Construction of nanostructures in aqueous solution from amphiphilic glucose‐derived polycarbonates

Carbohydrates are the fundamental building blocks of many natural polymers, their wide bioavailability, high chemical functionality, and stereochemical diversity make them attractive starting materials for the development of new synthetic polymers. In this work, one such carbohydrate, d ‐glucopyranoside, was utilized to produce a hydrophobic five‐membered cyclic carbonate monomer to afford sugar‐based amphiphilic copolymers and block copolymers via organocatalyzed ring‐opening polymerizations with 4‐methylbenzyl alcohol and methoxy poly(ethylene glycol) as initiator and macroinitiator, respectively. To modulate the amphiphilicities of these polymers acidic benzylidene cleavage reactions were performed to deprotect the sugar repeat units and present hydrophilic hydroxyl side chain groups. Assembly of the polymers under aqueous conditions revealed interesting morphological differences, based on the polymer molar mass and repeat unit composition. The initial polymers, prior to the removal of the benzylidenes, underwent a morphological change from micelles to vesicles as the sugar block length was increased, causing a decrease in the hydrophilic–hydrophobic ratio. Deprotection of the sugar block increased the hydrophilicity and gave micellar morphologies. This tunable polymeric platform holds promise for the production of advanced materials for implementation in a diverse range of applications. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019 , 57, 432–440     

Distinguishing Activities in the Photodynamic Arsenals of the Pigmented Ciliates Blepharisma sinuosum Sawaya, 1940 and Blepharisma japonicum Suzuki, 1954 (Ciliophora: Heterotrichea)

Blepharismins are photodynamic hypericin-like dianthrones produced as a variable pigment blend in Blepharisma ciliates and mostly studied in the Afro-Asiatic Blepharisma japonicum. The present work describes the bioactivity of pigments from the Brazilian Blepharisma sinuosum. Comparative analyses showed that the pigments from both species can trigger photo-induced modifications in phospholipids, but different redox properties and biological activities were assigned for each pigment blend. Stronger activities were detected for B. sinuosum pigments, with the lethal concentration LC₅₀ 10 × lower than B. japonicum pigments in light-irradiated tests against Bacillus cereus and less than half for treatments on the human HeLa tumor cells. HPLC showed B. sinuosum producing a simpler pigment blend, mostly with the blepharismin-C (~ 70%) and blepharismin-E (~ 30%) types. Each blepharismin engaged a specific dose–response profile on sensitive cells. The blepharismin-B and blepharismin-C were the most toxic pigments, showing LC₅₀ ~ 2.5–3.0 µm and ~ 100 µm on B. cereus and HeLa cells, respectively, after illumination. Similarity clustering analysis compiling the bioactivity data revealed two groups of blepharismins: the most active, B and C, and the less active, A, D and E. The B. sinuosum pigment blend includes one representative of each clade. Functional and medical implications are discussed.     

Effect of streamwise spacing on periodic and random unsteadiness in a bundle of short cylinders confined in a channel

While flow across long tube bundles is considered classical data, pin-fin arrays made up of short tubes have become a growing topic of interest for use in cooling gas turbine airfoils. Data from the literature indicate that decreasing streamwise spacing increases heat transfer in pin-fin arrays; however, the specific mechanism that causes increased heat transfer coefficients remains unknown. The present work makes use of time-resolved PIV to quantify the effects of streamwise spacing on the turbulent near wake throughout various pin-fin array spacings. Specifically, proper orthogonal decomposition was used to separate the (quasi-) periodic motion from vortex shedding and the random motion from turbulent eddies. Reynolds number flow conditions of 3.0?×?10³ and 2.0?×?10⁴, based on pin-fin diameter and velocity at the minimum flow area, were considered. Streamwise spacing was varied from 3.46 pin diameters to 1.73 pin diameters while the pin-fin height-to-diameter ratio was unity and the spanwise spacing was held constant at two diameters. Results indicated that (quasi-) periodic motions were attenuated at closer streamwise spacings while the level of random motions was not strongly dependent on pin-fin spacing. This trend was observed at both Reynolds number conditions considered. Because closer spacings exhibit higher heat transfer levels, the present results imply that periodic motions may not contribute to heat transfer, although further experimentation is required.     

Effect of the conserved oligosaccharides of recombinant monoclonal antibodies on the separation by protein A and protein G chromatography

Glycosylation of the conserved asparagine residue in CH2 domains of IgG molecules is an important post-translational modification. The presence of oligosaccharides is critical for structure, stability and biological function of IgG antibodies. Effect of the glycosylation states of recombinant monoclonal antibodies on protein A and protein G chromatography was evaluated. Antibodies lacking oligosaccharides eluted later from protein A and earlier from protein G columns than antibodies with oligosaccharides using a gradient of decreasing pH. Interestingly, different types of oligosaccharides also affected the elution of the antibodies. Antibodies with high mannose type oligosaccharides were enriched in later eluting fractions from protein A and earlier eluting fractions from protein G. While antibodies with more mature oligosaccharides, such as core fucosylated biantennary complex oligosaccharides with zero (Gal 0), one (Gal 1) or two (Gal 2) terminal galactoses, were enriched in earlier eluting fractions from protein A and in the later eluting fractions from protein G. However, analysis by enzyme-linked immunosorbent assay (ELISA) revealed that antibody binding affinity to protein A and protein G was not affected by the absence or presence of oligosaccharides. It was thus concluded that the elution difference of antibodies with or without oligosaccharides and antibodies with different types of oligosaccharides were due to differential structural changes around the CH2–CH3 domain interface under the low pH conditions used for protein A and protein G chromatography.     

Intraventricular thrombus formation in the LVAD-assisted heart studied in a mock circulatory loop

Left ventricular assist devices (LVADs) are mechanical pumps that are surgically attached to the left ventricle and aorta. Clinical studies show that LVADs improve patient health and quality of life, and dramatically reduce the mortality of cardiac failure. During periods of high LVAD support, blood flow occurs entirely through the LVAD, the aortic valve is continuously closed, and the heart operates in series with the pump. Thus the normal fluid dynamics of intraventricular flow are altered and linked to the development of thrombus in both the native heart and LVAD. Our goal in this study was to simulate a patient with a recurring thrombus and quantify the variations in the flow field in the LV as the thrombus developed. Particle image velocimetry measurements of transparent silicone models were performed for a range of LVAD support conditions. Results show that the presence of a small thrombus in the LVOT creates a favorable condition for further growth, especially in the presence of high LVAD support. As the thrombus enlarges, it begins to affect the normal vortex-flow pattern, further reducing flow rate and pulsatility in the LVOT. Evaluation of vortex dynamics and stasis regions in both patients and experimental models of LVAD support yield quantitative metrics that can be used to assess the risk of thrombus and the development of strategies to reduce this risk in LVAD patients.     

New In-Situ and Operando Facilities for Catalysis Science at NSLS-II: The Deployment of Real-Time,Chemical, and Structure-Sensitive X-ray Probes

The start of operations at the National Synchrotron Light Source II (NSLS-II) at Brookhaven National Laboratory heralded a new beginning for photon-science-based research capabilities in catalysis. This new facility builds on many years of pioneering work that was conducted at the NSLS synergistically by many scientists from academia, government labs, and industry. Over several decades, numerous discoveries in catalysis were driven through the emergence of an arsenal of tools at the NSLS that exploited the power of emerging X-ray methods encompassing scattering, spectroscopy, and imaging. In-situ and operando methodologies that coupled reactor environments directly with advanced analytical techniques paved a rapid path towards realizing an improved fundamental understanding at the frontiers of chemical science challenges of the day.     

Comparative and Combinatorial Effects of Resveratrol and Sacubitril/Valsartan alongside Valsartan on Cardiac Remodeling and Dysfunction in MI-Induced Rats

The development and progression of heart failure (HF) due to myocardial infarction (MI) is a major concern even with current optimal therapy. Resveratrol is a plant polyphenol with cardioprotective properties. Sacubitril/valsartan is known to be beneficial in chronic HF patients. In this study, we investigated the comparative and combinatorial benefits of resveratrol with sacubitril/valsartan alongside an active comparator valsartan in MI-induced male Sprague Dawley rats. MI-induced and sham-operated animals received vehicle, resveratrol, sacubitril/valsartan, valsartan alone or sacubitril/valsartan + resveratrol for 8 weeks. Echocardiography was performed at the endpoint to assess cardiac structure and function. Cardiac oxidative stress, inflammation, fibrosis, brain natriuretic peptide (BNP), creatinine and neutrophil gelatinase associated lipocalin were measured. Treatment with resveratrol, sacubitril/valsartan, valsartan and sacubitril/valsartan + resveratrol significantly prevented left ventricular (LV) dilatation and improved LV ejection fraction in MI-induced rats. All treatments also significantly reduced myocardial tissue oxidative stress, inflammation and fibrosis, as well as BNP. Treatment with the combination of sacubitril/valsartan and resveratrol did not show additive effects. In conclusion, resveratrol, sacubitril/valsartan, and valsartan significantly prevented cardiac remodeling and dysfunction in MI-induced rats. The reduction in cardiac remodeling and dysfunction in MI-induced rats was mediated by a reduction in cardiac oxidative stress, inflammation and fibrosis.