Reranking candidate gene models with cross-species comparison for improved gene prediction

Background: Most gene finders score candidate gene models with state-based methods, typically HMMs, by combining local properties (coding potential, splice donor and acceptor patterns, etc). Competing models with similar state-based scores may be distinguishable with additional information. In particular, functional and comparative genomics datasets may help to select among competing models of comparable probability by exploiting features likely to be associated with the correct gene models, such as conserved exon/intron structure or protein sequence features. Results: We have investigated the utility of a simple post-processing step for selecting among a set of alternative gene models, using global scoring rules to rerank competing models for more accurate prediction. For each gene locus, we first generate the K best candidate gene models using the gene finder Evigan, and then rerank these models using comparisons with putative orthologous genes from closely-related species. Candidate gene models with lower scores in the original gene finder may be selected if they exhibit strong similarity to probable orthologs in coding sequence, splice site location, or signal peptide occurrence. Experiments on Drosophila melanogaster demonstrate that reranking based on cross-species comparison outperforms the best gene models identified by Evigan alone, and also outperforms the comparative gene finders GeneWise and Augustus+. Conclusion: Reranking gene models with cross-species comparison improves gene prediction accuracy. This straightforward method can be readily adapted to incorporate additional lines of evidence, as it requires only a ranked source of candidate gene models

What Is Quality? A Management Discipline and the Translation Industry Get Acquainted

Una manera de contestar la pregunta "què és qualitat?" pot a començar amb el marc presentat per Garvin (1984). Aquest marc descriu cinc enfocaments que determinen qualitat: l'enfocament transcendent, el basat en el producte, el basat en l'usuari, el basat en la producció (Garvin utilitza el terme "manufactura") i el basat en el valor. Garvin no sosté que un d'aquests enfocaments sigui suficient per si mateix. Per contra, una visió multidimensional de la qualitat ha de comptar amb els cinc enfocaments. Aquest article descriu breument aquests cinc enfocaments sobre la qualitat i fa referència al treball d'alguns dels autors més reconeguts i amb major visibilitat en l'àmbit de la gestió de la qualitat. A continuació l'article debat els arguments a favor i en contra de l'aplicació dels diferents enfocaments sobre la gestió de la qualitat en la indústria de la traducció. Els autors d'aquest article estan en desacord entre ells sobre la rellevància de la gestió terminològica en la indústria de la traducció, però sí que coincideixen en què les parts interessades haurien d'adoptar alguna posició al respecte.One way to answer the question "What is translation quality?" is to start with a framework put forward by Garvin (1984). That framework describes five approaches to determining quality: Transcendent, Product-Based, User-Based, Production-Based ("manufacturing" being Garvin's term) and Value-Based. Garvin does not claim that any one of these approaches is sufficient unto itself. Rather, a well-rounded view of quality requires all five. The present article briefly describes these five approaches to quality and references the work of several of the most visible and respected people in the discipline of quality management. Following that presentation, the article discusses arguments for and against applying quality-management approaches to the translation industry. The authors of this article disagree about the relevance of quality management to the translation industry, but they do agree that stakeholders should take a position on the issue.Una manera de contestar la pregunta "¿qué es calidad?" puede en comenzar con el marco presentado por Garvin (1984). Dicho marco describe cinco enfoques que determinan calidad: el enfoque transcendente, el basado en el producto, el basado en el usuario, el basado en la producción (Garvin utiliza el término "manufactura") y el basado en el valor. Garvin no sostiene que uno de estos enfoques sea suficiente por sí mismo. Por el contrario, una visión multidimensional de la calidad debe contar con los cinco enfoques. Este artículo describe brevemente estos cinco enfoques sobre la calidad y hace referencia al trabajo de algunos de los autores más reconocidos y con mayor visibilidad del ámbito de la gestión de la calidad. A continuación el artículo debate los argumentos a favor y en contra de la aplicación de los diferentes enfoques sobre la gestión de la calidad en la industria de la traducción. Los autores de este artículo están en desacuerdo entre ellos sobre la relevancia de la gestión terminológica en la industria de la traducción, pero sí que coinciden en que las partes interesadas deberían adoptar alguna posición al respecto

Defining Translation Quality

Many problems in the translation industry revolve around customer dissatisfaction with someone's translation quality and disputes between translators when one is revising the work of the other. To determine whether someone has attained translation quality, one must be able to measure it. To measure translation quality, one must be able to define it. And to define translation quality, one must be able to define both translation and quality. Our two prior articles have addressed these terms respectively. Those articles do not resolve disagreements about these terms; indeed, we authors have unresolved disagreements among ourselves. However, the articles outline how different definitions can radically affect people's expectations about translation and quality. This third article builds on the first two and presents two contrasting definitions of translation quality, a narrow one and a broad one. The narrow definition matches with the narrow definition of translation in the first article and an emphasis on the transcendent view of quality in the second article, while the broad definition matches with the broad definition of translation the first article and an integration of the five approaches in quality management from the second article. The authors strongly disagree about which definition of translation quality is better for the translation industry. Rather than pretending to be the end of this discussion, it hopes to encourage a continuation of the debate that has taken place among the authors.Molts dels problemes de la indústria de la traducció giren al voltant de la insatisfacció del client amb la qualitat d'alguna traducció, així com amb conflictes entre traductors quan un revisa el treball d'un altre. Per determinar si algú ha arribat a la qualitat de traducció pactada, un ha de poder mesurar-la. Per poder mesurar la qualitat de la traducció, un ha de poder definir-la. I per definir la qualitat de la traducció, un ha de poder definir dos conceptes, traducció i qualitat. Els nostres dos articles anteriors han abordat aquests dos conceptes respectivament. Aquests articles no resolen les discrepàncies entre nosaltres. No obstant això, els articles exposen com les diferents definicions poden afectar radicalment les expectatives sobre traducció i qualitat. Aquest tercer article es basa en els dos articles anteriors i presenta dues definicions confrontades de qualitat en traducció: una més concreta i una altra més àmplia. La definició més concreta combina la definició més estricta de traducció del primer article amb la visió transcendent de qualitat del segon article. En canvi, la definició més àmplia combina la definició àmplia de traducció del primer article amb una integració dels cinc enfocaments sobre gestió de la qualitat del segon article. Els autors estan totalment en desacord pel que fa quina de les definicions de qualitat de traducció és millor per a la indústria de la traducció. En lloc d'optar per tancar aquest debat amb aquests articles, els autors esperen haver donat peu a continuar amb el debat d'una manera més amplia de com s'ha produït entre ells.Muchos de los problemas de la industria de la traducción giran en torno a la insatisfacción del cliente con la calidad de alguna traducción, así como con conflictos entre traductores cuando uno revisa el trabajo de otro. Para determinar si alguien ha alcanzado la calidad de traducción pactada, uno debe poder medirla. Para poder medir la calidad de la traducción, uno debe poder definirla. Y para definir la calidad de la traducción, uno debe poder definir ambos conceptos, traducción y calidad. Nuestros dos artículos anteriores han abordado estos dos conceptos respectivamente. Dichos artículos no resuelven las discrepancias entre nosotros. No obstante, los artículos exponen cómo las diferentes definiciones pueden afectar radicalmente las expectativas sobre traducción y calidad. Este tercer artículo se basa en los dos artículos anteriores y presenta dos definiciones confrontadas de calidad en traducción: una más concreta y otra más amplia. La definición más concreta combina la definición más estricta de traducción del primer artículo con la visión transcendente de calidad del segundo artículo. En cambio, la definición más amplia combina la definición amplia de traducción del primer artículo con una integración de los cinco enfoques sobre gestión de la calidad del segundo artículo. Los autores están totalmente en desacuerdo en cuanto cuál de las definiciones de calidad de traducción es mejor para la industria de la traducción. En lugar de optar por zanjar este debate con estos artículos, los autores esperan haber dado pie a continuar con el debate de un modo más amplio de como se ha producido entre ellos

Defining the Landscape of Translation

Aquest article és el primer d'una sèrie de tres articles sobre qualitat en traducció. Els articles se succeeixen entre si i tracten la definició de traducció, qualitat i finalment qualitat en traducció. En relació amb el significat de traducció, en la literatura dels estudis de traducció s'han proposat moltes definicions. No obstant això, aquest article no és una revisió de la bibliografia. Per contra, suposa una contribució que consisteix a descriure un "paisatge" en què diverses definicions de traducció es poden "sembrar". Aquest paisatge està delimitat per dos eixos, que són l'abast i les especificacions, i proporciona un marc per discutir qüestions com a) la relació entre traducció i localització i b) el paper de les especificacions en traducció. Dins d'aquest paisatge, aquest article presenta dues postures oposada sobre la definició de traducció. Els autors no arriben a un acord sobre quina d'aquestes postures és més útil, però coincideixen que les parts interessades han de definir amb claredat el concepte de traducció abans de poder tractar la noció de qualitat en traducció de forma significativa.This article is the first in a three-part series on translation quality. The articles build on one another by addressing definitions of translation, quality, and finally translation quality. Concerning the meaning of translation, many definitions have been proposed in the translation-studies literature. This article, however, is not a literature review. Instead, it describes a "landscape" within which various definitions of translation can be "planted." This landscape is delimited by two axes-namely, scope and specifications-and provides a framework for discussing such questions as (a) the relationship between translation and localization and (b) the role of translation specifications. Within that landscape, this article presents two opposing views about the definition of translation. The authors disagree about which of these views is most useful, but they agree that stakeholders must clearly define translation before they can meaningfully address translation quality.Este artículo es el primero de una serie de tres artículos sobre calidad en traducción. Losartículos se suceden entre sí y tratan la definición de traducción, calidad y finalmente calidaden traducción. En relación con el significado de traducción, en la literatura de los estudiosde traducción se han propuesto muchas definiciones. No obstante, este artículo noes una revisión de la bibliografía. Por el contrario, supone una contribución que consisteen describir un "paisaje" en el que varias definiciones de traducción se pueden "sembrar".Este paisaje está delimitado por dos ejes, que son alcance y especificaciones, y proporcionaun marco para discutir cuestiones como a) la relación entre traducción y localizacióny b) el papel de las especificaciones en traducción. Dentro de este paisaje, este artículopresenta dos posturas opuesta sobre la definición de traducción. Los autores no llegan aun acuerdo sobre cuál de estas posturas es más útil, pero coinciden en que las partes interesadasdeben definir con claridad el concepto de traducción antes de poder tratar lanoción de calidad en traducción de forma significativa

Metric Learning for Graph-based Domain Adaptation

Abstract In many domain adaption formulations, it is assumed to have large amount of unlabeled data from the domain of interest (target domain), some portion of it may be labeled, and large amount of labeled data from other domains, also known as source domain(s). Motivated by the fact that labeled data is hard to obtain in any domain, we design algorithms for the settings in which there exists large amount of unlabeled data from all domains, small portion of which may be labeled. We build on recent advances in graph-based semi-supervised learning and supervised metric learning. Given all instances, labeled and unlabeled, from all domains, we build a large similarity graph between them, where an edge exists between two instances if they are close according to some metric. Instead of using predefined metric, as commonly performed, we feed the labeled instances into metric-learning algorithms and (re)construct a data-dependent metric, which is used to construct the graph. We employ different types of edges depending on the domain-identity of the two vertices touching it, and learn the weights of each edge. Experimental results show that our approach leads to significant reduction in classification error across domains, and performs better than two state-of-the-art models on the task of sentiment classification

Characterization and calibration of the James Webb space telescope mirror actuators fine stage motion

The James Webb Space Telescope’s (Webb’s) deployable primary and secondary mirrors are actively controlled to achieve and maintain precise optical alignment on-orbit. Each of the 18 primary mirror segment assemblies (PMSAs) and the secondary mirror assembly (SMA) are controlled in six degrees of freedom by using six linear actuators in a hexapod arrangement. In addition, each PMSA contains a seventh actuator that adjusts radius of curvature (RoC). The actuators are of a novel stepper motor-based cryogenic two-stage design that is capable of sub-10 nm motion accuracy over a 20 mm range. The nm-level motion of the 132 actuators were carefully tested and characterized before integration into the mirror assemblies. Using these test results as an initial condition, knowledge of each actuator’s length (and therefore mirror position) has relied on software bookkeeping and configuration control to keep an accurate motor step count from which actuator position can be calculated. These operations have been carefully performed through years of Webb test operations using both ground support actuator control software as well as the flight Mirror Control Software (MCS). While the actuator’s coarse stage length is cross-checked using a linear variable differential transformer (LVDT), no on-board cross-check exists for the nm-level length changes of the actuators’ fine stage. To ensure that the software bookkeeping of motor step count is still accurate after years of testing and to test that the actuator position knowledge was properly handed off from the ground software to the flight MCS, a series of optical tests were devised and performed through the Center of Curvature (CoC) ambient optical test campaigns at the Goddard Space Flight Center (GSFC) and during the thermal-vacuum tests of the entire optical payload that were conducted in Chamber A at Johnson Space Center (JSC). In each test, the actuator Fine Step Count (FSC) value is compared to an external measurement provided by an optical metrology tool with the goal of either confirming the MCS database value, or providing a recommendation for an updated calibration if the measured FSC differs significantly from the MCS-based expectation. During ambient testing of the PMSA hexapods, the nm-level actuator length changes were measured with a custom laser deflectometer by measuring tilts of the PMSA. The PMSA RoC fine stage characterization was performed at JSC using multi-wave interferometric measurements with the CoC Optical Assembly (COCOA). Finally, the SMA hexapod fine stage characterization test was performed at JSC using the NIRCam instrument in the “pass-and-a-half” test configuration using a test source from the Aft-Optics System Source Plate Assembly (ASPA). In this paper, each of these three tests, subsequent data analyses, and uncertainty estimations will be presented. Additionally, a summary of the ensemble state of Webb’s actuator fine stages is provided, along with a comparison to a Wavefront Sensing and Control (WFSC)-based requirement for FSC errors as they relate to the optical alignment convergence of the telescope on-orbit

JWST mirror and actuator performance at cryo-vacuum

The James Webb Space Telescope (JWST) telescope’s Secondary Mirror Assembly (SMA) and eighteen Primary Mirror Segment Assemblies (PMSAs) are each actively controlled in rigid body position via six hexapod actuators. Each of the PMSAs additionally has a radius of curvature actuator. The mirrors are stowed to the mirror support structure to survive the launch environment and then must be deployed 12.5 mm to reach the nominally deployed position before the Wavefront Sensing & Control (WFSC) alignment and phasing process begins. JWST requires testing of the full optical system in a Cryogenic Vacuum (CV) environment before launch. The cryo vacuum test campaign was executed in Chamber A at the Johnson Space Center (JSC) in Houston Texas. The test campaign consisted of an ambient vacuum test, a cooldown test, a cryo stable test at 65 Kelvin, a warmup test, and finally a second ambient vacuum test. Part of that test campaign was the functional and performance testing of the hexapod actuators on the flight mirrors. This paper will describe the testing that was performed on all 132 hexapod and radius of curvature actuators. The test campaign first tests actuators individually then tested how the actuators perform in the hexapod system. Telemetry from flight sensors on the actuators and measurements from external metrology devices such as interferometers, photogrammetry systems and image analysis was used to demonstrate the performance of the JWST actuators. The mirror move commanding process was exercised extensively during the JSC CV test and many examples of accurately commanded moves occurred. The PMSA and SMA actuators performed extremely well during the JSC CV test, and we have demonstrated that the actuators are fully functional both at ambient and cryo temperatures and that the mirrors will go to their commanded positions with the accuracy needed to phase and align the telescope

Characterization and calibration of the James Webb space telescope mirror actuators fine stage motion

The James Webb Space Telescope’s (Webb’s) deployable primary and secondary mirrors are actively controlled to achieve and maintain precise optical alignment on-orbit. Each of the 18 primary mirror segment assemblies (PMSAs) and the secondary mirror assembly (SMA) are controlled in six degrees of freedom by using six linear actuators in a hexapod arrangement. In addition, each PMSA contains a seventh actuator that adjusts radius of curvature (RoC). The actuators are of a novel stepper motor-based cryogenic two-stage design that is capable of sub-10 nm motion accuracy over a 20 mm range. The nm-level motion of the 132 actuators were carefully tested and characterized before integration into the mirror assemblies. Using these test results as an initial condition, knowledge of each actuator’s length (and therefore mirror position) has relied on software bookkeeping and configuration control to keep an accurate motor step count from which actuator position can be calculated. These operations have been carefully performed through years of Webb test operations using both ground support actuator control software as well as the flight Mirror Control Software (MCS). While the actuator’s coarse stage length is cross-checked using a linear variable differential transformer (LVDT), no on-board cross-check exists for the nm-level length changes of the actuators’ fine stage. To ensure that the software bookkeeping of motor step count is still accurate after years of testing and to test that the actuator position knowledge was properly handed off from the ground software to the flight MCS, a series of optical tests were devised and performed through the Center of Curvature (CoC) ambient optical test campaigns at the Goddard Space Flight Center (GSFC) and during the thermal-vacuum tests of the entire optical payload that were conducted in Chamber A at Johnson Space Center (JSC). In each test, the actuator Fine Step Count (FSC) value is compared to an external measurement provided by an optical metrology tool with the goal of either confirming the MCS database value, or providing a recommendation for an updated calibration if the measured FSC differs significantly from the MCS-based expectation. During ambient testing of the PMSA hexapods, the nm-level actuator length changes were measured with a custom laser deflectometer by measuring tilts of the PMSA. The PMSA RoC fine stage characterization was performed at JSC using multi-wave interferometric measurements with the CoC Optical Assembly (COCOA). Finally, the SMA hexapod fine stage characterization test was performed at JSC using the NIRCam instrument in the “pass-and-a-half” test configuration using a test source from the Aft-Optics System Source Plate Assembly (ASPA). In this paper, each of these three tests, subsequent data analyses, and uncertainty estimations will be presented. Additionally, a summary of the ensemble state of Webb’s actuator fine stages is provided, along with a comparison to a Wavefront Sensing and Control (WFSC)-based requirement for FSC errors as they relate to the optical alignment convergence of the telescope on-orbit

Cannabidiol and cannabis-inspired terpene blends have acute prosocial effects in the BTBR mouse model of autism spectrum disorder

IntroductionCannabidiol (CBD) is a non-intoxicating phytocannabinoid with increasing popularity due to its purported therapeutic efficacy for numerous off-label conditions including anxiety and autism spectrum disorder (ASD). Those with ASD are commonly deficient in endogenous cannabinoid signaling and GABAergic tone. CBD has a complex pharmacodynamic profile that includes enhancing GABA and endocannabinoid signaling. Thus, there is mechanistic justification for investigating CBD’s potential to improve social interaction and related symptoms in ASD. Recent clinical trials in children with ASD support CBD’s beneficial effects in numerous comorbid symptoms, but its impact on social behavior is understudied.MethodsHere, we tested the prosocial and general anxiolytic efficacy of a commercially available CBD-rich broad spectrum hemp oil delivered by repeated puff vaporization and consumed via passive inhalation in the female cohort of the BTBR strain, a common inbred mouse line for preclinical assessment of ASD-like behaviors.ResultsWe observed that CBD enhanced prosocial behaviors using the 3-Chamber Test with a different vapor dose-response relationship between prosocial behavior and anxiety-related behavior on the elevated plus maze. We also identified that inhalation of a vaporized terpene blend from the popular OG Kush cannabis strain increased prosocial behavior independently of CBD and acted together with CBD to promote a robust prosocial effect. We observed similar prosocial effects with two additional cannabis terpene blends from the Do-Si-Dos and Blue Dream strains, and further reveal that these prosocial benefits rely on the combination of multiple terpenes that comprise the blends.DiscussionOur results illustrate the added benefit of cannabis terpene blends for CBD-based treatment of ASD

Discrete molecular dynamics can predict helical prestructured motifs in disordered proteins.

Intrinsically disordered proteins (IDPs) lack a stable tertiary structure, but their short binding regions termed Pre-Structured Motifs (PreSMo) can form transient secondary structure elements in solution. Although disordered proteins are crucial in many biological processes and designing strategies to modulate their function is highly important, both experimental and computational tools to describe their conformational ensembles and the initial steps of folding are sparse. Here we report that discrete molecular dynamics (DMD) simulations combined with replica exchange (RX) method efficiently samples the conformational space and detects regions populating alpha-helical conformational states in disordered protein regions. While the available computational methods predict secondary structural propensities in IDPs based on the observation of protein-protein interactions, our ab initio method rests on physical principles of protein folding and dynamics. We show that RX-DMD predicts alpha-PreSMos with high confidence confirmed by comparison to experimental NMR data. Moreover, the method also can dissect alpha-PreSMos in close vicinity to each other and indicate helix stability. Importantly, simulations with disordered regions forming helices in X-ray structures of complexes indicate that a preformed helix is frequently the binding element itself, while in other cases it may have a role in initiating the binding process. Our results indicate that RX-DMD provides a breakthrough in the structural and dynamical characterization of disordered proteins by generating the structural ensembles of IDPs even when experimental data are not available