Doctoral School

2024 EUA-CDE Annual Meeting
EUA: European University Association

"The role of data in shaping doctoral education", hosted by the UPC from 26 to 28 June 2024

Theses for defense agenda

Reading date: 27/05/2024

  • LIN, LI CHUN: Deciphering the role of mechanical stress during ageing and in neurodegenerative diseases
    Author: LIN, LI CHUN
    Thesis file: (contact the Doctoral School to confirm you have a valid doctoral degree and to get the link to the thesis)
    Programme: DOCTORAL DEGREE IN PHOTONICS
    Department: Institute of Photonic Sciences (ICFO)
    Mode: Normal
    Deposit date: 29/04/2024
    Reading date: pending
    Reading time: pending
    Reading place: pending
    Thesis director: KRIEG, MICHAEL
    Committee:
         PRESIDENT: MARTÍN BLANCO, ENRIQUE
         SECRETARI: SANDOVAL ÁLVAREZ, ÁNGEL
         VOCAL: PEREZ BROWNE, MARCOS FRANCISCO
    Thesis abstract: The locomotion of Caenorhabditis elegans (C. elegans) offers a unique platform for studying complex postures and motor behaviors. In this study, I investigated locomotor patterns across different ages and genetic backgrounds of C. elegans, utilizing customized tracking systems and advanced analysis techniques. A comprehensive examination of locomotion behaviors was conducted using the eigenworm approach. Eigenworms are the principal components of the animals¿ posture space. I identified specific eigenworms associated with forward movement, turning, and exaggerated bends. Notably, spectrin-mutant animals showed a strong correlation between their bending movements and a specific eigenworm for turning in wild-type animals. These findings suggest that eigenworms offer a universal framework to compare different types of worm movement and assess the effects of mutations. This paves the way for a more informative analysis of worm behavior, especially when combined with studies of neuronal networks.Additionally, I explored the role of proprioception in coordinating motor activities within C. elegans, employing genetic and modeling approaches. The focus of my research was to elucidate the mechanisms underlying proprioceptive feedback, including mechanical stress and neuronal signaling, with a focus on age-related deficits. My findings elucidate that the spectral network associated with a singular proprioceptive DVA interneuron, which modulates tension and compression states, serves as a critical determinant of body posture. Intriguingly, a striking resemblance was observed between animals of early ageing and the mutant animals for ß-spectrin, where both animals crawled with exaggerated body bends. Moreover, I show that proprioceptive neurons are found to encode body posture and exhibit age-dependent structural and functional alterations, including protein aggregation and decreased mechanical tension. Notably, spectrin, a cytoskeletal component, emerges as a key player in maintaining proprioceptive integrity during ageing.Furthermore, I investigated the molecular pathways underlying age-associated proprioceptive defects, more specifically, the role CLP-1 protease in the cleavage of UNC-70/ß-spectrin in ageing animals. Conditional knockout of clp-1 in DVA interneuron revealed altered locomotor behaviors, along with the pan-neuronal knockout of clp-1. Given the role of spectrin in proprioception through DVA interneuron suggests that clp-1 regulates spectrin in age-related neurodegeneration. Lastly, I explored the effect of ectopic expression of human ¿ßcrystalline on ageing. We hypothesized that ¿ß-crystallin (HSPB5), a small heat shock protein (sHsp), will stabilize ß-spectrin and shield it from clp-1 proteolytic degradation during ageing. I ectopically expressed the constitutively active 3E mutant of ¿ß-crystallin pan-neuronally or specifically in DVA. Through locomotion analysis of animals from young adult to adult day 6, I observed a modest rescue in the locomotion behavioral pattern in both DVA specific and pan-neuronally expressed ¿ß-crystallin animals. We speculate that constitutively active ¿ß-crystallin may bind to proteolytically vulnerable domains/residues of the UNC-70 protein, providing protection against proteases such as clp-1. Collectively, these findings contribute to our understanding of proprioceptive mechanisms in ageing and offer insights into potential therapeutic targets for age-related neurodegenerative diseases.

Reading date: 28/05/2024

  • JOSEPH, DIYA: Improving memory access efficiency for real-time rendering in tile-based GPU architectures
    Author: JOSEPH, DIYA
    Thesis file: (contact the Doctoral School to confirm you have a valid doctoral degree and to get the link to the thesis)
    Programme: DOCTORAL DEGREE IN COMPUTER ARCHITECTURE
    Department: (DAC)
    Mode: Normal
    Deposit date: 30/04/2024
    Reading date: pending
    Reading time: pending
    Reading place: pending
    Thesis director: GONZÁLEZ COLÁS, ANTONIO MARIA | ARAGÓN ALCARAZ, JUAN LUIS
    Committee:
         PRESIDENT: XEKALAKIS, POLYCHRONIS
         SECRETARI: JIMENEZ GONZALEZ, DANIEL
         VOCAL: DE LUCAS CASAMAYOR, ENRIQUE
    Thesis abstract: Following the growing demands of applications mobile GPUs have greatly evolved in the past decade with expectations for continued advancement. These developments must address the rising performance demands and prioritize energy efficiency to accommodate the energy and temperature constraints of battery-powered, handheld devices. Main memory accesses are one of the main sources of energy consumption and occasionally a source of performance bottleneck in GPUs. The adoption of Tile-Based Rendering (TBR) architecture for many mobile GPUs in the late 1990s, marks a leap towards energy efficiency for mobile GPUs by enhancing locality and minimizing bandwidth-intensive memory accesses.The objective of this thesis is to enhance memory access efficiency in TBR GPU architectures for graphics applications. The strategy involves fine-tuning the structures in the memory hierarchy or altering the memory access patterns directed towards the memory hierarchy. By capitalizing on the unique characteristics of graphics applications, the goal is to boost both performance and energy efficiency with minimal hardware adjustments, thereby avoiding any adverse impact on general-purpose workloads running on GPUs.TBR architectures introduce an overhead through the creation of a specialized data structure for tiling which is stored in memory and cached in L1 and shared L2 caches. The OPT replacement policy, has been formally proven as optimal for minimizing misses but it is near-impossible to implement in hardware. The first proposal in this thesis brings the OPT to life, for this data structure. Along with other improvements in the L2, this proposal called TCOR results in a 13.8% decrease in the memory hierarchy energy consumption and an increased throughput in the Tiling Engine. DTexL, the second proposal in this thesis, increases the aggregated capacity of certain L1 caches by reducing replication of memory blocks. Contemporary GPUs have multiple GPU cores and a scheduler that distributes work (warps) among them, focusing on load balancing. These load balancing techniques are detrimental to texture memory locality in the L1 caches. We propose a new workload scheduler that favours texture locality and to overcome the resulting load imbalance, we propose a minor modification to the GPU architecture. DTexL results in a 46.8% decrease in L2 Accesses, a 19.3% increase in performance and a 6.3% decrease in total GPU energy. All this with a negligible overhead.Literature is plentiful in works exploiting cache locality for GPUs. A majority of them explore replacement or bypassing policies. In our third proposal, we surpass this exploration by fabricating a formal proof for a no-overhead quasi-optimal caching technique in the shared L2 for textures. We exploit the frame-to-frame reuse of textures by traversing frames in a boustrophedonic manner w.r.t. the conventional frame-to-frame tile order. We first approximate the texture access trace to a circular trace and then forge a formal proof for our proposal being optimal for such traces. We call our proposal Boustrophedonic Frames.Hiding memory latency is becoming a problem in contemporary GPUs. To address this challenge, we introduce WaSP as the final work in this thesis, a lightweight warp scheduler tailored for GPUs in graphics applications. WaSP strategically mimics prefetching by initiating a select subset of warps, termed priority warps, early in execution to reduce memory latency for subsequent warps. WaSP reduces average memory latency while maintaining locality for the majority of warps. While maximizing memory parallelism utilization, WaSP prevents saturating the caches with misses to avoid filling up the MSHRs. This approach reduces cache stalls that halt further accesses to the cache. Overall, WaSP yields a 3.9% performance speedup with a negligible overhead.
  • KNAPP, CHRISTIAN: Quantitative Fluorescence Imaging of Spatiotemporal Dynamics of DNA Damage and DNA Replication in Health and Disease
    Author: KNAPP, CHRISTIAN
    Thesis file: (contact the Doctoral School to confirm you have a valid doctoral degree and to get the link to the thesis)
    Programme: DOCTORAL DEGREE IN PHOTONICS
    Department: Institute of Photonic Sciences (ICFO)
    Mode: Normal
    Deposit date: 30/04/2024
    Reading date: pending
    Reading time: pending
    Reading place: pending
    Thesis director: GARCÍA PARAJO, MARÍA | CAMPELO AUBARELL, FELIX
    Committee:
         PRESIDENT: MANZO, CARLO
         SECRETARI: KRIEG, MICHAEL
         VOCAL: SIMÖES DA SILVA CARDOSO, MARIA CRISTINA
    Thesis abstract: Genomic instability, caused by DNA damage, is the main determinant for cancer and aging. To safeguard genomic integrity, cells evolved complex mechanisms to ensure error-free DNA replication and DNA damage repair. However, cells are not always able to repair DNA damage, and have to halt proliferation in a state of senescence, or perform the programmed cell death, apoptosis, to prevent giving rise to tumors and to protect the organism. Yet, this loss of proliferative potential ultimately leads to aging of the organism.The significance of DNA damage repair is underlined by mutations in genes encoding DNA repair proteins, which lead to premature aging diseases associated with a wide spectrum of early-onset age-related diseases. Notably, Hutchinson-Gildford progeria syndrome (HGPS), the most severe premature aging disease, is not caused by mutations in a DNA repair protein, but in the nuclear intermediate filament protein lamin A. Nonetheless, DNA damage is considered a main driver of this disease.The affected protein lamin A is a main component of the nuclear lamina, which is an intermediate filament meshwork and one of the layers of the nuclear envelope which surrounds the nucleus. To date, the pathological mechanism how the mutant form of lamin A leads to DNA damage in HGPS is poorly understood.Here, we propose our hypothesis that this mutations disturbs the interactions between the nuclear lamina and peripheral DNA in a manner that mechanically interferes with the local progression of DNA replication sites. Consequently, our hypothesis predicts that DNA damage predominantly arises during DNA replication of peripheral DNA in close proximity to the nuclear lamina. This creates a spatial correlation between the occurrence of DNA damage and the nuclear periphery, as well as a temporal correlation with DNA replication of peripheral DNA which occurs during late S-phase of the cell cycle.Hence, in Chapter 3, we present our approach to characterize the spatiotemporal dynamics of DNA damage throughout the cell cycle. This approach employs simple reporter cell models of DNA damage and DNA replication, along with long-term multi-color fluorescence live cell imaging microcopy, and a quantitative analysis pipeline. This analysis pipeline monitors and follows cells over multiple days and quantifies DNA damage foci formed by fluorescent DNA damage repair proteins, and employs machine learning-based algorithms to classify distribution patterns of the DNA replication protein PCNA to perform post hoc in silico synchronization of cell cycles. In Chapter 4, we describe how we employed this approach to quantify DNA damage foci and to characterize their distributions throughout the cell cycle in cell models of HGPS. We conducted these experiments under different conditions and with different cell lines, however we could not detect differences between HGPS cell models and healthy controls. Finally, we discuss our findings as well as technical and biological aspects of our approach in the context of literature.In Chapter 5, we present an approach which we developed to study the influence of the mutant form of lamin A on the mobility of DNA replication sites, and thus to test the mechanical aspects of our hypothesis. This approach is based on single molecule tracking of the DNA replication protein PCNA. While we could not detect differences between HGPS cell models and healthy controls with this approach, we revealed two slow mobility states of PCNA within DNA replication sites. These two mobility states are consistent the the PCNA meshwork model proposed by Boehm et al. in 2016 and may represent DNA replication condensates.Finally, in Chapter 6, we summarize the main results of this thesis and discuss future and potential applications of our approaches to advance our understanding of the cell cycle-dependent dynamics of genome maintenance, and the structural organization of DNA replication sites.
  • MARTIN SAINT-LAURENCE, PABLO: Constitutive modeling of ultrafine-grained refractory high-entropy alloys obtained by powder metallurgy
    Author: MARTIN SAINT-LAURENCE, PABLO
    Thesis file: (contact the Doctoral School to confirm you have a valid doctoral degree and to get the link to the thesis)
    Programme: DOCTORAL DEGREE IN MATERIALS SCIENCE AND ENGINEERING
    Department: (CEM)
    Mode: Normal
    Deposit date: 17/04/2024
    Reading date: 28/05/2024
    Reading time: 11:30
    Reading place: EEBE (Escola d'Enginyeria Barcelona Est) Sala Polivalent de l'Edifici A, Edifici A, planta baixa, Campus Diagonal-Besòs
    Thesis director: CABRERA MARRERO, JOSE MARIA
    Committee:
         PRESIDENT: TORRALBA CASTELLÓ, JOSE MANUEL
         SECRETARI: LLORCA ISERN, NURIA
         VOCAL: CARREÑO GOROSTIAGA, FERNANDO
    Thesis abstract: Refractory high-entropy alloys (RHEAs) prepared by mechanical alloying followed by spark plasma sintering usually outweigh the high-temperature mechanical behavior of as-cast counterpart alloys. Despite that, few studies have been conducted in order to understand their deformation mechanisms associated with these alloys and their particular microstructures (ultrafine grain size and considerable presence of secondary phases). The present work reports the synthesis, the microstructural characterization, and the constitutive modeling the AlCrxFeMoNbTiV2 (x = 0.15, 0.4, 0.8) RHEAs prepared by powder metallurgy, aiming to contribute to the comprehension of the deformation mechanisms behind the high-temperature mechanical behavior of RHEAs obtained with this fabrication route, as well as of the composition-microstructure-properties of RHEAs.In order to do so, the study was divided into three parts. In the first one, the effect of composition and milling time over themicrostructural and particle evolution of the powder was investigated. In the second part, the effect of Cr content and of a heat treatment over phase formation, microstructure, and grain size was investigated. In the third part, the samples were subjected to compression testing between 950 °C and 1100 °C and between 0.0005 s-1 and 0.01 s-1 to obtain the constitutive equations of the peak stress. Additionally, the microstructure of some of the deformed samples was characterized to find microstructural hints associated with the different potential softening and deformation mechanisms. During the milling study, it was observed that most of the changes occurred during the firsts 50 h, resulting in an average particle size of 7 µm and a nanostructured bcc+hcp microstructure. Except for Mo, none of the constituent elements considerably affected the microstructure or the particle size of the milled powders. The as-sintered samples, fabricated using powder milled for 50 h, successfully presented an ultrafine-grained and multiphase microstructure, constituted by a V,Mo-rich bcc matrix, accompanied by Fe,Nb-rich Laves phases, Al2O3 particles, and Ti,Nb-rich carbides. For reference, a hardness of 1124 HV0.3 was obtained in the as-sintered samples. The average grain size of the matrix phase decreased from 0.40 µm to 0.21 µm with further Cr content; however, the high-temperature mechanical properties were not affected. On the other hand, after the heat treatment, the average grain size increased up to 1.5 µm without affecting the phase equilibrium though. In opposition to the Cr content, the heat treatment enhanced the yield strength in a considerable manner: a specific yield strength of 98 MPa·g-1·cm3 at 1000 °C was obtained in these samples, three times that of the as-sintered sample. Regarding the constitutive modeling, the power law excellently fitted the experimental data, resulting in an exponent of 2.45, indicating that grain boundary sliding governed the high-temperature deformation of the studied alloy, just as it does in ultrafine-grained size traditional alloys. Additionally, an elevated activation energy of 527 kJ·mol-1 was obtained, associated either with a high softening resistance as well as with the considerable presence of secondary phases. In the case of the heat-treated samples, dislocation climbing and glide seemed to govern the deformation (at least at 1000 °C), explaining the enhanced strength, attributed to the hindered grain boundary mobility due to the larger grain size.
  • MASDEU NAVARRO, MARTA: Distribution and cycling of volatile organic compounds in a tropical coral reef and the adjacent ocean.
    Author: MASDEU NAVARRO, MARTA
    Thesis file: (contact the Doctoral School to confirm you have a valid doctoral degree and to get the link to the thesis)
    Programme: DOCTORAL DEGREE IN MARINE SCIENCES
    Department: (DECA)
    Mode: Article-based thesis
    Deposit date: 24/04/2024
    Reading date: 28/05/2024
    Reading time: 11:00
    Reading place: Sala d'Actes Ramon Margalef de l'Institut de Ciències del Mar (Passeig Marítim de la Barceloneta 37-49, 08003, Barcelona).
    Thesis director: SIMÓ MARTORELL, RAFAEL
    Committee:
         PRESIDENT: RIBES LLORDES, MARTA
         SECRETARI: DEL CAMPO GARCIA-RAMOS, JAVIER
         VOCAL: LLUSIÀ BENET, JOAN
    Thesis abstract: Volatile organic compounds (VOCs) participate in ecologycal interactions and climate. In recent years it has been shown that coral reefs are producers of VOCs, but the entire collection of volatiles and the formation processes of many of these compounds within the reef remain to be described, as well as whether these processes are essentially biological (pelagic and benthic) or abiotic (driven by solar radiation and water temperature). To this aim, in this thesis we have studied the VOCs in the internal and external waters of the Mo'orea coral reef, in French Polynesia. This is a well-preserved reef, which is characterized by a virtual unidirectional flow of water and with strong currents, so that it allows to study the connection between the incoming waters, from the open ocean, and the inland waters, influenced by the components and processes of the reef.We have described the spatial and temporal variability of a series of VOCs with climate interest (COS, CS2, isoprene, iodometans (CH3I and CH2ClI), bromometans (CHBr3 and CH2BR2) and DMS), and non-volatile related compounds, such as dimethillefoniopropidated (DMSP), acrylate and dimethylphoxide (DMSO), within lagoon waters and nearby ocean waters. We also made comparisons with concurrent measurements of sea surface temperature, solar radiation, biogeochemical variables (nutrients, organic matter) and the taxonomic abundances and affiliations of the microbial microbial plankton in order to explain the interconnections between DMSP-derived compounds(DMSPC), VOCs and their environment through day/night cycles.The concentration of all the studied VOCs increased when water crossed the reef crest, with the bromomethans being the compounds that showed a greater increase. Incubation experiments with inner-reef waters around midday indicated that (a) photochemical reactions were the main source of COS and the main sink of DMS;(b) microbial plankton was the main source of DMS, isoprene and CH3I, and a major sink of COS;(c) algae were the main source of the polyhalomethanes CH2ClI, CHBr3 and CH2Br2; (d) carbonate sediments were a major source of CS2 and CH2ClI, DMS and isoprene, and the main COS loss. The dominant coral holobiont (Pocillopora sp.) was a source of only DMS and COS. Another studied coral (Acropora pulchra) was an important source of DMSPC, whose concentration near the polyps was parallel to the intensity of sunlight, with large increases during the day and decreases at night. This variation was probably generated by (i) the role of DMSPC as antioxidants for endosymbiotic Symbiodinoceae and for the coral itself, and (ii) the expulsion of endosymbionts under very high solar radiation intensities, as suggested by the molecular description of the microbial community. The identification and quantification of functional genes by metagenomics indicated that the bacteria near the A. pulchra colony were well prepared for the use and transformation of the DMSPC released by coral holobiont. Furthermore, the detailed study of the short-distance gradients of VOCs concentrations between the branches of A. pulchra illustrated the hydrographic complexity that occurs within a branched coral colony.In the deep, transparent and oligotrophic waters os the adjacent open ocean, VOCs were basically originated in planktonic activity but mainly regulated by light, with great importance of photochemical reactions that produced some compounds and destroyed others.In general, for a month, the reef was a net producer and net emitter of VOCs, compared to the open ocean. Using the most enriched VOCs in the reef, as well as nitrate and terrigenous dissolved organic matter, as tracers of reef waters that leave through the outflow channel, we estimated that 35% of the water that enters the reef across the crest is recirculated water of the same reef. This thesis advances our understanding about the production and cycling of VOCs in a tropical coral reef and its relationship with solar radiation.

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