A 65-nm CMOS Temperature-Compensated Mobility-Based Frequency reference for wireless sensor networks

For the first time, a temperature-compensated CMOS frequency reference based on the electron mobility in a MOS transistor is presented. Over the temperature range from -55°C to 125 °C, its frequency spread is less than ±0.5% after a two-point trim and less than ±2.7% after a one-point trim. These results make it suitable for use in Wireless Sensor Network nodes. Fabricated in a baseline 65-nm CMOS process, the 150 kHz frequency reference occupies 0.2 mm2 and draws 42.6 μA from a 1.2-V supply at room temperature.\ud \u

A 1.2-V 10- µW NPN-Based Temperature Sensor in 65-nm CMOS With an Inaccuracy of 0.2 °C (3σ) From 70 °C to 125 °C

An NPN-based temperature sensor with digital output transistors has been realized in a 65-nm CMOS process. It achieves a batch-calibrated inaccuracy of ±0.5 ◦C (3¾) and a trimmed inaccuracy of ±0.2 ◦C (3¾) over the temperature range from −70 ◦C to 125 ◦C. This performance is obtained by the use of NPN transistors as sensing elements, the use of dynamic techniques, i.e. correlated double sampling and dynamic element matching, and a single room-temperature trim. The sensor draws 8.3 μA from a 1.2-V supply and occupies an area of 0.1 mm2

Acidic Mammalian Chitinase and the Eye: Implications for Ocular Inflammatory Diseases

Chitinases have an important role in the defense of organisms against chitin-containing parasites. An acidic mammalian chitinase (AMCase) has been detected in epithelial cells in lung tissue samples taken from patients with asthma as well as in conjunctival epithelium of patients with inflammatory ocular diseases. Particularly, elevated AMCase activity has been observed in ocular tissues of patients with vernal keratoconjunctivitis, seasonal allergic conjunctivitis, and in patients affected by dry eye syndrome. This enzyme is induced via a TH2-specific, IL-13-dependent pathway. AMCase may thus be a key mediator of IL-13-induced responses in TH2-driven inflammatory ocular diseases

Near-Infrared, Light-Triggered, On-Demand Antiinflammatories and Antibiotics Release by Graphene Oxide/Elecrospun PCL Patch for Wound Healing

Very recently, significant attention has been focused on the adsorption and cell adhesion properties of graphene oxide (GO), because it is expected to allow high drug loading and controlled drug release, as well as the promotion of cell adhesion and proliferation. This is particularly interesting in the promotion of wound healing, where antibiotics and anti-inflammatories should be locally released for a prolonged time to allow fibroblast proliferation. Here, we designed an implantable patch consisting of poly(caprolactone) electrospun covered with GO, henceforth named GO–PCL, endowed with high ibuprofen (5.85 mg cm−2), ketoprofen (0.86 mg cm−2), and vancomycin (0.95 mg cm−2) loading, used as anti-inflammatory and antibiotic models respectively, and capable of responding to near infrared (NIR)-light stimuli in order to promptly release the payload ondemand beyond three days. Furthermore, we demonstrated the GO is able to promote fibroblast adhesion, a key characteristic to potentially provide wound healing in vivo

TAT decorated siRNA polyplexes for inhalation delivery in anti-asthma therapy

In this work, a novel protonable copolymer was designed to deliver siRNA through the inhalation route, as an innovative formulation for the management of asthma. This polycation was synthesized by derivatization of α,β-poly(N-2-hydroxyethyl)D,L-aspartamide (PHEA) first with 1,2-Bis(3-aminopropylamino)ethane (bAPAE) and then with a proper amount of maleimide terminated poly(ethylene glycol) (PEG-MLB), with the aim to increase the superficial hydrophilicity of the system, allowing the diffusion trough the mucus layer. Once the complexation ability of the copolymer has been evaluated, obtaining nanosized polyplexes, polyplexes were functionalized on the surface with a thiolated TAT peptide, a cell-penetrating peptide (CPP), exploiting a thiol-ene reaction. TAT decorated polyplexes result to be highly cytocompatible and able to retain the siRNA with a suitable complexation weight ratio during the diffusion process through the mucus. Despite polyplexes establish weak bonds with the mucin chains, these can diffuse efficiently through the mucin layer and therefore potentially able to reach the bronchial epithelium. Furthermore, through cellular uptake studies, it was possible to observe how the obtained polyplexes penetrate effectively in the cytoplasm of bronchial epithelial cells, where they can reduce IL-8 gene expression, after LPS exposure. In the end, in order to obtain a formulation administrable as an inhalable dry powder, polyplexes were encapsulated in mannitol-based microparticles, by spray freeze drying, obtaining highly porous particles with proper technological characteristics that make them potentially administrable by inhalation route

Development of polymer-based nanoparticles for Zileuton delivery to the lung : PMeOx and PMeOzi surface chemistry reduces interactions with mucins

In this paper, two amphiphilic graft copolymers were synthesized by grafting polylactic acid (PLA) as hydrophobic chain and poly(2-methyl-2-oxazoline) (PMeOx) or poly(2-methyl-2-oxazine) (PMeOzi) as hydrophilic chain, respectively, to a backbone of α,β-poly(N-2-hydroxyethyl)-D,L-aspartamide (PHEA). These original graft copolymers were used to prepare nanoparticles delivering Zileuton in inhalation therapy. Among various tested methods, direct nanoprecipitation proved to be the best technique to prepare nanoparticles with the smallest dimensions, the narrowest dimensional distribution and a spherical shape. To overcome the size limitations for administration by inhalation, the nano-into-micro strategy was applied, encapsulating the nanoparticles in water-soluble mannitol-based microparticles by spray-drying. This process has allowed to produce spherical microparticles with the proper size for optimal lung deposition, and, once in contact with fluids mimicking the lung district, able to dissolve and release non-aggregated nanoparticles, potentially able to spread through the mucus, releasing about 70% of the drug payload in 24hours.Peer reviewe

Teaching Theoretical Physics: the cases of Enrico Fermi and Ettore Majorana

We report on theoretical courses by Fermi and Majorana, giving evidence of the first appearance and further development of Quantum Mechanics teaching in Italy. On the basis of original documents, we make a comparison between Fermi's and Majorana's approaches. A detailed analysis is carried out of Fermi's course on Theoretical Physics attended by Majorana in 1927-28. Three (previously unknown) programs on advanced Physics courses submitted by Majorana to the University of Rome between 1933 and 1936 and the course he held in Naples in 1938 complete our analysis: Fermi's phenomenological approach resounded in Majorana, who however combined it with a deeper theoretical approach, closer to the modern way of presenting Quantum Mechanics.Comment: latex, 21 pages; a contribution in the centenary of the birth of Ettore Majoran

Development of a novel rapamycin loaded nano- into micro-formulation for treatment of lung inflammation

It has recently emerged that drugs such as the mTOR inhibitor rapamycin (Rapa) may play a key role in the treatment of airway inflammation associated with lung diseases, such as chronic obstructive pulmonary disease, asthma, and cystic fibrosis. Nevertheless, Rapa clinical application is still prevented by its unfavorable chemical-physical properties, limited oral bioavailability, and adverse effects related to non-specific biodistribution. In this paper, the design and production of a novel formulation of Rapa based on nano into micro (NiM) particles are detailed. To achieve it, Rapa-loaded nanoparticles were produced by nanoprecipitation of an amphiphilic pegylated poly-e-caprolactone/polyhydroxyethyl aspartamide graft copolymer. The obtained nanoparticles that showed a drug loading of 14.4 wt% (corresponding to an encapsulation efficiency of 82 wt%) did not interact with mucins and were able to release and protect Rapa from degradation in simulated lung and cell fluids. To allow their local administration to the lungs as a dry powder, particle engineering at micro-sized level was done by embedding nanoparticles into mannitol-based microparticles by spray drying. Obtained NiM particles had a mean diameter of about 2-mu, spherical shape and had good potential to be delivered to the lungs by a breath-activated dry powder inhalers. Rheological and turbidity experiments showed that these NiM particles can dissolve in lung simulated fluid and deliver the Rapa-loaded pegylated nanoparticles, which can diffuse through the mucus layer