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According to Heise, the realistic value of Goethe's poetry lay in his depiction of the extremes of human experience. According to Heise, in literature of the \"Epochenwandel\" between feudal and bourgeois society, man was depicted for the first time as an active subject, shaping his own destiny in a Utopian and anticipatory way. The antique tradition of free, often improper . . . table talk [combined] universalism . . . with the material bodily element (wine, food, carnal love), with awareness of the time element (youth, old age, the ephemeral nature of life . . .): they express a peculiar Utopian strain, the brotherhood of fellow-drinkers and of all men, the triumph of affluence and the victory of reason.0 \"Tisch-Ued\" is highly ironic seen in the context of the provinciality of the GDR. Man merkte, daß man nicht mehr Herr dieser Prozesse ist, aber daß man sich immer noch in dem Glauben wälmte, man könnte sie regulieren. * Mensching's performance of \"Prometheus\" must be seen in the context of the GDR \"Antike-Rezeption.\" [...]the 1960s the mythical figure of Prometheus had been viewed in accordance with the SED's one-sided reception of the Goethe poem.

The modern German political song is a hybrid of high and low culture. With its roots in the birth of mass culture in the 1920s, it employs communicative strategies of popular song. Yet its tendencies toward philosophical, poetic, and musical sophistication reveal intellectual aspirations. This volume looks at the influence of revolutionary artistic traditions in the lyrics and music of the 'Liedermacher' of east and west Germany: the rediscovery of the revolutionary songs of 1848 by the 1960s West German folk revival, the use of the profane \"carnivalesque\" street-ballad tradition by Wolf Biermann and the GDR duo Wenzel & Mensching, the influence of 1920s artistic experimentation on 'Liedermacher' such as Konstantin Wecker, and the legacy of Hanns Eisler's revolutionary song theory. The book also provides an insider perspective on the countercultural scenes of the two Germanys, examining the conditions in which political songs were written and performed. In view of the decline of the political song form since the fall of communism, the book ends with a look at German avant-garde techno's attempt to create a music that challenges conventional cultural perceptions and attitudes. CONTRIBUTORS: DAVID ROBB, ECKARD HOLLER, ANNETTE BLÜHDORN, PETER THOMPSON. David Robb is Senior Lecturer in German Studies at the Queen's University of Belfast.

The cultural history of 20th-century Germany, more perhaps than that of any other European country, was decisively influenced by political forces and developments. This volume of essays focuses on the relationship between German politics and culture, which is most obvious in the case of the Third Reich and the German Democratic Republic, where the one-party control of all areas of life was extended to the arts; these were expected to conform to the ideals of the day. But the relationship between politics and the arts has not always been one purely of coercion, censorship, collusion, and opportunism. Many writers greeted the First World War with quite voluntary enthusiasm; others conjured up the National Socialist revolution in intense Expressionist images long before 1933. The GDR was heralded by writers returning from Nazi exile as the anti-fascist answer to the Third Reich. And in West Germany, politics did not dictate artistic norms, nor was it greeted with any great enthusiasm among intellectuals, but writers did tend to ally themselves with particular parties. To an extent, the pre-1990 literary establishment in the Federal Republic was dominated by a left-liberal consensus that German division was the just punishment for Auschwitz. United Germany began its existence with a fierce literary debate in 1990-92, with leading literary critics arguing that East and West German literature had basically shored up the political order in the two countries. Now a new literature was required, one that was free of ideology, intensely subjective and experimental in its aesthetic. In 1998, the author Martin Walser called for an end to the author's role as \"conscience of the nation\" and for the right to subjective experience. This is the first book to examine this crucial relationship between politics and culture in Germany.

Non-neutralizing IgG to the V1V2 loop of HIV-1 gp120 correlates with a decreased risk of HIV-1 infection but the mechanism of protection remains unknown. This V1V2 IgG correlate was identified in RV144 Thai trial vaccine recipients, who were primed with a canarypox vector expressing membrane-bound gp120 (vCP1521) and boosted with vCP1521 plus a mixture gp120 proteins from clade B and clade CRF01_AE (B/E gp120). We sought to determine whether the mechanism of vaccine protection might involve antibody-dependent complement activation. Complement activation was measured as a function of complement component C3d deposition on V1V2-coated beads in the presence of RV144 sera. Variable levels of complement activation were detected two weeks post final boosting in RV144, which is when the V1V2 IgG correlate was identified. The magnitude of complement activation correlated with V1V2-specific serum IgG and was stronger and more common in RV144 than in HIV-1 infected individuals and two related HIV-1 vaccine trials, VAX003 and VAX004, where no protection was seen. After adjusting for gp120 IgA, V1V2 IgG, gender, and risk score, complement activation by case-control plasmas from RV144 correlated inversely with a reduced risk of HIV-1 infection, with odds ratio for positive versus negative response to TH023-V1V2 0.42 (95% CI 0.18 to 0.99, p = 0.048) and to A244-V1V2 0.49 (95% CI 0.21 to 1.10, p = 0.085). These results suggest that complement activity may have contributed in part to modest protection against the acquisition of HIV-1 infection seen in the RV144 trial.

BackgroundCystic fibrosis (CF) lung disease is defined by large numbers of neutrophils and associated damaging products in the airway. Delayed neutrophil apoptosis is described in CF although it is unclear whether this is a primary neutrophil defect or a response to chronic inflammation. Increased levels of neutrophil extracellular traps (NETs) have been measured in CF and we aimed to investigate the causal relationship between these phenomena and their potential to serve as a driver of inflammation. We hypothesised that the delay in apoptosis in CF is a primary defect and preferentially allows CF neutrophils to form NETs, contributing to inflammation.MethodsBlood neutrophils were isolated from patients with CF, CF pigs and appropriate controls. Neutrophils were also obtained from patients with CF before and after commencing ivacaftor. Apoptosis was assessed by morphology and flow cytometry. NET formation was determined by fluorescent microscopy and DNA release assays. NET interaction with macrophages was examined by measuring cytokine generation with ELISA and qRT-PCR.ResultsCF neutrophils live longer due to decreased apoptosis. This was observed in both cystic fibrosis transmembrane conductance regulator (CFTR) null piglets and patients with CF, and furthermore was reversed by ivacaftor (CFTR potentiator) in patients with gating (G551D) mutations. CF neutrophils formed more NETs and this was reversed by cyclin-dependent kinase inhibitor exposure. NETs provided a proinflammatory stimulus to macrophages, which was enhanced in CF.ConclusionsCF neutrophils have a prosurvival phenotype that is associated with an absence of CFTR function and allows increased NET production, which can in turn induce inflammation. Augmenting neutrophil apoptosis in CF may allow more appropriate neutrophil disposal, decreasing NET formation and thus inflammation.

A combination of therapeutic vaccination with Ad26/MVA and stimulation of innate immune responses leads to improved virologic control and delayed rebound in SIV-infected macaques following discontinuation of antiretroviral therapy. Combining anti-HIV vaccination and immuostimulant These authors demonstrate that combining an experimental vaccine—consisting of an adenovirus serotype 26 vector vaccine and an MVA vector vaccine (Ad26/MVA)—with the innate immune stimulant Toll-like receptor 7 leads to improved virologic control and delayed rebound following discontinuation of stable antiretroviral therapy in SIV-infected macaques. The development of immunologic interventions that can target the viral reservoir in HIV-1-infected individuals is a major goal of HIV-1 research 1 , 2 . However, little evidence exists that the viral reservoir can be sufficiently targeted to improve virologic control following discontinuation of antiretroviral therapy. Here we show that therapeutic vaccination with Ad26/MVA (recombinant adenovirus serotype 26 (Ad26) prime, modified vaccinia Ankara (MVA) boost) 3 , 4 and stimulation of TLR7 (Toll-like receptor 7) improves virologic control and delays viral rebound following discontinuation of antiretroviral therapy in SIV-infected rhesus monkeys that began antiretroviral therapy during acute infection. Therapeutic vaccination with Ad26/MVA resulted in a marked increase in the magnitude and breadth of SIV-specific cellular immune responses in virologically suppressed, SIV-infected monkeys. TLR7 agonist administration led to innate immune stimulation and cellular immune activation. The combination of Ad26/MVA vaccination and TLR7 stimulation resulted in decreased levels of viral DNA in lymph nodes and peripheral blood, and improved virologic control and delayed viral rebound following discontinuation of antiretroviral therapy. The breadth of cellular immune responses correlated inversely with set point viral loads and correlated directly with time to viral rebound. These data demonstrate the potential of therapeutic vaccination combined with innate immune stimulation as a strategy aimed at a functional cure for HIV-1 infection.

Overcoming the COVID-19 pandemic requires motivating the vast majority of Americans to get vaccinated. However, vaccination rates have become politically polarized, and a substantial proportion of Republicans have remained vaccine hesitant for months. Here, we explore how endorsements by party elites affect Republicans’ COVID-19 vaccination intentions and attitudes. In a preregistered survey experiment (n = 1,480), we varied whether self-identified Republicans saw endorsements of the vaccine from prominent Republicans (including video of a speech by former President Donald Trump), from the Democratic Party (including video of a speech by President Joseph Biden), or a neutral control condition including no endorsements. Unvaccinated Republicans who were exposed to the Republican elite endorsement reported 7.0% higher vaccination intentions than those who viewed the Democratic elite endorsement and 5.7% higher than those in the neutral control condition. These effects were statistically mediated by participants’ reports of how much they thought Republican politicians would want them to get vaccinated. We also found evidence of backlash effects against Democratic elites: Republicans who viewed the Democratic elite endorsement reported they would be significantly less likely to encourage others to vaccinate and had more negative attitudes toward the vaccine, compared with those who viewed the Republican elite endorsement or the neutral control. These results demonstrate the relative advantage of cues from Republican elites—and the risks of messaging from Democrats currently in power—for promoting vaccination among the largest vaccine-hesitant subgroup in the United States.

More than 1·8 million new cases of HIV-1 infection were diagnosed worldwide in 2016. No licensed prophylactic HIV-1 vaccine exists. A major limitation to date has been the lack of direct comparability between clinical trials and preclinical studies. We aimed to evaluate mosaic adenovirus serotype 26 (Ad26)-based HIV-1 vaccine candidates in parallel studies in humans and rhesus monkeys to define the optimal vaccine regimen to advance into clinical efficacy trials. We conducted a multicentre, randomised, double-blind, placebo-controlled phase 1/2a trial (APPROACH). Participants were recruited from 12 clinics in east Africa, South Africa, Thailand, and the USA. We included healthy, HIV-1-uninfected participants (aged 18–50 years) who were considered at low risk for HIV-1 infection. We randomly assigned participants to one of eight study groups, stratified by region. Participants and investigators were blinded to the treatment allocation throughout the study. We primed participants at weeks 0 and 12 with Ad26.Mos.HIV (5 × 1010 viral particles per 0·5 mL) expressing mosaic HIV-1 envelope (Env)/Gag/Pol antigens and gave boosters at weeks 24 and 48 with Ad26.Mos.HIV or modified vaccinia Ankara (MVA; 108 plaque-forming units per 0·5 mL) vectors with or without high-dose (250 μg) or low-dose (50 μg) aluminium adjuvanted clade C Env gp140 protein. Those in the control group received 0·9% saline. All study interventions were administered intramuscularly. Primary endpoints were safety and tolerability of the vaccine regimens and Env-specific binding antibody responses at week 28. Safety and immunogenicity were also assessed at week 52. All participants who received at least one vaccine dose or placebo were included in the safety analysis; immunogenicity was analysed using the per-protocol population. We also did a parallel study in rhesus monkeys (NHP 13-19) to assess the immunogenicity and protective efficacy of these vaccine regimens against a series of six repetitive, heterologous, intrarectal challenges with a rhesus peripheral blood mononuclear cell-derived challenge stock of simian-human immunodeficiency virus (SHIV-SF162P3). The APPROACH trial is registered with ClinicalTrials.gov, number NCT02315703. Between Feb 24, 2015, and Oct 16, 2015, we randomly assigned 393 participants to receive at least one dose of study vaccine or placebo in the APPROACH trial. All vaccine regimens demonstrated favourable safety and tolerability. The most commonly reported solicited local adverse event was mild-to-moderate pain at the injection site (varying from 69% to 88% between the different active groups vs 49% in the placebo group). Five (1%) of 393 participants reported at least one grade 3 adverse event considered related to the vaccines: abdominal pain and diarrhoea (in the same participant), increased aspartate aminotransferase, postural dizziness, back pain, and malaise. The mosaic Ad26/Ad26 plus high-dose gp140 boost vaccine was the most immunogenic in humans; it elicited Env-specific binding antibody responses (100%) and antibody-dependent cellular phagocytosis responses (80%) at week 52, and T-cell responses at week 50 (83%). We also randomly assigned 72 rhesus monkeys to receive one of five different vaccine regimens or placebo in the NHP 13-19 study. Ad26/Ad26 plus gp140 boost induced similar magnitude, durability, and phenotype of immune responses in rhesus monkeys as compared with humans and afforded 67% protection against acquisition of SHIV-SF162P3 infection (two-sided Fisher's exact test p=0·007). Env-specific ELISA and enzyme-linked immunospot assay responses were the principal immune correlates of protection against SHIV challenge in monkeys. The mosaic Ad26/Ad26 plus gp140 HIV-1 vaccine induced comparable and robust immune responses in humans and rhesus monkeys, and it provided significant protection against repetitive heterologous SHIV challenges in rhesus monkeys. This vaccine concept is currently being evaluated in a phase 2b clinical efficacy study in sub-Saharan Africa (NCT03060629). Janssen Vaccines & Prevention BV, National Institutes of Health, Ragon Institute of MGH, MIT and Harvard, Henry M Jackson Foundation for the Advancement of Military Medicine, US Department of Defense, and International AIDS Vaccine Initiative.

Biospecimens acquired during routine medical practice are the primary sources of molecular information about patients and their diseases that underlies precision medicine and translational research. In cancer care, molecular analysis of biospecimens is especially common because it often determines treatment choices and may be used to monitor therapy in real time. However, patient specimens are collected, handled, and processed according to routine clinical procedures during which they are subjected to factors that may alter their molecular quality and composition. Such artefactual alteration may skew data from molecular analyses, render analysis data uninterpretable, or even preclude analysis altogether if the integrity of a specimen is severely compromised. As a result, patient care and safety may be affected, and medical research dependent on patient samples may be compromised. Despite these issues, there is currently no requirement to control or record preanalytical variables in clinical practice with the single exception of breast cancer tissue handled according to the guideline jointly developed by the American Society of Clinical Oncology and College of American Pathologists (CAP) and enforced through the CAP Laboratory Accreditation Program. Recognizing the importance of molecular data derived from patient specimens, the CAP Personalized Healthcare Committee established the Preanalytics for Precision Medicine Project Team to develop a basic set of evidence-based recommendations for key preanalytics for tissue and blood specimens. If used for biospecimens from patients, these preanalytical recommendations would ensure the fitness of those specimens for molecular analysis and help to assure the quality and reliability of the analysis data.