Vacuum compression molding as a screening tool to investigate carrier suitability for hot-melt extrusion formulations

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. Hot-melt extrusion (HME) is the most preferred and effective method for manufacturing amorphous solid dispersions at production scale, but it consumes large amounts of samples when used for formulation development. Herein, we show a novel approach to screen the polymers by overcoming the disadvantage of conventional HME screening by using a minimum quantity of active pharmaceutical ingredient (API). Vacuum Compression Molding (VCM) is a fusion-based method to form solid specimens starting from powders. This study aimed to investigate the processability of VCM for the creation of amorphous formulations and to compare its results with HME-processed formulations. Mixtures of indomethacin (IND) with drug carriers (Parteck® MXP, Soluplus®, Kollidon® VA 64, Eudragit® EPO) were processed using VCM and extrusion technology. Thermal characterization was performed using differential scanning calorimetry, and the solid-state was analyzed via X-ray powder diffraction. Dissolution studies in the simulated gastric fluid were performed to evaluate the drug release. Both technologies showed similar results proving the effectiveness of VCM as a screening tool for HME-based formulations

Enhanced Li+ Transport in Ionic Liquid-Based Electrolytes Aided by Fluorinated Ethers for Highly Efficient Lithium Metal Batteries with Improved Rate Capability

FSI$^{-}$-based ionic liquids (ILs) are promising electrolyte candidates for long-life and safe lithium metal batteries (LMBs). However, their practical application is hindered by sluggish Li$^{+}$ transport at room temperature. Herein, it is shown that additions of bis(2,2,2-trifluoroethyl) ether (BTFE) to LiFSI-Pyr$_{14}$FSI ILs can effectively mitigate this shortcoming, while maintaining ILs′ high compatibility with lithium metal. Raman spectroscopy and small-angle X-ray scattering indicate that the promoted Li+ transport in the optimized electrolyte, [LiFSI]$_{3}$[Pyr$_{14}$FSI]$_{4}$[BTFE]$_{4}$ (Li$_{3}$Py$_{4}$BT$_{4}$), originates from the reduced solution viscosity and increased formation of Li$^{+}$-FSI$^{-}$ complexes, which are associated with the low viscosity and non-coordinating character of BTFE. As a result, Li/LiFePO$_{4}$ (LFP) cells using Li$_{3}$Py$_{4}$BT$_{4}$ electrolyte reach 150 mAh g$^{-1}$ at 1 C rate (1 mA cm$^{-2}$) and a capacity retention of 94.6% after 400 cycles, revealing better characteristics with respect to the cells employing the LiFSI-Pyr$_{14}$FSI (operate only a few cycles) and commercial carbonate (80% retention after only 218 cycles) electrolytes. A wide operating temperature (from −10 to 40 °C) of the Li/Li$_{3}$Py$_{4}$BT$_{4}$/LFP cells and a good compatibility of Li$_{3}$Py$_{4}$BT$_{4}$ with LiNi$_{0.5}$Mn$_{0.3}$Co$_{0.2}$O$_{2}$ (NMC532) are demonstrated also. The insight into the enhanced Li$^{+}$ transport and solid electrolyte interphase characteristics suggests valuable information to develop IL-based electrolytes for LMBs

Graz. Rosarium

Rosarium am Opernrin

SWIPE: a bolometric polarimeter for the Large-Scale Polarization Explorer

The balloon-borne LSPE mission is optimized to measure the linear polarization of the Cosmic Microwave Background at large angular scales. The Short Wavelength Instrument for the Polarization Explorer (SWIPE) is composed of 3 arrays of multi-mode bolometers cooled at 0.3K, with optical components and filters cryogenically cooled below 4K to reduce the background on the detectors. Polarimetry is achieved by means of large rotating half-wave plates and wire-grid polarizers in front of the arrays. The polarization modulator is the first component of the optical chain, reducing significantly the effect of instrumental polarization. In SWIPE we trade angular resolution for sensitivity. The diameter of the entrance pupil of the refractive telescope is 45 cm, while the field optics is optimized to collect tens of modes for each detector, thus boosting the absorbed power. This approach results in a FWHM resolution of 1.8, 1.5, 1.2 degrees at 95, 145, 245 GHz respectively. The expected performance of the three channels is limited by photon noise, resulting in a final sensitivity around 0.1-0.2 uK per beam, for a 13 days survey covering 25% of the sky.Comment: In press. Copyright 2012 Society of Photo-Optical Instrumentation Engineers. One print or electronic copy may be made for personal use only. Systematic reproduction and distribution, duplication of any material in this paper for a fee or for commercial purposes, or modification of the content of the paper are prohibite

PITX2 gain-of-function mutation associated with atrial fibrillation alters mitochondrial activity in human iPSC atrial-like cardiomyocytes

Atrial fibrillation (AF) is the most common cardiac arrhythmia worldwide; however, the underlying causes of AF initiation are still poorly understood, particularly because currently available models do not allow in distinguishing the initial causes from maladaptive remodeling that induces and perpetuates AF. Lately, the genetic background has been proven to be important in the AF onset. iPSC-derived cardiomyocytes, being patient- and mutation-specific, may help solve this diatribe by showing the initial cell-autonomous changes underlying the development of the disease. Transcription factor paired-like homeodomain 2 (PITX2) has been identified as a key regulator of atrial development/differentiation, and the PITX2 genomic locus has the highest association with paroxysmal AF. PITX2 influences mitochondrial activity, and alterations in either its expression or function have been widely associated with AF. In this work, we investigate the activity of mitochondria in iPSC-derived atrial cardiomyocytes (aCMs) obtained from a young patient (24 years old) with paroxysmal AF, carrying a gain-of-function mutation in PITX2 (rs138163892) and from its isogenic control (CTRL) in which the heterozygous point mutation has been reverted to WT. PITX2 aCMs show a higher mitochondrial content, increased mitochondrial activity, and superoxide production under basal conditions when compared to CTRL aCMs. However, increasing mitochondrial workload by FCCP or β-adrenergic stimulation allows us to unmask mitochondrial defects in PITX2 aCMs, which are incapable of responding efficiently to the higher energy demand, determining ATP deficiency

Sphingosine Kinases and Sphingosine 1-Phosphate Receptors: Signaling and Actions in the Cardiovascular System

The sphingosine kinases 1 and 2 (SphK1 and 2) catalyze the phosphorylation of the lipid, sphingosine, generating the signal transmitter, sphingosine 1-phosphate (S1P). The activation of such kinases and the subsequent S1P generation and secretion in the blood serum of mammals represent a major checkpoint in many cellular signaling cascades. In fact, activating the SphK/S1P system is critical for cell motility and proliferation, cytoskeletal organization, cell growth, survival, and response to stress. In the cardiovascular system, the physiological effects of S1P intervene through the binding and activation of a family of five highly selective G protein-coupled receptors, called S1PR1-5. Importantly, SphK/S1P signal is present on both vascular and myocardial cells. S1P is a well-recognized survival factor in many tissues. Therefore, it is not surprising that the last two decades have seen a flourishing of interest and investigative efforts directed to obtain additional mechanistic insights into the signaling, as well as the biological activity of this phospholipid, and of its receptors, especially in the cardiovascular system. Here, we will provide an up-to-date account on the structure and function of sphingosine kinases, discussing the generation, release, and function of S1P. Keeping the bull’s eye on the cardiovascular system, we will review the structure and signaling cascades and biological actions emanating from the stimulation of different S1P receptors. We will end this article with a summary of the most recent, experimental and clinical observations targeting S1PRs and SphKs as possible new therapeutic avenues for cardiovascular disorders, such as heart failure

VIALACTEA knowledge base homogenizing access to Milky Way data

The VIALACTEA project has a work package dedicated to "Tools and Infrastructure" and, inside it, a task for the "Database and Virtual Observatory Infrastructure". This task aims at providing an infrastructure to store all the resources needed by the, more purposely, scientific work packages of the project itself. This infrastructure includes a combination of: storage facilities, relational databases and web services on top of them, and has taken, as a whole, the name of VIALACTEA Knowledge Base (VLKB). This contribution illustrates the current status of this VLKB. It details the set of data resources put together; describes the database that allows data discovery through VO inspired metadata maintenance; illustrates the discovery, cutout and access services built on top of the former two for the users to exploit the data content