Bifunctional initiators: synthesis of phenylazo-formamidoethyl 4-t-butylazo-4-cyanovalerate

Summary The paper deals with the synthesis of the phenylazo-formamidoethyl 4-t-butylazo-4-cyanovalerate, a product which — by its two azo groups having different thermal stabilities — may be used in initiating processes of stepwise radicalic polymerization. The preparation is based on the condensation of the 4-t-butylazo-4-cyanovaleric acid chloride with N-hydroxy ethyl-phenylazoformamide (HEPF) in anhydrous chloroform, in the presence of pyridine. The initiator purification involves its passing over an alumina column, on using methylene chloride as eluent. HEPF is a new intermediate obtained by the reaction of the ethyl phenylazocarboxylate with ethanolamine. Both the HEPF structure and that of the bis-azo initiator is confirmed by elemental analysis and spectroscopic measurements (IR and H-NMR spectra), as well.     

Application of functionalised carbon nanotubes immobilised into chitosan films in amperometric enzyme biosensors

A new approach for building a bio-conductive interface for enzyme immobilisation is described. This strategy permits very simple preparation of the enzyme biosensor and also reveals direct electron transfer features. A graphite-epoxy resin composite (GrEC) electrode modified with functionalised multi-wall carbon nanotubes (MWCNTs) immobilised by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide together with N-hydroxysuccinimide (EDC–NHS) in a chitosan (Chit) matrix was prepared and characterised by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) in the presence of hexaammineruthenium (III) chloride. It was then used as a base for glucose oxidase (GOx) immobilisation by the simple method of crosslinking with glutaraldehyde (GA) with bovine serum albumin (BSA) as carrier protein. The resulting mediator-free biosensor was applied to the determination of glucose in amperometric mode at different applied potentials and the mechanism of reaction was also investigated by cyclic voltammetry, with and without dissolved oxygen in solution. Analytical parameters, as well as reproducibility, repeatability and stability were determined. Interferences were assessed using different compounds usually present in natural samples, such as wines, juices or blood, in order to evaluate the selectivity of the developed biosensor. The novel combination of carbon nanotubes immobilised with chitosan crosslinked with EDC–NHS and glucose oxidase immobilised by crosslinking with glutaraldehyde offers an excellent, easy to make biosensor for glucose determination without interferences.     

Near-Complete Remission of Glioblastoma in a Patient Treated with an Allogenic Dendritic Cell-Based Vaccine: The Role of Tumor-Specific CD4+T-Cell Cytokine Secretion Pattern in Predicting Response and Recurrence

Immunotherapy has brought hope to the fight against glioblastoma, but its efficacy remains unclear. We present the case of CST, a 25-year-old female patient with a large right-hemisphere glioblastoma treated with a dendritic–tumor cell fusion vaccine. CST showed a near-complete tumor response, with a marked improvement in her functional status and simultaneous increases in tumor-specific CD8+ and CD4+ T cells. Two months before recurrence, the frequency of tumor-specific T cells decreased, while that of IL-17 and CD4+ T cells increased. CST passed away 15 months after enrollment. In this illustrative case, the tumor-specific CD4+ T-cell numbers and phenotype behaved as treatment efficacy biomarkers, highlighting the key role of the latter in glioblastoma immunotherapy.     

Skin Inflammation Modulation via TNF-α, IL-17, and IL-12 Family Inhibitors Therapy and Cancer Control in Patients with Psoriasis

The systemic inflammatory syndrome concept is one of the foundations that stand at the basis of revolutionary modern and future therapies, based on the in-depth understanding of the delicate mechanisms that govern the collaboration between the systems and organs of the human body and, at the same time, the fine balance that ensures a reproach-free operation. An interesting concept that we propose is that of the environment-inadequacy status, a concept that non-specifically incorporates all the situations of the organism’s response disorders in the face of imprecisely defined situations of the environment. The correlation between these two concepts will define the future of modern medicine, along with the gene-adjustment mechanisms. Psoriasis is a clear example of an inadequate body response as a result of exposure to as of yet undefined triggers with an excessive systemic inflammatory reaction and hitherto insufficiently controllable. Modern biological therapies, such as TNF-α, IL-12 family, and IL-17 inhibitors, are intended to profoundly reshape the cytokine configuration of patients with inflammatory diseases such as psoriasis, with tremendous success in disease control. Yet, because of the important roles of cytokines in cancer promotion and control, concern was raised about the fact that the use of biologicals may alter immune surveillance and promote cancer progression. Both theoretical and practical data nevertheless showed that the treatment-induced control of cytokines may be beneficial for reducing the inflammatory milieu that promotes cancer and such have a beneficial role in maintaining health. We briefly present the intricate roles of those cytokine families on cancer control, with some debates on if their inhibition might or might not promote additional tumoral development.     

Molds and Resists Studies for Nanoimprint Lithography of Electrodes in Low-Voltage Polymer Thin-Film Transistors

A low-cost patterning of electrodes was investigated looking forward to replacing conventional photolithography for the processing of low-operating voltage polymeric thin-film transistors. Hard silicon, etched by sulfur hexafluoride and oxygen gas mixture, and flexible polydimethylsiloxane imprinting molds were studied through atomic force microscopy (AFM) and field emission gun scanning electron microscopy. The higher the concentration of oxygen in reactive ion etching, the lower the etch rate, sidewall angle, and surface roughness. A concentration around 30 % at 100 mTorr, 65 W and 70 sccm was demonstrated as adequate for submicrometric channels, presenting a reduced etch rate of 176 nm/min. Imprinting with positive photoresist AZ1518 was compared to negative SU-8 2002 by optical microscopy and AFM. Conformal results were obtained only with the last resist by hot embossing at 120 °C and 1 kgf/cm² for 2 min, followed by a 10 min post-baking at 100 °C. The patterning procedure was applied to define gold source and drain electrodes on oxide-covered substrates to produce bottom-gate bottom-contact transistors. Poly(3-hexylthiophene) (P3HT) devices were processed on high-κ titanium oxynitride (TiO _x N _y ) deposited by radiofrequency magnetron sputtering over indium tin oxide-covered glass to achieve low-voltage operation. Hole mobility on micrometric imprinted channels may approach amorphous silicon (～0.01 cm²/V s) and, since these devices operated at less than 5 V, they are not only suitable for electronic applications but also as sensors in aqueous media.     

Engineering DNA-Grafted Quatsomes as Stable Nucleic Acid-Responsive Fluorescent Nanovesicles

The development of artificial vesicles into responsive architectures capable of sensing the biological environment and simultaneously signaling the presence of a specific target molecule is a key challenge in a range of biomedical applications from drug delivery to diagnostic tools. Herein, the rational design of biomimetic DNA-grafted quatsome (QS) nanovesicles capable of translating the binding of a target molecule to amphiphilic DNA probes into an optical output is presented. QSs are synthetic lipid-based nanovesicles able to confine multiple organic dyes at the nanoscale, resulting in ultra-bright soft materials with attractiveness for sensing applications. Dye-loaded QS nanovesicles of different composition and surface charge are grafted with fluorescent amphiphilic nucleic acid-based probes to produce programmable FRET-active nanovesicles that operate as highly sensitive signal transducers. The photophysical properties of the DNA-grafted nanovesicles are characterized and the highly selective, ratiometric detection of clinically relevant microRNAs with sensitivity in the low nanomolar range are demonstrated. The potential applications of responsive QS nanovesicles for biosensing applications but also as functional nanodevices for targeted biomedical applications is envisaged.     

NanoPaint: A Tool for Rapid and Dynamic Imaging of Membrane Structural Plasticity at the Nanoscale

Single‐particle tracking with quantum dots (QDs) constitutes a powerful tool to track the nanoscopic dynamics of individual cell membrane components unveiling their membrane diffusion characteristics. Here, the nano‐resolved population dynamics of QDs is exploited to reconstruct the topography and structural changes of the cell membrane surface with high temporal and spatial resolution. For this proof‐of‐concept study, bright, small, and stable biofunctional QD nanoconstructs are utilized recognizing the endogenous neuronal cannabinoid receptor 1, a highly expressed and fast‐diffusing membrane protein, together with a commercial point‐localization microscope. Rapid QD diffusion on the axonal plasma membrane of cultured hippocampal neurons allows precise reconstruction of the membrane surface in less than 1 min with a spatial resolution of tens of nanometers. Access of the QD nanoconstructs to the synaptic cleft enables rapid 3D topological reconstruction of the entire presynaptic component. Successful reconstruction of membrane nano‐topology and deformation at the second time‐scale is also demonstrated for HEK293 cell filopodia and axons. Named “nanoPaint,” this super‐resolution imaging technique amenable to any endogenous transmembrane target represents a versatile platform to rapidly and accurately reconstruct the cell membrane nano‐topography, thereby enabling the study of the rapid dynamic phenomena involved in neuronal membrane plasticity.     

Nanogeometry matters: unexpected decrease of capillary adhesion forces with increasing relative humidity

The sticking effect between hydrophilic surfaces occurring at increasing relative humidity (RH) is an everyday phenomenon with uncountable implications. Here experimental evidence is presented for a counterintuitive monotonous decrease of the capillary adhesion forces between hydrophilic surfaces with increasing RH for the whole humidity range. It is shown that this unexpected result is related to the actual shape of the asperity at the nanometer scale: a model based on macroscopic thermodynamics predicts this decrease in the adhesion force for a sharp object ending in an almost flat nanometer-sized apex, in full agreement with experiments. This anomalous decrease is due to the fact that a significant growth of the liquid meniscus formed at the contact region with increasing humidity is hindered for this geometry. These results are relevant in the analysis of the dynamical behavior of nanomenisci. They could also have an outstanding value in technological applications, since the undesirable sticking effect between surfaces occurring at increasing RH could be avoided by controlling the shape of the surface asperities at the nanometric scale.     

Ethanol reforming and partial oxidation with Cu/Nb2O5 catalyst

Ethanol reforming and partial oxidation were studied on Cu/Nb₂O₅ and Ni/Al₂O₃ catalysts. Compared to the Ni/Al₂O₃ catalyst, the Cu/Nb₂O₅ catalyst presents conversion as high as Ni/Al₂O₃ catalyst, however, for the same level of formation of hydrogen it occurs at much lower temperature on the Cu/Nb₂O₅ catalyst, 200 °C lower than for the Ni/Al₂O₃ catalyst, with remarkable little formation of CO, which can be attributed to the strong interaction between copper and niobia. Temperature-programmed desorption (TPD-ethanol) and surface reactions (TPSR) of partial oxidation of ethanol showed formation of ethylene, acetaldehyde, ethane and mainly H₂ and CO₂ besides little methane. DRIFTS results are in accordance with TPD analysis and the formation of acetate species at room temperature suggests reactivity of the surface and its oxidative dehydrogenation capacity. The adsorption of ethanol gives rise to ethoxide species, which form acetate and acetaldehyde that can be oxidized to CO₂ via carbonate. A comparison with reported results for Cu/Al₂O₃ this catalyst is promising, yielding high level of H₂ with little CO production during reforming and partial oxidation reaction. The maximum H₂ formation for the partial oxidation of ethanol was 41% at ratio (O₂/Et) 0.8, increasing to 50% at ratio 1.5. The H₂/CO is around 10 for the partial oxidation and 7 for steam reforming, which is excellent, compared to the Ni/Al₂O₃ catalyst with a factor 4–8 lower.