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Biocompatibility and internalization of molecularly imprinted nanoparticles

Nano Research 2016年第11期9卷 3463-3477页

作者： Francesco Canfarotta Alicia Waters robyn sadler Paul McGill Antonio Guerreiro Dmitri Papkovsky Karsten Haupt Sergey Piletsky MIP Diagnostics Ltd. University of Leicester Fielding Johnson Building University Road Leicester LE 1 7RH UK School of Biochemistry and Cell Biology University College Cork College Road Cork Ireland GSK David Jack Centre for R&D Park Road Ware Hertfordshire SG 12 0DP UK Chemistry Department University of Leicester Leicester LE1 7RH UK Compiegne University of Technology CNRS Enzyme and Cell Engineering Laboratory Rue Roger Couttolenc CS 50319 50203 Compiegne Cedex France

Molecularly imprinted polymers （MIP） are receiving increasing attention thanks to their robustness, stability, and inexpensive manufacture compared with their bio-analogues such as antibodies. The molecular imprinting process can be defined as the generation of molecular recognition sites in a synthetic polymer. The template-derived sites created within a polymeric matrix allow MIPs （often referred as plastic antibodies） to selectively recognize and bind to the target molecule. Therefore, MIPs can be used in sensors and in separation and diagnostics. Owing to their size and functional properties, MIP nanoparticles （NPs） can potentially be used in biomedicine, but comprehensive analysis of their interaction with cells and in vitro toxicological tests must be performed first. Herein, we report the synthesis of bare and core-shell imprinted NPs using an innovative solid-phase approach and the toxicological evaluation of such NPs in different cell lines （HaCaT, MEFs, HT1080, and macrophages）. We also evaluated the influence of the protein corona on particle stability, the internalization of NPs in cells, and the influence of various surface coatings. Studies on the metabolic effects of imprinted NPs on fibroblasts showed that bare MIPs do not alter cell metabolism, whereas some issues arise when specific particle coatings are used. Furthermore, in vitro cytokine release studies revealed that macrophages were not activated in the presence of the MIPs evaluated in this study. The results suggest that MIP NPs are biocompatible, paving the way for their in vivo application.

关键词： pegylation core-shell toxicology inflammatory response particle uptake metabolism

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Impact of OCT scan-patterns in identifying morphological features of lamellar macular holes and macular pseudoholes

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International Journal of Ophthalmology(English edition) 2022年第7期15卷 1089-1094页

作者： Osman Murat Uyar Jonas Neubauer Francoise sadler Eva-Maria Konrad Faik Gelisken Department of Ophthalmology Ulus Liv HospitalIstanbul 34340Turkey Department of Ophthalmology Eberhard-Karls UniversityTuebingen 72076Germany

AIM:To evaluate the impact of the optical coherence tomography(OCT)scan patterns on the detection of the features associated with lamellar macular hole(LMH)and macular pseudohole(MPH).METHODS:This is a retrospective analysis of 100 consecutive eyes with LMH(n=41)and MPH(n=59)having at least three of the following OCT features,which include mandatory criteria for the diagnosis of LMH and MPH:Epiretinal membrane,epiretinal proliferation,verticalization,intraretinal cystoid spaces,foveoschisis,irregular foveal contour,foveal cavity with undermined edges,and ellipsoid line *** outcome measurement was the detection frequency of the features in three different OCT scan patterns:1)volume scan;2)six radial scans(R6);and 3)vertical and horizontal radial scans(R2).RESULTS:Of the total eight features,the maximal detection frequency was found as 4.45±1.45,4.35±1.47,and 3.70±1.59,by the volume,R6 and R2,respectively.R2 was inferior to the other patterns in detection of the total features(P<0.001),whereas R6 and volume patterns were found comparable(P=0.312).CONCLUSION:The physician should be aware that the selection of the OCT-scan pattern may influence the detection of mandatory morphological criteria for the diagnosis of LMH and MPH.

关键词： diagnosis epiretinal membrane lamellar macular hole macular pseudohole optical coherence tomography

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Properties of SN Ia progenitors from light curves and spectra

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Frontiers of physics 2013年第2期8卷 144-167页

作者： P. Hoflich P. Dragulin J. Mitchell B. sadler T. Diamond C. Gerardy Department of Physics Florida State University Talahassee USA FL 32306 Department of Physics Astronomy Clemson University Clemson USA SC 29634

With recent advances in theory and observations, direct connections emerge between the progenitors of Type Ia Supernovae （SNe Ia） and the observed light curves and spectra. A direct link is important for our understanding of the supernovae physics, the diversity of SNe Ia and the use of SNe Ia for high-precision cosmology because the details of the explosion depends sensitively on the initial conditions and the explosion scenario（s） realized in nature. Do SNe Ia originate from SD- or DD systems, and do they lead to Mcu mass explosions or dynamical mergers？ Does the statistical distribtion of SNe Ia depend on their environment which can be expected to change with redshift？ In this contribution, we will exam from the theoretical point of view the tell-tails for this connection, their consistency with the observations, and future directions. In a first section, we present the physics of the explosion, light curves and spectral formation in a nutshell to help understanding the connection. For details of the progenitor evolution and explosion physics, we refer to reviews and the other contributions in this issue. Each of the topical sections starts with a brief general review followed by a more detailed discussion of specific results. Because the youth of the field, some bias is unavoidable towards results obtained within our collaborations （and FSU）. The imprint of the metallicity, progenitor stars and properties such as the central density of the exploding WD are presented. IR spectroscopy, polarimetry and imaging of SNR remnants are discussed as a tool to test for the WD properties, magnetic fields and asymmetries. We discuss different classes of Type Ia supernovae, and their environment. Possible correlations between the spectroscopic and light curve properties of SN Ia are discussed. Finally, the overall emerging picture and future developments are discussed.

关键词： supernovae: general progenitors light curves spectra

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Parameter space for magnetization effects in high-energy-density plasmas

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Matter and Radiation at Extremes 2021年第6期6卷 36-44页

作者： James D.sadler Hui Li Kirk A.Flippo Los Alamos National Laboratory Los AlamosNew Mexico 87545USA

Magnetic fields are well known to affect the evolution of fluids via the J3B force,where J is the current density and B is the magnetic *** force leads to the influence of magnetic fields on hydrodynamics(magnetohydrodynamics).Magnetic fields are often neglected in modeling of high-energy-density plasmas,since J 3 B is very small compared with the plasma pressure ***,many experiments lie in a separate part of parameter space where the plasma is indirectly affected via magnetization of the heat flux and charged particle *** is true even for initially unmagnetized plasmas,since misaligned density and temperature gradients can self-generate magnetic *** comparing terms in the induction equation,we go on to estimate the regions of parameter space where these self-generated fields are strong enough to affect the hydrodynamics.

关键词： field magnetization energy

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Portal hypertension: Imaging of portosystemic collateral pathways and associated image-guided therapy

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World Journal of Gastroenterology 2017年第10期23卷 1735-1746页

作者： Murad Feroz Bandali Anirudh Mirakhur Edward Wolfgang Lee Mollie Clarke Ferris David James sadler Robin Ritchie Gray Jason Kam Wong Department of Radiology Foothills Medical Centre University of Calgary Division of Interventional Radiology Department of Radiology UCLA Medical Center

Portal hypertension is a common clinical syndrome, defined by a pathologic increase in the portal venous pressure. Increased resistance to portal blood flow, the primary factor in the pathophysiology of portal hypertension, is in part due to morphological changes occurring in chronic liver diseases. This results in rerouting of blood flow away from the liver through collateral pathways to low-pressure systemic veins. Through a variety of computed tomographic, sonographic, magnetic resonance imaging and angiographic examples, this article discusses the appearances and prevalence of both common and less common portosystemic collateral channels in the thorax and abdomen. A brief overview of established interventional radiologic techniques for treatment of portal hypertension will also be provided. Awareness of the various imaging manifestations of portal hypertension can be helpful for assessing overall prognosis and planning proper management.

关键词： Portal hypertension Diagnostic imaging Portosystemic collaterals Image-guided therapy

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Impaired gluconeogenesis in a porcine model of paracetamol induced acute liver failure

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World Journal of Gastroenterology 2011年第11期17卷 1457-1461页

作者： Konstantinos J Dabos Henry R Whalen Philip N Newsome John A Parkinson Neil C Henderson Ian H sadler Peter C Hayes John N Plevris Liver Cell Biology Laboratory Department of HepatologyUniversity of EdinburghEdinburghEH16 4SAUnited Kingdom Gastroenterology Unit Ioannina General Hospital Hatzikosta450-01 IoanninaGreece Gastroenterology Department Hatzikosta General HospitalLeoforos Makrygianni450-01 IoanninaGreece Department of Chemistry University of EdinburghEdinburghEH16 6AAUnited Kingdom

AIM:To investigate glucose homeostasis and in particular gluconeogenesis in a large animal model of acute liver failure(ALF).METHODS:Six pigs with paracetamol induced ALF under general anaesthesia were studied over 25 *** samples were withdrawn every five hours from a central *** animals were used as controls and were maintained under anaesthesia *** 1 H NMR spectroscopy we identified most gluconeogenic amino acids along with lactate and pyruvate in the animal plasma ***:No significant changes were observed in the concentrations of the amino acids studied in the animals maintained under anaesthesia *** we look at the ALF animals,we observed a statistically significant rise of lactate(P<0.003)and pyruvate(P<0.018) at the end of the *** also observed statistically significant rises in the concentrations of alanine(P<0.002),glycine(P<0.005),threonine(P< 0.048),tyrosine(P<0.000),phenylalanine(P<0.000) and isoleucine(P<0.01).Valine levels decreased significantly(P<0.05).CONCLUSION:Our pig model of ALF is characterized by an altered gluconeogenetic capacity,an impaired tricarboxylic acid(TCA)cycle and a glycolytic state.

关键词： Lactate Pyruvate Branch chain amino acids Aromatic amino acids

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Molecular dynamics reveal a novel kinase-substrate interface that regulates protein translation

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Journal of Molecular Cell Biology 2014年第6期8卷 473-485页

作者： Ming S. Liu Die.Wang Hiroyuki Morimoto Howard C.H. Yim Aaron T. Irving Bryan R.G. Williams Anthony J, sadler Centre for Cancer Research MIMR-PHI Institute of Medical Research Melbourne VIC 3168 Australia CSIRO - Computational Informatics and Digital Productivity Flagship Private Bag 10 Clayton South VlC 3169 Australia Department of Anatomy School of Medicine University of Occupational and Environmental Health Kitakyushu Fukuoka 807-8555 Japan Department of Molecular and Translational Science Monash University Melbourne VlC 3168 Australia

A key control point in gene expression is the initiation of protein translation, with a universal stress response being constituted by in- hibitory phosphoryiation of the eukaryotic initiation factor 2α （el F2oL）. In humans, four kinases sense diverse physiological stresses to regulate elF2α to control cell differentiation, adaptation, and survival. Here we develop a computational molecular model of elF2α and one of its kinases, the protein kinase R, to simulate the dynamics of their interaction. Predictions generated by coarse-grained dynamics simulations suggest a novel mode of action. Experimentation substantiates these predictions, identifying a previously unrecognized interface in the protein complex, which is constituted by dynamic residues in both elF2α and its kinases that are crucial to regulate protein translation. These findings call for a reinterpretation of the current mechanism of action of the el F2α kinases and demonstrate the value of conducting computational analysis to evaluate protein function.

关键词： molecular dynamics eukaryotic initiation factor 2α(elF2oc) elF2α kinases protein kinase R (PKR) protein translation kinase activity

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铝土矿的强化除铁方法

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轻金属 1992年第9期 1-5,14页

作者： Leon.Y.sadler 杨慧芬

本文研究的铝土矿除铁方法,包括以下四个过程:原矿细磨、焙烧、用还原气体将铝土矿中的弱磁性针铁矿和赤铁矿还原成强磁性的磁铁矿和金属铁,然后磁选除铁。原矿取自亚拉巴马铝土矿矿床,含Fe_2O_3 2.7％。经过以上处理,可获得含Fe_2O_3 ... 详细信息

本文研究的铝土矿除铁方法,包括以下四个过程:原矿细磨、焙烧、用还原气体将铝土矿中的弱磁性针铁矿和赤铁矿还原成强磁性的磁铁矿和金属铁,然后磁选除铁。原矿取自亚拉巴马铝土矿矿床,含Fe_2O_3 2.7％。经过以上处理,可获得含Fe_2O_3 1.5％,回收率为95％的除铁铝土矿产品,磁性产品含Fe_2O_3 21％。试验中,焙烧和H_2还原的温度均用800℃。一次磁选,磁选机的磁场强度为4000Gs。

关键词：铝土矿强化除铁

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β-酪蛋白与婴幼儿生长和发育

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临床儿科杂志 2014年第2期32卷 198-200页

作者： Michele J. sadler Nicholas Smith Rank Nutrition Ltd Bethersden Kent Edanz Group Ltd Kwun Tong Hong Kong

母乳是婴幼儿的首选营养源。世界卫生组织（WHO）建议婴儿出生后头6个月应完全以母乳喂养。此外，应坚持母乳辅以适当的固体食物喂养至少两年[1]。然而，并非所有婴儿均可得到母乳喂养，一些婴儿也无法获得捐赠母乳。在这种情况下需要... 详细信息

母乳是婴幼儿的首选营养源。世界卫生组织（WHO）建议婴儿出生后头6个月应完全以母乳喂养。此外，应坚持母乳辅以适当的固体食物喂养至少两年[1]。然而，并非所有婴儿均可得到母乳喂养，一些婴儿也无法获得捐赠母乳。在这种情况下需要用婴幼儿配方奶代替母乳。牛奶含有相对价廉的蛋白质与营养素且来源丰富，因此大多数婴幼儿配方奶均产自牛奶。但是，牛奶与母乳的蛋白质成分差异颇大。如，母乳主要含乳清蛋白，酪蛋白∶乳清蛋白约为40∶60（泌乳早期10∶90，泌乳后期50∶50），而牛奶的酪蛋白∶乳清蛋白则高达80∶20[2]。

关键词：婴幼儿酪蛋白母乳喂养发育生长世界卫生组织乳清蛋白固体食物

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Evaluating Watershed Vulnerability in Bernalillo County, New Mexico Using Expert Testimony, Fuzzy Analytic Hierarchy Process, and GIS

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Journal of Water Resource and Protection 2019年第7期11卷 866-885页

作者： Tracy sadler Clinton P. Richardson Phillip Miller Department of Civil and Environmental Engineering New Mexico Tech Socorro NM USA New Mexico Bureau of Geology & Mineral Resources New Mexico Tech Socorro NM USA

Geographic Information System (GIS) software was used to create a watershed vulnerability model for Bernalillo County, New Mexico. Watershed vulnerability was investigated as a function of soil erosion and infiltration criteria: precipitation, land slope, soil erodibility (K-factor), vegetation cover (NDVI), land use, drainage density, saturated hydraulic conductivity, and hydrologic soil group. Respective criteria weights were derived using a Fuzzy Analytic Hierarchy Process (FAHP) supported by expert opinion. A survey of 10 experts, representing New Mexico Institute of Mining and Technology (NMT), the New Mexico Bureau of Geology and Mineral Resources (NMBGMR), and the United States Geologic Survey (USGS), provided model input data for an integrated pair-wise comparison matrix for soil erosion and for infiltration. Individual criteria weights were determined by decomposing the respective fuzzy synthetic extent matrix using the centroid method. GIS layers were then combined based on criteria weights to produce maps of soil erosion potential and infiltration potential. A composite watershed vulnerability map was generated by equal weighting of each input map. Model results were categorized into five vulnerability categories: not vulnerable (N), slightly vulnerable (SV), moderately vulnerable (MV), highly vulnerable (HV), and extremely vulnerable (EV). The resulting FAHP/GIS model was used to generate a watershed vulnerability map of discrete areas in Bernalillo County, which may be vulnerable to stormwater run-off events and soil erosion. Such high volume run-off events can cause erosion damage to property and infrastructure. Alternatively, in areas near urban development, stormwater run-off may contribute non-point-source pollutant contamination of New Mexico’s surface water resources. The most problematic areas in Bernalillo County are present in the Eastern and Northwestern portions. However, less than 1% of the total area lies within the lowest and highest vulne

关键词： Stormwater Control Measures Fuzzy Analytic Hierarchy Process (FAHP) Multi-Criteria Decision Support Systems Geographic Information System Watershed Vulnerability

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