2,886 research outputs found
Photoelectro-chemical properties of anilino squaraine derivatives in LB films
No full textPhotocurrent generation from Langmuir-Blodgett (LB) overlays on indium tin oxide (ITO) electrodes, where the active components are 2,4-bis[4-(dibutylamino)-2-hydroxyphenyl]squaraine (1) and the unsubstituted analogue, 2,4-bis[4-(dibutylamino)phenyl]squaraine (2), have been investigated. Dye 1 shows improved behaviour compared with the latter and differences in performance are attributed to a modified aggregate structure, this being indicated by variations in the LB film spectra. The photocurrent generation is enhanced by the presence of electron accepters, e.g. N,N'-dimethyl-4,4'-bipyridinium diiodide (MV2+), but quenched by electron donors, e.g. hydroquinone (HQ). The concentration dependence is reported
Comments on author citations for nomenclatural novelties published in volume 15 of the Flora Reipublicae Popularis Sinicae (FRPS)
No full textLearning theories and interprofessional education: a user's guide
No full textThere is increasing interest in the theoretical underpinning of interprofessional education (IPE) and writers in this field are drawing on a wide range of disciplines for theories that have utility in IPE. While this has undoubtedly enriched the research literature, for the educational practitioner, whose aim is to develop and deliver an IPE curriculum that has sound theoretical underpinnings, this plethora of theories has become a confusing, and un-navigable quagmire. This article aims to provide a compass for those educational practitioners by presenting a framework that summarizes key learning theories used in IPE and the relationship between them. The study reviews key contemporary learning theories from the wider field of education used in IPE and the explicit applications of these theories in the IPE literature to either curriculum design or programme evaluation. Through presenting a broad overview and summary framework, the study clarifies the way in which learning theories can aid IPE curriculum development and evaluation. It also highlights areas where future theoretical development in the IPE field is required
Abstract LB-195: Bortezomib sensitizes glioblastoma for NK cell immunotherapy
No full textAbstract
Introduction: Glioblastoma (GBM) is the most aggressive and lethal brain cancer in adults where best available therapy combining surgery and concomitant chemo radiation prolongs patient survival from 12.1 to 14.6 months. Approximately half of the patients benefit from addition of Temozolomide chemotherapy (those with methylated promoter of the DNA repair gene O6 methylguanine DNA methyltransferase). Immunotherapy has demonstrated unprecedented efficacy in solid tumours and kill targets in unique ways to the conventional therapies. Natural Killer (NK) cells are attractive effectors not only because of their ability to recognize and kill malignant and virus infected cells, but also their potential for modifying the tumor microenvironment to pro-inflammatory state. We have previously demonstrated NK-cell cytotoxicity against GBM. Here we hypothesize that misfolded protein response induced by pretreatment with proteasome inhibitors will sensitize GBM cells to NK cell therapy.
Methods: IC50 doses of Bortezomib, Carfilzomib and MG132 proteasome inhibitors were determined by viability assays in P3, 2012-018 and P22 patient-derived GBM cells, as well as in normal human astrocytes (NHA). Phenotyping, time and dose dependent cytotoxicity/apoptosis and degranulation after combination therapy with Bortezomib and NK cells from healthy donors was conducted with flow cytometry and western blotting used to confirm protein signaling.
Results: We demonstrated that Bortezomib is the most suitable proteasome inhibitor as it selectively killed GBM cells at low doses (IC50 39-42nM) while requiring higher doses (70nM) for NHA cells. In contrast, Carfilzomib and MG132 killed better the NHA than GBM cells. Bortezomib was more effective in combination treatment with NK cells, than monotherapy of Bortezomib or NK cells. The IC50 dose of Bortezomib was reduced by 40% from 42nM at 48hrs to 25nM at 24hrs when combined with effector:target (E:T) ratio 5:1 NK cells (p&lt0.05). E:T ratio of NK cells was also reduced by 75% in combination therapy, NK cell monotherapy killed only 45% of GBM cells at 20:1 ratio. The killing efficacy of combination treatment was not mediated by increased stress ligand expression, but Bortezomib attenuated autophagy and induced late apoptotic GBM cell death. Although Bortezomib did not increase degranulation or kill NK cells, importantly, it rather induced NK cell differentiation to mature CD56dimCD16-NKG2D+ subsets previously associated with increased natural cytotoxicity.
Conclusion: Bortezomib was the best proteasome inhibitor against GBM that synergistically enhanced NK cell killing. Current work is investigating the mechanisms regulating the augmented differentiation and NK cell cytotoxicity during the combination therapy in vitro and in vivo in mice.
Citation Format: Andrea Gras Navarro, Aminur Rahman, Marzieh Bahador, Martha Chekenya Enger. Bortezomib sensitizes glioblastoma for NK cell immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr LB-195. doi:10.1158/1538-7445.AM2017-LB-195</jats:p
Photoelectrochemistry of Langmuir-Blodgett films of a C-60 iminodiacetic acid ester derivative on ITO electrodes
No full textThe photoelectrochemical response of a C-60 iminodiacetic acid ester derivative (C(60)IDA), deposited on ITO electrodes by means of the Langmuir-Blodgett technique, has been investigated. The anodic photocurrent observed on the modified electrode corresponds to an electron transfer from the electrolyte through the LB film to the electrode. The action spectrum of photocurrent indicates C60IDA as the photoactive species in the photoinduced electron transfer process. Positive bias voltage, reducing agent and higher pH of the solution are beneficial factors for generating higher photocurrent. The quantum yield for photocurrent generation is 0.94% and can be raised to 3.40% under favorable conditions. (C) 1998 Elsevier Science S.A. All rights reserved.Materials Science, MultidisciplinaryPhysics, Condensed MatterPolymer ScienceSCI(E)EI9ARTICLE3223-2279
The phosphatase inhibitor LB-100 creates neoantigens in colon cancer cells through perturbation of mRNA splicing
No full textAbstract Perturbation of protein phosphorylation represents an attractive approach to cancer treatment. Besides kinase inhibitors, protein phosphatase inhibitors have been shown to have anti-cancer activity. A prime example is the small molecule LB-100, an inhibitor of protein phosphatases 2A/5 (PP2A/PP5), enzymes that affect cellular physiology. LB-100 has proven effective in pre-clinical models in combination with immunotherapy, but the molecular underpinnings of this synergy remain understood poorly. We report here a sensitivity of the mRNA splicing machinery to phosphorylation changes in response to LB-100 in colorectal adenocarcinoma. We observe enrichment for differentially phosphorylated sites within cancer-critical splicing nodes of U2 snRNP, SRSF and hnRNP proteins. Altered phosphorylation endows LB-100-treated colorectal adenocarcinoma cells with differential splicing patterns. In PP2A-inhibited cells, over 1000 events of exon skipping and intron retention affect regulators of genomic integrity. Finally, we show that LB-100-evoked alternative splicing leads to neoantigens that are presented by MHC class 1 at the cell surface. Our findings provide a potential explanation for the pre-clinical and clinical observations that LB-100 sensitizes cancer cells to immune checkpoint blockade
Factorization of weakly compact operators between Banach spaces and Fréchet or (LB)-spaces
No full text[EN] In this note we show that weakly compact operators from a Banach space X into
a complete (LB)-space E need not factorize through a reflexive Banach space. If E is a Fréchet space, then weakly compact operators from a Banach space X into E factorize through a reflexive Banach space. The factorization of operators from a Fréchet or a complete (LB)-space into a Banach space mapping bounded sets into relatively weakly compact sets is also investigated.The research of the first author was partially supported by MEC and FEDER Project MTM2010-15200 and by GV Project Prometeo/2008/101. The support of the University of Aberdeen and the Universidad Polit´ecnica of Valencia is gratefully acknowledged.Bonet Solves, JA.; Wright, JM. (2012). Factorization of weakly compact operators between Banach spaces and Fréchet or (LB)-spaces. Matematicki Vesnik. 64(4):330-335. https://riunet.upv.es/handle/10251/58753S33033564
Simulating liquid droplets: A quantitative assessment of lattice Boltzmann and Volume of Fluid methods
No full textWhile various multiphase flow simulation techniques have found acceptance as predictive tools for processes involving immiscible fluids, none of them can be considered universally applicable. Focusing on accurate simulation of liquid-liquid emulsions at the scale of droplets, we present a comparative assessment of the single-component multiphase pseudopotential lattice Boltzmann method (PP-LB, classical and modified) and the Volume of Fluid method (VOF, classical and modified), highlighting particular strengths and weaknesses of these techniques. We show that a modified LB model produces spurious velocities 1–3 orders of magnitude lower than all VOF models tested, and find that LB is roughly 10 times faster in computation time, while VOF is more versatile. Simulating falling liquid droplets, a realistic problem, we find that despite identical setups, results can vary with the technique in certain flow regimes. At lower Reynolds numbers, all methods agree reasonably well with experimental values. At higher Reynolds numbers, all methods underpredict the droplet Reynolds number, while being in good agreement with each other. Particular issues regarding LB simulations at low density ratio are emphasized. Finally, we conclude with the applicability of VOF vis-à-vis PP-LB for a general range of multiphase flow problems relevant to myriad applications.Accepted Author ManuscriptChemE/Transport PhenomenaIntensified Reaction and Separation System
Nonadaptive Amino Acid Convergence Rates Decrease over Time.
No full textConvergence is a central concept in evolutionary studies because it provides strong evidence for adaptation. It also provides information about the nature of the fitness landscape and the repeatability of evolution, and can mislead phylogenetic inference. To understand the role of adaptive convergence, we need to understand the patterns of nonadaptive convergence. Here, we consider the relationship between nonadaptive convergence and divergence in mitochondrial and model proteins. Surprisingly, nonadaptive convergence is much more common than expected in closely related organisms, falling off as organisms diverge. The extent of the convergent drop-off in mitochondrial proteins is well predicted by epistatic or coevolutionary effects in our "evolutionary Stokes shift" models and poorly predicted by conventional evolutionary models. Convergence probabilities decrease dramatically if the ancestral amino acids of branches being compared have diverged, but also drop slowly over evolutionary time even if the ancestral amino acids have not substituted. Convergence probabilities drop-off rapidly for quickly evolving sites, but much more slowly for slowly evolving sites. Furthermore, once sites have diverged their convergence probabilities are extremely low and indistinguishable from convergence levels at randomized sites. These results indicate that we cannot assume that excessive convergence early on is necessarily adaptive. This new understanding should help us to better discriminate adaptive from nonadaptive convergence and develop more relevant evolutionary models with improved validity for phylogenetic inference
Constructing different 'bridges' for interfacial electron transfer in azobenzene LB/SAM composite bilayers
No full textTwo methods, Langmuir-Blodgett (LB) and self-assembly (SA), were used in the present work to fabricate certain interfacial structures for the study of long-range electron transfer. We have successfully constructed two different 'bridges' for the interfacial electron transfer in azobenzene LB/SAM composite bilayer systems. One has ionic bonding character, while the other has face-to-face hydrogen bonding at the interface of an ABD (4-octyl-4'-(3-carboxy-trimethylene-oxy)-azobenzene) LB monolayer and the underlying aminothiol SAM. These structures have been confirmed by using RA-FTIR and contact angle titration. Furthermore, the apparent electron transfer rate across the ionic bonding 'bridge' is much more rapid than in the hydrogen-bonded case, indicating that the interfacial structure plays a crucial role in the long-range electron transfer kinetics. (C) 1998 Elsevier Science S.A. All rights reserved.Chemistry, AnalyticalElectrochemistrySCI(E)EI14ARTICLE1119-12444
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