Towards Dead Time Inclusion in Neuronal Modeling

A mathematical description of the refractoriness period in neuronal diffusion modeling is given and its moments are explicitly obtained in a form that is suitable for quantitative evaluations. Then, for the Wiener, Ornstein-Uhlenbeck and Feller neuronal models, an analysis of the features exhibited by the mean and variance of the first passage time and of refractoriness period is performed.Comment: 12 pages, 1 figur

Promoting Citizenship and Personal Growth: A Model for Student-Athlete Excellence

Many institutions of higher education are searching/or ways to augment specific areas of a student-athlete's life: such as study skills, fitness awareness, or disordered eating. East Stroudsburg University has developed a model that provided the additional support systems with the goal of developing not only a more competitive athlete but also a more mature and responsible member of the university community. This model included a physical and psycho-social component. A multi-discipline staff attempted to encourage the student-athletes with the life skills and the interaction to develop these tools for their life after college

Destabilization and removal of immobilized enzymes adsorbed onto polyethersulfone ultrafiltration membranes by salt solutions

In this work the effectiveness of two saline solutions (NaCl and Na2SO4) to clean a permanently hydrophilic polyethersulfone (PESH) ultrafiltration (UF) membrane with a molecular weight cut-off (MWCO) of 30 kDa previously fouled with enzymatic solutions was investigated. The influence of protein concentration in the enzymatic solution during the fouling step and the effect of salt type during the cleaning procedure were studied. The protein aggregation was analyzed in solution and onto the membrane surface by using several techniques including Dynamic Light Scattering (DLS), Atomic Force Microscopy (AFM) and Infrared Spectroscopy with Attenuated Total Reflectance (ATR-FTIR). In addition, mechanisms that dominate membrane fouling were studied by fitting some mathematical models (Hermia's models adapted to crossflow filtration, a combined model based on the complete blocking and cake formation equations and a resistance-in-series model) to the experimental data. Fouling results showed that the complete blocking/adsorption on membrane surface was the predominant fouling mechanism. Regarding the cleaning results, higher cleaning efficiency and low residual protein concentration was obtained with NaCl solutions for all the feed solutions tested due to the favorable interaction between Cl and proteins.Maria-Jose Corbaton-Baguena wishes to gratefully acknowledge the financial support from the Spanish Ministry of Economy and Competitiveness through the grant EEBB-I-14-09011 (project CTM2010-20186). The authors acknowledge the European Union, Fondo Europeo di Sviluppo Regionale, The Ministero dell'Istruzione, dell'Universita e della Ricerca - MIUR, The Ministero dello Svilupppo Economic - MSE - for the financial support to the project "Sistemi tecnologici avanzati e processi integrati della filiera olivicola per la valorizzazione dei prodotti e dei sottoprodotti, lo sviluppo di nuovi settori e la creazione di sistemi produttivi Eco-compatibili" (PON Olio Piu, PON01_01545), within the framework PON Ricerca e Competitivita 2007-2013.Corbatón Báguena, MJ.; Gugliuzza, A.; Cassano, A.; Mazzei, R.; Giorno, L. (2015). Destabilization and removal of immobilized enzymes adsorbed onto polyethersulfone ultrafiltration membranes by salt solutions. Journal of Membrane Science. 486:207-214. https://doi.org/10.1016/j.memsci.2015.03.061S20721448

Preparation of Drug-Loaded PLGA-PEG Nanoparticles by Membrane-Assisted Nanoprecipitation

Purpose: The aim of this work is to develop a scalable continuous system suitable for the formulation of polymeric nanoparticles using membrane-assisted nanoprecipitation. One of the hurdles to overcome in the use of nanostructured materials as drug delivery vectors is their availability at industrial scale. Innovation in process technology is required to translate laboratory production into mass production while preserving their desired nanoscale characteristics. Methods: Membrane-assisted nanoprecipitation has been used for the production of Poly(D, L lactide-co-glycolide)-co-poly ethylene glycol] diblock) (PLGA-PEG) nanoparticles using a pulsed back-and-forward flow arrangement. Tubular Shirasu porous glass membranes (SPG) with pore diameters of 1 and 0.2 µm were used to control the mixing process during the nanoprecipitation reaction. Results: The size of the resulting PLGA-PEG nanoparticles could be readily tuned in the range from 250 to 400 nm with high homogeneity (PDI lower than 0.2) by controlling the dispersed phase volume/continuous phase volume ratio. Dexamethasone was successfully encapsulated in a continuous process, achieving an encapsulation efficiency and drug loading efficiency of 50% and 5%, respectively. The dexamethasone was released from the nanoparticles following Fickian kinetics. Conclusions: The method allowed to produce polymeric nanoparticles for drug delivery with a high productivity, reproducibility and easy scalability

P62/sqstm1/keap1/nrf2 axis reduces cancer cells death-sensitivity in response to zn(Ii)–curcumin complex

The hyperactivation of nuclear factor erythroid 2 p45-related factor 2 (NRF2), frequently found in many tumor types, can be responsible for cancer resistance to therapies and poor patient prognosis. Curcumin has been shown to activate NRF2 that has cytotprotective or protumorigenic roles according to tumor stage. The present study aimed at investigating whether the zinc–curcumin Zn(II)–curc compound, which we previously showed to display anticancer effects through multiple mechanisms, could induce NRF2 activation and to explore the underlying molecular mechanisms. Biochemical studies showed that Zn(II)–curc treatment increased the NRF2 protein levels along with its targets, heme oxygenase-1 (HO-1) and p62/SQSTM1, while markedly reduced the levels of Keap1 (Kelch-like ECH-associated protein 1), the NRF2 inhibitor, in the cancer cell lines analyzed. The silencing of either NRF2 or p62/SQSTM1 with specific siRNA demonstrated the crosstalk between the two molecules and that the knockdown of either molecule increased the cancer cell sensitivity to Zn(II)–curc-induced cell death. This suggests that the crosstalk between p62/SQSTM1 and NRF2 could be therapeutically exploited to increase cancer patient response to therapies

A double-ended queue with catastrophes and repairs, and a jump-diffusion approximation

Consider a system performing a continuous-time random walk on the integers, subject to catastrophes occurring at constant rate, and followed by exponentially-distributed repair times. After any repair the system starts anew from state zero. We study both the transient and steady-state probability laws of the stochastic process that describes the state of the system. We then derive a heavy-traffic approximation to the model that yields a jump-diffusion process. The latter is equivalent to a Wiener process subject to randomly occurring jumps, whose probability law is obtained. The goodness of the approximation is finally discussed.Comment: 18 pages, 5 figures, paper accepted by "Methodology and Computing in Applied Probability", the final publication is available at http://www.springerlink.co

Polycaprolactone multicore-matrix particle for the simultaneous encapsulation of hydrophilic and hydrophobic compounds produced by membrane emulsification and solvent diffusion processes

Co-encapsulation of drugs in the same carrier, as well as the development of microencapsulation processes for biomolecules using mild operating conditions, and the production of particles with tailored size and uniformity are major challenges for encapsulation technologies. In the present work, a suitable method consisting of the combination of membrane emulsification with solvent diffusion is reported for the production of multi-core matrix particles with tailored size and potential application in multi-therapies. In the emulsification step, the production of a W/O/W emulsion was carried out using a batch Dispersion Cell for formulation testing and subsequently a continuous azimuthally oscillating membrane emulsification system for the scaling-up of the process to higher capacities. In both cases precise and gentle control of droplet size and uniformity of the W/O/W emulsion was achieved, preserving the encapsulation of the drug model within the droplet. Multi-core matrix particles were produced in a post emulsification step using solvent diffusion. The compartmentalized structure of the multicore-matrix particle combined with the different chemical properties of polycaprolactone (matrix material) and fish gelatin (core material) was tested for the simultaneous encapsulation of hydrophilic (copper ions) and hydrophobic (α-tocopherol) test components. The best operating conditions for the solidification of the particles to achieve the highest encapsulation efficiency of copper ions and α-tocopherol of 99 (±4)% and 93(±6)% respectively were found. The multi-core matrix particle produced in this work demonstrates good potential as a co-loaded delivery system

New Zinc-Based Active Chitosan Films: Physicochemical Characterization, Antioxidant, and Antimicrobial Properties

The improvement of the antioxidant and antimicrobial activities of chitosan (CS) films can be realized by incorporating transition metal complexes as active components. In this context, bioactive films were prepared by embedding a newly synthesized acylpyrazolonate Zn(II) complex, [Zn(QPhtBu)2(MeOH)2], into the eco-friendly biopolymer CS matrix. Homogeneous, amorphous, flexible, and transparent CS@Znn films were obtained through the solvent casting method in dilute acidic solution, using different weight ratios of the Zn(II) complex to CS and characterized by powder X-ray diffraction (PXRD), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), Fourier transform infrared (FT-IR), Raman, and scanning electron microscopy (SEM) techniques. The X-ray single-crystal analysis of [Zn(QPhtBu)2(MeOH)2] and the evaluation of its intermolecular interactions with a protonated glucosamine fragment through hydrogen bond propensity (HBP) calculations are reported. The effects of the different contents of the [Zn(QPhtBu)2(MeOH)2] complex on the CS biological proprieties have been evaluated, proving that the new CS@Znn films show an improved antioxidant activity, tested according to the DPPH method, with respect to pure CS, related to the concentration of the incorporated Zn(II) complex. Finally, the CS@Znn films were tried out as antimicrobial agents, showing an increase in antimicrobial activity against Gram-positive bacteria (Staphylococcus aureus) with respect to pure CS, when detected by the agar disk-diffusion method