A convolutional autoencoder approach for mining features in cellular electron cryo-tomograms and weakly supervised coarse segmentation

Cellular electron cryo-tomography enables the 3D visualization of cellular organization in the near-native state and at submolecular resolution. However, the contents of cellular tomograms are often complex, making it difficult to automatically isolate different in situ cellular components. In this paper, we propose a convolutional autoencoder-based unsupervised approach to provide a coarse grouping of 3D small subvolumes extracted from tomograms. We demonstrate that the autoencoder can be used for efficient and coarse characterization of features of macromolecular complexes and surfaces, such as membranes. In addition, the autoencoder can be used to detect non-cellular features related to sample preparation and data collection, such as carbon edges from the grid and tomogram boundaries. The autoencoder is also able to detect patterns that may indicate spatial interactions between cellular components. Furthermore, we demonstrate that our autoencoder can be used for weakly supervised semantic segmentation of cellular components, requiring a very small amount of manual annotation.Comment: Accepted by Journal of Structural Biolog

\u3ci\u3eRealmente Tenemos la Capacidad\u3c/i\u3e: Engaging Youth to Explore Health in the Dominican Republic Through Photovoice

Youth are often at risk for physical and psychosocial illnesses, and yet their input is rarely included in health assessments and interventions. Two U.S.-based universities partnered with community stakeholders and youth in Las Malvinas II, Dominican Republic to explore factors that promote and/or hinder the health of youth in Las Malvinas II. Youth (n=8) conducted a photovoice, and identified six key health priorities: (1) good nutrition, (2) depression and poverty, (3) violence, (4) sports and neighborhood association, (5) education, and (6) sanitation and community infrastructure. Findings revealed youth’s exploration of complex multi-level determinants of health. This study suggests youth have nuanced understanding in regards to health. This paper presents the findings of the photovoice led by the youth as an illustrative case study of using CBPR-based methodologies to engage youth in local community health improvement efforts in Las Malvinas II, Dominican Republic

Realmente Tenemos la Capacidad: Engaging Youth to Explore Health in the Dominican Republic Through Photovoice

Youth are often at risk for physical and psychosocial illnesses, and yet their input is rarely included in health assessments and interventions. Two U.S.-based universities partnered with community stakeholders and youth in Las Malvinas II, Dominican Republic to explore factors that promote and/or hinder the health of youth in Las Malvinas II. Youth (n=8) conducted a photovoice, and identified six key health priorities: (1) good nutrition, (2) depression and poverty, (3) violence, (4) sports and neighborhood association, (5) education, and (6) sanitation and community infrastructure. Findings revealed youth’s exploration of complex multi-level determinants of health. This study suggests youth have nuanced understanding in regards to health. This paper presents the findings of the photovoice led by the youth as an illustrative case study of using CBPR-based methodologies to engage youth in local community health improvement efforts in Las Malvinas II, Dominican Republic

Damage Associated Molecular Pattern Molecule-Induced microRNAs (DAMPmiRs) in Human Peripheral Blood Mononuclear Cells

Endogenous damage associated molecular pattern molecules (DAMPs) released from necrotic, damaged or stressed cells are associated with an inflammatory response. Whether the microRNA (miR) expression signature of this response is different from that of a pathogen associated molecular pattern (PAMP)-stimulated inflammatory response is unknown. We report here that miR-34c and miR-214 are significantly expressed in fresh human peripheral blood mononuclear cells (PBMCs) exposed to DAMP-containing freeze-thaw lysates, or to conditioned media from serum-starved and glucose-deprived cells (p<6×10−4 and p<3.7×10−3), respectively. Interestingly, only miR-34c expression was differentially expressed in PBMCs exposed to freeze-thaw lysates or conditioned media from wildtype High Mobility Group B1 (HMGB1+/+) mouse embryonic fibroblast (MEF) cells, when compared to cultures exposed to lysates or conditioned media from HMGB1−/− MEFs. miR-155 expression in these cultures was negligible, but was significantly expressed in PBMCs stimulated with Lipopolysaccahride (LPS) or most other Toll-like receptor (TLR) ligands, making it the prototypic “PAMPmiR”. Exposure to a damaged human colorectal carcinoma cell line lysate (HCT116) similarly resulted in increased miR-34c and miR-214 levels. When PBMCs were pre-transfected with anti-miR-34c and then exposed to lysate, expression levels of IKKγ mRNA, a putative target of miR-34c, increased, while protein levels of IKKγ in cultures transfected with a pre-miR-34c were abrogated. Levels of miR-34c expression (as well as pro-inflammatory cytokines, IL-1β and TNFα) decreased when PBMC cultures were briefly pre-incubated with the K+ channel (inflammasome) inhibitor, glybenclamide, suggesting that inflammasome activation is upstream of miR-34c expression in response to DAMPs. Our findings demonstrate that a specific microRNA expression signature is associated with the inflammatory response to damaged/injured cells and carries implications for many acute and chronic inflammatory disorders

Nitrated Fibrinogen is A Biomarker of Oxidative Stress in Venous Thromboembolism

The pathogenesis of venous thromboembolism (VTE) is linked to inflammation and oxidant production, although specific markers for these pathways with pathological relevance to VTE have not been explored. The coagulant protein fibrinogen is posttranslationally modified by nitric oxide-derived oxidants to nitrated fibrinogen in both acute and chronic inflammatory states. Therefore, nitrated fibrinogen may serve as a marker of inflammation and oxidative stress in VTE. To test this hypothesis we enrolled subjects (n=251) presenting with suspected VTE at the University of Pennsylvania Hospital emergency department, 50 (19.9%) of whom were positive by imaging or 90-day follow-up. Mean nitrated fibrinogen was elevated in VTE-positive (62.7 nM, 95% CI 56.6–68.8) compared to VTE-negative patients (54.2 nM, 95% CI 51.4–57.1; P\u3c0.01). Patients in the highest quartile of nitrated fibrinogen had an increased risk of VTE compared with patients in the lowest quartile (OR 3.30; 95% CI 1.25–8.68; P\u3c0.05). This risk persisted after univariate adjustment for age, active cancer, and recent surgery, but not after multivariate adjustment. Mean fibrinogen levels measured either by the Clauss assay or by ELISA were not different between VTE-negative and VTE-positive patients. These data indicate that nitrated fibrinogen is an oxidative risk marker in VTE, providing a novel mechanistic link between oxidant production, inflammation, and VTE

Constraints on dark energy models from radial baryon acoustic scale measurements

We use the radial baryon acoustic oscillation (BAO) measurements of Gaztanaga et al. (2008) to constrain parameters of dark energy models. These constraints are comparable with constraints from other "non-radial" BAO data. The radial BAO data are consistent with the time-independent cosmological constant model but do not rule out time-varying dark energy. When we combine radial BAO and the Kowalski et al. (2008) Union type Ia supernova data we get very tight constraints on dark energy.Comment: 24 pages, 8 figures, 1 table. Minor changes to match the published versio

Revisión de literatura y propuesta metodológica para construir un proceso de asignación en investigación operativa - caso de estudio en asignación de docentes a materias

El propósito de este proyecto se centra en la construcción de una metodología para la correcta programación de un modelo de asignación de docentes a materias en la facultad de ingeniería industrial de la universidad ECCI, investigando los modelos meta heurísticos que permitan la adecuada asignación de docentes versus materias teniendo en cuenta el uso de las variables del entorno, dando cumplimiento a los requisitos exigidos por la universidad, tal como se halló en artículos realizados en universidades colombianas donde se lograron propuestas para mejorar el proceso de asignación que se desarrollaba en estas, partiendo de la diferencia que existe al asignar materias y docentes en instituciones educativas (colegios) y universidades; obteniendo así un método que favorezca a la correcta administración de los recursos de la universidad.Resumen Lista de formulas Lista de figuras Lista de tablas Lista de ilustraciones Introducción 1 Contexto del Proyecto 1.1 Problemática 1.1.1 Objetivos 1.1.1.1 Objetivo general Proponer una metodología basada en revisión de literatura para solucionar el problema de asignación de docentes a materias 1.1.1.2 Objetivos específicos 2 Marco teórico 2.1 Investigación de operaciones 2.1.1 Programación Dinámica 2.2 Metaheurística 2.2.1 Algoritmo genético 2.2.2 Enjambre de partículas 2.2.3 Búsqueda tabú (Tabú Search) 2.4.4 RECOCIDO SIMULADO: 2.4.5 GRASP (Greedy Randomized adaptive search Procedure): 3 Diseño y desarrollo metodológico 3.1 Diseño Metodológico 3.2 Metodología Propuesta 3.2.1 Variables 3.3 Segmentación del problema 3.4 Selección del Modelo 4 Conclusiones y recomendaciones 4.1 Conclusiones 4.2 RecomendacionesPregradoIngeniero en IndustrialIngeniería Industria

Size-dependent increase in RNA Polymerase II initiation rates mediates gene expression scaling with cell size

Cell size varies during the cell cycle and in response to external stimuli. This requires the tight coordination, or “scaling”, of mRNA and protein quantities with the cell volume in order to maintain biomolecules concentrations and cell density. Evidence in cell populations and single cells indicates that scaling relies on the coordination of mRNA transcription rates with cell size. Here we use a combination of single-molecule fluorescence in situ hybridisation (smFISH), time-lapse microscopy and mathematical modelling in single fission yeast cells to uncover the precise molecular mechanisms that control transcription rates scaling with cell size. Linear scaling of mRNA quantities is apparent in single fission yeast cells during a normal cell cycle. Transcription rates of both constitutive and regulated genes scale with cell size without evidence for transcriptional bursting. Modelling and experimental data indicate that scaling relies on the coordination of RNAPII transcription initiation rates with cell size and that RNAPII is a limiting factor. We show using real-time quantitative imaging that size increase is accompanied by a rapid concentration independent recruitment of RNAPII onto chromatin. Finally, we find that in multinucleated cells, scaling is set at the level of single nuclei and not the entire cell, making the nucleus the transcriptional scaling unit. Integrating our observations in a mechanistic model of RNAPII mediated transcription, we propose that scaling of gene expression with cell size is the consequence of competition between genes for limiting RNAPII