Evaluation of Durability of Existing Base Aggregates in Wisconsin Pavements

ABSTRACT EVALUATION OF DURABILITY OF EXISTING BASE AGGREGATES IN WISCONSIN PAVEMENTS by Mahmoud Dakwar The University of Wisconsin-Milwaukee, 2017 Under the Supervision of Professor Hani Titi Highways are an integral part of modern societies, and high volumes of traffic are serviced by highways every hour of the day year-round. The base-course aggregate layer acts as the foundation of the pavement system, and it supports the overlaying layers in the pavement structure. The objective of this research study was to evaluate the durability of existing base-course aggregates as they are impacted by external factors. Samples from fourteen sites were collected and additional data were obtained from other relevant studies. Aggregates from eleven sites out of the fourteen served in base layers. Durability and strength related lab tests were performed on the collected samples, and the test results along with the data from other studies were analyzed by utilizing visual comparison statistical procedures and regression statistical methods. For the eleven samples of existing base-course aggregates, the results of the Micro-Deval abrasion test showed that two samples exceeded a recommended threshold limit of 18%, the results of the sodium sulfate soundness test showed that none of the samples exceeded the Wis.DOT threshold limit of 18%, and the results of the aggregate absorption test showed that six of the samples exceeded a recommended threshold limit of 2%. For the entire data used in the study, the results of regression analyses showed that the regression model MD% Loss = 5.62 × Absorption + 2.09 (with R2 value of 0.86) can be used to make predictions and assess the performance quality of base-course aggregates accurately. The regression analyses results also demonstrated that the mass loss by sodium sulfate soundness test did not have strong correlations with either absorption or the mass loss by Micro-Deval abrasion

Exploring the HYDRAtion method for loading siRNA on liposomes : the interplay between stability and biological activity in human undiluted ascites fluid

Delivery of small interfering RNA (siRNA) is recently gaining tremendous attention for the treatment of ovarian cancer. The present study investigated the potential of different liposomal formulations composed of (2,3-dioleoyloxy-propyl)trimethylammonium (DOTAP) and 1,2-dioleoyl-sn-glycero-3phosphoethanolamine (DOPE) encapsulating siRNA (hydration method) for their ability to knockdown luciferase (Luc) activity in human ovarian cancer SKOV-3 cells. Fluorescence single particle tracking (fSPT) and fluorescence correlation spectroscopy (FCS) in human-undiluted ascites fluid obtained from a peritoneal carcinomatosis patient revealed that cationic hydra-lipoplexes (HYDRA-LPXs) and HYDRA-LPXs decorated with stable DSPE-PEG (DSPE HYDRA-LPXs) showed high stability during at least 24 h. HYDRA-LPXs decorated with sheddable C8 and C16 PEG-Ceramides (Cer HYDRA-LPXs) resulted in rapid and premature release of siRNA already in the first hours. Despite their role in preventing aggregation in vivo, liposomes decorated with stable PEG residues resulted in a poor transfection compared to the ones decorated with sheddable PEG residues in reduced serum conditions. Yet, the transfection efficiency of both Cer HYDRA-LPXs significantly decreased following 1 h of incubation in ascites fluid due to a drastic drop in the cellular uptake, while DSPE HYDRA-LPXs are still taken up by cells, but too stable to induce efficient gene silencing

Disregarded effect of biological fluids in siRNA delivery : human ascites fluid severely restricts cellular uptake of nanoparticles

Small interfering RNA (siRNA) offers a great potential for the treatment of various diseases and disorders. Nevertheless, inefficient in vivo siRNA delivery hampers its translation into the clinic. While numerous successful in vitro siRNA delivery stories exist in reduced-protein conditions, most studies so far overlook the influence of the biological fluids present in the in vivo environment. In this study, we compared the transfection efficiency of liposomal formulations in Opti-MEM (low protein content, routinely used for in vitro screening) and human undiluted ascites fluid obtained from a peritoneal carcinomatosis patient (high protein content, representing the in vivo situation). In Opti-MEM, all formulations are biologically active. In ascites fluid, however, the biological activity of all lipoplexes is lost except for lipofectamine RNAiMAX. The drop in transfection efficiency was not correlated to the physicochemical properties of the nanoparticles, such as premature siRNA release and aggregation of the nanoparticles in the human ascites fluid. Remarkably, however, all of the formulations except for lipofectamine RNAiMAX lost their ability to be taken up by cells following incubation in ascites fluid. To take into account the possible effects of a protein corona formed around the nanoparticles, we recommend always using undiluted biological fluids for the in vitro optimization of nanosized siRNA formulations next to conventional screening in low-protein content media. This should tighten the gap between in vitro and in vivo performance of nanoparticles and ensure the optimal selection of nanoparticles for further in vivo studies

Nanomedicine-based intraperitoneal therapy for the treatment of peritoneal carcinomatosis : mission possible?

A

High-pressure nebulization as application route for the peritoneal administration of siRNA complexes

Peritoneal carcinomatosis is a severe form of cancer in the abdomen, currently treated with cytoreductive surgery and intravenous chemotherapy. Recently, nebulization has been proposed as a less invasive strategy for the local delivery of chemotherapeutic drugs. Also, RNA interference has been considered as a potential therapeutic approach for treatment of cancer. In this study, Lipofectamine RNAiMAX/siRNA complexes and cyclodextrin/siRNA complexes are evaluated before and after nebulization. Nebulization of the siRNA complexes does not significantly lower transfection efficiency when compared to non-nebulized complexes. After incubation in ascites fluid, however, the cyclodextrin/siRNA complexes show a drastic decrease in transfection efficiency. For the Lipofectamine RNAiMAX/siRNA complexes, this decrease is less pronounced. It is concluded that nebulization is an interesting technique to distribute siRNA complexes into the peritoneal cavity, providing the complexes are stable in ascites fluid which might be present in the peritoneal cavity

Aqueous Extracts of Teucrium polium Possess Remarkable Antioxidant Activity In Vitro

Teucrium polium L. (Lamiaceae) (RDC 1117) is a medicinal plant whose species have been used for over 2000 years in traditional medicine due to its diuretic, diaphoretic, tonic, antipyretic, antispasmodic and cholagogic properties. The therapeutic benefit of medicinal plants is often attributed to their antioxidant properties. We previously reported that an aqueous extract of the leaves and stems of this plant could inhibit iron-induced lipid peroxidation in rat liver homogenate at concentrations that were not toxic to cultured hepatic cells. Others have reported that organic extracts of the aerial components of this plant could inhibit oxidative processes. Against this background, we felt further investigation on the antioxidant action of the extract of T. polium prepared according to traditional Arab medicine was warranted. Accordingly, we assessed (i) its ability to inhibit (a) oxidation of β-carotene, (b) 2,2′-azobis(2-amidinopropan) dihydrochloride (AAPH)-induced plasma oxidation and (c) iron-induced lipid peroxidation in rat liver homogenates; (ii) to scavenge the superoxide ([Formula: see text]) radical and the hydroxyl radical (OH(•)); (iii) its effects on the enzyme xanthine oxidase activity; (iv) its capacity to bind iron; and (v) its effect on cell glutathione (GSH) homeostasis in cultured Hep G2 cells. We found that the extract (i) inhibited (a) oxidation of β-carotene, (b) AAPH-induced plasma oxidation (c) Fe(2+)-induced lipid peroxidation in rat liver homogenates (IC(50) = 7 ± 2 μg ml(−1)); (ii) scavenged [Formula: see text] (IC(50) = 12 ± 3 μg ml(−1)) and OH(•) (IC(50) = 66 ± 20 μg ml(−1)); (iii) binds iron (IC(50) = 79 ± 17 μg ml(−1)); and (iv) tended to increase intracellular GSH levels resulting in a decrease in the GSSG/GSH ratio. These results demonstrate that the extract prepared from the T. polium possesses antioxidant activity in vitro. Further investigations are needed to verify whether this antioxidant effect occurs in vivo

Effect of native gastric mucus on in vivo hybridization therapies directed at Helicobacter pylori

Helicobacter pylori infects more than 50% of the worldwide population. It is mostly found deep in the gastric mucus lining of the stomach, being a major cause of peptic ulcers and gastric adenocarcinoma. To face the increasing resistance of H. pylori to antibiotics, antimicrobial nucleic acid mimics are a promising alternative. In particular, locked nucleic acids (LNA)/2'-OMethyl RNA (2'OMe) have shown to specifically target H. pylori, as evidenced by in situ hybridization. The success of in vivo hybridization depends on the ability of these nucleic acids to penetrate the major physical barriers-the highly viscoelastic gastric mucus and the bacterial cell envelope. We found that LNA/2'OMe is capable of diffusing rapidly through native, undiluted, gastric mucus isolated from porcine stomachs, without degradation. Moreover, although LNA/2'OMe hybridization was still successful without permeabilization and fixation of the bacteria, which is normally part of in vitro studies, the ability of LNA/2'OMe to efficiently hybridize with H. pylori was hampered by the presence of mucus. Future research should focus on developing nanocarriers that shield LNA/2'OMe from components in the gastric mucus, while remaining capable of diffusing through the mucus and delivering these nucleic acid mimics directly into the bacteria