Classic Revisited: Penal Theory in \u3cem\u3eParadise Lost\u3c/em\u3e

Milton\u27s great poem can be enjoyed as a supernatural adventure story in the epic tradition-indeed almost as a science-fiction fantasy. An incredibly powerful supernatural figure-call him Father-lives on planet Heaven somewhere in outer space, surrounded by lesser supernatural beings, called Angels. Father begets Son asexually, and declares his intent to give him vice regal authority. Infuriated at Son\u27s being promoted over him, the foremost Angel, L leads a third of the Angels in violent rebellion against Father and Son. At first it seems the rebels will best the loyal Angels. But Father sends in Son to defeat the rebels all by himself. He succeeds effortlessly, and packs them (now devils) all off to a dismal region of space, created by Father to be the devils\u27 Devil\u27s Island, called Hell. Father, having lost a third of his angels, and determined to complete L\u27s humiliation, creates a new planet and places on it an (initially) immortal couple that he\u27s created out of the dust on the planet\u27s surface

Classic Revisited: Penal Theory in \u3cem\u3eParadise Lost\u3c/em\u3e

Milton\u27s great poem can be enjoyed as a supernatural adventure story in the epic tradition-indeed almost as a science-fiction fantasy. An incredibly powerful supernatural figure-call him Father-lives on planet Heaven somewhere in outer space, surrounded by lesser supernatural beings, called Angels. Father begets Son asexually, and declares his intent to give him vice regal authority. Infuriated at Son\u27s being promoted over him, the foremost Angel, L leads a third of the Angels in violent rebellion against Father and Son. At first it seems the rebels will best the loyal Angels. But Father sends in Son to defeat the rebels all by himself. He succeeds effortlessly, and packs them (now devils) all off to a dismal region of space, created by Father to be the devils\u27 Devil\u27s Island, called Hell. Father, having lost a third of his angels, and determined to complete L\u27s humiliation, creates a new planet and places on it an (initially) immortal couple that he\u27s created out of the dust on the planet\u27s surface

Transcriptome analysis of <i>Streptococcus gordonii </i>Challis DL1 indicates a role for the biofilm-associated <i>fruRBA </i>operon in response to <i>Candida albicans</i>

Multiple levels of interkingdom signaling have been implicated in maintaining the ecological balance between Candida albicans and commensal streptococci to assure a state of oral health. To better understand the molecular mechanisms involved in the initial streptococcal response to the presence of C. albicans that can initiate oral surface colonization and biofilm formation, hypha-forming cells were incubated with Streptococcus gordonii cells for 30 minutes to assess the streptococcal transcriptome response. A genome wide microarray analysis and quantitative PCR validation of S. gordonii transcripts identified a number of genes, the majority of which were involved in metabolic functions that were differentially expressed in the presence of hyphae. The fruR, fruB and fruA genes encoding the transcriptional regulator, fructose-1-phosphate kinase, and fructose-specific permease, respectively, of the phosphoenolpyruvate-dependent fructose phosphotransferase system, were consistently up-regulated. An S. gordonii mutant in which these genes were deleted by allelic replacement, formed an architecturally-distinct, less robust biofilm with C. albicans than did parental strain cells. Complementing the mutant with plasmid borne fruR, fruB and fruA genes caused phenotype reversion, indicating that the genes in this operon played a role in dual species biofilm formation. This genome wide analysis of the S. gordonii transcriptional response to C. albicans has identified several genes that have potential roles in interkingdom signaling and responses

Serial characterisation of monocyte and neutrophil function after lung resection.

OBJECTIVES: The primary aim of this prospective study was to perform a comprehensive serial characterisation of monocyte and neutrophil function, circulating monocyte subsets, and bronchoalveolar lavage (BAL) fluid after lung resection. A secondary aim was to perform a pilot, hypothesis-generating evaluation of whether innate immune parameters were associated with postoperative pneumonia. METHODS: Forty patients undergoing lung resection were studied in detail. Blood monocytes and neutrophils were isolated preoperatively and at 6, 24 and 48 h postoperatively. BAL was performed preoperatively and immediately postoperatively. Monocyte subsets, monocyte responsiveness to lipopolysaccharide (LPS) and neutrophil phagocytic capacity were quantified at all time points. Differential cell count, protein and cytokine concentrations were measured in BAL. Pneumonia evaluation at 72 h was assessed using predefined criteria. RESULTS: After surgery, circulating subsets of classical and intermediate monocytes increased significantly. LPS-induced release of proinflammatory cytokines from monocytes increased significantly and by 48 h a more proinflammatory profile was found. Neutrophil phagocytosis demonstrated a small but significant fall. Factors associated with postoperative pneumonia were: increased release of specific proinflammatory and anti-inflammatory cytokines from monocytes; preoperative neutrophilia; and preoperative BAL cell count. CONCLUSIONS: We conclude that postoperative lung inflammation is associated with specific changes in the cellular innate immune response, a better understanding of which may improve patient selection and prediction of complications in the future

The Influence of the LINC00961/SPAAR Locus Loss on Murine Development, Myocardial Dynamics, and Cardiac Response to Myocardial Infarction

Long non-coding RNAs (lncRNAs) have structural and functional roles in development and disease. We have previously shown that the LINC00961/SPAAR (small regulatory polypeptide of amino acid response) locus regulates endothelial cell function, and that both the lncRNA and micropeptide counter-regulate angiogenesis. To assess human cardiac cell SPAAR expression, we mined a publicly available scRNSeq dataset and confirmed LINC00961 locus expression and hypoxic response in a murine endothelial cell line. We investigated post-natal growth and development, basal cardiac function, the cardiac functional response, and tissue-specific response to myocardial infarction. To investigate the influence of the LINC00961/SPAAR locus on longitudinal growth, cardiac function, and response to myocardial infarction, we used a novel CRISPR/Cas9 locus knockout mouse line. Data mining suggested that SPAAR is predominantly expressed in human cardiac endothelial cells and fibroblasts, while murine LINC00961 expression is hypoxia-responsive in mouse endothelial cells. LINC00961–/– mice displayed a sex-specific delay in longitudinal growth and development, smaller left ventricular systolic and diastolic areas and volumes, and greater risk area following myocardial infarction compared with wildtype littermates. These data suggest the LINC00961/SPAAR locus contributes to cardiac endothelial cell and fibroblast function and hypoxic response, growth and development, and basal cardiovascular function in adulthood

Hierarchical model for the scale-dependent velocity of seismic waves

Elastic waves of short wavelength propagating through the upper layer of the Earth appear to move faster at large separations of source and receiver than at short separations. This scale dependent velocity is a manifestation of Fermat's principle of least time in a medium with random velocity fluctuations. Existing perturbation theories predict a linear increase of the velocity shift with increasing separation, and cannot describe the saturation of the velocity shift at large separations that is seen in computer simulations. Here we show that this long-standing problem in seismology can be solved using a model developed originally in the context of polymer physics. We find that the saturation velocity scales with the four-third power of the root-mean-square amplitude of the velocity fluctuations, in good agreement with the computer simulations.Comment: 7 pages including 3 figure

Globalization, the ambivalence of European integration and the possibilities for a post-disciplinary EU studies

Using the work of Manuel Castells as a starting point, this article explores the ambivalent relationship between globalization and European integration and the variety of ways in which the mainstream political science of the EU has attempted to deal with this issue. The analysis here suggests that various 'mainstreaming' disciplinary norms induce types of work that fail to address fully the somewhat paradoxical and counter-intuitive range of possible relationships between globalization and European integration. The article explores critically four possible analytical ways out of this paradox—abandonment of the concept of globalization, the development of definition precision in globalization studies, the reorientation of work to focus on globalization as discourse, and inter- and post-disciplinarity. The argument suggests that orthodox discussions of the relationship require a notion of social geography that sits at odds with much of the literature on globalization and while greater dialogue between disciplines is to be welcomed, a series of profound epistemological questions need to be confronted if studies of the interplay between global and social process are to be liberated from their disciplinary chains

Functional characterisation of human pulmonary monocyte-like cells in lipopolysaccharide-mediated acute lung inflammation.

BACKGROUND: We have previously reported the presence of novel subpopulations of pulmonary monocyte-like cells (PMLC) in the human lung; resident PMLC (rPMLC, HLA-DR(+)CD14(++)CD16(+)cells) and inducible PMLC (iPMLC, HLA-DR(+)CD14(++)CD16(-) cells). iPMLC are significantly increased in bronchoalveolar lavage (BAL) fluid following inhalation of lipopolysaccharide (LPS). We have carried out the first functional evaluation of PMLC subpopulations in the inflamed lung, following the isolation of these cells, and other lineages, from BAL fluid using novel and complex protocols. METHODS: iPMLC, rPMLC, alveolar macrophages (AM), neutrophils, and regulatory T cells were quantified in BAL fluid of healthy subjects at 9 hours post-LPS inhalation (n = 15). Cell surface antigen expression by iPMLC, rPMLC and AM and the ability of each lineage to proliferate and to undergo phagocytosis were investigated using flow cytometry. Basal cytokine production by iPMLC compared to AM following their isolation from BAL fluid and the responsiveness of both cell types following in vitro treatment with the synthetic corticosteroid dexamethasone were assessed. RESULTS: rPMLC have a significantly increased expression of mature macrophage markers and of the proliferation antigen Ki67, compared to iPMLC. Our cytokine data revealed a pro-inflammatory, corticosteroid-resistant phenotype of iPMLC in this model. CONCLUSIONS: These data emphasise the presence of functionally distinct subpopulations of the monocyte/macrophage lineage in the human lung in experimental acute lung inflammation

Leadership in the British civil service: an interpretation

This article is essentially a polemic. The argument is that when politicians and officials now talk of ‘leadership’ in the British civil service they do not use that word in the way in which it was previously used. In the past leading civil servants, acting in partnership with ministers and within constitutional constraints, exercised leadership in the sense of setting example, inspiring confidence and encouraging loyalty. The loosening of traditional constitutional patterns, the marginalization of senior officials in the policy process and the emergence of business methods as the preferred model for public ­administration have led to a political and administrative environment in which leadership in the British civil service is now about encouraging patterns of behaviour which fit in with these changes. Leadership skills are now about ‘delivery’; they are not about motivation. It is time for politicians, officials and scholars to be open about this