Lakoff & Johnson lettori di Blumenberg? Le analogie tra metaforologia e teoria della metafora concettuale

This paper aims at showing the analogies between Hans Blumenberg’s Metaphorology and George Lakoff & Mark Johnson’s Conceptual Metaphor Theory. Starting from the analysis of the proportion for which ABSOLUTE METAPHOR: METAPHORICAL EXPRESSIONS = BACKGROUND METAPHOR: CONCEPTUAL METAPHOR, we propose to compare Blumenberg’s Metaphorology with Lakoff & Johnson’s Conceptual Metaphor Theory, outlining similarities and differences in reference to: (a) the fundamental notions on which the two theories are based, (b) the methods and (c) the relationship between language-thought-culture assumed by the two theories. However, the reconstruction of the relation between the two theoretical paradigms is not an end in itself as we will show that the two research paradigms could be integrated to overcome problematic aspects present in both theoretical perspectives

Room temperature chiral magnetic skyrmion in ultrathin magnetic nanostructures

Magnetic skyrmions are chiral spin structures with a whirling configuration. Their topological properties, nanometer size and the fact that they can be moved by small current densities have opened a new paradigm for the manipulation of magnetisation at the nanoscale. To date, chiral skyrmion structures have been experimentally demonstrated only in bulk materials and in epitaxial ultrathin films and under external magnetic field or at low temperature. Here, we report on the observation of stable skyrmions in sputtered ultrathin Pt/Co/MgO nanostructures, at room temperature and zero applied magnetic field. We use high lateral resolution X-ray magnetic circular dichroism microscopy to image their chiral N\'eel internal structure which we explain as due to the large strength of the Dzyaloshinskii-Moriya interaction as revealed by spin wave spectroscopy measurements. Our results are substantiated by micromagnetic simulations and numerical models, which allow the identification of the physical mechanisms governing the size and stability of the skyrmions.Comment: Submitted version. Extended version to appear in Nature Nanotechnolog

An efficient MRI agent targeting extracellular markers in prostate adenocarcinoma

Purpose: Prostate cancer (PCa) is the most widespread tumor affecting males in Western countries. We propose a novel MRI molecular tetrameric probe based on the heptadentate gadolinium (Gd)-AAZTA (6-amino-6-methylperhydro-1,4-diazepine-tetraacetic acid) that is able to in vivo detect PCa through the recognition of the fibrin-fibronectin (FB-FN) complex.Methods: The peptide CREKA (Cys-Arg-Glu-Lys-Ala), targeting the FB-FN complex in the reactive stroma of the tumor, was synthesized by solid phase peptide synthesis (SPPS) and conjugated to the tetramer dL-(Gd-AAZTA)(4). The resulting probe was characterized by H-1 relaxometry, tested in vitro on FB clots and in vivo on an orthotopic mouse model of PCa.Results: CREKA-dL-(Gd-AAZTA)(4) showed a remarkable relaxivity of 18.2 mM(Gd)(-1s-1) (0.47 T, 25 degrees C) because of the presence of 2 water molecules (q = 2) in the inner coordination sphere of each Gd3+ ion, whose rotational motion (tau(R)) is lengthened as the result of the relatively high molecular weight. The probe displayed a detectable affinity for plasma-derived FB clots. On intravenous injection of the probe in an orthotopic mouse model of PCa, a significant increase in the prostate T-1 contrast (similar to 40%) was observed. The MRI signal appears statistically higher either with respect to the one observed for the control probes and to the one detected when CREKA-dL-(Gd-AAZTA)(4) was administered to healthy animals.Conclusions: This study demonstrated the ability of the CREKA-dL-(Gd-AAZTA)(4) probe to specifically localize in prostate tumor after injection. The high relaxivity of the probe allows the reduction of the injected dose to 20 mu mol(Gd)/kg, yielding a good in vivo contrast enhancement in the region of prostate tumor

An efficient MRI agent targeting extracellular markers in prostate adenocarcinoma

Purpose: Prostate cancer (PCa) is the most widespread tumor affecting males in Western countries. We propose a novel MRI molecular tetrameric probe based on the heptadentate gadolinium (Gd)-AAZTA (6-amino-6-methylperhydro-1,4-diazepine-tetraacetic acid) that is able to in vivo detect PCa through the recognition of the fibrin-fibronectin (FB-FN) complex.Methods: The peptide CREKA (Cys-Arg-Glu-Lys-Ala), targeting the FB-FN complex in the reactive stroma of the tumor, was synthesized by solid phase peptide synthesis (SPPS) and conjugated to the tetramer dL-(Gd-AAZTA)(4). The resulting probe was characterized by H-1 relaxometry, tested in vitro on FB clots and in vivo on an orthotopic mouse model of PCa.Results: CREKA-dL-(Gd-AAZTA)(4) showed a remarkable relaxivity of 18.2 mM(Gd)(-1s-1) (0.47 T, 25 degrees C) because of the presence of 2 water molecules (q = 2) in the inner coordination sphere of each Gd3+ ion, whose rotational motion (tau(R)) is lengthened as the result of the relatively high molecular weight. The probe displayed a detectable affinity for plasma-derived FB clots. On intravenous injection of the probe in an orthotopic mouse model of PCa, a significant increase in the prostate T-1 contrast (similar to 40%) was observed. The MRI signal appears statistically higher either with respect to the one observed for the control probes and to the one detected when CREKA-dL-(Gd-AAZTA)(4) was administered to healthy animals.Conclusions: This study demonstrated the ability of the CREKA-dL-(Gd-AAZTA)(4) probe to specifically localize in prostate tumor after injection. The high relaxivity of the probe allows the reduction of the injected dose to 20 mu mol(Gd)/kg, yielding a good in vivo contrast enhancement in the region of prostate tumor

Novel Gastrin-Releasing Peptide Receptor Targeted Near-Infrared Fluorescence Dye for Image-Guided Surgery of Prostate Cancer

Purpose Prostate cancer (PCa), the most widespread male cancer in western countries, is generally eradicated by surgery, especially if localized. However, during surgical procedures, it is not always possible to identify malignant tissues by visual inspection. Among the possible consequences, there is the formation of positive surgical margins, often associated with recurrence. In this work, the gastrin-releasing peptide receptor (GRPR), overexpressed in the prostatic carcinoma and not in healthy tissues or in benign hyperplasia (BPH), is proposed as target molecule to design a novel near-infrared fluorescent (NIRF) probe for image-guided prostatectomy. Procedures The NIRF dye Sulfo-Cy5.5 was conjugated to a Bombesin-like peptide (BBN), targeting GRPR. The final product, called BBN-Cy5.5, was characterized and tested in vitro on PC-3, DU145, and LnCAP cell lines, using unconjugated Sulfo-Cy5.5 as control. In vivo biodistribution studies were performed by optical imaging in PC-3 tumor-bearing and healthy mice. Finally, simulation of the surgical protocol was carried out. Results BBN-Cy5.5 showed high water solubility and a good relative quantum yield. The ability of the probe to recognize the GRPR, highly expressed in PC-3 cells, was tested both in vitro and in vivo, where a significant tumor accumulation was achieved 24 h post-injection. Furthermore, a distinguishable fluorescent signal was visible in mice bearing PCa, when the surgery was simulated. By contrast, low signal was found in healthy or BPH-affected mice. Conclusions This work proposes a new NIRF probe ideal to target GRPR, biomarker of PCa. The promising data obtained suggest that the dye could allow the real-time intraoperative visualization of prostate cancer

Paramagnetic Phospholipid-Based Micelles Targeting VCAM-1 Receptors for MRI Visualization of Inflammation

Inflammation is signaled by the overexpression of epitopes on the vascular endothelium that primarily aim at recruiting immune cells into the inflamed area. The intravascular localization of these biomarkers makes them suitable targets for the MRI visualization of inflammation. Phospholipid-based nanosystems appear excellent candidates in virtue of their good biocompatibility, ability to deliver a high number of imaging units at the target site, and for the easy functionalization with targeting vectors. In this work, phospholipid-based micelles (hydrodynamic diameter of 20 nm) loaded with the amphiphilic Gd(III)-complex Gd-DOTAMA(C18)2 were vectorized with a small peptide able to specifically bind VCAM-1 receptors. The micelles displayed a high longitudinal relaxivity (36.4 s–1mmolGd–1 at 25 °C and 0.7 T). A 1H- and 17O-water relaxometry study indicated that the paramagnetic complex embedded in the nanoparticles adopted two isomeric conformations, likely reflecting the well-known square antiprismatic (SAP) and twisted square antiprismatic (TSAP) configurations typically observed in DOTA-like lanthanide complexes. Interestingly, the TSAP structure, showing a much faster exchange rate for the water molecule coordinated to the metal ion, was the most abundant, thus explaining the high relaxivity of the micellar agent. The systemic administration of the micelles into a lipopolysaccharide-induced murine model of acute inflammation successfully demonstrated the ability of the targeting agents to detect the diseased area by T1 contrast enhanced MRI