised suspicions that GNAS1 is imprinted. Despite this suggestion, in most tissues Gsα is biallelically encoded. In contrast, the large G protein XLαs, also encoded by GNAS1, is paternally derived. Because the inheritance of PHP-Ia predicts the existence of maternally, rather than paternally, expressed transcripts, we have investigated the allelic origin of other mRNAs derived from GNAS1. We find this gene to be remarkable in the complexity of its allele-specific regulation. Two upstream promoters, each associated with a large coding exon, lie only 11 kb apart, yet show opposite patterns of allele-specific methylation and monoallelic transcription. The more 5′ of these exons encodes the neuroendocrine secretory protein NESP55, which is expressed exclusively from the maternal allele. The NESP55 exon is 11 kb 5′ to the paternally expressed XLαs exon. The transcripts from these two promoters both splice onto GNAS1 exon 2, yet share no coding sequences. Despite their structural unrelatedness, the encoded proteins, of opposite allelic origin, both have been implicated in regulated secretion in neuroendocrine tissues. Remarkably, maternally (NESP55), paternally (XLαs), and biallelically (Gsα) derived proteins all are produced by different patterns of promoter use and alternative splicing of GNAS1, a gene showing simultaneous imprinting in both the paternal and maternal directions.