Functional Verification of Power Electronic Systems

This project is the final work of the degree in Industrial Electronics and Automatic Engineering. It has global concepts of electronics but it focuses in power electronic systems. There is a need for reliable testing systems to ensure the good functionality of power electronic systems. The constant evolution of this products requires the development of new testing techniques. This project aims to develop a new testing system to accomplish the functional verification of a new power electronic system manufactured on a company that is in the power electronic sector . This test system consists on two test bed platforms, one to test the control part of the systems and the other one to test their functionality. A software to perform the test is also designed. Finally, the testing protocol is presented. This design is validated and then implemented on a buck converter and an inverter that are manufactured at the company. The results show that the test system is reliable and is capable of testing the functional verification of the two power electronic system successfully. In summary, this design can be introduced in the power electronic production process to test the two products ensuring their reliability in the market

Saiph, a domain specific language for computational fluid dynamics simulations

Nowadays, High-Performance Computing (HPC) is assuming an increasingly central role in scientific research while computer architectures are becoming more and more hetero-geneous and using different parallel programming models and techniques. Under this scenario, the only way to successfully exploit an HPC system requires that computer and domain scientists work closely towards producing applications to solve domain problems, ensuring productivity and performance at the same time. Facing such purpose, Saiph is a Domain Specific Language designed to ease the task of solving couple and uncouple Partial Differential Equations (PDE’s), with a primary focusing on Computational Fluid Dynamics (CFD) applications. Saiph allows to model complex physical phenomena featured by PDE’s, easing the use of numerical methods and optimizations on different computer architectures to the users

Adaptive and architecture-independent task granularity for recursive applications

In the last few decades, modern applications have become larger and more complex. Among the users of these applications, the need to simplify the process of identifying units of work increased as well. With the approach of tasking models, this want has been satisfied. These models make scheduling units of work much more user-friendly. However, with the arrival of tasking models, came granularity management. Discovering an application’s optimal granularity is a frequent and sometimes challenging task for a wide range of recursive algorithms. Often, finding the optimal granularity will cause a substantial increase in performance. With that in mind, the quest for optimality is no easy task. Many aspects have to be considered that are directly related to lack or excess of parallelism in applications. There is no general solution as the optimal granularity depends on both algorithm and system characteristics. One commonly used method to find an optimal granularity consists in experimentally tuning an application with different granularities until an optimal is found. This paper proposes several heuristics which, combined with the appropriate monitoring techniques, allow a runtime system to automatically tune the granularity of recursive applications. The solution is independent of the architecture, execution environment or application being tested. A reference implementation in OmpSs—a task-parallel programming model—shows the programmability, ease of use and competitive performance of the proposed solution. Results show that the proposed solution is able to achieve, for any scenario, at least 75% of the performance of optimally tuned applications.This work has been supported by the Spanish Ministry of Science and Innovation (contract TIN2015-65316), the grant SEV-2015-0493 of Severo Ochoa Program awarded by the Spanish Government, and by Generalitat de Catalunya (contract 2014-SGR-1051)Peer ReviewedPostprint (author's final draft

Addressing Risks Derived From the Commodification of Substances of Human Origin: A European Proposal Applicable Worldwide

Commodification; Human substancesMercantilització; Substàncies humanesMercantilización; Sustancias humanasIn view of the public consultation recently launched by the World Health Organization on Regulatory Convergence of Cell and Gene Therapy Products and the Proposal for a Regulation on substances of human origin (SoHO) repealing the European Union Directives on Blood and on Tissues and Cells, an opportunity arises to define an ethical and transparent framework of collaboration between industry and authorities responsible for SoHO-derived products, comprising medicines, medical devices, transfusion, and transplantation. The commodification of SoHO-derived medicinal products and medical devices entails important risks to the sustainability of healthcare systems and threatens the equitable access of patients to innovative therapies. It may also jeopardize the principle of altruistic donation of SoHO that is required for the treatment and survival of thousands of patients every year. This article puts forward several proposals aimed at reconciling the ethical principles of voluntary and unpaid SoHO donation and the noncommercialization of the human body with obtaining a profit that allows business activities, while ensuring high quality, safety, and efficacy standards of tissues and cells for clinical use

A novel sigma factor reveals a unique regulon controlling cell-specific recombination in Mycoplasma genitalium

The Mycoplasma genitalium MG428 protein shows homology to members of the sigma-70 family of sigma factors. Herein, we found that MG428 activates transcription of recA, ruvA and ruvB as well as several genes with unknown function. Deletion of MG_428 or some of the up-regulated unknown genes led to severe recombination defects. Single cell analyses revealed that activation of the MG428-regulon is a rare event under laboratory growth conditions. A conserved sequence with sigma-70 promoter architecture (TTGTCA-N-ATTWAT) was identified in the upstream region of all of the MG428-regulated genes or operons. Primer extension analyses demonstrated that transcription initiates immediately downstream of this sigma70-type promoter in a MG428-dependent manner. Furthermore, mutagenesis of the conserved −10 and −35 elements corroborated the requirement of these regions for promoter function. Therefore, a new mycoplasma promoter directs transcription of a unique recombination regulon. Additionally, MG428 was found to interact with the RNAP core enzyme, reinforcing the predicted role of this protein as an alternative sigma factor. Finally, our results indicate that MG428 contributes to the generation of genetic diversity in this model organism. Since recombination is an important mechanism to generate antigenic variation, MG428 emerges as a novel factor contributing to M. genitalium virulence

Serum-free culture conditions for the generation of dendritic cells from cord blood CD34+ hematopoietic progenitors: phenotypic and functional analysis

Increasing pre-clinical and clinical data suggest the efficiency of dendritic cells (DCs) in cancer immunotherapy. Relapse after cord blood hematopoietic progenitors (CBHP) transplantation is an unresolved problem. DCs obtained from CBHP could be an interesting tool for relapse treatments, but the low number of CBHP hinder their use for DC generation

Activation of r20-dependent recombination and horizontal gene transfer in Mycoplasma genitalium

In the human pathogen Mycoplasma genitalium, homologous recombination is under the control of r, an alternative sigma factor that boosts the generation of genetic and antigenic diversity in the population. Under laboratory growth conditions, r activation is rare and the factors governing its intermittent activity are unknown. Two r-regulated genes, rrlA and rrlB, showed to be important for recombination of homologous DNA sequences in this bacterium. Herein, we demonstrate that rrlA and rrlB code for two small proteins that participate in a feed-forward loop essential for r function. In addition, we identify novel genes regulated by r and show that several non-coding regions, which function as a reservoir for the generation of antigenic diversity, are also activated by this alternative sigma factor. Finally, we reveal that M. genitalium cells can transfer DNA horizontally by a novel mechanism that requires RecA and is facilitated by r overexpression. This DNA transfer system is arguably fundamental for persistence of M. genitalium within the host since it could facilitate a rapid dissemination of successful antigenic variants within the population. Overall, these findings impose a novel conception of genome evolution, genetic variation and survival of M. genitalium within the hos

Cord blood Platelet Rich Plasma derivatives for clinical applications in non-transfusion medicine

Cord blood platelet rich plasma (CB-PRP) derivatives have been investigated as potential therapeutic agents for the treatment of diverse conditions including ocular surface disease and skin ulcers. We have developed processes for the formulation of several CB-PRP preparations, which have different composition and attributes. Here we describe the molecular characteristics of these preparations and we make recommendations as to their most appropriate clinical application based on functional and immunomodulatory profiles. We show that incubation of adult peripheral blood mononuclear cells (PBMCs) with all three preparations dramatically reduced the production of INFγ and the expression of NKG2D and CD107a in NK, NKT, and T cells thus diminishing their activation, we propose that the likely mechanism is the high levels of soluble NKG2D ligands present in plasma. Of the three preparations we investigated, CB platelet lysate (PL) and platelet releaseate (PR) have higher concentrations of trophic and pro-angiogenic factors, CB platelet poor plasma (PPP) has the lowest concentration of all analytes measured. Based on these finding we propose that CB-PR is the most suitable raw material for skin wound patches, while CB-PL and PPP can be used to prepare eye drops for severe ocular surface pathologies and inflammatory conditions such as corneal ulcers or severe dry eye disease, respectively

Optimized reagents for immunopotency assays on mesenchymal stromal cells for clinical use

Immunomodulation; Mesenchymal stromal cells; Quality & regulatory complianceImmunomodulació; Cèl·lules estromals mesenquimàtiques; Qualitat i compliment normatiuInmunomodulación; Células estromales mesenquimales; Calidad y cumplimiento normativoMultipotent mesenchymal stromal cells (MSC) offer new therapeutic opportunities based on their ability to modulate an imbalanced immune system. Immunomodulatory potency is typically demonstrated in vitro by measuring the presence of surrogate markers (i.e., indoleamine-2,3-dioxygenase, IDO; tumor necrosis factor receptor type 1, TNFR1) and/or functional assays in co-cultures (i.e., inhibition of lymphoproliferation, polarization of macrophages). However, the biological variability of reagents used in the latter type of assays leads to unreliable and difficult to reproduce data therefore making cross-comparison between batches difficult, both at the intra- and inter-laboratory levels. Herein, we describe a set of experiments aiming at the definition and validation of reliable biological reagents as a first step towards standardization of a potency assay. This approach is based on the co-culture of Wharton’s jelly (WJ)-derived MSC and cryopreserved pooled peripheral blood mononuclear cells. Altogether, we successfully defined a robust and reproducible immunopotency assay based on previously described methods incorporating substantial improvements such as cryopreservation of multiple vials of pooled peripheral blood mononuclear cells (PBMC) from 5 individual donors that enable a number of tests with same reagents, also reducing waste of PBMC from individual donors and therefore contributing to a more efficient and ethical method to use substances of human origin (SoHO). The new methodology was successfully validated using 11 batches of clinical grade MSC,WJ. Methods described here contribute to minimize PBMC donor variability while reducing costs, streamlining assay setup and convenience and laying the foundations for harmonization of biological reagents usage in standardized immunopotency assays for MSC.Open Access Funding provided by Universitat Autonoma de Barcelona. This work has been developed in the context of Red Española de Terapias Avanzadas (TERAV, expedient no. RD21/0017/0022) funded by Instituto de Salud Carlos III (ISCIII) in the context of NextGenerationEU’s Recovery, Transformation and Resilience Plan and by the Commission for Universities and Research of the Department of Innovation, Universities, and Enterprise of the Generalitat de Catalunya (2017 SGR 719)

Generation of a bank of clinical-grade, HLA-homozygous iPSC lines with high coverage of the Spanish population

BackgroundInduced pluripotent stem cell (iPSC)-derived cell therapies are an interesting new area in the field of regenerative medicine. One of the approaches to decrease the costs of iPSC-derived therapies is the use of allogenic homozygous human leukocyte antigen (HLA)-matched donors to generate iPSC lines and to build a clinical-grade iPSC bank covering a high percentage of the Spanish population.MethodsThe Spanish Stem Cell Transplantation Registry was screened for cord blood units (CBUs) homozygous for the most common HLA-A, HLA-B and HLA-DRB1 haplotypes. Seven donors were selected with haplotypes covering 21.37% of the haplotypes of the Spanish population. CD34-positive hematopoietic progenitors were isolated from the mononuclear cell fraction of frozen cord blood units from each donor by density gradient centrifugation and further by immune magnetic labeling and separation using purification columns. Purified CD34 + cells were reprogrammed to iPSCs by transduction with the CTS CytoTune-iPS 2.1 Sendai Reprogramming Kit.ResultsThe iPSCs generated from the 7 donors were expanded, characterized, banked and registered. Master cell banks (MCBs) and working cell banks (WCBs) from the iPSCs of each donor were produced under GMP conditions in qualified clean rooms.ConclusionsHere, we present the first clinical-grade, iPSC haplobank in Spain made from CD34 + cells from seven cord blood units homozygous for the most common HLA-A, HLA-B and HLA-DRB1 haplotypes within the Spanish population. We describe their generation by transduction with Sendai viral vectors and their GMP-compliant expansion and banking. These haplolines will constitute starting materials for advanced therapy medicinal product development (ATMP)