Manipulation and Generation of Supercurrent in Out-of-Equilibrium Josephson Tunnel Nanojunctions

We demonstrate experimentally manipulation of supercurrent in Al-AlO_x-Ti Josephson tunnel junctions by injecting quasiparticles in a Ti island from two additional tunnel-coupled Al superconducting reservoirs. Both supercurrent enhancement and quenching with respect to equilibrium are achieved. We demonstrate cooling of the Ti line by quasiparticle injection from the normal state deep into the superconducting phase. A model based on heat transport and non-monotonic current-voltage characteristic of a Josephson junction satisfactorily accounts for our findings.Comment: 4 pages, 4 colour figures, published versio

Functionalized Enzyme-Responsive Biomaterials to Model Tissue Stiffening in vitro

The mechanical properties of the cellular microenvironment play a crucial role in modulating cell function, and many pathophysiological processes are accompanied by variations in extracellular matrix (ECM) stiffness. Lysyl oxidase (LOx) is one of the enzymes involved in several ECM-stiffening processes. Here, we engineered poly(ethylene glycol) (PEG)-based hydrogels with controlled mechanical properties in the range typical of soft tissues. These hydrogels were functionalized featuring free primary amines, which allows an additional chemical LOx-responsive behavior with increase in crosslinks and hydrogel elastic modulus, mimicking biological ECM-stiffening mechanisms. Hydrogels with elastic moduli in the range of 0.5–4 kPa were obtained after a first photopolymerization step. The increase in elastic modulus of the functionalized and enzyme-responsive hydrogels was also characterized after the second-step enzymatic reaction, recording an increase in hydrogel stiffness up to 0.5 kPa after incubation with LOx. Finally, hydrogel precursors containing HepG2 (bioinks) were used to form three-dimensional (3D) in vitro models to mimic hepatic tissue and test PEG-based hydrogel biocompatibility. Hepatic functional markers were measured up to 7 days of culture, suggesting further use of such 3D models to study cell mechanobiology and response to dynamic variation of hydrogels stiffness. The results show that the functionalized hydrogels presented in this work match the mechanical properties of soft tissues, allow dynamic variations of hydrogel stiffness, and can be used to mimic changes in the microenvironment properties of soft tissues typical of inflammation and pathological changes at early stages (e.g., fibrosis, cancer)

CD44 targeted delivery of siRNA by using HA-decorated nanotechnologies for KRAS silencing in cancer treatment

KRAS is a small GTPase that regulates cell proliferation and survival. In tumors, the KRAS gene is mutated, and leading to unregulated tumor growth. Despite the recognized importance of KRAS in cancer, attempts to develop small molecule inhibitors have proved unsuccessful. An alternative strategy is gene silencing and the use of small nucleic acid sequences (e.g. siRNA, shRNA), has been reported to successfully downregulate KRAS. In this study we developed ternary nanocomplexes to deliver an anti-KRAS siRNA to colorectal cancer cells, exploiting the interaction of hyaluronic acid (HA) with CD44 as a means to achieve selective targeting of CD44-positive cancer cells. Two different polycations, poly(hexamethylene biguanide) and chitosan, were complexed with siRNA and coated with HA. Physico-chemical properties and stability of nanoparticles were characterized, including size, surface charge, and degree of siRNA protection. We demonstrate nanoparticle internalization (flow cytometry), siRNA cytosolic release (confocal microscopy) and KRAS silencing (RT-qPCR) in CD44+/KRAS+ colorectal cancer cell line, HCT-116. Further we demonstrate that the uptake of HA-decorated nanoparticles in cancer cells is higher when co-cultured with fibroblasts

Colorectal tumor 3D in vitro models: advantages of biofabrication for the recapitulation of early stages of tumour development

The majority of cancer-related in vitro studies are conducted on cell monolayers or spheroids. Although this approach has led to key discoveries, it still has a poor outcome in recapitulating the different stages of tumor development. The advent of novel three-dimensional (3D) systems and technological methods for their fabrication is set to improve the field, offering a more physiologically relevant and high throughput in vitro system for the study of tumor development and treatment. Here we describe the fabrication of alginate-based 3D models that recapitulate the early stages of colorectal cancer, tracking two of the main biomarkers for tumor development: CD44 and HIF-1α. We optimized the fabrication process to obtain alginate micro-beads with controlled size and stiffness, mimicking the early stages of colorectal cancer. Human colorectal HCT-116 cancer cells were encapsulated with controlled initial number, and cell viability and protein expression of said 3D in vitro models was compared to that of current gold standards (cell monolayers and spheroids). Our results evidenced that encapsulated HCT-116 demonstrated a high viability, increase in stem-like cell populations (increased expression of CD44) and reduced hypoxic regions (lower HIF-1a expression) compared to spheroid cultures. In conclusion we show that our biofabricated system is a highly reproducible and easily accessible alternative to study cell behavior, allowing to better mimic the early stages of colorectal cancer in comparison to other in vitro models. The use of biofabricated in vitro models will improve the translatability of results, in particular when testing strategies for therapeutic intervention

Lean Manufacturing na indústria de revestimento têxtil

This research aimed at the development and validation of an ultra-performance liquid chromatography (UPLC) method for the quantification of glutathione (GSH) in grape juice and in white wine after derivatisation with para-benzoquinone. The phenolic compounds catechin and caffeic acid that occur in white wine and have antioxidant effects, are also quantified in the same analysis. Catechin is the basic monomeric unit of grape and wine tannins and caffeic acid, when esterified with tartaric acid, plays a relevant role in Grape Reaction Product (GRP) formation. The analytical method proposed showed good linearity, repeatability and intermediate repeatability, as well as high recovery (>85%). It was applied for the quantification of GSH, catechin and caffeic acid in South African juices (12) and white wines (43). This novel method will have a large impact on the time and costs of the analyses for the wine industry through enabling rapid routine quantification of GSH, catechin and caffeic acid

The cost function of the data fusion process and its application

When the complete data fusion method is used to fuse inconsistent measurements, it is necessary to add to the measurement covariance matrix of each fusing profile a covariance matrix that takes into account the inconsistencies. A realistic estimate of these inconsistency covariance matrices is required for effectual fused products. We evaluate the possibility of assisting the estimate of the inconsistency covariance matrices using the value of the cost function minimized in the complete data fusion. The analytical expressions of expected value and variance of the cost function are derived. Modelling the inconsistency covariance matrix with one parameter, we determine the value of the parameter that makes the reduced cost function equal to its expected value and use the variance to assign an error to this determination. The quality of the inconsistency covariance matrix determined in this way is tested for simulated measurements of ozone profiles obtained in the thermal infrared in the framework of the Sentinel-4 mission of the Copernicus programme. As expected, the method requires sufficient statistics and poor results are obtained when a small number of profiles are being fused together, but very good results are obtained when the fusion involves a large number of profiles.</p

Precarious, Always-On and Flexible: A Case Study of Academics as Information Workers

The higher education landscape has changed in the last decades. The neoliberal restructuring of universities has led to transformations such as reducing public expenditure, allocating resources based on competition and quasi-market disciplines. These structural transformations have also an effect on the working conditions, practices and relations of subjects within universities. Questions that need to be addressed: How do different working contexts and conditions in the academia shape feelings of autonomy, flexibility and reputation on the one hand and precariousness, overwork and dissatisfaction on the other? What are the broader political realities and potentials in terms of solidarity, participation and democracy at universities? I address these questions based on a theoretical analysis and qualitative interviews with precariously employed academics

Photoinduced formation of gold nanoparticles into vinyl alcohol based polymers

Nanocomposites based on vinyl alcohol-containing polymers and nanostructured gold have been efficiently prepared by a UV photo-reduction process. The very fast process provided dispersed gold nanoparticles with average diameters ranging from 3 to 20 nm depending on the host polymer matrix and the irradiation time. Uniaxial drawing of the irradiated Au/polymer nanocomposites favours the anisotropic distribution of packed assemblies of gold particles, providing oriented films with polarization-dependent tunable optical properties. These pronounced dichroic properties suggest that the nanocomposite films could find potential applications as colour polarizing filters, radiation responsive polymeric objects and smart flexible films in packaging applications.16111058106

Enhanced intra-liposomal metallic nanoparticle payload capacity using microfluidics assisted self-assembly

Hybrids composed of liposomes (L) and metallic nanoparticles (NP) hold great potential for imaging and drug delivery purposes. However, the efficient incorporation of metallic nanoparticles into liposomes using conventional methodologies has so far proved to be challenging. In this study, we report the fabrication of hybrids of liposomes and hydrophobic gold nanoparticles of size 2-4 nm (Au) using a microfluidic assisted self-assembly process. The incorporation of increasing amounts of Au nanoparticles into liposomes was examined using microfluidics and compared to L-AuNP hybrids prepared by the reverse-phase evaporation method. Our microfluidics strategy produced L-AuNP hybrids with a homogeneous size distribution, smaller polydispersity index, and a 3-fold increase in loading efficiency when compared to those hybrids prepared using the reverse-phase method of production. Quantification of the loading efficiency was determined by ultraviolet spectroscopy, inductively coupled plasma mass spectroscopy and centrifugal field flow fractionation and confirmed qualitatively by transmission electron microscopy. The higher loading of gold nanoparticles into the liposomes achieved using microfluidics produced a slightly thicker and more rigid bilayer as determined with small angle neutron scattering. These observations were confirmed using fluorescent anisotropy and atomic force microscopy, respectively. Structural characterization of the liposomal-nanoparticle hybrids with cryo-electron microscopy revealed the co-existence of membrane-embedded and interdigitated nanoparticle-rich domains suggesting AuNP incorporation through hydrophobic interactions. The microfluidic technique that we describe in this study allows for the automated production of monodisperse liposomal-nanoparticle hybrids with high loading capacity highlighting the utility of microfluidics to improve the payload of metallic nanoparticles within liposomes, thereby enhancing their application for imaging and drug delivery