"On the Spot": travelling artists and Abolitionism, 1770-1830

Until recently the visual culture of Atlantic slavery has rarely been critically scrutinised. Yet in the first decades of the nineteenth century slavery was frequently represented by European travelling artists, often in the most graphic, sometimes voyeuristic, detail. This paper examines the work of several itinerant artists, in particular Augustus Earle (1793-1838) and Agostino Brunias (1730–1796), whose very mobility along the edges of empire was part of a much larger circulatory system of exchange (people, goods and ideas) and diplomacy that characterised Europe’s Age of Expansion. It focuses on the role of the travelling artist, and visual culture more generally, in the development of British abolitionism between 1770 and 1830. It discusses the broad circulation of slave imagery within European culture and argues for greater recognition of the role of such imagery in the abolitionist debates that divided Britain. Furthermore, it suggests that the epistemological authority conferred on the travelling artist—the quintessential eyewitness—was key to the rhetorical power of his (rarely her) images. Artists such as Earle viewed the New World as a boundless source of fresh material that could potentially propel them to fame and fortune. Johann Moritz Rugendas (1802-1858), on the other hand, was conscious of contributing to a global scientific mission, a Humboldtian imperative that by the 1820s propelled him and others to travel beyond the traditional itinerary of the Grand Tour. Some artists were implicated in the very fabric of slavery itself, particularly those in the British West Indies such as William Clark (working 1820s) and Richard Bridgens (1785-1846); others, particularly those in Brazil, expressed strong abolitionist sentiments. Fuelled by evangelical zeal to record all aspects of the New World, these artists recognised the importance of representing the harsh realities of slave life. Unlike those in the metropole who depicted slavery (most often in caustic satirical drawings), many travelling artists believed strongly in the evidential value of their images, a value attributed to their global mobility. The paper examines the varied and complex means by which visual culture played a significant and often overlooked role in the political struggles that beset the period

IRAS 21391+5802: The Molecular Outflow and its Exciting Source

We present centimeter and millimeter observations of gas and dust around IRAS 21391+5802, an intermediate-mass source embedded in the core of IC 1396N. Continuum observations from 3.6 cm to 1.2 mm are used to study the embedded objects and overall distribution of the dust, while molecular line observations of CO, CS, and CH3OH are used to probe the structure and chemistry of the outflows in the region. The continuum emission at centimeter and millimeter wavelengths has been resolved into three sources separated about 15 arcsec from each other, and with one of them, BIMA 2, associated with IRAS 21391+5802. The dust emission around this source shows a very extended envelope, which accounts for most of the circumstellar mass of 5.1 Msun. This source is powering a strong molecular outflow, elongated in the E--W direction, which presents a complex structure and kinematics. While at high outflow velocities the outflow is clearly bipolar, at low outflow velocities the blueshifted and redshifted emission are highly overlapping, and the strongest emission shows a V-shaped morphology. The outflow as traced by CS and CH3OH exhibits two well differentiated and clumpy lobes, with two prominent northern blueshifted and redshifted clumps. The curved shape of the clumps and the spectral shape at these positions are consistent with shocked material. In addition, CS and CH3OH are strongly enhanced toward these positions with respect to typical quiescent material abundances in other star-forming regions.Comment: 41 pages, including 11 figures, accepted for publication in ApJ (July 1); available at http://www.am.ub.es/~robert/Papers.html#las

PAM-2 decreases neuropathic pain in mice and modulates chemokine/cytokine production in human microglial cells

Background: People worldwide suffer from neuropathic pain, and indicated medications are often either not effective or induce tolerance and abuse. Therefore, there is an urgent need to identify additional therapeutic options to treat this form of pain. Nicotinic acetylcholine receptors (nAChRs), particularly a7-nAChRs, have been implicated in pain signaling. Therefore, this study was designed to investigate the extent to which the selective positive allosteric modulator (PAM) of a7 AChRs, PAM-2, modulates neuropathic pain. The working hypothesis, that PAM-2 inhibits inflammatory signaling and neuropathic pain, was tested using animal and cellular models.Methods: The anti-neuropathic pain activity of PAM-2 was assessed in two independent murine models of neuropathic pain. Briefly, neuropathic pain was induced in adult, male CD-1 mice (n=10/condition) via i.p. administration of either streptozotocin (STZ) or oxaliplatin (OXA). After 14 days, when neuropathic pain was present, mice were administrated with PAM-2 (1.0 or 3.0 mg/kg, p.o.) or vehicle. The pain threshold was subsequently determined by the cold plate test before and 15, 30, 45, and 60 min after treatment. In addition, C20 human microglial cells were exposed to interleukin (IL)-1B (20 ng/ml) or vehicle alone, and in combination with nicotine (3 uM), PAM-2 (1-100 uM), or nicotine + PAM-2 for 24 h. After 24 h, cytokine/chemokine levels in the culture media were measured by ELISA.Results: A single dose of PAM-2 (3.0 mg/kg) decreased both STZ- and OXA-induced neuropathic pain in mice. Repeated treatment with an inactive dose (1.0 mg/kg) of PAM-2 showed anti-pain activity in OXA-treated mice after 14, but not 7, days of treatment. Additionally, methyllycaconitine blocked the anti-pain effects elicited by PAM-2, supporting the view that a7 AChRs are instrumental in the anti-pain actions of PAM-2. Cellular experiments revealed that nicotine minimally inhibited IL-1B-induced IL-6 and interferon-gamma-induced chemotactic protein 10 expression in C20 human microglial cells, and that this inhibition was potentiated by PAM-2 (100 uM). However, we cannot rule out the possibility that PAM- 2 was cytotoxic in this cell culture model.Conclusions: These findings indicate that a7 AChRs are involved in neuropathic pain signaling and that a7-PAMs may potentially be used therapeutically. The extent to which these protective effects involve reduced neuroinflammation remains to be determined

Gene expression in primate liver during viral hemorrhagic fever

<p>Abstract</p> <p>Background</p> <p>Rhesus macaques infected with lymphocytic choriomeningitis virus (LCMV) provide a model for human Lassa fever. Disease begins with flu-like symptoms and progresses rapidly with fatal consequences. Previously, we profiled the blood transcriptome of LCMV-infected monkeys (M. Djavani et al J. Virol. 2007) showing distinct pre-viremic and viremic stages that discriminated virulent from benign infections. In the present study, changes in liver gene expression from macaques infected with virulent LCMV-WE were compared to gene expression in uninfected monkeys as well as to monkeys that were infected but not diseased.</p> <p>Results</p> <p>Based on a functional pathway analysis of differentially expressed genes, virulent LCMV-WE had a broader effect on liver cell function than did infection with non-virulent LCMV-Armstrong. During the first few days after infection, LCMV altered expression of genes associated with energy production, including fatty acid and glucose metabolism. The transcriptome profile resembled that of an organism in starvation: mRNA for acetyl-CoA carboxylase, a key enzyme of fatty acid synthesis was reduced while genes for enzymes in gluconeogenesis were up-regulated. Expression was also altered for genes associated with complement and coagulation cascades, and with signaling pathways involving STAT1 and TGF-β.</p> <p>Conclusion</p> <p>Most of the 4500 differentially expressed transcripts represented a general response to both virulent and mild infections. However, approximately 250 of these transcripts had significantly different expression in virulent infections as compared to mild infections, with approximately 30 of these being differentially regulated during the pre-viremic stage of infection. The genes that are expressed early and differently in mild and virulent disease are potential biomarkers for prognosis and triage of acute viral disease.</p

Results of a randomized, double-blind phase II clinical trial of NY-ESO-1 vaccine with ISCOMATRIX adjuvant versus ISCOMATRIX alone in participants with high-risk resected melanoma.

BACKGROUND: To compare the clinical efficacy of New York Esophageal squamous cell carcinoma-1 (NY-ESO-1) vaccine with ISCOMATRIX adjuvant versus ISCOMATRIX alone in a randomized, double-blind phase II study in participants with fully resected melanoma at high risk of recurrence. METHODS: Participants with resected stage IIc, IIIb, IIIc and IV melanoma expressing NY-ESO-1 were randomized to treatment with three doses of NY-ESO-1/ISCOMATRIX or ISCOMATRIX adjuvant administered intramuscularly at 4-week intervals, followed by a further dose at 6 months. Primary endpoint was the proportion free of relapse at 18 months in the intention-to-treat (ITT) population and two per-protocol populations. Secondary endpoints included relapse-free survival (RFS) and overall survival (OS), safety and NY-ESO-1 immunity. RESULTS: The ITT population comprised 110 participants, with 56 randomized to NY-ESO-1/ISCOMATRIX and 54 to ISCOMATRIX alone. No significant toxicities were observed. There were no differences between the study arms in relapses at 18 months or for median time to relapse; 139 vs 176 days (p=0.296), or relapse rate, 27 (48.2%) vs 26 (48.1%) (HR 0.913; 95% CI 0.402 to 2.231), respectively. RFS and OS were similar between the study arms. Vaccine recipients developed strong positive antibody responses to NY-ESO-1 (p≤0.0001) and NY-ESO-1-specific CD4+ and CD8+ responses. Biopsies following relapse did not demonstrate differences in NY-ESO-1 expression between the study populations although an exploratory study demonstrated reduced (NY-ESO-1)+/Human Leukocyte Antigen (HLA) class I+ double-positive cells in biopsies from vaccine recipients performed on relapse in 19 participants. CONCLUSIONS: The vaccine was well tolerated, however, despite inducing antigen-specific immunity, it did not affect survival endpoints. Immune escape through the downregulation of NY-ESO-1 and/or HLA class I molecules on tumor may have contributed to relapse

Tumor-expressed adrenomedullin accelerates breast cancer bone metastasis

INTRODUCTION: Adrenomedullin (AM) is secreted by breast cancer cells and increased by hypoxia. It is a multifunctional peptide that stimulates angiogenesis and proliferation. The peptide is also a potent paracrine stimulator of osteoblasts and bone formation, suggesting a role in skeletal metastases-a major site of treatment-refractory tumor growth in patients with advanced disease. METHODS: The role of adrenomedullin in bone metastases was tested by stable overexpression in MDA-MB-231 breast cancer cells, which cause osteolytic bone metastases in a standard animal model. Cells with fivefold increased expression of AM were characterized in vitro, inoculated into immunodeficient mice and compared for their ability to form bone metastases versus control subclones. Bone destruction was monitored by X-ray, and tumor burden and osteoclast numbers were determined by quantitative histomorphometry. The effects of AM overexpression on tumor growth and angiogenesis in the mammary fat pad were determined. The effects of AM peptide on osteoclast-like multinucleated cell formation were tested in vitro. A small-molecule AM antagonist was tested for its effects on AM-stimulated ex vivo bone cell cultures and co-cultures with tumor cells, where responses of tumor and bone were distinguished by species-specific real-time PCR. RESULTS: Overexpression of AM mRNA did not alter cell proliferation in vitro, expression of tumor-secreted factors or cell cycle progression. AM-overexpressing cells caused osteolytic bone metastases to develop more rapidly, which was accompanied by decreased survival. In the mammary fat pad, tumors grew more rapidly with unchanged blood vessel formation. Tumor growth in the bone was also more rapid, and osteoclasts were increased. AM peptide potently stimulated bone cultures ex vivo; responses that were blocked by small-molecule adrenomedullin antagonists in the absence of cellular toxicity. Antagonist treatment dramatically suppressed tumor growth in bone and decreased markers of osteoclast activity. CONCLUSIONS: The results identify AM as a target for therapeutic intervention against bone metastases. Adrenomedullin potentiates osteolytic responses in bone to metastatic breast cancer cells. Small-molecule antagonists can effectively block bone-mediated responses to tumor-secreted adrenomedullin, and such agents warrant development for testing in vivo

Reliable Identification of Binary Supermassive Black Holes from Rubin Observatory Time-Domain Monitoring

Periodic signatures in time-domain observations of quasars have been used to search for binary supermassive black holes. These searches, across existing time-domain surveys, have produced several hundred candidates. The general stochastic variability of quasars, however, can masquerade as a false-positive periodic signal, especially when monitoring cadence and duration are limited. In this work, we predict the detectability of binary supermassive black holes in the upcoming Rubin Observatory Legacy Survey of Space and Time (LSST). We apply computationally inexpensive sinusoidal curve fits to millions of simulated LSST Deep Drilling Field light curves of both single, isolated quasars and binary quasars. Period and phase of simulated binary signals can generally be disentangled from quasar variability. Binary amplitude is overestimated and poorly recovered for two-thirds of potential binaries due to quasar accretion variability. Quasars with strong intrinsic variability can obscure a binary signal too much for recovery. We also find that the most luminous quasars mimic current binary candidate light curves and their properties: false positive rates are 60\% for these quasars. The reliable recovery of binary period and phase for a wide range of input binary LSST light curves is promising for multi-messenger characterization of binary supermassive black holes. However, pure electromagnetic detections of binaries using photometric periodicity with amplitude greater than 0.1 magnitude will result in samples that are overwhelmed by false positives. This paper represents an important and computationally inexpensive way forward for understanding the true and false positive rates for binary candidates identified by Rubin.Comment: 21 pages, 14 figures, 3 table