Integrating comprehensive two-dimensional gas chromatography and downhole fluid analysis to validate a spill-fill sequence of reservoirs with variations of biodegradation, water washing and thermal maturity

Author Posting. © The Author(s), 2016. This is the author's version of the work. It is posted here for personal use, not for redistribution. The definitive version was published in Fuel 191 (2017): 538-554, doi:10.1016/j.fuel.2016.11.081.Optimization of crude oil production depends heavily on crude oil composition and its variation within individual reservoirs and across multiple reservoirs. In particular, asphaltene content has an enormous impact on crude oil viscosity and even the economic value of the fluids in the reservoir. Thus, it is highly desirable to understand the primary controls on crude oil composition and asphaltene distributions in reservoirs. Here, a complex oilfield in the North Sea containing six separate reservoirs is addressed. The crude oil is believed to have spilled out of deeper reservoirs into shallower reservoirs during the overall reservoir charging process. Asphaltene content is measured in-situ through downhole fluid analysis and is generally consistent with a spill-fill sequence in reservoir charging. Detailed compositional analysis of crude oil samples by comprehensive two-dimensional gas chromatography (GC×GC) is used to determine the extent and variation among the reservoirs of water washing, biodegradation and thermal maturity. Increased biodegradation and water washing in the shallower reservoirs is consistent with a spill-fill sequence. The water washing is evidently assisted by biodegradation. Moreover, analyses of four thermal maturity biomarkers show that shallower reservoirs contain less mature oil, again consistent with a spill-fill sequence. The combination of DFA for bulk compositional analysis and GC×GC for detailed compositional analysis with geochemical interpretation is an effective tool for unraveling complex oilfield scenarios

Derecho aduanero. Derecho del turismo

Como ya se expresara, casi todas las aristas que toca nuestra disciplina han sido afectadas por la aparición de esta nueva enfermedad que ha trastocado el estilo de vida en el mundo entero. Incertidumbre generalizada, paralización completa de actividades, pérdidas, reprogramaciones inciertas, suspensiones y despidos están a la orden del día desde principios de este particular año 2020. Este nuevo virus se ha extendido a lo largo y a lo ancho de todo el planeta. Ninguna actividad, industria, Estado, ha quedado al margen de la cadena de infección. En consecuencia, los Jefes de Estado han ido adoptando medidas para evitar que la población contraiga dicha patología. En resumen, ante la situación excepcional generada por la irrupción de la COVID-19, la posterior declaración de pandemia que realizara la OMS en fecha 11/03/2020 y las normativas de crisis dictadas por la mayoría de los Estados para contener la situación, el abordaje jurídico adquiere carácter extraordinario. Ya en condiciones normales la intermediación que realiza el agente de viajes entre los prestadores de servicios turísticos y consumidores es un tópico complejo. Es por ello, que el lector se encontrará con una solución de justicia contributiva cuya argumentación conjuga normas, principios y valores jurídicos. Su razonabilidad viene dada por el equilibrio que revela y dispensa, tanto a los operadores turísticos, agencias de viajes y consumidores. El término “cooperación” emerge como decisorio en orden a allanar la dificultad, el caos.Fil: Pesqueira Nozikovsky, M. Soledad. Universidad Nacional de Córdoba. Facultad de Derecho; Argentina.Fil: Frontera Villamil, Ernesto. Universidad Nacional de Córdoba. Facultad de Derecho; Argentina.Fil: Cinalli, Juan Marcelo. Universidad Nacional de Córdoba. Facultad de Derecho; Argentina.Fil: Rivarola, Hugo. Universidad Nacional de Córdoba. Facultad de Derecho; Argentina.Fil: Baigorria, Nelly. Universidad Nacional de Córdoba. Facultad de Derecho; Argentina.Fil: Cevallos, Diego. Universidad Nacional de Córdoba. Facultad de Derecho; Argentina.Fil: Ferronato, Victoria. Universidad Nacional de Córdoba. Facultad de Derecho; Argentina.Fil: Freijo, Maricel. Universidad Nacional de Córdoba. Facultad de Derecho; Argentina.Fil: Giubergia, M. Victoria. Universidad Nacional de Córdoba. Facultad de Derecho; Argentina.Fil: González Boarini, Paula. Universidad Nacional de Córdoba. Facultad de Derecho; Argentina.Fil: Hidalgo, Guadalupe. Universidad Nacional de Córdoba. Facultad de Derecho; Argentina.Fil: Latini Marramá, Ignacio. Universidad Nacional de Córdoba. Facultad de Derecho; Argentina.Fil: Luna, Iván. Universidad Nacional de Córdoba. Facultad de Derecho; Argentina.Fil: Mana, Noelia I. Universidad Nacional de Córdoba. Facultad de Derecho; Argentina.Fil: Núñez, Dante Ariel. Universidad Nacional de Córdoba. Facultad de Derecho; Argentina.Fil: Oliver, Lucía. Universidad Nacional de Córdoba. Facultad de Derecho; Argentina.Fil: Saimandi, Erika. Universidad Nacional de Córdoba. Facultad de Derecho; Argentina

The Cord Blood Insulin and Mitochondrial DNA Content Related Methylome

Mitochondrial dysfunction seems to play a key role in the etiology of insulin resistance. At birth, a link has already been established between mitochondrial DNA (mtDNA) content and insulin levels in cord blood. In this study, we explore shared epigenetic mechanisms of the association between mtDNA content and insulin levels, supporting the developmental origins of this link. First, the association between cord blood insulin and mtDNA content in 882 newborns of the ENVIRONAGE birth cohort was assessed. Cord blood mtDNA content was established via qPCR, while cord blood levels of insulin were determined using electrochemiluminescence immunoassays. Then the cord blood DNA methylome and transcriptome were determined in 179 newborns, using the human 450K methylation Illumina and Agilent Whole Human Genome 8 × 60 K microarrays, respectively. Subsequently, we performed an epigenome-wide association study (EWAS) adjusted for different maternal and neonatal variables. Afterward, we focused on the 20 strongest associations based on p-values to assign transcriptomic correlates and allocate corresponding pathways employing the R packages ReactomePA and RDAVIDWebService. On the regional level, we examined differential methylation using the DMRcate and Bumphunter packages in R. Cord blood mtDNA content and insulin were significantly correlated (r = 0.074, p = 0.028), still showing a trend after additional adjustment for maternal and neonatal variables (p = 0.062). We found an overlap of 33 pathways which were in common between the association with cord blood mtDNA content and insulin levels, including pathways of neurodevelopment, histone modification, cytochromes P450 (CYP)-metabolism, and biological aging. We further identified a DMR annotated to Repulsive Guidance Molecule BMP Co-Receptor A (RGMA) linked to cord blood insulin as well as mtDNA content. Metabolic variation in early life represented by neonatal insulin levels and mtDNA content might reflect or accommodate alterations in neurodevelopment, histone modification, CYP-metabolism, and aging, indicating etiological origins in epigenetic programming. Variation in metabolic hormones at birth, reflected by molecular changes, might via these alterations predispose children to metabolic diseases later in life. The results of this study may provide important markers for following targeted studies

The Micronemal Plasmodium Proteins P36 and P52 Act in Concert to Establish the Replication-Permissive Compartment Within Infected Hepatocytes

Within the liver, Plasmodium sporozoites traverse cells searching for a “suitable” hepatocyte, invading these cells through a process that results in the formation of a parasitophorous vacuole (PV), within which the parasite undergoes intracellular replication as a liver stage. It was previously established that two members of the Plasmodium s48/45 protein family, P36 and P52, are essential for productive invasion of host hepatocytes by sporozoites as their simultaneous deletion results in growth-arrested parasites that lack a PV. Recent studies point toward a pathway of entry possibly involving the interaction of P36 with hepatocyte receptors EphA2, CD81, and SR-B1. However, the relationship between P36 and P52 during sporozoite invasion remains unknown. Here we show that parasites with a single P52 or P36 gene deletion each lack a PV after hepatocyte invasion, thereby pheno-copying the lack of a PV observed for the P52/P36 dual gene deletion parasite line. This indicates that both proteins are equally important in the establishment of a PV and act in the same pathway. We created a Plasmodium yoelii P36mCherry tagged parasite line that allowed us to visualize the subcellular localization of P36 and found that it partially co-localizes with P52 in the sporozoite secretory microneme organelles. Furthermore, through co-immunoprecipitation studies in vivo, we determined that P36 and P52 form a protein complex in sporozoites, indicating a concerted function for both proteins within the PV formation pathway. However, upon sporozoite stimulation, only P36 was released as a secreted protein while P52 was not. Our results support a model in which the putatively glycosylphosphatidylinositol (GPI)-anchored P52 may serve as a scaffold to facilitate the interaction of secreted P36 with the host cell during sporozoite invasion of hepatocytes

The impact of tumor profiling approaches and genomic data strategies for cancer precision medicine

Background: The diversity of clinical tumor profiling approaches (small panels to whole exomes with matched or unmatched germline analysis) may engender uncertainty about their benefits and liabilities, particularly in light of reported germline false positives in tumor-only profiling and use of global mutational and/or neoantigen data. The goal of this study was to determine the impact of genomic analysis strategies on error rates and data interpretation across contexts and ancestries. Methods: We modeled common tumor profiling modalities—large (n = 300 genes), medium (n = 48 genes), and small (n = 15 genes) panels—using clinical whole exomes (WES) from 157 patients with lung or colon adenocarcinoma. We created a tumor-only analysis algorithm to assess germline false positive rates, the impact of patient ancestry on tumor-only results, and neoantigen detection. Results: After optimizing a germline filtering strategy, the germline false positive rate with tumor-only large panel sequencing was 14 % (144/1012 variants). For patients whose tumor-only results underwent molecular pathologist review (n = 91), 50/54 (93 %) false positives were correctly interpreted as uncertain variants. Increased germline false positives were observed in tumor-only sequencing of non-European compared with European ancestry patients (p < 0.001; Fisher’s exact) when basic germline filtering approaches were used; however, the ExAC database (60,706 germline exomes) mitigated this disparity (p = 0.53). Matched and unmatched large panel mutational load correlated with WES mutational load (r2 = 0.99 and 0.93, respectively; p < 0.001). Neoantigen load also correlated (r2 = 0.80; p < 0.001), though WES identified a broader spectrum of neoantigens. Small panels did not predict mutational or neoantigen load. Conclusions: Large tumor-only targeted panels are sufficient for most somatic variant identification and mutational load prediction if paired with expanded germline analysis strategies and molecular pathologist review. Paired germline sequencing reduced overall false positive mutation calls and WES provided the most neoantigens. Without patient-matched germline data, large germline databases are needed to minimize false positive mutation calling and mitigate ethnic disparities. Electronic supplementary material The online version of this article (doi:10.1186/s13073-016-0333-9) contains supplementary material, which is available to authorized users

Clinical Sequencing Exploratory Research Consortium: Accelerating Evidence-Based Practice of Genomic Medicine

Despite rapid technical progress and demonstrable effectiveness for some types of diagnosis and therapy, much remains to be learned about clinical genome and exome sequencing (CGES) and its role within the practice of medicine. The Clinical Sequencing Exploratory Research (CSER) consortium includes 18 extramural research projects, one National Human Genome Research Institute (NHGRI) intramural project, and a coordinating center funded by the NHGRI and National Cancer Institute. The consortium is exploring analytic and clinical validity and utility, as well as the ethical, legal, and social implications of sequencing via multidisciplinary approaches; it has thus far recruited 5,577 participants across a spectrum of symptomatic and healthy children and adults by utilizing both germline and cancer sequencing. The CSER consortium is analyzing data and creating publically available procedures and tools related to participant preferences and consent, variant classification, disclosure and management of primary and secondary findings, health outcomes, and integration with electronic health records. Future research directions will refine measures of clinical utility of CGES in both germline and somatic testing, evaluate the use of CGES for screening in healthy individuals, explore the penetrance of pathogenic variants through extensive phenotyping, reduce discordances in public databases of genes and variants, examine social and ethnic disparities in the provision of genomics services, explore regulatory issues, and estimate the value and downstream costs of sequencing. The CSER consortium has established a shared community of research sites by using diverse approaches to pursue the evidence-based development of best practices in genomic medicine

Serum neurofilament light chain levels are associated with white matter integrity in autosomal dominant Alzheimer's disease

Neurofilament light chain (NfL) is a protein that is selectively expressed in neurons. Increased levels of NfL measured in either cerebrospinal fluid or blood is thought to be a biomarker of neuronal damage in neurodegenerative diseases. However, there have been limited investigations relating NfL to the concurrent measures of white matter (WM) decline that it should reflect. White matter damage is a common feature of Alzheimer's disease. We hypothesized that serum levels of NfL would associate with WM lesion volume and diffusion tensor imaging (DTI) metrics cross-sectionally in 117 autosomal dominant mutation carriers (MC) compared to 84 non-carrier (NC) familial controls as well as in a subset (N = 41) of MC with longitudinal NfL and MRI data. In MC, elevated cross-sectional NfL was positively associated with WM hyperintensity lesion volume, mean diffusivity, radial diffusivity, and axial diffusivity and negatively with fractional anisotropy. Greater change in NfL levels in MC was associated with larger changes in fractional anisotropy, mean diffusivity, and radial diffusivity, all indicative of reduced WM integrity. There were no relationships with NfL in NC. Our results demonstrate that blood-based NfL levels reflect WM integrity and supports the view that blood levels of NfL are predictive of WM damage in the brain. This is a critical result in improving the interpretability of NfL as a marker of brain integrity, and for validating this emerging biomarker for future use in clinical and research settings across multiple neurodegenerative diseases

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe