A Secondary Structural Element in a Wide Range of Fucosylated Glycoepitopes

2017 ◽  
Vol 23 (48) ◽  
pp. 11598-11610 ◽  
Author(s):  
Thomas Aeschbacher ◽  
Mirko Zierke ◽  
Martin Smieško ◽  
Mayeul Collot ◽  
Jean-Maurice Mallet ◽  
...  
2016 ◽  
Vol 6 (2) ◽  
pp. 35-41 ◽  
Author(s):  
Michelle L.A. Nelson ◽  
Elizabeth Hanna ◽  
Stephen Hall ◽  
Michael Calvert

Background Approximately 80% of people who survive a stroke have on average five other conditions and a wide range of psychosocial issues. Attention to biopsychosocial issues has led to the identification of ‘complex patients’. No single definition of ‘patient complexity’ exists; therefore, applied health researchers seek to understand ‘patient complexity’ as it relates to a specific clinical context. Objective To understand how ‘patient complexity’ is conceptualized by clinicians, and to position the findings within the existing literature on patient complexity. Methods A qualitative descriptive approach was utilized. Twenty-three stroke rehabilitation clinicians participated in four focus groups. Results Five elements of patient complexity were identified: medical/functional issues, social determinant factors, social/family support, personal characteristics, and health system factors. Using biopsychosocial factors to identify complexity results in all patients being complex; operationalization of the definition led to the identification of systemic elements. A disconnect between acute, inpatient rehabilitation and community services was identified as a trigger for increased complexity. Conclusions Patient complexity is not a dichotomous state. If applying existing complexity definitions, all patients are complex. This study extends the understanding by suggesting a structural element of complexity from manageable to less manageable complexity based on ability to discharge.


Polymers ◽  
2021 ◽  
Vol 13 (20) ◽  
pp. 3555
Author(s):  
Patrich Ferretti ◽  
Gian Maria Santi ◽  
Christian Leon-Cardenas ◽  
Elena Fusari ◽  
Giampiero Donnici ◽  
...  

Additive manufacturing processes have evolved considerably in the past years, growing into a wide range of products through the use of different materials depending on its application sectors. Nevertheless, the fused deposition modelling (FDM) technique has proven to be an economically feasible process turning additive manufacture technologies from consumer production into a mainstream manufacturing technique. Current advances in the finite element method (FEM) and the computer-aided engineering (CAE) technology are unable to study three-dimensional (3D) printed models, since the final result is highly dependent on processing and environment parameters. Because of that, an in-depth understanding of the printed geometrical mesostructure is needed to extend FEM applications. This study aims to generate a homogeneous structural element that accurately represents the behavior of FDM-processed materials, by means of a representative volume element (RVE). The homogenization summarizes the main mechanical characteristics of the actual 3D printed structure, opening new analysis and optimization procedures. Moreover, the linear RVE results can be used to further analyze the in-deep behavior of the FDM unit cell. Therefore, industries could perform a feasible engineering analysis of the final printed elements, allowing the FDM technology to become a mainstream, low-cost manufacturing process in the near future.


2019 ◽  
Author(s):  
Zhijun Guo ◽  
Nan Jiang ◽  
Jessical moore ◽  
Colin McCoy ◽  
Monika Ziminska ◽  
...  

<p>The challenging post-surgery management of bone metastasis sees the needs for multi-functional bone scaffolds that offer multi-modal therapeutic functions. Through a nature-inspired layer-by-layer assembly process, we developed a unique multi-functional tissue scaffold that consists of porous polyurethane substrate and nanoscale chitosan/ graphene oxide hybrid coating. Alternative layers of drug laden chitosan and graphene oxide nanosheets were held together through strong electrostatic interaction, giving rise to a robust multilayer architecture with control over structural element orientation and chemical composition at nanoscale. For the first time, proof-of-concept on combining pH-controlled co-delivery of multiple therapeutic agents and photothermal therapy have demonstrated, in the context of malignant bone cancer treatment. Our scaffold system can be tailored to the patient’s specific needs through loading of bespoke therapeutic agents and offering on-demand photothermal therapy. The methodology can also be generalized to create functional surfaces for a wide range of biomedical devices as well as for applications beyond healthcare technology.</p>


2019 ◽  
Author(s):  
Zhijun Guo ◽  
Nan Jiang ◽  
Jessical moore ◽  
Colin McCoy ◽  
Monika Ziminska ◽  
...  

<p>The challenging post-surgery management of bone metastasis sees the needs for multi-functional bone scaffolds that offer multi-modal therapeutic functions. Through a nature-inspired layer-by-layer assembly process, we developed a unique multi-functional tissue scaffold that consists of porous polyurethane substrate and nanoscale chitosan/ graphene oxide hybrid coating. Alternative layers of drug laden chitosan and graphene oxide nanosheets were held together through strong electrostatic interaction, giving rise to a robust multilayer architecture with control over structural element orientation and chemical composition at nanoscale. For the first time, proof-of-concept on combining pH-controlled co-delivery of multiple therapeutic agents and photothermal therapy have demonstrated, in the context of malignant bone cancer treatment. Our scaffold system can be tailored to the patient’s specific needs through loading of bespoke therapeutic agents and offering on-demand photothermal therapy. The methodology can also be generalized to create functional surfaces for a wide range of biomedical devices as well as for applications beyond healthcare technology.</p>


2016 ◽  
Author(s):  
Artur Ulikowski ◽  
Anna Jaromin ◽  
Giorgia Brancolini ◽  
Luca Bellucci ◽  
Bartłomiej Furman

Indoles represent a structural element in a myriad of natural products and biologically active molecules. Of special importance are 2,3-disubstituted indoles. Thus, a number of methods for their synthesis have been described. However, these are often hampered by a number of limitations: they often offer poor regioselectivity and suboptimal functional group tolerance. Also, they can normally be adapted to the procurement of a small subclass of indoles only. We have developed an approach to 2,3-disubstituted indoles overcoming these obstacles. By selectively activating the amide carbonyl in isatin-derived oxindoles, we obtained a number of the title compounds in a regiospecific and functional group-tolerant manner. The methodology is normally characterized by excellent yields. The reaction proceeds by chemoselective partial reduction of the amide moiety to an iminium salt and a subsequent nucleophilic addition followed by dehydration, which furnishes the target indole. A number of nucleophiles, including C- and S-nucleophiles, have been examined. The obtained compounds were studied towards acetylcholinesterase (AChE) inhibitory activity, as the indole skeleton is often seen in the struc-ture of enzyme inhibitors. Cholinesterase inhibitors are used in the treatment of Alzheimer's disease, increasing available acetylcholine by decreasing the AChE activity. For the tested agents, properties like logP, logBBB (Blood-Brain Barier penetration) and Caco2 permeabilities were also calculated. Based on the predicted values, only two of them are able to penetrate into the CNS (central nervous system). Molecular docking was performed on the whole set of the syntesized indole derivatives, resulting in a wide range of AChE inhibitory activity. Molecular docking binding interactions reported the lowest energy conformations of the syntesized compounds and the key amino acid residues at the active binding site of AChE. The current synergy between computations and experiments provided the identification of the indole derivatives exhibiting the highest inhibitory activity. The presented results will provide theoretical guidance for further modification and optimization of the indole derivatives.


Molecules ◽  
2021 ◽  
Vol 26 (18) ◽  
pp. 5643
Author(s):  
Nicole A. Horenstein ◽  
Clare Stokes ◽  
Roger L. Papke

The α7 nicotinic acetylcholine receptor (nAChR) is an important target given its role in cognitive function as well as in the cholinergic anti-inflammatory pathway, where ligands that are effective at stabilizing desensitized states of the receptor are of particular interest. The typical structural element associated with a good desensitizer is the ammonium pharmacophore, but recent work has identified that a trivalent sulfur, in the positively charged sulfonium form, can substitute for the nitrogen in the ammonium pharmacophore. However, the breadth and scope of employing the sulfonium group is largely unexplored. In this work, we have surveyed a disparate group of sulfonium compounds for their functional activity with α7 as well as other nAChR subtypes. Amongst them, we found that there is a wide range of ability to induce α7 desensitization, with 4-hydroxyphenyldimethylsulfonium and suplatast sulfonium salts being the most desensitizing. The smallest sulfonium compound, trimethylsulfonium, was a partial agonist for α7 and other neuronal nAChR. Molecular docking into the α7 receptor extracellular domain revealed preferred poses in the orthosteric binding site for all but one compound, with typical cation–pi interactions as seen with traditional ammonium compounds. A number of the compounds tested may serve as useful platforms for further development of α7 desensitizing ability and for receptor subtype selectivity.


2006 ◽  
Vol 188 (13) ◽  
pp. 4610-4619 ◽  
Author(s):  
Marcus Miethke ◽  
Michael Hecker ◽  
Ulf Gerth

ABSTRACT The heat-inducible CtsR regulon of Bacillus subtilis codes for three Clp proteins with chaperone or protease activity. While the importance of ClpC and ClpP has been elucidated for a wide range of cellular adaptation processes, this study deals with the physiological role of B. subtilis ClpE. Northern experiments and reporter gene analyses revealed that ClpE is essential both for efficient CtsR-dependent gene derepression and for rerepression during heat stress. ClpEP was found to destabilize the global regulator CtsR after heat shock in vivo with different kinetics than ClpCP, which is known to degrade CtsR in vitro and in vivo upon heat stress. Furthermore, ClpE was localized at heat-generated inclusion bodies by electron microscopy. The comparison of radiolabeled aggregated protein fractions of wild-type and clpE mutant cells during heat stress displayed a significant delay of protein disaggregation in the absence of ClpE. A kinetic Western blotting approach confirmed the long-term residence of ClpE in the insoluble cell fraction rather than in the cytoplasmic fraction. These observations indicate the involvement of ClpE in global protein disaggregation. As a characteristic structural element of ClpE, the N-terminal zinc finger domain was proven to be essential for basal in vitro ATPase activity.


PLoS ONE ◽  
2015 ◽  
Vol 10 (10) ◽  
pp. e0141132 ◽  
Author(s):  
Marta Soszynska-Jozwiak ◽  
Paula Michalak ◽  
Walter N. Moss ◽  
Ryszard Kierzek ◽  
Elzbieta Kierzek

2006 ◽  
Vol 5-6 ◽  
pp. 383-390
Author(s):  
D.T.G. Katerelos ◽  
C. Galiotis

Composite laminates are used for the construction of a wide range of products; from civil infrastructure to aeronautical or space structures. Since all these structures cannot be built at once, but they are composed by several structural elements connected in various patterns, the problem of stress concentrations strikes importantly. Additionally, the structures are often designed in a “fail safe” manner, which bespeaks the damage tolerance of the material. This means that the structural element and the structure are called to operate in the presence of various forms of damage. Damage locations within a structural element or a structure cause stress rising. In the present paper experimental investigation of the stress concentration arising in composite laminates, (a) around a circular notch and (b) due to damage onset and growth during their lifetime, is presented. The experimental results are compared to analytical model predictions.


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