Synthesis and Characterization of Lipid Coated Nanoparticles as Drug Delivery Vehicles

Spherical monodisperse nanoparticles composed of gold or silver cores were modified with lipids as part of an ongoing project to utilize functionalized nanoparticles as drug delivery vehicles. A reduction reaction with sodium tri-citrate was used to synthesize nanoparticles that were characterized physically through a NanoSight LM10 HS particle sizer as well as optically with a Shimadzu UV-vis spectrophotometer. The particles were then characterized again after purification of excess ligands through centrifugation. Poly(allylamine hydrochloride) was added to flip the surface charge of the particles from negative to positive as well as to serve as a stabilizing agent. After purification, the particles were coated with lipids and spun to purify them. Characterization data suggest that the particles are successfully coated with both poly(allylamine hydrochloride) and lipids and that monodispersity was maintained, as evidenced by the measured changes in size and optical properties

Lipid Coated Gold Nanoparticle Cores: Synthesis and Characterization

Including environmental, industrial, and biomedical sciences, applications of gold nanoparticles are on the forefront of research in many areas. By altering the surface treatment of spherical gold nanoparticle cores, particularly those smaller than 100 nm (nanometers), one can influence their potential use in a number of ways. Lipid coated nanoparticles with specifically selected surface ligands can be used for multiple biomedical functions, including medical imaging, for use as colorimetric and plasmonic sensors within the body, and as cell or organelle specific targets for therapeutic drug delivery or cancer treatment. Here, spherical gold nanoparticles ranging in size from 8-40 nm (avg. diameter 23-48 nm) have been synthesized and coated with poly(allylamine hydrochloride) (PAH) and a mixed lipid solution of 1:1 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-L-serine (POPS) and lysophosphatidylcholine (LPC), two of the four major types of lipids found in the human body. Characterization was performed using a NanoSight LM10HS particle sizer, and shows a gradual increase in size after each step in the coating process for nanoparticle cores ranging in size from 16-27 nm. The thickness of these purified and lipid coated nanoparticles was consistently 2-3 times that of the PAH coated sample it was layered onto, suggesting a successful, multi-layered coat that ranges in size based on the PAH coated core size. UV-Vis spectroscopy shows a slight red shift, indicating an increase in size and change in refractive index, which supports the presence of lipid coating on the PAH coated gold nanoparticle cores

Enhanced Tissue Integration During Cartilage RepairIn VitroCan Be Achieved by Inhibiting Chondrocyte Death at the Wound Edge

Objective: Experimental wounding of articular cartilage results in cell death at the lesion edge. The objective of this study was to investigate whether inhibition of this cell death results in enhanced integrative cartilage repair. Methods: Bovine articular cartilage discs (6mm) were incubated in media containing inhibitors of necrosis (Necrostatin-1, Nec-1) or apoptosis (Z-VAD-FMK, ZVF) before cutting a 3mm inner core. This core was left in situ to create disc/ring composites, cultured for up to 6 weeks with the inhibitors, and analyzed for cell death, sulfated glycosaminoglycan release, and tissue integration. Results: Creating the disc/ring composites resulted in a significant increase in necrosis. ZVF significantly reduced necrosis and apoptosis at the wound edge. Nec-1 reduced necrosis. Both inhibitors reduced the level of wound-induced sulfated glycosaminoglycan loss. Toluidine blue staining and electron microscopy of cartilage revealed significant integration of the wound edges in disc/ring composites treated with ZVF. Nec-1 improved integration, but to a lesser extent. Push-out testing revealed that ZVF increased adhesive strength compared to control composites. Conclusions: This study shows that treatment of articular cartilage with cell death inhibitors during wound repair increases the number of viable cells at the wound edge, prevents matrix loss, and results in a significant improvement in cartilage-cartilage integration

Suspension polymerisation of vinyl chloride in presence of ultra fine filler particles

Polymer composites, filled with ultra fine particulate fillers, are alternatives to the conventional filled polymers. The reinforcement of the mechanical properties occurs to a greater extent when ultra fine particulate fillers are used in comparison with the conventional microdimensional fillers. To achieve all the benefits that the ultra fine fillers can provide, optimal dispersion as primary particles is essential. To achieve better dispersion of the inorganic particles in a polymer matrix, the ultra fine particles (UFP) are added to the polymerisation reactor so that they are dispersed in the monomer before polymerisation. Hence, the monomer is polymerised in the presence of the UFP (in situ). In this paper the effects of the UFP on the initial monomer dispersion are examined. The presence of the inorganic UFP in the polymerisation reactor influences the properties of the monomer phase and affects the drop size distribution. This in turn influences the grain sizes as well as their distribution, which influence the processability of the resin

Learning sources of variability from high-dimensional observational studies

Causal inference studies whether the presence of a variable influences an observed outcome. As measured by quantities such as the "average treatment effect," this paradigm is employed across numerous biological fields, from vaccine and drug development to policy interventions. Unfortunately, the majority of these methods are often limited to univariate outcomes. Our work generalizes causal estimands to outcomes with any number of dimensions or any measurable space, and formulates traditional causal estimands for nominal variables as causal discrepancy tests. We propose a simple technique for adjusting universally consistent conditional independence tests and prove that these tests are universally consistent causal discrepancy tests. Numerical experiments illustrate that our method, Causal CDcorr, leads to improvements in both finite sample validity and power when compared to existing strategies. Our methods are all open source and available at github.com/ebridge2/cdcorr

Obesity-Induced Colorectal Cancer Is Driven by Caloric Silencing of the Guanylin-GUCY2C Paracrine Signaling Axis.

Obesity is a well-known risk factor for colorectal cancer but precisely how it influences risks of malignancy remains unclear. During colon cancer development in humans or animals, attenuation of the colonic cell surface receptor guanylyl cyclase C (GUCY2C) that occurs due to loss of its paracrine hormone ligand guanylin contributes universally to malignant progression. In this study, we explored a link between obesity and GUCY2C silencing in colorectal cancer. Using genetically engineered mice on different diets, we found that diet-induced obesity caused a loss of guanylin expression in the colon with subsequent GUCY2C silencing, epithelial dysfunction, and tumorigenesis. Mechanistic investigations revealed that obesity reversibly silenced guanylin expression through calorie-dependent induction of endoplasmic reticulum stress and the unfolded protein response in intestinal epithelial cells. In transgenic mice, enforcing specific expression of guanylin in intestinal epithelial cells restored GUCY2C signaling, eliminating intestinal tumors associated with a high calorie diet. Our findings show how caloric suppression of the guanylin-GUCY2C signaling axis links obesity to negation of a universal tumor suppressor pathway in colorectal cancer, suggesting an opportunity to prevent colorectal cancer in obese patients through hormone replacement with the FDA-approved oral GUCY2C ligand linaclotide

Solar Wind Alpha Particles and Heavy Ions in the Inner Heliosphere Observed with MESSENGER

The Fast Imaging Plasma Spectrometer (FIPS) on the MErcury Surface, Space ENvironment, GEochemistry, and Ranging (MESSENGER) spacecraft has made the first in situ measurements of solar wind plasma in the inner heliosphere since the Helios 1 and 2 spacecraft in the 1980s. Although the core of the solar wind velocity distribution is obstructed by the spacecraft sunshade, a data analysis technique has been developed that recovers both bulk and thermal speeds to 10% accuracy and provides the first measurements of solar wind heavy ions (mass per charge >2 amu/e) at heliocentric distances within 0.5 AU. Solar wind alpha particles and heavy ions appear to have similar mean flow speeds at values greater than that of the protons by approximately 70% of the Alfvén speed. From an examination of the thermal properties of alpha particles and heavier solar wind ions, we find a ratio of the temperature of alpha particles to that of protons nearly twice that of previously reported Helios observations, though still within the limits of excessive heating of heavy ions observed spectroscopically close to the Sun. Furthermore, examination of typical magnetic power spectra at the orbits of MESSENGER and at 1 AU reveals the lack of a strong signature of local resonant ion heating, implying that a majority of heavy ion heating could occur close to the Sun. These results demonstrate that the solar wind at plus or minus 0.3 AU is a blend of the effects of wave–particle interactions occurring in both the solar corona and the heliosphere

Google haul out : Earth observation imagery and digital aerial surveys in coastal wildlife management and abundance estimation

© The Author(s), 2017. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Bioscience 67 (2017): 760–768, doi:10.1093/biosci/bix059.As the sampling frequency and resolution of Earth observation imagery increase, there are growing opportunities for novel applications in population monitoring. New methods are required to apply established analytical approaches to data collected from new observation platforms (e.g., satellites and unmanned aerial vehicles). Here, we present a method that estimates regional seasonal abundances for an understudied and growing population of gray seals (Halichoerus grypus) in southeastern Massachusetts, using opportunistic observations in Google Earth imagery. Abundance estimates are derived from digital aerial survey counts by adapting established correction-based analyses with telemetry behavioral observation to quantify survey biases. The result is a first regional understanding of gray seal abundance in the northeast US through opportunistic Earth observation imagery and repurposed animal telemetry data. As species observation data from Earth observation imagery become more ubiquitous, such methods provide a robust, adaptable, and cost-effective solution to monitoring animal colonies and understanding species abundances.We would like to thank generous support from International Fund for Animal Welfare, the Bureau of Ocean Energy, and the Oak Foundation for funding support for the telemetry devices

Electronic Medical Record Inaccuracies: Multicenter Analysis of Challenges with Modified Lung Cancer Screening Criteria.

The National Comprehensive Cancer Network expanded their lung cancer screening (LCS) criteria to comprise one additional clinical risk factor, including chronic obstructive pulmonary disease (COPD). The electronic medical record (EMR) is a source of clinical information that could identify high-risk populations for LCS, including a diagnosis of COPD; however, an unsubstantiated COPD diagnosis in the EMR may lead to inappropriate LCS referrals. We aimed to detect the prevalence of unsubstantiated COPD diagnosis in the EMR for LCS referrals, to determine the efficacy of utilizing the EMR as an accurate population-based eligibility screening trigger using modified clinical criteria. We performed a multicenter review of all individuals referred to three LCS programs from 2012 to 2015. Each individual\u27s EMR was searched for COPD diagnostic terms and the presence of a diagnostic pulmonary functionality test (PFT). An unsubstantiated COPD diagnosis was defined by an individual\u27s EMR containing a COPD term with no PFTs present, or the presence of PFTs without evidence of obstruction. A total of 2834 referred individuals were identified, of which 30% (840/2834) had a COPD term present in their EMR. Of these, 68% (571/840) were considered unsubstantiated diagnoses: 86% (489/571) due to absent PFTs and 14% (82/571) due to PFTs demonstrating no evidence of postbronchodilation obstruction. A large proportion of individuals referred for LCS may have an unsubstantiated COPD diagnosis within their EMR. Thus, utilizing the EMR as a population-based eligibility screening tool, employing expanded criteria, may lead to individuals being referred, potentially, inappropriately for LCS