1,209 research outputs found
Efficient Base-Catalyzed Kemp Elimination in an Engineered Ancestral Enzyme
The routine generation of enzymes with completely new active sites is a major unsolved problem in protein engineering. Advances in this field have thus far been modest, perhaps due, at least in part, to the widespread use of modern natural proteins as scaffolds for de novo engineering. Most modern proteins are highly evolved and specialized and, consequently, difficult to repurpose for completely new functionalities. Conceivably, resurrected ancestral proteins with the biophysical properties that promote evolvability, such as high stability and conformational diversity, could provide better scaffolds for de novo enzyme generation. Kemp elimination, a non-natural reaction that provides a simple model of proton abstraction from carbon, has been extensively used as a benchmark in de novo enzyme engineering. Here, we present an engineered ancestral beta-lactamase with a new active site that is capable of efficiently catalyzing Kemp elimination. The engineering of our Kemp eliminase involved minimalist design based on a single function-generating mutation, inclusion of an extra polypeptide segment at a position close to the de novo active site, and sharply focused, low-throughput library screening. Nevertheless, its catalytic parameters (k(cat)/K-M similar to 2.10(5) M-1 s(-1), k(cat)similar to 635 s(-1)) compare favorably with the average modern natural enzyme and match the best proton-abstraction de novo Kemp eliminases that are reported in the literature. The general implications of our results for de novo enzyme engineering are discussed.Human Frontier Science Program RGP0041/2017Spanish Government RTI-2018-097142-B100
EQC2019-006403-PFEDER/Junta de Andalucia-Consejeria de Economia y Conocimiento E.FQM.113.UGR1
FAST-SE: An Esb Based Framework for SLA Trading
SLA driven service transaction has been identified as a key challenge to take advantage of a SOA. FAST System provides a software framework for the automated creation of SLAs. in particular it have been developed as an extension to the ESB (Enterprise Service Bus) paradigm to create a transparent SLA management layer that drives any service invocation. Our framework has been successfully applied in two different scenarios and provides an extensible architecture to address new domains
WS-Governance Tooling: SOA Governance Policies analysis and authoring
Governance is a capital issue in current Service
Oriented Arcuitectures, and governance policies are at its base.
The governance policies definition must be supported by proper
languages and tools, allowing for comfortable and collaborative
editing, consistency checking and the evaluation policy meeting.
In this paper we present a policy analizer for WS-Governance
(a governance policy definition language created by authors,
described in [1]) together with an online editor and test suite with
classical examples of WS-Governance Documents for consistency
validation. Both the test model and the analysis tool prove the
suitability of WS-Governance to define SOA governance policiesComisión Interministerial de Ciencia y Tecnología (CICYT) SETI (TIN2009-07366)Junta de Andalucía TIC-2533Junta de Andalucía TIC-590
Automated analysis of feature models: Quo vadis?
Feature models have been used since the 90's to describe software product lines as a way of reusing common parts in a family of software systems. In 2010, a systematic literature review was published summarizing the advances and settling the basis of the area of Automated Analysis of Feature Models (AAFM). From then on, different studies have applied the AAFM in different domains. In this paper, we provide an overview of the evolution of this field since 2010 by performing a systematic mapping study considering 423 primary sources. We found six different variability facets where the AAFM is being applied that define the tendencies: product configuration and derivation; testing and evolution; reverse engineering; multi-model variability-analysis; variability modelling and variability-intensive systems. We also confirmed that there is a lack of industrial evidence in most of the cases. Finally, we present where and when the papers have been published and who are the authors and institutions that are contributing to the field. We observed that the maturity is proven by the increment in the number of journals published along the years as well as the diversity of conferences and workshops where papers are published. We also suggest some synergies with other areas such as cloud or mobile computing among others that can motivate further research in the future.Ministerio de Economía y Competitividad TIN2015-70560-RJunta de Andalucía TIC-186
Flapless implant surgery: a review of the literature and 3 case reports
Since the 1970s, modern Implantology is based on a concept of surgery with flap elevation. Gradually, several
clinical trials demonstrated that a mid-crestal incision gives similar success rates compared to those obtained using
the classical protocol.
However, over the past decade in medicine it has been established the concept of minimally invasive surgery, consisting in taking advantage of advancements experienced in diagnostic techniques and specific surgical instruments,
to perform surgical procedures infringing as less damage as possible to the patient
The present work aims to produce a thorough review of the literature published on the field of Implantology with
flapless surgery, to determine the current scientific evidence of the technique, along with illustrating the results with
different clinical cases.
After presenting the clinical cases, and the review of literature, we can say that flapless surgeries should be restricted to well-selected cases in which a proper clinical and radiological planning has been made. Patients treated with
anticoagulant drugs or medically compromised equally can get benefitted by this minimal invasion technique
El foro romano de Iuliobriga (Cantabria): nuevas investigaciones arqueológicas
This article offers a general interpretation of Iuliobriga’s forum, emphasizing its characteristics and peculiarities from the information obtained in the latest archaeological research. It focuses on the results of an excavation made in 2004 inside the church of Santa María in Retortillo. This archaeological dig has allowed us to broaden the view we had of the forum’s square, thanks to the discovery of a new functional space inside it. The archaeological research has also revealed information about the origin of the habitat in Iuliobriga and permits the forum to be dated with certainty in the Flavian period.Se ofrece una interpretación general del foro de Iuliobriga, destacando sus características y peculiaridades tras la información obtenida en las últimas investigaciones arqueológicas. En especial, se presentan los resultados de una excavación realizada en 2004 en el interior de la iglesia de Santa María de Retortillo, la cual ha permitido ampliar la visión que se tenía de la plaza porticada del foro, con el descubrimiento de un nuevo espacio funcional dentro de éste. La misma intervención arqueológica ha aportado datos sobre el origen del hábitat en Iuliobriga y sobre la datación flavia del conjunto monumental del foro
Hidratació i rendiment: pautes per a una elusió efectiva de la deshidratació per exercici
El rendiment de les capacitats físiques i mentals durant la pràctica esportiva o la competició, es troba disminuït sota condicions de deshidratació. La pèrdua de pes es deu a la pèrdua d’aigua (suor i respiració) i quan aquesta és important, afecta de manera decisiva els sistemes nerviós, cardiovascular, termoregulador, endocrí i/o metabòlic, i pot provocar fins i tot la mort. Per eludir aquests efectes negatius de la deshidratació així com la disminució del rendiment, l’atleta haurà de beure prou quantitat de líquid abans, durant, i després de la competició o la pràctica d’exercici. Idealment, la beguda serà una solució composta d’aigua, electròlits i carbohidrats, en quantitat adequada per garantir, d’una banda, un rendiment òptim durant la competició i, d’una altra, reposar eficaçment i completament les pèrdues hídriques, electrolítiques i energètiques. La composició i el volum de la beguda tindrà en compte els factors extrínsecs (temperatura, humitat, altitud, vent, etc.) que envolten la competició, els factors intrínsecs de l’atleta (nivell de deshidratació, problemes gastrointestinals, tipus de competició) i les pròpies característiques de la beguda (gust, temperatura, composició). En termes generals, els atletes no acostumen a beure, durant la pràctica esportiva, el volum necessari per reemplaçar la pèrdua de fluids i electròlits, cosa que fa que calgui establir pautes perquè ho facin. En aquest treball es presenten aquestes pautes i la base fisiològica que les sosté
Hidratación y rendimiento: pautas para una elusión efectiva de la deshidratación por ejercicio
El rendimiento de las capacidades físicas y mental durante la práctica deportiva o la competición, está mermado bajo condiciones de deshidratación. La pérdida de peso se debe a la pérdida agua (sudor y respiración) y cuando ésta es importante, afecta de manera decisiva a los sistemas nervioso, cardiovascular, termorregulador, endocrino y/o metabólico, pudiendo provocar incluso la muerte. Para eludir estos efectos negativos de la deshidratación así como la disminución del rendimiento, el atleta deberá beber suficiente cantidad de líquido antes, durante y después de la competición o la práctica de ejercicio. Idealmente, la bebida será una solución compuesta de agua, electrolitos y carbohidratos en cantidad adecuada para garantizar, por un lado, un óptimo rendimiento durante la competición y, por otro, reponer eficaz y completamente las pérdidas hídricas, electrolíticas y energéticas. La composición y el volumen de la bebida tendrá en cuenta los factores extrínsecos (temperatura, humedad, altitud, viento, etc.) que rodean la competición, los factores intrínsecos del atleta (nivel de deshidratación, problemas gastrointestinales, tipo de competición) y las propias características de la bebida (sabor, temperatura, composición). En términos generales, los atletas no suelen beber, durante la práctica deportiva, el volumen necesario para reemplazar la pérdida de fluidos y electrolitos, lo que hace necesario establecer pautas para que lo hagan. En el presente trabajo se presentan esas pautas y la base fisiológica que las sustentan
Infecciones orofaciales de origen odontogénico
La naturaleza polimicrobiana de las infecciones odontógenas
así como la heterogeneidad de los cuadros clínicos asociados
son consecuencia de la diversidad de la microbiota bucal y de
la complejidad anatómica y funcional de la cavidad oral. Así
mismo, estos procesos pueden dar lugar a múltiples complicaciones
que pueden limitarse a afecciones locales o derivar hasta
compromisos sistémicos.
En el tratamiento farmacológico de estas infecciones es crucial
la elección del antibiótico y la pauta posológica más eficaces.
La farmacodinamia proporciona los parámetros que hacen posible
valorar como varía la actividad de los antibióticos en función
del tiempo.
Como norma general, en el manejo inicial de las infecciones
orofaciales en el adulto, incluidas las infecciones odontógenas,
se utilizará amoxicilina/ac. Clavulánico en dosis de 875 mg de
amoxicilina y 125 mg de ac. clavulánico pautado cada 8 horas.
El cumplimiento terapéutico es clave para evitar la aparición
de resistencias, por lo que se ha de maximizar la aceptación por
parte de los pacientes. En este sentido se ha demostrado que la
nueva presentación de 2000/125 mg de Augmentine Plus pautado
cada 12 horas tanto en profilaxis como tratamiento disminuye
significativamente la tasa de complicaciones infecciosas
derivada de la extracción del tercer molar.The polymicrobial nature of the odontogenic infections as well
as the variety of associated conditions are a consequence of the
diversity of the buccal microbiota and the anatomical and
functional complexity of the oral cavity. In addition to this, all
these processes can give way to multiple complications which
range from the local to the systemic level.
The appropriate choice of antibiotic and posology is crucial in
the successful management of these infections. Pharmacodynamics
provides those parameters that make it possible to assess
how antibiotics activity varies in time. As a general rule, the
first step in the initial management of orofacial infections in
adults, included odontogenic infections, will be the
administration of 875 mg of amoxicillin and 125 mg of
clavulanic every 8 hours. Therapeutic compliance is paramount to avoid resistance,
therefore patient's acceptance must be sought. In this sense, it
has been proved that Augmentine Plus (2000/125) every twelve
hours both as profylaxis and as treatment significantly decreases
the rate of infective complications associated to extraction of
the third molar
Protection of Catalytic Cofactors by Polypeptides as a Driver for the Emergence of Primordial Enzymes
Enzymes catalyze the chemical reactions of life. For nearly half of known enzymes, catalysis requires the binding of
small molecules known as cofactors. Polypeptide-cofactor complexes likely formed at a primordial stage and became
starting points for the evolution of many efficient enzymes. Yet, evolution has no foresight so the driver for the primordial
complex formation is unknown. Here, we use a resurrected ancestral TIM-barrel protein to identify one potential
driver. Heme binding at a flexible region of the ancestral structure yields a peroxidation catalyst with
enhanced efficiency when compared to free heme. This enhancement, however, does not arise from proteinmediated
promotion of catalysis. Rather, it reflects the protection of bound heme from common degradation
processes and a resulting longer lifetime and higher effective concentration for the catalyst. Protection of catalytic
cofactors by polypeptides emerges as a general mechanism to enhance catalysis and may have plausibly benefited
primordial polypeptide-cofactor associations.Human Frontier Science Program grant RGP0041/2017National Science Foundation grant 2032315Department of Defense grant MURI W911NF-16-1-0372National Institutes of Health grant R01AR069137Spanish Ministry of Science and Innovation/ FEDER Funds grant PID2021-124534OB-100Grant PID2020-116261GB-I0
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