Poly(cyclodextrin)‐Polydrug Nanocomplexes as Synthetic Oncolytic Virus for Locoregional Melanoma Chemoimmunotherapy

Despite the approval of oncolytic virus (OV) therapy for advanced melanoma, its intrinsic limitations that include the risk of persistent viral infection and cost‐intensive manufacturing motivate the development of analogous approaches that are free from the disadvantages of virus‐based therapies. Herein, reported is a nanoassembly comprised of multivalent host–guest interactions between polymerized paclitaxel (pPTX) and nitric oxide‐incorporated polymerized β‐cyclodextrin (pCD‐pSNO) that through its bioactive components and when used locoregionally recapitulates the therapeutic effects of OV. The resultant pPTX/pCD‐pSNO exhibits significantly enhanced cytotoxicity, immunogenic cell death, dendritic cell (DC) activation, and T cell expansion in vitro compared to free agents alone or in combination. In vivo, intratumoral administration of pPTX/pCD‐pSNO results in activation and expansion of DCs systemically, but with a corresponding expansion of myeloid‐derived suppressor cells and suppression of CD8⁺ T cell expansion. When combined with antibody targeting cytotoxic T lymphocyte antigen‐4 that blunts this molecule's signaling effects on T cells, intratumoral pPTX/pCD‐pSNO treatment elicits potent anticancer effects that significantly prolong animal survival. This formulation thus leverages the chemo‐ and immunotherapeutic synergies of PTX and nitric oxide and suggests the potential for virus‐free nanoformulations to mimic the therapeutic action and benefits of OVs.     

Photomontage in the Present Perfect Continuous

In its first instance as art practice among the historical avant-garde, photomontage was considered indispensable for its claim to intervene in perceptual processes, stimulating a critical mode of apprehension that would redirect the viewer away from conventions of aesthetic experience and towards a lived reception of art with pronounced relevance to the sociopolitical landscape. The effect was understood as structural, that is, activated not so much by direct political content, but by the stark and shocking effects of juxtaposition. By this measure, one challenge to contemporary photomontage is clear: in a postindustrial and postdigital visual landscape dominated by the structural fragmentation of the attention economy, the ‘simultaneity of the radically disparate’ (as Peter Bürger put it) might no longer present as heterodoxy but rather threaten to sink into invisibility. Yet with the migration off-screen of the effects of electronic media, a new urgency around moving photomontage structures into physical, public space is rising in contemporary practices. Shannon Ebner’s multi-part project A Hudson Yard (2014–15) is emblematic of the new ways in which artists are manipulating photomontage as a form of fully sensory experience that gives the medium room to play critically in both virtual and material space. By constructing subtle interruptions of naturalised commercial space, A Hudson Yard activates a détournement of instrumentalised language, using structures of juxtaposition to divert the discursive surfaces of public space away from consumption and towards what could be called a public poesis.     

Bayesian Inference for ARFIMA Models

This article develops practical methods for Bayesian inference in the autoregressive fractionally integrated moving average (ARFIMA) model using the exact likelihood function, any proper prior distribution, and time series that may have thousands of observations. These methods utilize sequentially adaptive Bayesian learning, a sequential Monte Carlo algorithm that can exploit massively parallel desktop computing with graphics processing units (GPUs). The article identifies and solves several problems in the computation of the likelihood function that apparently have not been addressed in the literature. Four applications illustrate the utility of the approach. The most ambitious is an ARFIMA(2,d,2) model for the Campito tree ring time series (length 5405), for which the methods developed in the article provide an essentially uncorrelated sample of size 16,384 from the exact posterior distribution in under four hours. Less ambitious applications take as little as 4 minutes without exploiting GPUs.     

Identification and Composition of Clasper Scent Gland Components of the Butterfly Heliconius erato and Its Relation to Mimicry

The butterfly Heliconius erato occurs in various mimetic morphs. The male clasper scent gland releases an anti-aphrodisiac pheromone and additionally contains a complex mixture of up to 350 components, varying between individuals. In 114 samples of five different mimicry groups and their hybrids 750 different compounds were detected by gas chromatography/mass spectrometry (GC/MS). Many unknown components occurred, which were identified using their mass spectra, gas chromatography/infrared spectroscopy (GC/IR)-analyses, derivatization, and synthesis. Key compounds proved to be various esters of 3-oxohexan-1-ol and (Z)-3-hexen-1-ol with (S)-2,3-dihydrofarnesoic acid, accompanied by a large variety of other esters with longer terpene acids, fatty acids, and various alcohols. In addition, linear terpenes with up to seven uniformly connected isoprene units occur, e. g. farnesylfarnesol. A large number of the compounds have not been reported before from nature. Discriminant analyses of principal components of the gland contents showed that the iridescent mimicry group differs strongly from the other, mostly also separated, mimicry groups. Comparison with data from other species indicated that Heliconius recruits different biosynthetic pathways in a species-specific manner for semiochemical formation.     

The Egalitarian city: The restructuring of Amsterdam

Since the mid‐1970s, urban policy makers have responded to the pressures of fiscal crisis and unemployment by reducing expenditures and subsidizing business for the purpose of stimulating economic growth. The behaviour of urban governments largely corresponded with the argument of Paul Peterson that cities were forced to pursue economic growth at the expense of redistribution. Nevertheless, the response to economic forces, while generally in a market‐oriented direction, was not uniform within western cities. In particular, the Amsterdam municipality remains notable for its egalitarian policies when compared with London or New York. Housing policy has been a major instrument in maintaining the quality of life for the city's lower‐income population. Because subsidized housing units, as well as recipients of individual housing benefits, are scattered throughout the city, housing policy has sharply restricted spatial inequality of households by income. Moreover, the very large public subsidy involved in housing construction, by keeping rent levels low and thereby raising disposable income, has contributed substantially to popular welfare, mitigating class differentiation and thereby weakening resistance to residential integration of different income groups. This paper examines policies for physical and economic development in Amsterdam and their effect on social and spatial inequality. The conclusion briefly compares Amsterdam's trajectory with that of London and New York, then finally attempts to explain the continuing differences.