84 research outputs found

    Quantum correlations and spatial localization in one-dimensional ultracold bosonic mixtures

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    We present the complete phase diagram for one-dimensional binary mixtures of bosonic ultracold atomic gases in a harmonic trap. We obtain exact results with direct numerical diagonalization for small number of atoms, which permits us to quantify quantum many-body correlations. The quantum Monte Carlo method is used to calculate energies and density profiles for larger system sizes. We study the system properties for a wide range of interaction parameters. For the extreme values of these parameters, different correlation limits can be identified, where the correlations are either weak or strong. We investigate in detail how the correlation evolve between the limits. For balanced mixtures in the number of atoms in each species, the transition between the different limits involves sophisticated changes in the one- and two-body correlations. Particularly, we quantify the entanglement between the two components by means of the von Neumann entropy. We show that the limits equally exist when the number of atoms is increased, for balanced mixtures. Also, the changes in the correlations along the transitions among these limits are qualitatively similar. We also show that, for imbalanced mixtures, the same limits with similar transitions exist. Finally, for strongly imbalanced systems, only two limits survive, i.e., a miscible limit and a phase-separated one, resembling those expected with a mean-field approach.Comment: 18 pages, 8 figure

    Integrating T-cell epitope annotations with sequence and structural information using DAS

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    Immunoinformatics is an emerging new field that benefits from computational analyses and tools that facilitate the understanding of the immune system. A large number of immunoinformatics resources such as immune-related databases and analysis software are available through the World Wide Web for the benefit of the research community. However, immunoinformatics developments have sometimes remained isolated from mainstream bioinformatics. Therefore, there is clearly a need for integration, which will empower the exchange of data and annotations within the scientific community in a quick and efficient fashion. Here, we have chosen the Distributed Annotation System (DAS), for integrating in house annotations on experimental and predicted HLA I-restriction elements of CD8 T-cell epitopes with sequence and structural information

    Distinguishability, degeneracy and correlations in three harmonically trapped bosons in one-dimension

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    We study a system of two bosons of one species and a third boson of a second species in a one-dimensional parabolic trap at zero temperature. We assume contact repulsive inter- and intra-species interactions. By means of an exact diagonalization method we calculate the ground and excited states for the whole range of interactions. We use discrete group theory to classify the eigenstates according to the symmetry of the interaction potential. We also propose and validate analytical ansatzs gaining physical insight over the numerically obtained wavefunctions. We show that, for both approaches, it is crucial to take into account that the distinguishability of the third atom implies the absence of any restriction over the wavefunction when interchanging this boson with any of the other two. We find that there are degeneracies in the spectra in some limiting regimes, that is, when the inter-species and/or the intra-species interactions tend to infinity. This is in contrast with the three-identical boson system, where no degeneracy occurs in these limits. We show that, when tuning both types of interactions through a protocol that keeps them equal while they are increased towards infinity, the systems's ground state resembles that of three indistinguishable bosons. Contrarily, the systems's ground state is different from that of three-identical bosons when both types of interactions are increased towards infinity through protocols that do not restrict them to be equal. We study the coherence and correlations of the system as the interactions are tuned through different protocols, which permit to built up different correlations in the system and lead to different spatial distributions of the three atoms.Comment: 14 pages, 7 figure

    Aprendizaje basado en proyectos y trabajo en equipo para mejorar las competencias básicas

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    El aprendizaje basado en proyectos es una técnica de enseñanza/aprendizaje que utiliza un proyecto como eje principal del proceso de aprendizaje. Este aprendizaje, combinado con el trabajo en equipo permite mejorar la adquisición tanto de las competencias específicas como de las básicas. Desde hace tres años, en las asignaturas de bases de datos avanzadas del Grado de Ingeniería Informática de la Universidad Jaume I se utiliza de forma combinada el aprendizaje basado en proyectos y el trabajo en equipo. En este artículo se presenta la experiencia adquirida, las actividades del proyecto y las competencias alcanzadas en cada actividad. Por último, se analiza y evalúan los resultados obtenidos, proponiendo una serie de actuaciones de trabajo futuras

    Point-Of-Care CAR T-Cell Production (ARI-0001) Using a Closed Semi-automatic Bioreactor: Experience From an Academic Phase I Clinical Trial

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    Development of semi-automated devices that can reduce the hands-on time and standardize the production of clinical-grade CAR T-cells, such as CliniMACS Prodigy from Miltenyi, is key to facilitate the development of CAR T-cell therapies, especially in academic institutions. However, the feasibility of manufacturing CAR T-cell products from heavily pre-treated patients with this system has not been demonstrated yet. Here we report and characterize the production of 28 CAR T-cell products in the context of a phase I clinical trial for CD19+ B-cell malignancies (NCT03144583). The system includes CD4-CD8 cell selection, lentiviral transduction and T-cell expansion using IL-7/IL-15. Twenty-seven out of 28 CAR T-cell products manufactured met the full list of specifications and were considered valid products. Ex vivo cell expansion lasted an average of 8.5 days and had a mean transduction rate of 30.6 ± 13.44%. All products obtained presented cytotoxic activity against CD19+ cells and were proficient in the secretion of pro-inflammatory cytokines. Expansion kinetics was slower in patient's cells compared to healthy donor's cells. However, product potency was comparable. CAR T-cell subset phenotype was highly variable among patients and largely determined by the initial product. TCM and TEM were the predominant T-cell phenotypes obtained. 38.7% of CAR T-cells obtained presented a TN or TCM phenotype, in average, which are the subsets capable of establishing a long-lasting T-cell memory in patients. An in-depth analysis to identify individual factors contributing to the optimal T-cell phenotype revealed that ex vivo cell expansion leads to reduced numbers of TN, TSCM, and TEFF cells, while TCM cells increase, both due to cell expansion and CAR-expression. Overall, our results show for the first time that clinical-grade production of CAR T-cells for heavily pre-treated patients using CliniMACS Prodigy system is feasible, and that the obtained products meet the current quality standards of the field. Reduced ex vivo expansion may yield CAR T-cell products with increased persistence in vivo

    Deep Molecular Characterization of Milder Spinal Muscular Atrophy Patients Carrying the c.859G>C Variant in SMN2

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    Spinal muscular atrophy (SMA) is a severe neuromuscular disorder caused by biallelic loss or pathogenic variants in the SMN1 gene. Copy number and modifier intragenic variants in SMN2, an almost identical paralog gene of SMN1, are known to influence the amount of complete SMN proteins. Therefore, SMN2 is considered the main phenotypic modifier of SMA, although genotype-phenotype correlation is not absolute. We present eleven unrelated SMA patients with milder phenotypes carrying the c.859G>C-positive modifier variant in SMN2. All were studied by a specific NGS method to allow a deep characterization of the entire SMN region. Analysis of two homozygous cases for the variant allowed us to identify a specific haplotype, Smn2-859C.1, in association with c.859G>C. Two other cases with the c.859G>C variant in their two SMN2 copies showed a second haplotype, Smn2-859C.2, in cis with Smn2-859C.1, assembling a more complex allele. We also identified a previously unreported variant in intron 2a exclusively linked to the Smn2-859C.1 haplotype (c.154-1141G>A), further suggesting that this region has been ancestrally conserved. The deep molecular characterization of SMN2 in our cohort highlights the importance of testing c.859G>C, as well as accurately assessing the SMN2 region in SMA patients to gain insight into the complex genotype-phenotype correlations and improve prognostic outcomes

    Systematic Collaborative Reanalysis of Genomic Data Improves Diagnostic Yield in Neurologic Rare Diseases

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    Altres ajuts: Generalitat de Catalunya, Departament de Salut; Generalitat de Catalunya, Departament d'Empresa i Coneixement i CERCA Program; Ministerio de Ciencia e Innovación; Instituto Nacional de Bioinformática; ELIXIR Implementation Studies (CNAG-CRG); Centro de Investigaciones Biomédicas en Red de Enfermedades Raras; Centro de Excelencia Severo Ochoa; European Regional Development Fund (FEDER).Many patients experiencing a rare disease remain undiagnosed even after genomic testing. Reanalysis of existing genomic data has shown to increase diagnostic yield, although there are few systematic and comprehensive reanalysis efforts that enable collaborative interpretation and future reinterpretation. The Undiagnosed Rare Disease Program of Catalonia project collated previously inconclusive good quality genomic data (panels, exomes, and genomes) and standardized phenotypic profiles from 323 families (543 individuals) with a neurologic rare disease. The data were reanalyzed systematically to identify relatedness, runs of homozygosity, consanguinity, single-nucleotide variants, insertions and deletions, and copy number variants. Data were shared and collaboratively interpreted within the consortium through a customized Genome-Phenome Analysis Platform, which also enables future data reinterpretation. Reanalysis of existing genomic data provided a diagnosis for 20.7% of the patients, including 1.8% diagnosed after the generation of additional genomic data to identify a second pathogenic heterozygous variant. Diagnostic rate was significantly higher for family-based exome/genome reanalysis compared with singleton panels. Most new diagnoses were attributable to recent gene-disease associations (50.8%), additional or improved bioinformatic analysis (19.7%), and standardized phenotyping data integrated within the Undiagnosed Rare Disease Program of Catalonia Genome-Phenome Analysis Platform functionalities (18%)
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