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This article interprets David Lynch's Mulholland Drive (2001) to argue for the morphological influence cinematic images have on modernity's monstrous identity. It shows how Lynch's tactic of interweaving apparently discrete spaces of dream and reality – one often inverting or uncannily ironising the other – relies on the virtual space of cinema, which leaves a mark on understanding, irrespective of its apparent truth. To do so, I employ Peter Sloterdijk's philosophy of space – especially the spherology developed in his Spheres trilogy – and Bernard Stiegler's approach to cinematic phenomenology to consider the transferential force of cinema, and its power to cultivate and shape popular consciousness. Mulholland Drive is acutely aware of this force, and its interplay with the expectations and disappointments of Hollywood monstrosity inserts itself into the sphere-forming traffic of modern meaning-making. In doing so, I argue, the film takes up Lynch's familiar approach to irony and the weird to unwind the destructive uniformity of Hollywood hegemony. The productive bifurcations that result, inscribed in between cinema and consciousness, and forgettable as the very spheric intimacy of memory, gesture to what might live beyond discrete forms.

This essay will examine what it takes to be two foundational aspects of traditional metaphysics—the “concepts” of nothingness and nature—to offer a critical reading of how they enframe our understanding of “life.” It asserts that these two concepts are the limit point for metaphysical thought: the tangle that emerges when trying to overcome or reimagine them is an impasse encountered in pressing humanist concerns like ecological collapse, nihilism, alienation, and extinction. Readers of this journal may value a detailed, technical attempt at such an untangling; this article will suggest that a heightened sense of technics can be productive of a new image of thought, one that might escape the anthropocentric basis of these concerns.1 In doing so, the argument will insist on the flaw within certain metaphysical schematisms’ desire to appropriate, to form and hold sense into static and reproducible properties—a desire notably critiqued in Bernard Stiegler’s reading of technics. This flaw, it suggests, is constitutive of a sense of nature and nothingness based on property, one Stiegler notes is how we enframe being(s). It will then discuss Gilles Deleuze’s notable critiques of such “proper” enframing’s impossible limits and, following Deleuze, will turn to Marcel Proust’s writing as suggestive of a new image of thought—one that, focused on imagining (or enframing) nothingness through writing, inscribes an indelible remainder as that very imagination, suggesting that it is nothingness “it”self that will always remain.

Abstract Background We have shown that the differentiation of human-induced pluripotent stem cells (hiPSCs) into endothelial cells (ECs) is more efficient when performed with a 3-dimensional (3D) scaffold of biomaterial than in monolayers. The current study aims to further increase hiPSC-EC differentiation efficiency by deciphering the signaling pathways in 3D scaffolds. Methods and results We modified our 3D protocol by using U-46619 to upregulate both p38 mitogen-activated protein kinase (p38MAPK) and extracellular signal-regulated kinase 1/2 (ERK1/2) signaling, which increased the differentiation efficiency (as measured by CD31 expression) to as high as 89% in two established hiPSC lines. The differentiated cells expressed arteriovenous, but not lymphatic, markers; formed tubular structures and EC lumen in vitro; had significantly shorter population-doubling times than monolayer-differentiated hiPSC-ECs; and restored perfusion and vascularity in a murine hind limb ischemia model. The differentiation efficiency was also > 85% in three hiPSC lines that had been derived from patients with diseases or disease symptoms that have been linked to endothelial dysfunction. Conclusions These observations demonstrate that activating both p38MAPK and ERK1/2 signaling pathways with U-46619 improves the efficiency of arteriovenous hiPSC-EC differentiation and produces cells with greater proliferative capacity.

We derived a stable cell line from Chinese hamster embryonic fibroblasts by transduction of four mouse transcription factors (M3O, Sox2, Klf4, and n-Myc) using a lentiviral vector. The cell line possess all the characteristics of an induced pluripotent stem cell (iPSC) line. Given that Chinese hamster ovary (CHO) cells are the predominant host cells used for therapeutic protein production and no pluripotent stem cell line or other normal cell line has been isolated from Chinese hamster, this iPSC line may serve as a useful tool for research using CHO cells or even be used for deriving new cell lines.

Conventional protocols for differentiating human induced-pluripotent stem cells (hiPSCs) into smooth-muscle cells (SMCs) can be inefficient and generally fail to yield cells with a specific SMC phenotype (i.e., contractile or synthetic SMCs). Here, we present two novel hiPSC-SMC differentiation protocols that yield SMCs with predominantly contractile or synthetic phenotypes. Flow cytometry analyses of smooth-muscle actin (SMA) expression indicated that ~45% of the cells obtained with each protocol assumed an SMC phenotype, and that the populations could be purified to ~95% via metabolic selection. Assessments of cellular mRNA and/or protein levels indicated that SMA, myosin heavy chain II, collagen 1, calponin, transgelin, connexin 43, and vimentin expression in the SMCs obtained via the Contractile SMC protocol and in SMCs differentiated via a traditional protocol were similar, while SMCs produced via the Sythetic SMC protocol expressed less calponin, more collagen 1, and more connexin 43. Differences were also observed in functional assessments of the two SMC populations: the two-dimensional surface area of Contractile SMCs declined more extensively (to 12% versus 44% of original size) in response to carbachol treatment, while quantification of cell migration and proliferation were greater in Synthetic SMCs. Collectively, these data demonstrate that our novel differentiation protocols can efficiently generate SMCs from hiPSCs.

Perhaps one of the most significant achievements in modern science is the discovery of human induced pluripotent stem cells (hiPSCs), which have paved the way for regeneration therapy using patients' own cells. Cardiomyocytes differentiated from hiPSCs (hiPSC-CMs) could be used for modelling patients with heart failure, for testing new drugs, and for cellular therapy in the future. However, the present cardiomyocyte differentiation protocols exhibit variable differentiation efficiency across different hiPSC lines, which inhibit the application of this technology significantly. Here, we demonstrate a novel myocyte differentiation protocol that can yield a significant, high percentage of cardiac myocyte differentiation (>85%) in 2 hiPSC lines, which makes the fabrication of a human cardiac muscle patch possible. The established hiPSCs cell lines being examined include the transgene integrated UCBiPS7 derived from cord blood cells and non-integrated PCBC16iPS from skin fibroblasts. The results indicate that hiPSC-CMs derived from established hiPSC lines respond to adrenergic or acetylcholine stimulation and beat regularly for greater than 60 days. This data also demonstrates that this novel differentiation protocol can efficiently generate hiPSC-CMs from iPSC lines that are derived not only from fibroblasts, but also from blood mononuclear cells.