Strategies to Obtain Encapsulation and Controlled Release of Pentamidine in Mesoporous Silica Nanoparticles

Pentamidine (PTM), an antiprotozoal agent used in clinics as pentamidine isethionate salt (PTM-S), recently showed high potential also for the treatment of cancer and myotonic dystrophy type I. However, a severe limit to the systemic administration of PTM is represented by its nephrotoxicity, leading to the need for a system able to achieve a controlled release of the drug. In this study, mesoporous silica nanoparticles (MSNs) were employed for the first time to encapsulate PTM. PTM-S was first used for loading experiments into bare (MSN-OH) and aminopropyl, cyanopropyl and carboxypropyl-functionalized MSNs (MSN-NH2, MSN-CN and MSN-COOH respectively) but it was not adequately loaded in any MSNs. The free base of PTM (PTM-B) was then obtained from PTM-S and successfully loaded into MSNs. Specifically, MSN-COOH exhibited the highest loading capacity. In vitro evaluation of PTM-B kinetic release from the different MSNs was carried out. An influence of the functional groups in slowing the release of the drug, when compared to bare MSNs was observed. Altogether, these results demonstrate that MSN-COOH could be a promising system to achieve a controlled release of PTM.

Hyperacuity Bayesian methods to enhance temporal resolution of two-photon recording of the complex spikes in the cerebellar Purkinje cells

Two-photon imaging is a major recording technique in neuroscience but its low sampling rate imposes a severe limit of elucidating high temporal profiles of neuronal dynamics. Here we developed two hyperacuity Bayesian algorithms to improve spike detection and spike time precision, minimizing the estimation error supervised by the ground-truth given as the electrical spike signals. The benchmark showed that our algorithms outperformed other unsupervised algorithms maximizing the likelihood of the estimates for both experimental and simulation data. We argue that the supervised algorithms are useful tools to improve spike estimation of two-photon recording in case ground truth signals are available.

TIME VARIATION OF THE FINE STRUCTURE CONSTANT IN THE SPACETIME OF A COSMIC DOMAIN WALL

The gravitational field produced by a domain wall acts as a medium with spacetime-dependent permittivity ε. Therefore, the fine structure constant α=e2/4πε will be a time-dependent function at fixed position. The most stringent constraint on the time-variation of α comes from the natural reactor Oklo and gives [Formula: see text]. This limit constrains the tension of a cosmic domain wall to be less than σ ≲ 10-2 MeV 3, and then represents the most severe limit on the energy density of a cosmic wall stretching our Universe.

Coherent Emission in AGN: A Critique

The inverse Compton (IC) limit, TB1012 K, on synchrotron sources places a severe limit on models for intraday variables. The conventional limit is relaxed for proton synchrotron emission, or when acceleration balances IC losses. Coherent emission avoids the limit entirely but introduces other difficulties that have been inadequately discussed.

A Survey of Assistive Technology Applications in Schools and Recommendations for Practice

The Analysis of Technology Assistance for Children (ATAC) project was undertaken in recognition of the severe limit in information on current practices in field applications of assistive technology. Specifically, the ATAC project focused on investigating three problem areas: (1) the status of assistive technology in educational and related settings with school-age children with disabilities; (2) the benefits and barriers associated with using assistive technology for these youngsters; and (3) the effects of assistive technology use. A major aspect of the project involved a general survey of assistive technology use in special education classrooms across three states: Indiana, Kentucky, and Tennessee. This article presents the results of this effort, and discusses the implications in regard to improving practices in the field.