Aerosol Jet Printing of a Benzocyclobutene-Based Ink as Adhesive Material for Wafer Bonding Application

Aerosol jet printing (AJP) is an emerging additive manufacturing technology that is gaining increasing attention in the electronic field. Several studies have been carried out on the AJP of conductive, semiconductive, and dielectric polymers for electronic applications. However, wafer bonding is an application that is still uncovered by literature. Therefore, in this work, the AJP of benzocyclobutene (BCB) as a polymeric adhesive for wafer bonding is presented for the first time. A thorough characterization of the processing parameters is carried out to identify the most ideal conditions for printing at a relatively high speed. Then, square patterns are printed, proving the versatility of the AJP technology in terms of the reachable thickness of the deposited BCB patterns. Complex patterns with a resolution of approximate to 60 mu m are also printed. The bonding properties of the BCB are characterized from a morphological and mechanical point of view. In particular, the shear strength of the BCB coatings deposited with AJP is approximate to 39 MPa and it is comparable with the shear strength of BCB coating deposited by spin-coating. Consequently, AJP represents a valid alternative for the deposition of polymeric adhesive for wafer bonding

A Non-coded β2,2-Amino Acid with Isoxazoline Core Able to Stabilize Peptides Folding through an Unprecedented Hydrogen Bond

Dedicated to Prof. Cesare Gennari on the occasion of his 70th birthday New peptidomimetics containing a beta(2,)(2)-isoxazoline amino acid, i.e. 5-(aminomethyl)-3-phenyl-4,5-dihydroisoxazole-5-carboxylic acid (Isox-beta(2,)(2)AA), were prepared and studied by NMR and theoretical calculation. Although similar amino acid derivatives have already been prepared via 1,3-dipolar cycloaddition reaction, neither experimental details nor characterization were found and they were never used for peptide synthesis. Both enantiomers were inserted in peptide sequences to verify their ability to induce a secondary structure. We found that an unexpected conformation is given by R-Isox-beta(2,)(2)AA, inducing the folding of short peptides thanks to an unprecedented H-bond involving C=N of the isoxazoline side chain of our beta(2,)(2)-AA

Tuning PFKFB3 Bisphosphatase Activity Through Allosteric Interference

The human inducible phospho-fructokinase bisphosphatase isoform 3, PFKFB3, is a crucial regulatory node in the cellular metabolism. The enzyme is an important modulator regulating the intracellular fructose-2,6-bisphosphate level. PFKFB3 is a bifunctional enzyme with an exceptionally high kinase to phosphatase ratio around 740:1. Its kinase activity can be directly inhibited by small molecules acting directly on the kinase active site. On the other hand, here we propose an innovative and indirect strategy for the modulation of PFKFB3 activity, achieved through allosteric bisphosphatase activation. A library of small peptides targeting an allosteric site was discovered and synthesized. The binding affinity was evaluated by microscale thermophoresis (MST). Furthermore, a LC-MS/MS analytical method for assessing the bisphosphatase activity of PFKFB3 was developed. The new method was applied for measuring the activation on bisphosphatase activity with the PFKFB3-binding peptides. The molecular mechanical connection between the newly discovered allosteric site to the bisphosphatase activity was also investigated using both experimental and computational methods

An Electroactive Oligo-EDOT Platform for Neural Tissue Engineering

The unique electrochemical properties of the conductive polymer poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) make it an attractive material for use in neural tissue engineering applications. However, inadequate mechanical properties, and difficulties in processing and lack of biodegradability have hindered progress in this field. Here, the functionality of PEDOT:PSS for neural tissue engineering is improved by incorporating 3,4-ethylenedioxythiophene (EDOT) oligomers, synthesized using a novel end-capping strategy, into block co-polymers. By exploiting end-functionalized oligoEDOT constructs as macroinitiators for the polymerization of poly(caprolactone), a block co-polymer is produced that is electroactive, processable, and bio-compatible. By combining these properties, electroactive fibrous mats are produced for neuronal culture via solution electrospinning and melt electrospinning writing. Importantly, it is also shown that neurite length and branching of neural stem cells can be enhanced on the materials under electrical stimulation, demonstrating the promise of these scaffolds for neural tissue engineering

MediaChrom: exploring a new family of pyrimidoindolone-based polarity-sensitive dyes

The modern biological research asks for a continuous development of new fluorescent dyes characterized by improved performances and suitable to be used as markers or probes [1]. A particular class of dyes, called polarity-sensitive dyes have the unique features to display a different emission maximum as a function of the polarity of their molecular environment (media). This peculiarity makes polarity-sensitive dyes the ideal probes to monitor the local properties of particular cell districts as well as different type of biomolecular interactions [2]. Since many years, we have been interested in the development of new strategies for the synthesis and the functionalization of indoles and polycyclic indole-based heterocycles. In this context, we reported a domino approach to pyrimidoindolones [3] that displayed interesting fluorescence properties. Starting from these findings, a small library of original polarity-sensitive fluorescent dyes, nicknamed MediaChrom, has been prepared [4]. They are characterized by a pyrimidoindolone core fitted out with a conjugated push-pull system, and a linker for an easy coupling with biomolecules. The synthetic strategy involves a highly chemo- and regioselective gold catalyzed cycloisomerization as key step. The photophysical properties of MediaChrom dyes have been evaluated, and some potential biological applications have been spottily investigated. [1] Lakowicz, J. R. Principles of Fluorescence Spectroscopy, 3rd ed.; Springer: New York, 2006. [2] Klymchenko, A. S.; Mely, Y. In: Progress in Molecular Biology and Translational Science, Morris, M.C. Editor(s), Academic Press, 2013, Vol. 113, Cap. 2, 35. [3] Facoetti, D.; Abbiati, G.; d\u2019Avolio, L.; Ackermann, L.; Rossi, E. Synlett 2009, 2273. [4] Dell'Acqua, M.; Ronda, L.; Piano, R.; Pellegrino, S.; Clerici, F.; Rossi, E.; Mozzarelli, A.; Gelmi, M. L.; Abbiati, G. J. Org. Chem. 2015, 21, 10939. This work has been supported by Fondazione Cariplo, Grant No. 2012-0907

Rational design of a user-friendly aptamer/peptide-based device for the detection of staphylococcus aureus

The urgent need to develop a detection system for Staphylococcus aureus, one of the most common causes of infection, is prompting research towards novel approaches and devices, with a particular focus on point-of-care analysis. Biosensors are promising systems to achieve this aim. We coupled the selectivity and affinity of aptamers, short nucleic acids sequences able to recognize specific epitopes on bacterial surface, immobilized at high density on a nanostructured zirconium dioxide surface, with the rational design of specifically interacting fluorescent peptides to assemble an easy-to-use detection device. We show that the displacement of fluorescent peptides upon the competitive binding of S. aureus to immobilized aptamers can be detected and quantified through fluorescence loss. This approach could be also applied to the detection of other bacterial species once aptamers interacting with specific antigens will be identified, allowing the development of a platform for easy detection of a pathogen without requiring access to a healthcare environment

ß-Hairpin mimics containing a piperidine-pyrrolidine scaffold modulate the ß-amyloid aggregation process preserving the monomer species

Alzheimer’s disease is a neurodegenerative disorder linked to oligomerization and fibrillization of amyloid β peptides, with Aβ1-42 being the most aggregative and neurotoxic one. We report herein the synthesis and conformational analysis of Aβ1-42-amyloid related β-hairpin peptidomimetics, built on a piperidine-pyrrolidine semi rigid β-turn inducer and bearing two small recognition peptide sequences, designed on oligomeric and fibril structures of Aβ1-42. According to these peptide sequences, a stable β-hairpin or a dynamic equilibrium between two possible architectures was observed. These original constructs are able to greatly delay the kinetics of Aβ1-42 aggregation process as demonstrated by thioflavin-T fluorescence, and transmission electron microscopy. Capillary electrophoresis indicates their ability to preserve the monomer species, inhibiting the formation of toxic oligomers. Furthermore, compounds protect against toxic effects of Aβ on neuroblastoma cells even at substoichiometric concentrations. This study is the first example of acyclic small β-hairpin mimics possessing such a highly efficient anti-aggregation activity. The protective effect is more pronounced than that observed with molecules which have undergone clinical trials. The structural elements made in this study provide valuable insights in the understanding of the aggregation process and insights to explore the design of novel acyclic β-hairpin targeting other types of amyloid-forming proteins

Should I give kids money? The role of pocket money on at-risk behaviors in Italian adolescents

Background. Discussion on the impact of pocket money on positive behaviors is still debated. Objective. To investigate the effect of diverse money allowance schemes on risky behaviors (smoking, alcohol, binge drinking, drug use, gambling) during adolescence. Method. 989 students aged 15 from Lombardy (Italy) reported information on money availability in the 2018 wave of the Health Behaviour in School-aged Children study. To analyze the relationship between money availability and risky behaviors we computed odds ratios and 95% confidence intervals through unconditional multiple logistic regression models. Results. Spending more than 10€ weekly was associated with higher likelihood to smoke, binge drink or gamble. Receiving pocket money (rather than receiving money upon request) was related to higher likelihood to engage in risky behaviors. Conclusions. Pocket money may have a negative impact on adolescents, particularly with a substantial amount of money. More research is needed to understand why providing money only if needed may serve as a protective factor against risky behaviors

Control of Neural Stem Cell Survival by Electroactive Polymer Substrates

Stem cell function is regulated by intrinsic as well as microenvironmental factors, including chemical and mechanical signals. Conducting polymer-based cell culture substrates provide a powerful tool to control both chemical and physical stimuli sensed by stem cells. Here we show that polypyrrole (PPy), a commonly used conducting polymer, can be tailored to modulate survival and maintenance of rat fetal neural stem cells (NSCs). NSCs cultured on PPy substrates containing different counter ions, dodecylbenzenesulfonate (DBS), tosylate (TsO), perchlorate (ClO4) and chloride (Cl), showed a distinct correlation between PPy counter ion and cell viability. Specifically, NSC viability was high on PPy(DBS) but low on PPy containing TsO, ClO4 and Cl. On PPy(DBS), NSC proliferation and differentiation was comparable to standard NSC culture on tissue culture polystyrene. Electrical reduction of PPy(DBS) created a switch for neural stem cell viability, with widespread cell death upon polymer reduction. Coating the PPy(DBS) films with a gel layer composed of a basement membrane matrix efficiently prevented loss of cell viability upon polymer reduction. Here we have defined conditions for the biocompatibility of PPy substrates with NSC culture, critical for the development of devices based on conducting polymers interfacing with NSCs