Geminiviruses for biotechnology: the art of parasite taming

ConferenciaViruses are intracellular pathogens that have evolved efficient strategies for replication and expression of their proteins in the host cells. Geminiviruses – plant viruses with small circular single-stranded DNA genomes – effectively manipulate plant cell processes for viral functions, entailing great potential for biotechnological applications. This potentiality has been realized in the form of protein expression and gene-silencing vectors, and, more recently, vectors for genome editing – a technology that these viruses seem particularly well-suited to facilitate. This insight offers an overview of the biological properties of geminiviruses, with emphasis on those leveraging development of geminivirus-based replicons. It illustrates the basis for engineering geminivirus-based replicons and their applications. Furthermore, it discusses the reported use and future perspectives of geminivirus-based replicons for genome editing.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Genetic predisposition for Multiple Myeloma. Identification and functional characterization of risk variants

Multiple myeloma (MM) is a blood malignancy originating from plasma cells. First-degree relatives of patients with MM have two- to four-fold higher risk of MM. However, the molecular basis remains largely unknown. This Ph.D. project aims to identify novel DNA sequence variants predisposing to MM through genome-wide association studies (GWAS) and, subsequently, characterize identified variants functionally.Article I describes a systematic study where we screened for causal gene-regulatory variants at 21 MM risk loci. Article II describes a Nordic GWAS identifying the SOHLH2 (13q13.3) as a novel MM risk locus. Article III describes a novel international meta-analysis of GWAS data totalling 10 906 cases and 366 221 controls, identifying twelve new risk variants for MM accounted for by nine loci: 5q35.2 CPEB4, 6p22.2 BTN3A2, 9q21.33 DAPK1, 10q24.33 STN1, 10q25.2 MXI1, 19p13.3 NFIC, 21q11.2, SAMSN1 and a rare variant at 13q13.1 BRCA2. Finally, in Article IV, we explore the possibility of identifying transcription factors that mediate allele-specific gene-regulatory effects through combined use of CRISPR/Cas9 screening and epistasis analysis of gene expression data.The work presented in this thesis provides new insight into the mechanisms underlying genetic predisposition for multiple myeloma

Numerical and modeling error assessment of large-eddy simulation using direct-numerical-simulation-aided large-eddy simulation

We study the numerical errors of large-eddy simulation (LES) in isotropic and wall-bounded turbulence. A direct-numerical-simulation (DNS)-aided LES formulation, where the subgrid-scale (SGS) term of the LES is computed by using filtered DNS data is introduced. We first verify that this formulation has zero error in the absence of commutation error between the filter and the differentiation operator of the numerical algorithm. This method allows the evaluation of the time evolution of numerical errors for various numerical schemes at grid resolutions relevant to LES. The analysis shows that the numerical errors are of the same order of magnitude as the modeling errors and often cancel each other. This supports the idea that supervised machine learning algorithms trained on filtered DNS data might not be suitable for robust SGS model development, as this approach disregards the existence of numerical errors in the system that accumulates over time. The assessment of errors in turbulent channel flow also identifies that numerical errors close to the wall dominate, which has implications for the development of wall models

Coherent structures in turbulent boundary layers over an airfoil

This preliminary study is concerned with the identification of three-dimensional coherent structures, defined as intense Reynolds-stress events, in the turbulent boundary layer developing over the suction side of a NACA4412 airfoil at a Reynolds number based on the chord lenght and the incoming velocity of Rec = 200, 000. The scientific interest for such flows originates from the non-uniform adverse pressure gradient that affects the boundary-layer development. Firstly, we assess different methods to identify the turbulent-non-turbulent interface, in order to exclude the irrotational region from the analysis. Secondly, we evaluate the contribution of the considered coherent structures to the enhanced wall-normal velocity, characteristic of adverse pressure gradients. Our results show that it is necessary to limit the detection of coherent structures to the turbulent region of the domain, and that the structures reveal qualitative differences between the contributions of intense events to the wall-normal velocity in adverse-pressure-gradient and zero-pressure-gradient turbulent boundary layers

Intense reynolds-stress events in turbulent ducts

The aim of the present work is to investigate the role of intense Reynolds shear-stress events in the generation of the secondary flow in turbulent ducts. We consider the connected regions of flow where the product of the instantaneous fluctuations of two velocity components is higher than a threshold based on the long-time turbulence statistics, in the spirit of the three-dimensional quadrant analysis proposed by Lozano-Durán et al. (J. Fluid Mech., vol. 694, 2012, pp. 100–130). We examine both the geometrical properties of these structures and their contribution to the mean in-plane velocity components, and we perfom a comparison with turbulent channel flow at similar Reynolds number. The contribution to a certain mean quantity is defined as the ensemble average over the detected coherent structures, weighted with their own occupied volume fraction. In the core region of the duct, the contribution of intense events to the wall-normal component of the mean velocity is in very good agreement with that in the channel, despite the presence of the secondary flow in the former. Additionally, the shapes of the three-dimensional objects do not differ significantly in both flows. In the corner region of the duct, the proximity of the walls affects both the geometrical properties of the coherent structures and the contribution to the mean component of the vertical velocity. However, such contribution is less relevant than that of the complementary portion of the flow not included in such objects. Our results show that strong Reynolds shear-stress events are affected by the presence of a corner but, despite the important role of these structures in the dynamics of wall-bounded turbulent flows, their contribution to the secondary flow is relatively low, both in the core and in the corner

Contribution of Reynolds-stress structures to the secondary flow in turbulent ducts

The present work is aimed at evaluating the contribution to the secondary flow in duct flow with square and rectangular cross section from three-dimensional coherent structures, defined as intense Reynolds-stress events. The contribution to a certain mean quantity is defined as the ensemble average over the detected coherent structures, weighted with their own occupied volume fraction. Our analysis unveils that the contribution to the cross-stream components of the mean velocity is either very similar to the same contribution in channel flow, or almost negligible in respect to the contribution from the portion of the domain not occupied by coherent structures. These results suggest that the most intense events are not directly responsible for the secondary flow

Characterization of turbulent coherent structures in square duct flow

This work is aimed at a first characterization of coherent structures in turbulent square duct flows. Coherent structures are defined as connected components in the domain identified as places where a quantity of interest (such as Reynolds stress or vorticity) is larger than a prescribed non-uniform threshold. Firstly, we qualitatively discuss how a percolation analysis can be used to assess the effectiveness of the threshold function, and how it can be affected by statistical uncertainty. Secondly, various physical quantities that are expected to play an important role in the dynamics of the secondary flow of Prandtl's second kind are studied. Furthermore, a characterization of intense Reynolds-stress events in square duct flow, together with a comparison of their shape for analogous events in channel flow at the same Reynolds number, is presented

Modernización de los servicios de agua potable y alcantarillado sanitario de la UPIS San Miguel en la provincia de Chiclayo - Lambayeque

La presente Tesis lleva como título: Modernización de los servicios de agua potable y alcantarillado sanitario de la UPIS San Miguel en la provincia de Chiclayo – Lambayeque, proyecto desarrollado bajo la línea de investigación de Saneamiento, que nos permite plantear una propuesta técnica, debido a que la población de las localidades, se encuentra viviendo en condiciones inadecuadas por el deficiente acceso a los servicios de agua potable y alcantarillado; por lo que es necesario modernizar una red de Agua Potable y Alcantarillado para brindar un adecuado servicio de saneamiento básico, y reducir el grado de contaminación ambiental; al mismo tiempo se contribuye al desarrollo socio económico y salubridad de la población. Para cumplir con nuestra propuesta, utilizamos los softwares WaterCAD, teniendo en cuenta los parámetros de diseño establecidos en el Reglamento Nacional de EdificacionesThis Thesis is titled: Modernization of the drinking water and sanitary sewage services of the UPIS San Miguel in the province of Chiclayo - Lambayeque, a project developed under the Sanitation research line, which allows us to propose a technical proposal, due to that the population of the localities is living in inadequate conditions due to poor access to drinking water and sewage services; Therefore, it is necessary to modernize a Drinking Water and Sewage network to provide an adequate basic sanitation service, and reduce the degree of environmental contamination; At the same time, it contributes to the socio-economic development and health of the population. To comply with our proposal, we use WaterCAD software, taking into account the design parameters established in the National Building RegulationsTesi

Educació física emocional a secundària. El paper de la sociomotricitat

L’educació física pot exercir un paper destacat en l’educació de competències emocionals, les quals repercuteixen directament en el rendiment acadèmic de l’alumnat i en la millora del seu benestar subjectiu. En aquest treball es va examinar la vivència emocional d’adolescents en diferents classes de jocs esportius, amb presència i absència de competició. Va correspondre a un disseny quasi-ex-perimental de mesures repetides. Hi van participar 220 estudiants d’ESO i batxillerat de 5 centres educatius de Catalunya i València. Es van fer 4 sessions basades en diferents famílies de jocs esportius. A través de l’escala validada Games and emotions Scale (GES) els alumnes van identificar la vivència emocional originada en cada joc. L’anàlisi de les dades es va fer mitjançant equacions d’estimació generalitzades (GEE). El model va considerar els factors intraparticipants: 1) domini d’acció motriu; 2) competició i 3) tipus d’emoció i els factors entre-participants, que van ser: 1) gènere, i 2) historial esportiu. Dels resultats s’obtenen tres descobertes principals: a) el paper destacat dels jocs sociomotors per promoure emocions positives intenses; b) la presència d’adversaris (en jocs d’oposició i de cooperació-oposició) augmenta la intensitat de les emocions negatives; c) la introducció de la competició incrementa la intensitat de les emocions positives en els jocs psicomotors i els valors de les emocions negatives en els jocs sociomotors. Aquest estudi aporta arguments científics i recomanacions pràctiques per promoure una educació física emocional orientada cap al benestar subjectiu i a l’adquisició d’estils de vida saludables en adolescents