Consequences of refining biological networks through detailed pathway information : From genes to proteoforms

Biologiske nettverk kan brukes til å modellere molekylære prosesser, forstå sykdomsprogresjon og finne nye behandlingsstrategier. Denne avhandlingen har undersøkt hvordan utformingen av slike nettverk påvirker deres struktur, og hvordan dette kan benyttes til å forbedre spesifisiteten for påfølgende analyser av slike modeller. Det første som ble undersøkt var potensialet ved å bruke mer detaljerte molekylære data når man modellerer humane biokjemiske reaksjonsnettverk. Resultatene bekrefter at det er nok informasjon om proteoformer, det vil si proteiner i spesifikke post-translasjonelle tilstander, for systematiske analyser og viste også store forskjeller i strukturen mellom en gensentrisk og en proteoformsentrisk representasjon. Deretter utviklet vi programmatisk tilgang og søk i slike nettverk basert på ulike typer av biomolekyler, samt en generisk algoritme som muliggjør fleksibel kartlegging av eksperimentelle data knyttet til den teoretiske representasjonen av proteoformer i referansedatabaser. Til slutt ble det konstruert såkalte pathway-spesifikke nettverk ved bruk av ulike detaljnivåer ved representasjonen av biokjemiske reaksjoner. Her ble informasjon som vanligvis blir oversett i standard nettverksrepresentasjoner inkludert: små molekyler, isoformer og modifikasjoner. Strukturelle egenskaper, som nettverksstørrelse, graddistribusjon og tilkobling i både globale og lokale undernettverk, ble deretter analysert for å kvantifisere virkningene av endringene.Biological networks can be used to model molecular processes, understand disease progression, and find new treatment strategies. This thesis investigated how refining the design of biological networks influences their structure, and how this can be used to improve the specificity of pathway analyses. First, we investigate the potential to use more detailed molecular data in current human biological pathways. We verified that there are enough proteoform annotations, i.e. information about proteins in specific post-translational states, for systematic analyses and characterized the structure of gene-centric versus proteoform-centric network representations of pathways. Next, we enabled the programmatic search and mining of pathways using different models for biomolecules including proteoforms. We notably designed a generic proteoform matching algorithm enabling the flexible mapping of experimental data to the theoretic representation in reference databases. Finally, we constructed pathway-based networks using different degrees of detail in the representation of biochemical reactions. We included information overlooked in most standard network representations: small molecules, isoforms, and post-translational modifications. Structural properties such as network size, degree distribution, and connectivity in both global and local subnetworks, were analysed to quantify the impact of the added molecular entities.Doktorgradsavhandlin

Dinámica de las formas del P en suelos de la región sudoeste Pampeana: estudio de la incubación con fertilizante fosfatado

Las distintas formas de P en el suelo se encuentran en equilibrio dinámico, dependiente del ambiente edáfico (textura, materia orgánica y el pH) y del manejo agronómico (como la rotación de cultivos y la fertilización). El objetivo del estudio fue evaluar el efecto de la aplicación de P al suelo sobre los equilibrios de este elemento. Se seleccionaron nueve suelos y se les agregó 0, 50 y 100 μg de P g-1 de suelo, seguidamente se los sometió a incubación durante 0, 90, 180 y 360 días. El agregado de P produjo una caída inicial de las formas de P analizadas. Esta disminución fue más marcada y prolongada en los suelos poco profundos. La cantidad de P-Fe+Al formado durante el período estudiado dependió de la relación Fe+Al:Ca del suelo, con valores máximos cuando la relación fue alrededor de 15, y fue variable en el tiempo alcanzando el máximo a los 180 días. Por otro lado, la formación de P-Ca fue mucho más variable y presentó cambios importantes en el tiempo. Los equilibrios del P en los suelos someros se fueron modificando con el transcurso de la incubación, de manera tal que el P no cuantificado a los 90 y 180 días es detectado a los 360. Estas muestras fueron analizadas con microscopia electrónica y se observó la presencia de sustancias cristalizadas (90 y 180 días) indicando la formación de compuestos meta estables de P que podrían ser una de las transformaciones que sufre este elemento en el tiempo.Different soil P forms exist in a dynamic equilibrium, which depends on the edaphic atmosphere (texture, MO and pH) and on theagronomic management practices (crop rotation and fertilization).The objective of the study was to assess the effect of P application on a soil on the equilibrium of this element. Nine soils were selected and 0, 50 and 100 μg of P g-1 were added to these soils. Subsequently, the soil-P mixtures were incubated during 0, 90, 180 and 360 days. The P addition produced an initial decrease of the analyzed P forms. This decrease was more pronounced and persistent in time in the shallow soils. The amount of P-Fe+Al formed during the studied period depended on the soil Fe+Al:Ca relationship, reaching maximum values when the ratio was around 15. In addition, the amount of P-Fe+Al was variable in time and reached maximum values after 180 days of incubation. On the other hand, the formation of P-Ca was much more variable and presented important changes in time. The P balances in shallow soils changed throughout the incubation period; P that was not detected at days 90 and 180 was detected at day 360. These samples were analyzed by electron microscopy and the presence of crystallized substances was observed on days 90 and 180, indicating the formation of P metastable compounds whichcould be one of the transformations that this element suffers in time

Individualizing anaemia therapy

Individualized strategies for managing renal anaemia with erythropoiesis-stimulating agents (ESAs) need to be advanced. Recent outcomes from clinical studies prompted a narrowing of the guideline-recommended haemoglobin target (11–12 g/dL) due to increased mortality and morbidity when targeting higher haemoglobin concentrations. Maintaining a narrow target is a clinical challenge, as haemoglobin concentration tends to fluctuate. The goal of individualized treatment is to achieve the haemoglobin target at the lowest ESA dose while avoiding significant fluctuations in haemoglobin concentrations and persistently low or high concentrations. This may require changes to the ESA dose and dosing frequency over the course of treatment

Spectral transformations of measures supported on the unit circle and the Szegö transformation

17 pages, no figures.-- MSC2000 codes: 42C05, 15A23.MR#: MR2457097 (2009k:42046)Zbl#: Zbl 1169.42009In this paper we analyze spectral transformations of measures supported on the unit circle with real moments. The connection with spectral transformations of measures supported on the interval [−1,1] using the Szegö transformation is presented. Some numerical examples are studied.The work of the first author (L. Garza) was supported by a grant of Universidad Autónoma de Tamaulipas. The research of the third author (F. Marcellán) has been supported by Dirección General de Investigación, Ministerio de Educación y Ciencia of Spain, grant MTM 2006-13000-C03-02.Publicad

Orthogonal polynomials and measures on the unit circle. The Geronimus transformations

12 pages, no figures.-- MSC2000 codes: 42C05, 15A23.-- Published in Special Issue dedicated to William B. Gragg on the occasion of his 70th birthday.In this paper we analyze a perturbation of a nontrivial positive measure supported on the unit circle. This perturbation is the inverse of the Christoffel transformation and is called the Geronimus transformation. We study the corresponding sequences of monic orthogonal polynomials as well as the connection between the associated Hessenberg matrices. Finally, we show an example of this kind of transformation.The work of the first author (L. Garza) has been supported by a grant from the Universidad Autónoma de Tamaulipas. The work of the second author (J. Hernández) has been supported by a grant from the Fundación Universidad Carlos III de Madrid. The research of the third author (F. Marcellán) has been supported by Dirección General de Investigación, Ministerio de Educación y Ciencia of Spain, grant MTM 2006-13000-C03-02.Publicad

The Comparison Study of Short-Term Prediction Methods to Enhance the Model Predictive Controller Applied to Microgrid Energy Management

Electricity load forecasting, optimal power system operation and energy management play key roles that can bring significant operational advantages to microgrids. This paper studies how methods based on time series and neural networks can be used to predict energy demand and production, allowing them to be combined with model predictive control. Comparisons of different prediction methods and different optimum energy distribution scenarios are provided, permitting us to determine when short-term energy prediction models should be used. The proposed prediction models in addition to the model predictive control strategy appear as a promising solution to energy management in microgrids. The controller has the task of performing the management of electricity purchase and sale to the power grid, maximizing the use of renewable energy sources and managing the use of the energy storage system. Simulations were performed with different weather conditions of solar irradiation. The obtained results are encouraging for future practical implementation