Empiricism Without the Senses: How the Instrument Replaced the Eye

On receiving news of Galileo’s observations of the four satellites of Jupiter and the rugged face of the moon through his newly invented perspicillum, Kepler in great excitement exclaimed: Therefore let Galileo take his stand by Kepler’s side. Let the former observe the moon with his face turned skyward, while the latter studies the sun by looking down at a screen (lest the lens injure his eyes). Let each employ his own device, and from this partnership may there some day arise an absolutely perfect theory of the distances. This Hollywood-like scene of the two astronomers marching hand in hand toward the dawn of a new scientific era was no attempt by Kepler to appropriate Galileo’s success or to diminish the novelty of the telescope. On the contrary, Kepler repeatedly asserted how short sighted he was in misjudging the potential for astronomical observations inherent in lenses, and how radically Galileo’s instrument transformed the science of astronomy. It was a deep sense of recognition that beyond their different scientific temperaments and projects, they shared a common agenda of a new mode of empirical engagement with the phenomenal world: the instrument. For Kepler and Galileo, empirical investigation was no longer a direct engagement with nature, but an essentially mediated endeavor. The new instruments were not to assist the human senses, but to replace them

Scalable, ultra-resistant structural colors based on network metamaterials

Structural colors have drawn wide attention for their potential as a future printing technology for various applications, ranging from biomimetic tissues to adaptive camouflage materials. However, an efficient approach to realize robust colors with a scalable fabrication technique is still lacking, hampering the realization of practical applications with this platform. Here, we develop a new approach based on large-scale network metamaterials that combine dealloyed subwavelength structures at the nanoscale with lossless, ultra-thin dielectric coatings. By using theory and experiments, we show how subwavelength dielectric coatings control a mechanism of resonant light coupling with epsilon-near-zero regions generated in the metallic network, generating the formation of saturated structural colors that cover a wide portion of the spectrum. Ellipsometry measurements support the efficient observation of these colors, even at angles of 70°. The network-like architecture of these nanomaterials allows for high mechanical resistance, which is quantified in a series of nano-scratch tests. With such remarkable properties, these metastructures represent a robust design technology for real-world, large-scale commercial applications

Actively evolving subglacial conduits and eskers initiate ice shelf channels at an Antarctic grounding line

Ice-shelf channels are long curvilinear tracts of thin ice found on Antarctic ice shelves. Many of them originate near the grounding line, but their formation mechanisms remain poorly understood. Here we use ice-penetrating radar data from Roi Baudouin Ice Shelf, East Antarctica, to infer that the morphology of several ice-shelf channels is seeded upstream of the grounding line by large basal obstacles indenting the ice from below. We interpret each obstacle as an esker ridge formed from sediments deposited by subglacial water conduits, and calculate that the eskers’ size grows towards the grounding line where deposition rates are maximum. Relict features on the shelf indicate that these linked systems of subglacial conduits and ice-shelf channels have been changing over the past few centuries. Because ice-shelf channels are loci where intense melting occurs to thin an ice shelf, these findings expose a novel link between subglacial drainage, sedimentation and ice-shelf stability

Comprehensive molecular characterization of the hippo signaling pathway in cancer

Hippo signaling has been recognized as a key tumor suppressor pathway. Here, we perform a comprehensive molecular characterization of 19 Hippo core genes in 9,125 tumor samples across 33 cancer types using multidimensional “omic” data from The Cancer Genome Atlas. We identify somatic drivers among Hippo genes and the related microRNA (miRNA) regulators, and using functional genomic approaches, we experimentally characterize YAP and TAZ mutation effects and miR-590 and miR-200a regulation for TAZ. Hippo pathway activity is best characterized by a YAP/TAZ transcriptional target signature of 22 genes, which shows robust prognostic power across cancer types. Our elastic-net integrated modeling further reveals cancer-type-specific pathway regulators and associated cancer drivers. Our results highlight the importance of Hippo signaling in squamous cell cancers, characterized by frequent amplification of YAP/TAZ, high expression heterogeneity, and significant prognostic patterns. This study represents a systems-biology approach to characterizing key cancer signaling pathways in the post-genomic era

Topical and mucosal liposomes for vaccine delivery

Mucosal (and in minor extent transcutanous) stimulation can induce local or distant mucosa secretory IgA. Liposomes and other vesicles as mucosal and transcutaneous adjuvants are attractive alternatives to parenteral vaccination. Liposomes can be massively produced under good manufacturing practices and stored for long periods, at high antigen/vesicle mass ratios. However, their uptake by antigen-presenting cells (APC) at the inductive sites remains as a major challenge. As neurotoxicity is a major concern in intranasal delivery, complexes between archaeosomes and calcium as well as cationic liposomes complexed with plasmids encoding for antigenic proteins could safely elicit secretory and systemic antigen-specific immune responses. Oral bilosomes generate intense immune responses that remain to be tested against challenge, but the admixing with toxins or derivatives is mandatory to reduce the amount of antigen. Most of the current experimental designs, however, underestimate the mucus blanket 100- to 1000-fold thicker than a 100-nm diameter liposome, which has first to be penetrated to access the underlying M cells. Overall, designing mucoadhesive chemoenzymatic resistant liposomes, or selectively targeted to M cells, has produced less relevant results than tailoring the liposomes to make them mucus penetrating. Opposing, the nearly 10 μm thickness stratum corneum interposed between liposomes and underlying APC can be surpassed by ultradeformable liposomes (UDL), with lipid matrices that penetrate up to the limit with the viable epidermis. UDL made of phospholipids and detergents, proved to be better transfection agents than conventional liposomes and niosomes, without the toxicity of ethosomes, in the absence of classical immunomodulators.Fil: Romero, Eder Lilia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; ArgentinaFil: Morilla, María José. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología; Argentin