60 research outputs found

    A palace fit for the future: Desirability in temporal work

    Get PDF
    Research on the strategic organization of time often assumes that collective efforts are motivated by and oriented toward achieving desirable, although not necessarily well-defined, future states. In situations surrounded by uncertainty where work has to proceed urgently to avoid an impending disaster, however, temporal work is guided by engaging with both desirable and undesirable future outcomes. Drawing on a real-time, in-depth study of the inception of the Restoration and Renewal program of the Palace of Westminster, we investigate how organizational actors develop a strategy for an uncertain and highly contested future while safeguarding ongoing operations in the present and preserving the heritage of the past. Anticipation of undesirable future events played a crucial role in mobilizing collective efforts to move forward. We develop a model of future desirability in temporal work to identify how actors construct, link, and navigate interpretations of desirable and undesirable futures in their attempts to create a viable path of action. By conceptualizing temporal work based on the phenomenological quality of the future, we advance understanding of the strategic organization of time in pluralistic contexts characterized by uncertainty and urgency

    Meta-Analysis of Dilated Cardiomyopathy Using Cardiac RNA-Seq Transcriptomic Datasets.

    Get PDF
    Dilated cardiomyopathy (DCM) is one of the most common causes of heart failure. Several studies have used RNA-sequencing (RNA-seq) to profile differentially expressed genes (DEGs) associated with DCM. In this study, we aimed to profile gene expression signatures and identify novel genes associated with DCM through a quantitative meta-analysis of three publicly available RNA-seq studies using human left ventricle tissues from 41 DCM cases and 21 control samples. Our meta-analysis identified 789 DEGs including 581 downregulated and 208 upregulated genes. Several DCM-related genes previously reported, including MYH6, CKM, NKX2-5 and ATP2A2, were among the top 50 DEGs. Our meta-analysis also identified 39 new DEGs that were not detected using those individual RNA-seq datasets. Some of those genes, including PTH1R, ADAM15 and S100A4, confirmed previous reports of associations with cardiovascular functions. Using DEGs from this meta-analysis, the Ingenuity Pathway Analysis (IPA) identified five activated toxicity pathways, including failure of heart as the most significant pathway. Among the upstream regulators, SMARCA4 was downregulated and prioritized by IPA as the top affected upstream regulator for several DCM-related genes. To our knowledge, this study is the first to perform a transcriptomic meta-analysis for clinical DCM using RNA-seq datasets. Overall, our meta-analysis successfully identified a core set of genes associated with DCM

    Artificial Intelligence and Machine Learning to Fight COVID-19.

    Get PDF

    Genotype-phenotype correlation and description of two novel mutations in Iranian patients with glycogen storage disease 1b (GSD1b)

    Get PDF
    Background: Glycogen storage disease (GSD) is a rare inborn error of the synthesis or degradation of glycogen metabolism. GSD1, the most common type of GSD, is categorized into GSD1a and GSD1b which caused by the deficiency of glucose-6-phosphatase (G6PC) and glucose-6-phosphate transporter (SLC37A4), respectively. The high rates of consanguineous marriages in Iran provide a desirable context to facilitate finding the homozygous pathogenic mutations. This study designates to evaluate the clinical and genetic characteristics of patients with GSD1b to assess the possible genotype-phenotype correlation. Results: Autozygosity mapping was performed on nineteen GSD suspected families to suggest the causative loci. The mapping was done using two panels of short tandem repeat (STR) markers linked to the corresponding genes. The patients with autozygous haplotype block for the markers flanking the genes were selected for direct sequencing. Six patients showed autozygosity in the candidate markers for SLC37A4. Three causative variants were detected. The recurrent mutation of c.10421043delCT (p.Leu348Valfs*53) and a novel missense mutation of c.365G > A (p.G122E) in the homozygous state were identified in the SLC37A4. In silico analysis was performed to predict the pathogenicity of the variants. A novel whole SLC37A4 gene deletion using long-range PCR and sequencing was confirmed as well. Severe and moderate neutropenia was observed in patients with frameshift and missense variants, respectively. The sibling with the whole gene deletion has shown both severe neutropenia and leukopenia. Conclusions: The results showed that the hematological findings may have an appropriate correlation with the genotype findings. However, for a definite genotype-phenotype correlation, specifically for the clinical and biochemical phenotype, further studies with larger sample sizes are needed. © 2020 The Author(s)
    corecore