A quantitative screen for metabolic enzyme structures reveals patterns of assembly across the yeast metabolic network.

Despite the proliferation of proteins that can form filaments or phase-separated condensates, it remains unclear how this behavior is distributed over biological networks. We have found that 60 of the 440 yeast metabolic enzymes robustly form structures, including 10 that assemble within mitochondria. Additionally, the ability to assemble is enriched at branch points on several metabolic pathways. The assembly of enzymes at the first branch point in de novo purine biosynthesis is coordinated, hierarchical, and based on their position within the pathway, while the enzymes at the second branch point are recruited to RNA stress granules. Consistent with distinct classes of structures being deployed at different control points in a pathway, we find that the first enzyme in the pathway, PRPP synthetase, forms evolutionarily conserved filaments that are sequestered in the nucleus in higher eukaryotes. These findings provide a roadmap for identifying additional conserved features of metabolic regulation by condensates/filaments

Factor V Leiden and thrombosis in patients with systemic lupus erythematosus: a meta-analysis.

The aim of this study was to perform a meta-analysis of the association between the factor V Leiden polymorphism (FVL) and thrombosis among patients with systemic lupus erythematosus (SLE) and/or antiphospholipid antibody (aPL) positivity. Included studies recruited patients based on SLE or aPL-positive status, confirmed subjects' SLE diagnosis as defined by the American College of Rheumatology, and documented thrombotic events. Excluded studies were non-English or considered only arterial thrombosis. Individual patient data, available from 5 studies, together with unpublished data from 1210 European-American SLE patients from the UCSF Lupus Genetics Collection genotyped for FVL, were further analyzed. Seventeen studies (n=2090 subjects) were included in the initial meta-analysis. Unadjusted odds ratios (OR) were calculated to assess association of FVL with thrombosis. The OR for association of thrombosis with FVL was 2.88 (95% confidence interval (CI) 1.98-4.20). In the secondary analysis with our individual patient dataset (n=1447 European-derived individuals), SLE subjects with the FVL polymorphism still had more than two times the odds of thrombosis compared to subjects without this polymorphism, even when adjusting for covariates such as gender, age and aPL status. SLE and/or aPL-positive patients with the FVL variant have more than two times the odds of thrombosis compared to those without this polymorphism

Real time leak detection and isolation in pipelines: a comparison between Sliding Mode Observer and algebraic steady state method

The purpose of this paper is to compare two different algorithms used to detect and isolate water leaks in a pipeline. One method is based on a Sliding Mode Observer and the second method is an Algebraic method obtained from the pipeline model in steady state. Because of the simplicity of both methods, they can be easily implemented. The methods were tested offline with real time data and the Algebraic method was also implemented online. Satisfactory results are shown through some experiments.Consejo Nacional de Ciencia y Tecnologí

Inactivation of Eα and Eβ expression in inbred and wild mice by multiple distinct mutations, some of which predate speciation within Mus species

The H-2 MHC of mice encodes two functional class II heterodimeric proteins: AαAβ (A) and EαEβ (E). While failure to express the A protein has not been reported, a significant proportion of of H-2 haplotypes In both Inbred and wild mice do not express E proteins. We and others have previously characterized the molecular basis for defective E expression in haplotypes from Mus domestlcus (b, f, q, s, from inbred strains) and Af. castaneus (w17, wild-derived) species, identifying six distinct defects in the genes for Eα or Eβ. In this report we have extended these studies to other E- haplotypes, Including several from f-haplotype-bearlng M. domesticus mice (w29, w57, w302) and one derived from the Asian species M. bactrianus (w301). Analyses at the protein, RNA and DNA levels were employed to Identify the defects in the genes for Ea and Eb. At least one new defect was identified that prevents Eβ expression in a t-associated H-2 haplotypes (w57), bringing the number of distinct mutations causing the Eβ phenotype to seven. Another t-associated haplotype, w302, was found to share the same Eβ defect with mice of the inbred q haplotype and of the w17 haplotype from Af. castaneus, while its Ea gene contains the deletion carried also by the Inbred b and s haplotypes and by a number of wild haplotypes. The mutations in the Ea and Eb genes of the w301 haplotype from M. bactrianus were found to be Identical to those of the Inbred f haplotype. This indicates that the origin of the mutations in the Eb genes of the q, w17 and w302 haplotypes and in the Ea and Eb genes of the f and w301 haplotypes, predated speciation within Mus, thought to have occurred ∼0.35-1 million years ago. Their maintenance in mouse populations suggests that in certain conditions the failure to express EαEβ proteins may be advantageous and selected fo

Control óptimo aguas abajo de un canal de laboratorio

En este trabajo se presentan los resultados obtenidos al aplicar un regulador Óptimo Lineal Gaussiano en el control aguas abajo de un canal de laboratorio de dos tramos localizado en el laboratorio de la Escuela Superior de Ingenieros en Sistemas Industriales Avanzados de la región Rhone Alpes en Francia. Los resultados obtenidos ponen de manifiesto que es posible implementar el control aguas abajo en un canal mediante equipo electrónico. El regulador óptimo usado muestra satisfactorios resultados en el control del nivel aguas abajo al final de cada tramo

An algebraic observer for leak detection and isolation in plastic pipelines

In the continuation of authors' studies on leak diagnosis in pipelines, a new model-based Leak Detection and Isolation (LDI) algorithm is designed. This system only uses measures of flow and pressure coming from sensors placed at the ends of a pipeline. The present approach is based on a finite nonlinear pipeline model, and extended with variables related to the leak. On this basis, the purpose here is to investigate the use of a so-called algebraic observer to estimate the leak position and its magnitude. The corresponding observer design is thus presented, and its performances are illustrated both with simulation results, and experimental ones, with data taken from a real pipeline prototype.Consejo Nacional de Ciencia y TecnologíaInstitut Universitaire de FranceUniversidad Nacional de Colombi

Recognizing Delirium in the PICU: An Evidence-based Practice Improvement Project

Introduction: Pediatric delirium is underrecognized in the pediatric population and can lead to increased length of stay, hospital costs, and post-traumatic stress disorder (PTSD). Using a standardized screening tool to assess for delirium is an easy way for bedside nurses to evaluate patients and intervene as necessary. This quality improvement project aimed to implement the Cornell Assessment of Pediatric Delirium (CAPD) and complete a delirium screening on applicable patients once a shift \u3e 85% over four months. Methods: Between January 2020 to May 2020, bedside nurses completed a delirium screening assessment on applicable patients, first on paper and then through the electronic medical record (EMR). A retrospective chart review was conducted every two weeks to assess compliance and demographic data such as hospital length of stay, length of mechanical ventilation, Midazolam usage, and CAPD scores. Results: By the fourth week of implementation, 85% of nurses were compliant with screening. The aim was met and continued above 85% throughout the project. A positive delirium screen of more than 48 hours statistically increased length of stay (P \u3c .001). The average CAPD score pre-intervention to post-intervention and during and after intubation was significantly lower (P = .016 and P = .001, respectively). Conclusions: Providing the delirium screening tool in the Electronic Medical Record (EMR) increases compliance and ensures that the providers acknowledge the positive delirium screens. While the screen’s implementation was successful, additional measures are needed to manage and prevent delirium and improve patient care

A dynamic network approach for the study of human phenotypes

The use of networks to integrate different genetic, proteomic, and metabolic datasets has been proposed as a viable path toward elucidating the origins of specific diseases. Here we introduce a new phenotypic database summarizing correlations obtained from the disease history of more than 30 million patients in a Phenotypic Disease Network (PDN). We present evidence that the structure of the PDN is relevant to the understanding of illness progression by showing that (1) patients develop diseases close in the network to those they already have; (2) the progression of disease along the links of the network is different for patients of different genders and ethnicities; (3) patients diagnosed with diseases which are more highly connected in the PDN tend to die sooner than those affected by less connected diseases; and (4) diseases that tend to be preceded by others in the PDN tend to be more connected than diseases that precede other illnesses, and are associated with higher degrees of mortality. Our findings show that disease progression can be represented and studied using network methods, offering the potential to enhance our understanding of the origin and evolution of human diseases. The dataset introduced here, released concurrently with this publication, represents the largest relational phenotypic resource publicly available to the research community.Comment: 28 pages (double space), 6 figure

Rare Variants of Putative Candidate Genes Associated With Sporadic Meniere's Disease in East Asian Population

Objectives: The cause of Meniere's disease (MD) is unclear but likely involves genetic and environmental factors. The aim of this study was to investigate the genetic basis underlying MD by screening putative candidate genes for MD. Methods: Sixty-eight patients who met the diagnostic criteria for MD of the Barany Society were included. We performed targeted gene sequencing using next generation sequencing (NGS) panel composed of 45 MD-associated genes. We identified the rare variants causing non-synonymous amino acid changes, stop codons, and insertions/deletions in the coding regions, and excluded the common variants with minor allele frequency >0.01 in public databases. The pathogenicity of the identified variants was analyzed by various predictive tools and protein structural modeling. Results: The average read depth for the targeted regions was 1446.3-fold, and 99.4% of the targeted regions were covered by 20 or more reads, achieving the high quality of the sequencing. After variant filtering, annotation, and interpretation, we identified a total of 15 rare heterozygous variants in 12 (17.6%) sporadic patients. Among them, four variants were detected in familial MD genes (DTNA, FAM136A, DPT), and the remaining 11 in MD-associated genes (PTPN22, NFKB1, CXCL10, TLR2, MTHFR, SLC44A2, NOS3, NOTCH2). Three patients had the variants in two or more genes. All variants were not detected in our healthy controls (n = 100). No significant differences were observed between patients with and without a genetic variant in terms of sex, mean age of onset, bilaterality, the type of MD, and hearing threshold at diagnosis. Conclusions: Our study identified rare variants of putative candidate genes in some of MD patients. The genes were related to the formation of inner ear structures, the immune-associated process, or systemic hemostasis derangement, suggesting the multiple genetic predispositions in the development of MD

Data for Genetic Analysis Workshop (GAW) 15 Problem 2, Genetic Causes of Rheumatoid Arthritis and Associated Traits

For Genetic Analysis Workshop 15 Problem 2, we organized data from several ongoing studies designed to identify genetic and environmental risk factors for rheumatoid arthritis. Data were derived from the North American Rheumatoid Arthritis Consortium (NARAC), collaboration among Canadian researchers, the European Consortium on Rheumatoid Arthritis Families (ECRAF), and investigators from Manchester, England. All groups used a common standard for defining rheumatoid arthritis, but NARAC also further selected for a more severe phenotype in the probands. Genotyping and family structures for microsatellite-based linkage analysis were provided from all centers. In addition, all centers but ECRAF have genotyped families for linkage analysis using SNPs and these data were additionally provided. NARAC also had additional data from a dense genotyping analysis of a region of chromosome 18 and results from candidate gene studies, which were provided. Finally, smoking influences risk for rheumatoid arthritis, and data were provided from the NARAC study on this behavior as well as some additional phenotypes measuring severity. Several questions could be evaluated using the data that were provided. These include comparing linkage analysis using single-nucleotide polymorphisms versus microsatellites and identifying credible regions of linkage outside the HLA region on chromosome 6p13, which has been extensively documented; evaluating the joint effects of smoking with genetic factors; and identifying more homogenous subsets of families for whom genetic susceptibility might be stronger, so that linkage and association studies may be more efficiently conducted