Synthesis and Micellar Characterization of CBABC Type PLGA-PEO-PPO-PEO-PLGA Pentablock Copolymers

Poly(lactic-co-glycolic acid) (PLGA) were grafted to both ends of Pluronic (R) F68 ((EO)(75)(PO)(30)(EO)(75)) triblock copolymer to produce poly {(lactic acid)(m)-co-(glycolic acid)(n)}-b-poly(ethylene oxide)(75)-b-poly(propylene oxide)(30)-b-poly(ethylene oxide)(75)-b-poly{(lactic acid)(m)-co-(glycolic acid)(n)} (PLGA-F68-PLGA) pentablock copolymers. Molecular weights of PLGA blocks were controlled and five kinds of pentablock copolymers with different PLGA block lengths were synthesized using in-situ ring-opening polymerization of D,L-lactide and glycolide with tin(II) 2-ethylhexanoate (Sn(Oct)(2)) catalyst. PLGA-F68-PLGA pentablock copolymers were characterized by H-1- and C-13-NMR, GPC, and TGA. The numbers (2m, 2n) of repeating units for lactic acid and glycolic acid inside PLGA segments were obtained as (48, 17), (90, 23), (125, 40), (180, 59), and (246, 64), with H-1-NMR measurement. From NMR data, the resultant molecular weights were determined in the range of 12,700-29,700, which were similar to those obtained from GPC. Polydispersity index was increased in the range of 1.32-1.91 as the content of PLGA blocks increased. TG and DTG thermograms showed discrete degradation traces for PLGA and F68 blocks, which indicate the weight fractions of PLGA blocks in pentablock copolymers can be calculated by TO profile and it is possible to remove PLGA block selectively. Hydrodynamic radius and radius of gyration of pentablock copolymer micelle were obtained in the range of 46-68 nm and 31-49 nm, respectively, in very dilute (i.e. 0.005 wt %) aqueous solution of THF:H2O = 10:90 by volume at 25 degrees C.X1121Ysciescopu

A Survey on the Current Status and Future Challenges Towards Objective Skills Assessment in Endovascular Surgery

Minimally-invasive endovascular interventions have evolved rapidly over the past decade, facilitated by breakthroughs in medical imaging and sensing, instrumentation and most recently robotics. Catheter based operations are potentially safer and applicable to a wider patient population due to the reduced comorbidity. As a result endovascular surgery has become the preferred treatment option for conditions previously treated with open surgery and as such the number of patients undergoing endovascular interventions is increasing every year. This fact coupled with a proclivity for reduced working hours, results in a requirement for efficient training and assessment of new surgeons, that deviates from the “see one, do one, teach one” model introduced by William Halsted, so that trainees obtain operational expertise in a shorter period. Developing more objective assessment tools based on quantitative metrics is now a recognised need in interventional training and this manuscript reports the current literature for endovascular skills assessment and the associated emerging technologies. A systematic search was performed on PubMed (MEDLINE), Google Scholar, IEEXplore and known journals using the keywords, “endovascular surgery”, “surgical skills”, “endovascular skills”, “surgical training endovascular” and “catheter skills”. Focusing explicitly on endovascular surgical skills, we group related works into three categories based on the metrics used; structured scales and checklists, simulation-based and motion-based metrics. This review highlights the key findings in each category and also provides suggestions for new research opportunities towards fully objective and automated surgical assessment solutions

Harnack inequality for fractional sub-Laplacians in Carnot groups

In this paper we prove an invariant Harnack inequality on Carnot-Carath\'eodory balls for fractional powers of sub-Laplacians in Carnot groups. The proof relies on an "abstract" formulation of a technique recently introduced by Caffarelli and Silvestre. In addition, we write explicitly the Poisson kernel for a class of degenerate subelliptic equations in product-type Carnot groups

Fast Purcell-enhanced single photon source in 1,550-nm telecom band from a resonant quantum dot-cavity coupling

High-bit-rate nanocavity-based single photon sources in the 1,550-nm telecom band are challenges facing the development of fibre-based long-haul quantum communication networks. Here we report a very fast single photon source in the 1,550-nm telecom band, which is achieved by a large Purcell enhancement that results from the coupling of a single InAs quantum dot and an InP photonic crystal nanocavity. At a resonance, the spontaneous emission rate was enhanced by a factor of 5 resulting a record fast emission lifetime of 0.2 ns at 1,550 nm. We also demonstrate that this emission exhibits an enhanced anti-bunching dip. This is the first realization of nanocavity-enhanced single photon emitters in the 1,550-nm telecom band. This coupled quantum dot cavity system in the telecom band thus provides a bright high-bit-rate non-classical single photon source that offers appealing novel opportunities for the development of a long-haul quantum telecommunication system via optical fibres.Comment: 16 pages, 4 figure

An extracellular steric seeding mechanism for Eph-ephrin signaling platform assembly

Erythropoetin-producing hepatoma (Eph) receptors are cell-surface protein tyrosine kinases mediating cell-cell communication. Upon activation, they form signaling clusters. We report crystal structures of the full ectodomain of human EphA2 (eEphA2) both alone and in complex with the receptor-binding domain of the ligand ephrinA5 (ephrinA5 RBD). Unliganded eEphA2 forms linear arrays of staggered parallel receptors involving two patches of residues conserved across A-class Ephs. eEphA2-ephrinA5 RBD forms a more elaborate assembly, whose interfaces include the same conserved regions on eEphA2, but rearranged to accommodate ephrinA5 RBD. Cell-surface expression of mutant EphA2s showed that these interfaces are critical for localization at cell-cell contacts and activation-dependent degradation. Our results suggest a 'nucleation' mechanism whereby a limited number of ligand-receptor interactions 'seed' an arrangement of receptors which can propagate into extended signaling arrays

HBV DNA suppression during entecavir treatment in previously treated children with chronic hepatitis B

The aim of this study was to assess HBV DNA suppression after 24 weeks of treatment with entecavir in previously treated children with CHB. Thirty children aged 5–17 years (25 males and 5 females) with CHB were treated with entecavir 0.5 or 1 mg daily. Twenty-two children were HBeAg-positive, eight were HBeAg-negative, and in eight HBV polymerase mutations were detected. After 24 weeks of treatment, mean and median HBV DNA levels and ALT activity were lower versus baseline, overall and in both subgroups. The overall median HBV DNA level decreased from 1.2 x 107 IU/mL to 3.3 x 102 IU/mL (p < 0.000004), in HBeAg-positive from 7.8x107 IU/mL to 6.3x103 IU/mL (p < 0.00004), and in HBeAg-negative from 2.5x104 IU/mL to 5.01x101 IU/mL (p < 0.03). The serum HBV DNA disappearance was observed in 7/8 (88%) HBeAg-negative and in 5/22 (23%) HBeAg-positive patients. The overall mean ALT activity decreased from 164+ 290 U/L to 34.1+ 18.9 U/L (p < 0.000007), in HBeAg-positive from 214+326 U/L to 38.59+19.2 U/L (p < 0.000074), and in HBeAg-negative from 27+14 U/L to 20+8 U/L (p < 0.03). Twenty-four weeks of treatment with entecavir results in suppression of HBV DNA in a substantial proportion of children previously treated ineffectively with CHB

Voxel-wise comparisons of cellular microstructure and diffusion-MRI in mouse hippocampus using 3D Bridging of Optically-clear histology with Neuroimaging Data (3D-BOND)

A key challenge in medical imaging is determining a precise correspondence between image properties and tissue microstructure. This comparison is hindered by disparate scales and resolutions between medical imaging and histology. We present a new technique, 3D Bridging of Optically-clear histology with Neuroimaging Data (3D-BOND), for registering medical images with 3D histology to overcome these limitations. Ex vivo 120 × 120 × 200 μm resolution diffusion-MRI (dMRI) data was acquired at 7 T from adult C57Bl/6 mouse hippocampus. Tissue was then optically cleared using CLARITY and stained with cellular markers and confocal microscopy used to produce high-resolution images of the 3D-tissue microstructure. For each sample, a dense array of hippocampal landmarks was used to drive registration between upsampled dMRI data and the corresponding confocal images. The cell population in each MRI voxel was determined within hippocampal subregions and compared to MRI-derived metrics. 3D-BOND provided robust voxel-wise, cellular correlates of dMRI data. CA1 pyramidal and dentate gyrus granular layers had significantly different mean diffusivity (p > 0.001), which was related to microstructural features. Overall, mean and radial diffusivity correlated with cell and axon density and fractional anisotropy with astrocyte density, while apparent fibre density correlated negatively with axon density. Astrocytes, axons and blood vessels correlated to tensor orientation

Fabrication of Antireflective Sub-Wavelength Structures on Silicon Nitride Using Nano Cluster Mask for Solar Cell Application

We have developed a simple and scalable approach for fabricating sub-wavelength structures (SWS) on silicon nitride by means of self-assembled nickel nanoparticle masks and inductively coupled plasma (ICP) ion etching. Silicon nitride SWS surfaces with diameter of 160–200 nm and a height of 140–150 nm were obtained. A low reflectivity below 1% was observed over wavelength from 590 to 680 nm. Using the measured reflectivity data in PC1D, the solar cell characteristics has been compared for single layer anti-reflection (SLAR) coatings and SWS and a 0.8% improvement in efficiency has been seen

Modulation of Hepatic Amyloid Precursor Protein and Lipoprotein Receptor-Related Protein 1 by Chronic Alcohol Intake: Potential Link Between Liver Steatosis and Amyloid-β

Heavy alcohol consumption is a known risk factor for various forms of dementia and the development of Alzheimer’s disease (AD). In this work, we investigated how intragastric alcohol feeding may alter the liver-to-brain axis to induce and/or promote AD pathology. Four weeks of intragastric alcohol feeding to mice, which causes significant fatty liver (steatosis) and liver injury, caused no changes in AD pathology markers in the brain [amyloid precursor protein (APP), presenilin], except for a decrease in microglial cell number in the cortex of the brain. Interestingly, the decline in microglial numbers correlated with serum alanine transaminase (ALT) levels, suggesting a potential link between liver injury and microglial loss in the brain. Intragastric alcohol feeding significantly affected two hepatic proteins important in amyloid-beta (Aβ) processing by the liver: 1) alcohol feeding downregulated lipoprotein receptor-related protein 1 (LRP1, ∼46%), the major receptor in the liver that removes Aβ from blood and peripheral organs, and 2) alcohol significantly upregulated APP (∼2-fold), a potentially important source of Aβ in the periphery and brain. The decrease in hepatic LRP1 and increase in hepatic APP likely switches the liver from being a remover or low producer of Aβ to an important source of Aβ in the periphery, which can impact the brain. The downregulation of LRP1 and upregulation of APP in the liver was observed in the first week of intragastric alcohol feeding, and also occurred in other alcohol feeding models (NIAAA binge alcohol model and intragastric alcohol feeding to rats). Modulation of hepatic LRP1 and APP does not seem alcohol-specific, as ob/ob mice with significant steatosis also had declines in LRP1 and increases in APP expression in the liver. These findings suggest that liver steatosis rather than alcohol-induced liver injury is likely responsible for regulation of hepatic LRP1 and APP. Both obesity and alcohol intake have been linked to AD and our data suggests that liver steatosis associated with these two conditions modulates hepatic LRP1 and APP to disrupt Aβ processing by the liver to promote AD