Archaeometallurgical Analysis of the Provincial Silver Coinage of Judah: More on the Chaîne Opératoire of the Minting Process.

Silver coins were the first coins to be manufactured by mass production in the southern Levant. An assemblage of tiny provincial silver coins of the local (Judahite standard) and (Attic) obol-based denominations from the Persian and Hellenistic period Yehud and dated to the second half of the fourth century BCE were analyzed to determine their material composition. Of the 50 silver coins, 32 are defined as Type 5 (Athena/Owl) of the Persian period Yehud series (ca. 350-333 BCE); 9 are Type 16 (Persian king wearing a jagged crown/Falcon in flight) (ca. 350-333); 3 are Type 24 series (Portrait/Falcon) of the Macedonian period (ca. 333-306 BCE); and 6 are Type 31 (Portrait/Falcon) (ca. 306-302/1 BCE). The coins underwent visual testing, multi-focal light microscope observation, XRF analysis, and SEM-EDS analysis. The metallurgical findings revealed that all the coins from the Type 5, 16, 24, and 31 series are made of high-purity silver with a small percentage of copper. Based on these results, it is suggested that each series was manufactured using a controlled composition of silver-copper alloy. The findings present novel information about the material culture of the southern Levant during the Late Persian period and Macedonian period, as expressed through the production and use of these silver coins.

Nanoparticle-in-microparticle oral drug delivery system of a clinically relevant darunavir/ritonavir antiretroviral combination.

Nanonizationhas been extensively investigated to increase theoral bioavailability of hydrophobicdrugsin general andantiretrovirals(ARVs)used inthe therapy of the human immunodeficiency virus (HIV) infection in particular. Weanticipatedthatin the caseofprotease inhibitors, a family of pH-dependent ARVsthatdisplay high aqueous solubility undertheacidconditionsof thestomach andextremely low solubilityunder the neutral ones ofthe small intestine, this strategy might failowing to an uncontrolled dissolution-re-precipitation process that will take place along the gastrointestinal tract.To tackle thisbiopharmaceutical challenge, in this work, wedesigned, produced and fully characterized a novelNanoparticle-in-MicroparticleDelivery System(NiMDS)comprised of pure nanoparticlesofthefirst-line protease inhibitor darunavir(DRV) and itsboosting agentritonavir (RIT) encapsulated within film-coated microparticles.For this, a clinically relevant combination of pure DRV and RIT nanoparticles wassynthesized by a sequential nanoprecipitation/solvent diffusion and evaporation method employing sodium alginateas viscosity stabilizer. Then, pure nanoparticles were encapsulated within calcium alginate/chitosanmicroparticlesthat were film-coated with a series ofpoly(methacrylate) copolymers with differential solubility in the gastrointestinal tract. This coating ensured full stability under gastric-like pH and sustained drug release under intestinal one. PharmacokineticstudiesconductedinalbinoSpragueDawleyratsshowed that DRV/RIT-loadedNiMDSs containing 17% w/w drug loading based on dry weight significantlyincreasedthe oral bioavailabilityof DRVby 2.3-foldwith respect to both theunprocessedandthenanonized DRV/RIT combinations that showed statistically similar performance. Moreover, they highlighted the limited advantage of only drugnanonizationto improve the oral pharmacokinetics of protease inhibitors and the potential of our novel delivery approach to improve the oral pharmacokinetics of nanonized poorly water-soluble drugs displaying pH-dependent solubility. STATEMENT OF SIGNIFICANCE: Protease inhibitors (PIs) are gold-standard drugs in many ARV cocktails. Darunavir (DRV) is the latest approved PI and it is included in the 20th WHO Model List of Essential Medicines. PIs poorly-water soluble at intestinal pH and more soluble under gastric conditions. Drug nanonization represents one of the most common nanotechnology strategies to increase dissolution rate of hydrophobic drugs and thus, their oral bioavailability. For instance, pure drug nanosuspensions became the most clinically relevant nanoformulation. However, according to the physicochemical properties of PIs, nanonization does not appear as a very beneficial strategy due to the fast dissolution rate anticipated under the acid conditions of the stomach and their uncontrolled recrystallization and precipitation in the small intestine that might result in the formation of particles of unpredictable size and structure (e.g., crystallinity and polymorphism) and consequently, unknown dissolution rate and bioavailability. In this work, we developed a sequential nanoprecipitation method for the production of pure nanoparticles of DRV and its boosting agent ritonavir in a clinically relevant 8:1 wt ratio using alginate as viscosity stabilizer and used this nanosuspension to produce a novel kind of nanoparticle-in-microparticle delivery system that was fully characterized and the pharmacokinetics assessed in rats. The most significant points of the current manuscript are.

Improved Patency of ePTFE Grafts as a Hemodialysis Access Site by Seeding Autologous Endothelial Cells Expressing Fibulin-5 and VEGF.

Small caliber synthetic vascular grafts used for dialysis access sites have high failure rates due to neointima formation and thrombosis. Seeding synthetic grafts with endothelial cells (ECs) provides a biocompatible surface that may prevent graft failure. We tested the use of ePTFE grafts seeded with autologous ECs expressing fibulin-5 and vascular endothelial growth factor (VEGF), as a dialysis access site in a porcine model. We connected the carotid arteries and jugular veins of 12 miniature pigs using 7-mm ePTFE grafts; five grafts were seeded with autologous venous ECs modified to express fibulin-5 and VEGF, and seven unseeded grafts were implanted at the same location and served as controls. At 6 months, after completion of angiography, the carotid arteries and jugular veins with the connecting grafts were excised and fixed. Autologous EC isolation and transduction and graft seeding were successful in all animals. At 3 months, 4 of 5 seeded grafts and 3 of 7 control grafts were patent. At 6 months, 4 of 5 (80%) seeded grafts and only 2 of 7 (29%) control grafts were patent. Seeding ePTFE vascular grafts with genetically modified ECs improved long term small caliber graft patency. The biosynthetic grafts offer a novel therapeutic modality for vascular access in hemodialysis.

Observations of Ball-Lightning-Like Plasmoids Ejected from Silicon by Localized Microwaves.

This paper presents experimental characterization of plasmoids (fireballs) obtained by directing localized microwave power (<1 kW at 2.45 GHz) onto a silicon-based substrate in a microwave cavity. The plasmoid emerges up from the hotspot created in the solid substrate into the air within the microwave cavity. The experimental diagnostics employed for the fireball characterization in this study include measurements of microwave scattering, optical spectroscopy, small-angle X-ray scattering (SAXS), scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDS). Various characteristics of these plasmoids as dusty plasma are drawn by a theoretical analysis of the experimental observations. Aggregations of dust particles within the plasmoid are detected at nanometer and micrometer scales by both in-situ SAXS and ex-situ SEM measurements. The resemblance of these plasmoids to the natural ball-lightning (BL) phenomenon is discussed with regard to silicon nano-particle clustering and formation of slowly-oxidized silicon micro-spheres within the BL. Potential applications and practical derivatives of this study (e.g., direct conversion of solids to powders, material identification by breakdown spectroscopy (MIBS), thermite ignition, and combustion) are discussed.