Designing the Machine Age in America: Streamlining in the 20th Century

Streamlining, the major U.S. commercial design style of the 1930s, was promoted by industrial designers who sought to eliminate sales resistance just as aerodynamic streamlining was intended to eliminate wind resistance. Popularized in 1934 by two passenger trains, the Union Pacific railroads M-10,000 and the Burlington railroads Zephyr, the style was introduced into the automotive market through the Chrysler Airflow and was quickly incorporated into non-vehicular consumer products. While 1930s streamlining expressed a cultural desire for stability and stasis during the Great Depression, the postwar variant, exemplified by the sharply angled, flaring automotive tailfin, expressed a popular faith in limitless technological progress. The architect Eero Saarinen, who had learned streamlining in the industrial design office of Norman Bel Geddes in the late 1930s, brought postwar streamlining to full expression in such projects as the TWA terminal in New York and Dulles airport in northern Virginia. During the 1990s a nostalgic retro mode of streamlining appeared in such products as the New Beetle automobile, the first Apple iMac computer, and the Smart car

Youve Been with the Professors: Influence, Appropriation, and the Cultural Interpretation of Bob Dylan

Sean Wilentz, Bob Dylan in America. New York: Doubleday, 2010. 390 pp., 99 b..w illus., index. Greil Marcus, Bob Dylan: Writings 1968-2010. New York: PublicAffairs, 2010. xx, 483 pp, 14 b&w illus., index.American Studies as a discipline, at least as practiced in the United States, has sometimes attracted criticism that it encourages narcissistic navel-gazing by a culture whose socioeconomic base is affluent enough to afford that luxury. This complaint is especially prevalent in attacks on scholars who direct their attention to popular examples of the products of mass culture. A former colleague of mine, or example, often aimed sarcastic barbs at people who write about their record collections. At the least, he believed, such unprofessional scholars are too lazy to look beyond narrow personal interests; at worst, they project their own guilty pleasures onto the larger culture in a solipsistic gesture motivated by self-justification. Although my colleagues opinion reflected a bitter, ultimately dismissive attitude toward recent scholarship on contemporary mass culture, there is indeed a gray area where celebrity worship, fanboy obsession, and personal desire to claim cultural capital may blur traditional notions of scholarships neutral objectivity. Attempts to overcome such attacks often seek to prove by applying audience or reception theory that popular culture products do have substantive impact on the lives of those who consume them. That defense may appear questionable not only because reception is notoriously difficult to measure but also because critical theorys densely-worded, jargon-laden arguments may seem like self-serving obfuscation to readers already inclined to be skeptical of serious claims for popular or mass culture

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Common, low-frequency, rare, and ultra-rare coding variants contribute to COVID-19 severity

The combined impact of common and rare exonic variants in COVID-19 host genetics is currently insufficiently understood. Here, common and rare variants from whole-exome sequencing data of about 4000 SARS-CoV-2-positive individuals were used to define an interpretable machine-learning model for predicting COVID-19 severity. First, variants were converted into separate sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. The Boolean features selected by these logistic models were combined into an Integrated PolyGenic Score that offers a synthetic and interpretable index for describing the contribution of host genetics in COVID-19 severity, as demonstrated through testing in several independent cohorts. Selected features belong to ultra-rare, rare, low-frequency, and common variants, including those in linkage disequilibrium with known GWAS loci. Noteworthily, around one quarter of the selected genes are sex-specific. Pathway analysis of the selected genes associated with COVID-19 severity reflected the multi-organ nature of the disease. The proposed model might provide useful information for developing diagnostics and therapeutics, while also being able to guide bedside disease management. © 2021, The Author(s)

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Transatlantic Refractions: Ambivalence and Cultural Hybridity in the Euro-American Road Movie

This article analyses a variety of ways in which the “road movie” has been reinterpreted by modern European directors (German Wim Wenders, Finn Aki Kaurismäki) or American director Jim Jarmusch with his pronounced European sensibilities. Despite the ubiquity of American popular culture in many of these movies, the films themselves are far from representing a simple “colonization” on the part of American culture. The ambivalent view of the United States adopted by these men has helped transform a typically “American” genre into a new demonstration of transatlantic cultural hybridity