Why practice philosophy as a way of life?

This essay explains why there are good reasons to practice philosophy as a way of life. The argument begins with the assumption that we should live well but that our understanding of how to live well can be mistaken. Philosophical reason and reflection can help correct these mistakes. Nonetheless, the evidence suggests that philosophical reasoning often fails to change our dispositions and behavior. Drawing on the work of Pierre Hadot, the essay claims that spiritual exercises and communal engagement mitigate the factors that prevent us from living in accord- ance with our conceptions of the good life. So, many of us have reasons to engage in philosophical reasoning along with behavioral, cognitive, and social strategies to alter our behavior and attitudes so that they’re in line with our philosophical commitments. In these respects, many of us should practice philosophy as a way of life

A High-Resolution Map of Arabidopsis Recombinant Inbred Lines by Whole-Genome Exon Array Hybridization

Recombinant populations were the basis for Mendel's first genetic experiments and continue to be key to the study of genes, heredity, and genetic variation today. Genotyping several hundred thousand loci in a single assay by hybridizing genomic DNA to oligonucleotide arrays provides a powerful technique to improve precision linkage mapping. The genotypes of two accessions of Arabidopsis were compared by using a 400,000 feature exon-specific oligonucleotide array. Around 16,000 single feature polymorphisms (SFPs) were detected in ~8,000 of the ~26,000 genes represented on the array. Allelic variation at these loci was measured in a recombinant inbred line population, which defined the location of 815 recombination breakpoints. The genetic linkage map had a total length of 422.5 cM, with 676 informative SFP markers representing intervals of ~0.6 cM. One hundred fifteen single gene intervals were identified. Recombination rate, SFP distribution, and segregation in this population are not uniform. Many genomic regions show a clustering of recombination events including significant hot spots. The precise haplotype structure of the recombinant population was defined with unprecedented accuracy and resolution. The resulting linkage map allows further refinement of the hundreds of quantitative trait loci identified in this well-studied population. Highly variable recombination rates along each chromosome and extensive segregation distortion were observed in the population

Who punishes the leader? Leader culpability and coups during civil war

Who punishes leaders via coups during civil war? By distinguishing between different types of internal audiences within the government and their attempts to remove a leader forcefully, I illuminate the mechanisms that explain variation in who punishes the leader during wartime. I claim that whether leaders are culpable for the initiation of the war has an important implication for whether they are punished by members of the ruling coalition (i.e., those with access to decision-making and political power), or by those outside the ruling coalition. Empirical evidence supports my hypotheses: (i) culpable leaders are more likely to experience coup attempts led by those outside the leaders' ruling coalition, should the war go poorly; and (ii) nonculpable leaders are more likely to experience coups executed by members of their ruling coalition. The findings have important implications for how leaders respond to audience pressures as they consider whether to fight or settle

Usefulness of gene expression profiling of bronchoalveolar lavage cells in acute lung allograft rejection.

BackgroundChronic lung allograft dysfunction (CLAD) is the main limitation to long-term survival after lung transplantation. Because effective therapies are lacking, early identification and mitigation of risk factors is a pragmatic approach to improve outcomes. Acute cellular rejection (ACR) is the most pervasive risk factor for CLAD, but diagnosis requires transbronchial biopsy, which carries risks. We hypothesized that gene expression in the bronchoalveolar lavage (BAL) cell pellet (CP) could replace biopsy and inform on mechanisms of CLAD.MethodsWe performed RNA sequencing on BAL CPs from 219 lung transplant recipients with A-grade ACR (n = 61), lymphocytic bronchiolitis (n = 58), infection (n = 41), or no rejection/infection (n = 59). Differential gene expression was based on absolute fold difference >2.0 and Benjamini-adjusted p-value ≤0.05. We used the Database for Annotation, Visualization and Integrated Discovery Bioinformatics Resource for pathway analyses. For classifier modeling, samples were randomly split into training (n = 154) and testing sets (n = 65). A logistic regression model using recursive feature elimination and 5-fold cross-validation was trained to optimize area under the curve (AUC).ResultsDifferential gene expression identified 72 genes. Enriched pathways included T-cell receptor signaling, natural killer cell-mediated cytotoxicity, and cytokine-cytokine receptor interaction. A 4-gene model (AUC = 0.72) and classification threshold defined in the training set exhibited fair performance in the testing set; accuracy was 76%, specificity 82%, and sensitivity 60%. In addition, classification as ACR was associated with worse CLAD-free survival (hazard ratio = 2.42; 95% confidence interval = 1.29-4.53).ConclusionsBAL CP gene expression during ACR is enriched for immune response pathways and shows promise as a diagnostic tool for ACR, especially ACR that is a precursor of CLAD